Thermodynamic yield predictions for biodegradation through oxygenase activation reactions.
Activation reactions involve modification of recalcitrant substrates to forms that are more readily degradable. These reactions require specialized enzymes and cosubstrates, including molecular oxygen and reduced electron carriers. In these reactions, microorganisms invest electrons and cannot capture energy or carbon for synthesis. The subsequent degradation of the intermediates formed in activation reactions releases electrons, energy, and carbon that the organisms use for growth. The overall yield is reduced due to the required activation investments. A mathematical method to predict cell yields of oxygenase activation reactions is developed using electron and energy balances. Predicted yields are compared with experimental yields for methane, organic chelating agents, and aromatic hydrocarbons.


[Perioperative Management of Long-term Antidiabetic Therapy in Patients with Diabetes Mellitus].
Drug therapy, as well as diabetes technology, e.g. insulin pumps or sensor glucose measurement, have developed enormously in recent years. Their use differs according to the type of diabetes, secondary or concomitant diseases, and individual factors and target values. In the perioperative phase, diabetic patients are generally at increased risk of complications, including a derailment of glucose metabolism, an increased rate of cardiovascular events, worsening of preexisting renal insufficiency, and increased incidence of wound infections. In addition, drug class-specific side effects of antidiabetic therapy may occur. The prevalence of diabetes patients in anesthesiology is high and will continue to increase. In Germany, more than 8 million people are estimated to live with diabetes mellitus. The rate of new cases is about 600 000 per year. The distinction between type 1 and type 2 diabetes mellitus is essential. Diabetes therapy is becoming increasingly individualized; combination therapies are becoming more common. Therefore, the management of long-term medication should also be individualized. Substance-specific side effects or adverse effects, especially of oral antidiabetic agents, must be considered in the care of patients, e.g. euglycemic diabetic ketoacidosis under SGLT-2 inhibitors is a relevant problem. Insulin therapy is also evolving; knowledge of new preparations and of insulin pump therapy facilitates perioperative management. Both hypoglycemia and hyperglycemia, possibly with ketoacidosis, must be avoided. The purpose of this article is to provide an overview of the management of long-term medication in patients with diabetes mellitus.


WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation.
The actin cytoskeleton is critical to shape cells and pattern intracellular organelles, which collectively drives tissue morphogenesis. In multiciliated cells (MCCs), apical actin drives expansion of the cell surface necessary to host hundreds of cilia. The apical actin also forms a lattice to uniformly distribute basal bodies. This apical actin network is dynamically remodeled, but the molecules that regulate its architecture remain poorly understood. We identify the chromatin modifier, WDR5, as a regulator of apical F-actin in MCCs. Unexpectedly in MCCs, WDR5 has a function independent of chromatin modification. We discover a scaffolding role for WDR5 between the basal body and F-actin. Specifically, WDR5 binds to basal bodies and migrates apically, where F-actin organizes around WDR5. Using a monomer trap for G-actin, we show that WDR5 stabilizes F-actin to maintain lattice architecture. In summary, we identify a non-chromatin role for WDR5 in stabilizing F-actin in MCCs.


Enlargement of previously ligated popliteal aneurysm causing venous bypass graft occlusion.
A 72-year-old male patient presented with a thrombosed popliteal artery aneurysm measuring 15 x 8 cm 12 years following ligation and saphenous vein bypass grafting through a medial approach. The giant aneurysm, which had grown and compressed the previously functional vein bypass graft to the point of graft thrombosis, was causing a knee contracture that impeded ambulation. Resection via a posterior approach was accomplished without neurovascular compromise or the need for revascularization. This case underscores the value of aneurysm decompression in cases of large popliteal aneurysms to prevent further growth and attendant complications. Duplex surveillance of ligated popliteal aneurysms is warranted to exclude the possibility of future aneurysm expansion.


Lateral foot pain due to os vesalianum pedis in a young football player; a case report and review of the current literature.
Os vesalianum pedis is a rare accessory ossicle located at the 5th metatarsal base. This anatomic variation is typically asymptomatic and usually detected incidentally on routine foot radiographs. However, it may be a source of lateral foot pain and rarely become symptomatic following traumatic ankle injuries such as an inversion ankle sprain. To date, seven symptomatic os vesalianum pedis cases that required surgical treatment have been reported in the current literature. Herein, a 17-year-old professional football player with a symptomatic os vesalianum pedis was presented. The ossicle was surgically removed upon failure of conservative treatment. At the sixth month, the patient returned to sport without any restriction or pain. Clinical presentation, diagnosis, and treatment options of symptomatic os vesalianum pedis were discussed with an extensive literature review.


Core antigen tests for hepatitis C virus: a meta-analysis.
Diagnosis and monitoring of hepatitis C virus (HCV) infection relies mainly on the detection of HCV antibodies and HCV RNA. HCV antibody test has a longer window period and is not applicable in the immunosuppressed population. Although HCV RNA test reduces the window period, it is still not widely recommended because of its high cost and requirement of specific equipment. HCV core antigen is another direct virological marker which has been investigated in recent years. HCV core antigen assay is as simple as the HCV antibodies assay and can detect HCV infection only 1 day delay compared to the HCV RNA assay. In order to evaluate the application of HCV core antigen test in HCV diagnosis and management, we performed this meta-analysis. Twenty five articles were finally included in meta-analysis. All statistical analyses were performed with MetaDisc 1.4 and Stata 11.0. The pooled sensitivity of HCV core antigen assay was 0.84 (95 % CI, 0.83-0.85), and the pooled specificity was 0.98 (95 % CI, 0.97-0.98). HCV core antigen assays may not displace HCV RNA assays to be a definitive diagnosis of HCV infection until now. Considering the higher sensitivity (0.926) and specificity (0.991) of subgroup, HCV-cAg detection is a promising method as a confirmatory test for HCV antibody positive, therapy-naive individuals. Explored by meta-regression and subgroup analysis, possible sources of heterogeneity of specificity was found, while the heterogeneity of sensitivity was still significant.


Common bile duct stone caused by a foreign body: a case report and literature review.
Foreign bodies are very rare in the common bile duct. We report an unusual case of transient obstructive jaundice, due to a choledochal stone formed around an ingested woody fiber. Review of the literature.


Nitric oxide, N omega-hydroxy-L-arginine and breast cancer.
Nitric oxide has varied effects on human breast cancer cells. At low concentration (micromolar range) it increases proliferation by increasing synthesis of some cells cycle protein and in higher concentration (nanomolar range) it leads to cytostasis or apoptosis by decreasing the translation of some cell cycle proteins.


Impact of repeat myocardial revascularization on outcome in patients with silent ischemia after previous revascularization.
This study sought to compare the survival of asymptomatic patients with previous revascularization and ischemia, who subsequently underwent repeat revascularization or medical therapy (MT). Coronary artery disease is progressive and recurring; thus, stress myocardial perfusion scintigraphy (MPS) is widely used to identify ischemia in patients with previous revascularization. Of 6,750 patients with previous revascularization undergoing MPS between January 1, 2005, and December 31, 2007, we identified 769 patients (age 67.7 ± 9.5 years; 85% men) who had ischemia and were asymptomatic. A propensity score was developed to express the associations of revascularization. Patients were followed up over a median of 5.7 years (interquartile range: 4.7 to 6.4 years) for all-cause death. A Cox proportional hazards model was used to identify the association of revascularization with all-cause death, with and without adjustment for the propensity score. The model was repeated in propensity-matched groups undergoing MT versus revascularization. Among 769 patients, 115 (15%) underwent revascularization a median of 13 days (interquartile range: 6 to 31 days) after MPS. There were 142 deaths; mortality with MT and revascularization were 18.3% and 19.1% (p = 0.84). In a Cox proportional hazards model (chi-square test = 89.4) adjusting for baseline characteristics, type of previous revascularization, MPS data, and propensity scores, only age and hypercholesterolemia but not revascularization were associated with mortality. This result was confirmed in a propensity-matched group. Asymptomatic patients with previous revascularization and inducible ischemia on MPS realize no survival benefit from repeat revascularization. In this group of post-revascularization patients, an ischemia-based treatment strategy did not alter mortality.


Antiepileptic drugs for the treatment of neuropathic pain: a systematic review.
Many therapies have been proposed for the management of neuropathic pain, and they include the use of different antiepileptic drugs. However, the lack of high quality studies indicates that results on the different neuropathic disorders under study do not recommend a particular drug treatment. This study makes a systematic review of the published literature on the use of several antiepileptic drugs to treat neuropathic pain, and has the objective of considering both its clinical characteristics and pharmacological use, which will depend on their level of scientific evidence and will follow the principles of evidence-based dentistry. The articles were stratified according to their scientific evidence using the SORT criteria (Strength of Recommendation Taxonomy), and it included those articles that only have level 1 or 2. Randomized clinical trials were stratified according to their level of quality using the JADAD scale, an instrument described by Jadad et al. (7). to assess the quality of clinical trials, while studies with a level below 3 were discarded. Recently, type A or B recommendations are given in favor or against the use of antiepileptic drugs to treat neuropathic pain on the basis of their scientific quality.


Rapid stromal remodeling by short-term VEGFR2 inhibition increases chemotherapy delivery in esophagogastric adenocarcinoma.
Anti-angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit is limited, urging the improvement of combination therapies. We aimed to clarify the effects of vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration of drugs in esophagogastric adenocarcinoma (EAC). Patient-derived xenograft (PDX) models of EAC were subjected to long-term and short-term treatment with anti-VEGFR2 therapy followed by chemotherapy injection or multi-agent dynamic contrast-enhanced (DCE-) MRI and vascular casting. Long-term anti-VEGFR2-treated tumors showed a relatively lower flow and vessel density resulting in reduced chemotherapy uptake. On the contrary, short-term VEGFR2 targeting resulted in relatively higher flow, rapid vasodilation, and improved chemotherapy delivery. Assessment of the extracellular matrix (ECM) revealed that short-term anti-angiogenic treatment drastically remodels the tumor stroma by inducing nitric oxide synthesis and hyaluronan degradation, thereby dilating the vasculature and improving intratumoral chemotherapy delivery. These previously unrecognized beneficial effects could not be maintained by long-term VEGFR2 inhibition. As the identified mechanisms are targetable, they offer direct options to enhance the treatment efficacy of anti-angiogenic therapy combined with chemotherapy in EAC patients.


