Modeling of the Inhibitory Effect of Nanoparticles on Amyloid β Fibrillation.
Experiments have shown that charged nanoparticles (NP) inhibit, partially or completely, the aggregation of Aβ protein monomers into fibrils. The equilibrium fibril content is found to be inversely proportional to the concentration of NP. In this work, we report a kinetic model for the fibrillation of Aβ protein in the presence of NP. In the model, apart from nucleation, elongation and fragmentation processes, the effect of NP is considered to cause a conformational change to the protein monomer, making the latter incompatible for aggregation. The simulated results explain the growth kinetics of pure Aβ (1-40) protein, and the kinetics in the presence of NP. The NP-monomer interaction considered in the model captures the significant effect of NP on the fibrillation process at a very molar ratio (NP to Aβ monomer) as low as 10-4. The model predictions are compared with two different NP systems, namely, gold and silica NP. The model can be applied to explain the inhibitory effect of other additives such as small molecules, NP, lipids, and surfactants that show a similar inhibition trend for fibril formation of Aβ and other proteins.


Group cohesion and social support of the nurses in a special unit and a general unit in Korea.
To identify the degree of group cohesion and social support of nurses in special and general units in hospitals in Korea, and to compare group cohesion and social support between the two groups. The level of commitment nurses have to their organizations has been shown to correlate with work group cohesion and social support. The participants were 1751 nurses who were working in Korean hospitals. Data were collected using a structured questionnaire and were analysed using SAS. The statistical methods included: descriptive statistics, t-test, anova and Pearson's correlation coefficients. Group cohesion of nurses on special wards was significantly higher than for nurses on general wards. No significant difference was found between types of units in terms of social support. The degree of group cohesion was significantly different in terms of the respondents' clinical experience, position, religion, job satisfaction, number of supportive superiors and number of supportive peers. A statistically significant correlation was found between group cohesion scores and degree of social support. Hospital management can accomplish their goals more effectively through knowledge of the level of group cohesion, superior support and peer support for nursing staff in accordance with unit specialty.


Estimation of solar resource for vehicle-integrated photovoltaics in urban environments using image-based shade detection.
Vehicle-Integrated Photovoltaics (VIPV) in urban environments face challenges in accurately estimating solar resource due to dynamic shading effects. This research presents a methodology for evaluating VIPV solar resource by analyzing imagery and detecting shade conditions along driving routes. Street image mapping services and obstacle detection algorithms are utilized to determine the shaded or sunny condition of the vehicle at each point. The approach enables the calculation of solar irradiance, considering direct and diffuse components, and identifies energetically optimal driving routes. The methodology provides valuable insights for optimizing MPPT algorithms and assessing VIPV performance in urban settings. It offers a practical tool for sustainable mobility and renewable energy integration.


Interleukin-8 plays a significant role in IgE-mediated lung inflammation.
Interleukin (IL)-8 is a potentially important cytokine in allergic respiratory responses since it is released by many resident lung cells, and it is a potent granulocyte chemoattractant. Therefore, we induced an immunoglobulin (Ig)E-mediated response in human lung samples and studied whether IL-8 was produced in sufficient quantities to promote human neutrophil and eosinophil migration across naked filters and endothelial and pulmonary epithelial monolayers cultured on these filters. Fresh human lung fragments from 16 thoracotomy specimens were treated with either a 1:100 dilution of anti-IgE or buffer (control) for 30 min. All anti-IgE treated lung samples had significant release of histamine and neutrophil and eosinophil chemotactic activity. Fourteen of the 16 lung samples had a significant increase in IL-8 subsequent to anti-IgE treatment (p<0.01). Anti-IL-8 antibody (4 microg x mL[-1]) inhibited 42% and 53% of neutrophil and eosinophil chemotactic activity respectively, contained in supernatants from anti-IgE-treated lung samples. Finally, we found that IL-8 at a concentration near that measured after anti-IgE treatment of lung samples (2,000 pg x mL[-1]) induced neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial cell monolayers. Thus, human lung IgE-mediated responses in vitro results in the rapid release of interleukin-8 in amounts sufficient to affect a biological response, granulocyte transcellular migration, indicating that interleukin-8 may play a significant role in allergic respiratory diseases.


Direct Observation of Endocytosis Dynamics of Anti-ErbB Modified Single Nanocargoes.
The ErbB receptor family, including the epidermal growth factor receptor (EGFR) and ErbB2/3/4, regulate cell proliferation, differentiation, apoptosis, motility, etc., and their abnormalities can cause cancer and other diseases. Ligand-induced endocytosis of ErbB receptors is the key to various cancer treatment strategies, and different techniques have been developed to study this important process. Among them, single particle tracking (SPT) can reveal the spatiotemporal heterogeneity of ErbB receptors on the live cell membrane and has been used to characterize the EGFR dimerization process. Herein, we studied the endocytosis dynamics of two different ErbB receptors using dark-field microscopy. With anti-ErbB modified plasmonic gold nanorods (AuNRs) as probes, we compared the trajectories of individual anti-EGFR AuNRs (cAuNRs) and anti-ErbB AuNRs (tAuNRs) interacting with MCF-7 cells in situ in real time. The results revealed that the internalization rate of cAuNRs was faster than that of tAuNRs. Detailed SPT analysis suggests that cAuNRs enter cells through EGFR endocytosis pathway, and multiple intracellular transport modes sort the cAuNRs away from the transmembrane site. In contrast, the endocytosis resistance of ErbB2 slows down the cellular uptake rate of tAuNRs and causes some tAuNRs-ErbB2 complexes to be confined on the membrane with "circular" and "rolling circle" motions for a much longer time. Our results provide insights into the endocytosis process of the ErbB receptor family at the nanometer scale and could be potentially useful to develop cancer treatment strategies.


How to value a buy-in/buy-out.
Buy-ins and buy-outs provide an opportunity for both existing owners of medical practices and prospective new physicians. For physicians, buy-ins represent the chance to have a financial stake in the practice, under the physician control and direction. This article explores helpful guidelines for valuing the practice and provides perspective in viewing the situations of buy-in and buy-out.


Shift work with and without night work as a risk factor for fatigue and changes in sleep length: A cohort study with linkage to records on daily working hours.
We examined shift work with or without night work as a risk factor for fatigue and short or long sleep. In a prospective cohort study with 4- and 6-year follow-ups (the Finnish Public Sector study), we linked survey responses of 3,679 full-time hospital employees on sleep duration and fatigue to records on daily working hours in 2008 (baseline), 2012 and 2014. We used logistic regression to estimate risk ratios and their confidence intervals to examine whether continuous exposure to shift work or changes between shift work and day work were associated with short (≤6.5 hr) or long (≥9.0 hr) sleep over 24 hr and fatigue at work and during free days. Compared with continuous day work and adjusting for age, gender, education and fatigue/sleep duration at baseline, continuous shift work with night shifts was associated with increased fatigue during free days (risk ratio = 1.38, 95% confidence interval 1.17-1.63) and long sleep (risk ratio = 8.04, 95% confidence interval 2.88-22.5, without adjustment for education) after 6-year follow-up. Exposure to shift work without night shifts increased only long sleep after 6 years (risk ratio = 5.87, 95% confidence interval 1.94-17.8). A change from day work to shift work with or without night shifts was associated with an increased risk for long sleep, and a change from shift work to day work with a decreased risk for long sleep and fatigue. This study suggests that irregular shift work is a modifiable risk factor for long sleep and increased fatigue, probably reflecting a higher need for recovery.


A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension.
Persistent pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance after birth leading to right-to-left shunting and systemic arterial hypoxemia. Inhaled nitric oxide (NO) is effective in reducing the need for extracorporeal membrane oxygenation, but it has potential toxicities, especially in an oxygen-rich environment. A number of other NO-based molecules have been given by inhalation, but their structure-function relationships have not been established. Recent studies have raised the idea that toxic and beneficial properties can be separated. We synthesized a novel organic nitrate [ethyl nitrate (ENO2)], tested it in vitro, and administered it to hypoxic piglets. ENO2 lowered pulmonary artery pressure and raised the Po2 in arterial blood but did not alter systemic vascular resistance or methemoglobin levels. In addition, we tested the effect of ENO2 in the presence of the thiol glutathione, both in vivo and in vitro, and found its action to be enhanced. Although ENO2 is less potent than inhaled NO on a dose-equivalency basis, pretreatment of hypoxic animals with glutathione, which may be depleted in injured lungs, led to a markedly enhanced effect (largely mitigating the difference in potency). These results suggest that ENO2 may hold promise as a safe alternative to NO, particularly in hypoxemic conditions characterized by thiol depletion.


The satellite cell in male and female, developing and adult mouse muscle: distinct stem cells for growth and regeneration.
Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration.


Monomorphic ventricular tachycardia in 'Brugada syndrome': clinical case and literature review.
A 20-year-old white judoka was admitted for severe palpitations during exercise followed by syncope. The electrocardiogram on admission revealed a wide-complex monomorphic tachycardia at a rate of 260 beats/min, with right bundle brunch block morphology and right axis deviation. Following electrical cardioversion, the electrocardiogram showed sinus rhythm with type 1 pattern of Brugada syndrome. We describe in detail the clinical course, the results of electrophysiological study, and therapeutic management. We reviewed literature data concerning a few cases of 'atypical Brugada syndrome' characterized by monomorphic ventricular tachycardia as clinical arrhythmia.


Sea Surface Temperature, Surface Wind Divergence, and Convection over Tropical Oceans.
Large-scale convection over the warm tropical oceans provides an important portion of the driving energy for the general circulation of the atmosphere. Analysis of regional associations between ocean temperature, surface wind divergence, and convection produced two important results. First, over broad regions of the Indian and Pacific oceans, sea surface temperatures (SSTs) in excess of 27.5 degrees C are required for large-scale deep convection to occur. However, SSTs above that temperature are not a sufficient condition for convection and further increases in SST appear to have little effect on the intensity of convection. Second, when SSTs are above 27.5 degrees C, surface wind divergence is closely associated with the presence or absence of deep convection. Although this result could have been expected, it was also found that areas of persistent divergent surface flow coincide with regions where convection appears to be consistently suppressed even when SSTs are above 27.5 degrees C. Thus changes in atmospheric stability caused by remotely forced changes in subsidence aloft may play a major role in regulating convection over warm tropical oceans.


