Men, prostitution and the provider role: understanding the intersections of economic exchange, sex, crime and violence in South Africa.
South African policy makers are reviewing legislation of prostitution, concerned that criminalisation hampers HIV prevention. They seek to understand the relationship between transactional sex, prostitution, and the nature of the involved men. 1645 randomly-selected adult South African men participated in a household study, disclosing whether they had sex with a woman in prostitution or had had a provider relationship (or sex), participation in crime and violence and completing psychological measures. These became outcomes in multivariable regression models, where the former were exposure variables. 51% of men had had a provider relationship and expected sex in return, 3% had had sex with a woman in prostitution, 15% men had done both of these and 31% neither. Provider role men, and those who had just had sex with a woman in prostitution, were socially conservative and quite violent. Yet the men who had done both (75% of those having sex with a woman in prostitution) were significantly more misogynist, highly scoring on dimensions of psychopathy, more sexually and physically violent to women, and extensively engaged in crime. They had often bullied at school, suggesting that this instrumental, self-seeking masculinity was manifest in childhood. The men who had not engaged in sex for economic exchange expressed a much less violent, more law abiding and gender equitable masculinity; challenging assumptions about the inevitability of intersections of age, poverty, crime and misogyny. Provider role relationships (or sex) are normative for low income men, but not having sex with a woman in prostitution. Men who do the latter operate extensively outside the law and their violence poses a substantial threat to women. Those drafting legislation and policy on the sex industry in South Africa need to distinguish between these two groups to avoid criminalising the normal, and consider measures to protect women.


Performance-based financing for improving HIV/AIDS service delivery: a systematic review.
Although domestic HIV/AIDS financing is increasing, international HIV/AIDS financing has plateaued. Providing incentives for the health system (i.e. performance-based financing [PBF]) may help countries achieve more with available resources. We systematically reviewed effects of PBF on HIV/AIDS service delivery to inform WHO guidelines. PubMed, WHO Index Medicus, conference databases, and clinical trial registries were searched in April 2015 for randomised trials, comparative contemporaneous studies, or time-series studies. Studies evaluating PBF in people with HIV were included when they reported service quality, access, or cost. Meta-analyses were not possible due to limited data. This study is registered with PROSPERO, number CRD42015023207. Four studies, published from 2009 to 2015 and including 173,262 people, met the eligibility criteria. All studies were from Sub-Saharan Africa. PBF did not improve individual testing coverage (relative risk [RR], 1.00, 95% confidence interval [CI] 0.89 to 1.13), improved couples testing coverage (RR 1.11, 95% CI 1.02 to 1.20), and improved pregnant women testing coverage (RR 1.29, 95% CI 1.28-1.30). PBF improved coverage of antiretrovirals in pregnant women (RR 1.55, 95% CI 1.50 to 1.59), infants (RR 1.92, 95% CI 1.84 to 2.01), and adults (RR 1.74, 1.64 to 1.85). PBF reduced attrition (RR 0.84, 95% CI 0.74 to 0.96) and treatment failure (odds ratio 0.55, 95% CI 0.32 to 0.97). Potential harms were not reported. Although the limited data suggests PBF positively affected HIV service access and quality, critical health system and governance knowledge gaps remain. More research is needed to inform national policymaking.


Signal functions for measuring the ability of health facilities to provide abortion services: an illustrative analysis using a health facility census in Zambia.
Annually, around 44 million abortions are induced worldwide. Safe termination of pregnancy (TOP) services can reduce maternal mortality, but induced abortion is illegal or severely restricted in many countries. All abortions, particularly unsafe induced abortions, may require post-abortion care (PAC) services to treat complications and prevent future unwanted pregnancy. We used a signal-function approach to look at abortion care services and illustrated its utility with secondary data from Zambia. We refined signal functions for basic and comprehensive TOP and PAC services, including family planning (FP), and assessed functions currently being collected via multi-country facility surveys. We then used the 2005 Zambian Health Facility Census to estimate the proportion of 1369 health facilities that could provide TOP and PAC services under three scenarios. We linked facility and population data, and calculated the proportion of the Zambian population within reach of such services. Relevant signal functions are already collected in five facility assessment tools. In Zambia, 30 % of facilities could potentially offer basic TOP services, 3.7 % comprehensive TOP services, 2.6 % basic PAC services, and 0.3 % comprehensive PAC services (four facilities). Capability was highest in hospitals, except for FP functions. Nearly two-thirds of Zambians lived within 15 km of a facility theoretically capable of providing basic TOP, and one-third within 15 km of comprehensive TOP services. However, requiring three doctors for non-emergency TOP, as per Zambian law, reduced potential access to TOP services to 30 % of the population. One-quarter lived within 15 km of basic PAC and 13 % of comprehensive PAC services. In a scenario not requiring FP functions, one-half and one-third of the population were within reach of basic and comprehensive PAC respectively. There were huge urban-rural disparities in access to abortion care services. Comprehensive PAC services were virtually unavailable to the rural population. Secondary data from facility assessments can highlight gaps in abortion service provision and coverage, but it is necessary to consider TOP and PAC separately. This approach, especially when combined with population data using geographic coordinates, can also be used to model the impact of various policy scenarios on access, such as requiring three medical doctors for non-emergency TOP. Data collection instruments could be improved with minor modifications and used for multi-country comparisons.


Sex and limb differences in hip and knee kinematics and kinetics during anticipated and unanticipated jump landings: implications for anterior cruciate ligament injury.
In this study, the effects of temporal changes in unanticipated (UN) prelanding stimuli on lower limb biomechanics and the impact of sex and limb dominance on these variables during single-leg landings were determined. It was hypothesised that reductions in the time of prelanding UN stimuli, female sex, and the non-dominant limb would significantly increase high-risk landing biomechanics during UN jump landings. 26 (13 men and 13 women) had initial contact (IC) and peak stance (0-50%) phase (PS) lower limb joint kinematics and kinetics quantified during anticipated (AN) and UN single-leg (left and right) landings. Postlanding jump direction was governed via one of two randomly ordered light stimuli, presented either before initiation of the jump (AN), or 600 ms (UN1), 500 ms (UN2) or 400 ms (UN3) immediately before ground contact. Statistically significant (p<0.05) differences in IC hip posture and PS hip and knee internal rotation moments occurred in UN compared with AN landings. Differences were not observed, however, among UN conditions for any biomechanical comparisons. Significant (p<0.05) differences in specific IC and PS hip and knee postures and loads occurred between sexes and limbs. Neither of these factors, however, influenced movement condition effects. UN landings induce modifications in landing biomechanics that may increase anterior cruciate ligament injury risk in both men and women. These modifications, however, do not appear overly sensitive to the timing of the UN stimulus, at least within a temporal range affording a successful movement response. Expanding UN training to include even shorter stimulus-response times may promote the additional central control adaptations necessary to manoeuvre safely within the random sports setting.


Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance.
At birth, fetal distal lung epithelial (FDLE) cells switch from active chloride secretion to active sodium (Na+) reabsorption. Sodium ions enter the FDLE and alveolar type II (ATII) cells mainly through apical nonselective cation and Na(+)-selective channels, with conductances of 4-26 pS (picoSiemens) in FDLE and 20-25 pS in ATII cells. All these channels are inhibited by amiloride with a 50% inhibitory concentration of < 1 microM, and some are also inhibited by [N-ethyl-N-isopropyl]-2'-4'-amiloride (50% inhibitory concentration of < 1 microM). Both FDLE and ATII cells contain the alpha-, beta-, and gamma-rENaC (rat epithelial Na+ channels) mRNAs; reconstitution of an ATII cell Na(+)-channel protein into lipid bilayers revealed the presence of 25-pS Na+ single channels, inhibited by amiloride and [N-ethyl-N-isopropyl]-2'-4'-amiloride. A variety of agents, including cAMP, oxygen, glucocorticoids, and in some cases Ca2+, increased the activity and/or rENaC mRNA levels. The phenotypic properties of these channels differ from those observed in other Na(+)-absorbing epithelia. Pharmacological blockade of alveolar Na+ transport in vivo, as well as experiments with newborn alpha-rENaC knock-out mice, demonstrate the importance of active Na+ transport in the reabsorption of fluid from the fetal lung and in reabsorbing alveolar fluid in the injured adult lung. Indeed, in a number of inflammatory diseases, increased production of reactive oxygen-nitrogen intermediates, such as peroxynitrite (ONOO-), may damage ATII and FDLE Na+ channels, decrease Na+ reabsorption in vivo, and thus contribute to the formation of alveolar edema.


Are pre-school girls more likely to be under-nourished in rural Thatta, Pakistan?-a cross-sectional study.
Pakistan ranks third lowest on a global gender index (2013) and 13(th) highest on the prevalence of underweight among under-five children (2010). Through this population-based study, we examined gender differentials in the prevalence of stunting, wasting and under-weight defined by World Health Organization (WHO) Growth Standard among rural pre-school Pakistani children. We performed secondary analysis of data collected through a cross-sectional survey of Thatta district during 1992-93. Prevalence ratios were calculated for 1051 children aged 0-35 months from 95 randomly selected villages of rural Pakistan using a clustered adjusted log binomial model. Level 1 variables included child and household characteristics and level 2 included village characteristics. Based on the new WHO growth reference, a major proportion of children were stunted (52.9 %), wasted (22.9 %) and under-weight (46.5 %). In a two-level model, compared to boys, girls had significantly greater risk of stunting [Prevalence Ratio (PR) (95 % C.I.) = 1.18 (1.03, 1.36)] and under-weight [P.R. (95 % C.I.) 1.14 (1.03, 1.26)], after adjustment of maternal literacy and village variables. Risk of wasting did not differ with gender [P.R. (95 % C.I.) = 1.04 (0.99, 1.15)]. Mothers of stunted and underweight children were respectively, 21 and 20 % more likely to be illiterate than those of normally nourished children. Sick children were at 16 % greater risk of wasting than those not reported ill. Greater prevalence of stunting and under-weight among girls suggests adoption of a gender sensitive approach in nutritional intervention programmes. Prompt management of childhood illnesses may reduce prevalence of wasting. Better literacy among rural mothers may reduce prevalence of stunting and under-weight. Whether gender differences in nutrition status are an underlying pathway for excessive girl mortality in rural Thatta needs further examination.


