RANKL is a marker and mediator of local and systemic bone loss in two rat models of inflammatory arthritis.
RANKL is an essential mediator of bone erosions, but the role of RANKL in systemic bone loss had not been studied in arthritis. RANKL protein was increased in rat joint extracts and serum at the earliest stages of arthritis. Osteoprotegerin (OPG) treatment reversed local and systemic bone loss, suggesting that RANKL is both a marker and mediator of bone loss in arthritis. RANKL is well established as an essential mediator of bone erosions in inflammatory arthritis, but the role of RANKL in systemic bone loss in arthritis had not been studied. We hypothesized that serum RANKL could serve as both a mediator and as a novel biomarker for local and systemic bone loss in arthritis. We challenged this hypothesis in two established rat models of inflammatory arthritis. We sought to determine whether serum RANKL was elevated early in disease progression and whether RANKL suppression could prevent both local and systemic bone loss in these models. Detailed time-course studies were conducted in animals with collagen-induced (CIA) or adjuvant-induced (AIA) arthritis to evaluate the onset and progression of inflammation (paw swelling), bone erosions, osteoclast numbers, and RANKL protein levels in arthritic joints and in serum. Additional CIA and AIA rats (n=8/group) received placebo (PBS) or recombinant OPG (3 mg/kg three times weekly) for 10 days beginning 4 days after disease onset (first macroscopic evidence of hind paw erythema and edema) to assess the role of RANKL in local and systemic bone loss. RANKL protein was significantly elevated in the joints and serum of CIA and AIA rats within 1-2 days of disease onset. Increased RANKL levels were associated with local (hind paw) and systemic (vertebral) osteopenia in both models. The RANKL inhibitor OPG prevented local and systemic osteopenia in both models of established disease. RANKL protein is significantly increased both locally and systemically during the earliest stages of inflammatory arthritis in rats, suggesting that serum RANKL might have prognostic value for bone erosions and systemic osteopenia in this condition. RANKL inhibition through OPG prevented local and systemic bone loss in these arthritis models, suggesting that RANKL inhibition is a promising new approach for treating bone loss in arthritis.


Lactoferrin protects against lipopolysaccharide-induced acute lung injury in mice.
Lactoferrin (LF) plays various anti-inflammatory roles in inflammation experimentally induced by lipopolysaccharides (LPS). But the protective effects of LF on LPS-induced acute lung injury (ALI) have not been elucidated. In this study, we aimed to study the effects of LF on ALI caused by LPS in mice. At 1h before or after LPS injection, an intraperitoneal injection of LF (5mg/body) was administered. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analyses 12h after LPS exposure. We found that both prophylactic and therapeutic administration of LF significantly decreased the W/D ratio of the lung and protein concentration in the BALF. LF significantly reduced the pulmonary myeloperoxidase activity and the number of total cells in the BALF 12h after LPS challenge. LF treatment markedly attenuated lung edema, alveolar hemorrhage and inflammatory cells infiltration. Moreover, LF also decreased the production of TNF-α and increased interleukin-10 in the BALF. These results firstly indicate that LF may protect against LPS-induced ALI in mice.


PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week.
Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered revascularization procedures, but only CABG can prolong life in stable coronary artery disease. Thus, PCI and CABG mechanisms may differ. Viability and/or ischemia detection to guide revascularization have been unable to accurately predict treatment effects of CABG or PCI, questioning a revascularization mechanism for improving survival. By contrast, preventing myocardial infarction may save lives. However, the majority of infarcts are generated by non-flow-limiting stenoses, but PCI is solely focused on treating flow-limiting lesions. Thus, PCI cannot be expected to significantly limit new infarcts, but CABG may do so through providing flow distal to vessel occlusions. All comparisons of CABG to PCI or medical therapy that demonstrate survival effects with CABG also demonstrate infarct reduction. Thus, CABG may differ from PCI by providing "surgical collateralization," prolonging life by preventing myocardial infarctions. The evidence is reviewed here.


Change in cardiometabolic risk factors in a pilot safety-net plant-based lifestyle medicine program.
Interventions emphasizing healthful lifestyle behaviors are proliferating in traditional health care settings, yet there is a paucity of published clinical outcomes, outside of pay-out-of-pocket or employee health programs. We assessed weight, hemoglobin A1c (HbA1c), blood pressure, and cholesterol for 173 patients of the Plant-Based Lifestyle Medicine Program piloted in a New York City safety-net hospital. We used Wilcoxon signed-rank tests to assess changes in means, from baseline to six-months, for the full sample and within baseline diagnoses (i.e., overweight or obesity, type 2 diabetes, prediabetes, hypertension, hyperlipidemia). We calculated the percentage of patients with clinically meaningful changes in outcomes for the full sample and within diagnoses. The full sample had statistically significant improvements in weight, HbA1c, and diastolic blood pressure. Patients with prediabetes or overweight or obesity experienced significant improvements in weight and those with type 2 diabetes had significant improvements in weight and HbA1c. Patients with hypertension had significant reductions in diastolic blood pressure and weight. Data did not show differences in non-high-density lipoprotein cholesterol (non-HDL-C), but differences in low-density lipoprotein cholesterol (LDL-C) were approaching significance for the full sample and those with hyperlipidemia. The majority of patients achieved clinically meaningful improvements on all outcomes besides systolic blood pressure. Our study demonstrates that a lifestyle medicine intervention within a traditional, safety-net clinical setting improved biomarkers of cardiometabolic disease. Our findings are limited by small sample sizes. Additional large-scale, rigorous studies are needed to further establish the effectiveness of lifestyle medicine interventions in similar settings.


Mitogen-activated protein kinase pathways and cardiac surgery.
Mitogen-activated protein kinases are serine-threonine protein kinases that are involved in several processes important to cardiac surgery such as vascular permeability, cytokine production, vasomotor function, and reperfusion injury. Mitogen-activated protein kinases are expressed in multiple cell types including cardiomyocytes, vascular endothelial cells, and vascular smooth muscle cells. Mitogen-activated protein kinases function in cellular signal transduction cascades and are activated by a diverse range of stimuli including ischemia, shear stress, and vasoactive agents. Three major mitogen-activated protein kinase families were identified as the extracellular signal-regulated kinases, c-Jun NH(2)-terminal protein kinases, and p38 kinases. Extensive investigation has established roles for extracellular signal-regulated kinases, c-Jun NH(2)-terminal protein kinases, and p38 kinases in cardiovascular signal transduction pathways. Activity of these signal cascades may contribute to the increased pulmonary vascular permeability and myocardial reperfusion injury observed after cardiac surgery with cardioplegia and cardiopulmonary bypass. Recent findings from our laboratory suggest that alterations in the activity of myocardial extracellular signal-regulated kinase pathways occur as a result of cardioplegia-cardiopulmonary bypass in humans. In addition, these differences in extracellular signal-regulated kinase activity were shown to mediate coronary microcirculatory dysfunction associated with cardioplegia-cardiopulmonary bypass. The resulting deficit in coronary microcirculatory regulation may potentially lead to detrimental effects on organ perfusion and function. As mitogen-activated protein kinase pathways are further characterized, our potential to develop methods to prevent morbidity associated with cardiac surgery and cardiopulmonary bypass may be greatly improved.


Zellweger spectrum disorders: clinical overview and management approach.
Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features. A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine. There is currently no curative therapy, but supportive care is available. This review focuses on the management of patients with a ZSD and provides recommendations for supportive therapeutic options for all those involved in the care for ZSD patients.


Large Size Color-tunable Electroluminescence from Cationic Iridium Complexes-based Light-emitting Electrochemical Cells.
Solution-processable light-emitting electrochemical cells (LECs) with simple device architecture have become an attractive candidate for application in next generation lighting and flat-panel displays. Herein, single layer LECs employing two cationic Ir(III) complexes showing highly efficient blue-green and yellow electroluminescence with peak current efficiency of 31.6 cd A(-1) and 40.6 cd A(-1), respectively, have been reported. By using both complexes in the device, color-tunable LECs with a single spectral peak in the wavelength range from 499 to 570 nm were obtained by varying their rations. In addition, the fabrication of efficient LECs was demonstrated based on low cost doctor-blade coating technique, which was compatible with the roll to roll fabrication process for the large size production. In this work, for the first time, 4 inch LEC devices by doctor-blade coating were fabricated, which exhibit the efficiencies of 23.4 cd A(-1) and 25.4 cd A(-1) for the blue-green and yellow emission, respectively. The exciting results indicated that highly efficient LECs with controllable color could be realized and find practical application in large size lighting and displays.


Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis.
The aim was to evaluate urinary neopterin, a marker of pro-inflammatory state, as a potential biomarker of disease prognosis and progression in amyotrophic lateral sclerosis (ALS); and to compare its utility to urinary neurotrophin receptor p75 extracellular domain (p75ECD ). This was an observational study including 21 healthy controls and 46 people with ALS, 29 of whom were sampled longitudinally. Neopterin and p75ECD were measured using enzyme-linked immunoassays. Baseline and longitudinal changes in clinical measures, neopterin and urinary p75ECD were examined, and prognostic utility was explored by survival analysis. At baseline, urinary neopterin was higher in ALS compared to controls (181.7 ± 78.9 μmol/mol creatinine vs. 120.4 ± 60.8 μmol/mol creatinine, p = 0.002, Welch's t test) and correlated with the Revised ALS Functional Rating Scale (r = -0.36, p = 0.01). Combining previously published urinary p75ECD results from 22 ALS patients with a further 24 ALS patients, baseline urinary p75ECD was also higher compared to healthy controls (6.0 ± 2.7 vs. 3.2 ± 1.0 ng/mg creatinine, p < 0.0001) and correlated with the Revised ALS Functional Rating Scale (r = -0.36, p = 0.01). Urinary neopterin and p75ECD correlated with each other at baseline (r = 0.38, p = 0.009). In longitudinal analysis, urinary neopterin increased on average (±SE) by 6.8 ± 1.1 µmol/mol creatinine per month (p < 0.0001) and p75ECD by 0.19 ± 0.02 ng/mg creatinine per month (p < 0.0001) from diagnosis in 29 ALS patients. Urinary neopterin holds promise as marker of disease progression in ALS and is worthy of future evaluation for its potential to predict response to anti-inflammatory therapies.


Prolonged pneumoperitoneum time is an independent risk factor for intravesical recurrence after laparoscopic radical nephroureterectomy in upper tract urothelial carcinoma.
To evaluate the impact of pneumoperitoneum time on intravesical recurrence (IVR) in upper tract urothelial carcinoma (UTUC) patients who underwent laparoscopic radical nephroureterectomy (LRNU). We identified 129 UTUC patients who underwent LRNU at our three institutions from 2004 to 2014. We evaluated the association of IVR rate and patient clinico-pathological characteristics including operation time. By retrospectively reviewing all videotapes, we defined pneumoperitoneum time as being from the infusion of pressurized CO2 gas with a pressure of 10-12 mmHg to extirpation of the kidney. During the median follow-up of 31.1 months, 61 (47.3%) had subsequent IVR after LRNU. Multivariate analysis revealed that prolonged pneumoperitoneum time (HR = 1.81, p = 0.025) and presence of lymphovascular invasion (LVI) (HR = 1.53, p = 0.006) were independent risk factors for subsequent IVR. The 3-year and 5-year IVR free survival rates were 43.7% and 21.8% in patients with a prolonged pneumoperitoneum time of ≥150 min, which were significantly lower than those in their counterparts (59.0% and 48.3%, respectively, p = 0.024). The subsequent IVR rates were 27.3% for a pneumoperitoneum time of <90 min, 35.8% for that of 90-150 min, 55.0% for that of 150-210 min, 61.1% for that of 210-270 min, and 85.7% for that of >270 min. Prolongation of pneumoperitoneum time and presence of LVI might be associated with higher risk of subsequent IVR in UTUC patients who underwent LRNU.


CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.
The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate.


A novel genotoxicity assay of carbon nanotubes using functional macrophage receptor with collagenous structure (MARCO)-expressing chicken B lymphocytes.
Although carbon nanotubes (CNTs) are promising nanomaterials, their potential carcinogenicity is a major concern. We previously established a genetic method of analyzing genotoxicity of chemical compounds, where we evaluated their cytotoxic effect on the DT40 lymphoid cell line comparing DNA-repair-deficient isogenic clones with parental wild-type cells. However, application of our DT40 system for the cytotoxic and genotoxic evaluation of nanomaterials seemed to be difficult, because DT40 cells only poorly internalized nanoparticles. To solve this problem, we have constructed a chimeric gene encoding a trans-membrane receptor consisting of the 5' region of the transferrin receptor (TR) gene (to facilitate internalization of nanoparticles) and the 3' region of the macrophage receptor with collagenous structure (MARCO) gene (which is a receptor for environmental particles). We expressed the resulting MARCO-TR chimeric receptor on DNA-repair-proficient wild-type cells and mutants deficient in base excision repair (FEN1 (-/-)) and translesion DNA synthesis (REV3 (-/-)). We demonstrated that the chimera mediates uptake of particles such as fluorescence-tagged polystyrene particles and multi-walled carbon nanotubes (MWCNTs), with very poor uptake of those particles by DT40 cells not expressing the chimera. MWCNTs were cytotoxic and this effect was greater in FEN1 (-/-)and REV3 (-/-) cells than in wild-type cells. Furthermore, MWCNTs induced greater oxidative damage (measured as 8-OH-dG formation) and a larger number of mitotic chromosomal aberrations in repair-deficient cells compared to repair-proficient cells. Taken together, our novel assay system using the chimeric receptor-expressing DT40 cells provides a sensitive method to screen for genotoxicity of CNTs and possibly other nanomaterials.


Outlook: metformin use in infertile patients with polycystic ovary syndrome: an evidence-based overview.
Metformin is an insulin sensitizer currently used for treating type-2 diabetes mellitus and recently administered for inducing ovulatory menstrual cycles in oligo-amenorrhoeic patients with polycystic ovary syndrome (PCOS). The aim of the present review is to describe the efficacy of metformin as an ovulation inducer on the basis of the most important evidence-based medicine supported data, including meta-analyses and randomized controlled trials. Specifically, we reviewed the uses of metformin as first- and second-step treatment for PCOS related anovulatory infertility and as co-treatment in infertile PCOS patients who receive gonadotrophins. To date, there is evidence that metformin is effective for restoring normal menstrual cycles in anovulatory PCOS patients, and that it is more effective and cheaper than laparoscopic ovarian drilling as the second therapeutic step in PCOS patients previously defined as resistant to clomiphene citrate. Co-administration of metformin in PCOS patients treated with gonadotrophin improves the mono-ovulation rate and can prevent ovarian hyperstimulation syndrome in patients treated with gonadotrophins for IVF cycles.


Peripheral nerve functions may deteriorate parallel to the progression of microangiopathy in diabetic patients.
Our aim was to obtain information to help in the early detection of impaired nerve function and to assess the severity of diabetic symmetric polyneuropathy (DPN). Various somatic and autonomic nerve functions in 40 diabetics and 20 age-matched healthy volunteers were evaluated using six objective examinations: nerve conduction study, quantitative vibratory perception threshold, heart rate variability, Valsalva test, head-up tilt and quantitative sudomotor axonal reflex test (QSART). The diabetics were divided into three groups according to the severity of their microangiopathy. The nerve function data and level of impairment were compared between a healthy control and three diabetic groups. The relationships between nerve function data and clinical background were also examined using multivariate analysis. Results were as follows: (1) all nerve dysfunctions seemed to develop parallel to the progression of microangiopathy, (2) reduced nerve conduction velocity and elevated vibratory perception thresholds in the feet might be early detectable signs of DPN, (3) vasomotor and sudomotor sympathetic functions and cardiovagal functions seemed to deteriorate with the appearance of microangiopathy, (4) lowered compound muscle action potential seemed to appear at the advanced microangiopathic condition, (5) hypohydrosis was closely related to diabetic foot ulcers. In conclusion, nerve dysfunction in diabetics might generally progress with microangiopathy from somatic sensory nerve dysfunction to autonomic nerve dysfunction and then to somatic motor nerve dysfunction. Sympathetic sudomotor dysfunction might be a sensitive predictor of diabetic foot ulcer.


Synthesis and Sonodynamic Antibacterial Activity Evaluation of Three Novel Fluoroquinolone Compounds.
Three ciprofloxacin derivatives (CPDs) were synthesized. Also, their sonodynamic antibacterial activities and possible mechanism under ultrasound (US) irradiation were preliminarily investigated. Staphylococcus aureus and Escherichia coli were selected as the research objects. The sonodynamic antibacterial effects of three CPDs and their structure-effective relationship were explored by the inhibition rate. The reactive oxygen species (ROS) produced under US irradiation were detected by oxidative extraction spectrophotometry and used to analyze the sonodynamic antibacterial mechanism of three CPDs. Research indicated that three CPDs, named compound 1 (C1), compound 2 (C2) and compound 3 (C3), separately all had strong sonodynamic antibacterial activities. In addition, C3 had the strongest effect relative to the other CPDs. The study also found that CPDs' concentration, US irradiation time, US solution temperature and US medium could disturb their sonodynamic antimicrobial effects. Moreover, 1O2 and ·OH were the main types of ROS produced by C1 and C3; the ROS produced by C2 included 1O2, among other types. Results showed that all three CPDs could be activated to produce ROS after US irradiation. Among them, C3 displayed the highest ROS production and the utmost activity, which may be related to the introduction of the electron-giving group at the C-3 position of the quinoline backbone.


Hyperinsulinemia is a probable trigger for weight gain and hyperphagia in individuals with Prader-Willi syndrome.
Prader-Willi syndrome (PWS) is the most frequently diagnosed genetic cause of early childhood obesity. Individuals with PWS typically progress through 7 different nutritional phases during their lifetime. The main objective of this study was to assess potential factors, particularly insulin, that may be responsible for the weight gains in sub-phase 2a and their role in the subsequent increase in fat mass and obesity in sub-phase 2b and insatiable appetite in phase 3. Fasting plasma insulin levels were measured in children with PWS between the ages of 0-12 years and in age-matched non-PWS participants with early-onset major (clinically severe) obesity (EMO) and in healthy-weight sibling controls (SC). Participants with PWS in nutritional phases 1a and 1b had plasma insulin levels comparable to SC. However, the transition from phase 1b up to phase 3 in the PWS group was accompanied by significant increases in insulin, coinciding in weight gains, obesity, and hyperphagia. Only individuals with PWS in phase 3 had comparable insulin levels to the EMO group who were higher than the SC group at any age. Elevated insulin signaling is a probable trigger for weight gain and onset of hyperphagia in children with Prader-Willi syndrome. Regulating insulin levels early in childhood before the onset of the early weight gain may be key in modulating the onset and severity of obesity and hyperphagia in individuals with PWS, as well as in other young children with non-PWS early-onset obesity. Preventing or reversing elevated insulin levels in PWS with pharmacological agents and/or through diet restrictions such as a combined low carbohydrate, low glycemic-load diet may be a viable therapeutic strategy in combating obesity in children with PWS and others with early childhood obesity.


