Medical Genetics

Updates about ethical, legal and psychological implications of genetic testing in newborns, children and adolescents Manal M Thomas Middle East Journal of Medical Genetics 2018 7(2):51-61 Genetic diseases affect physical and psychological health status and social well-being of patients and their families. For that reason, many organizations in the genetic field have published new guidelines on ethical and legal issues regarding genetic testing in children and adolescents. This review article aims to highlight the guidelines regarding quality standards of genetic testing in children and adolescents stressing on the ethical, legal and psychological implications of genetic testing. Specific guidelines on genetic testing and laws must be designed in Egypt to regulate genetic testing and enhance patients' rights putting specific legislations that comply with our traditions and beliefs. More knowledge and educational programs are recommended for health professionals and the public about measures to prevent diseases and promote health behaviors.

Genetic syndromes with immunological disturbances Iman Aly Helwa Middle East Journal of Medical Genetics 2018 7(2):62-77 Generally speaking, immunodeficiency conditions express a genetic component. In some of these cases, patients may request medical advice due to immune disturbance rather than due to genetic abnormality. Sometimes, the immune defect is not encountered in all cases. Yet, in certain cases, it is realized after diagnosis, while in others the immune defect is not the main clinical problem at all. However, immune defects maybe fatal in some syndromes and require urgent intervention. This review presents a brief overview on the immune response and then delineate the genetic syndromes manifesting immunological abnormalities.

Genome-editing technologies: Advancement, clinical applications, and ethical concerns Wessam E Sharaf-Eldin, Heba A Hassan, Nagham M El-Bagoury, Mona L Essawi Middle East Journal of Medical Genetics 2018 7(2):78-87 Genome editing is a powerful technology capable of precisely manipulating somatic and germline genomic sequences. The field is progressing at a rapid pace with unprecedented applications in biology and medicine. This systematic review represents a guide to different mechanisms, tools, and delivery systems used in genome editing. In addition, related ethical concerns are highlighted. So far, the most recent developed tool, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated enzyme, represents the most widely used approach owing to its simple application and enhanced efficiency. Hence, the major part of the review focuses on the clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated enzyme technology and its diverse applicability.

Corpus callosum abnormalities in 64 Egyptian patients: Neuropsychological and genetic studies Mahmoud Y Issa, Samira Ismail, Nivine Helmy, Alaa K Kamel, Sherine K Amin, Olweya M Abdel Baky, Maha S Zaki Middle East Journal of Medical Genetics 2018 7(2):88-95 Introduction Corpus callosum (CC) connects the left and right cerebral hemispheres. It is the largest white matter structure in the brain connecting mainly homotopic, as well as heterotopic, brain areas of both hemispheres. It has a major role in everyday behavior. Agenesis of CC can occur as isolated finding on MRI, or more commonly, it is associated with large number of brain anomalies. Patients and methods Neuropsychological and genetic assessment was done for 64 cases with corpus callosum abnormalities, whose age ranged from 6 months to 11 years and 9 months, with a mean age of 3 years and 6 months. This study was done from January 2012 till December 2014. Results Overall, 12.5% of the cases had chromosomal aberrations, 14% of the cases had identified genetic syndrome, and 73% of the cases were nonsyndromic/unclassified. Variable degrees of mental subnormality were encountered among 58 (92.2%) of 64 studied patients. Conclusion Abnormalities of the CC are often associated with cognitive deficits, autism, and epilepsy.

Mutation analysis of the arylsulfatase B gene among Egyptian patients with Maroteaux–Lamy disorder Mona L Essawi, Nagham M Elbagoury, Ola M Sayed, Mona S Aglan, Mona M Ibrahim, Hala N Soliman, Ekram M Fateen Middle East Journal of Medical Genetics 2018 7(2):96-103 Background Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) (OMIM: # 253200), is an autosomal recessive lysosomal storage disorder. It is caused by deficiency of the enzyme arylsulfatase B (ARSB), also known as N-acetylgalactosamine-4-sulfatase. ARSB is responsible for the degradation of the glycosaminoglycans dermatan sulfate and chondroitin 4-sulfate. Deficiency of the ARSB enzyme leads to accumulation of partially degraded dermatan sulfate in the lysosomes especially in connective tissues leading to clinical complications. Aim This study aimed at identifying the molecular basis of MPS VI (Mucopolysaccharidosis VI) among 15 Egyptian patients. Method Patients were from 15 families, age ranged from 1year and 5 months to 11 years and 9 months(5.19±0.8) with parental consanguinity in 11 families out of 15 (73.3%). All patients were subjected to all necessary clinical, radiological and biochemical assessments. Molecular assessment was carried out by sequencing the 8 coding exons of the ARSB gene for the fifteen studied patients. Results The disease causing mutations were revealed in 13 patients. Four novel mutations; c.257delA, c.189insA, p.Ser94Leu and p.Leu51Pro were identified as well as four previously reported mutations; p.Leu82Arg, p.Ser96Arg, p.Arg160X and p.Arg160Gln. Conclusion The study highlights the heterogeneity of the mutational pattern which was obvious in finding novel mutations in homozygous forms in approximately 40% of the studied patients. Exons 1 and 2 seem to carry most of the mutations in the Egyptian MPS VI patients. Arginine at position 160 seems to be the most abundant mutational hot spot in the Egyptian MPS VI patients.

Assessment of serum level of vitamin D in infants and children with Down syndrome Manal M El-Hawary, Shahira M El-Shafie, Heba El-Awady, Tamer Ragab, Raooth Nabile Middle East Journal of Medical Genetics 2018 7(2):104-111 Background Vitamin D has multiple extraskeletal functions. Patients with Down syndrome (DS) are at more risk of vitamin D deficiency owing to multiple environmental and hormonal factors, so vitamin D supplementation plays a vital role in their lifestyle. Objective The aim of the study is to assess serum vitamin D level and to study the several factors that may affect its level in infants and children with DS. Patients and methods The study enrolled 50 children, where 30 of them were diagnosed as having DS (group I) and the other 20 were defined as a control group (group II). Detailed systemic examination was performed for all participants. Anthropometric measurements including weight, height, and head circumference were assessed. Blood samples were collected and evaluated for 25-hydroxy vitamin D level. Results The mean serum vitamin D level was 30.65 ± 20.64 in group I compared with 55.80 ± 22.79 in group II, with significant P value of less than 0.0001. In patients with DS, 6.7% were severely deficient (<10 ng/ml), 53.3% had insufficient serum vitamin D level (10–32 ng/ml), and 40% had adequate serum vitamin D level (>32 ng/ml). In group II, only 20% had insufficient serum vitamin D level and 80% had adequate level. Conclusion Vitamin D deficiency and insufficiency were more prevalent in patients with DS. Vitamin D insufficiency was also reported in the control group, which indicates that it is a common health problem even among healthy participants. Diet rich in vitamin D, adequate sun exposure, and vitamin D supplements prevent vitamin D deficiency.

Dysregulation of tumor necrosis factor-α and interleukin-6 as predictors of gestational disorders Hala T El-Bassyouni, Sahar M Abdel Raouf, Mona K Farag, Wasela M Nawito, Tarek M Salman, Khaled R Gaber Middle East Journal of Medical Genetics 2018 7(2):112-117 Background Approximately 7% of all pregnancies are complicated by gestational diabetes mellitus (GDM). Maternal complications pertaining to GDM are associated with a variety of complications in pregnancy, most notably preeclampsia (PE), which is characterized by an exaggerated systemic inflammatory response. The study aimed to examine the clinical significance of detection of the cytokine tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in pregnant women with GDM and PE. Patients and methods A total of 60 pregnant women, comprising 25 diagnosed with GDM, 15 with PE, and 20 controls normoglycemic and normotensive, were examined. TNF-α and IL-6 were estimated. Results IL-6 concentration was significantly higher in the pregnant females who developed GDM and PE later during pregnancy compared with the control group (P < 0.0001 and 0.003, respectively). TNF-α concentration showed only significant difference in the women who developed GDM later during pregnancy when compared with the control group (P < 0.0001). Conclusion TNF-α and IL-6 have been proposed to play an important role in the prediction of the pathogenesis of GDM and PE.

Genetic study of the association of specific language impairment to markers near FOXP2 gene Mohammed M Sayed-Ahmed, Samira Ismail, Alia M El-Shoubary, Mona L Essawi, Moushira E Zaki, Ahmed N Khattab Middle East Journal of Medical Genetics 2018 7(2):118-123 Background One important language gene is FOXP2, a mutation of which affects language and speech in relatively rare and severe forms. However, certain genetic markers adjacent to FOXP2 gene are highly suspected to be involved in common forms of specific language impairment (SLI). Identification of these genetic loci related to SLI may yield new insights into its causes, along with improved diagnosis, and treatment. Aim of the work To study the association of SLI to two genetic markers residing near FOXP2 gene, namely, the repeat unit GATA of D7S3052 marker and GATT tetranucleotide repeats in intron 6 of CFTR gene. Patients and methods The current study included 50 children with SLI and 50 normal controls, aged 3–8 years. All participants were subjected to genetic molecular association study as well as detailed protocol of assessment including full history and examination, and evaluation of language skills and mental ability (intelligence quotient). Results There was no difference between the SLI and normal groups regarding molecular results of GATT repeats of CFTR gene, and there was a nonsignificant difference regarding results of GATA repeats of D7S3052 marker (P > 0.05). Conclusion The association of SLI with D7S3052 marker near FOXP2 gene in current study is statistically nonsignificant. However, a statistical significance of this association could be expected with a larger number of cases, more diversity of SLI types and degrees, and more comprehensive procedures.