The pathogenesis of urticaria.
The underlying pathophysiology of chronic urticaria is mast cell activation, with release of histamine and other mast cell mediators. A weal producing factor has been identified in the serum of 60% of patients with chronic idiopathic urticaria. In half of these patients there is evidence for functional autoantibodies against the high affinity IgE receptor or IgE, or both. These autoantibodies release histamine from basophils and mast cells. It is therefore likely that there is an autoimmune basis for up to 30% of patients with idiopathic urticaria. In the other half of patients whose serum causes weals, the factor releases histamine from mast cells only and is as yet unidentified. So far no clinical difference has been associated with presence/absence or type of weal producing factor. Exacerbating factors in chronic urticaria such as aspirin, food additives, febrile illness and psychological stress should be identified and avoided. Treatment is symptomatic with the low sedation antihistamines. In the most severe cases not responding to conventional therapy and which may have the weal producing factor, treatments with non specific immune therapy such as cyclosporin, and intravenous gammaglobulin and also plasmapheresis have been promising.


HIV in pregnancy: a case of Pneumocystis (carinii) jiroveci pneumonia.
This review highlights the rising prevalence of HIV in pregnancy both in the developed and developing world. It focuses on the challenges of diagnosis and management of Pneumocystis (carinii) jiroveci pneumonia in an HIV-positive pregnant woman. Public health efforts need to continue addressing testing at the earliest opportunity, the psychosocial issues which impact negatively on the care of HIV-positive individuals and ways to reduce stigmatisation associated with this viral illness.


Super-size me: self biases increase to larger stimuli.
Prior work has shown that simple perceptual match responses to pairings of shapes and labels are more efficient if the pairing is associated with the participant (e.g., circle-you) than if it is associated with another familiar person (e.g., square-friend). There is a similar advantage for matching associations with high-value rewards (circle-£9) versus low-value rewards (square-£1) (Sui, He, & Humphreys Journal of Experimental Psychology: Human Perception and Performance, 38, 1105-1117, 2012). Here we evaluated the relations between the self- and reward-bias effects by introducing occasional trials in which the size of a shape was varied unexpectedly (large or small vs. a standard medium). Participants favored stimuli that were larger than the standard when stimuli were associated with the self, and this enhancement of self bias was predicted by the degree of self bias that participants showed to standard (medium) sized stimuli. Although we observed a correlation between the magnitudes of the self and reward biases over participants, reward-bias effects were not increased to large stimuli. The data suggest both overlapping and independent components of the self and reward biases, and that self biases are uniquely enhanced when stimuli increase in size, consistent with previously reported motivational biases favoring large stimuli.


Structure and metal binding properties of ZnuA, a periplasmic zinc transporter from Escherichia coli.
ZnuA is the periplasmic Zn(2+)-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn(2+)-bound, and Co(2+)-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn(2+) with Co(2+) results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn(2+) periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn(2+) (estimated K (d) < 20 nM), Co(2+), Ni(2+), Cu(2+), Cu(+), and Cd(2+), but not Mn(2+). Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn(2+) substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer.


Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma.
The diagnosis of renal cell carcinoma is accompanied by intravascular tumor thrombus in up to 10% of cases, of which nearly one-third of patients also have concurrent metastatic disease. Surgical resection in the form of radical nephrectomy and caval thrombectomy represents the only option to obtain local control of the disease and is associated with durable oncologic control in approximately half of these patients. The objective of this clinical review is to outline the preoperative evaluation for, and operative management of patients with locally advanced renal cell carcinoma with venous tumor thrombi involving the inferior vena cava. Cornerstones of the management of these complex patients include obtaining high-quality imaging to characterize the renal mass and tumor thrombus preoperatively, with further intraoperative real-time evaluation using transesophageal echocardiography, careful surgical planning, and a multidisciplinary approach. Operative management of patients with high-level caval thrombi should be undertaken in high-volume centers by surgical teams with capacity for bypass and invasive intraoperative monitoring. In patients with metastatic disease at presentation, cytoreductive nephrectomy and tumor thrombectomy may be safely performed with simultaneous metastasectomy if possible. In the absence of level one evidence, neoadjuvant targeted therapy should continue to be viewed as experimental and should be employed under the auspices of a clinical trial. However, in patients with significant risk factors for postoperative complications and mortality, and especially in those with metastatic disease, consultation with medical oncology and frontline targeted therapy may be considered.


Insulinotropic, glucose-lowering, and beta-cell anti-apoptotic actions of peptides related to esculentin-1a(1-21).NH2.
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1.1B4 human-derived pancreatic β-cells, and isolated mouse islets with no cytotoxicity at concentrations of up to 3 μM. The mechanism of insulinotropic action involved membrane depolarization and an increase in intracellular Ca2+ concentrations. The analogue [D-Lys14, D-Ser17]esculentin-1a(1-21).NH2 (Esc(1-21)-1c) was less potent in vitro than the all L-amino acid containing peptides and esculentin-1a(9-21) was inactive indicating that helicity is an important determinant of insulinotropic activity. However, intraperitoneal injection of Esc(1-21)-1c (75 nmol/kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion, whereas administration of esculentin-1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14) was without significant effect on plasma glucose levels. Esc(1-21)-1c (1 µM) protected BRIN-BD11 cells against cytokine-induced apoptosis (P < 0.01) and augmented proliferation of the cells (P < 0.01) to a similar extent as glucagon-like peptide-1. The data demonstrate that the multifunctional peptide Esc(1-21)-1c, as well as showing therapeutic potential as an anti-infective and wound-healing agent, may constitute a template for development of compounds for treatment of patients with Type 2 diabetes.


Humans Optimize Ground Contact Time and Leg Stiffness to Minimize the Metabolic Cost of Running.
Trained endurance runners appear to fine-tune running mechanics to minimize metabolic cost. Referred to as self-optimization, the support for this concept has primarily been collated from only a few gait (e.g., stride frequency, length) and physiological (e.g., oxygen consumption, heart rate) characteristics. To extend our understanding, the aim of this study was to examine the effect of manipulating ground contact time on the metabolic cost of running in trained endurance runners. Additionally, the relationships between metabolic cost, and leg stiffness and perceived effort were examined. Ten participants completed 5 × 6-min treadmill running conditions. Self-selected ground contact time and step frequency were determined during habitual running, which was followed by ground contact times being increased or decreased in four subsequent conditions whilst maintaining step frequency (2.67 ± 0.15 Hz). The same self-selected running velocity was used across all conditions for each participant (12.7 ± 1.6 km · h-1). Oxygen consumption was used to compute the metabolic cost of running and ratings of perceived exertion (RPE) were recorded for each run. Ground contact time and step frequency were used to estimate leg stiffness. Identifiable minimums and a curvilinear relationship between ground contact time and metabolic cost was found for all runners (r 2 = 0.84). A similar relationship was observed between leg stiffness and metabolic cost (r 2 = 0.83). Most (90%) runners self-selected a ground contact time and leg stiffness that produced metabolic costs within 5% of their mathematical optimal. The majority (n = 6) of self-selected ground contact times were shorter than mathematical optimals, whilst the majority (n = 7) of self-selected leg stiffness' were higher than mathematical optimals. Metabolic cost and RPE were moderately associated (r s = 0.358 p = 0.011), but controlling for condition (habitual/manipulated) weakened this relationship (r s = 0.302, p = 0.035). Both ground contact time and leg stiffness appear to be self-optimized characteristics, as trained runners were operating at or close to their mathematical optimal. The majority of runners favored a self-selected gait that may rely on elastic energy storage and release due to shorter ground contact times and higher leg stiffness's than optimal. Using RPE as a surrogate measure of metabolic cost during manipulated running gait is not recommended.


Norepinephrine suppresses wound macrophage phagocytic efficiency through alpha- and beta-adrenoreceptor dependent pathways.
The systemic response to injury is characterized by massive release of norepinephrine (NE) into the circulation as a result of global sympathetic activation. We have recently demonstrated that NE modulates the recruitment of macrophages to the cutaneous wound. We hypothesized that NE suppresses wound macrophage phagocytic function through canonical adrenergic signaling pathways. Murine wound macrophages were harvested at 5 days after injury and treated with physiologic and pharmacologic dose norepinephrine. Phagocytosis of green fluorescent protein-labeled Escherichia coli was assayed by flow cytometry. The signaling pathways mediating NE modulation of wound macrophage phagocytosis were interrogated by pharmacologic manipulation of alpha- and beta-adrenoreceptors (ARs), intracellular cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). Tissue specificity was determined by comparison of wound macrophages to splenic macrophages. Both physiologic and pharmacologic dose NE suppressed wound macrophage phagocytic efficiency. This effect was mediated by alpha- and beta-ARs in a dose-dependent fashion. Direct stimulation of cAMP-suppressed phagocytic efficiency and blockade of PKA signaling prevented NE-mediated suppression of phagocytic efficiency. Splenic macrophage phagocytic efficiency was less than that of wound macrophages and was not altered by NE. NE has a profound immunosuppressive effect on wound macrophage function that is tissue specific and appears to be mediated through adrenergic receptors and their canonical downstream signaling pathway. Attenuation of post-injury immunosuppression represents another potential mechanism by which beta-AR blockade may reduce morbidity and mortality after severe injury.


