Musical Hallucinations in an Elderly Female With Hearing Loss.

Musical hallucinations (MH) are rare auditory phenomena in which patients perceive music without a known source. Risk factors for MH include hearing loss, older age, female gender, epilepsy, and certain medications. This case report details the presentation, diagnosis, and treatment of an 82-year-old woman who developed MH following the onset of hearing loss.

Atypical Lyme Disease Rash: A Case Report.

Lyme disease (LD), caused in the United States primarily by sensu lato, is a tick-borne illness characterized by a spectrum of clinical manifestations depending on the stage of illness. Most clinicians are familiar with the classic bullseye appearance of the erythema migrans (EM) rash that occurs in the early stage of the disease. However, many providers may not be aware of alternate appearances for the rash.

Locally Directed Recombinant Adeno- Associated Virus-Mediated IGF-1 Gene Therapy Enhances Osteochondral Repair and Counteracts Early Osteoarthritis In Vivo.

Background: Restoration of osteochondral defects is critical, because osteoarthritis (OA) can arise.

Hypothesis: Overexpression of insulin-like growth factor 1 (IGF-1) via recombinant adeno-associated viral (rAAV) vectors (rAAV-IGF-1) would improve osteochondral repair and reduce parameters of early perifocal OA in sheep after 6 months in vivo.

Study Design: Controlled laboratory study.

Modulation of early osteoarthritis by tibiofemoral re-alignment in sheep.

Objective: To investigate whether tibiofemoral alignment influences early knee osteoarthritis (OA). We hypothesized that varus overload exacerbates early degenerative osteochondral changes, and that valgus underload diminishes early OA.

Method: Normal, over- and underload were induced by altering alignment via high tibial osteotomy in adult sheep (n = 8 each).

Written Communication From Pharmacy Benefit Managers: Is It Helpful?

Introduction: Physicians are experiencing greater burnout due to excessive time spent on paperwork. Pharmacy benefit managers (PBMs) are adding to this problem by sending excessive mail to physicians. This study examined these mailed communications to determine their frequency and if the physician acted upon them.

Accuracy of Personalized Computed Tomographic 3D Templating for Acetabular Cup Placement in Revision Arthroplasty.

: Revision hip arthroplasty presents a surgical challenge, necessitating meticulous preoperative planning to avert complications like periprosthetic fractures and aseptic loosening. Historically, assessment of the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has focused exclusively on primary hip arthroplasty. : In this retrospective study, we examined the accuracy of 3D templating for acetabular revision cups in 30 patients who underwent revision hip arthroplasty.

A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo.

Articular cartilage defects represent an unsolved clinical challenge. Photopolymerizable hydrogels are attractive candidates supporting repair. This study investigates the short-term safety and efficacy of two novel hyaluronic acid (HA)-triethylene glycol (TEG)-coumarin hydrogels photocrosslinked in situ in a clinically relevant large animal model.

Subgroup analysis of scientific performance in the field of arthroplasty.

Introduction: Arthroplasty is the final treatment option for maintaining mobility and quality of life in many primary degenerative and (post-) traumatic joint diseases. Identification of research output and potential deficits for specific subspecialties may be an important measure to achieve long-term improvement of patient care in this field.

Methods: Using specific search terms and Boolean operators, all studies published since 1945 to the subgroups of arthroplasty listed in the Web of Science Core Collection were included.

Validity and Accuracy of the Tilburg Frailty Indicator Part B for Identification of Frailty in Older Adults Consulting a Rural Geriatric Medicine Clinic.

The Tilburg Frailty Indicator (TFI) is a validated tool for determining frailty in older adults. This study examined the validity and accuracy of the TFI Part B (TFI-B) in a North American context. Seventy-two individuals ≥ 65 years of age recruited from a rural geriatric medicine clinic completed a set of self-reported and performance-based measures, including TFI-B.

Deciding on future fertility: considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation.

Research Question: What are the considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation (OTC)?

Design: Semi-structured in-depth interviews were conducted with girls with Turner syndrome and their parents until data saturation was reached. Participants were recruited through purposive sampling. Data were analysed using a thematic analysis approach.

Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors.

Mutations within Ras proteins represent major drivers in human cancer. In this study, we report the structure-based design, synthesis, as well as biochemical and cellular evaluation of nucleotide-based covalent inhibitors for KRasG13C, an important oncogenic mutant of Ras that has not been successfully addressed in the past. Mass spectrometry experiments and kinetic studies reveal promising molecular properties of these covalent inhibitors, and X-ray crystallographic analysis has yielded the first reported crystal structures of KRasG13C covalently locked with these GDP analogues.

In vivo rAAV-mediated human TGF-β overexpression reduces perifocal osteoarthritis and improves osteochondral repair in a large animal model at one year.

