Etiology of Meningoencephalitis in children aged less than 5 years.

BACKGROUND: The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age. MATERIAL AND METHODS: The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR. RESULTS: Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases. CONCLUSION: We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.

Relationship between tobacco use, alcohol consumption and non-communicable diseases among women in India: evidence from National Family Health Survey-2015-16.

BACKGROUND: Based on an increased prevalence of diabetes, asthma and hypertension among women in reproductive age, understanding the risk factors of non-communicable diseases (NCDs) is crucial to inform policy and program interventions to address the problem. In this study, we empirically assessed the associations of behavioural factors such as alcohol consumption and tobacco use and a variety of socioeconomic characteristics with prevalence of NCDs in adult women. METHODS: The data were derived from the National Family Health Survey conducted in 2015-16. The effective sample size for the present paper was 699,686 women aged 15-49 years in India. Descriptive statistics along with bivariate analysis were conducted to find the preliminary results. Additionally, multivariable logistic regression analysis was conducted to find the relationship between NCDs and behavioural factors such as alcohol consumption and tobacco use. Moreover, population attributable risk was estimated in the present study. RESULTS: It was revealed that 15.9% of women had any of the NCDs. A proportion of 0.8% of women smoked tobacco whereas 5.5% of women consumed smokeless tobacco. Also, a proportion of 1.2% of women consumed alcohol in the current study. The odds of having NCDs among women who smoked tobacco, consumed smokeless tobacco and consume alcohol were 16, 8 and 20% significantly higher than the odds of having NCDs among women who did not smoke tobacco, consume smokeless tobacco and consume alcohol respectively. The population attributable risk of having NCDs was 1.8% (p < 0.001) for women who smoked, 0.8% (p < 0.001) for women who consumed smokeless tobacco and 2.2% (p < 0.001) for women who consumed alcohol. Besides, the odds of having NCDs among overweight and obese women were 2.25 and 3.60 times greater than the odds of having NCDs among women who were underweight. CONCLUSION: The findings revealed that smoking and using smokeless tobacco and alcohol consumption were risk factors of NCDs in women. The findings also alarm the focus of maternal and child health programs on NCDs' risk factors like maternal obesity, due to their adverse health consequences on their children too. Also, the coexistence of higher levels of tobacco use and alcohol consumption requires different strategies to address the vulnerability of women towards NCDs, including screening and early detection of NCDs especially among those who smoke or chew tobacco and consume alcohol.

Population attributable risk for multimorbidity among adult women in India: Do smoking tobacco, chewing tobacco and consuming alcohol make a difference?

BACKGROUND: The present study aims to estimate the prevalence and correlates of multimorbidity among women aged 15-49 years in India. Additionally, the population attributable risk for multi-morbidity in reference to those women who smoke tobacco, chew tobacco, and consume alcohol is estimated. METHODS: The data was derived from the National Family Health Survey which was conducted in 2015-16. The effective sample size for the present paper 699,686 women aged 15-49 years in India. Descriptive statistics along with bivariate analysis were used to do the preliminary analysis. Additionally, binary logistic regression analysis was used to fulfil the objectives. RESULTS: About 1.6% of women had multimorbidity in India. The prevalence of multimorbidity was high among women from southern region of India. Women who smoke tobacco, chew tobacco and consume alcohol had 87% [AOR: 1.87CI: 1.65, 2.10], 18% [AOR: 1.18; CI: 1.10, 1.26] and 18% [AOR: 1.18; CI: 1.04, 1.33] significantly higher likelihood to suffer from multi-morbidity than their counterparts respectively. Population Attributable Risk for women who smoke tobacco was 1.2% (p<0.001), chew tobacco was 0.2% (p<0.001) and it was 0.2% (p<0.001) among women who consumed alcohol. CONCLUSION: The findings indicate the important role of lifestyle and behavioural factors such as smoking and chewing tobacco and consuming alcohol in the prevalence of multimorbidity among adult Indian women. The subgroups identified as at increased risk in the present study can be targeted while making policies and health decisions and appropriate comorbidity management can be implemented.

