Calcitonin delays the progress of early-stage mechanically induced osteoarthritis. In vivo, prospective study

SummaryBackground/rationaleIntroducing new or testing existing drugs in an attempt to modify the progress of osteoarthritis (OA) is of paramount importance.Questions/purposesThis study aims to determine the effect exerted by Calcitonin on the progress of early-stage osteoarthritic lesions.MethodsWe used 18, skeletally mature, white, female, New Zealand rabbits. OA was operatively induced in the right knee of each animal by the complete dissection of the anterior cruciate ligament, complete medial meniscectomy and partial dissection of the medial collateral ligament. Postoperatively, animals were divided into two groups. Starting on the ninth postoperative day and daily thereafter, group A animals (n = 9) received 10 IU oculus dexter (o.d.) of synthetic Calcitonin IntraMuscularly (I.M.); group B animals (n = 9) received equal volume of saline o.d. Three animals from each group were sacrificed at 1, 2 and 3 months following treatment's initiation. The extent and the grade of OA were assessed macroscopically, histologically and by radiographs, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)-scans. The Osteoarthritis Research Society International (OARSI) score, incorporating histological and macroscopic information, was calculated for each knee.ResultsOsteoarthritic changes in group A animals were less severe and progressed less rapidly when compared with those of group B animals (sham). This difference was statistically significant in the first and second month (P = 0.05), but not in the third month (P = 0.513).ConclusionsI.M. administration of Calcitonin seems to delay the progress of early-stage osteoarthritic lesions induced by mechanical instability in a rabbit experimental model

Impact of preoperative therapy on patterns of recurrence in pancreatic cancer

AbstractBackgroundA theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence.MethodsMedical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan–Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis.ResultsPreoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis.ConclusionsPreoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection

Condensation properties of stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

RNA regulation in mammalian cells requires complex physical compartmentalisation, using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic dystrophy type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). We report here the deregulation of stress granules (SGs) and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures is a consequence of the presence of CUGexp RNA.</p

Control and ultrasonic actuation of a gas-liquid interface in a microfluidic chip

This article describes the design and manufacturing of a microfluidic chip, allowing for the actuation of a gas-liquid interface and of the neighboring fluid. A first way to control the interface motion is to apply a pressure difference across it. In this case, the efficiency of three different micro-geometries at anchoring the interface is compared. Also, the critical pressures needed to move the interface are measured and compared to theoretical result. A second way to control the interface motion is by ultrasonic excitation. When the excitation is weak, the interface exhibits traveling waves, which follow a dispersion equation. At stronger ultrasonic levels, standing waves appear on the interface, with frequencies that are half integer multiple of the excitation frequency. An associated microstreaming flow field observed in the vicinity of the interface is characterized. The meniscus and associated streaming flow have the potential to transport particles and mix reagents

Social prescribing for people living with dementia (PLWD) and their carers: what works, for whom, under what circumstances and why – protocol for a complex intervention systematic review

\ua9 Author(s) (or their employer(s)) 2024.Introduction Dementia is a complex medical condition that poses significant challenges to healthcare systems and support services. People living with dementia (PLWD) and their carers experience complex needs often exacerbated by social isolation and challenges in accessing support. Social prescribing (SP) seeks to enable PLWD and their carers to access community and voluntary sector resources to support them address such needs. Existing research, however, does not describe what SP interventions are currently in place in dementia care. Little is known about the needs these interventions are designed to address, the reasons that lead PLWD and their carers to participate in them, their effectiveness and the extent to which they could increase positive health outcomes if adopted and how. Methods and analysis A complex intervention systematic review of SP for PLWD and/or their carers will be conducted using an iterative logic model approach. Six electronic (MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus and Cochrane/CENTRAL) and two grey literature databases (EThOS and CORE) were searched for publications between 1 January 2003 and June 2023, supplemented by handsearching of reference lists of included studies. Study selection, data extraction and risk of bias assessment, using Gough’s Weight of Evidence Framework, will be independently performed by two reviewers. A narrative approach will be employed to synthesise and report quantitative and qualitative data. Reporting will be informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Interventions extension statement and checklist. Ethics and dissemination No ethical approval is required due to this systematic review operating only with secondary sources. Findings will be disseminated through peer-reviewed publications, conference presentations and meetings with key stakeholders including healthcare professionals, patient and carer groups, community organisations (eg, the Social Prescribing Network and the Evidence Collaborative at the National Academy for Social Prescribing), policymakers and funding bodies. PROSPERO registration number CRD42023428625