Inter and intraspecific variation in nuclear DNA content in Aedes mosquitoes.
Haploid nuclear DNA of 23 species of Aedes, as determined by Feulgen cytophotometry, was found to vary 3-fold. This was accompanied by a 2-fold variation in total chromosomal length. There was a significant correlation (r = 0.765, P less than 0.001) between these two parameters. Genome size varied from 0.87 pg to 1.3 pg among 10 strains of Aedes albopictus, from wide geographic regions. Large scale differences in chromosomal DNA amounts have accompanied speciation and evolution in aedine mosquitoes.


Online mindfulness-enhanced cognitive behavioural therapy for anxiety and depression: Outcomes of a pilot trial.
Transdiagnostic internet-delivered cognitive behavioural therapies (iCBT) are effective for treating anxiety and depression, but there is room for improvement. In this study we developed a new Mindfulness-Enhanced iCBT intervention by incorporating formal and informal mindfulness exercises within an existing transdiagnostic iCBT program for mixed depression and anxiety. We examined the acceptability, feasibility, and outcomes of this new program in a sample of 22 adults with anxiety disorders and/or major depression. Participants took part in the 7-lesson clinician-guided online intervention over 14 weeks, and completed measures of distress (K-10), anxiety (GAD-7), depression (PHQ-9), mindfulness (FFMQ) and well-being (WEMBWS) at pre-, mid-, post-treatment, and three months post-treatment. Treatment engagement, satisfaction, and side-effects were assessed. We found large, significant reductions in distress (Hedges g = 1.55), anxiety (g = 1.39), and depression (g = 1.96), and improvements in trait mindfulness (g = 0.98) and well-being (g = 1.26) between baseline and post-treatment, all of which were maintained at follow-up. Treatment satisfaction was high for treatment-completers, with minimal side-effects reported, although adherence was lower than expected (59.1% completed). These findings show that it is feasible to integrate online mindfulness training with iCBT for the treatment of anxiety and depression, but further research is needed to improve adherence. A randomised controlled trial is needed to explore the efficacy of this program.


[Assessment of rumen fill in dairy cows for evaluation of the individual feed intake in herd management].
Postpartal disease complexes of dairy cows are frequently related to an insufficient feed intake around calving. The study examined the relationship between the rumen fill (RF) score and the feed intake. A further aim was to evaluate whether the RF score can be used in practice to estimate the cow's individual feed intake (in kg dry mass intake or fresh-mass intake per cow). In pluriparous cows (n = 109), the RF was scored daily according to the schema of Zaaijer and Noordhuizen (2003) modified by half-points between day 24 (± 4 days) ante partum (a. p.) and day 9 post partum (p. p.) as well as on days 28 (± 2 days) and 60 (± 2 days) p. p. The individual feed intake per cow was recorded. Additionally, measurements of the feed intake were performed every 4 hours over 24 hours (24-hour daily profiles) in 21 cows a. p. and in 10 cows p. p. There was a significant relationship between the RF score and the feed intake both a. p. and p. p. The number of days in milk greatly influenced this relationship. Immediately p. p., there was a response in the RF score of half a score with an additional intake of 3.5 kg dry matter, while a. p., a change of the PF score only occurred when the feed uptake was reduced by 18 kg dry matter. During the first week p. p., the RF score proved to be a sensitive measuring instrument for the individual feed intake. Because of its low response a. p., it was only suitable for the detection of animals at risk with a considerably reduced feed intake over several days. The RF score provides the most informative value during the first week p. p. to assess the increase in feed intake in the individual cow after calving. It is recommended to score the RF daily during the first 7-9 days p. p. and to evaluate it individually to detect risk animals with a reduced feed intake. During the dry period, only cows with a significantly reduced feed intake over several days can be detected and consequently treated early to prevent disorders p. p. During lactation (evaluated on days 28 and 60 p. p.), the RF score appears to be of very limited informative value regarding the individual feed intake.


Pleomorphism of hepatic regeneration.
The pleomorphism of hepatic regeneration was studied in acute liver injury and partial hepatectomy of rats. Increases in 3H-thymidine incorporation into the liver DNA fraction and in liver ornithine decarboxylase (ODC) activity were observed similarly in acute liver injury and following a two-thirds partial hepatectomy in normal rats. However, the increase in serum AFP levels was significant only in carbon tetrachloride (CCl4)-treated rats, and the portal-peripheral vein difference in plasma glucagon concentrations was great only in rats that underwent a partial hepatectomy. The weight of the remaining liver increased rapidly following a 67% hepatectomy in normal rats, but not in cirrhotic rats, of which three of five died within 6 days. Increases in liver prostaglandin E levels, 14C-orotate incorporation into the liver RNA fraction and hepatic ODC activity were observed up to 10 h following a partial hepatectomy of normal liver but not after similar removal of cirrhotic liver. Three kinds of hepatic regeneration, i.e., normal and pathologic regeneration following surgical removal of either normal or injured liver and repair of liver damage following chemically induced liver deficiency, were proposed from the observations.


Multifunctional interfaces for multiple uses: Tin(II)-hydroxyapatite for reductive adsorption of Cr(VI) and its upcycling into catalyst for air protection reactions.
Evidence collected to date by our group has demonstrated that tin(II)-functionalized hydroxyapatites (Sn/HAP) are a newly discovered class of ecofriendly reductive adsorbents for Cr(VI) removal from wastewaters. In this work an upgraded series of Sn/HAP materials assured a maximum removal capacity of ≈ 20 mgCr/g, doubling the previously reported value for Sn/HAP materials, thanks to higher Sn-dispersion as proved by X-ray photoelectron spectroscopy and electron microscopy. Insights on kinetics and thermodynamics of the reductive adsorption process are provided and the influence of pH, dosage, and nature of Cr(VI) precursors on chromium removal performances have been investigated. Pseudo-second-order kinetics described the interfacial reductive adsorption process on Sn/HAP, characterized by low activation energy (21 kJ mol-1), when measured in the 278-318 K range. Tests performed in the 2-6 pH interval showed similar efficiency in terms of Cr(VI) removal. Conventional procedures of recycling and regeneration resulted ineffective in restoring the pristine performances of the samples due to surface presence of both Sn(IV) and Cr(III). To overcome these weaknesses, the used samples (Sn + Cr/HAP) were upcycled into catalysts in a circular economy perspective. Used samples were tested as catalysts in gas-phase catalytic processes for air pollution remediation: selective catalytic reduction of NOx (NH3-SCR), NH3 selective catalytic Oxidation (NH3-SCO), and selective catalytic oxidation of methane to CO2. Catalytic tests enlightened the interesting activity of the upcycled Sn + Cr/HAP samples in catalytic oxidation processes, being able to selectively oxidize methane to CO2 at relatively low temperature.


Differing risk of cancer death among patients with lymph node metastasis after radical prostatectomy and pelvic lymph node dissection: identification of risk categories according to number of positive nodes and Gleason score.
To evaluate the outcomes in patients with node-positive prostate cancer (PCa) after radical prostatectomy (RP) and pelvic lymph node dissection (PLND) according to the number of positive lymph nodes (LNs). To identify different risk groups among patients with node-positive PCa. We evaluated 98 consecutive patients with pN1M0 PCa who underwent RP between November 1995 and May 2011. Kaplan-Meier and Cox proportional univariable and multivariable regression models were used to analyse the survival rates. Patients were divided into two groups according to number of positive LNs using the most informative positive LN theshold for predicting survival, then into three different risk groups according to number of positive LNs and pathological Gleason score (GS). Mean (range) follow-up was 68.4 (10-192) months. Patients with 1-3 positive LNs (n = 75; 76.5%) had significantly better cancer-specific survival (CSS) and overall survival (OS) compared with those with >3 positive nodes (n = 23; 23.4%; P < 0.01). Patients with 1-3 positive LNs and pathological GS ≤7 (Group 1) had significantly better CSS than those with >3 positive LNs or GS 8-10 (Group 2 [P = 0.015]). Group 2 patients, moreover, had significantly better CSS (P = 0.019) and OS (P = 0.021) than those with >3 positive LNs and GS 8-10 (Group 3). Patients with 1-3 positive LNs have higher CSS and OS rates than those with >3 metastatic LNs. Taking into account the pathological GS, as well as the number of positive nodes, three risk group categories with considerable differences in terms of survival can be found. Patients with LN-positive PCa should be stratified into different groups according to these two measures, to obtain a better prediction of oncological outcomes.


