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We have used a dissipative particle dynamics (DPD) model to study the movement of microparticles in a microfluidic device at extremely low Reynolds number (Re). The particles, immersed in a medium, are transported in the microchannel by a flow force and deflected transversely by an external force along the way. An in-house Fortran code is developed to simulate a two-dimensional fluid flow using DPD at Re ≥ 0.0005, which is two orders of magnitude less than the minimum Re value previously reported in the DPD literature. The DPD flow profile is verified by comparing it with the exact solution of Hagen-Poiseuille flow. A bioparticle based on a rigid spring-bead model is introduced in the DPD fluid, and the employed model is verified via comparing the velocity profile past a stationary infinite cylinder against the profile obtained via the finite element method. Moreover, the drag force and drag coefficient on the stationary cylinder are also computed and compared with the reported literature results. Dielectrophoresis (DEP) is investigated as a case study for the proposed DPD model to compute the trajectories of red blood cells in a microfluidic device. A mapping mechanism to scale the external deflecting force from the physical to DPD domain is performed. We designed and built our own experimental setup with the aim to compare the experimental trajectories of cells in a microfluidic device to validate our DPD model. These experimental results are used to investigate the dependence of the trajectory results on the Reynolds number and the Schmidt number. The numerical results agree well with the experiment results, and it is found that the Schmidt number is not a significant parameter for the current application; Reynolds numbers combined with the DEP-to-drag force ratio are the only important parameters influencing the behavior of particles inside the microchannel.

We conducted an animal experiment to assess the effect of adding pentoxifylline to amikacin to prevent amikacin-induced ototoxicity. This research was conducted on 24 rats arranged in four groups of 6. One group was injected with 200 mg/kg of intramuscular amikacin once daily for 14 days (AMK-only group). Another received 25 mg/kg of oral pentoxifylline and 200 mg/kg of intramuscular amikacin once daily for 14 days (PTX-AMK 14/14 group). A third group received 25 mg/kg of oral pentoxifylline for 28 days and 200 mg/kg of intramuscular amikacin once daily for 14 days on days 15 through 28 of the pentoxifylline regimen (PTX-AMK 28/14 group). Finally, a control group was administered 1 ml/day of 0.5% carboxymethyl cellulose for 28 days. Transient otoacoustic emissions (TOAEs) were statistically analyzed and serum urea and creatinine levels were measured before and after treatment. We found no significant differences in TOAEs among the groups at the study's onset, but after the experiment, TOAEs disappeared in all frequency bands in the AMK-only and PTX-AMK 14/14 groups. However, TOAEs were preserved in the PTX-AMK 28/14 group. In addition, the serum urea and creatinine levels in the PTX/AMK 28/14 group were significantly lower than the levels in the other two treatment groups (p < 0.05 for all), but not significantly different from those of the control group. We conclude, therefore, that 28 days of pentoxifylline treatment exerted a protective effect against amikacin-induced ototoxicity in rats.

This short communication introduces a continuous-flow, dielectrophoresis-based lateral fluid flow fractionation microdevice for detection/isolation of circulating tumor cells in the presence of other haematological cells. The device utilizes two sets of planar interdigitated transducer electrodes micropatterned on top of a glass wafer using standard microfabrication techniques. A microchannel with a single inlet and two outlets, realized in polydimethylsiloxane, is bonded on the glass substrate. The two sets of electrodes slightly protrude into the microchannel. Both of the electrode sets are energized with signals at different frequencies and different operating voltages ensuring that the cancer cells experience positive dielectrophoretic force from one set of the electrodes and negative dielectrophoretic force from the other array. Normal cells experience unequal negative dielectrophoretic forces from opposing sets of electrodes. The resultant dielectrophoretic forces on cancer and normal cells push them to flow towards their designed outlets. Successful isolation of green fluorescent protein-labelled MDA-MB-231 breast cancer cells from regular blood cells, both suspended in a sucrose/dextrose medium, is reported in this work., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Arterial hypertension represents a common complication of immunosuppressive therapy after liver transplantation (LT). The aim of the study is to evaluate the prevalence and risk factors associated with hypertension after LT. From a cohort of 323 cirrhotic patients who underwent LT from 2008 to 2012, 270 patients were retrospectively evaluated, whereas 53 (16.4%) patients deceased. Hypertension was defined as blood pressure ≥140/90 mm Hg in at least two visits and/or the need for antihypertensive therapy. The prevalence of hypertension was 15% before LT and significantly increased up to 53% after LT (P < .001). Mean follow-up was 43 ± 19 months. In normotensive (NT) subjects at baseline, 35.9% developed sustained hypertension after LT, whereas 15.2% developed transient hypertension within the first month after LT, and then returned NT. The development of sustained hypertension after LT was related to the mammalian target of rapamycin inhibitor treatment (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.26-13.48; P = .02), alcoholic cirrhosis before LT (OR, 3.38; 95% CI, 1.44-8.09; P = .005), and new-onset hepatic steatosis after LT (OR, 2.13; 95% CI, 1.10-4.11; P = .02). Tacrolimus, the etiology and severity of liver disease, and other immunosuppressive regimens were not related to the development of hypertension after LT. In our cohort, the prevalence of arterial hypertension has increased up to 53% after LT, and metabolic comorbidities and immunosuppressive treatment with mammalian target of rapamycin inhibitors are the risk factors for the development of hypertension after LT., (Copyright © 2018 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