Characterization of protein interaction among subunits of protein kinase CKII in vivo and in vitro.
Protein kinase CKII (CKII) is a ubiquitous protein serine/threonine kinase. CKII usually exists in tetrameric complexes composed of two catalytic (CKII alpha and/or CKII alpha') and two regulatory (CKII beta) subunits. In the present study, using a combined in vivo and in vitro approach, we have investigated the role of CKII subunits in the formation of the tetrameric structure of CKII and the formation of the polymeric structure of CKII holoenzyme. Our in vivo experiments show that CKII beta interacts with either another CKII beta or CKII alpha and that CKII alpha does not interact with another CKII alpha (or CKII alpha'). Our in vitro experiments also show that CKII beta is able to associate with both CKII alpha and another CKII beta and that CKII alpha exists as a monomeric form in solution. These data indicate that CKII beta mediates the formation of a tetramer by both the dimerization of CKII beta and the interaction of CKII beta with CKII alpha. The results of this study also suggest that CKII beta may be involved in the formation of the polymeric structure of the CKII holoenzyme.


Coronary microvascular disease: coronary flow reserve and the complementary role of positron emission tomography and angiography.
We present the case of a woman in her 30s with chronic residual chest pain accompanied by dyspnoea on exertion despite multiple evaluations and cardiac testing over a period of nearly 14 years. Ultimately, she underwent N-13 Ammonia positron emission tomography (PET) myocardial perfusion imaging, which demonstrated mild three-vessel microvascular disease. Coronary microvascular disease (CMD) plays a major role in determining myocardial ischaemia in many cardiovascular conditions. The diagnosis relies on indirect measurement of coronary flow reserve (CFR), which may be evaluated both invasively and non-invasively. Assessing CFR not only allows for successful diagnosis of CMD but holds powerful prognostic value for cardiovascular mortality. PET myocardial perfusion imaging is a complementary tool to coronary angiography to achieve diagnosis in a non-invasive, highly accurate and reproducible manner.


Non-centralised service for palliative stenting of malignant gastric outlet obstruction.
Malignant gastric outlet obstruction (GOO) is a common, debilitating and frequently pre-terminal symptom of intra-abdominal malignancies. Traditional 'gold standard' treatment has been palliative surgical gastro-enterostomy. Over the past two decades, use of self-expanding metallic stents (SEMSs) to relieve malignant GOO has become first-line treatment. We present the results from a single district general hospital in the UK in which malignant GOO was treated with SEMSs over a six-year period. All patients who underwent palliative stenting for malignant gastro-duodenal tumours in our centre for six years up to January 2013 were assessed retrospectively. Outcomes were assessed with regard to: technical and clinical success; return to oral nutrition; prevalence of complications and re-intervention; and overall survival. Thirty-two stents were implanted in 29 patients. Technical success was 100%. Clinical success and return to oral nutrition were both 91%. The prevalence of complications was 16%. The prevalence of re-intervention was 13%. Mean survival was 91 (range, 5-392) days. Median wait from decision to implant a stent to stent implantation was 1 (range, 0-14) day. Overall, 25 covered and nine uncovered stents were implanted. Stent implantation for GOO in this patient group is an established and preferable alternative to surgical intervention. Much of the treatment for malignancies of the upper gastrointestinal tract has now been centralised. Our data showed comparable results with published data for these procedures, with a high prevalence of success and low prevalence of major complications. It is of considerable benefit to these patients not to have to travel to a regional centre for stent implantation.


Activated PPARγ Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity.
Type 2 diabetes increases the risk for dementia, including Alzheimer's disease (AD). Pioglitazone (Pio), a pharmacological agonist of the peroxisome proliferator-activated receptor γ (PPARγ), improves insulin sensitivity and has been suggested to have potential in the management of AD symptoms, albeit through mostly unknown mechanisms. We here investigated the potential of Pio to counter synaptic malfunction and loss, a characteristic of AD pathology and its accompanying cognitive deficits. Results from experiments on primary mouse neuronal cultures and a human neural cell line (SH-SY5Y) show that Pio treatment attenuates amyloid β (Aβ)-triggered the pathological (mis-) processing of amyloid precursor protein (APP) and inhibits Aβ-induced accumulation and hyperphosphorylation of Tau. These events are accompanied by increased glutamatergic receptor 2B subunit (GluN2B) levels that are causally linked with neuronal death. Further, Pio treatment blocks Aβ-triggered missorting of hyperphosphorylated Tau to synapses and the subsequent loss of PSD95-positive synapses. These latter effects of Pio are PPARγ-mediated since they are blocked in the presence of GW9662, a selective PPARγ inhibitor. Collectively, these data show that activated PPARγ buffer neurons against APP misprocessing, Tau hyperphosphorylation and its missorting to synapses and subsequently, synaptic loss. These first insights into the mechanisms through which PPARγ influences synaptic loss make a case for further exploration of the potential usefulness of PPARγ agonists in the prevention and treatment of synaptic pathology in AD.


Addressable electrode array device with IDA electrodes for high-throughput detection.
An electrochemical device is proposed for high-throughput electrochemical detection that consists of 32 row and 32 column electrodes on a single glass substrate. The row and column electrodes are connected to interdigitated array (IDA) electrodes to form 1024 (32 × 32) addressable sensor points in the device. Electrochemical responses from each of the 1024 sensors were successfully acquired on the device within 1 min using redox cycling at individual IDA electrodes, which ensures application of the device to comprehensive, high-throughput electrochemical detection for enzyme-linked immunosorbent assay (ELISA), reporter gene assay for monitoring gene expressions, and DNA analysis.


Deconvoluting the Bioactivity of Calcium Phosphate-Based Bone Graft Substitutes: Strategies to Understand the Role of Individual Material Properties.
Calcium phosphate (CaP)-based ceramics are the most widely applied synthetic biomaterials for repair and regeneration of damaged and diseased bone. CaP bioactivity is regulated by a set of largely intertwined physico-chemical and structural properties, such as the surface microstructure, surface energy, porosity, chemical composition, crystallinity and stiffness. Unravelling the role of each individual property in the interaction between the biomaterial and the biological system is a prerequisite for evolving from a trial-and-error approach to a design-driven approach in the development of new functional biomaterials. This progress report critically reviews various strategies developed to decouple the roles of the individual material properties in the biological performance of CaP ceramics. It furthermore emphasizes on the importance of a comprehensive and adequate material characterization that is needed to enhance our knowledge of the property-function relationship of biomaterials used in bone regeneration, and in regenerative medicine in general.


Left Atrial Appendage Remodeling After Lariat Left Atrial Appendage Ligation.
Left atrial appendage (LAA) ligation with the Lariat device is being used for stroke prevention in atrial fibrillation. Residual leaks into the LAA are commonly reported after the procedure. Little is known about the anatomic LAA remodeling after Lariat ligation. In an exploratory study, we evaluated LAA 3-dimensional geometry via computed tomographic scan in 31 consecutive patients before Lariat closure and after a minimum of 30 days post procedure. Thirteen patients were classified as unfavorable cases based on anatomic criteria. Our population had an average age of 70±12 years, a mean CHADS2 (congestive heart failure, hypertension, age>75, diabetes mellitus, history of stroke) score of 3.2±1.2, a mean CHADS2VASC (CHADS2 in addition to female sex, ages 65-75, as well as double impact of age >75, vascular disease) of 4.2±1.5, and a mean HASBLED (hypertension, abnormal renal/liver function, stroke, bleeding predisposition/history, labile international normalized ratio, elderly, drugs/alcohol) bleeding score of 4.0±1.1. Successful suture deployment was achieved in all cases, but 3 patients had intraprocedural residual flow into the LAA (leak). On follow-up, 10 patients (32%) had recanalized residual LAA cavities, which were morphologically similar to the original LAA, albeit significantly smaller in volume (22.5±13.3% of the original volume). Recanalization was not associated with age, sex, comorbid conditions, stroke or bleeding risk scores, follow-up interval, baseline LAA volume, or morphology. Unfavorable cases had anatomic outcomes comparable with those of the anatomically favorable population. No patients have exhibited thromboembolism after 842±338 days post ligation. Incomplete LAA ligation after Lariat is common. However, the remodeled LAA cavity is dramatically reduced. Diminished cavity size and tightening of the LAA orifice may play a role in the reduction of thrombus formation.


Dry Beriberi Post Roux-en-Y Gastric Bypass Surgery.
Bariatric surgery is an effective strategy for achieving substantial weight loss, prolonging survival, and improving the comorbidities associated with obesity. Nutritional deficiency is a commonly recognized post-procedural complication. Here, we present a case of a patient with paresthesia, lower extremity weakness, and altered mental status one year following Roux-en-Y gastric bypass, who was found to have multiple vitamin and micronutrient deficiencies and was diagnosed with beriberi in the setting of profound thiamine deficiency.


Vital Signs: Changes in Opioid Prescribing in the United States, 2006-2015.
Prescription opioid-related overdose deaths increased sharply during 1999-2010 in the United States in parallel with increased opioid prescribing. CDC assessed changes in national-level and county-level opioid prescribing during 2006-2015. CDC analyzed retail prescription data from QuintilesIMS to assess opioid prescribing in the United States from 2006 to 2015, including rates, amounts, dosages, and durations prescribed. CDC examined county-level prescribing patterns in 2010 and 2015. The amount of opioids prescribed in the United States peaked at 782 morphine milligram equivalents (MME) per capita in 2010 and then decreased to 640 MME per capita in 2015. Despite significant decreases, the amount of opioids prescribed in 2015 remained approximately three times as high as in 1999 and varied substantially across the country. County-level factors associated with higher amounts of prescribed opioids include a larger percentage of non-Hispanic whites; a higher prevalence of diabetes and arthritis; micropolitan status (i.e., town/city; nonmetro); and higher unemployment and Medicaid enrollment. Despite reductions in opioid prescribing in some parts of the country, the amount of opioids prescribed remains high relative to 1999 levels and varies substantially at the county-level. Given associations between opioid prescribing, opioid use disorder, and overdose rates, health care providers should carefully weigh the benefits and risks when prescribing opioids outside of end-of-life care, follow evidence-based guidelines, such as CDC's Guideline for Prescribing Opioids for Chronic Pain, and consider nonopioid therapy for chronic pain treatment. State and local jurisdictions can use these findings combined with Prescription Drug Monitoring Program data to identify areas with prescribing patterns that place patients at risk for opioid use disorder and overdose and to target interventions with prescribers based on opioid prescribing guidelines.


