The Relationship Between Scoliosis, Spinal Bone Density, and Truncal Muscle Strength in Familial Dysautonomia Patients.

This combined retrospective and prospective study aimed to investigate the relationship between scoliosis, spinal bone mineral density (BMD), and truncal muscle strength in patients with familial dysautonomia (FD). A total of 79 FD patients (40 male, 39 female) aged 5-44 years were included. The severity of scoliosis, lumbar spine BMD (Z-score), and truncal muscle strength were assessed. Correlations were analyzed using Pearson's correlation coefficient. Inverse correlations were observed between scoliosis severity and BMD (r = - 0.328, p = 0.001), as indicated by increasingly negative Z-score values with worsening osteoporosis. There were also inverse correlations between scoliosis and truncal muscle strength (r = - 0.595, p < 0.001). The correlation between scoliosis and age was notable up to 22 years (r = 0.421, p = 0.01), but not in the older age group (22-44 years). Our study identified inverse correlations between osteoporosis and scoliosis, as well as between scoliosis and truncal muscle strength, in FD patients. These findings suggest that there may be a relationship between bone density, muscle strength, and the severity of spinal curvature in this population. While our results highlight the potential importance of early diagnosis and management of osteoporosis, and possibly the benefits of physical therapy to strengthen truncal muscles, further research is needed to determine the direct impact of these interventions on preventing the progression of scoliosis and its associated complications in FD patients. A long-term longitudinal study could provide more insights into these relationships and inform treatment strategies for FD patients.

A feasibility, randomised controlled trial of Club Connect: a group-based healthy brain ageing cognitive training program for older adults with major depression within an older people's mental health service.

BACKGROUND: Using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, we outline steps taken to implement an evidence-based cognitive training program, Club Connect, in older adults with major depressive disorder in an Older People's Mental Health Service in Sydney, Australia. The primary aim was to explore feasibility (or 'reach'), tolerability (or 'implementation'), and acceptability (or 'adoption'). The secondary aim was to explore the most sensitive clinical outcomes and measurement tools (i.e. 'effectiveness') to inform a formal randomised controlled trial, and to explore the healthcare resources used (i.e. costs) to assist decision-making by health care managers and policy-makers in relation to future resource allocation. METHODS: Using a single blinded feasibility design, 40 participants (mean age: 76.13 years, SD: 7.45, range: 65-95 years) were randomised to either (a) Club Connect, a 10-week group-based multifaceted program, comprising psychoeducation and computer-based cognitive training, or (b) a waitlist control group. RESULTS: Implementing group-based cognitive training within a clinical setting was feasible, well tolerated and accepted by participants. Further, cognitive training, in comparison to the waiting list control, was associated with moderate to very large effect size improvements in depression, stress and inhibition (ηp2 = 0.115-0.209). We also found moderate effect size improvements on measures of daily functioning, wellbeing and cognitive flexibility. Small effect size improvements for other cognitive and psychosocial outcomes were also observed. The average cost per person participating in in the intervention was AU$607.50. CONCLUSIONS: Our findings support the feasibility of implementing group-based cognitive training into a specialised clinical (public health) setting. This trial was registered on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000195156, 12/02/2019).

Modulation of brain serotonin by benzyl butyl phthalate in Fundulus heteroclitus (mummichog).

Endocrine-disrupting chemicals have been known to alter important animal behaviors by modulating serotonin (5-hydroxytryptamine, 5-HT) and dopamine. F. heteroclitus (mummichog) brain serotonin and dopamine levels were quantified by enzyme-linked immunosorbent assay (ELISA) following a 28-day exposure regimen involving daily doses of either 0.1 mg l-1 benzyl butyl phthalate (BBP) dissolved in acetone or acetone alone (0.1 mg l-1). No differences in mean brain mass or total protein homogenate were induced by exposure to the acetone vehicle or BBP in acetone. The acetone vehicle had no effect on dopamine, serotonin, or tyrosine hydroxylase levels, but acetone did decrease tryptophan hydroxylase levels (p = 0.011). Exposure to BBP in acetone decreased dopamine (p = 0.024), increased serotonin (p < 0.001), reduced tryptophan hydroxylase as compared to the acetone vehicle alone (p < 0.001), and had no significant effect on tyrosine hydroxylase levels. This study is the first to report modulation of F. heteroclitus brain serotonin and its enzyme tryptophan hydroxylase following sub-lethal exposure to BBP in an acetone vehicle. In addition, modulation of brain dopamine in F. heteroclitus, sans simultaneous modulation of tyrosine hydroxylase, was also observed. These findings support the use of F. heteroclitus for assessing sub-lethal BBP exposure.

Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma.

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.

Early intervention with Interleukin-1 Receptor Antagonist Protein modulates catabolic microRNA and mRNA expression in cartilage after impact injury.

