Effectiveness of nirmatrelvir/ritonavir (Paxlovid®) in preventing hospitalisation and death among COVID-19 patients: a prospective cohort study.

INTRODUCTION: Previous trials and real-world studies have shown that nirmatrelvir/ritonavir (Paxlovid®) reduces hospitalisation and deaths in symptomatic, high-risk, nonsevere COVID-19 patients. However, there was a scarcity of data on its effectiveness in the local setting. This study aimed to determine the effectiveness of Paxlovid® in reducing hospitalisation and mortality among COVID-19 patients and to identify the types of adverse events that occur after taking Paxlovid®. MATERIALS AND METHODS: A two-arm prospective cohort study was conducted among adult patients with COVID-19 categories 2 and 3 treated with Paxlovid® and a matched control group. A standard risk-stratified scoring system was used to establish Paxlovid® eligibility. All patients who were prescribed Paxlovid® and took at least one dose of Paxlovid® were included in the study. The control patients were selected from a centralised COVID-19 patient registry and matched based on age, gender and COVID-19 stage severity. RESULTS: A total of 552 subjects were included in the study and evenly allocated to the treatment and control groups. There was no statistically significant difference in 28-day hospitalisation after diagnosis [Paxlovid®: 26 (9.4%), Control: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or all-cause death [Paxlovid®: 2 (0.7%), Control: 3 (1.1%), OR 1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant reduction in hospitalisation duration, intensive care unit admission events or supplementary oxygen requirement in the treatment arm. Ethnicity, COVID-19 severity at diagnosis, comorbidities and vaccination status were predictors of hospitalisation events. CONCLUSION: In this two-arm study, Paxlovid® did not significantly lower the incidence of hospitalisation, all-cause death and the need for supplemental oxygen. Adverse effects were frequent but not severe. Paxlovid® efficacy varied across settings and populations, warranting further real-world investigations.

Bioequivalence and pharmacokinetic comparison of two fixed dose combination of Metformin/ Glibenclamide formulations in healthy subjects under fed condition.

AIM: This study is conducted to compare the pharmacokinetic profiles of two fixed dose combination of metformin/glibenclamide tablets (500mg/5 mg per tablet). MATERIALS AND METHODS: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods. RESULTS: The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693-1.0739, 0.9598- 1.0561 and 0.9220 - 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects. CONCLUSION: It can be concluded that the test preparation is bioequivalent to the reference preparation.

Influence of bariatric surgery on weight reduction and control of chronic disease among obese patients in Malaysia.

INTRODUCTION: This study was designed to determine the influence of bariatric surgery on changes in the body mass index (BMI), and the control of diabetes, hypertension and dyslipidaemia among obese patients in Malaysia. MATERIALS AND METHODS: This was a retrospective cohort study undertaken at a public tertiary care centre in the state of Perak, Malaysia. Information of obese patients who underwent bariatric surgery was obtained from their medical records. The changes in the BMI, HbA1C, systolic and diastolic blood pressure (SBP and DBP), and lipid levels between three months before and after the surgery were assessed. RESULTS: The patients (n=106) were mostly Malay (66.0%), had at least one comorbidity (61.3%), and had a mean age of 40.38±11.75 years. Following surgery, the BMI of the patients was found to reduce by 9.78±5.82kg/m2. For the patients who had diabetes (n=24) and hypertension (n=47), their mean HbA1C, SBP and DBP were also shown to reduce significantly by 2.02±2.13%, 17.19±16.97mmHg, and 11.45±12.63mmHg, respectively. Meanwhile, the mean total cholesterol, triglyceride and low-density lipoprotein levels of those who had dyslipidaemia (n=21) were, respectively, lowered by 0.91±1.18mmol/L, 0.69±1.11mmol/L and 0.47±0.52mmol/L. CONCLUSION: The findings suggest that in addition to weight reduction, bariatric surgery is helpful in improving the diabetes, hypertension and dyslipidaemia control among obese patients. However, a large-scale trial with a control group is required to verify our findings.

Utilization of Western medicine and traditional Chinese medicine among patients with Alzheimer's disease in Taiwan: a nationwide population-based study.

