Early rehabilitation vs. conventional immobilization in nonoperative treatment of proximal humeral fracture: a systematic review.

OBJECTIVE: Fractures of the proximal humerus (PHF) are commonly treated conservatively. Evidence suggests that a period of immobilization of one week or less may lead to some advantages compared to a traditional 3-4 weeks of immobilization. The purpose of this systematic review was to assess the clinical and radiological results in the case of early rehabilitation vs. delayed rehabilitation after PHF. MATERIALS AND METHODS: In July 2023, a literature search was carried out on the PubMed, MEDLINE, and Embase databases to identify all the randomized trials comparing early rehabilitation vs. delayed rehabilitation after PHF. The following data were extracted from each included study: patients' demographics, study design and level of evidence, follow-up times, treatment groups, evaluation scores adopted, and overall clinical and radiological findings. The quality of the trials was assessed using the Cochrane Risk of Bias Assessment. RESULTS: A total of 5 studies, including 378 patients and dealing with early vs. delayed rehabilitation in case of conservative treatment of PHF, were included in this study. Early rehabilitation was started within 1 week and consisted mainly of pendulum exercise and progressive passive mobilization. Early rehabilitation was associated with better pain and functional scores within the first 3 months in 3 studies. No difference in pain or function was reported at 6 months or longer follow-up, and no differences in complications rate were observed between early vs. delayed rehabilitation groups. CONCLUSIONS: This systematic review suggests that early mobilization within one week in case of conservative treatment of PHF leads to improved function recovery and reduced pain, especially in the first months of rehabilitation, without differences at longer follow-up and without increasing complications rate. Reducing immobilization time could accelerate function recovery and regaining independence in daily life activities.

Injection of biologic agents for treating severe knee osteoarthritis: is there a chance for a good outcome? A systematic review of clinical evidence.

OBJECTIVE: Osteoarthritis (OA) is the most common degenerative joint disease and the leading cause of disability in the adult population worldwide. The knee is the most prevalent site of symptomatic arthritis. Treatment options for OA include drugs, surgery and, more recently, biological treatments. Injectable ortho-biological treatments include autologous and more rarely heterologous preparations employed inside and outside the operating room to assist bone and soft tissue regeneration. Our aim was to analyze the rationale for use of injectable ortho-biological treatments such as platelet-rich plasma (PRP) and mesenchymal cells from bone marrow, adipose tissue, and placenta/umbilical cord, in patients with severe OA of the knee (Kellgren-Lawrence grade 4). MATERIALS AND METHODS: A search in PubMed, ScienceDirect and Google Scholar databases was performed using the following keywords: 'knee osteoarthritis' and 'biological treatment' or 'PRP' or 'adipose' or 'mesenchymal' or 'staminal' or 'stem cells'. Manual research throughout the reference lists of all retrieved articles was further conducted. RESULTS: A total of 16 articles was selected for this systematic review. The rationale for use of each ortho-biological treatment was discussed. The clinical application showed different therapeutic protocols, different follow-up periods, different outcomes analyzed and small sample size. CONCLUSIONS: Our study did not demonstrate uniform beneficial effects for the use of injectable ortho-biological. This prevents any advice for routine application in the treatment of severe knee OA (K-L IV). Further prospective clinical trials with randomization, larger sample size, and preliminary power calculation are needed to justify the use of injectable biologic agents in grade IV knee OA in everyday practice.

Evidence-based treatment choices for acute lateral ankle sprain: a comprehensive systematic review.

OBJECTIVE: Lateral ankle sprains are very common injuries that can be treated with different strategies. The aim of the present systematic review was to provide a comprehensive analysis on the treatment of acute lateral ankle sprains to clarify the possible differences in outcome between surgical and conservative management, different external supports, and different rehabilitation protocols. MATERIALS AND METHODS: A literature search on three different topics was carried out on PubMed, Scopus, and Web of Science databases on June 25th, 2021. The main objective of the literature search was to identify the randomized trials comparing: (1) surgery to conservative management, (2) different external supports, and (3) different rehabilitation protocols for the treatment of acute lateral ankle sprains. Two investigators extracted independently relevant data from each paper and assessed the quality of the trials using the Cochrane Risk of Bias Assessment. RESULTS: A total of 12 studies for the first topic, 8 for the second one and 4 for the last one were included in this review. 8 out of 12 RCTs demonstrated a superior outcome and better socio-economic impact of conservative treatment compared to surgical management. In the other two comparisons, due to the wide variety of braces used and the different rehabilitation protocols, inconclusive results were obtained. CONCLUSIONS: Conservative treatment should be the first choice for severe acute lateral ankle sprains, as it provides satisfactory functional outcomes without the risks and costs of surgery. It was not possible to identify the best external support, but a preference toward flexible braces emerged since they allow an earlier return to daily activities. The paucity of studies comparing different rehabilitation protocols precluded the possibility of defining the ideal one.