MicroRNA-mediated sensitization of lung cancer cells to chemotherapeutics: the roles of miR-21 and miR-155 Nnaemeka D Ndodo, Barnabas Danborno, Samuel S Adebisi Middle East Journal of Medical Genetics 2018 7(2):124-131 Background MicroRNAs (miRNAs) are conserved short 22-nucleotide RNAs with important roles in regulating gene expression. Misregulation of genes that control cell-cycle and cell-fate determination often contributes to cancer. The aims of this work were to evaluate the expressions of two oncogenic miRNA (oncomiRs), miR-21 and miR-155, in lung cancer, and to see whether reintroduction or inhibition of these would affect progression or aid sensitivities of the lung cancer cells to major chemotherapeutics. Methods This work involved cell culture of lung adenocarcinoma cells H358 and A549 and normal lung cells. It compared the miRNA expression profiles of two miRNAs (miR-21 and miR-155) in cancer and normal lung cell lines using real-time PCR and then treated with three known chemotherapeutics, namely cisplatin, etoposide and paclitaxel, and concluded by inhibiting overexpressed miRNA by transfecting the cancer cells with miRNA inhibitors, and proliferation was measured with sulforhodamine-B assay. Results showed that miR-21 was overexpressed in the entire cell lines used, which is consistent with the role of miR-21 as an oncomir, whereas miR-155 was downregulated, suggesting that miR-155 could be acting as a tumor suppressor. Furthermore, inhibition of miR-21 function in H358 lines using 50 nM Ambion anti-miR led to a decreased proliferation of H358 cells compared with the 50 nM anti-miR-155-treated group. Downregulation of miR-21 seems to sensitize lung cancer cells to chemotherapeutics (etoposide). Conclusion This work demonstrated that miR-21 at 50 nM might sensitize lung cancer cells to chemotherapeutics (etoposide) and that miR-155, a known oncogenic miRNA, seems to be acting as a tumor suppressor in lung cancer, which promises to be of immense therapeutic importance.

Fragile X syndrome: diagnosis by molecular characterization of FMR1 gene and clinical correlation Hoda M Abd El-Ghany, Eman A Ehssan, Menatalla K El-Deen, Rasha A Al-Gamal, Rania M Samy, Amany S El-Deen Middle East Journal of Medical Genetics 2018 7(2):132-138 Background One of the most common forms of inherited intellectual disability (ID) is fragile X syndrome (FXS), which is caused by expansion of cytosine–guanine–guanine trinucleotide repeat at the 5′ untranslated region of the fragile X mental retardation gene (FMR1) at Xq27. The cytosine–guanine–guanine repeat expansion leads to hypermethylation and inactive transcription of the gene. The present study aimed to detect expected FMR1 gene alleles by methylation-sensitive PCR and its clinical correlation for rapid screening of FXS among male patients with ID. Patients and methods The study included 50 male patients with ID and clinical features suggestive of FXS, who were compared with 50 healthy age-matched volunteers. All patients were subjected to full history taking, thorough clinical examination using a 15-item checklist [physical (big ears, joint hyperextensibility, Simian crease, wide forehead, macroorchidism, and elongated face) and neurological features (mental retardation, family history of mental retardation, poor eye contact, hand biting, hyperactivity, perservative speech, tactile defensiveness, hand flapping, and short attention span)], and karyotyping using GTG banding. Methylation-sensitive PCR technique after bisulfite treatment of DNA was applied for the detection of expanded alleles of the FMR1 gene. Results Clinical score in patients with abnormal alleles was significantly higher compared with patients with normal alleles. GTG-banding technique showed normal 46XY male karyotype for studied patients. Frequency of normal FMR1 gene alleles was detected in the control group (100%) and 44 (88%) patients. Abnormal alleles were detected in six (12%) patients: three (6%) patients with full mutation (FM) and three (6%) patients with premutation carrier. Conclusion Our study revealed that PCR-positive results of fragile X correlate with the checklist clinical score rather than a single clinical entity.

Microscopy and Ultrastructure

Potential toxic effect of bisphenol A on the cardiac muscle of adult rat and the possible protective effect of Omega-3: A histological and immunohistochemical study Noha Gamal Bahey, Hekmat Osman Abd Elaziz, Kamal Kamal Elsayed Gadalla Journal of Microscopy and Ultrastructure 2019 7(1):1-8 Bisphenol A (BPA) is intensely used in the production of polycarbonate plastics and epoxy resins. Recently, BPA has been receiving increased attention due to its link to various health problems that develop after direct or indirect human exposure. Previous studies have shown the harmful effect of high doses of BPA; however, the effect of small doses of BPA on disease development is controversial. The aim of this study was to investigate the effect of a low dose of BPA on the rat myocardium and to explore the outcome of coadministration of Omega-3 fatty acid (FA). Thirty adult male rats were divided equally into control group, BPA-treated group (1.2 mg/kg/day, intraperitoneally for 3 weeks), and BPA and Omega-3-treated group (received BPA as before plus Omega-3 at a daily dose of 300 mg/kg/day orally) for 3 weeks. Exposure to BPA resulted in structural anomalies in the rat myocardium in the form of disarrangement of myofibers, hypertrophy of myocytes, myocardial fibrosis, and dilatation of intramyocardial arterioles. On the other hand, mast cell density and media-to-lumen area ratio were not significantly altered. Interestingly, concomitant administration of Omega-3 FAs with BPA significantly reduced BPA-induced changes and provided a protective effect to the myocardium. In conclusion, exposure to a low dose of BPA could potentially lead to pathological alterations in the myocardium, which could be prevented by administration of Omega-3 FA.

Light and scanning electron microscopic examination of the chicken oviduct during the embryonic and posthatching stages Mohamed A.M. Alsafy, Samir A.A. El-Gendy, Ashraf A Karkoura, Doha Naguib Journal of Microscopy and Ultrastructure 2019 7(1):9-13 The present study aimed to study the sequence of developing the oviduct of the Alexandria chicken during the embryonic and posthatching period by using the light and scanning electron microscopic (SEM) examination. The Mullerian duct began to appear as left and right urogenital ridges composed of stratified cuboidal epithelium at the ventrolateral aspect of the mesonephros at the 5-day-old embryo. At the 6-day-old embryo, the left urogenital ridge canalized and the tubal wall surrounded a circular lumen composed of three cellular components; inner simple columnar epithelium, multilayers of mesenchymal cells, and outer stratified cuboidal epithelium. At the 8-day-old embryo, the inner tubal layer became composed of simple-to-pseudostratified ciliated columnar epithelium, the density of the mesenchymal cells increased, and the outer layer became simple squamous epithelium at the medial aspect of the duct and stratified epithelium at the lateral aspect of the duct. The left oviduct of the 1-day-old chick resembled the oviduct of 8-day-old embryo except the SEM observations of the tunica mucosa of the 1-day-old chick which showed extensive mucosal folds with many straight cilia. At the 1-week-old chick, the left oviduct showed a folded lumen surrounded by simple columnar ciliated epithelial layer followed by a layer of mesenchymal cells, many layers of smooth muscles surrounded the mesenchymal cells layer and outer simple squamous epithelium layer. At the 1-month-old chick, the left oviduct wall was composed of five layers surrounded by a star-shaped lumen.

Ultrastructural studies of acrosomal formation in the testis of male greater cane rat (Thryonomys swinderianus) AO Adebayo, AK Akinloye, AO Ihunwo, VO Taiwo, BO Oke Journal of Microscopy and Ultrastructure 2019 7(1):14-18 Purpose: In furthering the understanding of the process of spermatogenesis in the greater cane rat, this study describes the ultrastructural spermiogenic transformation and acrosomal formation in the testes of this hystricomorphic rodent that is currently undergoing domestication in parts of West Africa. Materials and Methods: Testicular samples were obtained from ten sexually mature cane rats that were perfused-fixed using Karnovsky's fixative (phosphate buffered 2% paraformaldehyde – 2.5% glutaraldehyde fixative at pH 7.4). The samples were processed for ultrastructural analysis and examined under the transmission electron microscope. Results: The testes of the cane rat showed uniqueness in its cellular associations and the ultrastructure of the spermatogenic cells especially in the formation of the acrosome. The spermatid differentiation and acrosomal formation occurred in 12 steps with the first three steps being the Golgi phase and the next three steps making up the cap phase. While the three steps that follow constitute the acrosomal phase, the last 3 steps make up the maturation phase. At the cap and acrosomal phases, the entire acrosomal system comprising the vesicle and granule covers the head of the spermatids with no clear indentation of the nuclear surface by the formed acrosome. Furthermore, elongated spermatids at the maturation phase contained abundance of nuclear vacuoles. Conclusion: This work has not only provided information that will further the understanding of spermatogenesis but also aid the understanding of acrosomal reaction in the reproduction of the greater cane rat.

Immunohistochemical expression of E- and N-Cadherin in nodular prostatic hyperplasia and prostatic carcinoma Rania Abdallah Abdallah, Asmaa Gaber Abdou, Moshira Abdelwahed, Hend Ali Journal of Microscopy and Ultrastructure 2019 7(1):19-27 Background: Different theories have been postulated to explain the development of nodular prostatic hyperplasia (NPH). Epithelial to mesenchymal transition (EMT) is a physiologic process in which the epithelial cells lose their polarity and cell-cell adhesion and acquire a mesenchymal phenotype. Aim: The aim of the present study is to investigate the potential role of E- and N-cadherin in the induction of EMT in NPH and prostatic carcinoma. Methods: This study was carried out on 55 cases of NPH and 20 cases prostatic carcinoma for evaluation of immunohistochemical expression of E and N cadherins. Results: Most NPH (54/55 cases, 98.2%) and all cases of prostatic carcinoma showed positive N-cadherin expression in prostatic glands and stroma. High percentage of N-cadherin expression by stromal cells was significantly in favor of prostatic carcinoma compared to NPH. High percentage of N-cadherin expression by epithelial cells of carcinoma group was significantly associated with young age while its high expression by stromal cells was significantly associated with multicentricity. About 96.4% of NPH and 75% of prostatic carcinoma showed positive E-cadherin expression with a significant difference. No significant association between E-cadherin and N-cadherins in both NPH and prostatic carcinoma was identified. Conclusions: The prominent expression of N-cadherin in large numbers of NPH and prostate carcinoma cases in the epithelial and stromal components could point to the occurrence of EMT in those diseases. It also opens a new gate for treatment of those patients by targeting N-cadherin molecule. The absence of inverse association between E-cadherin and N-cadherins in NPH and prostatic carcinoma may indicate that cadherin switch is not an essential step for the development of EMT.

Cytotoxic effects of extract of Acmella oleracea in the ovaries and midgut of Rhipicephalus sanguineus Latreille, 1806 (Acari: Ixodidae) female ticks Patrícia Rosa de Oliveira, Luis Adriano Anholeto, Rodney Alexandre Ferreira Rodrigues, André Arnosti, Gervásio Henrique Bechara, Karina Neoob de Carvalho Castro, Maria Izabel Camargo-Mathias Journal of Microscopy and Ultrastructure 2019 7(1):28-43 The present study investigated the effects of different concentrations of Acmella oleracea extract on the germinative cells and digestive processes of semi-engorged Rhipicephalus sanguineus females. For this experiment, 150 ticks were divided into five groups (30 individuals each). The animals were immersed for 5 min in different concentrations of the extract, distilled water, or ethanol 50%/DMSO 1%, dried, and kept in biological oxygen demand incubator for 7 days. The alterations were associated with the size of germinative cells and yolk granules; presence, size, and location of vacuoles in the cytoplasm of germinative cells; nuclear modifications in the germinative cells; damages to the nucleus and cytoplasm of the midgut generative cells; size of digestive cells; number of captured blood elements; accumulated digestive residues and digestive vacuoles in the digestive cells cytoplasm; and the number and distribution of proteins and polysaccharides in all the cells of both organs. The concentrations used in this study prevented an efficient and complete blood digestion by the midgut epithelial cells of the treated animals, resulting in the absence of the necessary nutrients to maintain the physiological events in the ectoparasites. In advanced stages, This can lead the ectoparasite to death. The germinative cells were highly impaired and probably not able to advance developmental stages (I–V) or complete vitellogenesis to be released during ovulation, which would prevent the females from originating a new individual. Thus, it can be concluded that the effects of A. oleracea are similar to those caused by chemical products widely recognized as effective to control ticks.

Renal oxidative stress and inflammatory response in perinatal Cyclosporine-A exposed rat progeny and its relation to gender Hany M El-Bassossy, Mohammed A Hassanien, Abdulhadi Bima, Fatma M Ghoneim, Ayman Zaky Elsamanoudy Journal of Microscopy and Ultrastructure 2019 7(1):44-49 Background and Aim of the Work: The current study postulated that cyclosporine A (CSA) could induce gender-specific renal damage. Hence, the current study aims to investigate the nephrotoxic effect of perinatal exposure of male and female rat progeny to CSA. Moreover, it aims to evaluate the oxidative stress and inflammation as a possible pathophysiologic mechanism. Materials and Methods: Female rats were randomly allocated to two groups of four and assigned to undergo either CSA (15 mg/kg/day; the 6th day after conception and continuing until the progeny were weaned) or vehicle treatment as control groups. At the age of 6 weeks, the progeny were divided into the following four groups: male progeny of control-group mothers (M-vehicle, 7); male progeny of CSA-treated mothers (M-CSA, 9); female progeny of control-group mothers (F-vehicle, 7); and female progeny of CSA-treated mothers (F-CSA, 6). Serum adiponectin, tumor necrosis factor-α (TNF-α) and creatinine, creatinine clearance, and urinary 8-isoprostane were measured. Histopathological examination by hematoxylin and eosin stain of Kidney was carried out. Results: Proteinuria and decreased creatinine clearance are significant in M-CSA than M-vehicle and F-CSA. 8-isoprostane is lower in F-CSA than F-vehicle. Increased TNF-α and decreased adiponectin levels in M-CSA than M-vehicle were observed. No significant differences were found in female rat groups. Conclusion: From the current study, it could be concluded that CSA could induce renal inflammation as well as oxidative stress that may explain the impaired renal function. The sex difference was a prominent finding in their vulnerability to CSA effects.

Orbital Rosai–Dorfman disease: A case report and literature review Basim Al-Maghrabi, Tarek Elnaggar, Osama Alamri, Jaudah Al-Maghrabi Journal of Microscopy and Ultrastructure 2019 7(1):50-52 A 53-year-old male presented with dropping of the right eyelid associated with decreased visual acuity for 4 months. He also complained of vertical diplopia especially when looking down. Ophthalmological examination revealed right blepharospasm associated with right hypertropia. There was palpable mass at the inferomedial aspect of the right eye. Magnetic resonance imaging revealed abnormal signal intensity in the right orbit inferior aspect occupying the orbital floor and measured 2.7 cm × 2.5 cm × 1.2 cm and showed enhancement on the postcontrast study. The patient underwent complete excision of the tumor. Histological examination of the mass revealed histiocytic proliferation with emperipolesis, with positive S100, positive CD68, and negative CD1a staining. These histological and immunohistochemical features are consistent with extranodal Rosai–Dorfman disease. There was no complication or recurrence after the complete excision.

Radiation and Cancer Research

Radiogenomics a New Marker on the Block Nagraj Gururaj Huilgol Journal of Radiation and Cancer Research 2018 9(4):131-131

Acute radiation syndrome: An update on biomarkers for radiation injury Vijay K Singh, Paola T Santiago, Madison Simas, Melissa Garcia, Oluseyi O Fatanmi, Stephen Y Wise, Thomas M Seed Journal of Radiation and Cancer Research 2018 9(4):132-146 The possible detonation of a radiological dispersal device or improvised nuclear device in a metropolitan city, or the accidental exposures to a radiation source, nuclear accidents, or the all-to-often threats of radiological/nuclear terrorism have led to the urgent need to develop essential analytic tools to assess such radiation exposures, especially radiation doses to exposed individuals. This exposure-assessing work using biological samples, and discipline, is known as biodosimetry. As of late, this field has progressed significantly as it has made use of the advances within newer areas of biologic analytics, namely omics (genomics, proteomics, metabolomics, and transcriptomics), lymphocyte kinetics, optically stimulated luminescence, and electron paramagnetic resonance technology in addition to conventional cytogenetic techniques. The use of automated high throughput platforms and the planning for laboratory surge capacity during the time of need are the latest developments in the field of biomarkers for biodosimetry. Such biomarkers are also needed for radiation exposure/dose conversion estimates that are essential for the development and application of radiation countermeasures, from animals to humans and that are currently being developed following the US Food and Drug Administration Animal Rule. Here, we present and discuss the current status of various biomarkers for assessing radiation dose after radiation exposure. It is anticipated that with the advent of improved biomarkers and associated biomarker platforms for the acute radiation syndrome, exposed victims can be more efficiently triaged and appropriately treated than is currently allowable. The latest advances in the field, and identify the areas where improvement is needed are also listed and discussed.