[Conditions for performing CT and MRI scans in pregnant and lactating patients].
Many women are pregnant during several percent of their lives. Occasionally, there is a need for neuroradiological examinations during pregnancy or lactation. In our clinical work, we regularly see that female patients are being withheld relevant diagnostic scans during pregnancy, due to insufficient knowledge or an unbalanced comparison between benefits and risks. This article describes the current knowledge regarding conditions for performing CT and MRI scans in pregnant and lactating patients, including the use of contrast media. PET scans and reactions to contrast media are briefly mentioned, but interventional radiology is not discussed.


Is the use of minimally invasive fusion technologies associated with improved outcomes after elective interbody lumbar fusion? Analysis of a nationwide prospective patient-reported outcomes registry.
Over the last decade, clinical investigators and biomedical industry groups have used significant resources to develop advanced technologies that enable less invasive spine fusions. These minimally invasive surgery (MIS) technologies often require increased expenditures by hospitals and payers. Although several small single center studies have suggested MIS technologies decrease surgical morbidity and reduce hospital stay, evidence documenting benefit from a patient perspective remains limited. Furthermore, MIS outcomes have yet to be evaluated from the perspective of multiple practice types representing the broad spectrum of US spine surgery. This study aimed to examine a population of patients who underwent one- or two-level interbody lumbar fusion diagnosed with lumbar stenosis or Grade 1 spondylolisthesis in an observational, prospective national registry for the purposes of determining how MIS and traditional open technologies affect postsurgical and patient-reported outcomes (PROs). This study used observational analysis of prospectively collected data. The sample consisted of cases from the National Neurosurgery Quality and Outcomes Database (N2QOD). Numeric rating scale for back and leg pain, Oswestry Disability Index, EuroQol-5D, return to work, and perioperative morbidity were the outcome measures. The N2QOD is a prospective PROs registry enrolling patients undergoing elective spine surgery from 60 hospitals in 27 US states via representative sampling. We analyzed the N2QOD aggregate dataset (2010-2014) to identify one- and two-level lumbar interbody fusion procedures performed for lumbar stenosis or Grade 1 spondylolisthesis with 12 months' follow-up where surgical instrumentation and implant types were clearly identified. Perioperative and 1-year outcomes were compared between cases performed with MIS enabling technologies versus traditional open technologies before and after propensity matching. There were 467 (24%) patients who underwent elective interbody lumbar fusion using MIS enabling technologies whereas 1,480 (76%) underwent the procedure using traditional open technologies. The MIS patients were slightly healthier (American Society of Anesthesiologists grade), had private insurance more frequently, and underwent two-level fusion less frequently. Unmatched, the MIS cohort was associated with reduced blood loss, a 0.7-day reduction in mean length of hospital stay, and 5% reduced need for post-discharge inpatient rehabilitation, but equivalent 90-day safety measures. After propensity matching, the MIS cohort remained associated with reduced blood loss and a shorter length of stay for one-level fusion (p<.05) but had equivalent length of stay for two-level fusion. Outcomes in all other 90-day safety measures were similar. In both unadjusted and propensity-matched comparison, MIS versus open technologies were associated with equivalent return to work, patient-reported pain, physical disability, and quality of life at 3 and 12 months' follow-up. In a representative sampling registry of elective interbody lumbar spine fusion procedures spanning 27 US states, nearly a quarter of procedures performed from 2010 to 2014 used minimally invasive enabling technologies. Regardless of approach, interbody lumbar fusion was associated with significant and sustained improvements in all measured health domains. When used in everyday care by a wide spectrum of spine surgeons in non-research settings, the use of MIS technologies was associated with reduced intraoperative blood loss but only a half-day reduction in mean length of hospital stay for one-level fusions. Minimally invasive surgery was not associated with any improved perioperative safety measures or 12-month outcomes. Although MIS enabling technologies may increase some in-hospital care efficiencies, MIS clinical outcomes are similar to open surgery for patients undergoing one- and two-level interbody lumbar fusions.


[Study of the positional relationship of nucleolar chromatin and nucleolar compartments in somatic nuclei OPF the ciliate Didinium nasutum].
We showed earlier that nucleoli in interphase ciliates Didinium nasutum, appearing on single ultrathin sections as individual structures, actually are parts of more complex network-like structures in which fibrillar component is located on periphery, and granular--in the central part of a nucleolus. It is known, that nucleolar organizers in D. nasutum are represented by chromatin bodies connected with nucleoli. In this work we used 3D reconstruction on the basis of serial ultrathin sections to study localization of chromatin bodies which by morphological criteria might correspond to nucleolar organizers. Our data showed, that all such chromatin bodies settled down outside of nucleoli, near the periphery of fibrillar component. Even those chromatin bodies which on single sections looked completely surrounded by fibrillar nucleolar component, actually settled down in fibrillar component cavities open to nucleoplasm. Analysis of distribution of nucleolar chromatin bodies allowed us to conclude that activity in different parts of interphase complex network-like nucleoli of D. nasutum is approximately the same.


Sensitive determination of erythrosine and other red food colorants using capillary electrophoresis with laser-induced fluorescence detection.
Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was applied to separation and sensitive determination of red food colorants. Diode pumped frequency-doubled Nd:YAG laser (532 nm) was used as an excitation source in a laboratory-built CE-LIF system. For highly fluorescent erythrosine B (E127), an extrapolated limit of detection (LOD) of 0.4 ng mL(-1) (S/N=3) was achieved. Extrapolated LODs of other tested red additives, such as carmoisine, E122 (0.5 microg mL(-1)); amaranth, E123 (0.2 microg mL(-1)); ponceau 4R, E124 (0.3 microg mL(-1)) and red 2G, E128 (0.3 microg mL(-1)) were about one-order lower compared to results obtained with CE with absorbance detection in UV/vis (CE-UV/vis). The main advantages of using CE-LIF for analysis of food samples are high selectivity and minimization of matrix effect. To our knowledge, this is the first use of CE-LIF for determination of red food colorants.


Gossypol-induced fitness gain and increased resistance to deltamethrin in beet armyworm, Spodoptera exigua (Hübner).
In plant-insect interactions, phytotoxins such as gossypol, exert a defensive role on behalf of the plant by interfering with the essential metabolic, biochemical and physiological pathways of herbivorous insects. The beet armyworm, Spodoptera exigua (Hübner), is a key pest for many important crops including a range of vegetables, ornamentals, and cotton. In this study, we investigated how resistance to deltamethrin relates to enzyme activity in gossypol-pretreated larvae of S. exigua. Following selection with deltamethrin insecticides on gossypol-pretreated larvae for 10 generations, the Gos-SEL population developed a 113.29-fold resistance. Under the same conditions, the Delta-SEL selected population showed a 69.76-fold increase in resistance along with corresponding levels of xenobiotic defense enzyme activity. Similarly, the fecundity of the Delta-SEL population together with male and female longevity were found to be significantly lower when compared with the Gos-SEL population and the laboratory susceptible-strain group (SS-Strain). In addition, the activities of cytochrome P450s in S. exigua were significantly enhanced when the insects were fed on a deltamethrin and gossypol-pretreated diet compared with being fed on deltamethrin alone. The reproductive capacity of S. exigua is significantly reduced in Delta-SEL and Gos-SEL populations compared with the control group (SS-Strain). Elevation of the major detoxification enzyme cytochrome P450 monooxygenase and esterase might have an important role in inducing tolerance to deltamethrin in gossypol-fed S. exigua populations. This study enhances our understanding of detoxification enzyme pathways for S. exigua gene expression and their role in responses to insecticides and plant secondary metabolites. © 2018 Society of Chemical Industry.


Current thinking on tonsillectomy and adenoidectomy.
Tonsillectomy and adenoidectomy, though less frequently performed now than in the 1930s, remain among the most common surgical procedures in the United States. The need for and benefits of tonsillectomy and adenoidectomy have been a source of controversy for several decades. Nonetheless, there are situations in which these procedures definitely are beneficial. Tonsillectomy and adenoidectomy are two distinct procedures with separate indications, and they are performed concurrently only when the specific indications for each coexist. Tonsillectomy is indicated by recurrent tonsillitis, peritonsillar abscess, chronic tonsillitis, tonsillar neoplasm, or tonsillar hypertrophy that is obstructive to the upper aerodigestive tract (respiratory distress, dysphagia, or interference with performance of an adenoidectomy). Adenoidectomy is indicated for nasal airway obstruction due to adenoidal enlargement from hypertrophic or inflammatory processes. Although correlation exists among obstructive adenoids, mouth breathing, and dentofacial anomalies, present evidence is not sufficient to justify adenoidectomy solely on the basis of craniofacial or dentofacial abnormalities. Today, elimination of an occult source of infection (once called focal infection) in patients with disorders such as rheumatic fever or serous otitis media is not a valid indication for either operation. Contraindications to tonsillectomy and adenoidectomy include bleeding disorders, familial anesthetic intolerance, velopharyngeal insufficiency, and concurrent disease that may enhance operative risks. Like all surgical procedures, tonsillectomy and adenoidectomy entail morbidity and risk of mortality. The most frequent complication of these operations is hemorrhage. Risk of mortality is approximately 0.006%. Mortality and morbidity can be minimized by appropriate preoperative evaluation, complete control of the airway with endotracheal anesthesia, and meticulous surgical technique.


Codivir suppresses SARS-Cov-2 viral replication and stabilizes clinical outcome: In vitro and Phase I clinical trial results.
Treatment of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) remains a significant challenge in the face of increased worldwide morbidity and mortality. The acute illness caused by SARS-CoV-2 is initiated by a viral phase, followed by an inflammatory phase. Numerous anti-inflammatory and anti-viral therapies, with a relatively minor clinical effect, have been applied. Developing a safe and efficient direct anti-viral treatment is essential as it can block disease progression before significant complications ensue and potentially prevent transmission. The present phase 1 study aimed to determine the safety of Codivir, a newly developed anti-viral agent, and to preliminarily assess its anti-viral activity in patients infected by COVID-19. In vitro studies were conducted to determine the direct anti-viral effect of Codivir using an immunofluorescence-based assay and to assess its cytotoxic effect by tetrazolium assay (MTT). In a phase I clinical trial, Codivir was administered for ten days in 12 patients who were followed for its safety. Patients were followed for clinical manifestations during administration. Sequential nasal viral PCR titers (Cycle Threshold, CT) were determined preceding and during treatment. In vitro, Codivir showed activity against SARS-CoV-2 with 90% viral replication suppression and minimal cytotoxicity. The anti-viral activity was demonstrated at the early stages of infection, post-entry of the virus in the cell. Codivir was safe in all 12 patients in phase I clinical trial and significantly suppressed viral replication in 5/7 fully assessed patients, with an anti-viral effect noted as early as three days. The present study's data support the safety of Codivir administration in humans and suggest its significant anti-COVID-19 effect. These results support the testing of the drug in more extensive controlled trials in patients with SARS-CoV-2.


Infection of Plasmodiophora brassicae in Chinese cabbage.
Brassica crops infected by Plasmodiophora brassicae can produce root galls (clubroots) and be prevented from growing normally. To understand the series of changes that occur in the host root during root gall production, the resistance character of 21 Chinese cabbage lines were identified and then resistant and susceptible lines were used for infection observation. Hydroponic technology system was used for plants growing, and the infection process of P. brassicae in the roots of resistant and susceptible Chinese cabbage was examined based on morphology and microscopic characteristics using micoscope. In susceptible Chinese cabbage, the root hair infection stage occurred over approximately 7 days after inoculation, the cortical infection happened over approximatly 14 days after inoculation, and clubroots formed in approximately 30 days after inoculation. However, in resistant Chinese cabbage, the pathogen could be prevented and maintained in the root hair infection stage. This research provides a foundation for the subsequent studies of cabbage resistance of P. brassicae.


Alternative Pathway for the Reaction Catalyzed by DNA Dealkylase AlkB from Ab Initio QM/MM Calculations.
AlkB is the title enzyme of a family of DNA dealkylases that catalyze the direct oxidative dealkylation of nucleobases. The conventional mechanism for the dealkylation of N1-methyl adenine (1-meA) catalyzed by AlkB after the formation of FeIV-oxo is comprised by a reorientation of the oxo moiety, hydrogen abstraction, OH rebound from the Fe atom to the methyl adduct, and the dissociation of the resulting methoxide to obtain the repaired adenine base and formaldehyde. An alternative pathway with hydroxide as a ligand bound to the iron atom is proposed and investigated by QM/MM simulations. The results show OH- has a small impact on the barriers for the hydrogen abstraction and OH rebound steps. The effects of the enzyme and the OH- ligand on the hydrogen abstraction by the FeIV-oxo moiety are discussed in detail. The new OH rebound step is coupled with a proton transfer to the OH- ligand and results in a novel zwitterion intermediate. This zwitterion structure can also be characterized as Fe-O-C complex and facilitates the formation of formaldehyde. In contrast, for the pathway with H2O bound to iron, the hydroxyl product of the OH rebound step first needs to unbind from the metal center before transferring a proton to Glu136 or other residue/substrate. The consistency between our theoretical results and experimental findings is discussed. This study provides new insights into the oxidative repair mechanism of DNA repair by nonheme FeII and α-ketoglutarate (α-KG) dependent dioxygenases and a possible explanation for the substrate preference of AlkB.


Analysis of immune responses in the sheep to synthetic peptides of foot-and-mouth disease virus using ovine polyclonal and monoclonal antibodies.
A 40-residue peptide incorporating residues 200-213 and 141-158 of foot-and-mouth disease virus VP1 capsid protein strain O1 Kaufbeuren was injected uncoupled into sheep, and the immune responses analysed. Direct-binding and inhibition experiments showed that the polyclonal antibody response was directed mainly against epitopes unique to the 40-residue peptide but absent from the constituent peptides containing residues 200-213 or 141-158, respectively. Further confirmation of the presence of unique epitopes on the 40-residue peptide was obtained from similar experiments performed with sheep monoclonal antibodies generated through the use of an aminopterin-sensitive sheep/mouse heterohybridoma cell line as a fusion partner. The sheep polyclonal antisera to the 40-residue peptide had high neutralization titres and were fully active in a mouse protection assay, whereas none of the sheep monoclonal antibodies conferred protection. The results suggest that the conformation of the 40-residue peptide is important for its ability to induce neutralizing antibodies.


Altering social cue perception impacts honey bee aggression with minimal impacts on aggression-related brain gene expression.
Gene expression changes resulting from social interactions may give rise to long term behavioral change, or simply reflect the activity of neural circuitry associated with behavioral expression. In honey bees, social cues broadly modulate aggressive behavior and brain gene expression. Previous studies suggest that expression changes are limited to contexts in which social cues give rise to stable, relatively long-term changes in behavior. Here we use a traditional beekeeping approach that inhibits aggression, smoke exposure, to deprive individuals of aggression-inducing olfactory cues and evaluate whether behavioral changes occur in absence of expression variation in a set of four biomarker genes (drat, cyp6g1/2, GB53860, inos) associated with aggression in previous studies. We also evaluate two markers of a brain hypoxic response (hif1α, hsf) to determine whether smoke induces molecular changes at all. We find that bees with blocked sensory perception as a result of smoke exposure show a strong, temporary inhibition of aggression relative to bees allowed to perceive normal social cues. However, blocking sensory perception had minimal impacts on aggression-relevant gene expression, althought it did induce a hypoxic molecular response in the brain. Results suggest that certain genes differentiate social cue-induced changes in aggression from long-term modulation of this phenotype.


Impact of Environmental Degradation on Human Health: An Assessment Using Multicriteria Decision Making.
Air pollution has emerged as a major global concern in recent decades as a result of rapid urbanization and industrialization, leading to a variety of adverse health outcomes. This research aims to investigate the influence of exposure to ambient and household particulate matter pollution (PM2.5), and ground-level ozone (O3) pollution on respiratory and cardiac mortality in Pakistan. We used grey incidence analysis (GIA) methodology to estimate the degree of proximity among selected variables and rank them based on mortality. Hurwicz's criterion is then adopted for further optimization by prioritizing the selected factors with the greatest influence on respiratory and cardiac mortality. The GIA findings revealed that asthma mortality is considerably impacted by exposure to ambient and household PM2.5 concentration while ischemic heart disease (IHD) mortality is potentially influenced by ground-level ozone exposure. Furthermore, results based on Hurwicz's analysis demonstrated that exposure to ambient PM2.5 concentration appeared as the most intensified factor of respiratory and cardiac mortality. This corroboration adds to the growing body of research demonstrating that exposure to ambient PM2.5 adversely leads to respiratory and cardiac risks, emphasizing the demand for further improvement of air quality in Pakistan. Besides, the suggested methodologies provide a valuable tool and additional practical knowledge for policymakers and decision-makers in drawing rational decisions.


[Juvenile nasopharyngeal angiofibroma].
Juvenile Juvenile nasopharyngeal angiofibroma (JNA) is a benign and highly vascular tumor. In this article we present a case treated in our institution. We present form of presentation, exploration and intra-arterial pre-operative embolization by neuroradiology, and the treatment with the Le Fort technique. JNA has a complex anatomy, high recurrence and special histopathology, therefore the surgery is very complex and as an with high morbidity. The pre-operative embolization has decrease the hemorragic complications. We review the literature the of the JNA nowadays.


Gout: an Asia-Pacific update.
Even though, Hippocrates recognized gout as an affection of older men and a product of high living long back in 5th century BC, this painful condition promises to accompany humanity to the 21st century. The incidence is progressively rising and females are also affected in the modern era. There are also regional and ethnic variations in the incidence, the genetics of which is being studied. The recommended best therapy for the acute attacks and long term prophylaxis has improved remarkably in the recent years. However, patients are often treated inadequately and risk factors for their disease are not well explored in daily practice. Although well designed long term studies of current and newer treatment are welcomed, educating doctors especially the primary care physicians who manage majority of gout cases, in optimizing the currently available management options would improve the present care.


Site-Specific RNA Editing of Stop Mutations in the CFTR mRNA of Human Bronchial Cultured Cells.
It is reported that about 10% of cystic fibrosis (CF) patients worldwide have nonsense (stop) mutations in the CFTR gene, which cause the premature termination of CFTR protein synthesis, leading to a truncated and non-functional protein. To address this issue, we investigated the possibility of rescuing the CFTR nonsense mutation (UGA) by sequence-specific RNA editing in CFTR mutant CFF-16HBEge, W1282X, and G542X human bronchial cells. We used two different base editor tools that take advantage of ADAR enzymes (adenosine deaminase acting on RNA) to edit adenosine to inosine (A-to-I) within the mRNA: the REPAIRv2 (RNA Editing for Programmable A to I Replacement, version 2) and the minixABE (A to I Base Editor). Immunofluorescence experiments show that both approaches were able to recover the CFTR protein in the CFTR mutant cells. In addition, RT-qPCR confirmed the rescue of the CFTR full transcript. These findings suggest that site-specific RNA editing may efficiently correct the UGA premature stop codon in the CFTR transcript in CFF-16HBEge, W1282X, and G542X cells. Thus, this approach, which is safer than acting directly on the mutated DNA, opens up new therapeutic possibilities for CF patients with nonsense mutations.


