EVOLUTION OF THE IEC AND EN STANDARDS FOR INDIVIDUAL MONITORING OF IONISING RADIATION.
This article presents the evolution of the International Electrotechnical Commission (IEC) and the European standards for individual monitoring of ionising radiation issued, respectively, from the committees IEC/Sub Committee 45B and European Committee for Electro-technical Standardization/Technical Committee 45B 'Radiation protection instrumentation'. Standards for passive individual photon and beta dosimetry systems as well as those for active individual monitors are discussed. A neutron ambient dose equivalent (rate) meter standard and a technical report concerning the determination of uncertainty in measurement are also covered.


Credibility of vaccine-related content on Twitter during COVID-19 pandemic.
During national COVID-19 vaccine campaigns, people continuously engaged on Twitter to receive updates on the latest public health information, and to discuss and share their experiences. During this time, the spread of misinformation was widespread, which threatened the uptake of vaccines. It is therefore critical to understand the reasons behind vaccine misinformation and strategies to mitigate it. The current research aimed to understand the content of misleading tweets and the characteristics of their corresponding accounts. We performed a machine learning approach to identify misinformation in vaccine-related tweets, and calculated the demographic, engagement metrics and bot-like activities of corresponding accounts. We found critical periods where high amounts of misinformation coincided with important vaccine announcements, such as emergency approvals of vaccines. Moreover, we found Asian countries had a lower percentage of misinformation shared compared to Europe and North America. Our results showed accounts spreading misinformation had an overall 10% greater likelihood of bot activity and 15% more astroturf bot activity than accounts spreading accurate information. Furthermore, we found that accounts spreading misinformation had five times fewer followers and three times fewer verified badges than fact-sharing accounts. The findings of this study may help authorities to develop strategies to fight COVID-19 vaccine misinformation and improve vaccine uptake.


'Your Tube': the role of different diets in children who are gastrostomy fed: protocol for a mixed methods exploratory sequential study.
Increasing numbers of children require having all, or part, of their nutritional intake via gastrostomy. More parents are using home-blended meals to feed their children, with many reporting beneficial effects such as improved gastro-oesophageal reflux, less constipation and less distress in their child.This study aims to identify the important outcomes of tube feeding in this population, compare the safety, outcomes and resource use of those on a home-blended diet compared with a formula diet and assess feasibility of long-term follow-up of children recruited to this study. This is a mixed methods study of children (aged 6 months to 18 years) who are gastrostomy feed dependent recruited via general, community and specialist paediatric and dietetic services. Workstream1 (WS1): a qualitative study involving semistructured interviews with parents (n~20) and young people (n~5-10), and focus groups with health professionals (n~25), will provide evidence of appropriate outcome measures and the feasibility/acceptability of proposed data collection methods for WS2. It will gather data on: desired outcomes of gastrostomy feeding, variability in diets and reasons; use of oral feeding; perceived benefits of the alternative diets, resources associated with gastrostomy feeding and safety issues. Data will be analysed using thematic analysis. WS2: a cohort study of 300 children who are gastrostomy fed. Data will be collected at months 0, 9 and 18 from parents, children (if appropriate) and clinicians using standardised measures and questionnaires developed specifically for the study. Data collected will include gastrointestinal symptoms, health and other outcomes (child, parent), dietary intake, anthropometry, healthcare usage, safety outcomes and resource use. Outcomes in the home-blended and formula groups will be compared using appropriate multiple regression analyses. The study has been approved by a research ethics committee (REC reference: 19/YH/0028). Results will be disseminated through publications and presentations for professionals and families. ISRCTN13977361.


Impaired regulation of brain mitochondria by extramitochondrial Ca2+ in transgenic Huntington disease rats.
Huntington disease (HD) is characterized by polyglutamine expansions of huntingtin (htt), but the underlying pathomechanisms have remained unclear. We studied brain mitochondria of transgenic HD rats with 51 glutamine repeats (htt(51Q)), modeling the adult form of HD. Ca(free)(2+) up to 2 mum activated state 3 respiration of wild type mitochondria with glutamate/malate or pyruvate/malate as substrates. Ca(free)(2+) above 2 mum inhibited respiration via cyclosporin A-dependent permeability transition (PT). Ruthenium red, an inhibitor of the mitochondrial Ca(2+) uniporter, did not affect the Ca(2+)-dependent activation of respiration but reduced Ca(2+)-induced inhibition. Thus, Ca(2+) activation was mediated exclusively by extramitochondrial Ca(2+), whereas inhibition was promoted also by intramitochondrial Ca(2+). In contrast, htt(51Q) mitochondria showed a deficient state 3 respiration, a lower sensitivity to Ca(2+) activation, and a higher susceptibility to Ca(2+)-dependent inhibition. Furthermore htt(51Q) mitochondria exhibited a diminished membrane potential stability in response to Ca(2+), lower capacities and rates of Ca(2+) accumulation, and a decreased Ca(2+) threshold for PT in a substrate-independent but cyclosporin A-sensitive manner. Compared with wild type, Ca(2+)-induced inhibition of respiration of htt(51Q) mitochondria was less sensitive to ruthenium red, indicating the involvement of extramitochondrial Ca(2+). In conclusion, we demonstrate a novel mechanism of mitochondrial regulation by extramitochondrial Ca(2+). We suggest that specific regulatory Ca(2+) binding sites on the mitochondrial surface, e.g. the glutamate/aspartate carrier (aralar), mediate this regulation. Interactions between htt(51Q) and distinct targets such as aralar and/or the PT pore may underlie mitochondrial dysregulation leading to energetic depression, cell death, and tissue atrophy in HD.


Veterinary nursing champion.
Belinda Andrews-Jones was recently appointed director of veterinary nursing at CVS; she is currently studying for a Masters degree in veterinary education.


Heterogeneity of schizophrenia.
One of the difficulties in defining schizophrenia is the possibility of its heterogeneity. Schizophrenia may be divided into organic and idiopathic on the basis of precipitating factors; the difference between the two is supported by evidence from family studies and differences in symptomatology. A further division of idiopathic schizophrenia may be made into typical and atypical schizophrenia based on differences in clinical features, family history, mode of inheritance, and prognosis. There is suggestive evidence that within typical schizophrenia, paranoid and nonparanoid subtypes may be idstinguished due to clinical and family differences. Within nonparanoid schizophrenia, simple, catatonic, and hebephrenic schizophrenia may also prove to be distinct entities. The available evidence for differentiating the subtypes of typical schizophrenia is inconclusive to date. However, several recent developments in the methodology of family research may lead to more convincing findings for differentiating subtypes within typical schizophrenia.


Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood.
Exposed subendothelial collagen acts as a substrate for platelet adhesion and thrombus formation after vascular injury. Synthetic collagen-derived triple-helical peptides, designated collagen-related peptide (CRP), GFOGER, and VWF-III, can specifically engage the platelet collagen receptors, glycoprotein VI and integrin alpha(2)beta(1), and plasma von Willebrand factor (VWF), respectively. Hitherto, the role of these 3 collagen-binding axes has been studied indirectly. Use of these uniform peptide substrates, rather than collagen fibers, provides independent control of each axis. Here, we use confocal imaging and novel image analysis techniques to investigate the effects of receptor-ligand engagement on platelet binding and activation during thrombus formation under flow conditions. At low shear (100s(-1) and 300s(-1)), both GFOGER and CRP are required for thrombus formation. At 1000s(-1), a combination of either CRP or GFOGER with VWF-III induces comparable thrombus formation, and VWF-III increases thrombus deposition at all shear rates, being indispensable at 3000s(-1). A combination of CRP and VWF-III is sufficient to support extensive platelet deposition at 3000s(-1), with slight additional effect of GFOGER. Measurement of thrombus height after specific receptor blockade or use of altered proportions of peptides indicates a signaling rather than adhesive role for glycoprotein VI, and primarily adhesive roles for both alpha(2)beta(1) and the VWF axis.


[Blood-activating and anti-inflammatory actions of Polygala fallax].
To observe the blood-activating and anti-inflammatory actions of Polygala fallax Hesml. (PFH) in this paper. A series of experiments were performed to show the blood-activating and anti-inflammatory actions of PFH, including acute blood-stagnation model in rats induced by dextran of high molecular mass, observation on microcirculation in mice, platelet aggregation in vitro in rabbits, acute inflammation in mice induced by xylene or histamine, and PC-DTH. PFH could remarkably decrease the whole blood relative viscosity. PFH could significantly dilate the micro-artery and micro-vein, increase the opening number of capillary in mice. However, PFH had no obvious effect on platelet aggregation induced by ADP in rabbits. PFH could significantly inhibit the increase of capillary permeability induced by histamine in mice, and decrease the mice ear-swelling induced by xylene. PFH could remarkably inhibit the induction-phase and attack-phase of PC-DTH in mice. The results suggested that PFH could improve the hemorrheologic character in blood-stagnation state, invigorate the micro-circulation, and inhibit inflammation process.


Laparoscopic management of abdominopelvic abscesses in tropical pyomyositis.
Tropical pyomyositis is a suppurative infectious disease of skeletal muscles. The most common causative organism is Staphylococcus aureus. Penicillin-resistant strains are frequently encountered. Abscesses may develop in muscle groups or body cavities remotely located from one another. We report a case of tropical pyomyositis presenting as a suppurative process in the left foreleg. Further workup, including CT scanning, demonstrated large, multi-loculated intraabdominal and pelvic abscesses. The abdominal and pelvic components were managed by laparoscopic exploration and drainage. This is the first known report of laparoscopic management of abdominopelvic abscesses associated with tropical pyomyositis.


ELISA reagent coverage evaluation by affinity purification tandem mass spectrometry.
Host cell proteins (HCPs) must be adequately removed from recombinant therapeutics by downstream processing to ensure patient safety, product quality, and regulatory compliance. HCP process clearance is typically monitored by enzyme-linked immunosorbent assay (ELISA) using a polyclonal reagent. Recently, mass spectrometry (MS) has been used to identify specific HCP process impurities and monitor their clearance. Despite this capability, ELISA remains the preferred analytical approach due to its simplicity and throughput. There are, however, inherent difficulties reconciling the protein-centric results of MS characterization with ELISA, or providing assurance that ELISA has acceptable coverage against all process-specific HCP impurities that could pose safety or efficacy risks. Here, we describe efficient determination of ELISA reagent coverage by proteomic analysis following affinity purification with a polyclonal anti-HCP reagent (AP-MS). The resulting HCP identifications can be compared with the actual downstream process impurities for a given process to enable a highly focused assessment of ELISA reagent suitability. We illustrate the utility of this approach by performing coverage evaluation of an anti-HCP polyclonal against both an HCP immunogen and the downstream HCP impurities identified in a therapeutic monoclonal antibody after Protein A purification. The overall goal is to strategically implement affinity-based mass spectrometry as part of a holistic framework for evaluating HCP process clearance, ELISA reagent coverage, and process clearance risks. We envision coverage analysis by AP-MS will further enable a framework for HCP impurity analysis driven by characterization of actual product-specific process impurities, complimenting analytical methods centered on consideration of the total host cell proteome.


Meals based on cod or veal in combination with high or low glycemic index carbohydrates did not affect diet-induced thermogenesis, appetite sensations, or subsequent energy intake differently.
The objective of this study was to investigate the acute effects of meals containing protein from either cod or veal in combination with high or low glycemic index (GI) carbohydrates, on diet-induced thermogenesis (DIT) (primary endpoint), appetite, energy intake (EI), as well as postpranidal ghrelin, glucose, and insulin responses. Twenty-three overweight men and women (mean ± SD age: 30.0 ± 7.6 y, BMI: 27.2 ± 1.4 kg/m2) consumed 4 test meals: cod with mashed potatoes (high GI carbohydrate), cod with wholegrain pasta (low GI carbohydrate), veal with mashed potatoes, and veal with wholegrain pasta (∼2010 kJ, ∼25.5 E% protein, ∼41.0 E% carbohydrate, ∼33.5 E% fat). Energy expenditure was measured at baseline and six times postprandially, each lasting 25 min. Additionally, appetite sensations were measured every half hour. Arterialized venous blood samples were drawn every 20 min until an ad libitum buffet-style lunch was served 3.5 h later. DIT did not differ between test meals (P > 0.05), and there were no differences in appetite sensations or ad libitum EI (all, P > 0.05). Meal-time interactions were found for glucose and insulin (P = 0.04 and P < 0.001). Pairwise comparisons revealed that glucose and insulin peaks were higher after the meals with high GI carbohydrates. No differences were found between meals with cod or veal in combination with carbohydrates with low or high GI on DIT, appetite sensations, or EI in overweight men and women. However, as expected meals with high GI carbohydrates resulted in higher glucose and insulin responses compared to meals with low GI carbohydrates regardless of protein source.


Digital replantation in forward surgical units: a cases study.
Noncombat-related hand injuries are common in current theatres of operations. Crushing is one of the most frequent mechanisms that may cause traumatic amputations of digits. In the military setting, management of these digital amputations is challenging regarding limitation in microsurgical means in medical treatment facilities and aeromedical evacuation delays out of the combat zone. Two cases of digital replantation performed in French forward surgical units are described. The first case was a complete distal amputation of the medius which was successfully replanted in the operating theatre of an aircraft carrier. No complication was observed after evacuation. Functional and aesthetic results were excellent. The second case was a ring finger avulsion revascularized in a role 2 facility in Central African Republic. Unfortunately, revascularization failed due to arterial thrombosis during evacuation. Digital, hand or more proximal upper extremity replantation may be considered for isolated amputations due to work-related accidents within the combat zone. For a surgeon trained to microsurgery, a microsurgical set and magnification loupes enable to attempt such procedures in austere conditions. The authors propose an algorithm of management in the field according to the type and level of amputation.


Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression.
In myelofibrosis, pathologically enhanced extracellular matrix production due to aberrant cytokine signalling and clonal megakaryocyte functions result(s) in impaired hemopoiesis. Disease progression is still determined by detecting reticulin and collagen fibrosis with Gomori's silver impregnation. Here, we tested whether the expression growth related biomarkers L-NGFR/CD271, phospho-ERK1-2 and CXCL12 can be linked to the functional activation of bone marrow stromal cells during primary myelofibrosis progression. Immunoscores for all tested biomarkers showed varying strength of positive statistical correlation with the silver impregnation based myelofibrosis grades. The intimate relationship between spindle shaped stromal cells positive for all three markers and aberrant megakaryocytes was likely to reflect their functional cooperation. L-NGFR reaction was restricted to bone marrow stromal cells and revealed the whole length of their processes. Also, L-NGFR positive cells showed the most intersections, the best statistical correlations with myelofibrosis grades and the strongest interrater agreements. CXCL12 reaction highlighted stromal cell bodies and a weak extracellular staining in line with its constitutive release. Phospho-ERK1-2 reaction showed a similar pattern to CXCL12 in stromal cells with an additional nuclear staining in agreement with its role as a transcription factor. Both p-ERK1-2 and CXCL12 were also expressed at a moderate level in sinus endothelial cells. Connexin 43 gap junction communication channels, known to be required for CXCL12 release to maintain stem cell niche, were also expressed progressively in the myelofibrotic stromal network as a support of compartmental functions. Our results suggest that, diverse growth related pathways are activated in the functionally coupled bone marrow stromal cells during myelofibrosis progression. L-NGFR expression can be a useful biological marker of stromal cell activation which deserves diagnostic consideration for complementing Gomori's silver impregnation.


Free fatty acid profiling in marine algae extract by LC-MS/MS and isolation as well as quantification of the ω-3 fatty acid hexadeca-4,7,10,13-tetraenoic acid.
Undaria pinnatifida (Wakame) alga contains high amounts of hexadeca-4Z,7Z,10Z,13Z-tetraenoic acid which was reported to decrease the efficiency of cisplatin chemotherapeutics. To obtain a fatty acid enriched extract of this ω-3 poly-unsaturated fatty acid as an analytical standard, Wakame was used as source material for its extraction. A two-step extraction protocol consisting of a liquid-liquid extraction followed by solid-phase extraction with 3-aminopropyl silica in accordance to a normal-phase elution mode was developed. An ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method based on sequential windowed acquisition of all theoretical fragment ion mass spectra allowed a simultaneous comprehensive group selective fatty acids profiling in untargeted manner and quantitative analysis of the targeted fatty acid. Hexadeca-4Z,7Z,10Z,13Z-tetraenoic acid was identified using high-resolution product ion spectra. The quantitative method was based on d5-deuterated hexadeca-4Z,7Z,10Z,13Z-tetraenoic acid which was employed as surrogate calibrant. Preliminary method validation was performed by evaluating detection and quantification limits, linear range, intra-assay and inter-day precision. Finally, a concentration of 421.2 ± 14.9 ng/mL (4% CV) of hexadeca-4Z,7Z,10Z,13Z-tetraenoic acid was determined in the extract which was further used as analytical standard.


Spiral Gradient Coil Design for Use in Cylindrical MRI Systems.
In magnetic resonance imaging, the stream function based method is commonly used in the design of gradient coils. However, this method can be prone to errors associated with the discretization of continuous current density and wire connections. In this paper, we propose a novel gradient coil design scheme that works directly in the wire space, avoiding the system errors that may appear in the stream function approaches. Specifically, the gradient coil pattern is described with dedicated spiral functions adjusted to allow the coil to produce the required field gradients in the imaging area, minimal stray field, and other engineering terms. The performance of a designed spiral gradient coil was compared with its stream-function counterpart. The numerical evaluation shows that when compared with the conventional solution, the inductance and resistance was reduced by 20.9 and 10.5%, respectively. The overall coil performance (evaluated by the figure of merit (FoM)) was improved up to 26.5% for the x -gradient coil design; for the z-gradient coil design, the inductance and resistance were reduced by 15.1 and 6.7% respectively, and the FoM was increased by 17.7%. In addition, by directly controlling the wire distributions, the spiral gradient coil design was much sparser than conventional coils.


Long-term management and outcome of lung transplantation in Japan.
The long-term survival after lung transplantation (LT) is favorable in Japan. However, long-term survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan.


Brunner's Gland Hyperplasia: A Massive Duodenal Lesion.
A 57-year-old male with a history of gastroesophageal reflux disease and esophageal strictures presented with melena and abdominal pain. He underwent an esophagogastroduodenoscopy, which revealed a 5-cm duodenal bulb mass causing partial obstruction of the gastric outlet. Endoscopic ultrasound showed a 5-cm, hypoechoic lesion, arising from the mucosal layer, with a large blood vessel feeding the lesion. Biopsy revealed benign Brunner's gland hyperplasia. The large mass was causing symptomatic obstruction of the pylorus and iron deficiency anemia, and had risk for malignant transformation. Due to its size it was not amenable to endoscopic removal. Subsequently, he underwent exploratory laparotomy with pyloroplasty, duodenotomy and partial duodenal resection. Surgical pathology showed Brunner's gland hyperplasia and was negative for malignancy.


Dissociating proportion congruent and conflict adaptation effects in a Simon-Stroop procedure.
Proportion congruent and conflict adaptation are two well known effects associated with cognitive control. A critical open question is whether they reflect the same or separate cognitive control mechanisms. In this experiment, in a training phase we introduced a proportion congruency manipulation for one conflict type (i.e. Simon), whereas in pre-training and post-training phases two conflict types (e.g. Simon and Spatial Stroop) were displayed with the same incongruent-to-congruent ratio. The results supported the sustained nature of the proportion congruent effect, as it transferred from the training to the post-training phase. Furthermore, this transfer generalized to both conflict types. By contrast, the conflict adaptation effect was specific to conflict type, as it was only observed when the same conflict type (either Simon or Stroop) was presented on two consecutive trials (no effect was observed on conflict type alternation trials). Results are interpreted as supporting the reactive and proactive control mechanisms distinction.