The existence of peste des petits ruminants (PPR) in domestic ruminants and camels in Sudan during 2008-2012 was investigated. Lung tissues and serum samples were randomly collected from sheep, goats, cattle, and camels at different areas of Sudan. A total of 12,384 serum samples were collected from clinically healthy 7413 sheep, 1988 camels, 1501 cattle, 1459 goats, and 23 gazelles at different areas in the Sudan. They were examined for PPR antibodies using competitive ELISA (cELISA). The overall detected seroprevalence of PPR in tested sera was 49.4%; seroprevalence values within species were 67.1, 48.2, 25.8, 2.1, and 21.7% in sheep, goat, cattle, camels, and gazelles, respectively. The highest seroprevalence (68.1%) was observed in sera collected from Darfur states, then the central states (54.3%). A total of 1276 lung tissue samples (623 sheep, 324 cattle, 220 camels, and 109 goats) were collected. The majority of lung samples were collected from clinically healthy animals that showed lesions on PM in slaughterhouses (95%) and during PPR outbreaks; samples were tested for PPR antigen using immunocapture ELISA (IcELISA). PPR antigen was detected in 233 out of the 1276 tested samples (18.3%). Positive results were observed in samples collected from clinically healthy and diseased animals. The observed prevalence values in each species were 33.6, 21.1, 15.4, and 12.3% in camel, goat, sheep, and cattle, respectively. PPR antigen was detected in samples from different areas; however, the highest prevalence (63.9%) was found in samples collected from the eastern states, then Khartoum state (28%). Trials for virus isolation were done in different cell cultures. Out of 30 IcELISA-positive samples inoculated in primary bovine and ovine kidney cells, Vero cells, the PPR virus was successfully isolated from 15 (eight sheep, five camels, and two goats) samples in the three cell culture types. Using RT-PCR, PPRV nucleic acid was detected in all 25 IcELISA-positive tested samples.

Elevated serum levels of cystatin C are found to be related to poor outcome and metastatic potential of some malignant disorders. To evaluate the clinical prominence of serum cystatin C in diffuse large B-cell lymphoma (DLBCL), blood samples were obtained from 58 patients at the time of diagnosis and paired blood samples were obtained from 22 patients at the time of remission. Also, serum cystatin C level was measured in matched healthy controls. Serum cystatin C levels were significantly more elevated in DLBCL patients than in controls ( p < 0.0001). Furthermore, paired-sample analysis revealed that pretreatment cystatin C levels were reduced significantly in patients who achieved remission after therapy ( p = 0.016). High serum cystatin C levels were correlated with age over 60 years ( p = 0.049), extra-nodal involvement ( p = 0.005) and with high serum lactate dehydrogenase (LDH) ( p < 0.013). Elevated serum cystatin C levels were associated with extra-nodal involvement and they were significantly reduced to normal range after the remission. However, Kaplan-Meier curves revealed no survival difference in the pretreatment serum cystatin C levels. Therefore, serum cystatin C may be a novel biomarker that reflects tumor burden in DLBCL but bears no prognostic significance regarding survival.

The treatment objective in diabetes is prevention of the onset or progression of complications. Intensive treatment reduces the risk of complications. The aim of the study was to evaluate glycemic control in patients with type 2 diabetes mellitus treated with metformin monotherapy at the maximal-tolerated dose. This retrospective, multicenter, observational study, enrolled patients ≥45-year old receiving metformin as monotherapy for at least 36 months. Data were collected on demographic and disease characteristics, clinical status, lifestyle, comorbidities, and diabetes complications at baseline, 9, 18, and 24 months. Primary study variables were percentage of patients achieving HbA1c <7 % and mean HbA1c reduction after 9 months. Eligible patients (n = 524, mean age 65.9 ± 7.9 years) had a mean age at diagnosis of 57.5 ± 7.9 years. A second antidiabetic drug was added in 24 % of patients (126/524); time to treatment escalation was 44.7 ± 25.1 months. Regarding primary study variables, 61.7 % of patients (322/522) achieved HbA1c of 7.0 % at 9 months, compared to 37.0 % of patients (194/524) at baseline; mean HbA1c was reduced from 7.30 ± 0.95 to 6.84 ± 0.86 % after 9 months. The estimated mean time of exposure above 7 % was 19 months, 15 months for patients ≥65-year old, and 21 months for younger patients. Regression analysis revealed that patients with longer disease duration, and patients <65-year old responded less well to metformin. A substantial number of patients continued to receive monotherapy instead of intensified therapy and were exposed to hyperglycemia.