[Description of aging dogs and fruit flies based on the kinetic theory].
The aim of the study is to assess the adequacy of model representations, accepted in the kinetic theory of aging of living systems, the analysis of the experimental data obtained on dogs and fruit flies. The work is illustrated by applying the need to develop a mathematical model of the kinetic theory of aging to describe the probability density of death, probability of death, the average duration of life of the considered biological systems in the natural conditions of existence, as well as for dogs with limited time and chronic RA-diciannove impact, and for Drosophila - high external temperature. Op-defined kinetic equation of aging and their parameters.


Sudden cardiac death in a young boy with multisystemic inflammatory syndrome in children (MISC).
A previously healthy 12-year-old boy presented to the emergency department on the seventh day of illness with classical symptoms of postinflammatory multisystemic syndrome in children temporally associated with SARS-CoV-2 (fever, vomiting, loose stools and rashes all over the body) with COVID-19 seropositivity, high inflammatory markers and elevated cardiac enzymes with cardiogenic shock with multiple organ dysfunction syndrome. After having improved over the first 48 hours following intravenous immunoglobulin and pulsed steroids, this young boy developed sudden cardiac arrest and died. No reversible cause could be identified at the time of resuscitation. Despite an apparent clinical recovery in the myocardial function, it is likely that the myocardium remains arrhythmogenic due to cytokine-induced myocardial inflammation. There are several reports in the literature of fatality in multisystemic inflammatory syndrome in children (MISC) due to cardiovascular complication during the acute phase of the illness. To the best of our knowledge, this is the first report of sudden cardiac death in a child with MISC days after recovery from critical illness, suggesting that fatal outcome remains a potential risk during follow-up, even when there is no evidence of coronary aneurysm. Further studies are needed to identify clinical characteristics of such high-risk children presenting with MISC. We will need to follow these children closely to understand what implications they may have in the long term, and this helps in raising awareness among families of such children.


Emerging technologies' role in reducing under-five mortality in a low-resource setting: Challenges and perceived opportunities by public health workers in Makonde District, Zimbabwe.
Under-five mortality (U5M) remains a global challenge, with Sub-Saharan Africa being the hardest hit. The coronavirus disease 2019 (COVID-19) has strained healthcare systems, threatening to reverse current gains in U5M health outcomes. It threatened progress made towards achieving United Nations Sustainable Development Goal 3 due to its strain on healthcare systems, resource reassignment and its prioritisation by health authorities globally. Low-resource settings inherently face unique challenges in fighting U5M and providing quality healthcare to under-fives, like understaffing, drug shortages, underfunding, skills gaps and lack of specialised healthcare equipment, contributing to high U5M rates. This study explored public health facilities' challenges in reducing U5M in a low-resource setting in Zimbabwe and public health workers' perceptions of emerging technologies' role in addressing those challenges. Twenty public health workers participated in interviews and a focus group. They perceived emerging technologies (ETs) as a panacea to the challenges by supporting data-driven healthcare, improving follow-up outcomes through automated reminders of medication and clinic visits, aiding diagnosis, continuous monitoring, health education, drug supply monitoring, critical supplies delivery and skills development. In this paper, emerging technology is any information and communication technology that has not been utilised to its full potential in Zimbabwe's public health domain. Findings indicate that public health workers in Makonde would welcome ETs to improve under-five health and well-being.


Assessing Reliability of Medical Record Reviews for the Detection of Hospital Adverse Events.
The purpose of this study was to assess the inter-rater reliability and intra-rater reliability of medical record review for the detection of hospital adverse events. We conducted two stages retrospective medical records review of a random sample of 96 patients from one acute-care general hospital. The first stage was an explicit patient record review by two nurses to detect the presence of 41 screening criteria (SC). The second stage was an implicit structured review by two physicians to identify the occurrence of adverse events from the positive cases on the SC. The inter-rater reliability of two nurses and that of two physicians were assessed. The intra-rater reliability was also evaluated by using test-retest method at approximately two weeks later. In 84.2% of the patient medical records, the nurses agreed as to the necessity for the second stage review (kappa, 0.68; 95% confidence interval [CI], 0.54 to 0.83). In 93.0% of the patient medical records screened by nurses, the physicians agreed about the absence or presence of adverse events (kappa, 0.71; 95% CI, 0.44 to 0.97). When assessing intra-rater reliability, the kappa indices of two nurses were 0.54 (95% CI, 0.31 to 0.77) and 0.67 (95% CI, 0.47 to 0.87), whereas those of two physicians were 0.87 (95% CI, 0.62 to 1.00) and 0.37 (95% CI, -0.16 to 0.89). In this study, the medical record review for detecting adverse events showed intermediate to good level of inter-rater and intra-rater reliability. Well organized training program for reviewers and clearly defining SC are required to get more reliable results in the hospital adverse event study.


The spectrum of human immunodeficiency virus infection in patients with factor IX deficiency (Christmas disease)
Early reports suggested that hemophiliacs with factor IX deficiency (Christmas Disease) may be at less risk for developing the acquired immunodeficiency syndrome (AIDS) than patients with classic hemophilia. We evaluated 12 factor IX deficient patients for clinical and immunologic abnormalities related to infection with the human immunodeficiency virus (HIV). Antibody to HIV was not detected in these patients prior to 1982. By 1985, 66 percent (eight of 12) patients were seropositive. All three concentrates available commercially before 1985 were associated with seropositivity. Furthermore, seropositive hemophiliacs had received on average significantly more factor IX concentrate than seronegative hemophiliacs (27,825 +/- 17,976 (S.D.) versus 1,250 +/- 1,500 factor units/year, (p less than 0.02). Half of the seropositive individuals had generalized lymphadenopathy with splenomegaly. Two seropositive patients have developed AIDS, one with cryptococcal meningitis and another with a large cell immunoblastic lymphoma. Infection with HIV has occurred with high frequency in hemophiliacs who received unmodified factor IX concentrates.


Aqueous solution synthesis of CaF2 hollow microspheres via the ostwald ripening process at room temperature.
Nearly monodispersive CaF2 hollow microspheres were synthesized by a facile aqueous solution route from the mixed aqueous solutions of CaCl2, Na2WO4, and NaF at room temperature. The as-prepared products were characterized by X-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy (TEM), high-resolution transmission electron microscopy, and N2 adsorption-desorption techniques. The CaF2 hollow microspheres have an average diameter of about 1.5 microm and a hollow interior of 0.5 microm. The shell is composed of numerous single-crystalline nanoparticles with diameter of about 20 nm. The morphologies and diameters of the CaF2 products are strongly dependent on the experimental parameters, such as the concentration of the aqueous NaF solution and the reaction temperature. The synthetic experiments indicate that the growth process of CaF2 hollow microspheres involves first the formation of CaWO4 solid microspheres and then the formation of CaF2 solid microspheres through the reaction between CaWO4 and F(-) ions controlled by the difference of the solubility product for CaWO4 and CaF2. Phenomenological elucidation based on TEM observations and XRD patterns of intermediate products at different precipitation stages indicates that the formation mechanism for the CaF2 hollow microspheres is related to the Ostwald ripening mechanism. N2 adsorption-desorption measurement shows that the CaF2 hollow microspheres possess a high Brunauer-Emmett-Teller surface area and porosity properties. The synthetic procedure is straightforward and represents a new example of the Ostwald ripening mechanism for the formation of inorganic hollow structures in an aqueous solution at room temperature.


Induction of heat shock protein 27 by hydroxyurea and its relationship to experimental metastasis.
Treatment of tumor cells with hydroxyurea (HU) has been shown to increase the experimental metastatic potential of these cells. We have previously described the induction of stress proteins (antioxidants) by HU in B16 murine melanoma cells and their relationship to the metastatic process. We have now investigated the induction by HU of another set of stress proteins, the heat shock proteins, and their role in experimental metastasis. HU markedly increased the cellular content of heat shock protein (hsp) 27 but not of hsp 90, 72/73, or 60 as measured by immunoblotting. The induction of hsp27 protein was preceded by a specific increase in hsp27 mRNA. Furthermore, HU-treated cells were more thermotolerant. To investigate the functional role of hsp27, human hsp27 cDNA was constitutively overexpressed in B16 cells at levels seen in HU-treated cells. In separate experiments, we induced a global increase in hsps by heat shock. Neither the hsp27 transfectants nor the heat-shocked cells demonstrated an increase in their experimental metastatic capacity. We conclude that hsp27 protein is increased by HU by the specific induction of hsp27 mRNA in B16 melanoma cells but increased hsp27 protein is not responsible for the increase in experimental metastasis. Since high levels of hsp27 are associated with metastatic disease in breast and ovarian cancers, but not in our experimental system, the functional role of hsp27 in metastasis requires further study.


Problem solving therapies for depression: a meta-analysis.
In the past decades, the effects of problem-solving therapy (PST) for depression have been examined in several randomized controlled studies. However, until now no meta-analysis has tried to integrate the results of these studies. We conducted a systematic literature search and identified 13 randomized studies examining the effects of PST, with a total of 1133 subjects. The quality of studies varied. The mean standardized effect size was 0.34 in the fixed effects model and 0.83 in the random effects model, with very high heterogeneity. Subgroup analyses indicated significantly lower effects for individual interventions in studies with subjects who met criteria for major depression, studies in which intention-to-treat analyses were conducted instead of completers-only analyses, and studies with pill placebo and care-as-usual control groups. Heterogeneity was high, and the subgroup analyses did not result in clear indications of what caused this high heterogeneity. This indicates that PST has varying effects on depression, and that it is not known to date what determines whether PST has larger of smaller effects. Although there is no doubt that PST can be an effective treatment for depression, more research is needed to ascertain the conditions and subjects in which these positive effects are realized.