Intracellular reactive oxygen species determine cancer stem cell radiosensitivity related to predictive biomarker for radiotherapy Kaushala Prasad Mishra Journal of Radiation and Cancer Research 2018 9(4):147-154 Cancer cells display a higher level of reactive oxygen species (ROS) mainly due to increased metabolic activities resulting in altered redox balance. Imbalance in redox arises when the generation of ROS exceeds antioxidants defense system. ROS are generated in cells from multiple pathways, but mitochondria contribute significantly to cellular ROS pool by oxidative phosphorylation. Elevated levels of ROS are implicated in cell transformation, proliferation, and tumorigenesis. ROS-mediated signaling pathways activate pro-oncogenes which regulate cancer progression, angiogenesis, and survival. Normal cells maintain intracellular homeostasis by developing an array of enzymatic antioxidant systems such as catalase, superoxide dismutase, and glutathione peroxidase. Chemotherapy and radiotherapy exert their cytotoxic effects on tumor cells by the generation of excessive ROS. The failure of therapies is attributable to a small fraction of core cells in tumor mass called cancer stem cells (CSCs) which have self-renewal property and exhibit proliferation, differentiation, and resistance to treatments. Both normal and CSCs maintain low-ROS level ascribed to stemness. This review describes role and relevance of ROS in CSC with particular emphasis on developing predictive biomarker for outcome of cancer radiotherapy. It is pointed out that CSCs maintain lower ROS homeostasis and evade cell death by increased level of endogenous antioxidants capacity in cancer cells. Search for regulators of ROS and surface markers in CSC may render them sensitive to radiation offering new and effective strategy for cancer treatment.

Breast cancer stem cells, epigenetics, and radiation Garima Sinha, Alejandra Ferrer, Yahaira Naaldijk, Caitlyn A Moore, Qunfeng Wu, Henning Ulrich, Pranela Rameshwar Journal of Radiation and Cancer Research 2018 9(4):155-164 Breast cancer remains a clinical problem despite advancements in the field. Cancer stem cells (CSCs) within the breast cancer population are implicated in cancer relapse. The dormant CSCs generally resist available treatment, thus challenging the current treatment paradigm. Radiation is an aggressive form of treatment typically used to reduce tumor mass in breast cancer patients. Several clinical and research-based studies have shown that radiation treatment cannot target all cancer cells, leaving behind radioresistant cells. The radioresistant cells have the potential to acquire stem cell-like features that render them untargetable with respect to the current technology. This review elaborates on cancer cells acquiring stem cell phenotype. In addition, we discuss the phenotype and function of cancer cells that are derived from radioresistant cells as well as indirect changes as a consequence to bystander effect. In addition, the epigenetic profile of the radioresistant cells plays a crucial role in the acquisition of cycling quiescence and stem cell-like phenotype and is detailed in this review.

Biomarkers in chronic obstructive pulmonary disease patients for prediction of lung cancer development Murali M S Balla, Pooja K Melwani, Amit Kumar, Badri N Pandey Journal of Radiation and Cancer Research 2018 9(4):165-176 According to the World Health Organization (2016), chronic obstructive pulmonary disease (COPD) and lung cancer (along with trachea and bronchial cancers) are third and sixth among 10 top causes of death globally. The association between lung cancer and COPD has been widely established owing to their common endogenous and exogenous risk factors. Mechanistically, lung cancer and COPD are interlinked diseases in many ways such as oxidative stress-associated DNA damage, inflammation, and telomere shortening. An increase in lung cancer has been well correlated with smoking, which is likely to occur up to five folds higher in smokers with COPD than normal lung function subjects. In majority of cases, lung cancer development, especially in COPD patients, is asymptomatic and only diagnosed at advanced stages with poor prognosis. The development of biomarkers for early prediction of lung cancer in both high- and low-risk COPD patients will help clinicians for their better follow-up, early diagnosis, and improved therapeutic management.

Medical imaging: Contribution toward background radiation and human exposure Shangamithra Visweswaran, Karthik Kanagaraj, Santhosh Joseph, Venkatachalam Perumal Journal of Radiation and Cancer Research 2018 9(4):177-182 Annual public exposure from background radiation is about 2.8 mSv which comes from both natural and manmade sources. The medical applications of ionizing radiation contribute around 98% of the manmade sources of background radiation. The annual per caput dose rose from 0.35 to 0.62 mSv by the worldwide usage of radiation diagnostic examinations. Based on the published reports, the diagnostic examinations – computed tomography (CT) scan and cerebral angiography are high (7.4 mSv and 9.3 mSv, respectively) in the average effective dose. In our study, we measured the entrance surface dose at different anatomical locations using thermoluminescence dosimeter in patients who underwent CT examinations and neurointerventional radiology procedures. The measured dose values range between 0.70 and 518.12 mGy for CT and 0.99 and 777.31 mGy for interventional procedures. Thus, X-radiation based procedures delivered a considerable amount of radiation dose to the patients. To minimize the risks of developing any health effects, safety measures should be taken to reduce the dose without compromising the image quality.

Enhanced DNA double strand break repair triggered by microbeam irradiation induced cytoplasmic damage Teruaki Konishi, Alisa Kobayashi, Tengku Ahbrizal Farizal Tengku Ahmad, Jun Wang Journal of Radiation and Cancer Research 2018 9(4):183-189 Objective: Direct exposure of the nucleus to radiation, is the primary cause of various radiobiological effects. However, the cytoplasm is equally exposed to radiation during treatments that result in activation of intracellular response. Thus, the present study is aimed at investigating (1) whether cytoplasmic irradiation affects double-strand breaks (DSBs) repair when the cytoplasm (C) and nucleus (N) is irradiated sequentially, and (2) whether the cytoplasmic irradiation alone is sufficient to induce DNA DSBs in the nucleus. Materials and Methods: To distinguish the radiobiological effects between nuclear and cytoplasmic irradiation, all the experiments were conducted using the SPICE - National Institute of Radiological Sciences microbeam (SPICE) that can target precisely the N and/or C with desired number of 3.4 MeV protons. We examined the kinetics of DSB repair in WI-38 normal human fibroblast cells that were irradiated by microbeam targeted to the N, C, or N + C. Cells were fixed at various time points between 1 and 24 h postirradiation. Subsequently, they were immunostained with antibodies against γ-H2AX, a DSB marker, and imaged, to quantify the residual DSB in each nucleus. Results: Microbeam irradiation induced significant γ-H2AX, directly proportional to the number of protons delivered per N. In the C-targeted cells, γ-H2AX levels did not increase significantly, compared to controls, 1-h postirradiation. However, 4-h postirradiation, γ-H2AX levels were significantly increased in C-targeted cells, compared to nonirradiated controls, and the increase was proportional to the number of protons delivered. Cells irradiated with 500 protons per N, showed lowered residual γ-H2AX levels in N + C cells additionally irradiated with 500 or 1000 protons targeted to the C, 16 and 24 h postirradiation, respectively. Conclusion: Our results suggest that cytoplasmic damage triggers enhanced repair of DSBs that are induced on nucleus irradiation.

Oral Sciences

Confronting the menace of predatory publishers of health journals HA Mosadomi Saudi Journal of Oral Sciences 2019 6(1):1-2

Dentinal crack formation after different obturation techniques Hale Ari Aydinbelge, Nazife Tugba Azmaz, Mine Ozcelik Yilmaz Saudi Journal of Oral Sciences 2019 6(1):3-7 Introduction: The aim of this investigation was to compare the incidence of dentinal crack after different obturation techniques. Materials and Methods: Fifty-five mandibular teeth with mature apices and straight root canals (>5°) that had been extracted for periodontal reasons were selected and stored in distilled water until use. The teeth were randomly assigned to five groups of 15 teeth each. The groups were as follows; (Group 1) no canal preparation, (Group 2) canal preparation, (Group 3) canal preparation and obturation with cold lateral condensation technique, (Group 4) canal preparation and obturation with warm vertical condensation (WVC) technique, and (Group 5) canal preparation and obturation with single-cone (SC) technique. Afterward, the teeth were horizontally sectioned at 3, 6, and 9 mm from the apex with a low-speed saw under water cooling. All slices were then viewed through a stereomicroscope at ×25 magnification and pictures were taken. The presence of dentinal crack was noted and analyzed using the Chi-square test. Results: The Group 1 had no dentinal crack. All the other groups resulted in dentinal crack. Groups 3 and 4 produced significantly more dentinal crack than the other groups in the 6 and 9 mm sections (P < 0.05). The Groups 3 and 4 produced significantly more dentinal crack in the 6 and 9 mm sections than 3 mm sections (P < 0.05). Conclusion: Under the conditions of this study, after root canal filling with the cold lateral and WVC techniques determined more dentinal cracks than the only preparation and SC technique. The SC technique seems to be an appropriate obturation technique.

