C-C Motif Ligand 7 (CCL7) and C-C Motif Chemokine Receptor 3 (CCR3) dysregulation in patients with scrub typhus and association with mortality.

BACKGROUND: Scrub typhus, caused by Orientia tsutsugamushi involves infiltration of a mixture of perivascular lymphocytes and macrophages into affected organs. We investigated if this is characterized by chemokine dysregulation. METHODS: mRNA expression of chemokines and receptors were screened in whole blood by cDNA microarray in a subgroup of patients and controls. Regulated transcripts were analyzed in plasma by enzyme immunoassays (chemokines) and in whole blood by qPCR (receptors) from scrub typhus patients (n=129), patients with similar febrile illness without Orentia tsutsugamushi infection (n=31) and healthy controls (n=31). RESULTS: (i) cDNA microarray identified dysregulation of the chemokines CCL18 and CCL23 and CCR3 receptor, in severe scrub typhus. (ii) Plasma CCL7, a ligand for CCR3, CCL18 and CCL23 were higher in scrub typhus patients, with a decline during follow-up. (iii) Conversely, mRNA levels of CCR3 and CCR8, the receptor for CCL18, were decreased in whole blood at hospital admission followed by an increase during follow-up. (iv) CCL7 was independently associated with disease severity. (v) Admission CCL7 levels were associated with short-time mortality. CONCLUSION: Our findings suggest CCL7 could represent a hitherto unknown pathogenic mediator in Orentia tsutsugamushi infection contributing to local and systemic inflammation.

Predictors and outcomes of multi-drug-resistant gram-negative bacteremia in patients with cancer: A retrospective cohort study at a tertiary cancer center in Oman.

Objectives: This study aimed to delineate the characteristics and outcomes of gram-negative bacteremia (GNB) in oncology patients; analyze the risk factors for multi-drug-resistant (MDR) GNB; and assess its impact on the recurrence of bloodstream infection (BSI), hospital stay, and 30-day mortality. Methods: Data, including demographics, clinical features, common cancers, and microbiologic findings, were collected retrospectively from electronic medical records of patients admitted with solid tumors and BSI episodes between January and December 2022. Fisher's exact tests were used to determine the effect of MDR-GNB on 30-day mortality and BSI recurrence. The Wilcoxon rank-sum test assessed the differences in the length of hospital stay. Logistic regression models identified the risk factors for MDR-GNB. Results: Among 1074 patients, 77 episodes of GNB bacteremia occurred in 59 individuals (47% male, median age 57.4 years). Of these, 37 (48%) were MDR-GNB. Carbapenem resistance was noted in 9.1% of GNB episodes. Previous antibiotic use was significantly associated with MDR-GNB (odds ratio 7.82; 95% confidence interval 2.52-24). MDR-GNB was linked to longer hospital stays (median 23 vs 10.5 days, P = 0.003) and higher recurrence rates than non-MDR-GNB (35.13% vs 5.0%, P <0.001). However, 30-day mortality did not significantly differ between the groups (35.14% vs 32.5%, P = 0.81). Conclusion: Previous antibiotic use predicted MDR-GNB in patients with solid tumor. MDR-GNB bacteremia increased the length of hospital stay and risk of recurrence compared with non-MDR-GNB bacteremia.

Prevalence and potential impact of human pegivirus-1 on HIV-1 disease progression among Indian PLHIV.

