Validation of malaria-attributed deaths using verbal autopsy studies: a systematic review.

BACKGROUND: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. METHODS: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. RESULTS: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. CONCLUSIONS: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.

Hybrid immunity from severe acute respiratory syndrome coronavirus 2 infection and vaccination in Canadian adults: A cohort study.

Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels. Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity. Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform. Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.

Antioxidant and Antibacterial Activities Evaluation, Phytochemical Characterisation of Rhizome from Angiopteris helferiana and Barks from Saurauia fasciculata in Nepal.

Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of Angiopteris helferiana and the bark of Saurauia fasciculata have been used widely to treat muscle fatigue, bone pain, fever, postpartum hemorrhage, and thirst by healers in Kaski and Tanahun districts, Nepal. However, scientific evidence towards their traditional uses is lacking till December, 2023. Therefore, we report the phytochemicals, total phenolic content (TPC), total flavonoid content (TFC), total carbohydrate content (TCC), antioxidant and antibacterial activities of A. helferiana and S. fasciculata extracts. Phytochemical analysis indicated that A. helferiana and S. fasciculata extracts were potential sources of chemicals such as phenols, flavonoids, tannins, terpenoids, saponins, and carbohydrates. The TPC, TFC, and TCC of extracts were determined by using an ultraviolet visible spectrophotometer. Among the extracts tested, A. helferiana extracts showed the highest phenolic and carbohydrate contents of 208.33 ± 12.96 mg of gallic acid equivalent/g and 564.16 ± 2.92 mg of D-glucose equivalent/g of dry extract, respectively. Similarly, S. fasciculata revealed the highest flavonoid content of 30.35 ± 0.1 mg quercetin equivalent/g of dry extract. The extract of A. helferiana and S. fasciculata exhibited potent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl radicals with an IC50 of 25.9 µg/ml and 31.07 µg/ml, respectively. The antibacterial activity of the A. helferiana and S. fasciculata extract against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was determined using an agar-well diffusion protocol that revealed the potential antibacterial activity of A. helferiana against E. coli. The present study will help validate the traditional uses of A. helferiana rhizomes and S. fasciculata barks as a healing medicine and inspire the researcher towards further research, development, and formulation.

Child, maternal, and adult mortality in rural Ethiopia in 2019: a cross-sectional mortality survey using electronic verbal autopsies.

Background: Ethiopia, with about 10% of Africa's population, has little direct information on causes of death, particularly in rural areas where 80% of Ethiopians live. In 2019-2020, we conducted electronic verbal autopsies (e-VA) to examine causes of death and quantify cause-specific mortality rates in rural Ethiopia. Methods: We examined deaths under 70 years in the three years prior to the survey dates (November 25, 2019-February 29, 2020) among 2% of East Gojjam Zone (Amhara Region) using registered deaths and adding random sampling in this cross-sectional study. Trained surveyors interviewed relatives of the deceased with central dual-physician assignment of causes as the main outcome. We documented details on age, sex and location of death, and derived overall rural death rates using 2007 Census data and the United Nations national estimates for 2019. To these, we applied our sample-weighted causes to derive cause-specific mortality rates. We calculated death risks for the leading causes for major age groups. Findings: We studied 3516 deaths: 55% male, 97% rural, and 68% occurring at home. At ages 5 and older, injuries were notable, accounting for over a third of deaths at 5-14 years, half of the deaths at ages 15-29 years, and a quarter of deaths at ages 30-69 years. Neonatal mortality was high, mostly from prematurity/low birthweight and infections. Among children under 5 (excluding neonates), infections caused nearly two-thirds of deaths. Most maternal deaths (84%) arose from direct causes. After injuries, especially suicide, assaults, and road traffic accidents, vascular disease (15%) and cancer (13%) were the leading causes among adults at 30-69 years. HIV/AIDS and tuberculosis deaths were also important causes among adults. Interpretation: Rural Ethiopia has a high burden of avoidable mortality, particularly injury, including suicide, assaults, and road traffic accidents. Funding: International Development Research Centre, and the Canadian Institutes of Health Research.

Secretory molecules from secretion systems fine-tune the host-beneficial bacteria (PGPRs) interaction.

