Outbreak of waterborne acute diarrheal disease in a South District village of Tripura: A public health emergency in the Northeast region of India.

Food and waterborne outbreaks are a neglected public health problem in India. However, it is important to identify the source of infection and the causative pathogen to curb the outbreak quickly and minimize mortality and morbidity. A retrospective descriptive study was conducted with a line list of 130 diarrheal cases. Epidemiological investigation and laboratory investigation were done. Data were collected from hospital case report forms as well as interviewed affected cases. A case of acute diarrheal disease was reported among the people in the village with abdominal pain, vomiting, and diarrhea from December 31, 2022 to January 3, 2023. Out of a total of 130 recorded cases, 33 stool samples were collected and were positive for Enteroaggregative Escherichia coli, Shigella flexneri 3a, and Shigella sonnei by cultural and molecular tests. The presumptive fecal pollution indicator assay indicated high coliform counts in the water samples (most probable number [MPN]-05) and the presence of Escherichia coli. The identified pathogens showed susceptibility to gentamicin and meropenem. People who used public drinking water were found to be infected with acute diarrheal disease (ADD). Quick identification of the causative pathogens and their antimicrobial resistance pattern helped correct antibiotic prescriptions and quick recovery of the patients without any deaths. Thus, a timely implementation of food and waterborne outbreak investigation is crucial to saving lives and preventing the spread of infection.

Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study.

BACKGROUND: Fungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. OBJECTIVE: The primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. METHODS: This multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. RESULTS: These Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. CONCLUSIONS: Fungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54672.

An integrated FoodNet in North East India: fostering one health approach to fortify public health.

BACKGROUND: Food safety is a critical factor in promoting public health and nutrition, especially in developing countries like India, which experience several foodborne disease outbreaks, often with multidrug-resistant pathogens. Therefore, implementing regular surveillance of enteric pathogens in the human-animal-environment interface is necessary to reduce the disease burden in the country. OBJECTIVE: To establish a network of laboratories for the identification of major food and waterborne pathogens prevailing in the northeast region of India through integrated surveillance of animal, food, human, and environment and investigate the antimicrobial susceptibility pattern of the pathogens of public health significance. METHODS: The Indian Council of Medical Research (ICMR) has identified FoodNet laboratories; based on their geographical location, inclination to undertake the study, preparedness, proficiency, and adherence to quality assurance procedures, through an 8-step process to systematically expand to cover the Northeastern Region (NER) with comprehensive diagnostic capacities for foodborne pathogens and diarrhea outbreak investigations. Network initiated in the NER given the unique food habits of the ethnic population. FINDINGS: This surveillance network for foodborne enteric pathogens was established in Assam, Arunachal Pradesh, Tripura, and Sikkim, and expanded to other four states, i.e., Manipur, Mizoram, Meghalaya, and Nagaland, thereby covering the entire NER by including nine medical and three veterinary centers. All these centers are strengthened with periodic training, technical support, funding, capacity building, quality assurance, monitoring, centralized digital data management, and website development. RESULTS: The ICMR-FoodNet will generate NER-specific data with close to real-time reporting of foodborne disease and outbreaks, and facilitate the updating of food safety management protocols, policy reforms, and public health outbreak response. During 2020-2023, 13,981 food samples were tested and the detection of enteric pathogens ranged from 3 to 4%. In clinical samples, the detection rate of the pathogens was high in the diarrheal stools (8.9%) when 3,107 samples were tested. Thirteen outbreaks were investigated during the study period. CONCLUSION: Foodborne diseases and outbreaks are a neglected subject. Given the frequent outbreaks leading to the deaths of children, it is crucial to generate robust data through well-established surveillance networks so that a strong food safety policy can be developed for better public health.

The Development of a Clinical Registry Digital Database on Invasive Fungal Infections in India: Advancing Epidemiological Understanding and Patient Care.

