Molecular Signatures for Microbe-Associated Colorectal Cancers.

Background: Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics. Methods: A Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused on Fusobacterium nucleatum ( Fn ), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice ( CPC-APC Min+/- ) and patients (FAP, Lynch Syndrome, PJS, and JPS). Results: The MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced upon Fn infection, but not in response to infection with other enteric bacteria or probiotics. MACS induction upon Fn infection was higher in CPC-APC Min+/- organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs. Conclusions: Computational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.

Predictive Models for Canadian Healthcare Workers Mental Health During COVID-19.

PURPOSE: COVID-19 impact on the population's mental health has been reported worldwide. Predicting healthcare workers' mental health and life stress is needed to proactively plan for future emergencies. DESIGN: Statistics Canada has surveyed Canadian healthcare workers and those working in healthcare settings to gauge their perceived mental health and perceived life stress. SETTING: A cross-sectional survey of healthcare workers in Canada. SUBJECTS: A sample of 18,139 healthcare workers respondents. ANALYSIS: Eight algorithms, including Logistic Regression, Random Forest (RF), Naive Bayes (NB), K Nearest Neighbours (KNN), Adaptive boost (AdaBoost), Multi-layer perceptron (MLP), XGBoost, and LightBoost. AUC scores, accuracy and precision were measured for all models. RESULTS: XGBoost provided the highest performing model AUC score (AUC = 82.07%) for predicting perceived mental health, and Random Forest performed the best for predicting perceived life stress (AUC = 77.74%). Perceived health, age group of participants, and perceived mental health compared to before the pandemic were found to be the most important 3 features to predict perceived mental health and perceived stress. Perceived mental health compared to before the pandemic was the most important predictor for perceived life stress. CONCLUSION: Our models are highly predictive of healthcare workers' perceived mental health and life stress. Implementing scalable, non-expensive virtual mental health solutions to address mental health challenges in the workplace could mitigate the impact of workplace conditions on healthcare workers' mental health.

Alanine aminotransferase elevation varies by ethnicity among Asian and Pacific Islander children with overweight or obesity.

BACKGROUND: Limited research on alanine aminotransferase (ALT) screening for metabolic dysfunction-associated steatotic liver disease (MASLD) among US Asian/Pacific Islander (PI) children necessitates investigation in this heterogeneous population. OBJECTIVE: Examine ALT elevation among Asian/PI children with overweight or obesity. METHODS: Elevated ALT prevalence (clinical threshold) and association with body mass index ≥85th percentile were compared among 18 402 Asian/PI and 25 376 non-Hispanic White (NHW) children aged 9-17 years using logistic regression. RESULTS: ALT elevation was more prevalent among Asian/PI (vs. NHW) males with overweight (4.0% vs. 2.7%), moderate (7.8% vs. 5.3%) and severe obesity (16.6% vs. 11.5%), and females with moderate (5.1% vs. 3.0%) and severe obesity (10.2% vs. 5.2%). Adjusted odds of elevated ALT were 1.6-fold and ~2-fold higher for Asian/PI (vs. NHW) males and females (with obesity), respectively. Filipino, Chinese and Southeast Asian males had 1.7-2.1-fold higher odds, but Native Hawaiian/PI (NHPI) and South Asian males did not significantly differ (vs. NHW). Filipina and Chinese females with obesity had >2-fold higher odds, Southeast and South Asian females did not differ and NHPI findings were mixed (vs. NHW). CONCLUSION: High elevated ALT prevalence among Asian/PI children with overweight and obesity emphasizes the need for MASLD risk assessment and examination of ethnic subgroups.

Technologies that empower women for better access to healthcare in India - A scoping review.

Women from low- and middle-income countries face challenges in accessing and utilising quality healthcare. Technologies can aid in overcoming these challenges and the present scoping review is aimed at summarising the range of technologies used by women and assessing their role in enabling Indian women to learn about and access healthcare services. We conducted a comprehensive search from the date of inception of database till 2022 in PubMed and Google Scholar. Data was extracted from 43 studies and were thematically analysed. The range of technologies used by Indian women included integrated voice response system, short message services, audio-visual aids, telephone calls and mobile applications operated by health workers. Majority of the studies were community-based (79.1%), from five states (60.5%), done in rural settings (58.1%) and with interventional design (48.8%). Maternal and child health has been the major focus of studies, with lesser representation in domains of non-communicable and communicable diseases. The review also summarised barriers related to using technology - from health system and participant perspective. Technology-based interventions are enabling women to improve awareness about and accessibility to healthcare in India. Imparting digital literacy and scaling up technology use are potential solutions to scale-up healthcare access among women in India.