Do low levels of alanine aminotransferase, a baseline marker of sarcopenia and frailty, associate with worse clinical outcomes among hospitalized COVID-19 patients? A Retrospective Cohort Study.
COVID-19 geoperdize lives. Not all the risk factors for negative outcomes are known. Sarcopenia and frailty are common, negatively affecting clinical outcomes. Studies have shown that sarcopenia and frailty are associated with worse outcomes. Our objective was to examine whether low ALT (Alanine-aminotranferase), a surrogate marker for sarcopenia, is associated with worse clinical outcomes among hospitalized COVID-19 patients. We reviewed cases of COVID-19 in a tertiary hospital, during three COVID-19 waves and examined correlations between ALT and mortality using crude, univariate and multivariate analysis for age, gender, hypertension, Chronic obstructive pulmonary disease and Congestive heart failure. 357 patients were included in this analysis. Median age was 69, 54% were males. Median ALT was 19 IU/L. During follow-up, 73 (20%) died. Patients with low ALT were more likely to die (HR 1.82, 95% CI 1.06-3.09, P=0.028). Other predictors for mortality were low albumin, background COPD, dyslipidemia, dementia, and malignancy. The multivariate analysis showed that low ALT was still an independent predictor of poor prognosis (HR 1.7, 95% CI 1.0-2.9, P=0.049). In our analysis of COVID-19 patients, low ALT levels were independently associated with increased risk of mortality, both as standalone and when incorporated into a multivariate analysis.


Pushing the limit: Resilience of an Arctic copepod to environmental fluctuations.
Life history strategies such as multiyear life cycles, resting stages, and capital breeding allow species to inhabit regions with extreme and fluctuating environmental conditions. One example is the zooplankton species Calanus hyperboreus, whose life history is considered an adaptation to the short and unpredictable growth season in the central Arctic Ocean. This copepod is commonly described as a true Arctic endemic; however, by statistically analyzing compiled observational data, we show that abundances are relatively low and later stages and adults dominate in the central Arctic Ocean basins, indicating expatriation. Combining data analyses with individual-based modeling and energy requirement estimation, we further demonstrate that while C. hyperboreus can reach higher abundances in areas with greater food availability outside the central Arctic basins, the species' resilience to environmental fluctuations enables the life cycle to be completed in the central Arctic basins. Specifically, the energy level required to reach the first overwintering stage-a prerequisite for successful local production-is likely met in some-but not all-years. This fine balance between success and failure indicates that C. hyperboreus functions as a peripheral population in the central Arctic basins and its abundance will likely increase in areas with improved growth conditions in response to climate change. By illustrating a key Arctic species' resilience to extreme and fluctuating environmental conditions, the results of this study have implications for projections of future biogeography and food web dynamics in the Arctic Ocean, a region experiencing rapid warming and sea ice loss.


[Effect of high-fat diet on expression of transient receptor potential vanilloid 1 in respiratory tract and dorsal root ganglion of mice].
To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability of sensory neurons. A total of 20 C57BL/6 mice were randomly divided into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored. After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic segments 3-4 were collected and immunohistochemical staining was performed. A patch clamp was used to measure the number of action potentials and TRPV1 current intensity in the DRG. After 7 weeks of feeding, the HFD group had significantly greater mean weight gain than the ND group (6.4±2.6 g vs 2.3±0.5 g; P<0.001). The HFD group had significantly higher expression of TRPV1 in the bronchus, pulmonary alveoli, and DRG than the ND group (P<0.05). Compared with the ND group, the HFD group had significant increases in the TRPV1 current intensity and number of action potentials in the DRG (P<0.05). High-fat diet induces a significant increase in body weight and leads to high expression of TRPV1 and high excitability in the respiratory system and the peripheral sensory neurons. This suggests that TRPV1 may be an important factor in the physiopathological mechanisms of bronchial hyperresponsiveness.


Pulmonary segmentectomy with tunneling stapler technique.
Pulmonary segmentectomy necessitates dissection of the lung parenchyma. Stapling is one method of dissecting the lung parenchyma. However, simple stapling of the segmental plane might result in restriction of residual lung inflation and a short margin from the lesion. Therefore, a technique of segmental plane dissection via staple incisions radially spreading out from the segmental bronchus stump has been developed, which is made possible by creating a tunnel passageway to maneuver the stapler's anvil. This procedure can reduce restriction of lung inflation and secure surgical margins from the lesion.


Polymer-Layer-Free Alignment for Fast Switching Nematic Liquid Crystals by Multifunctional Nanostructured Substrate.
A novel polymer-layer-free system for liquid-crystal alignment is demonstrated by various shaped indium tin oxide (ITO) patterns. Liquid crystals are aligned along the ITO line pattern and secondary sputtering lithography can change the shape of the ITO line pattern. Different shapes can control the direction and size of the pretilt angle. This effect eliminates defects and reduces the response time.


No association between schizophrenia susceptibility variants and macroscopic structural brain volume variation in healthy subjects.
Previous studies have suggested that genetic variants for schizophrenia susceptibility might contribute to structural brain volume variations in schizophrenia patients, including total brain volume, hippocampal volume, and amygdalar volume. However, whether these schizophrenia susceptibility variants are associated with macroscopic structural brain volume (i.e., intracranial volume, total brain volume, and hippocampal volume) in healthy subjects is still unclear. In this study, we investigated the associations between 47 schizophrenia susceptibility variants (from 25 well-characterized schizophrenia susceptibility genes) and cranial volume variation in a healthy Chinese sample (N = 1,013). We also extracted the association between these 47 schizophrenia risk variants and the macroscopic structural brain volume (intracranial volume, total brain volume and hippocampal volume) in a large healthy sample of European ancestry (ENIGMA sample, N = 5,775). We identified several single-nucleotide polymorphisms (SNPs) nominally associated with intracranial volume, total brain volume, and hippocampal volume at P < 0.05 (uncorrected). However, after Bonferroni corrections for multiple testing, no SNP showed significant association. Hence, our results do not support previous observations that schizophrenia susceptibility variants are associated with brain structure (e.g., hippocampal volume) in healthy individuals, and indicate that single schizophrenia risk variant may not contribute significantly to macroscopic brain structure (e.g., intracranial volume or hippocampal volume) variation in healthy subjects.


Genetic microdifferentiation in the Semai Senoi of Malaysia.
Blood samples, demographic and cultural data were collected from seven settlements of Semai Senoi, a swidden farming ethnic group of Malaysia. Three genetic loci (ABO blood group, hereditary ovalcytosis, and hemoglobin) were analyzed in a total sample of 546 individuals. These data indicate a considerable degree of genetic microdifferentiation in this area of the Semai distribution. Parent-offspring birthplace data (analyzed by means of a migration matrix) and settlement histories show that settlements are not strongly isolated. Genetic differences in the study area demonstrate a reasonable correspondence with migration and the history of the settlements. Genetic convergence also occurs through the addition of migrant groups to established populations leading to new patterns of marriage between donor and recipient groups. The genetic structure of the total Semai population through time thus comprises a mosaic of shifiting allele frequencies in a series of semi-isolated local populations.


[Trichoblastic fibroma].
A trichoblastic fibroma in the oval fossa of the left thigh of a 70 year old female is described. Basaloid cell complexes were surrounded by a moderately cellular, partly fibromyxoid stroma. Epithelial buds resembled the primitive hair germ which derives from the embryonal periderm. Epithelial layers, 1-2 cells thick, were enclosed in a hyalinized and condensed stroma. The development of a real hair bulb or a real hair matrix was not found.


Effects of eugenol on excitation-contraction coupling in skeletal muscle.
The effects of eugenol on the excitation-contraction coupling of the toad (Bufo paracnemis) sartorius were studied. Eugenol (0.1-2.5 mM) blocked the contracture induced by 80 mM K+. At 2.5 mM, it decreased the depolarization, induced by 80 mM K+, by 14 mV. This is not sufficient to explain the complete blockade of the potassium contracture. At higher concentrations (3-12 mM), eugenol induced contractures, without causing a depolarization of the membrane. Contractures were blocked by procaine and potentiated by caffeine and by cooling of the muscle. For concentrations of eugenol in the upper range of the dose-response curve (10 mM), the contracture was independent of the Ca++ concentration in the medium. At lower concentrations (5 mM), the contractures induced by eugenol were potentiated by divalent cations, in the order: Mg++ < Ba++ < Zn++ < Co++ < Ca++ < Mn++. We infer that the eugenol-induced contractures are caused, primarily, by a release of Ca++ from the sarcoplasmic reticulum and, secondarily, by a mechanism related to the presence of some divalent cations in the extracellular space.


Effect of Traumacel P on the growth of human dermal fibroblasts in vitro.
It has been postulated that Traumacel P, a haemostatic powder, might assist the wound-healing process. This in vitro study investigated the effect of the powder on human dermal fibroblasts. Experiments using fibroblasts from a 50-year-old donor were carried out using suspensions of Traumacel P ranging from 0.1 to 10.0 mg/ml. Dulbecco's Modified Eagle Medium with 10% or 0.4% foetal calf serum (FCS) and 5.5 mM or 25 mM glucose was used. The powder was either placed in contact with the cells or separated from them by a porous membrane. The response of the fibroblasts was assessed using the MTT assay. Concentrations of 0.5 mg/ml and 1.0 mg/ml stimulated the metabolic activity of the fibroblasts in both high and low glucose medium with 10% FCS, regardless of whether the powder was in contact with or separated from the cells. The greatest stimulation, to 174% of the controls, was produced by 0.5 mg/ml Traumacel P in low glucose/10% FCS with the powder in contact with the cells (p < 0.0001). Traumacel concentrations ranging from 0.5 to 5.0 mg/ml in 0.4% FCS significantly stimulated the metabolic activity of fibroblasts in low glucose medium, but not in the high glucose medium. These studies indicate that direct stimulation of fibroblast proliferation may be one of the ways in which Traumacel P aids the healing of ulcers observed in the clinic.


A five-patient prospective pilot study of a polycaprolactone based dermal filler for hand rejuvenation.
Hand rejuvenation is becoming more popular as a complementary procedure to facial treatments. Current options include the relatively invasive lipofilling and the less invasive dermal fillers treatments, of which the latter often is too short lasting. An ideal product would therefore be minimally invasive, however, providing longer lasting results. The objective of this pilot study is to evaluate the safety and efficacy of a polycaprolactone based dermal filler for hand rejuvenation. The dorsum of the hands of five subjects was treated with 1.0 mL polycaprolactone based dermal filler per hand. Subjects were seen for follow-up visits after 1, 4, 16, and 24 weeks. The results showed consistent and high patient satisfaction throughout the duration of the study using a Visual Analog Scale. Satisfaction was rated at 82% at 24 weeks and patients were 88% likely to return for repeat treatments on average. On the subject GAIS assessment, all subjects reported an improvement compared to pretreatment throughout the duration of the study. The physicians' GAIS results were very much improved (90%) and much improved (10%) compared to pretreatment throughout the 24 weeks follow-up. The data of this small pilot suggest that the polycaprolactone based dermal filler is safe, well tolerated and effective for hand rejuvenation, and potentially offers a valuable addition to the current treatment armamentum. Additional studies in a larger patient population should be performed to confirm these findings.


The progress in multiple myeloma.
Multiple myeloma (MM) is a neoplastic disease characterized by the proliferation of clonal plasma cells. This disease arises from an initial asymptomatic stage known as monoclonal gammopathy of unknown significance (MGUS). The clinical phenotype that lies between MGUS and MM is commonly known as smoldering multiple myeloma (SMM). In individuals with MGUS and SMM, the risk of progression to MM persists constantly. In MGUS, the progression rate to MM or a related malignancy is around 1% per year, while in SMM, the progression rate to MM is approximately 10% per year. Recently, myeloma was defined as a clonal proliferation of malignant plasma cells that results in end organ damage or myeloma-defining events. MM is a genetically complex disease that exhibits clinical and biological diversity. Currently, the revised International Staging System (R-ISS) is used for prognostication in newly diagnosed patients. For transplant-eligible patients with newly diagnosed MM, the standard of care treatment (SoC) regimen is induction therapy, followed by ASCT and maintenance therapy. In general, the recommended induction therapy is a triplet or quadruplet-agent therapy consisting of a proteasome inhibitor, an immunomodulatory compound, and/or a CD38 antibody in combination with dexamethasone. Myeloma patients who are ineligible for a transplant are typically treated with a triplet combination, which necessitates specialized knowledge of treatment adverse effects. Although the prognosis for patients with MM has significantly improved over time due to advances in treatment, the disease remains incurable and relapses are common. Because various immunotherapeutic agents, new drugs and combinations have become available, selecting the most effective treatment for patients with relapsed/refractory MM needs both art and science.


Cholesterol-conjugated let-7a mimics: antitumor efficacy on hepatocellular carcinoma in vitro and in a preclinical orthotopic xenograft model of systemic therapy.
A major challenge to the clinical utility of let-7 for hepatocellular carcinoma (HCC) therapy is the lack of an effective carrier to target tumours. We confirmed the high transfection efficiency of cholesterol-conjugated let-7a miRNA mimics (Chol-let-7a) in human HCC cells, as well as their high affinity for liver tissue in nude mice. However, their antitumor efficacy via systemic delivery remains unknown. We explored the effects of Chol-let-7a on HCC in vitro and in vivo. Cell viability and mobility, let-7a abundance and the target ras genes was measured. Live-cell image and cell ultrastructure was observed. Antitumor efficacy in vivo was analyzed by ultrasonography, hispatholgogy and transmission electronic microscopy in a preclinical model of HCC orthotopic xenografts with systemic therapy. Chol-let-7a inhibited the viability and mobility of HCC cells. Chol-let-7a was primarily observed in the cytoplasm and induced organelle changes, including autophagy. Mild changes were observed in the cells treated with negative control miRNA. Chol-let-7a reached HCC orthotopic tumours, significantly inhibited tumour growth, and prevented local invasion and metastasis. Compared to control tumours, Chol-let-7a-treated tumours showed more necrosis. Tumour cells showed no significant atypia, and mitoses were very rare after systemic Chol-let-7a therapy. Furthermore, let-7a abundance in orthotopic xenografts was coincident with a reduction in the expression of 3 human ras mRNAs and RAS proteins. Chol-let-7a exerted significant antitumor effects by down-regulating all human ras genes at the transcriptional and translational levels. Chol-let-7a inhibited cell proliferation, growth, and metastasis, and mainly functioned in the cytoplasm. Chol-let-7a represents a potential useful modified molecule for systemic HCC therapy.


Wave nucleation rate in excitable systems in the low noise limit.
Motivated by recent experiments on intracellular calcium dynamics, we study the general issue of fluctuation-induced nucleation of waves in excitable media. We utilize a stochastic Fitzhugh-Nagumo model for this study, a spatially extended nonpotential pair of equations driven by thermal (i.e., white) noise. The nucleation rate is determined by finding the most probable escape path via minimization of an action related to the deviation of the fields from their deterministic trajectories. Our results pave the way both for studies of more realistic models of calcium dynamics as well as of nucleation phenomena in other nonequilibrium pattern-forming processes.


Variation in Aedes aegypti Mosquito Competence for Zika Virus Transmission.
To test whether Zika virus has adapted for more efficient transmission by Aedes aegypti mosquitoes, leading to recent urban outbreaks, we fed mosquitoes from Brazil, the Dominican Republic, and the United States artificial blood meals containing 1 of 3 Zika virus strains (Senegal, Cambodia, Mexico) and monitored infection, dissemination, and virus in saliva. Contrary to our hypothesis, Cambodia and Mexica strains were less infectious than the Senegal strain. Only mosquitoes from the Dominican Republic transmitted the Cambodia and Mexica strains. However, blood meals from viremic mice were more infectious than artificial blood meals of comparable doses; the Cambodia strain was not transmitted by mosquitoes from Brazil after artificial blood meals, whereas 61% transmission occurred after a murine blood meal (saliva titers up to 4 log 10 infectious units/collection). Although regional origins of vector populations and virus strain influence transmission efficiency, Ae. aegypti mosquitoes appear to be competent vectors of Zika virus in several regions of the Americas.


Xenogenic Neural Stem Cell-Derived Extracellular Nanovesicles Modulate Human Mesenchymal Stem Cell Fate and Reconstruct Metabolomic Structure.
Extracellular nanovesicles, particularly exosomes, can deliver their diverse bioactive biomolecular content, including miRNAs, proteins, and lipids, thus providing a context for investigating the capability of exosomes to induce stem cells toward lineage-specific cells and tissue regeneration. In this study, it is demonstrated that rat subventricular zone neural stem cell-derived exosomes (rSVZ-NSCExo) can control neural-lineage specification of human mesenchymal stem cells (hMSCs). Microarray analysis shows that the miRNA content of rSVZ-NSCExo is a faithful representation of rSVZ tissue. Through immunocytochemistry, gene expression, and multi-omics analyses, the capability to use rSVZ-NSCExo to induce hMSCs into a neuroglial or neural stem cell phenotype and genotype in a temporal and dose-dependent manner via multiple signaling pathways is demonstrated. The current study presents a new and innovative strategy to modulate hMSCs fate by harnessing the molecular content of exosomes, thus suggesting future opportunities for rSVZ-NSCExo in nerve tissue regeneration.


Investigating the Reliability and Factor Structure of Kalichman's "Survey 2: Research Misconduct" Questionnaire: A Post Hoc Analysis Among Biomedical Doctoral Students in Scandinavia.
A precondition for reducing scientific misconduct is evidence about scientists' attitudes. We need reliable survey instruments, and this study investigates the reliability of Kalichman's "Survey 2: research misconduct" questionnaire. The study is a post hoc analysis of data from three surveys among biomedical doctoral students in Scandinavia (2010-2015). We perform reliability analysis, and exploratory and confirmatory factor analysis using a split-sample design as a partial validation. The results indicate that a reliable 13-item scale can be formed (Cronbach's α = .705), and factor analysis indicates that there are four reliable subscales each tapping a different construct: (a) general attitude to misconduct (α = .768), (b) attitude to personal misconduct (α = .784), (c) attitude to whistleblowing (α = .841), and (d) attitude to blameworthiness/punishment (α = .877). A full validation of the questionnaire requires further research. We, nevertheless, hope that the results will facilitate the increased use of the questionnaire in research.


Cloning, purification and preliminary crystallographic analysis of a putative DNA-binding membrane protein, YmfM, from Staphylococcus aureus.
The Staphylococcus aureus protein YmfM contains a helix-turn-helix motif and is thought to be a putative DNA-binding protein which is associated with the membrane through a C-terminal hydrophobic transmembrane anchor. Truncation of the protein by the removal of this C-terminal hydrophobic segment has enabled the overexpression of a soluble domain of S. aureus YmfM (DeltaYmfM) in Escherichia coli, which has been purified and subsequently crystallized. Crystals of DeltaYmfM diffract to beyond 1.0 A resolution and belong to one of the pair of enantiomorphic tetragonal space groups P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 45.5, c = 72.9 A and one molecule in the asymmetric unit. The crystals of DeltaYmfM have an unusually low V(M) of 1.6 A(3) Da(-1), which is one of the lowest values observed for any protein to date. A full structure determination is under way in order to provide insights into the function of this protein.


