International Retrovirology Association brings together scientists and clinicians to bridge discoveries about human T-lymphotropic viruses from the laboratory to clinical trials

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica . Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV

A blinded, randomized, controlled trial assessing conservative management strategies for frozen shoulder

BACKGROUND: There is little evidence for the optimal form of nonoperative treatment in the management of frozen shoulder. This study assesses the efficacy of current physiotherapy strategies. METHODS: All primary care referrals of frozen shoulder to our physiotherapy department were included during a 12-month period. Of these referrals, 17% met the inclusion criteria for primary idiopathic frozen shoulder. The 75 patients were randomly assigned to 1 of 3 groups: group exercise class, individual physiotherapy, and home exercises alone. A single independent physiotherapist, who was blinded to the treatment groups, made all assessments. Range of motion, Constant score, Oxford Shoulder Score, Short Form 36, and Hospital Anxiety and Disability Scale (HADS) outcome measures were performed at baseline, 6 weeks, 6 months, and 1 year. RESULTS: The exercise class group improved from a mean Constant score of 39.8 at baseline to 71.4 at 6 weeks and 88.1 at 1 year. There was a significant improvement in shoulder symptoms on Oxford and Constant scores (P < .001). This improvement was greater than with individual physiotherapy or home exercises alone (P < .001). The improvement in range of motion was significantly greater in both physiotherapy groups over home exercises (P < .001). HADS scores significantly improved during the course of treatment (P < .001). The improvement in HADS anxiety score was significantly greater in both physiotherapy intervention groups than in home exercises alone. CONCLUSIONS: A hospital-based exercise class can produce a rapid recovery from a frozen shoulder with a minimum number of visits to the hospital and is more effective than individual physiotherapy or a home exercise program

RAB1A Haploinsufficiency Phenocopies the 2p14-p15 Microdeletion and Is Associated With Impaired Neuronal Differentiation

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C\u3eT [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and a mosaic missense mutation (c.83T\u3eC [p.Leu28Pro]), were identified in three individuals with similar neurodevelopmental presentations. In rescue experiments, production of the full-length, but not the truncated, RAB1a rescued Golgi structure and cell proliferation in Rab1-depleted cells. In contrast, the missense-variant RAB1a disrupted Golgi structure despite intact Rab1 expression, suggesting a dominant-negative function of the mosaic missense mutation. Knock-down of RAB1A in cultured human embryonic stem cell-derived neurons resulted in impaired neuronal arborization. Finally, RAB1A is located within the 2p14-p15 microdeletion syndrome locus. The similar clinical presentations of individuals with RAB1A loss-of-function mutations and the 2p14-p15 microdeletion syndrome implicate loss of RAB1A in the pathogenesis of neurodevelopmental manifestations of this microdeletion syndrome. Our study identifies a RAB1A-related neurocognitive disorder with speech and motor delay, demonstrates an essential role for RAB1a in neuronal differentiation, and implicates RAB1A in the etiology of the neurodevelopmental sequelae associated with the 2p14-p15 microdeletion syndrome

Current management strategies for patellofemoral pain: an online survey of 99 practising UK physiotherapists

Background: Patellofemoral pain (PFP) is considered one of the commonest forms of knee pain. This study aimed to identify how physiotherapists in the United Kingdom (UK) currently manage patellofemoral pain (PFP), particularly in relation to exercise prescription, and response to pain. Methods: An anonymous survey was designed with reference to previous surveys and recent systematic reviews. Practising UK physiotherapists who treat patients with PFP were invited to take part via an invitation email sent through professional networks, the ‘interactive Chartered Society of Physiotherapy (iCSP)’ message board, and social media (Twitter). Descriptive statistics were used to analyse the data. Results: A total of 99 surveys were completed. Responders reported a wide range of management strategies, including a broad selection of type and dose of exercise prescription. The five most common management strategies chosen were: closed chain strengthening exercises (98%); education and advice (96%); open chain strengthening exercises (76%); taping (70%) and stretches (65%). Physiotherapists with a special interest in treating PFP were statistically more likely to manage patients with orthotics (P=0.02) and bracing (P=0.01) compared to physiotherapists without a special interest. Approximately 55% would not prescribe an exercise if it was painful. Thirty-one percent of physiotherapists would advise patients not to continue with leisure and/or sporting activity if they experienced any pain. Conclusion: Current UK practice in the management strategies of PFP is variable. Further high quality research on which to inform physiotherapy practice is warranted for this troublesome musculoskeletal condition

A global view of the OCA2-HERC2 region and pigmentation

Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160–170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535–542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele

Phenotypic expansion in DDX3X - a common cause of intellectual disability in females

De novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID) cases and are amongst the most common causes of ID especially in females. Forty-seven patients (44 females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique DDX3X variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or ID, and one fetus with abnormal ultrasound findings. Rare or novel phenotypes observed include respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders