Influence of egg parasitic fungus, Engyodontium aranearum against root knot nematode, Meloidogyne incognita

The indigenous egg parasitic fungal isolates, Engyodontium aranearum was evaluated for its nematicidal potential against root knot nematode, Meloidogyne incognita. The study revealed 53.75 per cent egg parasitization by the fungal isolate. Fungal colonies grew over the eggs and fungal hyphae penetrated the egg shells resulting in rupturing of egg shell layers, enzymatic digestion and empty eggs. The fungal culture filtrate was found to inhibit egg hatching by 83.42 per cent and caused upto 91.36 per cent juvenile mortality. This isolate also reduced the attraction of infective juveniles towards tomato root by 79.29 per cent. It seems to be a first report on the antinemic property of the fungus E. aranearum against root knot nematode, M. incognita and its effect was found comparable with Paecilomyces lilacinus which is known as an efficient nematode egg parasitic fungus

A multi-center, open-labeled, cluster-randomized study of the safety of double and triple drug community mass drug administration for lymphatic filariasis

BackgroundThe Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings.Methods and findingsLarge community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P ConclusionsIn this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA.Trial registrationClinicaltrials.gov registration number: NCT02899936

Point prevalence surveys of antimicrobial use among eight neonatal intensive care units in India: 2016

BACKGROUND: Information about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs). METHODS: As part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials. RESULTS: A total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%). CONCLUSIONS: The recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis

The risk of lung cancer related to dietary intake of flavonoids

It has been hypothesized that flavonoids in foods and beverages may reduce cancer risk through antioxidation, inhibition of inflammation, and other antimutagenic and antiproliferative properties. We examined associations between intake of five flavonoid subclasses (anthocyanidins, flavan-3-ols, flavones, flavonols, flavanones) and lung cancer risk in a population-based case-control study in Montreal, Canada (1,061 cases and 1,425 controls). Flavonoid intake was estimated from a food frequency questionnaire that assessed diet two years prior to diagnosis (cases) or interview (controls). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Overall, total flavonoid intake was not associated with lung cancer risk, the effect being similar regardless of sex and smoking level. However, low flavonoid intake from food, but not from beverages, was associated with an increased risk. The adjusted ORs (95% CIs) comparing the highest versus the lowest quartiles of intake were 0.63 (0.47-0.85) for total flavonoids, 0.82 (0.61-1.11) for anthocyanidins, 0.67 (0.50-0.90) for flavan-3-ols, 0.68 (0.50-0.93) for flavones, 0.62 (0.45-0.84) for flavonols, and 0.70 (0.53-0.94) for flavanones. An inverse association with total flavone and flavanone intake was observed for squamous cell carcinoma but not adenocarcinoma. In conclusion, low flavonoid intake from food may increase lung cancer risk

Association between primary hypothyroidism and metabolic syndrome and the role of C reactive protein: a cross–sectional study from South India

<p>Abstract</p> <p>Background</p> <p>Hypothyroidism (sub-clinical and overt) and metabolic syndrome are recognized risk factors for atherosclerotic cardiovascular disease. This study is an effort to identify the proposed association between these two disease entities and the risk factors involved in this association.</p> <p>Methods</p> <p>A cross – sectional study from a tertiary care teaching hospital in Chennai city, South India. 420 patients with metabolic syndrome (NCEP – ATP III criteria) were included in the study group. 406 appropriately age and sex matched controls having no features of metabolic syndrome (0 out of the 5 criteria) were compared with the study group. The study extended over a 5 year period. TSH, FT4 were measured for both the groups using electrochemiluminescence immuno assay. HsCRP was measured for all the patients in the study group. The baseline characteristics between the groups were compared with Student's't' test. Chi-square test was used to analyze the association between metabolic syndrome and hypothyroidism (overt and sub-clinical). Logistic regression analysis was applied to identify the association between hypothyroidism and the patient characteristics in the study group.</p> <p>Results</p> <p>Of the 420 patients in the study group, 240 were females (57.1%), 180 were males (42.9%) with mean age 51 ± 9.4 years. Of the 406 patients in the control group, 216 were females (53.2%), 190 males (46.8%) with mean age 49 ± 11.2 years. In the study group, 92 had sub-clinical hypothyroidism (SCH) (21.9%), 31 were overtly hypothyroid (7.4%) and 297 were euthyroid (70.7%). In the control group 27 patients had sub-clinical hypothyroidism (6.6%), 9 patients had overt hypothyroidism (2.2%) and 370 patients were euthyroid (91.2%). On comparison SCH (P < 0.001) and overt hypothyroidism (P < 0.001) were significantly associated with the study group as compared to the control group. Logistic regression analysis recognized the association between female gender (P = 0.021) and HsCRP (P = 0.014) with sub-clinical hypothyroidism and female gender (P = 0.01) with overt hypothyroidism in the study group.</p> <p>Conclusion</p> <p>Hypothyroidism is associated with metabolic syndrome and females are more at risk. Metabolic syndrome patients with a raised HsCRP are at significant risk of having sub-clinical hypothyroidism.</p

