Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

Gas phase Elemental abundances in Molecular cloudS (GEMS) II. On the quest for the sulphur reservoir in molecular clouds: the H2S case.

CONTEXT: Sulphur is one of the most abundant elements in the Universe. Surprisingly, sulphuretted molecules are not as abundant as expected in the interstellar medium and the identity of the main sulphur reservoir is still an open question. AIMS: Our goal is to investigate the H2S chemistry in dark clouds, as this stable molecule is a potential sulphur reservoir. METHODS: Using millimeter observations of CS, SO, H2S, and their isotopologues, we determine the physical conditions and H2S abundances along the cores TMC 1-C, TMC 1-CP, and Barnard 1b. The gas-grain model Nautilus is used to model the sulphur chemistry and explore the impact of photo-desorption and chemical desorption on the H2S abundance. RESULTS: Our modeling shows that chemical desorption is the main source of gas-phase H2S in dark cores. The measured H2S abundance can only be fitted if we assume that the chemical desorption rate decreases by more than a factor of 10 when n H > 2 × 104. This change in the desorption rate is consistent with the formation of thick H2O and CO ice mantles on grain surfaces. The observed SO and H2S abundances are in good agreement with our predictions adopting an undepleted value of the sulphur abundance. However, the CS abundance is overestimated by a factor of 5 - 10. Along the three cores, atomic S is predicted to be the main sulphur reservoir. CONCLUSIONS: The gaseous H2S abundance is well reproduced, assuming undepleted sulphur abundance and chemical desorption as the main source of H2S. The behavior of the observed H2S abundance suggests a changing desorption efficiency, which would probe the snowline in these cold cores. Our model, however, highly overestimates the observed gas-phase CS abundance. Given the uncertainty in the sulphur chemistry, we can only conclude that our data are consistent with a cosmic elemental S abundance with an uncertainty of a factor of 10.

Gas phase Elemental abundances in Molecular cloudS (GEMS): I. The prototypical dark cloud TMC 1.

GEMS is an IRAM 30m Large Program whose aim is determining the elemental depletions and the ionization fraction in a set of prototypical star-forming regions. This paper presents the first results from the prototypical dark cloud TMC 1. Extensive millimeter observations have been carried out with the IRAM 30m telescope (3 mm and 2 mm) and the 40m Yebes telescope (1.3 cm and 7 mm) to determine the fractional abundances of CO, HCO+, HCN, CS, SO, HCS+, and N2H+ in three cuts which intersect the dense filament at the well-known positions TMC 1-CP, TMC 1-NH3, and TMC 1-C, covering a visual extinction range from A V ~ 3 to ~20 mag. Two phases with differentiated chemistry can be distinguished: i) the translucent envelope with molecular hydrogen densities of 1-5×103 cm-3; and ii) the dense phase, located at A V > 10 mag, with molecular hydrogen densities >104 cm-3. Observations and modeling show that the gas phase abundances of C and O progressively decrease along the C+/C/CO transition zone (A V ~ 3 mag) where C/H ~ 8×10-5 and C/O~0.8-1, until the beginning of the dense phase at A V ~ 10 mag. This is consistent with the grain temperatures being below the CO evaporation temperature in this region. In the case of sulfur, a strong depletion should occur before the translucent phase where we estimate a S/H ~ (0.4 - 2.2) ×10-6, an abundance ~7-40 times lower than the solar value. A second strong depletion must be present during the formation of the thick icy mantles to achieve the values of S/H measured in the dense cold cores (S/H ~8×10-8). Based on our chemical modeling, we constrain the value of ζ H2 to ~ (0.5 - 1.8) ×10-16 s-1 in the translucent cloud.

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes.

AIMS: Short-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes. METHODS: In this study, 63 patients (age 59±8.3 years, baseline A1c 6.8±0.7%, diabetes duration 3.0±2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR). RESULTS: As expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P=0.02), decreased HOMA-IR (P<0.001), and reduced AUCglucagon (P<0.001). Of note, however, IIT had no significant impact on AUCGLP-1 (P=0.24) and reduced AUCGIP (P=0.02). CONCLUSION: Despite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.

