Effects of a neuromuscular joint-protective exercise therapy program for treatment of wrist osteoarthritis: a randomized controlled trial.

BACKGROUND: Individuals with wrist osteoarthritis (OA) can suffer from pain, muscular weakness, and impaired motion of the wrist, which can reduce the quality of life. While there is strong evidence that all patients with OA should receive first-line treatment with education and exercises, this approach has not yet been proposed for individuals with wrist OA. Therefore, this trial aimed to evaluate the effectiveness of a first line neuromuscular joint-protective exercise therapy program compared to a training program with range of motion (ROM) exercises in patients with wrist OA. METHODS: In this randomized controlled trial (RCT), 48 patients with symptomatic and radiographically confirmed wrist OA were randomly allocated to a 12-week self-management program with either a neuromuscular joint-protective exercise therapy program (intervention group) or a training program with ROM exercises only (control group). Our primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) with secondary outcome measures of grip strength, range of wrist motion, the Numerical Pain Rating, Scale (NPRS), the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Generalized Self-Efficacy Scale (GSES). The outcome measures were evaluated by a blinded assessor at baseline and 12 weeks. Between-groups differences were analyzed using the Mann-Whitney U test and within-group differences were analyzed with the Wilcoxon signed-rank test. RESULTS: A total of 41 participants were analyzed at 12 weeks. There were no significant differences in PRWE between the groups at 12 weeks (p = 0.27). However, DASH improved significantly in the intervention group compared to the control group (p = 0.02) and NPRS on load within the intervention group (p = 0.006). The difference in DASH should be interpreted with caution since it could be due to a non-significant increase (worsening) from baseline in the control group in combination with a non-significant decrease (improvement) in the intervention group. CONCLUSIONS: This RCT showed that the novel neuromuscular joint-protective exercise therapy program was not superior in reducing pain and improving function compared to a training program with ROM exercises at 12 weeks. Future research is warranted to evaluate the effectiveness of forthcoming exercise therapy treatment programs for patients with wrist OA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 10/05/2022. https://clinicaltrials.gov .

Unraveling pH Effects on Ultrafiltration Membrane Fouling by Extracellular Polymeric Substances: Adsorption and Conformation Analyzed with Localized Surface Plasmon Resonance.

Extracellular polymeric substances (EPSs) can conform and orient on the surface according to the applied aquatic conditions. While pH elevation usually removes EPSs from membranes, small changes in pH can change the adsorbed EPS conformation and orientation, resulting in a decrease in membrane permeability. Accordingly, EPS layers were tested with localized surface plasmon resonance (LSPR) sensing and quartz crystal microbalance with dissipation monitoring (QCM-D) using a hybrid sensor. A novel membrane-mimetic hybrid QCM-D-LSPR sensor was designed to indicate both "dry" mass and mechanical load ("wet" mass) of the adsorbed EPS. The effect of pH on the EPS layer's viscoelastic properties and hydrated thickness analyzed by QCM-D corroborates with the shift in EPS areal concentration, ΓS, and the associated EPS conformation, analyzed by LSPR. As pH elevates, the processes of (i) elevation in EPS layer's thickness (QCM-D) and (ii) decrease in the EPS areal density, ΓS (LSPR), provide a clear indication for changes in EPS conformation, which decrease the effective ultrafiltration (UF) membrane pore diameter. This decrease in the pore diameter together with the increase in surface hydrophobicity elevates UF membrane hydraulic resistance.

The effect of a randomised controlled lifestyle intervention on weight loss and plasma proneurotensin.

AIMS: Proneurotensin (Pro-NT) is a strong predictor of cardiometabolic disease including type 2 diabetes and obesity, however, the effect of lifestyle change on Pro-NT has not been investigated in this context. Middle Eastern (ME) immigrants represent the largest and fastest growing minority population in Europe and are a high-risk population for obesity and type 2 diabetes. In this randomised controlled lifestyle intervention (RCT) addressing ME immigrants to Sweden where weight-loss was previously studied as the main outcome, as a secondary analysis we aimed to study change in Pro-NT during follow-up and if baseline Pro-NT predicted weight loss. METHODS: Immigrants from the Middle East at high risk for type 2 diabetes were invited to participate in this RCT adapted lifestyle intervention of four months' duration. The intervention group (N = 48) received a culturally adapted lifestyle intervention comprising seven group sessions and a cooking class addressing healthier diet and increased physical activity. The control group (N = 44) received treatment as usual with information to improve lifestyle habits on their own. Data assessed using mixed effects regression. OUTCOMES: Primary outcome; change in Pro-NT. Secondary outcome; change in BMI in relation to baseline plasma concentration of Pro-NT. RESULTS: During the four months follow up, weight was significantly reduced in the intervention (-2.5 kg) compared to the control group (0.8 kg) (ß -0.12, 95% CI -0.24 to -0.01, P = 0.028). Pro-NT increased to a significantly greater extent in the intervention compared to the control group during follow up (28.2 vs. 3.5 pmol/L) (ß 11.4; 4.8 to 18.02, P < 0.001). Change over time in BMI was associated with baseline Pro-NT (ß 0.02; 0.01 to 0.04, P = 0.041). CONCLUSION: In consistence with data from surgical weight loss, this RCT paradoxically shows increased levels of Pro-NT during a multifactorial lifestyle intervention resulting in weight loss. Long term studies of Pro-NT following weight loss are needed. TRIAL REGISTRATION: This study is a secondary analysis of the RCT trial registered at www. CLINICALTRIALS: gov . REGISTRATION NUMBER: NCT01420198. Date of registration 19/08/2011. The performance and results of this trial conform to the CONSORT 2010 guidelines.

Psychometric properties of patient-reported outcome measures (PROMs) in wrist osteoarthritis: test-retest reliability and construct validity.

BACKGROUND: Patient-reported outcome measures (PROMs) are frequently used to assess the effects of treatments in patients with wrist osteoarthritis (OA), but their psychometric properties have not been evaluated in this group of patients. Our aim was to evaluate the psychometric properties of the Numeric Rating Scale (NRS pain at rest, pain on motion without load, and pain on load), the Disabilities of the Arm, Shoulder and Hand (DASH) and the Patient Rated Wrist Evaluation (PRWE) questionnaires in patients with wrist OA regarding test-retest reliability and construct validity. METHODS: The NRS, DASH and PRWE were self-administered by 50 patients (40 men and 10 women, mean age 66 years) in a postal survey on two occasions, two weeks apart. Test-retest reliability was evaluated by Kappa statistics and the Spearman rank correlation coefficients (rho) were calculated to evaluate construct validity. RESULTS: The Kappa coefficients for DASH, PRWE and NRS pain on motion without load and NRS pain on load were > 0.90, 95% CI ranging from 0.84 to 0.98, while NRS pain at rest was 0.83, 95% CI 0.73-0.92. The construct validity of the PROMs was confirmed by three formulated hypotheses: a higher correlation between PRWE and NRS (rho 0.80-0.91, p < 0.001) was found, compared to DASH and NRS (rho 0.68-0.80, p < 0.001); the NRS pain on motion without load and NRS pain on load correlated more strongly to PRWE and DASH (rho 0.71-0.91, p < 0.001) compared to NRS pain at rest (rho 0.68-0.80) and a high correlation between PRWE and DASH was found (rho 0.86, p < 0.001). CONCLUSIONS: The NRS, DASH and PRWE demonstrate excellent test-retest reliability and moderate to high construct validity in patients with wrist OA. These PROMs are highly related, but they also differ. Therefore, they complement each other in ensuring a comprehensive evaluation of perceived disability in wrist OA. As PRWE showed the highest test-retest reliability and the highest relation to the other PROMs, the sole use of the PRWE can be recommended in clinical practice.

Alterations to Cerebral Perfusion, Metabolite Profiles, and Neuronal Morphology in the Hippocampus and Cortex of Male and Female Mice during Chronic Exposure to a High-Salt Diet.

Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging.

Patients' experiences before and after total wrist fusion or total wrist arthroplasty: A qualitative study of patients with wrist osteoarthritis.

