Neonatal tetanus in the middle Black Sea region of Turkey.
We retrospectively analyzed 62 cases with neonatal tetanus (NT) seen in the Department of Pediatrics of Ondokuz Mayis University from 1989 to 2001. Epidemiological characteristics and prognostic factors on survival were investigated. We grouped the patients into two groups, the survivors and those who died. All patients were born in non-hygienic conditions, coming from rural regions. None of the mothers had been immunized against tetanus. The mortality rate was 40% (25 of 62 cases) and the only two poor prognostic factors on survival were age younger than five days at onset and the presence of fever. There was no significant difference between the two groups regarding the other known prognostic factors. Although the NT rate is declining, we must continue to protect against it by strictly enforcing preventive policies, especially in rural regions.


Suillus quiescens, a new species commonly found in the spore bank in California and Oregon.
Suillus quiescens sp. nov. is common under Pinus muricata on Santa Cruz and Santa Rosa Islands in the northern Channel Islands of California, and we subsequently found it fruiting at Point Reyes National Seashore on the central coast of California. Sequences from the internal transcribed spacer region show that it is distinct from all 44 species of Suillus tested, and features of its morphology separate it from all other unsequenced species. Suillus quiescens has a broader distribution than coastal California because it also was encountered as ectomycorrhizae on roots of pine seedlings from the eastern Sierra Nevada, coastal Oregon and the southern Cascade Mountains. The reason it had not been identified from these areas might be due to its resemblance to S. brevipes at maturity or it might be a rare fruiter that persists in the spore bank.


Papillary necrosis in renal allografts--report of 2 cases.
Two patients are reported in whom early and irreversible renal allograft rejection was associated with passage of necrotic papillary material in the urine. Evidence is presented for a causal relationship between rejection and medullary necrosis. Passage of a papilla is regarded as a definite indication for graft exploration.


Active versus passive training of a complex bimanual task: is prescriptive proprioceptive information sufficient for inducing motor learning?
Perceptual processes play an important role in motor learning. While it is evident that visual information greatly contributes to learning new movements, much less is known about provision of prescriptive proprioceptive information. Here, we investigated whether passive (proprioceptively-based) movement training was comparable to active training for learning a new bimanual task. Three groups practiced a bimanual coordination pattern with a 1:2 frequency ratio and a 90° phase offset between both wrists with Lissajous feedback over the course of four days: 1) passive training; 2) active training; 3) no training (control). Retention findings revealed that passive as compared to active training resulted in equally successful acquisition of the frequency ratio but active training was more effective for acquisition of the new relative phasing between the limbs in the presence of augmented visual feedback. However, when this feedback was removed, performance of the new relative phase deteriorated in both groups whereas the frequency ratio was better preserved. The superiority of active over passive training in the presence of augmented feedback is hypothesized to result from active involvement in processes of error detection/correction and planning.


The inducible nitric-oxide synthase modulates endothelin-1-dependent release of prostacyclin and inhibition of platelet aggregation ex vivo in the mouse.
Nitric oxide and other reactive oxygen species generated by nitric-oxide synthases (NOS) modulate, among several other cellular responses, the production of eicosanoids and platelet aggregation. The roles of specific NOS in these two phenomena remain to be determined. Thus, the present study assessed whether inducible NOS (iNOS) and endothelial NOS (eNOS) modulate in a similar manner the production of eicosanoids and platelet aggregation. Mice knocked out for eNOS (eNOS-/-) or iNOS (iNOS-/-) and their wild-type (WT) congeners were used to analyze agonist-induced increases in plasma levels of eicosanoids as well as inhibition of platelet aggregation ex vivo. Systemically administered endothelin-1 (ET-1) triggered an increase in plasma levels of 6-keto prostaglandin F(1alpha) (6-keto PGF(1alpha)) in WT and eNOS-/- but not in iNOS-/- mice. ET-1 (0.01-1 nmol/kg) also induced a dose-dependent inhibition of platelet aggregation in WT and eNOS-/- but not in iNOS-/- mice. Another agonist, bradykinin (10 nmol/kg), triggered the release of 6-keto PGF(1alpha) and inhibited platelet aggregation in all strains of mice studied. In addition, ADP-induced platelet aggregation in vitro was similarly reduced by iloprost (100 nM) in iNOS-/- mice and WT congeners. In another series of experiments, ET-1 (0.1 nmol/kg) significantly increased 8-isoprostane plasma levels in WT but not in iNOS-/- mice. Finally, a 3-week treatment with anti-oxidants inhibited the capacity of ET-1 to significantly increase plasma 6-keto PGF(1alpha) in WT mice. We show for the first time that iNOS is involved in the control of ET-1-induced prostacyclin release and related inhibition of platelet aggregation in the murine model.


Show me the way to stay home.
As the health system continues to evolve through the implementation of the electronic health record and other information technology initiatives, it is imperative that governments undergo a paradigm shift and recognize the need for strategic investment in home care (CHCA 2008a:7).


Morbidity Associated with Diverting Loop Ileostomies: Weighing Diversion in Rectosigmoid Resection.
Anterior resection with primary anastomosis is the procedure of choice for patients with rectosigmoid cancers with good sphincter function. Surgeons may perform an associated diverting loop ileostomy (DLI) to minimize the likelihood and/or the severity of an anastomotic leak. To examine the morbidity of DLIs, we performed a review of a prospectively maintained database. Participants included all patients at the Massachusetts General Hospital who underwent anterior resection from January 2013 to July 2015 for rectosigmoid cancers and who subsequently underwent adjuvant chemotherapy. The primary outcome was time to start of adjuvant chemotherapy. Secondary outcomes included length of hospitalization, perioperative complications, and 60-day postoperative complications. Inclusion criteria were met in 57 patients and DLI was performed in 21 (37%). The DLI group had higher estimated blood loss (431.7 vs 192.1 mL, P = 0.03) and a longer operation time (3.7 vs 2.3 hours, P = 0.0007). The DLI group took over a week longer to start adjuvant chemotherapy than the non-DLI group (median time to chemo: 43 vs 34 days, P = 0.002). Postoperatively, DLI was associated with a longer hospitalization (6.7 vs 3.1 days, P = 0.0003), more perioperative complications (57.1% vs 13.9%, P = 0.0006), and more 60-day readmissions or emergency department visits (38.1% vs 5.6%, P = 0.002). Ostomies are associated with appreciable morbidity. In turn, they do not eliminate postoperative complications. Surgeons should closely consider ostomy morbidity in rectosigmoid resection and institute a proactive approach toward identification and prevention of complications.


Modified Intervastus Approach to the Knee.
The modified intervastus approach to the anterior knee is an approach that may be used in the majority of patients undergoing total knee arthroplasty. This article presents the first description of this approach. The advantages of this approach include its extensile nature, similar to a medial parapatellar approach, and preservation of the extensor mechanism and the vastus medialis, leading to a more rapid return to active knee extension than is traditionally observed. The approach is also simple to perform, easy to close, and is compatible with more extensile approaches such as a quadriceps snip if required in revision scenarios.


Does culture create craving? Evidence from the case of menstrual chocolate craving.
Craving is considered a key characteristic of diverse pathologies, but evidence suggests it may be a culture-bound construct. Almost 50% of American women crave chocolate specifically around the onset of menstruation. Research does not support popular accounts implicating physiological factors in menstrual chocolate craving etiology. We tested the novel hypothesis that greater menstrual craving prevalence in the U.S. is the product of internalized cultural norms. Women of diverse backgrounds (n = 275) reported on craving frequency and triggers and completed validated measures of acculturation. Foreign-born women were significantly less likely to endorse menstrual chocolate craving (17.3%), compared to women born to U.S.-born parents (32.7%, p = .03) and second generation immigrants (40.9%, p = .001). Second generation immigrant and foreign-born women endorsing menstrual chocolate craving reported significantly greater U.S. acculturation and lower identification with their native culture than non-menstrual cravers (all p < .001). Findings inform our understanding of food cravings, with important implications for the study of cravings in other domains.


The Association between Apolipoprotein E Genotypes and Serum Malondialdehyde Level with End-Stage Renal Disease.
The Apolipoprotein E (ApoE) polymorphism plays an important role in the pathophysiology of end-stage renal disease (ESRD). Additionally, ApoE may contribute to the progression of oxidative stress. Thus, this study aimed to determine the ApoE gene polymorphism and evaluate the malondialdehyde (MDA) level in ESRD patients and healthy individuals. The present cross-sectional study was conducted at 2010 at Kermanshah University of Medical Sciences (Kermanshah, Iran). The study population comprised ESRD patients (n=136) and healthy individuals (n=137). The MDA level was assessed using high-performance liquid chromatography (HPLC), and the frequencies of ApoE gene alleles were analyzed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). The data were analyzed using Statistical Package for Social Sciences (SPSS), version 13. The significant differences of ApoE genotypes in case and control groups were assessed using Pearson's Chi square tests, and two-tailed Student's tests. A logistic regression model was used to calculate the odd ratio. P<0.05 was considered statistically significant. According to the results, ESRD patients had a higher frequency of the E2/E3 genotype than the healthy group (P<0.001). The results indicated that E3/E4 genotype frequency in the patients' group was higher than that of the control group (P=0.026). Furthermore, the E3/E2 (OR=5.7, 95% CI=2.68-12.14) (P<0.001) and E3/E4 (OR=1.57, 95% CI=1.05-2.34) (P=0.029) genotypes were found to increase the risk of ESRD. Moreover, the MDA level in ESRD patients was higher than the healthy individuals (P<0.001). The patients with E3/E2 (P<0.001) and E3/E4 (P<0.001) genotypes had a higher level of MDA than the control group. According to the findings, patients with ESRD had higher genotypes of E3/E2 and E3/E4, which suggests a higher risk of developing ESRD.


