Long-term Efficacy of Corticosteroid Injection for Carpal Tunnel Syndrome: A Systematic Review.

Carpal tunnel syndrome (CTS) is a debilitating condition that can cause significant morbidity. Corticosteroid injection (CI) is a popular treatment for CTS. Short-term benefits of CI for CTS have been reported, but there is little evidence on long-term outcomes. We performed a systematic review in the PubMed/MEDLINE and Cochrane Library databases to identify studies which reported outcomes of CI for CTS with at least 1-year follow-up. We identified 20 total studies and extracted data on outcomes such as number of patients needing eventual surgery or reinjection, complications, and functional scores. In included studies, 41.6% of patients underwent eventual carpal tunnel release surgery (CTRS), 29% underwent reinjection, there were no major and approximately 34/1133 (3.0%) minor complications, and median/mean time from CI to eventual CTRS ranged from 128 to 446 days. There was disparity on the long-term efficacy of CI for functional outcomes. The evidence indicates that CI is a very low risk procedure that has potential to improve symptoms enough to either prevent or, in most cases, delay the need for further reintervention. However, our conclusions are limited by the heterogeneity of available studies. There is a need for further, high-quality research on this topic.

Heterozygous Nonsense Variants in the Ferritin Heavy Chain Gene FTH1 Cause a Neuroferritinopathy.

Ferritin, the iron storage protein, is composed of light and heavy chain subunits, encoded by FTL and FTH1, respectively. Heterozygous variants in FTL cause hereditary neuroferritinopathy, a type of neurodegeneration with brain iron accumulation (NBIA). Variants in FTH1 have not been previously associated with neurologic disease. We describe the clinical, neuroimaging, and neuropathology findings of five unrelated pediatric patients with de novo heterozygous FTH1 variants. Children presented with developmental delay, epilepsy, and progressive neurologic decline. Nonsense FTH1 variants were identified using whole exome sequencing, with a recurrent variant (p.Phe171*) identified in four unrelated individuals. Neuroimaging revealed diffuse volume loss, features of pontocerebellar hypoplasia and iron accumulation in the basal ganglia. Neuropathology demonstrated widespread ferritin inclusions in the brain. Patient-derived fibroblasts were assayed for ferritin expression, susceptibility to iron accumulation, and oxidative stress. Variant FTH1 mRNA transcripts escape nonsense-mediated decay (NMD), and fibroblasts show elevated ferritin protein levels, markers of oxidative stress, and increased susceptibility to iron accumulation. C-terminus variants in FTH1 truncate ferritin's E-helix, altering the four-fold symmetric pores of the heteropolymer and likely diminish iron-storage capacity. FTH1 pathogenic variants appear to act by a dominant, toxic gain-of-function mechanism. The data support the conclusion that truncating variants in the last exon of FTH1 cause a disorder in the spectrum of NBIA. Targeted knock-down of mutant FTH1 transcript with antisense oligonucleotides rescues cellular phenotypes and suggests a potential therapeutic strategy for this pediatric neurodegenerative disorder.

Arthroscopic Treatment of Shoulder Stiffness With Rotator Cuff Repair Yields Similar Outcomes to Isolated Rotator Cuff Repair.

Purpose: To compare patient-reported and surgical outcome measures in patients with and without secondary shoulder stiffness (SSS) undergoing rotator cuff repair (RCR). Methods: Patients undergoing rotator cuff repair from 2014 to 2020 with complete patient-reported outcome measures (PROMs) by the short-form 12 survey (SF-12) were retrospectively reviewed to identify if operative intervention for SSS was performed alongside the RCR. Those patients with operative intervention for SSS were propensity matched to a group without prior intervention for stiffness by age, sex, laterality, body mass index, diabetes mellitus status, and the presence of a thyroid disorder. The groups were compared by rotator cuff tear (RCT) size, surgical outcomes, further surgical intervention, rotator cuff retear rate, postoperative range of motion (ROM), and SF-12 results at 1 year after surgery. Delta values were calculated for component scores of the SF-12 and ROM values by subtracting the preoperative result from the postoperative result. Results: A total of 89 patients with SSS were compared to 156 patients in the control group at final analysis. The patients in the SSS group experienced a significant improvement in the delta mental health component score (MCS-12) of the SF-12 survey that was not seen in the control group (P = .005 to P = .539). Both groups experienced significant improvement by the delta physical health component score (PCS-12) of the SF-12 survey (SSS: 7.68; P < .001; control: 6.95; P < .001). The SSS group also experienced greater improvement of their forward flexion (25.8° vs 12.9°; P = .005) and external rotation (7.13° vs 1.65°; P = .031) ROM than the control group. Conclusions: Operative intervention of SSS at the time of RCR has equivalent postoperative SF-12 survey outcome scores when compared to patients undergoing RCR without preoperative stiffness despite those patients having lower preoperative scores. Level of Evidence: Level III retrospective comparative study.