Numerous bacterial species associate with plants through commensal, mutualistic, or parasitic association, affecting host physiology and health. The mechanism for such association is intricate and involves the secretion of multiple biochemical substances through dedicated protein systems called secretion systems SS. Eleven SS pathways deliver protein factors and enzymes in their immediate environment or host cells, as well as in competing microbial cells in a contact-dependent or independent fashion. These SS are instrumental in competition, initiation of infection, colonization, and establishment of association (positive or negative) with host organisms. The role of SS in infection and pathogenesis has been demonstrated for several phytopathogens, including Agrobacterium, Xanthomonas, Ralstonia, and Pseudomonas. Since there is overlap in mechanisms of establishing association with host plants, several studies have investigated the role of SSs in the interaction of plant and beneficial bacteria, including symbiotic rhizobia and plant growth bacteria (PGPB). Therefore, the present review updates the role of different SSs required for the colonization of beneficial bacteria such as rhizobia, Burkholderia, Pseudomonas, Herbaspirillum, etc., on or inside plants, which can lead to a long-term association. Most SS like T3SS, T4SS, T5SS, and T6SS are required for the antagonistic activity needed to prevent competing microbes, including phytopathogens, ameliorate biotic stress in plants, and produce substances for successful colonization. Others are required for chemotaxis, adherence, niche formation, and suppression of immune response to establish mutualistic association with host plants.

Excess deaths in China during SARS-CoV-2 viral waves in 2022-2023.

Background: The extent to which the Omicron variant of SARS-CoV-2 raised death rates in China during its viral wave of December 2022-January 2023 remains largely undocumented. Methods: We worked with an established national survey organization to survey 8,004 adults in all 31 administrative areas of China to ask about deaths in families since January 2020. We examined age-specific death rates, focusing on deaths above age 60 years, and at 15-59 years. We compared these to the United Nations (UN) estimates of age-specific mortality in 2019. Findings: The survey participants were broadly similar to the 2020 census and other national surveys in age, sex, region, and smoking status, but had lower SARS-CoV-2 vaccination rates and higher education levels. There were no differences in reporting of deaths during the Omicron period (after November 2021) versus earlier. The survey captured 456 deaths, of which 329 occurred at ages 60+ years and 212 were of women. At ages 60+ years, death rates approximately doubled during December 2022-January 2023. Deaths at ages 15-59 years did not rise appreciably. The UN estimates approximately 675,000 deaths per month at ages 60+ years in 2019. If rates doubled nationally as in our survey, China had approximately 1.35 million excess deaths from December 2022-January 2023. Interpretation: China experienced a sharp but short increase in excess deaths among its elderly during the Omicron wave. If death registry data corroborate our estimates of substantial excess deaths in China, the worldwide estimates of excess deaths due to SARS-CoV-2 in 2022-2023 may need upward adjustment.

Reductions in smoking due to ratification of the Framework Convention for Tobacco Control in 171 countries.

Smoking globally kills over half of long-term smokers and causes about 7 million annual deaths. The World Health Organization Framework Convention for Tobacco Control (FCTC) is the main global policy strategy to combat smoking, but its effectiveness is uncertain. Our interrupted time series analyses compared before- and after-FCTC trends in the numbers and prevalence of smokers below the age of 25 years (when smoking initiation occurs and during which response to interventions is greatest) and on cessation at 45-59 years (when quitting probably occurs) in 170 countries, excluding China. Contrasting the 10 years after FCTC ratification with the income-specific before-FCTC trends, we observed cumulative decreases of 15.5% (95% confidence interval = -33.2 to -0.7) for the numbers of current smokers and decreases of -7.5% (95% CI = -10.6 to -4.5) for the prevalence of smoking below age 25 years. The quit ratio (comparing the numbers of former and ever smokers) at 45-59 years increased by 1.8% (1.2 to 2.3) 10 years after FCTC ratification. Countries raising taxes by at least 10 percentage points concurrent with ratification observed steeper decreases in all three outcomes than countries that did not. Over a decade across 170 countries, the FCTC was associated with 24 million fewer young smokers and 2 million more quitters.

Smoking Cessation and Short- and Longer-Term Mortality.