INTRODUCTION: Human pegivirus-1 (HPgV-1) influences the pathogenesis and outcome of viral infections. We investigated the prevalence and impact of HPgV-1 due to the paucity of studies on Indian people living with HIV (PLHIV). METHODOLOGY: Samples were collected from 347 treatment-naïve PLHIV; and 100 blood donors negative for HIV, HBV, and HCV. CD4+ T-cell and HIV-1 viral load were measured using flow-cytometry and quantitative polymerase chain reaction (qPCR), respectively. HPgV-1 was quantified and genotyped by qPCR and Sanger sequencing, respectively. RESULTS: HPgV-1 viremia in PLHIV and controls was 11% (38/347) and 1% (1/100), respectively. We found HPgV-1 genotype-2a in PLHIV and genotype-2b in controls. Male preponderance was seen in HIV-1 mono-infection and co-infection groups (166 vs. 143 and 33 vs. 5; p < 0.0001). The peak prevalence of HPgV-1 was at 31-50 years (p = 0.02). CD4+ T-cell count (245.5 vs. 240; p = 0.59) and HIV-1 log viral load (4.7 vs. 4.9; p = 0.50) were not significantly different between the HIV-1 mono-infected and coinfected individuals. However, a direct correlation existed between HpgV-1 viral load and CD4+ T-cell count (r = 0.27, p = 0.05) and an inverse correlation with HIV-1 viral load (r = -0.21, p = 0.10). CONCLUSIONS: This is the first study in India to estimate the HPgV-1 prevalence in PLHIV with the predominance of genotype-2a. HPgV-1 viremia had a moderate impact on CD4+ T-cells and HIV-1 viral load, which requires a longitudinal study to identify the beneficial influence on HIV-1 disease progression and outcome.

Human fascioliasis emergence in southern Asia: Complete nuclear rDNA spacer and mtDNA gene sequences prove Indian patient infection related to fluke hybridization in northeastern India and Bangladesh.

Fascioliasis is a snail-borne zoonotic disease with impact on the development of human subjects and communities. It is caused by two liver-infecting fasciolid trematode species, the globally-distributed Fasciola hepatica and the Africa/Asia-restricted but more pathogenic, larger F. gigantica. Fasciola gigantica is the cause of endemicity in livestock throughout the warm lowlands from Pakistan to southeastern Asia since old times. Human fascioliasis is emerging in this region at present, with an increase of patient reports. Complete sequences of rDNA ITS-1 and ITS-2 spacers and mtDNA nad1 and cox1 genes were obtained from fasciolid eggs found in the endoscopic bile aspirate from a patient of Arunachal Pradesh, northeastern India. Egg measurements, pronounced ITS heterozygosity, and pure F. gigantica mtDNA haplotypes demonstrate an infection by a recent F. gigantica-like hybrid. Sequence identities and similarities with the same DNA markers found in livestock from Bangladesh prove the human-infecting fasciolid to present identical ITSs and nad1 haplotypes and only one silent transversion in cox1 when compared to a widely-spread combined haplotype in animals. In northeastern India and Bangladesh, human fascioliasis emergence appears linked to increasing livestock prevalences due to: ruminant importation from other countries because of the increasing demand of rapidly growing human populations; numerous livestock movements, including transborder corridors, due to the uncontrolled small-scale household farming practices; and man-made introduction of F. hepatica with imported livestock into an area originally endemic for F. gigantica leading to frequent hybridization. Sequences, phylogenetic trees, and networks indicate that the origins of intermediate/hybrid fasciolids and factors underlying human infection risk differ in eastern and western South Asia. The emergence scenario in southern China and Vietnam resembles the aforementioned of northeastern India and Bangladesh, whereas in Pakistan it is linked to increasing monsoon rainfall within climate change combined with an impact of an extensive irrigation system. Past human-guided movements of pack animals along the western Grand Trunk Road and the eastern Tea-Horse Road explain the F. gigantica mtDNA results obtained. Physicians should be aware about these emerging scenarios, clinical pictures, diagnostic techniques and treatment. Government authorities must appropriately warn health professionals, ensure drug availability and improve livestock control.

Estimating the Seroincidence of Scrub Typhus using Antibody Dynamics after Infection.

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

A randomized trial of a wearable UV dosimeter for skin cancer prevention.

Background: Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. Despite guidelines on ultraviolet (UV) avoidance, it remains difficult for people to assess their exposure, as UV is invisible and the onset of UV-induced symptoms is delayed. Methods: In a prospective randomized trial, 97 elderly patients with a history of actinic keratoses (AK) were followed over 6 months. Fifty patients received UV counseling from a dermatologist and a wearable UV dosimeter that provided real-time and cumulative UV exposure. Forty-seven patients received only UV counseling from a dermatologist. Results: Over 75% of participants recorded UV exposure at least once a week during the summer. After 6 months of intervention, when comparing the device group to the control group, we observed a non-significant 20% lower ratio of incidence rates of AKs (95% CI = [-41, 55%], p-value = 0.44) and a significant 95% lower ratio of incidence rates of NMSCs (95% CI = [33, 99.6%], p-value = 0.024). Surveys demonstrated that the control group's score in self-perceived ability to participate in social activities significantly increased by 1.2 (p-value = 0.04), while in the device group, this score non-significantly decreased by 0.9 (p-value = 0.1). We did not observe changes, or between-group differences, in anxiety and depression surveys. Conclusion: This pilot clinical trial has a short duration and a small sample size. However, device adherence and quality of life questionnaires suggest a smartphone-connected wearable UV dosimeter is well accepted by an elderly population. This trial also indicates that a wearable UV dosimeter may be an effective behavioral change tool to reduce NMSC incidence in an elderly population with a prior history of AKs.Clinical trial registration: clinicaltrials.gov, identifier NCT03315286.

A Comparative Study of Acute Invasive Fungal Sinusitis During the First and Second Waves of the COVID-19 Pandemic.

We aimed to compare the demography, clinical profile, histopathology, fungal culture, radiology, surgery performed, medical therapy and outcomes of patients with acute invasive fungal sinusitis seen during the first and second waves of the COVID-19 pandemic by retrospectively reviewing their case records. Of 238 patients, 43(18.1%) presented during the first wave and 195(81.9%) during the second wave. Patients seen during the first wave were older (p = 0.04) and more likely to have visual impairment (p = 0.004), frozen eye (p = 0.012), altered sensorium (p = 0.007) and stage 3 disease (p = 0.03). Those seen during the second wave were more often COVID-19 positive and had newly diagnosed diabetes mellitus (p = 0.04)and stage 1 disease (p = 0.03). Most patients had a positive culture for Rhizopus species during both waves. Histopathology showed broad aseptate hyphae in all patients but angioinvasion was seen more often during the first wave (p = 0.04). The majority of patients were treated with endoscopic+/- open debridement followed by intravenous amphotericin B and oral posaconazole. While the overall survival rate was similar (first wave 65.1%; second wave 79%; p = 0.106), mortality after discharge was greater during the first wave (11.6% vs 1.5%; p = 0.001). Mortality was higher in patients with stage 3 disease (p = 0.003). Significant differences in clinical presentation, histopathology, radiological stage of disease and post-discharge survival were noted between the two waves of the COVID-19 pandemic, the causes for which were multi-factorial.

Distinct patterns of postoperative fever in paediatric neurosurgery patients.

PURPOSE: Postoperative fever is a common problem following neurosurgery but data on the causes among paediatric patients is sparse. In this report, we determined the incidence, causes, and outcomes of postoperative fever in paediatric neurosurgical patients (< 18 years), and contrasted the findings with an adult cohort published recently from our unit. METHODS: We recruited 61 patients who underwent 73 surgeries for non-traumatic neurosurgical indications over 12 months. A standard protocol was followed for the evaluation and management of postoperative fever. We prospectively collected data pertaining to operative details, daily maximal temperature, clinical features, and use of surgical drains, urinary catheters, and other adjuncts. Elevated body temperature of > 99.9 °F or 37.7 °C for > 48 h or associated with clinical deterioration or localising features was considered as "fever"; elevated temperature not meeting these criteria was classified as transient elevation in temperature (TET). RESULTS: Twenty-six patients (35.6%) had postoperative fever, more frequent than in adult patients. TET occurred in 12 patients (16.4%). The most common causes of fever were aseptic meningitis (34.6%), followed by urinary tract infections (15.4%), pyogenic meningitis, COVID-19, and wound infections. Postoperative fever was associated with significantly longer duration of hospital admission and was the commonest cause of readmission. CONCLUSION: In contrast to adults, early temperature elevations in paediatric patients may portend infectious and serious non-infectious causes of fever, including delayed presentation with aseptic meningitis, a novel association among paediatric patients. Investigation guided by clinical assessment and conservative antibiotic policy in keeping with the institutional microbiological profile provides the most appropriate strategy in managing paediatric postoperative fever.

Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome.

PURPOSE: The mechanisms that control inflammation in scrub typhus are not fully elucidated. The Notch pathways are important regulators of inflammation and infection, but have not been investigated in scrub typhus. METHODS: Plasma levels of the canonical Notch ligand Delta-like protein 1 (DLL1) were measured by enzyme immunoassay and RNA expression of the Notch receptors (NOTCH1, NOTCH2 and NOTCH4) in whole blood was analyzed by real-time PCR in patients with scrub typhus (n = 129), in patients with similar febrile illness without O. tsutsugamushi infection (n = 31) and in healthy controls (n = 31); all from the same area of South India. RESULTS: Our main results were: (i) plasma DLL1 was markedly increased in scrub typhus patients at hospital admission with a significant decrease during recovery. (ii) RNA expression of NOTCH4 was decreased at admission in whole blood. (iii) A similar pattern for DLL1 and NOTCH4 was seen in febrile disease controls. (iv) Admission DLL1 in plasma was associated with disease severity and short-term survival. (vi) Regulation of Notch pathways in O. tsutsugamushi-infected monocytes as evaluated by public repository data revealed enhanced canonical Notch activation with upregulation of DLL1 and downregulation of NOTCH4. CONCLUSION: Our findings suggest that scrub typhus patients are characterized by enhanced canonical Notch activation. Elevated plasma levels of DLL1 were associated with organ dysfunction and poor outcomes in these patients.

SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants.

The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has necessitated the development of broad cross-reactive vaccines. Recent findings suggest that enhanced antigen presentation could lead to cross-reactive humoral responses against the emerging variants. Toward enhancing the antigen presentation to dendritic cells (DCs), we developed a novel shikimoylated mannose receptor targeting lipid nanoparticle (SMART-LNP) system that could effectively deliver mRNAs into DCs. To improve the translation of mRNA, we developed spike domain-based trimeric S1 (TS1) mRNA with optimized codon sequence, base modification, and engineered 5' and 3' UTRs. In a mouse model, SMART-LNP-TS1 vaccine could elicit robust broad cross-reactive IgGs against Omicron sub-variants, and induced interferon-γ-producing T cells against SARS-CoV-2 virus compared with non-targeted LNP-TS1 vaccine. Further, T cells analysis revealed that SMART-LNP-TS1 vaccine induced long-lived memory T cell subsets, T helper 1 (Th1)-dominant and cytotoxic T cells immune responses against the SARS-CoV-2 virus. Importantly, SMART-LNP-TS1 vaccine produced strong Th1-predominant humoral and cellular immune responses. Overall, SMART-LNPs can be explored for precise antigenic mRNA delivery and robust immune responses. This platform technology can be explored further as a next-generation delivery system for mRNA-based immune therapies.

'Remediability Score' as a tool for selecting the most suitable remediation technology for contaminated sites.

Land gets contaminated due to different human activities like illegal industrial discharges, mining activities, and spillage of chemicals. The pollutants released through these activities can have prolonged effects on the environment and human health. Therefore, there is a need for immediate remediation of the contaminated site. Different remediation technologies are available for remediating a land contaminated with a particular contaminant. Selection of the most appropriate remediation technology among all those available would help in quick and efficient remediation of the land. There are multiple factors deciding the appropriateness of a technology for a given case. 'Remediability' is a term introduced in the scientific literature recently to describe the ease with which a contaminated land can be remediated and 'Remediability Score (RS)' quantifies remediability in a 0-100 scale. The higher the value of RS, the greater is the difficulty for remediation. The factors influencing remediability were presented before a group of experts in a Delphi process for assigning comparative importance. From the importance score obtained in a Saaty scale of 1 to 9, the weights of factors were calculated using Fuzzy AHP. The overall RS was calculated by taking the weighted impact of the factors after their magnitudes were normalized. RS for the various remediation technologies feasible for a contaminated site, Kuzhikandam, near Kochi, Kerala was calculated. The site was revealed to be contaminated with heavy metals and organic compounds in a field investigation. The most suitable technology for remediating the selected site was found to be vitrification with an RS of 22. The next best technology, stabilization/solidification, had an RS of 25. The study showed that RS can be a reliable matric for selecting the most suitable remediation technology for a contaminated site.

