Lateral Extra-articular Tenodesis Reduces Failure of Hamstring Tendon Autograft Anterior Cruciate Ligament Reconstruction: 2-Year Outcomes From the STABILITY Study Randomized Clinical Trial.

Background: Persistent anterolateral rotatory laxity after anterior cruciate ligament (ACL) reconstruction (ACLR) has been correlated with poor clinical outcomes and graft failure.

Hypothesis: We hypothesized that a single-bundle, hamstring ACLR in combination with a lateral extra-articular tenodesis (LET) would reduce the risk of ACLR failure in young, active individuals.

Study Design: Randomized controlled trial; Level of evidence, 1.

DNA sequence repeats identify numerous Type I restriction-modification systems that are potential epigenetic regulators controlling phase-variable regulons; phasevarions.

Over recent years several examples of randomly switching methyltransferases, associated with Type III restriction-modification (R-M) systems, have been described in pathogenic bacteria. In every case examined, changes in simple DNA sequence repeats result in variable methyltransferase expression and result in global changes in gene expression, and differentiation of the bacterial cell into distinct phenotypes. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria, with 17.

Shear force sensing of epithelial Na channel (ENaC) relies on -glycosylated asparagines in the palm and knuckle domains of αENaC.

Mechanosensitive ion channels are crucial for normal cell function and facilitate physiological function, such as blood pressure regulation. So far little is known about the molecular mechanisms of how channels sense mechanical force. Canonical vertebrate epithelial Na channel (ENaC) formed by α-, β-, and γ-subunits is a shear force (SF) sensor and a member of the ENaC/degenerin protein family.

Analysis of the Destabilization of Bacterial Membranes by Quaternary Ammonium Compounds: A Combined Experimental and Computational Study.

The mechanism of action of quaternary ammonium compound (QAC) antiseptics has long been assumed to be straightforward membrane disruption, although the process of approaching and entering the membrane has little modeling precedent. Furthermore, questions have more recently arisen regarding bacterial resistance mechanisms, and why select classes of QACs (specifically, multicationic QACs) are less prone to resistance. In order to better understand such subtleties, a series of molecular dynamics simulations were utilized to help identify these molecular determinants, directly comparing mono-, bis-, and triscationic QACs in simulated membrane intercalation models.

Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms.

New drugs are desperately needed to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report screening commercial kinase inhibitors for antibacterial activity and found the anticancer drug sorafenib as major hit that effectively kills MRSA strains. Varying the key structural features led to the identification of a potent analogue, PK150, that showed antibacterial activity against several pathogenic strains at submicromolar concentrations.

Targeting stigma of mental illness among primary care providers: Findings from a pilot feasibility study.

Stigmatizing attitudes among primary care (PC) providers potentially contribute to poor health outcomes for individuals with serious mental illness (SMI). In this pilot study, our primary aim is to test the feasibility, and preliminary implementation of two interventions (contact and education) to help change provider attitudes and behavior. Participants were 39 primary care providers from two Veterans Affairs medical centers with 19 randomized to the contact intervention and 20 to the education intervention.

Universality and diversity in human song.

What is universal about music, and what varies? We built a corpus of ethnographic text on musical behavior from a representative sample of the world's societies, as well as a discography of audio recordings. The ethnographic corpus reveals that music (including songs with words) appears in every society observed; that music varies along three dimensions (formality, arousal, religiosity), more within societies than across them; and that music is associated with certain behavioral contexts such as infant care, healing, dance, and love. The discography-analyzed through machine summaries, amateur and expert listener ratings, and manual transcriptions-reveals that acoustic features of songs predict their primary behavioral context; that tonality is widespread, perhaps universal; that music varies in rhythmic and melodic complexity; and that elements of melodies and rhythms found worldwide follow power laws.

Becomes Susceptible to Polymyxin B and Colistin in the Presence of PBT2.

() causes the sexually transmitted disease gonorrhea, which has a global incidence of 106 million cases per year. No vaccine is available to prevent the disease, and the emergence of multidrug resistant (MDR) strains makes an immediate public health threat. Here, we show that an ionophore, PBT2, can reverse the intrinsic resistance of to polymyxin B and colistin.

Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions.

Phasevarions (phase-variable regulons) are emerging as an important area of bacterial gene regulation. Many bacterial pathogens contain phasevarions, with gene expression controlled by the phase-variable expression of DNA methyltransferases via epigenetic mechanisms. Non-typeable Haemophilus influenzae (NTHi) contains the phase-variable methyltransferase modA, of which multiple allelic variants exist (modA1-21).

First Metatarsophalangeal Joint Space Area Decreases Within 1 Month After Implantation of a Polyvinyl Alcohol Hydrogel Implant: A Retrospective Radiographic Case Series.

In 2016, the U.S. Food and Drug Administration approved the first and only polyvinyl alcohol hydrogel implant for the treatment of hallux rigidus.

Solution structure, glycan specificity and of phenol oxidase inhibitory activity of Anopheles C-type lectins CTL4 and CTLMA2.

Malaria, the world's most devastating parasitic disease, is transmitted between humans by mosquitoes of the Anopheles genus. An. gambiae is the principal malaria vector in Sub-Saharan Africa.

Specific blood group antibodies inhibit Shigella flexneri interaction with human cells in the absence of spinoculation.