A Diagnostic Device for In-Situ Detection of Swine Viral Diseases: The SWINOSTICS Project.
In this paper, we present the concept of a novel diagnostic device for on-site analyses, based on the use of advanced bio-sensing and photonics technologies to tackle emerging and endemic viruses causing swine epidemics and significant economic damage in farms. The device is currently under development in the framework of the EU Commission co-funded project. The overall concept behind the project is to develop a method for an early and fast on field detection of selected swine viruses by non-specialized personnel. The technology is able to detect pathogens in different types of biological samples, such as oral fluids, faeces, blood or nasal swabs. The device will allow for an immediate on-site threat assessment. In this work, we present the overall concept of the device, its architecture with the technical requirements, and all the used innovative technologies that contribute to the advancements of the current state of the art.


Anlotinib combined with durvalumab in a patient with recurrent multifocal brain metastases of small cell lung cancer after definitive concurrent chemoradiotherapy and palliative radiotherapy of the lung and brain: a case report.
The brain is a common metastatic site of small cell lung cancer (SCLC), but systematic treatment options are limited by the blood-brain barrier. Currently, the optimal treatment regimen remains controversial, especially for patients already treated by brain radiotherapy. Anlotinib is a novel oral multitarget tyrosine kinase inhibitor which has shown significant improvement in progression-free survival and overall survival in third-line or beyond therapy of advanced SCLC in a randomized, double-blind phase II study (ALTER1202 trial) based on a Chinese population sample. Emerging data has also suggested that immunotherapy, such as the programmed death ligand 1 (PD-L1) inhibitor, has a relatively high response rate in brain metastatic SCLC, although there is a lack of large sample-size studies. Integrating anlotinib and immunotherapy for recurrent or relapsing brain metastases (BMs) of SCLC has not been previously reported, but it is possible that these two treatments may have synergistic effects and provide even better outcomes. Here, we present a case of stage III SCLC who developed lung and BMs after concurrent chemoradiotherapy (cCRT) and achieved radiographic locally complete regression following whole brain irradiation (WBI) with a simultaneous integrated boost (SIB) technique. Durvalumab was delivered as maintenance therapy. Asymptomatic multifocal recurrence of BMs occurred after the administration of the second dose of durvalumab. After administration of combined durvalumab and anlotinib, the BMs achieved near-complete regression and no severe toxicity was reported. This suggests a potential synergistic effect of combined durvalumab and anlotinib in previously treated BMs in a patient with SCLC and may provide a direction for future clinical decisions.


Association between adherence to Eat-Lancet diet and incidence and mortality of lung cancer: A prospective cohort study.
Previous research has shown that adhering to the Eat-Lancet diet (ELD) is associated with a lower risk of chronic diseases and mortality. However, the associations between ELD and lung cancer incidence and mortality are unclear. To address this gap, we conducted a prospective cohort study involving 101,755 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial in the USA. The ELD score was utilized to assess compliance with the ELD, with higher scores indicating greater compliance. We employed Cox regression analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ELD score with the incidence and mortality of lung cancer and its subtypes. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In total, 1706 cases of lung cancer and 1217 lung cancer-associated deaths were recorded during the study period. Our analysis revealed that higher ELD scores were significantly associated with a reduced incidence (HRQuartile 4 vs. Quartile 1 : 0.73; 95% CI: 0.60, 0.89; ptrend = 0.001) and mortality (HRQuartile 4 vs. Quartile 1 : 0.74; 95% CI: 0.59, 0.93; ptrend = 0.005) of lung cancer in a dose-response manner (all pnonlinearity > 0.05). The reliability of these results was supported by sensitivity analyses. Notably, these associations were primarily observed in non-small-cell lung cancer. In conclusion, our findings suggest that adherence to the ELD may be associated with a reduced risk of lung cancer incidence and mortality.


PERSISTENT MITOSIS OF TRANSFUSED HOMOLOGOUS LEUKOCYTES IN CHILDREN RECEIVING ANTILEUKEMIC THERAPY.
Temporary homologous bone marrow grafts were observed in three patients with acute leukemia, receiving intensive antileukemic treatment, following transfusion of peripheral blood cells from donors with chronic myelocytic leukemia. Persistent mitosis of the transfused cells, containing the Philadelphia chromosome marker, were detected by cytogenetic techniques 19, 39, and 52 days after transfusion.


Thermoluminescent characteristics of LiF:Mg,Ti from three manufacturers.
LiF:Mg,Ti thermoluminescent dosimeters (TLD's) were obtained from three manufacturers with the specification that they all lie within +/- 5% of the mean. All were chips of size 3 mm x 3 mm x 1 mm. The three sample groups were compared on the basis of their energy response, linearity of the thermoluminescent (TL) response with increasing exposure, sensitivity, and reproducibility of TL response. All TLD groups showed similar characteristics in energy response and linearity. This is to be expected since the base material and dopants were the same. However, the sensitivity varied among the three groups by as much as 40% and reproducibility measurements gave standard deviations ranging from 7% to 14% among the groups. Annealing procedures were identical in all cases, as were irradiation and readout conditions.


Identification of glypican as a dual modulator of the biological activity of fibroblast growth factors.
Heparan sulfate moieties of cell-surface proteoglycans modulate the biological responses to fibroblast growth factors (FGFs). We have reported previously that cell-associated heparan sulfates inhibit the binding of the keratinocyte growth factor (KGF), but enhance the binding of acidic FGF to the KGF receptor, both in keratinocytes, which naturally express this receptor, and in rat myoblasts, which ectopically express it (Reich-Slotky, R., Bonneh-Barkay, D., Shaoul, E., Berman, B., Svahn, C. M., and Ron, D. (1994) J. Biol. Chem. 269, 32279-32285). The proteoglycan bearing these modulatory heparan sulfates was purified to homogeneity from salt extracts of rat myoblasts by anion-exchange and FGF affinity chromatography and was identified as rat glypican. Affinity-purified glypican augmented the binding of acidic FGF and basic FGF to human FGF receptor-1 in a cell-free system. This effect was abolished following digestion of glypican by heparinase. Addition of purified soluble glypican effectively replaced heparin in supporting basic FGF-induced cellular proliferation of heparan sulfate-negative cells expressing recombinant FGF receptor-1. In keratinocytes, glypican strongly inhibited the mitogenic response to KGF while enhancing the response to acidic FGF. Taken together, these findings demonstrate that glypican plays an important role in regulating the biological activity of fibroblast growth factors and that, for different growth factors, glypican can either enhance or suppress cellular responsiveness.


Treatment evolution and new standards of care: implications for cost-effectiveness analysis.
Traditional approaches to cost-effectiveness analysis have not considered the downstream possibility of a new standard of care coming out of the research and development pipeline. However, the treatment landscape for patients may change significantly over the course of their lifetimes. To present a Markov modeling framework that incorporates the possibility of treatment evolution into the incremental cost-effectiveness ratio (ICER) that compares treatments available at the present time. . Markov model evaluated by matrix algebra. Measurements. The author evaluates the difference between the new and traditional ICER calculations for patients with chronic diseases facing a lifetime of treatment. The bias of the traditional ICER calculation may be substantial, with further testing revealing that it may be either positive or negative depending on the model parameters. The author also performs probabilistic sensitivity analyses with respect to the possible timing of a new treatment discovery and notes the increase in the magnitude of the bias when the new treatment is likely to appear sooner rather than later. Limitations. The modeling framework is intended as a proof of concept and therefore makes simplifying assumptions such as time stationarity of model parameters and consideration of a single new drug discovery. For diseases with a more active research and development pipeline, the possibility of a new treatment paradigm may be at least as important to consider in sensitivity analysis as other parameters that are often considered.


Brain Protection Effects of Mild Hypothermia Combined with Distant Ischemic Postconditioning and Thrombolysis in Patients with Acute Ischemic Stroke.
To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection, n = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline, n = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group (p < 0.05). While the SOD in the experimental group was significantly higher than in the control group (p < 0.05), the NIHSS scores decreased within groups (all p < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%, p < 0.05) and no significant differences were observed in the safety indices between the two groups (all p > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.


Regional versus general anesthesia in surgical patients with chronic obstructive pulmonary disease: does avoiding general anesthesia reduce the risk of postoperative complications?
Surgical patients with chronic obstructive pulmonary disease (COPD) are at increased risk of perioperative complications. In this study, we sought to quantify the benefit of avoiding general anesthesia in this patient population. Data from the National Surgical Quality Improvement Program database (2005-2010) were used for this review. Patients who met the National Surgical Quality Improvement Program definition for COPD and underwent surgery under general, spinal, epidural, or peripheral nerve block anesthesia were included in this study. For each primary current procedural terminology code with ≥ 1 general and ≥ 1 regional (spinal, epidural, or peripheral nerve block) anesthetic, regional patients were propensity score--matched to general anesthetic patients. Propensity scoring was calculated using all available demographic and comorbidity data. This match yielded 2644 patients who received regional anesthesia and 2644 matched general anesthetic patients. These groups were compared for morbidity and mortality. Groups were well matched on demographics, comorbidities, and type of surgery. Compared with matched patients who received regional anesthesia, patients who received general anesthesia had a higher incidence of postoperative pneumonia (3.3% vs 2.3%, P = 0.0384, absolute difference with 95% confidence interval = 1.0% [0.09, 1.88]), prolonged ventilator dependence (2.1% vs 0.9%, P = 0.0008, difference = 1.2% [0.51, 1.84]), and unplanned postoperative intubation (2.6% vs 1.8%, P = 0.0487, difference = 0.8% [0.04, 1.62]). Composite morbidity was 15.4% in the general group versus 12.6% (P = 0.0038, difference = 2.8% [0.93, 4.67]). Composite morbidity not including pulmonary complications was 13.0% in the general group versus 11.1% (P = 0.0312, difference = 1.9% [0.21, 3.72]). Thirty-day mortality was similar (2.7% vs 3.0%, P = 0.6788, difference = 0.3% [-1.12, 0.67]). As a test for validity, we found a positive association between pulmonary end points because patients with 1 pulmonary complication were significantly more likely to have additional pulmonary complications. The use of regional anesthesia in patients with COPD is associated with lower incidences of composite morbidity, pneumonia, prolonged ventilator dependence, and unplanned postoperative intubation.


