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Background: Stroke is a major cause of death and disability worldwide. Over the years, traditional medicines for stroke treatment have undergone tremendous progress, but few bibliometric studies have been performed. This study explored the trends and issues relating to the application of traditional medicine in stroke research., Methods: A bibliometric search was performed in the Web of Science Core Collection database to identify studies that investigated the application of traditional medicine in stroke management. CiteSpace VI and Excel 2016 were used to analyze information from the retrieved studies. Activity index and attractive index were used to explore the worldwide development modes., Results: A total of 1083 English articles published between 2004 and 2018 were identified. Over the last 15 years, the developments in research occurred in three geographic clusters. The development modes were investigated and classified into 4 categories. In mainland China, the number and impact of research showed an increasing trend over the study period. The United States played a leading role in this topic. Three clusters of institutes and the majority of authors mainly came from South Korea, Taiwan and mainland China. Reperfusion injury and angiogenesis were identified as the potential topics likely to dominate future research in this field., Conclusion: The progress of studies on traditional medicine for stroke could be explained by the global attention to traditional medicine, the geospatial proximity for research collabration, and the increasing resources invested. Based on a large amount of existing research, researchers engaged in this topic should objectively consider the influential studies to identify and solve the common issues worldwide.

Introduction: Simulation maintains patient safety by limiting the risk of errors. In the medical field, simulation is a method of learning that is developing more and more in the acute specialties but it is still not widespread in the field of respiratory medicine., Objective: To evaluate the efficacy of high fidelity simulation as a teaching tool in respiratory medicine., Methods and Population Studied: This was a prospective and descriptive study including students who had high fidelity simulation training sessions during their traineeship in respiratory medicine. Simulation learning took the form of four teaching sessions. The included students were assessed at the beginning and end of each session by a pre-test and post-test. Student satisfaction was assessed at the end of each session., Results: Comparing the average student score before and after the simulation session showed an improvement in post-test scores. This improvement was statistically significant for all four scenarios. The majority of students, 60% (N=13), were satisfied with the progress of their internship in the Respiratory Department., Conclusion: High fidelity simulation is a teaching method that allows the acquisition and/or optimization of several skills. Nevertheless, this method remains undeveloped in respiratory medicine., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Saponins are known for their bioactive and surfactant properties, showing applicability to the food, cosmetic and pharmaceutical industries. This work evaluated the saponins effects on Kluyveromyces lactis β-galactosidase activity and correlated these changes to the protein structure. Enzyme kinetic was evaluated by catalytic assay, protein structure was studied by circular dichroism and fluorescence, and isothermal titration calorimetry was used to evaluate the interactions forces. In vitro enzymatic activity assays indicated an increase in the protein activity due to the saponin-protein interaction. Circular dichroism shows that saponin changes the β-galactosidase secondary structure, favoring its protein-substrate interaction. Besides, changes in protein microenvironment due to the presence of saponin was observed by fluorescence spectroscopy. Isothermal titration calorimetry analyses suggested that saponins increased the affinity of β-galactosidase with the artificial substrate o-nitrophenyl-β-galactoside. The increase in the enzyme activity by saponins, demonstrated here, is important to new products development in food, cosmetic, and pharmaceutical industries., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The aim of current study was to investigate the expression of Cyclin D1 and Ki-67 in primary and metastatic oral squamous cell carcinoma (OSCC) and their different histological grades., Methods: Paraffin embedded 30 oral squamous cell carcinoma (15 each of primary and cervical lymph node metastatic OSCC) were included in the study. Cyclin D1 and Ki 67 expressions were evaluated by immunohistochemistry and compared in primary and lymph node metastasis of OSCC and their histological grades. The data was analyzed using SPSS software., Results: The mean age of patients with primary OSCC was 53.47 ±16.67 years and 61.47 ±11.94 years in patients with metastasis. Males were comparatively affected more than females with tongue as the most common site involved in both primary and metastatic tumours. The mean size of primary and metastatic tumour biopsies were 1.16 mm and 3.93 mm respectively. Comparison of the expression of Cyclin D1 in these primary and metastatic OSCC revealed a statistically significant difference (p = 0.003) whereas it was insignificant for Ki-67 (p = 0.715)., Conclusion: Cyclin D1 can be a useful marker in predicting aggressive or metastatic behaviour of OSCC on premier biopsies.

Background: Following spine surgery, different types of inhalational anesthetic agents can result in postoperative delirium (POD) that can increase perioperative/postoperative morbidity. Here, we compared the incidence of POD in adults undergoing spine surgery anesthetized with isoflurane versus desflurane., Methods: A prospective randomized double-blind clinical trial for patients undergoing spinal surgery was performed in 60 adults (aged 18-65 years); they were randomized to receive isoflurane or desflurane. On postoperative days 1 and 3, the diagnosis and severity of POD utilized 3D-Confusion Assessment Method (CAM) and CAM-severity delirium severity scores to assess patients' status. Multiple other variables which may have influenced the frequency/severity of POD were also studied., Results: For the two groups, the incidence of POD utilizing isoflurane and desflurane was similar on postoperative days 1 (10% vs. 13.3%, P > 0.05) and 3 (6.6% vs. 0%, P > 0.05). The severity scores of POD for both anesthetic agents were also similar on postoperative days 1 (1.5 vs. 1) and 3 (0.5 vs. 0.5). In addition, there was no significant association of POD with other perioperative factors., Conclusion: A significant number of patients undergoing spine surgery experience POD. However, the incidence and severity of POD remained similar when utilizing either isoflurane or desflurane., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Surgical Neurology International.)

Objectives: The best modality of administration of hydrocortisone during septic shock has been poorly evaluated and the guidelines remain unclear in this respect. This study aimed to compare bolus of hydrocortisone to a continuous infusion during septic shock., Design: Randomized controlled, open-label trial., Setting: Medical ICU of a university hospital., Patients: Adult patients with septic shock requiring more than 2 mg/h (approximately 33.3 μg/mn) of norepinephrine after adequate fluid administration were eligible.Patients already receiving corticosteroids or who have a contraindication to corticosteroids, patients who died within 24 h and those with a decision of not to resuscitate were excluded., Interventions: Patients were randomized either to receive hydrocortisone 200 mg/d by continuous infusion or by boluses of 50 mg every 6 h throughout the prescription of vasopressors with a maximum of 7 days., Results: Twenty-nine patients were included in each group. Shock reversal was significantly higher in the HC bolus group (66% vs. 35%, P = 0.008). The median time to shock reversal was 5 days (95% CI, 4.31-5.69) in the HC bolus group compared to 6 days (95% CI, 4.80-7.19) in the HC continuous infusion group (log Rank = 0.048). The number of hours spent with blood glucose ≥ 180 mg/dL was higher in the HC continuous infusion group with a median of 64 h [IQR (2-100)] versus 48 h [IQR (14-107)] in the HC bolus group, (P = 0.60), and daily insulin requirements were similar between the two groups (P = 0.63). The occurrence of other side effects, mortality, and ICU LOS were similar between the study groups., Conclusion: Hydrocortisone administered by intermittent bolus was associated with higher shock reversal at day 7 compared with a continuous infusion.

Background: Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID-ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU-acquired delirium., Methods: AID-ICU is an investigator-initiated, pragmatic, international, randomised, blinded, parallel-group, trial allocating adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. Trial participants will receive intravenous 2.5 mg haloperidol three times daily or matching placebo (isotonic saline 0.9%) if they are delirious. If needed, a maximum of 20 mg/daily haloperidol/placebo is given. An escape protocol, not including haloperidol, is part of the trial protocol. The primary outcome is days alive out of the hospital within 90 days post-randomisation. Secondary outcomes are number of days without delirium or coma, serious adverse reactions to haloperidol, usage of escape medication, number of days alive without mechanical ventilation; mortality, health-related quality-of-life and cognitive function at 1-year follow-up. A sample size of 1000 patients is required to detect a 7-day improvement or worsening of the mean days alive out of the hospital, type 1 error risk of 5% and power 90%., Perspective: The AID-ICU trial is based on gold standard methodology applied to a large sample of clinically representative patients and will provide pivotal high-quality data on the benefits and harms of haloperidol for the treatment ICU-acquired delirium., (© 2019 Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo -induced cellular network (iNet) 'webs', which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca 2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo , and may thereby accelerate future studies into the biology of GBM cellular networks., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Traditional cytotoxic agents which act through a DNA-alkylating mechanism are relatively non-specific, resulting in a small therapeutic window and thus limiting their effectiveness. In this study, we evaluate a panel of 24 non-alkylating Strathclyde Minor Groove Binders (S-MGBs), including 14 novel compounds, for in vitro anti-cancer activity against a human colon carcinoma cell line, a cisplatin-sensitive ovarian cancer cell line and a cisplatin-resistant ovarian cancer cell line. A human non-cancerous retinal epithelial cell line was used to measure selectivity of any response. We have identified several S-MGBs with activities comparable to cis-platin and carboplatin, but with better in vitro selectivity indices, particularly S-MGB-4, S-MGB-74 and S-MGB-317. Moreover, a comparison of the cis-platin resistant and cis-platin sensitive ovarian cancer cell lines reveals that our S-MGBs do not show cross resistance with cisplatin or carboplatin and that they likely have a different mechanism of action. Finally, we present an initial investigation into the mechanism of action of one compound from this class, S-MGB-4, demonstrating that neither DNA double strand breaks nor the DNA damage stress sensor protein p53 are induced. This indicates that our S-MGBs are unlikely to act through an alkylating or DNA damage response mechanism., (This journal is © The Royal Society of Chemistry 2019.)

Introduction and Hypothesis: This study aimed to assess the individual and interactive effects of delivery mode and age on the function of the external anal sphincter (EAS) by analyzing the motor unit properties with intramuscular electromyography (EMG). Results are expected to improve the understanding of delivery-related occult obstetric EAS injuries and its development over the aging process and further support early clinical detection and intervention., Methods: A total of 49 postpartum women were recruited into four test groups according to their age and delivery mode: young vaginal delivery (Y-VD), elderly vaginal delivery (E-VD), young cesarean section (Y-CS), and elderly cesarean section (E-CS) groups. Anorectal ultrasonography, manometry, and intramuscular EMG were employed for comprehensive evaluation of EAS function., Results: No significant difference in anorectal ultrasonography and most manometry measurements was associated with delivery age or mode. Intramuscular EMG, however, revealed a statistically significant difference in the characteristics of motor unit potentials (MUPs), including duration, turns, phases, and multiphase wave ratio between four subject groups. No significant interaction effect between age and delivery mode was found., Conclusions: Delivery mode and age have a significant effect on the neuromuscular function of the EAS, suggesting a potential protectiveness of cesarean section against impairment to the EAS. Our results do not provide significant evidence regarding the interaction effect of delivery mode and age; further investigations are needed to confirm this conclusion.

The establishment of an efficient and feasible biorefinery model depends on, among other factors, particularly the selection of the most appropriate microorganism. Mucor circinelloides is a dimorphic fungus species able to produce a wide variety of hydrolytic enzymes, lipids prone to biodiesel production, carotenoids, ethanol, and biomass with significant nutritional value. M. circinelloides also has been selected as a model species for genetic modification by being the first filamentous oleaginous species to have its genome fully characterized, as well as being a species characterized as a potential bioremediation agent. Considering the potential of replacing several nonrenewable feedstocks is widely dependent on fossil fuels, the exploitation of microbial processes and products is a desirable solution for promoting a green and sustainable future. Here, we introduce and thoroughly describe the recent and critical applications of this remarkable fungus within the context of developing a fungal-based biorefinery.