Optic nerve head blood flow regulation during changes in arterial blood pressure in patients with primary open-angle glaucoma.
Abnormal autoregulation of optic nerve head blood flow (ONHBF) has been postulated to play an important role in primary open-angle glaucoma (POAG). We used laser Doppler flowmetry (LDF) to estimate quantitatively the ONHBF and compared ONHBF autoregulation between glaucoma patients and healthy controls during isometric exercise. Forty patients with POAG and 40 healthy age- and sex-matched subjects underwent three periods of isometric exercise, each consisting of 2 min of handgripping. Optic nerve head blood flow (ONHBF) was measured continuously using LDF. Systemic blood pressure, intraocular pressure and ocular perfusion pressure were assessed in all participants. Isometric exercise was associated with an increase in ocular perfusion pressure during all handgripping periods in both groups (p < 0.001). However, there was no change in ONHBF in either group. Three of the glaucoma patients and two of the healthy subjects showed a consistent 10% decrease in blood flow during isometric exercise, in spite of an increase in their blood pressure. This difference between groups was not significant (p = 0.61). Four other glaucoma subjects showed a consistent increase in blood flow of more than 10% during isometric exercise, whereas this was not seen in healthy subjects (p = 0.035). This study suggests that abnormal ONHBF autoregulation is more often seen in patients with POAG than healthy control subjects. The relationship to the glaucoma disease process is currently unknown and requires further investigation.


Targeting physical activity in a low socioeconomic status population: observations from the Norwegian 'Romsas in Motion' study.
To summarise the main results of a community-based study on physical activity promotion - "Romsås in Motion". The study assessed changes in physical activity, body mass and psychosocial mediators of physical activity from a pseudo-experimental cohort study involving two districts with low socioeconomic status in Oslo, Norway. In 2000, baseline investigation included 2950 30-67-year-olds - 48% of those invited. At follow-up in 2003 we measured 1776 subjects (67% of those eligible). A set of theoretically informed strategies targeting individuals, groups and the environment were implemented, tailored towards groups with different psychosocial readiness for change. Net changes (the difference between changes in the intervention and control districts) and results of mediation analyses related to the effect of the intervention are reported. The increase in physical activity measured by two questionnaires was 9.5% (p = 0.008) and 8.1% (p = 0.02), respectively. The proportion who increased their body mass was reduced by 50% compared with the control district. Participation in walking and aerobic exercise groups, having seen the "Walk the stairs" poster and used the walk path, were particularly effective intervention components. The most promising psychosocial mediators of forward transition in stages of change were physical activity identity, perceived control, support from friends and family, and self-efficacy when facing psychological barriers. Through a theoretically informed, low-cost, population-based intervention programme an increase in physical activity levels and a reduced weight gain were observed. Mediation findings regarding forward transition in stages of change enhance our understanding of psychosocial mechanisms of behaviour change, and may prove helpful in guiding implementation and evaluation of future interventions.


Selective nucleophilic α-C alkylation of phenols with alcohols via Ti=Cα intermediate on anatase TiO2 surface.
C-C bond forming reaction by alkylation of aryl rings is a main pillar of chemistry in the production of broad portfolios of chemical products. The dominant mechanism proceeds via electrophilic substitution of secondary and tertiary carbocations over acid catalysts, forming multiple aryl alkylation products non-selectively through all secondary and tertiary carbons in the alkyl chains but producing little α-C alkylation products because primary carbocations are poorly stable. Herein, we report that anatase TiO2 (TiO2-A) catalyzes nucleophilic α-C alkylation of phenols with alcohols in high selectivity to simply linear alkylphenols. Experimental and computational studies reveal the formation of Ti=C- bond with the α-carbon of the alkyl group at oxygen vacancies of the TiO2-A surface. The subsequent α-C alkylation by selective substitution of phenol ortho-C-H bond is verified by deuterium exchanged substrate and DFT calculations.


Discharge coordinator intervention prevents hospitalizations in patients with COPD: a randomized controlled trial.
To test whether coordination of discharge from hospital reduces hospitalizations in patients with chronic obstructive pulmonary disease (COPD). Randomized controlled clinical trial. Specialized pulmonary hospital. Patients hospitalized for an acute exacerbation of COPD. Care as usual included routine patient education, supervised inhaler use, respiratory physiotherapy, and disease-related communication. The discharge coordinator intervention added assessment of patient situation and homecare needs. Patients and caregivers were actively involved and empowered in the discharge planning process, which was communicated with community medical professionals to provide continuity of care at home. The primary end-point of the study was the number of patients hospitalized because of worsening COPD. Key secondary end-points were time-to-COPD hospitalization, all-cause mortality, all-cause hospitalization, days alive and out of hospital, and health-related quality of life. Of 253 eligible patients (71 ± 9 years, 72% men, 87% GOLD III/IV), 118 were assigned to intervention and 135 to usual care. During a follow-up of 180 days, fewer patients receiving intervention were hospitalized for COPD (14% versus 31%, P = .002) or for any cause (31% versus 44%, P = .033). In time-to-event analysis, intervention was associated with lower rates of COPD hospitalizations (P = .001). A Cox model of proportional hazards, adjusted for sex, age, GOLD stage, heart failure, malignant disease, and long-term oxygen treatment, demonstrated that intervention reduced the risk of COPD hospitalization (hazard ratio 0.43, 95% confidence interval 0.24-0.77, P = .002). Among patients hospitalized for acute COPD exacerbation, discharge coordinator intervention reduced both COPD hospitalizations and all-cause hospitalizations.


Viologen-functionalized magnetic material for the removal of Iodine and benzanthracene in an aqueous solution.
The development of magnetically active adsorbents for effective iodine removal would be highly desirable to address environmental pollution and remediation. Herein, we demonstrated the synthesis of Vio@SiO2@Fe3O4 as an adsorbent via surface functionalisation of electron-deficient bipyridium (viologen) units on the surface of magnetically active silica-coated magnetite (Fe3O4) core. This adsorbent was characterised thoroughly using various analytical techniques, such as field emission scanning electron microscopy (FESEM), thermal gravimetric analysis, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FETEM), Brunauer-Emmett-Teller (BET) analysis and X-ray photon analysis (XPS). The removal of triiodide from the aqueous solution was monitored via the batch method. It revealed that the complete removal was achieved upon stirring for 70 min. The thermally stable and crystalline Vio@SiO2@Fe3O4 displayed efficient removal capacity even in the presence of other competing ions and at different pHs. The adsorption kinetics data were analysed following the pseudo-first-order and pseudo-second-order models. Further, the isotherm experiment showed that the maximum uptake capacity of iodine is 1.38 g/g. It can be regenerated and reused over multiple cycles to capture iodine. Further, Vio@SiO2@Fe3O4 displayed a good removal capacity toward toxic polyaromatic, Benzanthracene (BzA) pollutant with an uptake capacity of 2445 μg/g. This effective removal of toxic pollutants iodine/benzanthracene was attributed to the strong non-covalent electrostatic and π-π interaction with electron-deficient bipyridium units.


Elevated cortical zinc in Alzheimer disease.
To determine whether changes in brain biometals in Alzheimer disease (AD) and in normal brain tissue are tandemly associated with amyloid beta-peptide (Abeta) burden and dementia severity. The authors measured zinc, copper, iron, manganese, and aluminum and Abeta levels in postmortem neocortical tissue from patients with AD (n = 10), normal age-matched control subjects (n = 14), patients with schizophrenia (n = 26), and patients with schizophrenia with amyloid (n = 8). Severity of cognitive impairment was assessed with the Clinical Dementia Rating Scale (CDR). There was a significant, more than twofold, increase of tissue zinc in the AD-affected cortex compared with the other groups. Zinc levels increased with tissue amyloid levels. Zinc levels were significantly elevated in the most severely demented cases (CDR 4 to 5) and in cases that had an amyloid burden greater than 8 plaques/mm(2). Levels of other metals did not differ between groups. Brain zinc accumulation is a prominent feature of advanced Alzheimer disease (AD) and is biochemically linked to brain amyloid beta-peptide accumulation and dementia severity in AD.


Detrimental effects of temephos on male fertility: An in vitro study on a mouse model.
The World Health Organization recommends temephos as a nonsystemic organophosphorus pesticide due to its low mammalian toxicity compared with other chemical compounds. Although several studies have reported that temephos may be toxic under certain conditions, little research effort has been made to evaluate its effects on mammalian fertility. Therefore, the present study was designed to evaluate the effect of temephos on sperm functions and male fertility. Initially, cauda epididymis from mouse spermatozoa was incubated with temephos (0, 0.1, 1, 10, and 100 μM). Then, sperm motility and motion kinematics, capacitation status, intracellular adenosine triphosphate level, lactate dehydrogenase level, protein kinase A (PKA) activity, and degree of tyrosine phosphorylation were analyzed. Finally, the rates of fertilization and early embryonic development were evaluated. Sperm motility and motion kinematics were found to be significantly altered in temephos groups. In addition, the acrosome reaction and capacitation significantly increased and decreased in the 100 μM temephos group, respectively. Intracellular adenosine triphosphate levels significantly decreased in the 1, 10, and 100 μM temephos groups compared with that in the control group. Moreover, PKA activity and tyrosine phosphorylation significantly decreased in most temephos groups. Further, the rates of fertilization and early embryonic development significantly decreased in all temephos groups. Taken together, it was determined that temephos had harmful effects on male fertility. Therefore, the reproductive toxicity of temephos should be considered before its use.


The risk of venous thromboembolism and blood hyperlactatemia is associated with increased mortality among critically ill patients with Covid-19.
Coronavirus disease 2019 (Covid-19) following venous thromboembolism (VTE) and blood hyperlactatemia are associated with higher mortality. However, reliable biomarkers for this association remain to be elucidated. This study investigated the associations of VTE risk and blood hyperlactatemia with mortality among critically ill Covid-19 patients admitted to the intensive care unit (ICU). In this single-centre retrospective study, we included 171 patients aged ≥18 years with confirmed Covid-19 admitted to the ICU at a tertiary healthcare clinic in the Eastern region of Saudi Arabia between 1 March 2020 and 31 January 2021. Patients were divided into two groups: survivor and non-survivor. The survivors have been identified as the patients discharged from the ICU alive. The VTE risk was defined using a Padua prediction score (PPS) >4. The blood lactate concentration (BLC) cut-off value >2 mmol/L was used to determine the blood hyperlactatemia. Multi-factor Cox analysis showed that PPS >4 and BLC >2 mmol/L were more likely to be significantly associated with higher odds of ICU mortality in critically ill Covid-19 patients (hazard ratio [HR] = 2.80, 95% confidence interval [CI] = 1.00-8.08, p = 0.050; HR = 3.87, 95% CI = 1.12-13.45, p = 0.033, respectively). The Area under the Curve for VTE and blood hyperlactatemia were 0.62 and 0.85, respectively. VTE risk and blood hyperlactatemia have been associated with a higher mortality risk in critically ill Covid-19 patients who are hospitalized in the ICU in Saudi Arabia. According to our findings, these people needed more effective VTE prevention strategies based on a personalized assessment of their risk of bleeding. Moreover, persons without diabetes and other groups with a high risk of dying from COVID-19 may be recognized by measuring glucose as having elevated glucose and lactate jointly.


The Geriatric Patient One Year After Trauma: Palliative Performance Scale Predicts Functional Outcomes.
Frailty in trauma has been found to predict poor outcomes after injury including additional in-hospital complications, mortality, and discharge to dependent care. These gross outcome measures are insufficient when discussing long-term recovery as they do not address what is important to patients including functional status and quality of life. The purpose of this study is to determine if the Palliative Performance Scale (PPS) predicts mortality and functional status one year after trauma in geriatric patients. Prospective observational study of trauma survivors, age ≥55 years. Patients were stratified by pre-injury PPS high (>70) or low (≤70). Outcomes were functional status at 1 year measured by Glasgow Outcome Scale Extended (GOSE), Euroqol-5D and SF-36. Adjusted relative risks (aRR) were obtained using modified Poisson regression. Follow-up was achieved on 215/301 patients. Mortality was 30% in low PPS group vs 8% in the high PPS group (P<0.001). A greater percentage of patients in the high group had a good functional outcome at one year compared to patients in the low group (78% vs 30% p<0.001). The high PPS patients were more likely to have improvement of GOSE at 1 year from discharge compared to low group (66% vs 27% P<0.001). Low PPS independently predicted poor functional outcome (aRR, 2.64; 95% confidence interval, 1.79-3.89) and death at 1 year (aRR, 3.64; 95% confidence interval 1.68-7.92). An increased percentage of low PPS patients reported difficulty with mobility (91% vs 46% p<0.0001) and usual activities (82% vs 56% p=0.002). Both groups reported pain (65%) and anxiety/depression (47%). Low pre-Injury PPS predicts mortality and poor functional outcomes one year after trauma. Low PPS patients were more likely to decline, rather than improve. Regardless of PPS, most patients have persistent pain, anxiety, and limitations in performing daily activities.


Skeletal accumulation of bisphosphonates: implications for osteoporosis treatment.
Bisphosphonates (BPs), the gold-standard pharmacological treatment for osteoporosis, are unique in that they become physically bound to the bone matrix and therefore accumulate over time. This skeletal accumulation has important physiological implications that are not completely understood. To review concepts related to the biological effects of BP accumulation in the skeleton. Articles concerning skeletal accumulation of BP treatment were identified. Skeletal accumulation of BP, dictated by both chemical and biological factors, is dose-dependent, differs among skeletal sites and likely differs among the various BPs. Bisphosphonate embedded within the skeletal matrix has lasting biological effects, the results of which have both positive and negative implications for bone remodeling. As alternative anti-remodeling agents gain approval for treatment of osteoporosis, the property of skeletal accumulation will likely be unique to BPs and therefore may be the property that determines the future use of this drug class.


Interactions of Cellular Energetic Gene Clusters in the Alzheimer's Mouse Brain.
Alzheimer's disease (AD) is the most common cause of dementia in the aging population. The pathological characteristics include extracellular senile plaques and intracellular neurofibrillary tangles. In addition, mitochondrial dysfunction, oxidative stress, and neuroinflammation contribute to AD pathogenesis. In this study, we sought to determine the crosstalk between different pathways in the brain of 5XFAD mice, a mouse model for amyloid pathology, by RNA-seq analysis. We observed significant changes in the expression of genes (1288 genes; adj p value < 0.05; log2-fold > 1 and < 1) related to pathways including oxidation-reduction, oxidative phosphorylation, innate immune response, ribosomal protein synthesis, and ubiquitin proteosome system. The most striking feature was the downregulation of genes related to oxidation-reduction process with changes in the expression of a large number of mitochondrial genes. We also observed an upregulation of several immune response genes. Gene interaction network of oxidation-reduction related genes further confirmed a tight cluster of mitochondrial genes. Furthermore, gene interaction analysis of all the 1288 genes showed at least three distinct interaction clusters, with the predominant one relating to cellular energetics. In summary, we identified 1288 genes distinctly different in the 5XFAD brain compared to the WT brain and found cellular energetics to be the most distinct gene cluster in the AD mouse brain.


Sorbitol dehydrogenase of Aspergillus niger, SdhA, is part of the oxido-reductive D-galactose pathway and essential for D-sorbitol catabolism.
In filamentous fungi D-galactose can be catabolised through the oxido-reductive and/or the Leloir pathway. In the oxido-reductive pathway D-galactose is converted to d-fructose in a series of steps where the last step is the oxidation of d-sorbitol by an NAD-dependent dehydrogenase. We identified a sorbitol dehydrogenase gene, sdhA (JGI53356), in Aspergillus niger encoding a medium chain dehydrogenase which is involved in D-galactose and D-sorbitol catabolism. The gene is upregulated in the presence of D-galactose, galactitol and D-sorbitol. An sdhA deletion strain showed reduced growth on galactitol and growth on D-sorbitol was completely abolished. The purified enzyme converted D-sorbitol to D-fructose with K(m) of 50±5 mM and v(max) of 80±10 U/mg.


Sensory denervation of the plantar lumbrical muscle spindles in pyridoxine neuropathy.
Male albino rats treated with excessive amounts of pyridoxine developed an impairment of neuromuscular function. The equatorial region of the plantar lumbrical intrafusal muscle fibres was studied in the electron microscope and the calibre of the nerve fibres was determined in semi-thin sections of the posterior tibial nerves. Degeneration of the primary sensory endings coincided with the onset of ataxia, and in more advanced stages of the neuropathy as well as after a 2-month treatment-free period the equatorial region was denervated. There was a corresponding decrease in the number of large nerve fibres. It is considered essential that primary sensory endings of lumbrical muscle spindles should be included in studies of distally accentuated sensory neuropathies.


Secretion from bacterial versus mammalian cells yields a recombinant scFv with variable folding properties.
Escherichia coli (E. coli) is the most commonly used organism for expressing antibody fragments such as single chain antibody Fvs (scFvs). Previously, we have utilized E. coli to express well-folded scFvs for characterization and engineering purposes with the goal of using these engineered proteins as building blocks for generating IgG-like bispecific antibodies (BsAbs). In the study, described here, we observed a significant difference in the secondary structure of an scFv produced in E. coli and the same scFv expressed and secreted from chinese hamster ovary (CHO) cells as part of a BsAb. We devised a proteolytic procedure to separate the CHO-derived scFv from its antibody-fusion partner and compared its properties with those of the E. coli-derived scFv. In comparison to the CHO-derived scFv, the E. coli-derived scFv was found trapped in a misfolded, but monomeric state that was stable for months at 4 °C. The misfolded state bound antigen in a heterogeneous fashion that included non-specific binding, which made functional characterization challenging. This odd incidence of obtaining a misfolded scFv from bacteria suggests careful characterization of the folded properties of bacterially expressed scFvs is warranted if anomalous issues with antigen-binding or non-specificity occur during an engineering campaign. Additionally, our proteolytic methodology for obtaining significant levels of intact scFvs from highly expressed IgG-like antibody proteins serves as a robust method for producing scFvs in CHO without the use of designed cleavage motifs.