A well-structured digital database is essential for any national priority project as it can provide real-time data analysis and facilitate quick decision making. In recent times, particularly after the COVID-19 pandemic, invasive fungal infections (IFIs) have emerged as a significant public health challenge in India, affecting vulnerable population, including immunocompromised individuals. The lack of comprehensive and well-structured data on IFIs has hindered efforts to understand their true burden and optimize patient care. To address this critical knowledge gap, the ICMR has undertaken a Pan-India pioneer initiative to develop a network of Advanced Mycology Diagnostic research centres in different geographical zones of the country (ICMR-MycoNet). Under the aegis of this project, a clinical registry on IFIs in the ICUs is initiated. This process paper presents a detailed account of the steps involved in the establishment of a web-based data entering and monitoring platform to capture data electronically, ensuring robust and secure data collection and management. This system not only allows participating ICMR-MycoNet centres to enter patient information directly into the database using standardized Case Report Form (CRF) but also includes data validation checks to ensure the accuracy and completeness of entered data. It is complemented by a real-time, web-based, and adaptable data visualization platform. This registry aims to provide crucial epidemiological insights, promote evidence-based hospital infection control programs, and ultimately improve patient outcomes in the face of this formidable healthcare challenge.

A Novel Report of mycetoma with Spinal Spread due to Madurella fahalli from India.

Eumycetoma caused by Madurella fahalii, a drug-resistant fungus, has never been reported in India. Here, we describe a fatal case of eumycetoma with spinal involvement due to M. fahalii for the first time in India.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

INTRODUCTION: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM. METHODOLOGY: Cytokine levels in serum samples of CAM cases (n = 29) and COVID-19 patients without CAM (n = 20) were determined using luminex assay. Flow cytometric assays were carried out in 20 CAM cases and 10 controls for determination of frequency of NK cells, DCs, phagocytes, T cells and their functionalities. The cytokine levels were analyzed for their association with each other as well as with T cell functionality. The immune parameters were also analyzed with respect to the known risk factors such as diabetes mellitus and steroid treatment. RESULTS: Significant reduction in frequencies of total and CD56 + CD16 + NK cells (cytotoxic subset) was noted in CAM cases. Degranulation responses indicative of cytotoxicity of T cell were significantly hampered in CAM cases as compared to the controls. Conversely, phagocytic functions showed no difference in CAM cases versus their controls except for migratory potential which was found to be enhanced in CAM cases. Levels of proinflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-17, IL-1ß, IL-18 and MCP-1 were significantly elevated in cases as compared to the control with IFN-γ and IL-18 levels correlating negatively with CD4 T cell cytotoxicity. Steroid administration was associated with higher frequency of CD56 + CD16- NK cells (cytokine producing subset) and higher MCP-1 levels. Whereas diabetic participants had higher phagocytic and chemotactic potential and had higher levels of IL-6, IL-17 and MCP-1. CONCLUSION: CAM cases differed from the controls in terms of higher titers of proinflammatory cytokines, reduced frequency of total and cytotoxic CD56 + CD16 + NK cell. They also had reduced T cell cytotoxicity correlating inversely with IFN-γ and IL-18 levels, possibly indicating induction of negative feedback mechanisms while diabetes mellitus or steroid administration did not affect the responses negatively.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Mycobacterium tuberculosis strain lineage in mixed tribal population across India and Andaman Nicobar Island.

In India, the tribal population constitutes almost 8.6% of the nation's total population. Despite their large presence, there are only a few reports available on Mycobacterium tuberculosis (M. tb) strain prevalence in Indian tribal communities considering the mobile nature of this population and also the influence of the mainstream populations they coexist within many areas for their livelihood. This study attempts to provide critical information pertaining to the TB strain diversity, its public health implications, and distribution among the tribal population in eleven Indian states and Andaman & Nicobar (A&N) Island. The study employed a population-based molecular approach. Clinical isolates were received from 66 villages (10 states and Island) and these villages were selected by implying situation analysis. A total of 78 M. tb clinical isolates were received from 10 different states and A&N Island. Among these, 16 different strains were observed by spoligotyping technique. The major M. tb strains spoligotype belong to the Beijing, CAS1_DELHI, and EAI5 family of M. tb strains followed by EAI1_SOM, EAI6_BGD1, LAM3, LAM6, LAM9, T1, T2, U strains. Drug-susceptibility testing (DST) results showed almost 15.4% of clinical isolates found to be resistant to isoniazid (INH) or rifampicin (RMP) + INH. Predominant multidrug-resistant (MDR-TB) isolates seem to be Beijing strain. Beijing, CAS1_DELHI, EAI3_IND, and EAI5 were the principal strains infecting mixed tribal populations across India. Despite the small sample size, this study has demonstrated higher diversity among the TB strains with significant MDR-TB findings. Prevalence of Beijing MDR-TB strains in Central, Southern, Eastern India and A&N Island indicates the transmission of the TB strains.