Tannins are compounds with antinutrient properties that hinder food digestibility, prejudicing human and animal nutrition. This work aimed to evaluate the negative effects of tannic acid on Kluyveromyces lactis β-galactosidase catalytic activity and correlate these changes with the protein structure. β-Galactosidase activity decreased in the presence of tannins, which caused changes to the structure of the enzyme, as demonstrated by circular dichroism. It was verified that tannin binds to the protein by a static mechanism. Additionally, isothermal titration calorimetry suggested that tannic acid modified the molecular interaction between β-galactosidase and o-nitrophenyl-β-d-galactoside, reducing their affinity and prejudicing the protein activity. This study helps to understand the effects of tannins on the β-galactosidase structure and how they are related to the enzyme catalytic activity. The alterations in the conformation and activity of the enzyme should be taken into consideration when dairy products are consumed with tannin-rich food., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Single cell oil (SCO) was produced from enzymatically hydrolysed sugarcane bagasse by Mucor circinelloides. The fungus was cultured in the hydrolysate medium rich in glucose and xylose being able to assimilate both sugars simultaneously, attaining satisfactory values of lipid accumulation (25 wt%). The main concepts addressed herein were the utilization of these lipids for the production of (i) ethyl esters of fuel grade, and (ii) concentrate of polyunsaturated fatty acids for nutraceutical applications. It was noticed that the fungal lipids also contained carotenoids and that the fungal biomass presented lipolytic activity. The concept of integrating an M. circinelloides-based biorefinery into the sugarcane energy matrix may, thus, present a relevant alternative for the production of high value-added products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Sinoatrial node dysfunction and deafness (SANDD) syndrome is rare and characterized by a low heart beat and severe-to-profound deafness. Additional features include fatigue, dizziness, and episodic syncope. The sinoatrial node (SAN) drives heart automaticity and continuously regulates heart rate. The CACNA1D gene encoding the Ca v 1.3 protein expressed in inner hair cells, atria and SAN, induces loss-of-function in channel activity and underlies SANDD. To date, only one variant c.1208_1209insGGG:p.(G403_V404insG) has been reported for SANDD syndrome. We studied five Pakistani families with SANDD and characterized a new missense variant p.(A376V) in CACNA1D in one family, and further characterized the founder variant p.(G403_V404insG) in four additional pedigrees. We show that affected individuals in the four families which segregate p.(G403_V404insG) share a 1.03 MB haplotype on 3p21.1 suggesting they share a common distant ancestor. In conclusion, we identified new and known variants in CACNA1D in five Pakistani families with SANDD. This study is of clinical importance as the CACNA1D founder variant is only observed in families from the Khyber Pakhtunkhwa (KPK) province, in Pakistan. Therefore, screening patients with congenital deafness for SAN dysfunction in this province could ensure adequate follow-up and prevent cardiac failure associated with SAN.

Background: There is an emphasis on identity formation to complement the competency-based medical education in tomorrow's doctors, with a focus from "doing" to "being," to deeply learn the role as a health professional. Medical students spend a considerable time on internet-based online social networking platforms. These internet-based avenues can have certain implications in the formation of their identity., Methods: The aim of this article is to discuss a highly significant way to form the professional identity that is through online social networking, which can be labeled as digital professional identity (DPI)., Results: DPI is defined as "professional identity that develops through internet-based social interactions by utilizing online platforms and communication tools." Medical students develop certain constituents of professionalism as part of their lifelong professional identity during the course of their graduation. They learn the professional ways and means to communicate on internet-based social media platforms, which affect their professional identities., Discussion: We suggest to provide institutional guidance for the medical students regarding the usage of social networking sites and forming their DPIs as a medical professional by explaining the related advantages and disadvantages. In addition, accreditation bodies need to incorporate the aspect of DPI in their competencies for professionalism., Competing Interests: None

Objective: To determine the association of human resistin gene RETN C-420G single nucleotide polymorphism with type 2 diabetes mellitus in a specific ethnic population.., Methods: The controlled study was conducted from June 2012 to January 2015 at Military Hospital, Rawalpindi, Army Medical College, Rawalpindi, and the Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan. Patients with type 2 diabetes and healthy controls belonging to Pakistani Punjabi Rajput ethnic group were genotyped for human resistin gene RETNC-420G single nucleotide polymorphism. Serum resistin, serum insulin, fasting blood sugar, lipid profile, body mass index and insulin resistance was determined and correlated with genotypes. SPSS 18 was used for data analysis., Results: Of the 789 subjects, 539(68%) were diabetics and 250(32%) were controls. Serum resistin levels were significantly higher in diabetics than controls (p<0.05). The frequency of GG, GC and CC was 15(2.8%), 322(59.75%) and 202(37.5%) in diabtics. This single nucleotide polymorphism was associated with diabetes (p<0.02).Human resistin gene RETN C-420G single nucleotide polymorphism was not associated with serum resistin, insulin, body mass index, insulin resistance and dyslipidaemia in both groups (p<0.05 each)., Conclusions: Human resistin gene RETN C-420G single nucleotide polymorphism was found to be a risk factor for type 2 diabetes in Pakistani Punjabi Rajput population..

Pharmacological inhibition of uncontrolled cell growth with small-molecule inhibitors is a potential strategy for treating glioblastoma multiforme (GBM), the most malignant primary brain cancer. We showed that the synthetic small-molecule KHS101 promoted tumor cell death in diverse GBM cell models, independent of their tumor subtype, and without affecting the viability of noncancerous brain cell lines. KHS101 exerted cytotoxic effects by disrupting the mitochondrial chaperone heat shock protein family D member 1 (HSPD1). In GBM cells, KHS101 promoted aggregation of proteins regulating mitochondrial integrity and energy metabolism. Mitochondrial bioenergetic capacity and glycolytic activity were selectively impaired in KHS101-treated GBM cells. In two intracranial patient-derived xenograft tumor models in mice, systemic administration of KHS101 reduced tumor growth and increased survival without discernible side effects. These findings suggest that targeting of HSPD1-dependent metabolic pathways might be an effective strategy for treating GBM., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The ligands L 1 and L 2 both form separable dinuclear double-stranded helicate and mesocate complexes with Ru II . In contrast to clinically approved platinates, the helicate isomer of [Ru 2 (L 1 ) 2 ] 4+ was preferentially cytotoxic to isogenic cells (HCT116 p53 -/- ), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53 +/+ . Other structurally similar Ru II -containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be "tuned" to either genotype. In the search for compounds that can target difficult-to-treat tumours that lack the p53 tumour suppressor gene, [Ru 2 (L 1 ) 2 ] 4+ is a promising compound for further development., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Debate and role play for learning critical thinking and communication skills are being increasingly used in various undergraduate medical schools worldwide. We aim to compare students' views about effectiveness of two teaching strategies; debate and role play to exercise critical thinking and communication skills during problem-based learning (PBL). This is a comparative, cross-sectional, and questionnaire-based study. Our subjects were second year undergraduate female medical students enrolled in Imam Abdulrahman Bin Faisal University (IAU), College of Medicine from September 2014-2016, divided into 10 small PBL groups (10-13 students/group/year). Students rated role play and debate as equally effective in improving communication skills. Debate was rated superior to role play in "opening new avenues of thinking" (p-value is 0.01), whereas in "integration of knowledge of basic medical sciences with clinical skills" and "reflection of real life experience" students rated role play being superior to debate (p-value 0.01 and 0.00, respectively). Both role play and debate are well accepted by the students in PBL curriculum as an effective teaching methodology. Both are perceived equally good in improving students' communication skills. Few aspects of critical thinking are improved more by role plays compared to debate and vice versa. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:336-342, 2018., (© 2018 The International Union of Biochemistry and Molecular Biology.)