Perceived Teacher Discrimination and Depressive Feelings in Adolescents: The Role of National, Regional, and Heritage Identities in Flemish Schools.
Adolescents' identities are multiple, yet there is very little research that investigates the importance of intersecting identities, especially in relationship to teacher ethnic/racial discrimination and mental health. Multiplicity is often approached bi-dimensional (heritage and national identities) yet this study highlights the importance of regional identity. Regions are distinct socio-political contexts in relation to migration and integration dynamics. Hence, this study investigates for different combinations of national, heritage and regional identities (i.e. Flemish, Belgian and Turkish or Moroccan) the relationship between students' experiences with teacher ethnic/racial discrimination and students' depressive feelings. Latent Class Analysis of survey data involving a sample of 439 adolescents (Mage = 18, SD = 0.93; Girls = 49%) with Turkish (41%) or Moroccan origin in Flanders, shows three identification classes: full integration (35%), national integration (40%) and (weak) separation (24%). All these identity profiles had in common that heritage identification was high, yet they were highly distinct due to variation in national and regional identification. Additional, multilevel modelling showed that nationally integrated adolescents were less depressed than fully integrated adolescents. This finding illustrates the importance of adolescents' identity multiplicity for understanding their resilience in relation to teacher discrimination.


Endothelial cell-T lymphocyte interactions: IP[corrected]-10 stimulates rapid transendothelial migration of human effector but not central memory CD4+ T cells. Requirements for shear stress and adhesion molecules.
The chemokine interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10; CXCL10) has been implicated in recruitment of T cells into rejecting allografts yet appears ineffective at stimulating human peripheral blood CD4 T cells to transmigrate across tumor necrosis factor (TNF)-treated human endothelial cell (EC) monolayers in vitro. The same cells rapidly (within 15 min) transmigrate across TNF-treated EC monolayers overlaid with stromal cell-derived factor-1 alpha (SDF-1 alpha) and subjected to shear stress. The effector memory subset within the CD4 T cell population, defined as CD45RO, CD62L and CCR7, which constitutes less than 10% of total CD4 T cells, does respond to IP-10 but requires enrichment to be observed in this model. Central memory T cells do not respond to IP-10. Transendothelial migration of effector memory CD4 T cells requires TNF-pretreatment of the EC monolayer and application of venular shear force during the assay. TNF treatment of ECs may be effectively replaced by transduction of vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 but not E-selectin.


Immunoreactivity of HOXB13 in Neuroendocrine Neoplasms Is a Sensitive and Specific Marker of Rectal Well-Differentiated Neuroendocrine Tumors.
HoxB13 is a transcription factor involved in defining of posterior endodermal derivatives, including prostate and rectum. While it is used as a marker of prostatic adenocarcinoma, it has not been studied systematically in neuroendocrine neoplasms. Thus, we performed HoxB13 immunohistochemistry in tissue microarrays and the whole sections of 232 neuroendocrine neoplasms. These included 34 paragangliomas (PGs), 20 cauda equina neuroendocrine tumors (CENETs), 123 well-differentiated neuroendocrine tumors (WDNETs), and 55 neuroendocrine carcinomas (NECs). WDNETs were additionally analyzed with SATB2, and colorectal WDNETs with CDX2 and serotonin immunohistochemistry. In total, HoxB13 immunoreactivity was observed in 95% (19/20) CENETs, 10.6% (13/123) WDNETs, and 12.9% (7/54) NECs. No PGs were positive. Large intestine WDNETs expressed HoxB13 in 68.4% (13/19); five negative tumors originated in cecum and one in rectum. In rectum, 92.9% (13/14) WDNETs expressed HoxB13. HoxB13 was 92.9% sensitive and 100% specific, showing 100% positive predictive value for the rectal origin of WDNET. In NECs, HoxB13 was positive in 15.4% (2/13) GIT tumors and 80% (4/5) prostatic NECs, but in none of urinary bladder NECs (0/8). SATB2 was positive in 17.1% (21/123) WDNETs, including 78.9% (15/19) of colorectal WDNETs, 71.4% (5/7) appendiceal WDNETs, and 2.9% (1/34) small intestine WDNETs. All 4 SATB2-negative large bowel tumors originated in the cecum. When both markers combined, HoxB13+/SATB2+ immunoprofile was seen exclusively in rectal WDNETs (positive predictive value 100%), while HoxB13-/SATB2+ immunoprofile was highly suggestive of the appendiceal origin (positive predictive value 71.4%). Therefore, HoxB13 can be useful as an immunohistochemical marker of rectal WDNETs and prostatic NECs.


Mallory bodies: lesions of hepatocytes containing proteins of the keratin-myosin-epidermin group.
Mallory's alcoholic hyalin in hepatocytes was found also in other diseases and is now referred to as Mallory bodies. Data concerning their histochemical, immuno and electron microscopic properties are partly contradictory. In this study, early stages of Mallory bodies reacted strongly with configurational technics for myosins; affinity tended to decrease when material with the properties of keratohyalin and the matrix of stratum corneum was formed. Thus, many Mallory bodies contained histochemically distinct myoid and keratin-like proteins. Electron microscopists demonstrated thick and thin filaments resembling contractile systems in Mallory bodies; the failure of immunologists to visualize actomyosin may be due to the heterogeneity of these proteins. The currently popular term prekeratin has been applied to a variety of substances extracted from epidermis, hoof and hair under different conditions. The prekeratin of recent immunofluorescence studies seems to contain mainly epidermin and low molecular matrix proteins; both were studied extensively by chemists. Epithelial filaments, including tonofibrils and contractile fibrils regarded as a subgroup of myofibrils, were well known half a century ago, but were banished by electron microscopy. Observations in this study and data on epidermal actomyosin indicate that different proteins of the k-m-e-f group can indeed coexist in epithelial cells. The formation and resolution of Mallory bodies can be regarded as an example of the well known shifts of epithelial cells between secretory and keratinizing states.


HIV testing and related factors among 50 years and older MSM in China: results from a cross-sectional study.
ABSTRACTHIV prevalence has increased continuously, and the age groups most afflicted by the epidemic have also shifted to people aged above 50 years. Informed by the theory of HBM, we aimed to investigate related factors associated with regular HIV testing behavior. Cross-sectional data were collected using online questionnaire from geosocial networking (GSN) mobile application (apps) for MSM during May 2020 (N = 1259). Data were analyzed by univariate and multivariate logistic regression. Around 62.0% (n = 781) had received HIV testing before. Participants being divorced/widowed (AOR = 1.5,95%CI:1.1-2.0), being aware of HIV/AIDS-related knowledge (AOR = 1.8,95%CI:1.4-2.3), having disclosed sexual orientation (AOR = 1.9,95%CI:1.5-2.5), ever had sexually transmitted infections symptoms (STIs)before (AOR = 2.4,95%CI:1.8-3.2), having had≥2 sexual partners (AOR = 1.8,95%CI:1.4-2.3) and with high self-efficacy (AOR = 1.1,95%CI:1.0-1.1) were more likely to receive HIV testing. Findings suggest that many Chinses MSM aged 50 and above have not been tested for HIV. Interventions for promoting HIV testing should focus on expanding scales of HIV/STIs screening, providing HIV/AIDS-related knowledge, creating a more supportive social environment and improving self-efficacy of HIV testing.


Os cuboideum secundarium: a rare accessory ossicle with the potential to mimic a mass on magnetic resonance imaging.
Accessory ossicles are common incidental findings on radiographs of the ankle and foot. While typically asymptomatic and of no clinical significance, they are sometimes associated with local pain or even mistaken for pathological conditions such as fractures. Given the potential for misinterpretation, it is important to understand their typical locations and appearances. This case highlights an exceptionally rare accessory ossicle called the os cuboideum secundarium, located adjacent to the cuboid and calcaneus. Interestingly, this case demonstrates the potential for this rare ossicle to mimic a mass on magnetic resonance imaging (MRI). Furthermore, despite the significant improvements in the understanding of musculoskeletal pathology afforded by advancements in cross-sectional imaging techniques, this case is a reminder of certain pitfalls that remain. Lastly, it highlights the importance of radiographs as an initial diagnostic study in evaluating foot pain.


Ultrastructural localization of zinc in the hyperplastic prostate.
The localization of zinc was investigated in specimens of hyperplastic prostate by means of light microscopy, electron microscopy, and x-ray microanalysis. After fixation in glutaraldehyde plus hydrogen sulfide, representative sections were developed with sulfide-silver while, for comparison, other sections were not developed. Aggregation of the silver precipitation was seen on the secretory vacuoles of the developed sections. None of the deposits were detected on the nucleus, lysosomes, Golgi apparatus, or other cytoplasmic organelles. X-ray microanalysis was performed on these sections of hyperplastic prostate. X-ray energy spectrum analysis of the undeveloped sections revealed that the concentration of zinc on the electron-dense materials in the secretory vacuoles corresponded to the deposits of silver granules. The present investigation provides direct proof of the localization of ionized zinc in the cytoplasm of the hyperplastic prostate.


Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis.
Osteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 ± HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA.


Host defense development in gut and related disorders.
The gastrointestinal tract serves as an important interface between ingested elements from the external environment and the internal milieu of the person. Maturation of this intestinal barrier appears to occur along with the normal development of other organ systems. Evidence is presented for this maturational process, and the relation of this immature barrier to certain disease states seen in the neonatal period (e.g., infectious diarrhea, necrotizing enterocolitis, and allergic disease) is discussed.