[Clinical outcome measures in hand- and finger joint osteoarthritis from the patient perspective].
Osteoarthritis (OA) is the most common joint disease. While research activities in OA have concentrated on the knee and hip in recent years, knowledge and research results in the field of hand OA are still limited. In order to measure the effects of treatment or to obtain information on the course of a disease and the health status of a patient, outcome measures are commonly used in rheumatology. Such measures are variables which can be quantified and which represent either the perspective of health professionals or the perspective of patients or both. The aim of this article is to evaluate clinical outcome measures and corresponding instruments which are currently used for patients with hand OA, and to examine whether these measures and instruments represent the perspective of patients. For hand OA, measurements of disease activity and inflammation, function and performance, pain, mobility and stiffness, deformity and aesthetic damage are recommended by experts. Corresponding instruments are available for most of these outcome measures, but these often do not sufficiently represent the perspective of the patients. Some instruments lack reliability because standardized protocols for measurement have not yet been developed.


Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: role of hepatic nuclear factor-4alpha.
Mechanisms underlying dietary nutrient regulation of glucose-6-phosphatase (Glc-6-Pase) gene expression are not well understood. Here we investigated the effects of short-chain fatty acids on the expression of this gene in primary cultures of rat hepatocytes and H4IIE hepatoma cells. Propionate, butyrate, valerate, and caproate induced severalfold increases in the expression of Glc-6-Pase mRNA. In reporter gene assays, propionate, valerate, caproate, and also octanoate increased Glc-6-Pase promoter activity by 6-16-fold. Butyrate, by itself, had little or no effect on promoter activity, but it induced a robust increase (45-fold) in promoter activity in cells co-transfected with a plasmid expressing the transcription factor HNF-4alpha (alpha isoforms of hepatic nuclear factor 4). HNF-4alpha also enhanced promoter activity induced by other short-chain fatty acids. A dominant negative form of HNF-4alpha abrogated the fatty acid-induced promoter activity, a finding that accentuates a role for HNF-4alpha in the transcription process studied here. In cells transfected with HNF-4alpha, short-chain fatty acids and trichostatin A, an inhibitor of histone deacetylase, synergistically enhanced promoter activity, suggesting that hyperacetylation of histones is an important component of the transactivation of the Glc-6-Pase gene promoter by HNF-4alpha. Region-751/-466 of this promoter contains seven putative HNF-4alpha-binding motifs. Binding of HNF-4alpha to this region was confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays, indicating that HNF-4alpha is recruited to the Glc-6-Pase gene promoter during short-chain fatty acid-induced transcription from this promoter.


Pd(II)-catalyzed ortho-arylation of aryl phosphates and aryl hydrogen phosphates with diaryliodonium triflates.
Functionalized biaryl compounds were successfully synthesized using phosphates as the ortho-directing group in the Pd(II)/Pd(IV) catalytic cycle.


Asthma education taught by physical education teachers at grade schools: A randomised cluster trial.
Assess whether the Asthma, Sport and Health (ASAH) programme taught by teachers improves asthmatics' quality of life, asthma knowledge, and reduces school absenteeism. Randomised cluster trial parallel group. 2293 students (203 asthmatic) in the Intervention School group (IS) and 2214 in the Comparison School (CS) (224 asthmatic) belonging to primary school. Implementation of the educational programme "Asthma, Sport and Health" at grade schools, taught by physical education teachers. Quality of life according to the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). Asthma knowledge, asthma control, school absenteeism. After implementing the programme in the IS group, global quality of life improved significantly (p<0.001) as did their domains, symptoms (p<0.001), emotional function (p<0.001) and activity limitations (p<0.01), while in the CS group improvement was seen in global life quality (p<0.01) without any significant changes in the domains for emotional function and activity limitations. Asthma knowledge only increased in IS, among asthmatic students from 16.51 (CI 95% 16.04-16.98) to 18.16 (CI 95% 17.69-18.62) (p<0.001) and students without asthma from 15.49 (CI95% 15.36-15.63) to 17.50 (CI95% 17.36-17.64) (p<0.001). The multiple regression analysis showed that quality of life and its domains depend on asthma knowledge and above all, having well-controlled asthma. We found no decrease in school absenteeism. The ASAH programme improved certain quality of life aspects regarding asthma (emotional function and limitation of activities) and asthma knowledge, but it failed to reduce school absenteeism NCT01607749.


Artemisinin suppressed tumour growth and induced vascular normalisation in oral squamous cell carcinoma via inhibition of macrophage migration inhibitory factor.
Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported. Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF. Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells. Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.


The Duhring chamber. An improved technique for epicutaneous testing of irritant and allergic reactions.
For assessing skin reactions to irritants and allergens, chambers which confine the test substance to the site of application are much superior to conventional patch tests. Because the concentration and volume do not change appreciably, the method allows for quantification and yields more reproducible results. A new aluminum chamber has been designed which is more useful than its predecessor, the Finn chamber, mainly because of its increased capacity. Data are given to show that the intensity of irritant and allergic reactions is dependent on the quantities applied.


Impact of FDG PET on the preoperative staging of newly diagnosed breast cancer.
The main objective of this study was to determine the efficacy of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) to assess the impact of this technique in staging of patients with newly diagnosed breast cancer. Two hundred and seventy-one consecutive patients (median age = 51 +/- 11 years) with biopsy-proven primary breast cancer who were examined by FDG PET were enrolled in this prospective preoperative staging study. Whole-body FDG-PET images were acquired approximately 60 min after the intravenous administration of FDG (5.2 MBq/kg). Visual assessment and the maximum standardized uptake value (SUVmax) of breast lesions for semiquantitative analysis were carried out. The PET results were compared with the histopathology results. For the tumor, node, metastases (TNM) staging, 240 patients (250 breasts) were considered eligible based on the criteria that were established for this analysis. Significant differences were noted in SUVmax of lesions according to the TNM staging (p < 0.05). The average SUVmax of the primary tumor was calculated in patients with axillary involvement (n = 58) and for the ones without axillary metastasis (n = 79), and SUVmax were 4.1 +/- 3.5 and 2.8 +/- 2.3, respectively, with a significant difference between the two groups (p = 0.03). PET imaging revealed pathological FDG uptake in 54% (46/85) of patients with axillary lymph node metastases. The sensitivities of FDG PET for detecting axillary lymph node metastasis were found 41% in pN1, 67% in pN2, and 100% in pN3, and the specificity was 89% for pN0 stage. Detection of extra-axillary regional node or distant metastatic lesions revealed by PET scan in 22 of 24 patients resulted in a significant change in the TNM stage. Distant metastasis without axillary lymph node metastasis was noted in 21% (5/24) of patients. The results revealed that FDG PET upgraded TNM stage in 9.2% (22/240) of patients and 7.5% (18/240) of patients were diagnosed as having one or more distant metastases. FDG PET was able to identify extra-axillary regional nodal and distant lesions in newly diagnosed patients with breast cancer; FDG PET may alter the staging and management of therapy in patients with newly diagnosed breast cancer.


Brief Report: Stability and Chemical Characteristics of Injectable Ascorbic Acid for Patients With Cancer.
Intravenous ascorbic acid (IVAA) has been used extensively as part of the management plan for cancer patients in various medical clinics throughout the United States. The current research team has evaluated its effectiveness in patients with cancer as part of an ongoing research program. However, no data are available that support the chemical stability of intravenously injectable ascorbic acid (AA) to ensure its safety and efficacy in that patient population. Its clinical use as well as its use in research conducted in US Food and Drug Administration-approved clinical trials require validation of its stability. The study intended to evaluate the chemical stability of the compounded IVAA that it prepares. The research team conducted a stability analysis within a 6-h period, a period longer than the time required for most infusions, which typically take approximately 2 h. The study evaluated the stability of AA intravenous sets, which are compounded solutions for clinical or hospital use. The IVAA was prepared in sterile water, together with magnesium chloride (MgCl) and calcium gluconate (CaGluc) as buffers. The study took place at the Marcus Institute of Integrative Health at Thomas Jefferson University (Philadelphia, PA, USA). The study was performed for 2 dosages of an infusion set: 75 g and 100 g of IVAA. Interval testing included pH, particulate matter by light obscuration, and high-performance liquid chromatography assay. Analyses were performed at baseline and at 2-, 4-, and 6-h test intervals. The results demonstrated that IVAA remained highly stable throughout the 6-h period. It also passed the US Pharmacopeia's criteria for pH and particulates when used with a 0.2 µ filter. These data suggest that IVAA, when prepared with sterile water, in addition to MgCl and CaGluc, is highly stable and safe to use in patients for up to 6 h after preparation.


Comparison of cancer risk associated with low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction in women versus men.
Patients with cardiovascular disease are increasingly exposed to low-dose ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous studies have suggested that the malignancy risk associated with LDIR may be greatest in women and in young patients. We sought to compare the effect of LDIR on incident cancer across gender and age strata in a population-based cohort of patients with myocardial infarction (MI). All initially cancer-free patients with MI from 1996 to 2006 were identified in a province-wide administrative database. Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac LDIR exposure variable. Time-dependent multivariate Cox regression was used to determine the relation between cardiac LDIR and incident cancer. A time-lag covariate of 3 years was used wherein a de novo cancer could only be attributed to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR-associated risk of cancer was evaluated with stratified models and the addition of interaction terms. The study cohort consisted of 56,606 men and 26,255 women. For each millisievert of cardiac LDIR, women were more likely to develop a cancer (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age, noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the range studied (predominantly patients aged >50 years), age was not a determinant of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from cardiac imaging and therapeutic procedures after MI are at a greater risk of incident cancer compared with men after similar exposure. The extrapolated absolute risk from LDIR exposure would nonetheless be expected to be low.


Design, recombinant expression and convenient A-chain N-terminal europium-labelling of a fully active human relaxin-3 analogue.
Relaxin-3 (also known as INSL7) is a recently identified neuropeptide belonging to the insulin/relaxin superfamily. It plays a putative role in the regulation of food intake, in the stress response and in reproduction by activating the G-protein-coupled receptor, RXFP3. In a previous study, we prepared 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)/Eu(3+)-labelled human relaxin-3 as a tracer for the study of ligand-receptor interactions, which necessitated a complicated site-specific labelling strategy because human relaxin-3 contains four primary amine moieties, all of which react with the primary amine-specific modification reagent. To simplify the labelling procedure, in the present study we created an easily labelled, recombinant analogue of human relaxin-3 with only one primary amine moiety at the A-chain N-terminus. The analogue retained full activity and could be easily labelled by various functional probes at the A-chain N-terminus. The DOTA/Eu(3+)-labelled analogue retained high binding affinity for its cognate receptor, RXFP3, and thus represents a useful, nonradioactive and stable tracer for studying the interaction of RXFP3 with various natural or synthetic ligands. This new analogue is also a suitable template for the design of other relaxin-3 analogues that can be easily labelled with the DOTA/Eu(3+) moiety and used to study binding activity and interactions with various RXFP3 analogues in the future.


In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery.
Stimuli-sensitive block copolymer hydrogels, which are reversible polymer networks formed by physical interactions and exhibit a sol-gel phase-transition in response to external stimuli, have great potential in biomedical and pharmaceutical applications, especially in site-specific controlled drug-delivery systems. The drug may be mixed with a polymer solution in vitro and the drug-loaded hydrogel can form in situ after the in vivo administration, such as injection; therefore, stimuli-sensitive block copolymer hydrogels have many advantages, such as simple drug formulation and administration procedures, no organic solvent, site-specificity, a sustained drug release behavior, less systemic toxicity and ability to deliver both hydrophilic and hydrophobic drugs. Among the stimuli in the biomedical applications, temperature and pH are the most popular physical and chemical stimuli, respectively. The temperature- and/or pH-sensitive block copolymer hydrogels for biomedical applications have been extensively developed in the past decade. This review focuses on recent development of the preparation and application for drug delivery of the block copolymer hydrogels that respond to temperature, pH or both stimuli, including poly(N-substituted acrylamide)-based block copolymers, poloxamers and their derivatives, poly(ethylene glycol)-polyester block copolymers, polyelectrolyte-based block copolymers and the polyelectrolyte-modified thermo-sensitive block copolymers. In addition, the hydrogels based on other stimuli-sensitive block copolymers are discussed.


Time trend of PCB concentrations in surface sediments from a hypertrophic, macroalgae populated area of the lagoon of Venice.
The concentrations of polychlorinated biphenyls have been determined over a period of 1 year in surface sediments sampled monthly and semi-monthly in the lagoon of Venice. At the sampling station, due to the poor water circulation and an over-abundance of nutrients, macroalgae thrive in spring-summer and standing crops greater than 12 kg m-2 were determined. As a consequence of rapid algal decomposition, sediment PCB concentrations were observed to increase. In particular, on occasions when anoxia occurred at the end of July and all the biomass had decayed, PCB concentrations increased by more than one order of magnitude. In March, when macroalgae started to grow, concentrations were 13 ng g-1 (dry wt); in July-August they exceeded 100 ng g-1. The sediment PCB concentrations were restored to the previous values after algal biomass became negligible, in November. Concentrations of PCBs in young algae fronds were 27 +/- 12 ng g-1, and 121 +/- 4 ng g-1 in older fronds.


Migration of formaldehyde from 'biobased' bamboo/melamine cups: A Dutch retail survey.
Bamboo/melamine cups had become popular, due to their ecofriendly and sustainable image. Some cups are marketed as biobased and biodegradable. These cups are made from melamine-formaldehyde resin to which bamboo fibers or powder are added. They may release formaldehyde and melamine into the beverage. In 2019 the Netherlands Food and Consumer Product Safety Authority conducted a market study. 46 cups were sampled in duplicate and tested for formaldehyde migration. 88% of the cups complied with the migration limit of 15 mg/kg. Some cups showed very high migration values, over 200 mg/kg. There is a high exposure of formaldehyde from other sources (food, environment). When applying a realistic worst-case scenario of a daily intake of 0.4 L of beverage from the cups, the health based guidance value is exceeded at a migration of 19 mg/kg and higher. For some of the cups that had a high migration of formaldehyde, health risks may occur. For food-utensils for babies and young children, the exposure is higher due to their lower body weight. The SML does not provide sufficient protection for babies and young children. Bamboo is not authorized in the EU as additive for plastic food contact materials. Therefore the Netherlands, Belgium, Luxembourg and other EU member states have actively banned these products from the market. Finally, bamboo/melamine tableware would suggest having a 'green' image and would contribute to the goals of the circular economy to use biobased raw materials, but by using it in combination with melamine-formaldehyde resin may affect food safety.


Löffler endocarditis: a rare cause of acute cardiac failure.
We describe a patient with acute cardiogenic shock due to cardiac involvement in idiopathic hypereosinophilic syndrome (Löffler endocarditis). At the echocardiography, there was a huge mass in the left ventricular cavity, resulting in inflow- and outflow tract obstruction. The posterior leaflet of the mitral valve apparatus was completely embedded in a big (organized) thrombus mass. The patient was treated with high dose corticosteroids, however without effect. Partial remission was achieved after treatment with hydroxycarbamide. He was also treated with anticoagulants and high dose beta-blockers. The patient's condition improved remarkably after correction of the mitral valve insufficiency by a mitral valve bioprosthesis.


Xanthoma of a calcaneus.
Primary xanthoma in foot bones is an extremely rare event. In an individual without a family history of hyperlipemia, it is even a rarer finding. One case of a xanthoma of a calcaneus is presented in an otherwise asymptomatic 19-year-old normal lipidemic female. The previous literature is reviewed. The clinical findings and treatment course are presented.


Administration of erythropoietin fails to improve long-term healing or cardiac function after myocardial infarction in the rat.
Erythropoietin (epo), initially recognized and used clinically to increase erythropoiesis, has been shown to have beneficial effects on various other tissues in the setting of hypoxia and ischemia. Epo has been shown to reduce apoptosis after myocardial infarction, but few studies have evaluated the long-term effects of epo treatment on left ventricular (LV) remodeling, cardiac function, and blood flow after healing of a permanent coronary artery occlusion. The aim of this study was to assess the effects of epo treatment on the healed heart 6 weeks after myocardial infarction. Anesthetized rats underwent coronary artery occlusion and were treated with erythropoietin (5000 units/kg/day, n=21) or saline (n=20) the day before surgery, the day of, then for 5 days. At 6 weeks LV ventriculography to assess LV volumes and ejection fractions and histologic assessment of infarct size and LV cavity and wall dimensions were performed. Overall epo had no effect on LV remodeling or cardiac function. There were no significant differences in infarct morphology, infarct size (44+/-3% of the LV circumference versus 39+/-3%), LV cavity area, scar thickness, LV systolic volume, or ejection fraction (44+/-3% versus 39+/-3%) between the epo and saline groups, respectively. However, for any given size of myocardial infarct, LV ejection fraction was significantly higher in erythropoietin hearts and LV systolic volumes lower. Thus, in our model, treatment with epo had no long-term beneficial effect on LV remodeling after myocardial infarction but may have exerted some positive effect on LV function.


Normal saline slush preparation for renal surgery.
We describe a simple, rapid method to prepare normal saline slush with commercially available slush mugs that are gas-sterilized in routine fashion and stored in freezer. Slush can be prepared intraoperatively in 10 minutes with this method.


Patient-reported outcomes in clinical studies of patients with hypertrophic cardiomyopathy.
This study aimed to characterize patient-reported outcomes (PROs) in registered clinical studies of participants with hypertrophic cardiomyopathy (HCM). Therapy for HCM is primarily targeted toward alleviation of symptoms and improvement in function and quality of life. Yet, the contemporary landscape of PROs in HCM clinical research has not been investigated. ClinicalTrials.gov was queried to identify clinical studies of HCM that reported PROs as outcome measures. All studies of HCM as the disease condition were included, and PROs were identified using specific search terms in the Outcome Measures field. Study characteristics were collected and compared between those that did versus did not report PROs. From November 1987 to February 2022, 181 studies including participants with HCM were registered on ClinicalTrials.gov. Of these, 35 (19%) included PROs as outcome measures. Studies reporting PROs were more likely to be designated as interventional (85.7% vs. 46.6%; p < 0.001) and to involve randomization (65.7% vs. 24.7%; p = 0.003) compared with those that did not report PROs. Prior to 2007, no clinical studies that reported PROs were registered in ClinicalTrials.gov; however, PRO reporting has increased over the last 15 years. Of the 66 PRO tools or domains included as outcome measures, the Kansas City Cardiomyopathy Questionnaire was the most often used. Only approximately one in five registered clinical studies of participants with HCM report PROs. As medical, percutaneous, and surgical therapies for HCM continue to advance, HCM-specific PRO tools that assess the impacts of these new treatments on meaningful patient-related endpoints are urgently needed.


The potential of dendrimer in delivery of therapeutics for dentistry.
Dendrimers are hyperbranched nanoparticle structures along with its surface modifications can to be used in dental biomaterials for biomimetic remineralisation of enamel and dentin. The review highlights the therapeutic applications of dendrimers in the field of dentistry. It addresses the possible mechanisms of enhancement of mechanical properties of adhesives and resins structure. Dendrimers due to its unique construction of possessing inner hydrophobic and outer hydrophilic structure can act as drug carrier for delivery of antimicrobial drugs for treatment of periodontal diseases and at peripheral dental implant areas. Dendrimers due to its hyperbranched structures can provides a unique drug delivery vehicle for delivery of a drug at specific site for sustained release for therapeutic effects. Thus, dendrimers can be one of the most important constituents which can be incorporated in dental biomaterials for better outcomes in dentistry.