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking “back-differentiation” of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms

Severe axial vertebral rotation treated with a modified Boston brace: a case report

We report the case of a 13-year-old Caucasian girl suffering from severe axial rotation of the T5 to L4 vertebrae. The patient (initially examined during a school screening study) was at first considered to be suspicious of suffering from scoliosis due to a highly positive Adam's forward bending test. However, her radiographic evaluation revealed the existence of axial rotation in 12 of her vertebrae, without inclination in the sagittal and coronal planes. After an observation period of 12 months and due to the fact that both her physical appearance and the measured vertebral rotation deteriorated, the patient was given a modified thoracolumbar Boston brace that had an immediate positive derotational effect on all but two vertebrae. Twenty four months later, the progress of the vertebral rotation(s) seems to have been halted and most affected vertebrae appear to be stabilized in their new, 'post-brace', reduced position, with better results shown when the Boston brace is worn. The patient remains under constant medical observation. The application of a modified Boston brace seems to have served well (so far) a useful purpose for reducing and stabilizing this case of severe axial vertebral rotation, providing less deformity and (possibly) offering a better final cosmetic result

Social prescribing for people living with dementia (PLWD) and their carers: what works, for whom, under what circumstances and why - protocol for a complex intervention systematic review

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordINTRODUCTION: Dementia is a complex medical condition that poses significant challenges to healthcare systems and support services. People living with dementia (PLWD) and their carers experience complex needs often exacerbated by social isolation and challenges in accessing support. Social prescribing (SP) seeks to enable PLWD and their carers to access community and voluntary sector resources to support them address such needs. Existing research, however, does not describe what SP interventions are currently in place in dementia care. Little is known about the needs these interventions are designed to address, the reasons that lead PLWD and their carers to participate in them, their effectiveness and the extent to which they could increase positive health outcomes if adopted and how. METHODS AND ANALYSIS: A complex intervention systematic review of SP for PLWD and/or their carers will be conducted using an iterative logic model approach. Six electronic (MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus and Cochrane/CENTRAL) and two grey literature databases (EThOS and CORE) were searched for publications between 1 January 2003 and June 2023, supplemented by handsearching of reference lists of included studies. Study selection, data extraction and risk of bias assessment, using Gough's Weight of Evidence Framework, will be independently performed by two reviewers. A narrative approach will be employed to synthesise and report quantitative and qualitative data. Reporting will be informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Interventions extension statement and checklist. ETHICS AND DISSEMINATION: No ethical approval is required due to this systematic review operating only with secondary sources. Findings will be disseminated through peer-reviewed publications, conference presentations and meetings with key stakeholders including healthcare professionals, patient and carer groups, community organisations (eg, the Social Prescribing Network and the Evidence Collaborative at the National Academy for Social Prescribing), policymakers and funding bodies. PROSPERO REGISTRATION NUMBER: CRD42023428625.National Institute for Health and Care Research (NIHR

The involvement of cancer patients in the four stages of decision-making preceding continuous sedation until death: A qualitative study

BACKGROUND: Involving patients in decision-making is considered to be particularly appropriate towards the end of life. Professional guidelines emphasize that the decision to initiate continuous sedation should be made in accordance with the wishes of the dying person and be preceded by their consent. AIM: To describe the decision-making process preceding continuous sedation until death with particular attention to the involvement of the person who is dying. DESIGN: Qualitative case studies using interviews. SETTING/PARTICIPANTS: Interviews with 26 physicians, 30 nurses and 24 relatives caring for 24 patients with cancer who received continuous sedation until death in Belgium, the United Kingdom and the Netherlands. RESULTS: We distinguished four stages of decision-making: initiation, information exchange, deliberation and the decision to start continuous sedation until death. There was wide variation in the role the patient had in the decision-making process. At one end of the spectrum (mostly in the United Kingdom), the physician discussed the possible use of sedation with the patient, but took the decision themselves. At the other end (mostly in Belgium and the Netherlands), the patient initiated the conversation and the physician's role was largely limited to evaluating if and when the medical criteria were met. CONCLUSION: Decision-making about continuous sedation until death goes through four stages and the involvement of the patient in the decision-making varies. Acknowledging the potential sensitivity of raising the issue of end-of-life sedation, we recommend building into clinical practice regular opportunities to discuss the goals and preferences of the person who is dying for their future medical treatment and care