The Role of Youth Coping Strategies and Caregiver Psychopathology in Predicting Posttraumatic Stress Symptoms in Pediatric Burn Survivors.
Caregiver psychosocial functioning is repeatedly linked with postburn adjustment in pediatric burn survivors. However, few studies have examined youth characteristics as predictors, such as coping strategies. Furthermore, research has not explored how caregiver psychopathology and youth coping strategies interact to predict youth postburn adjustment. The aim of this study was to examine how youth coping strategies and caregiver anxiety and depression predict youth posttraumatic stress symptoms (PTSS). Forty-six youth between 7 and 17 years old (M = 12.5, SD = 2.65) and their caregivers were recruited from two U.S. burn centers. Youth and parents completed questionnaires that assessed demographics, caregiver anxiety, and depression, youth self-reports of coping strategies, and youth PTSS. Burn injury data (e.g. TBSA, time since injury) was obtained from medical record reviews. Hierarchical regressions were conducted with caregiver psychopathology (depression, anxiety), youth coping strategies (active, avoidant, distraction, social support), and the interaction between caregiver psychopathology and youth coping strategies as predictors and youth PTSS as the outcome variable. Higher levels of caregiver anxiety (βs = .36 to .42) and avoidance coping (βs = .38 to .43) were associated with more PTSS. Caregiver anxiety and depression moderated the association between youth use of distraction coping and youth PTSS. These findings reinforce the importance of assessing psychosocial functioning in pediatric burn survivors and their caregivers, and providing interventions to promote better psychosocial outcomes. Coping strategies may help reduce PTSS and buffer against the harmful influence of caregiver psychopathology. Future research may wish to pilot interventions that promote healthy coping.


Integral dose to the carotid artery in intensity modulated radiotherapy of carcinoma nasopharynx: extended field IMRT versus split-field IMRT.
To evaluate the integral dose to carotid vessels in extended field intensity modulated radiotherapy (IMRT) (including the lower neck nodes in IMRT field) and split field IMRT (using separate single anterior field to treat lower neck nodes) in cancer nasopharynx. Dosimetric data from 10 patients of carcinoma nasopharynx, undergoing IMRT, were evaluated in this prospective study. The carotid vessels were contoured from sternoclavicular joints upto the base of skull. IMRT plans were generated for all patients with extended field and split field IMRT techniques using nine coplanar beams with 6 MV photons. A dose of 70 Gy to planning target volume (PTV) 70 Gy, 59.4 Gy to PTV 59.4 Gy and 54 Gy to PTV 54 Gy was delivered in 33 fractions. The dose constraints were similar for both the techniques. The integral dose to the carotid arteries was calculated as the mean dose times the volume (mean dose Χ volume) in units of liter-gray. The mean dose to the carotid vessels in the extended field IMRT was 63.88 ± 0.97 Gy (mean dose ± SD) and it was 64.43 ± 0.73 Gy for the split field technique. The integral dose in the extended field versus split field technique was 0.29 ± 0.0207 and 0.32 ± 0.0213 liter-gray, respectively. The difference was statistically significant (P < 0.013). Extended field IMRT delivers a slightly lower integral dose to carotid arteries in treatment of cancer nasopharynx while maintaining good dose homogeneity to the PTV 54 Gy and can be preferred over split field radiotherapy.


The Patient Typology about deprescribing and medication-related decisions: A quantitative exploration.
This study aimed to test the adequacy of a quantitative measure of our qualitatively developed Patient Typology-categories of older adults' attitudes towards medicines and medicine decision-making-and identify characteristics associated with each Typology. We conducted secondary data analyses of a subset of survey item measures of adults (≥65 years) who were members of online survey panels in Australia, the United Kingdom, the United States and the Netherlands (n = 4688). Multinomial logistic regression analyses assessed associations between demographic, psychosocial and medication-related measures. Mean age was 71.5 (5), and 47.5% of participants were female. Factors associated with an increased likelihood of identifying with Typology 1 'Attached to medicines' over Typology 2 'Open to deprescribing' were higher positive attitude towards polypharmacy (RRR = 1.12, p = <0.001) and higher need for certainty (RRR = 1.11, p = 0.039). Factors associated with an increased likelihood of identifying with Typology 3 'Defers (medication decision-making) to others' over Typology 2 were older age (RRR = 1.47 per 10-year age increase, p = <0.001) and a decreased likelihood of prior deprescribing experience (RRR = 0.73, p = 0.033). This study provides validation of the Typology with large samples from four countries, with the quantitatively-measured typologies generally aligning with the qualitatively derived categories. Our Patient Typology measure provides a succinct way researchers can assess attitudes towards deprescribing.


fusB is an allele of nadD, encoding nicotinate mononucleotide adenylyltransferase in Escherichia coli.
Isolation of the temperature-sensitive Escherichia coli mutant 72c has been described previously. The mutant allele was named fusB and causes a pleiotropic phenotype, the most striking features of which, besides temperature sensitivity, are the inability to grow on synthetic medium and supersensitivity to trimethoprim, an antibiotic that inhibits the C1 metabolism. This work shows that the fusB mutation is a frameshift mutation in the nadD gene that encodes nicotinate mononucleotide adenylyltransferase. The frameshift leads to a change of the last 10 amino acids and an addition of 17 amino acids. This lesion, renamed nadD72, leads to very little NAD+ and NADPH synthesis at the permissive temperature and essentially no synthesis at the non-permissive temperature. As a comparison, a new mutation in the nadD gene, with an amino acid change in the ATP-binding site, has been isolated. Its NAD+ synthesis is decreased at 30 degrees C but the level is still sufficient to support normal growth. At 42 degrees C, NAD+ synthesis is reduced further, which leads to temperature sensitivity on minimal medium. This mutation was designated nadD74. Thus, a small decrease in NAD+ levels affects ability to grow on minimal medium at 42 degrees C, while a large decrease leads to a more pleiotropic phenotype.


Collection of blood in heparinized tubes does not alter the molecular distribution or forms of IGFBP-3 and IGF.
The major serum carrier of the insulin-like growth factors (IGFs) is IGF-binding protein-3 (IGFBP-3) that exists in the circulation associated with IGF and an acid labile subunit to form a ternary (158-kDa) complex. It has been reported that heparin disrupts the IGF carrying capacity of the ternary complex and is a potent inhibitor of ternary complex reformation (Clemmons et al., 1983; Baxter, 1990). Thus, the aim of this study was to determine if, in a clinical setting where blood may be collected in both nonheparinized and heparinized tubes, heparin alters the molecular distribution or immunoreactive measurement of IGFBP-3 and IGF-I. Two different collection modalities were examined: protocol 1, blood was drawn and immediately centrifuged and aliquotted; and protocol 2, blood was drawn, left at room temperature for 2 h and then at 4°C overnight prior to centrifugation. Samples were drawn from a normal adult and from a growth hormone-deficient (GHD) child and subjected to neutral size-exclusion chromatography to separate the ternary 158-kDa complex from the binary IGFBP-3-IGF (approx 50 kDa) complex. Fractions were then subjected to Western ligand blot (WLB), western immunoblot (WIB), and measurement of IGFBP-3 by immunoradiometric assay (IRMA), while the IGF distribution was measured by radioimmunoassay (RIA) following acidic size-exclusion chromatography. In both serum and plasma of a normal adult, WLB detected a 45-40-kDa IGFBP-3 doublet eluting primarily within the 158-kDa IGFBP region (i.e., ternary complex). Similarly, assessment of immunoreactive IGFBP-3 by WIB showed a 45-40-kDa IGFBP-3 doublet, as well as a 29 kDa immunoreactive form primarily eluting in the 158-kDa IGFBP region of the chromatography. Measurement of IGFBP-3 by IRMA confirmed these findings. No difference between serum and plasma was detected in either collection protocol. RIA of IGF-I revealed that the ternary complex carried the majority of the circulating IGF-I and that there was no difference between serum and plasma. Assessment of serum and plasma of a GHD child showed reduced serum concentrations of IGFBP-3 but no difference in the IGFBP profiles between serum and plasma. These data demonstrate that the collection of blood in heparinized tubes does not alter the molecular distribution or forms of IGFBP-3 and IGF-I.


Radionuclide imaging of soft tissue masses with Tc-99m DTPA.
A scintigraphic study was carried out on 48 patients presenting with palpable soft tissue masses. Imaging was carried out using Tc-99m DTPA in three phases (dynamic, blood pool after 5 minutes, followed by late scans after 2 hours). The resultant uptake of the agent was categorized as consistently positive (14 cases), initially positive but progressively negative (7 cases), initially negative but progressively positive (7 cases), and consistently negative (20 cases). Histopathologic examinations were carried out for all cases following biopsy. A variety of malignant and benign masses were found to localize DTPA, whereas all masses that did not concentrate the agent were proven to be lipomas. In order to determine whether the uptake of DTPA bore any relationship to blood flow, additional studies using Tc-99m labeled red cells were carried out on 15 patients with soft tissue tumors. There was no correlation between blood flow or pooling and the degree of Tc-99m DTPA uptake by the palpable masses. The sensitivity of DTPA uptake as indicative of nonlipomatous tissue was 100%, and its specificity was 91%. The predictive probability that a lesion was a liopoma if there was no DTPA uptake at any phase was 100%.


Improved speedup bounds for parallel alpha-Beta search.
In this paper we investigate the ``mandatory-work-first'' approach to parallel alpha-beta search first proposed by Akl, Barnard, and Doran. This approach is based on a version of alpha-beta search without deep cutoffs and a two-stage evaluation process, the second stage of which is often pruned. Our analysis shows that for best-first ordering on the lookahead tree, this approach provides greater speedup than the Palphabeta tree-splitting technique, and that for worst-first ordering, mandatory work first provides only slightly worse speedup than Palphabeta.


Ventromedial hypothalamic lesions impair glucoregulation in response to endotoxin.
The purpose of the present study was to determine the role of the ventromedial hypothalamus (VMH) in regulating counter-regulatory hormone release and the increase in glucose flux that is observed after injection of endotoxin [lipopolysaccharide (LPS)]. Bilateral lesions of the VMH were produced electrolytically 2 wk before the experiment; sham-operated rats served as controls. [3-3H]glucose was infused to assess whole body glucose flux before and for 4 h after intravenous injection of Escherichia coli LPS. In control rats, LPS increased the plasma concentrations of glucose and lactate and the rates of glucose appearance and disappearance. In these animals, LPS also produced sustained elevations in corticosterone, glucagon, and catecholamines. In contrast, the glucose metabolic response to LPS was attenuated by > 50% in VMH-lesioned rats. These changes were associated with a blunted increase in the plasma concentration of glucagon, epinephrine, and norepinephrine in VMH-lesioned rats compared with control animals. There was no difference in the plasma concentrations of corticosterone or TNF-alpha between the two groups after LPS or the responsiveness of sham- and VMH-lesioned rats to an infusion of either glucagon or epinephrine. These data indicate that the VMH plays a central role in regulating the secretion of glucagon and catecholamines and the stimulation of glucose flux after LPS.


Downregulation of CRHBP is associated with trophoblast invasion inhibition in recurrent pregnancy loss.
Corticotropin-releasing hormone binding protein (CRHBP) is fundamental to the stress response and plays an important role in parturition during pregnancy. This study shows that abnormal CRHBP expression could be an early warning sign of recurrent pregnancy loss and that CRHBP knockdown could suppress HTR8/SVneo cell invasion by the PKC signaling pathway via interacting with CRH receptor 2. Trophoblast invasion is critical for placentation and pregnancy success. Trophoblast dysfunction results in many pregnancy complications, including recurrent pregnancy loss (RPL). Corticotropin-releasing hormone binding protein (CRHBP) is fundamental to the stress response and plays an important role in parturition during pregnancy via binding with CRH. To further characterize its function in early pregnancy, we explored the expression of CRHBP in villi during early pregnancy. Compared with normal pregnant women, we demonstrated that the expression of CRHBP decreased in the trophoblasts and villi in RPL patients and that knockdown of CRHBP expression could suppress HTR8/SVneo cell invasion significantly. Our further exploration indicated that the capacity of CRHBP for regulating trophoblast invasion was associated with the PKC signaling pathway via interacting with CRH receptor 2. These findings might provide a new fundamental mechanism for successful pregnancy and a new diagnostic and therapeutic target for RPL.


German recommendations for critically ill patients with COVID‑19.
Since December 2019, a novel coronavirus (severe acute respiratory syndrome-coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The majority of patients presents with mild symptoms of coronavirus disease 2019 (COVID-19). However, about 5% become critically ill and require intensive care treatment. Acute hypoxemic failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to ICU admission. At that point, bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS). To date there is no specific treatment available-the main goal of supportive therapy is to ascertain adequate oxygenation. Early intubation and repeated prone positioning are key elements in treating hypoxemic COVID-19 patients. Strict adherence to basic infection control measures (including hand hygiene) and use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be avoided where possible and carried out with utmost precaution.


Cricotracheal resection in children weighing less than 10 kg.
To review cricotracheal resection (CTR) in children weighing less than 10 kg. Retrospective study of 17 patients (mean follow-up, 23 months) from 3 ear, nose, and throat pediatric centers. Seventeen children (10 boys and 7 girls; mean age, 14.6 months; and mean weight, 7.6 kg) undergoing CTR from June 1995 to March 2003. Decannulation rates and endoscopies. The cause was congenital subglottic stenosis in 2 children (12%) and acquired subglottic stenosis in 15 (88%). All but 1 had grade 3 or 4 stenosis. The mean hospitalization duration was 34 days. Single-stage CTR was performed in 11 children (65%), with peroperative decannulation in 7. Extubation of these patients occurred between days 3 and 9. Decannulation of the other 6 patients was performed after a median of 15 days. Sixteen (94%) of the 17 children were decannulated. Four patients required additional carbon dioxide laser treatment for subsequent glottic or subglottic edema or granulomas, but no reintubation was necessary. One child could not be decannulated because of bronchopulmonary disease, and subglottic stenosis recurred. Long-term tracheotomy was avoided in all other patients. Another child died of cardiac disease. All other patients remained free of significant subglottic stenosis at follow-up. Cricotracheal resection in small children weighing less than 10 kg was a safe and effective procedure for severe subglottic stenosis. To our knowledge, this is the first reported attempt of CTR in this weight category, providing results comparable to those published in older children.


An appraisal of endoscopic retrograde cholangiopancreatography (ERCP) for pancreaticobiliary disease in children: our institutional experience in 231 cases.
Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool used by clinicians in the diagnosis and management of pancreaticobiliary disease. The safety and utility of ERCP for adults has been well documented. However, experience with ERCP for pediatric patients remains limited. This study aimed to examine the utility and safety of ERCP for diagnosis and therapy in pediatric surgical conditions. An institutional review board-approved retrospective chart review of all children younger than 21 years who underwent ERCP at a single children's hospital between 1992 and 2008 was performed. Age, sex, medical history, presenting symptoms, laboratory values, and discharge diagnoses were recorded. The ERCP findings, interventions performed, complications, and associated surgical procedures also were recorded. A total of 231 ERCPs were performed for 167 children (98 girls and 69 boys) ages 62 days to 21 years. The mean patient age was 11.4 years, with 11% (n = 18) of the ERCPs performed for children younger than 2 years. Common indications for ERCP included chronic or recurrent pancreatitis (n = 106), acute pancreatitis (n = 42), and choledocholithiasis (n = 26). Additional indications included choledochal cyst (n = 2), congenital biliary obstruction (n = 2), and malignant biliary obstruction (n = 1). Therapeutic interventions were performed in 159 cases (69%) including sphincterotomy (n = 96), stone extraction (n = 55), and stent insertion (n = 52). Complications occurred for only 11 patients (4.76%), including 7 cases of post-ERCP pancreatitis. The use of ERCP for imaging resulted in surgical procedures in 58 cases. Endoscopic retrograde cholangiopancreatography was used most commonly for children with pancreatitis and gallstone disease. It was used frequently for infants with a low complication rate. The majority of patients required therapeutic intervention, suggesting an important role for ERCP in the management of pancreaticobiliary disease in infants and children.


Endoscopic gastric polypectomies.
Results of 48 consecutive endoscopic gastric polypectomies were reviewed. The most frequent complaint initiating diagnostic workup was epigastric discomfort. Hyperplastic polyps predominated, followed by adenomatous polyps, carcinoids, and other. Two adenomatous polyps contained foci of in situ malignant change. The low incidence of malignant change in adenomatous polyps (17%) can be accounted for by the smaller size (mean 1.4 cm) than that in other reports. No malignancy was found in or in conjunction with hyperplastic site (two) and poor patient compliance (one)--and no deaths. Endoscopic gastric polypectomy has been demonstrated to be a safe and effective therapy for gastric polyps. For adenomatous gastric polyps, endoscopic removal when the polyp is less than 2 cm in diameter will yield a low incidence of malignant change.


A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging.
Previous reports have suggested that estrogen replacement therapy (ERT) in women may exert a protective effect on their risk of developing Alzheimer's disease (AD). We investigated this relationship in the Baltimore Longitudinal Study of Aging (BLSA), a prospective multidisciplinary study of normal aging conducted by the National Institute on Aging. The sample consisted of 472 post- or perimenopausal women followed for up to 16 years in the BLSA. We documented ERT prospectively at each BLSA visit, and we categorized women who had used oral or transdermal estrogens at anytime as ERT users. We used Cox proportional hazards models with time-dependent covariates to estimate the relative risk of developing AD after ERT as compared with women who had not used estrogen replacement. Approximately 45% of the women in the cohort had used ERT, and we diagnosed 34 incident cases of AD (NINCDS/ADRDA criteria) during follow-up, including nine estrogen users. After adjusting for education, the relative risk for AD in ERT users as compared with nonusers was 0.46 (95% CI, 0.209-0.997), indicating a reduced risk of AD for women who had reported the use of estrogen. Our data did not show an effect for duration of ERT usage. Our finding offers additional support for a protective influence of estrogen in AD. Randomized clinical trials are necessary to confirm this association, which could have significant public health impact.


Effects of 6/85-strain Mycoplasma gallisepticum vaccination alone at ten weeks of age or in conjunction with F-strain Mycoplasma gallisepticum inoculation overlays at twenty-two or forty-five weeks of age on the reproductive and digestive organs of commercial egg-laying hens.
Two trials were conducted to determine the effects of a prelay 6/85-strain Mycoplasma gallisepticum (6/85MG) vaccination alone or in conjunction with time-specific F-strain M. gallisepticum (FMG) inoculation overlays on the gross reproductive and digestive organ characteristics of commercial egg-laying hens. In each trial, the following 4 treatments were applied: 1) sham vaccination at 10 wk of age; 2) vaccination of 6/85MG at 10 wk; 3) 6/85MG at 10 wk overlaid by FMG inoculation at 22 wk; and 4) 6/85MG at 10 wk overlaid by FMG at 45 wk. Two birds per isolation pen (experimental replicate unit) were necropsied at the end of both trials to observe the effects of treatment on liver weight, liver lipid and moisture concentrations, incidence of fatty liver hemorrhagic syndrome, ovary weight, mature ovarian follicle numbers, and the total and segmental weights, lengths, and histologies of the oviduct and small intestine. The applied treatments affected only liver moisture. Liver moisture content was greater in birds vaccinated with 6/85MG at 10 wk alone or in conjunction with FMG at 45 wk in comparison with sham vaccinated controls and birds that received a 6/85MG vaccination at 10 wk overlaid by an FMG inoculation at 22 wk. Prelay 6/85MG vaccinations may be a suitable substitute for prelay FMG inoculations, and FMG overlays during lay on prelay 6/85MG vaccinations may also provide continual protection against field-strain MG infections without eliciting any subsequent suppressive effects on performance, as noted in an earlier study.


The D-alanine content of lipoteichoic acid is crucial for Lactobacillus plantarum-mediated protection from visceral pain perception in a rat colorectal distension model.
The mechanisms leading to positive effects of probiotics in irritable bowel syndrome and inflammatory bowel disease have not been clarified, but the possible involvement of cell wall components is widely discussed. Reduction of the D-alanine content of lipoteichoic acid (LTA) in Lactobacillus plantarum (Dlt(-) mutant) enhanced its anti-inflammatory properties in a mouse colitis model. Another lactobacillus species inhibited visceral pain perception in response to colorectal distension (CRD) in rats. Therefore, we investigated if LTA modification influences the constitutive intestinal pain perception in addition to modulation of cytokine release. Male Sprague-Dawley rats were gavaged with L. plantarum, L. plantarum Dlt(-) mutant or buffer control, respectively and the responses to CRD were tested in this non-inflammatory model. Tumour necrosis factor (TNF), interferon (IFN)-gamma and interleukin (IL)-10 release were measured in colon tissue homogenates and upon anti-CD3/CD28 activation of isolated splenocytes and mesenteric lymphocytes. Control animals showed significant bradycardia following noxious CRD, whereas only the L. plantarum Dlt(-) mutant inhibited the response. The mutant also decreased the activation-induced release of TNF and IFN-gamma from mesenteric T cells and the IL-10 concentration in colonic tissue, while increasing the activation-induced secretion of IL-10 in splenocytes and mesenteric lymphocytes and the baseline IL-10 release of splenocytes. In conclusion, d-alanine depletion of LTA in L. plantarum inhibited visceral pain perception in healthy, non-inflamed rats. Regardless of the non-inflammatory nature of the model decreased visceral pain perception was seen in parallel with anti-inflammatory properties.


Reprogramming and multi-lineage transdifferentiation attenuate the tumorigenicity of colorectal cancer cells.
Significant advances have been made in reprogramming various somatic cells into induced pluripotent stem cells (iPSCs) and in multi-lineage differentiation (transdifferentiation) into different tissues. These manipulable transdifferentiating techniques may be applied in cancer therapy. Limited works have been reported that cancer cell malignancy can be switched to the benign phenotypes through reprogramming techniques. Here, we reported that two colorectal cancer (CRC) cell lines (DLD1, HT29) could be reprogrammed into iPSCs (D-iPSCs, H-iPSCs). D- and H-iPSCs showed reduced tumorigenesis. Furthermore, we successfully induced D- and H-iPSCs differentiation into terminally differentiated cell types such as cardiomyocyte, neuron, and adipocyte-like cells. Impressively, the differentiated cells exhibited further attenuated tumorigenesis in vitro and in vivo. RNA-Seq further indicated that epigenetic changes occurred after reprogramming and transdifferentiation that caused reduce tumorigenicity. Overall, our study indicated that CRC cells can be reprogrammed and further differentiate to terminally differentiated lineages with attenuation of their malignancy in vitro and in vivo. The current work sheds light on a potential multi-lineage differentiation therapeutic strategy for colorectal cancer.


A novel test for host-symbiont codivergence indicates ancient origin of fungal endophytes in grasses.
Significant phylogenetic codivergence between plant or animal hosts (H) and their symbionts or parasites (P) indicates the importance of their interactions on evolutionary time scales. However, valid and realistic methods to test for codivergence are not fully developed. One of the systems where possible codivergence has been of interest involves the large subfamily of temperate grasses (Pooideae) and their endophytic fungi (epichloae). These widespread symbioses often help protect host plants from herbivory and stresses and affect species diversity and food web structures. Here we introduce the MRCALink (most-recent-common-ancestor link) method and use it to investigate the possibility of grass-epichloë codivergence. MRCALink applied to ultrametric H and P trees identifies all corresponding nodes for pairwise comparisons of MRCA ages. The result is compared to the space of random H and P tree pairs estimated by a Monte Carlo method. Compared to tree reconciliation, the method is less dependent on tree topologies (which often can be misleading), and it crucially improves on phylogeny-independent methods such as ParaFit or the Mantel test by eliminating an extreme (but previously unrecognized) distortion of node-pair sampling. Analysis of 26 grass species-epichloë species symbioses did not reject random association of H and P MRCA ages. However, when five obvious host jumps were removed, the analysis significantly rejected random association and supported grass-endophyte codivergence. Interestingly, early cladogenesis events in the Pooideae corresponded to early cladogenesis events in epichloae, suggesting concomitant origins of this grass subfamily and its remarkable group of symbionts. We also applied our method to the well-known gopher-louse data set.


Long-Term Audiometric and Clinical Outcomes Following Stapedectomy With the Shape Memory Nitinol Stapes Prosthesis.
To assess long-term hearing outcomes following stapedectomy using a self-crimping shape memory nitinol prosthesis. The results were compared with those of a group of patients who received a conventional prosthesis. Retrospective case review. Tertiary referral center. All patients who underwent stapedectomy for otosclerosis between July 2001 and November 2008 with a minimum dataset of preoperative, early postoperative (≤2 yr), and late postoperative (≥6 yr) audiometry were included. Fifty-six patients with a nitinol prosthesis and 27 patients with a titanium prosthesis met the inclusion criteria. Stapedectomy using a nitinol or conventional prosthesis. Hearing outcomes by audiological assessment. Mean duration of follow up was 9.5 (standard deviation [SD] 1.4) years in the nitinol group and 12.6 (SD 2.1) years in the titanium group. The early and late mean postoperative air-bone gaps (ABGs) were 9.7 and 9.8 dB in the nitinol group and 11.0 and 12.6 dB in the titanium group, respectively. The proportion of patients achieving an ABG less than or equal to 20 dB at early and late follow up was 96% and 96% in the nitinol group and 92% and 86% in the titanium group respectively. The excellent closure of the ABG achieved at early follow up remains remarkably stable up to 12 years using a self-crimping shape memory nitinol prosthesis. There is no evidence that firm fixation of the hook around the long process of incus has a detrimental effect in the long-term.


Delegation can make (or break) your career.
Delegation is not a soft skill. Physician executives who do not delegate well and strategically cannot expect to achieve the top jobs now or in the future. It's not enough to have great communications skills to convey your vision. You won't achieve that vision alone; you must have a great team to bring that vision to fruition. However, you can't delegate your first and most important step--self-assessment. To maximize your strengths and minimize your weaknesses, you'll need a clear view of what makes you tick. Then start thinking about your executive role in these terms: Conceptualize work mandates as projects; choose people who are better than you for your team; and try to work yourself out of a job. By learning to delegate, physician executives can make their own careers (as well as those on their team) richer and more fulfilled.


Targeting Mitochondrial Dysfunction for the Treatment of Diabetic Complications: Pharmacological Interventions through Natural Products.
Diabetes mellitus is a chronic hyperglycemic condition with deleterious effects on microcirculation, resulting in diabetic complications. Chronic hyperglycemia induces the generation of reactive oxygen species (ROS), which are the key pathological triggers in the development of diabetic complications. ROS are responsible for the activation of various pathways involved in the genesis of diabetic complications, mitochondrial dysfunction, as well as insulin resistance. The review describes normal mitochondrial physiology and abnormal alterations, which occur in response to hyperglycemia. Mitochondrial biogenesis is a highly regulated process mediated by several transcription factors, wherein mitochondrial fusion and fission occur in harmony in a normal healthy cell. However, this harmony is disrupted in hyperglycemic condition indicated by alteration in functions of essential transcription factors. Hyperglycemia-induced mitochondrial dysfunction plays a key role in diabetic complications, pancreatic β-cell dysfunction, as well as skeletal muscle insulin resistance as demonstrated by various in vitro, preclinical, and clinical studies. The review focuses on the various factors involved in mitochondrial biogenesis and maintenance of healthy mitochondrial function. Several phytoconstituents act through these pathways, either directly by stimulating biogenesis or indirectly by inhibiting or preventing dysfunction, and produce a beneficial effect on overall mitochondrial function. These phytoconstituents have enormous potential in amelioration of diabetic complications by restoring normal mitochondrial physiology and need detailed evaluation by preclinical and clinical studies. Such phytoconstituents can be included as nutraceuticals or adjuvant therapy to the mainstream treatment of diabetes.


Group-beneficial traits, frequency-dependent selection and genotypic diversity: an antibiotic resistance paradigm.
The evolution of group-beneficial traits potentially allows the survival of 'cheaters' that would otherwise be unfit. Here we describe experimental work on group-beneficial traits and the consequences of frequency-dependent selection in the context of bacterial antibiotic resistance. We constructed a 'self-limited antibiotic resistant' (SLAR) strain of Escherichia coli in which a TEM-1 beta-lactamase was anchored to the inner membrane. In pairwise competition experiments between the SLAR strain and ampicillin-sensitive strains, only the SLAR strain survived in the presence of ampicillin. We also constructed a 'shared antibiotic resistant' (SAR) strain in which TEM-1 beta-lactamase protected both the SAR strain and nearby sensitive cells, thus acting as a model for a genetically defined group-beneficial trait. In pairwise competition experiments of the SAR strain against two different sensitive strains of E. coli, we found that the sensitive strains maintained themselves at frequencies of 5-12% in the presence of ampicillin. When the relative cost of the SAR strain was lowered, its equilibrial frequency rose. Sensitive strains also arose from pure cultures of the SAR strain. In these cases, too, the sensitive 'cheaters' were maintained in ampicillin at frequencies comparable to those observed in the previous competitions. These results suggest that traits which benefit other group members can permit survival of genotypes that otherwise would be eliminated by natural selection, and allow the maintenance of greater genetic variation upon which evolution can operate.


Dietary patterns and risk of cancer of the oral cavity and pharynx in Uruguay.
From 1995 to 2002, a case-control study on food groups and risk of cancer of the oral cavity and pharynx was conducted in Montevideo, Uruguay. Two hundred thirty cases were frequency-matched to 460 controls on age, residence, and urban/rural status. The study was restricted to men. The relationship between foods and risk of oral and pharyngeal squamous cell carcinoma was examined through: 1) individual food group analysis, 2) factor analysis, and 3) determination of empirical scores. The results were similar. Factor analysis generated 2 patterns, which were labeled as "stew" and "vegetables and fruits." The stew pattern loaded positively on boiled meat, cooked vegetables, potato, and sweet potato. This pattern was directly associated with risk of oral and pharyngeal cancer [odds ratio (OR), 3.75; 95% confidence interval (CI), 1.99-7.06; P value for trend=0.0002]. The vegetables and fruits factor loaded positively on raw vegetables, citrus fruits, other fruits, liver, fish, and desserts. This pattern was inversely associated with risk of oropharyngeal carcinoma (OR, 0.34; 95% CI, 0.18-0.64; P value for trend=0.0008). Joint effects of high intake of risk foods and low intake of protective foods were associated with a risk of 12.0 (95% CI, 4.1-34.6). Our study confirms the important role of dietary factors in oral and pharyngeal cancer risk and suggests that the analysis of dietary patterns is a powerful tool to investigate the links between nutrition and cancer.


Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in C. elegans.
Animal behavior is directed by the integration of sensory information from internal states and the environment. Neuroendocrine regulation of diverse behaviors of Caenorhabditis elegans is under the control of the DAF-7/TGF-β ligand that is secreted from sensory neurons. Here, we show that C. elegans males exhibit an altered, male-specific expression pattern of daf-7 in the ASJ sensory neuron pair with the onset of reproductive maturity, which functions to promote male-specific mate-searching behavior. Molecular genetic analysis of the switch-like regulation of daf-7 expression in the ASJ neuron pair reveals a hierarchy of regulation among multiple inputs-sex, age, nutritional status, and microbial environment-which function in the modulation of behavior. Our results suggest that regulation of gene expression in sensory neurons can function in the integration of a wide array of sensory information and facilitate decision-making behaviors in C. elegans.


The control of peroxidase-catalysed iodination and de-iodination.
It has been demonstrated that the H2O2/l ratio is a critical factor in the control of iodination and de-iodination of covalently bound tyrosyl residues in proteins and free iodotyrosines by peroxidase enzymes. This has been shown for myeloperoxidase (MPO) isolated from normal human polymorphonuclear lymphocytes in particular, and also for peroxidase of animal origin such as thyroid peroxidase (TPO) and lactoperoxidase (LPO). It has been shown that the H2O2/l ratio exerts a controlling influence on MPO-catalysed reactions of fully iodinated tyrosines, e.g. di-iodotyrosine, and of partially and completely iodinated thyronines such as thyroxine and tri-iodothyronine. Using an in vivo model system it has been shown that MPO catalyses the sequential events of iodination, iodine exchange and de-iodination of tyrosines and, furthermore, that all three reactions are influenced by the rate of H2O2 generation and the iodide concentration of the reaction medium. The action of MPO on iodothyronine substrates only affects de-iodination irrespective of whether the iodothyronine is partially iodinated, as in tri-iodothyronine, or completely iodinated, as in thyroxine. This MPO-catalysed de-iodination of thyroxine and tri-iodothyronine can also be regulated by the H2O2/l ratio. Moreover, the results show that MPO-catalysed iodine exchange can only occur in completely iodinated tyrosines such as di-iodotyrosine (DIT). Iodine exchange in partially iodinated tyrosines such as mono-iodotyrosine (MIT) or in iodothyronines (T3 and T4) cannot be catalysed by MPO irrespective of the H2O2/l ratio. These results introduce a new concept which may be important in understanding the control of thyroid activity in thyroid disease and the control of MPO activity in biological defence mechanisms in man.


Kidney paired donation: principles, protocols and programs.
Due to the ongoing shortage of deceased-donor organs, novel strategies to augment kidney transplantation rates through expanded living donation strategies have become essential. These include desensitization in antibody-incompatible transplants and kidney paired donation (KPD) programs. KPD enables kidney transplant candidates with willing but incompatible living donors to join a registry of other incompatible pairs in order to find potentially compatible transplant solutions. Given the significant immunologic barriers with fewer donor options, single-center or small KPD programs may be less successful in transplanting the more sensitized patients; the optimal solution for the difficult-to-match patient is access to more potential donors and large multicenter or national registries are essential. Multicenter KPD programs have become common in the last decade, and now represent one of the most promising opportunities to improve transplant rates. To maximize donor-recipient matching, and minimize immunologic risk, these multicenter KPD programs use sophisticated algorithms to identify optimal match potential, with simultaneous two-, three- or more complex multiway exchanges. The article focuses on the recent progresses in KPD and it also reviews some of the differences and commonalities across four different national KPD programs.


Efficiency of physical therapy on postural imbalance after stroke: study protocol for a systematic review and meta-analysis.
Stroke frequently results in balance disorders, leading to lower levels of activity and a diminution in autonomy. Current physical therapies (PT) aiming to reduce postural imbalance have shown a large variety of effects with low levels of evidence. The objectives are to determine the efficiency of PT in recovering from postural imbalance in patients after a stroke and to assess which PT is more effective. We will search several databases from inception to October 2015. Only randomised controlled trials assessing PT to recover from poststroke postural imbalance in adults will be considered.Outcome measures will be the Berg Balance Scale (BBS), the Postural Assessment Scale for Stroke (PASS), the 'weight-bearing asymmetry' (WBA), the 'centre of pressure' (COP) and the 'limit of stability' (LOS). WBA, COP and LOS are measured by a (sitting or standing) static evaluation on force plate or another device.Two independent reviewers will screen titles, abstracts and full-text articles, evaluate the risk of bias and will perform data extraction. In addition to the outcomes, measures of independence will be analysed. This study will aim at determining the effects of PT on the function (WBA, COP, LOS), the activity (BBS, PASS) and the independence of patients. Subgroup analyses will be planned according to the location of brain lesion (hemispheric, brainstem or cerebellum), the time since stroke (early, late, chronic), the PT (type, main aim (direct effect or generalisation), overall duration), the type of approaches (top-down or bottom-up) and the methodological quality of studies. No ethical statement will be required. The results will be published in a peer-reviewed journal. This meta-analysis aims at managing the rehabilitation after postural imbalance by PT after a stroke. Prospero CRD42016037966;Pre-results.


Long-term stability of circumferential silicone sponge scleral buckling exoplants.
The historical extrusion/explantation rate of silicone sponge scleral buckle exoplants is 3.5 to 24.4%. This contrasts with the published 0.6 to 1.2% explantation rate of solid silicone elements. Previously reported silicone sponge exoplants studies were noncircumferential (quadrantic or multiple). This study was undertaken to assess the long-term stability of 360 degrees circumferentially placed 3 x 5 mm silicone sponge exoplants. Interventional case series of 840 consecutive circumferentially placed 3 x 5 mm silicone sponge exoplants. A retrospective review of operative reports and patient charts was performed. A total of 552 patients had documented follow-up over 1 year. Median follow-up was 32.8 months. Six patients underwent removal of the scleral buckling element (two for diplopia, one acute postoperative infection, and three for extrusion). Median time to removal was 7.3 months. Extenuating circumstances contributed to two of the three extrusions. Of the entire series, fewer than 1% of patients required removal of the silicone sponge implant. Excluding patients with less than 1 year of documented follow-up, the long-term infection/extrusion rate was 0.7%. Circumferentially placed silicone scleral buckling sponge elements are very stable and are well tolerated. The explantation/extrusion rate is comparable to published solid silicone element series.


Model Selection of Nested and Non-Nested Item Response Models Using Vuong Tests.
In this paper, we apply Vuong's general approach of model selection to the comparison of nested and non-nested unidimensional and multidimensional item response theory (IRT) models. Vuong's approach of model selection is useful because it allows for formal statistical tests of both nested and non-nested models. However, only the test of non-nested models has been applied in the context of IRT models to date. After summarizing the statistical theory underlying the tests, we investigate the performance of all three distinct Vuong tests in the context of IRT models using simulation studies and real data. In the non-nested case we observed that the tests can reliably distinguish between the graded response model and the generalized partial credit model. In the nested case, we observed that the tests typically perform as well as or sometimes better than the traditional likelihood ratio test. Based on these results, we argue that Vuong's approach provides a useful set of tools for researchers and practitioners to effectively compare competing nested and non-nested IRT models.


Calcium antagonists.
Drugs which interfere with the voltage-activated inward displacement of calcium ions into excitable cells, including those of the myocardium, atrial and ventricular nodes, and smooth muscle cells, have become known as calcium antagonists. These drugs are a heterogeneous group, and differ from one another in chemistry, tissue specificity, potency and bioavailability. The prototype of the group is verapamil. Other calcium antagonists are nifedipine and diltiazem. The therapeutic applications of these compounds include the relief of angina pectoris, and the management of hypertension, ischaemic heart disease and, in certain instances, arrhythmias. Calcium antagonists are also useful in the management of oesophageal achalasia, Raynaud's disease, and hypertrophic obstructive cardiomyopathy, and may be of use in premature labour.


Arthroscopic Posteromedial Capsular Release.
Post-traumatic or postsurgical flexion contractures of the knee can significantly limit function and lead to gait abnormalities. In this setting, interventions to regain full extension may include bracing, physical therapy, and open or arthroscopic surgery. Open surgical approaches to restore full motion often demand extensive recovery and promote further adhesions and loss of motion, which has led to the advent of arthroscopic techniques to address these pathologies. We present a safe, effective, and reproducible arthroscopic technique for posteromedial capsular release to address knee flexion contractures.


Planned place of birth in New Zealand: does it affect mode of birth and intervention rates among low-risk women?
Midwives providing care as lead maternity caregivers in New Zealand provide continuity of care to women who may give birth in a variety of settings, including home, primary units, and secondary and tertiary level hospitals. The purpose of this study was to compare mode of birth and intrapartum intervention rates for low-risk women planning to give birth in these settings under the care of midwives. Data for a cohort of low-risk women giving birth in 2006 and 2007 were extracted from the Midwifery Maternity Provider Organisation database. Mode of birth, intrapartum interventions, and neonatal outcomes were compared with results adjusted for age, parity, ethnicity, and smoking. Women planning to give birth in secondary and tertiary hospitals had a higher risk of cesarean section, assisted modes of birth, and intrapartum interventions than similar women planning to give birth at home and in primary units. The risk of emergency cesarean section for women planning to give birth in a tertiary unit was 4.62 (95% CI: 3.66-5.84) times that of a woman planning to give birth in a primary unit. Newborns of women planning to give birth in secondary and tertiary hospitals also had a higher risk of admission to a neonatal intensive care unit (RR: 1.40, 95% CI: 1.05-1.87; RR: 1.78, 95% CI: 1.31-2.42) than women planning to give birth in a primary unit. Planned place of birth has a significant influence on mode of birth and rates of intrapartum intervention in childbirth.


