CCR9 signaling in dendritic cells drives the differentiation of Foxp3+ Tregs and suppresses the allergic IgE response in the gut

The chemokine receptor CCR9 and its only known ligand CCL25 play an important role in gut inflammation and autoimmune colitis. The function of CCR9-CCL25 in the migration of immune cells is well characterized. However, its role in the immune cell differentiation is mostly not known. Using dextran sodium sulfate (DSS)-induced gut inflammation model, we showed that CCR9⁺ dendritic cells (DCs) specifically CD11b⁻CD103⁺ DCs were significantly increased in the gut-associated lymphoid tissues (GALT) compared to control mice. These CCR9⁺ DCs express lower MHC II and CD86 molecules and had regulatory surface markers (FasL and latency-associated peptide, LAP) in the GALT. In the presence of CCL25, CCR9⁺ DCs promoted in vitro differentiation of Foxp3⁺ regulatory CD4⁺ T cells (Tregs). CCL25-induced differentiation of Tregs was due to intrinsic signaling in the DCs but not through CD4⁺ T cells, which was driven by the production of thymic stromal lymphopoietin (TSLP) and not IL-10. Furthermore, adoptive transfer of CCR9⁺ DCs in C57BL/6 mice promoted Tregs but reduced the Th17 cells in the GALT, and also suppressed the OVA-specific gut-allergic response. Our results suggest CCR9⁺ DCs have a regulatory function and may provide a new cellular therapeutic strategy to control gut inflammation and allergic immune reaction.     

Areca catechu—From farm to food and biomedical applications

The family Arecaceae includes 181 genera and 2,600 species with a high diversity in physical characteristics. Areca plants, commonly palms, which are able to grow in nearly every type of habitat, prefer tropical and subtropical climates. The most studied species Areca catechu L. contains phytochemicals as phenolics and alkaloids with biological properties. The phenolics are mainly distributed in roots followed by fresh unripe fruits, leaves, spikes, and veins, while the contents of alkaloids are in the order of roots, fresh unripe fruits, spikes, leaves, and veins. This species has been reputed to provide health effects on the cardiovascular, respiratory, nervous, metabolic, gastrointestinal, and reproductive systems. However, in many developing countries, quid from this species has been associated with side effects, which include the destruction of the teeth, impairment of oral hygiene, bronchial asthma, or oral cancer. Despite these side effects, which are also mentioned in this work, the present review collects the main results of biological properties of the phytochemicals in A. catechu. This study emphasizes the in vitro and in vivo antioxidant, antimicrobial, anticancer, and clinical effectiveness in humans. In this sense, A. catechu have demonstrated effectiveness in several reports through in vitro and in vivo experiments on disorders such as antimicrobial, antioxidant, or anticancer. Moreover, our findings demonstrate that this species presents clinical effectiveness on neurological disorders. Hence, A. catechu extracts could be used as a bioactive ingredient for functional food, nutraceuticals, or cosmeceuticals. However, further studies, especially extensive and comprehensive clinical trials, are recommended for the use of Areca in the treatment of diseases.     

Evaluation of third molar maturity index (I3M) in assessing the legal age of subjects in an Indian Goan population

India affords special laws and exemptions to minors under the criminal, marriage, labour and administrative laws. Many perpetrators claim to be a minor in the hope of a lenient trial and verdict. The authorities often rely upon forensic experts to provide evidence-based reports. The third molar can be relied upon in the assessment of legal age as it continues developing into the early twenties. The method established by Cameriere et al in 2008 provides an objective method for the accurate evaluation of legal age. Our study was designed to analyze and validate the efficacy of Third Molar Maturity index (I3M) in an Indian Goan population and compare it to published literature. 542 panoramic radiographs of subjects aged between 14 and 24 years were evaluated. The chronologic age increased as I3M reduced. There was no evidence of sexual dimorphism in third molar development across various I3M classes (p>0.05). Receiver Operator Characteristic Curve was plotted for males and females which showed an Area Under Curve of 0.95 (95% CI, 0.92-0.97) and 0.93 (95% CI, 0.90-0.96) respectively. 2x2 contingency tables were used to test the performance of various I3M cut-off values ranging from I3M=0.02 to 0.14. I3M = 0.08 showed the most promising results for the assessment of legal age. Our study achieved a high degree of accurate classification of 0.90 and 0.88 for males and females respectively. Results demonstrate a sensitivity of 0.899 and 0.854 and specificity of 0.90 and 0.93 for males and females respectively. The positive likelihood ratios were 9.88 and 12.44 while negative likelihood ratio was 0.11 and 0.15 for males and females respectively. A favourable Bayes Post Test Probability of 0.95 was noted for both males and females. These results allow us to strongly recommend the use of I3M for the assessment of legal age in an Indian Goan population.     

Relative Prevalence and Outcome of Fetal Neural Tube Defect in a Developing Country

Objectives

To find out the relative prevalence of fetal neural tube defect (NTD) and its outcome in terms of survival at birth and beyond 2 years of age.

Methods

A 10-year prospective (2008–2018) observational study was performed, which included all prenatally detected fetal NTD. Two-year follow-up was done in cases of pregnancies resulting in live birth, in terms of their survival, physical morbidity and developmental delay.

Results

NTD was seen in 401/648 (62%) cases among the central nervous system malformations. More than half of the cases (54.1%) presented after 20 weeks of gestation, and 42.8% of the mothers were primiparous. Spina bifida was seen in 206 cases, anencephaly in 144, encephalocele in 43, whereas iniencephaly was seen in only eight cases. Associated anomalies were present in 51.2%. Only 19.0% cases were live-born, and merely 11% were alive beyond 2 years of age. Among types of spina bifida, lumbosacral meningomyocele was the most common (41.6%), whereas thoracic was the rarest (8.7%). After 2 years, physical disability was observed in more than half of the cases who survived.

Conclusions

NTD is one of the commonest malformations with high mortality, and the physical and mental sub-normality is high among those who survive.

     

Intradialytic hypotension and vascular access thrombosis

Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.     

Circulatory and hepatic failure at admission predicts mortality of severe scrub typhus patients: A prospective cohort study

Objective: To study the spectrum and outcome of severe scrub typhus in adult patients and to predict the hospital mortality by organ failure on admission.Methods: This was a prospective observational cohort study conducted between July 2017 and October 2020 at the medical emergency centre of PGIMER, Chandigarh, India. One hundred and twenty-six patients aged ≥13 years were diagnosed with scrub typhus. Severe disease was defined as the presence of organ failure based on the Sequential Organ Failure Assessment(SOFA) score on admission.Results: About two-thirds of the patients were from geographic regions outside the endemic sub-Himalayan belt. Fever(99.21%) and dyspnea(79.36%) were the most frequent complaints. Respiratory failure(81.75%) was the most common organ failure, followed by hepatic(52.38%), coagulative(47.62%), circulatory(33.33%), renal(21.43%), and cerebral dysfunction(13.49%). The median(Q1, Q3) SOFA score was 8(6, 9), and 48.41% of the patients had a quick-SOFA score ≥2. Organ supports with invasive ventilation(40.48%), vasopressors(36.51%), and renal replacement therapy(7.14%) were frequently required. The in-hospital mortality was 11.90% and was independently predicted by circulatory and hepatic failures on multivariate logistic regression(OR 11.12, 95% CI 1.73-71.31 and OR 8.49, 95% CI 1.18-61.41, respectively).Conclusions: Most patients had pulmonary dysfunction; circulatory or hepatic failure on admission strongly predicts death.