Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Associations of linear growth with body composition of perinatally HIV-infected African adolescents

The prevalence of poor linear growth among African children with perinatally acquired HIV remains high. There is concern that poor linear growth may to lead to later total and central fat deposition and associated non-communicable disease risks. We investigated associations between height-for-age Z score (HAZ) and total and regional fat and lean mass measured by dual-energy X-ray absorptiometry, expressed as internal population Z scores, among 839 Zimbabwean and Zambian perinatally HIV-infected male and female adolescents aged 11-19 years. Stunting (HAZ < -2) was present in 37 % of males and 23 % of females. HAZ was strongly positively associated with total, trunk, arm and leg fat mass and lean mass Z scores, in analyses controlling for pubertal stage, socio-economic status and HIV viral load. Associations of linear growth with lean mass were stronger than those with fat outcomes; associations with total and regional fat were similar, indicating no preferential central fat deposition. There was no evidence that age of starting antiretroviral therapy was associated with HAZ or body composition. Non-suppressed HIV viral load was associated with lower lean but not fat mass. The results do not support the hypothesis that poor linear growth or stunting are risk factors for later total or central fat deposition. Rather, increased linear growth primarily benefits lean mass but also promotes fat mass, both consistent with larger body size. Nutritional and/or HIV infection control programmes need to address the high prevalence of stunting among perinatally HIV-infected children in order to mitigate constraints on the accretion of lean and fat mass

The impact of Vitamin D supplementation on musculoskeletal health outcomes in children, adolescents, and young adults living with HIV: A systematic review

Objective: HIV-positive children, adolescents, and young adults are at increased risk poor musculoskeletal outcomes. Increased incidence of vitamin D deficiency in youth living with HIV may further adversely affect musculoskeletal health. We investigated the impact of vitamin D supplementation on a range of musculoskeletal outcomes among individuals aged 0–25 years living with HIV. Methods: A systematic review was conducted using databases: PubMed/Medline, CINAHL, Web of Knowledge, and EMBASE. Interventional randomised control trials, quasi-experimental trials, and previous systematic reviews/meta-analyses were included. Outcomes included: BMD, BMC, fracture incidence, muscle strength, linear growth (height-for-age Z-score [HAZ]), and biochemical/endocrine biomarkers including bone turnover markers. Results: Of 497 records, 20 studies met inclusion criteria. Thirteen studies were conducted in North America, one in Asia, two in Europe, and four in Sub-Saharan Africa. High-dose vitamin D supplementation regimens (1,000–7,000 IU/day) were successful in achieving serum 25-hydroxyvitamin-D (25OHD) concentrations above study-defined thresholds. No improvements were observed in BMD, BMC, or in muscle power, force and strength; however, improvements in neuromuscular motor skills were demonstrated. HAZ was unaffected by low-dose (200–400 IU/day) supplementation. A single study found positive effects on HAZ with high-dose supplementation (7,000 vs 4,000IU/day). Conclusions: Measured bone outcomes were unaffected by high-dose vitamin D supplementation, even when target 25OHD measurements were achieved. This may be due to: insufficient sample size, follow-up, intermittent dosing, non-standardised definitions of vitamin D deficiency, or heterogeneity of enrolment criteria pertaining to baseline vitamin D concentration. High-dose vitamin D may improve HAZ and neuromuscular motor skills. Adequately powered trials are needed in settings where HIV burden is greatest

Expert judgement reveals current and emerging UK climate-mortality burden

Weather and climate patterns play an intrinsic role in societal health, yet a comprehensive synthesis of specific hazard–mortality causes does not currently exist. Country-level health burdens are thus highly uncertain, but harnessing collective expert knowledge can reduce this uncertainty, and help assess diverse mortality causes beyond what is explicitly quantified. Here, surveying 30 experts, we provide the first structured expert judgement of how weather and climate directly impact mortality, using the UK as an example. Current weather-related mortality is dominated by short-term exposure to hot and cold temperatures leading to cardiovascular and respiratory failure. We find additional underappreciated health outcomes, especially related to long-exposure hazards, including heat-related renal disease, cold-related musculoskeletal health, and infectious diseases from compound hazards. We show potential future worsening of cause-specific mortality, including mental health from flooding or heat, and changes in infectious diseases. Ultimately, this work could serve to develop an expert-based understanding of the climate-related health burden in other countries

Effect of inpatient rehabilitation treatment ingredients on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with unplanned admission: An overview review

BACKGROUND: To synthesise the evidence for the effectiveness of inpatient rehabilitation treatment ingredients (versus any comparison) on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with an unplanned hospital admission. METHODS: A systematic search of Cochrane Library, MEDLINE, Embase, PsychInfo, PEDro, BASE, and OpenGrey for published and unpublished systematic reviews of inpatient rehabilitation interventions for older adults following an unplanned admission to hospital from database inception to December 2020. Duplicate screening for eligibility, quality assessment, and data extraction including extraction of treatment components and their respective ingredients employing the Treatment Theory framework. Random effects meta-analyses were completed overall and by treatment ingredient. Statistical heterogeneity was assessed with the inconsistency-value (I(2)). RESULTS: Systematic reviews (n = 12) of moderate to low quality, including 44 non-overlapping relevant RCTs were included. When incorporated in a rehabilitation intervention, there was a large effect of endurance exercise, early intervention and shaping knowledge on walking endurance after the inpatient stay versus comparison. Early intervention, repeated practice activities, goals and planning, increased medical care and/or discharge planning increased the likelihood of discharge home versus comparison. The evidence for activities of daily living (ADL) was conflicting. Rehabilitation interventions were not effective for functional mobility, strength, or quality of life, or reduce length of stay or mortality. Therefore, we did not explore the potential role of treatment ingredients for these outcomes. CONCLUSION: Benefits observed were often for subgroups of the older adult population e.g., endurance exercise was effective for endurance in older adults with chronic obstructive pulmonary disease, and early intervention was effective for endurance for those with hip fracture. Future research should determine whether the effectiveness of these treatment ingredients observed in subgroups, are generalisable to older adults more broadly. There is a need for more transparent reporting of intervention components and ingredients according to established frameworks to enable future synthesis and/or replication. TRIAL REGISTRATION: PROSPERO Registration CRD42018114323. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-022-03169-2

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass

External tagging does not affect the feeding behavior of a coral reef fish, Chaetodon vagabundus (Pisces: Chaetodontidae)

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of for personal use, not for redistribution. The definitive version was published in Environmental Biology of Fishes 86 (2009): 447-450, doi:10.1007/s10641-009-9545-9.Increasingly, the ability to recognize individual fishes is important for studies of population dynamics, ecology, and behavior. Although a variety of methods exist, external tags remain one of the most widely applied because they are both effective and cost efficient. However, a key assumption is that neither the tagging procedure nor the presence of a tag negatively affects the individual. While this has been demonstrated for relatively coarse metrics such as growth and survival, few studies have examined the impact of tags and tagging on more subtle aspects of behavior. We tagged adult vagabond butterflyfish (Chaetodon vagabundus) occupying a 30-ha insular reef in Kimbe Bay, Papua New Guinea, using a commonly-utilized t-bar anchor tag. We quantified and compared feeding behavior (bite rate), which is sensitive to stress, of tagged and untagged individuals over four separate sampling periods spanning four months post-tagging. Bite rates did not differ between tagged and untagged individuals at each sampling period and, combined with additional anecdotal observations of normal pairing behavior and successful reproduction, suggest that tagging did not adversely affect individuals.The authors gratefully acknowledge funding from the Fulbright Program, National Science Foundation and the Australian Research Council

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals