Biodiversity of microorganisms in the Baltic Sea: the power of novel methods in the identification of marine microbes.

Until recently, the data on the diversity of the entire microbial community from the Baltic Sea were relatively rare and very scarce. However, modern molecular methods have provided new insights into this field with interesting results. They can be summarized as follows. (i) Although low salinity causes a reduction in the biodiversity of multicellular species relative to the populations of the North-East Atlantic, no such reduction occurs in bacterial diversity. (ii) Among cyanobacteria, the picocyanobacterial group dominates when considering gene abundance, while filamentous cyanobacteria dominate in means of biomass. (iii) The diversity of diatoms and dinoflagellates is significantly larger than described a few decades ago; however, molecular studies on these groups are still scarce. (iv) Knowledge gaps in other protistan communities are evident. (v) Salinity is the main limiting parameter of pelagic fungal community composition, while the benthic fungal diversity is shaped by water depth, salinity, and sediment C and N availability. (vi) Bacteriophages are the predominant group of viruses, while among viruses infecting eukaryotic hosts, Phycodnaviridae are the most abundant; the Baltic Sea virome is contaminated with viruses originating from urban and/or industrial habitats. These features make the Baltic Sea microbiome specific and unique among other marine environments.

Myeloid Deficiency of Heparan Sulfate 6-O-Endosulfatases Impairs Bone Marrow Hematopoiesis.

The heparan sulfate (HS) 6-O-endosulfatases or the Sulfs (Sulf1 and Sulf2) are the only known enzymes that can modify HS sulfation status extracellularly and have been shown to regulate diverse biological processes. The role of the Sulfs in bone marrow (BM) hematopoiesis is not known. In this study, we generated a novel mouse line with myeloid-specific deletion of the Sulfs by crossing Sulf1/2 double floxed mice with the LysM-cre line. The LysM-Sulf knockout (KO) male mice exhibited age-dependent expansion of hematopoietic stem cells and the granulocyte-monocyte lineages in the BM, whereas common lymphoid progenitors and B lymphocyte populations were significantly reduced. Although megakaryocytic and erythroid progenitors were not reduced in the BM, the LysM-Sulf KO males suffered age-dependent reduction of red blood cells (RBCs) and platelets in the peripheral blood, suggesting that the production of RBCs and platelets was arrested at later stages. In addition, LysM-Sulf KO males displayed progressive splenomegaly with extramedullary hematopoiesis. Compared to males, LysM-Sulf KO females exhibited a much-reduced phenotype, and ovariectomy had little effect. Mechanistically, reduced TGF-ß/Smad2 but enhanced p53/p21 signaling were observed in male but not female LysM-Sulf KO mice. Finally, HS disaccharide analysis via LC-MS/MS revealed increased HS 6-O-sulfation in the BM from both male and female LysM-Sulf KO mice, however, the distribution of 6-O-sulfated motifs were different between the sexes with compensatory increase in Sulf1 expression observed only in LysM-Sulf KO females. In conclusion, our study reveals that myeloid deficiency of the Sulfs leads to multilineage abnormalities in BM hematopoiesis in an age- and sex-dependent manner.

Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation.

The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting touch through mechanoreceptors in the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicates that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.

Temporal differential effects of post-injury alcohol consumption in a mouse model of blast-induced traumatic brain injury.

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.

Using Quality Improvement to Expand and Align State Public Health Long-Term Follow-up Data Collection Across Newborn Screening Conditions.

CONTEXT: Despite the undeniable success of newborn screening (NBS), numerous barriers exist regarding long-term follow-up (LTFU) of children with conditions included in NBS. Furthermore, there is a focus on condition-specific follow-up with no national guidelines for standard quality measures collected by state public health LTFU programs. PROGRAM: Minnesota Department of Health (MDH) Longitudinal Follow-up for NBS. IMPLEMENTATION: A state public health LTFU for NBS quality improvement (QI) project was carried out with collaboration between MDH project team members and a QI Steering Team who provided clinical, public health, education, caregiver, and community perspectives and expertise to MDH. Relevant measures were selected from existing data elements, and additional measures were developed based on exchange between MDH project team and the QI Steering Team. Potential data sources were explored and prioritized. Processes for querying existing data sources such as death records were refined, new sources such as electronic health records and paper/PDF health records were established, and data collection was piloted. The Minnesota Electronic Disease Surveillance System was modified, and an electronic data form was created to promote consistent data abstraction from sources. Throughout the project, progress was evaluated and shared. At project conclusion, MDH project team and the QI Steering Team reviewed project outcomes and approaches to evolve the project into ongoing surveillance. EVALUATION: Five common public health LTFU measures were determined. Overall, 77% of attempted measures were successfully collected. Primary and secondary data sources were adopted. In addition, collected data resulted in 7% of cases that were closed to further public health LTFU, often related to a move out of state. DISCUSSION: This project established the feasibility of state public health LTFU surveillance of outcomes and health care use by collecting a common data set applicable across NBS conditions.

Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study.

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.

Anthropogenic modification of a giant ground sloth tooth from Brazil supported by a multi-disciplinary approach.

Identifying evidence of human modification of extinct animal remains, such as Pleistocene megafauna, is challenging due to the similarity of anthropogenic and non-anthropogenic taphonomic features observed under optical microscopy. Here, we re-investigate a Late Pleistocene ground sloth tooth from northeast Brazil, previously suggested as human-modified based only on optical observation. To characterize the macro- and micro-morphological characteristics of the marks preserved in this tooth and evaluate potential human modification, we used stereomicroscope and scanning electron microscopy (SEM) supplemented by energy dispersive spectroscopy (EDS), UV photoluminescence (UV/PL), synchrotron-based X-ray fluorescence (SR-XRF), and synchrotron micro-computed tomography (SR-µCT). These methods allowed us to discriminate non-anthropogenic taphonomic features (root and sedimentary damage), anthropogenic marks, and histological features. The latter shows the infiltration of exogenous elements into the dentine from the sediments. Our evidence demonstrates the sequence of anthropogenic and non-anthropogenic taphonomic modification of this tooth and supports its initial intentional modification by humans. We highlight the benefits of emerging imaging and spectral imaging techniques to investigate and diagnose human modification in fossil and archaeological records and propose that human modification of tooth tissues should be further considered when studying possibly anthropogenically altered fossil remains.

A nurse-led intervention for carers of people with high-grade glioma: A case series of carers reporting high distress.

Background: Carers play an important role in supporting patients diagnosed with high-grade glioma (HGG). However, this experience is frequently distressing and many carers require support. Objectives: To describe unmet needs of highly distressed carers of people with HGG and recommendations and referrals made by a nurse to support them within the Care-IS trial. Methods: Descriptive case series. Carers of people with HGG in the Care-IS trial reporting severe anxiety and/or depression at baseline and/or 4 months and high distress at baseline (during chemoradiotherapy) and at 4 months were included. Carers completed the Partner and Caregiver Supportive Care Needs Scale and Brain Tumor Specific Unmet Needs Survey for carers at baseline, 2, 4, 6, and 12 months. Monthly nurse telephone assessments documented carers' needs, recommendations, and referrals made. Data are reported descriptively. Results: Four highly distressed carers were identified (N = 98). Each reported a moderate-high need at ≥1 timepoint for: financial support and/or travel insurance; making life decisions in uncertainty; information about cancer prognosis/likely outcome; and coping with unexpected treatment outcomes. Specific brain tumor unmet needs were: adjusting to changes in personality, mental and thinking abilities, and accessing government assistance. Nurses provided information about treatment, side effects, and practical support. Recommendations for clinical care and referrals to community-based services, and medical specialists were offered. Conclusions: Highly distressed carers have diverse support needs in many domains, which can change over time. Nurses were critical in identifying carers' needs, providing support, and making referrals. Carers' distress and needs require ongoing screening and management.

Identifying clinically meaningful subgroups following open reduction and internal fixation for proximal humerus fractures: a risk stratification analysis for mortality and 30-day complications using machine learning.

Background: Identification of prognostic variables for poor outcomes following open reduction internal fixation (ORIF) of displaced proximal humerus fractures have been limited to singular, linear factors and subjective clinical intuition. Machine learning (ML) has the capability to objectively segregate patients based on various outcome metrics and reports the connectivity of variables resulting in the optimal outcome. Therefore, the purpose of this study was to (1) use unsupervised ML to stratify patients to high-risk and low-risk clusters based on postoperative events, (2) compare the ML clusters to the American Society of Anesthesiologists (ASA) classification for assessment of risk, and (3) determine the variables that were associated with high-risk patients after proximal humerus ORIF. Methods: The American College of Surgeons-National Surgical Quality Improvement Program database was retrospectively queried for patients undergoing ORIF for proximal humerus fractures between 2005 and 2018. Four unsupervised ML clustering algorithms were evaluated to partition subjects into "high-risk" and "low-risk" subgroups based on combinations of observed outcomes. Demographic, clinical, and treatment variables were compared between these groups using descriptive statistics. A supervised ML algorithm was generated to identify patients who were likely to be "high risk" and were compared to ASA classification. A game-theory-based explanation algorithm was used to illustrate predictors of "high-risk" status. Results: Overall, 4670 patients were included, of which 202 were partitioned into the "high-risk" cluster, while the remaining (4468 patients) were partitioned into the "low-risk" cluster. Patients in the "high-risk" cluster demonstrated significantly increased rates of the following complications: 30-day mortality, 30-day readmission rates, 30-day reoperation rates, nonroutine discharge rates, length of stay, and rates of all surgical and medical complications assessed with the exception of urinary tract infection (P < .001). The best performing supervised machine learning algorithm for preoperatively identifying "high-risk" patients was the extreme-gradient boost (XGBoost), which achieved an area under the receiver operating characteristics curve of 76.8%, while ASA classification had an area under the receiver operating characteristics curve of 61.7%. Shapley values identified the following predictors of "high-risk" status: greater body mass index, increasing age, ASA class 3, increased operative time, male gender, diabetes, and smoking history. Conclusion: Unsupervised ML identified that "high-risk" patients have a higher risk of complications (8.9%) than "low-risk" groups (0.4%) with respect to 30-day complication rate. A supervised ML model selected greater body mass index, increasing age, ASA class 3, increased operative time, male gender, diabetes, and smoking history to effectively predict "high-risk" patients.

Endoscopic Retrolabyrinthine Craniotomy for Exposure of the Trigeminal Nerve Root Entry Zone: Volumetric Analysis of Anatomic Exposure in the Cadaver.

BACKGROUND AND OBJECTIVES: Exposure of the root entry zone (REZ) of the trigeminal nerve (TN) for microvascular decompression is commonly obtained with a retrosigmoid approach, with or without endoscopic assistance. We hypothesized that adequate exposure of the TN REZ could be obtained through an endoscopic retrolabyrinthine (RL) approach. We aim to quantify exposure of the REZ of the TN using endoscopic RL approach, with and without drilling of the suprameatal tubercle of the internal auditory canal. METHODS: Surgical dissection was performed bilaterally on 3 embalmed cadaveric human heads at the anatomy laboratory of the House Institute. Heads were scanned for volumetric analysis using 3D Slicer software both before and after dissection. Extent of exposure was quantified in 2 ways: first, by assessment of the surgeon's ability to visualize 16 predetermined anatomic landmarks with the endoscope and second, we estimated the "working" area by placing fiducials under the fully endoscopic view and calculating the resultant 3D volume. RESULTS: Using the standard endoscopic RL approach, an average of 13.8 landmarks (range 12-16) was visualized. The estimated working volume exposed by the RL on each side of each head varied from 189.28 to 527.85 mm3. Drilling of the suprameatal tubercle provided both increases in landmark visualization and, on average, an additional 55 mm3 of working volume. CONCLUSION: The endoscopic RL approach is a viable alternative to the standard retrosigmoid approach. Potential advantages of the RL include a more lateral trajectory that minimizes the need for cerebellar retraction and a shorter working distance and shallower angle to the cerebellopontine angle. Potential disadvantages include longer surgery time, increased technical difficulty of exposure, and potential for cerebrospinal fluid leak and or hearing loss.

Indole-3-Butyric Acid, a Natural Auxin, Protects against Fenton Reaction-Induced Oxidative Damage in Porcine Thyroid.

We present results on the potential protective antioxidant properties of indole-3-butyric acid. Indole-3-butyric acid is an indole derivative defined as an auxin and widely known as a plant growth regulator. It naturally occurs in Arabidopsis thaliana, which is applied as a model plant in genetic studies. Oxidative damage to membrane lipids (lipid peroxidation; LPO) in porcine thyroid homogenates was induced by Fenton reaction substrates (Fe2+ + H2O2). Iron (Fe2+) was used in very high concentrations of 1200, 600, 300, 150, 75, 37.5, 18.75, 9.375, 4.687, and 2.343 µM. Indole-3-butyric acid (10.0, 5.0, 2.5, 1.25, and 0.625 mM) was applied to check whether it prevents the above process. The LPO level, expressed as malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration, was measured spectrophotometrically. Expectedly, Fenton reaction substrates, in a Fe2+ concentration-dependent manner, increased LPO level, with the lowest effective concentration of iron being 9.375 µM. In the case of almost all concentrations of indole-3-butyric acid, this auxin has exhibited very promising antioxidant protection, with the most effective concentrations being 10.0 and 5.0 mM; however, as low concentrations of indole-3-butyric acid at 1.25 mM was still effective. Indole-3-butyric acid used alone did not change the basal level of LPO, which is a favourable effect. To summarise, indole-3-butyric acid has protective antioxidant properties against experimentally induced oxidative damage to membrane lipids in the thyroid, and this is for the first time documented in the literature. This compound can be considered a natural protective agent present in plants, which can serve as a dietary nutrient.