Intraocular lens explantation following cataract surgery: Indications, techniques, and video demonstrations.
As techniques for modern cataract surgery have expanded and premium intraocular lens (IOL) use is now widespread, patient expectations are high. The need for IOL explantation, whilst still low, remains an ongoing issue. Intraocular lens explantation can be challenging for a number of reasons and as such we have introduced an additional technique to add to the surgeon's repertoire. Bimanual haptic stripping of fibrosis at the specific area where the haptic is adherent to the capsular bag is an effective strategy to aid in dissection of haptics without compromising the capsule or zonules. Given the challenges associated with IOL explantation, newly designed IOLs need to avoid these "sticking points" at which the IOLs interact with the fibrosed capsule. Techniques we have evolved and which are described below should assist anterior segment surgeons to facilitate IOL removal in an efficient and safe way.


Study of Single Nucleotide Polymorphisms Associated with Breast Cancer Patients among Arab Ancestries.
The aim of this study is to investigate the single nucleotide polymorphisms (SNPs) associated with breast cancer in our population of Arab patients. We investigated 26 breast cancer patients and an equal number of healthy age- and sex-matched control volunteers. We examined the exome wide microarray-based biomarkers and screened 243,345 SNPs for their possible significant association with our breast cancer patients. Successfully, we identified the most significant (p value ≤9.14 × 10-09) four associated SNPs [SNRK and SNRK-AS1-rs202018563G; BRCA2-rs2227943C; ZNF484-rs199826847C; and DCPS-rs1695739G] among persons with breast cancer versus the healthy controls even after Bonferroni corrections (p value <2.05 × 10-07). Although our patients' numbers were limited, the identified SNPs might shed some light on certain breast cancer-associated functional multigenic variations in Arab patients. We assert on the importance of more extensive large-scale analysis to confirm the candidate biomarkers and possible target genes of breast cancer among Arab ancestries.


The Nomogram of Clitoral Length and Width in Iranian Term and Preterm Neonates.
Background and Objectives: Clitoromegaly is an important parameter in the evaluation of ambiguous genitalia in neonates, but the normative data for clitoral size in newborns have racial/ethnic differences. The present study aimed to determine clitoral length (CL) and clitoral width (CW) values and establish cutoff measurement to define clitoromegaly in both term and preterm Iranian neonates for the first time. Methods: A total number of 580 female newborn infants delivered at 28-42 weeks of gestation were enrolled in the study, and their CL and CW were measured on the first 72 h of birth. Data about birth weight (BW), body length (BL), and head circumference (HC) of newborns; mothers' age; and gestational age (GA) were recorded, too. Results were presented as mean ± standard deviation (SD) for quantitative variables and were summarized by frequency (percentage) for categorical variables. Backward stepwise regression analysis was used for prediction of CL and CW. Results: Among 580 Iranian female newborns studied, 187 were term neonates and the other 393 newborns were preterm. Mean ± SD values of CL were 6.11 ± 0.39 mm in term infants and 5.45 ± 0.64 mm in preterm infants (P < 0.001). Mean ± SD values of CW were 4.22 ± 0.43 in term infants and 3.68 ± 0.53 in preterm infants (P < 0.001). Regression analysis showed that CL was correlated with GA considered by last menstrual period, BL, BW, and HC; and CW was associated with GA, BL, and BW. Conclusion: This study suggests normative values (mean + 1, 2, and 3 SD) of CL and CW according to GA, which can be used as a reference for Middle East's newborns, especially Iranian newborn babies.


Reaction ensemble Monte Carlo technique and hypernetted chain approximation study of dense hydrogen.
In spite of the simple structure of hydrogen, up to now there is no unified theoretical and experimental description of hydrogen at high pressures. Recent results of Z-pinch experiments show a large deviation from those obtained by laser driven ones. Theoretical investigations including ab initio computer simulations show considerable differences at such extreme conditions from each other and from experimental values. We apply the reaction ensemble Monte Carlo technique on one hand and a combination of the hypernetted chain approximation with the mass action law on the other to study the behavior of dense hydrogen at such conditions. The agreement between both methods for the equation of state and for the Hugoniot curve is excellent. Comparison to other methods and experimental results is also performed.


Antibody coefficients for the diagnosis of equine protozoal myeloencephalitis.
Diagnosis of equine protozoal myeloencephalitis (EPM) remains a challenge for equine practitioners. Current utilized methods have inadequate sensitivity and specificity, because of a high number of false positive results. Evaluation of antibody indices to Sarcocystis neurona should provide high sensitivity and specificity for diagnosis of EPM. Archived samples from 29 clinical patients. Archived serum and cerebrospinal fluid (CSF) samples from clinical patients with either EPM (14) or cervical vertebral compressive myelopathy (CVM) (15) were examined and tested for anti-S. neurona antibodies by the SnSAG2 ELISA. The results were used to calculate the antibody index (AI) and C-value. Sensitivity and specificity were calculated, and the AI, C-value, immunoglobulin G (IgG) concentrations, and anti-S. neurona titers compared. In addition, negative CSF was spiked in varying concentrations with blood from a horse with a high anti-S. neurona titer, and the tests repeated. Results demonstrated that the IgG concentration, anti-S. neurona titer, AI, and C-value were significantly higher (P < .05) in horses with EPM than in those with CVM. Sensitivity and specificity of the AI was 71 and 100%, respectively, and that of the C-value was 86 and 100%, respectively. In addition, the AI and C-value from the samples spiked with S. neurona positive blood remained below 1 (eg, negative) in CSF with a red blood cell (RBC) count up to 10(5) RBC/μL. CONCLUSIONS/CLINICAL IMPORTANCE: Results of the study demonstrate the value of calculating the AI and C-value in the diagnosis of EPM in horses. In addition, the test is robust in the presence of blood contamination.


How does creating a concept map affect item-specific encoding?
Concept mapping has become a popular learning tool. However, the processes underlying the task are poorly understood. In the present study, we examined the effect of creating a concept map on the processing of item-specific information. In 2 experiments, subjects learned categorized or ad hoc word lists by making pleasantness ratings, sorting words into categories, or creating a concept map. Memory was tested using a free recall test and a recognition memory test, which is considered to be especially sensitive to item-specific processing. Typically, tasks that promote item-specific processing enhance free recall of categorized lists, relative to category sorting. Concept mapping resulted in lower recall performance than both the pleasantness rating and category sorting condition for categorized words. Moreover, concept mapping resulted in lower recognition memory performance than the other 2 tasks. These results converge on the conclusion that creating a concept map disrupts the processing of item-specific information.


Effect of right ventricular function and pulmonary pressures on heart failure prognosis.
The relationship of right ventricular function and pulmonary systolic pressure in patients with congestive heart failure was evaluated to risk-stratify them. The study included 147 consecutive patients with symptomatic heart failure who underwent clinical and laboratory examination and echocardiography including Doppler tissue echocardiography. They were followed for a mean of 11.2+/-6.4 months. During follow-up, 16 patients died and 45 patients had nonfatal cardiac events. There were 60 readmissions for heart failure. Pulmonary artery systolic pressure and right ventricular systolic function were inversely related (r(2)=0.66, P<.001). On Cox multivariate survival analysis, early worsening of pulmonary arterial pressures was an independent prognostic predictor (hazard ratio, 0.44; confidence interval, 0.28-0.91, P=.024). The patients with pulmonary hypertension and right ventricular systolic dysfunction had the worst prognosis. The assessments of right ventricular function help to risk-stratify patients with heart failure. The early worsening of pulmonary hypertension is a powerful predictor of worse prognosis.


Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents: a pilot study.
The prevalence of mood disorders in children is a growing global concern. Omega-3 fatty acids (FA) are emerging as a promising adjuvant therapy for depressive disorder (DD) in paediatric patients. The primary objective of this pilot, single-centre, randomized, double-blind controlled study was to compare the efficacy of an Omega-3 FA fish oil emulsion with a control oil emulsion alongside standard treatment for depressive symptoms in children and adolescents suffering from depressive disorder (DD) and mixed anxiety depressive disorder (MADD). 38 children (12 patients were treated and diagnosed for at least 1 month before enrolment, 26 patients were first-time diagnosed as DD) aged 11-17 years were randomised 1:1 to the intervention (Omega-3 FA, 19 patients) or active comparator (Omega-6 FA, 19 patients) groups. Children's depression inventory (CDI) ratings were performed at baseline, every 2 weeks for a 12-week intervention period and at 4-week post-intervention. 35 patients (17 in Omega-3 and 18 in Omega-6 groups) who completed the whole intervention period were evaluated. Patients from Omega-3 group were stratified according to diagnosis into two subgroups (DD-10/17 and mixed anxiety depressive disorder (MADD)-7/17 patients) and in the Omega-6 group into DD-10/18 and MADD-8/18 patients. Groups were evaluated separately. Differences between-groups were tested with the Student´s t test or non-parametric Mann-Whitney U test. Two-way ANOVA with repeated measures and Friedman test were used to analyse the Treatment effect for response in CDI score. p < 0.05 was considered significant in all statistical analyses. Significant reductions in CDI scores in 35 analysed patients who completed 12 weeks intervention were observed after 12 weeks of intervention only in the Omega-3 group (p = 0.034). After stratification to depressive disorder and mixed anxiety depressive disorder subgroups, the DD subgroup receiving the Omega-3 FA fish oil showed statistically greater improvement (score reduction after 8 week treatment of -9.1 CDI, p = 0.0001) when compared to the MADD subgroup (score reduction after 8 week treatment -4.24 CDI, p = 0.271). CDI scores were reduced in the Omega-3 group and the depression subgroup had greater improvement than the mixed depressive/anxiety group. An Omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant supplement during the treatment of depressive disorders in children. Trial registration ISRCTN81655012.


