Total Margin Control Is Superior to Traditional Margin Assessment for Treatment of Low-Stage Penile Squamous Cell Carcinoma.

PURPOSE: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes. MATERIALS AND METHODS: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy. Local recurrence, metastasis, and disease-specific death were assessed via multivariable Cox proportional hazard models. RESULTS: The cohort consisted of 189 patients. Median age at diagnosis was 62 years. Median tumor diameter was 1.3 cm. The following outcomes of interest occurred: 30 local recurrences, 13 metastases, and 5 disease-specific deaths. Primary tumors were excised with PDEMA (N = 30), excision/circumcision (N = 110), or penectomy/glansectomy (N = 49). Of patients treated with traditional margin assessment (non-PDEMA), 12% had narrow or positive margins. Five-year proportions were as follows with respect to local recurrence-free survival, metastasis-free survival, and disease-specific survival/progression-free survival, respectively: 100%, 100%, and 100% following PDEMA; 82%, 96%, and 99% following excision/circumcision; 83%, 91%, and 95% following penectomy/glansectomy. A limitation is that this multi-institutional cohort study was not externally validated. CONCLUSIONS: Initial results are encouraging that PDEMA surgical management effectively controls early-stage penile squamous cell carcinoma.

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study.

BACKGROUND: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. OBJECTIVES: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. METHODS: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. RESULTS: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). CONCLUSIONS: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

Azathioprine hypersensitivity syndrome manifesting as subcutaneous Sweet syndrome and acute pancreatitis.

Azathioprine (AZA) is a commonly used immunosuppressive therapy that has been implicated in a number of cutaneous and systemic inflammatory reactions. Initiation of AZA has been associated with a hypersensitivity syndrome manifesting as acute pancreatitis and Sweet syndrome. Subcutaneous Sweet syndrome is a rare variant of Sweet syndrome where the dominant localization of inflammation is within the subcutaneous fat; it is commonly associated with underlying myeloproliferative disease. However, it has not been reported in the literature as a cutaneous manifestation of AZA hypersensitivity syndrome. We present a unique case of acute pancreatitis and biopsy-proven subcutaneous Sweet syndrome following the initiation of AZA with resolution upon discontinuation.

Serial Subtraction Alters Lateral Step-down Tibiofemoral Kinematics in Healthy Adults.

This study evaluated the effects of two types of cognitive dual-tasking on three-dimensional knee kinematics during the lateral step-down. 19 healthy individuals (22.05±1.61 yrs., 173.92±9.21 cm, 67.99±12.65 kg) participated in this study. Participants completed 5 repetitions of a lateral step-down task for each leg and each testing condition (control, Stroop, and serial subtraction by seven). An electromagnetic motion sensor was attached to the femur via compression clamp placed about the medial and lateral epicondyles. Another sensor was attached 2 cm below the ipsilateral tibial tuberosity. A custom MATLAB algorithm located the knee joint axis of rotation from dynamic knee flexion and extension. Discrete kinematics at peak flexion were used in this study. Paired samples t-tests were used to compare average frontal, transverse, and sagittal plane knee position at maximum flexion between conditions for each leg. No significant differences were found for either limb between control and Stroop conditions. Comparisons revealed significant differences in frontal and transverse plane knee angles at peak flexion between the control and serial subtraction by seven conditions. These findings indicate serial subtraction by seven requires different cognitive processing abilities which may cause greater interference with some aspects of motor control.

The effect of clear aligners on speech: a systematic review.