Emerging drug--resistance and guidelines for treatment of malaria.
The increasing prevalence of multi-resistant Plasmodium falciparum malaria worldwide is a serious public health threat to the global control of malaria, especially in poor countries like Pakistan. In many countries choloroquine-resistance is a huge problem, accounting for more than 90% of malaria cases. In Pakistan, resistance to choloroquin is on the rise and reported in up to 16- 62% of Plasmodium falciparum. four to 25% of Plasmodium falciparum also reported to be resistant to sulfadoxine-pyrimethamine and several cases of delayed parasite clearance have been observed in patients with Plasmodium falciparum malaria treated with quinine. In this article we have introduced the concept of artemisinin- based combination therapy (ACT) and emphasize the use of empiric combination therapy for all patients with Plasmodium falciparum malaria to prevent development of drug resistance and to obtain additive and synergistic killing of parasite.


Ozone monitoring instrument observations of interannual increases in SO2 emissions from Indian coal-fired power plants during 2005-2012.
Due to the rapid growth of electricity demand and the absence of regulations, sulfur dioxide (SO2) emissions from coal-fired power plants in India have increased notably in the past decade. In this study, we present the first interannual comparison of SO2 emissions and the satellite SO2 observations from the Ozone Monitoring Instrument (OMI) for Indian coal-fired power plants during the OMI era of 2005-2012. A detailed unit-based inventory is developed for the Indian coal-fired power sector, and results show that its SO2 emissions increased dramatically by 71% during 2005-2012. Using the oversampling technique, yearly high-resolution OMI maps for the whole domain of India are created, and they reveal a continuous increase in SO2 columns over India. Power plant regions with annual SO2 emissions greater than 50 Gg year(-1) produce statistically significant OMI signals, and a high correlation (R = 0.93) is found between SO2 emissions and OMI-observed SO2 burdens. Contrary to the decreasing trend of national mean SO2 concentrations reported by the Indian Government, both the total OMI-observed SO2 and annual average SO2 concentrations in coal-fired power plant regions increased by >60% during 2005-2012, implying the air quality monitoring network needs to be optimized to reflect the true SO2 situation in India.


Incidence rates of stroke in the eighties: the end of the decline in stroke?
Studies of the population of Rochester, Minnesota, have provided the only data on temporal trends for the incidence of stroke in North America. Among the residents of Rochester, the average annual incidence rate of stroke declined by 46%, from 213 to 115 per 100,000 population, between 1950-1954 and 1975-1979. The decline occurred in all age and sex groups, but it occurred earlier in women than in men. The rates stabilized in the 1970s, and did so earlier in women. For 1980-1984, the incidence rate of stroke was 17% higher than that for 1975-1979. The onset of the decline in incidence rates coincided with the introduction of effective antihypertensive therapy, but stabilized and increased rates were associated with continuing improvement in the control of hypertension. The increase in the incidence rates of stroke coincided with the introduction of computed tomography, which appeared to increase the detection of less severe strokes.


The Radioprotective Effects of Melatonin and Nanoselenium on DNA Double-Strand Breaks in Peripheral Lymphocytes Caused by I-131.
One of the treatment modalities for thyroid cancer and hyperthyroidism is radioiodine-131 (I-131) therapy. The use of this therapeutic modality is not completely safe and can lead to oxidative stress, eventually DNA damages. However, these radiation-induced damages can be reduced by antioxidants. This study aimed to investigate the potential radioprotective effects of melatonin and selenium nanoparticles (SeNPs) on DNA double-stranded breaks (DSBs) caused by I-131. After obtaining informed consent, 6 ml blood was taken from each volunteer. The samples were divided into two general groups of control (without I-131) and with I-131. Each group was also divided into three subgroups, including without antioxidant, melatonin, and SeNPs. The samples of control group were incubated for 2 h after adding the antioxidants. The samples of I-131 group were first incubated for 1 h with the antioxidants and then the samples re-incubated for another 1 h after adding the I-131. Then, the samples were prepared for γH2AX assay. The findings showed that after 1 h of incubation with 20 μCi I-131/2 mL, the DSB levels increased by 102.9% in comparison with the control group. In the I-131 group, there were significant reductions of the DSB levels after incubation with melatonin (P < 0.001) and SeNPs (P < 0.001) in comparison with the without antioxidant subgroup. Furthermore, the DSB levels at the melatonin + I-131 and the SeNPs + I-131 subgroups decreased to 38% and 30%, respectively, compared to the I-131 subgroup. According to the obtained findings, it can be concluded that the use of melatonin and SeNPs (as radioprotector agents) can reduce the DSB levels induced by I-131 in peripheral lymphocytes.


Outcome and clinical, pathological, and immunohistochemical factors associated with prognosis for dogs with early-stage anal sac adenocarcinoma treated with surgery alone: 34 cases (2002-2013).
OBJECTIVE To determine survival time and metastatic rate for dogs with early-stage anal sac adenocarcinoma (ASACA) treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for those dogs. DESIGN Retrospective case series. ANIMALS 34 dogs with early-stage, nonmetastatic ASACA that were treated with surgery only. PROCEDURES Medical record databases of 2 referral hospitals were searched to identify dogs examined between 2002 and 2013 that had a diagnosis of nonmetastatic ASACA that was < 3.2 cm at its largest diameter. Only dogs that received surgical treatment alone were included in the study. For each dog, information extracted from the medical record included signalment, clinical and diagnostic test findings, tumor characteristics, and outcome. When available, archived tumor specimens were histologically reviewed and tumor characteristics were described; Ki-67 and E-cadherin expressions were evaluated by use of immunohistochemical methods. Clinical, pathological, and immunohistochemical factors were assessed for associations with survival time and tumor recurrence and metastasis rates. RESULTS Median survival time was 1,237 days. Seven dogs had tumor recurrence and 9 dogs developed metastatic disease at a median of 354 and 589 days, respectively, after primary tumor removal. Cellular pleomorphism was positively associated with development of metastatic disease. No other factors evaluated were associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated dogs with early-stage nonmetastatic ASACA generally had a favorable outcome following surgical removal of the primary tumor alone. Routine rectal examination may be a simple and useful method for detection of dogs with early-stage ASACA.


What a coincidence! The effects of incidental similarity on compliance.
Four studies examined the effect of an incidental similarity on compliance to a request. Undergraduates who believed they shared a birthday (Study 1), a first name (Study 2), or fingerprint similarities (Study 3) with a requester were more likely to comply with a request than participants who did not perceive an incidental similarity with the requester. The findings are consistent with past research demonstrating that people often rely on heuristic processing when responding to requests and with Heider's description of unit relationships in which perceived similarities lead to positive affect. Consistent with the unit relation interpretation, participants did not increase compliance when hearing about an incidental similarity with someone other than the requester or when they believed the feature they shared with the requester was common.


The Fear of COVID-19 Scale: Development and Initial Validation.
The emergence of the COVID-19 and its consequences has led to fears, worries, and anxiety among individuals worldwide. The present study developed the Fear of COVID-19 Scale (FCV-19S) to complement the clinical efforts in preventing the spread and treating of COVID-19 cases. The sample comprised 717 Iranian participants. The items of the FCV-19S were constructed based on extensive review of existing scales on fears, expert evaluations, and participant interviews. Several psychometric tests were conducted to ascertain its reliability and validity properties. After panel review and corrected item-total correlation testing, seven items with acceptable corrected item-total correlation (0.47 to 0.56) were retained and further confirmed by significant and strong factor loadings (0.66 to 0.74). Also, other properties evaluated using both classical test theory and Rasch model were satisfactory on the seven-item scale. More specifically, reliability values such as internal consistency (α = .82) and test-retest reliability (ICC = .72) were acceptable. Concurrent validity was supported by the Hospital Anxiety and Depression Scale (with depression, r = 0.425 and anxiety, r = 0.511) and the Perceived Vulnerability to Disease Scale (with perceived infectability, r = 0.483 and germ aversion, r = 0.459). The Fear of COVID-19 Scale, a seven-item scale, has robust psychometric properties. It is reliable and valid in assessing fear of COVID-19 among the general population and will also be useful in allaying COVID-19 fears among individuals.


The use of in vitro systems to assess cancer mechanisms and the carcinogenic potential of chemicals.
Carcinogenesis is a highly complex, multi-stage process that can occur over a relatively long period before its clinical manifestation. While the sequence in which a cancer cell acquires the necessary traits for tumour formation can vary, there are a number of mechanisms that are common to most, if not all, cancers across the spectrum of possible causes. Many aspects of carcinogenesis can be modelled in vitro. This has led to the development of a number of mechanistically driven, cell-based assays to assess the pro-carcinogenic and anti-carcinogenic potential of chemicals. A review is presented of the current in vitro models that can be used to study carcinogenesis, with examples of cigarette smoke testing in some of these models, in order to illustrate their potential applications. We present an overview of the assays used in regulatory genotoxicity testing, as well as those designed to model other aspects that are considered to be hallmarks of cancer. The latter assays are described with a view to demonstrating the recent advances in these areas, to a point where they should now be considered for inclusion in an overall testing strategy for chemical carcinogens.


