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Global health programs are compelled to demonstrate impact on their target populations. We study an example of social franchising - a popular healthcare delivery model in low/middle-income countries - in the Ugandan private maternal health sector. The discrepancies between the program's official profile and its actual operation reveal the franchise responded to its beneficiaries, but in a way incoherent with typical evidence production on social franchises, which privileges simple narratives blurring the details of program enactment. Building on concepts of not-knowing and the production of success, we consider the implications of an imperative to maintain ambiguity in global health programming and academia.

To assess self-perceived health and sense of coherence (SOC) in adolescents with spina bifida (SB) in the West Bank, Palestine, compared to a healthy reference group. Further, to assess the association between impairment levels in the adolescents with SB and their self-perceived health and SOC.

Fifty adolescents with SB and 150 healthy adolescents completed measures of self-perceived health - the Pediatric Quality of Life Inventory (PedsQL

4.0) - and SOC. The rehabilitation center nurses identified the physical impairments of the adolescents with SB from their medical records, and classified them by impairment severity.

Adolescents with SB reported lower self-perceived health (PedsQL median 55, IQR 42-67), than the reference group (median 85, IQR 74-90),

 < 0.001, and lower SOC (median 47, IQR 44-50) than the reference group (median 55, IQR 44-61),

 < 0.001. Pamapimod research buy Impairment level was inversely associated with both self-perceived health and SOC.

The low self-perceived health and SOC among adolespresents barriers to the social engagement of adolescents with SB, and new ways are needed to enhance their participation in the society to promote their self-concept and wellbeing.Sexual health data on transgender and non-binary (TNB) people in the United Kingdom are limited. TNB individuals experience significant socioeconomic and stigma-related disadvantages. Sexual health morbidity and unmet need is likely to be significant. We compared the sexual health outcomes of TNB and cisgender users of London's online sexual health service. Of 119329 users that registered with the e-service between 30.4.19 and 31.12.19, 504 (0.42%) identified as TNB 302 TNB users requested 463 kits. 78.4% (363/463) of kits were returned. 99.4% of dispatched kits included throat and rectal swabs for gonorrhoea and chlamydia testing. STI/HIV test positivity was 5.5% syphilis, 4.8% chlamydia, 3.4% gonorrhoea and 0.7% HIV positive. HIV prevalence amongst TNB individuals was 4.3%. 19.9% of TNB individuals engaged in chemsex, group sex, or fisting and were more likely to engage in sex work. 97.7% gave the service 4/5 or 5/5 star rating. We observed high positivity rates of HIV/STIs amongst TNB individuals and significant levels of high-risk sexual activity. Service users rated the service highly. Given TNB often have complex healthcare needs, some of which cannot be met entirely online, physical clinics must work collaboratively with e-services to support and protect this marginalised population.Introduction Ixekizumab (IXE), a high affinity humanized monoclonal antibody that selectively targets interleukin-17A, is approved in the United States (US) and the European Union (EU) for pediatric patients with moderate to severe plaque psoriasis. This review summarizes ixekizumab use in the phase 3, randomized, double-blind, placebo-controlled study in pediatric patients with moderate to severe plaque psoriasis and provides some clinical pearls we have learned after using the drug in the pediatric population for the past 3 years.Areas covered Review of IXORA-PEDS trial data, general literature review pertaining to the systemic treatment of pediatric psoriasis as well as our clinical experience with IXEExpert opinion IXE is the only IL17 antagonist for pediatric psoriasis and is a welcome addition to our armamentarium.

The maxillary nerve courses very close to the globe, rendering cats - with their large eyes - at risk of globe penetration during infraorbital or maxillary nerve blocks. Therefore, the goals of the study were to compare the distribution and potential complications of three infraorbital or maxillary regional injection techniques.

Twenty-three bilateral maxillae of cat cadavers were used in a randomised blinded trial. Each maxilla was injected with a 0.2 ml 11 mixture of lidocaine 2% and a contrast medium by one of three injection techniques infraorbital foramen (IOF; n = 14); infraorbital canal (IOC; n = 16); or maxillary foramen (MF; transpalpebral approach; n = 16) using a 25 G 1.6 cm needle. CT imaging of each cadaver head was performed before and after injections. A radiologist scored injectate distribution (none [0], mild [1], moderate [2], large [3]) in four locations rostral, central and caudal IOC, and at the MF, for which the distribution side was also determined. Comparisons were performed with ordinal logistic mixed effects (

<0.05).