Strategies and challenges of carbon materials in the practical applications of lithium metal anode: a review.
Lithium (Li) metal is strongly considered to be the ultimate anode for next-generation high-energy-density rechargeable batteries due to its lowest electrochemical potential and highest specific capacity. However, Li metal anode has limitations, involving inevitable dendritic Li growth, nonuniform Li deposition, enormous volume expansion, and ultimate electrode pulverization, which lead to rapid decrease in Coulombic efficiency and short circuits, significantly hindering its practical use. Various strategies have been proposed to solve uncontrollable dendritic Li growth and parasitic electrochemical reactions. Carbon materials and their composites with excellent structure tunability and properties have been explored to solve these issues and have shown great potential applications in Li metal anodes. This review presents various protective strategies of Li metal anode based on carbon materials. The rational design of carbon materials with specific functionalities in Li metal anode protecting solutions and manufacturing methods of composite electrodes with metallic Li and carbon materials are discussed in detail. In addition, a comprehensive understanding of the challenges and our outlook on the future development of carbon materials for stabilizing Li metal anodes in practical applications are discussed and prospected.


A perspective on liquid salts for energy and materials.
Liquid salts comprising molten salts and ionic liquids offer important media to address both energy and materials challenges. Here we review topics presented in this Faraday Discussion volume related to improved electrowinning of metals, optimisation of processes, new electrochemical device concepts, chemistry in ionic liquids, conversion of biomass, carbon chemistry and nuclear applications. The underlying phenomenology is then reviewed and commentary given. Some future applications are then discussed, further exemplifying the high potential rewards achievable from these chemistries.


Drug utilization, safety and clinical use of Actos and Avandia.
The impetus for this review was recent increased warnings of cardiovascular toxicity, fractures and bladder cancer associated with glitazone use. A drug utilization review was performed regarding the use of Actos (pioglitazone) and Avandia (rosiglitazone) at Cooper Green Mercy Hospital (CGMH), an inner city safety net hospital in Birmingham, Alabama. Pharmacy records were reviewed hospital-wide to determine usage patterns of all anti-diabetic medications. Medline and the FDA websites were searched for articles on safety and efficacy of pioglitazone and rosiglitazone. Considerations were relative utilization profile, comparative efficacy, indications, relative cost, and safety profile of the two available medications in this drug class. On the basis of all of these factors, a hospital-wide switch of all rosiglitazone prescriptions to all pioglitazone was implemented, which was estimated to result in savings of $83,000 for the first year. No episodes of worsening of control of diabetes were anticipated, nor were episodes of decreased efficacy or adverse effects as a result of automatically switching patients from rosiglitazone to pioglitazone at the time of prescription filling. The conclusions can be summarized in a number of key points. • Clinicians should follow the American Diabetes Association guidelines [1] for treatment. • The basis for diabetic control is weight loss, diet and exercise. • Initial medication management for type II Diabetes Mellitus includes metformin and insulin. • There are no circumstances in which use of glitazone medications is preferable to other medication groups, and there are no clinical circumstances in which use of glitazone medications is absolutely necessary, as opposed to other classes of diabetic medication. • There are significant contraindications, warnings and precautions to use of glitazones, which must be taken into consideration before use in every individual patient. • Glitazones in particular should not be used in the following circumstances: congestive heart failure (CHF), concurrent bladder cancer or severe osteoporosis.


Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats.
Blockade of gamma-aminobutyric acid (GABA) in the posterior hypothalamic nucleus elicits cardiorespiratory stimulation in anesthetized rats. The present study was conducted to test the hypothesis that blockade of GABA in this cardiostimulatory area of the posterior hypothalamus in conscious animals would elicit a defense reaction characterised by a "fight or flight" response. Blockade of GABA was achieved by injecting bicuculline methiodide (BMI 1-25 ng) and picrotoxin (4-100 ng), two post-synaptic GABA antagonists and isoniazid (INH 35 and 70 micrograms), an inhibitor of the synthesis of GABA, bilaterally into the posterior hypothalamus through chronically implanted microinjection cannulae. All three drugs produced dose-dependent increases in locomotor activity, suggesting an "escape" reaction which was quantified as number of crossings and rearings. The effects of bicuculline and picrotoxin appeared immediately after the injection while those of isoniazid appeared much more slowly, attaining peak effects 24 +/- 1 min after injection. Injection of either strychnine (38 ng) into the posterior hypothalamus or bicuculline into the lateral hypothalamic area (LHA) or the dorso-medial/ventro-medial hypothalamus (DMH/VMH) did not elicit a significant increase in locomotor behavior. These results suggest that both the physiological and locomotor components of the hypothalamic defense reaction may be under tonic GABAergic inhibition in the region of the posterior hypothalamus.


Solar water disinfection (SODIS): Impact on hepatitis A virus and on a human Norovirus surrogate under natural solar conditions.
This study evaluates the effectiveness of solar water disinfection (SODIS) in the reduction and inactivation of hepatitis A virus (HAV) and of the human Norovirus surrogate, murine Norovirus (MNV-1), under natural solar conditions. Experiments were performed in 330 ml polyethylene terephthalate (PET) bottles containing HAV or MNV-1 contaminated waters (10(3) PFU/ml) that were exposed to natural sunlight for 2 to 8 h. Parallel experiments under controlled temperature and/or in darkness conditions were also included. Samples were concentrated by electropositive charged filters and analysed by RT-real time PCR (RT-qPCR) and infectivity assays. Temperature reached in bottles throughout the exposure period ranged from 22 to 40ºC. After 8 h of solar exposure (cumulative UV dose of ~828 kJ/m2 and UV irradiance of ~20 kJ/l), the results showed significant (P<0.05) reductions from 4.0 (+/-0.56)x10(4) to 3.15 (+/-0.69)x10(3) RNA copies/100ml (92.1%, 1.1 log) for HAV and from 5.91 (+/-0.59)x10(4) to 9.24 (+/-3.91)x10(3) RNA copies/100 ml (84.4%, 0.81 log) for MNV-1. SODIS conditions induced a loss of infectivity between 33.4% and 83.4% after 4 to 8 h in HAV trials, and between 33.4% and 66.7% after 6 h to 8 h in MNV-1 trials. The results obtained indicated a greater importance of sunlight radiation over the temperature as the main factor for viral reduction.


Cineangiographic study of the venous drainage of the femoral neck in children.
The purpose of the study was to examine the venous flow of the femoral neck using cineradiography, paying special attention to various draining routes and their sensitivity to disturbances. The cine technique served to show that changes seen in various diseases are not artefacts caused by changes of the position of the hip. In normal hips the preferred route for contrast medium was the medial circumflex vein. In internal rotation, flow through the gluteal vein was most easily disturbed, but contrast medium did not flow to the diaphysis. In hips with Perthes' disease, drainage through the veins of the neck was disturbed, and contrast medium flowed to the diaphysis. In postoperative hips the dominating draining route was the lateral circumflex vein.


Functional genetic variants of the IFN-λ3 (IL28B) gene and transcription factor interactions on its promoter.
Interferon lambda 3 (IFN-λ3 or IFNL3, formerly IL28B), a type III interferon, modulates immune responses during infection/inflammation. Several human studies have reported an association of single nucleotide polymorphisms (SNP) in the IFNL3 locus with expression level of IFNL3. Previous genetic studies, in the context of hepatitis C virus infections, had predicted three regulatory SNPs: rs4803219, rs28416813 and rs4803217 that could have functional/causal roles. Subsequent studies confirmed this prediction for rs28416813 and rs4803217. A dinucleotide TA-repeat variant (rs72258881) has also been reported to be regulating the IFN-λ3 promoter. In this study, we tested all these genetic variants using a sensitive reporter assay. We show that the minor/ancestral alleles of both rs28416813 and rs4803217, together have a strong inhibitory effect on reporter gene expression. We also show an interaction between the two principal transcription factors regulating IFNL3 promoter: IRF7 and NF-kB RelA/p65. We show that IRF7 and p65 physically interact with each other. By using a transient ChIP assay, we show that presence of p65 increases the promoter occupancy of IRF7, thereby leading to synergistic activation of the IFNL3 promoter. We reason that, in contrast to p65, a unique nature of IRF7 binding to its specific DNA sequence makes it more sensitive to changes in DNA phasing. As a result, we see that IRF7, but not p65-mediated transcriptional activity is affected by the phase changes introduced by the TA-repeat polymorphism. Overall, we see that three genetic variants: rs28416813, rs4803217 and rs72258881 could have functional roles in controlling IFNL3 gene expression.


Microbiota is structured by gut regions, life stage, and diet in the Black Soldier Fly (Hermetia illucens).
The larvae of the Black Soldier Fly (Hermetia illucens) provide numerous ecological benefits, leading to significant commercial advancements. These benefits include the bioconversion of low-value waste into high-value feed and soil amendments. Understanding how the bacterial and eukaryotic microbiota communities affect host performance becomes vital for the optimization and specialization of industrial-scale rearing. This study investigates H. illucens-associated microbiota taxonomic composition and dynamics across the developmental cycle (eggs, neonates, larvae, prepupae, and imago X0 to second generation X1) when reared on two substrates: (i) plant-based (Housefly Gainesville diet) and (ii) animal-based (poultry hatchery waste). By using the 16S gene amplicon metataxonomic approach, we found that the results revealed that bacterial microbiota inherited from parents reared on a different substrate may have induced dysbiosis in the progeny. Specifically, the interaction networks of individuals reared on hatchery waste showed a high prevalence of negative interactions and low connectivity. Proteobacteria (39-92%), Firmicutes (4-39%), Bacteroidota (1-38%), and Actinobacteria (1-33%). In animal feed-reared individuals, Firmicutes reached the highest relative abundance (10-80%), followed by Proteobacteria (6-55%), Actinobacteria (1-31%), and Bacteroidota (0-22%). The rearing substrate was the main driver of microbiota composition, while the developmental stage influenced only the whole individual's bacterial microbiota composition. Gut regions were associated with distinct bacterial composition and richness, with diversity decreasing along the digestive tract. For the first time, microeukaryotes of the microbiota other than Fungi were investigated using 18S genetic marker amplicon sequencing with novel blocking primers specific to the Black Soldier Fly. Microeukaryotes are a neglected part of multitrophic microbiota communities that can have similar effects on their hosts as bacterial microbiota. Microeukaryotes from seven orders were identified in black soldier flies, including potential pathogens (e.g., Aplicomplexa group). Nucletmycea were the dominant class throughout development, followed by Holozoa and Stramenophiles. The eukaryote microbiota was structured by developmental stages but not by gut regions. Insights from this study are a stepping stone toward the microbiological optimization of black soldier flies for industrial rearing, highlighting how a synthetic microbiota assembly should be tailored to the rearing environment of the larvae at a targeted developmental stage.