Transcriptional repression mediated by repositioning of genes to the nuclear lamina.

Nuclear compartmentalization seems to have an important role in regulating metazoan genes. Although studies on immunoglobulin and other loci have shown a correlation between positioning at the nuclear lamina and gene repression, the functional consequences of this compartmentalization remain untested. We devised an approach for inducible tethering of genes to the inner nuclear membrane (INM), and tested the consequences of such repositioning on gene activity in mouse fibroblasts. Here, using three-dimensional DNA-immunoFISH, we demonstrate repositioning of chromosomal regions to the nuclear lamina that is dependent on breakdown and reformation of the nuclear envelope during mitosis. Moreover, tethering leads to the accumulation of lamin and INM proteins, but not to association with pericentromeric heterochromatin or nuclear pore complexes. Recruitment of genes to the INM can result in their transcriptional repression. Finally, we use targeted adenine methylation (DamID) to show that, as is the case for our model system, inactive immunoglobulin loci at the nuclear periphery are contacted by INM and lamina proteins. We propose that these molecular interactions may be used to compartmentalize and to limit the accessibility of immunoglobulin loci to transcription and recombination factors.

Using altered specificity Oct-1 and Oct-2 mutants to analyze the regulation of immunoglobulin gene transcription.

Oct-1 and Oct-2 represent the prototypical example of related transcription factors with identical DNA recognition properties. They bind functionally critical octamer elements found in diverse regulatory sequences. It has not been possible to determine directly if these factors are functionally redundant or selective when interacting with different regulatory sequences in the appropriate cell type. An equivalent pair of altered DNA-binding specificity mutants of Oct-1 and Oct-2 are used to examine their function from varied regulatory contexts in B cells. These factors function as redundant activators of immunoglobulin (Ig) gene promoters (Vkappa and VH) and a histone H2B promoter. The structural basis of redundancy resides in the highly conserved DNA-binding POU domain, because this domain of either protein can activate transcription from both Ig and H2B promoters. We find that the nature of a distal enhancer dictates the relative potency of Oct-1 versus Oct-2 bound to a promoter. Oct-1 preferentially stimulates transcription from a VH or Vkappa promoter in combination with enhancers from the IgH or Igkappa locus, respectively. In this context, the more potent action of Oct-1 is dependent on a region external to the POU domain. These results suggest that Oct-1 may be the critical regulator of Ig gene transcription during B cell development and provide an explanation for selective Ig isotype expression defects in Oct-2 and OCA-B null mice.

Expression of a novel murine homeobox gene in the developing cerebellar external granular layer during its proliferation.

The TGIF homeobox gene encodes a homeoprotein that represses the 9-cis retinoic acid receptor-dependent transcription activation. To investigate the potential role of this gene in vertebrate development, we have isolated cDNA clones of the murine TGIF (mTGIF) gene and analyzed its expression pattern during mouse embryogenesis and postnatal development by Northern analysis, reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ hybridization histochemistry. mTGIF transcripts were detected at day E16 in the emerging external granular layer (EGL), the cells of which arise from the proliferating cerebellar neuroepithelium. Expression of mTGIF transcripts was also detected at day E16 in the proliferating cells in the neuroepithelium of the hippocampal formation. Following gestation, mTGIF expression increases to a maximum between postnatal days 5 and 10 (PN5 and PN10) in the rapidly expanding cerebellar EGL. mTGIF transcripts are no longer detectable when EGL proliferation ceases on approximately day PN15. Throughout embryo development and in the adult mice, TGIF is detected in a restricted number of tissues, mostly in proliferating and differentiating cell lineages, such as tongue and testis. Our results suggest that the TGIF gene regulates target genes involved in the proliferation, migration, and/or differentiation of particular neuronal cell lineages in the developing brain.

A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif.

We describe here a novel homeobox gene, denoted TGIF (5"TG3' interacting factor), which belongs to an expanding TALE (three amino acid loop extension) superclass of atypical homeodomains. The TGIF homeodomain binds to a previously characterized retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE), which contains an unusual DNA target for a homeobox. The interactions of both the homeprotein TGIF and receptor RXR alpha with the CREBPII-RXRE DNA motif occur on overlapping areas and generate a mutually exclusive binding in vitro. Transient cellular transfections demonstrate that TGIF inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. TGIF transcripts were detected in a restricted number of tissues. The canonical binding site of TGIF is conserved and is an integral part of several responsive elements which are organized like the CRBPII-RXRE. Hence, a novel auxiliary factor to the steroid receptor superfamily may participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.