RecP, a new minor pathway of general recombination in Escherichia coli encoded by plasmid R1drd-19.
Plasmid R1drd-19 markedly improves the recombination deficiency of recB and recBrecC mutants of Escherichia coli K12 as measured by Hfr crosses and increases their resistance to uv inactivation. The effect correlates with the production of an ATP-dependent ds DNA exonuclease in recB/R1drd-19 cells. This paper further investigates the suppressive effect of plasmid R1drd-19 on the recB mutation of E. coli. The gene(s) responsible for the effect was localized to the 13.1-kb EcoRI-C fragment of the resistance transfer factor (RTF) portion of R1drd-19. The plasmid-encoded activity does not merely replace the RecBCD enzyme failure but differs in several significant ways. It promotes a hyper-recombinogenic phenotype, as judged by the phenomenon of super oligomerization of the tester pACYC184 plasmid in recB/R1drd-19 cells and two inter- and intramolecular plasmid recombination test systems. It is probably not inhibited by lambda Gam protein and does not restrict plating of T4gp2 mutant. No significant homology between the E. coli chromosomal fragment carrying recBrecCrecD genes and the EcoRI-C fragment of R1drd-19 was observed. It is suggested that the plasmid-encoded recombination activity is involved in a new minor recombination pathway (designated RecP, for Plasmid). RecP resembles in some traits the RecBCD-independent pathways RecE and RecF but differs in activity and perhaps substrate specificity from the main RecBCD pathway.


Transmission of hepatitis C virus by occupational percutaneous injuries in South Korea.
Korea is an endemic area of hepatitis. Hepatitis C virus (HCV) infections caused by occupational percutaneous injuries are a serious problem for healthcare workers and there has been a gradual increase in the number of HCV infections. We therefore determined the transmission rate of HCV after occupational percutaneous injury. This was a retrospective cohort study reviewing all occupational blood exposure reports made between January 1, 2004, and December 31, 2008, at a university-affiliated acute care hospital. Over the 5-year study period, there were 1,516 accidents of occupational exposure to blood; of these, 327 (21.6%) were to the blood of HCV-infected patients and 3 (0.9%) healthcare workers became infected with HCV (95% CI 0.6-8.8). In Korea, although the bloodborne accidents leading to exposure to HCV occurred frequently (21.6%), the transmission rate was very low (0.92%).


Laryngeal stenosis in epidermolysis bullosa dystrophica.
Epidermolysis bullosa dystrophica is a rare hereditary skin disease of infancy in which minor trauma causes blister formation. We report a rare case of epidermolysis bullosa dystrophica (recessive) with a stenosis of the larynx due to epiglottic deformity. We performed a tracheotomy, and we detained a trachea aperture in the long term this time. In a characteristic of a disease though stimulation to the trachea causes the erosion on a trachea mucous membrane, postoperative course was uneventful and we are going to observe it in future.


Bilateral one-stage total hip replacement in rheumatoid arthritis and SPA.
Sixteen cases of bilateral total one-stage hip replacements in patients with rheumatoid arthritis or ankylosing spondylitis are reviewed. Special reference is given to peroperative problems, complications, and indications in a hospital with on intensive care unit. The indications are discussed and the results compared with larger series published earlier in literature. One-stage procedure proves to be a proper alternative in cases with severe bilateral disease. The rate of complications is comparable to that of unilateral procedures. A marked decrease in time consumption can be achieved.


At the Root of the Repair Debate: Outcomes After Elective Aortic Root Replacements for Aortic Insufficiency With Aneurysm.
There is growing interest in aortic valve-sparing and valve repair operations, but the ideal operation and timing of intervention in these generally younger patients undergoing operations for aortic insufficiency (AI) and dilated ascending aorta remains controversial. Root replacements at a single institution from 2002 to 2014 were reviewed. Inclusion criteria were age younger than 70 and presence of moderate or greater aortic insufficiency (AI), with or without aortic aneurysm. Of 1,425 root replacements, 220 patients were considered in the final analysis. Moderate AI was present in 87 patients and severe AI in 133 patients. The 30-day mortality was 0% in moderate AI patients and 2% (n = 3) in severe AI patients (p = 0.3). Freedom from reoperation was 95% at 10 years. Severe preoperative AI was associated with worse long-term survival compared with moderate AI (hazard ratio, 2.6; p = 0.04). Patients undergoing root replacement with moderate AI had similar survival compared with the age- and gender-matched United States population (log-rank p = 0.93), whereas patients with severe AI had significantly worse survival (log-rank p = 0.02). Other multivariable predictors of decreased long-term survival were age (hazard ratio, 1.1; p = 0.01) and preoperative renal failure (hazard ratio, 6.9; p < 0.01). Elective root replacement operations in patients younger than 70 are associated with low rates of mortality and reoperation, which should be considered the benchmark operation for aortic valve-sparing or repair operations in similar patients. Worse survival was associated with severe AI and older age, suggesting earlier intervention may be an appropriate therapeutic strategy in selected patients.


Phallic reconstruction during exenterative surgery for invasive urethral carcinoma.
A technique is described for phallic reconstruction after wide surgical excision of squamous cell carcinoma of the bulbomembranous urethra. Two cases in which this technique was used are presented with followup information at 9 and 12 months.


Time of arrival of wheat germ agglutinin-HRP conjugates in superior colliculus after intraocular injections in the rat.
Rats received intravitreal injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGHRP) or labeled with fluorescein isothiocyanate (WGFITC). SDS polyacrylamide gel electrophoresis of WGHRP demonstrated that little or no native horseradish peroxidase (HRP) was present in the injected conjugate. Under the conditions employed in these experiments, evidence for the orthograde transport of WGHRP but not of WGFITC was observed. In a separate experiment carried out under similar circumstances, WGFITC was retrogradely transported. Thus WGFITC does not appear to be a sensitive probe for studies of efferent projections. The earliest time of arrival of WGHRP in the contralateral superior colliculus (SC) was determined in order to establish the most rapid rate of anterograde transport of WGHRP. Retinal ganglion cell axon terminals in SC were first labeled 4 h after an intraocular injection of WGHRP which is equivalent to a transport rate of about 108 mm/day. This rate of transport is approximately half that reported for native HRP. It is concluded that the superior sensitivity of WGHRP over native HRP as an anterogradely transported marker cannot be ascribed to a more rapid rate of orthograde transport of WGHRP.


Relationship between SUVmax on 18F-FDG PET and PD-L1 expression in hepatocellular carcinoma.
Our study was to investigate the correlation between 18F-FDG uptake in HCC and tumor PD-L1 expression in HCC, and assess the value of 18F-FDG PET/CT imaging for predicting PD-L1 expression in HCC. A total of 102 patients with confirmed HCC were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of HCC lesions were assessed using 18F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. The SUVmax of HCC primary tumors was higher in patients with poorly differentiated HCC, large tumor size, portal vein tumor thrombus, lymph node and distant metastases, and death. The SUVmax of HCC are correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. PD-L1 expression was significantly correlated with tumor SUVmax, tumor differentiation, tumor size, portal vein tumor thrombosis, and patient survival status and infiltrating M2 macrophages. Further, our results confirmed that SUVmax, portal vein tumor thrombosis, and the number of infiltrating M2 macrophages were closely related to PD-L1 expression and were independent risk factors by multivariate analysis. The combined assessment of SUVmax values and the presence of portal vein tumor thrombosis by 18F-FDG PET/CT imaging can help determine PD-L1 expression in HCC. FDG uptake in HCC was positively correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. The combined use of SUVmax and portal vein tumor thrombosis by PET/CT imaging assess the PD-L1 expression better in HCC. These findings also provide a basis for clinical studies to assess the immune status of tumors by PET/CT.


Development of a saliva collection device for use in the field.
For monitoring biomarkers, saliva has several distinct advantages over other biological fluids. Saliva sampling is relatively non-invasive and enables the collection from either adults or infants under many different circumstances. However, there is no collection device that can be speedily used for analysis in the field. The aim of the present study was to evaluate the suitability of a new device, termed Muddler, compared with commercially available collection devices. Saliva was collected from healthy volunteers. The collection devices such as Muddler, eye sponge, Salivette® Cotton (SC) and Salivette® Synthetic (SS) were evaluated in terms of the volume and/or composition of the collected saliva. The amounts of immunoglobulin A (IgA) and lactofferin in saliva were assessed by the enzyme-linked immunosorbent assays with the corresponding antibodies. Amylase activity was measured using a commercially available kit, and high molecular weight complexes including mucin were assessed by SDS-PAGE staining. A newly developed Muddler, which was made of plastic plate, was the best device for collecting a constant volume of saliva among all the devices examined in the present study. Furthermore, Muddler can collect without change in composition of salivary proteins such as IgA, lactoferrin, amylase, and mucin complex, whereas the levels of the salivary proteins obtained with all the commercial devices used were clearly different from those in original saliva. The newly developed Muddler was the best collection device in terms of the accuracy of collection and the reliability of measurements among all the devices examined in the present study.


Does the uterine microbiota affect the reproductive outcomes in women with recurrent implantation failures?
Inefficiency of in vitro fertilization (IVF) programs can be caused by implantation failures. The uterine microbiota can influence the implantation process. However, it still remains unclear whether opportunistic microorganisms detected in the endometrium have a negative impact on the implantation success. The aim of our study was to evaluate the influence of the uterine microbiota on the embryo implantation success in patients undergoing assisted reproductive technologies. The study included 130 women diagnosed with infertility. The patients were divided into three groups: group I included women with the first IVF attempt (n = 39); group II included patients with recurrent implantation failure following embryo transfer with ovarian stimulation (n = 27); group III consisted of women with recurrent implantation failure following frozen-thawed embryo transfer (n = 64). We performed microbiological examination of the embryo transfer catheter which was removed from the uterine cavity after embryo transfer; cervical discharge of all the patients was studied as well. Thirty patients were selected for metagenomic sequencing. The study showed that the uterine cavity is not free of microorganisms. A total of 44 species of microorganisms were detected: 26 species of opportunistic organisms and 18 species of commensals (14 species of lactobacilli and 4 species of bifidobacteria). Obligate anaerobic microorganisms and Gardnerella vaginalis were detected more frequently in group I compared to group III (strict anaerobes-15.4 and 1.6%; G. vaginalis-12.8 and 1.6%, respectively) (p < 0.05). However, this fact did not have a negative influence on the pregnancy rate: it was 51.3% in group I, it was 29.6% and 35.9% in women with recurrent implantation failures, respectively. Opportunistic microorganisms which were revealed in low or moderate titers (103-105 CFU/ml) in the uterine cavity and cervical canal did not affect the pregnancy rate in the women in the study groups. The microflora of the uterine cavity and cervical canal differed in qualitative composition in 87.9% of patients, therefore, we can suggest that the uterine cavity may form its own microbiota. The microbiota of the uterine cavity is characterized by fewer species diversity compared to the microbiota of the cervical canal.


