Rehabilitation outcomes in Huntington disease patients with low body mass index

Objectives:A catabolic state and a progressive body weight loss are a well-documented hallmark of Huntington Disease (HD). No study is still available on the effectiveness of intensive in-hospital rehabilitation in HD patients with low body mass index (BMI).Methods:Twenty HD patients with low BMI value were enrolled in this study. Disease severity was assessed before and after rehabilitation by the Barthel Index, the Total Functional Capacity Scale, and the Physical Performance Test.Results:BMI-scores correlated with clinical measures before and after rehabilitation. All patients showed an improvement in outcome measures (p<0.001), and an increase in BMI values (p<0.001) after rehabilitation. Effectiveness of rehabilitation correlated with the values of BMI assessed before reheducational programs (p=0.024) and with BMI values observed in each patient in the three months before admission to hospital (p=0.002).Conclusions:Findings of the current study show that the effectiveness of the rehabilitation is positively correlated with the BMI values and confirm the efficacy of in-hospital intensive rehabilitation as a valid strategy finalized to improve neuromotor performances and global functional recovery even in HD patients with low BMI and at risk of malnutrition.     

Associations of body mass index with cancer incidence among populations,genders, and menopausal status: A systematic review and meta-analysis

In order to further reveal the differences of association between body mass index (BMI) and cancer incidence across populations, genders, and menopausal status, we performed comprehensive meta-analysis with eligible citations. The risk ratio (RR) of incidence at 10 different cancer sites (per 5 kg/m² increase in BMI) were quantified separately by employing generalized least-squares to estimate trends, and combined by meta-analyses. We observed significantly stronger association between increased BMI and breast cancer incidence in the Asia⿿Pacific group (RR 1.18:1.11⿿1.26) than in European⿿Australian (1.05:1.00⿿1.09) and North-American group (1.06:1.03⿿1.08) (meta-regression p < 0.05). No association between increased BMI and pancreatic cancer incidence (0.94:0.71⿿1.24) was shown in the Asia⿿Pacific group (meta-regression p < 0.05), whereas positive associations were found in other two groups. A significantly higher RR in men was found for colorectal cancer in comparison with women (meta-regression p < 0.05). Compared with postmenopausal women, premenopausal women displayed significantly higher RR for ovarian cancer (pre- vs. post- = 1.10 vs. 1.01, meta-regression p < 0.05), but lower RR for breast cancer (pre- vs. post- = 0.99 vs. 1.11, meta-regression p < 0.0001). Our results indicate that overweight or obesity is a strong risk factor of cancer incidence at several cancer sites. Genders, populations, and menopausal status are important factors effecting the association between obesity and cancer incidence for certain cancer types.     

Uncertainty in allometric exponent estimation: a case study in scaling metabolic rate with body mass

Many factors could influence the allometric scaling exponent β estimation, but have not been explored systematically. We investigated the influences of three factors on the estimate of β based on a data set of 626 species of basal metabolic rate and mass in mammals. The influence of sampling error was tested by re-sampling with different sample sizes using a Monte Carlo method. Small random errors were introduced to measured data to examine their influence on parameter estimations. The influence of analysis method was also evaluated by applying nonlinear and linear regressions to the original data. Results showed that a relative large sample size was required to lower statistical inference errors. When sample size n was 10% of the base population size (n=63), 35% of the samples supported β=2/3, 39% supported β=3/4, and 15% rejected β=0.711, even though the base population had a β=0.711. The controversy surrounding the estimation of β in the literature could be partially attributable to such small sample sizes in many studies. Measurement errors in body mass and base metabolic rate, especially in body mass, could largely increase alpha and beta errors. Analysis methods also affected parameter estimations. Nonlinear regressions provided better estimates of the scaling exponent that were significantly higher than these commonly estimated by linear regressions. This study demonstrated the importance of the quantity and quality of data as well as analysis method in power law analysis, raising caution in interpreting power law results. Meta-data synthesis using data from independent studies seems to be a proper approach in the future, but caution should be taken to make sure that such measurements are made using similar protocols.     