Prevalence of pulmonary tuberculosis among the tribal populations in India.

IMPORTANCE: There is no concrete evidence on the burden of TB among the tribal populations across India except for few studies mainly conducted in Central India with a pooled estimation of 703/100,000 with a high degree of heterogeneity. OBJECTIVE: To estimate the prevalence of TB among the tribal populations in India. DESIGN, PARTICIPANTS, SETTING: A survey using a multistage cluster sampling design was conducted between April 2015 and March 2020 covering 88 villages (clusters) from districts with over 70% tribal majority populations in 17 States across 6 zones of India. The sample populations included individuals ≥15 years old. MAIN OUTCOME AND MEASURES: Eligible participants who were screened through an interview for symptoms suggestive of pulmonary TB (PTB); Two sputum specimens were examined by smear and culture. Prevalence was estimated after multiple imputations for non-coverage and a correction factor of 1.31 was then applied to account for non-inclusion of X-ray screening. RESULTS: A total of 74532 (81.0%) of the 92038 eligible individuals were screened; 2675 (3.6%) were found to have TB symptoms or h/o ATT. The overall prevalence of PTB was 432 per 100,000 populations. The PTB prevalence per 100,000 populations was highest 625 [95% CI: 496-754] in the central zone and least 153 [95% CI: 24-281] in the west zone. Among the 17 states that were covered in this study, Odisha recorded the highest prevalence of 803 [95% CI: 504-1101] and Jammu and Kashmir the lowest 127 [95% CI: 0-310] per 100,000 populations. Findings from multiple logistic regression analysis reflected that those aged 35 years and above, with BMI <18.5 Kgs /m2, h/o ATT, smoking, and/or consuming alcohol had a higher risk of bacteriologically positive PTB. Weight loss was relatively more important symptom associated with tuberculosis among this tribal populations followed by night sweats, blood in sputum, and fever. CONCLUSION AND RELEVANCE: The overall prevalence of PTB among tribal groups is higher than the general populations with a wide variation of prevalence of PTB among the tribal groups at zone and state levels. These findings call for strengthening of the TB control efforts in tribal areas to reduce TB prevalence through tribal community/site-specific intervention programs.

Understanding health care-seeking behaviour of the tribal population in India among those with presumptive TB symptoms.

BACKGROUND AND OBJECTIVES: Understanding the drivers for care-seeking among those who present with symptoms of TB is crucial for early diagnosis of TB and prompt treatment, which will in turn halt further TB transmission. While TB is a challenge among the tribal population, little is known about the care-seeking behaviour and the factors influencing care-seeking behaviour among the tribal population across India. METHODOLOGY: This community-based descriptive study was carried out in 17 states of India across 6 zones, covering 88 villages from tribal districts with over 70% tribal population. The sample population included individuals ≥15 years old who were screened through an interview for symptoms suggestive of pulmonary TB (PTB), currently and/or previously on anti-TB treatment. Those with symptoms were then assessed on their health-seeking behavior using a semi-structured interview schedule. RESULTS: Among 74532 eligible participants screened for symptoms suggestive of TB, 2675 (3.6%) were found to be presumptive TB cases. Of them, 659 (24.6%) sought care for their symptoms. While 48.2% sought care after a week, 19.3% sought care after one month or more, with no significant difference in the first point of care; 46.9% approaching a private and 46.7% a public facility. The significant factors influencing care-seeking behaviour were knowledge on TB (OR: 4.64 (3.70-5.83), p < 0.001), age<35 years (OR: 1.60 (1.28-2.00), p < 0.001), co-morbidities like asthma (OR: 1.80 (1.38-2.35), p < 0.001) and blood pressure (OR: 2.59 (1.75-3.85), p < 0.001), symptoms such as blood in sputum (OR: 1.69 (1.32-2.16), p < 0.001), shortness of breath (OR: 1.43 (1.19-1.72), p < 0.001) and weight loss (OR: 1.59 (1.33-1.89), p < 0.001). The cough was the most often reported symptom overall. There were gender differences in symptoms that prompted care-seeking: Males were more likely to seek care for weight loss (OR: 1.78 (1.42-2.23), p<0.001), blood in the sputum (OR: 1.69 (1.25-2.28), p<0.001), shortness of breath (OR: 1.49 (1.18-1.88), p<0.001) and fever (OR: 1.32 (1.05-1.65), p = 0.018). Females were more likely to seek care for blood in sputum (OR: 1.68 (1.10-2.58), p = 0.018) and shortness of breath (OR = 1.35, (1.01-1.82), p = 0.048). The cough did not feature as a significant symptom that prompted care-seeking. CONCLUSION: Delayed healthcare-seeking behaviour among those with symptoms presumptive of TB in the tribal population is a major concern. Findings point to differences across gender about symptoms that prompt care-seeking in this population. Gender-sensitive interventions with health system strengthening are urgently needed to facilitate early diagnosis and treatment among this population.

Antibacterial metabolites from Bipolaris specifera, an endophytic fungus from the endemic medicinal plant, Zingiber nimmonii (J. Graham) Dalzell.

Eleven fungal endophytes were isolated from the plant parts of Z. nimmonii (J. Graham) Dalzell, an endemic species of the Western Ghats, India, a biodiversity hotspot area. The endophytic isolates were characterized by the sequencing of the Internal Transcribed Spacer (ITS) regions and designated as strains by depositing ITS sequences in the Gen Bank sequence database. All the strains were cultured in Potato Dextrose broth (PDB, 500 mL) contained in Erlenmeyer flasks to obtain the secondary metabolites. The culture filtrate was extracted with ethyl-acetate (EA) three times and concentrated by flash evaporation to obtain EA crude dry extract. The strains were evaluated for the antibacterial potentials against six pathogenic bacterial strains viz., Bacillus subtilis (MTCC 121), Staphylococcus aureus (MTCC 7443) Pseudomonas aeruginosa (MTCC 7093), Escherichia coli (MTCC 729), Enterobacter aerogenes (MTCC 111) and Klebsiella pneumoniae (MTCC 661). Nine endophytic fungal extracts except Alternaria consortiale and Hypocrea lixi showed inhibitory activities against at least two of the six test bacterial strains. Bipolaris specifera (KM114290) exhibited the highest inhibition zones ranging from 15.1 ± 0.3 to 26.7 ± 1.1 mm (diameter), against all six test bacteria in the agar disk diffusion assay, and with Minimum Inhibitory Concentrations (MIC's) of 0.04-0.14 mg/mL, followed by Aspergillus terreus. B. specifera extract was therefore selected and characterized for the identification of antibacterial compounds by chromatographic techniques. Seven antibacterial compounds viz., (1) Bicyclo[3.2.0]heptan-2-one, 6-hydroxy-5-methyl-6-vinyl; (2) Adipic acid divinyl ester; (3) 1,4-Naphthoquinone, 6-acetyl-2,5-dihydroxy; (4) Decanedioic acid, 3,7-dimethyl ester; (5) (Z)-4-Hexenoic acid 2-acetyl-2-methyl-ethyl ester and (6) Butanoic acid 2-acetyl-3-methyl-methyl ester and (7) Caffeic acid, were identified through liquid and gas chromatography. These compounds are mainly volatile esters of fatty acids, phenolics and adipic acid found rare in nature. This study envisages the possible drug discovery using endophytes from traditional and endemic medicinal species.