Attitudes toward HIV testing, awareness of HIV campaigns, and using social networking sites to deliver HIV testing messages in the age of social media: a qualitative study of young black men.

This study assessed attitudes toward HIV and awareness of previous HIV prevention campaigns among young black men in the United States of America (USA). The study also ascertained the appropriateness of HIV testing messages for young black men and explored the use of social networking sites to deliver HIV testing messages for social media marketing campaigns. Nineteen (n = 19) black male college students attending a public university in Atlanta, GA, USA from September 2016 to October 2016 participated in three focus groups. The focus groups consisted of a group interview querying experiences with HIV and STI testing, awareness of HIV campaigns, solicited feedback on campaign messages and the use of social networking sites to deliver messages. Data analysis involved the grounded theory approach to identify emergent themes. Fear, stigma and low risk perception were discussed as barriers to HIV testing. HIV prevention, social support and new sexual partners were discussed as reasons for testing. There was a general lack of awareness of existing HIV testing campaigns. Messaging with a universal appeal and disseminated through Twitter, Instagram and Snapchat may counter narratives of fear, stigma and low risk perception to increase HIV testing among young black men.

The prognostic value of tumour-stroma ratio in primary breast cancer with special attention to triple-negative tumours: a review.

PURPOSE: There is a strong need to improve the prognostication of breast cancer patients in order to prevent over- and undertreatment, especially when considering adjuvant chemotherapy. Tumour stroma characteristics might be valuable in predicting disease progression. METHODS: Studies regarding the prognostic value of tumour-stroma ratio (TSR) in breast cancer are evaluated. RESULTS: A high stromal content is related to a relatively poor prognosis. The most pronounced prognostic effect of this parameter seems to be observed in the triple-negative breast cancer (TNBC) subtype. CONCLUSIONS: TSR assessment might represent a simple, fast and reproducible prognostic factor at no extra costs, and could possibly be incorporated into routine pathological diagnostics. Despite these advantages, a robust clinical validation of this parameter has yet to be established in prospective studies.

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients.

BACKGROUND: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. PATIENTS AND METHODS: A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. RESULTS: From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). CONCLUSIONS: Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. CLINICAL TRIALS NUMBER: NCT01544686 (Clinicaltrials.gov).

c-myc in whitefish (Coregonus lavaretus): structure, expression, and insights into possible posttranscriptional regulatory mechanism.

c-myc has a crucial function in growth control, differentiation, and apoptosis of vertebrate cells. Despite the important role of c-myc in mediating the biological effects, studies of c-myc gene expression and factors that control it in organisms other than mammals, such as fish, have been rare. In the current study, we asked whether c-myc mRNA of whitefish, a feasible organism for pollution monitoring in aquatic systems and a model in toxicological research, contains activity sites for regulatory motifs in its 5'- and 3'-UTRs, similar to those found in mammals. We were particularly interested in whether miRNA-34, a known negative regulator of c-myc's in mammals, is able to regulate c-myc in fish. To answer these questions, we determined the mRNA sequence of whitefish c-myc and inferred the structure of the protein that it codes for. We found that the active sites of mRNA and structures of the inferred c-myc protein are similar to those found in mammals and other fish. Remarkably, levels of c-myc mRNA expression were very high in ovaries compared to other tissues of whitefish, thus corroborating previous data in fish. Using bioinformatic searches on c-myc 3'-UTR, we confirmed the presence of two miRNA-34a (miR-34a) response elements. Luciferase reporter assay showed that activity of reporters containing either the miR response elements or entire c-myc 3'-UTR was significantly reduced (p < 0.001) by ectopic expression of miR-34a. Therefore, we further investigated possible involvement of miR-34a in c-myc gene silencing by profiling the expression of both genes in livers of whitefish treated for 8, 24, 48 h with MC-LR, a potent c-myc inducer in mammals. Although the difference was only significant at p = 0.08, the expression of c-myc mRNA in challenged whitefish after 24 h of the treatment was notably higher than that in livers of control fish. Concurrently, we noticed slight but significant up-regulation of miR-34a after 24 and 48 h of the challenge (p < 0.05); however, we found no significant correlation of the c-myc mRNA levels and miR-34a expression. Together, these results suggest that miR-34a might regulate c-myc gene expression in whitefish liver; however, their involvement in MC-LR hepatotoxicity should be clarified in future studies.

