NEJM Resident E-Bulletin

Adding Azithromycin to Seasonal Malaria Chemoprevention: Does the addition of azithromycin to seasonal malaria chemoprevention reduce overall childhood mortality and morbidity? Prevention of Opioid Overdose: When is coprescription of naloxone indicated for a patient receiving opioids?

FEATURED ONLINE HIGHLIGHT CASE CHALLENGE A Woman with Abdominal Pain and Fever A 38-year-old woman with a history of Crohn's disease was admitted to the hospital because of abdominal pain and fever. Despite appropriate medical treatment, she had progressive worsening of clinical symptoms. What is the most likely diagnosis? Vote and comment. Find the answers in the full text of the case, to be published on June 20.

Teaching Topic Adding Azithromycin to Seasonal Malaria Chemoprevention ORIGINAL ARTICLE Effect of Adding Azithromycin to Seasonal Malaria Chemoprevention D. Chandramohan and Others         The frequent contact between children and health care workers that is needed for seasonal malaria chemoprevention provides an opportunity for the delivery of other health interventions. Chandramohan et al. conducted a randomized, double-blind, placebo-controlled trial to determine whether the addition of azithromycin to the monthly sulfadoxine–pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention would reduce mortality and morbidity among African children living in Burkina Faso and Mali. Clinical Pearls   What is the approach to seasonal malaria chemoprevention in the Sahel and sub-Sahel regions of Africa? Malaria transmission is concentrated during a few months of the year in much of the Sahel and sub-Sahel regions of Africa. In these areas, seasonal malaria chemoprevention — the administration of sulfadoxine–pyrimethamine plus amodiaquine to children at monthly intervals three or four times during the malaria-transmission season — has been a highly effective approach to malaria control.   Has mass administration of azithromycin for trachoma control reduced the incidence of other types of infections? Mass administration of azithromycin has been a highly effective approach to trachoma control. Reductions in the incidences of skin, gastrointestinal, and respiratory infections have been recorded after mass administration of azithromycin. Morning Report Questions Q. Does the addition of azithromycin to seasonal malaria chemoprevention reduce overall childhood mortality and morbidity? A. In the trial by Chandramohan et al., among children in Burkina Faso and Mali, the addition of azithromycin to the antimalarial agents used for seasonal malaria chemoprevention did not result in a lower incidence of death or hospital admission that was not due to trauma or surgery than antimalarial agents plus placebo. The authors noted that the incidences of clinic visits for gastrointestinal infections, upper respiratory tract infections, and nonmalarial febrile illnesses, without adjustment for multiple comparisons, were lower among children who received antimalarial agents plus azithromycin than among those who received antimalarial agents plus placebo. Q. Are the findings of Chandramohan et al. similar to those of the MORDOR (Mortality Reduction after Oral Azithromycin) trial? A. The findings of the trial by Chandramohan et al. contrast with those of the MORDOR trial conducted in Malawi, Niger, and Tanzania, in which azithromycin was given to children younger than 5 years of age twice a year for 2 years and then was associated with a 13.5% (95% CI, 6.7 to 19.8) lower overall all-cause mortality than placebo, with the effect being most marked in Niger. There are several possible explanations for the different outcomes of these two trials. One possible explanation is that azithromycin, which has antimalarial activity, contributed to decreased mortality in the MORDOR trial partly through its effect on malaria, and this benefit was lost when an additional, effective antimalarial combination was given at the same time as azithromycin. However, the effect of azithromycin on malaria has been inconsistent when azithromycin has been given in mass drug administration programs. In addition, all the children in the trial by Chandramohan et al. received sulfadoxine–pyrimethamine, which has weak antimicrobial properties, and this may have reduced the potential benefit of adding another antimicrobial to the regimen. Finally, coverage with a pneumococcal conjugate vaccine was high among children in the trial by Chandramohan et al., and this may have reduced the potential benefit of azithromycin in lowering mortality from pneumonia.

