Notes

Monocytes and also macrophages throughout ANCA-associated vasculitis.
Phytosterols are bioactive food components widely present in cell membranes of plants, especially in nuts and oilseeds. In recent years, many studies have shown that phytosterols possess therapeutic potentials for nonalcoholic fatty liver disease (NAFLD). This review summarizes the effects of phytosterols from in vitro and in vivo studies to lower the levels of total cholesterol (TC) and triglycerides (TG), and the evidence supporting the potential of phytosterols against NAFLD. The potential mechanisms by which phytosterols improve NAFLD may include (i) competition with cholesterol; (ii) regulation of key factors involved in cholesterol and TG metabolism; and (iii) inhibition of liver inflammation and (iv) regulation of liver fatty acid composition. In summary, phytosterols are potential natural ingredients with good safety profile against NAFLD, which deserve more future studies.
We evaluated whether combining a humanized antidisialoganglioside monoclonal antibody (hu14.18K322A) throughout therapy improves early response and outcomes in children with newly diagnosed high-risk neuroblastoma.

We conducted a prospective, single-arm, three-stage, phase II clinical trial. Six cycles of induction chemotherapy were coadministered with hu14.18K322A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose interleukin-2 (IL-2). The consolidation regimen included busulfan and melphalan. fMLP When available, an additional cycle of parent-derived natural killer cells with hu14.18K322A was administered during consolidation (n = 31). Radiation therapy was administered at the end of consolidation. Postconsolidation treatment included hu14.18K322A, GM-CSF, IL-2, and isotretinoin. Early response was assessed after the first two cycles of induction therapy. End-of-induction response, event-free survival (EFS), and overall survival (OS) were evaluated.

Sixty-four patients received hu14.1dding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of-induction response rates, and yielded an encouraging 3-year EFS. These results, if validated in a larger study, may be practice changing.I've had serious misgivings about writing this article, because from living the experience day by day, it's hard to believe my accomplishments merit the attention. To skirt this roadblock, I forced myself to pretend I was in a conversation with my trainees, trying to distill the central driving forces of my career in science. The below chronicles my evolution from would-be astronaut/ballerina to budding developmental biologist to devoted T cell immunologist. It traces my work from a focus on intrathymic events that mold developing T cells into self-major histocompatibility complex (MHC)-restricted lymphocytes to extrathymic events that fine-tune the T cell receptor (TCR) repertoire and impose the finishing touches on T cell maturation. It is a story of a few personal attributes multiplied by generous mentors, good luck, hard work, perseverance, and knowing when to step down. Expected final online publication date for the Annual Review of Immunology, Volume 40 is April 2022. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.
The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment.

This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (11) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopatys a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.Background Feeding abilities of preterm neonates differ based on their gestational and postnatal maturity. Maturity of sucking pattern and improved coordination between sucking and swallowing and breathing, which is seen in babies with a gestation of 32 weeks onward, makes trial of oral feeds more successful in these babies. The oral feeds can be given either with a cup and spoon or a paladai. However, we observed that the milk spilt during feeding was an issue due to a wider spout of the paladai. Feeding through syringe is practiced in many neonatal units. However, there is a lack of scientific literature regarding the syringe feeding of neonates. We hypothesized that giving oral feeds using a syringe could reduce the spillage of milk. This study was done to compare the volume of feeds wasted (spillover) during oral feeding between paladai and syringe feeding. Methods The order of feeding of 75 nurse baby pairs was randomized to either the syringe or the paladai groups. The volume of milk spilt was assessed by weighing a gauze pad placed under the neck of the baby before and after feeds. Time taken to complete the feeds, the rate of feeding, and events like vomiting and choking after feeding were noted. Feeding satisfaction among the nurses was recorded on a 5-point Likert scale. Results The average mean time for completion of feeds by paladai was 9 minutes against 8.9 minutes in syringe feeding. The median rate of feeding was 3.57 minutes in the paladai group and 3.5 minutes in the syringe group. The median spillover volume was 3.33 mL in the paladai feeds and 3.23 mL in the intervention group. Seventy percent of the nurses reported better satisfaction with syringe feeds compared to paladai feeds. Conclusion This study demonstrates that the milk spillover (wastage) during syringe feeding is not different from paladai feeds. However, the majority of nurses felt the syringe feeding was more satisfactory than paladai feeding. CTRI Reg. No CTRI/2021/05/033479 dated 07.05.2021.Bedaquiline is a diarylquinoline antimycobacterial drug and a key component of several regimens in clinical development for the treatment of tuberculosis (TB) but with ongoing phase 3 trials that include assessment of simplified dosing. A pharmacokinetic-pharmacodynamic model of bedaquiline Mycobacterium tuberculosis-killing kinetics in adults with pulmonary TB was developed to inform dose selection of bedaquiline-containing regimens. The model parameters were estimated with data from the 14-day early bactericidal activity (EBA) study TMC207-CL001 conducted in Cape Town, South Africa. The study included 60 adult males and females with drug-susceptible pulmonary TB, who were administered bedaquiline with loading doses on the first 2 days followed by once-daily 100 mg, 200 mg, 300 mg, or 400 mg. The modeling results included expected values (means ± standard deviations [SDs]) for a maximum drug kill rate constant equal to 0.23 ± 0.03 log10 CFU/mL sputum/day, a half-maximum effective plasma concentration equal to 1.6 ± 0.3 mg/L, and an average time to onset of activity equal to 40 ± 7 h. Model simulations showed that once-daily 200 mg, 300 mg, and 400 mg (without loading doses) attained 40%, 50%, and 60%, respectively, of an expected maximum 14-day EBA equal to 0.18 log10 CFU/mL/day, or 10 h/day assessed by liquid culture time to positivity (TTP). Additional simulations illustrated efficacy outcomes during 8 weeks of treatment with the recommended and alternative dosages. The results demonstrate a general mathematical and statistical approach to the analysis of EBA studies with broad application to TB regimen development.Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 ± 0.016, 0.053 ± 0.017, 0.043 ± 0.016, and 0.019 ± 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 ± 0.028 for the HRZE group and 0.154 ± 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483.Kinetoplastid parasites cause diverse neglected diseases in humans and livestock, with an urgent need for new treatments. The survival of kinetoplastids depends on their uniquely structured mitochondrial genome (kDNA), the eponymous kinetoplast. Here, we report the development of a high-content screen for pharmacologically induced kDNA loss, based on specific staining of parasites and automated image analysis. As proof of concept, we screened a diverse set of ∼14,000 small molecules and exemplify a validated hit as a novel kDNA-targeting compound.This study was designed to evaluate the prevalence of antifungal resistance, genetic mechanisms associated with in vitro induction of azole and echinocandin resistance and genotyping of Candida krusei, which is intrinsically resistant to fluconazole and is recovered from clinical and nonclinical sources from different countries. Our results indicated that all the isolates were susceptible or had the wild phenotype (WT) to azoles, amphotericin B, and only 1.27% showed non-WT for flucytosine. Although 70.88% of the isolates were resistant to caspofungin, none of them were categorized as echinocandin-resistant as all were susceptible to micafungin and no FKS1 hot spot 1 (HS1) or HS2 mutations were detected. In vitro induction of azole and echinocandin resistance confirmed the rapid development of resistance at low concentrations of fluconazole (4 μg/ml), voriconazole (0.06 μg/ml), and micafungin (0.03 μg/ml), with no difference between clinical and nonclinical isolates in the resistance development. Overexpression of ABC1 gene and FKS1 HS1 mutations were the major mechanisms responsible for azole and echinocandin resistance, respectively.
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