Antipneumococcal activity of neuraminidase inhibiting artocarpin.

Streptococcus (S.) pneumoniae is a major cause of secondary bacterial pneumonia during influenza epidemics. Neuraminidase (NA) is a virulence factor of both pneumococci and influenza viruses. Bacterial neuraminidases (NAs) are structurally related to viral NA and susceptible to oseltamivir, an inhibitor designed to target viral NA. This prompted us to evaluate the antipneumococcal potential of two NA inhibiting natural compounds, the diarylheptanoid katsumadain A and the isoprenylated flavone artocarpin. Chemiluminescence, fluorescence-, and hemagglutination-based enzyme assays were applied to determine the inhibitory efficiency (IC(50) value) of the tested compounds towards pneumococcal NAs. The mechanism of inhibition was studied via enzyme kinetics with recombinant NanA NA. Unlike oseltamivir, which competes with the natural substrate of NA, artocarpin exhibits a mixed-type inhibition with a Ki value of 9.70 µM. Remarkably, artocarpin was the only NA inhibitor (NAI) for which an inhibitory effect on pneumococcal growth (MIC: 0.99-5.75 µM) and biofilm formation (MBIC: 1.15-2.97 µM) was observable. In addition, we discovered that the bactericidal effect of artocarpin can reduce the viability of pneumococci by a factor of >1000, without obvious harm to lung epithelial cells. This renders artocarpin a promising natural product for further investigations.

Survey of the therapeutic approach and efficacy of pentosan polysulfate for the prevention and treatment of equine osteoarthritis in veterinary practice in Australia.

OBJECTIVE: To survey veterinary practitioners in Australia on how they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA), the treatment of OA when PPS is combined with other drugs, and the efficacy of PPS compared with other disease-modifying osteoarthritic drugs. DESIGN: Practitioners were contacted by email, which contained a link to an online survey. RESULTS: A total of 76 responses (34.5%) to the survey were received. Respondents most commonly used PPS as prophylactic therapy prior to competition (80.3%). As a prophylactic agent, PPS was considered by 48.2% of respondents to have high efficacy. The most common dose regimen for prevention and treatment of OA was 3 mg/kg, intramuscularly, once weekly for 4 weeks followed by monthly injections. Most respondents (78%) combined PPS with other drugs for treatment of OA. Intra-articular corticosteroids and hyaluronate (HA) was the most common drug combination used with PPS. PPS was preferred as a prophylactic agent when compared with HA (88.7% vs 11.3%). For treating OA, 83% of respondents considered a combination of PPS, HA and glucosamine to be more efficacious than PPS alone. However, the most common reason not to use this combination was cost (79.1%). CONCLUSION: All respondents used PPS for prophylaxis and/or treatment of OA despite limited published scientific evidence proving its efficacy in horses. Further research is necessary to provide evidence of the clinical efficacy of PPS for the prevention and treatment of OA in horses.

Trajectories to death in patients with burn injury.