Objective: Osteoarthritis (OA) is a serious consequence of focal osteochondral defects. Gene transfer of human transforming growth factor beta (hTGF-β) with recombinant adeno-associated virus (rAAV) vectors offers a strategy to improve osteochondral repair. However, the long-term in vivo effects of such rAAV-mediated TGF-β overexpression including its potential benefits on OA development remain unknown.

Sclerosing Mesenteritis: A Rare Cause of Abdominal Pain.

Sclerosing mesenteritis (SM) is a rare inflammatory fibrotic disease of the small intestine mesenteric fat often discovered incidentally on a CT scan. Clinical manifestations depend on the mass effect on the viscera and vessels. The most common symptoms are abdominal pain, bloating, and nausea.

Axial alignment is a critical regulator of knee osteoarthritis.

Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model.

A Randomized Open-Label Study of Two Methods of Proton Pump Inhibitors Discontinuation.

Background Proton pump inhibitors (PPIs) are effective in treating gastroesophageal reflux disease (GERD). Unfortunately, they are often inappropriately prescribed and long-term use has potential adverse effects. A single best method for discontinuation of PPIs does not currently exist.

Hydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivo.

The regeneration of focal articular cartilage defects is complicated by the reduced quality of the repair tissue and the potential development of perifocal osteoarthritis (OA). Biomaterial-guided gene therapy may enhance cartilage repair by controlling the release of therapeutic sequences in a spatiotemporal manner. Here, the benefits of delivering a recombinant adeno-associated virus (rAAV) vector coding for the human insulin-like growth factor I (IGF-I) via an alginate hydrogel (IGF-I/AlgPH155) to enhance repair of full-thickness chondral defects following microfracture surgery after one year in minipigs versus control (lacZ/AlgPH155) treatment are reported.

KRasG12C inhibitors in clinical trials: a short historical perspective.

KRas is the most frequently mutated oncogene in human cancer, and even 40 years after the initial discovery of Ras oncogenes in 1982, no approved drug directly targets Ras in Ras-driven cancer. New information and approaches for direct targeting of mutant Ras have fueled hope for the development of direct KRas inhibitors. In this review, we provide a comprehensive historical perspective of the development of promising KRasG12C inhibitors that covalently bind to the mutated cysteine residue in the switch-II pocket and trap the protein in the inactive GDP bound state.

Post-Influenza Vaccine Subdeltoid bursitis.

A 61-year-old female presented three months following an influenza vaccination with ongoing pain since the injection and was diagnosed by MRI with subdeltoid bursitis. The patient received a short course of prednisone and several months of physical therapy before returning to pain-free function. The primary reason for injection-related subdeltoid bursitis is improper administration.

Thermosensitive Hydrogel Based on PEO-PPO-PEO Poloxamers for a Controlled In Situ Release of Recombinant Adeno-Associated Viral Vectors for Effective Gene Therapy of Cartilage Defects.

Advanced biomaterial-guided delivery of gene vectors is an emerging and highly attractive therapeutic solution for targeted articular cartilage repair, allowing for a controlled and minimally invasive delivery of gene vectors in a spatiotemporally precise manner, reducing intra-articular vector spread and possible loss of the therapeutic gene product. As far as it is known, the very first successful in vivo application of such a biomaterial-guided delivery of a potent gene vector in an orthotopic large animal model of cartilage damage is reported here. In detail, an injectable and thermosensitive hydrogel based on poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO poloxamers, capable of controlled release of a therapeutic recombinant adeno-associated virus (rAAV) vector overexpressing the chondrogenic sox9 transcription factor in full-thickness chondral defects, is applied in a clinically relevant minipig model in vivo.

Topographic modeling of early human osteoarthritis in sheep.

Articular cartilage damage occurring during early osteoarthritis (OA) is a key event marking the development of the disease. Here, we modeled early human OA by gathering detailed spatiotemporal data from surgically induced knee OA development in sheep. We identified a specific topographical pattern of osteochondral changes instructed by a defined meniscal injury, showing that both cartilage and subchondral bone degeneration are initiated from the region adjacent to the damage.

Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and a Report on a Unique DFG-in/Leu-in Conformation of Mitogen-Activated Protein Kinase Kinase 7 (MKK7).

Pyrazolopyrimidines are well-established as covalent inhibitors of protein kinases such as the epidermal growth factor receptor or Bruton's tyrosine kinase, and we recently described their potential in targeting mitogen-activated protein kinase kinase 7 (MKK7). Herein, we report the structure-activity relationship of pyrazolopyrimidine-based MKK7 inhibitors and solved several complex crystal structures to gain insights into their binding mode. In addition, we present two structures of apo-MKK7, exhibiting a DFG-out and an unprecedented DFG-in/Leu-in conformation.