Distribution of microplastics in seafloor sediments and their differential assimilation in nearshore benthic molluscs along the south-west coast of India.

Spatial and temporal distribution of microplastics (MPs) in the nearshore seafloor sediments along the Southwest coast of India and their patterns of accumulation in selected infaunal and epibenthic molluscs with diverse feeding strategies were investigated. Along the 300-km coastal stretch, which is one of the most productive and biodiversity rich regions of the eastern Arabian Sea, notable levels of MP contamination in both sediment (617.7 items/kg dry weight) and molluscs (5.39 items/g) was recorded. The concentration of MPs in sediments also varied seasonally, with a higher prevalence during the post-monsoon season. Among the four molluscan groups studied, the highest MP abundance was recorded among scavenging gastropod Pseudominolia biangulosa (9.13 items/g), followed by microcarnivore scaphopod Tesseracme quadrapicalis (5.96 items/g). In comparison, the suspension feeding bivalve, Anadara hankeyana and deposit feeding clam Jitlada philippinarum had lesser accumulation of MPs (2.98 items/g and 3.50 items/g respectively). The majority of MPs in sediments and within molluscs were less than 250 µm in size (89.14%) and were predominantly fibres and fragments. Chemical characterisation of MPs revealed eleven types of polymers dominated by polyethylene (PE) and polypropylene (PP). Present study identified positive correlations between ingested MP polymers and the feeding strategies of molluscs. Higher values for the ecological risk assessment indices (PHI, PLI and PERI) in most of the stations indicated the severity of plastic pollution in the region. Molluscs being a major contributor to the benthic food web is also a connecting link to higher trophic levels. Hence understanding the specificity in the MPs accumulation pattern within this group has far reaching significance in utilizing them as potential bioindicators for pollution studies in marine ecosystems.

Reverse vaccinology and immunoinformatics approach to design a chimeric epitope vaccine against Orientia tsutsugamushi.

Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi and it is reportedly associated with up to 20 % of hospitalized cases of febrile illnesses. The major challenge of vaccine development is the lack of identified antigens that can induce both heterotypic and homotypic immunity including the production of antibodies, cytotoxic T lymphocyte, and helper T lymphocytes. We employed a comprehensive immunoinformatic prediction algorithm to identify immunogenic epitopes of the 56-kDa type-specific cell membrane surface antigen and surface cell antigen A of O. tsutsugamushi to select potential candidates for developing vaccines and diagnostic assays. We identified 35 linear and 29 continuous immunogenic B-cell epitopes and 51 and 27 strong-binding T-cell epitopes of major histocompatibility complex class I and class II molecules, respectively, in the conserved and variable regions of the 56-kDa type-specific surface antigen. The predicted B- and T-cell epitopes were used to develop immunogenic multi-epitope candidate vaccines and showed to elicit a broad-range of immune protection. A stable interactions between the multi-epitope vaccines and the host fibronectin protein were observed using docking and simulation methods. Molecular dynamics simulation studies demonstrated that the multi-epitope vaccine constructs and fibronectin docked models were stable during simulation time. Furthermore, the multi-epitope vaccine exhibited properties such as antigenicity, non-allergenicity and ability to induce interferon gamma production and had strong associations with their respective human leukocyte antigen alleles of world-wide population coverage. A correlation of immune simulations and the in-silico predicted immunogenic potential of multi-epitope vaccines implicate for further investigations to accelerate designing of epitope-based vaccine candidates and chimeric antigens for development of serological diagnostic assays for scrub typhus.

Clinical Implementation of "Plan of the Day" Strategy in Definitive Radiation Therapy of Cervical Cancer: Online Adaptation to Address the Challenge of Organ Filling Reproducibility.

PURPOSE: Definitive pelvic intensity modulated radiation therapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging. METHODS AND MATERIALS: In this prospective, nonrandomized phase 2 study, patients with cervical cancer International Federation of Gynecology and Obstetrics (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic chemoradiotherapy with a prespecified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive image-guided radiotherapy (IGRT), with a library of 3 IMRT (volumetric modulated arc therapy) plans with incremental expansions of clinical target volume (CTV) to planning target volume (PTV) (primary) margins (small, 0.7 cm; adequate, 1 cm; and large, 1.5 cm) and a backup motion robust 3-dimensional conformal radiotherapy plan; the appropriate plan is chosen based on pretreatment cone beam computed tomography (CBCT) ("plan of the day" approach). RESULTS: Fifty patients with a median age of 49 years (IQR, 45-56 years) received definitive radiation therapy (45-46 Gy in 23-25 fractions to pelvis, with simultaneous integrated boost to gross nodes in 15 patients) with the aforementioned IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning computed tomography (CT) and CBCT bladder volumes were 417 and 373 cc, respectively. Significant interfractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were postchemotherapy sessions (P ≤ .001), pre-CBCT protocol duration (P = .001), and grades of chemotherapy induced nausea vomiting (P = .001). Significantly higher variation in bladder filling was noted in patients with older age (P = .014) and larger planning CT bladder volume (P ≤ .001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from the first to the fifth week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion and without any significant factors affecting it. Although in 19% and 2% of sessions large IMRT PTV and 3-dimensional conformal radiotherapy were necessary to cover the primary target, respectively, reduction in treated volume was possible in 43% of sessions with small PTV selection instead of standard adequate PTV (36% sessions). Plan of the day selection had a moderate to strong correlation with nonabsolute dispersion of bladder filling (Spearman ρ =0.4; P = .001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade 3 toxicity. CONCLUSIONS: Interfractional variation in organ filling (especially bladder) is inevitable despite fixed pretreatment protocol in definitive settings (intact cervix). Despite the logistical challenges, adaptive IGRT in the form of plan of the day based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimize geometric uncertainties in radical IG-IMRT of cervical cancer.

Clinical, laboratory profile and molecular characterization of Orientia tsutsugamushi among fatal scrub typhus patients from Karnataka, India.

BACKGROUND: Scrub typhus is a vector-borne infection caused by the obligate intracellular organism Orientia tsutsugamushi. In some cases, scrub typhus can result in severe complications, multiorgan failure and death. OBJECTIVE: To study the clinical and laboratory profiles of patients who succumbed to scrub typhus. METHODS: A prospective cohort study was conducted from August 2019 through April 2023 on scrub typhus patients admitted to our hospital. Clinical and laboratory parameters of all the patients were recorded, and blood samples were drawn. To confirm scrub typhus, a nested polymerase chain reaction (nPCR) was performed in collected samples. Viable amplicons were sequenced, and phylogenetic analyses were performed to identify infecting genotypes. RESULTS: A total of 261 patients were enrolled. Of these, nine (3.45%) patients succumbed at a median (Interquartile Range) duration of 5 (1.5, 10.5) days after admission. Sepsis with septic shock (9, 100%) and acute kidney injury (AKI) (6, 66%) were noted among the succumbed patients. All the succumbed patients (100%) required intensive care admission, inotropic and ventilatory support. While 5 (55%) patients required dialysis, two (22%) required blood transfusion. Three (33%) patient samples were co-positive for Leptospira IgM, and four (44%) patients had superinfection with Candida tropicalis, multi-drug-resistant (MDR) E. Coli sepsis, pan drug-resistant (PDR) Acinetobacter Baumanii, and Klebsiella pneumoniae. Phylogenetic analysis revealed Orientia tsutsugamushi Japanese Gilliam-variant (JG-v) like (50%), Karp-like (37.5%), and Japanese Gilliam (JG) like (12.5%) strains among succumbed patients. CONCLUSION: Delay in scrub typhus diagnosis can result in severe complications, septic shock, and multisystem organ failure, culminating in death.

Characterization and source apportionment of microplastics in Indian composts.