Effectiveness of fibreoptic endoscopic evaluation of swallowing and dietary intervention during home-visit dental care in older individuals.
Currently, patients with dysphagia are receiving dietary management that deviates from their original swallowing function. To evaluate the clinical significance of fibreoptic endoscopic evaluation of swallowing (FEES) and dietary intervention (DI) by multi-professional collaboration during visit care for determining the actual oral intake status in patients with dysphagia. Five hundred and eighteen patients with dysphagia underwent FEES, focusing on the penetration-aspiration scale, and DI. Oral intake status was categorised using the functional oral intake scale (FOIS). FOIS scores at the first visit, after FEES, and at the reassessment were compared. At the first visit, 34.7% of the patients had an FOIS score of level 1 (no oral intake) and 65.3% had a score of level 2 or higher (capable of oral intake). Following FEES, 7.1% of patients had an FOIS score of level 1, and 44.4% had a score of level 2 with resumption of oral intake. At the reassessment, 489 patients (94.4%) were capable of oral ingestion (FOIS level 2 or higher). There were significant differences between the distributions of FOIS scores at the first visit and following FEES (P < .01) and between those at the first visit and at the reassessment (P < .01). Regarding tube feeding, 17 (5.9%) of 289 patients, who had received tube feeding at the first visit, were completely capable of oral intake following FEES and at the reassessment. Appropriate evaluation of swallowing function using FEES and DI helps to understand the definite swallowing function in patients with dysphagia.


Activity of albendazole-ivermectin combination and other filaricidal drugs against infective larvae, preadult, microfilariae and adult worms of Molinema dessetae in the rodent Proechimys oris.
The efficacy of albendazole-ivermectin combination was tested an adult and developing stages of Molinema dessetae in the rodent Proechimys oris. Albendazole and ivermectin, both given alone, suramin and diethylcarbamazine were used as reference compounds. The drug combination (albendazole at 10 mg/kg/ day x 5 days and Ivermectin at 0.04 mg/kg/day x 5 days) was effective against infective larvae and preadult worms, and substantially reduced the number of live adult worms. The known filaricidal agents, diethylcarbamazine (400 mg/kg twice daily x 5 days), ivermectin (0.2 mg/kg/day x 5 days), and suramin (40 mg/kg/day x 5 days), as well as albendazole (50 mg/kg/day x 5 days) were active on infective larvae, preadult worms, microfilariae and adult worms. All drugs had the same level of efficacity on infective larvae. Albendazole had the highest efficacy against adult and preadult worms and diethylcarbamazine was the most active on microfilariae. Although the drug combination was not as effective against preadult and adult worms as albendazole alone, the results indicate that albendazole-ivermectin combination at a low dose had prophylactic effect and suggest a possible macrofilaricidal activity.


What Is the Optimal Light Source for Optical Mapping Using Voltage- and Calcium-Sensitive Dyes?
Optical mapping is a fluorescence-based physiological method to image spreading of action potential in excitable tissues, such as the heart and central nervous system. Because of the requirements for high speed imaging in low light conditions, highly sensitive high-speed cameras together with an optical system with maximum photon efficiency are required. While the optimization of these two components is relatively straightforward, the choice of the perfect light source is less simple; depending on the other (usually fixed) components, various parameters may acquire different weight in decision-making process. Here we describe the rationale for building an optical mapping setup and consider the relative advantages and disadvantages of three different commonly available light sources: mercury vapor lamp (HBO), xenon lamp (XBO), and light emitting diode (LED). Using the same optical system (fluorescence macroscope) and high-speed camera (Ultima L), we have tested each of the sources for its ability to provide bright and even illumination of the field of view and measured its temporal fluctuations in intensity. Then we used each in the actual optical mapping experiment using isolated, perfused adult mouse heart or chick embryonic heart to determine the actual signal to noise ratio at various acquisition rates. While the LED sources have undergone significant improvements in the recent past, the other alternatives may still surpass them in some parameters, so they may not be the automatic number one choice for every application.


Expression and function of the integrin alpha9beta1 in bovine aortic valve interstitial cells.
Aortic valve interstitial cells (VIC), the most prevalent valve leaflet cells, have not been well studied. However, recent interest in constructing tissue-engineered living heart valves has provided motivation to further an understanding of the molecular and cellular biology of VIC. Since cell-extracellular matrix interactions are critical for tissue morphogenesis, adhesive interactions and integrin function in VIC were investigated. Bovine and baboon VIC were isolated and characterized by morphology, cytoskeletal protein expression and integrin expression. The interaction of VIC integrin alpha9beta1 with osteopontin, a ligand known to be up-regulated in the wounded valve, was examined. The ability of bovine VIC alpha9beta1 to mediate adhesion, focal contact formation, migration and proliferation when plated on the immobilized osteopontin substrates, was investigated. Cultured bovine VIC possessed characteristics of both fibroblasts and smooth muscle cells. Like fibroblasts, bovine VIC had an elongated morphology with long cytoplasmic processes. Like smooth muscle cells, bovine VIC expressed alpha-smooth muscle actin and SM22alpha. Using fluorescent flow cytometry, the surface expression of integrins alpha9beta1 and alpha(v)beta3 in bovine VIC and integrins alpha1beta1, alpha2beta1, and alpha5beta1 in baboon VIC was identified. Expression of alpha9beta1 in cultured VIC and in native valve leaflets was further confirmed by Western blot and RT-PCR analysis. Bovine VIC were found to adhere to the 30N fragment of osteopontin in an alpha9beta1-dependent manner, and this interaction was mediated through the SVVYGLR motif. Bovine VIC also formed focal contacts through the alpha9beta1 integrin, but osteopontin (30N) did not stimulate migration or proliferation of bovine VIC through the integrin alpha9beta1. Integrin alpha9beta1 appears to be predominantly involved in controlling anchorage rather than movement or proliferation, in bovine VIC. For tissue engineering, knowledge of the VIC integrin profile can be applied to the rational design of scaffolds with the appropriate ligands for tissue formation. The VIC a9beta1-SVVYGLR interaction could be exploited to promote cell anchorage within a tissue engineering scaffold.


The Relationship between Inter-Arm Blood Pressure Difference and Coronary Artery Disease Severity Calculated by the SYNTAX Score.
The inter-arm systolic blood pressure difference (IASBPD) is closely related to cardiovascular mortality and morbidity. The SYNTAX score indicates the extent and complexity of coronary artery disease, which are determined by coronary angiography. The aim of our study is to examine the relationship between the IASBPD (which is easily calculated in routine practice) and the SYNTAX score. 104 patients were included in this cross-sectional study. The IASBPD was calculated by blood pressure measurements obtained simultaneously from both arms. The SYNTAX score was calculated by coronary angiography. Patients were divided into two groups: those with a high SYNTAX score (≥20) and those with a low SYNTAX score (<20). The mean IASBPD values were significantly higher in the group with a high SYNTAX score (≥20) (p<0.001). The patients with IASBPD≥10 were more likely to have a high SYNTAX score compared to the patients with IASBPD<10 (p<0.001). Multiple logistic regression analysis revealed that only the IASBPD values were found to be independently associated with high SYNTAX score (OR: 1.717 (CI: 1.307-2.257), p<0.001). The IASBPD values obtained by only blood pressure measurements are closely related to the extent of coronary artery disease.


Avian auditory pathways show met-enkephalin-like immunoreactivity.
Pathways associated with a recently defined region of the avian auditory thalamus, the shell of the nucleus ovoidalis (Ov), were examined for met-enkephalin immunoreactivity. The presence of enkephalin-like immunoreactive (ELI) perikarya within the medial margin of the inferior colliculus (ICM), afferent to the Ov shell, implicated ICM as a source of ELI fibers within the Ov shell and tract. The shell also contained ELI perikarya and its targets, including the ventromedial hypothalamus and caudoventral paleostriatal complex, were characterized by ELI fields. These data suggest that enkephalinergic auditory pathways, in parallel with traditionally recognized auditory projections, target regions of the avian basal forebrain.


The development of genetic resistance to myxomatosis in wild rabbits in Britain.
The presence of genetic resistance to myxomatosis in a sample of wild rabbits from one area in England was reported in 1977. Rabbits from three other areas in Great Britain have been tested subsequently, and all cases showed similar resistance to a moderately virulent strain of myxoma virus. Rabbits from one area also showed a significant degree of resistance to a fully virulent strain of virus. It is concluded that genetic resistance to myxomatosis is widespread in wild rabbit populations in Britain. The implications of the results are discussed in relation to the co-evolution of the disease and its host.


Partitioning of herbivore hosts across time and food plants promotes diversification in the Megastigmus dorsalis oak gall parasitoid complex.
Communities of insect herbivores and their natural enemies are rich and ecologically crucial components of terrestrial biodiversity. Understanding the processes that promote their origin and maintenance is thus of considerable interest. One major proposed mechanism is ecological speciation through host-associated differentiation (HAD), the divergence of a polyphagous species first into ecological host races and eventually into more specialized daughter species. The rich chalcid parasitoid communities attacking cynipid oak gall wasp hosts are structured by multiple host traits, including food plant taxon, host gall phenology, and gall structure. Here, we ask whether the same traits structure genetic diversity within supposedly generalist parasitoid morphospecies. We use mitochondrial DNA sequences and microsatellite genotypes to quantify HAD for Megastigmus (Bootanomyia) dorsalis, a complex of two apparently generalist cryptic parasitoid species attacking oak galls. Ancient Balkan refugial populations showed phenological separation between the cryptic species, one primarily attacking spring galls, and the other mainly attacking autumn galls. The spring species also contained host races specializing on galls developing on different host-plant lineages (sections Cerris vs. Quercus) within the oak genus Quercus. These results indicate more significant host-associated structuring within oak gall parasitoid communities than previously thought and support ecological theory predicting the evolution of specialist lineages within generalist parasitoids. In contrast, UK populations of the autumn cryptic species associated with both native and recently invading oak gall wasps showed no evidence of population differentiation, implying rapid recruitment of native parasitoid populations onto invading hosts, and hence potential for natural biological control. This is of significance given recent rapid range expansion of the economically damaging chestnut gall wasp, Dryocosmus kuriphilus, in Europe.


