Outcomes of Threaded Intramedullary Headless Nail Fixation for Metacarpal Fractures.

Metacarpal fractures are common and may require operative treatment; however, there is no gold standard fixation technique. K-wires are used for simplicity and flexibility but require immobilization and can lead to complications. Dorsal plating provides greater stability than K-wires but is subject to its own limitations. Intramedullary threadless nails have reduced time to union and improved range of motion (ROM) but may not provide the stability of plating. Intramedullary screws allow rapid return to activity and increased stability; however, compression forces may shorten metacarpals, producing non-anatomic reduction. The ExsoMed INnateTM threaded intramedullary nail (ExsoMed, Aliso Viejo, CA, USA) was developed with tall threads, a diameter fitting the metacarpal canal cortical purchase, stability, and no compression to prevent fracture displacement and shortening. We designed a prospective study to evaluate INnateTM nail fixation in metacarpal fractures. Visual analog scale (VAS) pain score, total active motion (TAM), radiographic union, and return to normal activity were recorded at each postoperative visit. Descriptive statistics were performed for endpoints. Fifty-eight patients were included with a median age of 38.7 years. The INnateTM nail was used in 80 fractured metacarpals. The 4th and 5th metacarpals were most frequently involved. The most common mechanisms of injury were blunt trauma and motor vehicle collisions. Approximately 31% of patients had multiple, concurrent fractures (16 patients required two nails; two required three nails). The mean follow-up was 9.9 weeks. The mean time to radiographic union was 9.1 weeks. The final visual analog scale (VAS) pain score was 1.1. The mean time to return to work and/or normal activities was 9.7 weeks, and the mean percentage of normal activity resumed was 89.1%.

A strict requirement in proteasome substrates for spacing between ubiquitin tag and degradation initiation elements.

Proteins are typically targeted to the proteasome for degradation through the attachment of ubiquitin chains and the proteasome initiates degradation at a disordered region within the target protein. Yet some proteins with ubiquitin chains and disordered regions escape degradation. Here we investigate how the position of the ubiquitin chain on the target protein relative to the disordered region modulates degradation and show that the distance between the two determines whether a protein is degraded efficiently. This distance depends on the type of the degradation tag and is likely a result of the separation on the proteasome between the receptor that binds the tag and the site that engages the disordered region.

Evolution of Androgen Deprivation Therapy (ADT) and Its New Emerging Modalities in Prostate Cancer: An Update for Practicing Urologists, Clinicians and Medical Providers.

Androgen deprivation therapy (ADT) has been the main management strategy for prostate cancer for more than eight decades, nowadays achieved commonly by administration of luteinizing hormone-releasing hormone agonists. ADT markedly suppresses androgen hormones with the long-term risks of adverse events such as muscle weakness, impairment of glucose and lipid metabolism, impotence, osteoporosis, and secondary fractures. Extensive research has provided significantly better insight into the dynamics of ADT including identification of the benefits of sequential and combination therapies. This has led to the development of new pharmaceutical ADT modalities. This review provides a general overview of the evolution of ADT in the context of the new emerging pharmaceutical ADT modalities so that clinicians and medical providers have a better understanding of personalizing the available ADT options with their different risk-benefit profiles.

Evaluation of the Quality of Evidence of the Association of Foods and Nutrients With Cardiovascular Disease and Diabetes: A Systematic Review.

Importance: Poor diet is a leading global factor associated with cardiometabolic disease (CMD). Understanding the quality of evidence of the associations between specific dietary factors and CMD, including effect size (relative risk [RR]) and uncertainty, is essential to guide policy and consumer actions to achieve healthy diet and public health goals. Objective: To assess the quality of evidence of the associations between specific dietary factors and CMD as well as the quantitative evidence for RRs and the uncertainty of these risk estimates. Evidence Review: PubMed and the reference lists of eligible articles were searched between May 1, 2015, and February 26, 2021, for systematic reviews with meta-analyses of randomized clinical trials and prospective cohort studies that analyzed the consumption of 1 or more of the dietary factors of interest; reported dose-response meta-analyses; included healthy adults; and assessed 1 or more of the outcomes of interest. Study characteristics and RR estimates were extracted in duplicate. For identified associations, quality of evidence was assessed using the Bradford-Hill criteria for causation. Findings: A total of 2058 potentially relevant reports were identified, from which 285 full-text articles were assessed for eligibility. The final selection of articles included 28 meta-analyses representing 62 associations between diet and CMD. Among these associations, 10 foods, 3 beverages, and 12 nutrients had at least probable evidence of associations with coronary heart disease, stroke, and/or diabetes. Most RRs ranged from 0.87 to 0.96 per daily serving change for protective associations and from 1.06 to 1.15 per daily serving change for harmful associations. Most identified associations were protective (n = 38) and a smaller number were harmful (n = 24), with a higher risk associated with higher intake. Conclusions and Relevance: This systematic review summarized the current quality of evidence of the associations of specific dietary factors with coronary heart disease, stroke, and diabetes. These findings may inform dietary guidance, the assessment of disease burden in specific populations, policy setting, and future research.

Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene.

BACKGROUND: Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases. METHODS: We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations. RESULTS: We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19-21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor ß-integrin 1 (ITGß1). CONCLUSIONS: FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.

Adaptive properties of human cementum and cementum dentin junction with age.

OBJECTIVES: The objective of this study was to evaluate age related changes in physical (structure/mechanical properties) and chemical (elemental/inorganic mineral content) properties of cementum layers interfacing dentin. METHODS: Human mandibular molars (N=43) were collected and sorted by age (younger=19-39, middle=40-60, older=61-81 years). The structures of primary and secondary cementum (PC, SC) types were evaluated using light and atomic force microscopy (AFM) techniques. Chemical composition of cementum layers were characterized through gravimetric analysis by estimating ash weight and concentrations of Ca, Mn, and Zn trace elements in the analytes through inductively coupled plasma mass spectroscopy. The hardness of PC and SC was determined using microindentation and site-specific reduced elastic modulus properties were determined using nanoindentation techniques. RESULTS: PC contained fibrous 1-3 µm wide hygroscopic radial PDL-inserts. SC illustrated PC-like structure adjacent to a multilayered architecture composing of regions that contained mineral dominant lamellae. The width of the cementum dentin junction (CDJ) decreased as measured from the cementum enamel junction (CEJ) to the tooth apex (49-21 µm), and significantly decreased with age (44-23 µm; p<0.05). The inorganic ratio defined as the ratio of post-burn to pre-burn weight increased with age within primary cementum (PC) and secondary cementum (SC). Cementum showed an increase in hardness with age (PC (0.40-0.46 GPa), SC (0.37-0.43 GPa)), while dentin showed a decreasing trend (coronal dentin (0.70-0.72 GPa); apical dentin (0.63-0.73 GPa)). SIGNIFICANCE: The observed physicochemical changes are indicative of increased mineralization of cementum and CDJ over time. Changes in tissue properties of teeth can alter overall tooth biomechanics and in turn the entire bone-tooth complex including the periodontal ligament. This study provides baseline information about the changes in physicochemical properties of cementum with age, which can be identified as adaptive in nature.