Microplastics (MP), small plastic particles under 5 mm, are pollutants known to carry heavy metals in ecosystems. Composts are a significant source of soil microplastics. This study examined MSW composts from Kochi and Kozhikode in India for microplastic concentrations and heavy metals' accumulation thereon. Microplastics were isolated using zinc chloride density separation, with Fenton's reagent used for organic matter oxidation. Resin types were identified using FTIR analysis that showed the presence of PE, PP, PS, nylon, PET, and allyl alcohol copolymer. In Kozhikode's compost, the average concentration of microplastics was 840 ± 30 items/kg, while Kochi had 1600 ± 111 items/kg, mainly polyethylene films. PE was the most prevalent resin, comprising 58.3% in Kozhikode and 73.37% in Kochi. Heavy metal analysis of MP showed significant concentrations of lead, cadmium, zinc, copper, and manganese adsorbed on the surface of microplastics. The concentrations of heavy metals in the MP before Fenton oxidation ranged from 1.02 to 2.02 times the corresponding concentrations in compost for Kozhikode and 1.23 to 2.85 times for Kochi. Source apportionment studies revealed that 64% of microplastics in Kozhikode and 77% in Kochi originated from single-use plastics. Ecological risk indices, PLI and PHI, showed that composts from both locations fall under hazard level V. The study revealed that compost from unsegregated MSW can act as a significant source of microplastics and heavy metals in the soil environment, with single-use plastics contributing major share of the issue.

Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

BACKGROUND: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic, a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction. AIM: To describe the clinical and laboratory characteristics, outcomes, and management of these patients, and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders. METHODS: This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital, between May and August 2021, who fulfilled clearly defined inclusion and exclusion criteria. Outcome was assessed by a change in PaO2/FiO2 ratio and levels of inflammatory markers before and after immunomodulation, duration of mechanical ventilation after starting treatment, and survival to discharge. RESULTS: Five patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction at a median interquartile range (IQR) duration of 32 (23-35) d after the onset of symptoms. These patients had elevated inflammatory markers, required mechanical ventilation for 13 (IQR 10-23) d, and responded to glucocorticoids and/or intravenous immunoglobulin. One patient died (20%). CONCLUSION: This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome - Adults by the paucity of extrapulmonary organ involvement. The diagnosis can be considered in patients presenting with delayed respiratory worsening, that is not attributable to cardiac dysfunction, fluid overload or ongoing infections, and associated with an increase in systemic inflammatory markers like C-reactive protein, inteleukin-6 and ferritin. A good response to immunomodulation can be expected. This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Are physicians ready for precision antibiotic prescribing? A qualitative analysis of the acceptance of artificial intelligence-enabled clinical decision support systems in India and Singapore.

OBJECTIVES: Artificial intelligence (AI)-driven clinical decision support systems (CDSSs) can augment antibiotic decision-making capabilities, but physicians' hesitancy in adopting them may undermine their utility. We conducted a cross-country comparison of physician perceptions on the barriers and facilitators in accepting an AI-enabled CDSS for antibiotic prescribing. METHODS: We conducted in-depth interviews with physicians from the National Centre for Infectious Diseases (NCID), Singapore, and Christian Medical College Vellore (CMCV), India, between April and December 2022. Our semi-structured in-depth interview guides were anchored on Venkatesh's UTAUT model. We used clinical vignettes to illustrate the application of AI in clinical decision support for antibiotic prescribing and explore medico-legal concerns. RESULTS: Most NCID physicians felt that an AI-enabled CDSS could facilitate antibiotic prescribing, while most CMCV physicians were sceptical about the tool's utility. The hesitancy in adopting an AI-enabled CDSS stems from concerns about the lack of validated and successful examples, fear of losing autonomy and clinical skills, difficulty of use, and impediment in work efficiency. Physicians from both sites felt that a user-friendly interface, integration with workflow, transparency of output, a guiding medico-legal framework, and training and technical support would improve the uptake of an AI-enabled CDSS. CONCLUSION: In conclusion, the acceptance of AI-enabled CDSSs depends on the physician's confidence with the tool's recommendations, perceived ease of use, familiarity with AI, the organisation's digital culture and support, and the presence of medico-legal governance of AI. Progressive implementation and continuous feedback are essential to allay scepticism around the utility of AI-enabled CDSSs.