Protein engineering using variational free energy approximation.

Engineering proteins is a challenging task requiring the exploration of a vast design space. Traditionally, this is achieved using Directed Evolution (DE), which is a laborious process. Generative deep learning, instead, can learn biological features of functional proteins from sequence and structural datasets and return novel variants.

Repurposing a Fully Reducing Polyketide Synthase toward 2-Methyl Guerbet-like Lipids.

In nature, thousands of diverse and bioactive polyketides are assembled by a family of multifunctional, "assembly line" enzyme complexes called polyketide synthases (PKS). Since the late 20th century, there have been several attempts to decode, rearrange, and "reprogram" the PKS assembly line to generate valuable materials such as biofuels and platform chemicals. Here, the first module from () PKS12, an unorthodox, "modularly iterative" PKS, was modified and repurposed toward the formation of 2-methyl Guerbet lipids, which have wide applications in industry.

Ambulatory surgery center versus outpatient hospitals: a comparison of reimbursements for patients undergoing anterior cervical discectomy and fusion.

Background Context: While some studies have demonstrated that ambulatory surgery centers (ASCs) are associated with reduced costs of orthopedic procedures, there is no consensus in the current literature as to the impact of ASCs versus hospital-based outpatient departments (HOPDs) on anterior cervical discectomies and fusions (ACDFs).

Purpose: This study sought to (1) compare immediate procedure reimbursements, patient out-of-pocket expenditures, and surgeon reimbursements for ACDFs performed at ASCs versus HOPDs and (2) identify factors predicting facility utilization.

Study Design: Retrospective cross-sectional study.

Developing deprotectase biocatalysts for synthesis.

Organic synthesis often requires multiple steps where a functional group (FG) is concealed from reaction by a protecting group (PG). Common PGs include -carbobenzyloxy (Cbz or Z) of amines and -butyloxycarbonyl (OBu) of acids. An essential step is the removal of the PG, but this often requires excess reagents, extensive time and can have low % yield.

Preoperative Cervical Epidural Steroid Injections: Utilization and Postoperative Complications in ACDF, PCDF, and Decompression.

Study Design: Retrospective cohort study.

Objective: Identify factors associated with cervical epidural steroid injection (CESI) receipt before anterior cervical discectomy and fusion (ACDF), posterior cervical decompression and fusion (PCDF), or decompression; evaluate the association between CESI receipt and 90-day postoperative complications; and determine characteristics of CESI associated with complications.

Summary Of Background Data: Previous literature has suggested that a preoperative CESI may increase the risk of postoperative complications.

Anterior vertebral body tethering shows clinically comparable shoulder balance outcomes to posterior spinal fusion.

Purpose: Posterior spinal fusion (PSF) is the current gold standard in surgical treatment for adolescent idiopathic scoliosis. Vertebral body tethering (VBT) is a fusionless alternative. Shoulder balance is an important metric for outcomes and patient satisfaction.

Does Medicare Insurance Mitigate Racial/Ethnic Disparities in Access to Lumbar Spinal Surgery When Compared to Commercial Insurance?

Study Design: Retrospective cohort study.

Objective: Compare disparities in lumbar surgical care utilization in Commercially insured versus Medicare patients.

Summary Of Background Data: While disparities in spinal surgery have been previously described, less evidence exists on effective strategies to mitigate them.

Assessment of Risk Factors and Rate of Conversion to Total Hip Arthroplasty Within 2 Years After Hip Arthroscopy Utilizing a Large Database of Commercially Insured Patients in the United States.

Background: The conversion rate of hip arthroscopy (HA) to total hip arthroplasty (THA) has been reported to be as high as 10%. Despite identifying factors that increase the risk of conversion, current studies do not stratify patients by type of arthroscopic procedure.

Purpose/hypothesis: To analyze the rate and predictors of conversion to THA within 2 years after HA.