BACKGROUND: With unprecedented survival rates in modern burn care, there is increasing focus on optimizing long-term functional outcomes. However, 3% to 8% of patients admitted to burn centers still die of injury. Patterns in which these patients progress to death remain poorly characterized. We hypothesized that burn nonsurvivors will follow distinct temporal distributions and patterns of decline, parallel to the trimodality of deaths previously described for trauma. METHODS: We retrospectively identified all adult deaths from 1995 to 2007 in the National Burn Repository database (n = 5,975) and at our regional burn center (n = 237). We stratified patients by age and analyzed injury and death characteristics. We used objective criteria to allocate nonsurvivors to one of four trajectories: early rapid decline, early organ failure, late sudden death, or late-onset decline. RESULTS: The greatest concentration of deaths in both samples and age groups occurred within 72 hours of injury and decreased subsequently with no later mortality peak. Death was most often caused by burn shock within the first week of injury, cardiogenic shock or lung injury in Weeks 1 to 2, and sepsis/multiorgan failure after Week 2. In decreasing frequency, trajectories to death fit the pattern of early rapid decline (58%), early organ failure (20%), late-onset decline (16%), and late sudden death (6%). CONCLUSION: Most burn deaths follow a pattern of early rapid decline or early organ failure manifested by death or critical illness within several days of the burn. These findings indicate that more than three quarters of burn deaths are attributable to failure or significant decompensation beginning in the resuscitation phase. Sporadic deaths later in hospitalization are uncommon. Despite significant advances in burn resuscitation, our data indicate that ongoing efforts to mitigate deaths in modern burn care should still focus on care improvements in the resuscitation phase. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Growth factor plus preemptive ('just-in-time') plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure.

Lenalidomide is associated with suboptimal autologous hematopoietic stem cell (AHSC) mobilization. We hypothesized that growth factor plus preemptive plerixafor is an effective strategy for AHSC mobilization in multiple myeloma (MM) despite prior exposure to lenalidomide. We retrospectively reviewed patient characteristics and mobilization outcomes of 89 consecutive MM patients undergoing first mobilization with filgrastim or pegfilgrastim +/- preemptive plerixafor using a previously validated algorithm based on day 4 peripheral blood CD34+ cell count (PB-CD34+) and mobilization target. Outcomes were analyzed according to the extent of prior exposure to lenalidomide: no prior exposure (group A, n=40), 1- 4 cycles (group B, n=30) and >4 cycles (group C, n=19). Multivariate analysis yielded only age and number of cycles of lenalidomide as negatively associated, and mobilization with pegfilgrastim as positively associated with higher PB-CD34+. Only 45% of patients in group A required plerixafor vs 63% in groups B and 84% in C, P=0.01. A higher proportion of patients in group A (100%) met the mobilization target than in groups B (90%) or C (79%), P=0.008. All patients yielded at least 2 × 10(6) CD34+/kg. Growth factor mobilization with preemptive plerixafor is an adequate upfront mobilization strategy for MM patients regardless of prior exposure to lenalidomide.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 ± 10.1 years and 313 (37.2 percent) patients were males. MetS was detected in 662 (78.6 percent) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 ± 30.8; two: 92.9 ± 28.1; three: 84.0 ± 25.1; four: 83.8 ± 28.5, and five: 79.0 ± 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL·min-1·1.73 (m²)-1) 2.82-fold (95 percentCI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95 percentCI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95 percentCI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

A prospective study of uric acid by glucose tolerance status and survival: the Rancho Bernardo Study.