Objectives: To find out the possible protective effect of cilostazol against amikacin-induced ototoxicity., Methods: This study was carried out on 24 adult male rats classified into 4 equal groups of 6 animals each. (1) The control group was administered saline (1 ml/day, p.o.) for 14 days. (2) The amikacin group was administered amikacin (200 mg/kg, i.m.) once daily for 14 days. (3) The cilostazol-amikacin (14 days) group was administered cilostazol (30 mg/kg, p.o.) once daily and amikacin (200 mg/kg, i.m.) once daily for 14 days. (4) The cilostazol (28 days)-amikacin (14 days) group was administered cilostazol (30 mg/kg, p.o.) once daily for 28 days and amikacin (200 mg/kg, i.m.) once daily for 14 days. Changes in the transient evoked otoacoustic emissions (TEOAEs) in the 4 groups were interpreted statistically., Results: No reported significant differences in TEOAE levels were detected between the groups at the start of the study. In all frequency bands, TEOAEs disappeared after amikacin treatment in the amikacin-alone group and remained absent in the amikacin-cilostazol (14 days) group, while TEOAEs reappeared in the amikacin-cilostazol (28 days) group., Conclusion: Cilostazol treatment for 28 days had a protective effect against amikacin-induced ototoxicity in rats., (© 2016 S. Karger AG, Basel.)

Idiopathic oligoathenoteratozoospermia (iOAT) is a common finding in the evaluation of male infertility. Oxidative stress (OS) may underlie its pathology. Tamoxifen and l-carnitine are used to treat idiopathic male infertility. The aim of this work was to detect the efficacy of tamoxifen and l-carnitine on sperm parameters, sperm ultrastructure and seminal OS in iOAT patients. Sixty patients were recruited for this study and divided into three groups; the 1st was treated with tamoxifen, 2nd with l-carnitine and 3rd with both drugs. Semen analysis, malondialdehye (MDA) level and transmission electron microscopy were performed before and after three months treatment. The first group showed significant improvement in MDA levels, sperm concentration, sperm morphology, ultrastructural head, acrosomal and mitochondrial anomalies (P < 0.01). Other parameters were not significantly improved. In the 2nd group, significant improvements in MDA, sperm motility, sperm morphology, ultrastructural mitochondrial and tail anomalies were detected (P < 0.01). No significant improvement in the other parameters. Third group showed improvement in MDA, all semen parameters and all ultrastructural anomalies (P < 0.01). In conclusion, tamoxifen and l-carnitine are effective in improving seminal OS, semen parameters and sperm ultrastructure. Combination of both drugs is superior to monotherapy., (© 2014 Blackwell Verlag GmbH.)

Concerns raised by several animal studies, case reports, and pharmacovigilance warnings over incretin-based therapy potentially exposing type two diabetes patients to an elevated risk of pancreatitis have cast a shadow on the overall safety of this class of drugs. This systematic review evaluates the data from observational studies that compared treatment with or without incretins and the risk of pancreatitis. We searched PubMed for publications with the key terms incretins or GLP-1 receptor agonists or DPP-4 inhibitors or sitagliptin or vildagliptin or saxagliptin or linagliptin or alogliptin or exenatide or liraglutide AND pancreatitis in the title or abstract. Studies were evaluated against the following criteria: design (either cohort or case-control); outcome definition (incidence of pancreatitis); exposure definition (new or current or past incretins users); and comparison between patients receiving incretins or not for type 2 diabetes. Two authors independently selected the studies and extracted the data. Six studies meeting the inclusion criteria were reviewed. No difference was found in the overall risk of pancreatitis between incretin users and non-users (odds ratio 1.08; 95 % CI [0.84-1.40]). A risk increase lower than 35 % cannot be excluded according to the power calculation. This systematic review and meta-analysis suggests that type 2 diabetes patients receiving incretin-based therapy are not exposed to an elevated risk of pancreatitis. Limitations of this analysis are the low prevalence of incretin users and the lack of a clear distinction by the studies between therapy with DPP-4 inhibitors or with GLP-1 receptor agonists.

The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use., (© 2014 John Wiley & Sons Ltd.)

Background: Hepatitis B virus recurrence after liver transplantation (LT) has practically disappeared with a prophylaxis combining anti-hepatitis B surface antigen Immunoglobulins (HBIg) and antiviral drugs. Recently, cost-saving requirements pushed us to move from a fixed schedule of 50,000 IU intravenous HBIg in the first month after LT to an "on demand" administration guided by close monitoring of HBV surface antigen (HBsAg) and anti-HBV surface Antigen antibody (HBsAb) with a serological target of HBsAg negative and HBsAb>300 mIU/mL. In this context, we investigated the meaning of HBsAg quantitative determination at LT in predicting the need of HBIg in the first month after LT., Methods: From February 2012 to July 2013, we performed 35 LTs in HBsAg-positive patients, 18 of whom had hepatitis Delta virus coinfection (Delta-positive). Anti-HBV prophylaxis was based on nucleos(t)ide analogues from day 1 post-LT and intravenous HBIg (10,000 IU intraoperatively and, in the following days, 5,000 IU and 2,500 IU pulses to reach and maintain the serological target)., Results: The HBsAg quantitative level at LT was significantly higher in Delta-positive recipients. Complete negativization of HBsAg and HBsAb serum level>300 mIU/mL was achieved on day 3 in Delta-positive and on day 2 in Delta-negative. A positive linear correlation between HBsAg quantitative level at LT and HBIg administered in the first month after LT was observed (RHO=.788), with a total of 32,500 IU HBIg used in HDV-positive and 22,000 IU in HDV-negative recipients (P=.0016). Compared to the old schedule, we saved a median of 14,750 IU in HDV-positive and 28,000 IU in Delta-negative. No HBV recurrence was observed in a median follow-up of 10.5 months., Conclusions: Delta-positive patients need higher doses of HBIg to reach the serological target after LT because they have greater HBsAg quantitative levels at LT. In future studies, pre-LT HBsAg quantitative determination will be helpful to predict the actual need of HBIg early after LT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Renal or hepatic impairment, often encountered in patients with type 2 diabetes, influences the pharmacokinetics and bioavailability of antihyperglycemic agents. An emerging concern is whether pharmacotherapy with incretin-based agents, the most recent drug classes to be introduced for type 2 diabetes, can be safely used in patients with renal insufficiency or hepatic damage. This literature review examines the results of studies on these novel drug classes, with a view to provide the practitioner with a balanced, evidence-based position when considering incretin-based therapies in patients with type 2 diabetes and impaired kidney or liver function. All currently available dipeptidyl peptidase-4 (DPP-4) inhibitors appear to be appropriate pharmacotherapeutic choices in patients with declining renal function, with linagliptin affording the added advantage of not requiring dose adjustment or periodic monitoring of drug-related kidney function. In contrast, caution is warranted with the use of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with moderate or severe renal impairment. The slightly wider evidence base for liraglutide than for exenatide or lixisenatide is not sufficient to support its use in severe renal impairment. What little evidence there is for incretin-based therapies in hepatic impairment has come from a few past hoc analysis of clinical trials, with most precautions and warnings reflecting the paucity of knowledge about incretin efficacy or safety in this condition.

Backgrounds and Aims: To compare direct costs of four different care models and health outcomes in adults with type 2 diabetes., Methods and Results: We used multiple independent data sources to identify 25,570 adults with type 2 diabetes residing in Turin, Italy, as of 1 July 2003. Data extracted from administrative data databases were used to create four care models ranging in organization from highly structured care (integrated primary and specialist care) to progressively less structured care (unstructured care). Regression analyses, adjusted for main confounders, were applied to examine the differences between the models in direct costs, mortality, and diabetes-related hospitalizations rates over a 4-year period. In patients managed according to the unstructured care model (i.e., usual care by a primary care provider and without strict guidelines adherence), excess of all-cause mortality was 84% and 4-year direct cost was 8% higher than in those managed according to the highly structured care model. Cost ratio analysis revealed that the major cost driver in the unstructured care model was hospital admissions, which were 31% higher than the rate calculated for the more structured care models. In contrast, spending on prescription medications and specialist consultations was higher in the highly structured care model., Conclusion: A diabetes care model that integrates primary and specialty care, together with practices that adhere to guideline recommendations, was associated with a reduction in all-cause mortality and hospitalizations, as compared with less structured models, without increasing direct health costs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Postoperative vision loss (POVL) after spine surgery is a rare but devastating outcome. We present the first case-control study from a single institution for POVL with the diagnoses of ischemic optic neuropathy or central vision loss after complex spine surgery., Methods: POVL cases following spine surgeries between December 1995 and December 2010 at the Cleveland Clinic were identified retrospectively using administrative codes. Each instance of POVL was matched to 5 case-control patients based on age, gender, body mass index, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and hematocrit. Duration of anesthesia, fluid volumes, and hemodynamic measurements were then compared between POVL cases and control cases using Wilcoxon rank sum test., Results: Six patients developed POVL. These patients had significantly greater blood loss (P=0.002, Wilcoxon test) and a significantly greater volume of red blood cells transfused (P=0.006) than the control patients. No other intraoperative measures differed significantly after Bonferroni correction for multiple outcomes., Conclusion: We found that patients with POVL had significantly greater blood loss and significantly more red blood cell transfusions than their matched controls.

