Variability in addictive and carcinogenic potential of smokeless tobacco products marketed in Mumbai, India: a surveillance study.

Background: India has the highest incidence worldwide of smokeless tobacco (SLT)-associated oral cancer, accounting for nearly 70% of all SLT users globally. Nicotine and tobacco-specific N-nitrosamines (TSNA) play critical roles in the addictive and carcinogenic potential, respectively, of SLT products. Our group has previously reported substantial variability in nicotine and TSNA levels across a small SLT product sample in India, calling for systematic surveillance. However, there is no information available on the current levels of these constituents in Indian SLT. Methods: We analysed 321 samples representing 57 brands of eight popular types of manufactured SLT products purchased from five local markets in Mumbai, India between August, and September 2019. The sampling locations were Mumbai Central, Kurla, Thane, Vashi, and Airoli. Product pH, moisture content, total and unprotonated (biologically available) nicotine, and TSNA levels were measured at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbai. Findings: Total nicotine content ranged from 0.45 to 35.1 mg/g across products. The unprotonated nicotine fraction contributed 0.1-100% of the total nicotine content. The carcinogenic TSNA levels ranged 0.06-76 ug/g for N'-nitrosonornicotine (NNN), 0.02-19.2 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 0.01-6.51 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Consistent with our previous study, we observed substantial variations across different brands of the same product type. Interpretation: This is the most extensive and the first within-country study to report brand-specific nicotine and TSNA levels in SLT products marketed in Mumbai, India. Our results show that levels of these constituents remain extremely variable across Indian SLT and are strikingly high in many products. Enhanced public education and continued efforts to reduce SLT use prevalence in India are critical for reducing the global burden of SLT-associated morbidity and mortality. Regulation of nicotine and TSNA levels in SLT products should be considered. Funding: This work was supported by the National Institutes of Health (USA) grant R01-TW010651 and, in part, by grants R01-CA180880 and R50-CA211256. The LC-MS/MS analysis was supported in part by XII Plan project funding from the Department of Atomic Energy, Government of India.

Antibiotic Diversity Index: A novel metric to assess antibiotic variation among hospitalized children.

BACKGROUND: Despite nationally endorsed treatment guidelines and stewardship programs, variation and deviation from evidence-based antibiotic prescribing occur, contributing to inappropriate use and medication-related adverse events. Measures of antibiotic prescribing variability can aid in quantifying this problem but are not adequate. OBJECTIVE: The objective of this study is to develop a standardized metric to quantify antibiotic prescribing variability (diversity) within and across children's hospitals, and to examine its association with outcomes. METHODS: We performed a cross-sectional study of empiric antibiotic exposure among children hospitalized during 2017-2019 with one of 15 common pediatric infections using the Pediatric Health Information System database. Encounters for children with complex chronic conditions, transfers in, and birth hospitalizations were excluded. Using the Shannon-Weiner entropy index, we quantified antibiotic diversity for each infection type using the d-measure of diversity. Generalized linear mixed-effects models were used to examine the association between hospital-level antibiotic diversity and risk-adjusted length of stay and costs. RESULTS: A total of 79,515 hospitalizations for common pediatric infections were included. Antibiotic diversity varied within and across hospitals. Infections with low mean antibiotic diversity included appendicitis (mean diversity [mDiv] = 4.9, SD = 2.5) and deep neck space infections (mDiv = 5.9, SD = 1.9). Infections with high mean antibiotic diversity included pneumonia (mDiv = 23.4, SD = 5.6) and septicemia/bacteremia (mDiv = 28.5, SD = 12.1). There was no statistically significant association between hospital-level antibiotic diversity and risk-adjusted LOS or costs. CONCLUSIONS: We developed and applied a novel metric to quantify diversity in antibiotic prescribing that permits comparisons across hospitals and can be leveraged to identify high-priority areas for local and national stewardship interventions.

Using Low-cost Videoscopes to Obtain Accurate Video "Oral Selfies" as Screening for HPV-associated Oropharyngeal Cancer: A New Screening Technology?