OBJECTIVE: To assess the effect of clear aligners on the speech of patients undergoing orthodontic therapy through a systematic review of the literature. Search methods and selection criteria: The protocol of this systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) CRD42021278694. An electronic search of the Scopus, Embase, Pubmed, and Web of Science databases was done for papers published between January 2000 till September 2021. Studies that evaluated speech difficulties in patients undergoing orthodontic treatment with clear aligners using objective and subjective analyses were included. The evaluated primary outcome was speech difficulties. Secondary outcomes were time to adaptation and recovery from speech difficulties. Study quality was assessed based on the Cochrane Handbook for Systematic Reviews of Interventions Handbook guidelines and ROBINS-I tool. RESULTS: Two hundred and eighty-three articles were screened to identify seven studies (n = 332 patients) that assessed speech difficulty with aligners, of which two were randomized trials. Meta-analysis was not performed due to the heterogeneity in the study designs. Five studies compared speech difficulty with aligners to fixed appliances. Two studies showed a moderate risk of bias and five studies had a serious risk of bias. Level of evidence was downgraded to low due to the methodological insufficiencies and risk of bias in the studies. All seven studies reported that aligners could influence the clarity and delivery of speech, similar to fixed appliances. Various phonemes were affected including /s/,/z/,/zh/,/sh/,/th/,/ch/ on wearing aligners. Errors in articulation of consonants and sibilants were noted with lisping and speech impairment. These speech difficulties were temporary and most patients recovered in 7-14 days while few patients took 30-60 days to recover. CONCLUSION: The likelihood of speech difficulties appears high with clear aligners. However, patients adapt quickly and speech returns to normal. The results of this review must be interpreted with caution and more well-designed randomized trials examining long-term effects of aligners on speech are indicated. CLINICAL SIGNIFICANCE: Orthodontists should counsel patients opting for clear aligner treatment of the potential transient speech difficulties. REGISTRATION: The protocol for this systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) CRD42021278694.

Toll-like receptors change morphine-induced antinociception, tolerance and dependence: Studies using male and female TLR and signalling gene KO mice.

Toll-like receptors (TLR) have been proposed as a site of action that alters opioid pharmacodynamics. However, a comprehensive assessment of acute opioid antinociception, tolerance and withdrawal behaviours in genetic null mutant strains with altered innate immune signalling has not been performed. Nor has the impact of genetic deletion of TLR2/4 on high-affinity opioid receptor binding. Here we show that diminished TLR signalling potentiates acute morphine antinociception equally in male and female mice. However, only male TIR8 null mutant mice showed reduced morphine analgesia. Analgesic tolerance was prevented in TLR2 and TLR4 null mutants, but not MyD88 animals. Withdrawal behaviours were only protected in TLR2-/- mice. In silico docking simulations revealed opioid ligands bound preferentially to the LPS binding pocket of MD-2 rather than TLR4. There was no binding of [3H](-)-naloxone or [3H]diprenorphine to TLR4 in the concentrations explored. These data confirm that opioids have high efficacy activity at innate immune pattern recognition binding sites but do not bind to TLR4 and identify critical pathway and sex-specific effects of the complex innate immune signalling contributions to opioid pharmacodynamics. These data further support the behavioural importance of the TLR-opioid interaction but fail to demonstrate direct evidence for high-affinity binding of the TLR4 signalling complex to ligands.

Dipeptidyl peptidase-4 inhibitor-associated cutaneous eruptions: a retrospective observational study.

BACKGROUND: Dipeptidyl peptidase (DPP)-4 plays a complex role in immune regulation and its inhibition can have effects on the pathogenesis of various skin diseases. Studies have shown that DPP-4 inhibitors are associated with an increased risk of bullous pemphigoid (BP). AIM: To analyse the clinical and histopathological features of cutaneous adverse events in patients on DPP-4 inhibitors. METHODS: We performed a retrospective review of patients with suspected DPP-4 inhibitor-associated cutaneous adverse events, at a tertiary teaching hospital from 1 January 2017 to 31 December 2020. Exclusion criteria included previous history of chronic skin disease and lack of histopathological reports or follow-up records. The clinical characteristics, latency period, Naranjo Adverse Drug Reaction Probability Scale and clinical outcomes were evaluated. RESULTS: In total, 18 patients (10 men, 8 women; mean age 68.6 years, range 38-89 years) were included. The DPP-4 inhibitors used were teneligliptin (n = 6), vildagliptin (n = 6), sitagliptin (n = 4), linagliptin (n = 1) and saxagliptin (n = 1). The mean interval between therapy initiation and lesion onset was 8.8 months (range 1-24 months). The dermatoses noted were BP (n = 12; 66.6%), lichenoid dermatitis (n = 4; 22.2%), psoriasiform dermatitis (n = 1; 5.6%) and spongiotic dermatitis (n = 1; 5.6%). Eight patients (44.4%) had necrotic keratinocytes as one of the distinct histological features. Causality assessment using the Naranjo scale rated the causative role of DPP-4 inhibitors as 'possible' in all patients. Of the 18 patients, 11 (61.1%) noted improvement in their condition following discontinuation of DPP-4 inhibitors, with 5 having complete remission within 6 months of stopping the drug. CONCLUSION: DPP-4 inhibitor-associated dermatoses are not necessarily limited to BP. It is necessary to recognize the possibility of other dermatoses in patients on DPP-4 inhibitors as drug substitution/cessation may improve disease morbidity.