Understanding Prescribing Practices and Patient Experiences with Renin Angiotensin System Inhibitors Use in Chronic Kidney Disease: A Qualitative Study.

Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve outcomes but are underutilized in patients with chronic kidney disease (CKD). Little is known about reasons for discontinuation and lack of reinitiating these medications. We aimed to explore clinicians' and patients' experiences and perceptions of ACEI/ARB use in CKD.

There Is Wide Variation in Platelet-rich Plasma Injection Pricing: A United States Nationwide Study of Top Orthopaedic Hospitals.

Background: Demand for platelet-rich plasma (PRP) injections for osteoarthritis has dramatically increased in recent years despite conflicting evidence regarding its efficacy and highly variable pricing in the top orthopaedic centers in the United States, because PRP is typically not covered by insurance. A previous study investigating the mean price of PRP injections obtained information only from centers advertising online the availability of PRP injections. Thus, there is a need for further clarification of the overall availability and variability in cost of PRP injections in the orthopaedic community as well as an analysis of relevant regional demographic and hospital characteristics that could be associated with PRP pricing.

Documented Adverse Drug Reactions and Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease.

Introduction: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation.

Methods: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group).

Synthesis of 'joint class' curricula at high volume joint replacement centres and a preliminary model for development and evaluation.

Rationale: Preoperative patient education through 'joint class' has potential to improve quality of care for total joint replacement (TJR). However, no formal guidance exists regarding curriculum content, potentially resulting in inter-institutional variation.

Objective: We aimed to (a) synthesize curriculum components of 'joint classes' across high-volume institutions and (b) develop a preliminary theory of change model for development and evaluation guided by the existing curricula and related literature.

Hip Arthroscopy Trends: Increasing Patient Out-of-Pocket Costs, Lower Surgeon Reimbursement, and Cost Reduction With Utilization of Ambulatory Surgery Centers.

Purpose: To (1) report on trends in immediate procedure reimbursement, patient out-of-pocket expenditures, and surgeon reimbursement in hip arthroscopy (2) compare trends in ambulatory surgery centers (ASC) versus outpatient hospitals (OH) utilization; (3) quantify the cost differences (if any) associated with ASC versus OH settings; and 4) determine the factors that predict ASC utilization for hip arthroscopy.

Methods: The cohort for this descriptive epidemiology study was any patient over 18 years identified in the IBM MarketScan Commercial Claims Encounter database who underwent an outpatient hip arthroscopy, identified by Current Procedural Terminology codes, in the United States from 2013 to 2017. Immediate procedure reimbursement, patient out-of-pocket expenditure, and surgeon reimbursement were calculated, and a multivariable model was used to determine the influence of specific factors on these outcome variables.

Ambulatory Surgery Centers Significantly Decrease Total Health Care Expenditures in Primary Anterior Cruciate Ligament Reconstruction.

Background: Anterior cruciate ligament reconstruction (ACLR) is a commonly performed orthopaedic procedure. The volume and cost of ACLR procedures are increasing annually, but the drivers of these cost increases are not well described.

Purpose: To analyze the modifiable drivers of total health care utilization (THU), immediate procedure reimbursement, and surgeon reimbursement for patients undergoing ACLR using a large national commercial insurance database from 2013 to 2017.

Ethical challenges in genetic research among Philippine Indigenous Peoples: Insights from fieldwork in Zamboanga and the Sulu Archipelago.

The Philippines, with the recent discovery of an archaic hominin in Luzon and an extensive ethnolinguistic diversity of more than 100 Indigenous peoples, is crucial to understanding human evolution and population history in Island Southeast Asia. Advances in DNA sequencing technologies enable the rapid generation of genomic data to robustly address questions about origins, relatedness, and population movements. With the increased genetic sampling in the country, especially by international scientists, it is vital to revisit ethical rules and guidelines relevant to conducting research among Indigenous peoples.

Coupled Natural Fusion Enzymes in a Novel Biocatalytic Cascade Convert Fatty Acids to Amines.