INTRODUCTION: For patients with advanced wrist osteoarthritis (OA), total wrist fusion (TWF) is the standard surgical treatment, although total wrist arthroplasty (TWA) has become a plausible motion-preserving alternative. PURPOSE: To explore patients' experiences of living with advanced wrist OA before and after surgery with either a TWF or a TWA. Furthermore, we wanted to explore the expectations of surgery, appraisal of results, and the adaptation strategies used to overcome challenges in everyday life. STUDY DESIGN: Qualitative descriptive. METHODS: A purposive sample of 13 patients with advanced wrist OA surgically treated with TWF (n = 7) or TWA (n = 6) was recruited. Semistructured interviews were conducted and analyzed using qualitative content analysis. RESULTS: Four categories are described: the problematic wrist, the breakpoint, appraisal of the results, and adaptation to challenges in everyday life. Pain relief was the primary expectation of surgery, and involvement in the discussion regarding different surgical options had a positive effect on the appraisal of results. The participants' ability to perform tasks in everyday life appeared to be more related to their level of pain than the range of wrist motion. Successful coping strategies were developed, enabling the participants to become more independent and adapt to challenges in daily life. CONCLUSIONS: Previous surgical experiences, occupation, and amount of wrist motion influenced the participants' expectations, surgical choice with either a TWF or a TWA, and the appraisal of results. The findings contribute valuable insights to both surgeons and hand therapists about the importance of having the patient's individual expectations and needs in focus.

PNPLA3 variant M148 causes resistance to starvation-mediated lipid droplet autophagy in human hepatocytes.

The mechanism of how patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant M148 is associated with increased risk of development of hepatic steatosis is still debated. Here, we propose a novel role of PNPLA3 as a key player during autophagosome formation in the process of lipophagy. A human hepatocyte cell line, HepG2 cells, expressing recombinant I148 or 148M, was used to study lipophagy under energy deprived conditions, and lipid droplet morphology was investigated using florescence microscopy, image analysis and biochemical assays. Autophagic flux was studied using the golden-standard of LC3-II turnover in combination with the well characterized GFP-RFP-LC3 vector. To discriminate between, perturbed autophagic initiation and lysosome functionality, lysosomes were characterized by Lysotracker staining and LAMP1 protein levels as well as activity and activation of cathepsin B. For validation, human liver biopsies genotyped for I148 and 148M were analyzed for the presence of LC3-II and PNPLA3 on lipid droplets. We show that the M148-PNPLA3 variant is associated with lipid droplets that are resistant to starvation-mediated degradation. M148 expressing hepatocytes reveal decreased autophagic flux and reduced lipophagy. Both I148-PNPLA3 and M148-PNPLA3 colocalize and interact with LC3-II, but the M148-PNPLA3 variant has lower ability to bind LC3-II. Together, our data indicate that PNPLA3 might play an essential role in lipophagy in hepatocytes and furthermore that the M148-PNPLA3 variant appears to display a loss in this activity, leading to decreased lipophagy.

When age really matters; ferritin reference intervals during infancy revisited.

Infants are at risk for iron deficiency. Despite research advances, assessing iron stores during infancy remains a challenge to the clinician. Ferritin is the first-choice laboratory marker for measuring iron stores but it is today still unclear how to evaluate reference intervals among infants. We have studied Swedish infants (n = 456), born at term after normal pregnancies. Ferritin was measured at birth (umbilical cord sample), 48-72 h, 4 months and 12 months. Lower and upper reference interval limits were constructed as the 2.5th and 97.5th percentiles. By a large study population, we were able to use more stringent measures to avoid interference from the acute phase response than previous reports on ferritin reference intervals. When we used mathematical transformation we furthermore avoided potential information loss in precision and confirmed earlier reports of sex differences. At the lower reference interval limits there were small differences between sexes. For the higher limits, the differences were more pronounced in the older infant. At 0-3 d of age we observed a difference between the sexes of only 5% at the upper limits. The differences peaked at 12 months, where the boys' upper 97.5th percentile was 56% compared to girls.

AMPK activation by A-769662 and 991 does not affect catecholamine-induced lipolysis in human adipocytes.

Activation of AMP-activated protein kinase (AMPK) is considered an attractive strategy for the treatment of type 2 diabetes. Favorable metabolic effects of AMPK activation are mainly observed in skeletal muscle and liver tissue, whereas the effects in human adipose tissue are only poorly understood. Previous studies, which largely employed the AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR), suggest an antilipolytic role of AMPK in adipocytes. The aim of this work was to reinvestigate the role of AMPK in the regulation of lipolysis, using the novel allosteric small-molecule AMPK activators A-769662 and 991, with a focus on human adipocytes. For this purpose, human primary subcutaneous adipocytes were treated with A-769662, 991, or AICAR, as a control, before being stimulated with isoproterenol. AMPK activity status, glycerol release, and the phosphorylation of hormone-sensitive lipase (HSL), a key regulator of lipolysis, were then monitored. Our results show that both A-769662 and 991 activated AMPK to a level that was similar to, or greater than, that induced by AICAR. In contrast to AICAR, which as expected was antilipolytic, neither A-769662 nor 991 affected lipolysis in human adipocytes, although 991 treatment led to altered HSL phosphorylation. Furthermore, we suggest that HSL Ser660 is an important regulator of lipolytic activity in human adipocytes. These data suggest that the antilipolytic effect observed with AICAR in previous studies is, at least to some extent, AMPK independent.

Neuroprotective effects of vitamin D on high fat diet- and palmitic acid-induced enteric neuronal loss in mice.

BACKGROUND: The role of vitamin D in obesity and diabetes is debated. Obese and/or diabetic patients have elevated levels of free fatty acids, increased susceptibility to gastrointestinal symptoms and are suggested to have altered vitamin D balance. The enteric nervous system is pivotal in regulating gastrointestinal activity and high fat diet (HFD) has been shown to cause loss of enteric neurons in ileum and colon. This study investigates the effect of vitamin D on HFD- and palmitic acid-induced enteric neuronal loss in vivo and in vitro. METHODS: Mice were fed either a normal diet (ND) or HFD supplemented with varying levels of vitamin D (from 0x to 20x normal vitamin D level) for 19 weeks. Ileum and colon were analyzed for neuronal numbers and remodeling. Primary cultures of myenteric neurons from mouse small intestine were treated with palmitic acid (4x10-4M) and/or 1α,25-hydroxy-vitamin D3 (VD, 10-11- 10-7M) with or without modulators of lipid metabolism and VD pathways. Cultures were analyzed by immunocyto- and histochemical methods. RESULTS: Vitamin D supplementation had no effect on enteric neuronal survival in the ND group. HFD caused substantial loss of myenteric neurons in ileum and colon. Vitamin D supplementation between 0-2x normal had no effect on HFD-induced neuronal loss. Supplementation with 20x normal, prevented the HFD-induced neuronal loss. In vitro supplementation of VD prevented the palmitic acid-induced neuronal loss. The VD receptor (VDR) was not identified in enteric neurons. Enteric glia expressed the alternative VD receptor, protein disulphide isomerase family A member 3 (PDIA3), but PDIA3 was not found to mediate the VD response in vitro. Inhibition of peroxisome proliferator-activated receptor gamma (PPARγ) and immune neutralization of isocitrate lyase prevented the VD mediated neuroprotection to palmitic acid exposure. CONCLUSIONS: Results show that VD protect enteric neurons against HFD and palmitic acid induced neuronal loss. The mechanism behind is suggested to be through activation of PPARγ leading to improved neuronal peroxisome function and metabolism of neuronal lipid intermediates.

Lessons from Dwarf8 on the strengths and weaknesses of structured association mapping.

The strengths of association mapping lie in its resolution and allelic richness, but spurious associations arising from historical relationships and selection patterns need to be accounted for in statistical analyses. Here we reanalyze one of the first generation structured association mapping studies of the Dwarf8 (d8) locus with flowering time in maize using the full range of new mapping populations, statistical approaches, and haplotype maps. Because this trait was highly correlated with population structure, we found that basic structured association methods overestimate phenotypic effects in the region, while mixed model approaches perform substantially better. Combined with analysis of the maize nested association mapping population (a multi-family crossing design), it is concluded that most, if not all, of the QTL effects at the general location of the d8 locus are from rare extended haplotypes that include other linked QTLs and that d8 is unlikely to be involved in controlling flowering time in maize. Previous independent studies have shown evidence for selection at the d8 locus. Based on the evidence of population bottleneck, selection patterns, and haplotype structure observed in the region, we suggest that multiple traits may be strongly correlated with population structure and that selection on these traits has influenced segregation patterns in the region. Overall, this study provides insight into how modern association and linkage mapping, combined with haplotype analysis, can produce results that are more robust.

Clinical and Patient-Reported Outcomes After Total Wrist Arthroplasty and Total Wrist Fusion: A Prospective Cohort Study with 2-Year Follow-up.

Background: The functional benefits of total wrist arthroplasty (TWA) over total wrist fusion (TWF) are unknown. The purpose of this prospective cohort study was to compare TWA and TWF with respect to functional outcomes and activity limitations at up to 2 years postoperatively. Methods: Between 2015 and 2020, we enrolled all adult patients undergoing TWA or TWF for the management of symptomatic end-stage wrist arthritis at 1 hand surgery department. The primary outcome was the Patient-Rated Wrist Evaluation (PRWE). The secondary outcomes were the visual analog scale (VAS) for pain at rest, on motion, and on loading; grip strength; Disabilities of the Arm, Shoulder and Hand (DASH); and range of motion. Patients completed questionnaires and were examined by the same physiotherapist at baseline and at 3, 6, 12, and 24 months postoperatively. Mixed-model analyses adjusting for age, diagnosis, the preoperative value of the dependent variable, and time since surgery were performed to compare differences in PRWE scores, VAS pain scores, and grip strength between TWA and TWF. Results: Of the 51 patients who had been included at baseline, 47 (18 in the TWA group and 29 in the TWF group) responded to questionnaires and underwent examinations at up to 2 years postoperatively. At baseline, the 2 groups did not differ in terms of age, sex, diagnosis (inflammatory or noninflammatory arthritis), PRWE score, VAS pain score, grip strength, DASH score, or range of motion. No differences between the groups were found for the PRWE (ß, -0.1; 95% confidence interval [CI], -14 to 13; p = 0.99), VAS pain at rest (ß, -3.3; 95% CI, -15 to 9; p = 0.58), VAS pain on loading (ß, -5.3; 95% CI, -22 to 11; p = 0.52), or grip strength (ß, -0.02; 95% CI, -0.18 to 0.14; p = 0.80) on the adjusted mixed-model analyses. Conclusions: Among patients with symptomatic end-stage wrist arthritis, those who underwent TWA did not demonstrate short-term outcomes, including patient-reported disability, pain, and grip strength, superior to those of patients who underwent TWF. These findings call into question the widespread use of TWA. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.

Advanced breast cancers represent a major therapeutic challenge due to their refractoriness to treatment. Cancer-associated fibroblasts (CAFs) are the most abundant constituents of the tumor microenvironment and have been linked to most hallmarks of cancer. However, the influence of CAFs on therapeutic outcome remains largely unchartered. Here, we reveal that spatial coincidence of abundant CAF infiltration with malignant cells was associated with reduced estrogen receptor (ER)-α expression and activity in luminal breast tumors. Notably, CAFs mediated estrogen-independent tumor growth by selectively regulating ER-α signaling. Whereas most prototypical estrogen-responsive genes were suppressed, CAFs maintained gene expression related to therapeutic resistance, basal-like differentiation, and invasion. A functional drug screen in co-cultures identified effector pathways involved in the CAF-induced regulation of ER-α signaling. Among these, the Transforming Growth Factor-ß and the Janus kinase signaling cascades were validated as actionable targets to counteract the CAF-induced modulation of ER-α activity. Finally, genes that were downregulated in cancer cells by CAFs were predictive of poor response to endocrine treatment. In conclusion, our work reveals that CAFs directly control the luminal breast cancer phenotype by selectively modulating ER-α expression and transcriptional function, and further proposes novel targets to disrupt the crosstalk between CAFs and tumor cells to reinstate treatment response to endocrine therapy in patients.

Patterns of childhood adverse events are associated with clinical characteristics of bipolar disorder.

BACKGROUND: Previous studies in bipolar disorder investigating childhood trauma and clinical presentations of the illness have mainly focused on physical and sexual abuse. Our aim was to explore further the relationship between childhood trauma and disease characteristics in bipolar disorder to determine which clinical characteristics were most strongly associated with childhood trauma total score, as well as subtypes of adverse childhood events, including physical, sexual, emotional abuse and neglect. METHODS: 141 Patients with bipolar disorder were consecutively recruited, and disease history and clinical characteristics were assessed. History of childhood abuse was obtained using the Childhood Trauma Questionnaire (CTQ). Statistical methods used were factor analysis, Poisson and linear regression, and generalized additive modeling (GAM). RESULTS: The factor analysis of CTQ identified three factors: emotional abuse/neglect, sexual abuse and physical abuse. There were significant associations between CTQ total score and earlier onset of illness, reduced level of psychosocial functioning (GAF; Global Assessment of Functioning) and decreased number of hospitalization, which mainly were due to the factor emotional abuse/neglect. Physical abuse was significantly associated with lower GAF scores, and increased number of mood episodes, as well as self-harm. Sexual abuse was significantly associated with increased number of mood episodes. For mood episodes and self-harm the associations were characterized by great variance and fluctuations. CONCLUSIONS: Our results suggest that childhood trauma is associated with a more severe course of bipolar illness. Further, childhood abuse (physical and sexual), as well as emotional abuse and neglect were significantly associated with accelerating staging process of bipolar disorder. By using specific trauma factors (physical abuse, sexual abuse and emotional abuse/neglect) the associations become both more precise, and diverse.