Cooperation of protein kinase A and Ras/ERK signaling pathways is required for AP-1-mediated activation of fibroblast growth factor-inducible response element (FiRE).
Recent studies suggest a crucial role for protein kinase A (PKA) in the regulation of growth factor signaling. However, the effect of PKA on the transcription of growth factor-responsive genes has drawn far less attention. Here we have investigated the signaling mechanisms involved in the activation of an activator protein-1 (AP-1)-driven, growth factor-specific enhancer element, fibroblast growth factor-inducible response element (FiRE). The activation was found to be mediated by three phorbol 12-O-tetradecanoate-13-acetate-response element-related DNA elements of FiRE, including motif 4 and two distinct elements of motif 5 (referred to as M5-1 and M5-2). All three elements were required for full FiRE activity. Stimulation of cells with fibroblast growth factor-2 (FGF-2) induced the binding of AP-1 to motif 4 and M5-2, whereas M5-1 did not show detectable binding. The FGF-2-induced FiRE activation appeared to require cooperational function of the Ras/ERK and PKA pathways. Inhibition of either of the pathways abolished the binding of AP-1 complexes to motif 4 and motif 5 and the subsequent FiRE activation. By contrast, costimulation of cells with FGF-2 and the PKA activator 8-bromo-cyclic AMP increased the binding of AP-1 to FiRE and potentiated the level of transcriptional activity. The cooperational function of these two pathways was confirmed by experiments with cell lines stably expressing 4-hydroxytamoxifen-inducible oncogenic Raf-1 (DeltaRaf-1:ER[DD]). Noticeably, the induction systems showed variations with respect to regulation of AP-1-driven activation of FiRE. These differences were likely to originate from the ability of these two systems to induce the differential activation pattern of the Ras/ERK pathway.


[The influence of type 2 diabetes mellitus on early and late results of percutaneous coronary intervention for non-st segment elevation myocardial infarction].
The aim: We aimed at assessing the prognostic significance of diabetes mellitus in patients with NSTEMI treated with PCI as well as determining the independent predictors of worse prognosis. Materials and methods: We performed a retrospective analysis of 830 patients hospitalized between January 2006 and December 2012 with diagnoses of NSTEMI and undergoing angiography and percutaneous coronary interventions. Patients were divided into two groups: with diabetes mellitus (246 patients) and without diabetes mellitus (584 patients). All patients were followed up at 30 days, 12 months, and 24 months. Results: Diabetes mellitus was an independent risk factor for the occurrence of complex endpoints (HR, 1.64) at the 24-month follow-up visit: myocardial infarction not ending with death analyzed alone (HR, 1.82), death analyzed together with myocardial infarction not ending with death (HR, 1.65), and repeated revascularization performed due to the presence of ischemia (HR, 1.63) Moreover, diabetes mellitus was one of the factors influencing 24-month mortality, but its independent influence was at the threshold of significance (HR, 1.46; p=0.08). In the multiple factor analysis the independent risk factors for death at the 24-month follow-up were: creatinine concentration on admission, LVEF, age, and cardiogenic shock during hospitalization. Conclusions: Despite similar efficacy of percutaneous coronary intervention, diabetes mellitus was associated with a worse in-hospital and long-term outcomes. Diabetes mellitus did not affect long-term mortality.


Regulat-INGs in tumors and diseases: Focus on ncRNAs.
ING family genes (Inhibitor of Growth) are tumor suppressor genes that play a vital role in cell homeostasis. It has been shown that their expression is lost or diminished in many cancers and other diseases. The main mechanisms by which they are regulated in oncogenesis have not yet been fully elucidated. The involvement of non-coding RNAs (ncRNAs) and in particular microRNAs (miRNAs) in post-transcriptional gene regulation is well established. miRNAs are short sequences (18-25 nucleotides) that can bind to the 3 'UTR sequence of the targeted messenger RNA (mRNA), leading to its degradation or translational repression. Interactions between the ING family and miRNAs have been described in some cancers but also in other diseases. The involvement of miRNAs in ING family regulation opens up new fields of investigation, particularly for targeted therapies. In this review, we will summarize the regulatory mechanisms at the RNA and protein level of the ING family and focus on the interactions with ncRNAs.


Cancer cell membrane-coated biomimetic platform for targeted therapy of breast cancer in an orthotopic mouse model.
The long circulation time and targeting drug delivery at tumor sites are still the main challenges of nanodrug delivery systems for antitumor activity. Herein, a cancer cell membrane-coated biomimetic nanodrug delivery system was fabricated. The paclitaxel (PTX)-loaded poly(lactic acid) (PLA) nanoparticles (PPNs) were used as the inner cores and 4T1 cancer cell membranes were coated on the surface of PPNs as the outer shells. The biomimetic platform was noted as CPPNs. The CPPNs exhibited proper sizes for the enhanced permeability and retention (EPR) effect and could maintain stability in a simulated physiological environment. The CPPNs exhibited a better antitumor effect than PPNs and free PTX in vitro. Moreover, due to the immune escape and homologous targeting abilities endowed by the cancer cell membrane coating, the CPPNs could efficiently accumulate and long-term exist at tumor sites. In the orthotopic 4T1 breast cancer mouse model, the CPPNs effectively inhibited the progression of tumor by increasing the apoptosis and necrosis areas within tumor tissues. In addition, the toxic side effects of PTX was also alleviated in the CPPNs group. As a result, CPPNs can be a promising biomimetic nanodrug delivery system for the enhanced and targeted therapy of breast cancer.


The death mechanism of the harmful algal bloom species Alexandrium tamarense induced by algicidal bacterium Deinococcus sp. Y35.
Harmful algal blooms (HABs) cause a variety of deleterious effects on aquatic ecosystems, especially the toxic dinoflagellate Alexandrium tamarense, which poses a serious threat to marine economic and human health based on releasing paralytic shellfish poison into the environment. The algicidal bacterium Deinococcus sp. Y35 which can induce growth inhibition on A. tamarense was used to investigate the functional mechanism. The growth status, reactive oxygen species (ROS) content, photosynthetic system and the nuclear system of algal cells were determined under algicidal activity. A culture of strain Y35 not only induced overproduction of ROS in algal cells within only 0.5 h of treatment, also decrease the total protein content as well as the response of the antioxidant enzyme. Meanwhile, lipid peroxidation was induced and cell membrane integrity was lost. Photosynthetic pigments including chlorophyll a and carotenoid decreased along with the photosynthetic efficiency being significantly inhibited. At the same time, photosynthesis-related gene expression showed down-regulation. More than, the destruction of cell nuclear structure and inhibition of proliferating cell nuclear antigen (PCNA) related gene expression were confirmed. The potential functional mechanism of the algicidal bacterium on A. tamarense was investigated and provided a novel viewpoint which could be used in HABs control.


Mortality in traffic accidents with older adults in Colombia.
OBJECTIVE To analyze the traffic accident mortality in the Colombian older adults during the 1998-2012 period and show the loss of productive years and mortality from this cause. METHODS Quantitative study of the trend analysis of deaths in Colombia in traffic accidents, from 1998 to 2012, according to death records and population projected by the Colombian National Administrative Department of Statistics. Frequency distribution profile of the deceased, death rates per hundred thousand inhabitants, potential years of life lost and calculation of excess mortality by age in the over 60 were made. RESULTS In the study period 100,758 deaths occurred in traffic accidents, 6,717 annual average, of which 18.5% occurred in people aged 60 years and over. The predominated deaths were men; the risk of dying was 32.15 per hundred thousand people in this age range, with double risk of dying those under 60 years. CONCLUSIONS The young population has a higher proportion of deaths, but those over 60 years are at increased risk of death, leading to the need to turn our gaze to the improvement of road infrastructure and standards, to educate the population in self-care and compliance with safety measures and prepare society for an ever more adult population, more numerous and more prone to take risks.


Potential Gene Interactions in the Cell Cycles of Gametes, Zygotes, Embryonic Stem Cells and the Development of Cancer.
This review is to explore whether potential gene interactions in the cell cycles of gametes, zygotes, and embryonic stem (ES) cells are associated with the development of cancer. MEDPILOT at the Central Library of the University of Cologne, Germany (Zentralbibliothek Köln) that covers 5,800 international medical journals and 4,300 E-journals was used to collect data. The initial searches were done in December 2012 and additional searches in October 2013-May 2015. The search terms included "cancer development," "gene interaction," and "ES cells," and the time period was between 1998 and 2015. A total of 147 articles in English language only were included in this review. Transgenerational gene translation is implemented in the zygote through interactions of epigenetic isoforms of transcription factors (TFs) from parental gametes, predominantly during the first two zygote cleavages. Pluripotent transcription factors may provide interacting links with mutated genes during zygote-to-ES cell switches. Translation of post-transcriptional carcinogenic genes is implemented by abnormally spliced, tumor-specific isoforms of gene-encoded mRNA/non-coding RNA variants of TFs employing de novo gene synthesis and neofunctionalization. Post-translationally, mutated genes are preserved in pre-neoplastic ES cell subpopulations that can give rise to overt cancer stem cells. Thus, TFs operate as cell/disease-specific epigenetic messengers triggering clinical expression of neoplasms. Potential gene interactions in the cell cycle of gametes, zygotes, and ES cells may play some roles in the development of cancer.


Abnormalities in neural progenitor cells in a dog model of lysosomal storage disease.
Lysosomal storage disorders constitute a large group of genetic diseases, many of which are characterized by mental retardation and other neurologic symptoms. The mechanisms of neural dysfunction remain poorly understood. Because neural progenitor cells (NPCs) are fundamentally important to normal brain development and function, we investigated NPC properties in a canine model of mucopolysaccharidosis VII (MPS VII). MPS VII is a lysosomal storage disorder characterized by defects in the catabolism of glycosaminoglycans. NPCs were isolated from the olfactory bulb, cerebellum, and striatal subventricular zone of normal and MPS VII (beta-glucuronidase-deficient) postnatal dog brains. Canine NPCs (cNPCs) from normal and MPS VII brains had similar growth curves, but cerebellar-derived cNPCs grew significantly slower than those derived from other regions. In differentiation assays, MPS VII cNPCs from the striatal subventricular zone and cerebellum generated fewer mature neuronal and/or glial cells than normal, and MPS VII olfactory bulb-derived cNPCs retained significantly more phenotypically immature cells. These differences were only present at the earliest time point after isolation; at later passages, there were no differences attributable to genotype. The data suggest that MPS VII cNPCs respond differently to developmental cues in vivo, probably because of the diseased neural microenvironment rather than intrinsic cellular deficits.


