Nonoperative Versus Operative Treatment of Displaced Ankle Fractures in Diabetics.
Diabetes is a risk factor for complications related to displaced ankle fractures. Limited literature exists comparing complication rates in nonoperative versus operative treatment of displaced ankle fractures in diabetics. No study has highlighted the natural history of nonoperative treatment of displaced ankle fractures in diabetics. We retrospectively reviewed all adult ankle fractures from September 2011 through December 2014. Inclusion was limited to ambulatory adults (>18 years) with closed, displaced (widened mortise) ankle fractures with diabetes mellitus. Nonoperative treatment consisted of closed reduction and casting. Fractures were classified according to the Lauge-Hansen and AO-Weber classification systems. All operative fractures underwent open reduction internal fixation (ORIF) within 3 weeks of injury. Functional outcomes and complication rates were compared. Of 28 displaced diabetic ankle fractures, 20 were treated nonoperatively (closed reduction and casting) and 8 operatively (ORIF within 3 weeks of injury). Mean follow-up was 7 months (range 3-18 months). Age, insulin-dependent diabetes, and AO type B fracture rate were similar in nonoperative and operative cohorts, but fracture dislocation rate was significantly higher among operative fractures (87.5% vs 40%; P = .04). Nonoperative treatment was associated with a 21-fold increased odds of complication compared with operative treatment (75% vs 12.5%, OR 21.0, P = .004). Complication rate following unintended ORIF for persistent nonunion or malunion in nonoperatively treated patients was significantly greater compared with immediate ORIF (100% vs 12.5%, P = .005). Nonoperative treatment of displaced diabetic ankle fractures was associated with unacceptably high complication rates when compared to operative treatment. Level III, retrospective comparative series.


Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models.
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis of LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted with synphilin-1 (SP1), a cytoplasmic protein that interacts with α-synuclein and has implications in PD pathogenesis. LRRK2 interacted with the N-terminus of SP1 whereas SP1 predominantly interacted with the C-terminus of LRRK2, including kinase domain. Co-expression of SP1 with LRRK2 increased LRRK2-induced cytoplasmic aggregation in cultured cells. Moreover, SP1 also attenuated mutant LRRK2-induced toxicity and reduced LRRK2 kinase activity in cultured cells. Knockdown of SP1 by siRNA enhanced LRRK2 neuronal toxicity. In vivo Drosophila studies, co-expression of SP1 and mutant G2019S-LRRK2 in double transgenic Drosophila increased survival and improved locomotor activity. Expression of SP1 protects against G2019S-LRRK2-induced dopamine neuron loss and reduced LRRK2 phosphorylation in double transgenic fly brains. Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role.


Mechanisms of B-cell synapse formation predicted by Monte Carlo simulation.
The clustering of B-cell receptor (BCR) molecules and the formation of the protein segregation structure known as the "immunological synapse" at the contact region between B cells and antigen presenting cells appears to precede antigen (Ag) uptake by B cells. The mature B-cell synapse is characterized by a central cluster of BCR/Ag molecular complexes surrounded by a ring of LFA-1/ICAM-1 complexes. In this study, we investigate the biophysical mechanisms that drive immunological synapse formation in B cells by means of Monte Carlo simulation. Our approach simulates individual reaction and diffusion events on cell surfaces in a probabilistic manner with a clearly defined mapping between our model's probabilistic parameters and their physical equivalents. Our model incorporates the bivalent nature of the BCR as well as changes in membrane shape due to receptor-ligand binding. We find that differences in affinity and bond stiffness between BCR/Ag and LFA-1/ICAM-1 are sufficient to drive synapse formation in the absence of membrane deformation. When significant membrane deformation occurs as a result of receptor-ligand binding, our model predicts the affinity-dependent mechanism needs to be complemented by a BCR signaling-driven shift in LFA-1 affinity from low to high in order for synapses to form.


Alcohol Consumption and Breast Cancer Risk According to Hormone Receptor Status in Japanese Women: A Case-Control Study.
Alcohol consumption is a risk factor for breast cancer in Western countries, but few studies have evaluated the risk for Japanese women, who have a relatively low alcohol intake. This case-control study investigated the association of alcohol consumption with breast cancer risk according to estrogen-receptor and progesterone-receptor (ER/PgR) status in Japanese women. From female patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2011, 1,256 breast cancer cases (669 ER+/PgR+, 162 ER+/PgR-, 21 ER-/PgR+, 305 ER-/PgR-, and 99 missing) and 2,933 controls were selected. Alcohol-related measures were assessed using a self-administered questionnaire. Unconditional logistic regression analysis was performed. Alcohol-related measures were not associated with breast cancer risk among the women overall. Moreover, no association was observed between ever drinking and the risk of a concordant receptor subtype (ER+/PgR+ or ER-/PgR-). Conversely, ever drinking was inversely associated with the risk of discordant subtype (ER+/PgR-, odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.41-0.95; ER-/PgR+, OR = 0.44, 95% CI: 0.14-1.42). For ER+/PgR-, an inverse association with the amount of alcohol consumed per day was observed (P for trend = 0.04), and this inverse association was limited to premenopausal women. Alcohol consumption may have differential effects on concordant and discordant receptor subtypes of breast cancer. In view of the low frequency of discordant subtype in Japanese women and their relatively low alcohol intake, our findings may provide a clue for elucidating the etiology of breast cancer rather than for preventing discordant subtype.


Relationship between methods of monitoring training load and physiological indicators changes during 4 weeks cross-country skiing altitude training.
This study aimed to: (i) analyze the load characteristics of 4 weeks cross-country skiing altitude training; (ii) analyze the relationships between methods of monitoring training load and physiological indicators changes of elite male Chinese cross-country skiers during this period. Practitioners collected load data during 4 weeks of altitude training camp. Participants performed maximal oxygen uptake, lactate threshold, body composition, and skierg power test before and after the training camp to investigate the changes in physiological performance. Edwards TRIMP, Lucia TRIMP, and session rating of perceived exertion were collected as internal load. Training distance, time recorded by the Catapult module were collected as external load. The result revealed a " pyramid " pattern in the load characteristics during the altitude training camp. The correlation between luTRIMP and percent change in physiological indicators was highest. Percentage changes in lactate threshold velocity (r = .78 [95% CI -.01 to .98]), percentage changes in lactate threshold HR (r = .71 [95% CI .14- .99]), percentage changes in maximum HR (r = .83 [95% CI .19-1.00]), percentage changes in skierg power-to-weight ratio (r = .75 [95% CI -.28 to .98]) had very large relationships with luTRIMP. In cross-country skiing altitude training, training loads should be reasonably controlled to ensure that athletes do not become overly fatigued. Methods of training load monitoring that combine with athletes' physiological characteristics and program characteristics have the highest dose-response relationships, it is an important aspect of cross-country ski training load monitoring. The luTRIMP could be a good monitoring tool in cross-country skiing altitude training.


Intraglomerular deposition of coagulation-fibrinolysis factors and a platelet membrane antigen in various glomerular diseases.
The intraglomerular location of coagulation-fibrinolysis factors (CFF) and a platelet membrane antigen (glycoprotein IIb-IIIa; GPIIb-IIIa) was determined in 101 patients with various glomerular diseases. Renal biopsy specimens were examined by immunofluorescence microscopy, using antisera against fibrinogen/fibrin reactive antigen (FRA), cross-linked fibrin degradation products (XL-FDP), fibronectin (FN), factor XIII-subunit a (F-XIIIa), plasminogen (Plg), alpha 2-plasmin inhibitor (alpha 2-PI) and GPIIb-IIIa. Intraglomerular deposits of the CFF were found at high rates in patients with IgA glomerulonephritis (GN), membranous nephropathy (MN) and lupus GN. The coexistence of deposits of these factors was ascertained by the double-staining method. The deposition rates of XL-FDP and GPIIb-IIIa were very low in patients with minimal-change nephrotic syndrome and focal glomerulosclerosis. Some cases of diabetic glomerulosclerosis (DGS) showed CFF deposition. FRA deposits associated with F-XIIIa and FN may indicate the presence of the cross-linked fibrin. Furthermore, the presence of Plg deposits together with alpha 2-PI and XL-FDP suggests the deposition of fibrin followed by fibrinolysis, but not of fibrinogen, and the coexistence of GPIIb-IIIa suggests the involvement of platelets in the reactions. These studies provide evidence that stabilized fibrin deposition with subsequent fibrinolysis and platelet activation take place in glomeruli in a fairly large proportion of patients with IgA GN, MN and lupus GN and in some cases of DGS.


Indications for compression therapy in venous and lymphatic disease consensus based on experimental data and scientific evidence. Under the auspices of the IUP.
The aim of this study was to review published literature concerning the use of compression treatments in the management of venous and lymphatic diseases and establish where reliable evidence exists to justify the use of medical compression and where further research is required to address areas of uncertainty. The authors searched medical literature databases and reviewed their own collections of papers, monographs and books for papers providing information about the effects of compression and randomized clinical trials of compression devices. Papers were classified in accordance with the recommendations of the GRADE group to categorize their scientific reliability. Further classification was made according to the particular clinical problem that was addressed in the papers. The review included papers on compression stockings, bandages and intermittent pneumatic compression devices. The International Compression Club met once in Vienna and corresponded by email in order to reach an agreement of how the data should be interpreted. A wide range of compression levels was reported to be effective. Low levels of compression 10-30 mmHg applied by stockings are effective in the management of telangiectases after sclerotherapy, varicose veins in pregnancy, the prevention of edema and deep vein thrombosis (DVT). High levels of compression produced by bandaging and strong compression stockings (30-40 mmHg) are effective at healing leg ulcers and preventing progression of post-thrombotic syndrome as well as in the management of lymphedema. In some areas no reliable evidence was available to permit recommendations of level of compression or duration of treatment. These included: management of varicose veins to prevent progression, following surgical treatment or sclerotherapy for varicose veins, and the level of compression required to treat acute DVT. This review shows that whilst good evidence for the use of compression is available in some clinical indications, there is much still to be discovered. Little is know about dosimetry in compression, for how long and at what level compression should be applied. The differing effects of elastic and short-stretch compression are also little understood.