First- and second-year aboveground growth and productivity of two Populus hybrids grown at ambient and elevated CO(2).
Two hybrid poplar (Populus) clones (the fast-growing clone Beaupré (P. trichocarpa Torr. and Gray x P. deltoides Bartr. ex Marsh.) and the slow-growing clone Robusta (P. deltoides Bartr. ex Marsh. x P. nigra L.)) were grown from hardwood cuttings for one or two growing seasons (1993-1994) in either ambient or elevated (= ambient + 350 micro mol mol(-1)) CO(2) in open-top chambers at the University of Antwerpen. Both clones responded positively to the elevated CO(2) treatment with increased stem volume and aboveground biomass production; however, the clones exhibited different response strategies to the elevated CO(2) treatment, and the responses varied with cutting age and duration of exposure. Clone Beaupré responded to the elevated CO(2) treatment with increases in leaf area and leaf area index during both the first and second growing seasons, but little increase in height growth. Clone Robusta exhibited increased height growth, leaf biomass and total leaf nitrogen content in response to elevated CO(2), but no increase in leaf area index. The elevated CO(2) treatment increased the total number of branches and total branch biomass in both clones during both growing seasons. At the end of the first growing season, woody stem biomass of the fast- and slow-growing clones was increased by 38 and 55%, respectively. At the end of the second growing season, stem volume was increased by 43% in clone Beaupré and by 58% in clone Robusta. The increase in stem volume was a result of the stimulation of both height and diameter growth in the slow-growing clone, whereas only height growth was stimulated in the fast-growing clone. In the fall of the first growing season, the average date of bud set in clone Robusta was advanced by 4 days in the elevated CO(2) treatment; there were no other significant effects of the elevated CO(2) treatment on bud set. The elevated CO(2) treatment enhanced leaf C/N ratios in both clones in both years.


[Forensic-medical assessment of irritant distribution on the target in gas firearm shots].
Distribution of irritant on the target after a shot from a 99 mm gas gun ME-38 COMPACT from different distances and gas gun MAUZER (a 9 mm HSc model) in use of different ammunition was studied. There is a correlation between irritant distribution characteristics, distance of shot and cartridge brand.


Where does IT fit in your practice? Information technology trends.
The future role of information technology in the medical industry is never clear, but we can identify some trends, such as electronic medical records and database management systems. Many of these trends can boost productivity for practices, but all managers need to carefully analyze their needs and understand the products to see how they may or may not help their individual practice.


[Neurobiological foundations of thought and language disorder in schizophrenia].
Alterations in thought and language are core symptoms of schizophrenia. Studies with structural and functional imaging (fMRI) as well as magneto/electroencephalography (EEG, MEG) on language in schizophrenia are reviewed which will help to reveal the correlates of formal thought disorder (FTD) and concretism. A model will be presented, where brain structure, function, receptorchemistry, cognitive deficits and psychopathology of language related phenomena are integrated. Positive formal thought disorder is correlated with a "functional" lesion in the superior temporal gyrus, part of Wernickes area. There is secondly a dysfunction of the semantic network, which is due to a language lateralisation deficit in the lateral temporal lobe in FTD. Further, a dysfunctional verbal self monitoring and error correction process in part responsible for FTD. Taken together, there is much evidence that the lateral temporal lobes bilaterally are predominantly involved in the generation of positive formal thought disorder in schizophrenia.


[Giant tongue leading to dysphagia in light chain amyloidosis patient].
Macroglossia as a clinical manifestation of systemic amyloidosis is a rare condition, occurring in less than 9% of all types of amyloidosis. The aim of this report is to present the diagnostic approach of a patient with macroglossia, providing a systematic approach and considering relevant diagnostic possibilities during their evaluation. We present the case of a 60-year-old man who presented with a progressively enlarging giant tongue for six months, causing dysphagia and reduced oral opening. A tongue biopsy was taken, which histopathologically exhibited homogenous eosinophilic amyloid-like material. Congo red staining showed amyloid material with red dye under light microscopy and apple-green birefringence under polarized light. Bone marrow biopsy showed 30% plasma cells, allowing for a definitive diagnosis of soft tissue amyloidosis. Although it is a benign lesion, localized amyloidosis should be differentiated from systemic forms. The approach of patients with macroglossia is complex due to the diagnostic possibilities, from endocrinological causes, neoplastic, and even by deposit; Being an isolated sign in a patient is a challenge in its approach, because the involvement of the airway is the main complication to avoid in these patients.


Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.
Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT). Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.


Alcohol abuse and dependence in a national sample of psychiatric patients.
To examine clinical characteristics and services being provided to Alcohol Abuse/Dependent (AAD) patients in current psychiatric practice. In a national sample of psychiatrists (N = 417), each provided data on three preselected patients (N = 1,245; 51.8% women) that included demographics, DSM-IV diagnoses, treatment setting and health-plan measures. Logistic regression was used to compare patients with and without an AAD diagnosis. Only 12% of patients (n = 151) had an AAD diagnosis. AAD patient care was more frequently subject to utilization review and restriction or specification of medications to be prescribed (formulary). Psychiatrists also perceived greater restrictions on AAD patient care (e.g., requirements to use specific practice guidelines or treatment algorithms). Findings suggest that health care systems are subjecting treatment patients with AAD to greater scrutiny and may be limiting the extent and nature of care provided to these patients. The low prevalence of AAD among patients being seen by psychiatrists also warrants further attention. Study findings highlight the utility of practice-based research in addiction psychiatry.


Ketoconazole therapy for systemic fungal infections: inadequacy of standard dosage regimens.
We treated 29 patients with ketoconazole for systemic mycoses. Twenty-two had coccidioidomycosis, 5 had histoplasmosis, and 2 had sporotrichosis. Of the 25 patients who received 200 mg/day, 16% improved on that dose. Of 17 patients who did not improve on 200 mg/day, 71% responded after the dose was increased to 400 or 800 mg/day. Treatment periods ranged from 21 days to more than 600 days. Five patients relapsed. In 2, ketoconazole had been reduced in dose or discontinued. In 3, the drug was still being given. Ketoconazole is effective in suppressing disease in various mycoses. However, patients may require high doses for prolonged periods to achieve maximal benefit.


The Effect of Message Framing on African American Women's Intention to Participate in Health-Related Research.
This study examined the effect of message framing on African American women's intention to participate in health-related research and actual registration in ResearchMatch (RM), a disease-neutral, national volunteer research registry. A community-engaged approach was used involving collaboration between an academic medical center and a volunteer service organization formed by professional women of color. A self-administered survey that contained an embedded message framing manipulation was distributed to more than 2,000 African American women attending the 2012 national assembly of The Links, Incorporated. A total of 391 surveys were completed (381 after exclusion: 187 containing the gain-framed message and 194 containing the loss-framed message). The majority (57%) of women expressed favorable intentions to participate in health-related research, and 21% subsequently enrolled in RM. The effect of message framing on intention was moderated by self-efficacy. There was no effect of message framing on RM registration; however, those with high self-efficacy were more than 2 times as likely as those with low self-efficacy to register as a potential study volunteer in RM (odds ratio = 2.62, 95% confidence interval [1.29, 5.33]). This investigation makes theoretical and practical contributions to the field of health communication and informs future strategies to meaningfully and effectively include women and minorities in health-related research.


The active FMR1 promoter is associated with a large domain of altered chromatin conformation with embedded local histone modifications.
We have analyzed the effects of gene activation on chromatin conformation throughout an approximately 170-kb region comprising the human fragile X locus, which includes a single expressed gene, FMR1 (fragile X mental retardation 1). We have applied three approaches: (i) chromosome conformation capture, which assesses relative interaction frequencies of chromatin segments; (ii) an extension of this approach that identifies domains whose conformation differs from the average, which we developed and named chromosome conformation profiling; and (iii) ChIP analysis of histone modifications. We find that, in normal cells where FMR1 is active, the FMR1 promoter is at the center of a large ( approximately 50 kb) domain of reduced intersegment interactions. In contrast, in fragile X cells where FMR1 is inactive, chromatin conformation is uniform across the entire region. We also find that histone modifications that are characteristic of active genes occur tightly localized around the FMR1 promoter in normal cells and are absent in fragile X cells. Therefore, the expression-correlated change in conformation affects a significantly larger domain than that marked by histone modifications. Domain-wide changes in interaction probability could reflect increased chromatin expansion and may also be related to an altered spatial disposition that results in increased intermingling with unrelated loci. The described approaches are widely applicable to the study of conformational changes of any locus of interest.


Telephone-based depression self-management in Hispanic adults with epilepsy: a pilot randomized controlled trial.
Depression is associated with adverse outcomes in epilepsy but is undertreated in this population. Project UPLIFT, a telephone-based depression self-management program, was developed for adults with epilepsy and has been shown to reduce depressive symptoms in English-speaking patients. There remains an unmet need for accessible mental health programs for Hispanic adults with epilepsy. The purpose of this study was to evaluate the feasibility, acceptability, and effects on depressive symptoms of a culturally adapted version of UPLIFT for the Hispanic community. Hispanic patients with elevated depressive symptoms (n = 72) were enrolled from epilepsy clinics in New York City and randomized to UPLIFT or usual care. UPLIFT was delivered in English or Spanish to small groups in eight weekly telephone sessions. Feasibility was assessed by recruitment, retention, and adherence rates and acceptability was assessed by self-reported satisfaction with the intervention. Depressive symptoms (PHQ-9 scores) were compared between study arms over 12 months. The mean age was 43.3±11.3, 71% of participants were female and 67% were primary Spanish speakers. Recruitment (76% consent rate) and retention rates (86-93%) were high. UPLIFT participants completed a median of six out of eight sessions and satisfaction ratings were high, but rates of long-term practice were low. Rates of clinically significant depressive symptoms (PHQ-9 ≥5) were lower in UPLIFT versus usual care throughout follow-up (63% vs. 72%, 8 weeks; 40% vs. 70%, 6 months; 47% vs. 70%, 12 months). Multivariable-adjusted regressions demonstrated statistically significant differences at 6 months (OR = 0.24, 95% CI, 0.06-0.93), which were slightly reduced at 12 months (OR = 0.30, 95% CI, 0.08-1.16). Results suggest that UPLIFT is feasible and acceptable among Hispanic adults with epilepsy and demonstrate promising effects on depressive symptoms. Larger trials in geographically diverse samples are warranted.


Skin sensitization study of bee venom (Apis mellifera L.) in guinea pigs and rats.
Bee venom (Apis mellifera L., BV) possessing a rich source of pharmacologically active substances has the potential to be used as a cosmetic ingredient for antiaging, antiinflammatory and antibacterial functions. The aim of this study was to assess the skin sensitization of BV on experimental animals using the Buehler test. Guinea pigs were randomly allocated into three groups of BV-sensitization, positive control-sensitization, and ethyl alcohol-sensitization group for induction and challenge. On the other hand, two groups of rats were administered with BV at doses of 0 and 1500 mg/kg. Clinical signs, mortality and body weight changes were continually monitored during the study period. No treatment-related clinical signs or body weight changes were observed in both animal models. The average skin reaction evaluated by erythema and edema on the challenge sites, and sensitization rate in the BV-sensitization group of guinea pigs were substantially low compared with those in positive control group, representing a negligible sensitizing potential of BV. It was concluded that BV was well tolerated and exhibited no dermal irritation potential in guinea pigs and rats. Our findings may provide a developmental basis of BV for a cosmetic ingredient or external application for topical uses.


Effects of La Crosse virus infection on the host-seeking behavior and levels of two neurotransmitters in Aedes triseriatus.
La Crosse virus (LACV) infection has been shown to manipulate the blood-feeding behaviors of its main vector, Aedes triseriatus. Here, we investigated the effects of virus infection on serotonin and dopamine and their potential roles in host-seeking. In mosquitoes, serotonin depletion has been shown to interfere with blood-feeding but not host-seeking. Dopamine depletion does not affect either blood-feeding or host-seeking; elevations of dopamine, however, has been shown to inhibit host-seeking. The purpose of this study was to determine the effects of LACV infection on the host-seeking behavior of and neurotransmitter levels in Ae. triseriatus. Host-seeking behavior was evaluated using a uni-port olfactometer and a membrane feeder assay. Levels of serotonin and dopamine in infected and control mosquito heads were measured using HPLC-ED. Infection with LACV significantly inhibited the activation and attraction of Ae. triseriatus females to a host. A higher proportion of uninfected Ae. triseriatus females were activated by the presence of a host compared to infected mosquitoes and more uninfected mosquitoes were full responders (95.7%) compared to infected ones (91.1%). However, infection with LACV did not significantly affect the landing, probing, or blood-feeding rates of female mosquitoes. LACV-infected mosquitoes had lower serotonin levels than controls (104.5 vs 138.3 pg/head) while the dopamine levels were not affected by infection status (282.3 vs 237 pg/head). Our work suggests that virus-induced reduction of serotonin is related to previously reported blood-feeding alterations in LACV-infected mosquitoes and could lead to enhanced transmission and increased vectorial capacity. In addition, some aspects of host-seeking were inhibited by virus infection.


Developmental trajectories for young children with 16p11.2 copy number variation.
Copy number variation at 16p11.2 is associated with diverse phenotypes but little is known about the early developmental trajectories and emergence of the phenotype. This longitudinal study followed 56 children with the 16p11.2 BP4-BP5 deletion or duplication between the ages of 6 months and 8 years with diagnostic characterization and dimensional assessment across cognitive, adaptive, and behavioral domains. Linear mixed modeling revealed distinct developmental trajectories with deletions showing VIQ gains but declines in motor and social abilities while duplications showed VIQ gains and steady development across other domains. Nonparametric analyses suggest distinct trajectories and early cognitive abilities for deletion carriers who are ultimately diagnosed with intellectual disability and developmental coordination disorder as well as distinct trajectories and early social communication and cognitive abilities for duplication carriers diagnosed with ASD and intellectual disability. Findings provide predictions for patient developmental trajectories, insight into mean functioning of individuals with 16p11.2 at early ages, and highlight the need for ongoing monitoring of social and motor functioning and behavioral symptomatology to improve treatment planning. © 2017 Wiley Periodicals, Inc.


Cloning of CviPII nicking and modification system from chlorella virus NYs-1 and application of Nt.CviPII in random DNA amplification.
The cloning and expression of the CviPII DNA nicking and modification system encoded by chlorella virus NYs-1 is described. The system consists of a co-linear MTase encoding gene (cviPIIM) and a nicking endonuclease encoding gene (cviPIINt) separated by 12 nt. M.CviPII possesses eight conserved amino acid motifs (I to VIII) typical of C5 MTases, but, like another chlorella virus MTase M.CviJI, lacks conserved motifs IX and X. In addition to modification of the first cytosine in CCD (D = A, G or T) sequences, M.CviPII modifies both the first two cytosines in CCAA and CCCG sites as well. Nt.CviPII has significant amino acid sequence similarity to Type II restriction endonuclease CviJI that recognizes an overlapping sequence (RG--CY). Nt.CviPII was expressed in Escherichia coli with or without a His-tag in a host pre-modified by M.CviPII. Recombinant Nt.CviPII recognizes the DNA sequence CCD and cleaves the phosphodiester bond 5' of the first cytosine while the other strand of DNA at this site is not affected. Nt.CviPII displays site preferences with CCR (R = A or G) sites preferred over CCT sites. Nt.CviPII is active from 16 to 65 degrees C with a temperature optimum of 30-45 degrees C. Nt.CviPII can be used to generate single-stranded DNAs (ssDNAs) for isothermal strand-displacement amplification. Nt.CviPII was used in combination with Bst DNA polymerase I large fragment to rapidly amplify anonymous DNA from genomic DNA or from a single bacterial colony.


An Extraordinary Voice Expressed Through Humor: A Tribute to Casey Quinlan.
The Journal of Participatory Medicine introduces Extraordinary Lives, a new journal section celebrating the voices and work of steadfast advocates of participatory medicine that we have lost. This inaugural essay spotlights Casey Quinlan, a patient activist who effectively used her humor and incisive analysis of health care to encourage others to strive for meaningful change. A first-generation "professional patient," Casey served as a role model who inspired many to share their stories and achieve genuine partnerships in care delivery. A maker of "good trouble," her voice and stance were part of her power and influence in disrupting the status quo. We present her fight for personal access to health data, her aspiration for personally customized evidence, and her drive for all people to control their health and their health care.


[Self-expanding metallic endoprosthesis in the treatment of recurrent ureteral stenosis].
To describe two cases of recurrent fibrotic stricture of the uretero-vesical junction treated with a metallic self-expanding endoprosthesis which has successfully achieved patency of the stenotic area in the medium-term. Two cases of difficult ureteral stricture are described. Both cases presented obstruction of the terminal ureter by abundant fibrotic tissue in the bladder wall following radical prostatectomy in one case and TUR in the other for non-infiltrating bladder carcinoma. Several attempts to recover patency by endoscopic resection and placement of a double-J stent in these patients had previously failed. The patients were therefore submitted to resection of the fibrotic area and insertion of a self-expanding endoprosthesis (Wallstent), which was eventually enclosed by fibrous tissue at its vesical portion. Both cases underwent resection again and another endoprosthesis (Memotherm) was inserted to extend the previous prosthesis 1 cm within the bladder lumen. When the endoprosthesis is placed in the uretero-vesical junction with its tip flush with the bladder wall, it is eventually enclosed by fibrous tissue, which invariably leads to recurrent obstruction. We have found that extending the prosthesis 1 cm within the bladder lumen can overcome the foregoing complication, although the long-term results have as yet to be established.


Identification of an rsh gene from a Novosphingobium sp. necessary for quorum-sensing signal accumulation.
The stringent response is a mechanism by which bacteria adapt to environmental stresses and nutritional deficiencies through the synthesis and hydrolysis of (p)ppGpp by RelA/SpoT enzymes. Alphaproteobacteria and plants contain a single Rsh enzyme (named for RelA/SpoT homolog) that is bifunctional. Here we report the identification of a new species of bacteria belonging to the genus Novosphingobium and characterization of an rsh mutation in this plant tumor-associated isolate. Isolate Rr 2-17, from a grapevine crown gall tumor, is a member of the Novosphingobium genus that produces the N-acyl-homoserine lactone (AHL) quorum-sensing (QS) signals. A Tn5 mutant, Hx 699, deficient in AHL production was found to have an insertion in an rsh gene. The Rsh protein showed significant percent sequence identity to Rsh proteins of alphaproteobacteria. The Novosphingobium sp. rsh gene (rsh(Nsp)) complemented the multiple amino acid requirements of the Escherichia coli relA spoT double mutant by restoring the growth on selection media. Besides QS signal production, the rsh mutation also affects soluble polysaccharide production and cell aggregation. Genetic complementation of the Hx 699 mutant with the rsh(Nsp) gene restored these phenotypes. This is the first discovery of a functional rsh gene in a member of the Novosphingobium genus.


Aseismic uplift in southern california: an alternative interpretation.
The previously reported uplift in southern California may have resulted from systematic errors in leveling rather than tectonic activity. Errors are inferred from correlation between changes in elevation and topography at short and long wavelengths. Corrected data show no significant vertical motion except at the time of the San Fernando earthquake. Possible sources of error include inadequate rod calibration and refraction.


[Tissue culture investigations on the distinction between hereditary and sporadic retinoblastoma (author's transl)].
The growth pattern in tissue culture of cells derived from retinoblastoma is different for all cases with known heredity and most of the cases with unknown heredity. It is concluded that those of the latter, that show a growth pattern that is identical with that of the hereditary cases, represent the hereditary cases in the group with unknown heredity.


Improving growth status of Asian refugee children in the United States.
To analyze the trend and pattern of the nutrition status of Southeast Asian refugee children and other low-income children in the United States. Descriptive analysis of the growth data from the Pediatric Nutrition Surveillance System of the Centers for Disease Control, Atlanta, Ga, from 1980 through 1989. Children under 5 years of age from low-income families enrolled in public health clinics in 12 selected states. Asian refugee children experienced a progressive and significant decline in the prevalence of low birth weight, low height-for-age, and low weight-for-age, while these nutritional indexes remained stable for low-income white, black, and Hispanic children. By 1989, the growth status of Asian children was near that of other ethnic groups. The marked improvement of growth status among Asian refugee children over a short period suggests that the poor growth status often observed among recently immigrated Asian children is primarily related to nutritional and health factors, rather than genetic factors. In assessing the growth of Asian or immigrant children, it would be helpful to take their family and early childhood background into account.