Analysis of linkage between lymphotoxin alpha haplotype and polymorphisms in 5'-flanking region of tumor necrosis factor alpha gene associated with efficacy of infliximab for Crohn's disease patients

Tumor necrosis factor (TNF)alpha is increased in patients with Crohn's disease (CD) and considered to play an important role in the inflammation. Infliximab (IFX) is used as a therapeutic agent for CD. Recently, it was reported that homozygosity for a lymphotoxin alpha (LTA) haplotype (LTA 1-1-1-1) may identify subgroups with a poor response to IFX. In the present study, we characterized the linkage of the LTA haplotype with SNPs in the 5'-flanking region of the TNFalpha gene. In subjects who had homozygosity for each LTA haplotype, 6 nucleotide variations, -857C > T, -522C > G, -357A > C, -261C > G, -159G > T and -96G > T, were found in the 5'-flanking region of the TNFalpha gene. As for linking with the allele, only -857T met the LTA haplotype 1-1-1-1. We concluded that the differences in therapeutic effects of IFX among patients with CD may be explained in part by the induction ability of TNFalpha via the -857C > T polymorphism.     

Disseminated aspergillosis following infliximab therapy in an immunosuppressed patient with Crohn's disease and chronic hepatitis C: a case study and review of the literature

A 55-year-old white woman with a greater than 25-year history of Crohn's disease developed disseminated aspergillosis following combination therapy with Methylprednisolone, azathioprine, and infliximab. The patient was hospitalized 11 days after initiation of infliximab for respiratory symptoms and developed respiratory failure, coma, and died. Postmortem examination revealed disseminated Aspergillus fumigatus involving multiple organs. This case demonstrates that combined treatment with infliximab, methylprednisone, and azathioprine may induce severe immunosuppression and depressed cellular immunity, leading to severe opportunistic infections. Given the increasing use of antitumor necrosis factor agents, physicians should be aware of the risk of opportunistic infections and be vigilant about diagnosing and aggressively treating these infections to reduce the risk of disseminated disease.     

Vitamin D receptor TaqI and ApaI polymorphisms: A comparative study in patients with Behçet’s disease and Rheumatoid arthritis in Tunisian population

Recent genetic surveys have identified vitamin D receptor (VDR) as a susceptibility gene for several autoimmune diseases. This study was designed to investigate the association of VDR gene polymorphisms with Behçet’s disease (BD) and Rheumatoid arthritis (RA). A case–control study including 151 BD, 106 RA patients and an appropriate number of healthy control subjects were performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Association between TaqI polymorphism and BD was marginal under codominant and recessive models (P = 0.078 and P = 0.058, respectively). After stratification, we found evidence for a significant association between TaqI polymorphism and BD in the elderly subjects (P = 0.037). The minor ApaI a allele tended to confer an increased risk for BD susceptibility (P = 0.087). BD patients with VDR homozygous AA or aa genotypes were at increased risk for development of erythema nodosum (EN) skin manifestation (P = 0.038). No significant association was observed for VDR ApaI and TaqI polymorphisms with RA risk (P > 0.05). TaqI and ApaI polymorphisms might be modestly implicated in BD pathogenesis. They could be considered as potential biomarkers in BD rather than susceptibility genes. However, TaqI and ApaI seemed not to be implicated in RA pathogenesis.     

参苓白术散结合双歧杆菌四联活菌片对肥胖症患者代谢状况和脂肪因子及肠道菌群平衡影响的前瞻性研究

通过前瞻性研究探讨参苓白术散联合双歧杆菌四联活菌片对肥胖症患者代谢状况、脂肪因子及肠道菌群平衡的影响, 为临床干预方案的制定提供参考。

选取2018年10月至2020年10月我院112例肥胖症患者行前瞻性研究, 应用随机数字表法分为观察组(n=56)和对照组(n=56)。对照组患者予以饮食、运动等常规干预, 观察组患者在对照组基础上予以参苓白术散联合双歧杆菌四联活菌片治疗。两组患者均干预3个月。比较两组患者临床疗效、干预前和干预3个月后肥胖相关指标[体质量、体质量指数(BMI)、体脂百分率、肥胖度]、糖脂代谢指标[空腹血糖(FBG)、空腹胰岛素(FINS)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、脂肪因子[脂联素(APN)、抵抗素(resistin)、瘦素(LP)]、炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)]水平和肠道菌群(双歧杆菌、乳杆菌、拟杆菌、肠杆菌、肠球菌)数量。