Micro-computed tomographic analysis of filling porosity of two different obturation techniques Amal A Almohaimede, Marwa M Almutairi, Haya M Alyousef, Ebtissam M Almadi Saudi Journal of Oral Sciences 2019 6(1):8-12 Introduction: The ideal root filling material should have inert properties, good adhesive ability, and result in void-free obturation along the root canals. The aim of this in vitro study was to compare the quality of two root canal obturation techniques; cold lateral (CL) condensation and continuous wave (CW) condensation, through measuring the volume of gaps and voids by using micro-computed tomography (micro-CT). Materials and Methods: Forty-extracted teeth with single canal were instrumented with profile rotary files, and divided into two groups as follows: CL condensation (n = 20), and CW obturation (n = 20). The teeth in each obturation group were scanned twice using micro-CT scan. The resultant images were rendered in proprietary software (NRecon version 1.6.9.4) to obtain three-dimensional (3D) pre- and post-obturation records of each specimen. The 3D images were imported into CT Analyser version 1.17.7.2 for volume measurement of voids and gaps in the apical third at 1 mm, 3 mm, and 5 mm. The analysis of variance test was used to compare the mean volume of voids and gaps between the two obturation groups in each level in the apical third (1 mm, 3 mm, and 5 mm). Furthermore, it was used to compare the mean volume of voids and gaps between the three different levels apically in each obturation technique. Results: CW obturation technique had more voids volume at the three different apical levels (1 mm: 0.19 ± 0.16, 3 mm: 0.76 ± 0.81, and 5 mm: 1.36 ± 1.44) compared to CL condensation technique at the same three levels (1 mm: 0.14 ± 0.21, 3 mm: 0.46 ± 0.46, and 5 mm: 1.10 ± 0.93) with no statistical significant difference between them (P < 0.05). Conclusions: None of the root canals filled teeth were voids-free, and there was no statistically significant difference between the two obturation techniques regarding the gaps volume apically.

In vitro assessment of human enamel surface composition bleached with two different bleaching agents Nazish Fatima Ahmed Saudi Journal of Oral Sciences 2019 6(1):13-17 Background: Varieties of methods are available for more obstinate tooth discoloration such as crowns, veneer, and micro and macro abrasion of enamel, but tooth bleaching gained high patient acceptance. The aim of the present research was to estimate changes in surface enamel composition after bleaching 16% carbamide peroxide (CP) (home-use bleaching) with 38% hydrogen peroxide (HP) (in office bleaching). Materials and Methods: A total of 90 enamel slabs from 45 sound human third molars were randomly divided into three groups. Of three groups, per group had thirty samples (n = 30), of which samples of Group 1 were placed in artificial saliva at 37°C in incubator (Memart, Germany) during complete experiment. Sample of Groups 2 and 3 was treated with power whitening gel (White Smile 2011, Germany) and tooth whitening pen (white Smile 2011, Germany), respectively. Later on, after bleaching treatment, discs were thoroughly washed and stored in artificial saliva at 37°C in incubator. Chemical analysis was done with energy dispersive spectroscopy (Edx) detector to detect changes in surface composition. Results: Energy dispersive X-ray spectroscopy (Edx) analysis showed no significant difference between all the three groups for Ca% mass (P > 0.99) and Ca% atomic (P > 0.99), C% mass (P = 0.78) and C% atomic (P = 0.76), and O% mass (P > 0.99) and O% atomic (P = 0.28). Similar results were shown for Na, Mg, P, and F. Conclusion: Statistically insignificant effect was observed on enamel composition with both bleaching agents (38% HP and 16% CP).

Oral health-related quality of life and associated factors of elderly population in Port Harcourt, Nigeria Omoigberai Bashiru Braimoh, Grace Onyenashia Alade Saudi Journal of Oral Sciences 2019 6(1):18-24 Aim: The objective of this study was to assess the impact of oral health on quality of life in a representative sample of elderly population in Port Harcourt, Nigeria, and to evaluate its associations with dental caries, periodontal disease, subjective oral measures, and sociodemographic factors. Subjects and Methods: The study was a cross-sectional observational research design. Participants were selected by systematic random sampling, and data were collected using a self-developed questionnaire and oral examination. Data analysis was done using SPSS version 20. Chi-square and logistic regression analysis was used to establish association between variables. Significance was determined at 95% confidence interval and statistical significance inferred at P < 0.05. Results: The prevalence of negative impact of oral health on quality of life was 38.1%. The mean Oral Health Impact Profile-14 score was 11.15 ± 8.36; the highest mean was recorded for physical pain (2.87 ± 1.17). Painful aching, 48.1%, was the highest impact on quality of life experienced by the participants. Female gender, younger elderly, poor self-perception of oral health, dental caries, and periodontitis produced a higher significant negative impact of oral disease on the quality of life. Conclusion: The prevalence of negative impact recorded in this study was comparable to that obtained in other similar studies. The study revealed that sociodemographic variables and subjective and clinical oral measures impact significantly on the oral health-related quality of life of the participants. The study suggests the need for these factors to be considered when planning oral health intervention program for the elderly.

Oral cancer awareness, knowledge, and practices among Saudi general dentists Zayed Ali Assiri, Abdulrahman Ahmed Alshehri, Alia Khalid Alfadhel Saudi Journal of Oral Sciences 2019 6(1):25-30 Objectives: The present study aimed to investigate oral cancer (OC) awareness, knowledge, and practices among Saudi general dentists. Materials and Methods: We included dentists who were recognized and licensed by the Saudi Commission for Health Specialties. They were e-mailed officially with a 28-item questionnaire and constructed to investigate the study objectives. Results: The final sample included 326 dentists. About 85.6% of the participants reported their awareness; this was confirmed when similar percentage (87.4%) stated that there are etiological factors other than tobacco and alcohol for OC. Only 34.7% of the participants had sufficient knowledge concerning the prevention and detection of OC. Concerning the referral, 53.4% referred their patients to oral medicine specialist. Conclusions: Our findings revealed that chances exist to improve the knowledge, increase awareness, and develop right practices toward OC. Furthermore, our results revealed that dentists believed their knowledge was insufficient to detect OCs, although most of them showed reasonable level of knowledge about some aspects of diagnosing OCs. All these emphasize general dentists' role in the prevention and diagnosis and the need to improve dentists' knowledge and practices toward OC.

Association of nutritional status and dental health among 3–6-year-old children of a South Indian population KL Girish Babu, Priya Subramaniam, KS Madhusudan Saudi Journal of Oral Sciences 2019 6(1):31-36 Background: Nutrition promotes healthy development and maintenance of oral health. Chronic malnutrition affects tooth exfoliation and renders the permanent teeth susceptible to caries.Aim: To assess the nutritional status and dental health in 3–6-year-old children.Materials and Methods: A cross-sectional epidemiological study was conducted on a representative sample of 1459 children, aged 3–6 years, and visiting the Integrated Child Development Centers (anganwadi) of T. Narasipura Taluk, Mysore, India. Nutritional status was evaluated by measuring body mass index (BMI) and mid-upper arm circumference (MUAC). Oral examination was carried out using a noninvasive technique with the child sitting in an upright position under good natural light. Dental caries, enamel hypoplasia, and oral mucosal status were recorded according to the WHO criteria. Results: Nutritional status according to BMI showed 41% of children to be underweight and according to MUAC only 0.82% of children were undernourished. A highest (41.7%) number of underweight children were seen in 3–4 years age group, with a higher number of females being affected. The prevalence of dental caries was 61.07% and was highest in 3–4 years age group. More number of females were affected with dental caries than males. The prevalence of enamel hypoplasia was 8.7%. Association of dental health status with BMI was significant with dental caries. Conclusions: Forty-one percent of children were underweight and the prevalence of underweight children increased with age. The prevalence of dental caries and enamel hypoplasia were 61% and 8.7%, respectively.

Root canal retreatment of permanent mandibular second molar with extruded foreign particles Yousef Hamad Al-Dahman, Abdullah Yousef Al-Hawwas, Asma Suliman Al-Jebaly Saudi Journal of Oral Sciences 2019 6(1):37-40 This article describes a successful management of permanent mandibular second molar presented with extruded foreign particles. Root canal foreign bodies in or beyond the root canal system may affect the treatment outcome. Attempts for removal of such materials are challenging and can jeopardize the tooth structure. Therefore, a proper diagnosis and treatment planning for such cases is critical to achieving adequate outcomes.

Dental and craniofacial anomalies associated with Axenfeld–Rieger syndrome Amit Khatri, Prerna Beniwal, Namita Kalra, Rishi Tyagi Saudi Journal of Oral Sciences 2019 6(1):41-44 Axenfeld–Rieger syndrome (ARS) is a rare, autosomal dominant disorder with genetic and morphologic variability and characterized by ocular and nonocular clinical findings. Midface hypoplasia and maxillary hypodontia are classical presenting features of this syndrome. This case report describes a dental condition, immediate treatment required and a long-term treatment approach toward a patient 5-year-of-age with ARS, who presented with significant ocular and dental anomalies.

Clinical Ophthalmology

Live surgical broadcasts: Are there some lessons to be learned from the Johnson and Johnson's articular surface replacement hip implant case? Jatinder Bali, Renu T Bali Journal of Clinical Ophthalmology and Research 2019 7(1):1-3

Clinical study of efficacy of probing as a treatment for epiphora in adults CV Kavitha, Sahana R Manipur, Pavana Acharya, BR Lakshmi Journal of Clinical Ophthalmology and Research 2019 7(1):5-7 Background/Context: Probing is a simple operative procedure, can be performed easily in adults under local anesthesia, and is associated with minimal postoperative morbidity. The study aimed to determine the efficacy of probing in adults with epiphora due to common canalicular block (CCB) and nasolacrimal duct obstruction (NLDO). Materials and Methods: A prospective, interventional study was conducted on 44 patients with epiphora. Probing was done through upper and lower canaliculus under local anesthesia in all patients with epiphora due to CCB and NLDO. Probing was considered successful if the epiphora had been resolved or reduced to an acceptable level and if the lacrimal system was patent on lacrimal syringing for 6 months. Results: Patients comprised 36 women and eight men with the age group between 25 and 80 years who had epiphora for 3–24 months. Twenty-six patients had common CCB and 18 had complete NLDO. Complete patency was achieved in 12 and 5 and partial patency in 9 and 6 patients with CCB and NLDO, respectively. Treatment was successful in 72.72% of the patients. Ten patients underwent uneventful cataract surgery and 12 failed cases needed dacryocystectomy. Conclusion: Since probing is a simple, quick, cost-effective, and daycare procedure with low morbidity and obviates the need for further nasolacrimal surgery, probing can be recommended as an initial treatment in adults with epiphora.

Visual outcome of difficult cataract surgeries in a tertiary care center in India Ranjana Pande, Smita Mohod Harne, Namrata Bhuta Journal of Clinical Ophthalmology and Research 2019 7(1):9-11 Purpose: The purpose of this study is to determine the percentage of difficult cataracts out of total cataracts admitted in a tertiary care center, to study the intra- and postoperative complications in patients with difficult cataracts undergoing cataract surgery, and to determine their visual outcomes. Materials and Methods: This is a retrospective, noncomparative, single-institutional, observational study. The study was conducted on patients who were admitted over 2 years (January 2013–December 2014). Of these, patients with difficult cataracts (according to inclusion criteria) were screened and preoperatively evaluated. These patients underwent manual small incision cataract surgery and were followed up on the 1st, 7th, and 40th postoperative days. These cases were monitored for postoperative visual acuity (VA) and complications. The postoperative complications were graded according to the Oxford Cataract Treatment and Evaluation Team (OCTET) definitions and analyzed. Results: Of 5766 patients, 1858 (32.2%) patients presented with difficult cataracts. Hypermature and mature cataracts (24.9%), hard cataracts (20.02%), and pseudoexfoliation (33.04%) constituted as the major causes. Of these, 820 (44.1%) patients presented with no complications postoperatively. According to the OCTET grading, 44.9% of patients had Grade I, 9.5% had Grade II, and 1.83% had Grade III complications; the most common postoperative complication was corneal edema (39.2%). A total of 21.9% had VA <6/60 on postoperative day 1, which reduced to 5.27% on day 40 (P < 0.001). The patients with V/A >6/18 increased from 44.1% on day 1 to 61.8% on day 40 (P < 0.001). Conclusion: Visual morbidity remains high among patients with difficult cataracts, especially in patients with pseudoexfoliation and corneal pathology. Patients with hypermature cataract and Grade III–IV cataracts have a better visual outcome.

Choroidal thickness in type 2 diabetic patients with various stages of diabetic macular edema and retinopathy: A prospective study from central India Shilpi H Narnaware, Prashant K Bawankule, Dhananjay V Raje, Moumita Chakraborty Journal of Clinical Ophthalmology and Research 2019 7(1):12-17 Background: The objective of this study is to assess the changes in choroidal thickness in patients with type 2 diabetes with diabetic macular edema (DME) and diabetic retinopathy (DR), using enhanced-depth imaging (EDI) spectral domain optical coherence tomography (OCT). Materials and Methods: A total of 164 eyes from 104 patients were divided into no DR, DR without DME, and DR with DME. Eyes were also divided according to subtypes of DME. Subfoveal choroidal thickness (SFChT) and parafoveal choroidal thickness (PFChT) at 500 μm, 1000 μm and 1500 μm were measured using EDI-OCT and compared across groups. Results: A sample of 104 patients with diabetes consisted of 28 females and 76 males. The adjusted mean SFChT was 266.1 ± 42.40 μm in no DR eyes, 258.32 ± 39.52 μm in DR without DME eyes, and 246.11 ± 35.42 μm in DR with DME eyes (P = 0.028). The adjusted mean SFChT was 242.5 ± 33.04 μm in spongy edema eyes, 242.05 ± 39.73 μm in cystic edema eyes, and 247.9 ± 39.54 μm in serous retinal detachment eyes (P < 0.006). Conclusions: In eyes with DR, there is an overall thinning of the choroid on EDI-OCT. The subfoveal choroid was significantly thinner in eyes with DR and DME, specifically in cystic type of DME, as compared to those without DR. A decreased choroidal thickness may lead to tissue hypoxia and consequently increase the level of vascular endothelial growth factor, resulting in the breakdown of the blood-retinal barrier and development of macular edema.

Reduction in preexisting against the rule astigmatism in temporal manual small incision cataract surgery: Can curvilinear incision be a better choice? Karunanithy Palanisamy, P Amudha, R Amudhavalli, Ramalingam Munisamy, Arun Tipandjan Journal of Clinical Ophthalmology and Research 2019 7(1):18-21 Background: To address the issue of ATR astigmatism in patients who undergo temporal manual small incision cataract surgery (MSICS) surgery. Aim: The aim is to find out whether an incision that is made parallel to the limbus (curvilinear) while doing temporal MSICS can reduce the preexisting against-the-rule astigmatism (ATR). Settings and Design: The study was conducted on those patients who came for cataract surgery in a government general hospital. Materials and Methods: One hundred and five patients with cataract and ATR astigmatism of ≥1D were divided into three groups each with 35 patients. Group A patients underwent curvilinear incision temporal MSICS, Group B straight line incision temporal MSICS, and Group C limbal incision temporal phacoemulsification. The amount of change in ATR astigmatism in each group was calculated by comparing preoperative and postoperative keratometry readings. Statistical Analysis: All data were evaluated using SPSS version 19.0. To test the significant difference between pre- and post-operative astigmatism in each group, paired t-test was used. To test the significant difference in astigmatism between the three groups, ANOVA was used. Results: The reduction in the mean astigmatism in Group A was 0.89D, in Group B 0.62D, and in Group C 0.086D. The significant reduction of the ATR astigmatism in Group A and Group B could be due to the flattening of the horizontal curvature which is higher in patients with ATR astigmatism. Among these two groups, the curvilinear incision produced more flattening than the straight line incision. Conclusion: If a curvilinear (limbus parallel) is done while doing temporal MSICS in patients with higher ATR astigmatism, there can a significant reduction of ATR astigmatism giving a better uncorrected visual acuity.

Multiple retained intraocular glass foreign body with late-onset retinal detachment Prabhushanker Mahalingam, Tasneem Topiwalla, Geetha Ganesan Journal of Clinical Ophthalmology and Research 2019 7(1):22-24 Successful management of intraocular foreign body (IOFB) is deemed possible by the advent of superior surgical procedures, even in those patients who present late. We report a case of a 46-year-old male, who presented with sudden onset of defective vision in his right eye of 2 days duration and with a previous history of trauma following bulb blast at the age of 5 years. Examination revealed retinal detachment with multiple intraocular glass foreign body in his right eye. The primary management, in this case, was phaco-aspiration of lens through limbal tunnel, scleral buckling, 23G pars plana vitrectomy, IOFB removal through anterior segment, endolaser, and silicone oil injection. After 6 months, silicone oil was removed, and posterior chamber intraocular lens was implanted. This is a rare case wherein multiple glass IOFBs had remained quiescent in the eye for more than four decades resulting in retinal detachment at a later date and successful management with good visual outcome was possible.

Keratoactinomycosis: A rare case report Pradnya Krishnakant Bhole, Dipali P Parmar Journal of Clinical Ophthalmology and Research 2019 7(1):24-26 A 50-year-old female farmer, with a history of vegetative trauma, presented to a tertiary eye care center, with right eye ulcerative keratitis, initially treated elsewhere as fungal keratitis, refractory to conventional antifungal therapy. A corneal scraping was done and it revealed Gram-positive filamentous Actinomyces bacteria. Treatment with topical penicillin (100,000 U/ml) showed a complete resolution of the corneal infection, within 2 weeks of therapy. Actinomyces keratitis is a rare clinical condition. A history of ocular vegetative trauma, with a clinical picture similar to fungal keratitis, leads to delay in the diagnosis of such rare presentations of posttraumatic keratoactinomycosis, which otherwise shows a good response to topical penicillin therapy. A corneal scraping done helps in timely diagnosis and effective treatment.

Malingering versus dissociative disorder: A clinical dilemma!! Shobha G Pai, Madhurima Nayak, Jayanthi Kalary, SS Krithishree Journal of Clinical Ophthalmology and Research 2019 7(1):27-29 Malingering and dissociation coincide with the mode of presentation. Dissociation and attention-deficit hyperactivity disorder (ADHD) can coexist due to their similar etiology. We report a case of dissociative disorder in a boy with ADHD presenting with sudden visual diminution. To our knowledge, though common, such case has not been reported in the literature. A 9-year-old boy, a case of ADHD on atomoxetine (25 mg) and risperidone (0.25 mg), was brought by his apprehensive mother, with sudden diminution of vision in his right eye for 1 week. On examination, his visual acuity was 20/120 in the right eye and 20/20 in the left eye, even on repeating with various charts. His anterior segment, fundus, and cycloplegic retinoscopy were normal. Visually evoked potential was normal in both the eyes. With a suspicion of malingering, +20D in front of the left eye. The test was positive for malingering, and the mother was reassured. The kid was sent to the psychiatry department for further counseling. They diagnosed it as a dissociative disorder. Simple tests for malingering still have an important role in ophthalmology. Children cannot be underestimated in their ability to malinger, but at the same time, dissociative disorder should be borne in mind before labeling a patient as a case of malingering. Because once the label of malingering is given, then it is a human tendency to form a prejudice idea about that patient and later that the patient would not get proper medical assistance.

Smartphone-based monochromatic green filter fundus imaging Ashish A Ahuja, Olukorede O Adenuga Journal of Clinical Ophthalmology and Research 2019 7(1):30-30

Incidence of various causes of infectious keratitis in the part of rural central India and its visual morbidity: Prospective hospital-based observational study Pratik Narendra Mohod, Archana Sunil Nikose, Pradnya Mukesh Laddha, Shadwala Bharti Journal of Clinical Ophthalmology and Research 2019 7(1):31-34 Introduction: Infectious keratitis is potential causes for vision loss in India. Early recognition with prompt diagnosis and rapid institution of appropriate therapy will significantly improve visual prognosis. Aim: The aim of this study was to evaluate the incidence of various causes of infectious keratitis in this part of rural central India, predisposing factor and visual morbidity. Materials and Methods: This was a prospective observational hospital-based study conducted at the Department of Ophthalmology, at a tertiary care hospital, in the part of rural central India. Data related to socioeconomic status, predisposing factor, and course of disease was collected. Results were analyzed on the basis of history, slit lamp examination, and appropriate laboratory investigation. Results: During the period of January 2015 to February 2017 total 680 patients were examined in cornea specialty clinic, of which 88 were diagnosed with infective keratitis and were included in the study. Majority of patients of infectious keratitis were in between 41 and 60 (41%) age group followed by 21–40 (23%) and incidence in male was higher (61%) as compared to female. Prevalence of Fungal keratitis (59.09%) was higher than bacterial (19.31%) and viral (17.04%) in this part of India. Ocular trauma and occupational accidents were the most common (42%) among farmer. Majority of corneal ulcer (68%) healed, 11% had no change in ulcer status, 4% was progressed, and 10% perforated. About 53% had stable best-corrected visual acuity (BCVA) as compared to BCVA at the time of presentation and in 34% BCVA improved. Conclusion: Incidence of fungal corneal ulcer is higher among various causes of infectious keratitis in this part of rural central India. Agricultural injuries are the main predisposing factor for infectious keratitis in this region. Prompt diagnosis and early appropriate treatment on the basis of laboratory investigation can helps the community to reduce the burden of corneal blindness.

Chest Diseases and Tuberculosis

Dilemma of community-acquired pneumonia Lamia H Shaaban The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):1-4 The lungs are particularly susceptible to infection, owing to continuous direct interaction with the external atmosphere in the process of gas exchange, and many anatomical facts, such as the presence of the pharynx, which constitutes a common pathway for both of the lung and stomach. With the process of development of many new generations of antibiotics, pneumonia still continues to be an important unsolved problem worldwide. Community-acquired pneumonia is still considered a problem and is associated with significant morbidity and mortality with cost load, especially with the emergent pathogens that presented with aggressive pictures of community-acquired pneumonia.

Prognostic values of neutrophilic count and neutrophil–lymphocyte ratio among chronic obstructive pulmonary disease patients admitted with acute exacerbation Ibrahim Dwedar, Mohamed Ali, Hossam M Abdel-Hamid The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):5-8 Introduction Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammatory pathway with neutrophils and lymphocytes representing the main cells of inflammation. Patients and methods A prospective study was designed to assess the neutrophilic count as well as neutrophil–lymphocyte ratio (NLR) as predictors of mortality among patients admitted in the hospital with acute exacerbation COPD. Fifty COPD patients were admitted to Ain Shams Hospital complaining of acute exacerbation. They were followed up during their course inside the hospital with routine blood tests assessment. Results From the 50 patients admitted, eight patients died along their in-hospital course. No differences regarding their ages and sex. Total leucocytic count (TLC), neutrophilic count, lymphocytes, and NLR were found to be significantly higher in the nonsurvival versus the survival groups. Mean C-reactive protein values showed no significant difference between both the subgroups. The nonsurvival group tend to stay more days in the respiratory care unit in comparison to the survival group. Conclusion The neutrophilic count and the NLR were strongly valuable inflammatory markers with reported higher sensitivity and specificity in predicting the mortality among COPD patients admitted for acute exacerbation.

Does vitamin D deficiency worsen the hospital outcome in patients with acute exacerbation of chronic obstructive pulmonary disease? Mohamed F Abdel Ghany, Hoda A Makhlouf, Aliae A.R.M Hussein, Amal A Mahmoud The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):9-13 Background There are limited data about the hospital outcome in hospitalized patients diagnosed as chronic obstructive pulmonary disease (COPD) with concomitant deficiency of vitamin D. Objectives To assess the level of serum 25-hydroxyvitamin D in patients with severe exacerbation of COPD and to find if there is any correlations between vitamin D and clinical, functional parameters, as well as survival, days of hospital stay, and need for ICU admission. Patients and methods In this case–control study, 60 patients with acute exacerbation COPD requiring hospital admission were recruited and 24 healthy controls. Chest radiography, spirometry, arterial blood gases, 6 min walking distance, modified Medical Research Council dyspnea scale, and St George Respiratory Questionnaire were assessed. Serum 25-hydroxyvitamin D level was measured by enzyme-linked immunosorbent assay. Results About 90% COPD patients had vitamin D deficiency. Serum vitamin D levels were statistically significantly lower in COPD with and without comorbidities when compared with normal controls (P<0.001) but COPD with or without comorbidities did not differ statistically (P>0.05). No significant correlation was found between serum 25-hydroxyvitamin D and survival; days of hospital stay or need for mechanical ventilation. As well, no significant correlation between vitamin D and forced expiratory volume in the 1 s %, 6 min walking distance, modified Medical Research Council, or St George Respiratory Questionnaire scores was found. Conclusion Vitamin D deficiency is found in most COPD patients. However, in patients suffering from severe exacerbation, the presence of low vitamin D levels did not have any effect on survival, days of hospital stay, or need for mechanical ventilation.

Assessment of prevalence of active pulmonary tuberculosis among patients with ocular tuberculosis Heba A Eshmawey, Eiman M Abd El Latif, Hadir A.S Okasha The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):14-23 Background Tuberculosis (TB) is considered a multisystemic disease showing many extrapulmonary presentations. TB uveitis is one of the common forms of extrapulmonary TB. The lung is still the first organ to be attacked by TB, and pulmonary TB is the only infectious form of the disease. Aim The aim of the study was to detect the prevalence of active pulmonary TB among patients with TB uveitis. Patients and methods The present study included 37 patients with diagnosis of ocular TB on the basis of previous history, ocular examination, and exclusion of other suspected causes of uveitis. In addition, positive tuberculin skin test, or positive interferon-gamma release assays were carried out. All included patients were subjected to sputum examination for acid-fast bacilli and plain radiography of chest P-A view, and certain cases had a bronchoalveolar lavage. Patients with active pulmonary TB were detected. Both groups (patients with active pulmonary TB and patients with free chest) were compared with regard to all the previously mentioned studied parameters. Results The mean age of the studied patients was 34.8±12.5 years. All the studied patients showed positive tuberculin test with a mean of 18.5±3.4 mm. With regard to the Quantiferon Gold test, 34 patients (91.9%) had positive results. Concerning radiography, only 10 (27%) patients had normal radiograph, the rest of the patients showed various radiological lesions. Thirty (81.1%) patients were diagnosed to have active pulmonary TB. Sputum examination for acid-fast bacilli revealed that 22 (59.5%) patients had positive results; an additional eight patients (who had negative results on sputum examination) showed positive results when they underwent a bronchoalveolar lavage. There was no statistically significant difference with regard to all the previously mentioned parameters between patients with active pulmonary TB and patients with a free chest. Conclusion The present study revealed that a considerable percentage of the patients with TB uveitis had active pulmonary TB.