Preferential localization of γH2AX foci in euchromatin of retina rod cells after DNA damage induction.
DNA damage may lead to cell transformation, senescence, or death. Histone H2AX phosphorylation, immunodetected as γH2AX foci, is an early response to DNA damage persisting even after DNA repair. In cycling mammalian cells with canonical nuclear architecture, i.e., central euchromatin and peripheral heterochromatin, γH2AX foci map preferentially to euchromatin. Mice retina rods are G0 cells displaying an inverted nuclear architecture 28 days after birth (P28). Rod nuclei exhibit one or two central constitutive heterochromatin chromocenters encircled by facultative heterochromatin. Euchromatin resides at the nuclear periphery, extending to the equator in cells with two chromocenters. To assess the impact of chromatin relocation in the localization of DNA damage, γH2AX and TUNEL foci induced ex vivo by radiomimetic bleomycin were mapped in H3K4me3 immunolabeled P28 rod nuclei. A preferential localization of γH2AX foci in euchromatin was detected together with foci clustering. Besides, a decay of H3K4me3 signal at γH2AX foci sites was observed. TUNEL and γH2AX foci exhibited similar localization patterns in BLM-treated rod cells thus excluding curtailed access of anti-γH2AX antibodies to heterochromatin. Lack of γH2AX foci in rod chromocenters appears to be unrelated to the occurrence of mid-range foci movements. Foci clusters may arise through DNA double-strand break proximity, local non-directional chromatin movements or chromatin relaxation. H3K4me3 signal reduction at γH2AX foci could stem from local chromatin decondensation or downregulation of histone H4 methylation. The observed topology of DNA damage in retina-differentiated rods indicates that euchromatin is damage-prone, regardless of the canonical or inverted nuclear architecture of mammalian cells.


Early oocyte triggering followed by in vitro maturation is a good approach in women with resistance ovary syndrome: A case-series.
Some women represent the inability to respond to endogenous and exogenous gonadotropins during in vitro fertilization/intracytoplasmic sperm injection cycles leading to the follicular developmental arrest. The women with resistant ovaries could benefit from in vitro maturation. This case-series presents pregnancies resulting from initially scheduled conventional in vitro fertilization which led to arrested cycles because of resistant ovary syndrome. The protocol was changed to early oocyte triggering for 15 women due to the small follicles ≤ 12 mm in diameter on day 15 after stimulation with high doses of exogenous gonadotrophins instead of cycle cancellation. Germinal vesicle and metaphase I oocytes that were retrieved from follicles were matured in vitro and inseminated by intracytoplasmic sperm injection. Twenty formed embryos were transferred on day 3 after oocyte retrieval. This resulted in a 30.76% chemical pregnancy out of which no abortion occurred. Therefore, we reported a 30.76% singleton ongoing pregnancy. It seems that early oocyte triggering followed by in vitro maturation may be considered as a good modality in women experiencing follicular resistance to gonadotropins. These cycles can be rescued from cancellation with satisfactory clinical outcomes.


Markerless Eye-Hand Kinematic Calibration on the iCub Humanoid Robot.
Humanoid robots are resourceful platforms and can be used in diverse application scenarios. However, their high number of degrees of freedom (i.e., moving arms, head and eyes) deteriorates the precision of eye-hand coordination. A good kinematic calibration is often difficult to achieve, due to several factors, e.g., unmodeled deformations of the structure or backlash in the actuators. This is particularly challenging for very complex robots such as the iCub humanoid robot, which has 12 degrees of freedom and cable-driven actuation in the serial chain from the eyes to the hand. The exploitation of real-time robot sensing is of paramount importance to increase the accuracy of the coordination, for example, to realize precise grasping and manipulation tasks. In this code paper, we propose an online and markerless solution to the eye-hand kinematic calibration of the iCub humanoid robot. We have implemented a sequential Monte Carlo algorithm estimating kinematic calibration parameters (joint offsets) which improve the eye-hand coordination based on the proprioception and vision sensing of the robot. We have shown the usefulness of the developed code and its accuracy on simulation and real-world scenarios. The code is written in C++ and CUDA, where we exploit the GPU to increase the speed of the method. The code is made available online along with a Dataset for testing purposes.


Measuring Electronically Shared Rape Myths: Scale Creation and Correlates.
Increased access to information online (e.g., social media) provides opportunities for exposure to rape myths (i.e., false beliefs about incidents of sexual assault). Social media, in particular, may serve a critical role in shaping rape culture. Thus, it is important to identify ways to assess online exposure to rape myths, especially given the influence online exposure may have on offline behaviors. Data were analyzed from 2,609 18-25-year-old participants (mean age = 20.9 years; 46.1% male; 71.6% White) recruited in 2017 through social media to complete an online survey on experiences and perceptions of sexual violence. We used exploratory and confirmatory factor analyses (EFA, CFA) to evaluate the relatedness of nine items adapted to reflect rape myths posted by friends on social media. We split the sample into training (50%) and testing (50%) sets for the EFA and CFA, respectively, then evaluated the correlation between experiences of sexual violence, substance use, and social media use and exposure to online rape myths. Eigenvalues (1-factor: 5.509; 2-factor: 0.803; 3-factor: 0.704; 4-factor: 0.482), factor loadings, fit statistics (RMSEA: 0.03; CFI: 0.99; TLI: 0.99; SRMR: 0.057), interpretability, and existing theory supported a 1-factor solution, which was supported by CFA fit statistics (RMSEA: 0.021; CFI: 0.99; TLI: 0.99; SRMR: 0.038). Cronbach's alpha of the nine items was .77. Greater exposure to online rape myths was associated with greater likelihood of attempted rape perpetration (β = .052, SE = .016, p < .005), rape victimization (β = .045, SE = .009, p < .005), use of illicit drugs (β = .021, SE = 0.008, p < .05), being male (β = .017, SE = .008, p < .05), and being younger (β = -.008, SE = .002, p < .005). Our findings support assessing exposure to online rape myths, which may be important for informing sexual violence prevention and intervention efforts.


Patient-ventilator asynchrony during assisted mechanical ventilation.
The incidence, pathophysiology, and consequences of patient-ventilator asynchrony are poorly known. We assessed the incidence of patient-ventilator asynchrony during assisted mechanical ventilation and we identified associated factors. Sixty-two consecutive patients requiring mechanical ventilation for more than 24 h were included prospectively as soon as they triggered all ventilator breaths: assist-control ventilation (ACV) in 11 and pressure-support ventilation (PSV) in 51. Gross asynchrony detected visually on 30-min recordings of flow and airway pressure was quantified using an asynchrony index. Fifteen patients (24%) had an asynchrony index greater than 10% of respiratory efforts. Ineffective triggering and double-triggering were the two main asynchrony patterns. Asynchrony existed during both ACV and PSV, with a median number of episodes per patient of 72 (range 13-215) vs. 16 (4-47) in 30 min, respectively (p=0.04). Double-triggering was more common during ACV than during PSV, but no difference was found for ineffective triggering. Ineffective triggering was associated with a less sensitive inspiratory trigger, higher level of pressure support (15 cmH(2)O, IQR 12-16, vs. 17.5, IQR 16-20), higher tidal volume, and higher pH. A high incidence of asynchrony was also associated with a longer duration of mechanical ventilation (7.5 days, IQR 3-20, vs. 25.5, IQR 9.5-42.5). One-fourth of patients exhibit a high incidence of asynchrony during assisted ventilation. Such a high incidence is associated with a prolonged duration of mechanical ventilation. Patients with frequent ineffective triggering may receive excessive levels of ventilatory support.


The level of serum pro-matrix metalloproteinase-2 as a prognostic factor in patients with invasive ductal breast cancer.
This paper analyses data of 150 female patients undergoing surgical treatment for invasive ductal breast cancer at the University Hospital for Tumors from January 2006 to January 2007. The control group consisted of 50 healthy women. The patients were classified into three groups, depending on their tumor differentiation, i.e. grade I, II and III tumor groups. Each group consisted of 50 patients. Traditional prognostic factors including: age, tumor size and differentiation grade, axillary lymph node status, presence of distant metastases, steroid receptor findings, vascular invasion of the primary tumor, presence of an extensive intraductal component (EIC) in the primary tumor, HER-2 protein expression were evaluated. Both the patients' and controls' serum levels of proMMP-2 (pro-matrix metalloproteinase-2) were assessed using the ELISA method. The aim of the study was to assess pathohistological prognostic factors and the level of serum proMMP-2 in the three patient groups and the controls, compare the relationship between the prognostic factors and the level of serum proMMP-2 in the patient groups, and upon the results, determine possible features of proMMP-2 as a prognostic factor in breast cancer patients. The study results showed no difference in proMMP-2 concentrations between the three patient groups and the controls. No statistically significant difference in the serum proMMP-2 concentration was found between the patient groups, although the grade III group values were the highest showing a trend toward statistical significance. Comparison of proMMP-2 and prognostic factors revealed a statistically significant correlation between proMMP-2 and age in patients with histologic grade I tumors. There was no statistically significant correlation between circulating proMMP-2 and other pathohistological prognostic factors.


Only the carrot, not the stick: incorporating trust into the enforcement of regulation.
New enforcement strategies allow agents to gain the regulator's trust and consequently face a lower audit probability. Prior research suggests that, in order to prevent lower compliance, a reduction in the audit probability (the "carrot") must be compensated with the introduction of a higher penalty for non-compliance (the "stick"). However, such carrot-and-stick strategies reflect neither the concept of trust nor the strategies observed in practice. In response to this, we define trust-based regulation as a strategy that incorporates rules that allow trust to develop, and using a generic (non-cooperative) game of tax compliance, we examine whether trust-based regulation is feasible (i.e., whether, in equilibrium, a reduction in the audit probability, without ever increasing the penalty for non-compliance, does not lead to reduced compliance). The model shows that trust-based regulation is feasible when the agent sufficiently values the future. In line with the concept of trust, this strategy is feasible when the regulator is uncertain about the agent's intentions. Moreover, the model shows that (i) introducing higher penalties makes trust-based regulation less feasible, and (ii) combining trust and forgiveness can lead to a lower audit probability for both trusted and distrusted agents. Policy recommendations often point toward increasing deterrence. This model shows that the opposite can be optimal.