Non-vaccine strategies for cholera prevention and control: India's preparedness for the global roadmap.

BACKGROUND: Recently World Health Organization's Global Task Force on Cholera Control (GTFCC) has published a global roadmap for prevention and control of cholera. We review preparedness of existing governmental non-vaccine programs and strategies for cholera prevention and control in India. We also describe strengths and gaps in the context of implementation of the global roadmap. METHODS: We reviewed published literature on non-vaccine based strategies for prevention and control of cholera in India and analyzed strengths and weaknesses of Government of India's major anti-cholera and ante-diarrhea initiatives under Integrated Disease Surveillance Program (IDSP), National Rural Health Mission (NRHM), and other disease surveillance platforms. RESULTS: The first strategy of the WHO global roadmap, namely, preparedness for early detection and outbreak containment, has been addressed by the IDSP. NRHM complements IDSP activities by focusing on sanitation, hygiene, nutrition, and safe drinking water. We identified the need to adopt stricter case definitions and data validation protocols. Multi-sectoral approach to prevent cholera occurrences and re-occurrences [the second suggested strategy in the global roadmap], highlights identification of hotspots and implementing strategies based on transmission dynamics. We recommend development of comprehensive models by integrating data sources beyond the national programs to eliminate cholera hotspots in India. Implementing the third proposed strategy in the global roadmap, coordinated technical support, resource mobilization, and partnerships at local and global levels, has major challenges in India due to structural issues related to health systems and health programs. CONCLUSION: Even with a robust public health infrastructure, absence of a national cholera program might have resulted in lack of specific focus and concerted efforts for cholera prevention and control in India. A National Taskforce for Cholera Control must develop India-specific 'National Cholera Prevention and Response Road Map' with an appropriate administrative and financially viable framework for its implementation.

Procalcitonin as a prognostic marker for sepsis: a prospective observational study.

BACKGROUND: Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up. RESULTS: Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels <7 ng/ml showed higher cumulative survival than those with level [greater than or equal to]7 ng/ml (69.1% vs. 39.5%, p = 0.02). No such effect was observed in relation to C-reactive protein. Procalcitonin levels [greater than or equal to]7 ng/ml predicted mortality with a hazard ratio of 2.6(1.1-6.3). CONCLUSIONS: A Procalcitonin value [greater than or equal to]7 ng/ml obtained at the time of admission to the ICU is a predictor of short-term mortality and thus may allow the identification of those septic patients at increased mortality risk, and help improve their treatment.

Expression of osteogenic molecules in the caudate nucleus and gray matter and their potential relevance for Basal Ganglia calcification in hypoparathyroidism.

BACKGROUND: Basal ganglia calcification (BGC) is an interesting example of ectopic calcification in patients with hypoparathyroidism. Its pathogenesis and reasons for predilection of calcification at basal ganglia are not clear. OBJECTIVE: To assess the expression of osteogenesis-related molecules in the caudate nucleus and surface gray matter (an area spared from calcification) and discuss potential relevance of the results in context of BGC in idiopathic hypoparathyroidism. METHODS: Caudate nucleus and gray matter were obtained from 14 autopsies performed in accidental deaths. The mRNA expression of bone transcription factors (RUNX2/osterix), bone morphogenetic proteins (BMPs) 2 and 4, osteonectin, osteopontin, osteocalcin, vitamin D receptor, calcium sensing-receptor, Na phosphate transporters (PiTs) 1 and 2, N-methyl-D-aspartate receptor 2B (NMDAR2B), carbonic anhydrase II (CA-II), PTH1 receptor (PTH1R), PTH2R, and PTHrP were assessed by RT-PCR. Western blot, spot densitometry, and immunohistochemistry were performed to assess protein expression of molecules showing differences in mRNA expression between caudate and gray tissues. RESULTS: The mean mRNA expression of PiT1 (11.0 ± 10.39 vs 32.9 ± 20.98, P = .003) and PTH2R (1.6 ± 1.47 vs 13.7 ± 6.11, P = .001) were significantly lower in the caudate nucleus than the gray matter. The expression of osteonectin, osteopontin, and CA-II were significantly higher in the caudate nucleus than the gray matter (P = .01, .001, and .04, respectively). The mRNA expression of other molecules was comparable in the 2 tissues. The protein expression of both CA-II and osteonectin was 24% higher and PiT1 17% lower in caudate than the gray matter. The differences in the PTH2R and osteopontin protein expression were not appreciable. CONCLUSIONS: The presence of several osteogenic molecules in caudate nucleus indicates that BGC would probably be the outcome of an active process. The differences in expression of these molecules in caudate over gray matter could favor BGC at this site in the unique biochemical milieu of hypoparathyroid state.