Background: Previous studies have yielded conflicting results about the association between incretin therapies and acute pancreatitis. We aimed to compare the occurrence of acute pancreatitis in a population of patients with type 2 diabetes who received incretins compared with those who received other antidiabetic treatment., Methods: In our population-based matched case-control study, we extracted information from an administrative database from Piedmont, Italy (containing data for 4·4 million inhabitants). From a dataset of 282,429 patients receiving treatment with antidiabetic drugs for type 2 diabetes, we identified 1003 cases older than 41 years who had been admitted to hospital for acute pancreatitis between Jan 1, 2008, and Dec 31, 2012, and 4012 controls who were matched for sex, age, and time of start of antidiabetic therapy. We compared incretin exposure in cases and controls with a conditional logistic regression model, expressed as odds ratios (ORs [95% CI]). We adjusted all analyses for risk factors of acute pancreatitis, as ascertained by hospital discharge records, and concomitant use of metformin or glibenclamide., Findings: The mean age of cases and controls (72·2 years [SD 11·1]) was high, as expected in an unselected diabetic population in Europe. After adjustment for available confounders, use of incretins in the 6 months before hospital admission was not associated with increased risk of acute pancreatitis (OR 0·98, 95% CI 0·69-1·38; p=0·8958)., Interpretation: Our findings suggest that, in an unselected population, use of incretins is not associated with an increased risk of acute pancreatitis. Larger studies are needed to clarify whether age or type of incretin therapy could affect the risk of acute pancreatitis in patients with type 2 diabetes., Funding: Chaira Medica Association, Chieri, Italy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: No data on the prevalence of erectile dysfunction (ED) in subjects with newly diagnosed Type 2 diabetes mellitus (T2DM) are currently available., Aim: The aim of the present study was to estimate the prevalence of ED and its associated causes in a sample of male patients with recently diagnosed DM (<24 months) attending a diabetes care center., Methods: The study comprised two phases: a cross-sectional analysis and a longitudinal reassessment of the data collected during the first phase. During the first phase, 1503 subjects (mean age 58.7±8.9 yr) from 27 centers were interviewed: 666 (43.3%) reported experiencing ED, 499 of which (mean age 58.8±8.8 yr) agreed to participate in the study (final enrolment rate, 33.3%). Concurrent morbidities were hypertension (55.3%), dyslipidemia (39.5%), and coronary heart disease (7.8%); chronic complications were neuropathy (8.9%), nephropathy (12.6%) and retinopathy (7.6%) in about one third of the sample at enrolment., Results: Overall, about 20% of the patients reported having used ED drugs, but more than 50% had abandoned therapy because of the drug's ineffectiveness or high cost. The prevalence of hypogonadism was 46.9% (total testosterone level, 3.5 ng/ml). Some 20% of patients reported symptoms suggestive of depression., Conclusion: The present study provides data showing a high prevalence of ED, hypogonadism and depressive symptoms among male patients with newly diagnosed T2DM. Further analysis of the data will elucidate the specific determinants of such conditions and their longitudinal significance.

The anesthetic plan for patients undergoing awake craniotomy, when compared to craniotomy under general anesthesia, is different, in that it requires changes in states of consciousness during the procedure. This retrospective review compares patients undergoing an asleep-awake-asleep technique for craniotomy (group AW: n = 101) to patients undergoing craniotomy under general anesthesia (group AS: n = 77). Episodes of desaturation (AW = 31% versus AS = 1%, p < 0.0001), although temporary, and hypercarbia (AW = 43.75 mmHg versus AS = 32.75 mmHg, p < 0.001) were more common in the AW group. The mean arterial pressure during application of head clamp pins and emergence was significantly lower in AW patients compared to AS patients (pinning 91.47 mmHg versus 102.9 mmHg, p < 0.05 and emergence 84.85 mmHg versus 105 mmHg, p < 0.05). Patients in the AW group required less vasopressors intraoperatively (AW = 43% versus AS = 69%, p < 0.01). Intraoperative fluids were comparable between the two groups. The post anesthesia care unit (PACU) administered significantly fewer intravenous opioids in the AW group. The length of stay in the PACU and hospital was comparable in both groups. Thus, asleep-awake-asleep craniotomies with propofol-dexmedetomidine infusion had less hemodynamic response to pinning and emergence, and less overall narcotic use compared to general anesthesia. Despite a higher incidence of temporary episodes of desaturation and hypoventilation, no adverse clinical consequences were seen., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The time to achieve good metabolic control after diagnosis is essential for type 2 diabetes patients because it can influence long-term prognosis. This study aimed to elucidate the predictive role of several clinical and organization factors in normalizing metabolism within 6 months. A multi-centered, retrospective, observational study on 960 patients, with diabetes duration of 12 months or less, consecutively seen in 123 Italian clinics, was undertaken. Information about clinic's organization, along with data abstracted from medical records at enrollment (first visit) and after 6 months (follow-up visit), was collected. At 6 months, HbA1c dropped by -3.1 ± 2.2 points in those who achieved HbA1c <7 % (responders), whereas in non-responders (HbA1c ≥7 %), the mean reduction was -1.8 ± 1.9. The intervention markedly reduced lipids, blood pressure, BMI, and waist circumference, especially in responders. The presence of a diabetes team correlated with a likelihood of HbA1c normalization (OR 1.94, 1.17-3.22). By contrast, indicators of advanced disease such as previous retinopathy (0.53, 0.29-0.98), use of secretagogues (0.40, 0.25-0.64), high levels of HbA1c at first visit and related insulin use emerged as adverse factors. Early detection of diabetes, along with human resources and organization, was found to play a crucial role in rapidly attaining good metabolic control.

