Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Testing a global standard for quantifying species recovery and assessing conservation impact.

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard

Geriatric Patients Undergoing Outpatient Surgery in the United States: A Retrospective Cohort Analysis on the Rates of Hospital Admission and Complications

Introduction This study is a retrospective cohort analysis that describes key clinical outcomes in elderly individuals who undergo outpatient surgical procedures. In particular, we report same-day admission, 30-day mortality, 30-day complications, and 30-day readmission rates for three separate age groups undergoing frequent outpatient, general surgical procedures.MethodsPatients ≥18 years old who underwent the 10 most common outpatient surgical procedures in the National Surgical Quality Improvement Program database from 2017 to 2019 and who underwent general anesthesia were included in the study. The primary outcome of interest was hospital admission, defined as hospital length of stay >0 days. Secondary outcomes of interest included 30-day readmission, 30-day mortality, and 30-day postoperative complications. The primary exposure variable of interest was age, which was divided into <65 years of age (reference cohort), 65-79 years of age, and ≥80 years of age. For univariate analysis, to measure differences in the outcomes and patient characteristics, we used chi-squared tests. Our primary method of analysis was multivariable logistic regression.ResultsThose who were ≥80 and 65-79 years of age compared to <65 years of age had higher odds of same-day admission, 30-day mortality, composite postoperative complications, and readmission. Patients who were ≥80 years old had higher odds of same-day admission for laparoscopic cholecystectomy, partial mastectomy, laparoscopic inguinal hernia repair, inguinal hernia repair, umbilical hernia repair, laparoscopic removal of adnexal structures, and lumbar laminotomy.ConclusionIncreasing age, particularly greater than 80 years or older and 65-79 years of age group, is associated with an increased rate of same-day hospital admissions and complications after ambulatory surgery

Risk Factors Associated With Mortality in Patients With Otogenic Brain Abscess.

ObjectiveOtogenic brain abscess is a well-recognized clinical condition that describes brain abscess secondary to an ear infection or mastoiditis. Current evidence remains limited on risk factors associated with mortality as most data are from case series. We aimed to 1) report the mortality rate among patients who did and did not receive mastoidectomy 2) identify factors associated with inpatient mortality.Study designRetrospective cohort study.SettingMulti-institutional.PatientsWe identified a cohort of patients for years 2008 to 2014 who in their inpatient hospitalization carried the diagnoses of both brain abscess and infectious ear disease.InterventionsInpatient neurotology and neurosurgical procedures.Main outcome measuresA multivariable logistics regression model was built to identify the factors associated with inpatient mortality.ResultsThe final analysis included 252 patients, of which 84 (33.3%) underwent mastoidectomy. The rate of inpatient morbidity and mortality were 17.5% and 4.0%, respectively. The rate of mortality in patients without mastoidectomy versus those with mastoidectomy was 4.2% versus 3.6%, respectively (p > 0.99). The odds of inpatient mortality were significantly increased for every 10-year increase in age (odds ratio [OR] 2.73, 95% confidence interval [CI]: 1.39-7.01, p = 0.011) and for Black compared to White patients (OR: 45.81, 95% CI: 4.56-890.92, p = 0.003).ConclusionOlder age and Black race were associated with increased odds of inpatient mortality and there were no significant differences in mortality between mastoidectomy cohorts. This research serves to generate further hypotheses for larger observational studies to investigate the association between sociodemographic factors and surgical variables with outcomes among this surgical population

Multiple cholesterol recognition/interaction amino acid consensus (CRAC) motifs in cytosolic C tail of Slo1 subunit determine cholesterol sensitivity of Ca\u3csup\u3e2+\u3c/sup\u3e- and voltage-gated K\u3csup\u3e+\u3c/sup\u3e (BK) channels

Large conductance, Ca2+- and voltage-gated K+ (BK) channel proteins are ubiquitously expressed in cell membranes and control a wide variety of biological processes. Membrane cholesterol regulates the activity of membrane-associated proteins, including BK channels. Cholesterol modulation of BK channels alters action potential firing, colonic ion transport, smooth muscle contractility, endothelial function, and the channel alcohol response. The structural bases underlying cholesterol-BK channel interaction are unknown. Such interaction is determined by strict chemical requirements for the sterol molecule, suggesting cholesterol recognition by a protein surface. Here, we demonstrate that cholesterol action on BK channel-forming Cbv1 proteins is mediated by their cytosolic C tail domain, where we identified seven cholesterol recognition/interaction amino acid consensus motifs (CRAC4 to 10), a distinct feature of BK proteins. Cholesterol sensitivity is provided by the membrane-adjacent CRAC4, where Val-444, Tyr-450, and Lys-453 are required for cholesterol sensing, with hydrogen bonding and hydrophobic interactions participating in cholesterol location and recognition. However, cumulative truncations or Tyr-to-Phe substitutions in CRAC5 to 10 progressively blunt cholesterol sensitivity, documenting involvement of multiple CRACs in cholesterol-BK channel interaction. In conclusion, our study provides for the first time the structural bases of BK channel cholesterol sensitivity; the presence of membrane-adjacent CRAC4 and the long cytosolic C tail domain with several other CRAC motifs, which are not found in other members of the TM6 superfamily of ion channels, very likely explains the unique cholesterol sensitivity of BK channels. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

An Update on Racial and Ethnic Differences in Neuraxial Anesthesia for Cesarean Delivery.

Background Racial and ethnic differences in the use of neuraxial anesthesia compared with general anesthesia are less studied, particularly in obstetrical anesthesia. Here, we aimed to provide an update on the association between race and ethnicity, and the use of neuraxial anesthesia for cesarean delivery in the United States (US). Methods We used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data File 2019. We extracted cases that had a primary surgery defined with Current Procedural Terminology (CPT) code for cesarean delivery (59510, 59514, and 59515) and cesarean after attempted vaginal delivery in parturients with a prior history of cesarean (59618, 59620, and 59622). Multivariable logistic regression was used to report the association of race and ethnicity with primary anesthetic technique. Results There were 12,876 parturients included in the study. Compared with White parturients, Black (adjusted odds ratio (aOR) = 0.71, 95% confidence interval (CI): 0.57-0.88, p = 0.001) and American Indian or Alaska Native (aOR = 0.22, 95% CI: 0.12-0.40, p < 0.001) parturients had lower odds of receiving neuraxial compared with general anesthesia. There were no significant differences in the odds of neuraxial anesthesia between non-Hispanic and Hispanic cohorts. Conclusions While we do observe racial differences in anesthetic technique, Hispanic patients did not have significantly lower odds of neuraxial anesthesia. This study highlights the importance of an update to prior studies, as the current study suggests a lack of disparity between non-Hispanic and Hispanic parturients. While the results here are encouraging, a multidisciplinary approach is necessary to further address racial disparities