Prevalence and significance of NALP5 autoantibodies in patients with idiopathic hypoparathyroidism.

CONTEXT: Role of parathyroid autoimmunity in idiopathic hypoparathyroidism (IH) is not clear. Recently, parathyroid-specific NACHT leucine-rich-repeat protein 5 (NALP5) autoantibodies (Ab) have been reported in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. OBJECTIVE: Our objective was to assess prevalence and significance of NALP5 Ab in patients with IH. DESIGN AND SETTING: This was a case-control study at a tertiary care hospital. SUBJECTS: Subjects included 145 patients with IH recruited from 1998-2011 and 152 healthy controls. METHODS: Immunoprecipitation (IP) and Western blot (WB) assays were performed using ³5S-labeled NALP5 protein produced by in vitro transcription-translation and recombinant NALP5 protein in Escherichia coli, respectively. AIRE gene sequencing was performed in NALP5 Ab-positive patients. RESULTS: One of 145 patients (0.69%) and none of the 152 controls had NALP5 Ab on IP assay. Nine of 147 patients (6.12%) and four of 152 controls (2.63%) had NALP5 Ab on WB. One patient with NALP5 Ab on IP (36.6 sd score), also positive on WB, had a frameshift p.Ala386Serfs*38 AIRE gene mutation and adrenocortical Ab. Eight subjects with NALP5 Ab detected on WB had normal AIRE gene sequence. CONCLUSIONS: IP is currently the best assay to detect clinically relevant NALP5 Ab. Presence of NALP5 Ab in only one patient with IH who also had AIRE gene mutation suggests that these Ab are exceptionally rare in IH (0.69%) and, when present, occur in context of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

Bacteriology of a most popular street food (Panipuri) and inhibitory effect of essential oils on bacterial growth.

Bacteriology of Panipuri was studied and the antibacterial effect of eight essential oils (EOs) was established on pathogens found in Panipuri. Samples were collected from twelve respective vendors from different locations in Baripada city, Orissa. Samples were fractionated into two parts viz. khatta pani and smashed potato masala used in Panipuri. Total plate count and isolation of pathogenic bacteria were done on both basal and selective media. Coliforms were detected primarily by presumptive test and confirmed subsequently, using Eosine Methylene Blue Agar. Selected colonies were pure cultured and identified through staining and an array of biochemical reactions. Antibiogram pattern of the pathogens and their susceptibility towards eight different EOs were performed. Antibacterial efficacy of four EOs in food sample was studied. Aerobic bacterial load of solid samples was observed to be more than in the liquid samples. Coliform-positive samples were found to be of 80.33%. Pathogenic bacteria like Escherichia coli, Klebsiella sp., Enterobactor sp., Bacillus sp., Enterococcus sp., Micrococcus tetragens, Salmonella paratyphi, Shigella dysenteriae and Vibrio sp. were detected. Antibiogram studies of the isolates showed multiple antibiotic resistance index (MRI;%) ranging from 15 to 92%. Among the EOs studied Cinnamon and Clove oils showed maximum antibacterial activity. Antibacterial efficacy showed that Clove and Cinnamon oils were comparatively of superior quality than Turmeric leaf and Japanese mint oils to kill food borne pathogens. Although it was a preliminary endeavor, the present study is a prerequisite in understanding the significance of pathogenic microorganisms in street foods and use of EOs as both antibacterial agents and food preservatives.