(1) 干预3个月后, 观察组患者总有效率为85.71%(48/56), 高于对照组的69.64%(39/56), 而体质量、BMI、体脂百分率、肥胖度水平均低于对照组(均P < 0.05)。(2)与干预前比较, 干预3个月后两组患者FBG、FINS、TC、TG、LDL-C、HDL-C水平均降低, 同时观察组低于对照组(均P < 0.05)。(3)干预3个月后, 两组患者血清APN水平高于干预前, resistin、LP水平低于干预前, 同时观察组均优于对照组(均P < 0.05)。(4)与干预前比较, 干预3个月后两组患者血清TNF-α、IL-6、IL-1β水平均呈降低趋势, 同时观察组降低幅度大于对照组(均P < 0.05)。(5)观察组患者干预3个月后肠道双歧杆菌、乳杆菌、拟杆菌数量均高于对照组, 而肠杆菌、肠球菌数量均低于对照组(均P < 0.05)。

参苓白术散、双歧杆菌四联活菌片联合干预方案在肥胖症患者中的应用效果理想, 可有效控制肥胖, 促进患者体质量降低, 同时对机体糖脂代谢、脂肪因子、炎症因子水平及肠道菌群均有良好调节作用, 临床应用价值较高。

     

Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism

Introduction

Classical homocystinuria is a rare genetic disease caused by cystathionine β-synthase deficiency, resulting in homocysteine accumulation. Growing evidence suggests that reduced fat mass in patients with classical homocystinuria may be associated with alterations in choline and homocysteine pathways. This study aimed to evaluate the body composition of patients with classical homocystinuria, identifying changes in body fat percentage and correlating findings with biochemical markers of homocysteine and choline pathways, lipoprotein levels and bone mineral density (BMD) T-scores.

Methods

Nine patients with classical homocystinuria were included in the study. Levels of homocysteine, methionine, cysteine, choline, betaine, dimethylglycine and ethanolamine were determined. Body composition was assessed by bioelectrical impedance analysis (BIA) in patients and in 18 controls. Data on the last BMD measurement and lipoprotein profile were obtained from medical records.

Results

Of 9 patients, 4 (44%) had a low body fat percentage, but no statistically significant differences were found between patients and controls. Homocysteine and methionine levels were negatively correlated with body mass index (BMI), while cysteine showed a positive correlation with BMI (p < 0.05). There was a trend between total choline levels and body fat percentage (r = 0.439, p = 0.07). HDL cholesterol correlated with choline and ethanolamine levels (r = 0.757, p = 0.049; r = 0.847, p = 0.016, respectively), and total cholesterol also correlated with choline levels (r = 0.775, p = 0.041). There was no association between BMD T-scores and body composition.

Conclusions

These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism.     

Analysis of longitudinal changes in dyspnea of patients with chronic obstructive pulmonary disease: an observational study

Background

Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD). However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea.

Methods

We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years. We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status. Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George’s Respiratory Questionnaire (SGRQ) were also used. Dyspnea at the end of exercise tolerance tests was measured using the Borg scale.

Results

The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097). Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV₁) (correlation of determination (r²) = 0.05-0.19), diffusing capacity for carbon monoxide (r² = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r² = 0.14-0.17), although these correlations were weak. Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements.

Conclusion

Dyspnea worsened over time in patients with COPD. However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements. Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status. Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements.     

Exercise training with negative pressure ventilation improves exercise capacity in patients with severe restrictive lung disease: a prospective controlled study

Background

Exercise training is of benefit for patients with restrictive lung disease. However, it tends to be intolerable for those with severe disease. We examined whether providing ventilatory assistance by using negative pressure ventilators (NPV) during exercise training is feasible for such patients and the effects of training.

Methods

36 patients with restrictive lung disease were prospectively enrolled for a 12-week multidisciplinary rehabilitation program. During this program, half of them (n:18; 60.3 ± 11.6 years; 6 men; FVC: 32.5 ± 11.7% predicted ) received regular sessions of exercise training under NPV, whilst the 18 others (59.6 ± 12.3 years; 8 men; FVC: 37.7 ± 10.2% predicted) did not. Exercise capacity, pulmonary function, dyspnea and quality of life were measured. The primary endpoint was the between-group difference in change of 6 minute-walk distance (6MWD) after 12 weeks of rehabilitation.

Results

All patients in the NPV-exercise group were able to tolerate and completed the program. The between-group differences were significantly better in the NPV-exercise group in changes of 6MWD (34.1 ± 12.7 m vs. -32.5 ± 17.5 m; P = 0.011) and St George Score (−14.5 ± 3.6 vs. 11.8 ± 6.0; P < 0.01). There was an improvement in dyspnea sensation (Borg’s scale, from 1.4 ± 1.5 point to 0.8 ± 1.3 point, P = 0.049) and a small increase in FVC (from 0.85 ± 0.09 L to 0.91 ± 0.08 L, P = 0.029) in the NPV-exercise group compared to the control group.