Validation of Breast Idea Volume Estimator Application in Transfeminine People.

Background: Accurate estimation of breast volume is important as researchers aim to achieve optimal feminization for transfeminine people. The Breast Idea Volume Estimator (BIVE) application allows estimation of breast volume using two-dimensional (2D) photographs but has not been validated in the chests of people who have undergone testosterone-mediated puberty. Methods: To estimate breast volume, clinical photographs and 3D scans were collected at baseline and 6 months, as a prespecified secondary outcome of a randomized clinical trial of antiandrogen therapy in transfeminine people commencing hormone therapy. BIVE was used to estimate breast volume by two independent researchers and compared with the gold standard of 3D scan calculated volume at different timepoints. Statistical analysis was performed, including the mean absolute difference, standard error of measurement, and intraclass correlation, to determine accuracy, precision, and interrater agreement. Results: Clinical photography and 3D scans were collected from 82 breasts of 41 participants. The median (interquartile range) age of participants was 25 (22-28) years, and the median (interquartile range) body mass index was 24.6 (21.2-28.9) kg/m2. The BIVE sagittal and transverse algorithms demonstrated robust performance, with mean absolute difference less than 20 mL and intraclass correlation greater than 0.87 indicating clinical reliability with high interrater agreement. Conclusions: BIVE provided an accurate, precise, and reliable measure of breast volume in the chests of people who have undergone testosterone-mediated puberty, compared with the gold standard of 3D scan.

Exploring the Link between Premature Ovarian Insufficiency, Insomnia and Circadian Pathways.

OBJECTIVE: To establish an interaction network for genes related to premature ovarian insufficiency (POI) and insomnia, and to identify biological processes that connect POI to the physiological clock. METHODS: Previously reported lists of genes associated to POI and insomnia were contrasted and their intersection was used as input on protein-protein interaction analyses. POI-associated genes were contrasted with gene expression markers for neural circadian control and enriched pathways among their shared content were dissected. RESULTS: The functional network generated from the intersection between POI and insomnia gene lists pointed to the central nervous system as the most relevant cellular context for this connection. After identifying POI-associated genes that play a role in neural circadian patterns, we observed the disruption of pathways related to the hypothalamic-pituitary-gonadal axis as the major genetic link between ovarian function and circadian neural circuits. CONCLUSIONS: These findings highlight neurological mechanisms that support the POI-insomnia interplay.

Effect of spironolactone and cyproterone acetate on breast growth in transgender people: a randomized clinical trial.

CONTEXT: Transgender people with sex recorded male at birth desiring feminization commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol, but the optimal anti-androgen is unclear. OBJECTIVE: To assess the effect of anti-androgens on breast development. We hypothesized this would be greater in those treated with cyproterone acetate than spironolactone due to more potent androgen receptor antagonism and suppression of serum total testosterone concentrations. DESIGN: Randomised clinical trial 2020-2022. SETTING: Outpatient endocrinology clinic. PARTICIPANTS: Transgender people aged 18+ years old commencing feminizing gender affirming hormone therapy. INTERVENTIONS: Standardized estradiol therapy plus either spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months. MAIN OUTCOME MEASURES: Primary outcome was breast development as measured by the breast chest distance. Secondary outcomes included estimated breast volume, suppression of serum total testosterone concentration <2nmol/L and Gender Preoccupation and Stability Questionnaire (GPSQ). RESULTS: Sixty-three people (median age 25 years) were enrolled, randomized and included in intention-to-treat analysis (cyproterone acetate n=32, spironolactone n=31). At six months, there was no between-group difference in breast chest distance (mean difference 0.27 cm, 95% CI -0.82 to 1.35, p=0.6) or estimated breast volume (mean difference 17.26 mL, 95% CI -16.94 to 51.47, p=0.3). Cyproterone acetate was more likely to suppress serum testosterone concentration to <2 nmol/L (odds ratio 9.01, 95% CI 1.83 to 4.44, p=0.008). Changes in GPSQ were similar between groups. CONCLUSION: Anti-androgen choice should be based on clinician and patient preference with consideration of side effects. Further research is needed to optimize breast development in transgender people.

Outcomes for older people with screening detected versus existing chronic kidney disease: Cohort study with data linkage.