Trajectories of depressive symptoms among young adults in Texas 2014-2018: a multilevel growth curve analysis using an intersectional lens.

INTRODUCTION: Research has demonstrated disparities in depressive symptoms among people who are marginalized. However, more work should examine depressive symptoms through an intersectional lens, recognizing that multiple systems of privilege and oppression interlock to create unique struggles where multiple marginalized identities meet. Recent methodological developments have advanced quantitative intersectionality research using multilevel modeling to partition variance in depressive symptoms to person-level sociodemographic variables and intersectional-level social strata. The purpose of this study is to leverage these methods to examine trajectories of depressive symptoms among young adults in Texas through an intersectional lens. METHODS: Multilevel modeling was used to examine the longitudinal trajectories of depressive symptoms among 3575 young adults from 24 colleges in Texas assessed seven times between Fall 2014 and Spring 2018. Intersectional identities included sex, race/ethnicity, and sexual and gender minority identities. The model examined time nested within individuals and individuals nested within intersectional social strata. RESULTS: Young adults in Texas experienced an increase in depressive symptoms from 2014-2018. Those with female, Hispanic, AAPI, other race/ethnicity, or LGBTQ + identities experienced more depressive symptoms. After controlling for the main effects of the sociodemographic variables, 0.08% of variance in depressive symptoms remained attributed to the effects of intersectional identities. CONCLUSION: Evaluating disparities in depressive symptoms through an intersectional lens offers a more complete description of the epidemiology of depressive symptoms. Communities and institutions that serve marginalized people should consider the elevated burden of depressive symptoms that marginalized people may carry, and integrate culturally competent psychoeducation, assessments, and therapies where possible.

Difficult life events affect lower extremity illness.

BACKGROUND: Given the relationship between psychological distress and activity tolerance (capability), a stressful life event might diminish accommodation, increase symptoms, and induce a person to seek specialty care. As a first step to investigate this possibility, this study addressed whether difficult life events are associated with greater activity intolerance and pain intensity. METHODS: A cohort of 127 patients seeking specialty care for lower extremity symptoms completed questionnaires that inquired about difficult life events within the last 12 months as derived from the Holmes Rahe Life Stress Inventory, and recorded pain intensity on an 11-point ordinal scale, activity tolerance [Patient Reported Outcomes Measurement Information System Physical Function Computer Adaptive Test (CAT)], symptoms of anxiety (GAD-2; 2 item version of the Generalized Anxiety Disorder questionnaire), symptoms of depression (PROMIS Depression CAT), self-efficacy when in pain (Pain Self-Efficacy Questionnaire, 2 question version), and demographics. The treating clinician indicated if the disease was established (e.g. arthritis) or relatively new (e.g. sprain/strain). Bivariate and multivariable analyses sought factors associated with activity intolerance and pain intensity. RESULTS: Greater activity intolerance was associated with difficult life events in bivariate analyses (t = 2.13, MD = 3.18, 95% C.I. = 0.22-6.13, p = 0.04) and in multivariable analyses that excluded symptoms of depression. Greater pain intensity was not associated with difficult life events, but was associated with surgeon rating of established disease (ß = 1.20, 95% C.I. = 0.33-2.08, p < 0.01), greater symptoms of anxiety (MD = 3.35, s = 1.72; ρ = 0.30, p < 0.01), and less education (ß = - 1.06, 95% C.I. = - 1.94- - 0.18, p = 0.02) (no college degree). CONCLUSION: When a musculoskeletal specialist identifies less activity tolerance (less capability) than anticipated for a given injury or pathology, they can anticipate a potential difficult life event, and expect alleviation of symptoms and improved capability as the stress is ameliorated with time and support. Specialists can be prepared to direct people to community or professional support if requested.