Objective: To determine the effect of sodium phenytoin on the apical ectodermal ridges (AER) of chick wing buds by using the software program Image-J., Study Design: An experimental study., Place and Duration of Study: Department of Anatomy, Regional Center, College of Physicians and Surgeons Pakistan (CPSP), Islamabad, from January 2014 to January 2015., Methodology: Sixty fertilised chicken eggs of 'Egyptian fayoumi' breed were selected and separated into experimental (B) and control (A) groups, each having 30 eggs. A single dose of 3.5 mg sodium phenytoin was injected into each egg of the experimental group. The controls were injected with the same volume of normal saline. Developing embryos were extracted 96 hours (day 4) after incubation and histological sections were cut at 5 μm thickness. These sections were stained with Feulgen Nuclear and Light Green. The area of apical ectodermal ridges of chick wing buds was calculated by employing Image-J and subjected to statistical analysis., Results: The difference between the mean values of the area of apical ectodermal ridges of experimental and control groups, as calculated by Image-J, was found to be statistically insignificant., Conclusion: Change in the area of the apical ectodermal ridges in experimental chicks, following phenytoin exposure, was insignificant as proven on the basis of quantification by Image-J.

In any job setting, the sudden or expected death of a coworker can cause profound grief and loss. Moreover, in academic settings there are unique challenges that warrant further discussion. Given the aging of the nursing professoriate, the shortage of nursing faculty, and the medical advances prolonging our life expectancy, we can forecast a greater frequency of loss of faculty while employed. The impact of a faculty member death on colleagues, staff, and students can cause great distress and therefore requires careful attention and consideration for all. As Deans and Directors at Schools of Nursing, how do we navigate grief and mourning, supporting others while experiencing some of the same feelings ourselves? This requires a careful balance, as our actions can create an impact on the culture and health of our colleges and schools of nursing and those who work and attend classes therein., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The incidence and risk factors for delirium vary among studies., Objective: We aimed to determine the incidence, risk factors, and impact on outcome of delirium in a medical Intensive Care Unit (ICU) in Tunisia using a prospective observational study., Patients: All consecutive patients admitted to the ICU between May 2012 and April 2013 were included if they were aged more than 18 years and had an ICU stay of more than 24 h. Patients who had a cardiac arrest or have a history of dementia or psychosis were excluded. Patients eligible for the study were evaluated by the medical staff to detect delirium using the CAM-ICU., Results: A total of 206 patients were included, 167 did not present delirium and 39 (19%) were analyzed for delirium. Delirious patients had a significantly longer duration of mechanical ventilation (10 days[6-20] vs. 2 days[0-7]) respectively and length of stay in ICU (21.5 days [10.5-32.5] vs. 8 days [5-13]), with no impact on mortality. Delirium was associated with high incidence of unintentional removal of catheters (39% vs. 9%; P < 0.0001), endotracheal tubes (18% vs. 1%; P < 0.0001), and urinary catheters (28% vs. 2%, P < 0.0001). In multivariable risk regression analysis, age (odds ratio [OR] = 4.1, 95% confidence interval [CI]: 1.39-12.21; P = 0.01), hypertension (OR = 3.3, 95% CI: 1.31-8.13; P = 0.011), COPD (OR = 3.5, 95% CI: 1.47-8.59; P = 0.005), steroids (OR = 2.8, 95% CI: 1.05-7.28; P = 0.038), and sedation (OR = 5.4, 95% CI: 2.08-13.9; P < 0.0001) were independent risk factors for delirium. We did not find a relationship between delirium and mortality., Conclusion: Delirium is frequent in the ICU and is associated with poor outcome. Several risk factors for delirium are linked to intensive care environment., Competing Interests: There are no conflicts of interest.

Objective: To observe the effects of Shisha smoke on submucosal glands of trachea of mice; and compare it with tracheal glands of mice exposed to cigarette smoke., Study Design: Randomised controlled trial., Place and Duration of Study: Department of Anatomy, Islamic International Medical College, Rawalpindi, in collaboration with National Institute of Health (NIH), Islamabad from October 2013 till April 2014., Methodology: Sample comprised of 40 adult male mice of strain BALB/c. They were randomly divided into three groups. Control group was labelled as Group 'C'. The mice in this group were kept in a whole body smoke exposure chamber and were exposed to fresh air. Shisha group was labelled as Group 'SS', and the mice in this group were exposed to Shisha smoke. Mice in the third group labelled as Group CS were exposed to cigarette smoke. All the mice were dissected after an exposure period of eight weeks. Tracheal tissue was stained and examined microscopically for submucosal gland hypertrophy and compared with the control group, using Reid's Index. An Index of more than 0.4 is termed as hypertrophy., Results: There was significant submucosal gland hypertrophy in groups CS and SS as compared to group C. There was also significant difference in the frequency of mucosal hypertrophy between SS (93.7%) and CS groups (53.3%), which was found statistically significant (p<0.001)., Conclusion: Shisha smoking was significantly associated with mucosal hypertrophy when compared with cigarette smoking and controls. Shishasmoke contains higher level of toxicants as compared to cigarette smoke, and it causes more oxidative damage of tissues.

Purpose of Review: Weakened pelvic floor support is believed to be the main cause of various pelvic floor disorders. Modern theories of pelvic floor support stress on the structural and functional integrity of multiple structures and their interplay to maintain normal pelvic floor functions. Connective tissues provide passive pelvic floor support while pelvic floor muscles provide active support through voluntary contraction. Advanced modern medical technologies allow us to comprehensively and thoroughly evaluate the interaction of supporting structures and assess both active and passive support functions. The pathophysiology of various pelvic floor disorders associated with pelvic floor weakness is now under scrutiny from the combination of (1) morphological, (2) dynamic (through computational modeling), and (3) neurophysiological perspectives. This topical review aims to update newly emerged studies assessing pelvic floor support function among these three categories., Recent Findings: A literature search was performed with emphasis on (1) medical imaging studies that assess pelvic floor muscle architecture, (2) subject-specific computational modeling studies that address new topics such as modeling muscle contractions, and (3) pelvic floor neurophysiology studies that report novel devices or findings such as high-density surface electromyography techniques. We found that recent computational modeling studies are featured with more realistic soft tissue constitutive models (e.g., active muscle contraction) as well as an increasing interest in simulating surgical interventions (e.g., artificial sphincter). Diffusion tensor imaging provides a useful non-invasive tool to characterize pelvic floor muscles at the microstructural level, which can be potentially used to improve the accuracy of the simulation of muscle contraction. Studies using high-density surface electromyography anal and vaginal probes on large patient cohorts have been recently reported. Influences of vaginal delivery on the distribution of innervation zones of pelvic floor muscles are clarified, providing useful guidance for a better protection of women during delivery. We are now in a period of transition to advanced diagnostic and predictive pelvic floor medicine. Our findings highlight the application of diffusion tensor imaging, computational models with consideration of active pelvic floor muscle contraction, high-density surface electromyography, and their potential integration, as tools to push the boundary of our knowledge in pelvic floor support and better shape current clinical practice.