Teaching Topic Prevention of Opioid Overdose REVIEW ARTICLE Prevention of Opioid Overdose K.M. Babu, J. Brent, and D.N. Juurlink    All opioid overdoses share a common characteristic: a first opioid exposure. When acute moderate or severe pain necessitates the use of opioids, prescribers should limit the course to the lowest dose and shortest duration possible. Even brief opioid courses have potential long-term consequences. Clinical Pearls   Is there a validated instrument that can estimate the risk of opioid overdose? The revised Risk Index for Overdose or Severe Opioid-Induced Respiratory Depression (RIOSORD) is a validated instrument used to estimate the risk of overdose in opioid-treated patients. The predicted probability of opioid-induced respiratory depression within 6 months after initiation ranges from 1.9% in the lowest-risk group to 83.4% in the highest-risk group. Despite several practical limitations (including the length of the index and a lack of clinician familiarity), the use of RIOSORD can guide risk–benefit decisions and facilitate reassessment of risk over time.   How do prescription drug monitoring programs assist clinicians? Prescription drug monitoring programs (PDMPs) allow the assessment of a patient's prescription opioid history, and a patient-specific query is required before opioid initiation in several states. In areas without a legislative mandate, PDMP inquiries are infrequently completed; recognized obstacles include time, workload, and poor integration into existing electronic medical records. However, PDMPs can identify doctor shopping, concomitant benzodiazepine prescriptions, and evidence of an undisclosed opioid use disorder, such as previous receipt of buprenorphine prescriptions. These signals should prompt clinicians to screen for an opioid use disorder and offer treatment when present. This evaluation can be accomplished through the Rapid Opioid Dependence Screen, which can be administered in under 2 minutes. Morning Report Questions Q. Describe an alternative to gradual opioid tapering as a way to decrease the use of high-dose opioids in patients with chronic pain. A. Clinicians should engage patients receiving high-dose opioids in shared decision making about the merits of gradual dose reduction — specifically, a more favorable balance of benefits versus harms. These discussions are frequently difficult. An alternative to gradual tapering involves transitioning patients from high-dose opioids to buprenorphine, a medication commonly used for the treatment of opioid use disorder. Buprenorphine is a high-affinity partial agonist at mu-opioid receptors that has a ceiling effect on sedation and respiratory depression without a clinically relevant ceiling on analgesia. As is the case with full opioid agonists, buprenorphine causes modest reductions in chronic pain, as compared with placebo, whereas its anxiolytic and antidepressant effects may reflect antagonism at kappa-opioid receptors. Transitioning from full agonists to buprenorphine not only reduces the risk of accidental overdose but frequently imparts subjective improvements in pain, function, sleep, and constipation. Q. When is coprescription of naloxone indicated for a patient receiving opioids? A. Coprescribing of naloxone is increasingly accepted as a valuable tool in patients who are taking opioids for chronic pain. In a large observational study involving patients who were receiving long-term opioid therapy, those who were prescribed naloxone and provided with information on the risk of overdose had 63% fewer emergency department visits at 1 year than those who did not receive such treatment. Naloxone is generally well received by patients and prescribers in the primary care setting. The CDC guideline recommends coprescription of naloxone when patients who have a history of overdose or substance use disorder are prescribed opioids; it is also recommended in patients who are receiving a daily morphine-equivalent dose of more than 50 mg and in those receiving benzodiazepines concurrently.

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QUOTE OF THE WEEK "In this 15-year follow-up study, we found that 5.6 years of intensive glucose lowering that led to a median separation of 1.5 percentage points in the glycated hemoglobin curves did not result in a significantly lower risk of major cardiovascular events than standard therapy." P.D. Reaven and Others, Original Article,  "Intensive Glucose Control in Patients with Type 2 Diabetes — 15 Year Follow-up"

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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per μL have a low probability of invasive bacterial infection (IBI)

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection

Paul L. Aronson, Veronika Shabanova, Eugene D. Shapiro, Marie E. Wang, Lise E. Nigrovic, Christopher M. Pruitt, Adrienne G. DePorre, Rianna C. Leazer, Sanyukta Desai, Laura F. Sartori, Richard D. Marble, Sahar N. Rooholamini, Russell J. McCulloh, Christopher Woll, Fran Balamuth, Elizabeth R. Alpern, Samir S. Shah, Derek J. Williams, Whitney L. Browning, Nipam Shah, Mark I. Neuman, for the Febrile Young Infant Research Collaborative

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OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI).

METHODS: We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated.

RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79–0.86]) and incorporated into an IBI score: age <21 days (1 point), highest temperature recorded in the emergency department 38.0–38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per μL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%–99.9%) and 31.3% (95% CI: 26.3%–36.6%), respectively. All 26 infants with meningitis had scores ≥2.

CONCLUSIONS: Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per μL have a low probability of IBI.

Accepted January 16, 2019.

Copyright © 2019 by the American Academy of Pediatrics

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Environmental Monitoring and Assessment

Distribution, toxicity, and origins of polycyclic aromatic hydrocarbons in soils in Ulsan, South Korea Abstract This study was conducted to investigate the concentrations, distributions, toxicities, and sources of polycyclic aromatic hydrocarbons (PAHs) in the soils from different areas in Ulsan, South Korea. Samples were collected from 41 sites, including a waste treatment facilities area (WA), traffic facilities area (TA), child playground area (CA), industrial area (IA), railroad facilities area (RA), ore and iron scraps fields area (OA), and residential area (ReA). Ulsan was chosen for research area because it used to be an environmental hot spot in South Korea, and 16 PAHs in the US EPA priority pollutant list were selected. The concentration of total PAHs (t-PAHs) ranged from 61.7 to 12,421 μg/kg, and the average concentration of t-PAHs was 706.9 μg/kg. The distribution of PAHs by ring number indicated that the portion followed the order of 4 rings > 5 rings > 3 rings > 6 rings > 2 rings. According to PAH origin indices, LMW/HMW (low molecular weight 2–3 ring PAHs over high molecular weight 4–6-ring PAHs), phenanthrene/anthracene ratio and fluoranthene/pyrene ratio, benzo(g,h,i)perylene/indeno (1,2,3-c,d)pyrene ratio, vehicular emissions, and the combustion of fossil fuel were the sources of PAHs. The strong correlation (R2 = 0.995) between t-PAHs and total carcinogenic PAHs (t-PAHcarc) indicated that the concentration of t-PAHcarc increased in proportion with that of t-PAHs. The toxic equivalent concentrations (TEQs) of PAHs in the soils ranged from 44.0 to 1929.9 μg TEQ/kg. It is imperative to set regulatory levels for PAHs for periodic monitoring and rapid remediation action of contaminated soils, because there are no national standards in South Korea for 15 PAHs with the exception of benzo(a)pyrene.