Torsion of a Pedunculated Subserosal Leiomyoma: A Rare Cause of Acute Abdominal Pain.

Uterine leiomyomas are benign uterine tumors arising from the smooth muscle cells of the myometrium. Most of them are asymptomatic, and rarely do they present with symptoms like infertility, abdominal distension, and acute abdomen. According to experts, the most common cause of acute abdomen is torsion of a pedunculated subserosal leiomyoma, which is an extremely rare and life-threatening surgical emergency. Here, we discuss a case of torsion of a subserosal leiomyoma where the patient, a 40-year-old female with severe abdominal pain, was misdiagnosed with a twisted ovarian cyst. Ultrasonography and contrast-enhanced computed tomography (CECT) revealed a right-sided ovarian tumor and a twisted subserosal myoma, respectively. Thus, surgical intervention with myomectomy was done.

Planning for a Crisis: Predicting Anxiety in a Population During COVID-19 Using Machine Learning.

COVID-19 impact on population mental health has been reported around the world. Statistics Canada has conducted a survey among Canadian population to gauge mental health challenges they experienced, specifically in terms of anxiety. We create a machine learning model to predict anxiety symptoms as measured by the General Anxiety Scale among the sample of 45,989 respondents to the survey. Eight algorithms including Logistic Regression, Random Forest, Naive Bayes, K Nearest Neighbours, Adaptive boost, Multi linear perceptron, XGBoost and LightBoost. LightBoost provided the highest performing model AUC score (AUC=87.45%). In addition, the features "perception of mental health compared to before physical distancing", "perceived life stress", and "perceived mental health" were found to be the most important three features to predict anxiety. A limitation of this study is that the sample is not representative of the Canadian population. Preparing for virtual care interventions during a crisis need to take into considerations these factors.

A Comparative Study of the Effectiveness of Transdermal Nitroglycerine Patches and Oral Nifedipine in Prolongation of Pregnancy in Women With Preterm Labour.

Backgrounds A significant contributor to newborn morbidity and mortality is preterm birth. Several techniques have been employed to identify patients at risk of premature labour. However, these predictors are not always effective because of their multifactorial aetiology. Preterm labour can be suppressed largely through tocolysis. This study compared the effectiveness and safety of transdermal nitroglycerine and oral nifedipine in preventing premature labour. Methods This study was done at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra, from December 2020 to November 2022, on 130 women presenting with preterm labour pains between 28 and 37 weeks of gestational age. All the women selected were randomized into two equal groups by using the envelope method. Sixty-five women were given a nitroglycerine patch (Group A), and the rest (65 women) were given an oral nifedipine tablet (group B). The variables studied were mean days of prolongation of pregnancy, treatment outcome, steroid coverage, along with feto-maternal outcomes among both groups. Results The percentage of women whose pregnancy was prolonged for at least 48 hours in the nitroglycerine group was 75.3%, and in the nifedipine group it was 93.8%. Failure to achieve tocolysis, defined as delivery within 48 hours, was seen significantly more in the nitroglycerine group (24.6%) than in the nifedipine group (6.1%). The overall foetal outcomes were comparable in both groups. Conclusion Oral nifedipine was found to be superior to transdermal nifedipine patches in terms of efficacy and safety in the management of preterm labour, with a better side effect profile.

Qualitative and Quantitative Evaluation of Morpho-Metabolic Changes in Bone Cartilage Complex of Knee Joint in Osteoarthritis Using Simultaneous 18F-NaF PET/MRI-A Pilot Study.