Goat farming plays an important role in the Sri Lankan rural economy. Sri Lankan indigenous (SLI) goats and their crossbreds are reared mainly under extensive management and indiscriminately exposed to pathogens and parasites. This study was designed to evaluate resistance to haemonchosis in SLI goats and their Jamnapari crossbreds (JCB) in the dry zone of Sri Lanka. Twenty SLI and 20 JCB 4-month-old male goats were artificially challenged with 5000 H. contortus L 3 larvae . Faecal egg counts (FEC), body weights, FAffa MAlan CHArt (FAMACHA®) scores, packed cell volumes (PCV), red blood cell counts, total and differential white blood cell counts, blood haemoglobin contents, serum total protein and albumin contents, and serum pepsinogen and antibody levels were determined at 0, 21, 28, 35 and 42days after challenge. Effects of measurement time were significant for all variables (P<0.05). Breed effects approached significance (P=0.06) and measurement time×breed interaction was significant (P<0.05) for FEC. Peak FEC occurred at day 35 in both goat types, and JCB goats had higher FEC than SLI goats at days 28 (P<0.001), 35 (P<0.10), and 42 (P<0.10). Means for FEC at day 35 were 1783±446 eggs per gram of feces (epg) for SLI kids and 3329±850 epg for JCB kids. Haematological parameters, serum chemistry, and FAMACHA scores suggested that SLI goats were recovering from parasitic infection by day 42, whereas JCB goats had increasing severity of anaemia. Means for PCV in SLI goats decreased from 26.8±0.7% at day 0 to 19.7±0.9% at day 35 and thereafter increased to 20.2±0.9% at day 42. Means for PCV in JCB goats declined from 25.9±0.6% at day 0 to 17.2±0.9% at day 42. Eosinophilia was observed in both genotypes. The JCB goats were heavier than SLI goats and had higher antibody titres, reflecting higher levels of parasitism. Both goat types significantly increased in body weight during the experiment and therefore tolerated parasite infection without severe production losses. We concluded that SLI goats were more resistant to haemonchosis than JCB goats, but that JCB goats were somewhat resilient to parasitic infection. Substantial variability in measurements associated with parasite infection in both breeds indicated potential to improve parasite resistance. Phenotypic information should be coupled with genomic information to identify appropriate breeding goals for future selection programs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The comparative studies on grading in subarachnoid hemorrhage (SAH) had several limitations such as the unclear grading of Glasgow Coma Scale 15 with neurological deficits in World Federation of Neurosurgical Societies (WFNS), and the inclusion of systemic disease in Hunt and Hess (H&H) scales. Their differential incremental impacts and optimum cut-off values for unfavourable outcome are unsettled. This is a prospective comparison of prognostic impacts of grading schemes to address these issues. SAH patients were assessed using WFNS, H&H (including systemic disease), modified H&H (sans systemic disease) and followed up with Glasgow Outcome Score (GOS) at 3 months. Their performance characteristics were analysed as incremental ordinal variables and different grading scale dichotomies using rank-order correlation, sensitivity, specificity, positive predictive value, negative predictive value, Youden's J and multivariate analyses. A total of 1016 patients were studied. As univariate incremental variable, H&H sans systemic disease had the best negative rank-order correlation coefficient (-0.453) with respect to lower GOS (p < 0.001). As univariate dichotomized category, WFNS grades 3-5 had the best performance index of 0.39 to suggest unfavourable GOS with a specificity of 89% and sensitivity of 51%. In multivariate incremental analysis, H&H sans systemic disease had the greatest adjusted incremental impact of 0.72 (95% confidence interval (CI) 0.54-0.91) against a lower GOS as compared to 0.6 (95% CI 0.45-0.74) and 0.55 (95% CI 0.42-0.68) for H&H and WFNS grades, respectively. In multivariate categorical analysis, H&H grades 4-5 sans systemic disease had the greatest impact on unfavourable GOS with an adjusted odds ratio of 6.06 (95% CI 3.94-9.32). To conclude, H&H grading sans systemic disease had the greatest impact on unfavourable GOS. Though systemic disease is an important prognostic factor, it should be considered distinctly from grading. Appropriate cut-off values suggesting unfavourable outcome for H&H and WFNS were 4-5 and 3-5, respectively, indicating the importance of neurological deficits in addition to level of consciousness.

Objective: To determine the frequencies of adiponectin (ADIPOQ) C-11377G, tumor necrosis factor-alpha (TNF-α) G-308A and TNF-αG-238Asingle nucleotide polymorphisms (SNP) and their association with serum levels in Pakistani T2DM and healthy population., Study Design: Case control study., Place and Duration of Study: Military Hospital, Rawalpindi, Army Medical College and Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan, from June 2012 till 2014., Methodology: Cases (n=539) and controls (n=250) comprising of T2DM and healthy subjects, respectively, belonging to Pakistani Punjabi Rajput ethnicity were genotyped for SNPs. Serum adiponectin, TNF-α, insulin, blood sugar fasting (BSF), lipid profile, body mass index (BMI), and insulin resistance (IR) was determined and correlated with genotypes., Results: Serum TNF-αwas significantly higher and adiponectin was lower in T2DM than healthy controls (p < 0.003 and 0.0001, respectively, Mann-Whitney U-test). The frequency of ADIPOQ CC, GC and GG was 340 (63.1%), 167 (31%) and 32 (5.9%) in T2DM patients. ADIPOQ -11377 SNPwas not significantly associated with T2DM [OR = 1.116 (95% CI 0.811.53), p = 0.27- Fisher's exact test]. Genotypes deviated from Hardy-Weinberg equilibrium. Minor alleles of TNF-αG-308A and TNF-αG-238Awere not found in either groups., Conclusion: Frequency of ADIPOQ -11377 risk allele is low and does not functionally affect the serum adiponectin levels; hence, ADIPOQ C-11377G SNPis not a risk factor for T2DM in Pakistani Punjabi Rajput patients. Moreover, TNF-αG-308A and TNF-αG-238ASNPs are not prevalent in this ethnic group.

