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Background Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines. Methods In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012–2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models. Results Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9). Conclusions Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.

The NASA mission Perfect Crystals used the microgravity environment on the International Space Station (ISS) to grow crystals of human manganese superoxide dismutase (MnSOD) - an oxidoreductase critical for mitochondrial vitality and human health. The mission’s overarching aim is to perform neutron protein crystallography (NPC) on MnSOD to directly visualize proton positions and derive a chemical understanding of the concerted proton electron transfers performed by the enzyme. Large crystals that are perfect enough to diffract neutrons to sufficient resolution are essential for NPC. This combination, large and perfect, is hard to achieve on Earth due to gravity-induced convective mixing. Capillary counterdiffusion methods were developed that provided a gradient of conditions for crystal growth along with a built-in time delay that prevented premature crystallization before stowage on the ISS. Here, we report a highly successful and versatile crystallization system to grow a plethora of crystals for high-resolution NPC.

Background: We describe the implementation of a remote operational model to provide targeted, multi-faceted social services during the coronavirus disease 2019 (COVID-19) pandemic at the East Harlem Health Outreach Partnership (EHHOP), a student-run, physician-supervised free clinic (SRFC) that serves uninsurable residents of East Harlem in New York City (NYC). The model attempts to mitigate the economic consequences of the pandemic while also safely meeting the needs of patients who were quarantined or otherwise medically vulnerable. Methods: We outline a step-by-step approach required to transition social services to a remote model, across six key workflows: (1) student volunteer recruitment, (2) fundraising, (3) grocery and financial grant allocation, (4) medication delivery, (5) mask delivery and patient education, and (6) broader community engagement. Results: Within 20 days of the first known case of COVID-19 in NYC, we established a protocol for remote care and expanded social services. From March to July 2020, EHHOP volunteers made 221 medication and 172 mask kit no-contact deliveries. To address food and housing insecurity, 140 patients were provided financial grants and an additional 109 received food deliveries. This comprehensive response was supported through emergency fundraising efforts that generated $66,690. Conclusions: By focusing on support for basic needs including food, medication, personal protective equipment, and patient education, EHHOP was able to bolster the safety-net for marginalized patients otherwise excluded from national economic recovery efforts and ensure continuous care for patients with chronic medical illness. EHHOP’s operational model for safe, remote delivery of social services provides other clinics with a framework to guide current and future emergency responses.

The COVID-19 pandemic continues to disrupt everyday life, with constantly emerging SARS-CoV-2 variants threatening to render current vaccines ineffective. Small-molecule antivirals can provide an important therapeutic treatment option that is subject to challenges caused by the virus variants. The viral main protease (Mpro) is critical for the virus replication and thus is considered an attractive drug target for specific protease inhibitors. We performed the design and characterization of three reversible covalent hybrid inhibitors BBH-1, BBH-2 and NBH-2, whose structures were derived from those of hepatitis C protease inhibitors boceprevir and narlaprevir. A joint X-ray/neutron structure of the Mpro/BBH-1 complex demonstrated that a Cys145 thiolate reaction with the inhibitor’s keto-warhead creates a negatively charged oxyanion, similar to that proposed for the Mpro-catalyzed peptide bond hydrolysis. Protonation states of the ionizable residues in the Mpro active site adapt to the inhibitor, which appears to be an intrinsic property of Mpro. Structural comparisons of the hybrid inhibitors with PF-07321332 revealed unconventional interactions of PF-07321332 with Mpro which may explain its more favorable enthalpy of binding and consequently higher potency. BBH-1, BBH-2 and NBH-2 demonstrated comparable antiviral properties in vitro relative to PF-07321332, making them good candidates for further design of improved antivirals.

Introduction: In New York City (NYC), expanding the reach of thrombectomy-capable stroke centers (TSC) is key to combating socioeconomic disparities in stroke care. The Area Deprivation Index (ADI), a validated, neighborhood-level composite measure (scored 1-100) that includes income, education, employment, and housing quality, has informed healthcare delivery but has not been used to identify disadvantaged neighborhoods with poor access to stroke care. We sought to evaluate the impact of establishing Mount Sinai Queens Hospital (MSQ) as a TSC in 2017 on transfer times and to explore the association between ADI and stroke care access. Methods: Thrombectomy patient pick-up addresses were obtained through Emergency Medical Services runsheets from June 2016 to July 2021 and matched to census-tract level ADI scores from Neighborhood Atlas. Preliminary analyses compared both ADIs and time to stroke care access in both Queens and Manhattan. The primary outcome measure was the duration between ambulance arrival and groin puncture. Simple linear regression and T-tests were used to assess the association between ADI and time to groin puncture by borough. Results: Among 517 cases between 2016-2021, the average ADI of pick-up locations was 10.35 (range: 1 - 70.5). Across all centers, higher ADI (greater deprivation) was significantly associated with increased time to groin puncture (p = 0.024). Notably, Queens patients were picked up in census tracts with higher ADI (p=0.0289) but had a faster pick up to groin puncture time (p=0.006). Conclusions: Across urban census tracts, a higher ADI was associated with delays in access to thrombectomy. Thrombectomy centers in areas with higher ADI can play a role in reducing healthcare disparities for stroke patients.

Here we describe the development and implementation of a telehealth model for vulnerable, uninsured residents of East Harlem in New York City during the coronavirus disease 2019 (COVID-19) pandemic at a student-run, physician-supervised free clinic. The East Harlem Health Outreach Partnership completed 43 primary care follow-up and 78 urgent telehealth encounters during a six-week trial period during the COVID-19 outbreak, and 40 patients were managed for either suspected or confirmed COVID-19 diagnoses. Telehealth is a useful tool to provide rapid, high-quality care to a large patient population during a pandemic. Challenges include the lack of access to updated technology among patients of lower socioeconomic status and rapidly evolving management guidelines for COVID-19. Telehealth is essential for supporting vulnerable populations during times of reduced physical contact, including the COVID-19 pandemic, but can be applied broadly to all free clinics to augment access.

This meeting abstract was removed due to the OA licensing requirements of this journal. The full abstract is listed here : https://www.svin.org/files/SVIN_2021_Abstracts_for_Web.pdf

Human manganese superoxide dismutase (MnSOD) is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers (CPETs) are used by the enzyme to rid the mitochondria of O2•−, a precursor to other harmful reactive oxygen and nitrogen species. The mechanisms of CPET-utilizing enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules involved in catalysis while controlling the redox state of the enzyme. Here, neutron diffraction of redox-controlled MnSOD crystals revealed the all-atom structures of Mn3+SOD and Mn2+SOD delivering unique data on sites of differential protonation. A novel mechanism is proposed from the direct observation of glutamine deprotonation, the involvement of Tyr and His with altered pKas, and three unusual strong-short hydrogen bonds that change with the oxidation state of the metal. Quantum calculations provide insight into the electronic modulation of the observed structures.

BACKGROUND Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. METHODS We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and

The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).

Postoperative pulmonary complications play an important role in the risk for patients undergoing noncardiothoracic surgery. Postoperative pulmonary complications are as prevalent as cardiac complications and contribute similarly to morbidity, mortality, and length of stay. Pulmonary complications may even be more likely than cardiac complications to predict long-term mortality after surgery. The purpose of this guideline is to provide guidance to clinicians on clinical and laboratory predictors of perioperative pulmonary risk before noncardiothoracic surgery. It also evaluates strategies to reduce the perioperative pulmonary risk and focuses on atelectasis, pneumonia, and respiratory failure. The target audience for this guideline is general internists or other clinicians involved in perioperative management of surgical patients. The target patient population is all adult persons undergoing noncardiothoracic surgery. Ann Intern Med. 2006;144:575-580. www.annals.org For author affiliations, see end of text. RECOMMENDATIONS Recommendation 1: All patients undergoing noncardiothoracic surgery should be evaluated for the presence of the following significant risk factors for postoperative pulmonary complications in order to receive pre- and postoperative interventions to reduce pulmonary risk: chronic obstructive pulmonary disease, age older than 60 years, American Society of Anesthesiologists (ASA) class of II or greater, functionally dependent, and congestive heart failure. The following are not significant risk factors for postoperative pulmonary complications: obesity and mild or moderate asthma. Recommendation 2: Patients undergoing the following procedures are at higher risk for postoperative pulmonary complications and should be evaluated for other concomitant risk factors and receive pre- and postoperative interventions to reduce pulmonary complications: prolonged surgery (3 hours), abdominal surgery, thoracic surgery, neurosurgery, head and neck surgery, vascular surgery, aortic aneurysm repair, emergency surgery, and general anesthesia. Recommendation 3: A low serum albumin level (35 g/L) is a powerful marker of increased risk for postoperative pulmonary complications and should be measured in all patients who are clinically suspected of having hypoalbuminemia; measurement should be considered in patients with 1 or more risk factors for perioperative pulmonary complications.

Current guidelines recommend use of written action plans and peak flow monitoring as key components of asthma care. Our study assesses whether written action plans, with or without peak flow monitoring, have an independent effect on outcomes when used as a component of asthma self-management.This was a systematic review of published studies. Two independent reviewers followed a prospective protocol for study selection and data abstraction. Outcome data were synthesized qualitatively; they were not appropriate for quantitative meta-analysis. Our comprehensive literature search used MEDLINE, EMBASE, the Cochrane Library, and a hand search of recent bibliographies. The search was limited to full-length, peer-reviewed articles with abstracts in English. The studies were randomized controlled trials that compared the outcomes of an asthma self-management intervention with and without the use a written action plan. The primary outcomes of interest are utilization measures, such as hospitalizations and ER visits. Other outcomes of interest include measures of symptom control and lung function.There were 1501 evaluable patients with asthma; 1410 adults and 91 children.We measured the frequency of waiting and examination room companions, the reasons for accompaniment, the influence on the encounter, and the overall helpfulness of the companion as assessed by patients and companions. We also determined the physicianamprsquos assessment of the companionamprsquos influence, helpfulness, and behavior during the encounter.Nine randomized controlled trials enrolling a total of 1501 patients met selection criteria. The majority of comparisons in these studies do not demonstrate improved outcomes associated with a written action plan. There are notable methodologic limitations: studies reporting negative findings lack sufficient power, and studies reporting positive findings demonstrate systematic bias.Although written action plans are widely used, there is insufficient evidence to determine whether their use, with or without peak flow monitoring, improves outcomes.

Following the passage of Hurricane Katrina, New Orleans was left with 80% of its land area flooded. In some locations, the flood waters were over 30 feet deep. In the heat and stagnation, the waters quickly became heavily polluted. Pump out operations began in early September 2005 to get the city dried out quickly. Lake Pontchartrain was the primary receiving water body. A variety of approaches were evaluated to achieve treatment with minimal impact on pumping operations. Some of these included; sorbet booms in the channels and the lake near outfalls, oil and debris removal skimmers in channels and near outfalls, sediment control devises for hot spots, application of flocculation chemicals, aerators in the channels and near the outfalls, etc. Over 100 water quality sampling sites were set-up throughout the city to characterise water conditions as the pump out proceeded. High risk areas were identified in a dynamic process and decisions make for best corrective action. Lake Pontchartrain continues to be monitored and long term rehabilitation efforts will be predicated on water quality monitoring results. Lessons learned from a water quality perspective during this massive disaster are presented with the goal of assisting future recovery efforts.