Quality of life after radical prostatectomy.
Radical prostatectomy is a standard approach to the management of prostate cancer. As the oncological outcome has improved, focus has drawn to the postoperative amelioration of health-related quality of life (HRQOL). The instruments that have already been used, or may be used, in assessing the HRQOL postoperatively in men with prostate cancer are presented. Urinary and sexual dysfunction as well as fecal incontinence form the three possible major complications after surgery which affect the patient's quality of life. Meticulous counseling regarding the potential morbidity associated with the operation that may affect the patient's quality of life should be made before the patient gives his informed consent. Questionnaires only partially help to identify patients with dysfunction, especially sexual and bowel dysfunction, and careful patient counseling with their partners present is the best way to evaluate the presence of dysfunction pre- or postoperatively.


Cytokeratin expression in central mucoepidermoid carcinoma and glandular odontogenic cyst.
Central mucoepidermoid carcinoma (MEC) is an entity whose origin is still controversial. Glandular odontogenic cyst (GOC) is a recently described lesion whose relationship to low-grade central MEC has been reported in the literature. Our aim was to assess the cytokeratin (CK) profile of central MEC and GOC, and compare the results with CK expression in salivary gland MEC and odontogenic cysts and tumors. Eighty-five cases, including 6 central MECs, 23 salivary gland MECs, 10 GOCs, 34 odontogenic cysts and 12 ameloblastomas, were studied through immunohistochemistry using eleven monoclonal anti-CK antibodies. All central MECs expressed CKs 5, 7, 8, 14, and 18 and all GOCs expressed CKs 5, 7, 8, 13, 14, and 19. Comparing CK expression from GOC and central MEC we found differences in CKs 18 (30% vs 100%) and 19 (100% vs 50%). Central MEC and GOC are probably distinct entities with CK profiles similar to lesions of glandular and odontogenic origins, respectively, and expression of CKs 18 and 19 could be useful in their differential diagnosis.


The detection of inferior vena caval thrombosis with computed tomography.
Two cases are reported in which computed tomography demonstrated inferior vena caval thrombosis following intravenous administration of contrast material. This observation appears to have its greatest application in the staging of abdominal neoplasms, particularly renal-cell carcinoma.


Ancient islands acted as refugia and pumps for conifer diversity.
Island species are thought to be extinction-prone because of small population sizes, restricted geographical distribution and limited dispersal ability. However, the topographical and environmental heterogeneity, geographical isolation and stability of islands over long timescales could create refugia for taxa whose source area is threatened by environmental changes. We address this possibility by inferring the evolution of the New Caledonia (NC) and New Zealand (NZ) conifer diversity, which represents over 10% of the world's diversity for this group. We estimate speciation and extinction rates in relation to the presence/absence on these islands, and dispersal rates between the islands and surrounding areas. We also test the Eocene submersion of NC and the Oligocene drowning of NZ by comparing the fit of biogeographical scenarios using ancestral area estimations. We find that extinction rates were significantly lower for island species, and dispersal "out of islands" was higher. A model including a diversification shift when NC emerged better explains the diversification dynamics. Biogeographical analyses corroborate that conifers experienced high continental extinctions, but survived on islands. NC and NZ have thus contributed to the world's conifer diversity as "island refugia", by maintaining early-diverging lineages from continents during environmental changes on continents. These ancient islands also acted as "species pumps", providing species into adjacent areas. Our study highlights the important but neglected role of islands in promoting the evolution and conservation of biodiversity.


Morphologic and biologic correlation of hyperplastic and neoplastic renal lesions occurring in Buffalo and Fischer strain rats ingesting n-4-(4'-fluorobiphenyl) acetamide.
Hyperplastic and neoplastic lesions of the kidney induced in inbred Buffalo and Fisher strain rats with 0.04% N-4-(4'-fluorobiphenyl) acetamide were transplanted s.c. to rats of the same strain. Hyperplastic renal lesions ("areas" or nodules) did not survive and grow. Carcinomas of the kidney grew and killed the animals. Growth was related to the size and the degree of differentiation of the carcinoma. It is concluded that the histologic pattern of hyperplastic and neoplastic lesions of the kidney can be correlated with the results obtained on transplantation.


Improving quality control of yucca extracts used as food additives by screening antimicrobial activity using NMR metabolomics.
Yucca schidigera is mainly distributed in southwestern US and the northern desert of Mexico. Its extract is widely used as a food additive for its antimicrobial activity. However, this antimicrobial activity is subject to significant variability across production lots. Yucca extracts are natural products and their composition is affected by their cultivation area and weather. Manufacturer deal with natural products such as food additives pay particularly close attention to quality control. In the present study, NMR metabolomics methods were used to screen the antimicrobial activity of yucca extracts. Yucca extracts were subjected to principal component analysis (PCA) and categorized on a score plot of their 1H NMR spectral data according to their antimicrobial activity. Furthermore, hierarchical cluster analysis (HCA) was also used to classify yucca extracts based on their antimicrobial activity. Classification using PCA and HCA was dependent upon saponin content, particularly that of schidigera-saponin A1 and D1, which was further confirmed by HPLC analysis of the yucca extracts. We demonstrated that NMR-based metabolomics is a potentially useful tool to use in combination with conventional quality control methods for yucca extracts used as food additives. We envisage this method as tool for initially screening the extracts prior to carrying out the officially recommended quality control tests.


Meniscal repair devices: a clinical and biomechanical literature review.
The development of new approaches to arthroscopic meniscal repair has spurred the concomitant publication of studies reviewing their use and biomechanical properties. The purpose of this article is to review both the devices and the literature surrounding their clinical and biomechanical properties. Literature review. Studies were initially gathered using a MEDLINE search, and additional information was found through cross references. We evaluate a series of studies comparing sutures, suture anchors, screws, staples, and a variety of other devices in terms of initial fixation strength, degradation profile, performance under cyclical loading, and clinical success. In the traditional suture studies, vertical sutures are clearly superior to both horizontal sutures and knot-end techniques in terms of initial fixation strength and performance under cyclical loading. Unfortunately, multidevice studies have been less consistent and less conclusive. the Linvatec Biostinger, Smith & Nephew T-fix, and Bionx Meniscus Arrow have separately been shown to have superior initial fixation strength on par with suture techniques. After cyclical loading, horizontal sutures, vertical sutures, 16-mm Arrows, 13-mm Arrows, and the Smith & Nephew T-fix generally show higher fixation strengths. Only the Bionx Arrow, Linvatec Biostinger, and Clearfix Screw have been shown to retain their initial fixation strengths through four months of hydrolysis time. Data suggest that the biomechanical performance of some devices is nearly equivalent to current suture techniques. Ultimately, the combination of a simplified surgical technique, high clinical healing rates (75%-92%), and relatively minor complications makes these devices attractive for properly indicated meniscal tears.


Role of right atrial endocardial structures as barriers to conduction during human type I atrial flutter. Activation and entrainment mapping guided by intracardiac echocardiography.
The importance of barriers in atrial flutter has been demonstrated in animals. We used activation and entrainment mapping, guided by intracardiac echocardiography (ICE), to determine whether the crista terminalis (CT) and eustachian ridge (ER) are barriers to conduction during typical atrial flutter in humans. In eight patients, ICE was used to guide the placement of 20-pole and octapolar catheters along the CT and interatrial septum and a roving catheter to nine sites: just posterior (1) and anterior (2) to the CT along the lateral right atrium, at the fossa ovalis (3), and just posterior and anterior to the ER at the low posterolateral (4 and 5), low posterior (6 and 7), and low posteromedial (8 and 9) right atrium. Entrainment was performed, and each site was considered within the flutter circuit if the postpacing interval-flutter cycle length (PPI-FCL) and the stimulus time-activation time (stim time-act time) were < 10 msec. Split potentials were recorded along the CT with components activated in a low-to-high pattern and a high-to-low pattern. Conduction times, as percentage of FCL, were significantly different at sites on either side of the CT and ER: site 1 (33 +/- 13%) and site 2 (43 +/- 12%) (P = .02), site 4 (48 +/- 24%) and site 5 (75 +/- 8.9%) (P = .02), and site 6 (22 +/- 10%) and site 7 (82 +/- 5.3%) (P = .0009). During entrainment, no surface fusion was observed at sites 5, 7, or 9. The PPI-FCL and stim time-act time were not significantly different than 0 at sites 2, 7, 5, or 9, indicating that they were within the flutter circuit, whereas sites 1, 3, 4, and 6 were not. ICE enabled the correlation of functional electrophysiological properties with specific anatomic landmarks, identifying the CT and ER as barriers to conduction during human atrial flutter.


[Lymphedema: anatomy, physiology and pathophysiology of lymphedema, definition and classification of lymphedema and lymphatic vascular malformations].
Lymphedema is a chronic disease associated with a congenital or acquired disorder of the lymphatic vessels or lymph nodes. Untreated lymphedema can lead to complications and disability. Clinical Lymphology deals not only with lymphedema of the extremities but also of the head, the genitals and the internal organs (lymphostatic enteropathy, chylaskos, chylothorax, chylopericard etc). Symptoms of this disorder are often misdiagnosed or not recognized. Ignorance and trivialization of lymphedema causes insufficient treatment, which then is not carried out to the extent as it is possible today by scientific findings. Even today delayed or not optimal treatment causes a long ordeal for many patients.The fact that lymphedema for those affected is a major psychological and social burden, which is limiting the quality of life, has also often been unregarded. The knowledge of anatomy, physiology and pathophysiology as well as the knowledge of causes are necessary for diagnosis, so that early treatment can be initiated.