Tambjamine YP1 is a pyrrole-containing natural product. Analysis of the enzymes encoded in the "" biosynthetic gene cluster (BGC) identified a unique di-domain biocatalyst (TamH). Sequence and bioinformatic analysis predicts that TamH comprises an N-terminal, pyridoxal 5'-phosphate (PLP)-dependent transaminase (TA) domain fused to a NADH-dependent C-terminal thioester reductase (TR) domain.

Interprofessional Collaboration Between a Clinical Pharmacist and Specialty Physicians to Treat Hepatitis C in an Interdisciplinary Medical Practice Setting.

Describes the activities of a clinical pharmacist in a gastroenterology (GI) clinic providing services to hepatitis C virus (HCV) patients, with a focus on practice management activities and tools. Located inside a GI specialty clinic in Fort Worth, Texas, the pharmacist provides comprehensive medication management under a collaborative practice agreement (CPA). Once referred by the GI physician, the pharmacist has face-to-face patient visits, develops the care plan, orders medications, and follows patients through sustained virologic response and the development of a hepatocellular carcinoma surveillance plan.

BioWF: A Naturally-Fused, Di-Domain Biocatalyst from Biotin Biosynthesis Displays an Unexpectedly Broad Substrate Scope.

The carbon backbone of biotin is constructed from the C di-acid pimelate, which is converted to an acyl-CoA thioester by an ATP-dependent, pimeloyl-CoA synthetase (PCAS, encoded by BioW). The acyl-thioester is condensed with ʟ-alanine in a decarboxylative, Claisen-like reaction to form an aminoketone (8-amino-7-oxononanoic acid, AON). This step is catalysed by the pyridoxal 5'-phosphate (PLP)-dependent enzyme (AON synthase, AONS, encoded by BioF).

A Laboratory Exercise Simulating Antibody and Antigen Reactions of the Ouchterlony Double Immunodiffusion Assay Using Inorganic Salts.

The Ouchterlony double immunodiffusion assay is a serological technique used in the detection of antibodies and antigens for diagnostic purposes and also used in immunology laboratory courses as a common teaching assay where students observe the geometrical precipitation line patterns that form in the agarose, elucidating degrees of homology between antigens. In this classical technique, students must wait several hours to days to obtain results when protein antigens and antibodies are used. Furthermore, these proteins degrade over time if not frozen or stored in the refrigerator and are the most expensive consumables of the laboratory exercise.

Genetic origins and diversity of bushpigs from Madagascar (Potamochoerus larvatus, family Suidae).

The island of Madagascar, situated off the southeast coast of Africa, shows the first evidence of human presence ~ 10,000 years ago; however, other archaeological data indicates a settlement of the modern peoples of the island distinctly more recent, perhaps > 1500 years ago. Bushpigs of the genus Potamochoerus (family Suidae), are today widely distributed in Madagascar and presumed to have been introduced from Africa at some stage by human immigrants to the island. However, disparities about their origins in Madagascar have been presented in the literature, including the possibility of endemic subspecies, and few empirical data are available.

European and Asian contribution to the genetic diversity of mainland South American chickens.

Chickens () from the Americas have long been recognized as descendants of European chickens, transported by early Europeans since the fifteenth century. However, in recent years, a possible pre-Columbian introduction of chickens to South America by Polynesian seafarers has also been suggested. Here, we characterize the mitochondrial control region genetic diversity of modern chicken populations from South America and compare this to a worldwide dataset in order to investigate the potential maternal genetic origin of modern-day chicken populations in South America.

East African origins for Madagascan chickens as indicated by mitochondrial DNA.

The colonization of Madagascar by Austronesian-speaking people during AD 50-500 represents the most westerly point of the greatest diaspora in prehistory. A range of economically important plants and animals may have accompanied the Austronesians. Domestic chickens () are found in Madagascar, but it is unclear how they arrived there.