Atlantic salmon Salmo salar in the chalk streams of England are genetically unique.
Recent research has identified genetic groups of Atlantic salmon Salmo salar that show association with geological and environmental boundaries. This study focuses on one particular subgroup of the species inhabiting the chalk streams of southern England, U.K. These fish are genetically distinct from other British and European S. salar populations and have previously demonstrated markedly low admixture with populations in neighbouring regions. The genetic population structure of S. salar occupying five chalk streams was explored using 16 microsatellite loci. The analysis provides evidence of the genetic distinctiveness of chalk-stream S. salar in southern England, in comparison with populations from non-chalk regions elsewhere in western Europe. Little genetic differentiation exists between the chalk-stream populations and a pattern of isolation by distance was evident. Furthermore, evidence of temporal stability of S. salar populations across the five chalk streams was found. This work provides new insights into the temporal stability and lack of genetic population sub-structuring within a unique component of the species' range of S. salar.


Extraordinary Role of Bi for Improving Thermoelectrics in Low-Solubility SnTe-CdTe Alloys.
As an environment-friendly alternative to traditional PbTe, many attempts have recently been made to improve thermoelectric SnTe. Effective strategies are mainly focused on valence band convergence, nanostructuring, interstitial defects, and alloying solubility. In particular, alloying SnTe with CdTe/GeTe triggers an inherent decline of valence band offset effectively owing to a high solubility of ∼20% of CdTe. However, to what level an additional element doping in low-solubility SnTe-CdTe alloys can play a role in enhancing the thermoelectric performance still remains a mystery. Here, a new strategy is shown that unexpected Bi doping, by alloying with only ∼3% CdTe, induces a significant enhancement of the thermoelectric figure of merit ZT to be ∼240% (ZT up to ∼1.3) at 838 K, which is mainly determined by the dramatically reduced lattice thermal conductivity above 800 K deriving from the exotic Bi doping and Cu-interstitial defects. More interestingly, combining experimental and theoretical evidences, the Bi-doping-driven band convergence is also beneficial to the improvement of thermoelectric performance below 800 K. The present findings demonstrate the extraordinary role of Bi for advancing the thermoelectric performance in SnTe alloys.


Computational design and discovery of nanomolar inhibitors of IκB kinase β.
IκB kinase β (IKKβ) is a useful target for the discovery of new medicines for cancer and inflammatory diseases. In this study, we aimed to identify new classes of potent IKKβ inhibitors based on structure-based virtual screening, de novo design, and chemical synthesis. To increase the probability of finding actual inhibitors, we improved the scoring function for the estimation of the IKKβ-inhibitor binding affinity by introducing proper solvation free energy and conformational destabilization energy terms for putative inhibitors. Using this modified scoring function, we have been able to identify 15 submicromolar-level IKKβ inhibitors that possess the phenyl-(4-phenyl-pyrimidin-2-yl)-amine moiety as the molecular core. Decomposition analysis of the calculated binding free energies showed that a high biochemical potency could be achieved by lowering the desolvation cost and the conformational destabilization for the inhibitor required for binding to IKKβ as well as by strengthening the interactions in the ATP-binding site. The formation of two hydrogen bonds with backbone amide groups of Cys99 in the hinge region was found to be necessary for tight binding of the inhibitors in the ATP-binding site. From molecular dynamics simulations of IKKβ-inhibitor complexes, we also found that complete dynamic stability of the bidentate hydrogen bond with Cys99 was required for low nanomolar-level inhibitory activity. This implies that the scoring function for virtual screening and de novo design would be further optimized by introducing an additional energy term to measure the dynamic stability of the key interactions in enzyme-inhibitor complexes.


Selectively Targeting and Differentiating Vancomycin-Resistant Staphylococcus aureus via Dual Synthetic Fluorescent Probes.
Many Staphylococcus bacteria are pathogenic and harmful to humans. Noticeably, some Staphylococcus, including vancomycin-resistant S. aureus (VRSA), have become notoriously resistant to antibiotics and have spread rapidly, becoming threats to public health. Here, we designed a dual fluorescent probe scheme combining siderophores and antibiotics as the guiding units to selectively target VRSA and vancomycin-sensitive S. aureus (VSSA) in complex bacterial samples. Siderophore-mediated iron uptake is the key pathway by which S. aureus acquires iron in limited environments. Therefore, the siderophore-derivative probe could differentiate between S. aureus and other bacteria. Moreover, by fine-tuning the vancomycin-derivative probes, we could selectively target only VSSA, further differentiating VRSA and VSSA. Finally, by combining the siderophore-derivative probe and the vancomycin-derivative probe, we successfully targeted and differentiated between VRSA and VSSA in complicated bacterial mixtures.


A Case Report of Post-traumatic Osteomyelitis with Gap Non-union of Humerus with Segmental Bone Defect and Scarred Skin Treated with Open Reduction Internal Fixation with Osteomyocutaneous Fibula.
Non-union of closed humerus fractures is estimated to be about 5.5% and this figure is even higher in open fractures. In cases of non-union of the humerus with segmental bone defect, if a conventional treatment has failed, free fibular transfer is often considered for satisfactory bone union. In some cases, where there is severe scarring due to multiple previous surgeries. In such cases, skin cover may not be adequate and tight closures often lead to necrosis and failure excision. Segmental bone defects of the upper limb that is >6 cm with soft-tissue coverage defects have limited options for reconstruction. Osteomyocutaneous fibula may provide to be a valuable option in such cases. This is a report a case of a 27-year-old male presented with a history of road traffic accident with Gustilo-Anderson Grade 3 B open fracture of humerus midshaft. He developed humerus osteomyelitis, for which he underwent surgical debridement. He presented to us with gap non-union with segmental bone loss. The overlying skin was scarred and had significant limb shortening. Treatment options for such a case are reconstruction or amputation. Challenges for reconstruction were to deal with the segmental bone loss and the soft-tissue defect following scar excision. We tackled both these challenges with an osteomyocutaneous fibula flap. At 1-year follow-up, the humerus showed union and flap uptake was good. Osteomyocutaneous fibula flap is a valuable treatment options in such complicated cases allowing for both bone union and soft-tissue coverage with a single surgical procedure.


Association of FTO and PPARG polymorphisms with obesity in Portuguese women.
We evaluated the association between risk of obesity in the Portuguese population and two obesity-related single-nucleotide gene polymorphisms: fat-mass and obesity-associated (FTO) rs9939609 and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282. A total of 194 Portuguese premenopausal female Caucasians aged between 18 and 50 years (95 with body mass index [BMI] ≥30 g/m(2), 99 controls with BMI 18.5-24.9 kg/m(2)) participated in this study. The association of the single-nucleotide polymorphisms with obesity was determined by odds ratio calculation with 95% confidence intervals. Significant differences in allelic expression of FTO rs9939609 (P<0.05) were found between control and case groups, indicating a 2.5-higher risk for obesity in the presence of both risk alleles when comparing the control group with the entire obese group. A fourfold-higher risk was found for subjects with class III obesity compared to those with classes I and II. No significant differences in BMI were found between the control and case groups for PPARG rs1801282 (P>0.05). For the first time, a study involving an adult Portuguese population shows that individuals harboring both risk alleles in the FTO gene locus are at higher risk for obesity, which is in agreement to what has been reported for other European populations.


[Intestinal obstruction caused by colorectal neoplasms].
The Authors report their ten-year experience in 85 cases of colorectal carcinoma presenting with large bowel obstruction. They underline the high morbidity and mortality of such condition related to the late diagnosis and the poor general conditions of the patients. After reviewing the literature they point out that the best treatment consists in dealing both with the intestinal obstruction and its cause during the same operative time. The post-operative mortality after radical treatment is acceptable especially when compared to derivative procedures.


Antihypertensive activity of a new ACE-inhibitor, SCH 33844, during repeated administration in spontaneously hypertensive rats.
The antihypertensive activity of SCH 33844, a new angiotensin converting enzyme inhibitor, was investigated in conscious spontaneously hypertensive rats during a 3-week treatment regimen and for 1 week following drug withdrawal. SCH 33844 was given once daily at 2 dose levels (1 and 5 mg/kg orally) and its effects were compared with those of captopril (60 mg/kg orally). Systolic blood pressure was recorded twice weekly just before administration and at varying time intervals up to 6 hr after dosing; recordings were continued for 1 week after drug withdrawal. SCH 33844 was found to produce dose-related antihypertensive effects. Given at 1 mg/kg, the compound elicited small but significant blood pressure changes during the treatment. After drug withdrawal, systolic blood pressure returned to pre-drug levels within 1 week. SCH 33844 at 5 mg/kg, and captopril at 60 mg/kg, both reduced blood pressure markedly and to a similar extent. After each administration the effect was rapid in onset, lasted for over 6 hr and was not subject to tolerance. Drug withdrawal resulted in a gradual return of systolic blood pressure toward pre-treatment levels within 1 week, with no evidence of rebound phenomena. These results indicate that SCH 33844, like captopril, produces an effective antihypertensive action throughout a repeated dosing.


Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals.
Calorie restriction (CR) delays the development of age-associated disease and increases lifespan in rodents, but the effects in humans remain uncertain. Determine the effect of 6 months of CR with or without exercise on cardiovascular disease (CVD) risk factors and estimated 10-year CVD risk in healthy non-obese men and women. Thirty-six individuals were randomized to one of three groups for 6 months: Control, 100% of energy requirements; CR, 25% calorie restriction; CR+EX, 12.5% CR+12.5% increase in energy expenditure via aerobic exercise. CVD risk factors were assessed at baseline, 3 and 6 months. After 6 months, CR and CR+EX lost approximately 10% of body weight. CR significantly reduced triacylglycerol (-31+/-15mg/dL) and factor VIIc (-10.7+/-2.3%). Similarly CR+EX reduced triacylglycerol (-22+/-8mg/dL) and additionally reduced LDL-C (-16.0+/-5.1mg/dL) and DBP (-4.0+/-2.1mmHg). In contrast, both triacylglycerol (24+/-14mg/dL) and factor VIIc (7.9+/-2.3%) were increased in the Control group. HDL-cholesterol was increased in all groups while hsCRP was lower in the Controls versus CR+EX. Estimated 10-year CVD risk significantly declined from baseline by 29% in CR (P<0.001) and 38% in the CR+EX (P<0.001) while remaining unchanged in the Control group. Based on combined favorable changes in lipid and blood pressure, caloric restriction with or without exercise that induces weight loss favorably reduces risk for CVD even in already healthy non-obese individuals.


The effect of abstract versus concrete framing on judgments of biological and psychological bases of behavior.
Human behavior is frequently described both in abstract, general terms and in concrete, specific terms. We asked whether these two ways of framing equivalent behaviors shift the inferences people make about the biological and psychological bases of those behaviors. In five experiments, we manipulated whether behaviors are presented concretely (i.e. with reference to a specific person, instantiated in the particular context of that person's life) or abstractly (i.e. with reference to a category of people or behaviors across generalized contexts). People judged concretely framed behaviors to be less biologically based and, on some dimensions, more psychologically based than the same behaviors framed in the abstract. These findings held true for both mental disorders (Experiments 1 and 2) and everyday behaviors (Experiments 4 and 5), and yielded downstream consequences for the perceived efficacy of disorder treatments (Experiment 3). Implications for science educators, students of science, and members of the lay public are discussed.


Identification and Evolutionary Analysis of Cotton (Gossypium hirsutum) WOX Family Genes and Their Potential Function in Somatic Embryogenesis.
WUSCHEL-related homeobox (WOX) proteins participate profoundly in plant development and stress responses. As the difficulty of somatic embryogenesis severely constrains cotton genetic modification, in this study, we identified and comprehensively analyzed WOX genes in cotton. As a result, 40 WOX genes were identified in the upland cotton genome. All these cotton WOX genes were classified into three clades, ancient, intermediate, and modern clades, based on the phylogenetic analysis of previous studies. The majority (24) of the cotton WOX genes belonged to the modern clade, in which all gene members contain the vital functional domain WUS-box, which is necessary for plant stem cell regulation and maintenance. Collinearity analysis indicated that the WOX gene family in cotton expanded to some degree compared to Arabidopsis, especially in the modern clade. Genome duplication and segmental duplication may greatly contribute to expansion. Hormone-response- and abiotic-stress-response-related cis-acting regulatory elements were widely distributed in the promoter regions of cotton WOX genes, suggesting that the corresponding functions of stress responses and the participation of development processes were involved in hormone responses. By RNA sequencing, we profiled the expression patterns of cotton WOX genes in somatic embryogenesis. Only about half of cotton WOX genes were actively expressed during somatic embryogenesis; different cotton WOX genes may function in different development stages. The most representative, GhWOX4 and GhWOX13, may function in almost all stages of somatic embryogenesis; GhWOX2 and GhWOX9 function in the late stages of embryo patterning and embryo development during cotton somatic embryogenesis. Co-expression analysis showed that the cotton WOXs co-expressed with genes involved in extensive genetic information processing, including DNA replication, DNA repair, homologous recombination, RNA transport, protein processing, and several signaling and metabolism pathways, in which plant hormones signal transduction, MAPK signaling pathways, phosphatidylinositol signaling systems, and ABC transporters, as well as the metabolism of fatty acid; valine, leucine, and isoleucine biosynthesis; and cutin, suberine, and wax biosynthesis, were most significantly enriched. Taken together, the present study provides useful information and new insights into the functions of cotton WOX genes during somatic embryogenesis. The specific regulatory roles of some WOX genes in somatic embryogenesis are worthy of further functional research.


Comparison of four antiseptic preparations for skin in the prevention of contamination of percutaneously drawn blood cultures: a randomized trial.
A number of skin antiseptics have been used to prevent the contamination of blood cultures, but the comparative efficacies of these agents have not been extensively evaluated. We therefore sought to compare the efficacy of four skin antiseptics in preventing blood culture contamination in a randomized, crossover, investigator-blinded study conducted in an emergency department and the inpatient wards of a university hospital. The patient group included all patients from whom blood samples were obtained percutaneously for culture. Skin antisepsis was performed with 10% povidone-iodine, 70% isopropyl alcohol, tincture of iodine, or povidone-iodine with 70% ethyl alcohol (i.e., Persist). The blood culture contamination rate associated with each antiseptic was then determined. A total of 333 (2.62%) of 12,692 blood cultures were contaminated during the study period compared to 413 (3.21%) of 12,859 blood cultures obtained during the previous 12-month period (relative risk = 0.82; 95% confidence interval, 0.71 to 0.94; P = 0.006). During the study, the contamination rates were determined to be 2.93% with povidone-iodine, 2.58% with tincture of iodine, 2.50% with isopropyl alcohol, and 2.46% with Persist (P = 0.62). We detected no significant differences in the blood culture contamination rates among these four antiseptics, although there was some evidence suggesting greater efficacy among the alcohol-containing antiseptics. Among the evaluated antiseptics, isopropyl alcohol may be the optimal antiseptic for use prior to obtaining blood for culture, given its convenience, low cost, and tolerability.


Emerging and Evolving Technology in Colon and Rectal Surgery.
Minimally invasive surgery has changed the way we manage many colon and rectal pathologies. Multiple techniques, from straight laparoscopic procedures, to hand-assisted and single-port techniques are available, requiring surgeons to go through various learning curves. Robotic surgery is a relatively novel technique in general surgery which appears to hold most promise for rectal resection. Laparoscopic rectal procedures are difficult, and even in experienced hands, conversion rates are around 17%. Robotic surgery may be a point of difference in these cases, despite a long learning curve and higher costs. This article will describe the role of robotics in colorectal surgery. Room set up, port placement, and docking strategies will be described for common procedures, with emphasis on a hybrid robotic low anterior resection.


Girls' schooling in Tanzania: the key to HIV/AIDS prevention?
This article explores the relationship between schooling for girls and HIV/AIDS prevention in the United Republic of Tanzania. It is based on a survey administered to upper-level primary school students in rural Tanzania designed to ascertain their numeracy and literacy skills as well as their knowledge of HIV/AIDS. The findings show that female students generally have stronger literacy and numeracy skills but less knowledge about HIV/AIDS than their male counterparts. This suggests that general education may not be the best vaccine against HIV/AIDS for young women; rather, AIDS-specific education and skills training may be required to increase the likelihood of prevention because of gender differences in how young people utilize knowledge acquired in school.


INCIPIENT REPRODUCTIVE ISOLATION BETWEEN TWO SYMPATRIC MORPHS OF THE INTERTIDAL SNAIL LITTORINA SAXATILIS.
The study of speciation in recent populations is essentially a study of the evolution of reproductive isolation mechanisms between sub-groups of a species. Prezygotic isolation can be of central importance to models of speciation, either being a consequence of reinforcement of assortative mating in hybrid zones, or a pleiotropic effect of morphological or behavioral adaptation to different environments. To suggest speciation by reinforcement between incipient species one must at least know that gene flow occurs, or have recently occurred, and that assortative mating has been established in the hybrid zone. In Galician populations of the marine snail Littorina saxatilis, two main morphs appear on the same shores, one on the upper-shore barnacle belt and the other in the lower-shore mussel belt. The two morphs overlap in distribution in the midshore where hybrids are found together with pure forms. Allozyme variation indicates that the two parental morphs share a common gene pool, although within shores, gene flow between morphs is less than gene flow within morphs. In this study, we observed mating behavior in the field, and we found that mating was not random in midshore sites, with a deficiency of heterotypic pairs. Habitat selection, assortative mating, and possibly sexual selection among females contributed to the partial reproductive isolation between the pure morphs. Sizes of mates were often positively correlated, in particular, in the upper shore, indicating size-assortative mating too. However, this seemed to be a consequence of nonrandom microdistributions of snails of different sizes. Because we also argue that the hybrid zone is of primary rather than secondary origin, this seems to be an example of sympatric reproductive isolation, either established by means of reinforcement or as a by-product to divergent selection acting on other characters.


A Simple Predictive Factor for Mortality in Fontan Surgery: Serum Hypo-Osmolality.
Close follow-up is important after the Fontan procedure, which is a palliative surgical method for a single ventricle. In this period, serum osmolality is an important parameter with the advantages of easy to obtain and poor outcome prediction. Patients who had undergone Fontan operation between May 2011 and February 2017 were retrospectively evaluated. Patients were divided into three groups based on their serum osmolality values: hypoosmolar (Group 1), isosmolar (Group 2), and hyperosmolar (Group 3). Demographics, clinical information and postoperative data of the groups were compared. Forty-three patients had undergone extracardiac Fontan operation in the study period. There were 8, 19 and 16 patients in Groups 1, 2 and 3, respectively. Among the three groups, postoperative intubation and length of hospital stay, prolonged pleural effusion, need for inotropic support and mortality were statistically significantly higher in Group 1. After the Fontan procedure, one of the determinants of cardiac output might be affected by serum osmolality. Decreased serum osmolality might be associated with poor prognosis after Fontan procedure. Serum osmolality monitoring may be beneficial to improve postoperative outcomes in these patients.


Evaluation of hypermetabolic mediastinal-hilar lymph nodes determined by PET/CT with EBUS-TBNA and calculation of SUVmax cutoff values in differentiation of malignancy.
Computed tomography (CT) and positron emission tomography (PET) are the most commonly used methods for diagnosis and staging in both malignant and benign diseases of the lung parenchyma and mediastinum. Endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration biopsy (TBNA) has become widespread in recent years because it allows minimally invasive tissue sampling. PET-CT has high sensitivity in the diagnosis of malignancy but has low specificity. The false positive rate is high with the SUVmax 2.5 cutoff value, which is widely used in studies about malignancy. In our study, we evaluated lymph nodes with high F18-fluorodeoxyglucose (FDG) uptake on PET/CT and sampled by EBUS-TBNA. We aimed to calculate the new SUVmax cutoff values in the differentiation of malignancy. Our study included 103 patients who were examined for any reason and who underwent biopsy with EBUS-TBNA due to mediastinal or hilar lymph node enlargement on PET-CT. The relationship between PET-CT findings and EBUS findings, EBUS-TBNA results was evaluated. Biopsies were taken from 140 lymph nodes in 103 patients included in our study, and 39 (27.8%) were diagnosed as malignant. In our study, when the SUVmax cutoff value in PET-CT is taken as 2.54, the sensitivity is 98%, but the specificity remains at the level of 12%. When the SUVmax cutoff value in PET-CT was taken as 4.58, the sensitivity was 92% and the specificity was 49%. When this value was accepted as 5.25, and 6.09 the sensitivity was respectively 90% and 85%, the specificity was respectively 52% and 60%. In evaluations, we conducted in order to determine different SUVmax cutoff values that can be used for higher sensitivity and specificity in malignancy studies, the cutoff values were 4.58, 5.25, and 6.09. It is thought that these cutoff values will be useful both for diagnosing malignancy and for distinguishing benign pathologies.


Methodology to Identify Poly-ADP-Ribose Polymerase 1 (PARP1)-mRNA Targets by PAR-CLiP.
There is a long list of important RNA-binding proteins (RBP) involved in different steps of gene expression through posttranscriptional modifications: pre-mRNA splicing, mRNA stabilization, polyadenylation, mRNA export from nucleus to the cytoplasm, and translation. The critical role of RNA-protein interaction necessitates a continuous identification of proteins involved in this process. Here we describe the identification of Poly-ADP-Ribose Polymerase 1 (PARP1) as an RNA binding protein involved in RNA splicing.


Unilateral strabismus surgery in patients with exotropia results in postoperative lateral incomitance.
To determine whether unilateral strabismus surgery creates lateral incomitance in patients with exotropia. Patients >7 years of age with intermittent or constant exotropia who underwent unilateral horizontal rectus muscle surgery between December 2009 and January 2012 were prospectively evaluated. Prism and alternate cover testing was performed with distance fixation in primary position, right gaze, and left gaze after 1 hour of monocular occlusion. Measurements were obtained within 1 month prior to surgery, within 1 week after surgery, and >3 months after surgery. The surgical procedure varied according to the surgeon's discretion. The change in deviation induced by strabismus surgery in lateral gaze was expressed as a percentage of the change in deviation induced in primary position. A total of 12 patients met inclusion criteria. Of the 11 patients with postoperative examinations within 1 week after surgery, 10 (91%) had greater surgical effect with gaze toward the operated eye (P = 0.007). All 9 patients with >3 months' follow-up had greater surgical effect with gaze toward the operated eye (P = 0.003). On average, the surgical effect in gaze toward the operated eye was 120% of that achieved in primary position; in gaze away from the operated eye, 75% (P < 0.001). Three patients had diplopia in lateral gaze toward the operated eye that remained >6 months after surgery. Unilateral strabismus surgery induces lateral incomitance that may cause diplopia >6 months after surgery in patients with exotropia. This should be considered when planning strabismus surgery and counseling patients.


Reducing Playback Rate of Audiovisual Speech Leads to a Surprising Decrease in the McGurk Effect.
We report the unexpected finding that slowing video playback decreases perception of the McGurk effect. This reduction is counter-intuitive because the illusion depends on visual speech influencing the perception of auditory speech, and slowing speech should increase the amount of visual information available to observers. We recorded perceptual data from 110 subjects viewing audiovisual syllables (either McGurk or congruent control stimuli) played back at one of three rates: the rate used by the talker during recording (the natural rate), a slow rate (50% of natural), or a fast rate (200% of natural). We replicated previous studies showing dramatic variability in McGurk susceptibility at the natural rate, ranging from 0-100% across subjects and from 26-76% across the eight McGurk stimuli tested. Relative to the natural rate, slowed playback reduced the frequency of McGurk responses by 11% (79% of subjects showed a reduction) and reduced congruent accuracy by 3% (25% of subjects showed a reduction). Fast playback rate had little effect on McGurk responses or congruent accuracy. To determine whether our results are consistent with Bayesian integration, we constructed a Bayes-optimal model that incorporated two assumptions: individuals combine auditory and visual information according to their reliability, and changing playback rate affects sensory reliability. The model reproduced both our findings of large individual differences and the playback rate effect. This work illustrates that surprises remain in the McGurk effect and that Bayesian integration provides a useful framework for understanding audiovisual speech perception.


ABA Represses the Expression of Cell Cycle Genes and May Modulate the Development of Endodormancy in Grapevine Buds.
Recently, the plant hormone abscisic acid (ABA) has been implicated as a key player in the regulation of endodormancy (ED) in grapevine buds (Vitis vinifera L). In this study, we show that in the vine, the expression of genes related to the biosynthesis of ABA (VvNCED1; VvNCED2) and the content of ABA are significantly higher in the latent bud than at the shoot apex, while the expression of an ABA catabolic gene (VvA8H3) showed no significant difference between either organ. A negative correlation between the content of ABA and transcript levels of cell cycle genes (CCG) was found in both tissues. This result suggested that ABA may negatively regulate the expression of CCG in meristematic tissues of grapevines. To test this proposition, the effect of ABA on the expression of CCG was analyzed in two meristematic tissues of the vine: somatic embryos and shoot apexes. The results indicated that cell cycle progression is repressed by ABA in both organs, since it down-regulated the expression of genes encoding cyclin-dependent kinases (VvCDKB1, VvCDKB2) and genes encoding cyclins of type A (VvCYCA1, VvCYCA2, VvCYCA3), B (VvCYCB), and D (VvCYCD3.2a) and up-regulated the expression of VvICK5, a gene encoding an inhibitor of CDKs. During ED, the content of ABA increased, and the expression of CCG decreased. Moreover, the dormancy-breaking compound hydrogen cyanamide (HC) reduced the content of ABA and up-regulated the expression of CCG, this last effect was abolished when HC and ABA were co-applied. Taken together, these results suggest that ABA-mediated repression of CCG transcription may be part of the mechanism through which ABA modulates the development of ED in grapevine buds.


Reconstruction of the nipple: a new technique.
We propose a simple one-stage procedure for nipple reconstruction. The fundamental basis, the technique itself, and the results obtained demonstrate that a single-flap reconstruction achieves a nipple that will keep its shape 15 months later.


Functional Connectivity and Anxiety Improvement After Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.
Anxiety is one of the most common and disturbing non-motor symptoms of Parkinson's disease (PD). However, few studies have explored the relationship between functional connectivity (FC) and the rate of anxiety improvement after subthalamic nucleus deep brain stimulation (STN-DBS). Therefore, in this study, we aimed to explore the correlation between FC and the rate of anxiety improvement in patients with PD who underwent STN-DBS. The resting-state functional magnetic resonance imaging (rs-fMRI) data of 62 patients with anxious PD (aPD), 68 patients with PD without anxiety (naPD), and 64 healthy controls (HCs) were analyzed according to FC. Intergroup comparison and correlation analyses of anxiety improvement rates were performed. The HC, aPD and naPD groups of zFCs were then used for the ANOVA test, and the results were FDR-corrected. There were 24 significant differences in FCs between the three groups. Post tests were conducted between groups found that 15 significantly different FCs were observed between the naPD and aPD groups. In addition, the two FCs in patients with aPD were significantly correlated with the rate of improvement in anxiety. We found that the two FCs in patients with aPD (olfactory cortex and inferior frontal gyrus [IFG] pars orbitalis; inferior temporal gyrus and posterior orbital gyrus) were significantly correlated with the rate of improvement in anxiety. Our study may help us understand the underlying mechanisms by which STN-DBS improves anxiety in PD patients and identify more effective treatment strategies.


Modification of cellular membranes conveys cryoprotection to cells during rapid, non-equilibrium cryopreservation.
Rapid cooling and re-warming has been shown promising to cryopreserve living cells, which cannot be preserved by conventional slow freezing methods. However, success is limited by the cytotoxicity of highly concentrated cryoprotective agents. Recent results have shown that cryoprotective agents do not need to suppress intracellular ice crystals completely to allow for survival after cryopreservation. Cryoprotective agents like DMSO or ethylene glycol can also lead to a tolerance of cells towards intracellular ice. It is however unclear by which mechanism this tolerance is achieved. These substances are also known to modulate properties of cellular membranes. It is shown here that cryoprotective DMSO and ethylene glycol have a clear influence on the mobility of lipids in the plasma membrane of HeLa cells. To isolate changes of the properties of plasma membranes from effects on ice formation, the membrane properties were modulated in absence of cryoprotective agents. This was achieved by changing their sterol content. In cells with elevated sterol content, an immobile lipid fraction was present, similar to cells treated with DMSO and ethylene glycol. These cells showed also significantly increased plasma membrane integrity after rapid freezing and thawing in the absence of classical cryoprotective agents. However, their intracellular lysosomes, which cannot be enriched with sterols, still got ruptured. These results clearly indicate that a modulation of membrane properties can convey cryoprotection. Upon slow cooling, elevated sterol content had actually an adverse effect on the plasma membranes, which shows that this effect is specific for rapid, non-equilibrium cooling processes. Unraveling this alternative mode of action of cryoprotection should help in the directed design of novel cryoprotective agents, which might be less cytotoxic than classical, empirically-found cryoprotective agents.


Distinguishing features of preseptal and orbital cellulitis.
The differential diagnosis between orbital cellulitis and preseptal cellulitis is important as is the need to differentiate between an allergic response or infectious cellulitis of the eye. This article will examine the case of a 15-month-old boy who was brought to an emergency department with an oedematous right eye. The research about diagnosis and treatment will be evaluated and orbital cellulitis will be explored in more detail including the symptoms and complications.


Cranioplasty as the return-to-work factor - 112 patients with cranial defects treated in the Department of Neurosurgery at the Medical University of Lodz.
The number of craniectomies and the consequent reconstructive procedures has grown during the past decades. Cranial defects and methods of their repair could have some influence on work capability of the patients and their employability. The authors analyzed a group of 112 patients with cranial defects treated in the Department of Neurosurgery at the Medical University of Lodz, Poland, in the course of the katamnestic period longer than 6 months after reconstructive operation, and observed them between February 2008 and February 2015. Their work capability and employment were compared, all the patients were interviewed concerning the reasons for not working according to the Social Insurance Institution predication procedure. Before the cranioplasty, all the patients were capable of working without limitations according to biological criteria and 89 of them were employed. Twenty-three not working people consisted of 6 pupils, 7 retired and 10 not working for other reasons. During the period between the craniectomy and the cranioplasty, 88 patients were capable of working and only 2 were employed. After the reconstruction, 93 were capable of working without limitations and 16 - with limitations. Forty-seven were employed during the period of the follow-up, the rest of patients consisted of 2 pupils, 13 retired and 50 not working for various reasons. Cranioplasty is a very important factor contributing to return to work. This outcome may be seen as having a great social value and be added to the functions of cranial repair as protective, esthetic and normalizing the intracranial pressure previously described in the literature. Int J Occup Med Environ Health 2017;30(5):803-809.


[Determination of 18 polychlorinated biphenyls in camellia seeds by multiple vortex and gas chromatography-triple quadrupole mass spectrometry].
A method based on the cleaning effects of different sorbents and gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS/MS) was developed for the determination of 18 polychlorinated biphenyls (PCBs) in camellia seeds. The camellia seeds were extracted with acetonitrile, salted out with sodium chloride, then cleaned-up by QuEChERS with anhydrous MgSO4, C18, primary secondary amine (PSA), and multi walled carbon nanotubes (NANO) using multiple vortex after the centrifugal separation, and finally analyzed by GC-QQQ-MS/MS in multiple reaction monitoring mode via positive electrospray ionization. All the 18 PCBs could be completely separated with an excellent linear relationship. The limits of detection for the 18 PCBs were 5 μg/kg. For all the samples, the mean spiked recoveries was 109.2% with relative standard deviations (RSDs) of 2.9%-6.2% (n=3). The extraction, purification and analytical methods were developed and assessed. The method was successfully applied to the 48 samples from three main producing provinces of camellia seeds. All the 18 PCBs were not detected from the 48 samples.


Yeast Extract Stimulates Ginsenoside Production in Hairy Root Cultures of American Ginseng Cultivated in Shake Flasks and Nutrient Sprinkle Bioreactors.
One of the most effective strategies to enhance metabolite biosynthesis and accumulation in biotechnological systems is the use of elicitation processes. This study assesses the influence of different concentrations of yeast extract (YE) on ginsenoside biosynthesis in Panax quinquefolium (American ginseng) hairy roots cultivated in shake flasks and in a nutrient sprinkle bioreactor after 3 and 7 days of elicitation. The saponin content was determined using HPLC. The maximum yield (20 mg g-1 d.w.) of the sum of six examined ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1) in hairy roots cultivated in shake flasks was achieved after application of YE at 50 mg L-1 concentration and 3 day exposure time. The ginsenoside level was 1.57 times higher than that attained in control medium. The same conditions of elicitation (3 day time of exposure and 50 mg L-1 of YE) also favourably influenced the biosynthesis of studied saponins in bioreactor cultures. The total ginsenoside content was 32.25 mg g-1 d.w. and was higher than that achieved in control medium and in shake flasks cultures. Obtained results indicated that yeast extract can be used to increase ginsenoside production in hairy root cultures of P. quinquefolium.


The major autolysin of Staphylococcus lugdunensis, AtlL, is involved in cell separation, stress-induced autolysis and contributes to bacterial pathogenesis.
Staphylococcus lugdunensis is a human skin commensal organism, but it is considered as a virulent Staphylococcus species. In a previous study, we described the first S. lugdunensis autolysin, AtlL. This enzyme displays two enzymatic domains and generates two peptidoglycan hydrolases, an N-acetylmuramoyl-l-alanine amidase and an N-acetylglucosaminidase. In this study, to further investigate the functions of this autolysin, a ΔatlL mutant was constructed. The microscopic examination of the mutant showed cell aggregates and revealed a rough outer cell surface demonstrating, respectively, the roles of AtlL in cell separation and peptidoglycan turnover. This ΔatlL mutant exhibited a lower susceptibility to Triton X-100-induced autolysis assays and appears to be more resistant to cell wall antibiotic-induced lysis and death compared with its parental strain. The atlL mutation affected the biofilm formation capacity of S. lugdunensis. Furthermore, the ΔatlL mutant showed trends toward reduced virulence using the Caenorhabditis elegans model. Overall, AtlL appears as a major cell wall autolysin of S. lugdunensis implicated in cell separation, in stress-induced autolysis and in bacterial pathogenesis.


Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.
Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.


The possible role of human papillomavirus infection in the development of lichen sclerosus.
Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown origin predominantly affecting the anogenital area that causes pruritus and pain and is associated with an increased risk of malignancy. In some cases, LS vanishes after application of imiquimod, raising the question whether human papillomavirus (HPV) may have an etiopathogenic role in anogenital LS. The databases MEDLINE and Embase were systematically searched using the PRISMA guidelines. Twenty-seven papers were included that reported the prevalence of HPV in LS and in LS associated with neoplasia. HPV was identified in 0-80% (median 22%) of all LS cases. The prevalence of HPV was higher among male patients with LS (median 29%) than among female patients (median 8%). HPV16 was the most prevalent genotype, but the distribution of genotypes indicates that even low-risk HPV can cause LS. The diverging detection rates are probably due to small sample sizes in the reviewed papers and different detection methods. Factors possibly underestimating the prevalence of HPV are a selective search for high-risk HPV, DNA destruction in fixed tissue, focally residing HPV, and possibly a clearing of HPV before the time of biopsy. Seventy-five percent of sexually active people acquire HPV during their lifetime, thus HPV alone is not a cause of LS. Genetic and immunological host factors and viral factors other than type are likely to contribute. Future studies should include patients with a short duration of symptoms, and biopsies should be multiple and fresh.


Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation.
In vivo, eosinophils localize to airway cholinergic nerves in antigen-challenged animals, and inhibition of this localization prevents antigen-induced hyperreactivity. In this study, the mechanism of eosinophil localization to nerves was investigated by examining adhesion molecule expression by cholinergic nerves. Immunohistochemical and functional studies demonstrated that primary cultures of parasympathetic nerves express vascular cell adhesion molecule-1 (VCAM-1) and after cytokine pretreatment with tumor necrosis factor-alpha and interferon-gamma intercellular adhesion molecule-1 (ICAM-1). Eosinophils adhere to these parasympathetic neurones after cytokine pretreatment via a CD11/18-dependent pathway. Immunohistochemistry and Western blotting showed that a human cholinergic nerve cell line (IMR-32) expressed VCAM-1 and ICAM-1. Inhibitory experiments using monoclonal blocking antibodies to ICAM-1, VCAM-1, or CD11/18 and with the very late antigen-4 peptide inhibitor ZD-7349 showed that eosinophils adhered to IMR-32 cells via these adhesion molecules. The protein kinase C signaling pathway is involved in this process as a specific inhibitor-attenuated adhesion. Eosinophil adhesion to IMR-32 cells was associated with the release of eosinophil peroxidase and leukotriene C(4). Thus eosinophils adhere to cholinergic nerves via specific adhesion molecules, and this leads to eosinophil activation and degranulation; this may be part of the mechanism of eosinophil-induced vagal hyperreactivity.


MassChroQ: a versatile tool for mass spectrometry quantification.
Recently, many software tools have been developed to perform quantification in LC-MS analyses. However, most of them are specific to either a quantification strategy (e.g. label-free or isotopic labelling) or a mass-spectrometry system (e.g. high or low resolution). In this context, we have developed MassChroQ (Mass Chromatogram Quantification), a versatile software that performs LC-MS data alignment and peptide quantification by peak area integration on extracted ion chromatograms. MassChroQ is suitable for quantification with or without labelling and is not limited to high-resolution systems. Peptides of interest (for example all the identified peptides) can be determined automatically, or manually by providing targeted m/z and retention time values. It can handle large experiments that include protein or peptide fractionation (as SDS-PAGE, 2-D LC). It is fully configurable. Every processing step is traceable, the produced data are in open standard formats and its modularity allows easy integration into proteomic pipelines. The output results are ready for use in statistical analyses. Evaluation of MassChroQ on complex label-free data obtained from low and high-resolution mass spectrometers showed low CVs for technical reproducibility (1.4%) and high coefficients of correlation to protein quantity (0.98). MassChroQ is freely available under the GNU General Public Licence v3.0 at http://pappso.inra.fr/bioinfo/masschroq/.


[Disseminated intravascular coagulation--a case report].
A 31 year-old T1PoAoL1 female developed the early Disseminated Intravascular Coagulation (DIC) signs after cesarean section. The patient had recovery completely after transabdomen total hysterectomy (TAH) and blood products transfusion. Case presentation, literature review, possible pathogenetic mechanism and treatment of DIC were discussed.


Study of local anesthetics. Part 123: HPLC study of pentacaine, heptacaine and carbisocaine.
A relationship between the capacity factor k' of pentacaine, heptacaine and carbisocaine and mobile phase composition (content of methanol and water, ionic strength and pH) has been studied by HPLC. It has been found that there is a linear relationship between log k' and the content of methanol in the mobile phase in the range 80-100% (vol) of methanol. The ionic strength of solute also has an influence on log k'. When the amount of solute is higher than 0.25 mol/l, than its influence on log k' is not important. The pH = pK inflection point of sigmoidal dependence k' = f(pH) can be found.


Canthin-6-one alkaloids from Picrasma quassioides and their cytotoxic activity.
A new alkaloid, 4,5-dimethoxy-10-hydroxycanthin-6-one (1), was isolated from the stem of Picrasma quassioides Bennet (Simaroubaceae) together with four known canthin-6-one alkaloids, 8-hydroxycanthin-6-one (2), 4,5-dimethoxycanthin-6-one (3), 5-hydroxy-4-methoxycanthin-6-one (4), and 3-methylcanthin-5,6-dione (5). Their structures were elucidated on the basis of spectroscopic data. The cytotoxic activity of the canthin-6-one alkaloids was evaluated using human nasopharyngeal carcinoma (CNE2) and human liver cancer (Bel-7402) cell lines. Among these isolates, compounds 1-4 exhibited significant cytotoxic activity against CNE2 cell line.


Injury-induced physiological events that may modulate gene expression in neurons and glia.
Damage to the brain triggers a host of reactive responses in neurons and glia which are seen at sites of focal injury as well as at sites that are at a distance from the injury. Although many of these responses have been studied extensively, the signals that initiate the different responses have not been fully characterized, and it is still not understood how focal injury affects neurons and glia in distant sites. The present review summarizes recent findings that suggest that physiological events that occur at the time of the injury or during the early postlesion period can play an important and variable role in modulating neuronal and glial responses to injury. We focus on the events that occur in the hippocampal formation following unilateral lesions of the entorhinal cortex - a model system that has been used extensively for studies of cellular responses following focal brain injury. This lesion destroys the cells of origin of a massive excitatory projection to the dentate gyrus and hippocampus proper. Over time, the denervated neurons in the hippocampal formation are almost completely reinnervated as a result of local sprouting of systems that survive the lesion. Thus, this model system has been useful for studying cellular responses to both denervation and reinnervation. We summarize the information that this injury triggers physiological events that can strongly modulate gene expression in neurons and glia, including episodes of spreading depression that occur at the time of the injury, seizures that occur during the early postlesion period, the loss of afferent drive which leads to decreases in postsynaptic activity, and the restoration of activity that occurs in conjunction with reinnervation. We describe recent studies which suggest that some of these physiological events occur to a variable extent in different animals, especially the episodes of spreading depression and the recurrent seizures. Thus, the spatial pattern and temporal dynamics of altered gene expression following this "model" experimental injury may vary from animal to animal. The fact that physiological events strongly modulate the reactive changes in gene expression that occur following injury has important implications for understanding the sequelae of injury, and offers new opportunities for experimental and therapeutic interventions that may improve cellular repair, regeneration, and recovery of function.