Endovascular treatment of traumatic thoracic aortic aneurysms: report of five cases and review of the literature.
Endovascular stent-grafting of the aorta, as an alternative to open surgical techniques, is gaining in popularity everyday, especially in high-risk patients. Acute or chronic traumatic lesions of the descending aorta, especially after motor vehicle accidents, constitute such a group with a high-risk of morbidity and mortality. Here, we report the successful endovascular repair of acute and chronic traumatic thoracic aortic aneurysms after motor vehicle accidents in five patients.


Fear, Efficacy, and Environmental Health Risk Reporting: Complex Responses to Water Quality Test Results in Low-Income Communities.
Reducing disease from unsafe drinking-water is a key environmental health objective in rural Sub-Saharan Africa, where water management is largely community-based. The effectiveness of environmental health risk reporting to motivate sustained behaviour change is contested but as efforts to increase rural drinking-water monitoring proceed, it is timely to ask how water quality information feedback can improve water safety management. Using cross-sectional (1457 households) and longitudinal (167 participants) surveys, semi-structured interviews (73 participants), and water quality monitoring (79 sites), we assess water safety perceptions and evaluate an information intervention through which Escherichia coli monitoring results were shared with water managers over a 1.5-year period in rural Kitui County, Kenya. We integrate the extended parallel process model and the precaution adoption process model to frame risk information processing and stages of behaviour change. We highlight that responses to risk communications are determined by the specificity, framing, and repetition of messaging and the self-efficacy of information recipients. Poverty threatscapes and gender norms hinder behaviour change, particularly at the household-level; however, test results can motivate supply-level managers to implement hazard control measures-with effectiveness and sustainability dependent on infrastructure, training, and ongoing resourcing. Our results have implications for rural development efforts and environmental risk reporting in low-income settings.


Cosmetic ethnobotany practiced by tribal women of Kashmir Himalayas.
Himalayan mountain populations have been dependent upon indigenous plant resources for their health care for many years. Tribal women are interested in use of local herbs for cosmetic purposes. The present work is based on the results of research conducted on cosmetic uses of some important plants by the tribal women in District Poonch, Azad Kashmir Pakistan. An ethno botanical survey was carried out during summer 2012. The data were collected from 310 female informants from 16 villages using questionnaire method and semi structured interviews. A total of 39 plants species belonging to 20 families, being used for various cosmetic purposes were recorded. Indigenous species are traditionally used by the locals for problems including acne (16%), hair growth (11%), bad breath (12%), facial spots (9%), allergy, (9%), fairness (8%), wrinkles (8%), eye and lip care (9%). Seventy different recipes were recorded to be practiced by locals using herbal parts. The major plant parts utilized in herbal recipes included fruit (32.8%), Leaves (25.2%), seeds (13.4%) and roots (8.9%). Women of older (>30 years) age group showed greater (67%) response regarding knowledge and practice of cosmetic herbs. This study was the 1(st) ever project focusing on cosmetic perspectives of ethno-botany in the area. Our study contributes to an improved understanding of ignored aspect of cosmetic ethnobotany among the local women. Further detailed investigations are recommended to record and preserve precious ethno-botanical knowledge of the area.


Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats.
To determine whether the basal forebrain-hippocampal cholinergic system supports sexually dimorphic functionality, male and female Long-Evans rats were given either selective medial septum/vertical limb of the diagonal band (MS/VDB) cholinergic lesions using the neurotoxin 192 IgG-saporin or a control surgery and then postoperatively tested in a set of standard spatial learning tasks in the Morris water maze. Lesions were highly specific and effective as confirmed by both choline acetyltransferase/parvalbumin immunostaining and acetylcholinesterase histochemistry. Female controls performed worse than male controls in place learning and MS/VDB lesions failed to impair spatial learning in male rats, both consistent with previous findings. In female rats, MS/VDB cholinergic lesions facilitated spatial reference learning. A subsequent test of learning strategy in the water maze revealed a female bias for a response, relative to a spatial, strategy; MS/VDB cholinergic lesions enhanced the use of a spatial strategy in both sexes, but only significantly so in males. Together, these results indicate a sexually dimorphic function associated with MS/VDB-hippocampal cholinergic inputs. In female rats, these neurons appear to support sex-specific spatial learning processes.


Symposium: Helicobacter pylori and clinical risks--focus on gastro-oesophageal reflux disease.
Helicobacter pylori is a gastric pathogen that is a major cause of peptic ulcer disease, has a role in mucosa-associated lymphoid tissue (MALT) lymphoma and is associated with gastric cancer. Yet, in a large proportion of the human population, H. pylori infection has no apparent adverse clinical consequences. Furthermore, recent research suggests that H. pylori may even confer protection against gastroesophageal reflux disease. The conflicting evidence surrounding H. pylori infection was discussed at a sponsored symposium in Helsinki, introduced by Professor P. Malfertheiner, with papers presented by Dr H. J. O'Connor, Professor R. M. Genta, Dr P. Unge and Professor A. T. R. Axon. Emerging epidemiological and retrospective evidence suggests that the presence of H. pylori infection may provide some protection against gastroesophageal reflux disease, but there is other evidence that shows no benefit of H. pylori for the protection of the oesophagus. It was felt that prospective, multicentre studies are needed to explore the H. pylori-gastroesophageal disease relationship further, to avoid confusing potential benefits with known risks. Following the symposium, a discussion on the relative risks and benefits for H. pylori eradication was provided by Professor Axon and Professor Blaser. Eradication of H. pylori has been recommended in a series of management guidelines issued by consensus groups. However, accurate estimates of the relative risks and benefits of H. pylori infection in the general population, as well as in specific patient groups, is essential in order to develop a management strategy.


The never ending road: improving, adapting and refining a needs-based model to estimate future general practitioner requirements in two Australian states.
Health workforce planning models have been developed to estimate the future health workforce requirements for a population whom they serve and have been used to inform policy decisions. To adapt and further develop a need-based GP workforce simulation model to incorporate current and estimated geographic distribution of patients and GPs. A need-based simulation model that estimates the supply of GPs and levels of services required in South Australia (SA) was adapted and applied to the Western Australian (WA) workforce. The main outcome measure was the differences in the number of full-time equivalent (FTE) GPs supplied and required from 2013 to 2033. The base scenario estimated a shortage of GPs in WA from 2019 onwards with a shortage of 493 FTE GPs in 2033, while for SA, estimates showed an oversupply over the projection period. The WA urban and rural models estimated an urban shortage of GPs over this period. A reduced international medical graduate recruitment scenario resulted in estimated shortfalls of GPs by 2033 for WA and SA. The WA-specific scenarios of lower population projections and registrar work value resulted in a reduced shortage of FTE GPs in 2033, while unfilled training places increased the shortfall of FTE GPs in 2033. The simulation model incorporates contextual differences to its structure that allows within and cross jurisdictional comparisons of workforce estimations. It also provides greater insights into the drivers of supply and demand and the impact of changes in workforce policy, promoting more informed decision-making.


The effects of lesions to noradrenergic projections from the locus coeruleus and lateral tegmental cell groups on conditioned taste aversion in the rat.
Lesions of the coeruleo-cortical noradrenergic projections caused marked cortical noradrenaline depletions but were not associated with deficits in the acquisition or extinction of a conditioned taste aversion (CTA). Lesions of lateral tegmental noradrenergic projections resulted in marked hypothalamic noradrenaline depletions, enhanced neophobia to the novel taste of saccharin, unimpaired acquisition but prolonged extinction of the CTA. However, when animals with lateral tegmental noradrenergic lesions received extensive preconditioning exposure to saccharin, acquisition of the CTA was attenuated and extinction was more rapid than in controls. Alterations in CTA learning and extinction following lesions of the lateral tegmental noradrenergic system appear to reflect alterations in the way that animals with lesions react toward the hedonic aspects of taste-related stimuli rather than alterations in associational or attentional mechanisms.


The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis.
Several studies have suggested worsening in inflammatory bowel disease (IBD) activity following fecal microbiota transplantation (FMT). We aimed to assess the risk of worsening in IBD activity following FMT. An electronic search was conducted using MEDLINE (1946-June 2016), EMBASE (1954-June 2016) and Cochrane Central Register of Controlled Trials (2016). Studies in which FMT was provided to IBD patients for IBD management or (Clostridium difficile infection) CDI treatment were included. The primary outcome was the rate of worsening in IBD activity. Twenty-nine studies with 514 FMT-treated IBD patients were included. Range of follow up was 4 weeks to 3 y. The pooled rate of IBD worsening was 14.9% (95% CI 10-21%). Heterogeneity was detected: I2 D 52.1%, Cochran Q test D 58.1, p D 0.01. A priori subgroup analyses were performed. Although not significant, the pooled rate of worsening in IBD activity following FMT for CDI (22.7% (95% CI: 13-36%)) was higher compared with FMT for IBD (11.1% (95% CI 7-17%)). Rates of worsening in IBD after lower GI FMT delivery revealed a higher rate of worsening in IBD activity (16.5% (95% CI: 11-24%)) compared with upper GI delivery (5.6% (95% CI: 2-16%)). Rates of worsening in high quality studies and randomized controls trials (RCTS) suggested a marginal risk of worsening in IBD activity (4.6%, (95% CI: 1.8-11%). Rates of IBD worsening are overall marginal across high quality RCTS. It is unknown if the FMT itself led to the worsening of IBD in this small fraction or if this represents alternative etiologies.


A multivariate pattern recognition study of risk-factors indicating postoperative thromboembolism despite low-dose heparin in major abdominal surgery.
The object of the present investigation was to identify those who, among high-risk patients, would "break through" low-dose heparin prophylaxis and develop thromboembolism after major abdominal surgery. Twenty-nine variables (clinical characteristics, pre- and postoperative coagulation and fibrinolytic factors) from 19 patients with and 26 patients without thromboembolism were analyzed by means of a multivariate supervised pattern recognition technique (SIMCA). We found no statistically significant difference between patients with and without thromboembolism. Thus, in the studied group of high-risk patients it was not possible to identify a predictive index for selection of individual patients liable to develop postoperative thromboembolism despite low-dose heparin prophylaxis in major abdominal surgery.