BACKGROUND AND PURPOSE: Large-scale studies of utilization of medical services among patients with Alzheimer's disease (AD) are lacking. We aimed to investigate the usage of Western medicine and traditional Chinese medicine (TCM) among these patients in Taiwan. METHODS: We analyzed one million samples from the National Health Insurance Research Database in Taiwan. Patients (n = 1814) newly diagnosed with AD in 2001-2010 were divided into TCM users (n = 528) and non-TCM users (n = 1286). RESULTS: Compared with non-TCM users, TCM users were younger, had a higher female:male ratio and higher utilization rate of Western medicine. The median interval between diagnosis and the first TCM consultation was 7.92 months. Donepezil and rivastigmine were commonly prescribed medications. Chinese herbal medicine was the most popular treatment among TCM users. CONCLUSIONS: This study revealed the specific usage patterns of TCM and non-TCM medical services among patients with AD. The information could be used for improving the healthcare of patients with AD.

Antibiotic treatment of zebrafish mycobacteriosis: tolerance and efficacy of treatments with tigecycline and clarithromycin.

Zebrafish (Danio rerio) are a popular model organism used in a growing number of research fields. Maintaining healthy, disease-free laboratory fish is important for the integrity of many of these studies. Mycobacteriosis is a chronic bacterial infection caused by several Mycobacterium spp. and is the second most common disease found in laboratory zebrafish. Current mycobacteriosis control measures recommend the removal of infected fish and in severe outbreaks, depopulation. These measures can be effective, but less disruptive measures should be assessed for controlling mycobacteriosis, particularly when valuable and rare lines of fish are affected. Here, the in vivo efficacy of two drug candidates, tigecycline (1 µg g-1 ) and clarithromycin (4 µg g-1 ), was tested in adult zebrafish experimentally infected with Mycobacterium chelonae. We assessed both short (14 day)- and long-term (30 day) treatments and evaluated fecundity and pathological endpoints. Fecundity and histology results show that zebrafish tolerated antibiotics. Antibiotic treatments did not significantly impact the prevalence of acid-fast granulomas; however, the severity of infections (acid-fast granuloma intensity) was significantly decreased following treatments.

Subdural hematoma in diabetic patients.

BACKGROUND AND PURPOSE: Subdural hematoma (SDH) is associated with a high mortality rate. However, the risk of SDH in diabetic patients has not been well studied. The aim of the study was to examine the risk of SDH in incident diabetic patients. METHODS: From a universal insurance claims database of Taiwan, a cohort of 28,045 incident diabetic patients from 2000 to 2005 and a control cohort of 56,090 subjects without diabetes were identified. The incidence and hazard ratio of SDH were measured by the end of 2010. RESULTS: The mean follow-up years were 7.24 years in the diabetes cohort and 7.44 years in the non-diabetes cohort. The incidence of SDH was 1.57-fold higher in the diabetes cohort than in the non-diabetes cohort (2.04 vs. 1.30 per 1000 person-years), with an adjusted hazard ratio of 1.63 [95% confidence interval (CI) 1.43-1.85]. The stratified data showed that adjusted hazard ratios were 1.51 (95% CI 1.28-1.77) for traumatic SDH and 1.89 (95% CI 1.52-2.36) for non-traumatic SDH. The 30-day mortality rate for those who developed SDH in the diabetes cohort was 8.94%. CONCLUSIONS: This study demonstrates that incident diabetic patients are at higher risk of SDH than individuals without diabetes. Proper intervention for diabetic patients is necessary for preventing the devastating disorder.

Angiotensin II receptor blocker prevents upper gastrointestinal bleeding in hypertensive patients with chronic kidney disease not on dialysis.

AIMS: Investigate if angiotensin II receptor blocker (ARB) decreases risk of upper gastrointestinal bleeding (UGIB) in hypertensive patients with chronic kidney disease (CKD) not on dialysis. METHODS: All hypertensive patients with CKD not on dialysis in outpatient department of China Medical University Hospital from 2003 to May 2013 were enrolled. The risk of UGIB was analysed using Cox proportional hazard regression. RESULTS: A total of 2744 hypertensive CKD patients including 1515 male and 1229 female, aged 64.9 ± 13.8 years old in a median of 1.9 (0.9-3.9) years were analysed. The incidence of UGIB was 4.5 per 100 patient-years. ARB was associated with a decreased risk of UGIB (p < 0.001) with an adjusted hazard ratio (HR) of 0.533 [95% confidence interval (CI) 0.404-0.703]. A history of UGIB, Helicobacter pylori infection, diabetes, lower estimated glomerular filtration rate, elevated blood urea nitrogen and decreased serum albumin were independently associated with an increased risk of UGIB. CONCLUSIONS: Angiotensin II receptor blocker is associated with a decreased risk of UGIB in hypertensive CKD patients not on dialysis, independent of their renal function, history of gastrointestinal bleeding and nutrition status.