OBJECTIVE: The purpose of this controlled laboratory study was to determine the efficacy of Interleukin-1 Receptor Antagonist Protein (IRAP) treatment as an early intervention strategy by examining the changes in microRNA and mRNA expression in cartilage in an ex-vivo porcine knee joint impact model. METHODS: Custom impact device was used to create replicable injury ex-vivo to intact porcine knee joint. Injury was caused by dropping a 10 kg weight one time from 1 m directly above the knee in extension. One hour after impact 20 µg/ml IRAP solution was intra-articularly injected. At 8 h post-injury, cartilage samples were harvested for cell viability and genetic expression analysis. Genetic expression of miR-27b, miR-140, miR-125b, ADAMTS-4, ADAMTS-5, MMP-3, IL-1ß, and TNF-α were analyzed by RT-PCR. Cell viability image analysis was performed using ImageJ software. Groups were compared by analysis of variance (ANOVA) followed by Tukey's post-hoc test. A P-value <0.05 was considered significant. RESULTS: At 8 h after IRAP treatment, expressions of ADAMTS-4, ADAMTS-5, MMP-3, IL-1ß, and TNF-α in cartilage were significantly down-regulated from injury group (all P < 0.001). MiR-140, miR-125b, and miR-27b expressions were significantly up-regulated after treatment as compared to control and injury groups (all P < 0.001). CONCLUSION: This study demonstrates that IRAP treatment administered during acute phase of cartilage impact injury increases expression levels of miR-140, miR-125b, and miR-27b in cartilage, indicating increased inhibition of their respective matrix-degrading enzymes. Clinically, these findings support the potential of IRAP treatment as an early intervention strategy for the prevention of cartilage degeneration after impact injury.

Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

Density-Dependent Oviposition by Female Aedes albopictus (Diptera: Culicidae) Spreads Eggs Among Containers During the Summer but Accumulates Them in the Fall.

When possible, oviparous females should deposit eggs in sites that maximize the future performance of their offspring. Therefore, studies of oviposition behavior may uncover parameters important to offspring fitness. Gravid female Aedes albopictus (Skuse) were given a choice of containers with leaf infusion or plain water, either open or with a cover with a small opening, and their behavior was compared under summer (long day, higher temperature) or fall (short day, lower temperature) regimes. Open containers with leaf infusion were always preferred, but over time, summer females expanded their choices to oviposit in all containers and follow-up experiments indicated that the number of eggs laid was inversely correlated to the number of eggs present. In contrast, fall females laying diapausing eggs that do not hatch until the spring, accumulated eggs in open containers with food resulting in high egg densities. Combined, these results demonstrate a seasonal shift that suggests either high winter egg mortality or safety in numbers. It also demonstrates that female Ae. albopictus change their behavior based on cues associated with expected added risk, which varies across time and space. The wide distribution of summer eggs across container types may contribute to the fast expansion of Ae. albopictus across its invasive range, but egg accumulation in the fall may be exploited for control.

Platelet-rich plasma induces annulus fibrosus cell proliferation and matrix production.

PURPOSE: Platelet-rich plasma (PRP) contains growth factors and creates a 3D structure upon clotting; PRP or platelet lysate (PL) might be considered for annulus fibrosus (AF) repair. METHODS: Bovine AF cells were cultured with 25% PRP, 50% PRP, 25% PL, 50% PL, or 10% FBS. After 2 and 4 days, DNA, glycosaminoglycan (GAG), and mRNA levels were analyzed. Histology was performed after injection of PRP into an AF defect in a whole disc ex vivo. RESULTS: By day 4, significant increases in DNA content were observed in all treatment groups. All groups also showed elevated GAG synthesis, with highest amounts at 50% PL. Collagen I and II expression was similar between groups; aggrecan, decorin, and versican expression was highest at 25% PL. Injection of PRP into the AF defect resulted in an increased matrix synthesis. CONCLUSIONS: Platelet-rich preparations increased the matrix production and cell number and may therefore be considered to promote AF repair.

Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity.

BACKGROUND: Bile acids (BAs) are nutrient-responsive hormones that modulate energy balance through cell surface and nuclear receptors. Postprandial plasma BAs have been found to be decreased in obesity. OBJECTIVE: We aimed to determine whether meal-stimulated circulating BA levels are altered by Roux-en-Y gastric bypass (RYGB), an operation that modifies the neurohumoral determinants of food intake and energy expenditure to cause significant and durable weight loss. DESIGN: Longitudinal study measuring fasting and postprandial plasma BAs before and after RYGB. SUBJECTS: Five obese surgical patients and eight lean controls underwent frequent blood sampling after a standard liquid meal. Obese subjects were also tested at 1, 4 and 40 weeks after RYGB. Primary and secondary circulating BAs, as well as their glycine and taurine conjugates, were measured via reverse-phase high-performance liquid chromatography/mass spectroscopy. RESULTS: We found that postprandial excursion of conjugated BAs was 52.4% lower in obese than in lean individuals by area-under-the-curve (AUC) analysis (378 vs 793 µmol min l(-1), respectively, P<0.05). By 40 weeks after RYGB, the meal-induced rise in conjugated BAs increased by 55.5% to the level of healthy lean controls (378 pre-op vs 850 µmol min l(-) post-op by AUC analyses, P<0.05). In contrast, postprandial concentrations of unconjugated BAs were similar in lean and obese individuals and were not affected by surgery. CONCLUSION: In light of the growing evidence that BAs have key roles in glucose, lipid and energy homeostasis, the observation that RYGB normalizes the blunted postprandial circulating BA response in obesity suggests that BAs may contribute to the improvement in meal-related physiology seen after RYGB. Further studies are warranted to examine this hypothesis and to determine the degree to which an augmented BA response to nutrient ingestion may mediate the increased incretin response, brown adipose tissue activation and thermic effect of feeding that has been observed after this operation.

Perioperative pulmonary complications.

PURPOSE OF REVIEW: This article reviews current concepts in perioperative pulmonary management. RECENT FINDINGS: Preoperative risk assessment tools for perioperative pulmonary complications (POPCs) are evolving for both children and adults. Intraoperative management strategies have a demonstrable effect on outcomes. Late POPCs may be preceded by clinical signs. SUMMARY: POPCs are common and lead to significant resource utilization. Optimal POPC risk mitigation must span all phases of surgical care. Preoperative assessment may identify patients at risk and effectively lower their risk by identifying targeted interventions. Intra-operative strategies impact postoperative outcome. POPCs continue to be a concern for several days postoperatively. We review the current literature on this broad subject with a focus on implementable interventions for the clinician.

Freak waves in the linear regime: a microwave study.

Microwave transport experiments have been performed in a quasi-two-dimensional resonator with randomly distributed conical scatterers. At high frequencies, the flow shows branching structures similar to those observed in stationary imaging of electron flow. Semiclassical simulations confirm that caustics in the ray dynamics are responsible for these structures. At lower frequencies, large deviations from Rayleigh's law for the wave height distribution are observed, which can only partially be described by existing multiple-scattering theories. In particular, there are "hot spots" with intensities far beyond those expected in a random wave field. The results are analogous to flow patterns observed in the ocean in the presence of spatially varying currents or depth variations in the sea floor, where branches and hot spots lead to an enhanced frequency of freak or rogue wave formation.

Voriconazole is safe and effective as prophylaxis for early and late fungal infections following allogeneic hematopoietic stem cell transplantation.

Seventy-two patients undergoing allogeneic transplantation were treated with voriconazole (VOR) as antifungal prophylaxis starting from day -2 of transplantation and continuing until withdrawal of immunosuppression. Patients were assessed for safety and the incidence of definite, probable, or possible fungal infection throughout transplantation was evaluated. VOR was well tolerated. Only 14% of patients required interruption of VOR therapy because of toxicity: liver toxicity (8%), cardiac Q-T interval prolongation (1%), or other side effects (5%). In the early post-transplant period (<120 days), only 2 patients developed invasive fungal infection: 1 mucormycosis infection and 1 disseminated Aspergillus infection. In the late post-transplant period (>120 days), no patients developed probable or definite fungal infection while receiving VOR. No Candida infections were seen in either period. These data suggest that fungal prophylaxis with VOR following allogeneic transplantation is safe and effective.

Early Cultivated Beans (Phaseolus vulgaris) from an Intermontane Peruvian Valley.

Examples of fully domesticated common beans (Phaseolus vulgaris) and lima beans (Phaseolus lunatus) were recovered from deposits in Guitarrero Cave (PAn 14-102) in the Callejón de Huaylas, Ancash, Peru. Carbon-14 dates for stratum II, in which the earliest beans were found, range from 7,680 +/- 280 to 10,000 +/- 300 years before the present.

Mars: new absorption bands in the spectrum.

New absorption bands have been found in the near-infrared spectrum of Mars by Fourier spectroscopy. They are tentatively identified in part as due to reduced gases in the Martian atmosphere.

Beans for valdivia.

Carbonized remains of Canavalia beans were recovered from archaeological deposits excavated at Real Alto (OGCh-12), southwestern Ecuador. The identification, context and dating of the earliest beans from Real Alto demonstrate their use from the beginning of Valdivia (about 3300 B.C.) and the Early Formative in coastal Ecuador.

The fork in the road: HIV as a potential positive turning point and the role of spirituality.

We interviewed 147 HIV-positive people regarding their key life-changing experiences - involving profound changes in attitudes, behaviors, beliefs (including spiritual beliefs), or self-views - to determine the prominence of HIV as the key positive/negative turning point. HIV was the key turning point, for 37% (26% positive, 11% negative), whereas for 63% of our sample it was not. Characteristics associated with perceiving HIV as the most positive turning point included having a near-death experience from HIV, increasing spirituality after HIV diagnosis, and feeling chosen by a Higher Powerto have HIV. Notably, perceived antecedents of viewing HIV as the key positive turning point were hitting rock bottom and calling on a Higher Power. Conversely, viewing HIV as the most negative turning point was associated with declining spirituality after diagnosis. Spirituality can both negatively and positively affect coping with HIV. Promoting positive spiritual coping may offer new counseling approaches. Further, for the majority of the participants, HIV is not the key turning point, which may be an indicator of the normalization of HIV with the advent of effective treatment.

Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation.

To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gp140trk in the NGF-responsive PC12 cell line. Here we demonstrate that overexpression of gp140trk results in marked changes in NGF-induced differentiation. Whereas PC12 cells elaborated neurites after 2 days of continuous exposure to NGF, PC12 cells overexpressing gp140trk by 20-fold(trk-PC12) began this process within hours. Compared with wild-type PC12 cells, trk-PC12 exhibited an increase in both high and low affinity NGF-binding sites. Furthermore, trk-PC12 cells displayed an enhanced level of NGF-dependent gp140trk autophosphorylation, and this activity was sustained for many hours following ligand binding. The tyrosine phosphorylation or activity of several cellular proteins, such as PLC-gamma 1, PI-3 kinase, and Erk1 and the expression of the mRNA for the late response gene transin were also sustained as a consequence of gp140trk overexpression. The data indicate that overexpression of gp140trk in PC12 cells markedly accelerates NGF-induced differentiation pathways, possibly through the elevation of gp140trk tyrosine kinase activity.

Fluids for prevention and management of acute kidney injury.

Fluids are the only known method of attenuating renal injury. Furthermore, whether for hydration, resuscitation or renal replacement therapy, fluid prescriptions must be tailored to the fluid and electrolyte, cardiovascular status and residual renal function of the patient. Different fluids have significantly different effects both on volume expansion as well as on the electrolyte and acid-base balance; while controversial, different fluids may even influence renal function differently. This systematic review focuses on fluids for prevention and management of acute kidney injury. We have reviewed the available evidence and have made recommendations for clinical practice and future studies.

Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families.

Our primary aim was to determine the extent to which intraplasmic retinyl palmitate (RP) transfers to other lipoprotein particles when chylomicron remnants are not produced and/or the plasma RP residence time is increased. The study was conducted on three familial type I hyperlipoproteinemic patients, four lipoprotein lipase (LpL)-deficient heterozygotes, and three controls on a metabolic research unit. To each subject, a fat load was administered containing 16% of total daily calories in type I patients, 40% in heterozygotes and controls, plus 60,000 U/m2 vitamin A. Triglyceride (TG) and RP levels were evaluated in chylomicron and nonchylomicron fractions. Delay in the clearance of chylomicron fraction RP and the marked deficiency in nonchylomicron-RP (presumed lack of remnant production) in all three type I patients suggests that RP does not demonstrate significant intraplasmic transfer from chylomicrons to existent apolipoprotein B100 particles. In contrast to noncoincident TG and RP peaking in the normal subject, heterozygotes were found to demonstrate coincident plasma TG and RP curves, which is consistent with a common catabolic pathway for both TG and RP and inconsistent with intraplasmic RP transfer. This corroborates reports on compromised chylomicron clearance in heterozygotes. We conclude that RP is an appropriate representative marker for intestinally derived particles in LpL-deficient or partially deficient individuals.

Determining the mechanical properties of a radiochromic silicone-based 3D dosimeter.

New treatment modalities in radiotherapy (RT) enable delivery of highly conformal dose distributions in patients. This creates a need for precise dose verification in three dimensions (3D). A radiochromic silicone-based 3D dosimetry system has recently been developed. Such a dosimeter can be used for dose verification in deformed geometries, which requires knowledge of the dosimeter's mechanical properties. In this study we have characterized the dosimeter's elastic behaviour under tensile and compressive stress. In addition, the dose response under strain was determined. It was found that the dosimeter behaved as an incompressible hyperelastic material with a non-linear stress/strain curve and with no observable hysteresis or plastic deformation even at high strains. The volume was found to be constant within a 2% margin at deformations up to 60%. Furthermore, it was observed that the dosimeter returned to its original geometry within a 2% margin when irradiated under stress, and that the change in optical density per centimeter was constant regardless of the strain during irradiation. In conclusion, we have shown that this radiochromic silicone-based dosimeter's mechanical properties make it a viable candidate for dose verification in deformable 3D geometries.