Human papillomavirus (HPV)-related oropharyngeal cancers associated with sexual contact are increasing, with high rates in men who have sex with men. HPV-related cancers have the advantage of being frequently detectable through oropharyngeal visual examination and having much higher survival rates than classic oropharyngeal cancers. It has been demonstrated that gay and bisexual men can take smartphone oropharyngeal "selfies" of sufficient quality for screening. However, there is an issue with the inability to move the tongue to allow a clear view of the palatine tonsils, where a majority of oropharyngeal cancer cases occur. We attempted to investigate the feasibility of using commercially available videoscopes to visualize the oropharynx. Fourteen healthy volunteers used a provided low-cost commercial endoscope to video their oropharynx. Participants used the videoscope connected to a laptop and could visualize the oropharynx on the screen. Attempts were observed, and the process was noted. A focus group of participants was carried out immediately afterwards to ascertain barriers and facilitators to using the videoscopes. All participants were able to use the videoscope and obtain videos of sufficient clarity to note major oropharyngeal landmarks. The palatine tonsils were initially difficult to visualize because the tongue could not be sufficiently controlled. Participants were given time to practice using visual cues to control the position of the tongue, which helped in obtaining good videos. Videoscopes can be used effectively with minimal instruction and provide a better view than still images, as they illuminate and magnify the site. Low-cost commercially available videoscopes may be an improvement over smartphone "selfies".

Grazing camels under semi-extensive production system: selectivity, feed intake capacity, digestion and energy expenditure.

BACKGROUND: It was proposed that camels are more effective than other livestock species in selecting plants for their nutritional value. They may self-regulate their voluntary feed intake to satisfy their nutritional needs. This study was designed to investigate camels' feeding selectivity and ability to cover nutritional requirements when grazing alfalfa (high in protein) and/ or barley (high in energy) in a desert climate. METHODS: Eighteen lactating camels were equally divided into three feeding treatments. They grazed daily on alfalfa, barley, or a mixed pasture of both, for two periods of one month each. The concentrate supplement was individually administered at 40 g/kg BW0.75, divided into two equal parts, in the morning and in afternoon. Total energy expenditure (EE) was estimated by heart rate (HR) monitors for 48 h after being calibrated by oxygen consumption using an upgraded face mask open-circuit respiratory system. RESULTS: During the first period, camels had a greater forage intake and digestibility when they grazed barley rather than alfalfa, while those grazing mixed pasture performed intermediately. In the second period, camels had a similar forage intake and digestibility among treatments due to a decline in barley intake and digestibility compared to the first period, which was expected since the preferred plant part gradually shifted from barley grains to predominantly straw as a function of time. Similar HR and EE were found across periods and treatments. As a result of greater gross and digestible energy intake in period 1, a better energy balance in period 1 was observed compared to period 2. Camels better utilize barley than alfalfa. Grazing on barley had a higher energy balance than grazing alfalfa alone or in combination with barley. However, camels grazing barley produced lower milk yield and energy than those grazing alfalfa alone or in combination with barley, with no interaction detected between period and treatment. CONCLUSIONS: Lactating camels are able to self-regulate their voluntary intake to cover their energy requirements when they are grazing barley and/or alfalfa supplemented with a concentrate supplement at 40 g/kg BW0.75. Grazing barley is better utilized by camels than alfalfa. The chemical and physical properties of plant species play an important role in the selectivity of foraging camels. It also impacts their intake and digestibility, which is negatively associated with the proportion of cell wall content consumed.

Intraoperative margin assessment with near real time pathology during partial gland ablation of prostate cancer: A feasibility study.

BACKGROUND: In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. METHODS: About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. RESULTS: Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. CONCLUSION: SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted.

Chemotaxonomy compared to morphological and anatomical taxonomy of five Hibiscus species.

Hibiscus is a charismatic genus of the Malvaceae family that is noted for its diversity, lacking identifiable characteristics for distinguishing its various species. Therefore, there is an urgent need to develop authentication methods for genus delimitation and species delineation. The present study aims to discern the taxonomic relationships between the well-known, globally familiar, and economically important five Hibiscus species, namely: H. × rosa-sinensis, H. sabdariffa, H. schizopetalus, H. syriacus and H. tiliaceus based on traditional morphological and anatomical characteristics compared to the contemporary chemotaxonomy. In this context, the leaf-based methanolic extracts of the studied species were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS) to estimate their secondary metabolites similarity. In addition, selected qualitative morphological and anatomical traits including leaf venation patterns, epidermal micromorphology, stomata types and trichomes diversity, petiole serial sectioning (outline, adaxial groove features, vasculature traces arrangement), and midrib characteristics of the studied species were investigated. The results of both chemotaxonomy and traditional taxonomy exhibited a remarkable agreement in the delineation of the five studied species. Specifically, the chemotaxonomy-based dendrogram separates the studied species into two main clusters with the H. sabdariffa as an outlier species in a single cluster and the remaining four species as another cluster with variant distances in its similarity indices. Similarly, the traditional morphological and anatomical characteristics revealed distinct traits for H. sabdariffa compared to the remaining four species. The findings of this study highlight the significance of integrating the structural features with phytochemicals profiling as a potential approach that could be harnessed for the delineation of the taxonomically challenging Hibiscus genus.

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In this narrative medicine essay, a pediatric infectious disease physician relates how he has learned to understand the protective role of code-shifting in his life and how that understanding has aided him in promoting an inclusive environment in academic medicine.

Single cell regulatory architecture of human pancreatic islets suggests sex differences in ß cell function and the pathogenesis of type 2 diabetes.

Type 2 and type 1 diabetes (T2D, T1D) exhibit sex differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), hormone secretion, and bioenergetics. In nondiabetic (ND) donors, sex differences in islet cells gene accessibility and expression predominantly involved sex chromosomes. Islets from T2D donors exhibited similar sex differences in sex chromosomes differentially expressed genes (DEGs), but also exhibited sex differences in autosomal genes. Comparing ß cells from T2D vs. ND donors, gene enrichment of female ß cells showed suppression in mitochondrial respiration, while male ß cells exhibited suppressed insulin secretion. Thus, although sex differences in gene accessibility and expression of ND ß cells predominantly affect sex chromosomes, the transition to T2D reveals sex differences in autosomes highlighting mitochondrial failure in females.

Fibula Free Flap Reconstruction of Cervical Spine Defects: A Multi-Institutional Study.

INTRODUCTION: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique. METHOD: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected. RESULTS: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion. CONCLUSION: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Predictors of Contralateral Disease in Men With Unilateral Lesions on Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: To evaluate predictors of contralateral clinically significant prostate cancer (csPCa) in men with biopsy-proven unilateral lesions on magnetic resonance imaging (MRI). METHODS: We retrospectively identified men with no prior diagnosis of PCa with unilateral biopsy-confirmed csPCa within PI-RADS 2-5 lesions within our institutional biopsy database. Multivariate logistic regression was used to identify clinical predictors of contralateral disease. RESULTS: Four hundred ninety men met study inclusion criteria, of which 385 men (78.6%) had no contralateral csPCa and 105 men (21.4%) had contralateral csPCa (Fig. 1). Prior negative biopsy (OR 0.34 [0.14, 0.75], P = .012), prostate-specific antigen density (OR 18.8 [2.77, 249], P = .017), and tumor location in the transverse plane ("Posterior": OR 1.93 [1.02, 3.87], P = .048; "Throughout Transverse Plane": OR 6.56 [2.26, 19.6], P < .001) were significantly associated with contralateral csPCa in multivariate logistic regression models. However, there appear to be no attributes within the MRI-targeted tumor that reliably predict contralateral csPCa (Table 2). CONCLUSION: Approximately 20% of men with unilateral MRI findings and csPCa on targeted biopsy were found to have contralateral csPCa on systematic biopsy (SB). Prior negative biopsy was associated with a decreased odds of contralateral csPCa. Prostate-specific antigen density and tumor in the posterior aspect of or throughout the transverse plane were associated with increased odds of contralateral csPCA. Consideration of these clinical factors may afford an opportunity to only use SB in cases in which the odds of contralateral csPCa are high.

Clinician Perspectives on Continuous Monitor Use in a Children's Hospital: A Qualitative Study.

BACKGROUND AND OBJECTIVES: Variation in continuous cardiopulmonary monitor (cCPM) use across children's hospitals suggests preference-based use. We sought to understand how clinical providers make decisions to use cCPMs. METHODS: We conducted a qualitative study using semi-structed interviews with clinicians (nurses, respiratory therapists [RTs], and resident and attending physicians) from 2 hospital medicine units at a children's hospital. The interview guide employed patient cases and open-ended prompts to elicit information about workflows and decision-making related to cCPM, and we collected basic demographic information about participants. We used an inductive approach following thematic analysis to code transcripts and create themes. RESULTS: We interviewed 5 nurses, 5 RTs, 7 residents, and 7 attending physicians. We discovered that clinicians perceive a low threshold for starting cCPM, and this often occurred as a default action at admission. Clinicians thought of cCPMs as helping them cope with uncertainty. Despite acknowledging considerable flaws in how cCPMs were used, they were perceived as a low-risk intervention. Although RNs and RTs were most aware of the patient's current condition and number of alarms, physicians decided when to discontinue monitors. No structured process for identifying when to discontinue monitors existed. CONCLUSIONS: We concluded that nurses, physicians, and RTs often default to cCPM use and lack a standardized process for identifying when cCPM should be discontinued. Interventions aiming to reduce monitor use will need to account for or target these factors.