Conclusion

Exercise training with NPV support is feasible for patients with severe restrictive lung diseases, and improves exercise capacity and health-related quality of life.     

Metabolic changes in the basal ganglia of patients with Huntington's disease: an in situ hybridization study of cytochrome oxidase subunit I mRNA

On the basis of the functional model of the basal ganglia developed in the 1980s and the neuropathological findings in Huntington's disease (HD), changes in the neuronal activity of the basal ganglia have previously been proposed to explain the abnormal movements observed in this pathology. In particular, it has been stated that the neurodegenerative process affecting the basal ganglia in the disease should provoke a hypoactivity in the internal segment of the pallidum (GPi) that could explain choreic movements observed in the disease. To test this functional hypothesis, we performed an in situ hybridization study on control and HD brains postmortem, taking cytochrome oxidase subunit I (COI) mRNAs expression as index of neuronal activity. As most of the HD patients studied were under chronic neuroleptic (NL) treatment, we also studied the brains of non-HD patients under chronic NL treatment. Our results show that in HD brain the number of neurons expressing COI mRNA tends to be lower in the striatum, GPe and GPi, suggesting a severe involvement of these structures during the neurodegenerative process. Moreover, COI mRNA level of expression was markedly reduced within neurons of the putamen and GPe. Surprisingly, COI mRNA expression was not modified in the GPi in HD brains compared with controls. This paradoxical result in the GPi may be explained by the antagonistic effect of GPe hypoactivity and the degenerative process involving neurons of GPi. Our results indicate that the functional modifications, and consequently the pathophysiology of abnormal movements, observed in HD basal ganglia are more complex than expected from the currently accepted model of the basal ganglia organization.     

Distribution and binding of 18F-labeled and 125I-labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: a whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients

One of the major pathological landmarks of Alzheimer's disease and other neurodegenerative diseases is the presence of amyloid deposits in the brain. The early non-invasive visualization of amyloid is a major objective of recent diagnostic neuroimaging approaches, including positron emission tomography (PET), with an eye on follow-up of disease progression and/or therapy efficacy. The development of molecular imaging biomarkers with binding affinity to amyloid in the brain is therefore in the forefront of imaging biomarker and radiochemistry research. Recently, a dodecamer peptide (amino acid sequence=QSHYRHISPAQV; denominated D1 or ACI-80) was identified as a prospective ligand candidate, binding with high ex vivo affinity to L-Aβ-amyloid (K(d): 0.4 μM). In order to assess the ligand's capacity to visualize amyloid in Alzheimer's disease (AD), two (125)I labeled and three (18)F labeled analogues of the peptide were synthesized and tested in post mortem human autoradiography experiments using whole hemisphere brain slices obtained from deceased AD patients and age matched control subjects. The (18)F-labeled radioligands showed more promising visualization capacity of amyloid that the (125)I-labeled radioligands. In the case of each (18)F radioligands the grey matter uptake in the AD brains was significantly higher than that in control brains. Furthermore, the grey matter: white matter uptake ratio was over ~2, the difference being significant for each (18)F-radioligands. The regional distribution of the uptake of the various radioligands systematically shows a congruent pattern between the high uptake regions and spots in the autoradiographic images and the disease specific signals obtained in adjacent or identical brain slices labeled with histological, immunohistochemical or autoradiographic stains for amyloid deposits or activated astrocytes. The present data, using post mortem human brain autoradiography in whole hemisphere human brains obtained from deceased AD patients and age matched control subjects, support the visualization capacity of the radiolabeled ACI-80 analogues of amyloid deposits in the human brain. Further studies are warranted to explore the usefulness of the (18)F-labeled analogues as in vivo molecular imaging biomarkers in diagnostic PET studies.     

The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease

Background

Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case–control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed.

Methods

The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR–RFLP assay. Anthropometric measurements were measured in all participants.

Results

There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p = 0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA + AA genotypes in male CHD patients (p = 0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age < 55 (OR = 2.837, p = 0.001) and TC ≥ 5.18 mmol/L (OR = 1.970, p = 0.027) in male subjects. However, this association was not observed in female patients (p > 0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age < 55 years.

Conclusion

These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.     

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study

BackgroundCardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn’t been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state.MethodsThis is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls).ResultssP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases.ConclusionOur study supports the previous researches’ results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.