Inhomogeneity of sediment samples in analysis of hexabromocyclododecane Abstract The repeatability test of the analytical method for hexabromocyclododecane (HBCD) was conducted with sediment sample. The maximum HBCD concentration exceeded the minimum by a factor of 90 even though the identical sediment samples were used. Therefore, we examined which step of the analytical method was the factor causing variability. We examined the blank test, and confirmation test of the extraction and purified procedure. From these results, we confirmed that there was nothing wrong with the accuracy of our analytical method. These results indicate that the variability of HBCD concentration in the repeatability test was attributed not to the analytical method, but to the inhomogeneity of the sediment sample. Aluminum, silicon, and organic carbon in sediments were measured to compare the variability of these concentrations with that of HBCD concentration. These concentrations were similar values within identical samples which showed variability in HBCD concentration. HBCD concentration in several samples did not correlate with organic carbon content. These results suggests that sediment samples were homogeneous by itself, and HBCD was heterogeneously distributed in spite of homogeneity of organic carbon in sediment. The sediment sample with variability in HBCD concentration showed different HBCD diastereomer compositions in identical sediment. It implies that the sample contained HBCD derived from different histories or point sources. Even though we increased sample amounts to analyze the homogeneity of the sample, HBCD concentration varied within identical samples if the sample had a hot spot. Past monitoring data may contain overestimation or underestimation of HBCD concentration in sediment.

Heavy metal accumulation in surface sediments of the Ganga River (India): speciation, fractionation, toxicity, and risk assessment Abstract We investigated the distribution of different fractions of eight heavy metals (Zn, Cr, Cu, Pb, Cd, Ni, Fe, and Mn) in the bed sediment of the Ganga River. The study was conducted during summer low flow (March to June 2017) considering a 285-km middle stretch of the Ganga River between the Allahabad upstream and the Varanasi downstream. To assess the metal levels from a toxicological perspective, we tested the relationships between metals and sediment microbial/extracellular enzyme activities. Most of the metals showed a large fraction in residual form. However, Zn, Pb, and Cd showed about 20–30% share in the exchangeable form. The total metal concentration poorly reflected the toxicity but the exchangeable fractions did show strong negative correlations (r = − 0.83 to − 0.63; p < 0.01) with microbial/enzyme activities. Also, the nutrients and organic carbon showed strong positive correlations (r = 0.62 to 0.89; p < 0.001) with microbial/enzyme activity. The phosphate showed a strong negative correlation (r = −0.82; p < 0.001) with alkaline phosphatase. The principal component analysis (PCA) and the indices such as contamination factor (CF), enrichment factor (EF), pollution load index (PLI), geoaccumulation index (Igeo), and risk assessment code (RAC) revealed moderate to severe contamination with strong anthropogenic influence. As per the United States Environmental Protection Agency, the metal concentrations at many locations were in the highly toxic range. The study has relevance from a toxicological perspective and for the management of the Ganga River.

Spatial distribution and ecological risk assessment of trace metals in surface sediments of Lake Qaroun, Egypt Abstract A suite of trace metals was determined in twenty surface sediments collected from Lake Qaroun, which is designated as a natural reserve in 1989 to examine their spatial distribution and their potential environmental impact on the lake. Contamination factor (Cf), enrichment factor (EF), geoaccumulation index (Igeo), and pollution load index (PLI) are applied to evaluate the quality of the lake. The highest concentrations were detected in the eastern portion of the lake near Al-Bats drain. The levels of Ba exceeded the toxicity reference value (TRV) (20 ng/g dw) set by US EPA for all sediments, while sediments collected from Al-Bats region exceeded the TRV for Zn (68 ng/g dw). Arsenic, Ba, Sn, Co, Cu, and Hg are poorly correlated with background value of Fe suggesting anthropogenic activities over the entire lake. The values of Cf and Igeo confirmed that the eastern portion of the lake has been found moderately to considerably contaminated by As, Sn, and Zn. Sediments collected from the eastern location (S1) were very highly enriched of Sn (22.47); however, the other eastern locations were highly enriched of Sn, As, Cd, Co, and Ba. It is clear that sites near Al-Bats and El-Wadi drains are hot spots, which got immense amounts of domestic, agricultural, and industrial wastes. Behind the influence of these discharges, concentrations are decreased. The PLI over the entire lake ranged from 0.247 to 0.801 for all sites, which reflect unpolluted status.

Demand prediction and regulation zoning of urban-industrial land: Evidence from Beijing-Tianjin-Hebei Urban Agglomeration, China Abstract As a main type of urban construction land, urban-industrial land is used to provide the judging criteria for construction land scale in the planning period when urban population, industrial development, investment scale, and other conditions are uncertain in China; however, research on expected indicator such as urban-industrial land in overall land use plan mainly focuses on qualitative analysis; quantitative analysis research has not yet been carried out. Using MATLAB R2016a software modeling tools to establish GM (1, 1) model and RBF neural network model, respectively, this paper predicted the demand of urban-industrial land in Beijing-Tianjin-Hebei Urban Agglomeration. Comparing the predicated results with the actual value of urban-industrial land in Beijing, Tianjin, and 11 prefecture-level cities in Hebei Province, we determined the reasonable prediction model for urban-industrial land after testing the accuracy of the two prediction models. The results showed that the RBF neural network model was the more reasonable prediction model for urban-industrial land. Using the predicted results of the RBF neural network model, combining expected indicators of overall land use plan (2006–2020) in Beijing and Tianjin, as well as 11 prefecture-level cities in Hebei Province in the planning target year, determined remaining usable time of urban-industrial land. Finally, combined with the actual scale of urban-industrial land in 2015 and the predicated scale of urban-industrial land in 2020, the remaining usable time of each city's urban-industrial land was calculated in terms of the average annual growth rate of urban-industrial land from 2009 to 2015. According to the comparative relationship between the remaining usable time and the remaining time of the overall land use plan (5 years), urban-industrial lands were divided into three kinds of regulation zones: reasonable reduction zone, optimized adjustment zone, and core development zone. The policy implications for urban-industrial land in each regulation zone were also provided. This paper can provide reference for regulation zoning of urban-industrial land in developing countries and regions.