Surgeon Estimations of Acetabular Cup Orientation Using Intraoperative Fluoroscopic Imagining Are Unreliable.

Background: Accurate acetabular cup orientation is associated with decreased revision rates and improved outcomes of primary total hip arthroplasty. This study assesses surgeon's ability to estimate both the acetabular component inclination and anteversion angles via intraoperative fluoroscopy (IF) images. Methods: We surveyed orthopedic surgeons to estimate acetabular component inclination and anteversion based on 20 IF images of total hip arthroplasty through a direct anterior approach. Postoperative computed-tomography scans were used to calculate the true inclination and anteversion component angles. The absolute difference between the true and estimated values was calculated to determine the mean and standard deviation of the survey results. Interrater reliability was determined through interclass correlation coefficients. Results: A majority of surgeons preferred the direct anterior approach (83.3%) and utilized IF during surgery (70%). Surgeons surveyed were on average 5.9° away from the true value of inclination (standard deviation = 4.7) and 8.8° away from the true value of anteversion (standard deviation = 6.0). Respondents were within 5° of both inclination and anteversion in 19.7% of cases, and within 10° in 57.3% of cases. All surgeons were determined to have poor reliability in estimating anteversion (interclass correlation coefficient < 0.5). Only 2 surgeons were determined to have moderate reliability when estimating inclination. Conclusions: Surgeons, when solely relying on IF for the estimation of anteversion and inclination, are unreliable. Utilization of other techniques in conjunction with IF would improve observer reliability.

Heterozygous Nonsense Variants in the Ferritin Heavy Chain Gene FTH1 Cause a Novel Pediatric Neuroferritinopathy.

Ferritin, the iron storage protein, is composed of light and heavy chain subunits, encoded by FTL and FTH1 , respectively. Heterozygous variants in FTL cause hereditary neuroferritinopathy, a type of neurodegeneration with brain iron accumulation (NBIA). Variants in FTH1 have not been previously associated with neurologic disease. We describe the clinical, neuroimaging, and neuropathology findings of five unrelated pediatric patients with de novo heterozygous FTH1 variants. Children presented with developmental delay, epilepsy, and progressive neurologic decline. Nonsense FTH1 variants were identified using whole exome sequencing, with a recurrent de novo variant (p.F171*) identified in three unrelated individuals. Neuroimaging revealed diffuse volume loss, features of pontocerebellar hypoplasia and iron accumulation in the basal ganglia. Neuropathology demonstrated widespread ferritin inclusions in the brain. Patient-derived fibroblasts were assayed for ferritin expression, susceptibility to iron accumulation, and oxidative stress. Variant FTH1 mRNA transcripts escape nonsense-mediated decay (NMD), and fibroblasts show elevated ferritin protein levels, markers of oxidative stress, and increased susceptibility to iron accumulation. C-terminus variants in FTH1 truncate ferritin's E-helix, altering the four-fold symmetric pores of the heteropolymer and likely diminish iron-storage capacity. FTH1 pathogenic variants appear to act by a dominant, toxic gain-of-function mechanism. The data support the conclusion that truncating variants in the last exon of FTH1 cause a novel disorder in the spectrum of NBIA. Targeted knock-down of mutant FTH1 transcript with antisense oligonucleotides rescues cellular phenotypes and suggests a potential therapeutic strategy for this novel pediatric neurodegenerative disorder.

Conformation and dynamic interactions of the multipartite genome in Agrobacterium tumefaciens.

Bacterial species from diverse phyla contain multiple replicons, yet how these multipartite genomes are organized and segregated during the cell cycle remains poorly understood. Agrobacterium tumefaciens has a 2.8-Mb circular chromosome (Ch1), a 2.1-Mb linear chromosome (Ch2), and two large plasmids (pAt and pTi). We used this alpha proteobacterium as a model to investigate the global organization and temporal segregation of a multipartite genome. Using chromosome conformation capture assays, we demonstrate that both the circular and the linear chromosomes, but neither of the plasmids, have their left and right arms juxtaposed from their origins to their termini, generating interarm interactions that require the broadly conserved structural maintenance of chromosomes complex. Moreover, our study revealed two types of interreplicon interactions: "ori-ori clustering" in which the replication origins of all four replicons interact, and "Ch1-Ch2 alignment" in which the arms of Ch1 and Ch2 interact linearly along their lengths. We show that the centromeric proteins (ParB1 for Ch1 and RepBCh2 for Ch2) are required for both types of interreplicon contacts. Finally, using fluorescence microscopy, we validated the clustering of the origins and observed their frequent colocalization during segregation. Altogether, our findings provide a high-resolution view of the conformation of a multipartite genome. We hypothesize that intercentromeric contacts promote the organization and maintenance of diverse replicons.

Union Is Strength: Target-Based and Whole-Cell High-Throughput Screens in Antibacterial Discovery.

Antimicrobial resistance is one of the greatest global health challenges today. For over 3 decades, antibacterial discovery research and development have been focused on cell-based and target-based high-throughput assays. Target-based screens use diagnostic enzymatic reactions to look for molecules that can bind directly to and inhibit the target. Target-based screens are applied only to proteins that can be successfully expressed and purified and the activity of which can be effectively measured using a biochemical assay. Often the molecules found in these in vitro screens are not active in cells due to poor permeability or efflux. On the other hand, cell-based screens use whole cells and look for growth inhibition. These screens give higher numbers of hits than target-based assays and can simultaneously test many targets of one process or pathway in their physiological context. Both strategies have advantages and disadvantages when used separately. In the past 15 years, our increasing knowledge of bacterial physiology has led to the development of innovative and sophisticated technologies to perform high-throughput screening combining these two strategies and thus minimizing their disadvantages. In this review, we discuss recent examples of high-throughput approaches that used both target-based and whole-cell screening to find new antibacterials, the new insights they have provided, and how this knowledge can be applied to other in vivo-validated targets to develop new antimicrobials.

Lysosomal dysfunction impairs mitochondrial quality control and is associated with neurodegeneration in TBCK encephaloneuronopathy.

Biallelic variants in the TBCK gene cause intellectual disability with remarkable clinical variability, ranging from static encephalopathy to progressive neurodegeneration (TBCK-Encephaloneuronopathy). The biological factors underlying variable disease penetrance remain unknown. Since previous studies had suggested aberrant autophagy, we tested whether mitophagy and mitochondrial function are altered in TBCK -/- fibroblasts derived from patients exhibiting variable clinical severity. Our data show significant accumulation of mitophagosomes, reduced mitochondrial respiratory capacity and mitochondrial DNA content, suggesting impaired mitochondrial quality control. Furthermore, the degree of mitochondrial dysfunction correlates with a neurodegenerative clinical course. Since mitophagy ultimately depends on lysosomal degradation, we also examined lysosomal function. Our data show that lysosomal proteolytic function is significantly reduced in TBCK -/- fibroblasts. Moreover, acidifying lysosomal nanoparticles rescue the mitochondrial respiratory defects in fibroblasts, suggesting impaired mitochondrial quality control secondary to lysosomal dysfunction. Our data provide insight into the disease mechanisms of TBCK Encephaloneuronopathy and the potential relevance of mitochondrial function as a biomarker beyond primary mitochondrial disorders. It also supports the benefit of lysosomal acidification strategies for disorders of impaired lysosomal degradation affecting mitochondrial quality control.

Natural Transformation in a Classical-Biotype Vibrio cholerae Strain.