Background: Liver transplantation (LT) with grafts from hepatitis B core antibody (HBcAb)-positive donors has been the object of recent studies, suggesting different outcomes depending on the etiology of viral cirrhosis in the recipient., Methods: From November 2002 to December 2009, we transplanted 124 livers from hepatitis B surface antigen (HBsAg)-negative HBcAb-positive deceased heart-beating donors to adult recipients with viral cirrhosis, classified as: HBsAg positive (group 1; n = 63); hepatitis C virus (HCV) RNA positive (group 2; n = 52); and simultaneously HBsAg and HCV-RNA positive (group 3; n = 9). Immunosuppression included a calcineurin inhibitor, mycophenolate, and steroids (tapered to suspension in 6 months). In all groups, anti-HBV prophylaxis was performed with anti-HBs immunoglobulins and nucleos(t)idic analogues., Results: The groups were similar regarding donor, recipient, donor-recipient match, transplant procedure, variables, and treatment of acute rejection, except for younger recipient age in group 1 (P = .009), lower recipient body mass index in group 3 (P = .03), and longer cold ischemia time in group 2 (P = .003). Median follow-up for surviving grafts was 63 (range, 16-102) months. No case of recurrent or de novo hepatitis B occurred. The prevalence of histologically proven recurrent HCV hepatitis was similar in groups 2 and 3 (65% vs 78%). Graft survival at 5 years was 86% in group 1, 35% in group 2, and 31% in group 3 (P < .0001 for group 1 vs 2; P < .01 for group 1 vs 3). On multivariate analysis, independent predictors of worse graft survival were HCV infection in the recipient (HR 8.08, 95% CI 3.36-17.97; P < .0001) and MELD at LT ≥25 (HR 3.72, 95% CI 1.12-12.37; P = .032)., Conclusions: The presence of HCV infection in the recipient is the factor which most negatively influenced the outcome of LT using grafts from HBcAb-positive donors. Allocation of such grafts should consider the type of viral cirrhosis among LT candidates., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Recent data from Italian studies have shown excellent results of liver transplantation (LT) in hepatitis B virus (HBV)-infected patients with grafts from hepatitis B core antibody (HBcAb)-positive donors, whereas such grafts in hepatitis C virus (HCV)-infected recipients have displayed poorer outcomes. We investigated the results of LT with HBcAb-positive grafts in patients with ongoing HBV and HCV coinfections., Methods: From August 1999 to December 2009, we performed 27 adult primary LTs from deceased heart-beating donors into recipients showing hepatitis B surface antigen (HBsAg)- and HCV-RNA-positivity simultaneously: 12 patients received a graft from an HBsAg-negative HBcAb-positive donor (core+D group) and 15 from an HBcAb-negative donor (core-D group). Immunosuppression included a calcineurin inhibitor, antimetabolite and steroids which were suspended at 6 months. Anti-HBV prophylaxis was always perfomed with anti-HBs immunoglobulins and nucleos(t)idic analogues., Results: The groups were similar regarding variables of donor, recipient, donor-recipient match, LT procedure, and acute rejection treatment. Median follow-up for surviving grafts was 67 months (range, 16-141). Among all patients, HCV-RNA remained positive after LT. The prevalence of histologically proven recurrent HCV hepatitis was similar in the 2 groups: 83% core+D vs 73% core-D. No recurrent HBV hepatitis occurred during the follow-up. Graft survival at 5 years was significantly lower in the core+D group (core+D 48% vs core-D 87%; P = .018), in which a significantly higher prevalence of graft loss was caused by HCV recurrence (core+D 5/12, 42% vs core-D 1/15, 7%; P = .03). All of the 5 core+D patients who lost their grafts due to HCV recurrence did not receive anti-HCV therapy (4 owing to an aggressive disease and 1 because of patient refusal)., Conclusions: Outcomes of LT in patients with ongoing HBV and HCV coinfection are adversely affected by donor HBcAb positivity, an effect that is mainly mediated by the dismal course of HCV recurrence after LT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Despite the heightened awareness of diabetes as a major health problem, evidence on the impact of assistance and organizational factors, as well as of adherence to recommended care guidelines, on morbidity and mortality in diabetes is scanty. We identified diabetic residents in Torino, Italy, as of 1st January 2002, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations to compare primary versus specialty care management of diabetes and the fulfillment of a quality-of-care indicator based on existing screening guidelines (GCI). Then, we performed regression analyses to identify associations of these factors with mortality and cardiovascular morbidity over a 4 year-follow-up. Patients with the lowest degree of quality of care (i.e. only cared for by primary care and with no fulfillment of GCI) had worse RRs for all-cause (1.72 [95% CI 1.57-1.89]), cardiovascular (1.74 [95% CI 1.50-2.01]) and cancer (1.35 [95% CI 1.14-1.61]) mortality, compared with those with the highest quality of care. They also showed increased RRs for incidence of major cardiovascular events up to 2.03 (95% CI 1.26-3.28) for lower extremity amputations. Receiving specialist care itself increased survival, but was far more effective when combined with the fulfillment of GCI. Throughout the whole set of analysis, implementation of guidelines emerged as a strong modifier of prognosis. We conclude that management of diabetic patients with a pathway based on both primary and specialist care is associated with a favorable impact on all-cause mortality and CV incidence, provided that guidelines are implemented.