Optimization and validation of headspace solid-phase microextraction method coupled with gas chromatography–triple quadrupole tandem mass spectrometry for simultaneous determination of volatile and semi-volatile organic compounds in coking wastewater treatment plant Abstract Industrial wastewater could be an important source for the emission of volatile (VOCs) and semi-volatile organic compounds (SVOCs), but little is known about it. In this study, a method for the identification and quantitation of 43 VOCs and SVOCs in coking wastewater was developed using a solvent-free equilibrium extraction method on the basis of headspace solid-phase microextraction accompanied by gas chromatography–triple quadrupole tandem mass spectrometry (HS-SPME-GC-MS/MS). To ensure good extraction efficiency, the parameters that have an effect on the HS-SPME-GC-MS/MS process were carefully optimized, in terms of fiber exposure time and temperature, pH, salt additives, sample volume, and desorption time. The HS-SPME method showed good linearity range with coefficients of determination (R2) ≥ 0.991 and achieving a satisfactory recoveries value (70–120%) with good relative standard deviations (RSDs) < 20% (precision). Furthermore, the purposed approach proved to be sensitive with low detection limits, where the values ranged from 0.03 to 3.01 μg/L. The real sample analysis result showed that 43 of VOCs and SVOCs were detected in raw coking wastewater, with 3-cresol as the dominant ones. Further, the method revealed that seven phenols, 11 polycyclic aromatic hydrocarbons, and five BTEX were detected even in the treated effluent. In conclusion, the HS-SPME method developed in this study is simple in sample preparation, convenient, sensitive, and could satisfy the requirement of the analysis of VOCs and SVOCs in coking wastewater.

Aquatic insect communities in small stream in the south of Brazil Abstract Pollution of rivers and streams, by anthropic action, is characterized as an environmental, social, and sanitary problem. Factors such as the association between the marginal vegetation, the distribution of the substrates in the riverbed, and the availability of allochthonous organic matter influence the distribution and composition of the aquatic entomofauna. The objective of this study was to analyze the structure of aquatic insect communities in a pasture stream in northern Paraná, southern Brazil, with emphasis on the groups of indicators of good water quality, thus inferring the conditions of its preservation. Samples were collected from July to October in three parts of the stream (P1, P2, and P3), where the insect faune was collected with the aid of a sieve in the foliage substrate and washing of rocks and decomposing pieces of wood. A total of 1323 individuals were collected, being Chironomidae (Diptera) the most abundant taxon. The analysis of the biotic indices (EPT/Chironomidae, IBF, BMWP, and BMWP/ASPT) and diversity indicated better preservation conditions at points P1 and P3 where the riparian forest was well preserved, with less exposure to the stream bed. In P2, the entomofauna presented less diversity and the biotic indexes indicated loss of water quality, showing the impacts of changes in the marginal vegetation of this section. In a generally preserved aquatic environment, small changes in its vegetation are sufficient to cause an imbalance in the aquatic insect community, showing the efficiency of these organisms as bio-indicators and the sensitivity of biotic indexes.

Investigating the effect of several factors on concentrations of bioaerosols in a well-ventilated hospital environment Abstract This study characterized and quantified the bacterial and fungal bioaerosols in nine wards of the Razavi Hospital (Mashhad, Iran) that is equipped with an advanced heating, ventilating, and air conditioning (HVAC) system including HEPA filters for air cleaning. In this study, 432 samples were taken from the indoor air of multiple hospital wards during the morning and afternoon shifts during summer and autumn. The particle number concentrations with sizes of > 0.3, > 0.5, > 1, > 2, > 5, and > 10 μm were measured using a 6-channel handheld particle counter. A greater diversity of bioaerosol types were observed during the morning shifts and during summer. The microbial load was not affected significantly by the temperature, relative humidity, working shift, season, and number of visitors, indicating the effectiveness of a well-designed ventilation system to eliminate site-specific variations. For microbial number concentrations, a significant correlation was only observed between the number of particles with a diameter of > 10 μm and the airborne microbial loading. Thus, passive sampling may not properly reflect the actual concentrations of smaller bioaerosols. In conclusion, HEPA filters in the HVAC system successfully decreased the bioaerosol concentrations in the hospital environment. Additionally, we recommend that active sampling be used in cases where a well-functioning HVAC system exists.

EventFinder: a program for screening remotely captured images Abstract Camera traps are becoming ubiquitous tools for ecologists. While easily deployed, they require human time to organize, review, and classify images including sequences of images of the same individual, and non-target images triggered by environmental conditions. For such cases, we developed an automated computer program, named EventFinder, to reduce operator time by pre-processing and classifying images using background subtraction techniques and color histogram comparisons. We tested the accuracy of the program against images previously classified by a human operator. The automated classification, on average, reduced the data requiring human input by 90.8% with an accuracy of 96.1%, and produced a false positive rate of only 3.4%. Thus, EventFinder provides an efficient method for reducing the time for human operators to review and classify images making camera trap projects, which compile a large number of images, less costly to process. Our testing process used medium to large animals, but will also work with smaller animals, provided their images occupy a sufficient area of the frame. While our discussion focuses on camera trap image reduction, we also discuss how EventFinder might be used in conjunction with other software developments for managing camera trap data.