Retrospective study of morbidity and mortality of raptors admitted to Colorado State University Veterinary Teaching Hospital during 1995 to 1998.
A retrospective study was conducted to identify causes of morbidity and mortality of free-living raptors in northeast Colorado and the surrounding areas of Nebraska and Wyoming. The study included 409 raptors, representing 23 species, admitted to the Colorado State University Veterinary Teaching Hospital, Fort Collins, Colorado, USA, from 1995 to 1998. Causes of morbidity and mortality were identified as trauma (66.3%), orphaned young (15.6%), unknown (9.0%), infectious disease (4.4%), metabolic and nutritional disease (2.2%), toxicosis (2.0%), and degenerative disease (0.5%). Trauma was the most frequent cause of morbidity and mortality for all species and during all seasons.


Sustainable biopolymer soil stabilisation: the effect of microscale chemical characteristics on macroscale mechanical properties.
Sustainable biopolymer additives offer a promising soil stabilisation methodology, with a strong potential to be tuned to soil's specific nature, allowing the tailoring of mechanical properties for a range of geotechnical applications. However, the biopolymer chemical characteristics driving soil mechanical property modifications have yet to be fully established. Within this study we employ a cross-scale approach, utilising the differing galactose:mannose (G:M) ratios of various Galactomannan biopolymers (Guar Gum G:M 1:2, Locust Bean Gum G:M 1:4, Cassia Gum G:M 1:5) to investigate the effect of microscale chemical functionality upon macroscale soil mechanical properties. Molecular weight effects are also investigated, utilising Carboxy Methyl Cellulose (CMC). Soil systems comprising of SiO2 (100%) (SiO2) and a Mine Tailing (MT) exemplar composed of SiO2 (90%) + Fe2O3 (10%) (SiO2 + Fe) are investigated. The critical importance of biopolymer additive chemical functionality for the resultant soil mechanical properties, is demonstrated..For Galactomannan G:M 1:5 stabilised soils the 'high-affinity, high-strength', mannose-Fe interactions at the microscale (confirmed by mineral binding characterisation) are attributed to the 297% increase in the SiO2 + Fe systems Unconfined Compressive Strength (UCS), relative to SiO2 only. Conversely for SiO2 Galactomannan-stabilised soils, when increasing the G:M ratio from 1:2 to 1:5, a 85% reduction in UCS is observed, attributed to mannose's inability to interact with SiO2. UCS variations of up to a factor of 12 were observed across the biopolymer-soil mixes studied, in line with theoretically and experimentally expected values, due to the differences in the G:M ratios. The limited impact of molecular weight upon soil strength properties is also shown in CMC-stabilised soils. When considering a soil's stiffness and energy absorbance, the importance of biopolymer-biopolymer interaction strength and quantity is discussed, further deciphering biopolymer characteristics driving soil property modifications. This study highlights the importance of biopolymer chemistry for biopolymer stabilisation studies, illustrating the use of simple low-cost, accessible chemistry-based instrumental tools and outlining key design principles for the tailoring of biopolymer-soil composites for specific geotechnical applications. The online version contains supplementary material available at 10.1007/s11440-022-01732-0.


Naltrexone + Bupropion Combination for the Treatment of Binge-eating Disorder with Obesity: A Randomized, Controlled Pilot Study.
Binge-eating disorder (BED), the most prevalent eating disorder, is associated strongly with obesity and functional impairments. Few evidence-based treatments for BED exist; a pharmacotherapy effective in reducing both binge eating and weight needs to be identified. This placebo-controlled double-blind pilot RCT evaluated the acute effects of naltrexone + bupropion (NB) on BED with obesity and examined the longer-term effects through 6-month follow-up after the discontinuation of medication. Twenty-two adult patients with BED were randomized to receive 12 weeks of double-blind treatment with fixed-dose NB (naltrexone + bupropion XL 50/300 mg) or placebo. Independent (blinded) researcher-clinicians evaluated patients at major outcome time points (baseline, posttreatment, and 6-month follow-up after the treatment period); patients were also evaluated for the tracking of course/tolerability throughout treatments and at 3-month follow-up. Primary outcomes were changes from baseline in binge-eating frequency and percentage weight. Secondary outcomes were changes in eating-disorder psychopathology and depression. A total of 22 patients were enrolled (86.4% women; mean age, 50.4 years), with 77.3% of patients completing treatments; completion rates (NB, 83.3%; placebo, 70.0%) and adverse events did not differ significantly between NB and placebo. Analyses revealed significant reductions from baseline in binge-eating, eating-disorder psychopathology, depression, and weight during treatment, but these changes with NB did not differ significantly from those with placebo. The percentage of patients who attained 3% weight loss was significantly greater with NB than with placebo (45.5% vs 0%); weight-loss and binge-eating reductions were significantly correlated in the group that received NB. At 6-month follow-up, outcomes remained improved relative to baseline, with no significant differences between NB and placebo. The findings from this pilot RCT suggest that NB was well-tolerated in these patients with BED and comorbid obesity. Most outcomes were not statistically different between NB and placebo. A larger-scale, adequately powered RCT is needed for determining the efficacy of NB in the treatment of BED. ClinicalTrials.gov identifier: NCT02317744.


Value of testis biopsy in the diagnosis of systemic amyloidosis.
To evaluate testis biopsy as a diagnostic tool in systemic amyloidosis, to assess how amyloidosis affects testicular tissue, and to examine the relationship between testicular amyloidosis and infertility. Testicular biopsies from 72 patients with confirmed systemic amyloidosis were examined for amyloid deposition after Congo red and crystal violet staining. A rectal biopsy was also done in each case, and the results were compared with the testicular biopsy findings. Testicular amyloid deposition was detected in 62 (86.1%) of 72 patients. Fifty-one (85%) of 60 patients with secondary amyloidosis, 11 (91.7%) of 12 patients with primary amyloidosis, and 28 (87.5%) of 32 patients with familial Mediterranean fever showed amyloid deposition in the testis. Rectal biopsies were positive in 40 cases (55.6%). Only 4 of the 62 patients with testicular amyloid showed normal spermatogenesis. The remaining 58 exhibited abnormal spermatogenesis, and 77.7% of patients had seconder infertility. Of 62 patients with positive testis biopsies, 30 had serum creatinine levels less than 1.5 mg/dL, and 29 patients with testicular amyloid manifested nephrotic syndrome. The testis biopsy is a valuable and more sensitive method than rectal biopsy for diagnosing systemic amyloidosis. The results also showed that testicular amyloidosis causes infertility at a higher rate than expected.


Which clinical errors lead to the referral of UK paediatricians to the National Clinical Assessment Service?
The aim of this study was to determine which clinical errors lead to the referral of UK paediatricians to the National Clinical Assessment Service (NCAS). Data for the 10-year period from 1 April 2001 to 31 March 2011 were analysed. Referrals are classified into clinical, behavioural and health related. Clinical referrals can be general, relating to general deficiencies in knowledge and skills, or specific and concerned with a critical incident. Specific clinical referrals were analysed. There were 259 paediatric cases in this period. There were 110 (42 %) clinical concerns in the 259 cases. In 47 of the 110 cases, these were general concerns. There were 63 cases where specific clinical concerns had led to the referral. These were: diagnosis and management of child protection cases, 19; prescribing errors, 13; diagnosis other than child protection cases, 12; treatment incidents, 7; difficulties with transfer of a patient to another unit, 6; poor resuscitation, 4; and slow response to an emergency, 2. In 16 of the cases, the patient died. This analysis reveals some different errors to those in other studies of paediatric litigation and complaints. Mistakes in child protection cases were the commonest reason for referral to NCAS. Prescribing errors were the second commonest cause. Difficulties in the diagnosis and treatment of a range of different conditions accounted for the next biggest group of referrals. This study helps highlight areas of paediatrics, such as child protection and prescribing, where training needs to be improved in order to improve patient safety.


Roles of protein kinase C and alpha-tocopherol in regulation of signal transduction for GATA-4 phosphorylation in HL-1 cardiac muscle cells.
Our previous study demonstrated that endothelin-1 induced a phosphorylation of GATA-4 transcription factor, which plays important roles in cardiac hypertrophy and failure. The goal of the present study was to determine whether protein kinase C (PKC) is involved in the signaling pathway, and, if so, whether alpha-tocopherol inhibits the GATA-4 phosphorylation. Treatment of HL-1 adult mouse cardiac muscle cells with PMA, a known activator of PKC, induced a transient phosphorylation of GATA-4. PMA also phosphorylated MEK and ERK, and PMA-induced GATA-4 phosphorylation was blocked by an MEK inhibitor, PD98059, suggesting that PMA phosphorylates GATA-4 via the MEK-ERK pathway. Treatment of HL-1 cells with 1 microM PMA for 24 h resulted in a downregulation of PKC. In PKC-downregulated cells, PMA- or ET-1-induced GATA-4 phosphorylation was suppressed, suggesting the role of PKC in GATA-4 phosphorylation. However, alpha-tocopherol (5--100 microM) did not inhibit the phosphorylation of GATA-4 or ERK in HL-1 cells. In contrast, alpha-tocopherol potently inhibited the PMA-induced ERK activation in smooth muscle cells. Our studies in HL-1 cells showed that PKC inhibitors, such as calphostin C and chelerythrin, failed to inhibit the PMA signaling. Furthermore, HL-1 cells appear to possess a unique PKC-signaling mechanism as PKC is constitutively phosphorylated and PMA did not cause further phosphorylation. Thus, in HL-1 cardiac muscle cells, PMA activates the MEK-ERK-GATA-4 pathway, apparently via a PKC-independent mechanism.