Background and Objectives: Awake "no touch" extubation requires performing extubations only when the patient spontaneously wakes up without any kind of stimulation during emergence from general anesthesia. The aim of this study was to evaluate absolutely awake extubation "no touch" technique in adult patients, scheduled for elective nasal and paranasal sinus surgeries under general anesthesia as regard to emergence airway complications., Methods: A total of 60 adult patients were randomly allocated into one of two equal groups according to the method of extubation: Group I: Standard fully awake, Group II: Absolutely "no touch" awake extubation (absolutely no stimulation no touch was allowed until patients were able to open their eyes). The incidence of laryngospasm and its grade according to a four-point scale was reported. Occurrence of airway events (excessive secretions, breath-holding, coughing, hoarseness, biting, as well as the number and severity of any desaturation episodes), oozing from the wound, and postoperative sore throat were also recorded. The heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure measured at the end of surgery served as baseline values, and subsequent measurements were taken within 30 minutes after the end of surgery., Results: There was absolutely no case of laryngeal spasm or episode of desaturation among patients who were extubated with the "no touch" technique. On the other hand, there were 3 cases of laryngeal spasm in standard fully awake group. Severity of coughing, excessive secretions and breath holding, hoarseness, biting, and occurrence of non-purposeful movements of the limbs were significantly less in the absolutely "no touch" technique awake technique. The changes in HR, SBP, and DBP during emergence extubation were significantly less in "no touch" technique technique group. However, oozing from the wound was significantly higher with standard fully awake extubation. However, there were no significant differences between the two groups regarding the incidence of postoperative sore throat (39 and 36%, respectively)., Conclusion: The results of the present study showed that awake "no touch" technique technique for tracheal extubation produces less airway-related complications, as well as minimal hemodynamic response during emergence from general anesthesia in nasal and paranasal surgeries. It could be a safe alternative for tracheal extubation in airway surgery.

Dissipative particle dynamics with energy conservation (eDPD) was used to study natural convection via Rayleigh-Bénard (RB) problem and a differentially heated enclosure problem (DHE). The current eDPD model implemented the Boussinesq approximation to model the buoyancy forces. The eDPD results were compared to the finite volume solutions and it was found that the eDPD method predict the temperature and flow fields throughout the natural convection domains properly. The eDPD model recovered the basic features of natural convection, such as development of plumes, development of thermal boundary layers, and development of natural convection circulation cells (rolls). The eDPD results were presented via temperature isotherms, streamlines, velocity contours, velocity vector plots, and temperature and velocity profiles. Further useful quantities, such as Nusselt number was calculated from the eDPD results and found to be in good agreement with the finite volume calculations.

Allergic contact dermatitis (ACD) is a cell-mediated, delayed type IV immunologic reaction. Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from a complex interaction between immunologic, genetic, and environmental factors. Pityriasis rosea (PR) is a self-limited eruption of unknown etiology. Immune cell infiltrate is a constant feature in the inflammatory skin diseases. Here, we performed phenotypical characterization of the immune cells in ACD, AD and PR (ten cases each). We performed immunohistochemical stains for B cells (CD20), T cells (CD3), histiocytes (CD68) and T cells with cytotoxic activity (granzyme-B). The data were compared with findings in 20 specimens of normal skin. The results were scored as mean values of positively stained immune cells. Immunohistochemistry showed significantly high counts of immune cells in lesional skin (ACD, AD and PR) compared to the normal one (p < 0.05). In the lesional skin, the immune cells were composed predominantly of CD3(+) T lymphocytes and CD68(+) cells (histiocytes). Some of the CD3(+) cells were granzyme B(+). The counts of some immune cells (CD3(+) and CD68(+)) were high in ACD compared to AD and PR. The counts of CD20(+) and granzyme B(+) cells were high in PR compared to ACD and AD. However, these differences did not reach the level of statistical significance. The present data describe the profile of the immune cell infiltrate in AD, ACD and PR. The cell-mediated immunity seems to have critical role in the development of these lesions.

Background: The percentage of diabetic patients who do not benefit from the protective effect of aspirin is larger than in other populations at cardiovascular risk., Objective: We compared the ability of aspirin to suppress TxA2 and platelet activation in vivo, in type-2 diabetics vs. high-risk non-diabetic patients., Methods: Urinary 11-dehydro-TXB2, plasma sCD40 L, and sP-selectin were measured, together with indices of low-grade inflammation, glycemic control, and lipid profile, in 82 patients with type-2 diabetes and 39 without diabetes, treated with low doses of aspirin., Results: Urinary 11-dehydro-TxB2, plasma sCD40L and sP-selectin were significantly higher in diabetics than in controls: [38.9 (27.8-63.3) vs. 28.5 (22.5-43.9) ng mmol(-1) of creatinine, P = 0.02], [1.06 (0.42-3.06) vs. 0.35 (0.22-0.95) ng mL(-1); P = 0.0001], [37.0 (16.8-85.6) vs. 20.0 (11.2-35.6) ng mL(-1), P = 0.0001], respectively. The proportion of individuals with diabetes increased across quartiles of 11-dehydro-TxB2, sCD40L, and sP-selectin, with the highest quartiles of 11-dehydro-TxB2, sCD40L and sP-selectin, including 66%, 93.3%, and 93.3% of individuals with diabetes. Markers of platelet activation positively correlated with indices of glycemic control but not with markers of low-grade inflammation., Conclusions: Platelet dysfunction associated with insufficient glycemic control, may mediate persistent platelet activation under aspirin treatment.