Point-of-care Lung Ultrasound Is More Sensitive than Chest Radiograph for Evaluation of COVID-19.
Current recommendations for diagnostic imaging for moderately to severely ill patients with suspected coronavirus disease 2019 (COVID-19) include chest radiograph (CXR). Our primary objective was to determine whether lung ultrasound (LUS) B-lines, when excluding patients with alternative etiologies for B-lines, are more sensitive for the associated diagnosis of COVID-19 than CXR. This was a retrospective cohort study of all patients who presented to a single, academic emergency department in the United States between March 20 and April 6, 2020, and received LUS, CXR, and viral testing for COVID-19 as part of their diagnostic evaluation. The primary objective was to estimate the test characteristics of both LUS B-lines and CXR for the associated diagnosis of COVID-19. Our secondary objective was to evaluate the proportion of patients with COVID-19 that have secondary LUS findings of pleural abnormalities and subpleural consolidations. We identified 43 patients who underwent both LUS and CXR and were tested for COVID-19. Of these, 27/43 (63%) tested positive. LUS was more sensitive (88.9%, 95% confidence interval (CI), 71.1-97.0) for the associated diagnosis of COVID-19 than CXR (51.9%, 95% CI, 34.0-69.3; p = 0.013). LUS and CXR specificity were 56.3% (95% CI, 33.2-76.9) and 75.0% (95% CI, 50.0-90.3), respectively (p = 0.453). Secondary LUS findings of patients with COVID-19 demonstrated 21/27 (77.8%) had pleural abnormalities and 10/27 (37%) had subpleural consolidations. Among patients who underwent LUS and CXR, LUS was found to have a higher sensitivity than CXR for the evaluation of COVID-19. This data could have important implications as an aid in the diagnostic evaluation of COVID-19, particularly where viral testing is not available or restricted. If generalizable, future directions would include defining how to incorporate LUS into clinical management and its role in screening lower-risk populations.


Assessing spatial inequalities in accessing community pharmacies: a mixed geographically weighted approach.
Geographical accessibility is an important determinant for the utilisation of community pharmacies. The present study explored patterns of spatial accessibility with respect to pharmacies in Liguria, Italy, a region with particular geographical and demographic features. Municipal density of pharmacies was proxied as the number of pharmacies per capita and per km2, and spatial autocorrelation analysis was performed to identify spatial clusters. Both non-spatial and spatial models were constructed to predict the study outcome. Spatial autocorrelation analysis showed a highly significant clustered pattern in the density of pharmacies per capita (I=0.082) and per km2 (I=0.295). Potentially under-supplied areas were mostly located in the mountainous hinterland. Ordinary least-squares (OLS) regressions established a significant positive relationship between the density of pharmacies and income among municipalities located at high altitudes, while no such association was observed in lower-lying areas. However, residuals of the OLS models were spatially auto-correlated. The best-fitting mixed geographically weighted regression (GWR) models outperformed the corresponding OLS models. Pharmacies per capita were best predicted by two local predictors (altitude and proportion of immigrants) and two global ones (proportion of elderly residents and income), while the local terms population, mean altitude and rural status and the global term income functioned as independent variables predicting pharmacies per km2. The density of pharmacies in Liguria was found to be associated with both socio-economic and landscape factors. Mapping of mixed GWR results would be helpful to policy-makers.


The diabetic diet: a model for Americans.
The nutrition management of individuals with diabetes mellitus now closely parallels the goals of the model American diet. Emphasizing this positive relationship with the use of team education and treatment will improve clinical success and enhance the quality of life for people with diabetes.


Purinergic Profiling of Regulatory T-cells in Patients With Episodic Migraine.
Objectives: Immune responses in migraine are poorly characterized, yet implicated in the disease pathogenesis. This study was carried out to characterize purinergic profiles of T-cells in patients with episodic migraine without aura (MWoA) to provide mechanistic evidence for ATP and adenosine involvement in modulation of immune regulation in migraine. Methods: Peripheral blood samples were obtained from patients with migraine (n = 16) and age-matched control subjects (n = 21). Subsets of T-cells were identified by flow cytometry based on specific membrane markers. Results: Migraine patients showed reduced total T-cell counts in the peripheral blood. Whereas the total number of CD3+CD4+, CD3+CD8+, or regulatory T lymphocytes (Treg) was not changed, the proportion of Treg CD45R0+CD62L- and CD45R0-CD62L- cells was increased. Interestingly, in migraine, less Treg cells expressed CD39 and CD73 suggesting disrupted ATP breakdown to adenosine. The negative correlations were observed between the duration of migraine and the relative number of CD73+CD39- Tregs and total number of CD73-positive CD45R0+CD62L+ Tregs. Conclusion: Obtained data indicate that T-cell populations are altered in episodic migraine and suggest the involvement of Tregs in the pathophysiology of this disorder. Reduced expression of CD39 and CD73 suggests promotion of ATP-dependent pro-inflammatory and reduction of adenosine-mediated anti-inflammatory mechanisms in migraine.


Perceived facilitators of and barriers to healthful eating among university students.
Photovoice, an innovative qualitative research method in health care, has not been used to its full potential in nutrition/dietetics. We explored the use of Photovoice to determine perceived facilitators of and barriers to healthful eating among university students. The study included 28 students enrolled in a 2008 introductory nutrition class. The students participated in a camera orientation session to review ethics and privacy issues. They took photographs and selected two for discussion in a focus group moderated by a graduate student who used a semi-structured facilitation guide. Researchers coded the transcripts, analyzed the pictures and students' written comments about the project, and ensured data trustworthiness through credibility, dependability, confirmability, and transferability of data and methods. Six major themes emerged as facilitators and/or barriers: environment, nutrition knowledge, convenience foods, time, media influence, and food cost. More than one-third of the students thought the study "stimulated their critical thinking." They felt more empowered in sharing their perceptions and "getting their voices heard." Photovoice was a useful, "motivating," and "engaging" method for research on nutrition knowledge and dietary patterns of university students. Registered dietitians and other health professionals may benefit from the use of the Photovoice method when they are working with students.


Identifying and characterizing casein kinase II in human platelets.
We have recently shown that inhibition of protein phosphatases in platelets causes increases in protein phosphorylations with a concomitant inhibition of platelet responses. The burst in protein phosphorylation appears to be catalyzed by messenger-independent protein kinases. The aim of the present study was to characterize the presence of broad families of protein kinases found in platelets. Lysates of control and thrombin-stimulated platelets were prepared, and proteins were separated on MONO Q fast protein liquid chromatography. In addition to the presence of histone protein kinase and tyrosine kinase activities, human platelets contain casein kinase II (CKII) activity as assessed by phosphorylation of a specific substrate peptide. Western blot analysis and immunogold electron microscopy studies further showed the presence of alpha-, alpha'-, and beta-subunits of CKII. The enzyme appears to be distributed throughout the cytosol and not secreted after thrombin treatment. Immunoprecipitation studies suggest that at least some of the holoenzymes exist as an alpha alpha' beta 2 complex. Although no activation of the enzyme was detected after thrombin treatment, our results show that CKII is a major messenger-independent protein kinase in platelets.


Unusual presentations of eosinophilic gastroenteritis: case series and review of literature.
Eosinophilic gastroenteritis (EG) is an uncommon disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, and is usually associated with dyspepsia, diarrhea and peripheral eosinophilia. Diffuse gastrointestinal tract and colonic involvement are uncommon. The endoscopic appearance may vary from normal to mucosal nodularity and ulceration. Gastrointestinal obstruction is unusual and is associated with predominantly muscular disease. We present five unusual cases of EG associated with gastric outlet and duodenal obstruction. Two cases presented with acute pancreatitis and one had a history of pancreatitis. Four cases responded well to medical therapy and one had recurrent gastric outlet obstruction that required surgery. Four out of the five cases had endoscopic and histological evidence of esophagitis and two had colitis. Two patients had ascites. These cases reaffirm that EG is a disorder with protean manifestations and may involve the entire gastrointestinal tract. Gastric outlet and/or small bowel obstruction is an important though uncommon presentation of EG. It may also present as esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.


Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis.
Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr -/-.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (-17%) and hepatic steatosis (-22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.


Withdrawing payment for nonscientific drug therapy. Intended and unexpected effects of a large-scale natural experiment.
Little is known about the effect on clinical decision making of nonreimbursement for ineffective medical technologies. Using a time-series design, we studied the effects of cessation of government payment for 12 categories of drugs of questionable efficacy (Drug Efficacy Study Implementation drugs) in a random sample of the New Jersey Medicaid population (N=390 465) and in four cohorts of regular users of these products. We measured changes in the overall levels of prescriptions, expenditures, and physicians' use of substitute drugs. Although withdrawn drugs accounted for 7% of prescriptions in the base year, there was no measurable reduction in overall drug use or expenditures after the regulation; prescription rates actually rose from 0.86 to 1.00 monthly prescriptions per enrollee throughout the 42-month study. Controlling for preexisting trends, an estimated drop in the use of study drugs of 21.7 prescriptions per 1000 enrollees per month was offset by an increase in the use of substitute drugs of 33.7 prescriptions. Both desirable and unimproved therapeutic substitutions were observed. Used alone, curtailment of reimbursement for marginally effective therapies results in both desirable and unintended clinical substitutions and may not reduce costs. Supplementing such restrictions with education may be necessary to promote practices that are more therapeutically and economically appropriate.


Transcatheter aortic valve implantation with the Evolut platform for bicuspid aortic valve stenosis: the international, multicentre, prospective BIVOLUTX registry.
Prospective data about transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BAV) patients are limited. We aimed to evaluate the clinical impact of the Evolut PRO and R (34 mm) self-expanding prostheses in BAV patients and explore the impact of different computed tomography (CT) sizing algorithms in a prospective registry. A total of 149 bicuspid patients were treated in 14 countries. The primary endpoint was the intended valve performance at 30 days. Secondary endpoints were 30-day and 1-year mortality, severe patient-prosthesis mismatch (PPM) and the ellipticity index at 30 days. All study endpoints were adjudicated according to Valve Academic Research Consortium 3 criteria. The mean Society of Thoracic Surgeons score was 2.6% (1.7-4.2). Type I L-R BAV was observed in 72.5% of the patients. Evolut valve sizes 29 and 34 mm were utilised in 49.0% and 36.9% of the cases, respectively. The 30-day cardiac death rate was 2.6%; the 1-year cardiac death rate was 11.0%. Valve performance at 30 days was observed in 142/149 (95.3%) patients. The mean aortic valve area post-TAVI was 2.1 (1.8-2.6) cm2, and the mean aortic gradient was 7.2 (5.4-9.5) mmHg. No patient had more than moderate aortic regurgitation at 30 days. PPM was observed in 13/143 (9.1%) surviving patients and was severe in 2 patients (1.6%). Valve function was maintained at 1 year. The mean ellipticity index remained 1.3 (interquartile range 1.2-1.4). Overall, 30-day and 1-year clinical and echocardiography outcomes were similar between the two sizing strategies. BIVOLUTX demonstrated a favourable bioprosthetic valve performance and good clinical outcomes after TAVI with the Evolut platform in patients with bicuspid aortic stenosis. No impact from the sizing methodology could be identified.


Complications of acute pancreatitis.
In 1925, Sir Berkeley Moynihan stated that "acute pancreatitis is the most terrible of all the calamities that occur in connection with the abdominal viscera." The case of M.H. clearly reflects the accuracy of that statement. It should be pointed out that through the exceptional, dedicated care provided by all members of the health care team, a young woman whose predicted mortality approached 100 percent was restored to her previous state of good health, and has since delivered a healthy baby girl by cesarean section. This illustrates that the nurse who possesses a sound understanding of the complications of acute pancreatitis and the pathophysiologic processes responsible, can integrate this knowledge into the management of the patient and improve the quality of care.


Activation of the renin-angiotensin system in hyperoxia-induced lung fibrosis in neonatal rats.
Oxygen toxicity plays an important role in lung injury and may lead to bronchopulmonary dysplasia. We previously demonstrated that hyperoxia activated the renin-angiotensin system (RAS) in cultured human fetal lung fibroblasts. To examine whether the upregulation of RAS components is associated with hyperoxia-induced lung fibrosis in neonatal Sprague-Dawley rats. Experimental rat pups were exposed to 1 week of >95% O(2) and a further 2 weeks of 60% O(2). Control pups were exposed to room air over the same periods. Lung tissues were taken for biochemical and histochemical assays on postnatal days 7 and 21. Hyperoxia significantly increased total collagen content and the expression of type I collagen and alpha smooth muscle actin when compared to control rats. RAS components including angiotensinogen, angiotensin-converting enzyme, angiotensin II, and angiotensin II type 1 receptor were significantly upregulated by hyperoxia. The results also demonstrated that only the extracellular signal-regulated kinase (ERK) signaling pathway was activated by hyperoxia exposure. p38 mitogen-activated protein kinase and c-Jun N-terminal kinase were not activated. Local RAS activation is involved in the pathogenesis of hyperoxia-induced lung fibrosis in neonatal rats. ERK phosphorylation might mediate angiotensin II type 1 receptor activation.


Askival: An altered feldspathic cumulate sample in Gale crater.
Askival is a light-toned, coarsely crystalline float rock, which was identified near the base of Vera Rubin Ridge in Gale crater. We have studied Askival, principally with the ChemCam instrument but also using APXS compositional data and MAHLI images. Askival and an earlier identified sample, Bindi, represent two rare examples of feldspathic cumulate float rocks in Gale crater with >65% relict plagioclase. Bindi appears unaltered whereas Askival shows textural and compositional signatures of silicification, along with alkali remobilization and hydration. Askival likely experienced multiple stages of alteration, occurring first through acidic hydrolysis of metal cations, followed by deposition of silica and possible phyllosilicates at low T and neutral-alkaline pH. Through laser-induced breakdown spectroscopy compositional analyses and normative calculations, we suggest that an assemblage of Fe-Mg silicates including amphibole and pyroxene, Fe phases, and possibly Mg-rich phyllosilicate are present. Thermodynamic modeling of the more pristine Bindi composition predicts that amphibole and feldspar are stable within an upper crustal setting. This is consistent with the presence of amphibole in the parent igneous rocks of Askival and suggests that the paucity of amphiboles in other known Martian samples reflects the lack of representative samples of the Martian crust rather than their absence on Mars.


Prevention of mother-to-child transmission of human immunodeficiency virus among pregnant women using injecting drugs in Ukraine, 2000-10.
To compare clinical status, mother-to-child transmission (MTCT) rates, use of prevention of (PMTCT) interventions and pregnancy outcomes between HIV-infected injecting drug users (IDUs) and non-IDUs. Prospective cohort study conducted in seven human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Centres in Ukraine, 2000-10. Pregnant HIV-infected women, identified before/during pregnancy or intrapartum, and their live-born infants (n = 6200); 1028 women followed post-partum. Maternal and delivery characteristics, PMTCT prophylaxis, MTCT rates, preterm delivery (PTD) and low birth weight (LBW). Of 6200 women, 1111 (18%) reported current/previous IDU. The proportion of IDUs diagnosed with HIV before conception increased from 31% in 2000/01 to 60% in 2008/09 (P < 0.01). Among women with undiagnosed HIV at conception, 20% of IDUs were diagnosed intrapartum versus 4% of non-IDUs (P < 0.01). At enrolment, 14% of IDUs had severe/advanced HIV symptoms versus 6% of non-IDUs (P < 0.001). IDUs had higher rates of PTD and LBW infants than non-IDUs, respectively, 16% versus 7% and 22% versus 10% (P < 0.001). IDUs were more likely to receive no neonatal or intrapartum PMTCT prophylaxis compared with non-IDUs (OR 2.81, p < 0.001). MTCT rates were 10.8% in IDUs versus 5.9% in non-IDUs; IDUs had increased MTCT risk (adjusted odds ratio 1.32, P = 0.049). Fewer IDUs with treatment indications received HAART compared with non-IDUs (58% versus 68%, P = 0.03). Pregnant human immunodeficiency virus-infected injecting drug users in Ukraine have worse clinical status, poorer access to prevention of mother-to-child transmission prophylaxis and highly active antiretroviral therapy, more adverse pregnancy outcomes and higher risk of mother-to-child transmission than non-injecting drug user women.


Primary acquired Grynfeltt Hernia: two new cases and literature review.
We report two cases of the very rare Primary Acquired Grynfeltt Hernia. The related abdominal wall defects were repaired, by open surgery, placing a partially absorbable plug and mesh. The observation and management of these two new cases prompted us to review the literature with the purpose of suggesting the most appropriate surgical approach and technique. A 60 years old female patient showing a swelling at the left lumbar region, and a 76 years old male patient showing evidence of a tumefaction located at the right lumbar region, were diagnosed at our department with Primary Acquired Grynfeltt Hernia. Postoperative courses were uneventful and the patients were discharged from hospital respectively on the third and second postoperative day. Follow-up at thirty days, six months, two and three years showed no signs of recurrence. Primary Acquired Grynfeltt Hernia is one of the rarest abdominal hernias. In literature there are no comparative studies showing which type of surgical approach should be preferred for this specific abdominal wall defect. In our department, open surgery was successfully performed for the treatment of two new cases of Primary Acquired Grynfeltt Hernias and, second time in literature, partially absorbable plug and mesh were placed in order to repair the causative abdominal wall defect. Based on our experience and literature review, we consider open hernia repair with partially absorbable plug and mesh as an appropriate and advisable surgical approach for not complicated cases of Primary Acquired Grynfeltt Hernia. Surgery is performed rapidly, effortlessly and securely if the patient is under general anesthesia, in lateral decubitus position with the operating table flexed at the level of the iliac crest. Primary Acquired Grynfeltt Hernia, Lumbar Hernia.


Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.
Long-term muscle denervation leads to severe and irreversible atrophy coupled with loss of force and motor function. These factors contribute to poor functional recovery following delayed reinnervation. The authors' previous work demonstrated that temporarily suturing a sensory nerve to the distal motor stump (called sensory protection) significantly reduces muscle atrophy and improves function following reinnervation. The authors have also shown that 1 month of electrical stimulation of denervated muscle significantly improves function and reduces atrophy. In this study, the authors tested whether a combination of sensory protection and electrical stimulation would enhance functional recovery more than either treatment alone. Rat gastrocnemius muscles were denervated by cutting the tibial nerve. The peroneal nerve was then sutured to the distal tibial stump following 3 months of treatment (i.e., electrical stimulation, sensory protection, or both). Three months after peroneal repair, functional and histologic measurements were taken. All treatment groups had significantly higher muscle weight (p<0.05) and twitch force (p<0.001) compared with the untreated group (denervated), but fiber type composition did not differ between groups. Importantly, muscle weight and force were significantly greater in the combined treatment group (p<0.05) compared with stimulation or sensory protection alone. The combined treatment also produced motor unit counts significantly greater than sensory protection alone (p<0.05). The combination treatment synergistically reduces atrophy and improves reinnervation and functional measures following delayed nerve repair, suggesting that these approaches work through different mechanisms. The authors' research supports the clinical use of both modalities together following peripheral nerve injury.


Youth audience segmentation strategies for smoking-prevention mass media campaigns based on message appeal.
Mass media interventions are among the strategies recommended for youth cigarette smoking prevention, but little is known about optimal methods for reaching diverse youth audiences. Grades 4 through 12 samples of youth from four states (n = 1,230) rated smoking-prevention messages in classroom settings. Similar proportions of African American, Hispanic, and White youth participated. Impact of audience characteristics on message appeal ratings was assessed to provide guidance for audience segmentation strategies. Age had a strong effect on individual message appeal. The effect of gender also was significant. Message ratings were similar among the younger racial/ethnic groups, but differences were found for older African American youth. Lower academic achievement was associated with lower appeal scores for some messages. Age should be a primary consideration in developing and delivering smoking-prevention messages to youth audiences. The unique needs of boys and girls and older African American adolescents should also be considered.


Quantitative Genomic Dissection of Soybean Yield Components.
Soybean is a crop of major economic importance with low rates of genetic gains for grain yield compared to other field crops. A deeper understanding of the genetic architecture of yield components may enable better ways to tackle the breeding challenges. Key yield components include the total number of pods, nodes and the ratio pods per node. We evaluated the SoyNAM population, containing approximately 5600 lines from 40 biparental families that share a common parent, in 6 environments distributed across 3 years. The study indicates that the yield components under evaluation have low heritability, a reasonable amount of epistatic control, and partially oligogenic architecture: 18 quantitative trait loci were identified across the three yield components using multi-approach signal detection. Genetic correlation between yield and yield components was highly variable from family-to-family, ranging from -0.2 to 0.5. The genotype-by-environment correlation of yield components ranged from -0.1 to 0.4 within families. The number of pods can be utilized for indirect selection of yield. The selection of soybean for enhanced yield components can be successfully performed via genomic prediction, but the challenging data collections necessary to recalibrate models over time makes the introgression of QTL a potentially more feasible breeding strategy. The genomic prediction of yield components was relatively accurate across families, but less accurate predictions were obtained from within family predictions and predicting families not observed included in the calibration set.


Assessing the associations among trait and state levels of deliberate and spontaneous mind wandering.
Recent research has demonstrated that mind wandering can be subdivided into spontaneous and deliberate types, and this distinction has been found to hold at both the trait and state levels. However, to date, no attempts have been made to link trait-level spontaneous and deliberate mind wandering with state-level assessments of these two subtypes of mind wandering. Here we evaluated whether trait-level deliberate and spontaneous mind wandering map onto state levels of these subtypes of mind wandering. Results showed correspondence between trait-level reports of spontaneous and deliberate mind wandering and their state-level counterparts, indicating that people's reports on the intentionality of their mind wandering in the laboratory correspond to their reports of the intentionality of mind wandering in everyday life. Thus, the trait- and state-level scales of mind wandering were found to validate each other: Whereas the state-level measures provided some construct validity for the trait-level measures, the trait-level measures indicated that the state-level measures may be generalizable to everyday situations.


Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenomas.
Selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR), and selenoprotein P (SePP) contain molecular selenium in form of selenocysteines within their active center. They are involved in the defense of reactive oxygen species, which otherwise may cause DNA damage and alterations of protein function. Selenium intake has been linked to colon carcinogenesis in epidemiological and interventional studies. In a double-blinded, placebo-controlled trial, we demonstrate that carriers of colon adenomas present with low basal serum levels of selenium and plasma glutathione peroxidase (pGPx) activity before treatment, but both parameters can be normalized by interventional selenium supplementation. GPx activity in colon mucosa was enhanced in the verum group, albeit this had only borderline significance. No change of activity was observed for mucosal TrxR activity on selenium supplementation. In summary, our results confirm the existence of low selenium levels in patients prone to colon adenomas and show that by selenium supplementation this can be normalized. If prospective trials confirm that selenium supplementation reduces colon cancer incidence rates, it may be concluded that selenium supplementation should be recommended for patients at risk.


[Changes in the mucosa of the small intestine in white rats in the process of digestion].
Morphological and morphometric studies of the small intestine of albino rats have shown that its villi undergo cyclic changes. These changes involve the death, growth and maturation of the villi. Digestion intensifies proliferative processes in the small intestinal mucosa. The data obtained support the conception that the death of the villi is a morphological expression of secretion (excretion) and absorption in the small intestine.


Functional imaging: where do we go from here?
As highly invasive and infiltrative tumors, gliomas are hard to delineate from healthy brain parenchyma, even with the microscope enhanced eye of an experienced neurosurgeon. However, the surgical goal remains maximum extent of tumor volume resection with a preservation of neurological function. With functional data integrated and visualized in the navigation system, postoperative morbidity can be reduced. With the so far well established techniques diffusion-tensor-imaging (DTI) based fiber tractography and functional MRI (fMRI), white matter tracts or eloquent cortical areas can be displayed. With magnetic resonance spectroscopy (MRS) and also positron emmission computed tomography (PET), methods displaying brain metabolism are also widely used. However, further technical and computational development of these methods has already shown extended insights in brain networks and pathologies and promises further reduction of postoperative morbidity, while used in navigation systems. In addition to these methods, novel techniques have already been implemented and successfully used in the clinical routine. In this way, this review summarizes recent developments in DTI, fMRI, MRSI and PET, also with their use during neurosurgical operations, but also gives introduction in novel methods like navigated transcranial magnetic stimulation (nTMS) or advanced diffusion models as base for fiber tracking.


Short-term and long-term effectiveness of powered toothbrushes in promoting periodontal health during orthodontic treatment: A systematic review and meta-analysis.
Although powered toothbrushes have been reported to reduce gingivitis more than manual toothbrushes in the general population, the evidence regarding orthodontic patients has been inconclusive. Thus, we aimed to compare their effectiveness in relation to any available parameter regarding oral health in orthodontic patients with fixed appliances. Searches without restrictions for published and unpublished literature and hand searching took place up to August 2017. Oral-health relevant data from randomized controlled trials of at least 4-weeks duration comparing powered and manual tooth brushing without supervision were reviewed. Data were classified as short term (assessments at 1-3 months) and long term (assessments at >3 months), and the random-effects method was used to combine treatment effects. Individual study risk of bias was assessed using the Cochrane Risk of Bias Tool, and the quality of evidence was evaluated according to the Grades of Recommendation, Assessment, Development and Evaluation approach. The initially identified articles were finally reduced to 9 randomized controlled trials investigating the periodontal health in 434 patients. Eight studies followed patients up to 3 months, and 1 up to 12 months during treatment. One study was at low and the rest at unclear risk of bias. Overall, in the short term, there was low-quality evidence that powered toothbrushes provide a statistically significant benefit compared with manual brushing with regard to the gingival index (weighted mean difference, -0.079; 95% confidence interval, -0.146 to -0.012; P = 0.021) and indexes assessing gingival bleeding (standardized mean difference, -0.637; 95% confidence interval, -1.092 to -0.183; P = 0.006). In the long term, only 1 available study showed a statistically significant benefit of powered over manual toothbrushes with regard to gingival index and bleeding. No differences were observed in probing pocket depth and relative attachment loss. For the rotation-oscillation brushes that involved the greatest body of evidence, statistically significant reductions in gingival index and bleeding were demonstrated only in the long-term study. No included study provided quantified measurements regarding caries activity. Overall, powered toothbrushes may promote gingival health better than manual toothbrushes in orthodontic patients. However, no type demonstrated clear superiority. Better study standardization and reporting in longer follow-up studies are necessary to elucidate the clinical relevance of these results.


Is acute promyelocytic leukemia a curable disease? Treatment strategy for a long-term survival.
The major cause of early death in acute promyelocytic leukemia (APL), the high risk of a bleeding diathesis is now successfully counteracted within a few days by differentiation therapy using ATRA. Moreover, no resistance to this drug has been recorded during induction when the usual presence of PML/RAR alpha was confirmed by molecular study (some M3 cases do lack rearrangement of PML/RAR alpha). Paradoxically, a hypercoagulable clotting tendency may occur in these patients during the first month of ATRA treatment. Leucocyte activation (retinoic acid syndrome), often secondary to hyperleukocytosis, is prevented by early addition of chemotherapy when WBCs exceed defined limits, and is successfully treated by high dose corticosteroids. Routine acquired progressive in vivo resistance to all trans retinoic acid (ATRA) requires consolidation of ATRA-induced complete remission (CR) with intensive chemotherapy. Prevention of relapses using maintenance therapy is questionable and has not been tested in randomized trials. Actually the event-free survival of APL patients treated by the combination of ATRA and chemotherapy is 80% at 1 year, and the cure of 50% of patients is within our reach.


Non-communicable diseases increased risk of recurrent tuberculosis in epidemic area of Human Immunodeficiency Virus infection, Thailand.
In recent decades, many countries in Southeast Asia such as Thailand reported an increase of non-communicable diseases (NCDs) and are faced with double burden of NCDs and communicable diseases such as tuberculosis. Recurrent tuberculosis (TB) has been reported in association with Human Immunodeficiency Virus infection (HIV) and diabetes mellitus, however the association between recurrent TB and other NCDs has not been well investigated in this region. A retrospective cohort study was conducted to determine risk of recurrent TB associated with NCDs in an endemic area of HIV in Thailand. Of 1,444 pulmonary TB patients who are registered and had completed a course of treatment during 2003-2012, 99 were diagnosed for recurrent TB (1.954 per 100 TB cases-year). After adjusting for HIV, age, sex, and previous TB treatment outcome, Poisson regression revealed significant risk of recurrent TB among patient with diabetes mellitus (RR=2.76; 95% CI=1.66-4.59), with chronic obstructive pulmonary disease (RR=2.16; 95% CI=1.33-3.49) and with liver cirrhosis (RR=4.45; 95% CI=2.23-8.87). Regular routine screening for TB among patients with liver cirrhosis, diabetes mellitus and chronic obstructive pulmonary disease should be established to improve prevention and control of TB in endemic areas of TB and HIV.


Obesity and low levels of physical activity impact on cardiopulmonary fitness in older men after treatment for prostate cancer.
The purpose of this study was to compare fitness parameters and cardiovascular disease risk of older and younger men with prostate cancer (PCa) and explore how men's fitness scores compared to normative age values. 83 men were recruited post-treatment and undertook a cardiopulmonary exercise test (CPET), sit-to-stand, step-and-grip strength tests and provided blood samples for serum lipids and HbA1c. We calculated waist-to-hip ratio, cardiovascular risk (QRISK2), Charlson comorbidity index (CCI) and Godin leisure-time exercise questionnaire [GLTEQ]. Age-group comparisons were made using normative data. Men > 75 years, had lower cardiopulmonary fitness, as measured by VO2 Peak (ml/kg/min) 15.8 + 3.8 p < 0.001, and lower grip strength(28.6+5.2 kg p < 0.001) than younger men. BMI ≥30kg/m2 and higher blood pressure all contributed to a QRisk2 score indicative of 20% chance of cardiovascular risk within 10 years (mean: 36.9-6.1) p < 0.001. Age, BMI and perceived physical activity were significantly associated with lower cardiopulmonary fitness. Men with PCa > 75 years had more cardiovascular risk factors compared to normative standards for men of their age. Although ADT was more frequent in older men, this was not found to be associated with cardiopulmonary fitness, but obesity and low levels of physical activity were. Secondary prevention should be addressed in men with PCa to improve men's overall health.


Characterization of pulp derived nanocellulose hydrogels using AVAP® technology.
Bioinspiration from hierarchical structures found in natural environments has heralded a new age of advanced functional materials. Nanocellulose has received significant attention due to the demand for high-performance materials with tailored mechanical, physical and biological properties. In this study, nanocellulose fibrils, nanocrystals and a novel mixture of fibrils and nanocrystals (blend) were prepared from softwood biomass using the AVAP® biorefinery technology. These materials were characterized using transmission and scanning electron microscopy, and atomic force microscopy. This analysis revealed a nano- and microarchitecture with extensive porosity. Notable differences included the nanocrystals exhibiting a compact packing of nanorods with reduced porosity. The NC blend exhibited porous fibrillar networks with interconnecting compact nanorods. Fourier transform infrared spectroscopy and X-ray diffraction confirmed a pure cellulose I structure. Thermal studies highlighted the excellent stability of all three NC materials with the nanocrystals having the highest decomposition temperature. Surface charge analysis revealed stable colloid suspensions. Rheological studies highlighted a dominance of elasticity in all variants, with the NC blend being more rigid than the NC fibrils and nanocrystals, indicating a double network hydrogel structure. Given these properties, it is thought that these materials show great potential in (bio)nanomaterial applications where careful control of microarchitecture, surface topography and porosity are required.


A holistic model to assess risk factors of fasciolosis in Ankole cattle.
In recent decades, remote sensing (RS) technology and geographical information systems (GIS) were increasingly used as tools for epidemiological studies and the control of zoonotic diseases. Fasciolosis, a zoonotic disease caused by a trematode parasite (Fasciola spp.), is a good candidate for the application of RS and GIS in epidemiology because it is strongly influenced by the environment, i.e. the habitat of the intermediate host. In this study, we examined variables which may increase the fasciolosis risk of Ankole cattle in the degraded and overgrazed Mutara rangelands of north-eastern Rwanda. The risk variables considered included three environmental variables (normalized difference vegetation index, NDVI; normalized difference moisture index, NDMI; normalized difference water index, NDWI), two landscape metric variables (rangeland proportion, building density), two geological variables (poorly-drained soil proportion, elevation) and three animal husbandry variables (herd size, adult proportion and the body condition score). Fasciola spp. prevalence was used as the dependent variable, sampling season as a fixed factor and four principal components (PCs, condensed from the ten risk variables) as covariates in a univariate General Linear Model. Fasciola spp. prevalence was positively correlated to rangeland proportion, cattle herd size in rural areas, adult proportion and individual body condition. Moreover, high Fasciola spp. prevalence was found in densely vegetated areas with high moisture (high values of NDVI and NDMI), in combination with large proportions of poorly-drained soil at low elevations. Future investigations should focus on increased sampling across the Mutara rangelands to prepare a predictive, spatial fasciolosis risk map that would help to further improve sustainable land-use management.


The effect of Echinacea purpurea (L.) Moench extract on experimental prostate hyperplasia.
The aim of this study was to examine the effect of purple coneflower (Echinacea purpurea L. Moench) on the prostate gland of rats using an experimental model of benign prostate hyperplasia (BPH). The animals were administered 50 mg/kg of extract preparation for 4 and 8 weeks and the prostate mass and structural degenerative changes were evaluated in the course of the experiment. The administration of E. purpurea extract to rats with hyperplasia for 4 and 8 weeks gradually and significantly reduced the prostate mass and reversed the degenerative changes in the structure of the prostate gland. The present investigation suggests extract of purple coneflower prevents the development of BPH.


Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians.
More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation. Sixteen vegetarians and eight omnivores participated in this interventional study with oral supplementation of 2 g L-carnitine for 12 weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma carnitine concentration, but maintained skeletal muscle carnitine stores compared to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents were also not different from omnivores. Maximal oxygen uptake (VO2max) and workload (P max) per bodyweight (bicycle spiroergometry) were not significantly different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for 1 h) revealed no significant differences between vegetarians and omnivores (respiratory exchange ratio, blood lactate and muscle metabolites). Supplementation with L-carnitine significantly increased the total plasma carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle carnitine content in vegetarians (13%). Despite this increase, P max and VO2max as well as muscle phosphocreatine, lactate and glycogen were not significantly affected by carnitine administration. Vegetarians have lower plasma carnitine concentrations, but maintained muscle carnitine stores compared to omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine stores and slightly increases the skeletal muscle carnitine content in vegetarians, but without affecting muscle function and energy metabolism.


Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study.
Background and Purpose- Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion. We determined whether patients with rapid neurological improvement (RNI) 24 hours after thrombectomy were more likely to have a favorable clinical outcome in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3). Methods- All patients who underwent thrombectomy in DEFUSE 3 were included. RNI was defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale or National Institutes of Health Stroke Scale zero to one 24 hours after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale score and a dichotomous analysis for 90-day independence (modified Rankin Scale score, 0-2). Results- Ninety-one patients in DEFUSE 3 underwent thrombectomy with follow-up data; 31 patients (34%) experienced RNI (RNI+) after thrombectomy and 60 patients (66%) did not (RNI-). Patient demographics and stroke presentation and imaging details were similar between RNI+ and RNI- patients. Reperfusion (Thrombolysis in Cerebral Infarction 2b-3) after thrombectomy was achieved in 26 (84%) RNI+ and 43 (72%) RNI- ( P=0.2). Symptomatic intracranial hemorrhage occurred in no RNI+ and 8% of RNI- patients ( P=0.2). RNI was associated with a favorable modified Rankin Scale shift at day 90 (odds ratio, 3.8; CI, 1.7-8.6; P=0.001) and higher rates of modified Rankin Scale zero to 2 (61% versus 37%; odds ratio, 2.7; CI, 1.1-6.7; P=0.03). Mortality was 3% in RNI+ versus 18% in RNI- ( P=0.05). RNI+ patients had lower median 24-hour National Institutes of Health Stroke Scale (5 [interquartile range (IQR), 1-7] versus 13 [IQR, 7.5-21]; P<0.001), smaller 24-hour infarction volume (21 [IQR, 5-32] versus 65 [IQR, 27-145] mL; P<0.001), and less 24-hour infarct growth (8 [IQR, 1-18] versus 37 [IQR, 16-105] mL; P<0.001) compared with RNI- patients. Hospital stay was shorter in RNI+ (3.7 [IQR, 2.9-7.1] versus 7.4 [IQR, 5.2-12.1] days in RNI-; P<0.001). Conclusions- RNI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. RNI was a favorable prognostic sign following late-window thrombectomy in DEFUSE 3. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.


Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology.
Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA/TOF results in a relative low diagnostic yield. OA/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA/TOF have increased substantially and these patients start families; thus, the detection and a proper interpretation of these dominant inherited pathogenic variants are of great importance for these patients and for our understanding of OA/TOF aetiology.