Polo-like kinase 3 is Golgi localized and involved in regulating Golgi fragmentation during the cell cycle.
The Golgi apparatus undergoes extensive fragmentation during mitosis in animal cells. Protein kinases play a critical role during fragmentation of the Golgi apparatus. We reported here that Polo-like kinase 3 (Plk3) may be an important mediator during Golgi breakdown. Specifically, Plk3 was concentrated at the Golgi apparatus in HeLa and A549 cells during interphase. At the onset of mitosis, Plk3 signals disintegrated and redistributed in a manner similar to those of Golgi stacks. Nocodazole activated Plk3 kinase activity, correlating with redistribution of Plk3 signals and Golgi fragmentation. In addition, treatment with brefeldin A (BFA), a Golgi-specific poison, also resulted in disappearance of concentrated Plk3 signals. Plk3 interacted with giantin, a Golgi-specific protein. Expression of Plk3, but not the kinase-defective Plk3 (Plk3(K52R)), resulted in significant Golgi breakdown. Given its role in cell cycle progression, Plk3 may be a protein kinase involved in regulation of Golgi fragmentation during the cell cycle.


Promoting Sexual Consent Principles in the Sexual and Reproductive Health Care of Adolescents and Young Adults.
Mutual sexual consent is an essential component of healthy sexual relationships. The ability to communicate with a partner about any physical/sexual contact, including kissing, touching, or sexual intercourse, is necessary for a mutually respectful relationship. Healthcare clinicians (HCCs) and health education programs should stress the importance of sexual consent and recognize the frequency of nonconsensual sexual activity and sexual violence among adolescents and young adults (AYAs). HCCs and those who work with youth need to be aware of the cultural context and norms along with legal parameters for sexual consent in their geographic area. Infrastructure support, including programs to develop clinician skills, time for thoughtful and sensitive discussions about sexual consent, and community referral options, is necessary for HCCs to be able to have the skills and time to review the important aspects of sexual consent with their patients. Research is needed to advance evidence-based practices to prevent nonconsensual sexual contact among AYAs and to effectively disseminate and implement best practices.


Improving the design of RCTs in non-radiographic axial spondyloarthritis.
Concerns have been raised that randomized placebo-controlled trials (RCTs) in non-radiographic axial spondyloarthritis (nr-axSpA) might be failing to identify patients that best show differences in clinical response rates between those receiving active drug and those receiving placebo therapies; in addition, some studies might even be showing spurious differences in responses to TNF and IL-17 inhibitor therapies. In particular, the most recent phase III RCTs in nr-axSpA have reported variable and generally lower response rates than observed in phase III trials of patients with ankylosing spondylitis and in trials conducted a decade ago in patients with early axSpA who were selected on the basis of axial inflammation evident on MRI scans. We argue that these observations at least partly reflect an RCT design that does not take full advantage of MRI to select patients who are responsive to therapy because the current MRI-based inclusion criteria cannot identify patients with axSpA with sufficient specificity. We propose that future studies should be designed using revised patient inclusion criteria based on expanded MRI evaluation and the application of data-driven definitions of a positive MRI for inflammatory and structural lesions typical of axSpA reported in an international multicentre analysis of MRI scans from the Assessment of SpondyloArthritis International Society (ASAS) classification cohort.


Role of Advanced Gastrointestinal Endoscopy in the Comprehensive Management of Neuroendocrine Neoplasms.
Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent tumors with good prognoses, some NENs exhibit aggressive behavior. Timely diagnosis, risk stratification, and management can often be a challenge. In general, small NENs without local invasion or lymphovascular involvement can often be managed using minimally invasive advanced endoscopic techniques, while larger lesions and those with evidence of lymphovascular invasion require surgery, systemic therapy, or a combination thereof. Ideal management requires a comprehensive and accurate understanding of the stage and grade of the tumor. With the recent advancements, a therapeutic advanced endoscopist can play a pivotal role in diagnosing, staging, and managing this rare condition. High-definition white light imaging and digital image enhancing technologies like narrow band imaging (NBI) in the newer endoscopes have improved the diagnostic accuracy of traditional endoscopy. The refinement of endoscopic ultrasound (EUS) over the past decade has revolutionized the role of endoscopy in diagnosing and managing various pathologies, including NENs. In addition to EUS-directed diagnostic biopsies, it also offers the ability to precisely assess the depth of invasion and lymphovascular involvement and thus stage NENs accurately. EUS-directed locoregional ablative therapies are increasingly recognized as highly effective, minimally invasive treatment modalities for NENs, particularly pancreatic NENs. Advanced endoscopic resection techniques like endoscopic submucosal dissection (ESD), endoscopic submucosal resection (EMR), and endoscopic full-thickness resection (EFTR) have been increasingly used over the past decade with excellent results in achieving curative resection of various early-stage gastrointestinal luminal lesions including NENs. In this article, we aim to delineate NENs of the different segments of the gastrointestinal (GI) tract (esophagus, gastric, pancreatic, and small and large intestine) and their management with emphasis on the endoscopic management of these tumors.


Untangling the relationship between developmental and evolutionary integration.
Patterns of integration and modularity among organismal traits are prevalent across the tree of life, and at multiple scales of biological organization. Over the past several decades, researchers have studied these patterns at the developmental, and evolutionary levels. While their work has identified the potential drivers of these patterns at different scales, there appears to be a lack of consensus on the relationship between developmental and evolutionary integration. Here, we review and summarize key studies and build a framework to describe the conceptual relationship between these patterns across organismal scales and illustrate how, and why some of these studies may have yielded seemingly conflicting outcomes. We find that among studies that analyze patterns of integration and modularity using morphological data, the lack of consensus may stem in part from the difficulty of fully disentangling the developmental and functional causes of integration. Nonetheless, in some empirical systems, patterns of evolutionary modularity have been found to coincide with expectations based on developmental processes, suggesting that in some circumstances, developmental modularity may translate to evolutionary modularity. We also advance an extension to Hallgrímsson et al.'s palimpsest model to describe how patterns of trait modularity may shift across different evolutionary scales. Finally, we also propose some directions for future research which will hopefully be useful for investigators interested in these issues.


Protein engineering of ribonucleases.
Natural bovine seminal RNase possesses a potent antitumor action. We have mutagenized monomeric bovine pancreatic RNase A, devoid of any cytotoxic action, to insert residues present at corresponding positions in the subunit of dimeric, antitumor, seminal RNase. Like naturally dimeric seminal RNase, the mutant dimeric RNases display selective toxicity for malignant cells, which is absent in the monomeric mutants.


Models with discrete latent variables for analysis of categorical data: a framework and a MATLAB MDLV toolbox.
Studies in the social and behavioral sciences often involve categorical data, such as ratings, and define latent constructs underlying the research issues as being discrete. In this article, models with discrete latent variables (MDLV) for the analysis of categorical data are grouped into four families, defined in terms of two dimensions (time and sampling) of the data structure. A MATLAB toolbox (referred to as the "MDLV toolbox") was developed for applying these models in practical studies. For each family of models, model representations and the statistical assumptions underlying the models are discussed. The functions of the toolbox are demonstrated by fitting these models to empirical data from the European Values Study. The purpose of this article is to offer a framework of discrete latent variable models for data analysis, and to develop the MDLV toolbox for use in estimating each model under this framework. With this accessible tool, the application of data modeling with discrete latent variables becomes feasible for a broad range of empirical studies.


Reduced Puncture Time and Radiation Exposure of Percutaneous Transpedicular Puncture with Electronic Conductivity Device: A Randomized Clinical Trial.
The present study introduced an electronic conductivity device (ECD) to reduce time of percutaneous transpedicular puncture and frequency of patient valid radiation exposure in percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP). A randomized self-control clinical study was undertaken. Medical records of patients with vertebral compression fractures (VCFs) for bilateral PKP or PVP were collected, and each side was performed randomly with ECD or conventional trocar. We enrolled 61 patients (44 women, 17 men) with 75 vertebras with VCF. Compared with the conventional fluoroscopy group, significant reductions in puncture time (504.33 ± 152.03 vs. 652.68 ± 167.60 seconds; P < 0.001) and fluoroscopy frequency (5.11 ± 1.23 vs. 8.15 ± 1.83; P < 0.001) for each percutaneous puncture were observed in the ECD group. When compared with the VCFs ≤50% group, the 2 indexes in the VCFs >50% group were significantly increased. And in the ECD group, the learning curve in the VCFs >50% group showed a steeper decreasing trend than that in the VCFs ≤50% group. No complications were observed in any patient. ECD could reduce puncture time of percutaneous transpedicular puncture and exposure of radiation in PVP and PKP. ECD has more benefits in complicated transpedicular puncture in patients with vertebral compression >50%.


Estimating glomerular filtration rate in healthy dogs using inulin without urine collection.
The goals of this study were to determine if the glomerular filtration rate (GFR) in dogs could be estimated by plasma inulin clearance and/or infusion inulin clearance analyses without urine collection, and to compare these results with GFR values obtained by urinary inulin clearance analysis. The dogs included in this study were healthy 20 beagles. Inulin clearance values were obtained by urinary inulin clearance, infusion inulin clearance, and plasma inulin clearance techniques. Urinary inulin clearance was 4.09±0.52 ml min(-1) kg(-1) (body weight); infusion inulin clearance, 4.01±0.49 ml min(-1) kg(-1); and plasma inulin clearance, 4.14±0.66 ml min(-1) kg(-1). The urinary inulin clearance was strongly correlated with infusion inulin clearance and weakly correlated with plasma inulin clearance. The GFR for dogs can be estimated by infusion and plasma inulin clearance analyses by blood sampling alone, without urine collection.