[Developmental abnormalities in humans].
Recently, tremendous advances have been made in our understanding of pre- and perinatal death and congenital anomaly, but many aspects of the field remain unknown and require the continued collaboration of workers in many clinical and basic science disciplines. Most of mankind dies before, not after birth, mostly due to chromosome abnormalities arising during pregenesis. A few trisomy 13 and 18 cases survive till birth by virtue of placental mosaicism; even trisomy 21 is an 80% prenatally lethal and a postnatally sublethal syndrome. Most aneuploid individuals surviving postnatally have sex chromosomes abnormalities (47,XXY, 47,XYY, 47,XXX). Until recently the term "monsters" was applied to many abnormalities of blastogenesis--i.e. the disruptions and malformations arising during the first 4 weeks of embyronic development (till the end of mesoderm formation). This includes not only acardia/acephaly, but also holoprosencephaly, sirenomelia, gross defects of cord, body wall and -stalk formation and conjoined twins, but also non-conjoined monozygotic twins with apparent high prenatal mortality and a high incidence of midline anomalies. One of the most important recent insights has been that associations, e.g. the VACTERAL association, and the relatively characteristic combination of anomalies seen in infants of diabetic mothers, represent disruptions of blastogenesis. The latter represent a particularly satisfying development in the field since it has been shown that control of the woman's blood sugar levels before, during and after conception helps to reduce the high incidence of defects of blastogenesis in infants of diabetic mothers. Most malformations arise during organogenesis in secondary or epimorphic fields and mostly represent anomalies of incomplete, less commonly of abnormal differentiation. An important distinction must be made between mild malformations (all-or-none defects of organogenesis) which are relatively innocuous and common in the population but never normal, and minor anomalies which are graded defects of phenogenogenesis (i.e. of the developmental processes during the fetal period (weeks 8-10 p.c.), and the most frequent anomalies in aneuploidy syndromes with resulting loss of family resemblance.(ABSTRACT TRUNCATED AT 400 WORDS)


A Mature NK Profile at the Time of HIV Primary Infection Is Associated with an Early Response to cART.
Natural killer (NK) cells are major effectors of the innate immune response. Despite an overall defect in their function associated with chronic human immunodeficiency virus (HIV) infection, their role in primary HIV infection is poorly understood. We investigated the modifications of the NK cell compartment in patients from the ANRS-147-Optiprim trial, a study designed to examine the benefits of intensive combination antiretroviral therapy (cART) in patients with acute or early primary HIV infection. Multiparametric flow cytometry combined with bioinformatics analyses identified the NK phenotypes in blood samples from 30 primary HIV-infected patients collected at inclusion and after 3 months of cART. NK phenotypes were revealed by co-expression of CD56/CD16/NKG2A/NKG2C and CD57, five markers known to delineate stages of NK maturation. Three groups of patients were formed according to their distributions of the 12 NK cell phenotypes identified. Their virological and immunological characteristics were compared along with the early outcome of cART. At inclusion, HIV-infected individuals could be grouped into those with predominantly immature/early differentiated NK cells and those with predominantly mature NK cells. Several virological and immunological markers were improved in patients with mature NK profiles, including lower HIV viral loads, lower immune activation markers on NK and dendritic cell (DC), lower levels of plasma IL-6 and IP-10, and a trend to normal DC counts. Whereas all patients showed a decrease of viremia higher than 3 log10 copies/ml after 3 months of treatment, patients with a mature NK profile at inclusion reached this threshold more rapidly than patients with an immature NK profile (70 vs. 38%). In conclusion, a better early response to cART is observed in patients whose NK profile is skewed to maturation at inclusion. Whether the mature NK cells contributed directly or indirectly to HIV control through a better immune environment under cART is unknown. The NK maturation status of primary infected patients should be considered as a relevant marker of an immune process contributing to the early outcome of cART that could help in the management of HIV-infected patients.


Androgen Therapy in Women.
Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. Testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD). However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause. In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms "HSDD," "DHEA in women," "testosterone in women," and "androgens in women," and reviewed most references from all relevant articles. Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known. A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.


The Evolution and Transmission of Epidemic GII.17 Noroviruses.
In recent decades, the GII.4 norovirus genotype has predominated in epidemics worldwide and been associated with an increased rate of evolutionary change. In 2014, a novel GII.17 variant emerged and persisted, causing large outbreaks of gastroenteritis in China and sporadic infections globally. The origin, evolution, and transmission history of this new variant are largely unknown. We generated 103 full capsid and 8 whole-genome sequences of GII.17 strains collected between August 2013 and November 2015 in Guangdong, China. Phylogenetic analyses were performed by integrating our data with those for all publically available GII.17 sequences. The novel emergent lineage GII.17_Kawasaki_2014 most likely originated from Africa around 2001 and evolved at a rate of 5.6 × 10(-3) substitutions/site/year. Within this lineage, a new variant containing several important amino acid changes emerged around August 2013 and caused extensive epidemics in 2014-2015. The phylodynamic and epidemic history of the GII.17_Kawasaki lineage shows similarities with the pattern observed for GII.4 norovirus evolution. Virus movements from Hong Kong to neighboring coastal cities were frequently observed. Our results provide new insights into GII.17 norovirus evolution and transmission and highlight the potential for a rare norovirus genotype to rapidly replace existing strains and cause local epidemics.


The co-expression of 2B4 (CD244) and CD160 delineates a subpopulation of human CD8+ T cells with a potent CD160-mediated cytolytic effector function.
Within human CD8+ T lymphocytes, the CD27-CD45RAhigh or CD56+ phenotypes contribute to precisely define the cells with CTL effector function. Novel markers were demonstrated to correlate with CTL properties, such as the 2B4 (CD244) receptor, a member of the CD2 subset of the immunoglobulin superfamily or the glycosylphosphatidylinositol-anchored CD160 receptor. We performed a study of these markers to further define the population of effectors with CTL functions. Here we show that cytotoxic subpopulations defined by surface markers CD160, CD56 and CD57 are mostly contained in the 2B4+CD8+ T cell population. Expression of CD160 identifies two populations in the 2B4+ population. The 2B4+CD160+ subset expresses a bona fide CTL phenotype. The co-expression of 2B4 and CD160 defines T cells containing high amounts of perforin and granzyme B. During CTL ontogeny, an up-regulation of 2B4 and CD160 is observed from a naive to a terminally differentiated phenotype. Finally, we demonstrated that CD160 triggering failed to induce cytotoxicity per se, but costimulated CD3-redirected killing. We conclude that the co-expression of 2B4 and CD160 defines a CD8+ T lymphocyte subpopulation with high CTL activity.


ACR Appropriateness Criteria® Suspected Physical Abuse-Child.
The youngest children, particularly in the first year of life, are the most vulnerable to physical abuse. Skeletal survey is the universal screening examination in children 24 months of age and younger. Fractures occur in over half of abused children. Rib fractures may be the only abnormality in about 30%. A repeat limited skeletal survey after 2 weeks can detect additional fractures and can provide fracture dating information. The type and extent of additional imaging for pediatric patients being evaluated for suspected physical abuse depends on the age of the child, the presence of neurologic signs and symptoms, evidence of thoracic or abdominopelvic injuries, and social considerations. Unenhanced CT of the head is the initial study for suspected intracranial injury. Clinically occult abusive head trauma can occur, especially in young infants. Therefore, head CT should be performed in selected neurologically asymptomatic physical abuse patients. Contrast-enhanced CT of the abdomen/pelvis is utilized for suspected intra-abdominal or pelvic injury. Particular attention should be paid to discrepancies between the patterns of injury and the reported clinical history. Making the diagnosis of child abuse also requires differentiation from anatomical and developmental variants and possible underlying metabolic and genetic conditions. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Control of the multimillennial wildfire size in boreal North America by spring climatic conditions.
Wildfire activity in North American boreal forests increased during the last decades of the 20th century, partly owing to ongoing human-caused climatic changes. How these changes affect regional fire regimes (annual area burned, seasonality, and number, size, and severity of fires) remains uncertain as data available to explore fire-climate-vegetation interactions have limited temporal depth. Here we present a Holocene reconstruction of fire regime, combining lacustrine charcoal analyses with past drought and fire-season length simulations to elucidate the mechanisms linking long-term fire regime and climatic changes. We decomposed fire regime into fire frequency (FF) and biomass burned (BB) and recombined these into a new index to assess fire size (FS) fluctuations. Results indicated that an earlier termination of the fire season, due to decreasing summer radiative insolation and increasing precipitation over the last 7.0 ky, induced a sharp decrease in FF and BB ca. 3.0 kyBP toward the present. In contrast, a progressive increase of FS was recorded, which is most likely related to a gradual increase in temperatures during the spring fire season. Continuing climatic warming could lead to a change in the fire regime toward larger spring wildfires in eastern boreal North America.


The Italian genome reflects the history of Europe and the Mediterranean basin.
Recent scientific literature has highlighted the relevance of population genetic studies both for disease association mapping in admixed populations and for understanding the history of human migrations. Deeper insight into the history of the Italian population is critical for understanding the peopling of Europe. Because of its crucial position at the centre of the Mediterranean basin, the Italian peninsula has experienced a complex history of colonization and migration whose genetic signatures are still present in contemporary Italians. In this study, we investigated genomic variation in the Italian population using 2.5 million single-nucleotide polymorphisms in a sample of more than 300 unrelated Italian subjects with well-defined geographical origins. We combined several analytical approaches to interpret genome-wide data on 1272 individuals from European, Middle Eastern, and North African populations. We detected three major ancestral components contributing different proportions across the Italian peninsula, and signatures of continuous gene flow within Italy, which have produced remarkable genetic variability among contemporary Italians. In addition, we have extracted novel details about the Italian population's ancestry, identifying the genetic signatures of major historical events in Europe and the Mediterranean basin from the Neolithic (e.g., peopling of Sardinia) to recent times (e.g., 'barbarian invasion' of Northern and Central Italy). These results are valuable for further genetic, epidemiological and forensic studies in Italy and in Europe.