High prevalence of childhood trauma in patients with schizophrenia spectrum and affective disorder.

OBJECTIVE: Childhood trauma (CT) is a major risk factor for various psychiatric disorders. We wanted to determine the prevalence of CT in a catchment area-based sample of schizophrenia spectrum and affective disorder (including bipolar disorder and depressive episodes with psychotic features) and to explore potential differences in types of CT between the diagnostic groups. METHOD: Three hundred five patients were recruited consecutively from psychiatric units at 3 major hospitals in Oslo, Norway, diagnosed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Traumatic childhood events were assessed with Childhood Trauma Questionnaire. RESULTS: Eighty-two percent of the patients had experienced one or more CT events, the most frequent subtype of trauma being emotional neglect. The schizophrenia spectrum group reported significantly more physical abuse and physical neglect than the affective group. CONCLUSION: A high prevalence of CT in patients with severe mental disorder was detected. This reminds us of the importance of exploring this issue when we treat such patients. The mechanisms behind these differences are unclear. Further research is needed to study potential associations between CT and the clinical picture of the disorder.

A self-managed exercise therapy program for wrist osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Post-traumatic wrist osteoarthritis (OA) can eventually lead to pain, muscular weakness, and stiffness of the wrist, which can affect the function of the entire upper limb and reduce the quality of life. Although there is strong evidence that all patients with OA should be offered adequate education and exercises as a first-line treatment, an effective self-management program, including structured education and therapeutic exercises, has not yet been introduced for individuals with wrist OA. This trial aims to evaluate the effectiveness of an exercise therapy program with joint protective strategies to improve neuromuscular control (intervention group) compared to a training program with range of motion exercises (control group). METHODS: This is a single-blinded randomized controlled trial (RCT) with two treatment arms in patients with symptomatic and radiographically confirmed wrist OA. The trial will be conducted at a hand surgery department. The participants will be randomly assigned either to a neuromuscular exercise therapy program or to a training program with range of motion exercises only. Participants in both groups will receive a wrist orthosis and structured education on wrist anatomy, pathophysiology, and joint protective self-management strategies. The programs consist of home exercises that will be performed twice a day for 12 weeks. The Patient-Rated Wrist Evaluation (PRWE) is the primary outcome measure of pain and function. Wrist range of motion (ROM), grip strength, the Numeric Pain Rating scale (NPRS), Disabilities of the Arm, Shoulder, and Hand (DASH), the General Self-Efficacy Scale (GSES), Global Rating of Change (GROC), and conversion to surgery are the secondary measures of outcome. Assessments will be performed at baseline and at 3, 6, and 12 months after baseline by a blinded assessor. DISCUSSION: The upcoming results from this trial may add new knowledge about the effectiveness of a self-managed exercise therapy program on pain and function for individuals with wrist OA. If the present self-management program proves to be effective, it can redefine current treatment strategies and may be implemented in wrist OA treatment protocols. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 27 April 2022. https://clinicaltrials.gov .

Safety and immunogenicity of the group B streptococcus vaccine AlpN in a placebo-controlled double-blind phase 1 trial.

Group B streptococcus (GBS) is a leading cause of life-threatening neonatal infections and subsets of adverse pregnancy outcomes. Essentially all GBS strains possess one allele of the alpha-like protein (Alp) family. A maternal GBS vaccine, consisting of the fused N-terminal domains of the Alps αC and Rib (GBS-NN), was recently demonstrated to be safe and immunogenic in healthy adult women. To enhance antibody responses to all clinically relevant Alps, a second-generation vaccine has been developed (AlpN), also containing the N-terminal domain of Alp1 and the one shared by Alp2 and Alp3. In this study, the safety and immunogenicity of AlpN is assessed in a randomized, double-blind, placebo-controlled, and parallel-group phase I study, involving 60 healthy non-pregnant women. AlpN is well tolerated and elicits similarly robust and persistent antibody responses against all four Alp-N-terminal domains, resulting in enhanced opsonophagocytic killing of all Alp serotypes covered by the vaccine.