Background: The "gold standard" for instrumentation of unstable thoracolumbar fracture-dislocations is pedicle screw and rod fixation. Although traditional treatment supports long-segment posterior fixation (LSPF), more recent studies show short-segment posterior fixation (SSPF) may be effective, but incur higher failure rates. Here, we evaluated the effectiveness of SSPF in the management of unstable thoracolumbar injuries and analyzed the factors impacting long-term outcomes., Methods: In this retrospective analysis of 91 patients with thoracolumbar fractures managed with SSPF alone, we assessed the clinical and radiological parameters at preoperative, postoperative, and follow-up intervals along with reasons for failures of SSPF., Results: We analyzed 91 patients (mean age: 33.5 years; Male: Female = 50:41) with thoracolumbar fractures treated with SSPF over a median follow-up period of 30 months. SSPF failures were observed in 26 of 91 (28.6%) patients; the median time to implant failure was 17 months. On univariate analysis, statistically significant factors contributing to failure of SSPF included the presence of a burst fracture, a preoperative LSC (load-sharing classification) score >6, and translation/dislocation. With multinomial regression analysis, the only factor predictive for SSPF failure was the patients' postoperative ambulatory status., Conclusion: Patients with thoracolumbar facture dislocations, subjected to axial spinal loading postoperatively, should not be considered for SSPF alone. The following factors also contributed to SSPF failures: a burst fracture, a preoperative LSC score of >6, and/or presence of transverse dislocation., Competing Interests: There are no conflicts of interest.

Stress is a vulnerable state to cellular homeostasis which leads to oxidative damage via free radical generation. The acute stress induces alteration in antioxidant enzyme activities to an extent which produce oxidative stress and causes certain pathological conditions. The use of Nigella sativa L. oil (NSO) in folk medicine has increased throughout the world for the prevention or treatment of various ailments because of potent antioxidant properties. In the present study, potential therapeutic effects of NSO on memory in both unrestrained and 2h restrained rats were observed. Shortterm memory (STM) and long-term memory (LTM) were assessed by elevated plus maze (EPM) and Morris water maze (MWM) respectively. The present study also demonstrated the effect of NSO on lipid peroxidation (LPO) and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) along with the activity of acetyl cholinesterase (AChE). The results obtained from the present study showed that 2h restraint stress significantly enhanced both short-term memory (p<0.01) and long-term memory (p<0.05) in rats. Pretreatment with NSO at a dose of 0.2ml/kg/day also significantly improved STM (p<0.05) in restrained rats and LTM (p<0.01) in unrestrained rats. This study also showed significantly decreased (p<0.01) LPO and significantly increased (p<0.01) endogenous antioxidant enzymes activity in NSO treated restrained rats. Similarly significant decreased (p<0.01) AChE activity was also observed in NSO treated unrestrained and 2h restrained rats. Therefore, current findings suggested that repeated administration of NSO may exert memory enhancing effects against restrained stress and it can be used for therapeutic purpose because of having fewer side effects.

Background: Previous small-scale studies have demonstrated the feasibility of providing remote specialty care via virtual visits. We assessed the feasibility and benefits of a one-time consultation between a remote Parkinson Disease (PD) specialist and an individual with PD at home on a larger scale., Methods: We conducted a multicenter noncontrolled cohort of virtual visits administered over videoconferencing between remote PD specialists and individuals with PD in their home. Specialists performed a patient history and a PD-specific physical examination and provided recommendations to patients and their local physicians. The primary outcome measures were feasibility, as measured by the proportion of visits completed as scheduled, and the 6-month change in quality of life, as measured by the Parkinson's Disease Questionnaire 39. Additional outcomes included satisfaction with visits and interest in future virtual visits., Results: A total of 277 participants from 5 states enrolled, 258 participants completed virtual visits with 14 different physicians, and 91% of visits were completed as scheduled. No improvement in quality of life was observed at 6 months (0.4-point improvement; 95% confidence interval -1.5 to 0.6; p = 0.39). Overall satisfaction with virtual visits was high among physicians (94% satisfied or very satisfied) and patients (94% satisfied or very satisfied), and 74% of participants were interested in receiving future care via virtual visits., Conclusions: Providing specialty care remotely into the homes of individuals with PD is feasible, but a one-time visit did not improve quality of life. Satisfaction with the visits was high among physicians and patients, who were interested in receiving such care in the future., Classification of Evidence: This study provides Class IV evidence that for patients with PD, remote specialty care is feasible but does not improve quality of life., Clinicaltrialsgov Identifier: NCT02144220.

Background/aim: This study aimed to find a link between sperm mitochondrial DNA mutations and male infertility in Pakistan., Materials and Methods: DNA from semen samples was extracted and amplified by PCR using 7.8-kb deletion-specific primers. The PCR products were separated on agarose gel, visualized under UV-illumination, and then photographed. The results were genotyped and the data were analyzed using SPSS., Results: Deletion analysis of the 8.7-kb fragment by long PCR revealed multiple deletions. The frequency of deletion was much higher in infertile groups as compared to the control group. Further, on comparison between different subtypes of infertile groups, the deletions were highest in the oligoasthenoteratozoospermia (OAT) group. The statistical analysis of case and control groups showed a significant association of the 8.7-kb deletion with human male infertile groups (P = 0.031), and particularly a very significant association with the OAT subgroup (P = 0.019)., Conclusion: A significant association has been found between human male infertility and mtDNA deletions in an 8.7-kb segment of sperm mtDNA in a Pakistani population.

This paper focuses on design, fabrication and characterization of a biomimetic, compact, low-cost and lightweight 3D printed humanoid hand (TCP Hand) that is actuated by twisted and coiled polymeric (TCP) artificial muscles. The TCP muscles were recently introduced and provided unprecedented strain, mechanical work, and lifecycle (Haines et al 2014 Science 343 868-72). The five-fingered humanoid hand is under-actuated and has 16 degrees of freedom (DOF) in total (15 for fingers and 1 at the palm). In the under-actuated hand designs, a single actuator provides coupled motions at the phalanges of each finger. Two different designs are presented along with the essential elements consisting of actuators, springs, tendons and guide systems. Experiments were conducted to investigate the performance of the TCP muscles in response to the power input (power magnitude, type of wave form such as pulsed or square wave, and pulse duration) and the resulting actuation stroke and force generation. A kinematic model of the flexor tendons was developed to simulate the flexion motion and compare with experimental results. For fast finger movements, short high-power pulses were employed. Finally, we demonstrated the grasping of various objects using the humanoid TCP hand showing an array of functions similar to a natural hand.

Background: Stress urinary incontinence is a significant problem in young female athletes, but the pathophysiology remains unclear because of the limited knowledge of the pelvic floor support function and limited capability of currently available assessment tools. The aim of our study is to develop an advanced computer modeling tool to better understand the dynamics of the internal pelvic floor during highly transient athletic activities., Methods: Apelvic model was developed based on high-resolution MRI scans of a healthy nulliparous young female. A jump-landing process was simulated using realistic boundary conditions captured from jumping experiments. Hypothesized alterations of the function of pelvic floor muscles were simulated by weakening or strengthening the levator ani muscle stiffness at different levels. Intra-abdominal pressures and corresponding deformations of pelvic floor structures were monitored at different levels of weakness or enhancement., Findings: Results show that pelvic floor deformations generated during a jump-landing process differed greatly from those seen in a Valsalva maneuver which is commonly used for diagnosis in clinic. The urethral mobility was only slightly influenced by the alterations of the levator ani muscle stiffness. Implications for risk factors and treatment strategies were also discussed., Interpretation: Results suggest that clinical diagnosis should make allowances for observed differences in pelvic floor deformations between a Valsalva maneuver and a jump-landing process to ensure accuracy. Urethral hypermobility may be a less contributing factor than the intrinsic sphincteric closure system to the incontinence of young female athletes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction and Hypothesis: Knowledge of the innervation of pelvic floor and sphincter muscles is of great importance to understanding the pathophysiology of female pelvic floor dysfunctions. This report presents our high-density intravaginal and intrarectal electromyography (EMG) probes and a comprehensive innervation zone (IZ) imaging technique based on high-density EMG readings to characterize the IZ distribution., Methods: Both intravaginal and intrarectal probes are covered with a high-density surface electromyography electrode grid (8 × 8). Surface EMG signals were acquired in ten healthy women performing maximum voluntary contractions of their pelvic floor. EMG decomposition was performed to separate motor-unit action potentials (MUAPs) and then localize their IZs., Results: High-density surface EMG signals were successfully acquired over the vaginal and rectal surfaces. The propagation patterns of muscle activity were clearly visualized for multiple muscle groups of the pelvic floor and anal sphincter. During each contraction, up to 218 and 456 repetitions of motor units were detected by the vaginal and rectal probes, respectively. MUAPs were separated with their IZs identified at various orientations and depths., Conclusions: The proposed probes are capable of providing a comprehensive mapping of IZs of the pelvic floor and sphincter muscles. They can be employed as diagnostic and preventative tools in clinical practices.

DNA analysis has become an essential intelligence tool in the criminal justice system for the identification of possible offenders. However, it appears that about half of the processed DNA samples contains too little DNA for analysis. This study looks at DNA success rates within 28 different categories of trace exhibits and relates the DNA concentration to the characteristics of the DNA profile. Data from 2260 analyzed crime samples show that cigarettes, bloodstains, and headwear have relatively high success rates. Cartridge cases, crowbars, and tie-wraps are on the other end of the spectrum. These objective data can assist forensics in their selection process.The DNA success probability shows a positive relation with the DNA concentration. This finding enables the laboratory to set an evidence-based threshold value in the DNA analysis process. For instance, 958 DNA extracts had a concentration value of 6 pg/μL or less. Only 46 of the 958 low-level extracts provided meaningful DNA profiling data., (© 2016 American Academy of Forensic Sciences.)

Objectives: Since the ageing population demands a response to ensure older people remain healthy and active, we studied the dynamics of a recently proposed healthy ageing phenotype. We drew the phenotype's trajectories and tested whether their levels and rates of change are influenced by health behaviours, comorbidities and socioeconomic positions earlier in the life course., Design and Outcomes: The English Longitudinal Ageing Study, a prospective, nationally representative sample of people aged ≥50 years, measured a set of eight biomarkers which make up the outcome of the healthy ageing phenotype three times over nearly a decade (N2004=5009, N2008=5301, N2013=4455). A cluster of health behaviours, comorbidities and socioeconomic positions were also measured repeatedly. We assessed the phenotype's distribution non-parametrically, then fitted linear mixed models to phenotypic change and further examined time interactions with gender and socioeconomic position. We ran additional analyses to test robustness., Results: Women had a wider distribution of the healthy ageing phenotype than men had. The phenotype declined annually by -0.242 (95% confidence interval [CI]: -0.352, -0.131). However, there was considerable heterogeneity in the levels and rates of phenotypic change. Women started at higher levels, then declined more steeply by -0.293 (CI: -0.403, -0.183) annually, leading to crossover in the trajectories. Smoking and physical activity assessed on the Allied Dunbar scale were strongly associated with the trajectories., Conclusion: Though marked by secular decline, the trajectories of the healthy ageing phenotype showed distinct socioeconomic gradients. The trajectories were also susceptible to variations in health behaviours, strengthening the case for serial interventions to attain healthy and active ageing., (Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.)

Iron is an essential micronutrient for living organisms as it is involved in a broad variety of important biological processes. However, free iron inside the cell could be potentially toxic, generating hydroxyl radicals through the Fenton reaction. Dps (DNA-binding protein from starved cells) belongs to a subfamily of ferritins and can store iron atoms inside the dodecamer. The presence of a ferroxidase centre, composed of highly conserved residues, is a signature of this protein family. In this study, we analysed the role of two conserved histidine residues (H25 and H37) located at the ferroxidase centre of the Campylobacter jejuni Dps protein by replacing them with glycine residues. The C. jejuni H25G/H37G substituted variant showed reduced iron binding and ferroxidase activities in comparison with wt Dps, while DNA-binding activity remained unaffected. We also found that both CjDps wt and CjDps H25G/H37G were able to bind manganese atoms. These results indicate that the H25 and H37 residues at the ferroxidase centre of C. jejuni Dps are not strictly required for metal binding and oxidation.

Inappropriate sinus tachycardia is defined as sinus tachycardia at rest (heart rate ≥100 bpm) in sitting position or/and as an average heart rate ≥90 bpm during 24-hour Holter monitoring. The most common symptoms are palpitation, dizziness, chest discomfort, orthostatic intolerance, and fatigue. Sometimes, the symptoms can be severe and debilitating, and its etiology is not well understood. Pharmacological approaches present limitation because of their relatively small effectiveness, intolerance, or side effects.In this series of cases of inappropriate sinus tachycardia, the authors report 3 cases refractory to conventional pharmacological therapy, in which the authors were not tempted for ablation of the sinus node. The authors, however, use another therapeutic approach, which was renal sympathetic denervation, to reduce sympathetic activity in the sinus node, and consequently reduce tachycardia with improvement of symptoms.Three months after renal sympathetic denervation, all patients were not using any type of medication, and reported no more symptoms. The authors know that this is the first report using the renal sympathetic denervation for the treatment of inappropriate sinus tachycardia. Studies with a larger number of patients, a longer time of follow-up, and a control group, however, should be performed.

Central vein disease is defined as at least 50% narrowing up to total occlusion of central veins of the thorax including superior vena cava, brachiocephalic, subclavian, and internal jugular vein. Thrombosis due to intravascular leads occurs in approximately 30% to 45% of patients early or late after implantation of a pacemaker by transvenous access.In this case, we report a male patient, 65-years old, hypertensive, type 2 diabetic, with atherosclerotic disease, coronary artery disease, underwent coronary artery bypass surgery in the past 10 years, having already experienced an acute myocardial infarction, bearer automatic implantable cardioverter defibrillator for 8 years after an episode of aborted sudden death due to ischemic cardiomyopathy, presenting left superior vena cava syndrome. The use of clopidogrel and rivaroxaban for over a year had no benefit on symptoms improvement.After atrial and ventricular leads extraction, a new shock lead was positioned in the right ventricle using active fixation and a new atrial lead was positioned in the right atrium, passing inside of the stents. Two days after the procedure the patient was asymptomatic and was discharged.

Purpose: To assess whether our ureteroscopic real-time navigation system has the possibility to reduce radiation exposure and improve performance of ureteroscopic maneuvers in surgeons of various ages and experience levels., Materials and Methods: Our novel ureteroscopic navigation system used a magnetic tracking device to detect the position of the ureteroscope and display it on a three-dimensional image. We recruited 31 urologists from five institutions to perform two tasks. Task 1 consisted of finding three internal markings on the phantom calices. Task 2 consisted of identifying all calices by ureteroscopy. In both tasks, participants performed with simulated fluoroscopy first, followed by our navigation system. Accuracy rates (AR) for identification, required time (T) for completing the task, migration length (ML), and time exposed to simulated fluoroscopy were recorded., Results: The AR, T, and ML for both tasks were significantly better with the navigation system than without it (Task 1 with simulated fluoroscopy vs with navigation: AR 87.1 % vs 98.9%, P=0.003; T 355 s vs 191 s, P<0.0001; ML 4627 mm vs 2701 mm, P<0.0001. Task 2: AR 88.2% vs 96.7%, P=0.011; T 394 s vs 333 s, P=0.027; ML 5966 mm vs 5299 mm, P=0.0006). In both tasks, the participants used the simulated fluoroscopy about 20% of the total task time., Conclusions: Our navigation system, while still under development, could help surgeons of all levels to achieve better performances for ureteroscopic maneuvers compared with using fluoroscopic guidance. It also has the potential to reduce radiation exposure during fluoroscopy.

There are many factors driving health care reform, including unsustainable costs, poor outcomes, an aging populace, and physician shortages. These issues are particularly relevant to neurology. New reimbursement models are based on value and facilitated by the use of multidisciplinary teams. Integration of advanced practice providers (APPs) into neurology practice offers many advantages with new models of care. Conversely, there are many and varied challenges financially and logistically with these practice models. The American Academy of Neurology has formed a Work Group to address the needs of both neurologists and neurologic APPs and monitor the effect of APPs on quality and cost of neurologic care.

Tenofovir disoproxil fumarate (Tenofovir DF) is a nucleotide analogue. This multicentre study reports retrospectively the long-term efficacy and safety data with tenofovir DF treatment in nucleosid(t)e-naive, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients. Thirty-one patients (11 females, 20 males) received 245 mg tenofovir DF per diem. All patients' initial serum hepatitis B virus (HBV) DNA levels were over 2,000 IU/ml. Serum alanine aminotransferase (ALT) levels, HBeAg, hepatitis B e antibodies (anti-HBe), hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (Anti-HBs), HBV DNA, creatinine and urea levels were evaluated at baseline, and at weeks 12, 24, 48 and 96 during therapy. Thirty-one patients completed 96 weeks of treatment. Mean age was 37.6 ± 9.4 years. The initial mean value of ALT was 79 ± 39.9 IU/L. At baseline, mean of fibrosis (Ishak) of liver biopsies was 2.3 ± 0.7. Two of the patients (5.9%) achieved HBV DNA less than 300 copies at week 12 of treatment and 97.1 % at week 96. HBeAg loss was observed in 6.7% of patients. At week 96, HBsAg loss was not observed in any of the patients. Mean ALT at week 48 was 32.7 U/L, at week 96 32.6 U/L. Renal safety was good. Creatinine remained stable. Tenofovir DF was well tolerated and produced potent, continuous viral suppression with increasing HBeAg loss.

Forensic DNA casework is currently regarded as one of the most important types of forensic evidence, and important decisions in intelligence and justice are based on it. However, errors occasionally occur and may have very serious consequences. In other domains, error rates have been defined and published. The forensic domain is lagging behind concerning this transparency for various reasons. In this paper we provide definitions and observed frequencies for different types of errors at the Human Biological Traces Department of the Netherlands Forensic Institute (NFI) over the years 2008-2012. Furthermore, we assess their actual and potential impact and describe how the NFI deals with the communication of these numbers to the legal justice system. We conclude that the observed relative frequency of quality failures is comparable to studies from clinical laboratories and genetic testing centres. Furthermore, this frequency is constant over the five-year study period. The most common causes of failures related to the laboratory process were contamination and human error. Most human errors could be corrected, whereas gross contamination in crime samples often resulted in irreversible consequences. Hence this type of contamination is identified as the most significant source of error. Of the known contamination incidents, most were detected by the NFI quality control system before the report was issued to the authorities, and thus did not lead to flawed decisions like false convictions. However in a very limited number of cases crucial errors were detected after the report was issued, sometimes with severe consequences. Many of these errors were made in the post-analytical phase. The error rates reported in this paper are useful for quality improvement and benchmarking, and contribute to an open research culture that promotes public trust. However, they are irrelevant in the context of a particular case. Here case-specific probabilities of undetected errors are needed. These should be reported, separately from the match probability, when requested by the court or when there are internal or external indications for error. It should also be made clear that there are various other issues to consider, like DNA transfer. Forensic statistical models, in particular Bayesian networks, may be useful to take the various uncertainties into account and demonstrate their effects on the evidential value of the forensic DNA results., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)