Cortical Bone Area Predicts Incident Fractures Independently of Areal Bone Mineral Density in Older Men.
Areal bone mineral density (aBMD) measured using dual-energy X-ray absorptiometry (DXA) is used clinically to predict fracture but does not discriminate between trabecular and cortical bone assessment. This study aimed to investigate whether information on cortical and trabecular bone predict fracture risk independently of aBMD and clinical risk factors. Cortical area, bone mass, porosity, and trabecular bone volume fraction (BVTV) were measured at the tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in 456 men (80.2 ± 3.5 years) recruited from the general population in Gothenburg, Sweden. aBMD was measured using DXA. Incident fractures (71 men) were X-ray verified. Associations were evaluated using Cox regression. Cortical area [hazard ratio (HR) per standard deviation (SD) decrease, 2.05; 95% confidence interval (CI), 1.58 to 2.65], cortical bone mass (HR, 2.07; 95% CI, 1.58 to 2.70), and BVTV (HR, 1.62; 95% CI, 1.26 to 2.07), but not cortical porosity, were independently associated with fracture risk. These associations remained after adjustment for femoral neck aBMD and Fracture Risk Assessment risk factors (area: HR 1.96, 95% CI, 1.44 to 2.66; mass: HR 1.99, 95% CI, 1.45 to 2.74; BV/TV: HR 1.46, 95% CI, 1.09 to 1.96). After entering BV/TV and cortical area or bone mass simultaneously in the adjusted models, only the cortical parameters remained important predictors of fracture. HR-pQCT measurement of cortical area and mass might add clinically useful information for the evaluation of fracture risk.


Gene Expression Clustering and Selected Head and Neck Cancer Gene Signatures Highlight Risk Probability Differences in Oral Premalignant Lesions.
Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan-Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis. Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, p = 0.0052) and they expressed four enriched hallmarks: "TGF beta signaling" "angiogenesis", "unfolded protein response", "apical junction". Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters. Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve the identification of adequate prognosticators in OPLs.


Stress, Depression and Quit Attempt Outcomes among Unmotivated Smokers.
Stress and depressive symptoms have been linked to a reduced likelihood of sustaining smoking cessation. Because stress and depressive symptoms may negatively affect motivation to quit, stress and depression may also be important for whether or not smokers make a quit attempt. To examine the relationship between perceived stress and depressive symptoms and initiating a quit attempt in a smoking cessation induction trial. We conducted a secondary analysis of existing data from a randomized clinical trial (N = 255) comparing motivational interviewing to health education and brief advice for smoking cessation induction in smokers with low motivation to quit. We observed positive associations between baseline predictors and quit attempts at week 12 (r = 0.192, p < 0.01 for depressive symptoms and r = 0.136, p < 0.05 for perceived stress). Logistic regression models revealed similar significant positive associations between baseline perceived stress and baseline depressive symptoms and making a quit attempt by week 12 (OR = 1.5, CI:1.03, 2.19 and OR = 1.03, 95% CI: 1.01, 1.06; respectively). Unexpectedly, this study found generally small but consistently positive associations between baseline depressive symptoms and baseline perceived stress and making a quit attempt by week 12. The results can be viewed as encouraging in that interventions to encourage quit attempts do not appear counter-productive for individuals higher in stress and depressive symptoms, but these patients very likely will need additional supports to sustain abstinence.


A randomized controlled intervention with fish oil versus sunflower oil from 9 to 18 months of age: exploring changes in growth and skinfold thicknesses.
n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), from fish oil (FO), in rodents have been shown to reduce adipogenesis. Evidence of an effect on adipose tissue mass in humans is limited, and no studies have specifically aimed to elucidate this in infancy. To explore whether n-3 LCPUFA intake affects adipose tissue growth, we randomly allocated 154 healthy infants to daily supplementation with FO or sunflower oil (SO) from 9 to 18 mo of age and measured z-score changes in various anthropometric assessments of body size and skinfold thicknesses and plasma adipokine concentrations. Among the 133 completing infants, erythrocyte n-3 PUFA increased more in those receiving FO than in infants receiving SO [12.2 ± 0.7 (mean ± SE) versus 2.0 ± 0.4 fatty acid percentage (FA%), p < 0.001] with a concomitant larger decrease in n-6 PUFA (-8.9 ± 0.7 versus -0.9 ± 0.6 FA%, p < 0.001). We found no association between FO consumption relative to SO consumption and any of the anthropometric measures related to the size of the fat mass, but infants in the FO group had a lower skinfold ratio (triceps/subscapular) at 18 mo than those in SO group (p = 0.02). Our findings do not support the hypothesis that dietary n-3 LCPUFA is important for infant fat mass, but future studies testing this specifically are warranted.


Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8.
The Ski2-like RNA helicase Brr2 is a core component of the spliceosome that must be tightly regulated to ensure correct timing of spliceosome activation. Little is known about mechanisms of regulation of Ski2-like helicases by protein cofactors. Here we show by crystal structure and biochemical analyses that the Prp8 protein, a major regulator of the spliceosome, can insert its C-terminal tail into Brr2's RNA-binding tunnel, thereby intermittently blocking Brr2's RNA-binding, adenosine triphosphatase, and U4/U6 unwinding activities. Inefficient Brr2 repression is the only recognizable phenotype associated with certain retinitis pigmentosa-linked Prp8 mutations that map to its C-terminal tail. Our data show how a Ski2-like RNA helicase can be reversibly inhibited by a protein cofactor that directly competes with RNA substrate binding.


Peer-supported self-management for people discharged from a mental health crisis team: a randomised controlled trial.
High resource expenditure on acute care is a challenge for mental health services aiming to focus on supporting recovery, and relapse after an acute crisis episode is common. Some evidence supports self-management interventions to prevent such relapses, but their effect on readmissions to acute care following a crisis is untested. We tested whether a self-management intervention facilitated by peer support workers could reduce rates of readmission to acute care for people discharged from crisis resolution teams, which provide intensive home treatment following a crisis. We did a randomised controlled superiority trial recruiting participants from six crisis resolution teams in England. Eligible participants had been on crisis resolution team caseloads for at least a week, and had capacity to give informed consent. Participants were randomly assigned to intervention and control groups by an unmasked data manager. Those collecting and analysing data were masked to allocation, but participants were not. Participants in the intervention group were offered up to ten sessions with a peer support worker who supported them in completing a personal recovery workbook, including formulation of personal recovery goals and crisis plans. The control group received the personal recovery workbook by post. The primary outcome was readmission to acute care within 1 year. This trial is registered with ISRCTN, number 01027104. 221 participants were assigned to the intervention group versus 220 to the control group; primary outcome data were obtained for 218 versus 216. 64 (29%) of 218 participants in the intervention versus 83 (38%) of 216 in the control group were readmitted to acute care within 1 year (odds ratio 0·66, 95% CI 0·43-0·99; p=0·0438). 71 serious adverse events were identified in the trial (29 in the treatment group; 42 in the control group). Our findings suggest that peer-delivered self-management reduces readmission to acute care, although admission rates were lower than anticipated and confidence intervals were relatively wide. The complexity of the study intervention limits interpretability, but assessment is warranted of whether implementing this intervention in routine settings reduces acute care readmission. National Institute for Health Research.


Medications for opioid use disorder among pregnant women referred by criminal justice agencies before and after Medicaid expansion: A retrospective study of admissions to treatment centers in the United States.
Criminal justice involvement is common among pregnant women with opioid use disorder (OUD). Medications for OUD improve pregnancy-related outcomes, but trends in treatment data among justice-involved pregnant women are limited. We sought to examine trends in medications for OUD among pregnant women referred to treatment by criminal justice agencies and other sources before and after the Affordable Care Act's Medicaid expansion. We conducted a serial, cross-sectional analysis using 1992-2017 data from pregnant women admitted to treatment facilities for OUD using a national survey of substance use treatment facilities in the United States (N = 131,838). We used multiple logistic regression and difference-in-differences methods to assess trends in medications for OUD by referral source. Women in the sample were predominantly aged 18-29 (63.3%), white non-Hispanic, high school graduates, and not employed. Over the study period, 26.3% (95% CI 25.7-27.0) of pregnant women referred by criminal justice agencies received medications for OUD, which was significantly less than those with individual referrals (adjusted rate ratio [ARR] 0.45, 95% CI 0.43-0.46; P < 0.001) or those referred from other sources (ARR 0.51, 95% CI 0.50-0.53; P < 0.001). Among pregnant women referred by criminal justice agencies, receipt of medications for OUD increased significantly more in states that expanded Medicaid (n = 32) compared with nonexpansion states (n = 18) (adjusted difference-in-differences: 12.0 percentage points, 95% CI 1.0-23.0; P = 0.03). Limitations of this study include encounters that are at treatment centers only and that do not encompass buprenorphine prescribed in ambulatory care settings, prisons, or jails. Pregnant women with OUD referred by criminal justice agencies received evidence-based treatment at lower rates than women referred through other sources. Improving access to medications for OUD for pregnant women referred by criminal justice agencies could provide public health benefits to mothers, infants, and communities. Medicaid expansion is a potential mechanism for expanding access to evidence-based treatment for pregnant women in the US.


Trends in mammography 1991-96 and the impact of nationwide screening in The Netherlands.
To investigate the impact of the population based breast screening programme on total uptake of mammography in the Netherlands. The Netherlands; breast screening programme for women aged 50-69; 21,820 women who participated in the 1991-96 Health Interview Survey (HIS). HIS data linked to data related to the start of the screening programme in different municipalities investigating mammography use, reasons for mammography, and further assessment procedures. Among women aged 50-69 the percentage who had recently undergone mammography (in the year of the HIS or two years before) increased from 20% in 1991 to 70% in 1996, which was entirely due to screening. The percentage of women in this age group who had had a recent clinical mammogram (outside the screening programme) varied between 8 and 12% and did not change significantly in municipalities without screening. There was no change in the uptake of mammography among women under 50 years of age. Among women over 70 there was only a small increase in this percentage from 6 to 13%, partially due to screening mammograms. In municipalities in which screening had started, precaution is mentioned as a reason for a recent clinical mammogram among women aged less than 70 more often than in municipalities without screening. Furthermore, mammography performed because of complaints is mentioned less in all age groups after the introduction of screening. After a clinical mammogram, further assessment procedures (cytology/needle biopsies 8%, biopsies 10%) were considered necessary about 10 times more often than after a screening mammogram. Although the screening programme has almost no impact on the frequency of mammography in women who underwent a clinical mammogram, there has been a shift in reasons for these mammograms more towards reasons of prevention. Screening mammograms lead to a much smaller percentage of additional examinations than do clinical mammograms.


Solid-phase plate-reader quantification of specific PCR products by measurement of band-specific ethidium bromide fluorescence.
Real-time PCR is widely employed to quantify PCR products across a range of applications. However, accurate real-time PCR is not always technically feasible, and alternative methods for PCR product quantification can be expensive and time consuming to validate. We have developed an inexpensive, rapid, and immediately accessible protocol to quantify PCR products, by measuring ethidium bromide fluorescence of PCR products excised from agarose gels. This protocol has relevance to a broad range of methods in molecular biology where quantification of PCR products is necessary.


Directing migration of endothelial progenitor cells with applied DC electric fields.
Naturally-occurring, endogenous electric fields (EFs) have been detected at skin wounds, damaged tissue sites and vasculature. Applied EFs guide migration of many types of cells, including endothelial cells to migrate directionally. Homing of endothelial progenitor cells (EPCs) to an injury site is important for repair of vasculature and also for angiogenesis. However, it has not been reported whether EPCs respond to applied EFs. Aiming to explore the possibility to use electric stimulation to regulate the progenitor cells and angiogenesis, we tested the effects of direct-current (DC) EFs on EPCs. We first used immunofluorescence to confirm the expression of endothelial progenitor markers in three lines of EPCs. We then cultured the progenitor cells in EFs. Using time-lapse video microscopy, we demonstrated that an applied DC EF directs migration of the EPCs toward the cathode. The progenitor cells also align and elongate in an EF. Inhibition of vascular endothelial growth factor (VEGF) receptor signaling completely abolished the EF-induced directional migration of the progenitor cells. We conclude that EFs are an effective signal that guides EPC migration through VEGF receptor signaling in vitro. Applied EFs may be used to control behaviors of EPCs in tissue engineering, in homing of EPCs to wounds and to an injury site in the vasculature.


Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer.
To systematically review the literature to determine the prevalence and clinical outcomes of second primary oropharyngeal squamous cell carcinoma (OPSCC). Search strategies created with a medical librarian were implemented using multiple databases in October 2019. The population of interest included adults age >18 years with a p16+ or human papillomavirus-positive OPSCC. The outcome was a synchronous or metachronous second primary OPSCC. Inclusion and exclusion criteria were designed to capture all study designs. In total, 685 records were identified by the search strategy. Two reviewers independently performed the review, extracted data, and performed a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A random-effects model was used for the meta-analysis. A total of 2470 patients with 35 second primary OPSCCs from 15 studies were identified. The pooled prevalence of second primary OPSCC was 1.4% (range, 0%-14.3%). In the random-effects model, the prevalence was estimated at 1.3% (95% CI, 0.7%-2.3%; P = .51, I2 = 52%). Of the 30 patients with treatment information, 26 (86.7%) received surgical treatment, while 4 (13.3%) underwent nonsurgical therapy. Of the 29 patients with available survival information, 22 (75.9%) had no evidence of disease at last follow-up, 5 (17.2%) ultimately died of disease, and 2 (6.9%) were alive with disease. Overall, the rate of second primary OPSCC in patients with an index p16+ OPSCC is low, and most patients are successfully treated. Insufficient evidence currently exists to recommend routine elective tonsillectomy during surgical treatment of p16+ OPSCC.


Serum thyroxine and triiodothyronine responses of hyperthyroid cats to thyrotropin.
To document circulating total thyroxine (T4) and triiodothyronine (T3) responses after administration of thyrotropin (thyroid-stimulating hormone [TSH]) to hyperthyroid and healthy cats and assess the value of these responses as an additional diagnostic test for hyperthyroidism. Prospective case series. 21 healthy and 40 hyperthyroid cats. Serum total T4 and T3 concentrations were measured by radioimmunoassay before and 6 hours after administration of 0.5 IU of bovine TSH/kg of body weight. In healthy cats, serum total T4 concentration increased after administration of TSH (mean +/- SD, 114.0 +/- 36.4 nmol/L) representing a mean increment 3 times baseline concentration (mean +/- SD, 33.7 +/- 7.6 nmol/L). In hyperthyroid cats, the relative increase in serum total T4 concentration was significantly (P < 0.001) different; baseline values (mean +/- SD, 236.2 +/- 146.0 nmol/L) increased minimally after TSH administration (mean +/- SD, 308.1 +/- 178.9 nmol/L) There was a significant negative correlation (rs = -0.366) between relative increase in serum total T4 concentration after TSH administration and baseline concentration in hyperthyroid cats. In 3 cats with equivocal baseline serum total T4 concentration, the T4 response to TSH administration was indistinguishable from that in healthy cats. Serum total T3 response to TSH administration was significantly (P < 0.001) lower in hyperthyroid, compared with healthy, cats but the T3 response in healthy cats was more variable than that for T4 Thyrotoxic cats with high baseline serum total T4 concentration have a limited T4 response to TSH stimulation. Hyperthyroid cats with equivocal baseline serum total T4 concentrations have T4 response after TSH stimulation similar to those of healthy cats. Measurement of serum total T3 concentration provides no additional information. The TSH response test is of limited value in diagnosing hyperthyroidism in cats.


1 H NMR-based metabolomics study for identifying urinary biomarkers and perturbed metabolic pathways associated with severity of IgA nephropathy: a pilot study.
The severity of IgA nephropathy (IgAN), the most common primary glomerulonephritis, is judged on the basis of histologic and clinical features. A limited number of studies have considered molecular signature of IgAN for this issue, and no reliable biomarkers have been presented non-invasively for use in patient evaluations. This study aims to identify metabolite markers excreted in the urine and impaired pathways that are associated with a known marker of severity (proteinuria) to predict mild and severe stages of IgAN. Urine samples were analysed using nuclear magnetic resonance from biopsy-proven IgAN patients at mild and severe stages. Multivariate statistical analysis and pathway analysis were performed. The most changed metabolites were acetoacetate, hypotaurine, homocysteine, L-kynurenine and phenylalanine. Nine metabolites were positively correlated with proteinuria, including mesaconic acid, trans-cinnamic acid, fumaric acid, 5-thymidylic acid, anthranilic acid, indole, deoxyguanosine triphosphate, 13-cis-retinoic acid and nicotinamide riboside, while three metabolites were negatively correlated with proteinuria including acetoacetate, hypotaurine and hexanal. 'Phenylalanine metabolism' was the most significant pathway which was impaired in severe stage in comparison to mild stage of IgAN. This study indicates that nuclear magnetic resonance is a versatile technique that is capable of detecting metabolite biomarkers in combination with advanced multivariate statistical analysis. Copyright © 2017 John Wiley & Sons, Ltd.


Perspectives on Components of an Online Training and Support Program for Dementia Family Caregivers in India: A Focus Group Study.
There is a considerable need for support interventions for caregivers of people with dementia in developing countries, such as India. The purpose of the study was to identify the components and understand the acceptability of an online training and support program for dementia caregivers in India. Three focus group discussions were carried out with dementia caregivers (2) and health professionals (1) to understand the requirements of an online training and support program from their perspective. The commonly recurring themes were identified and defined using thematic content analysis. The expectations from an online training and support program were wide-ranging from information about identification and management of dementia to support caregiver well-being. Use of simple language, cultural relevance, and an interactive design were suggestions to facilitate the use of the support program. Lack of time, difficulty in accessing the internet, lack of awareness about the portal, difficulty in reaching the rural population were anticipated as challenges in using the program. The study highlights the requisite components of a first of its kind online training and support program in India by integrating the experiences, motivations, challenges, and expectations of caregivers and professionals involved in dementia care. The focus group discussions in the current study provide a road map for the development of an online caregiver training and support program underlying the perspectives of the stakeholders for the consolidation of an effective dementia care program for lower resourced settings.


Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy.
Despite the recent successes of using immune modulatory Abs in patients with cancer, autoimmune pathologies resulting from the activation of self-reactive T cells preclude the dose escalations necessary to fully exploit their therapeutic potential. To reduce the observed and expected toxicities associated with immune modulation, here we describe a clinically feasible and broadly applicable approach to limit immune costimulation to the disseminated tumor lesions of the patient, whereby an agonistic 4-1BB oligonucleotide aptamer is targeted to the tumor stroma by conjugation to an aptamer that binds to a broadly expressed stromal product, VEGF. This approach was predicated on the premise that by targeting the costimulatory ligands to products secreted into the tumor stroma, the T cells will be costimulated before their engagement of the MHC-peptide complex on the tumor cell, thereby obviating the need to target the costimulatory ligands to noninternalizing cell surface products expressed on the tumor cells. Underscoring the potency of stroma-targeted costimulation and the broad spectrum of tumors secreting VEGF, in preclinical murine tumor models, systemic administration of the VEGF-targeted 4-1BB aptamer conjugates engendered potent antitumor immunity against multiple unrelated tumors in subcutaneous, postsurgical lung metastasis, methylcholantrene-induced fibrosarcoma, and oncogene-induced autochthonous glioma models, and exhibited a superior therapeutic index compared with nontargeted administration of an agonistic 4-1BB Ab or 4-1BB aptamer.


A Case of Amiodarone Pulmonary Toxicity with Short-term Amiodarone Use.
This is the case of a 92-year-old female who was hospitalized one month prior to admission for symptomatic paroxysmal atrial fibrillation, requiring intravenous amiodarone. Following her previous admission, she was placed on one month of amiodarone 200 mg twice daily, with a one week transition to 200 mg daily. The patient subsequently developed progressive shortness of breath and dry cough over a period of several weeks. Initial imaging showed diffuse bilateral coarse patchy interstitial infiltration on chest X-ray and bibasilar pleural effusions and scattered bilateral opacities on CTA chest. In an elderly patient presenting with dyspnea and dry cough, as well as interstitial opacities on imaging, amiodarone pulmonary toxicity should be considered despite short-term low-dose use.


Habitual sugar intake and cognitive function among middle-aged and older Puerto Ricans without diabetes.
Intake of added sugars, mainly fructose and sucrose, has been associated with risk factors for cognitive impairment, such as obesity, the metabolic syndrome and type 2 diabetes. The objective of this analysis was to examine whether habitual intakes of total sugars, added sugars, sugar-sweetened beverages or sweetened solid foods are associated with cognitive function. The present study included 737 participants without diabetes, aged 45-75 years, from the Boston Puerto Rican Health Study, 2004-9. Cognitive function was measured with a battery of seven tests: Mini-Mental State Examination (MMSE), word list learning, digit span, clock drawing, figure copying, and Stroop and verbal fluency tests. Usual dietary intake was assessed with a validated FFQ. Greater intakes of total sugars, added sugars and sugar-sweetened beverages, but not of sugar-sweetened solid foods, were significantly associated with lower MMSE score, after adjusting for covariates. Adjusted OR for cognitive impairment (MMSE score < 24) were 2.23 (95 % CI 1.24, 3.99) for total sugars and 2.28 (95 % CI 1.26, 4.14) for added sugars, comparing the highest with lowest intake quintiles. Greater intake of total sugars was also significantly associated with lower word list learning score. In conclusion, higher sugar intake appears to be associated with lower cognitive function, but longitudinal studies are needed to clarify the direction of causality.


Recurrent Spontaneous Pneumothorax during the Recovery Phase of ARDS Due to H1N1 Infection.
The pregnant patients are prone to influenza A (H1N1) virus infection, which may rapidly progress to lower respiratory tract infection and subsequent respiratory failure and acute respiratory distress syndrome (ARDS). Pneumothorax might develop in ARDS under mechanical ventilation. But post-ARDS pneumothorax in spontaneously breathing patient has not been reported in the literature. We report a 31-year old pregnant woman infected with influenza A (H1N1) virus and progressed to ARDS. Mechanical ventilation with high PEEP improved patient's gas exchange parameters within 3 weeks. However spontaneous pneumothorax was developed one week after she weaned off the ventilator. After successful drainage therapy, the patient was discharged. However she re-admitted to the hospital because of a recurrent pneumothorax one week later. She was discharged in good health after being treated with negative continuous pleural aspiration for 10 days. Influenza might cause severe pulmonary infection and death. In addition to diffuse alveolar damage, sub-pleural and intrapulmonary air cysts might occur in influenza-related ARDS and may lead to spontaneous pneumothorax. This complication should always be considered during the recovery period of ARDS and a long-term close follow-up is necessary.


Testosterone and group size in cliff swallows: testing the "challenge hypothesis" in a colonial bird.
The "challenge hypothesis" states that increases in testosterone levels of male animals during the breeding season are directly related to the extent of intrasexual competition for resources or mates that they experience. Although often tested in territorial species, the challenge hypothesis has not been evaluated for colonial animals that live in groups of different sizes and that thus experience different intensities of intrasexual competition. We measured circulating testosterone levels of male and female cliff swallows (Petrochelidon pyrrhonota) in southwestern Nebraska, where these birds nest in colonies of widely different sizes. Males had significantly higher testosterone levels than females, as expected. For males especially, there was a seasonal rise in testosterone levels early in the nesting cycle, corresponding to the period when birds were establishing nest ownership and egg laying, and then a fall as they switched to parental duties. Testosterone levels varied significantly with colony size; for both sexes, birds in larger colonies had higher levels of testosterone than those in smaller colonies when controlling for date. Age and body mass were not related to testosterone levels. Higher levels of testosterone for birds of both sexes in larger colonies probably reflect greater competition for matings, often extra pair, in the more social nesting situations. The results support the predictions of the challenge hypothesis.


Bariatric Surgery Is a Safe and Effective Option for Patients with Inflammatory Bowel Diseases: A Case Series and Systematic Review of the Literature.
Questions remain regarding both the safety and efficacy of bariatric surgery in patients with inflammatory bowel diseases (IBD), including the effects of bariatric surgery on the course of disease. We report a case series from a tertiary care IBD referral center and review the existing literature regarding the safety and efficacy of bariatric surgery in IBD patients. Examine the safety and efficacy of bariatric surgery in IBD patients. Explore possible effects of weight loss on postoperative IBD course. We performed a retrospective review of patients at our center undergoing bariatric surgery with a concurrent IBD diagnosis, collecting baseline characteristics, surgery type, and postoperative course (including IBD outcomes and weight loss). Data from these patients were combined with available data from the existing literature to calculate standardized means with standard error, variance, and confidence intervals (CI). Data from 13 patients who had undergone bariatric surgery at our facility were combined with data from 8 other studies to create a study population of 101 patients. Of these, 61 had Crohn's disease, 37 ulcerative colitis, and 3 IBD-unspecified, with a mean preoperative BMI of 44.2 (95% CI 42.9-45.7). Following surgery, a mean excess weight loss of 68.4% was demonstrated (95% CI, 65.7-71.2). Of the 101 patients, 22 experienced early and 20 experienced late postoperative complications. Postoperatively, 10 patients experienced a flare of IBD, 20 remained in remission, and 7 patients were able to discontinue immunosuppressive therapy. Based on available studies, bariatric surgery appears to be both an effective and safe option for weight loss in patients with IBD.


Assessment of the accuracy of a new tool for the screening of smartphone addiction.
To translate, adapt and validate the Smartphone Addiction Inventory (SPAI) in a Brazilian population of young adults. We employed the translation and back-translation method for the adaptation of the Brazilian version SPAI (SPAI-BR). The sample consisted of 415 university students. Data was collected through an electronic questionnaire, which consisted of the SPAI-BR and the Goodman Criteria (gold standard). The retests were carried out 10-15 days after the initial tests with 130 individuals. The SPAI-BR maintained semantic, idiomatic and conceptual equivalences from the original scale. The Confirmatory Factor Analysis confirmed the One-factor model of the SPAI with good fit indexes (x2 = 767.861, CFI = 0.913, TLI = 0.905, RMSE = 0.061, WRMR = 1.465). The Kuder-Richardson Coefficient showed good internal consistency. The analysis of the ROC curve established an area under the curve of 86.38%. The Intraclass-Correlation Coefficient of 0.926 between the test and the retest demonstrated an excellent temporal stability. The high correlation between SPAI-BR and the Goodman Criteria (rs = 0.750) established the convergent validity. The SPAI-BR is a valid and reliable tool for the detection of Smartphone Addiction in Brazilian university students.


Exercise electrocardiogram testing in two brothers with different outcome - a case study exercise testing in master cyclists.
The cases of two brothers training and competing as master cyclists and both preparing for a cycling tour are presented. The older brother aged 66 years went first to the primary care physician and presented with an asymptomatic depression in the exercise stress test of the ST segment in V5 and V6 during recovery after complete exhaustion. Coronary angiography revealed a multi vessel coronary artery disease and he underwent bypass surgery. One year later, he successfully completed his planned cycling tour of ~600 km in seven stages and covering ~12,000 m of total ascent. The younger brother aged 59 years went a few months later to the primary care physician and also performed asymptomatic exercise stress testing without changes in the ST segments. Unfortunately, 2 months later he suffered a cardiac arrest during his cycling tour and survived following immediate successful cardiopulmonary resuscitation on the road by his cycling colleagues. Immediate invasive coronary arteriography showed a complete stenosis of the trunk of arteria coronaria sinistra (left coronary artery), a 40%-50% stenosis of ramus circumflexus, and a 20% stenosis of arteria coronaria dextra (right coronary artery). The left coronary artery was dilated and he continued cycling 2 months later. In both brothers, familial hypercholesterolemia was the main cardiovascular risk factor for the multi vessel coronary artery disease. A negative exercise electrocardiogram in siblings with an increased risk for coronary artery disease seemed not to exclude an advanced multi vessel coronary artery disease. In master athletes with asymptomatic exercise electrocardiogram but a positive family history, further examinations should be performed in order to detect relevant stenosis in coronary arteries.