Global exchange and accumulation of non-native plants.

All around the globe, humans have greatly altered the abiotic and biotic environment with ever-increasing speed. One defining feature of the Anthropocene epoch is the erosion of biogeographical barriers by human-mediated dispersal of species into new regions, where they can naturalize and cause ecological, economic and social damage. So far, no comprehensive analysis of the global accumulation and exchange of alien plant species between continents has been performed, primarily because of a lack of data. Here we bridge this knowledge gap by using a unique global database on the occurrences of naturalized alien plant species in 481 mainland and 362 island regions. In total, 13,168 plant species, corresponding to 3.9% of the extant global vascular flora, or approximately the size of the native European flora, have become naturalized somewhere on the globe as a result of human activity. North America has accumulated the largest number of naturalized species, whereas the Pacific Islands show the fastest increase in species numbers with respect to their land area. Continents in the Northern Hemisphere have been the major donors of naturalized alien species to all other continents. Our results quantify for the first time the extent of plant naturalizations worldwide, and illustrate the urgent need for globally integrated efforts to control, manage and understand the spread of alien species.

The Vibrio cholerae type VI secretion system can modulate host intestinal mechanics to displace gut bacterial symbionts.

Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain Aeromonas veronii was displaced by V. cholerae expressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of A. veronii, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident microbiota by the host. Deleting an actin cross-linking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening V. cholerae's ability to kill A. veronii in vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering.

Impact of Multiplex Testing on the Identification of Pediatric Clostridiodes Difficile.

OBJECTIVES: To evaluate whether the implementation of a multiplex gastrointestinal pathogen panel (GIP) was associated with changes in Clostridioides difficile (C difficile) testing and detection rates. STUDY DESIGN: We conducted an observational study using interrupted time series analysis and included pediatric patients with testing capable of detecting C difficile. From 2013 to 2015 ("conventional diagnostic era"), stool testing included C difficile-selective polymerase chain reaction and other pathogen-specific tests. From 2015 to 2017 ("GIP era"), C difficile polymerase chain reaction was available along with the GIP, which detected 22 pathogens including C difficile, and replaced the need for additional tests. Outcomes included C difficile testing and detection rates in ambulatory, emergency department, and inpatient settings. RESULTS: There were 6841 tests performed and 1214 C difficile positive results. Across the 3 settings, GIP era had significantly higher C difficile testing (1.7-2.3 times higher) and C difficile detection rates (1.9-3.4 times higher) compared with conventional diagnostic era. After adjusting for the number of tests performed, detection rates were no longer significantly different. Of C difficile positive GIPs, 31% were coinfected with another organism. With GIP testing, patients 1 year of age had a significantly higher C difficile percent positivity than 2-year-old (P = .02) and 3- to 18-year-old children (P < .01). Younger children with C difficile were more likely to be coinfected (P < .01). CONCLUSIONS: Introducing a multiplex panel led to increased C difficile testing, which resulted in increased C difficile detection rates and potential identification and treatment of colonized patients. This highlights an important target for diagnostic stewardship and the challenges associated with multiplex testing.

Disruption of thermogenic UCP1 predated the divergence of pigs and peccaries.