Vibrio cholerae causes the gastrointestinal illness cholera, which spreads throughout the globe in large pandemics. The current pandemic is caused by O1 El Tor biotype strains, whereas previous pandemics were caused by O1 classical biotype strains. El Tor V. cholerae is noted for its ability to acquire exogenous DNA through chitin-induced natural transformation, which has been exploited for genetic manipulation of El Tor strains in the laboratory. In contrast, the prototypical classical strain O395 lacks this ability, which was suspected to be due to a mutation in the regulatory gene hapR HapR and the regulator TfoX control expression of a third competence regulator, QstR. We found that artificial induction of both TfoX and QstR in the presence of HapR in O395 was required for efficient DNA uptake. However, natural transformation in the classical strain is still orders of magnitude below that of an El Tor strain. O395 expressing HapR could also undergo natural transformation after growth on chitin, which could be increased by artificial induction of TfoX and/or QstR. A plasmid that expresses both TfoX and QstR was created that allowed for consistent DNA uptake in O395 carrying a hapR plasmid. This technique was also used to facilitate cotransformation into O395 of unmarked DNA (ΔlacZ, ΔflaA, ΔflgG) for multiplex genome editing by natural transformation (MuGENT). These results demonstrate that the classical biotype O395 strain is functionally capable of DNA uptake, which allows for the rapid genetic manipulation of its genome.IMPORTANCE Natural transformation (uptake of exogenous DNA) in Vibrio cholerae has contributed to the evolution of these human pathogens. Classical biotype V. cholerae strains were responsible for the first six cholera pandemics but were replaced by El Tor biotype V. cholerae in the current pandemic. This study demonstrates that classical V. cholerae is functionally capable of natural transformation, but inactivation of the transformation regulator HapR and inherent levels of transformation that are lower than those of El Tor V. cholerae suggest that the classical biotype may be less able to utilize natural transformation for horizontal gene transfer.

Resultados de una cohorte de pacientes tratados con osteopatía en un hospital polivalente / Results of a cohort of patients treated with osteopathy in a polivalent hospital

Introducción: la osteopatía aborda al paciente de manera global y aplica técnicas de tratamiento manual. Se realizó una evaluación retrospectiva sobre 447 pacientes para conocer los resultados del tratamiento del dolor lumbar y cervical. Material y métodos: fueron incluidos en este estudio 447 pacientes con diagnóstico de lumbalgia y cervicalgia (77,4% de sexo femenino). Los pacientes atendidos ya habían realizado tratamientos convencionales sin haber conseguido resultados satisfactorios. Se evaluó a los pacientes con la escala de valor numérico de dolor (EVN), y los puntajes (scores) de Oswestry (ODI) y el índice de discapacidad de la región cervical (NDI). Los 4 osteópatas intervinientes son profesionales certificados en esta disciplina. Resultados: el 42,8% de los pacientes fueron derivados por el Servicio de Traumatología y el 41,3% por el Servicio de Medicina Familiar. El 34,2% tuvieron diagnóstico de dolor lumbar y al 20,81% se le diagnosticó dolor cervical. Tanto en la valoración del dolor como en los scores utilizados se encontraron diferencias estadísticamente significativas entre la primera y la última sesión. Discusión: en pacientes con diagnóstico de lumbalgia y cervicalgia que no habían obtenido resultados satisfactorios con tratamientos convencionales previos, el tratamiento osteopático derivó en mejoras significativas en todos los parámetros estudiados. (AU)

Introduction: osteopathy addresses the patient globally and applies manual treatment techniques. A retrospective evaluation was carried out on 447 patients to know the results of the treatment of lumbar and cervical pain. Material and methods: 447 patients with a diagnosis of low back pain and cervical pain (77.4% female) were included in this study. The patients already had undergone conventional treatments without having achieved satisfactory results. The patients were evaluated with the numerical value of pain scale (VNS), and Oswestry scores (ODI) and the index of disability of the cervical region (NDI). The 4 intervening osteopaths are certified professionals in this discipline. Results: 42.8% of the patients were referred by the Traumatology Service and 41.3% by the Family Medicine Service. 34.2% had a diagnosis of lumbar pain and 20.8% were diagnosed with neck pain. Statistically significant differences were found between the first and last sessions in both the pain assessment and the scores used. Discussion: in patients with low back pain and neck pain who had not obtained satisfactory results with previous conventional treatments, osteopathic treatment resulted in significant improvements in all the parameters evaluated. (AU)

New cloning vectors to facilitate quick allelic exchange in gram-negative bacteria.

New cloning vectors have been developed with features to enhance quick allelic exchange in gram-negative bacteria. The conditionally replicative R6K and transfer origins facilitate conjugation and chromosomal integration into a variety of bacterial species, whereas the sacB gene provides counterselection for allelic exchange. The vectors have incorporated the lacZ alpha fragment with an enhanced multicloning site for easy blue/white screening and priming sites identified for efficient in vivo assembly or other DNA assembly cloning techniques. Different antibiotic resistance markers allow versatility for use with different bacteria, and transformation into an Escherichia coli strain capable of conjugation enables a quick method for allelic exchange. As a proof of principle, the authors used these vectors to inactivate genes in Vibrio cholerae and Salmonella typhimurium.