Background Articular cartilage (AC) loss and deterioration, as well as bone remodeling, are all symptoms of osteoarthritis (OA). As a result, an ideal imaging technique for researching OA is required, which must be sensitive to both soft tissue and bone health. Objective The aim of this study was to assess the potential of simultaneous 18F sodium fluoride (18F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI) to identify as well as classify osseous metabolic abnormalities in knee OA and to see if degenerative changes in the cartilage and bone on MRI might be correlated with subchondral 18F-NaF uptake on PET. Methods Sixteen (32 knees) volunteers with no past history of knee injury, with or without pain, were enrolled for the research from January to July 2021. The images of both knees were taken utilizing an molecular magnetic resonance (mMR) body matrix coil on a simultaneous PET/MRI biograph mMR. The acquisition was conducted after 45 minutes of intravenous infusion of 18F-NaF 185-370 MBq (5-10 mCi) over one PET bed for 40 minutes, while MRI sequences were performed simultaneously. Results All pathologies showed significantly higher maximum standardized uptake value (SUV max ) than the background. Thirty-four subchondral magic spots were identified on 18F-NaF PET without any structural alteration on MRI. Bone marrow lesions (BMLs) and osteophytes with higher MRI osteoarthritis knee score (MOAKS) score showed higher 18F-NaF uptake (grade1˂grade2˂grade3). BMLs had corresponding AC degeneration. There was discordance between grade 1 osteophytes (86.6%), sclerosis (53.7%) and grade 1 BML in cruciate ligament insertion site (91.66%); they did not have high uptake of 18F-NaF. In case of cartilage, there was significant difference between AC grades and average subchondral SUV max and T2* relaxometry (grade0˂grade1˂grade2˂grade3˂grade4). BMLs are much more metabolically active than other pathologies, while sclerosis is the least. We also found that the subchondral uptake was statistically increased in the areas of pathology: Conclusion 18F-NaF PET/MRI was able to detect knee abnormalities unseen on MRI alone and simultaneously assessed metabolic and structural markers of knee OA across multiple tissues in the joint. Thus, it is a promising tool for detection of early metabolic changes in OA.

Serum LDH Levels in Normotensive and Preeclamptic-Eclamptic Pregnant Women and Its Correlation With Fetomaternal Outcome.

Background One of the most prevalent medical issues observed during pregnancy is hypertension. Hypertensive disorders of pregnancy (HDP) and their consequences affect around 5-10% of all pregnancies globally. Preeclampsia is caused by endothelial dysfunction, which causes widespread endothelial leakage and contributes to potentially fatal consequences, such as eclampsia, placental abruption, disseminated intravascular coagulation (DIC), severe renal failure, pulmonary edema, and hepatocellular necrosis. As a result, looking for predictive markers for at-risk pregnancies that can suggest poor maternal or fetal outcomes is critical. Elevated levels of lactate dehydrogenase (LDH), as a sign of cellular damage and dysfunction, can be utilized as a biochemical marker in pregnancy-induced hypertension (PIH) as it represents the severity of the disease, and the occurrence of problems, and has also been demonstrated to co-relate with fetomaternal outcomes. Methodology A total of 230 singleton pregnant women of 28-40 weeks of gestational age were enrolled in this study. All women were divided into two groups - normotensive and preeclamptic-eclamptic groups; the second group was further divided into mild preeclampsia, severe preeclampsia, and eclampsia, based on blood pressure and the presence of proteinuria. Serum lactate dehydrogenase levels were measured in both groups and correlated with their fetomaternal outcome. Results Mean serum lactate dehydrogenase (LDH) level in eclamptic women was 1515.86 ± 754, in severely preeclamptic women was 932.2 ± 448, mild preeclamptic women were 580.5±213, while in normotensive women mean LDH level was 378.6 ± 124. The difference between normotensive and preeclamptic-eclamptic women was statistically significant (p < 0.001). The complications in the preeclamptic-eclamptic group were increased significantly in women with LDH > 800 IU/L, 600-800 IU/L compared to those who had < 600 IU/L LDH levels. Conclusions Serum LDH levels were significantly higher in women of preeclamptic-eclamptic group compared to the normotensive pregnant women. Higher LDH levels were positively correlated with disease severity and maternal complications like placental abruption, hemolysis elevated liver enzymes low platelet count (HELLP), disseminated intravascular coagulation (DIC), acute renal failure, intracranial hemorrhage, pulmonary edema, and maternal death and for fetal complications like preterm, intrauterine growth restriction (IUGR), APGAR at 1 minute < 7, APGAR at 5 minutes < 7, low birth weight (LBW), neonatal intensive care unit (NICU) admission and intrauterine fetal death (IUFD).

An Open Label, Randomized, Multicenter Study of Elafibranor in Children With Nonalcoholic Steatohepatitis.

OBJECTIVES: Nonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for nonalcoholic steatohepatitis (NASH). The aims were to (1) describe pharmacokinetics (PK), safety, and tolerability of oral elafibranor at 2 doses (80 and 120 mg) in children 8-17 years and (2) assess changes in aminotransferases. METHODS: Children with NASH were randomized to open-label elafibranor 80 mg or 120 mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least 1 dose. Standard descriptive statistics and PK analyses were performed. RESULTS: Ten males [mean 15.1 years, standard deviation (SD) 2.2] with NASH were randomized to 80 mg (n = 5) or 120 mg (n = 5). Baseline mean alanine aminotransferase (ALT) was 82 U/L (SD 13) and 87 U/L (SD 20) for 80 mg and 120 mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80 mg and 120 mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC 0-24 , respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120 mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks. CONCLUSIONS: Once daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120 mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH.

Prevalence of Elevated ALT in Adolescents in the US 2011-2018.

OBJECTIVE: The objective of this study is to characterize suspected nonalcoholic fatty liver disease (NAFLD) using elevated alanine aminotransferase (ALT) in a diverse and nationally representative cohort of adolescents and to characterize higher ALT elevation in adolescents with obesity. METHODS: Data from the National Health and Nutrition Examination Survey 2011-2018 were analyzed for adolescents 12-19 years. Participants with causes for elevated ALT other than NAFLD were excluded. Race and ethnicity, sex, body mass index (BMI), and ALT were examined. Elevated ALT was defined as >22 U/L (females) and >26 U/L (males) using the biologic upper normal limit (ULN). Elevated ALT thresholds up to 2X-ULN were examined among adolescents with obesity. Multivariable logistic regression was used to determine the association of race/ethnicity and elevated ALT, adjusting for age, sex, and BMI. RESULTS: Prevalence of elevated ALT in adolescents was 16.5% overall and 39.5% among those with obesity. For White, Hispanic, and Asian adolescents, prevalence was 15.8%, 21.8%, and 16.5% overall, 12.8%, 17.7%, and 27.0% in those with overweight, and 43.0%, 43.5%, and 43.1% in those with obesity, respectively. Prevalence was much lower in Black adolescents (10.7% overall, 8.4% for overweight, 20.7% for obesity). Prevalence of ALT at 2X-ULN was 6.6% in adolescents with obesity. Hispanic ethnicity, age, male sex, and higher BMI were independent predictors of elevated ALT. CONCLUSIONS: Prevalence of elevated ALT in U.S. adolescents is high, affecting 1 in 6 adolescents during 2011-2018. The risk is highest in Hispanic adolescents. Asian adolescents with elevated BMI may comprise an emerging risk group for elevated ALT.

Association of Hepatic Steatosis with Adipose and Muscle Mass and Distribution in Children.

Background: Pediatric studies have shown associations between hepatic steatosis and total body fat, visceral fat, and lean mass. However, these associations have not been assessed simultaneously, leaving their relative importance unknown. Objective: To evaluate associations between hepatic steatosis and total-body adiposity, visceral adiposity, and lean mass in children. Method: In children at risk for fatty liver, hepatic steatosis, adipose, and lean mass were estimated with magnetic resonance imaging and dual-energy X-ray absorptiometry. Results: Two hundred twenty-seven children with mean age 12.1 years had mean percent body fat of 38.9% and mean liver fat of 8.4%. Liver fat was positively associated with total-body adiposity, visceral adiposity, and lean mass (P < 0.001), and negatively associated with lean mass percentage (P < 0.001). After weight adjustment, liver fat was only positively associated with measures of central adiposity (P < 0.001). Visceral adiposity also had the strongest association with liver fat (P < 0.001). Conclusions: In children, hepatic steatosis is more strongly associated with visceral adiposity than total adiposity, and the association of lean mass is not independent of weight or fat mass. These relationships may help guide the choice of future interventions to target hepatic steatosis.

Nonalcoholic fatty liver disease risk and histologic severity are associated with genetic polymorphisms in children.