Sciatic nerve function following hindlimb thermal injury.
Peripheral neuropathy occurs in approximately 20% of patients with major burns and seriously impairs rehabilitation. We describe an experimental model which permits elevation of the tissue temperature in the region of the distal sciatic nerve trunk of rats at a reproducible rate to a predetermined level without inflicting concomitant major cutaneous injury. Radiofrequency current is delivered through parallel copper electrodes mounted in a chamber into which the limb has been inserted. In the present experiments, tissue temperature was arbitrarily elevated to 47 degrees C for 30 sec in 62 rats. There were 43 normal controls. The posterior tibial branch was the most intensively studied, as some of its conduction characteristics can be serially assessed percutaneously. Conduction block, which was apparently irreversible, was present in 67% of posterior tibials by 24 hr postinjury. In branches which were still excitable, prolongation of the absolute refractory period was the most consistent abnormality noted. Slowing of conduction, as evidenced by prolongation of inflection velocity or peak velocity, was never observed. However, this injury resulted in selective conduction failure of sural--but not of peroneal--fibers which conducted at 40 m/sec or greater. Fiber modality is an important determinant of the vulnerability to direct thermal injury of peripheral nerve in vivo.


Hormonal stimulation of 3H-orotic acid incorporation into RNA by serum-free cultured hepatocytes.
Insulin and dexamethasone greatly stimulate the incorporation of 3H-orotic acid into RNA. Such a stimulation is associated to an increase in the uptake of the labelled precursor into the acid soluble fraction as well as in the the specific radioactivity of the nucleoside plus nucleotide pool suggesting that hormone supplementation does not affect RNA synthesis by cultured cells. The lack of effect of insulin and dexamethasone on the level of total RNA polymerase activity in nuclei isolated from cultured hepatocytes is in line with this assumption. The hormone stimulated uptake of orotic acid is dependent on protein synthesis since it is completely abolished by cycloheximide.


Chemical trace XRF analysis to detect sharp force trauma in fresh and burned bone.
Forensic anthropologists may not always be able to differentiate heat-induced fractures from fractures with other aetiologies, namely sharp force traumas, with clear nefarious impact on medico-legal conclusions. The objective of this study was to experimentally investigate if blade chemical traces are transferred to defleshed bone tissue and if they remain there after a burning event. This was accomplished by prompting sharp force traumas in 20 macerated fresh pig ribs with five different instruments, namely a stainless steel knife, an artisanal knife and a ceramic kitchen knife, a small axe and a large axe. Another pig rib was used as control, not being subjected to any trauma. All instruments were probed by X-ray fluorescence (XRF) to establish the composition of each blade. Bone samples, both pre-burned and post-burned (at 500 °C, 700 °C, 900 °C and 1100 °C), were then probed by XRF. All sharp force instruments left detectable chemical traces on pre-burned bone, although not in all samples. Furthermore, traces were still detected after experimental burning in most cases. Potentially, XRF can provide relevant information about the aetiology of fractures in burned and unburned bones, although the effect of soft tissues and diagenesis must still be investigated.


[Effects of m-nifedipine on left ventricular diastolic function and Ca2+ content of myocardial and cerebral mitochondria and artery tissues in left ventricular hypertrophied rats].
Left ventricular hypertrophy (LVH) was induced by renal hypertension in rats. m-Nifedipine (m-Nif, ig 20 mg.kg-1.d-1 for 9 wk) decreased LV weight in the renovascular hypertensive rats (P < 0.01). The LV compliance in LVH group was significantly decreased compared with that in sham- operated group. The LV stiffness constant, Ca2+ content in left ventricular myocardial and cerebral mitochondria, aorta, and tail artery were markedly raised. m-Nif could markedly reduce the LV stiffness constant, improve the LV compliance, and decrease the Ca2+ content of left ventricular myocardial mitochondria and tissues of artery from LVH rats. These effects of m-Nif were similar to those of nifedipine at the same dosage.


General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum.
Along unmyelinated central axons, synapses occur at focal swellings called axonal varicosities (boutons). The mechanisms regulating how frequently synapses and varicosities occur along axons remain poorly understood. Here, to investigate varicosity distribution patterns and the extent to which they may be conserved across different axons, we analyzed varicosity numbers and positions along fluorescently labeled axon branches in hippocampal area CA1 (CA3-to-CA1 "Schaffer collateral" axons) and five other synaptic regions of rat hippocampus and cerebellum. Varicosity spacing varied by region; e.g., 3.7 +/- 0.6 microm (mean +/- SD) for CA3-to-CA1 axons and 5.2 +/- 1.0 microm for cerebellar parallel fibers. Surprisingly, when 56 axons from these different regions were pooled into a single heterogeneous group, a general relationship emerged: the spacing variability (SD) was a constant fraction of the mean spacing, suggesting that varicosities along different axons are distributed in a fundamentally similar, scaled manner. Varicosity spacing was neither regular nor random but followed a pattern consistent with random synaptic distributions and the occurrence of multiple-synapse boutons. A quantitative model reproduced the salient features of the data and distinguished between two proposed mechanisms relating axonal morphogenesis and synaptogenesis.


Crouched posture maximizes ground reaction forces generated by muscles.
Crouch gait decreases walking efficiency due to the increased knee and hip flexion during the stance phase of gait. Crouch gait is generally considered to be disadvantageous for children with cerebral palsy; however, a crouched posture may allow biomechanical advantages that lead some children to adopt a crouch gait. To investigate one possible advantage of crouch gait, a musculoskeletal model created in OpenSim was placed in 15 different postures from upright to severe crouch during initial, middle, and final stance of the gait cycle for a total of 45 different postures. A series of optimizations was performed for each posture to maximize transverse plane ground reaction forces in the eight compass directions by modifying muscle forces acting on the model. We compared the force profile areas across all postures. Larger force profile areas were allowed by postures from mild crouch (for initial stance) to crouch (for final stance). The overall ability to generate larger ground reaction force profiles represents a mechanical advantage of a crouched posture. This increase in muscle capacity while in a crouched posture may allow a patient to generate new movements to compensate for impairments associated with cerebral palsy, such as motor control deficits.


Pre- and Paralinguistic Vocal Production in ASD: Birth Through School Age.
We review what is known about how pre-linguistic vocal differences in autism spectrum disorder (ASD) unfold across development and consider whether vocalization features can serve as useful diagnostic indicators. Differences in the frequency and acoustic quality of several vocalization types (e.g., babbles and cries) during the first year of life are associated with later ASD diagnosis. Paralinguistic features (e.g., prosody) measured during early and middle childhood can accurately classify current ASD diagnosis using cross-validated machine learning approaches. Pre-linguistic vocalization differences in infants are promising behavioral markers of later ASD diagnosis. In older children, paralinguistic features hold promise as diagnostic indicators as well as clinical targets. Future research efforts should focus on (1) bridging the gap between basic research and practical implementations of early vocalization-based risk assessment tools, and (2) demonstrating the clinical impact of targeting atypical vocalization features during social skill interventions for older children.


Identification of genes involved in tumor-like properties of embryonic stem cells.
Embryonic stem (ES) cells are pluripotent stem cells derived from preimplantation stage embryos. ES cells proliferate infinitely while maintaining pluripotency. These properties make them attractive sources for stem cell therapies and regenerative medicine. However, undifferentiated ES cells produce tumors when transplanted, which may preclude their therapeutic usage. It is largely unknown why ES cells can possess tumorigenicity without having chromosomal abnormalities. In this chapter, we introduce the methods to identify genes that play roles in tumor-like properties of ES cells.


Efficacy and tolerability of Guizhi-Shaoyao-Zhimu decoction in gout patients: a systematic review and Meta-analysis.
Guizhi-Shaoyao-Zhimu decoction (GSZD), a famous ancient oriental Chinese prescription, has been widely used for thousands of years to treat 'arthromyodynia'. The clinical studies of GSZD for the treatment of gout were systematically reviewed to evaluate its clinical efficacy and safety. All randomized controlled trials (RCTs) related to GSZD and gout were collected starting from the database establishment until 29 February 2020, from the Embase, PubMed, Cochrane Library, Web of Knowledge, VIP and other databases. This systematic review and meta-analysis were performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, and all analysis of the test was completed using Stata (SE12.0) and Revman (5.3). A total of 535 studies were searched, and 13 studies were included in our meta-analysis (n = 1056 participants). Compared with the conventional western medicine treatments, GSZD treatment yielded a significantly increase in the number of clinically effective patients (OR = 3.67, 95%CI = 2.39-5.64, p = 0.57), an improved mean reduction in the level of uric acid (MD = -54.06; 95% CI = -69.95 to -38.17). Meanwhile, the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were also significantly decreased after the GSZD treatment with no increased relative risk of side-effects. Our present works suggested that GSZD could be considered as an effective alternative remedy for clinical treatment of gout. In addition, it also provides a scientific basis for GSZD to be better applied in clinic in the future.


HDlive rendering image of adnexal tumors: preliminary report.
Our objective is to present our first experience of adnexal tumors reconstructed employing the HDlive rendering mode. Seven adnexal tumors (one case each of chocolate cyst, benign cystic teratoma, serous cystadenofibroma, and torsion of the hydrosalpinx, and three cases of ovarian cancer) were studied using the HDlive rendering mode. In the case of the chocolate cyst, the smooth inner wall with numerous tiny projections was clearly identified. In the case of benign cystic teratoma, a smooth hair ball inside the cyst was evident. In the case of the serous cystadenofibroma, a smooth, solid projection and relatively smooth septum were noted. In the three cases of ovarian cancer, numerous irregular papillae and irregular, thick septae were depicted. In the case of the bilateral hydrosalpinx with torsion of the right tube, different fluid contents were recognized. The HDlive rendering mode provides anatomically realistic features such as macroscopic specimens for physicians and pathologists due to the complete depiction of the inner surface of the adnexal tumors.