Effects of shielding the radiosensitive superficial organs of ORNL pediatric phantoms on dose reduction in computed tomography.
In computed tomography (CT), some superficial organs which have increased sensitivity to radiation, receive doses that are significant enough to be matter of concern. Therefore, in this study, the effects of using shields on the amount of dose reduction and image quality was investigated for pediatric imaging. Absorbed doses of breasts, eyes, thyroid and testes of a series of pediatric phantoms without and with different thickness of bismuth and lead were calculated by Monte Carlo simulation. Appropriate thicknesses of shields were chosen based on their weights, X-ray spectrum, and the amount of dose reduction. In addition, the effect of lead shield on image quality of a simple phantom was assessed quantitatively using region of interest (ROI) measurements. Considering the maximum reduction in absorbed doses and X-ray spectrum, using a lead shield with a maximum thickness of 0.4 mm would be appropriate for testes and thyroid and two other organs (which are exposed directly) should be protected with thinner shields. Moreover, the image quality assessment showed that lead was associated with significant increases in both noise and CT attenuation values, especially in the anterior of the phantom. Overall, the results suggested that shielding is a useful optimization tool in CT.


From general practice to primary care: the industrialisation of family medicine in Britain.
Health services are multi-unit enterprises providing multi-component services, and organisationally are equivalent to very large, diversified companies. Although public health services like Britain's National Health service (NHS) are not for-profit enterprises, they may share characteristics of such enterprises, particularly where these characteristics offer methods of cost-containment. Since all health services, however organised, face the same problem of resources being insufficient to meet demand for health care, they exhibit an underlying tendency towards solving problems in health care using mechanisms borrowed from other industries. This paper attempts to answer the question: to what extent has general practice (family medicine) in Britain's NHS adopted industrial modes of organisation from productive (for-profit) industries?


Expression of human papillomavirus types 6b and 16 L1 open reading frames in Escherichia coli: detection of a 56,000-dalton polypeptide containing genus-specific (common) antigens.
The human papillomavirus (HPV) genome contains two large open reading frames (ORFs), designated L1 and L2. To characterize the antigenic properties of the L1 ORF-encoded proteins, we cloned the L1 ORFs of HPV6b and HPV16 in plasmids, and these were expressed in Escherichia coli. First, the HPV6b DNA, representing 85.2% of the L1 ORF, was cloned in pUC19 and expressed in E. coli JM83 and RB791 as a 160,000-molecular-weight (160K) fusion protein with E. coli beta-galactosidase (6bL1/beta-gal). Second, the HPV16 DNA, representing 89.8% of the L1 ORF, was cloned in pKK233-2 and expressed as a 56K protein (16L1) in strain RB791. Both the 6bL1/beta-gal and 16L1 proteins cross-reacted with anti-bovine papillomavirus type 1 (BPV1) antibody raised against disrupted BPV1 particles. An antibody raised against the 6bL1/beta-gal fusion protein reacted with the 16L1 protein and also with native papillomavirus antigens in human genital condyloma and bovine fibropapilloma tissues, as determined by biotin-streptavidin staining. Furthermore, the anti-6bL1/beta-gal antibody recognized a 54K protein which seemed to be a major capsid protein of BPV1 and also a 56K protein of biopsies harboring HPV6 or HPV11. From these results we concluded that the papillomavirus L1 gene product contains genus-specific (common) antigens and that the HPV6 and HPV11 L1 genes specify the 56K capsid protein.


Bottom-up, Chip-Scale Engineering of Low Threshold, Multi-Quantum-Well Microring Lasers.
Integrated, on-chip lasers are vital building blocks in future optoelectronic and nanophotonic circuitry. Specifically, III-V materials that are of technological relevance have attracted considerable attention. However, traditional microcavity laser fabrication techniques, including top-down etching and bottom-up catalytic growth, often result in undesirable cavity geometries with poor scalability and reproducibility. Here, we utilize the selective area epitaxy method to deterministically engineer thousands of microring lasers on a single chip. Specifically, we realize a catalyst-free, epitaxial growth of a technologically critical material, InAsP/InP, in a ring-like cavity with embedded multi-quantum-well heterostructures. We elucidate a detailed growth mechanism and leverage the capability to deterministically control the adatom diffusion lengths on selected crystal facets to reproducibly achieve ultrasmooth cavity sidewalls. The engineered devices exhibit a tunable emission wavelength in the telecommunication O-band and show low-threshold lasing with over 80% device efficacy across the chip. Our work marks a significant milestone toward the implementation of a fully integrated III-V materials platform for next-generation high-density integrated photonic and optoelectronic circuits.


MRI in chronic recurrent multifocal osteomyelitis.
To review our experience of chronic recurrent multifocal osteomyelitis (CRMO) and to assess the value of MRI in this rare disease, which mainly affects children and adolescents. Seventeen patients from our departments were reviewed. All underwent conventional radiography and MRI, and most had bone scintigraphy. All had undergone bone biopsy, with microbiological and histopathological examinations, to exclude infectious disease, tumours and tumour-like lesions. CRMO affects predominantly the tubular bones of the limbs, followed by the clavicle and the spine. Other locations are rare. Diagnosis is important in avoiding unnecessary diagnostic procedures and to initiate appropriate therapy, and is usually based on a characteristic course and the appearances on radiography. However, CRMO lesions of tubular bones and the spine exhibit quite characteristic MRI features which support the diagnosis, while the appearance of the early clavicular lesion is non-specific. At all sites of CRMO in the skeleton, MRI is valuable in assessing the extent and activity of the lesion. It may exclude pyogenic involvement of the bone and soft tissues and guide effective biopsy.


The HIV Care Cascade Among Transgender Women with HIV in Canada: A Mixed-Methods Study.
Scant research has explored the engagement of transgender (trans) women living with HIV (WLWH) in the HIV care cascade, particularly in universal health care settings like Canada. This convergent parallel, mixed-methods study drew on cross-sectional quantitative data from 50 trans WLWH in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) and qualitative semistructured interview data from a subsample of 11 participants. Descriptive analyses were used to describe proportions of trans WLWH at five steps of the HIV care cascade and bivariate analyses to determine associations between hypothesized barriers/facilitators and HIV care cascade outcomes. Framework analysis was used to describe barriers and facilitators to HIV care engagement. Quantitative and qualitative data were then compared and contrasted. While use of purposive sampling, including recruitment through AIDS Service Organizations and HIV clinics, may have led to oversampling of trans WLWH who already had access to care, gaps were still seen in antiretroviral therapy (ART) outcomes (current ART use: 78%; ≥95% adherence among those currently taking ART: 67%). The number of years living with HIV was positively associated with HIV care cascade engagement. Factors associated with lower engagement included: higher health-related quality of life, depressive and post-traumatic stress disorder symptoms, barriers to access to care, transphobia, HIV-related stigma, and housing insecurity. Qualitative findings converged and expanded on how physical health, and social and structural marginalization, influence trans WLWH's engagement in HIV care. Qualitative findings elaborated on the importance of ART-related factors in impeding or facilitating engagement, including concerns about feminizing hormone-ART drug-drug interactions. Mixed-methods findings reveal how trans WLWH experience barriers common to other people living with HIV, and also experience unique barriers as a result of trans and HIV experiences.


The early outcome of single-incision versus multi-port laparoscopic cholecystectomy.
Single-incision laparoscopic cholecystectomy (SILC) is a newly developed method of performing cholecystectomy and has been increasingly used. The aim of this study is to see if SILC has any advantages over conventional (three-port) laparoscopic cholecystectomy (CLC). In this cross-sectional study, 52 patients who underwent SILC (group A) during the period from May 2011 to March 2013 were compared with 62 patients who underwent CLC (group B) at two centers affiliated to Shiraz University of Medical Sciences in Shiraz, Iran. Data were gathered on operation time, pre- and postoperative complications, patients' postoperative pain, pain reliever use, duration of hospital stay, and return to work, and these data were compared using SPSS software version 16. The mean age of patients was 38.01 ± 13.24 in group A and 44.82 ± 15.11 in group B. Mean body mass index (BMI) was 23.97 ± 4.78 and 26.22 ± 4.67 in groups A and B, respectively. The mean operation time was 76.4 ± 29.0 min in group A and 72.9 ± 24.1 min in group B (P = 0.496). Preoperative complications were 3.8% in group A and 0 in group B (P = 0.206). Postoperative complications were 17.3% in group A and 11.3% in group B (P = 0.423). The mean for early postoperative pain revealed no significant difference (P = 0.814), but the mean pain on discharge was significantly higher in group A patients (P = 0.034). Regarding the mean admission time and return to normal activity, we found no significant differences. SILC does not have any special advantages over CLC with regard to surgical outcomes, but it can be a safe alternative to CLC, especially in patients concerned about cosmoses.


Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers.
Two novel glucosylated zinc(ІІ) phthalocyanines 7a-7b, as well as the acetyl-protected counterparts 6a-6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a-7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake. Upon illumination, both photosensitizers show high cytotoxicity with IC50 as low as 0.032 µM toward MCF-7 cells, which are attributed to their high cellular uptake and low aggregation tendency in the biological media, promoting the generation of intracellular reactive oxygen species (ROS). Confocal laser fluorescence microscopic studies have also revealed that they have high and selective affinities to the lysosomes, but not the mitochondria, of MCF-7 cells. The results show that these two glucosylated zinc(II) phthalocyanines are potential anticancer agents for targeting photodynamic therapy.