Uncoupling protein 1 (UCP1) governs non-shivering thermogenesis in brown adipose tissue. It has been estimated that pigs lost UCP1 ∼20 million years ago (MYA), dictating cold intolerance among piglets. Our current understanding of the root causes of UCP1 loss are, however, incomplete. Thus, examination of additional species can shed light on these fundamental evolutionary questions. Here, we investigated UCP1 in the Chacoan peccary (Catagonus wagneri), a member of the Tayassuid lineage that diverged from pigs during the late Eocene-mid Oligocene. Exons 1 and 2 have been deleted in peccary UCP1 and the remaining exons display additional inactivating mutations. A common nonsense mutation in exon 6 revealed that UCP1 was pseudogenized in a shared ancestor of pigs and peccaries. Our selection pressure analyses indicate that the inactivation occurred 36.2-44.3 MYA during the mid-late Eocene, which is much earlier than previously thought. Importantly, pseudogenized UCP1 provides the molecular rationale for cold sensitivity and current tropical biogeography of extant peccaries.

Loop Diuretics-Analysis of Efficacy Data for the Perioperative Clinician.

HEART FAILURE (HF) is one of the most common causes of hospitalization in the United States. Loop diuretics (LD) are the mainstay of treatment in the management of acute and chronic HF. Although they generally are effective in relieving symptoms and reducing congestion, LD have not been shown to significantly affect morbidity and mortality. The initial decongestion strategy for management of HF is likely to be an LD, with evidence suggesting that an initial "high-dose" strategy either by twice-daily bolus injection or by continuous infusion is likely to be more successful than an initial lower dose in respect to relief of symptoms but at the expense of increased worsening of renal function. This review focuses on the current state of evidence of different strategies related to the use of LD in the treatment of congestive symptoms in critically ill patients and presents a summary of the body of evidence regarding dosages, timing, and different diuretic agents.

The Global Naturalized Alien Flora (GloNAF) database.

This dataset provides the Global Naturalized Alien Flora (GloNAF) database, version 1.2. GloNAF represents a data compendium on the occurrence and identity of naturalized alien vascular plant taxa across geographic regions (e.g. countries, states, provinces, districts, islands) around the globe. The dataset includes 13,939 taxa and covers 1,029 regions (including 381 islands). The dataset is based on 210 data sources. For each taxon-by-region combination, we provide information on whether the taxon is considered to be naturalized in the specific region (i.e. has established self-sustaining populations in the wild). Non-native taxa are marked as "alien", when it is not clear whether they are naturalized. To facilitate alignment with other plant databases, we provide for each taxon the name as given in the original data source and the standardized taxon and family names used by The Plant List Version 1.1 (http://www.theplantlist.org/). We provide an ESRI shapefile including polygons for each region and information on whether it is an island or a mainland region, the country and the Taxonomic Databases Working Group (TDWG) regions it is part of (TDWG levels 1-4). We also provide several variables that can be used to filter the data according to quality and completeness of alien taxon lists, which vary among the combinations of regions and data sources. A previous version of the GloNAF dataset (version 1.1) has already been used in several studies on, for example, historical spatial flows of taxa between continents and geographical patterns and determinants of naturalization across different taxonomic groups. We intend the updated and expanded GloNAF version presented here to be a global resource useful for studying plant invasions and changes in biodiversity from regional to global scales. We release these data into the public domain under a Creative Commons Zero license waiver (https://creativecommons.org/share-your-work/public-domain/cc0/). When you use the data in your publication, we request that you cite this data paper. If GloNAF is a major part of the data analyzed in your study, you should consider inviting the GloNAF core team (see Metadata S1: Originators in the Overall project description) as collaborators. If you plan to use the GloNAF dataset, we encourage you to contact the GloNAF core team to check whether there have been recent updates of the dataset, and whether similar analyses are already ongoing.

Immotile Active Matter: Activity from Death and Reproduction.