Impact of the pattern of interstitial lung disease on mortality in rheumatoid arthritis: A systematic literature review and meta-analysis.
An important extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). The relationship between the usual interstitial pneumonia (UIP) pattern and mortality in patients with RA is unclear. The purpose of this study was to complete a systematic literature review and meta-analysis on the association between RA-ILD pattern and mortality risk. We performed a systematic literature review through December 12, 2018. Study characteristics, unadjusted and adjusted relative risks (RR) of mortality for ILD pattern were extracted from the identified studies and quality assessments were performed. RR for mortality (RA-UIP vs. other RA-ILD) was pooled using inverse variance weighting and random effects models. Ten retrospective cohort studies met our eligibility criteria. A total of 1256 RA-ILD patients were included with 484 total deaths. Meta-analysis yielded a pooled RR of 1.66 (95% confidence interval1.07 to 2.56) for death among those with UIP RA-ILD compared with other patterns. In sub-group analysis when pooling studies comparing UIP to NSIP pattern of RA-ILD, the RR was 2.39 (95% CI 0.86-6.68). Through a systematic literature review and meta-analysis, we found UIP pattern to be associated with a higher mortality risk in RA-ILD compared to other patterns of RA-ILD although more recent studies emphasize the importance of pulmonary physiology and the extent of lung involvement as significant predictors of mortality rather than the pattern of RA-ILD. Recognizing the small number of studies satisfying eligibility and inconsistent accounting for confounders, further study of mortality risk in RA-ILD is needed with standardized assessment of various RA, ILD, and patient-related factors.


Medication errors detected in non-traditional databases: types of errors in methotrexate dosing as listed in four different Danish registers.
We have looked for medication errors involving the use of low-dose methotrexate, by extracting information from Danish sources other than traditional pharmacovigilance databases. We used the data to establish the relative frequencies of different types of errors. We searched four databases for cases involving low-dose methotrexate between 1999 and 2011: the Danish Patient Safety Databases (DPSD), controlled by the Danish National Agency for Patients' Rights and Complaints, the Patient Compensation Association (PCA), the Danish Poison and Information Centre (DPIC), and the online database of the Department for Patient Complaints (DPC). We categorized the place where the error occurred, the processes and types of error involved, the person responsible, and the clinical outcome. We identified 173 errors. In 109 (63%), either harm resulted or could not be excluded; of these, 26 (15%) resulted in serious harm, including nine deaths (5%); 53 (31%) involved incorrect daily administration; and 107 (62%) involved a dosing error. Sixteen events (9.2%) concerned insufficient or faulty monitoring, with four serious outcomes and two deaths. Prescription errors involving daily rather than weekly administration, by hospital physicians, were most likely to result in serious outcomes, including deaths. The error mechanism was evaluated in 129 events. Action-based errors comprised 50 % and knowledge-based errors 34 %. Action-based errors were more likely to result in completed errors, whereas knowledge-based errors more often resulted in near misses. The medication errors in this survey were most often action-based (50%) and knowledge-based (34%), suggesting that greater attention should be paid to education and surveillance of medical personnel who prescribe and monitor methotrexate, particularly physicians, who accounted for 40% of the errors.


Pap smear quality parameters of 3 sampling devices used by auxiliary nurse midwives on symptomatic rural Indian women.
To determine whether auxiliary nurse midwives (ANMs) could make good-quality Pap smears after focused training and to determine which sampling device is most effective in their hands in field practice areas. In a downstaging cervical cancer screening program, 394 symptomatic rural Indian women between the ages of 35 and 60 were identified by the ANMs in 2 villages, with a total population of 14,747, and were invited to have a smear taken. Two hundred of these symptomatic women responded. The ANMs were educated to render information on screening for cervical cancer and to take smears with 3 sampling devices--Ayre spatula, modified spatula (with extended tip) and Cytobrush (Medscand AB, Malmö, Sweden). The smears were evaluated for 6 adequacy parameters. Smears made by gynecologists were used as controls. To establish the superiority of a method, chi2 tests were used. All smears made by the ANMs could be used to render a cytologic diagnosis. The adequacy parameters of all the smears made by ANMs at least matched those of the gynecologists. The best results were obtained with modified spatula (with extended tip) and combination of Cytobrush with modified spatula. Since only 50% of symptomatic rural women came for Pap testing, we conclude it is not easy to motivate women for such testing, even if a large-scale educational effort is made. ANMs can be taught to take reasonably good qualisuperior sampling device for ANMs is ty Pap smears. The superior sampling device for ANMs is the modified spatula (with extended tip).


Chloroplast genes are expressed during intracellular symbiotic association of Vaucheria litorea plastids with the sea slug Elysia chlorotica.
The marine slug Elysia chlorotica (Gould) forms an intracellular symbiosis with photosynthetically active chloroplasts from the chromophytic alga Vaucheria litorea (C. Agardh). This symbiotic association was characterized over a period of 8 months during which E. chlorotica was deprived of V. litorea but provided with light and CO2. The fine structure of the symbiotic chloroplasts remained intact in E. chlorotica even after 8 months of starvation as revealed by electron microscopy. Southern blot analysis of total DNA from E. chlorotica indicated that algal genes, i.e., rbcL, rbcS, psaB, psbA, and 16S rRNA are present in the animal. These genes are typically localized to the plastid genome in higher plants and algae except rbcS, which is nuclear-encoded in higher plants and green (chlorophyll a/b) algae. Our analysis suggests, however, that similar to the few other chromophytes (chlorophyll a/c) examined, rbcS is chloroplast encoded in V. litorea. Levels of psbA transcripts remained constant in E. chlorotica starved for 2 and 3 months and then gradually declined over the next 5 months corresponding with senescence of the animal in culture and in nature. The RNA synthesis inhibitor 6-methylpurine reduced the accumulation of psbA transcripts confirming active transcription. In contrast to psbA, levels of 16S rRNA transcripts remained constant throughout the starvation period. The levels of the photosystem II proteins, D1 and CP43, were high at 2 and 4 months of starvation and remained constant at a lower steady-state level after 6 months. In contrast, D2 protein levels, although high at 2 and 4 months, were very low at all other periods of starvation. At 8 months, de novo synthesis of several thylakoid membrane-enriched proteins, including D1, still occurred. To our knowledge, these results represent the first molecular evidence for active transcription and translation of algal chloroplast genes in an animal host and are discussed in relation to the endosymbiotic theory of eukaryote origins.


Quantitative assessment of sensitizing potency using a dose-response adaptation of GARDskin.
Hundreds of chemicals have been identified as skin sensitizers. These are chemicals that possess the ability to induce hypersensitivity reactions in humans, giving rise to a condition termed allergic contact dermatitis. The capacity to limit hazardous exposure to such chemicals depends upon the ability to accurately identify and characterize their skin sensitizing potency. This has traditionally been accomplished using animal models, but their widespread use offers challenges from both an ethical and a scientific perspective. Comprehensive efforts have been made by the scientific community to develop new approach methodologies (NAMs) capable of replacing in vivo assays, which have successfully yielded several methods that can identify skin sensitizers. However, there is still a lack of new approaches that can effectively measure skin sensitizing potency. We present a novel methodology for quantitative assessment of skin sensitizing potency, which is founded on the already established protocols of the GARDskin assay. This approach analyses dose-response relationships in the GARDskin assay to identify chemical-specific concentrations that are sufficient to induce a positive response in the assay. We here compare results for 22 skin sensitizers analyzed using this method with both human and LLNA potency reference data and show that the results correlate strongly and significantly with both metrics (rLLNA = 0.81, p = 9.1 × 10-5; rHuman = 0.74, p = 1.5 × 10-3). In conclusion, the results suggest that the proposed GARDskin dose-response methodology provides a novel non-animal approach for quantitative potency assessment, which could represent an important step towards reducing the need for in vivo experiments.


Lipid headgroup discrimination by antimicrobial peptide LL-37: insight into mechanism of action.
Interaction of the human antimicrobial peptide LL-37 with lipid monolayers has been investigated by a range of complementary techniques including pressure-area isotherms, insertion assay, epifluorescence microscopy, and synchrotron x-ray scattering, to analyze its mechanism of action. Lipid monolayers were formed at the air-liquid interface to mimic the surface of the bacterial cell wall and the outer leaflet of erythrocyte cell membrane by using phosphatidylglycerol (DPPG), phosphatidylcholine (DPPC), and phosphatidylethanolamine (DPPE) lipids. LL-37 is found to readily insert into DPPG monolayers, disrupting their structure and thus indicating bactericidal action. In contrast, DPPC and DPPE monolayers remained virtually unaffected by LL-37, demonstrating its nonhemolytic activity and lipid discrimination. Specular x-ray reflectivity data yielded considerable differences in layer thickness and electron-density profile after addition of the peptide to DPPG monolayers, but little change was seen after peptide injection when probing monolayers composed of DPPC and DPPE. Grazing incidence x-ray diffraction demonstrated significant peptide insertion and lateral packing order disruption of the DPPG monolayer by LL-37 insertion. Epifluorescence microscopy data support these findings.


A 2 D high accuracy slope measuring system based on a Stitching Shack Hartmann Optical Head.
We present a 2D Slope measuring System based on a Stitching Shack Hartmann Optical Head (SSH-OH) aiming to perform high accuracy optical metrology for X-ray mirrors. This system was developed to perform high-accuracy automated metrology for extremely high quality optical components needed for synchrotrons or Free Electrons Lasers (FEL), EUV lithography and x-ray astronomy with slope error accuracy better than 50 nrad rms.