Treatment outcomes of patients on non-Revised National Tuberculosis Control Programme (private) anti-tuberculosis regimen from a tertiary-care centre in Kerala, India Akhilesh Kunoor, Rakesh Purushothama Bhat Suseela, Mithula Raj, Rajesh Chemmarissery Thankappan, Ponneduthamkuzhi Thomas James The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):24-27 Introduction Although standardised tuberculosis (TB) treatment in India is delivered by the public sector through the Revised National TB Control Programme (RNTCP), majority of patients in the country are treated with private anti-TB drugs. The objective of the study was to assess the treatment outcome of patients initiated on non-RNTCP regimen from a private tertiary-care centre from January to June 2016. Patients and methods A nonconcurrent cohort study was done which followed up the patients who have been initiated on private anti-TB regimen from a private tertiary-care centre in Kerala, India, during the first and second quarter of 2016. Details of further visits were sought from the hospital health management information system. A phone call interview was done with all patients, 9–12 months after treatment initiation. Results There were 81 patients who were initiated on private anti-TB regimen. Of them, 26 were of pulmonary TB and 55 were of extrapulmonary tuberculosis (EPTB). Among pulmonary TB, 17 (65.38%) cases and in EPTB, 41 (74.54%) cases had successful treatment outcome. The overall success of the non-RNTCP regimen was 71.6%. In pulmonary TB, six (23.1%) cases and in EPTB 11 (20%) cases came under lost to follow-up category. Conclusion The results calls for urgent actions to have a system in place for tracking patients initiated on private anti-TB drugs so as to ensure the standards of TB care. The national programme may further strengthen monitoring of treatment adherence in private sector with established ICT-based treatment support models.

Raised dsDNA autoantibodies in tuberculosis patients Faheem Shahzad, Atia Ali, Abid Mushtaq, Khursheed Javaid, Afzaal Nazir, Amna Pervez, Mohammad Kashif, Noman Bashir, Afia Abbas, Romeeza Tahir, Shah Jahan, Nadeem Afzal The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):28-31 Background Tuberculosis (TB) is caused by Mycobacterium tuberculosis. M. tuberculosis can become dormant, resist the hostile environment of the phagosome, and trigger a delayed-type hypersensitivity reaction leading to chronic infection and granuloma formation. In granulomas, destruction of tissues results in the release of intracellular self-antigens that may provoke the development of autoantibodies. Therefore, the present cross-sectional study was conducted to detect anti-dsDNA antibodies in local TB patients. Patients and methods In all, 160 patients were recruited for this comparative study. Anti-dsDNA antibodies were detected by enzyme-linked immunosorbent assay. Independent Student’s t test was used to compare mean anti-dsDNA values between TB patients and healthy individuals. A p value less than or equal to 0.05 was considered as statistically significant. Results Anti-dsDNA antibodies were high in TB patients as compared with healthy controls and the difference between the two groups was statistically significant (P<0.0001). No significant association of dsDNA autoantibody between TB patients and healthy controls was obtained. Similarly, no significant association of dsDNA autoantibodies was obtained in drug resistance TB patients and TB patients without drug resistance. Conclusion Increased level of dsDNA autoantibody was detected in TB patients and its level was clinically significant in TB patients, but no association of this autoantibody was established with TB.

Hurdle in the eradication of tuberculosis: delay in diagnosis Jayasri H Gali, Harsha V Varma, Aruna K Badam The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):32-38 Objective Identifying the factors responsible for the delay in the diagnosis of tuberculosis (TB). Patients and methods In this retrospective study, data on pulmonary and extrapulmonary forms of TB, registered for the treatment at the directly observed treatment, short course, centre were analysed. Results Of 163 patients, 34 (20.86%) were diagnosed at the first visit. The delay in seeking medical care ranged from 0 to 25 days from the diagnosis. A total of 110 (67%) patients started on the same day or the day after diagnosis, less than 1 month in 33 (20.25%) and 1–3 months in 83 (51%). Delay from patient and health services (both combined) ranged from half a month to 48 months; the mean±SD diagnostic delay was 4.09±4.19 days (range: 0–24 days), whereas the mean±SD treatment delay (n=162) was 2.19±3.89 days. of the 124 patients who received medical help, 90% of them did so within six months of onset of Symptoms. There was a statistically significant difference in patients’ delay in receiving the treatment/medical care by sex. Mean±SD delay for pulmonary and extrapulmonary TB was 48±24 and 240±386 days, respectively. Conclusion Delay in diagnosis is a preventable factor. Patient delay is longer compared with healthcare delays. Active surveillance, even in the urban areas by healthworkers, may help in reducing this delay.

Role of echocardiographic tissue Doppler imaging in the assessment of myocardial diastolic dysfunction in children with diffuse lung diseases Waleed Mohamed Elguindy, Maryam Ali Abdelkader The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):39-43 Background Pulmonary arterial hypertension (PAH) is a common complication of prolonged diffuse lung diseases in children. It is considered a crucial factor of morbidity, mortality, and severity of the disease in these children. Conventional echocardiography is an indirect tool to assess pulmonary hypertension (PH) with a limited sensitivity compared with right heart catheterization and requires well-trained physicians. So, the aim of the current study was to determine the role of echocardiographic tissue Doppler imaging in the assessment of the effect of pulmonary hypertension on right ventricular functions in children with prolonged, diffuse lung diseases and if it can have a predictive role of the secondary right ventricular (RV) dysfunction in these children. Patients and methods This is a case–control study in which 40 children with diffuse lung diseases were recruited from the chest clinic, Ain Shams University Hospitals. The patients were classified into PH and non-PH groups according to the echocardiographic measurement of mean PAP greater than 25 mmHg. Results Patients with PAH had significantly higher RV stroke volume as well as indexed RV systolic and diastolic areas. Furthermore, these patients had significantly higher RV myocardial performance index and E/E′ ratio suggesting diastolic dysfunction as well as decreased compliance. Conclusion Although conventional echocardiography could detect changes in RV dimensions and stroke volume, tissue Doppler imaging could further highlight changes in RV diastolic functions as well as compliance secondary to PAH.

Functional evaluation of patients with progressive systemic sclerosis-associated diffuse parenchymal lung disease Ahmed A.A Hussieny, Yosri M.K Akl, Reem I Elkorashy, Amira I Mostafa, Doaa H Attia, Mohamed Faheem, Fatma E.-Z Ahmed The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):44-49 Background Interstitial lung diseases are common features in scleroderma that seem to add to the morbidity and mortality of the disease. Other complications that may occur with scleroderma are pulmonary hypertension. Aim to evaluate the functional status of patients with progressive systemic sclerosis-associated diffuse parenchymal lung disease. Methodology A total of 44 adult patients with a confirmed diagnosis of scleroderma were included. The disease severity was assumed by using the grading of the inter-incisor distance and finger-to-palm distance. Assessment of the chest high-resolution computed tomography (HRCT) was performed, and then functional assessment in the form of arterial blood gas, spirometry, 6-min walk distance, and echocardiography was performed. Results There were no significant differences between the scleroderma with diffuse parenchymal lung disease and those with normal HRCT regarding the measured and calculated parameters, except for the pulmonary artery systolic pressure, which was significantly higher in the normal HRCT group than those with interstitial lung disease.

Idiopathic pulmonary fibrosis and subclinical hypothyroidism: an underestimated comorbidity Heba H AboElNaga, Alyaa A ElSherbeny, Emad A AbdelHady The Egyptian Journal of Chest Diseases and Tuberculosis 2019 68(1):50-56 Background Idiopathic pulmonary fibrosis (IPF) is the most damaging and mysterious form of lung fibrogenesis, with worldwide growing prevalence and mortality. Subclinical hypothyroidism (SCH) is evidenced that its prevalence is still higher in patients with IPF. Objectives To study the incidence of SCH in patients with IPF in comparison with the controls with a focus on the different clinical characteristics and spirometry measurements. Patients and methods The research involved 50 patients who were diagnosed as IPF and 30 healthy participants, enrolled from the outpatient clinic departments of pulmonary medicine of October 6 University Hospital. The patients performed spirometry tests, high-resolution computed tomography chest, and thyroid function test. Results There were significant differences in spirometry data and thyroid-stimulating hormone level between the IPF and the control group, indicating more prevalence of SCH in IPF patients. IPF patients diagnosed with SCH have a significant decline in some spirometry measurements than those with IPF only. Conclusion The prevalence and clinical outcomes of SCH in patients with IPF certainly require advanced research, since the thyroid function tests were not done regularly for most patients with IPF. This study intensely proposes that in future encouraging management should be further studied to enhance the prognosis of IPF patients.