Unlike equilibrium atomic solids, biofilms-soft solids composed of bacterial cells-do not experience significant thermal fluctuations at the constituent level. However, living cells stochastically reproduce and die, provoking a mechanical response. We investigate the mechanical consequences of cellular death and reproduction by measuring surface-height fluctuations of biofilms containing two mutually antagonistic strains of Vibrio cholerae that kill one another on contact via the type VI secretion system. While studies of active matter typically focus on activity via constituent mobility, here, activity is mediated by reproduction and death events in otherwise immobilized cells. Biofilm surface topography is measured in the nearly homeostatic limit via white light interferometry. Although biofilms are far from equilibrium systems, measured surface-height fluctuation spectra resemble the spectra of thermal permeable membranes but with an activity-mediated effective temperature, as predicted by Risler, Peilloux, and Prost [Phys. Rev. Lett. 115, 258104 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.258104]. By comparing the activity of killer strains of V. cholerae with that of genetically modified strains that cannot kill each other and validating with individual-based simulations, we demonstrate that extracted effective temperatures increase with the amount of death and reproduction and that death and reproduction can fluidize biofilms. Together, these observations demonstrate the unique physical consequences of activity mediated by death and reproduction events.

Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor.

BACKGROUND & AIMS: Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline drug-induced liver injury (DILI) in a well-phenotyped cohort of patients. METHODS: Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls. Human leukocyte antigen (HLA) binding of minocycline was assessed using AutoDock Vina. RESULTS: Among the 25 cases, 80% were female, median age was 19years and median latency from drug start to DILI onset was 318days. At presentation, 76% had acute hepatocellular liver injury, median ALT 1,077U/L (range: 63 to 2,333), median bilirubin 4.5mg/dl (range: 0.2 to 16.7), and 90% had a +ANA. During follow-up, 50% were treated with corticosteroids and no participants died or required a liver transplant. A significant association was noted between HLA-B∗35:02 and risk for minocycline DILI; a 16% carrier frequency in DILI cases compared to 0.6% in population controls (odds ratio: 29.6, 95% CI: 7.8-89.8, p=2.5×10-8). Verification of HLA-B∗35:02 imputation was confirmed by sequence-based HLA typing. HLA-B∗35:02 carriers had similar presenting features and outcomes compared to non-carriers. In silico modeling studies support the hypothesis that direct binding of minocycline to this novel HLA risk allele might be an important initiating event in minocycline DILI. CONCLUSION: HLA-B∗35:02 is a rare HLA allele that was more frequently identified in the 25 minocycline DILI cases compared to population controls. If confirmed in other cohorts, this HLA allele may prove to be a useful diagnostic marker of minocycline DILI. LAY SUMMARY: Development of liver injury following prolonged use of minocycline for acne is a rare but potentially severe form of drug-induced liver injury. Our study demonstrates that individuals who are HLA-B∗35:02 carriers are at increased risk of developing minocycline related liver injury. These results may help doctors more rapidly and confidently diagnose affected patients and possibly reduce the risk of liver injury in individuals receiving minocycline going forward.

A Comparative Analysis of Oral Health on the Santo Domingo Pueblo Reservation.

The study was done to compare oral health data from a tribe in a relatively accessible location between Santa Fe and Albuquerque, New Mexico to national American Indian data and broader US data sets. Participants (N = 399) were recruited via random sampling of housing units. Dental health measures included DMFT/dmft and dental sealants. Comparisons were made using data from large-scale oral health surveillance studies. There was no difference in oral health for 3-5 year olds compared to a recent study of AI/AN preschool children. Compared to the general US population, Santo Domingo Pueblo children and adults showed higher prevalence of untreated decay. Children ages 5-19 had higher rates of sealant retention on permanent teeth, and adults showed lower prevalence of complete tooth retention. The children ages 5-19 and 12-19 with at least one sealant have significantly lower DMFT and less untreated decay than those without sealants. However, the percentage of children with and without sealants who had untreated decay was still more than two times higher than the general US population. Oral health of American Indian children and adults in Santo Domingo Pueblo was worse compared to the general US population but similar to previous results reported for the same Indian Health Service Area even though their location is less isolated than many other tribes.