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Objective: An estimated 5.5 million people in England have high‐impact chronic pain, which is severe pain associated with significant disability. Current models of healthcare often fail to address their broad range of symptoms and address their complex non‐medical needs. Methods: A pilot project was designed with the aim of improving the quality of care and addressing unmet needs of patients high‐impact musculoskeletal (MSK) pain through providing a personalised approach to their pain and wider psychosocial needs. The model comprised a longer initial appointment with a general practitioner, a later follow‐appointment, and support of the multidisciplinary team (MDT) (informally and through a formal MDT meeting) with both primary care clinicians and specialists based in secondary care. Results: Forty six patients were seen using this model, with prominent themes of consultations including self‐management, social needs, mental health and understanding their diagnosis. Evaluation of the pilot demonstrated improvements in MSK and non‐MSK symptoms, together with improved patient confidence in self‐management and knowledge and understanding of their condition. Multidisciplinary working proved to be invaluable in addressing patients' wider needs but also upskilling and supporting primary care clinicians. Primary care staff also found it to be a satisfying way to care for patients, and developed increasing skills and confidence in supporting patients with chronic pain. Conclusion: This model of care appears to be an effective way to help primary care teams to provide more holistic personalised care to a group of patients who are highly complex and so often forgotten. [ABSTRACT FROM AUTHOR]

In the foreword of this booo, edited and authored mainly from Maryland, California and Florida, we are reminded that 'with AIDS, nothing is as usual'. Its ingredients -- sex, death, [...]

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.

Objective: Men who have sex with men (MSM) are the key population most affected by HIV in Europe. We performed the first European multicenter, simple-randomized parallel-group study to test the effectiveness of a theory-guided computer-assisted intervention to improve safer sex among HIV-positive men who have sex with men., Methods: Between February, 2011 and February, 2013, 112 participants were enrolled in 8 different European HIV-care settings. Intervention participants received 3 individual counseling sessions facilitated by trained service providers using computer-assisted tools. The control-group received sexual health advice delivered as part of regular HIV care. Outcome behavior (self-reported condom use at last intercourse; combined HIV transmission risk score), its influencing factors, and mediating variables were assessed at baseline, and at 3 and 6 months follow-up. Mixed effects models were used to compare primary outcomes (condom use at last intercourse, HIV transmission risk score), and mediation analysis to explore intervention effects., Results: Condom use at last intercourse increased more among intervention than control participants at 3 months follow-up (odds ratio of 3.83; P = 0.03), but not significantly at 6 months follow-up. Intervention participants reported a lower transmission risk at 3 months follow-up than controls (odds ratio compared with baseline of 11.53 and 1.28, respectively; P = 0.008), but this effect became nonsignificant at 6 months. Intervention effects were mediated by the proximal variables, self-efficacy to negotiate condom use and condom attitudes., Conclusions: This intervention showed short-term effectiveness. The intervention should be replicated in other settings, eventually investigating if booster-counseling sessions would yield a longer lasting effect.

The pathogenesis of multiple sclerosis (MS), a devastating neuroinflammatory disorder of the central nervous system, has been presumed to involve the possible importance of the receptor for advanced glycation end products (RAGE). The aim of this study was to investigate the relevance of the genetic polymorphisms of RAGE in MS patients. A total of 168 patients with MS were enrolled; 136 healthy blood donors served as controls. The -374 T/ A, -479 T/C, and the G82S polymorphisms of RAGE were determined by restriction fragment length polymorphism (RFLP). There was a significant difference in RAGE -374 T/A genotype distribution between the controls and the MS patients. The AA homozygote variants were detected in 8% of the patients with MS, as compared with 19% of healthy controls (OR=2.75; 95% CI=1.319-5.733, p = 0.007). No differences were observed between the MS patients and the controls, concerning the frequencies of the -479 T/C and G82S genotypes of the RAGE. Our results revealed an association between the -374 T/A polymorphism of the RAGE promoter and MS. The genetic variant -374 AA (which has previously been shown to exert significant effects on transcriptional activity) can be considered a preventive factor as regards the occurrence of MS. Our findings support the view that RAGE plays a role in the development of MS.

Objective: Helicobacter pylori-induced gastric inflammation is dependent on the persistence of the microorganism in the gastric epithelium. Modulation of the host epithelial antimicrobial responses may be a critical determinant in H. pylori-induced gastritis. Human beta-defensins (hBDs) are important components of the host defence at mucosal surfaces. The aim of the present study was to investigate the relevance of three single nucleotide polymorphisms (SNPs) of the human beta defensin-1 (hBD-1) gene in H. pylori-induced gastritis and to assess the mRNA expression of hBD-1 in H. pylori-infected AGS cells., Material and Methods: Three SNPs of the beta defensin DEFB1 gene, DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946), were genotyped either by Custom TaqMan SNP genotyping assays or by restriction fragment length polymorphism (RFLP) in 150 patients with chronic active gastritis; 100 serologically H. pylori-positive subjects without gastric or duodenal symptoms served as controls. hBD-1 mRNA expression in AGS cells was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR)., Results: Significant differences in frequencies of the GA and AA genotypes of G-52A SNPs were observed between patients with chronic active gastritis and healthy controls. The maximum level of hBD-1 mRNA expression in AGS cells was observed at 24 h after infection with H. pylori, this not being dependent on the presence of the cag pathogenicity island (PAI)., Conclusions: The results of these genetic and in vitro experiments suggest that not only the inducible, but also the constitutive form of hBD may be important in the pathogenesis of H. pylori-induced gastritis.

Objective: It has been suggested that deficient defensin expression is associated with the chronic inflammation of Crohn's disease. The regional localization of Crohn's disease, ileal or colonic disease can be linked to different defensin profiles. As constitutive beta-defensin 1 has a colonic expression, we considered it of interest to investigate single nucleotide polymorphisms (SNPs) of the beta-defensin 1 gene (DEFB1) in Crohn's disease., Material and Methods: Three SNPs of the DEFB1 gene, DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946), were genotyped either by Custom TaqMan SNP genotyping assays or by restriction fragment length polymorphisms (RFLP) in 190 patients with Crohn's disease and 95 Hungarian controls., Results: It was found that the G-20A and C-44G SNPs had a strong association with the colonic and ileocolonic localizations of the disease, respectively, but no association was detected for the ileal localization. A significantly higher frequency of the GA genotype of G-20A was observed among patients with colonic localization (60%) as compared with healthy controls (39%), with an odds ratio (OR) of 2.39. The GG genotype of C-44G SNP, which is regarded as a protective genotype, was much less frequent (4%) among patients than among controls (12%), OR 3.367., Conclusions: These results indicate that genetic variations in the DEFB1 gene encoding constitutive human beta-defensin 1 may be associated with the risk for Crohn's disease and may determine disease phenotype, e.g. colonic localization.