BACKGROUND: Chronic Kidney Disease (CKD) is a common health problem, associated with increased risk of cardiovascular disease (CVD), end stage kidney disease (ESKD), and premature death. A third of people aged≥70 years have CKD, many of whom are undiagnosed, but little is known about the value of screening. AIM: To compare the risk of adverse health outcomes between people with an existing diagnosis of CKD and those identified on screening. To identify factors associated with mortality in CKD. DESIGN & SETTING: Prospective cohort study of 892 primary care patients aged≥60 years with CKD (existing and screening detected) in Oxfordshire, with data linkage to civil death registry and secondary care. METHOD: Hazard Ratios (HR) and 95% Confidence Intervals (CI) were estimated using Cox proportional-hazard models to compare the risk of all-cause mortality, hospitalisation, CVD, ESKD separately, and as a composite between CKD groups, as well as to identify factors associated with mortality. RESULTS: After a median follow-up of 3-5 years, 49 people died, 493 were hospitalised, 57 had an incident CVD event, and 0 had an ESKD event. There was no difference in the composite outcome between those existing CKD and those identified on screening (HR 0.94, CI 0.67-1.33). Older age (HR 1.10, CI 1.06-1.15), male sex (HR 2.31, CI 1.26-4.24), and heart failure (HR 5.18, CI 2.45-10.97) were associated with increased risk of death. CONCLUSION: Screening older people for CKD may be of value, as their risk of short-term mortality, hospitalisation, and CVD is comparable to people routinely diagnosed. Larger studies with longer follow-up in more diverse and representative populations of older adults are needed to corroborate these findings.

Increasing participation in resistance training using outdoor gyms: A study protocol for the ecofit type III hybrid effectiveness implementation trial.

Background: In this paper we outline the protocol for an implementation-effectiveness trial of ecofit, a multi-component mHealth intervention aimed at increasing participation in resistance and aerobic physical activity using the outdoor built environment (i.e., outdoor gyms) and social support. We have previously demonstrated the efficacy and effectiveness of the ecofit program in insufficiently active people with (or at risk of) type 2 diabetes and community-dwelling adults, respectively. The objective of this trial is to compare the effects of two implementation support models (i.e., 'Low' versus 'Moderate') on the reach (primary outcome), uptake, dose received, impact and fidelity of the ecofit program. Research design and methods: This hybrid type III implementation-effectiveness study will be evaluated using a two-arm randomized controlled trial, including 16 outdoor gym locations in two large regional municipalities in New South Wales, Australia. Outdoor gym locations will be pair-matched, based on an established socio-economic status consensus-based index (high versus low), and randomized to the 'Low' (i.e., ecofit app only) or 'Moderate' (i.e., ecofit app, face-to-face workout sessions and QR codes) implementation support group. The primary outcome of 'reach' will be measured using a modified version of the 'System for Observing Play and Recreation in Communities', capturing outdoor gym use amongst community members. Conclusion: This implementation-effectiveness trial will evaluate the effects of different levels of implementation support on participation in resistance-focused physical activity using mHealth and outdoor gyms across the broader community. This may guide widespread dissemination for councils (municipalities) nation-wide wanting to promote outdoor gym usage. Trial registry: This trial was preregistered with the Australian and New Zealand Clinical Trial Registry (ACTRN12624000261516).

Spray drying of a zinc complexing agent for inhalation therapy of pulmonary fibrosis.

Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis.

Yoga as Potential Therapy for Burnout: Health Technology Assessment Report on Efficacy, Safety, Economic, Social, Ethical, Legal and Organizational Aspects.

PURPOSE OF REVIEW: This health technology assessment aimed to systematically assess the efficacy and safety of yoga as therapy for burnout. Economic, ethical, legal, social and organizational aspects were considered as well. RECENT FINDINGS: Yoga as a therapy has been shown to have positive effects on a range of symptoms, including stress, anxiety and depression. Regarding work-related stress and burnout, the effects of yoga have mainly been examined in a preventative context. Meta-analyses revealed no effects on burnout severity comparing yoga with passive controls in general. Compared with passive controls, yoga had a positive effect on subjective stress. Compared to active control, yoga had an effect on the burnout subscale depersonalization on individual study level. Yoga may have positive effects on burnout, but the results are mixed. Common definitions and standardized diagnostic tools are necessary to improve research and further assess yoga as therapy for burnout. TRIAL REGISTRATION: The HTA is registered with PROSPERO, CRD42022299405, on 6th February 2022.

Retrospective epidemiological study of the width of maxillary diastema in patients from northeastern Bulgaria.

INTRODUCTION: A maxillary diastema (MD) is identified when the gap between the central incisors exceeds 0.5 mm. It poses an a and phonetic concern, often seen in mixed dentition and occasionally continuing into permanent dentition.