Umbilical cord clamping in the early phases of the COVID-19 era - a systematic review and meta-analysis of reported practice and recommendations in guidelines.

OBJECTIVES: At the beginning of the COVID-19 pandemic, delayed umbilical cord clamping (CC) at birth may have been commonly discouraged despite a lack of convincing evidence of mother-to-neonate SARS-CoV-2 transmission. We aimed to systematically review guidelines, and reports of practice and to analyze associations between timing of CC and mother-to-neonate SARS-CoV-2 transmission during the early phases of the pandemic. METHODS: Major databases were searched from December 1, 2019, to July 20, 2021. INCLUSION: studies and guidelines describing CC practice in women with SARS-CoV-2 infection during pregnancy until 2 postnatal days, giving birth to live-born neonates. EXCLUSION: no extractable data. Two reviewers independently screened studies for eligibility and assessed study quality. Pooled prevalence rates were calculated. RESULTS: Forty-eight studies (1476 neonates) and 40 guidelines were included. Delayed CC was recommended in 70.0% of the guidelines. Nevertheless, delayed CC was reported less often than early CC: 262/1476 (17.8%) vs 511/1476 (34.6%). Neonatal SARS-CoV-2 positivity rates were similar following delayed (1.2%) and early CC (1.3%). Most SARS-CoV-2 transmissions (93.3%) occurred in utero. CONCLUSION: Delayed CC did not seem to increase mother-to-neonate SARS-CoV-2 transmission. Due to its benefits, it should be encouraged even in births where the mother has a SARS-CoV-2 infection. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42020199500.

Hyper high haemoglobin content in red blood cells and erythropoietic transitions postnatally in infants of 22 to 26 weeks' gestation: a prospective cohort study.

OBJECTIVE: Blood cell populations, including red blood cells (RBC) unique to the extremely preterm (EPT) infant, are potentially lost due to frequent clinical blood sampling during neonatal intensive care. Currently, neonatal RBC population heterogeneity is not described by measurement of total haemoglobin or haematocrit. We therefore aimed to describe a subpopulation of large RBCs with hyper high haemoglobin content, >49 pg (Hyper-He) following EPT birth. DESIGN: Prospective observational cohort study. SETTING: Two Swedish study centres. PARTICIPANTS: Infants (n=62) born between gestational weeks 22+0 to 26+6. METHODS: Prospective data (n=280) were collected from March 2020 to September 2022 as part of an ongoing randomised controlled trial. Blood was sampled from the umbilical cord, at postnatal day 1-14, 1 month, 40 weeks' postmenstrual age and at 3 months' corrected age. RESULTS: At birth, there was a considerable inter-individual variation; Hyper-He ranging from 1.5% to 24.9% (median 7.0%). An inverse association with birth weight and gestational age was observed; Spearman's rho (CI) -0.38 (-0.63 to -0.07) and -0.39 (-0.65 to -0.05), respectively. Overall, Hyper-He rapidly decreased, only 0.6%-5.0% (median 2.2%) remaining 2 weeks postnatally. Adult levels (<1%) were reached at corresponding term age. CONCLUSION: Our results point to gestational age and birth weight-dependent properties of the RBC population. Future work needs to verify results by different measurement techniques and elucidate the potential role of differing properties between endogenous and transfused RBCs in relation to neonatal morbidities during this important time frame of child development. TRIAL REGISTRATION NUMBER: NCT04239690.

Characterization of the lipid droplet proteome of a clonal insulin-producing ß-cell line (INS-1 832/13).

Lipids are known to play a crucial role both in the normal control of insulin release and in the deterioration of ß-cell function, as observed in type 2 diabetes. Despite this established dual role of lipids, little is known about lipid storage and handling in ß-cells. Here, we isolated lipid droplets from oleate-incubated INS-1 832/13 cells and characterized the lipid droplet proteome. In a total of four rounds of droplet isolation and proteomic analysis by HPLC-MS/MS, we identified 96 proteins that were specific to droplets. The proteins fall into six categories based on function or previously observed localization: metabolism, endoplasmic reticulum/ribosomes, mitochondria, vesicle formation and transport, signaling, and miscellaneous. The protein profile reinforces the emerging picture of the lipid droplet as an active and dynamic organelle involved in lipid homeostasis and intracellular trafficking. Proteins belonging to the category mitochondria were highly represented, suggesting that the ß-cell mitochondria and lipid droplets form a metabolic unit of potential relevance for insulin secretion.