A laboratory-based predictive pathway for the development of high-level resistance to corallopyronin A, an inhibitor of bacterial RNA polymerase.

Unlabelled: The continued emergence of strains that express resistance to multiple antibiotics, including the last drug for empiric monotherapy (ceftriaxone), necessitates the development of new treatment options to cure gonorrheal infections. Toward this goal, we recently reported that corallopyronin A (CorA), which targets the switch region of the β' subunit (RpoC) of bacterial DNA-dependent RNA polymerase (RNAP), has potent anti-gonococcal activity against a panel of multidrug-resistant clinical strains. Moreover, in that study, CorA could eliminate gonococcal infection of primary human epithelial cells and gonococci in a biofilm state.

Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018.

Background: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes.

Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects.

Treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and expensive. Current reconstructive methods include surgical correction of injuries, short-term bone stabilization, and long-term use of bone grafting solutions, including implantation of (i) allografts which are prone to implant failure or infection, (ii) autografts which are limited in supply. Current bone regenerative approaches have consistently relied on BMP2 application with or without addition of stem cells.

Intestinal barrier dysfunction in murine sickle cell disease is associated with small intestine neutrophilic inflammation, oxidative stress, and dysbiosis.

The intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3-fold increase in intestinal permeability as assessed via FITC-dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice ( = 4,  < 0.

Bacterial and viral infections among adults hospitalized with COVID-19, COVID-NET, 14 states, March 2020-April 2022.

Background: Bacterial and viral infections can occur with SARS-CoV-2 infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood.

Methods: We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system, to investigate the occurrence of bacterial and viral infections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection between March 2020 and April 2022. Clinician-driven testing for bacterial pathogens from sputum, deep respiratory, and sterile sites were included.

Systemic Immune Modulation Alters Local Bone Regeneration in a Delayed Treatment Composite Model of Non-Union Extremity Trauma.

Bone non-unions resulting from severe traumatic injuries pose significant clinical challenges, and the biological factors that drive progression towards and healing from these injuries are still not well understood. Recently, a dysregulated systemic immune response following musculoskeletal trauma has been identified as a contributing factor for poor outcomes and complications such as infections. In particular, myeloid-derived suppressor cells (MDSCs), immunosuppressive myeloid-lineage cells that expand in response to traumatic injury, have been highlighted as a potential therapeutic target to restore systemic immune homeostasis and ultimately improve functional bone regeneration.

Development of systemic immune dysregulation in a rat trauma model of biomaterial-associated infection.

Orthopedic biomaterial-associated infections remain a major clinical challenge, with Staphylococcus aureus being the most common pathogen. S. aureus biofilm formation enhances immune evasion and antibiotic resistance, resulting in a local, indolent infection that can persist long-term without symptoms before eventual hardware failure, bone non-union, or sepsis.

JAGGED1 stimulates cranial neural crest cell osteoblast commitment pathways and bone regeneration independent of canonical NOTCH signaling.

Craniofacial bone loss is a complex clinical problem with limited regenerative solutions. Currently, BMP2 is used as a bone-regenerative therapy in adults, but in pediatric cases of bone loss, it is not FDA-approved due to concerns of life-threatening inflammation and cancer. Development of a bone-regenerative therapy for children will transform our ability to reduce the morbidity associated with current autologous bone grafting techniques.

Obstructive Lung Disease and Obstructive Sleep Apnea (OLDOSA) cohort study: 10-year assessment.

Study Objectives: Asthma, chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea (OSA) are very prevalent disorders. Their coexistence in the same individual has an unclear effect on natural history and long-term outcomes.

Methods: The OLDOSA (Obstructive Lung Disease and Obstructive Sleep Apnea) cohort enrolled 4,980 veterans with an acute hospitalization and in whom asthma, COPD, OSA, overlapping conditions, or none of these disorders at baseline had been diagnosed.

Lower Limb Rigidity Is Associated with Frequent Falls in Parkinson's Disease.

Background And Objective: The role of muscle rigidity as an etiological factor of falls in Parkinson's disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures.

Methods: We examined the associations between Unified Parkinson's Disease Rating Scale-Part III (motor) rigidity subscores and the history of monthly or more frequent falls in 216 individuals with PD (age, 66 ± 10 years; 36% female; disease duration, 7 ± 5 years) with logistic regression.

HIV Infection and Incidence of Cardiovascular Diseases: An Analysis of a Large Healthcare Database.

Background People living with HIV ( PLWH ) experience higher risk of myocardial infarction ( MI ) and heart failure ( HF ) compared with uninfected individuals. Risk of other cardiovascular diseases ( CVD s) in PLWH has received less attention. Methods and Results We studied 19 798 PLWH and 59 302 age- and sex-matched uninfected individuals identified from the MarketScan Commercial and Medicare databases in the period 2009 to 2015.