Risk Factors for Outpatient Use of Antibiotics in Children with Acute Respiratory Illnesses.
Antibiotics for acute respiratory illness (ARI) constitute most pediatric medication use and contribute to the emergence of antimicrobial resistance. We investigated antibiotic prescription risk factors for ARI in pediatric clinics and clinical follow-up in individuals prescribed and not prescribed antibiotics. In this observational study, we enrolled children ages 2 to 17 years old presenting with ARI with fever to two academic pediatric primary care outpatient clinics during influenza season 2013-2014. We collected information on demographics, initial symptoms, medical conditions, laboratory tests, discharge diagnoses, treatments, and 30 days of follow-up medical encounters. Factors associated with antibiotic prescription receipt were evaluated using logistic regression. Of 206 consented and enrolled children, 59 (29%) were prescribed antibiotics, 51 of 59 (86%) for indicated diagnoses: 34 for streptococcal pharyngitis, 15 for acute otitis media (AOM), and 2 for pneumonia. Discharge diagnoses were the only factors independently associated with an antibiotic prescription. Of children prescribed/not prescribed an antibiotic, 17%/17% received follow-up telephone calls and 27%/17% had follow-up visits related to ARI within 30 days. Two children with AOM were prescribed a second antibiotic during follow-up, and one developed Clostridium difficile colitis. Eighteen of 206 (9%) additional children were prescribed antibiotics within 30 days for ARI symptoms, 17 for streptococcal pharyngitis, AOM, pneumonia, or sinusitis; one was prescribed antibiotics for influenza-like illness. Among study children 2 to 17 years old with outpatient ARI, 29% were prescribed antibiotics at the initial visit and another 9% were prescribed antibiotics during the 30-day follow-up (most were for appropriate indications). Further decreasing antibiotic use in similar settings will likely require wider implementation of watchful waiting for AOM, a change in guidelines for pharyngitis management, and/or reductions in these diseases.


Observations on the use of ready-to-use and point-of-care activated parenteral products in automated dispensing cabinets in U.S. hospitals.
The use of ready-to-use (RTU) and point-of-care (POC) activated parenteral products and their storage in automated dispensing cabinets (ADCs) in U.S. hospitals were evaluated. A survey on the use of RTU and POC activated parenteral products, including storage and dispensing of the products, was developed and sent electronically to hospital pharmacy administrators. Survey respondents were identified using the American Society of Health-System Pharmacists' member database. Of the 4070 surveys sent, 965 (23.7%) were completed and returned. Most pharmacy administrators (94.7%) reported that their institution used some form of RTU and POC activated parenteral product, with 74% using ADCs to dispense these products. Efficiency was the most common reason cited for storage of RTU and POC activated products in ADCs. Facilities varied on reasons for not implementing this technology, with 47 facilities citing implementation costs, limited number of RTU and POC activated products on the hospital's formulary, lack of available pediatric formulations, and safety concerns as the main reasons. More than half of respondents noted space limitations as the greatest challenge to adding RTU and POC activated products to ADCs. Nearly three fourths of survey respondents reported using RTU and POC products in conjunction with ADCs; however, the approach to including these products in ADCs varied based on the characteristics, policies, and preferences of the individual facility. Advantages of RTU and POC products identified by respondents included enhanced safety benefits, increased dispensing efficiency, cost avoidance due to reduced waste, and improved compliance with federal and state regulations.


Effect of intravitreal or sub-tenon triamcinolone acetonide injection at completion of vitrectomy on peripheral retinochoroidal thickness in eyes with proliferative diabetic retinopathy.
The effect of triamcinolone acetonide (TA) on the peripheral retinochoroidal thickness was determined after pars plana vitrectomy (PPV) with scatter photocoagulation in eyes with proliferative diabetic retinopathy. The peripheral retinochoroidal thickness was measured at 5 mm from the limbus in the four quadrants using anterior segment optical coherence tomography before, and 3 days, and 1 and 2 weeks after the surgery. The total peripheral thickness was significantly thicker than the baseline thickness after PPV alone (P < 0.001; 18 eyes), PPV combined with intravitreal TA injection (IVTA; P = 0.011; 19 eyes), and PPV combined with sub-tenon TA injection (STTA; P = 0001; 23 eyes). The total peripheral thickness in the PPV group at 3 days after surgery was significantly thicker than that of the PPV + IVTA (P = 0.015) and of the PPV + STTA groups (P = 0.016). Multiple linear regression analyses showed that the injection of TA by the two routes and the number of photocoagulation burns were significantly correlated with the total peripheral thicknesses at 3 days after the surgery. The results indicate that the PPV with large number of intraoperative scatter photocoagulation burns caused an increase in the total peripheral thickness and an administration of either IVTA and STTA can reduced the degree of thickening.


Structure-Function Analysis of the GlyR α2 Subunit Autism Mutation p.R323L Reveals a Gain-of-Function.
Glycine receptors (GlyRs) containing the α2 subunit regulate cortical interneuron migration. Disruption of the GlyR α2 subunit gene (Glra2) in mice leads to disrupted dorsal cortical progenitor homeostasis, leading to a depletion of projection neurons and moderate microcephaly in newborn mice. In humans, rare variants in GLRA2, which is located on the X chromosome, are associated with autism spectrum disorder (ASD) in the hemizygous state in males. These include a microdeletion (GLRA2∆ex8-9) and missense mutations in GLRA2 (p.N109S and p.R126Q) that impair cell-surface expression of GlyR α2, and either abolish or markedly reduce sensitivity to glycine. We report the functional characterization of a third missense variant in GLRA2 (p.R323L), associated with autism, macrocephaly, epilepsy and hypothyroidism in a female proband. Using heterosynapse and macroscopic current recording techniques, we reveal that GlyR α2R323L exhibits reduced glycine sensitivity, but significantly increased inhibitory postsynaptic current (IPSC) rise and decay times. Site-directed mutagenesis revealed that the nature of the amino acid switch at position 323 is critical for impairment of GlyR function. Single-channel recordings revealed that the conductance of α2R323Lβ channels was higher than α2β channels. Longer mean opening durations induced by p.R323L may be due to a change in the gating pathway that enhances the stability of the GlyR open state. The slower synaptic decay times, longer duration active periods and increase in conductance demonstrates that the GlyR α2 p.R323L mutation results in an overall gain of function, and that GlyR α2 mutations can be pathogenic in the heterozygous state in females.


Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study.
Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence. This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types. During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (ptrend<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (ptrend<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (prend<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status. Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types. World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.


[Clinical associations between photoreceptor status and visual outcomes in diabetic macular edema].
to investigate morphological changes and visual acuity response to ranibizumab therapy in patients with different OCT-types of diabetic macular edema (DME) as well as different state of the inner and outer photoreceptor segments (IS and OS) and the outer limiting membrane (OLM); to study relationships between functional and morphological parameters before and after the treatment; to study the effect of glycated hemoglobin levels on morphological parameters and ME duration. The study included 113 patients (113 eyes) with DME, who underwent 3 once-monthly intravitreal injections of ranibizumab (the mean patient age, 63.5±2.2 years; men, 51.3%; type 2 diabetes, 81.4%). Basing on the results of OCT, 3 groups were formed: group 1 (40 patients) - intact IS and OS; group 2 (32 patients) - disturbed photoreceptor segments integrity, but intact OLM; group 3 (41 patients) - destruction of both layers. Visual acuity at baseline and after the treatment was the highest in group 1 (p<0.05). In all groups, most parameters that indicated the state of photoreceptor segments and the OLM improved. Correlation analysis revealed a statistically significant negative correlation between visual acuity at baseline and after the treatment and morphological parameters (p<0.05). There was also a direct correlation between the morphometric parameters at baseline and after the treatment (p<0.05). The most favorable type of DME in terms of preserving the integrity of photoreceptor segments and the OLM was sponge-like edema, while DME with neuroepithelial detachment and mixed-type DME were prognostically unfavorable. Moreover, the state of photoreceptors and the OLM depended on the duration of ME and the level of glycated hemoglobin. Thus, the integrity of the inner and outer photoreceptor segments as well as the outer limiting membrane can contribute to prognosis for functional outcomes in DME patients that receive antiangiogenic therapy.


Solid-vapour reactions as a post-synthetic modification tool for molecular crystals: the enclathration of benzene and toluene by Werner complexes.
The enclathration of benzene and toluene by Werner complexes has been described. In the case of toluene, time-lapse PXRD analysis reveals that solid-liquid and solid-vapour reactions proceed according to different pathways. These preliminary results suggest that solid-liquid reactions destroy the host structure, whereas the solid-vapour reactions allow post-synthetic modification.


Influence of embolism and imipramine on kinetics of serotonin uptake by dog lung.
We previously presented a model from which the kinetic parameters Km and Vmax for serotonin uptake by the lung can be obtained from multiple indicator-dilution data. The purpose of the present study was to determine whether experimentally induced changes in lung endothelial function would be revealed in the kinetic parameters calculated using the model. In experiments using isolated dog lung lobes, embolization with 550-microns glass beads was used to reduce the vascular volume and perfused surface area. Imipramine was used to inhibit the serotonin uptake mechanism. In addition, we studied the influence of the vasodilator papaverine, which in previous studies had been used to block the serotonin-induced vasoconstriction. Embolization, imipramine, and papaverine all significantly reduced percentage uptake of serotonin. The kinetic analysis revealed a significant decrease in the maximum serotonin uptake rate (Vmax) with all three experimental manipulations. In addition, imipramine significantly increased Km. The results indicate that the kinetic parameters obtained from the model do respond to transport inhibition and changes in endothelial surface area, further supporting their usefulness as indexes of endothelial function.