Subdural hematoma in patients with end-stage renal disease receiving hemodialysis.

BACKGROUND AND PURPOSE: Hemodialysis (HD) may increase the risk of acute subdural hematoma (SDH) with high fatality, but the extent of this disease in non-western populations is unclear. The incidence of and fatality from SDH in patients with end-stage renal disease (ESRD) on HD were examined for an Asian population. METHODS: A cohort of 4709 newly diagnosed ESRD patients on HD from 1998 to 2010 and a control cohort of 18 663 subjects without any kidney disease were identified from a universal insurance claims database in Taiwan. The incidence and hazard of SDH for the two cohorts and 30-day mortality from SDH were measured by the end of 2010. RESULTS: The incidence of SDH was 4.47-fold higher in the HD cohort than in the control cohort (56.3 vs. 12.6 per 10 000 person-years) with an adjusted hazard ratio (HR) of 3.81 (95% CI 2.77-5.25). HD patients with SDH had a high odds of 30-day mortality with an adjusted odds ratio of 6.34 (95% CI 2.37-16.9). CONCLUSIONS: ESRD patients with HD were demonstrated to be at high risk of subsequent SDH and to have a high mortality risk from SDH. Proper care for HD patients is necessary to prevent the devastating disorder.

Historical connectivity, contemporary isolation and local adaptation in a widespread but discontinuously distributed species endemic to Taiwan, Rhododendron oldhamii (Ericaceae).

Elucidation of the evolutionary processes that constrain or facilitate adaptive divergence is a central goal in evolutionary biology, especially in non-model organisms. We tested whether changes in dynamics of gene flow (historical vs contemporary) caused population isolation and examined local adaptation in response to environmental selective forces in fragmented Rhododendron oldhamii populations. Variation in 26 expressed sequence tag-simple sequence repeat loci from 18 populations in Taiwan was investigated by examining patterns of genetic diversity, inbreeding, geographic structure, recent bottlenecks, and historical and contemporary gene flow. Selection associated with environmental variables was also examined. Bayesian clustering analysis revealed four regional population groups of north, central, south and southeast with significant genetic differentiation. Historical bottlenecks beginning 9168-13,092 years ago and ending 1584-3504 years ago were revealed by estimates using approximate Bayesian computation for all four regional samples analyzed. Recent migration within and across geographic regions was limited. However, major dispersal sources were found within geographic regions. Altitudinal clines of allelic frequencies of environmentally associated positively selected outliers were found, indicating adaptive divergence. Our results point to a transition from historical population connectivity toward contemporary population isolation and divergence on a regional scale. Spatial and temporal dispersal differences may have resulted in regional population divergence and local adaptation associated with environmental variables, which may have played roles as selective forces at a regional scale.

Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

Gene polymorphisms of adiponectin and leptin receptor are associated with early onset of type 2 diabetes mellitus in the Taiwanese population.

OBJECTIVE: Adipocytokine genes encoding adiponectin (ADIPOQ) and the leptin receptor (LEPR) affect glucose and fatty acid metabolism. The purpose of this study was to examine the association between early-onset type 2 diabetes mellitus (T2DM) and variability within these two genes in the Han Chinese population of Taiwan. SUBJECTS: A cross-sectional study of 999 patients from the Han Chinese population of Taiwan with early-onset T2DM (n=264; age at diagnosis, 20 to <45 years) and late-onset T2DM (n=735; age at diagnosis, ~45 years) was performed. Blood samples from T2DM patients were taken for DNA extraction, and levels of serological markers were measured at enrollment. Seven single-nucleotide polymorphisms (SNPs) were selected for genotyping (three SNPs in AIDPOQ and four SNPs in LEPR) by polymerase chain reaction in each patient. RESULTS: Polymorphisms at the position rs10937273 in ADIPOQ and at the positions rs1892534 and rs2211651 in LEPR were statistically associated with early-onset T2DM (P=0.0246, 0.0014 and 0.0012, respectively). C-reactive protein levels were significantly different among the early-onset T2DM patients with different genotypes at the SNPs rs1892534 and rs2211651 in LEPR (P=0.003 and P=0.004, respectively). In addition, fasting glucose levels were also significantly different among different genotypes at the SNP rs1892534 in LEPR (P=0.038). CONCLUSION: We conclude that the polymorphisms in the adipocytokine genes ADIPOQ and LEPR are significantly associated with the age at diagnosis of T2DM in the Han Chinese population of Taiwan.

Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes.

AIMS: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years. METHODS: Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia. RESULTS: For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001). CONCLUSION: Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.

Adherence to tyrosine kinase inhibitors among adult chronic myeloid leukemia patients in a Malaysia hospital.

Background Tyrosine kinase inhibitors have been demonstrated to improve the survival of patients with chronic myeloid leukaemia. However, medication adherence is vital for patients on chronic treatment. Objective The objective of the current study was to evaluate response to treatment, adherence by patients to tyrosine kinase inhibitors and factors associated with adherence and response. Setting A haematology clinic in a regional referral hospital in Malaysia. Method Patients aged ≥ 13 years who had been on imatinib or nilotinib for ≥ 12 months were included in this cross-sectional study. An optimal response was defined as the achievement of major molecular response at 12 months of treatment. Patient medication adherence was determined using the average medication possession ratio based on the dispensing records. The patients were considered adherent if the medication possession ratio was > 90%. Multiple logistic regression was performed to evaluate the factors associated with adherence. The association of adherence with molecular response was analysed by univariate logistic regression. Main outcome measure The primary outcome measures were the proportion of patients who achieved optimal response and the medication possession ratio. Results A total of 151 patients were screened, and 71 patients were included. Twenty-eight patients (39%) achieved major molecular response at 12 months of treatment. The median time to achieve this was 15.5 months (an interquartile range of 15). The mean medication possession ratio for imatinib and nilotinib was 0.94 (± 0.14) and 0.96 (± 0.10), respectively, but this difference was without statistical significance (t  =  - 0.517, p  =  0.610). Nausea and vomiting (odds ratio [OR] of 0.25, 95% confidence interval [CI]: 0.07-0.83, p  =  0.023) and disease phase at diagnosis (OR of 0.20, 95% CI 0.04-1.06, p  =  0.059) were associated with patient adherence. An association was not found between patient adherence and molecular response (OR of 1.03, 95% CI 0.35-3.09, p  =  0.956). Conclusion The patients in this study demonstrated a relatively deep molecular response and optimal adherence. Nevertheless, one fourth of them were noncompliant with imatinib. Therefore, active interventions are warranted to prevent treatment-associated adverse events and improve adherence.

Cigarette smoking and proteinuria in Taiwanese men with Type 2 diabetes mellitus.

AIMS: Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose-response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. METHODS: Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was > or = 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. RESULTS: Compared with non-smokers, those who had smoked 15-30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34-5.76, P < 0.01) and 3.20 (95% CI 1.74-5.86, P < 0.001) times more likely to develop proteinuria. The dose-response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects (P = 0.001) and in subgroups with relatively short duration of diabetes mellitus (P < 0.001), good blood pressure control (P = 0.001) and those of young age (P = 0.007). CONCLUSIONS: The current study shows a clear dose-response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control.

Influence of predialysis comorbidity and damage accrual on mortality in lupus patients treated with peritoneal dialysis.

OBJECTIVE: Although there have been many studies on systemic lupus erythematosus (SLE) patients, there are few data about survival analysis of lupus patients receiving dialysis. Therefore, the objective of this study is to analyze risk factors predicting mortality in lupus patients treated with peritoneal dialysis (PD). In addition, we also delineate the relationship between predialysis comorbid illnesses, damage accrual, and mortality in lupus patients undergoing PD. METHODS: This longitudinal cohort study included 38 lupus patients undergoing PD between 1990 and 2008. The clinical parameters, disease activity (non-renal SLEDAI, nrSLEDAI), comorbid illnesses, and damage accrual were collected. We applied the Charlson Comorbidity Index (CCI), Khan Index, and Davies Index to elucidate the impact of predialysis comorbidity on mortality. Moreover, we examined prognostic value of predialysis SDI (Systemic Lupus International Collaborating Clinics Disease Damage Index) for lupus PD patients. RESULTS: There were 33 women and five men included for analysis. The mean age at PD entry was 32.2 +/- 10.4 years and mean duration of PD was 39.7 +/- 22.4 months. The nrSLEDAI score during PD significantly decreased, compared to the predialysis one (2.13 +/- 2.09 vs. 4.00 +/- 3.08, p < 0.001). All comorbidity indices and SDI scores were significantly and positively correlated with each other (p < 0.001). Univariate Cox regression analysis showed that serum creatinine level, date at PD entry, and the CCI were predictors for mortality. The predialysis nrSLEDAI and SDI scores did not have roles in predicting mortality of lupus PD patients. CONCLUSIONS: The predialysis CCI, instead of SDI, determines an increased risk for mortality in lupus patients treated with PD. The prognosis of lupus patients treated with PD largely depends on the severity of predialysis comorbidity, especially cardiovascular diseases.