BACKGROUND: Smoking cessation reduces mortality and morbidity. However, the extent and rapidity at which cessation reduces contemporary death rates from smoking-related illnesses remain uncertain. METHODS: We pooled current or former versus never cigarette smoker hazard ratios from four national cohorts with linkage to death registries in the United States, United Kingdom, Norway, and Canada among adults 20 to 79 years of age from 1974 to 2018. We calculated excess risk differences and survival, comparing current or never smokers with age-specific cessation and cessation fewer than 3, 3 to 9, or 10 or more years earlier. RESULTS: Among 1.48 million adults followed for 15 years, 122,697 deaths occurred. Adjusting for age, education, alcohol use, and obesity, current smokers had higher hazard ratios for death compared with never smokers (2.8 for women, 2.7 for men). Survival between 40 and 79 years of age was 12 and 13 years less in women and men, respectively, who smoked compared with never smokers (about 24 to 26 years of life lost for smokers who died from smoking combined with zero loss for smokers who did not die from smoking). Former smokers showed lower hazard ratios (1.3 in both women and men). Short-term cessation for fewer than 3 years was associated with a lower excess risk of 95% in women and 90% in men younger than 40 years of age, with notable beneficial associations also in women and men 40 to 49 years of age (81% and 61%, respectively) and 50 to 59 years of age (63% and 54%, respectively). Cessation at every age was associated with longer survival, particularly cessation before 40 years of age. Among all ages and compared with continued smoking, cessation of fewer than 3 years potentially averted 5 years of life lost and cessation for 10 or more years averted about 10 years of life lost, yielding survival similar to that of never smokers. CONCLUSIONS: Quitting smoking at any age, but particularly in younger years, was associated with lower excess mortality overall and from vascular, respiratory, and neoplastic diseases. Beneficial associations were evident as early as 3 years after cessation. (Funded by Canadian Institutes of Health Research [FDN-154277].)

Exploring the labour market outcomes of the risk factors for non-communicable diseases: A systematic review.

Objective: To look at the associations between labour market outcomes and major risk factors for non-communicable diseases (NCDs) (smoking, heavy alcohol consumption), key metabolic changes resultant of the risk factors (overweight and obesity, hypertension, type 2 diabetes), and major depressive disorder, and examine any gender differences. Design: Systematic review of cohort and longitudinal studies, to establish causality between exposures and outcomes. Methods: A systematic literature search was conducted in MEDLINE (Ovid), Embase (Ovid), EconLit (EBSCO), EconPapers, and Cochrane Database of Systematic Reviews, from inception to July 2022 for all peer-reviewed literature published, guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) framework. Results: 109 studies were eligible for this review. All studies were published in English. 96% of the studies were conducted in high-income countries with 63% from Europe and Central Asia. High BMI was the most frequently reported exposure (reported by 46% of the studies), while income was the most studied outcome (reported by 33% of studies). Though not all estimates presented in the literature can be interpreted as causal impacts, 77% of the studies reported significant (p < 0.05) adverse associations between the exposures and outcomes. Conclusions: All of the studies included in this review that looked at plausible causal relationships between NCD risk factors and labour market outcomes were from high-income and upper-middle-income countries (USA, northern European countries, and South Korea). Based on these studies, we found that individuals with overweight or obesity, diabetes, hypertension, depressive disorders, excessive alcohol use, and cigarette use are more likely to have lower rates of employment, lower income, and higher rates of sickness absence and disability pension.

Ethical and cultural implications for conducting verbal autopsies in South and Southeast Asia: a qualitative study.

INTRODUCTION: Causes of deaths often go unrecorded in lower income countries, yet this information is critical. Verbal autopsy is a questionnaire interview with a family member or caregiver to elicit the symptoms and circumstances preceding a death and assign a probable cause. The social and cultural aspects of verbal autopsy have gotten less attention than the technical aspects and have not been widely explored in South and Southeast Asia settings. METHODS: Between October 2021 and March 2023, prior to implementing a verbal autopsy study at rural sites in Bangladesh, Cambodia, Laos, Myanmar and Thailand, focus group discussions were conducted with village heads, religious leaders and community members from varied demographic backgrounds. Thematic analysis elucidated customs and traditional views surrounding death to understand local ethnocultural sensitivities. RESULTS: We found that death rituals varied greatly among religions, ethnicities and by socioeconomic status. Mourning periods were reported to last 3-100 days and related to the cause of death, age and how close the deceased person was to the family. Participants advised that interviews should happen after mourning periods to avoid emotional distress, but not long after so as to avoid recall bias. Interviewers should be introduced to respondents by a trusted local person. To provide reassurance and confidentiality, a family's residence is the preferred interview location. Interview questions require careful local language translation, and community sensitisation is important before data collection. CONCLUSION: Verbal autopsy is acceptable across a wide range of cultural settings in Southeast Asia, provided that local norms are preidentified and followed.