The median (range) total distribution score of the IOC and MF technique were significantly higher compared with the IOF technique (6.5 [4-12], 4 [2-8] and 0 [0-10], respectively). The total IOC score was also significantly higher compared with the MF technique. Injectate distribution at the MF was significantly more central following IOC injection compared with MF injection, which distributed centrolaterally. None of the techniques resulted in intraocular injection.

The IOC and MF techniques produced a satisfactory spread of the mixture that could result in effective maxillary anaesthesia in cats. Further studies are required to determine the effectiveness and safety of these techniques.

The IOC and MF techniques produced a satisfactory spread of the mixture that could result in effective maxillary anaesthesia in cats. Further studies are required to determine the effectiveness and safety of these techniques.The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique - hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe - a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. link2 HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.Animal models clearly illustrate that the maintenance of skeletal muscle mass depends on the function and interaction of a heterogeneous population of resident and infiltrating mononuclear cells. Several lines of evidence suggest that mononuclear cells also play a role in muscle wasting in humans, and targeting these cells may open new treatment options for intervention or prevention in sarcopenia. Methodological and ethical constraints have perturbed exploration of the cellular characteristics and function of mononuclear cells in human skeletal muscle. Thus, investigations of cellular phenotypes often depend on immunohistochemical analysis of small tissue samples obtained by needle biopsies, which do not match the deep phenotyping of mononuclear cells obtained from animal models. Here, we have developed a protocol for fluorescence-activated cell sorting (FACS), based on single-cell RNA-sequencing data, for quantifying and characterizing mononuclear cell populations in human skeletal muscle. Muscle stem cells, fibro-adipogenic progenitors, and two subsets of macrophages (CD11c+/-) are present in needle biopsies in comparable quantities per milligram tissue to open surgical biopsies. We find that direct cell isolation is preferable due to a substantial shift in transcriptome when using preculture before the FACS procedure. Finally, in vitro validation of the cellular phenotype of muscle stem cells, fibro-adipogenic progenitors, and macrophages confirms population-specific traits. This study demonstrates that mononuclear cell populations can be quantified and subsequently analyzed from needle biopsy material and opens the perspective for future clinical studies of cellular mechanisms in muscle wasting.Thrombospondin-1 (TSP1) is the prototypical member of a family of secreted proteins that modulate cell behavior by engaging with molecules in the extracellular matrix and with receptors on the cell surface. CD47 is widely displayed on many, if not all, cell types and is a high-affinity TSP1 receptor. CD47 is a marker of self that limits innate immune cell activities, a feature recently exploited to enhance cancer immunotherapy. Another major role for CD47 in health and disease is to mediate TSP1 signaling. TSP1 acting through CD47 contributes to mitochondrial, metabolic, and endocrine dysfunction. Studies in animal models found that elevated TSP1 expression, acting in part through CD47, causes mitochondrial and metabolic dysfunction. Clinical studies established that abnormal TSP1 expression positively correlates with obesity, fatty liver disease, and diabetes. The unabated increase in these conditions worldwide and the availability of CD47 targeting drugs justify a closer look into how TSP1 and CD47 disrupt metabolic balance and the potential for therapeutic intervention.Maintaining mitochondrial function and dynamics is crucial for cellular health. In muscle, defects in mitochondria result in severe myopathies where accumulation of damaged mitochondria causes deterioration and dysfunction. Importantly, understanding the role of mitochondria in disease is a necessity to determine future therapeutics. One of the most common myopathies is mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), which has no current treatment. Recently, patients with MELAS treated with rapamycin exhibited improved clinical outcomes. However, the cellular mechanisms of rapamycin effects in patients with MELAS are currently unknown. link3 In this study, we used cultured skin fibroblasts as a window into the mitochondrial dysfunction evident in MELAS cells, as well as to study the mechanisms of rapamycin action, compared with control, healthy individuals. We observed that mitochondria from patients were fragmented, had a threefold decline in the average speed of motility, a twofold reduced mitochondrial membrane potential, and a 1.5- to 2-fold decline in basal respiration. Despite the reduction in mitochondrial function, mitochondrial import protein Tim23 was elevated in patient cell lines. MELAS fibroblasts exhibited increased MnSOD levels and lysosomal function when compared with healthy controls. Treatment of MELAS fibroblasts with rapamycin for 24 h resulted in increased mitochondrial respiration compared with control cells, a higher lysosome content, and a greater localization of mitochondria to lysosomes. Our studies suggest that rapamycin has the potential to improve cellular health even in the presence of mtDNA defects, primarily via an increase in lysosomal content.

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