OBJECTIVES: Little is known about uric acid (UA) levels and mortality in the context of glycaemia. We examined whether serum UA levels predict all-cause and cardiovascular disease (CVD) mortality differentially in older adults by glucose tolerance status. DESIGN AND METHODS: Between 1984 and 1987, 2342 community-dwelling men and women had an oral glucose tolerance test, UA measurement, and assessment of traditional CVD risk factors. We defined glucose tolerance status as normoglycaemia (NG), pre-diabetes (pre-DM), and type 2 diabetes mellitus (T2DM). Ninety per cent were followed for vital status up to 23 years. Death certificates were coded using the Ninth International Classification of Diseases. RESULTS: Baseline age was 69.5 years; 44.4% were men. At baseline 939 had NG, 957 pre-DM, and 446 T2DM. The mean UA by glucose tolerance status was 327.1, 362.8, and 374.7 micromol L(-1). During follow-up, there were 1318 deaths 46.8% attributed to CVD. In Cox-regression analysis, each 119 micromol L(-1) (2 mg dL(-1)) increment in UA levels predicted an increased hazard ratio (HR) for all-cause deaths independent of age, smoking, body mass index, alcohol, physical activity, diuretic use and estimated glomerular filtration rate in all groups (NG: HR 1.25 95% CI 1.06-1.47, P =0.005; pre-DM: HR 1.20 95% CI 1.06-1.37, P = 0.04; T2DM: HR 1.20 95% CI 1.01-1.47, P = 0.04). After adjusting for CVD risk factors, the UA association with CVD mortality was significant only in the pre-DM and T2DM groups. CONCLUSION: All-cause mortality was independently associated with UA in all groups, but UA predicted CVD mortality only in those with abnormal glucose tolerance.

Degree of catecholamine hypersecretion is the most important determinant of intra-operative hemodynamic outcomes in pheochromocytoma.

Pheochromocytoma resection is often complicated by intra-operative hypertension and post-resection hypotension. Factors associated with these hemodynamic alterations are not well defined. The aim of this study was to analyse the clinical-laboratory features associated with hemodynamic parameters during pheochromocytoma resection. Twenty-seven patients submitted to tumor resection - either open (no.=18) or video laparoscopic - between 1978-2007 were included. Nineteen received pre-operative alpha-blockers. Intra-operative hemodynamic data analysed were: maximum and minimum mean arterial blood pressure (MABP), no. of severe hypertensive (systolic BP >200 mmHg) and hypotensive episodes (MABP <60 mmHg), maximum and minimum heart rate (HR), no. of episodes of tachycardia and bradycardia, need to receive iv intra-operative treatment for hypertension and hypotension and the volume of fluids administered during surgery. Patients were 39.4+/-14.4-yr-old, 66% women. Intra-operative hemodynamic parameters were not different in patients submitted to open or video laparoscopic resection. Maximum intraoperative HR and the percentage of patients with HR>100 beats/min were higher in patients without pre-operative alpha- blocker treatment (no.=8). Pre-operative urinary vanylmandelic acid was positively associated with intra-operative maximum MABP (r=0.535, p=0.047) and with maximum transoperative systolic BP (r=0.805, p=0.016). Pre-operative urinary catecholamine (Pearson correlation r=0.575, p=0.03) and vanylmandelic acid (Pearson correlation r=0.605, p=0.04) levels were associated with maximum intra- operative MABP, adjusted for the presence of pheochromocytoma symptoms, surgical approach and pre-operative alpha-blockers. In conclusion, the degree of pre-operative catecholamine secretion was the most important aspect of transoperative BP control.

The prevalence of chronic diabetic complications and metabolic syndrome is not associated with maternal type 2 diabetes

The maternal history of type 2 diabetes mellitus (DM) has been reported more frequently in patients with type 2 DM than paternal history. The aim of the present study was to determine if there was an association between maternal history of DM and the presence of chronic complications or metabolic syndrome (MetS) in patients with type 2 DM. A cross-sectional study was conducted with 1455 patients with type 2 DM. All outpatients with type 2 diabetes attending the endocrine clinics who fulfilled the eligibility criteria were included. Familial history of DM was determined with a questionnaire. Diabetic complications were assessed using standard procedures. The definition of MetS used was that of the World Health Organization and the National Cholesterol Education Program's Adult Treatment Panel III report criteria. Maternal history of DM was present in 469 (32.3 percent), absent in 713 (49.1 percent) and unknown in 273 patients (18.7 percent). Paternal history of DM was positive in 255 (17.6 percent), negative in 927 (63.8 percent) and unknown in 235 patients (16.1 percent). The frequency of microvascular chronic complications in patients with and without a positive maternal history of DM was similar: diabetic nephropathy (51.5 vs 52.5 percent), diabetic retinopathy (46.0 vs 41.7 percent), and diabetic sensory neuropathy (31.0 vs 37.1 percent). The prevalence of macrovascular chronic complications and MetS was also similar. Patients with type 2 DM were more likely to have a maternal than a paternal history of DM, although maternal history of DM was not associated with an increased prevalence of chronic complications or MetS.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95 percentCI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95 percentCI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95 percentCI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100 percent to the odds for diabetic retinopathy (OR = 2.01, 95 percentCI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