Taxation of tobacco, alcohol, and sugar-sweetened beverages: reviewing the evidence and dispelling the myths.

The article reviews the large body of evidence on how taxation affects the consumption of tobacco, alcohol, and sugar-sweetened beverages (SSB). There is abundant evidence that demand for tobacco, alcohol, and SSB is price-responsive and that tax changes are quickly passed on to consumers. This suggests that taxes can be highly effective in changing consumption and reducing the burden of diseases associated with consuming these products. Tobacco, alcohol, and SSB industries oppose taxation on similar grounds, mostly on the regressivity of taxes since regressive taxes take a larger percentage of income from low income earners than from middle and high income earners; but also on the effects taxes might have on employment and economic activity; and, in the case of tobacco, the effects taxation has on illicit trade.Contrary to industry arguments, evidence shows that taxation may have short-term negative financial consequences for low-income households. However, medium and long-term financial benefits from reduced healthcare costs, better health, and welfare largely compensate for such consequences. Moreover, taxation does not negatively affect aggregate economic activity or employment, as consumers switch demand to other products that generate employment and may compensate for any employment loss in taxed sectors. Evidence also shows the revenues generated are generally spent on labour-intensive services. In the case of illicit trade in tobacco, evidence shows that illicit trade has not increased globally (rather the opposite) despite increases in tobacco taxes. Profit-maximising smugglers increase illicit cigarette prices along with the increases in licit cigarette prices. This implies that even when increased taxes divert some demand to the illicit market, they push prices up in the illicit market, discouraging consumption.

Rhamnolipid production by Pseudomonas aeruginosa (SSL-4) on waste engine oil (WEO): Taguchi optimization, soil remediation, and phytotoxicity investigation.

ABSTRACTEnvironmental concerns and rising biosurfactant demand emphasize the need for this study. The objective is to maximize rhamnolipid-biosurfactant production by Pseudomonas aeruginosa (SSL-4) utilizing waste engine oil (WEO) as the sole substrate for use in soil bioremediation and commercial production. Using an L16 Taguchi orthogonal array, a signal-to-noise ratio, and an analysis of variance (ANOVA), the effects of environmental (pH, incubation temperature) and dietary parameters (carbon source concentration, carbon/nitrogen (C/N) and carbon/phosphorus (C/P) ratio) are examined. Variations of the following parameters were made within a carefully selected range: incubation temperature of 25-40℃, pH range of 5-11, WEO concentration of 1-7% (v/v), and C/N and C/P ratios of 10-40. Response variables in this batch study include surface tension reduction (mN/m), dry cell biomass (DCBM) (g/L), and rhamnolipids yield based on substrate consumption, YP/S (g/g). Rhamnolipid was synthesized under optimal conditions, providing a yield of 21.42 g/g. The oil recovery of 74.05 ± 1.481% was achieved from oil-contaminated soil at a CMC of ∼70 mg/L. FTIR, 1H NMR, and UPLC-MS techniques were utilized for the characterization of rhamnolipids, and AAS for determining heavy metals concentration in WEO and residual waste engine oil (RWEO). The Germination Index (GI) of ∼82.55% indicated no phytotoxicity associated with synthesized rhamnolipid.

Could vaccinating adults against malaria materially reduce adult mortality in high-transmission areas?

After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

Adult malaria mortality during 2019 at Bo Government Hospital, Sierra Leone.

It is uncertain whether malaria is an important cause of death among adults in endemic areas. We performed a chart review of adults admitted to Bo Government Hospital during 2019. Of 893 admissions, 149 (59% female, mean age 58.5 years) had a laboratory diagnosis of malaria and 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [30%] versus 16/129 [12.4%], p=0.031).  Our results suggest that malaria is a common cause of death in hospitalized Sierra Leonian adults.

The evolution of SARS-CoV-2 seroprevalence in Canada: a time-series study, 2020-2023.

BACKGROUND: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity. METHODS: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age. RESULTS: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia. INTERPRETATION: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.

Characterizing the type 6 secretion system (T6SS) of E. cloacae SBP-8 and its role in pathogenesis and bacterial competition.