BACKGROUND AND AIMS: NAFLD is the most common chronic liver disease in children. Large pediatric studies identifying single nucleotide polymorphisms (SNPs) associated with risk and histologic severity of NAFLD are limited. Study aims included investigating SNPs associated with risk for NAFLD using family trios and association of candidate alleles with histologic severity. APPROACH AND RESULTS: Children with biopsy-confirmed NAFLD were enrolled from the NASH Clinical Research Network. The Expert Pathology Committee reviewed liver histology. Genotyping was conducted with allele-specific primers for 60 candidate SNPs. Parents were enrolled for trio analysis. To assess risk for NAFLD, the transmission disequilibrium test was conducted in trios. Among cases, regression analysis assessed associations with histologic severity. A total of 822 children with NAFLD had mean age 13.2 years (SD 2.7) and mean ALT 101 U/L (SD 90). PNPLA3 (rs738409) demonstrated the strongest risk ( p = 2.24 × 10 -14 ) for NAFLD. Among children with NAFLD, stratifying by PNPLA3 s738409 genotype, the variant genotype associated with steatosis ( p = 0.005), lobular ( p = 0.03) and portal inflammation ( p = 0.002). Steatosis grade associated with TM6SF2 ( p = 0.0009), GCKR ( p = 0.0032), PNPLA3 rs738409 ( p = 0.0053), and MTTP ( p = 0.0051). Fibrosis stage associated with PARVB rs6006473 ( p = 0.0001), NR1I2 ( p = 0.0021), ADIPOR2 ( p = 0.0038), and OXTR ( p = 0.0065). PNPLA3 rs738409 ( p = 0.0002) associated with borderline zone 1 NASH. CONCLUSIONS: This study demonstrated disease-associated SNPs in children with NAFLD. In particular, rs6006473 was highly associated with severity of fibrosis. These hypothesis-generating results support future mechanistic studies of development of adverse outcomes such as fibrosis and generation of therapeutic targets for NAFLD in children.

Expulsion of Infarcted Myoma Following Ultrasound-Guided Uterine Artery Embolization: A Fertility-Preserving Approach.

The most frequent benign tumor of the female pelvis, uterine fibroids (leiomyomas), have a lifetime frequency of about 70% among Caucasian women. The most preferred treatment for fibroids is still hysterectomy, albeit there are issues with its misuse. Today, uterine artery embolization (UAE) is a well-recognized minimally invasive treatment for symptomatic fibroids. A 29-year-old female came with heavy menstrual bleeding for two months. Ultrasonography revealed a large fibroid of 8cm x 7cm in the posterior wall of the myometrium. She underwent uterine artery embolization for the same. The fibroid was expelled through the vagina in small portions over one month following the intervention. There was a significant reduction in the fibroid size with a considerable amount of symptomatic relief to the patient within a month. The most prevalent benign pelvic tumor, uterine fibroids, affects over 40% of women of reproductive age. Uterine artery embolization is a safe and successful alternative to surgery for treating symptomatic fibroids, with significantly lower morbidity and mortality. It also preserves fertility, giving the patient hope for a future pregnancy.

Association of water, sanitation, hygiene and food practices with enteric fever in a paediatric cohort in North India.

BACKGROUND: Our aim was to assess the association of water, sanitation and hygiene (WASH) and food practices with culture-confirmed enteric fever in children <15 years of age. METHODS: We followed a cohort of 6000 children from an urban low socioeconomic neighbourhood in South Delhi for 2 years to estimate burden of culture-confirmed enteric fever. Risk ratios (RRs) were estimated to study the association between WASH practices and enteric fever. We assessed the microbiological quality of drinking water and conducted geospatial analysis to evaluate the distribution of enteric fever cases around households with contaminated drinking water. RESULTS: A total of 5916 children in 3123 households completed survey. Piped water (82%) was the major source of household drinking water. One-third (32%) of the households treated water before consumption. Almost all households had sanitary toilets (99.9%) and 16% used shared toilets. Consumption of food from street vendors and unnamed ice creams more than once a week was observed in children from 12.7% and 38.4% households, respectively. Eighty culture-confirmed enteric fever cases were reported. The risk of enteric fever was 71% higher in children belonging to households having food from outside once a week or more (RR 1.71, 95% CI 1.00 to 2.94). The RR for enteric fever in children living in households with availability of safe drinking water was 0.75 (95% CI 0.45 to 1.26). We found that 14.8% of the households had presence of coliforms or Escherichia coli in their household drinking water. The odds of having a case of enteric fever within a 5 and 25 m buffer zone around households with contaminated drinking water were 4.07 (95% CI 0.81 to 20.5) and 1.44 (95% CI 0.69 to 3.00), respectively. CONCLUSION: In addition to WASH practices, optimal food hygiene may have a role in urban low socioeconomic population to control enteric fever. TRIAL REGISTRATION NUMBER: CTRI/2017/09/009719.

Antenatal Ultrasonographic Diagnosis of a Constellation of Alobar Holoprosencephaly, Ethmocephaly, and Hydronephrosis in a Case of Early-Onset Intrauterine Growth Retardation: A Case Report.

Alobar holoprosencephaly is a congenital malformation that results from failure of the forebrain/prosencephalon to divide into right and left halves. Despite the literature on the genetic and chromosomal abnormalities associated with this condition, information on additional causes and explanations for variability in phenotypic expressivity are lacking. We report a case of early-onset intrauterine growth retardation with alobar holoprosencephaly, ethmocephaly, and hydronephrosis diagnosed on antenatal ultrasonography in a 27-year-old primigravida with no known risk factors or family history. The combination of holoprosencephaly with associated midline facial anomalies and the genitourinary abnormality, in this case, constitutes a rare phenotypic presentation. This case emphasizes the importance of antenatal ultrasonography in the early detection of lethal anomalies like alobar holoprosencephaly. The pregnancy was safely terminated in accordance with the mother's decision.

Incidence of lab-confirmed dengue fever in a pediatric cohort in Delhi, India.

BACKGROUND: Our aim was to estimate the overall and age-specific incidence of lab-confirmed dengue fever using ELISA based assays among children 6 months to 15 years in Delhi. METHODS: We enrolled a cohort of 984 children aged 6 months to <14 years in South Delhi and followed-up weekly for fever for 24 months or till 15 completed years of child-age. Households of the enrolled children were geo-tagged. NS1, IgM and IgG assays were conducted using ELISA method to confirm dengue fever in children with ≥3 consecutive days of fever. Molecular typing was done in a subset of NS1 positive cases to identify the circulating serotypes. PRINCIPAL FINDINGS: We had a total of 1953 person-years (PY) of follow up. Overall, there were 4208 episodes of fever with peaks during June to November. The overall incidence (95%CI) of fever was 215/100 PY (209 to 222). A total of 74/1250 3-day fever episodes were positive for acute dengue fever (NS1 and/or IgM positive). The overall incidence (95%CI) of acute dengue fever was 37.9 (29.8 to 47.6) per 1000 PY; highest among children aged 5 to 10 years (50.4 per 1000 PY, 95% CI 36.5 to 67.8). Spatial autocorrelation analysis suggested a clustering pattern for the dengue fever cases (Moran's Index 0.35, z-score 1.8, p = 0.06). Dengue PCR was positive in 16 of the 24 specimens tested; DEN 3 was the predominant serotype identified in 15/24 specimens. CONCLUSIONS: We found a high incidence of dengue fever among under 15-year children with clustering of cases in the community. DEN 3 was the most commonly circulating strain encountered. The findings underscore the need for development of affordable pre-vaccination screening strategy as well as newer dengue vaccines for young children while continuing efforts in vector control.

Metronidazole-Induced Encephalopathy (MIE).

Metronidazole is an antibiotic often used to treat bacterial infections in the vagina, skin, liver, stomach, joints, brain and spinal cord, heart, lungs, or bloodstream. It is an essential drug for treating anaerobic bacterial infections, microaerophilic bacterial infections, and protozoal infections. It is cytotoxic to many facultative anaerobic microorganisms. Metronidazole can be taken by most children and adults but might not be suitable for some people. It may produce different neurologic side effects like cerebellar dysfunction, peripheral neuropathy, vestibulotoxicity, visual impairment, encephalopathy, ataxic gait, seizures, dysarthria, and cochleotoxicity. We report a case of a gentleman in his early 60s with a liver abscess and a history of three weeks of use of metronidazole therapy presenting with altered sensorium, abnormal gait, and slurring of speech. MRI brain showed bilateral symmetrical hyperintensities involving the dentate nuclei of the cerebellum and dorsal brain stem without evidence of any diffusion restriction suggestive of metronidazole-induced encephalopathy (MIE).

Cladophialophora bantiana brain abscess with lymphadenitis.

Cerebral phaeohyphomycosis refers to central nervous system infection by dematiaceous mould or by dark walled fungi which contain the dark pigment melanin in their cell wall which adds to the virulence of fungus. These dematiaceous fungi can cause a variety of central nervous infections including invasive sinusitis, brain abscess, meningitis, myelitis and arachnoiditis. Cladophialophora bantiana among these dematiaceous fungi is the most common cause of brain abscess in immunocompetent and immunocompromised individuals and is known to occur worldwide though is predominantly reported from subtropical regions especially the Asian subcontinent. It is difficult to differentiate these abscesses radiologically from high-grade gliomas, primary central nervous system lymphoma or other infections including toxoplasmosis, nocardiosis, tuberculosis and listeriosis. We describe a 19-year-old male patient with a cerebral abscess caused by C. bantiana where the diagnosis could be suspected by typical MR spectroscopic findings and by identifying the fungus from a lymph node biopsy.