Background: Neurotrophin (NT)-3 and its high-affinity receptor tyrosine kinase C (Trk C) are essential for nervous system development. These members of the NT family are also involved in murine hair morphogenesis and cycling. However, their role in human hair follicle (HF) biology remains to be elucidated., Objectives: To explore the role of NTs in human skin and HF biology., Methods: The immunoreactivity (IR) of NT-3 and Trk C was studied in human scalp skin and HFs by immunofluorescent and light microscopic immunohistology. Skin biopsies were obtained from normal human scalp containing mainly anagen VI HFs from women (age 53-57 years) undergoing elective plastic surgery., Results: Both NT-3 and Trk C showed prominent, yet distinct, IR patterns in human scalp anagen HFs (anagen VI), whereas they were weakly expressed in catagen and increased again in telogen HFs. Within HF compartments, NT-3 IR was prominent in the outer root sheath, inner root sheath, dermal papilla and connective tissue sheath. Trk C IR was prominent in all HF epithelial and mesenchymal compartments. Outside the HF, both NT-3 and Trk C showed prominent IR in the epidermis, sebaceous glands and sweat glands., Conclusions: These observations provide the first indication that NT-3 and Trk C are expressed in human scalp skin and HFs, and suggest that Trk C-mediated signalling is involved not only in murine but also in human HF biology. They may be useful in determining therapeutic strategies for the treatment of hair cycle and skin-related disorders.

Objective: To assess the types, distributions, and numbers of immune cell infiltrates in the testes of men with azoospermia., Design: Prospective study., Setting: University research and clinical institutes., Patient(s): Thirty-one men with azoospermia showing normal spermatogenesis (n = 10), germ cell maturation arrest (GA, n = 12), and Sertoli cell-only syndrome (SCO, n = 9)., Intervention(s): Testicular tissue biopsies. Sections were stained with routine (hematoxyline and eosin), special (Masson Trichrome, Gordon, Periodic Acid Schiff, Aldehyde Fuchsin, and Orcein stains), and immunoperoxidase stains (using monoclonal antibodies for B and T cells and CD68 macrophages)., Main Outcome Measure(s): Serum levels of T, FSH, and LH in addition to histopathological analysis., Result(s): Hormonal profiles were unremarkable in all patients. Marked deposition of the reticular and collagen fibers was seen more in abnormal than normal spermatogenesis. The immune (B and T lymphocytes and CD68 macrophages) and mast cells were found in the interstitium, tubular walls, and lumens of all the testes analyzed. The differential counts of these cells (B and T lymphocytes, CD68 macrophages, and mast cells, respectively) were higher in SCO (1.66 +/- 0.46, 9.14 +/- 1.30, 2.26 +/- 1.68, 3.35 +/- 0.23) and GA (2.03 +/- 0.48, 4.70 +/- 1.00, 2.61 +/- 0.70, and 4.18 +/- 0.13) when compared with those in normal spermatogenesis (1.22 +/- 0.19, 5.41 +/- 0.58, 1.55 +/- 0.33, and 2.26 +/- 0.13). Increased cellular counts were not statistically significant for T and B cells and macrophages. However, these differences were statistically significant for mast cells., Conclusion(s): Abnormal spermatogenesis is associated with increased numbers of the immune and mast cells. Our findings may reflect an exaggerated immune response in these cases.

Incidence rate of the harder adverse immunization reactions in the Program of the vaccination children in Federation Bosnia and Herzegovina is similar in the terms of kind and frequency as in the countries with high quality programme of the vaccination. In the period from 2002-2003 year cases of the adverse reactions were not registered, as vaccinal form of polyomyelitis, toxic syndrome or sudden acute deaths. The adverse events following immunization were classified in relation to 100,000 applicated vaccines, the incidence rate of supurative lymphadenitis at BCG vaccination reported are 32@100000, anaphylaxia at MMR vaccination 0.8@100000, DTP vaccination encephalopathy 1@100000 and at TT vaccination anaphylaxia 2@100000 administered vaccines.

Thrombolysis may achieve recanalization in cases of occlusion of the cerebral vessels. If therapy is initiated in good time, development of cerebral infarction may be at least partially prevented. Thrombolytic treatment was performed in 14 patients at the Wagner-Jauregg Hospital within a period of one year. Urokinase was given locally, while rtPA was applied locally and/or systemically. 4 patients had an occlusion of the internal carotid artery, 6 an occlusion of the middle cerebral artery, and 4 an occlusion of the basilar artery. Complete recanalization was achieved in 6 patients, partial recanalization in 4, and no recanalization in 4. The neurological outcome of the cases with complete recanalization was good with the exception of one patients who died. Partial recanalization resulted in a fair outcome in 2 patients, while the other 2 died. 3 out of the 4 patients in whom no recanalization was achieved died. Our findings show that this form of therapy may considerably improve the natural history of the disease, provided recanalization is achieved in good time. They encourage us to continue this form of therapy and to work at improving the therapeutic criteria.