A phytotoxic impact of phenolic compounds in olive oil mill wastewater on fenugreek " Trigonella foenum-graecum " Abstract The objective of this study is the determination of the chemical structure of nine phenolic molecules responsible for the phytotoxic action on the germination of the plant species "Trigonella foenum-graecum". The phytotoxic action was evaluated by calculating the germination index of the plant species for a period of 5 days of incubation. The analysis of the physicochemical properties of phenolic molecules shows that hydrophobicity is a key factor in phytotoxicity. The sublethal concentration varies as follows: hydroquinone (0.91 mM), 4-aminophenol (0.85 mM), phenol (0.75 mM), gallic acid (0.59 mM), caffeic acid (0.56 mM), 3,5-di-tert-butylcatechol (0,45 mM), quercetin (0.33 mM), oleuropein (0.3 mM), and catechol (0.13 mM). Phytotoxicity varies depending on the nature and position of the substituents on the aromatic ring. The reactivity of this type of molecule is partly linked to the presence of catechol function that can play the main role in phytotoxicity of the Fenugreek.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Healthy and Safe Swimming

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Pools, hot tubs/spas, and water playgrounds are great places to have fun, be active, or just relax. Learn how to stay healthy and safe when in the water this summer!

Swimming is one of the most popular sports activities in the United States. Just 2.5 hours of physical activity per week, including water-based activity, has health benefits, no matter our age.

As with any form of physical activity, we increase the health benefits when we each do our part to decrease the risks of illness and injury.

Share the Fun, Not the Germs!

Heading to the pool this summer? Help ensure healthy and safe swimming experiences for everyone by following simple steps.

Swimming is a fun way to be healthy and spend time with family and friends. However, it's important not to swim or let your kids swim if  they have diarrhea. Just one diarrheal incident in the water can release millions of diarrhea-causing germs like Crypto (short for Cryptosporidium), Giardia, Shigella, norovirus, and E. coli. This can make other swimmers sick if they swallow a mouthful of contaminated water.

Most germs are killed within minutes by common pool disinfectants like chlorine or bromine, but Crypto is a germ that can survive in properly chlorinated water for more than 7 days. This is why Crypto is the leading cause of U.S. outbreaks linked to swimming.

Swim Healthy, Be Healthy!

We can all help protect ourselves and our loved ones from germs by following a few simple but effective steps.

Most superstores, hardware stores, and pool supply stores sell test strips.

For free test strips, visit the Water Quality & Health Council (WQHC)'s Healthy Pools pageexternal icon.

Before getting in…

• Don't swim or let children swim if sick with diarrhea.
• Check out the latest inspection results. You can find inspection scores online or on-site.
• Do your own mini-inspection. Use test strips to make sure disinfectant (chlorine or bromine) level and pH are correct.
  • Free chlorine concentration of at least 1 ppm in pools and water playgrounds
  • Bromine concentration of at least 3 ppm in pools and water playgrounds
  • pH 7.2–7.8
• Shower for at least 1 minute before you get into the water. This will remove most of the dirt and sweat on your body.

Once in…

• Don't swallow the water.
• Don't pee in the water.
• Take kids on bathroom breaks and check diapers every hour.
• Change diapers in a bathroom or diaper-changing area—not poolside—to keep germs away from the pool.

Visit CDC's Healthy Swimming website to learn more and order FREE printed healthy swimming materials.

Download CDC's health promotion materials to help spread the word about the importance of staying healthy and safe in the water this summer and all year long!

Prevent Injury

Staying safe in and around the water is important, too. Don't forget drowning prevention. Drowning is a leading cause of unintentional injury death among children 1–14 years old. In fact, drowning kills more young children 1–4 years old than anything else except birth defects.

Of drowning victims who survive and are treated in emergency rooms, more than half are hospitalized or transferred for further care. They often experience brain damage, which can cause memory problems, learning disabilities, or permanent loss of basic functioning. Swimmers can prevent drowning by learning swimming skills, by wearing life vests, and by swimming under the close supervision of parents, caregivers, or lifeguards who know cardiopulmonary resuscitation (CPR).

Visit CDC's Sun Safety website to learn more about how to protect yourself and loved ones from skin cancer.

Remember: Think Healthy. Swim Healthy. Be Healthy! This summer and year round, let's follow CDC's Steps of Healthy Swimming to protect ourselves and our loved ones from illness and injury when swimming or playing in the water.

Page last reviewed: May 17, 2019

Content source:

National Center for Emerging and Zoonotic Infectious Diseases, Division of Foodborne, Waterborne, and Environmental Diseases

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Experimental Biology and Medicine*

Microbiome in Healthcare and Medicine Editor: Horst von Recum Addressing the presence of unwanted bacteria and fungi following medical procedures has long been a major healthcare concern. Infection applications can range from wounds, to surgical sites to biomedical implants. This Special Issue broadly addresses new knowledge in microbiome-related research, particularly in regards to medicine and healthcare. We hope it can serve as a state-of-the-art review of recent advances, suitable for experts in the field, as well as a primer for the novice to understand what areas are involved and gain a rapid understanding of how these different topics have come together. Read the issue

Cell mimicry and synthetic biology: tools, applications, and emerging conceptual framework Editors: Oscar Ces and Yuval Elani This thematic issue is the first contribution to the journal category, adding to the journal's heritage of exploring cutting edge aspects of the life sciences. The issue contains articles that cover the wide synthetic biology spectrum, including plant synthetic biology, protocell research, artificial cell therapeutic agents, cell-free synthesis and protein reconstitution in cell-mimics, and topography design of synthetic cell membranes. The editors of this issue hope that it will be of value both for experiments in bottom-up and top-down synthetic biology, as well as to general Experimental Biology and Medicine readers. Read the issueExperimental Biology and Medicine*

Pharmacological inhibition of Bax-induced cell death: Bax-inhibiting peptides and small compounds inhibiting Bax
Kelsey Jensen, David Jasen WuWong, Sean Wong, Mieko Matsuyama, Shigemi Matsuyama
First Published March 5, 2019; pp. 621–629
Abstract
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Bax is an essential mediator of mitochondria-dependent programed cell death. Bax belongs to the Bcl-2 family of proteins and its activities are regulated through interaction with other member proteins in the Bcl-2 family. To date, several apoptosis-inducing drugs activating Bax have been developed, and some of them are already in the market as therapeutics against cancer. However, at present, there are no clinically effective pharmacological Bax inhibitors protecting essential cells. Previously, we developed Bax-Inhibiting Peptides (BIPs) that belong to the peptide group of Cell-Penetrating Peptides (CPPs). CPPs have the ability to deliver cargo molecules into the cell. In this review, we will describe the mechanism of action of BIPs together with the recent applications of BIPs in disease models in vitro and in vivo. However, BIPs have several limitations in their use to treat human diseases, and other types of Bax inhibitors need to be developed for future therapeutics. Recently, several groups reported the successful development of novel small compounds inhibiting Bax. We will review these Bax inhibitors to discuss current strategies to develop pharmacological Bax inhibitors.

Impact statement
Bax induces mitochondria-dependent programed cell death. While cytotoxic drugs activating Bax have been developed for cancer treatment, clinically effective therapeutics suppressing Bax-induced cell death rescuing essential cells have not been developed. This mini-review will summarize previously reported Bax inhibitors including peptides, small compounds, and antibodies. We will discuss potential applications and the future direction of these Bax inhibitors.

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Biomedical Engineering
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Bioengineering approaches to organ preservation ex vivo
Meghan Pinezich, Gordana Vunjak-Novakovic
First Published March 19, 2019; pp. 630–645
Abstract
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The advent of successful solid organ transplantation is undoubtedly among the most significant medical achievements of the 20th century. Despite advances in the field of transplantation since its inception over 50 years ago, our approach to donor organ preservation outside of the body remains unchanged. Recently, attempts have been made to replace static cold storage with more sophisticated ex vivo machine perfusion. Rather than cooling the organ on ice to slow metabolic processes, machine perfusion aims to support normal metabolic function in a near-physiologic environment and to provide a platform on which the organ can be evaluated, preserved, and recovered. Ex vivo machine perfusion devices have demonstrated early success with respect to transplant outcomes in heart, lung, and liver, with perfusion times limited to several hours. The continued development of more advanced perfusion systems is likely to extend the duration of ex vivo organ support to days or even weeks, and enable recovery of initially unsuitable donor organs. In this review, we discuss recent clinical and pre-clinical studies, state-of-the-art organ preservation technologies, existing limitations, and a perspective on future developments.

Impact statement
Over the past several decades, ex vivo perfusion has emerged as a promising technology for the assessment, preservation, and recovery of donor organs. Many exciting pre-clinical findings have now been translated to clinical use, and successful transplantation following ex vivo perfusion has been achieved for heart, lung, and liver. While machine perfusion provides distinct advantages over traditional cold preservation, many challenges remain, including that of long-term (multi-day) ex vivo support. Here, we provide an overview of the current status of ex vivo machine perfusion in the pre-clinical and clinical setting and share our perspective on the future direction of the field.

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Endocrinology and Nutrition
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Intestinal phosphate absorption: The paracellular pathway predominates?
Matthew Saurette, R Todd Alexander
First Published February 14, 2019; pp. 646–654
Abstract
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Hyperphosphatemia is nearly universal in patients with advanced chronic kidney disease and end stage renal disease. Given the considerable negative sequelae associated with hyperphosphatemia, i.e. increased cardiovascular disease, hastening of renal failure and death, reducing serum phosphate is a goal of therapy. In the absence of sufficient renal function, intestinal phosphate absorption is the remaining target to reduce plasma phosphate levels. Much work has been done with respect to understanding transcellular phosphate absorption. Both animal studies using inducible or intestinal NaPi-2b knockout mice and specific NaPi-2b inhibitors revealed this transporter as the primary mechanism mediating transcellular phosphate absorption in the intestine. However, this has not translated into effective phosphate lowering therapies in patients with kidney disease. More recently, it was observed that inhibition of the epithelial sodium hydrogen exchanger, sodium–hydrogen exchanger isoform 3 (NHE3), or its genetic deletion, decreases intestinal phosphate absorption. The mechanism mediating this effect is through increased transepithelial resistance and reduced paracellular phosphate permeability. Thus, NHE3 inhibition reduces paracellular phosphate permeability in the intestine. The transepithelial potential difference across intestinal epithelium is lumen negative and phosphate commonly exists as a divalent anion. Further, consumption of the typical Western diet provides a large lumen to blood phosphate concentration gradient. Based on these observations we argue herein that the paracellular phosphate absorption route is the predominant pathway mediating intestinal phosphate absorption in humans.

Impact statement
This review summarizes the work on transcellular intestinal phosphate absorption, arguing why this pathway is not the predominant pathway in humans consuming a "Western" diet. We then highlight the recent evidence which is strongly consistent with paracellular intestinal phosphate absorption mediating the bulk of intestinal phosphate absorption in humans.

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Choline transport for phospholipid synthesis: An emerging role of choline transporter-like protein 1
Vera Hedtke, Marica Bakovic
First Published February 18, 2019; pp. 655–662
Abstract
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This review provides a summary of recent discoveries in choline transport and the proteins mediating it with a specific focus on the choline transporter-like proteins (CTL)/solute carriers 44 A (SLC44A) and their role in phospholipid metabolism. Since its initial cloning, particularly, the CTL1/SLC44A1 transporter has been investigated further and its ubiquitous expression characterized in various cells and tissues of mouse, rat, and human origin. We describe the role of this choline transporter both in the plasma membrane and in the mitochondria and summarize novel aspects of choline transport regulation in the muscle, nervous system, and cancer.

Impact statement
This review will provide a summary of recent advances in choline transport research and highlight important novel areas of focus in the field.

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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Mycoses

Need to re‐look cut‐off of Aspergillus Specific IgE Levels in Children with ABPA
Manvi Singh  Anil Chauhan  Nandini Paul  Nishant Jaiswal  Shreya Singh  Arunaloke Chakrabarti  Meenu Singh
First published: 01 June 2019 https://doi.org/10.1111/myc.12949
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12949
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Abstract
Background
The cut‐offs for total and specific IgE used for diagnosing ABPA in children have been adopted from adult literature and have not been validated in the pediatric population.

Objective
To establish the ideal cut‐offs of Total IgE and Aspergillus Specific IgE for the diagnosis of ABPA in children.

Methods
This study was a prospective observational case‐control study, conducted in a tertiary care hospital in North India, enrolling 140 children with partly controlled and uncontrolled asthma. Seventy children had ABPA based on the Rosenberg‐Patterson Criteria (Cases) whereas 70 children were without ABPA(Controls). All children were subjected to clinical examination and investigations like Absolute eosinophil count, Total IgE, Aspergillus Specific IgE, Aspergillus Skin Prick Test, and Radiological tests. ROC curve analysis was done to determine the ideal cut‐offs of Total and specific IgE to diagnose ABPA.

Results
The ROC curve analysis determined 1204IU/L as the cut‐off value of total IgE with a sensitivity of 79.7% (95%CI 68.31 to 88.44%) and specificity of 53.1% (95%CI 40.23 to 65.7). The ROC analysis of specific IgE levels of children with ABPA determined the cut‐off value of 0.49 KAU/L with a sensitivity of 94.03% (95%CI 85.41 to 98.35) and specificity of88.89% (95%CI 75.94 to 96.29%).

Conclusion
We propose that the cut‐offs of total and specific IgE need to be relooked in the pediatric population. Cut‐offs of Total IgE as 1204 IU/L and for Aspergillus‐specific IgE as 0.49KAU/L seem appropriate. Large multicentric studies should be conducted to determine the ideal values for diagnosing pediatric ABPA.

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Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations
Anne‐Grete Märtson  Anette Veringa  Edwin R. van den Heuvel  Martijn Bakker  Daan Touw  Tjip S. van der Werf  Lambert F. R. Span  Jan‐Willem C. Alffenaar
First published: 30 May 2019 https://doi.org/10.1111/myc.12948
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12948
The copyright line for this article was changed on 4 June 2019 after original online publication.
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Abstract
Background
Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimize drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets.

Materials/methods
Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7mg/L for prophylaxis or <1.5 mg/L for treatment) or high (>3.75mg/L) the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations.

Results
Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples were measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations a dosage change was recommended. In 54 (25%) of all measured posaconazole concentrations resulted in recommendation for dosage alteration. In the longitudinal analysis the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations.

Conclusions
Adequate posaconazole exposure was shown in in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.

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Mating genotypes and susceptibility profiles of clinical isolates of Candida glabrata from Turkey
Engin Kaplan  Deniz Aktaş  Şükran Önder  Banu Metin  Aylin Döğen  Yasemin Oz  Macit Ilkit
First published: 28 May 2019 https://doi.org/10.1111/myc.12945
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12945
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Abstract
Background
The sexual cycle of Candida glabrata is not known; however, genomic evidence is indicative of recombination among subpopulations and the genome harbors genes necessary for undergoing mating and meiosis, which may increase fitness. The relationship between specific mating type‐like (MTL) loci and antifungal susceptibility is not well understood in C. glabrata.

Objectives
We investigated different combinations of clinical C. glabrata isolate mating types and their antifungal susceptibility profiles.

Methods
Allele profiles of the mating genes of 103 clinical C. glabrata isolates were identified and their antifungal susceptibility to azoles, echinocandins, and amphotericin B was compared.

Results
The majority (88.3%) of screened isolates harboured the a allele in the locus. The MTL1, MTL2, and MTL3 loci harbored a (88.3%), a (95.1%), and α (71.8%) alleles, respectively. The C. glabrata isolates were susceptible to echinocandins but displayed high minimal inhibitory concentrations (MICs) for azoles. The MIC ranges and MIC90 values of all isolates were 1.0–≥64 and 8.0 μg mL−1 for fluconazole, 0.06–≥16.0 and 0.5 μg mL−1 for voriconazole, 0.06–≥16.0 and 1.0 μg mL−1 for posaconazole, ≤0.015–0.06, and 0.03 μg mL−1 for caspofungin, ≤0.015–0.06 and 0.015 μg mL−1 for anidulafungin, and 0.5–2 and 2.0 μg mL−1 for amphotericin B, respectively. The mating gene alleles of the clinical C. glabrata isolates were not associated with differences in the MICs of the tested antifungals, except for the MTL3 α‐allele and echinocandins.

Conclusions
The mating genotypes of the clinical C. glabrata isolates had no recognizable common effect on antifungal susceptibility.

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Biofilm formation by Candida auris isolated from colonizing sites and candidemia cases
Rachna Singh  Mahaldeep Kaur  Arunaloke Chakrabarti  Shamanth A. Shankarnarayan  Shivaprakash M. Rudramurthy
First published: 27 May 2019 https://doi.org/10.1111/myc.12947
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12947
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Abstract
Background
Candida auris, an emerging nosocomial pathogen, exhibits phenotypic variation. Non‐aggregating C. auris isolates display greater biofilm‐forming capacity and virulence than aggregate‐forming isolates. Most of the studies till date have focused on clinical isolates. The biofilm‐forming capacity of colonizing isolates remains uninvestigated.

Objectives
The present study aimed to elucidate the biofilm‐forming capacity of the colonizing isolates of C. auris, correlate it with their aggregation behavior and antifungal susceptibility, and compare it with that of the isolates from blood‐stream infection.

Methods
Colonizing and clinical (candidemia) isolates of C. auris were screened for aggregation behavior, biofilm‐forming capacity and antifungal susceptibility testing. Aggregation behavior was assessed microscopically. Biofilm‐forming capacity was determined on 96‐well flat‐bottomed microtiter plates. Antifungal susceptibility testing was performed by broth microdilution assay.

Results
Aggregative and non‐aggregative phenotypes were found to be predominantly associated with colonizing and clinical isolates respectively, with the former ones being stronger biofilm producers in the colonizing group. Non‐aggregative isolates in the colonizing group showed lower susceptibility to amphotericin B and fluconazole than aggregative isolates. In contrast, no association was noted between biofilm formation, aggregation behavior, and antifungal susceptibility amongst the clinical isolates.

Conclusion
Biofilm formation is a strain‐dependent trait in C. auris, strongly associated with the type and phenotypic behavior of the isolates. Colonizing isolates of this fungus were found to be predominantly aggregative in nature, with a higher biofilm‐forming capacity than non‐aggregative ones.

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Epidemiology and antifungal susceptibility patterns of Candida isolates from Greek women with vulvovaginal candidiasis
Sofia Maraki  Viktoria Eirini Mavromanolaki  Dimitra Stafylaki  Eleni Nioti  George Hamilos  Anna Kasimati
First published: 27 May 2019 https://doi.org/10.1111/myc.12946
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/myc.12946
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Abstract
Background
Vulvovaginal candidiasis (VVC) is a common infection of the genital tract affecting millions of women worldwide. Data on epidemiological trends of VVC in Greece are scarce.

Objective
This study was undertaken to evaluate the prevalence of VVC among symptomatic women in Crete, Greece, identify the Candida species involved and determine their susceptibility to antifungals.

Patients/Methods
Over a six‐year period (2012‐2017), 10,256 symptomatic women with vaginitis were evaluated. Isolation of yeasts was performed on Sabouraud dextrose agar with chloramphenicol, and the isolates were identified using the API 20 C AUX and/or the Vitek 2 YST card. Susceptibility of the isolates to amphotericin, fluconazole, voriconazole and flucytosine, was determined by the Vitek 2 automated system. The results were interpreted according to Clinical and Laboratory Standards criteria.

Results
Vaginal swab cultures of 1,217 (11.9%) women yielded Candida species. Recurrent VVC was documented in 62 (5.1%) of them. C. albicans was the most frequently isolated species (75.6%), followed by C. glabrata (13.6%). Overall, resistance rates to amphotericin B, fluconazole, voriconazole, and flucytosine were 0.2%, 6.6%, 1.4%, and 2.1%, respectively. Fluconazole resistance of C. albicans significantly increased in the second period of the study (2015‐2017) (P=0.031).

Conclusion
This study demonstrated that VVC is a common infection among women in our region, with C. albicans being the predominant species involved. Although resistance to antifungals was infrequent, resistance to fluconazole among C. albicans isolates was found to significantly increase with time. Continued surveillance of changes in species distribution and susceptibility to antifungals are necessary to guide treatment.

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Dermatological manifestations of fungal infection in patients with febrile neutropaenia: A review of the literature
Austin J. Maddy  Nelson Sanchez  Bhavarth S. Shukla  Andrea D. Maderal
First published: 09 May 2019 https://doi.org/10.1111/myc.12928
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Abstract
Febrile neutropaenia (FNP) is a common cause of morbidity and mortality in immunocompromised patients. Although most infections are caused by bacterial pathogens, fungal infections are becoming increasingly more common. Due to its rarity, the diagnosis of fungal infections in febrile neutropenic patients is often delayed. To provide current clinical features, epidemiology, aetiology, diagnosis and treatment of cutaneous involvement of fungal infection in patients with FNP. A retrospective literature review of PubMed was performed, with no language or publishing data restrictions, yielding 116 results. We queried each case for cutaneous lesions associated with fungal pathogens in FNP. We found 54 publications with 215 reported cases of cutaneous manifestations of fungal injury in patients with FNP. This study is limited in that it is a literature review of a disease that is likely underreported. Cutaneous lesions caused by yeasts such as Candida and Trichosporon manifest as diffuse erythematous papules and usually do not develop central necrosis or eschar, while moulds will present as tender nodules that subsequently develop eschar and necrosis. Recognising the cutaneous manifestations of fungal disease can assist in the diagnosis and management of these infections.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com