Effects of fumarate on ruminal ammonia accumulation and fiber digestion in vitro and nutrient utilization in dairy does.

The objective of this study was to evaluate effects of fumarate on ruminal ammonia accumulation and fiber digestion in vitro and on feed intake and nutrient utilization in dairy does. Batch cultures of mixed rumen microorganisms were used to study effects of different concentrations of fumarate on fermentation with various N sources (ammonia as ammonium bicarbonate, casein amino acids, casein peptides, gelatin peptides) and feeds (bermudagrass hay, mixed diet of 60% bermudagrass hay plus 40% concentrate) for 6 and 24h, respectively. Substrates were grouped into pairs for separate incubations. Monosodium fumarate was added to incubation tubes to achieve final concentrations of 0, 5, and 10mM fumarate. More ammonia accumulated at the end of incubation with added ammonium bicarbonate. Ammonia concentration was higher for peptide compared with amino acid incubation, and for casein peptide compared with gelatin peptide. Addition of fumarate linearly decreased ammonia for all N sources and for feed substrates. For all substrate types, fumarate treatment increased acetate, propionate, and total volatile fatty acids (VFA), decreased acetate to propionate ratio, and tended to reduce branched-chain VFA. Digestion of feed neutral detergent fiber (NDF) by rumen microorganisms was improved by fumarate along with elevated endoglucanase and xylanase activities. In an animal metabolism experiment, 8 dairy does (4 per treatment) were used in a completely randomized design for 21 d. Does were fed a hay plus concentrate diet without (control) or with fumarate (6 g/head per day) supplementation to determine feed intake, whole-tract nutrient digestibility, and N utilization. Fumarate treatment did not affect weight change or feed intake but increased whole-tract digestion of gross energy, crude protein, and cellulose. Digested N was increased by fumarate supplementation; however, N retention was unaffected. Plasma glucose concentration was elevated with fumarate but urea N concentration remained unchanged. Fumarate addition had significant effects on rumen microbial fermentation by decreasing ammonia and branched-chain VFA, and by increasing acetate and propionate, and NDF digestion. These effects were reflected in the improvement in whole-tract gross energy, crude protein, and cellulose digestion and elevated plasma glucose concentration when dairy does were supplemented with fumarate.

The reproducibility of the virtual organ computer-aided analysis program for evaluating 3-dimensional power Doppler ultrasonography of diffuse thyroid disorders.

AIM: The aim of this study was to evaluate the intra- observer and inter-observer reproducibility of 3-dimensional (3D) power Doppler ultrasonography with the virtual organ computer-aided analysis (VOCAL) program for measuring thyroid volume and vascular indices in patients with diffuse thyroid disorders. MATERIALS AND METHODS: Patients with diffuse goiters were examined by 3D ultrasonography from August 2005 to July 2006. The parameters for vascular assessment included the vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and thyroid size, and were obtained using the VOCAL program. This program used plane A and a 30 degrees rotational step. Intra-observer and inter-observer repeatability are presented as intra-class correlation coefficient (intra-CC) and inter-class correlation coefficient (inter-CC), with values >0.70 being acceptable. RESULTS: Sixty-three patients in total were enrolled for this study, including 19 patients with simple goiter and 44 patients with autoimmune thyroid disease (AITD) (23 Graves' disease, 21 Hashimoto's thyroiditis). Thyroid volume and 3 vascular indices showed excellent reproducibility in the AITD group (intra- CC>0.9373 and inter-CC>0.8763) and its subgroups. The VI had excellent consistent reproducibility in the simple goiter group (intra-CC>0.8987 and inter-CC>0.8881), but the other parameters did not. CONCLUSIONS: Based on this study, 3D power Doppler ultrasonography with the VOCAL program is a reliable tool for evaluating diffuse thyroid disorders due to an autoimmune process. The VI is the most reliable parameter.

Serum aluminum level correlates with arterial stiffness in haemodialysis patients.