Despite the relevance of E. cloacae as an opportunistic pathogen, very little is known about its pathogenicity mechanism and the factors influencing its virulence. The mechanism of E. cloacae pathogenicity appears to be complex and multifactorial, with the presence of different putative virulence factors whose role is still not clear in the development of the disease. In this study, we systematically investigated the role of T6SS (type six secretion system) of E. cloacae SBP-8, an environmental isolate, in eukaryotic and bacterial cell interaction. Analysis of the genome sequence of E. cloacae SBP-8 revealed the presence of sets of genes coding for the expression of one complete T6SS cluster, which is similar to T6SS-1 cluster of E. cloacae ATCC 13047 (clinical isolates). In addition, an Hcp effector protein was detected in the secretome, and this secretion depended on ClpV, an Atpase of T6SS, confirming that strain SBP-8 produces functional T6SS. Deletion of T6SS-associated gene clpV did not induce any significant change in the life span and rate of colonization in C. elegans. No major significant change was observed in the expression profiling of antimicrobial genes (clec-60, clec-85, clec-87 and lys-1) and toll-like receptor (toll-1) gene, involved in stimulating an immune response against the pathogen. No difference in the ability to invade and proliferate in intestinal cells and phagocytosis by macrophages was observed. In addition, we demonstrated that the ability of E. cloacae SBP-8 to out-compete Escherichia coli was reliant upon its T6SS in contact-dependent manner. Our results show that T6SS of the environmental isolates is required for interbacterial competition but not for invasion and proliferation inside host cells.

PCR Test Positivity and Viral Loads during Three SARS-CoV-2 Viral Waves in Mumbai, India.

SARS-CoV-2 polymerase chain reaction (PCR) tests generally report only binary (positive or negative) outcomes. Quantitative PCR tests can provide epidemiological information on viral transmission patterns in populations. SARS-CoV-2 transmission patterns during India's SARS-CoV-2 viral waves remain largely undocumented. We analyzed 2.7 million real-time PCR testing records collected in Mumbai, a bellwether for other Indian cities. We used the inverse of cycle threshold (Ct) values to determine the community-level viral load. We quantified wave-specific differences by age, sex, and slum population density. Overall, PCR positivity was 3.4% during non-outbreak periods, rising to 23.2% and 42.8% during the original (June-November 2020) and Omicron waves (January 2022), respectively, but was a surprisingly low 9.9% during the Delta wave (March-June 2021; which had the largest increase in COVID deaths). The community-level median Ct values fell and rose ~7-14 days prior to PCR positivity rates. Viral loads were four-fold higher during the Delta and Omicron waves than during non-outbreak months. The Delta wave had high viral loads at older ages, in women, and in areas of higher slum density. During the Omicron wave, differences in viral load by sex and slum density had disappeared, but older adults continued to show a higher viral load. Mumbai's viral waves had markedly high viral loads representing an early signal of the pandemic trajectory. Ct values are practicable monitoring tools.

Biochemical and metabolic signatures are fundamental to drought adaptation in PGPR Enterobacter bugandensis WRS7.

Drought alone causes more annual loss in crop yield than the sum of all other environmental stresses. There is growing interest in harnessing the potential of stress-resilient PGPR in conferring plant resistance and enhancing crop productivity in drought-affected agroecosystems. A detailed understanding of the complex physiological and biochemical responses will open up the avenues to stress adaptation mechanisms of PGPR communities under drought. It will pave the way for rhizosphere engineering through metabolically engineered PGPR. Therefore, to reveal the physiological and metabolic networks in response to drought-mediated osmotic stress, we performed biochemical analyses and applied untargeted metabolomics to investigate the stress adaptation mechanisms of a PGPR Enterobacter bugendensis WRS7 (Eb WRS7). Drought caused oxidative stress and resulted in slower growth rates in Eb WRS7. However, Eb WRS7 could tolerate drought stress and did not show changes in cell morphology under stress conditions. Overproduction of ROS caused lipid peroxidation (increment in MDA) and eventually activated antioxidant systems and cell signalling cascades, which led to the accumulation of ions (Na+, K+, and Ca2+), osmolytes (proline, exopolysaccharides, betaine, and trehalose), and modulated lipid dynamics of the plasma membranes for osmosensing and osmoregulation, suggesting an osmotic stress adaption mechanism in PGPR Eb WRS7. Finally, GC-MS-based metabolite profiling and deregulated metabolic responses highlighted the role of osmolytes, ions, and intracellular metabolites in regulating Eb WRS7 metabolism. Our results suggest that understanding the role of metabolites and metabolic pathways can be exploited for future metabolic engineering of PGPR and developing bio inoculants for plant growth promotion under drought-affected agroecosystems.