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR–validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.National Institutes of Health (U.S.)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (NIAMS) (K08-AR054615))National Cancer Institute (U.S.) (NIH/(NCI) (R01-CA118750))National Cancer Institute (U.S.) (NIH/(NCI) R01-CA130795))Juvenile Diabetes Research Foundation InternationalAmerican Cancer SocietyHoward Hughes Medical Institute (Early career scientist)Stanford University (Graduate Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship

The impact of priming on dentally induced social judgements: An experimental study

ObjectiveTo ascertain the effects of priming to consider tooth appearance (i.e. exposure to a ‘tooth whitening television advert’) versus control (a ‘non-dental’ television advert) on social judgements of tooth colour in a group of Caucasians.MethodsTwo groups of Caucasians randomly assigned to watch either a tooth-whitening advert (experimental, N = 67) or a bread advert (control, N = 62). All rated the measures of social perceptions: friendliness, popularity, social life, success, intelligence, graduation, introversion/extroversion, happiness, self-confidence, attractiveness, age-estimation and satisfaction, after watching either of the adverts and viewing three digitally modified photographs (Darkened, natural and whitened teeth) of different Caucasian adults (males and females) separately.ResultsThere were no statistically significant differences for all the measures of social perception between the groups. Nevertheless, the questions that inquired about popularity, friendliness, success, intelligence, happiness, self-confidence, attractiveness and satisfaction were consistently rated higher for all three tooth shades in the experimental than the control groups. Further, within the experimental and control groups, higher ratings were given to the faces with whitened teeth than the natural and darkened teeth.ConclusionsPriming has little impact on dentally induced social judgements as this study failed to demonstrate statistically significant differences. Nevertheless, both groups gave the highest subjective ratings for the faces with whitened teeth and the tooth-whitening advert group associated the faces in the photographs with higher subjective ratings than the non-dental advert group irrespective of the tooth shade. One reason for this could be the way media affects the psychological well-being.Clinical significance statementThe almost universal exposure to idealised tooth appearance in the media may increase demand for aesthetic treatments. Standardising the colour of the tooth plays a huge impact and making individuals to view a tooth whitening advert just prior to a procedure might influence patient choices.</p

A Legionella toxin exhibits tRNA mimicry and glycosyl transferase activity to target the translation machinery and trigger a ribotoxic stress response

A widespread strategy employed by pathogens to establish infection is to inhibit host-cell protein synthesis. Legionella pneumophila, an intracellular bacterial pathogen and the causative organism of Legionnaires' disease, secretes a subset of protein effectors into host cells that inhibit translation elongation. Mechanistic insights into how the bacterium targets translation elongation remain poorly defined. We report here that the Legionella effector SidI functions in an unprecedented way as a transfer-RNA mimic that directly binds to and glycosylates the ribosome. The 3.1 Å cryo-electron microscopy structure of SidI reveals an N-terminal domain with an 'inverted L' shape and surface-charge distribution characteristic of tRNA mimicry, and a C-terminal domain that adopts a glycosyl transferase fold that licenses SidI to utilize GDP-mannose as a sugar precursor. This coupling of tRNA mimicry and enzymatic action endows SidI with the ability to block protein synthesis with a potency comparable to ricin, one of the most powerful toxins known. In Legionella-infected cells, the translational pausing activated by SidI elicits a stress response signature mimicking the ribotoxic stress response, which is activated by elongation inhibitors that induce ribosome collisions. SidI-mediated effects on the ribosome activate the stress kinases ZAKα and p38, which in turn drive an accumulation of the protein activating transcription factor 3 (ATF3). Intriguingly, ATF3 escapes the translation block imposed by SidI, translocates to the nucleus and orchestrates the transcription of stress-inducible genes that promote cell death, revealing a major role for ATF3 in the response to collided ribosome stress. Together, our findings elucidate a novel mechanism by which a pathogenic bacterium employs tRNA mimicry to hijack a ribosome-to-nuclear signalling pathway that regulates cell fate

Outpatient Administration of Car T-Cell Therapies Using a Strategy of No Remote Monitoring and Early CRS Intervention

Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days and then twice weekly through day 30. The primary end point was to determine 3-, 7-, and 30-day post-CAR T-cell infusion hospitalizations. Early CRS intervention involved administering tocilizumab as an outpatient for grade ≥1 CRS. Fifty-eight patients received outpatient CAR T-cell infusion (33 myeloma, 24 lymphoma, and 1 acute lymphoblastic leukemia). Of these, 17 (41%), 16 (38%), and 9 patients (21%) were admitted between days 0 to 3, 4 to 7, and 8 to 30 after CAR T-cell infusion, respectively. The most common reason for admission was CAR T-cell-related toxicities (33/42). Hospitalization was prevented in 15 of 35 patients who received tocilizumab for CRS as an outpatient. The nonrelapse mortality rates were 1.7% at 1 month and 3.4% at 6 months. In conclusion, we demonstrate that the administration of commercial CAR T-cell therapies in an outpatient setting is safe and feasible without intensive remote monitoring using an early CRS intervention strategy