Metagenomic Profiling and Microbial Metabolic Potential of Perdido Fold Belt (NW) and Campeche Knolls (SE) in the Gulf of Mexico.

The Gulf of Mexico (GoM) is a particular environment that is continuously exposed to hydrocarbon compounds that may influence the microbial community composition. We carried out a metagenomic assessment of the bacterial community to get an overall view of this geographical zone. We analyzed both taxonomic and metabolic markers profiles to explain how the indigenous GoM microorganims participate in the biogeochemical cycling. Two geographically distant regions in the GoM, one in the north-west (NW) and one in the south-east (SE) of the GoM were analyzed and showed differences in their microbial composition and metabolic potential. These differences provide evidence the delicate equilibrium that sustains microbial communities and biogeochemical cycles. Based on the taxonomy and gene groups, the NW are more oxic sediments than SE ones, which have anaerobic conditions. Both water and sediments show the expected sulfur, nitrogen, and hydrocarbon metabolism genes, with particularly high diversity of the hydrocarbon-degrading ones. Accordingly, many of the assigned genera were associated with hydrocarbon degradation processes, Nitrospira and Sva0081 were the most abundant in sediments, while Vibrio, Alteromonas, and Alcanivorax were mostly detected in water samples. This basal-state analysis presents the GoM as a potential source of aerobic and anaerobic hydrocarbon degradation genes important for the ecological dynamics of hydrocarbons and the potential use for water and sediment bioremediation processes.

Left Atrial "Pinball" Thrombus Causing Recurrent Syncope.

A 75-year-old female was admitted due to a syncopal episode. Transesophageal echocardiography demonstrated severe mitral stenosis with a 5 cm, free-floating, left atrial thrombus intermittently obstructing the mitral valve orifice; she underwent thrombus removal and mitral valve replacement.

The Cardiovascular effects of chocolate.

The antioxidants as polyphenols, especially flavanols present in cocoa, exert a favorable effect on endothelium vasodilation, modulate inflammatory markers, and decrease platelet aggregation, lipid oxidation and insulin resistance. Recent nutritional intervention trials and molecular studies demonstrate that consumption of cocoa, particularly rich in flavanols, is beneficial to promote cardiovascular health. This review describes the cardiovascular effects of chocolate.

Tethered cord in children: a clinical classification with urodynamic correlation.

PURPOSE: Tethered cord was classified based on clinical presentation and correlated with urodynamic and uroradiographic findings. MATERIALS AND METHODS: A total of 54 children underwent cord untethering from 1993 through 2000. Preoperative magnetic resonance imaging, fluorourodynamics and renal ultrasound were performed in all cases, and postoperative (mean 16 months) fluorourodynamics was done in 33. The conus was at L-2 or lower, with or without a thickened filum in 51 patients and 3 older children with voiding dysfunction had normal cords. RESULTS: Children were classified into group 1-19 with orthopedic deformities (scoliosis or lower limb abnormalities, group 2-16 with cutaneous back lesions, group 3-13 with voiding dysfunction (VD) or urinary tract infection without cutaneous lesions and group 4-6 with associated syndromes. In group 1, 3 patients (16%) had preoperative hyperreflexia (HR) which improved postoperatively in 2, HR developed in 1, none had hydronephrosis or reflux (VUR), 5 (26%) had voiding dysfunction (VD) and 4 improved postoperatively. In group 2, 4 patients (25%) had preoperative HR and all improved postoperatively, and 5 (31%) had VUR and 2 improved postoperatively. In group 3, 11 patients (85%) had HR and 2 (15%) were areflexic preoperatively and 6 (areflexic 1, HR 5) improved postoperatively, 3 (23%) had VUR and 2 improved postoperatively, and 7 (54%) had improved VD but 5 (71%) were on anticholinergics. All 3 patients with VD/normal cords had preoperative HR, and 1 improved, 1 had preoperative VUR which resolved and 1 clinically improved but was on anticholinergics. In group 4, 5 patients (83%) had HR and 2 improved, 2 (33%) had VUR and both improved, and 3 (50%) had VD and 1 improved. CONCLUSIONS: Older children who present with orthopedic problems have rare neurourological abnormalities many of which resolve after surgery. Similarly, infants who are diagnosed early with a cutaneous back lesion can have urodynamic abnormalities, which also have a high rate of resolution. Older children who present with VD have the highest incidence of urodynamic abnormalities. While many seem improved clinically after surgery, they require anticholinergics. All patients with VATER's syndrome should be evaluated prospectively for tethered cord.