Assessment of aspiration risk in acute ischaemic stroke--evaluation of the simple swallowing provocation test.

BACKGROUND: Aspiration is a common complication in acute stroke patients and is strongly associated with a poor outcome. Due to an insufficient sensitivity and specificity of clinical bedside tests, further refinements are needed to improve the accuracy of clinical aspiration screening in acute stroke. OBJECTIVE: To assess the ability of the simple 2-step swallowing provocation test (SPT) to detect aspiration risk in acute stroke patients. METHODS: 100 consecutive patients with first-ever stroke were examined by SPT and fiberoptic endoscopic evaluation of swallowing (FEES) within 72 hours of stroke onset. Using FEES as an objective instrumental technique to evaluate dysphagia, statistical measures representing the ability of SPT to detect aspiration risk were calculated. RESULTS: The incidence of endoscopically proven aspiration risk was 81%. The 1st-step SPT had a sensitivity of 74.1% and a specificity of 100%. Although the 2nd-step SPT showed the same 100% specificity, sensitivity was significantly lower. False-negative results of SPT appeared predominantly in subjects exhibiting leakage of liquids to pyriform sinus without a pronounced delay in swallow onset. CONCLUSIONS: In acute stroke patients with an impairment of the pharyngeal phase of swallowing, 1st-step SPT reliably detects aspiration risk. In patients with a sole or predominant impairment of the oral phase of swallowing and a relatively intact pharyngeal phase, SPT fails to detect aspiration risk sufficiently. In the latter group, FEES or additional clinical features more specifically indicating oral-phase pathology should be considered to accurately judge the patient's aspiration risk.

Degradation of 2-fluorophenol by the brown-rot fungus Gloeophyllum striatum: evidence for the involvement of extracellular Fenton chemistry.

Iron-containing liquid cultures of the brown-rot basidiomycete Gloeophyllum striatum degraded 2-fluorophenol. Two simultaneously appearing degradation products, 3-fluorocatechol and catechol, were identified by gas chromatography and mass spectrometry (GC-MS). Concomitantly, fluoride was produced at approximately 50% of the amount that theoretically could be achieved upon complete dehalogenation. Defluorination was strongly inhibited in the presence of either the hydroxyl radical scavenger mannitol or superoxide dismutase, as well as in the absence of iron. The addition of the natural iron chelator oxalate caused a clear but less extensive inhibition, whereas supplementation with the artificial iron chelator nitrilotriacetic acid increased fluoride production. Extracellular 2-fluorophenol degradation was evidenced by defluorination, observed upon addition of 2-fluorophenol to cell-free culture supernatants derived from iron-containing fungal cultures. Ultrafiltered culture supernatants oxidized methanol to formaldehyde, known as a product of the reaction of methanol with hydroxyl radical. In addition, G. striatum was found to produce metabolites extractable with ethyl acetate that are capable of reducing Fe3+. GC-MS analysis of such extracts revealed the presence of several compounds. The mass spectrum of a prominent peak matched those previously reported for 2,5-dimethoxyhydroquinone and 4,5-dimethoxycatechol, fungal metabolites implicated to drive hydroxyl radical production in Gloeophyllum. Taken together, these findings further support an extracellular Fenton-type mechanism operative during halophenol degradation by G. striatum.