Plaque modification of severely calcified coronary lesions via orbital atherectomy: Single-center observations from a complex Veterans Affairs cohort.

Background: Orbital atherectomy (OA) is a known alternative to other atherectomy devices. However, some complex patient demographics (eg, left ventricular ejection fraction <25%) were excluded from the first-in-human trial (ORBIT I) and the pivotal FDA device approval trial (ORBIT II) which evaluated the safety and efficacy of OA in severely calcified de novo coronary lesions. This single-operator cohort study aimed to examine the impact of OA on a real-world complex Veterans Affairs patient subset.

Osteopontin isoforms differentially promote arteriogenesis in response to ischemia via macrophage accumulation and survival.

Osteopontin (OPN) is critical for ischemia-induced neovascularization. Unlike rodents, humans express three OPN isoforms (a, b, and c); however, the roles of these isoforms in post-ischemic neovascularization and cell migration remain undefined. Our objective was to determine if OPN isoforms differentially affect post-ischemic neovascularization and to elucidate the mechanisms underlying these differences.

Biological evaluation and finite-element modeling of porous poly(para-phenylene) for orthopaedic implants.

Unlabelled: Poly(para-phenylene) (PPP) is a novel aromatic polymer with higher strength and stiffness than polyetheretherketone (PEEK), the gold standard material for polymeric load-bearing orthopaedic implants. The amorphous structure of PPP makes it relatively straightforward to manufacture different architectures, while maintaining mechanical properties. PPP is promising as a potential orthopaedic material; however, the biocompatibility and osseointegration have not been well investigated.

A Novel Technique for Accelerated Culture of Murine Mesenchymal Stem Cells that Allows for Sustained Multipotency.

Bone marrow derived mesenchymal stem cells (MSCs) are regularly utilized for translational therapeutic strategies including cell therapy, tissue engineering, and regenerative medicine and are frequently used in preclinical mouse models for both mechanistic studies and screening of new cell based therapies. Current methods to culture murine MSCs (mMSCs) select for rapidly dividing colonies and require long-term expansion. These methods thus require months of culture to generate sufficient cell numbers for feasibility studies in a lab setting and the cell populations often have reduced proliferation and differentiation potential, or have become immortalized cells.

Harmonic subtraction for evaluating right ventricle ejection fraction from planar equilibrium radionuclide angiography.

We report an initial investigation of a subtraction-based method to estimate right ventricle ejection fraction (RVEF) from ECG-gated planar equilibrium radionuclide angiography (ERNA) data. Twenty-six consecutive patients referred for scintigraphic evaluation of cardiac function prior to chemotherapy had ECG-gated first-pass (FP) imaging and ERNA imaging performed following the same radiotracer injection. RVEF was computed from FP images (RVEF) and separately from ERNA images (RVEF).

Garlic-Induced Surgical Bleeding: How Much Is Too Much?

A patient underwent C2-T2 decompression and fusion with excessive intraoperative bleeding and no clear source. The patient denied the use of blood-thinning medications, but had consumed the equivalent of 12 g garlic daily in the days leading up to the surgery. He was treated with desmopressin acetate (DDAVP) and cryoprecipitate with adequate control of bleeding.

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century.

Neisseria gonorrhoeae is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea.

Sagittal Plane Correction Using the Lateral Transpsoas Approach: A Biomechanical Study on the Effect of Cage Angle and Surgical Technique on Segmental Lordosis.

Study Design: Cadaveric biomechanical study.

Objective: To determine the degree of segmental correction that can be achieved through lateral transpsoas approach by varying cage angle and adding anterior longitudinal ligament (ALL) release and posterior element resection.

Summary Of Background Data: Lordotic cage insertion through the lateral transpsoas approach is being used increasingly for restoration of sagittal alignment.

Pathologic findings in patients with targeted magnetic resonance imaging-guided prostate needle core biopsies.

In contrast to the routine (non-targeted) sampling approach of transrectal ultrasound guided biopsies (TRUS-GB), targeted magnetic resonance imaging-guided biopsies (TMRI-GB) target regions of the prostate suspicious for prostate cancer (PCa), based on findings on multiparametric MRI. We sought to examine the pathologic findings identified on TMRI-GB, due to the fact that there are limited studies on this in the Pathology literature. A search was made through our Urologic Pathology files for prostate needle core biopsies that were obtained via TMRI-GB.

Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders.

This study examined the short- and long-term neuroprotective and analgesic activity of honokiol (a naturally occurring lignan isolated from Magnolia) on developing brains in neonates exposed to inflammatory pain, known to cause neuronal cell death. Postnatal day 4 (P4) neonatal rat pups were subjected to intraplantar formalin injection to four paws as a model of severe neonatal pain. Intraperitoneal honokiol (10 mg/kg) or corn oil vehicle control was administered 1 h prior to formalin insult, and animals were maintained on honokiol through postnatal day 21 (P21).