[Results of hypoglossal-facial and hypoglossal-hypoglossal anastomoses].
From September 1976 to November 1991 a series of 34 patients with peripheral iatrogenal facial paralysis after removal of cerebellopontine angle tumors or parotid-gland surgery were treated by hypoglossal-facial anastomosis (hypoglossal-facial/hypoglossal-hypoglossal in 38.24% of cases). Patients were divided into two groups: Group A with early anastomosis and Group B with delayed anastomosis. In the first group, 57.14% of the cases presented "excessive reinnervation"; and in the second group, 95.0% of cases presented "good" or "excellent" results. In this paper we analyze and discuss our results and review the literature.


Inferior cardiac nerve activity in the cat during occlusion of the mesenteric artery.
A number of studies in this and other laboratories using hemodynamic and pharmacologic evidence have suggested that occlusion of the mesenteric artery evokes a pressor reflex initiated by mesenteric baroreceptors. To provide additional evidence in support of this hypothesis, neurophysiological recordings were made of inferior cardiac nerve activity during mesenteric artery occlusion (MAO). The results indicate that MAO enhances inferior cardiac nerve activity in the cat, providing that the carotid sinus nerves have been cut. Cutting of the mesenteric nerves further facilitates cardiac nerve activity and abolishes the response to mesenteric artery occlusion. The evidence suggests that MAO evokes a reflex sympathetic discharge which is subject to override by the carotid sinus depressor reflex. The afferent limb of the reflex is characterized by a tonic depressor outflow from the mesenteric pressure receptors.


Genetic determinants of resistance to fusidic acid among clinical bacteremia isolates of Staphylococcus aureus.
Resistance to fusidic acid in Staphylococcus aureus is caused by mutation of the elongation factor G (EF-G) drug target (FusA class) or by expression of a protein that protects the drug target (FusB and FusC classes). Recently, two novel genetic classes of small-colony variants (SCVs) were identified among fusidic acid-resistant mutants selected in vitro (FusA-SCV and FusE classes). We analyzed a phylogenetically diverse collection of fusidic acid-resistant bacteremia isolates to determine which resistance classes were prevalent and whether these were associated with particular phylogenetic lineages. Each isolate was shown by DNA sequencing and plasmid curing to carry only one determinant of fusidic acid resistance, with approximately equal frequencies of the FusA, FusB, and FusC genetic classes. The FusA class (mutations in fusA) were distributed among different phylogenetic types. Two distinct variants of the FusC class (chromosomal fusC gene) were identified, and FusC was also distributed among different phylogenetic types. In contrast, the FusB class (carrying fusB on a plasmid) was found in closely related types. No FusE-class mutants (carrying mutations in rplF) were found. However, one FusA-class isolate had multiple mutations in the fusA gene, including one altering a codon associated with the FusA-SCV class. SCVs are frequently unstable and may undergo compensatory evolution to a normal growth phenotype after their initial occurrence. Accordingly, this normal-growth isolate might have evolved from a fusidic acid-resistant SCV. We conclude that at least three different resistance classes are prevalent among fusidic acid-resistant bacteremia isolates of S. aureus.


[Methods of X-ray protection. Comparative analysis of conditions of radiographic protection utilization by dental professionals].
In this work, the authors examined the condition and uses of the relation to radiation protection. The authors personally gave a questionnaire to about seventy dentists, of all specialities marking up almost 12% of the dentists of the state. This questionnaire was compared to other questionnaires from São Paulo and João Pessoa cities. According to the data obtained we can present the following conclusion: The acknowledge level of safety in relation to radiation protection with patients, dentists and attendants here is similar to São Paulo city but this below standard. A better understanding and stricter observation of the recommendation of FEDERATION DENTAIRE INTERNATIONALE is necessary.


Effects of serotonin on memory impairments produced by ethanol.
Subjects treated with low or high doses of ethanol demonstrated impaired memory, particularly in tests involving the recall of poorly learned information. Zimelidine, an inhibitor of serotonin reuptake, reversed this ethanol-induced impairment. The serotonin neurotransmitter system may mediate learning and memory in humans and may determine some of the effects of alcohol on higher mental functions.


Evidence of leopard predation on bonobos (Pan paniscus).
Current models of social organization assume that predation is one of the major forces that promotes group living in diurnal primates. As large body size renders some protection against predators, gregariousness of great apes and other large primate species is usually related to other parameters. The low frequency of observed cases of nonhuman predation on great apes seems to support this assumption. However, recent efforts to study potential predator species have increasingly accumulated direct and indirect evidence of predation by leopards (Panthera pardus) on chimpanzees and gorillas. The following report provides the first evidence of predation by a leopard on bonobos (Pan paniscus).


The Midwifery services framework: What is it, and why is it needed?
Most low- and middle-income countries failed to meet the Millennium Development Goal targets for maternal, newborn and child health, and even more ambitious targets have been set under the Sustainable Development Goals and the Ending Preventable Maternal Mortality initiative. This means that many countries will need to accelerate progress on sexual, reproductive, maternal and newborn health over the next few years. Recent years have seen the publication of a large and convincing body of evidence about the potential of midwifery to make a significant contribution to this acceleration, but little practical guidance has emerged to help countries invest in midwifery services so that their health systems can meet the increasing need for sexual, reproductive, maternal and newborn health care. To help fill this gap, the International Confederation of Midwives designed and launched the Midwifery Services Framework, a new tool to guide countries through the process of strengthening and developing their midwifery services. This first of a series of three papers introduces the MSF, explains why it is needed, how it was developed, its guiding principles and its anticipated outcomes and impact. The other two papers explain the process of implementing the Midwifery Services Framework, and lessons learned in the first countries to start implementation.


Economic evaluation of voriconazole for the treatment of candidemia in Canadian adults.
Candidemia is a common cause of nosocomial bloodstream infection. When selecting therapeutic treatments for candidemia, cost-effectiveness is an important consideration. The present study assessed the cost-effectiveness of voriconazole for the treatment of candidemia. A decision-analytical model was used for evaluating the cost-effectiveness of voriconazole compared with a regimen of conventional amphotericin B (CAB) followed by fluconazole (FLU) in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting, based on the Global Candidemia Study. The time frame of the model was 98 days (14 weeks). Model parameters were based primarily on clinical outcome, and resource use data collected from the clinical trial were used. Supplemental data were obtained from an independent panel of 12 Canadian experts for parameters not available from the clinical trial. Unit costs were collected from Canadian sources. The outcome variables selected in the study were the number of patients cured within 98 days, the number of patients surviving at 98 days and the number of patients avoiding toxicity. Incremental costs per outcome were calculated to compare the cost-effectiveness analyses (both probabilistic and one-way sensitivity analyses were performed). The cost-effectiveness analysis demonstrated a difference of $1,121 in the total average cost of treatment with voriconazole ($70,489) versus CAB/FLU ($69,368). While the costs of voriconazole exceeded the costs of CAB/FLU, these costs were almost completely offset by lower hospitalization costs. While patients in both treatment arms experienced cure rates of 41%, both the percentage of patients surviving at day 98 (64.5% versus 58.2%) and the percentage of patients avoiding toxicity (64.5% versus 52.5%) were higher in the voriconazole arm. Accounting for differences in total costs and clinical outcomes, this analysis estimated an incremental cost per patient surviving at day 98 of $17,739, and an incremental cost per patient avoiding toxicity of $9,298. In the case of cost per patient cured, voriconazole had a higher cost ($1,121) than CAB/FLU. The results of the deterministic and probabilistic sensitivity analyses indicated that the model was robust. Results of the decision-analytical model provided evidence to support the cost-effectiveness of voriconazole relative to a regimen of CAB/FLU in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting.


Epithelial plasticity in the mammary gland.
Many epithelial tissues rely on multipotent stem cells for the proper development and maintenance of their diverse cell lineages. Nevertheless, the identification of multipotent stem cell populations within the mammary gland has been a point of contention over the past decade. In this review, we provide a critical overview of the various lineage-tracing studies performed to address this issue and conclude that although multipotent stem cells exist in the embryonic mammary placode, the postnatal mammary gland instead contains distinct unipotent progenitor populations that contribute to stage-specific development and homeostasis. This begs the question of why differentiated mammary epithelial cells can exhibit stem cell behavior in culture. We speculate that such reprogramming potential is repressed in situ under normal conditions but revealed in vitro and might drive breast cancer development.


Mechanisms of genetic control of immune responses. II. Nonresponsiveness in BALB/c GT-specific cell-mediated immune responses does not correlate with the absence of functional T cells or the induction of suppressor T cells.
The mechanisms underlying Ir gene control of CMI were addressed by examining the DTH and Tprlf responses specific for the synthetic polymers GT, GAT, and GA. We show that BALB/c mice (GAT/GA responders, GT nonresponders) primed with GT fail to develop DTH and Tprlf responses specific for GT, GAT, or GA. GAT immunization resulted in DTH responses that could be elicited not only with GAT and GA but also with GT, demonstrating that GT-specific TDH are present in nonresponder mice. GT-specific DTH was transferred with Thy-1+ Lyt-1+2-, H-2 I-restricted, nylon wool nonadherent cells. GA-primed BALB/c mice developed GAT- and GA-, but not GT-specific DTH responses, indicating that GA and GT do not cross-react at the T-cell level. The ability of GAT [but not a mixture of GA plus GT, or GT electrostatically complexed to the immunogenic carrier MBSA (GT-MBSA)] to induce GT-specific DTH suggested a requirement for covalent linkage of stimulatory 'GA' and nonstimulatory 'GT' determinants present on the GAT molecule. Similarly, GT-specific in vitro Tprlf responses could be demonstrated in GAT-primed mice exhibiting significant levels of GT-specific DTH but not in GT- or GT-MBSA-primed mice. Tolerization experiments also suggested that GT-specific Th were involved in the development of GT-specific DTH in GAT-primed mice. The GT nonresponsiveness of BALB/c mice for DTH and Tprlf responses could not be reversed by treatments designed to abrogate Ts activity (priming with GT-MBSA and CY injection), nor could GT-primed cells be shown to inhibit the development or elicitation of GT-specific CMI in GAT-primed mice during the afferent and/or efferent stages of DTH. Our results suggest that GT nonresponsiveness does not result from the absence of GT-specific T cells or preferential induction of Ts. The results are discussed in the context of hole-in-the-repertoire and antigen presentation (determinant selection) models of Ir gene control.


The Role of Macrophage-Inducible C-Type Lectin in Different Stages of Chronic Liver Disease.
The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.


Nutritional bias as a new mode of adjusting sex allocation.
Sex biases in the allocation of resources to offspring occur in a broad range of taxa. Parents have been shown to achieve such biases either by producing numerically more of one sex or by providing the individuals of one sex with a greater quantity of resources. In addition, skews in allocation could occur if the offspring of one sex receive resources of higher quality (greater nutritional or energetic value by weight or volume), although this mode of adjustment has, to our knowledge, never been demonstrated. We compared the types of prey and the metabolizable energy provisioned to male and female nestlings in one of the most sexually size dimorphic of all birds, the brown songlark, Cinclorhamphus cruralis. Within broods, we found that males not only received more prey than their smaller sisters, but also prey of apparently higher quality. This dietary disparity could result either from mothers actively discriminating between the sexes when providing prey or from competition among siblings. We suggest that sex differences in offspring diet quality may occur in a wide range of other taxa and function as an additional mechanism of sex allocation adjustment.


Reducing salt in bread: a quasi-experimental feasibility study in a bakery in Lima, Peru.
To explore salt content in bread and to evaluate the feasibility of reducing salt contained in 'pan francés' bread. The study had two phases. Phase 1, an exploratory phase, involved the estimation of salt contained in bread as well as a triangle taste test to establish the amount of salt to be reduced in 'pan francés' bread without detection by consumers. In Phase 2, a quasi-experimental, pre-post intervention study assessed the effects of the introduction of low-salt bread on bakery sales. A municipal bakery in Miraflores, Lima, Peru. Sixty-five clients of the bakery in Phase 1 of the study; sales to usual costumers in Phase 2. On average, there was 1·25 g of salt per 100 g of bread. Sixty-five consumers were enrolled in the triangle taste test: fifty-four (83·1 %) females, mean age 58·9 (sd 13·7) years. Based on taste, bread samples prepared with salt reductions of 10 % (P=0·82) and 20 % (P=0·37) were not discernible from regular bread. The introduction of bread with 20 % of salt reduction, which contained 1 g of salt per 100 g of bread, did not change sales of 'pan francés' (P=0·70) or other types of bread (P=0·36). Results were consistent when using different statistical techniques. The introduction of bread with a 20 % reduction in salt is feasible without affecting taste or bakery sales. Results suggest that these interventions are easily implementable, with the potential to contribute to larger sodium reduction strategies impacting the population's cardiovascular health.


Effectiveness of Photodynamic Therapy and Nd-YAG Laser Treatment for Obstructed Tracheobronchial Malignancies.
Since 1980, advanced lung carcinomas were treated with palliative laser therapy for the purpose of opening the endobronchial stenosis and obstruction by either photodynamic therapy (PDT) or Nd-YAG laser treatment at Tokyo Medical University. A total of 258 lesions were treated, 81 by PDT and 177 by Nd-YAG laser treatment. PDT achieved effective results in 61 (75%) of 81 lesions. In the Nd-YAG laser group, 143 (81%) of 177 lesions showed effective results. When the tumor was located in the trachea or main bronchi, effective results were obtained in 73% (19 of 26) of cases treated by PDT and in 93% of cases (64 of 69) treated by Nd-YAG laser. However, in cases in which the tumor was located in lobar or segmental bronchi, the tumor response was effective in 76% (42 of 55) of PDT-treated patients and 73% (79 of 108) of Nd-YAG laser-treated patients. With a mortality rate of 0%, the greatest advantage of PDT over Nd-YAG treatment was safety. Considering complications, PDT seems to be useful for obstruction of lobar and segmental bronchus. Nevertheless, when deciding among alternative therapies, physicians treating patients with advanced lung carcinoma should give careful consideration to the benefit and complications of both laser therapies and decide the most suitable modality.


A subanalysis of Taiwanese patients from ODYSSEY South Korea and Taiwan study evaluating the efficacy and safety of alirocumab.
Alirocumab can provide significant reductions in low-density lipoprotein cholesterol (LDL-C). However, data regarding its efficacy and safety in Asians are limited. A subgroup analysis of Taiwanese patients (n = 116) in a randomized trial evaluating the efficacy and safety of alirocumab in South Korea and Taiwan (ODYSSEY KT, clinicaltrials.gov Identifier: NCT02289963) was performed. Patients with hypercholesterolemia at high cardiovascular risk on maximally tolerated statin were randomized to alirocumab (75 mg every 2 weeks; with dose increased to 150 mg at Week 12 if LDL-C ≥ 70 mg/dL at Week 8) or placebo for 24 weeks. The primary efficacy endpoint was the percent change in LDL-C from baseline to Week 24. Safety was assessed for a total of 32 weeks. At Week 24, the percent change in calculated LDL-C in the alirocumab group (n = 57) was -51%, whereas that in the placebo group (n = 59) was 2.5%. Alirocumab significantly improved other lipid parameters, including non-high-density lipoprotein cholesterol, apolipoprotein B and A1, lipoprotein (a), high-density lipoprotein cholesterol, and total cholesterol. A significantly higher proportion of patients in the alirocumab group reached an LDL-C target below 70 mg/dL than those in the placebo group (81.3% vs 15.4%). The incidence of treatment-emergent adverse events was comparable between both groups. Alirocumab treatment provided a favorable effect on LDL-C levels and other lipid parameters, and was generally well-tolerated in patients from Taiwan. The results of current analysis were consistent with the overall ODYSSEY phase 3 program.


A multicenter propensity score-matched analysis of lymphadenectomy in N1-positve lung cancer.
Selective mediastinal lymph node dissection based on lobe-specific metastases is widely recognized in daily practice. However, the significance of mediastinal lymph node dissection for N1-positive tumors has not been elucidated. We retrospectively reviewed 359 patients with N1-positive lung cancer who underwent lobectomy with systematic mediastinal lymph node dissection (systematic lymph node dissection) (n = 150) and lobe-specific mediastinal lymph node dissection (lobe-specific lymph node dissection) (n = 209). The operative and postoperative results and their propensity score-matched pairs were compared. The factors affecting survival were assessed using competing risk and multivariable analyses. The cumulative incidence of recurrence and the cumulative incidence of cancer-specific death were not significantly different between systematic and lobe-specific lymph node dissection in entire cohort. In the propensity score-matched cohort (83 pairs), systematic lymph node dissection tended to detect N2 lymph node metastasis more frequently (55.4 vs. 41%, P = 0.087). Eleven patients (13.2%) in the systematic lymph node dissection group had a metastatic N2 lymph node 'in the systematic lymph node dissection field' that lobe-specific lymph node dissection did not dissect. The oncological outcomes between patients undergoing systematic lymph node dissection (5-year cumulative incidence of recurrence, 62.1%; 5-year cumulative incidence of cancer-specific death, 27.9%) and lobe-specific lymph node dissection (5-year cumulative incidence of recurrence, 60.1%; 5-year cumulative incidence of cancer-specific death, 23.3%) were similar. The propensity score-adjusted multivariable analysis for cumulative incidence of recurrence revealed that the prognosis associated with systematic lymph node dissection was comparable with the prognosis with lobe-specific lymph node dissection (hazard ratio, 1.17; 95% confidence interval, 0.82-1.67; P = 0.37). The extent of lymph node dissection can affect accurate pathological staging; however, it was not associated with survival outcome in the treatment of N1-positive lung cancer.


[Kidney trauma in children].
The article analyzes methods of diagnostics and treatment of 198 children aged from 3 to 14 years with closed traumas of the kidney. To diagnose the closed traumas of the kidneys excretory urography and echography were used. Laparoscopy was used for associated injuries in the complex of diagnostic methods. Conservative methods were used for treatment of 159 children with closed traumas of the kidney, 39 of them (14%) had indications for operative treatment. Nephrectomy was performed in 13 of these children having severe injuries. Long-term results were followed-up in 123 children. In 14 of them different sequelae of the trauma mere detected at the remote period.


Differential increases in the expression of intermediate filament proteins and concomitant morphological changes of transdifferentiating rat hepatic stellate cells observed in vitro.
The primary function of hepatic stellate cells (HSCs) is the storage of vitamin A. However, they are also responsible for liver fibrosis and are therapeutic targets for treatment of liver cirrhosis. Among the many molecular markers that define quiescent or activated states of HSCs, the characteristics of type III intermediate filaments are of particular interest. Whereas vimentin and desmin are upregulated in activated HSCs, glial fibrillary acidic protein is downregulated in activated HSCs. The functional differences between vimentin and desmin are poorly understood. By time-course quantifications of several molecular markers for HSC activation, we observed that the expression of vimentin preceded that of desmin during the transdifferentiation of HSCs. The immunoreactivity of vimentin in transdifferentiated HSCs was more intense in perinuclear regions compared to that of desmin. We propose that the delayed expression of desmin following the expression of vimentin and the peripheral localization of desmin compared to vimentin are both related to the more extended phenotype of transdifferentiating HSCs observed in vitro.