[Severe social phobia with obsessive-compulsive symptoms--case study].
The case of a young patient with social phobia and obsessive-compulsive disorder is analysed. A lot of complicated symptoms started from a very young age (around the first year of life) and made slow but active progress. The patient stopped attending school at the age of fourteen. Since then he stayed at home and is totally inactive in a social sense. The complex therapy started six months ago and included cognitive-behavioural--systemic therapy with venlafaxine (150 mg per day) pharmacotherapy. The patient is much better, but he still neither speaks, nor is socially more active.


A survey of helminths in freshwater animals from some areas in Chiang Mai.
Thirteen freshwater animals consisting of 8 species of fish, 1 species of shrimps and crabs and 3 species of mollusks collected during September 2000 from 8 sites in 4 districts of Chiang Mai Province: Hang Dong, San Pa Tong, Chom Tong and Hot were investigated for helminthes. Two metacercariae were recovered from 4 species of fish with the prevalence of 80.32%; Metacercariae of Stellantchasmus falcatus were found in the body cavity and under the scales of Dermogenus pusillus (39.34%) and the metacercariae of Haplorchoides sp were found only under the scales of Mystacoleucus marginatus, Systomus orphoides and Rasbora paviei, (40.98%). Adult of Acanthocephala, Pallisentis sp also recovered from the intestine of Trichopsis vittatus (3.29%). Moreover, Pleurolophocercous cercaria and redia were found in mollusk (Lymnaea sp) with the prevalence of 45.65%.


Aedes albopictus (Diptera: Culicidae) population density and structure in southwest Louisiana.
Pupal density, wing length at emergence, host-seeking female abundance, and host-seeking female wing length and parity were determined monthly for a population of Aedes albopictus (Skuse) in a southwestern Louisiana tire dump from January 1988 through January 1989. Pupae and host-seeking females were first collected in April. Pupal densities were consistently high from June through September. Host-seeking female abundance was highest during July and August. Average female wing length was longest during spring, declined in midsummer, and increased slightly during fall. Average wing length was negatively correlated with average pupal density during the month of collection and with average air temperature recorded the previous month. Host-seeking females had consistently longer wings than emerging females, and parous host-seeking females had longer wings than nulliparous host-seeking females. Average wing length of the parous host-seeking females was consistently long throughout the season. Parity of host-seeking females parity was highest during July when approximately 21 parous host-seeking females were collected per hour. These results indicate that seasonal patterns in immature population density influence average body size and parity structure in Ae. albopictus.


Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents.
Two analogues of 3-(dimethylsulfonio)propanoate (DMSP), 3-(diallylsulfonio)propanoate (DAllSP), and 3-(allylmethylsulfonio)propanoate (AllMSP), were synthesized and fed to marine bacteria from the Roseobacter clade. These bacteria are able to degrade DMSP into dimethyl sulfide and methanethiol. The DMSP analogues were also degraded, resulting in the release of allylated sulfur volatiles known from garlic. For unknown compounds, structural suggestions were made based on their mass spectrometric fragmentation pattern and confirmed by the synthesis of reference compounds. The results of the feeding experiments allowed to conclude on the substrate tolerance of DMSP degrading enzymes in marine bacteria.


Structure and alternative splicing of the rat 7-dehydrocholesterol reductase gene.
The enzyme 7-dehydrocholesterol reductase (Dhcr7) catalyzes the reduction of 7-dehydrocholesterol (DHC), the terminal reaction of the pathway of cholesterol biosynthesis. We report the isolation and characterization of the genomic DNA encoding rat Dhcr7 that contains nine exons and eight introns distributed over 15944 nucleotides (nts) and a consensus GT-AG at each exon/intron junction. Unexpectedly, we have found the occurrence of at least five isoforms of Dhcr7, designated as Dhcr7-AS (alternatively spliced)-1 (1474 nts), -2 (1595 nts), -3 (1602 nts), -4 (1723 nts) and -5 (1287 nts), which was believed to be caused by alternative usage of three 5' noncoding exons. Furthermore, Dhcr7-AS-1 was found to be differentially expressed in six tissues examined while Dhcr7-AS-2 was expressed mainly in liver and brain. Interestingly, human Dhcr7 gene in HepG2 cells produced no detectable isoform while mouse Dhcr7 gene in L929 cells produced three isoforms, suggesting a difference in alternative splicing between species. Thus, regulation of Dhcr7 through the combined mechanisms of tissue-specific transcription and differential alternative splicing appears unique among enzymes characterized from the entire post-lanosterol pathway in cholesterol biosynthesis.


Biological activities of skin secretions of the salamander Tylototriton verrucosus.
Water-soluble skin secretions of salamander Tylototriton verrucosus, first described by Anderson in 1871, were studied for their biological and enzymatic activities. They were found to be toxic to mice with an intraperitoneal LD50 of 11.5 mg/kg. Using Sephadex G-75 gel filtration, it was proven that the toxic components of the secretions are proteins with molecular weights ranging from 30,000 to 50,000 Da. The secretions of T. verrucosus display a wide spectrum of antimicrobial activities and also contain both proteolytic activity and trypsin inhibitory activity. In contrast, neither hemolytic nor hemorrhagic activities were found. The secretions were determined to have phospholipase A2 activity; however, no acetylcholine esterase activity was detectable under the assay conditions.


Wear analysis of the Bryan Cervical Disc prosthesis.
In vitro wear testing of the Bryan Cervical Disc prosthesis was performed in a cervical spine simulator. The biologic response was assessed in chimpanzee and goat animal models. Determine the wear characteristics of the Bryan disc. Large joint arthroplasties fail most commonly by wear and consequent formation of particulate material, which induces an inflammatory response. Therefore, measuring the wear characteristics of the new spinal disc replacements is important. Six prosthetic assembles were tested to 10 or 40 million cycles by load and motion and 3 additional assemblies were tested by load only in a cervical spine simulator. Any debris was examined using ASTM standards. The local biologic response to the prosthesis was examined in two chimpanzees. Nine goats were used to assess the biologic response in both local and distant tissues. Arthrodesis was performed on three additional control goats that received an allograft and an anterior cervical plate. Wear results: cervical spine simulators that applied the loads and motions associated with activities of daily living produced wear particulate at a rate of 1.2 mg per million cycles. Device height decreased 0.02 mm per million cycles with approximately 77% of this decrease due to gradual creep of the nucleus under the constant compressive load. Particles generated were granular in shape with a mean feret diameter of 3.9 microm. All animals tolerated placement of the Bryan disc. Wear debris was present in the periprosthetic and epidural spaces in some animals. However, no significant inflammatory response was observed. No wear material was found distant from the implant in draining lymph tissue, the liver, or the spleen. The Bryan disc has satisfactory wear characteristics and does not produce a significant inflammatory response.


Hyperpolarized NMR study of the impact of pyruvate dehydrogenase kinase inhibition on the pyruvate dehydrogenase and TCA flux in type 2 diabetic rat muscle.
The role of pyruvate dehydrogenase in mediating lipid-induced insulin resistance stands as a central question in the pathogenesis of type 2 diabetes mellitus. Many researchers have invoked the Randle hypothesis to explain the reduced glucose disposal in skeletal muscle by envisioning an elevated acetyl CoA pool arising from increased oxidation of fatty acids. Over the years, in vivo NMR studies have challenged that monolithic view. The advent of the dissolution dynamic nuclear polarization NMR technique and a unique type 2 diabetic rat model provides an opportunity to clarify. Dynamic nuclear polarization enhances dramatically the NMR signal sensitivity and allows the measurement of metabolic kinetics in vivo. Diabetic muscle has much lower pyruvate dehydrogenase activity than control muscle, as evidenced in the conversion of [1-13C]lactate and [2-13C]pyruvate to HCO3- and acetyl carnitine. The pyruvate dehydrogenase kinase inhibitor, dichloroacetate, restores rapidly the diabetic pyruvate dehydrogenase activity to control level. However, diabetic muscle has a much larger dynamic change in pyruvate dehydrogenase flux than control. The dichloroacetate-induced surge in pyruvate dehydrogenase activity produces a differential amount of acetyl carnitine but does not affect the tricarboxylic acid flux. Further studies can now proceed with the dynamic nuclear polarization approach and a unique rat model to interrogate closely the biochemical mechanism interfacing oxidative metabolism with insulin resistance and metabolic inflexibility.


Intratumoral Lentivector-Mediated TGF-β1 Gene Downregulation As a Potent Strategy for Enhancing the Antitumor Effect of Therapy Composed of Cyclophosphamide and Dendritic Cells.
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs). We observed that s.c. inoculation of both MC38 cells with silenced expression of TGF-β1 (MC38/shTGF-β1) and direct intratumoral application of shTGFβ1 LVs contributed to reduction of suppressor activity of myeloid cells and Tregs in tumor. Contrary to expectations, in mice bearing wild tumor, the application of shTGFβ1 LVs prior to vaccination with bone marrow-derived DC stimulated with tumor antigens (BMDC/TAg) did not influence myeloid-derived suppressor cell (MDSC) infiltration into tumor. As a result, we observed only minor MC38 tumor growth inhibition (TGI) accompanied by systemic antitumor response activation comparable to that obtained for negative control (shN). However, when the proposed scheme was complemented by pretreatment with a low dose of CY, we noticed high MC38 TGI together with decreased number of MDSCs in tumor and induction of Th1-type response. Moreover, in both schemes of treatment, LVs (shTGFβ1 as well as shN) induced high influx of CTLs into tumor associated probably with the viral antigen introduction into tumor microenvironment. Concluding, the application of shTGFβ1 LVs alone or in combination with DC-based vaccines is not sufficient for long-lasting elimination of suppression in tumor. However, simultaneous reduction of TGF-β1 in tumor microenvironment and its remodeling by pretreatment with a low dose of CY facilitates the settlement of peritumorally inoculated DCs and supports them in restoration and activation of a potent antitumor response.


Two-dimensional aperiodic nonlinear photonic crystal in a dual-wavelength Nd:YVO₄ laser for pulsed orange generation.
We report the design and construction of a highly integrated two-dimensional (2D) aperiodic nonlinear photonic crystal (NPC) for working in a diode-pumped, dual-wavelength (1064 and 1342 nm) Nd:YVO₄ laser to demonstrate a compact, high-peak-power intracavity sum-frequency generator (ISFG) radiating at orange 593.5 nm. The 2D aperiodic NPC was built in quasi-phase-matched LiNbO₃whose crystal domain was structured based on the aperiodic optical superlattice technique to best achieve its simultaneous performance of a dual-wavelength electro-optic Bragg Q-switch and a SFG in the Nd:YVO₄ laser. When the NPC device was driven with a 350-V Q-switching voltage and a 1-kHz switching rate, we measured pulse energy of ~4.3 μJ (or peak power of ~531 W) at orange 593.5 nm from the constructed ISFG with 5.28-W diode power.


Control of exposure to hexavalent chromium and ozone in gas metal arc welding of stainless steels by use of a secondary shield gas.
Previous work has demonstrated that the shield gas composition in gas metal arc welding can have a considerable effect on hexavalent chromium [Cr(VI)] concentration in the fume and on ozone concentrations near the arc. Normally a single shield gas is used. This paper describes a double shroud torch that allows used of concentric shield gases of different compositions. A solid stainless steel wire was used for welding. The double shroud torch used secondary shield gases containing small amounts of the reducing agents NO and C2H4. The Cr(VI) concentration in the fume and ozone concentration at a fixed point relative to the arc were measured and compared with results when using a single shield gas. Use of the reducing agents in secondary shielding using the double shroud torch was found to offer advantages for ozone concentration reduction compared with use in a conventional torch, but this was not found to be an advantage for reducing Cr(VI) concentrations.


[Membrane protein characterization by photoactivatable localization microscopy].
The on-site labeling and localization tracking of membrane proteins in pathogenic bacteria are tedious work. In order to develop a novel protein labeling technology at super resolution level (nanometer scale) using the photoactivatable localization microscopy (PALM), the chimeric protein of the outer membrane protein A (OmpA) of Mycobacterium tuberculosis and the photoactivatable mEos2m protein were expressed in the non-pathogenic Mycobacterium smegmatis. The recombinant bacteria were fixed on slide, activated by 405 nm laser and subject to PALM imaging to capture photons released by the fusion protein. Meanwhile, colony and cell morphology were visualized under regular fluorescent stereomicroscope and upright fluorescent microscope to characterize fluorescence conversion and protein localization. The fusion proteins formed a "belt"-like structure on cell membrane of M. smegmatis under PALM, providing direct evidence of on-site imaging of membrane proteins. Expression of fusion protein did not compromise the localization properties of OmpA. Thus, mEos2m could be used as a labeling probe to track localizations of non-oligomer oriented membrane proteins. This indicates non-pathogenic M. smegmatis could be served as a model strain to characterize the function and localization of the proteins derived from pathogenic M. tuberculosis. This is the first report using PALM to characterize localization of membrane proteins.


Novel immunotherapy and treatment modality for severe food allergies.
In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy. We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management. Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.


Pleural effusion in systemic lupus erythematosus.
Three cases of systemic lupus erythematosus (SLE) with pleural effusion are reviewed. The characteristics of the effusions are presented, and the literature pertaining to lupus-related effusions is reviewed. There is great heterogeneity in lupus pleural effusions. The presence of polymorphonuclear neutrophils as the predominant white cell, while consistent with SLE, should raise the possibility of complicating bacterial infection. The presence of lupus erythematosus (LE) cells in the fluid seems to be the most specific diagnostic criterion.


Butyl isocyanide as a probe of the activation mechanism of soluble guanylate cyclase. Investigating the role of non-heme nitric oxide.
Nitric oxide (NO) is a physiologically relevant activator of the hemoprotein soluble guanylate cyclase (sGC). In the presence of NO, sGC is activated several hundredfold above the basal level by a mechanism that remains to be elucidated. The heme ligand n-butyl isocyanide (BIC) was used to probe the mechanism of NO activation of sGC. Electronic absorption spectroscopy was used to show that BIC binds to the sGC heme, forming a 6-coordinate complex with an absorbance maximum at 429 nm. BIC activates sGC 2-5-fold, and synergizes with the allosteric activator YC-1, to activate the enzyme 15-25-fold. YC-1 activates the sGC-BIC complex, and leads to an increase in both the V(max) and K(m). BIC was also used to probe the mechanism of NO activation. The activity of the sGC-BIC complex increases 15-fold in the presence of NO, without displacing BIC at the heme, which is consistent with previous reports that proposed the involvement of a non-heme NO binding site in the activation process.


Kudoa azevedoi n. sp. (Myxozoa, Multivalvulida) from the oocytes of the Atlantic horse mackerel Trachurus trachurus (Perciformes, Carangidae) in Tunisian coasts.
A new species Kudoa azevedoi sp. n. (Myxozoa, Multivalvulida) is described in Trachurus trachurus Linnaeus, 1758 (Carangidae) from fishing harbors in Tunisian coasts using spore morphology and SSU rDNA sequence data. The parasite occurs only in ovaries within oocytes of mature and immature specimens. Spores are quadrate in shape in apical view with rounded edges, having four shell valves and four symmetrical polar capsules. They are of small sizes and measure 3.5±0.41 (3-4.2)×4.5±0.44 (4-5.2) length by width. The polar capsules are pyriform in shape measuring 1.5±0.22 (1.5-2)×0.75±0.14 (0.5-1) μm. Infected oocytes are hypertrophied, whitish colored, and filled with mature spores. Plasmodia are tubular and ramified from the inner membrane toward the center of the oocyte. Phylogenetic analysis based on small subunit ribosomal DNA sequences shows the highest similarity (96%) with the ovary parasite Kudoa ovivora. Some morphological details and spore dimensions support the creation of a new species in the genus Kudoa. Mean prevalence among examined females is of about 55.5%. It varies between localities and length of fish. The present myxosporea is the second Kudoa species reported in fish ovaries.


Regulating appetite in broilers for improving body and muscle development - A review.
Appetite is the desire for feed and water and the voluntary intake of feed and is an important regulator of livestock productivity and animal health. Economic traits such as growth rate and muscle development (meat deposition) in broilers are directly correlated to appetite. Factors that may influence appetite include environmental factors, such as stress and temperature variation, and animal-specific factors, such as learning period, eating capacity and preferences. Feed preferences have been reported to be determined in early life, and this period is important in broilers due to their fast growth and relatively short growth trajectories. This may be of importance when contemplating the use of more circular and sustainable feeds and the optimization of appetite for these feeds. The objective of this review was to review the biological mechanisms underlying appetite using data from human, animal and bird models and to consider the option for modulating appetite particularly as it relates to broiler chickens.


[Morgagni's hernia in infancy].
Morgagni's hernia is an uncommon type of diaphragmatic hernia fairly exceptional in pediatric age. A case of Morgagni's hernia, observed by chance in a 15-month-old infant, is presented. The authors present the fundamental embryogenic stages of the diaphragm and stress the clinical manifestations and diagnostic procedures to reach the diagnosis, as well as the advantages of early treatment in order to prevent possible complications.


Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex.
Complete deficiency in activity-dependent neuroprotective protein (ADNP), a heterochromatin 1-binding protein, results in dramatic changes in gene expression, neural tube closure defects, and death at gestation day 9 in mice. To further understand the cellular roles played by ADNP, the HEK293 human embryonic kidney cell line that allows efficient transfection with recombinant DNA was used as a model for the identification of ADNP-interacting proteins. Recombinant green fluorescent protein (GFP)-ADNP was localized to cell nuclei. When nuclear extracts were subjected to immunoprecipitation with specific GFP antibodies followed by polyacrylamide gel electrophoresis, several minor protein bands were observed in addition to GFP-ADNP. In-gel protein digests followed by mass spectrometry identified BRG1, BAF250a, and BAF170, all components of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin remodeling complex, as proteins that co-immunoprecipitate with ADNP. These results were verified utilizing BRG1 antibodies. ADNP short hairpin RNA down-regulation resulted in microtubule reorganization and changes in cell morphology including reduction in cell process formation and cell number. These morphological changes are closely associated with the SWI/SNF complex multifunctionality. Taken together, the current study uncovers a molecular basis for the essential function of the ADNP gene and protein.


Deleterious effect of right ventricular pacing in patients with cardiac transthyretin amyloidosis: potential clinical benefit of cardiac resynchronization therapy.
Cardiac amyloidosis involvement is associated with a detrimental outcome including frequent arrhythmias, heart failure, and conduction disturbances which may need permanent pacing. We report two cases of patients with transthyretin amyloidosis (ATTR) who developed heart failure and depressed left ventricular ejection fraction (LVEF) following permanent right ventricular (RV) pacing but highly responded to cardiac resynchronization therapy (CRT). The impact of RV pacing and CRT in cardiac amyloidosis is not known. In our cases, the detrimental effect of permanent RV pacing on left ventricular (LV) systolic function and heart failure symptoms was suggested by both permanent RV pacing mediated functional and LV function decline and LV systolic dysfunction reversal following CRT along with QRS width reduction. Whether cardiac resynchronization should be readily recommended in ATTR patients who need ventricular pacing whatever the LVEF deserves further investigation.


Site of origin of 2,7-FAA-induced rat leukemia.
Oral administration of N,N'-2,7-fluorenylenebis-acetamide (2,7-FAA) induces mature granulocytic and erythroblastic leukemia in rats. We compared the primary site of mature granulocytic leukemia with that of erythroblastic leukemia. The nodular foci of solitary lesions and comspicuously large foci of scattered lesions were considered to be the primary site. They appeared mainly in the bone marrow of various bones. The primary site of mature granulocytic leukemia appeared more frequently in short bones than in long bones. On the contrary, that of erythroblastic leukemia appeared more frequently in long bones than in short bones. The origin of mature granulocytic leukemia seems to be concerned with bone tissue, while erythroblastic leukemia may have little relation with bone tissue.


