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Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3γ (the mouse homolog of human REG3α), and the absence of REG3γ in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3γ production and prevented apoptosis of both intestinal stem cells (ISCs) and Paneth cells, but this protection was completely abrogated in Reg3g-/- mice. In vitro, addition of REG3α reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3α/γ to promote crypt regeneration may offer a novel, nonimmunosuppressive approach for GVHD and perhaps for other diseases involving the ISC niche, such as inflammatory bowel disease.

Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up.

Non-surgical penile enhancement using dermal fillers is a growing trend, yet traditional techniques often result in uneven volume distribution, poor integration, increased risk of filler migration and/or vascular complications. These limitations reduce aesthetic quality and patient satisfaction. We introduce the Cylindrical Dartos-Buck Smooth (CDS) technique, a novel single-entry, cannula-based method designed for even filler distribution within the sub-Dartos/Buck's fascial plane to achieve natural, uniform penile augmentation. We present the case of a 29-year-old male who underwent the CDS technique with 15 mL of dermal filler via an 18-G blunt-tip cannula through a single mid-shaft entry point. Dermal filler was deposited in structured micro-droplets along the target fascial layer. At six-month follow-up, the patient demonstrated a 0.63-inch increase in girth, natural tactile feel, uniform volume distribution and no complications. The patient and the injecting doctor completed a modified (adapted for penile enhancement) Global Aesthetic Improvement Scale (GAIS) to assess the results. The clinical GAIS score at six months was 2, and the patient GAIS score was 1, indicating an excellent clinical outcome and strong patient satisfaction.  The CDS technique provides enhanced control, superior contouring and improved safety compared to traditional penile filler approaches. Further studies are recommended to assess long-term outcomes and broader clinical utility.

Pulmonary embolism (PE) is an important cause of in-hospital mortality. Many patients are admitted to the intensive care unit (ICU) either due to hemodynamic instability or severe hypoxemia. Few reports have addressed the outcome of patients with PE; however, none were from ICUs in the Middle East. To describe the demographics, clinical presentation, risk factors and outcome of patients with PE admitted to the medical ICU and to identify possible factors associated with poor prognosis. Data were collected retrospectively by reviewing the records of patients admitted to the medical ICU with primary diagnosis of PE between January 2001 and June 2007. Demographic, clinical, radiological and therapeutic data were collected on admission to ICU. Fifty-six patients (43% females) with PE were admitted to the ICU during the study period. Their mean age was 40.6 ± 10.6 years. Seven patients (12.5%) had massive PE with hemodynamic instability and 15 (26.8%) had submassive PE. The remaining patients were admitted due to severe hypoxemia. Recent surgery followed by obesity were the most common risk factors (55.4 and 28.6%, respectively). Four patients with massive PE received thrombolysis because the remaining three had absolute contraindications. Fatal gastrointestinal bleeding occurred in one patient post thrombolysis. Additionally, two patients with massive PE and five with submassive PE died within 72 h of admission to the ICU, resulting in an overall mortality rate of 14%. Nonsurvivors were older and had a higher prevalence of immobility and cerebrovascular diseases compared with survivors. The mortality rate of patients with PE admitted to the ICU in our center was comparable to other published studies. Older age, immobility as well as coexistent cerebrovascular diseases were associated with a worse outcome.

The graft-versus-leukemia (GVL) effect after allogeneic hematopoietic cell transplant (HCT) can prevent relapse but the risk of severe graft-versus-host disease (GVHD) leads to prolonged intensive immunosuppression and possible blunting of the GVL effect. Strategies to reduce immunosuppression in order to prevent relapse have been offset by increases in severe GVHD and nonrelapse mortality (NRM). We recently validated the MAGIC algorithm probability (MAP) that predicts the risk for severe GVHD and NRM in asymptomatic patients using serum biomarkers. In this study we tested whether the MAP could identify patients whose risk for relapse is higher than their risk for severe GVHD and NRM. The multicenter study population (n = 1604) was divided into two cohorts: historical (2006–2015, n = 702) and current (2015–2017, n = 902) with similar NRM, relapse, and survival. On day 28 post-HCT, patients who had not developed GVHD (75% of the population) and who possessed a low MAP were at much higher risk for relapse (24%) than severe GVHD and NRM (16 and 9%); this difference was even more pronounced in patients with a high disease risk index (relapse 33%, NRM 9%). Such patients are good candidates to test relapse prevention strategies that might enhance GVL.

Statistics highlight child neglect is the most common form of child maltreatment within the United Kingdom. The research described here was an exploratory study which used the pragmatic approach of a survey design to explore how social workers identify child neglect. Social workers complete assessments of children in need of help and protection and this assessment process determines whether a referral should be responded to as a child in need of support (as per Section 17, Children Act 1989) or as a child in need of protection (as per Section 47, Children Act 1989). The definition of child neglect is provided by the Department for Education for use by social workers in its assessment. However, the usefulness of the definition of child neglect is questioned within the literature due to differences in the breath and scope of what is considered a basic need and differences in what are considered to be adequate standards of provision to meet them.The study used an online survey directed at members of the British Association of Social Workers (BASW) and social workers from one Local Authority in the North West of England. There were five sections in the online survey: information on participants’ demographics, the second category focussed on caseloads, identification of child neglect, resources to support the identification of child neglect resources and finally the health and wellbeing of social workers.The major findings were that factors relating to the child were most salient when assessing neglect. This is in clear contrast to previous studies using the same criteria which found that factors relating to the parent were the most significant. The definition of child neglect provided by the Department for Education was highlighted as being problematic with approximately two thirds of participants reporting that the definition was helpful but over a third of participants found it unhelpful. Challenges in defining child neglect appear to be exacerbated by a lack of agreement among professionals from the same group on the nature of neglect. Up to one third of participants reported that they did not feel equipped to work with families in cases of neglect, and approximately half of participants reported that they were not able to follow up on concerns due to their workload.The implication of the findings is that whilst neglect continues to be a primary reason for social work intervention, social work practitioners appear to be working with a definition which the majority find helpful yet acknowledge that there is much less consensus on the nature of neglect. This is a concerning matter as social work practitioners are working with ambiguity yet are agents of the state protecting children from harm when they are unclear about thresholds and level of need.

This work provides novel insights into the intersection between two critical areas of immunology, the CD1d-invariant NKT (iNKT) axis and B cells. CD1d is a non-polymorphic, MHC class I-like molecule, which presents phospho- and glycosphingo-lipid antigens to a subset of CD1d-restricted T cells called iNKT cells. CD1d is expressed on a variety of antigen presenting cells and the CD1d-iNKT cell axis regulates nearly all aspects of the innate and adaptive immune response. Expression of CD1d on B cells allows these cells to form cognate interactions with iNKT cells. Emerging evidence suggests, however, that expression of CD1d on B cells is variable, both on \"normal\" B cells during humoral immune responses, and also on \"pathological\" B cells in certain B cell disorders. In this work, I investigate in detail the expression of CD1d on B cells across a range of conditions. Using both human and murine germinal centre (GC) B cells as a model for normal B cells, I show for the first time that CD1d expression changes dynamically, both at the surface protein and transcriptional level. CD1d falls to a nadir as a naïve B cell enters the GC, and subsequently rises again in post GC B cells. I then provide evidence that the loss of CD1d expression is paralleled in pathological B cells, specifically in Epstein-Barr Virus infection of B cells and the plasma cell disorder Multiple Myeloma. In these conditions, CD1d is again downregulated at both the surface and transcriptional level. Having established that CD1d expression is lost in certain scenarios, I attempt to elucidate the biological significance of this downregulation. I approach this aim by attempting to constitutively express CD1d in murine GC B cells, and subsequently assessing the GC reaction. Constitutive expression of CD1d is achieved by two distinct methods, either by using adoptive transfer of Cd1d1 transduced haematopoietic stem cells or by using a CD1d transgenic mouse model. I show that both of these approaches represent a feasible way to constitutively express CD1d in murine GC B cells, but cannot establish a definitive biological role for CD1d downregulation in murine GC B cells. Finally, I investigate the transcriptional mechanisms governing the downregulation of CD1d, in either normal or pathological B cells. By analysing GC and MM B cells, I provide the first evidence that both retinoic acid signalling and bivalent chromatin domains act as a dual regulatory mechanism of CD1d. These findings demonstrate a new concept in the field of MM biology, specifically that MM B cells (like lymphomas) are able to \"hijack\" physiological pathways for disease propagation. Although previous work has highlighted the ability of all-trans retinoic acid (ATRA) alone to increase CD1d expression, this uncovering of a dual mechanism provides the rationale to use both ATRA and the polycomb-repressive complex inhibitor GSK343 to restore CD1d expression. I show that this is a more effective strategy than ATRA alone in increasing CD1d expression. Although this will need to be validated in further in vivo models, this ability to further increase CD1d expression may be of great therapeutic importance in the emerging field of tumour immunotherapy.