Lignin: Drug/Gene Delivery and Tissue Engineering Applications.

Lignin is an abundant renewable natural biopolymer. Moreover, a significant development in lignin pretreatment and processing technologies has opened a new window to explore lignin and lignin-based bionanomaterials. In the last decade, lignin has been widely explored in different applications such as drug and gene delivery, tissue engineering, food science, water purification, biofuels, environmental, pharmaceuticals, nutraceutical, catalysis, and other interesting low-value-added energy applications. The complex nature and antioxidant, antimicrobial, and biocompatibility of lignin attracted its use in various biomedical applications because of ease of functionalization, availability of diverse functional sites, tunable physicochemical and mechanical properties. In addition to it, its diverse properties such as reactivity towards oxygen radical, metal chelation, renewable nature, biodegradability, favorable interaction with cells, nature to mimic the extracellular environment, and ease of nanoparticles preparation make it a very interesting material for biomedical use. Tremendous progress has been made in drug delivery and tissue engineering in recent years. However, still, it remains challenging to identify an ideal and compatible nanomaterial for biomedical applications. In this review, recent progress of lignin towards biomedical applications especially in drug delivery and in tissue engineering along with challenges, future possibilities have been comprehensively reviewed.

Total Synthesis of an Immunogenic Trehalose Phospholipid from Salmonella Typhi and Elucidation of Its sn-Regiochemistry by Mass Spectrometry.

Diphosphatidyltrehalose (diPT) is an immunogenic glycolipid, recently isolated from Salmonella Typhi. Despite rigorous structure elucidation, the sn-position of the acyl chains on the glycerol backbone had not been unequivocally established. A stereoselective synthesis of diPT and its regioisomer is reported herein. Using a hybrid MS3 approach combining collisional dissociation and ultraviolet photodissociation mass spectrometry for analysis of the regioisomers and natural diPT, the regiochemistry of the acyl chains of this abundant immunostimulatory glycolipid was established.

Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria.

Salmonella species are among the world's most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6'-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6'-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.

Formal Total Synthesis of Amphidinolide Q.

With the preparation of macrolactone 33a we describe a formal total synthesis of amphidinolide Q. The corresponding seco acid 32 originated from an aldol reaction between methyl ketone 6 and methyl (E)-3-methyl-4-oxobut-2-enoate (5). The synthesis of ketone 6 (C5-C16 fragment) started with desymmetrized meso-diol 9. Chain extension reactions involving cyanide, lithium trimethylsilylacetylide, and a Wittig reaction led to aldehyde 22. The two additional stereocenters at C11 and C13 were set by a Noyori transfer hydrogenation on alkynone 14 and a Feringa-Minnaard methyl cuprate addition on enoate 21. The but-1-ene-2-yl subunit on the side chain terminus was created from an unsaturated aldehyde by a substitution reaction on a derived allylic tosylate.

Twist1 induces distinct cell states depending on TGFBR1-activation.

Basic helix-loop-helix transcription factor Twist1 is a master regulator of Epithelial-Mesenchymal Transition (EMT), a cellular program implicated in different stages of development as well as metastatic dissemination of carcinomas. Here, we show that Twist1 requires TGF-beta type-I receptor (TGFBR1)-activation to bind an enhancer region of downstream effector ZEB1, thereby inducing ZEB1 transcription and EMT. When TGFBR1-phosphorylation is inhibited, Twist1 generates a distinct cell state characterized by collective invasion, simultaneous proliferation and expression of endothelial markers. By contrast, TGFBR1-activation directs Twist1 to induce stable mesenchymal transdifferentiation through EMT, thereby generating cells that display single-cell invasion, but lose their proliferative capacity. In conclusion, preventing Twist1-induced EMT by inhibiting TGFß-signaling does not generally block acquisition of invasion, but switches mode from single-cell/non-proliferative to collective/proliferative. Together, these data reveal that transient Twist1-activation induces distinct cell states depending on signaling context and caution against the use of TGFß-inhibitors as a therapeutic strategy to target invasiveness.