BACKGROUND: In addition to pulse wave velocity (PWV), serum aluminum level is predictive of mortality in haemodialysis (HD) patients. This cross-sectional study evaluated the correlations between serum aluminum and brachial-ankle PWV (baPWV). METHODS: One hundred twenty-seven HD patients (average age 58.46 +/- 9.95 years) were enrolled. Medical data were obtained via chart reviews and hospital database. Associations between biomarker levels and baPWV were analysed by multiple linear regression. RESULTS: Serum aluminum, high sensitivity C-reactive protein (hsCRP), age, pulse pressure (PP), mean arterial pressure (MAP) and diabetes mellitus (DM) are important correlates of baPWV. CONCLUSION: Further, hsCRP, PP, age and DM are positively related to arterial stiffness in HD patients.

Prognostic predictors of technique and patient survival in elderly Southeast Asian patients undergoing continuous ambulatory peritoneal dialysis.

The population of elderly patients entering chronic dialysis programmes is increasing. Elderly patients are susceptible to malnutrition and have multiple complicating disorders in addition to uraemia. Selecting appropriate dialysis modality is particularly critical in elderly patients. Continuous ambulatory peritoneal dialysis (CAPD) has many advantages to elderly patients; however, the clinical outcome varies for elderly CAPD patients. In comparison with Westerners, Southeast Asians have a small body mass index and may be more suited to CAPD therapy. To identify the prognostic predictors in elderly Southeast Asian patients, this historical cohort study analysed 144 patients aged > or = 65 years at initiation of CAPD. A group of haemodialysis (HD) patients aged > or = 65 years was utilised as the control group. Survival curves for patient and technique were derived from Kaplan-Meier analysis and were further analysed by Cox-Mantel log-rank test. To elucidate the impact of individual factors on patient survival, various significant univariables were further subjected to multivariate analysis. No significant increase existed for relative risk of technique failure in elderly patients compared with younger patients. This analytical data indicates that CAPD was as good as HD for elderly uraemic patients regarding to the patient survival. Diabetes, dependent patients, low albumin levels and previous HD history were significant poor prognostic factors for survival of elderly CAPD patients. In conclusion, CAPD is an effective modality of renal replacement therapy for Southeast Asian elderly patients. The technique survival was not affected by patient age.

Responses of photosynthesis and component processes to drought and temperature stress: are Mediterranean trees fit for climate change?

Global warming is raising concerns about the acclimatory capacity of trees and forests, especially in Mediterranean-type ecosystems. The sensitivity of photosynthesis to temperature is a key uncertainty for projecting the magnitude of terrestrial feedbacks on future climate change. While boreal, temperate and tropical species have been comparatively well investigated, our study provides the first comprehensive overview of the seasonal acclimatory responses of photosynthesis and its component processes to temperature in four Mediterranean climax species under natural conditions. We quantified seasonal changes in the responses of net photosynthesis (Anet), stomatal conductance (gs), mesophyllic conductance (gm) and electron-transport rate (Jcf), and investigated their sensitivity to drought and temperature stress in sunlit and shaded leaves of four Mediterranean tree species (Quercus ilex L., Pinus halepensis Mill., Arbutus unedo L. and Quercus pubescens Willd.). Sunlit leaves, but not shaded leaves, showed a pronounced seasonality in the temperature responses of Anet, gs, gm and Jcf. All four species and variables showed a remarkably dynamic and consistent acclimation of the thermal optimum (Topt), reaching peaks in summer ~29-32 °C. Changes in the shape of the response curves were, however, highly species-specific. Under severe drought, Topt of all variables were on average 22-29% lower. This was accompanied by narrower response curves above all in P. halepensis, reducing the optimal range for photosynthesis to the cooler morning or evening periods. Wider temperature-response curves and less strict stomatal control under severe drought were accompanied by wilting and drought-induced leaf shedding in Q. ilex and Q. pubescens and by additional branch dieback in A. unedo. Mild winter conditions led to a high Topt (~19.1-22.2 °C), benefitting the evergreen species, especially P. halepensis. Seasonal acclimation of Anet was explained better by gs and gm being less pronounced in Jcf. Drought was thus a key factor, in addition to growth temperature, to explain seasonal acclimation of photosynthesis. Severe drought periods may exceed more frequently the high acclimatory capacity of Mediterranean trees to high ambient temperatures, which could lead to reduced growth, increased leaf shedding and, for some species such as A. unedo, increased mortality risk.