Disparities and social inequities: is the health of African American women still in peril?
An amalgam of health concerns differentially affects the behavioral, psychological, and physical well-being of African American women. These disparities are both the result of, and contributors to, marked differences in the perception, interpretation and treatment of various psychological disorders and chronic medical conditions. Data show that African American women are diagnosed with more chronic and debilitating illnesses than found in the general population, and are often misdiagnosed with a myriad of psychiatric and medical disorders. Despite these findings, ambiguity remains about the contextual factors that affect the physical and mental well-being of African American women. The focus of this review was not to describe all psychological or medical conditions with deleterious outcomes among African American women, but rather collectively address identified mental and physical health issues prevailing among African American women. This approach addresses the urgent need to better understand the health needs of African American women in the United States, and demonstrates how advancing our knowledge of this marginalized group may lead to sustaining mental and physical health-related dialogue, while advancing policy.


Adaptive sympatric speciation of polychromatic "roundfin" sailfin silverside fish in Lake Matano (Sulawesi).
The significance of sympatric speciation is one of the most controversial topics in evolutionary biology. Theory suggests that different factors can lead to speciation in full geographical contact, including selection and nonrandom mating. Strict criteria have been established for assessing sympatric speciation, which have been met in only a very few cases. Here, we investigate differentiation among sympatric morphospecies and color morphs of "roundfin" sailfin silversides (Telmatherinidae), small freshwater fish endemic to ancient Lake Matano in Central Sulawesi (Indonesia). Morphospecies are distinct according to body shape (geometric morphometrics), population structure (population-level amplified fragment length polymorphism [AFLP] markers), ecology, and mating behavior (habitat transects, stomach contents). Explorative genome scans based on AFLPs indicate that divergent selection affects only 1.3-4.2% of the analyzed loci, suggesting an early stage of speciation. Transect data demonstrate strong assortative mating and adaptive niche differentiation. However, we find no restrictions in gene flow among the conspicuous male color morphs. In summary, our data are consistent with a sympatric mode of divergence among three morphospecies under conditions effectively ruling out allopatric scenarios. Substantial, but incomplete, reproductive isolation suggests an early stage of speciation, most likely due to ecological selection pressure.


Initial retrocolic endoscopic tunnel approach: A promising technique for radical right hemicolectomy.
Complete mesocolic excision with central vascular ligation for colonic cancers improves overall survival. To achieve better short term and oncological results, different laparoscopic techniques have been described for right-sided colonic cancers. Laparoscopic right hemicolectomy by the Initial Retrocolic Endoscopic Tunnel Approach (IRETA) is proposed to be easy and offer desired oncological resection; we present our results with IRETA. The data of all patients who underwent right hemicolectomy by IRETA for colonic cancer between January 2019 and March 2020 were retrospectively analysed for demographics, clinical features, oncological completeness of resected specimen, complications, hospital stay, morbidity and mortality. A total of eight patients (05 males and 03 females) were identified. The mean operating time was 190 ± 32.40 minutes. Margins of all resected specimens were free of tumour except for one in which retro-peritoneal circumferential resection margin was positive. On average 13.75 ± 2.63 lymph nodes were retrieved. Except for wound infection in one patient, no other morbidity was seen. Laparoscopic radical right hemicolectomy by IRETA is safe and gives desired oncological results.


Extended-spectrum beta-lactamases in urinary isolates of Escherichia coli, Klebsiella pneumoniae and other gram-negative bacteria in a hospital in Eastern Province, Saudi Arabia.
To evaluate the prevalence and antimicrobial susceptibility of extended spectrum beta-lactamase (ESBL) producing gram-negative organisms isolated from patients with urinary tract infection (UTI). We carried out this study at Almana General Hospital, Eastern Province, Kingdom of Saudi Arabia, during the period August 2003 to October 2004. We studied urinary isolates of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Enterobacter spp and Pseudomonas aeruginosa (P. aeruginosa) for ESBL production and antimicrobial susceptibility. We studied a total of 2302 urinary gram-negative isolates for the presence of ceftazidime resistance and ESBL. The isolates included E. coli (1238), K. pneumoniae (522), Enterobacter spp (138) and P. aeruginosa (404). Of the 2302 isolates, 232 (10%) were ceftazidime resistant and 204 (8.9%) were ESBL producers. We detected ESBL in 119 (9.6%) E. coli, 59 (11.3%) K. pneumoniae, 14 (10.14%) Enterobacter species and 12 (2.97%) P. aeruginosa isolates. The ESBL-producing strains were most commonly isolated from patients with indwelling Foley s catheter [131 (64.2%)] and those in the long-term care ward [90 (44.2%)]. Only 26 (12.7%) ESBL-producing isolates were from outpatients. More than 89% of the ESBL producers were susceptible to imipenem and meropenem. Amikacin and piperacillin/tazobactam were active against 68% and 45% of the isolates. Susceptibility to gentamicin and ciprofloxacin was 22.5% and 14%. The least active antibiotic was cefepime (11.8%). This study shows the presence of ESBL producers in uropathogens from both inpatients and outpatients and demonstrates their high resistance to various classes of antimicrobial agents.


Degrees of difference among minority female juvenile offenders' psychological functioning, risk behavior engagement, and health status: a latent profile investigation.
Given the increase in the number of female youth who come in contact with the juvenile justice system, particularly those from ethnic minority backgrounds, concerns have been raised about the health status of this population. Using a latent profile analysis, we identified health profiles using indicators of psychological well-being, health risk behaviors, and health status. Participants included 153 minority adolescent females (M=15.13, SD=1.70) who were currently in a juvenile diversion program. Results indicated that a three-class solution fit the data optimally. Profiles included girls with low to moderate health risks (n=35; 22.9%), higher mental health symptoms (n=68; 44.4%), and a combination of multiple health risks (n=50; 32.7%). Additionally, demographic, contextual and offense-related variation existed across health profiles. Treatment and policy implications are discussed.


Review of the therapeutic uses of liraglutide.
Glucagon-like peptide (GLP-1) is a neuroendocrine hormone that increases blood glucose and is a drug target for treatment of type 2 diabetes. Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the treatment of type 2 diabetes in the United States and Europe. It also has been studied for weight loss. The purpose of this article is to review all of the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions, cost, and place in therapy of liraglutide. Literature searches of MEDLINE between 1969 and September 2010, International Pharmaceutical Abstracts between 1970 and September 2010, American Diabetes Association Meeting abstracts (2008-2010), and European Association for the Study of Diabetes abstracts (2008-2010) were performed using liraglutide, Victoza, and NN2211 as key terms. Thirteen randomized controlled trials were identified and summarized. Liraglutide has been shown to increase glucose-dependent insulin release by 34% to 118% and reduce postprandial glucagon levels by 20%. Studies showed that liraglutide, as monotherapy and in combination with glimepiride, metformin, and/or rosiglitazone, lowers glycosylated hemoglobin (HbA(1c)) between 0.84% and 1.5%. Transient nausea was reported by 7% to 40% of subjects. Severe hypoglycemia-glucose <55 mg/dL-was observed by 2.5% of subjects in 1 trial. Liraglutide safely and effectively reduces HbA(1c) in patients with type 2 diabetes. The most recent American Diabetes Association guidelines recommended a GLP-1 agonist along with metformin as a second-tier therapy for type 2 diabetes. Although the American Association of Clinical Endocrinologists/American College of Endocrinologists' guidelines recommended it for first-line monotherapy in patients with HbA(1c) between 6.5% and 7.5% and with metformin if HbA(1c) is between 7.6% and 8.5%, liraglutide should be considered for patients who cannot tolerate first-line agents or if an additional agent is needed to help reach target HbA(1c) goals.


Knowledge and attitudes of family practice residents toward geriatric patients.
The knowledge and attitudes of family practice residents toward geriatric patients was surveyed in eight residencies. Since geriatric care will, in the future, become a more important aspect of the family physician's practice, it is important to ascertain the knowledge and attitude level of physicians in training concerning their geriatric patients. Three aspects of this study indicate serious deficits in the educational background of these residents: the number and quality of courses offered to them is inadequate; they demonstrate a paucity of knowledge concerning the aged; the residents show a low preference for working with the aged. Clearly, medical education should address these needs and deficits.


Super-Earths, M Dwarfs, and Photosynthetic Organisms: Habitability in the Lab.
In a few years, space telescopes will investigate our Galaxy to detect evidence of life, mainly by observing rocky planets. In the last decade, the observation of exoplanet atmospheres and the theoretical works on biosignature gasses have experienced a considerable acceleration. The most attractive feature of the realm of exoplanets is that 40% of M dwarfs host super-Earths with a minimum mass between 1 and 30 Earth masses, orbital periods shorter than 50 days, and radii between those of the Earth and Neptune (1-3.8 R⊕). Moreover, the recent finding of cyanobacteria able to use far-red (FR) light for oxygenic photosynthesis due to the synthesis of chlorophylls d and f, extending in vivo light absorption up to 750 nm, suggests the possibility of exotic photosynthesis in planets around M dwarfs. Using innovative laboratory instrumentation, we exposed different cyanobacteria to an M dwarf star simulated irradiation, comparing their responses to those under solar and FR simulated lights. As expected, in FR light, only the cyanobacteria able to synthesize chlorophyll d and f could grow. Surprisingly, all strains, both able or unable to use FR light, grew and photosynthesized under the M dwarf generated spectrum in a similar way to the solar light and much more efficiently than under the FR one. Our findings highlight the importance of simulating both the visible and FR light components of an M dwarf spectrum to correctly evaluate the photosynthetic performances of oxygenic organisms exposed under such an exotic light condition.