Toxicity of Boswellia dalzielii (Burseraceae) Leaf Fractions Against Immature Stages of Anopheles gambiae (Giles) and Culex quinquefasciatus (Say) (Diptera: Culicidae).
Mosquitoes are vectors of several human pathogens, and great attention has recently been placed on insecticides from plant-derived products, in search for mosquito control agents. This study, thus, investigated the potency of Boswellia dalzielii methanol leaf extract and its four fractions as mosquito ovicide, larvicide, and pupicide against Anopheles gambiae and Culex quinquefasciatus. The plant products were tested at the following concentrations: 125, 250, 500, 1000, and 2000 ppm on eggs and 312.5, 625, 1250, and 2500 ppm on the larvae and pupae of the mosquitoes. For results, hatchability of A. gambiae eggs was reduced to 5% with n-hexane fraction at 2000 ppm. Among the plant products tested, n-hexane fraction was most toxic against A. gambiae (LC50 = 385.9 ppm) and C. quinquefasciatus (LC50 = 3394.9 ppm). The n-hexane fraction of B. dalzielii might be used as a mosquitocidal agent in the breeding sites of A. gambiae and C. quinquefasciatus.


[Rational distribution of resources in intensive medicine. Analysis of admission and discharge criteria at intensive care units].
Cost-containment in health care has become a major issue in today's practice of medicine. With its needs in advanced technologies and skilled personnel, intensive care is among the most expensive of all hospital activities. This fact makes the analysis of indications for intensive care unit admission, as well as early discharge, of paramount importance: patients who are not likely to benefit from intensive care are at the extremes of disease severity, since low-risk patients are not ill enough to need ICU admission and high-risk patients have a very high mortality, irrespective of intensive care treatment. In this paper we discuss, based on published evidence, the formulation of recommendations for admission and early discharge from ICUs, and also present the Society of Critical Care Medicine guidelines, on this subject.


QUATgo: Protein quaternary structural attributes predicted by two-stage machine learning approaches with heterogeneous feature encoding.
Many proteins exist in natures as oligomers with various quaternary structural attributes rather than as single chains. Predicting these attributes is an essential task in computational biology for the advancement of proteomics. However, the existing methods do not consider the integration of heterogeneous coding and the accuracy of subunit categories with limited data. To this end, we proposed a tool that can predict more than 12 subunit protein oligomers, QUATgo. Meanwhile, three kinds of sequence coding were used, including dipeptide composition, which was used for the first time to predict protein quaternary structural attributes, and protein half-life characteristics, and we modified the coding method of the functional domain composition proposed by predecessors to solve the problem of large feature vectors. QUATgo solves the problem of insufficient data for a single subunit using a two-stage architecture and uses 10-fold cross-validation to test the predictive accuracy of the classifier. QUATgo has 49.0% cross-validation accuracy and 31.1% independent test accuracy. In the case study, the accuracy of QUATgo can reach 61.5% for predicting the quaternary structure of influenza virus hemagglutinin proteins. Finally, QUATgo is freely accessible to the public as a web server via the site http://predictor.nchu.edu.tw/QUATgo.


[Effects of KC-404 on bronchial anaphylactic reactions].
The effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a] pyridine (KC-404), a new anti-allergic agent with a unique mode of action, on bronchial anaphylactic reactions were investigated in guinea pigs and rats. The inhibitory effects of orally administered KC-404 on systemic anaphylactic reaction caused by intravenous antigen and on anaphylactic bronchoconstriction caused by inhaled antigen in guinea pigs actively sensitized with egg albumin were observed at doses of 100 mg/kg and 10 mg/kg, respectively. When these animals were pretreated with diphenhydramine and atropine before antigen challenge, the inhibitory effects of KC-404 were markedly enhanced; doses as low as 0.25 to 0.5 mg/kg p.o. were effective in this situation. In guinea pigs similarly sensitized as above, KC-404 injected i.v. after the maximum development of antigen-induced constriction of airways resulted in a rapid dilatation. KC-404 was about 100 times as potent as aminophylline in this respect. KC-404 inhibited passive anaphylactic bronchoconstriction in rats mediated by an IgE antibody at an oral dose of 2.5 mg/kg. The inhibitory effect of KC-404 (10 mg/kg) persisted for at least 6 hr. These results indicate that KC-404 is orally effective in inhibiting anaphylactic bronchoconstrictions mediated by IgE as well as IgG antibodies. Furthermore, KC-404 is suggested to be able to control the SRS-A-induced component of bronchospasm.


[Subcutaneous Metabolites Involving Acupoint Sensitization Induced by Myocardial Ischemia and Acupuncture Stimulation in Rabbits].
The present study aimed at observing the profile of metabolites in sensitized acupoints induced by myocardial ischemia (MI) and the effect of acupuncture intervention on the changes of the metabolites so as to explore the material basis of acupoint sensitization. A total of 20 New Zealand rabbits were randomly and equally divided into a control group and a model group. The MI model was established by occlusion of the anterior descending branch of the left coronary artery with a controllable air balloon inflation method for 5 min/time, twice a day (4-hours' interval) for continuous 5 days (the first stage of MI). After one day's rest, another 5 days' occlusion was conducted again (the second stage of MI) in the same way. The rabbits of the control group were treated with the same procedures but without occlusion. Subcutaneous microdialysis fluid samples were collected from "Neiguan" (PC 6), "Shenmen" (HT 7), "Xinshu" (BL 15), and "Taixi" (KI 3) regions on day 8(after recovery from operation), 14 (the first stage of MI), and 20 (the second stage of MI), as well as collected from PC 6 region during and post-acupuncture stimulation of PC 6, respectively. Manual acupuncture stimulation was applied to the right PC 6 for 30 min. Partial least squares -linear discriminant analysis (PLS-DA) was used to identify different metabolism patterns of the microdialysis fluid sample between groups and at different time-points in the same one group, and the distinct metabolites as the potential markers between groups were weighted via the values of variable importance in the projection (VIP) in combination with t-test analysis. An area under the curve (AUC) >1.0 indicated a test exhibiting good discrimination between groups. Six metabolites identified to be significantly different between the control and model groups were L-glutamic acid, phenylalanine and 3-hydroxyisobutyric acid (which were significantly increased relevant to the control group), and L-histidine, octadecanedioic acid and 9-keto palmitic acid (significantly decreased relevant to the control group) in the microdialysate of PC 6, HT 7 and BL 15 regions. In the microdialysate of PC 6, 4 metabolites including L-glutamic acid, octadecanedioic acid and 8-isohydroxy PGF 2 α (significantly increased), as well as L-histidine (markedly decreased) were identified to be considerably different between the model and control groups. After acupuncture for 30 min, the AUC level of L-glutamic acid was further significantly increased (P<0.05), that of L-histidine obviously decreased, and those of octadecanedioic acid and 8-isohydroxy PGF 2 α turned back nearly to the level of pre-MI. L-glutamic acid, phenylalanine, 3-hydroxyisobutyric acid, L-histidine, octadecanedioic acid and 9-keto palmitic acid from PC 6, HT 7 and BL 15 regions may be used as the material biomarker for MI-induced sensitization of these acupoints. Manual acupuncture intervention of PC 6 induces a significant change of L-histidine and L-glutamic acid in the local subcutaneous tissues.


Timing and outcomes for radical cystectomy in nonmuscle invasive bladder cancer.
To provide an overview on the available clinical and pathological factors in high-risk nonmuscle invasive bladder cancer (NMIBC) patients that help to approximate the risk of progression to muscle invasion and identify 'the' patients requiring timely cystectomy. The value of a high-quality transurethral tumor resection is pointed out. Outcomes following radical cystectomy are compared with a primarily bladder preserving strategy. Carcinoma in situ within the prostatic urethra of NMIBC patients impacts on patient's outcome. Therefore, biopsies taken from the prostatic urethra improve the initial tumor staging accuracy. Lamina propria substaging may provide more detailed prognostic information. Lympho-vascular invasion within the transurethral resection specimen may help to detect patients who benefit from timely cystectomy. Recent findings from patients undergoing radical cystectomy including super-extended lymphadenectomy for clinically NMIBC confirm the substantial rate (25%) of tumor understaging. The fact that almost 10% were found to harbor lymph node metastases underlines the necessity to perform a meticulous lymphadenectomy in NMIBC patients undergoing radical cystectomy. High-quality transurethral bladder tumor resection including underlying muscle fibers is of utmost importance. Nevertheless, tumor understaging remains an issue of concern and warrants the value of a second transurethral resection in high-risk NMIBC patients. There is a persisting lack of rigid therapeutic recommendations in patients with high-risk NMIBC. Instead, treatment strategy is based on individual risk factors. However, irrespective of initial treatment strategy, there is a subgroup of high-risk NMIBC patients with progressive disease, leading almost inevitably to death.


The use of the Primary Care Assessment Tool (PCAT): an integrative review and proposed update.
This study proposes an integrative review of the literature based on articles and publications on the use of the Primary Care Assessment Tool (PCAT) as a tool for evaluating these services, discussing the results found in Brazil and in other countries of the world, from the initial matrix conceived by Professor Barbara Starfield's team and proposing updates for the Brazilian version. We identified 124 studies, of which 42 were selected after full reading and according to the established inclusion criteria. Of this subtotal, 17 (40.5%) were Brazilian studies. There is a need to update items of each tool's attribute, in particular "access - first contact", including new forms of doctor-patient communication such as: email, mobile application messages, use of videoconference software for communication and even use of telemedicine, among others. PCAT's use, application and calculation of scores is simple, which makes it useful and suitable for use in the local management of services, especially in its short version.