Triazolam in cirrhosis: pharmacokinetics and pharmacodynamics.
Although it is frequently stated that patients with cirrhosis are more sensitive to benzodiazepines, the relative roles of impaired elimination and altered responsiveness have not been clarified. We evaluated the pharmacokinetics, pharmacodynamics, and sensitivity to triazolam in six patients with clinically stable cirrhosis and six age-matched control subjects. Our findings show that there were no significant differences between the patients with cirrhosis and the control subjects in any of the pharmacokinetic parameters. Drug effect, measured as postural sway, was also similar in the patients with cirrhosis and control subjects; therefore the ratio of effect area under the curve to concentration area under the curve, a measure of sensitivity, did not differ significantly between the patients with cirrhosis and the control subjects. Because triazolam is metabolized by P4503A, we hypothesized that the effects of cirrhosis on drug metabolism may differ with respect to the specific P450 responsible for the oxidation of this drug. These effects may differ because of the relative sparing of a specific P450 and because of an extrahepatic site of metabolism.


Rainwater harvesting and Leucaena leucocephala biomass rates effects on soil moisture, water use efficiency and Sorghum bicolor [(L.) Moench] productivity in a semi-arid area in Zimbabwe.
Sorghum is one of the major staple crops in Sub Saharan Africa but its production is mainly limited by moisture stress, frequent droughts and soil infertility, especially in the smallholder farming systems. This raises the need to develop climate smart options to improve sorghum production. The objective was to assess the effects of rainwater harvesting and use of different Leucaena leucocephala biomass rates on soil moisture content, rainwater use efficiency, and stover and grain yields in two sorghum varieties (Macia and SV1). The experiment was laid as a randomized complete block design in split-split plot arrangement from 2017/2018 to 2019/2020 season. The results show that tied contour (TC) and infiltration pits (IPs) significantly (P < 0.05) increased soil moisture content than standard contour (SC). Soil moisture content increased gradually with the increase in soil depth (20-40 cm > 0-20 cm), with 2018/2019 season having the maximum soil moisture content. Soil moisture content also increased with the increase in application rates of Leucaena biomass. Grain and stover yields were significantly (P < 0.05) increased by all Leucaena biomass application rates with higher yield observed in 2018/2019 season. SC had significantly lower grain and stover yields at all Leucaena biomass application rates. TC and IPs had comparable rainwater use efficiency compared to SC. Rainwater use efficiency increased with application rates of Leucaena biomass across all seasons and varieties. TC and IPs are better adaptive mechanisms against drought spells in semi-arid areas and can be combined with 10 t ha-1 of Leucaena biomass due to better yield increments realized. © 2022 Society of Chemical Industry.


Chitosan: antimicrobial action upon staphylococci after impregnation onto cotton fabric.
High levels of viable Staphylococcus aureus, which are often found on inflamed skin surfaces, are usually associated with atopic dermatitis. Textiles, owing to their high specific surface area and intrinsic hydrophilicity, retain moisture while also providing excellent environmental conditions for microbial growth and proliferation. Recently, a number of chemicals have been added to textiles, so as to confer antimicrobial activity. To evaluate the antimicrobial action of chitosan upon selected skin staphylococci. We isolated staphylococci from normal skin of 24 volunteers and studied their survival upon contact with chitosan-impregnated cotton fabric. Low and high molecular weight chitosans were used at two concentrations; all four did effectively reduce the growth of some staphylococci (namely Staph. aureus), by up to 5 log cycles, thus unfolding a potential towards control and even prevention of related skin disorders. Our data suggest an effective, but selective antibacterial action of chitosans towards skin bacteria. The possibility to use a natural biopolymer incorporated in a textile to alleviate and even treat some of the symptoms associated with this skin condition may raise an alternative to existing medical treatments. The selectivity observed prevents full elimination of bacteria from the skin surface, which is an advantage.


Prevention of infection in acute leukemia.
In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.


HCG-induced changes in the number of rat testis LH/HCG receptors.
Adult male rats were injected subcutaneously with a mixture of hCG and [125I]hCG (3, 5, 10, 100 or 1000 IU), and killed 3, 6, 16, 24 or 48 h after injection. Specific uptake of [125I]hCG by the testes as well as the remaining in vitro binding capacity were measured. Cycloheximide (1.5 mg/kg) was given together with hCG to another group of animals. The effect of hCG on testicular LH/hCG receptors was found to consist of two phases: first, 6--16 h after injection, a significant increase in the binding capacity occurred, which was found with the lower 3--10 IU doses of hCG. Thereafter there was a pronounced decrease in receptor concentration, which was directly correlated to the dose of hCG. Experiments with cycloheximide suggest that the decrease in binding, but not the increase, is at least partly dependent on protein synthesis.


Extracellular reduced glutathione increases neuronal vulnerability to combined chemical hypoxia and glucose deprivation.
In addition to its intracellular antioxidant role, reduced glutathione (GSH) is released by CNS cells and may mediate or modulate excitatory neurotransmission. Although extracellular GSH levels rise in the ischemic cortex, its effect on the viability of energy-compromised neurons has not been defined. In this study, we tested the hypothesis that exogenous GSH would increase the vulnerability of cultured cortical neurons to azide-induced chemical hypoxia combined with glucose deprivation. Thirty minutes azide exposure in a glucose-free buffer was tolerated by most neurons, with release of less than 10% of neuronal LDH over the subsequent 21-25 h. Concomitant treatment with 10-100 microM GSH increased cell death in a concentration-dependent fashion, to 71.6+/-5.1% of neurons at 100 microM; GSH alone was nontoxic. Injury was blocked by the selective N-methyl-d-aspartate (NMDA) antagonist MK-801 but not by the AMPA/kainate antagonist NBQX. The sulfhydryl reducing agent mercaptoethanol (10-100 microM) mimicked the action of GSH; however, the zinc chelator ethylenediaminetetraacetic acid (EDTA) was ineffective. Two GSH analogues that lack a sulfhydryl group, S-hexylglutathione (SHG) and oxidized glutathione (GSSG), were inactive per se but attenuated the effect of both GSH and mercaptoethanol. These results suggest that micromolar concentrations of GSH enhance neuronal loss due to energy depletion by altering the extracellular redox state, resulting in increased NMDA receptor activation.


Nomenclatural notes and typification of nine names related to Jasminum (Oleaceae).
Lectotypes are designated here for the following nine validly published names: Jasminumalongense, J.anodontum, J.eberhardtii, J.harmandianum, J.lang, J.laxiflorum, J.pierreanum, J.rufohirtum, and J.sinense. Jasminumlang is reinstated as a distinct species.


Diabetes Risk and Control in Multi-ethnic US Immigrant Populations.
The goal of this review is to assess current evidence on diabetes risk and control among adult immigrants in the USA. Patterns of diabetes risk in US immigrants may reflect global diabetes trends. Asian, Black, and Latinx immigrants all see a diabetes disadvantage relative to US-born Whites. Diabetes risk in Asian immigrants also surpasses US-born Asians. Relative diabetes risk among all groups increases with time in the USA. Research to explain patterns in diabetes risk and control among immigrants has broadened from lifestyle factors to include multi-level, life course influences on trajectories of risk. Some determinants are shared across groups, such as structural racism, healthcare access, and migration stress, whereas others such as diet are embedded in sending country culture. Current literature on diabetes in immigrant populations suggests a need to shift towards a transnational lens and macro-level social determinants of health framework to understand diabetes risk and potential prevention factors.


Usefulness of heart-type fatty acid-binding protein in patients with severe sepsis.
The purpose of the study was to evaluate the value of heart-type fatty acid-binding protein (hFABP) as a novel clinical biomarker in patients with severe sepsis. Serum concentrations of hFABP and traditional cardiac biomarkers including cardiac troponin I, creatine kinase-MB, and B-type natriuretic peptides levels were measured within 6 hours after admission in 93 severe septic patients. The value of hFABP for the diagnosis of sepsis-related myocardial dysfunction (SRMD) and for the prediction of 28-day mortality was evaluated by receiver operating characteristics curve analysis. The prognostic value of elevated hFABP was subsequently confirmed by multivariate Cox proportional hazards analysis and Kaplan-Meier survival analysis. Heart-type fatty acid-binding protein was elevated (≥ 4.5 ng/mL) in 58 (62.4%) patients; patients with elevated hFABP appeared more likely to have SRMD (84.5% vs 31.4%, P < .001) and have higher prevalence of 28-day death (37.9% vs 8.6%, P = .002). Heart-type fatty acid-binding protein offered superior value over conventional biomarkers in both diagnosis of SRMD (area under the curve, 0.767; P < .001) and prediction of 28-day death (area under the curve, 0.805; P < .001). Serum hFABP is frequently elevated among patients with severe sepsis and appears to be associated with SRMD. Elevated hFABP independently predicts 28-day mortality in severe sepsis.


Otoacoustic emission in myasthenia gravis patients and the role of efferent activation.
We performed transient evoked otoacoustic emission (TEOAE) measurements on 29 ears of myasthenia gravis (MG) patients. The purpose of the study was to support the role of acetylcholine (ACh) in the efferent innervation of cochlear outer hair cells (OHCs). Another aim was to establish additional diagnostic tools for the early determination of MG. Initially, threshold audiometry and impedance measurements showed normal values on the ears examined. The main finding was that TEOAE values were significantly lower in MG patients than in healthy controls. Mestinon, a reversible cholinesterase inhibitor, resulted in a significant increase in mean values of TEOAEs, although these values were still lower than normal. The results suggest that in MG, acetylcholine receptor (AChR) autoantibodies inhibit the function of OHC AChRs. Thus, the TEOAE generated by the active movements of OHCs is decreased in MG. Mestinon prevents the degradation of ACh, and thus stimulates efferent function and increases TEOAE values. The results obtained in this study support the role of ACh in the efferent function of OHC, as well as the impaired function of hair cell AChRs in MG patients. Consequently, measuring TEOAEs may be useful in the early diagnosis of some forms of MG. These results reinforce the importance of collaboration between neurologists and otolaryngologists in the management of diseases with pathological neurotransmission.