The classical models of investigating Shigella flexneri adherence and invasion of tissue culture cells involve either bacterial centrifugation (spinoculation) or the use of AfaE adhesin to overcome the low infection rate observed in vitro. However clinically, S. flexneri clearly adheres and invades the human colon in the absence of 'spinoculation'.

Urbanization reduces genetic connectivity in bobcats (Lynx rufus) at both intra- and interpopulation spatial scales.

Urbanization is a major factor driving habitat fragmentation and connectivity loss in wildlife. However, the impacts of urbanization on connectivity can vary among species and even populations due to differences in local landscape characteristics, and our ability to detect these relationships may depend on the spatial scale at which they are measured. Bobcats (Lynx rufus) are relatively sensitive to urbanization and the status of bobcat populations is an important indicator of connectivity in urban coastal southern California.

Cystic fibrosis transmembrane conductance regulator modulators reduce the risk of recurrent acute pancreatitis among adult patients with pancreas sufficient cystic fibrosis.

Background: Approximately 1 in 5 patients with pancreas sufficient cystic fibrosis (PS-CF) will develop acute pancreatitis (AP). It is not known whether ivacaftor alone or in combination with other CFTR (cystic transmembrane regulator) modulators (tezacaftor or lumacaftor) can reduce the risk of AP in patients with PS-CF and AP history.

Methods: We retrospectively queried the CF registry at our institution for adult patients with PS-CF, a documented history of AP and initiation of CFTR modulators for pulmonary indications.

Complex Multilevel Control of Hemolysin Production by Uropathogenic Escherichia coli.

Uropathogenic (UPEC) is the major cause of urinary tract infections. Nearly half of all UPEC strains secrete hemolysin, a cytotoxic pore-forming toxin. Here, we show that the prevalence of the hemolysin toxin gene () is highly variable among the most common 83 sequence types (STs) represented on the EnteroBase genome database.

Rupture of an Infected Renal Cyst Secondary to a Renocolic Fistula in Autosomal Dominant Polycystic Kidney Disease.

We present a rare case of retroperitoneal rupture of an infected renal cyst secondary to a renocolic fistula in a patient with autosomal dominant polycystic kidney disease (ADPKD). Intraperitoneal rupture of infected cysts in ADPKD resulting in peritonitis has been described, but to our knowledge, this is the first reported case of retroperitoneal rupture. Cyst infections are a common complication of ADPKD and are difficult to treat, potentially leading to sepsis and death.

Women in Podiatry and Medicine.

The role of female physicians has advanced among western medicine. Women now constitute a majority within medical schools, and the number of women in podiatric medicine and surgery has increased over the last 5 decades. Conversely, female physicians continue to face barriers to closing the gender gap.

Updates in Tendinopathy Treatment Options.

Tendinopathy is a common but disabling condition. The term describes a complex, multifaceted pathology of the tendon characterized by pain, decreased function, and reduced exercise tolerance. Tendinopathy accounts for up to 30% of general practice musculoskeletal consultations.

Transcriptome Sequencing Data Sets for Determining Gene Expression Changes Mediated by Phase-Variable DNA Methyltransferases in Nontypeable Haemophilus influenzae Strains Isolated from Patients with Chronic Obstructive Pulmonary Disease.

Nontypeable (NTHi) is a major bacterial cause of exacerbations in chronic obstructive pulmonary disease (COPD). Here, we report high-depth coverage transcriptome sequencing (RNA-seq) data from two NTHi strains, each encoding a different phase-variable methyltransferase. phase variation results in gene expression differences.

Human glycan expression patterns influence Group A streptococcal colonization of epithelial cells.

Colonization of the oropharynx is the initial step in Group A (GAS) pharyngeal infection. We have previously reported that the highly virulent M1T1 GAS clone attaches to oral epithelial cells M1 protein interaction with blood group antigen carbohydrate structures. Here, we have identified that colonization of human oral epithelial cells by GAS serotypes M3 and M12 is mediated by human blood group antigens [ABO(H)] and Lewis (Le) antigen expression.

Co-Imagining the Futures of Implementation Precision Medicine Using Scenario Analysis and Design Fiction.

Precision medicine has a long history dating to the early 20th century when inquiries into the biochemical basis of large person-to-person variations in susceptibility to human diseases and response to medicines had first begun. Yet, personalized medicine in the 21st century is far from being "future-proof." Emerging technologies such as artificial intelligence, and changing human values and preferences, call for anticipatory, rather than reactive, approaches to the governance of precision medicine futures.

Identification of Candidate Protein Markers in Skeletal Muscle of Laminin-211-Deficient CMD Type 1A-Patients.

Laminin-211 deficiency leads to the most common form of congenital muscular dystrophy in childhood, MDC1A. The clinical picture is characterized by severe muscle weakness, brain abnormalities and delayed motor milestones defining MDC1A as one of the most severe forms of congenital muscular diseases. Although the molecular genetic basis of this neurological disease is well-known and molecular studies of mouse muscle and human cultured muscle cells allowed first insights into the underlying pathophysiology, the definition of marker proteins in human vulnerable tissue such as skeletal muscle is still lacking.

MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.

Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and specific small-molecule inhibitor of the NLRP3 pathway, but its molecular target is not defined. Here, we show that MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, thereby blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation.