Electrical stimulation of right Schaffer collateral in Trpm4−/− knockout and wild type rats were used to study the role of Trpm4 channels for signal processing in the hippocampal formation. Stimulation induced neuronal activity was simultaneously monitored in the CA1 region by in vivo extracellular field recordings and in the entire brain by BOLD fMRI measurements. In wild type and Trpm4−/− knockout rats, consecutive 5 Hz pulse trains elicited similar neuronal responses in the CA1 region and similar BOLD responses in the stimulated right hippocampus. Stimulus-related positive BOLD responses were also found in the left dorsal hippocampus. In contrast to the right dorsal hippocampus, baseline BOLD signals in the left hippocampus significantly decreased during consecutive stimulation trains. Similarly, slowly developing significant declines in baseline BOLD signals, in absence of any positive BOLD responses, were also observed in the right entorhinal, right piriform cortex, right basolateral amygdala and right dorsal striatum whereas baseline BOLD signals remained almost stable in the corresponding left regions. Furthermore, significant declines in baseline BOLD signals were found in the prefrontal cortex and prelimbic/infralimbic cortex. Because significant baseline BOLD declines were only observed in target regions of the right dorsal hippocampus, it might reflect functional connectivity between these regions. In all observed regions the decline in baseline BOLD signals was significantly delayed and less pronounced in Trpm4−/− knockout rats when compared to wild type rats. Thus, either Trpm4 channels are involved in mediating these baseline BOLD shifts or functional connectivity of the hippocampus is impaired in Trpm4−/− knockout rats.
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Publication date: Available online 13 December 2018
Source: NeuroImage
Author(s): Pierluigi Selvaggi, Peter C.T. Hawkins, Ottavia Dipasquale, Gaia Rizzo, Alessandro Bertolino, Juergen Dukart, Fabio Sambataro, Giulio Pergola, Steven C.R. Williams, Federico Turkheimer, Fernando Zelaya, Mattia Veronese, Mitul A. Mehta
Abstract
As a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed Arterial Spin Labelling (ASL) rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor (D2R) antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D2R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BPND) template maps of the high affinity D2-antagonist Positron Emission Tomography (PET) ligand [18F]Fallypride and with brain post-mortem microarray mRNA expression data for the DRD2 gene from the Allen Human Brain Atlas (ABA). For all antipsychotics, rCBF changes were directly proportional to brain D2R densities and DRD2 mRNA expression measures, although PET BPND spatial profiles explained more variance as compared with mRNA profiles (PET R2 range = 0.20–0.60, mRNA PET R2 range 0.04–0.20, pairwise-comparisons all pcorrected<0.05). In addition, the spatial coupling between ΔCBF and D2R profiles varied between the different antipsychotics tested, possibly reflecting differential affinities. Overall, these results indicate that the functional effects of antipsychotics as measured with rCBF are tightly correlated with the distribution of their target receptors in striatal and extra-striatal regions. Our results further demonstrate the link between neurotransmitter targets and haemodynamic changes reinforcing rCBF as a robust in-vivo marker of drug effects. This work is important in bridging the gap between pharmacokinetic and pharmacodynamics of novel and existing compounds.
Graphical abstract
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Publication date: Available online 13 December 2018
Source: NeuroImage
Author(s): Lin Chen, Zhiliang Wei, Kannie Chan, Shuhui Cai, Guanshu Liu, Hanzhang Lu, Philip C. Wong, Peter C.M. van Zijl, Tong Li, Jiadi Xu
Abstract
The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.
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Publication date: Available online 13 December 2018
Source: NeuroImage
Author(s): Rui Cao, Jun Li, Chenchu Zhang, Zhiyi Zuo, Song Hu
Abstract
Cerebral small vessel disease has been linked to cognitive, psychiatric and physical disabilities, especially in the elderly. However, the underlying pathophysiology remains incompletely understood, largely due to the limited accessibility of these small vessels in the live brain. Here, we report an intravital imaging and analysis platform for high-resolution, quantitative and comprehensive characterization of pathological alterations in the mouse cerebral microvasculature. By exploiting multi-parametric photoacoustic microscopy (PAM), microvascular structure, blood perfusion, oxygenation and flow were imaged in the awake brain. With the aid of vessel segmentation, these structural and functional parameters were extracted at the single-microvessel level, from which vascular density, tortuosity, wall shear stress, resistance and associated cerebral oxygen extraction fraction and metabolism were also quantified. With the use of vasodilatory stimulus, multifaceted cerebrovascular reactivity (CVR) was characterized in vivo. By extending the classic Evans blue assay to in vivo, permeability of the blood-brain barrier (BBB) was dynamically evaluated. The utility of this enabling technique was examined by studying cerebrovascular alterations in an established mouse model of high-fat diet-induced obesity. Our results revealed increased vascular density, reduced arterial flow, enhanced oxygen extraction, impaired BBB integrity, and increased multifaceted CVR in the obese brain. Interestingly, the 'counterintuitive' increase of CVR was supported by the elevated active endothelial nitric oxide synthase in the obese mouse. Providing comprehensive and quantitative insights into cerebral microvessels and their responses under pathological conditions, this technique opens a new door to mechanistic studies of the cerebral small vessel disease and its implications in neurodegeneration and stroke.
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This study intends to assess the prevalence of temporomandibular disorders and its clinical signs in Chinese students.
Materials and methods
Search strategies were performed in 7 electronic databases, and the reference lists from potentially relevant studies were searched manually. Only observational studies that met the eligibility criteria were selected. A validated instrument was used to evaluate the quality of the included studies. A random‐effects model was used to calculate the pooled prevalence of temporomandibular disorders and its clinical signs.
Results
23 articles that met the eligibility criteria were included in this review and meta‐analysis. The prevalence of temporomandibular disorders was 29.1% (95% confidence interval [CI], 23.7‐35.1; n= 12702), and a significant difference was observed between males and females. The most prevalent sign was temporomandibular joint sounds (17.4%; 95% confidence interval, 13.8‐20.6; n =6615) followed by abnormal jaw movement (12.3%; 95% confidence interval, 9.1‐16.7; n=5496) and pain (9.9%; 95% confidence interval, 7.4‐13; n=4552).
Conclusions
The overall prevalence of temporomandibular disorders in Chinese students was approximately 29.1%, and a statistically significant difference was observed between males and females. The most prevalent sign was temporomandibular joint sounds (17.4%), followed by abnormal jaw movement (12.3%) and pain (9.9%).
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The effects and complications of hybrid procedure (combined carotid endarterectomy and carotid stenting) to revascularize chronic long-segment occlusion of internal carotid artery (ICA) are currently unknown and the purpose of this study.
Methods
Sixty-five patients with long-segment occlusion of ICA were prospectively enrolled and divided into two groups of revascularization with hybrid operation (n = 30) and medication group (n = 35), and clinical and angiographic data were analyzed.
Results
The duration from symptom onset to revascularization ranged 17–120 days (mean 40.5 ± 5.0) in the hybrid operation, with a success revascularization rate of 100%. All patients had thrombi extracted with the clot length ranging 5–8 cm (mean 6.3 ± 0.9). The thrombolysis in cerebral infarction grade (TICI) was significantly (P < 0.0001) greater immediately after (median 2,) than before recanalization (0). Periprocedural complications included recurrent laryngeal nerve injury in one patient and intracranial hemorrhage in another (6.7%), but no severe neurological deficits occurred. The symptoms were significantly (P < 0.0001) improved after compared with before operation, with the modified Rankin score of 2.5 ± 0.6 at 3 months postoperation which was significantly (P < 0.0001) improved compared with before revascularization (3.4 ± 0.6). Follow-up angiography revealed patent ICA in all patients with hybrid operation. In the medication alone group, no significant (P > 0.05) improvement was observed with the mRS score of 3.5 ± 0.8 at admission and 3.4 ± 0.7 at 3 months, which was significantly (P < 0.001) greater than in the hybrid operation.
Conclusion
Hybrid operation may be safe and effective in revascularizing long-segment occlusion of internal carotid artery for prevention of further ischemic events.
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Diabetic retinopathy (DR), also known as diabetic eye disease, is one of the most common complications of diabetes mellitus and most common cause of low vision and blindness in India. It is a progressive condition with microvascular alterations that lead to retinal ischemia and macular edema. A number of recent advances have emerged in the diagnosis and management of DR. These advances could provide the means to develop major public health strategies to prevent DR and better management of diabetic retinopathy.
A study of blood lead levels in young myocardial infarction patients
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Ramesh Ayil Nagarajan, Sudhagar Mookkappan, Mark Christopher Arokiaraj, Aneesh Basheer, Nayyar Iqbal DOI:10.4103/jcrsm.jcrsm_26_18
Background: The toxicity due to lead is a widely researched sphere of public interest. Positive associations have been identified between lead exposure and coronary heart disease and cardiac rhythm disturbance. This study has been undertaken in general population to determine whether the blood lead level has any role in cardiovascular disease. Aims and Objectives: To estimate the blood levels in young patients with Myocardial Infarction and compare with the older patients. Settings and Design: A descriptive cross-sectional study was conducted among 100 patients with Myocardial Infarction [MI] admitted in a private medical college over a Study Period of 12 months categorized into 2 groups of 50 each based on age <45 yrs and >45 yrs. Materials and Methods: Patients with ECG changes suggestive of Myocardial Infarction and elevated CKMB and Troponin I were included and patients with other than the conventional risk factors were excluded. Patients were further investigated for complete blood count, fasting lipid profile, serum electrolytes, 2D echocardiograph, CK-MB, Troponin I and blood lead levels. Results: The prevalence of MI was 94% and 8% in men and women of the younger group whereas 74% in men and slightly higher percentage of 26% in women of the older group. The mean blood lead levels was 8.392 mg/dl with a standard deviation of 4.5 mg/dl among younger patients as compared to mean of 15.048 mg/dl with standard deviation of 2.5 mg/dl indicating a significant increase in blood lead levels as the age progresses, though the lead levels were in normal range. Conclusion:The study revealed a significant correlation of serum lead concentration with progression of age, though no such correlation was found with Myocardial Infarction. However further studies with healthy participants, larger sample size and data in regards to specific occupation, life style and geographic location can yield significant results to attribute serum lead as a risk factor for developing cardiovascular disease.
The incidence and prevalence of adverse drug reactions among medical inpatients in a Nigerian University Teaching Hospital
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Peter Ehizokhale Akhideno, Olumuyiwa John Fasipe, Ambrose Ohumagho Isah DOI:10.4103/jcrsm.jcrsm_20_18
Aim: Evaluating the incidence, prevalence, and pattern of adverse drug reactions (ADRs) with the extent to which they influence cost of healthcare is often informative and useful in patients' management, policymaking and safety considerations. Methods: The patients admitted into the internal medicine wards of a university teaching hospital, South-South Nigeria over a 9-month period from December 2013 to August 2014 were prospectively recruited for the study and followed up till discharge. Results: Five hundred and seven patients were evaluated during the study, out of which 269 (53.1%) of them were males and 238 (46.9%) were females. The mean age of the study population was 48.9 ± 17.8 years (median of 46 years). ADRs had an incidence of 6.5%, while its prevalence rate was 10.1%. The cost of treating ADR was ₦ 161668.00 ($1243.60), equivalent to 1.9% of the total cost of all medications used by patients during admission. The case fatality rate for ADRs was 7.8%, while ADR-related mortality rate was 0.8%. The most frequently affected body systems were the central nervous system and the gastrointestinal system corresponding to insulin use (causing neuroglycopenic symptoms) and nonsteroidal anti-inflammatory drugs (NSAIDs) use (causing NSAID-induced gastroenteritis/GIT bleeding) respectively. Conclusions: The incidence and prevalence of ADRs were clinically significant among these medical inpatients. In this study, ADRs increase patients morbidity, mortality, cost of health care, and duration of hospital stay as it has been shown by previous studies. Insulin caused the highest number of ADRs, suggesting the need for individual diabetic patients to acquire and learn the appropriate regular use of glucometers.
George Thomas, Anulekha Mary John, Jibily Joy, Sherin Sarah Mathew, Alice David DOI:10.4103/jcrsm.jcrsm_32_18
Background/Objectives: Herbal brews other than tea/coffee are becoming popular. We observed that these interfered with absorption of thyroxine. Since no prior studies have examined this, we sought to estimate this interaction effect, if any. Materials and Methods: This study was conducted among outpatients of a tertiary care hospital in India. Patients on thyroxine replacement were interviewed regarding the drink used with thyroxine. Various herbal brews used were compared against plain water. Thyroid-stimulating hormone was measured and compared. Results: Total of 121 patients fulfilled the inclusion and exclusion criteria, and 69 (57.0%) patients among them took thyroxine with a herbal brew. Various herbal products included cutch-tree (Karingali) 26 (37.7%), herbal mixture (Dahashamini) 28 (40.6%), and others 15 (21.7%). Risk of not achieving euthyroidism with any herbal brew was 7.6 times high (odds ratio [OR] 7·6 with 95% confidence interval [CI]: 3·1–18·5) as against plain water and was the highest for cutch, OR 12.4 with 95% CI: 4.0–38.0. Conclusions: Several patients take thyroxine with water brewed with herbal products. Effectiveness of thyroxine was greatly reduced when taken with herbal brews.
Comparison of four different methods of smear preparation for Gram staining of positively flagged automated blood culture bottles
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Jyoti Nain, R Deepashree, Pratibha Tamang, Prasanna Bhat, Suman Prakash, R Sneha, T Kalpana, G Anitha, Apurba Sankar Sastry DOI:10.4103/jcrsm.jcrsm_34_18
Introduction: Gram staining of smears prepared from positively flagged blood culture bottles plays a vital role because its accurate interpretation helps the clinicians to modify empirical therapy as well as to perform the direct susceptibility test, which reduces the turnaround time by 24 h to initiate pathogen-directed antimicrobial therapy. However, the interpretation of direct Gram stain from blood culture bottles has always been at risk of errors in interpreting. Aim: The present study was conducted to find the agreement between the blood culture broth Gram stain finding of four different methods (conventional, water wash, blood film, and drop and rest) of smear preparation with the culture smear Gram stain result and also to compare the quantity of charcoal and resin particles present in the Gram stained smears made from four different smear preparation methods. Method and Result: Smears were made from 500 positively flagged automated blood culture bottles using the four different methods and then compared for agreement with the culture smear Gram stain using kappa statistics and were found to be maximum for the blood film method (0.637), followed by drop and rest (0.570), water-wash (0.496), and conventional method (0.475). The 3+ grading for resin/charcoal was found in 184 (36.80%) smears, 169 (33.80%), 93 (18.60%), and 26 (5.20%) smears prepared by water-wash, conventional, drop and rest, and blood film method, respectively. The interference caused by resin/charcoal was maximum when smears were prepared by the conventional method resulting in high inaccurate interpretation. Conclusion: In this study, the agreement between direct smear preparation methods from positively flagged blood culture broth with the culture smear Gram stain was found to be maximum for the blood film method, followed by drop and rest, waterwash, and conventional method.It was also observed that the least amount of resin/charcoal was encountered when the direct smears were prepared using the blood film method.Hence, we found that the blood film method helps in interpreting the Gram stained smears from positively flagged blood culture broth more accurately compared to other methods.
Effect of regular treatment, follow-up, and lifestyle practices in diabetic patients with ocular manifestations attending a tertiary care hospital in Puducherry, India
p. 104
Nivedha S Raman, Amod Hansdak DOI:10.4103/jcrsm.jcrsm_33_18
Background: The last few decades have witnessed the growth of diabetes mellitus which is affecting all sections of the society. Complications of diabetes and its management present a still further challenge to health care providers. Methods: A hospital-based cross-sectional study was conducted at Pondicherry Institute of Medical Sciences, India, to find out the treatment and follow-up of patients with diabetes mellitus and also to estimate ocular manifestations among the study subjects. Results: Regular treatment was found among 80% while regular follow-up was seen in 55.7% of the diabetic patients. Two-thirds of the patients were on oral hypoglycemic agents only. 18.6% of the patients tested their blood glucose levels once a month. Visit to an ophthalmologist was made in the last 12 months by 32.9% of them. Ocular manifestations were present in both vegetarians 80% and non-vegetarians 76% respectively. Diabetics practicing sedentary lifestyle had more ocular manifestations 87% as compared to 62.5% in those who did not exercise. Ocular manifestation was also higher among those with elevated blood glucose levels 74.4% in comparison to 61.3% among those with normal blood glucose levels.Conclusion: This study highlights the importance of regular treatment and follow-up by patients with diabetes in relation to development of ocular manifestations. Exercise in diabetes is a key factor in delaying complications such as retinopathy.
Neha Sivaguru, KM Indira, K Pradeep, L Gopinath, Nayyar Iqbal DOI:10.4103/jcrsm.jcrsm_36_18
Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiographical syndrome of varying etiologies. It is characterized by headache, confusion, seizures, visual loss, and raised blood pressure along with magnetic resonance imaging abnormalities. It is associated with a number of conditions such as hypertension, eclampsia, vasculitis, chemotherapeutic drugs, and postpartum state. We report the case of a 28-year-old female who developed PRES on her 8th day of postpartum along with subarachnoid hemorrhage.
Acute pulmonary embolism (PE) is a relatively common complication after major orthopedic surgeries with a high mortality rate. We present a case of L4–L5 disc prolapse with radiculopathy posted for spinal instrumentation and fusion surgery who developed PE perioperatively. It was diagnosed initially with point-of-care echocardiography and confirmed with computed tomography pulmonary angiography. The patient was thrombolyzed with streptokinase, following which she developed bleeding from the surgical site which was managed conservatively with blood transfusions. The patient recovered well and discharged after a week. The management of PE tests the skills of the anesthetist with respect to detection and rapid hemodynamic management.
Bilateral absence of third and fourth lumbricals: A case report with clinico-evolutionary insight
p. 116
NA Priyadharshini, V Dinesh Kumar, R Rajprasath DOI:10.4103/jcrsm.jcrsm_16_18
Lumbricals are wormlike, intrinsic muscle of the hand. During routine dissection of a male cadaver of age approximately ranging between 50 and 55 years, the absence of third and fourth lumbricals on both the palm was observed. First and second lumbricals showed no anatomical variation. Other muscles of hypothenar eminence supplied by deep branch of ulnar nerve which also supplies the third and fourth lumbricals were normal. Lumbricals are principle extensors of interphalangeal joint, and its role in flexion of metacarpophalangeal joint is meager. Variability in the presence of medial two lumbricals has evolutionary correlation and also shows its minimal role in the extension of interphalangeal joint of its respective digits. Henceforth, knowledge of absence of lumbricals is crucial for surgeons while planning for hand surgery.
Perioperative myocardial infarction (PMI) in patients without a prior history of coronary artery disease is quite rare. Diagnosing PMI is also quite challenging because of a myriad of events mimicking MI during the perioperative period. we are reporting of PMI leading to cardiac arrest which was successfully resuscitated with the help of a multidisciplinary team. Cardiologist opinion was obtained, and angiogram was done which showed block in left anterior descending artery for which he was stented with drug-eluting stent and discharged a week after with full neurological recovery. The mechanism for triggering PMI in our case is quite inconclusive.