Palmar arthroplasty for the treatment of the stiff swan-neck deformity.
Palmar arthroplasty for the treatment of the stiff swan-neck deformity in rheumatoid arthritis is designed to correct the mechanical block to flexion that is caused by palmar plate adhesions (which obliterate the retrocondylar recess) and by collateral ligament contracture and adhesions. This procedure can be performed at the same time as correction of the primary cause of proximal interphalangeal joint (PIP) hyperextension (e.g., intrinsic tightness or flexor tenosynovitis) and can also be supplemented with superficialis tenodesis to minimize recurrent hyperextension. Postoperative flexor dynamic traction, which is started at 24 to 48 hours and continued for a minimum of 3 to 4 weeks, is critical to the maintenance of motion. Arthroplasty in 47 PIP joints in 14 hands of 9 patients demonstrate an increase in motion from +20 degrees hyperextension and 9.5 degrees flexion to -7 degrees extension and 72 degrees flexion postoperatively.


The early treatment of type 2 diabetes.
The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages.


Origin and health risks of indoor radon.
Radon has always been a component of ground and air and it has been present in increased concentrations from the moment humans first sought shelter inside dwellings. Recent improvements in the energy efficiency of dwellings have led to increased concentrations of radon and to increased risks of lung cancer. To quantify the magnitude of this risk, well-designed epidemiological studies, including surveys of representative dwellings, are needed, and several are being implemented. In the meantime, the EPA and other agencies have offered guidance on monitoring procedures and remedial measures appropriate for the problem on indoor radon. Recent disclosures of relatively high concentrations of radon and radon decay products in homes in several parts of the country have increased public concern about the problem. More information and education are needed about the health risks of radon, the desirability of implementing monitoring procedures for radon, and about remediation measures when detected levels are above average. Educational resources are needed in communities to address local issues when they arise. These resources should include knowledgeable individuals who can work with state and county health officials to put public concerns into perspective within the local context. Physicians, other health professionals, and medical scientists have the knowledge and credentials to be these individuals. To provide health professionals with knowledge and skills to communicate with the public about the health risks of radon, the American Medical Association has prepared an authoritative report and initiated a series of regional seminars on the origin and health risks of radon.(ABSTRACT TRUNCATED AT 250 WORDS)


Electrophysiologic pacing of vocal cord abductors in bilateral recurrent laryngeal nerve paralysis.
We have reconfirmed our previous findings that controlled, reproducible, sustained, discrete vocal cord abduction can be achieved synchronously with respiration by electrophysiologic stimulation of the paralyzed posterior cricoarytenoid muscles. Moreover, we have demonstrated that this can be triggered synchronously by employing the normal physiologic chest wall movements that occur on respiration. To our knowledge, this represents the first report of functionally paced vocal fold abduction with respiration employing physiologic chest wall motions using an implantable device, and may represent an important step in the development of a physiologic approach to bilateral recurrent laryngeal nerve paralysis.


Survival and cell mediated immunity after burn injury in aged mice.
The elderly are less able to survive burn injury than young healthy individuals. Regardless of age, burn victims often succumb to secondary infections rather than the primary injury. Since immune responses diminish with age, it is likely that aged individuals are predisposed to a poor outcome by virtue of their weak immune system. Elevated production of macrophage-derived mediators, including interleukin-6 (IL-6), may lead to post-injury immunosuppression in young adults. Healthy aged individuals produce high circulating levels of these mediators; therefore, the combination of the age and burn trauma could further suppress immune responses and contribute to the rapid demise of aged burn patients. Herein, the effects of age and burn trauma using a murine scald injury model were examined. After injury, aged mice are less likely to survive, are unable to mount immune responses, and produce more IL-6 when compared to young adult mice given the same size injuries. Enhancing our understanding of the mechanisms responsible for regulating cell-mediated immune responses after injury could lead to the development of therapies designed to treat aged burn patients.


Cardiac arrhythmias associated with volume-assured pressure support mode in a patient with autonomic dysfunction and mitochondrial disease.
A 15-year-old boy with autonomic dysfunction and mitochondrial disease was diagnosed with sleep-related hypoventilation at 6 years of age and treated with bilevel positive airway pressure therapy. At 12 years of age, treatment was transitioned to volume-assured pressure support (VAPS) due to clinical evidence of respiratory muscle weakness. Subsequent titration polysomnogram revealed the emergence of cardiac arrhythmia (isolated premature ventricular contractions, bigeminy, and trigeminy) while on VAPS mode that improved after transition to bilevel positive airway pressure therapy. During the titration study, higher tidal volumes correlated with increased pressures and the presence of arrhythmia. Prior to initiation of VAPS therapy, the patient had normal electrocardiogram evaluations. This case highlights the potential relationship between VAPS therapy and cardiac arrhythmias, especially in patients with underlying conditions with associated cardiac abnormalities, such as autonomic dysfunction and mitochondrial disease. While using VAPS mode, patients should be closely monitored for cardiac rhythm abnormalities.


Optimizing the lysis step in CTAB DNA extractions of silica-dried and herbarium leaf tissues.
The use of cetyltrimethylammonium bromide (CTAB) is an effective and inexpensive method of extracting DNA from plants. The CTAB protocol is frequently modified to optimize DNA extractions, but experimental approaches rarely perturb a single variable at a time to systematically infer their effect on DNA quantity and quality. We investigated how chemical additives, incubation temperature, and lysis duration affected DNA quantity and quality. Altering those parameters influenced DNA concentrations and fragment lengths, but only extractant purity was significantly affected. CTAB and CTAB plus polyvinylpyrrolidone buffers produced the highest DNA quality and quantity. Extractions from silica gel-preserved tissues had significantly higher DNA yield, longer DNA fragments, and purer extractants compared to herbarium-preserved tissues. We recommend DNA extractions of silica gel-preserved tissues that include a shorter and cooler lysis step, which results in purer extractions compared to a longer and hotter lysis step, while preventing fragmentation and reducing time.


The effect of external medium composition on membrane water permeability of zebrafish (Danio rerio) embryos.
The effect of external medium composition on chorion and plasma membrane permeability of zebrafish (Danio rerio) embryos was investigated in this study. Initially, survival of embryos spawned into varying strengths (10-40%) of Hank's solution (HBSS) was assessed. Development and hatching rates for embryos spawned into 30% and 40% HBSS were significantly lower than those obtained with embryos spawned into system water. The effect of embryo survival in 30% HBSS with different calcium levels was then investigated. Embryo survival in calcium free 30% HBSS or 30% HBSS with 10x the standard calcium concentration was similar to survival in standard 30% HBSS. Membrane water permeability was determined by measuring the floatation time of embryos in test solutions made up with heavy water (D2O) instead of deionized water. Intact embryos at early developmental stages were less permeable than later stages irrespective of the external medium that they were spawned into. In system water, the floatation time of embryos at one-cell and two-cell stages were 1323+/-83 and 1189+/-55 s, respectively, compared to 432+/-6 and 353+/-10 s at the high and 50% epiboly stages. Change of external medium composition had no effect on membrane permeability of intact embryos at early developmental stages. However, at later stages embryos spawned into 30% HBSS were less permeable than embryos spawned into system water, irrespective of calcium concentration. The flotation time of embryos at the high stage increased from 432+/-6s in system water to 468+/-10s in 30% HBSS. The study on dechorionated embryos showed that change of external medium composition had no effect on plasma membrane permeability.


Tuberculous otitis media: a clinical record.
The clinical picture of tuberculous otitis media has changed since previously documented. In our series of 31 patients, it was found that severe conductive hearing loss, abundant pale granulations, and denuded malleus handle are constant findings and, in our opinion, are significant clinical features of the pathology. The disease can also manifest itself as an acute mastoiditis. As regards to investigations, bacteriology is considered as being unreliable. This is attributed to secondary organisms interfering with the growth of the tubercle bacillus, as well as the fastidious nature of the bacillus itself. We regard histology as the most reliable means of attaining a definitive diagnosis. Treatment was with a four drug antituberculous regime administered over 6 months. Streptomycin was excluded in all but one case due to its ototoxicity. We believe TB otitis media to be secondary to an established chronic otitis media in the majority of cases.


Minimal change nephrotic syndrome developing during postoperative interferon-beta therapy for malignant melanoma.
A 64-year-old man presented with proteinuria during postoperative interferon (IFN)-beta therapy against malignant melanoma. Renal pathologic findings were consistent with minimal change nephrotic syndrome (MCNS) showing extensive foot process effacement of visceral glomerular epithelial cells (podocyte). Nephrotic range proteinuria gradually regressed after stoppage of local injection of IFN-beta without glucocorticoid treatment. To our knowledge this is the first report that demonstrates histological abnormalities of the glomerulus associated with postoperative IFN-beta therapy for the malignant melanoma.


Molecular study of a large cohort of 109 haemophilia patients from Cuba using a gene panel with next generation sequencing-based technology.
In several countries, molecular diagnosis of haemophilia A (HA) and B (HB) is hampered by a lack of resources for DNA analysis. The advent of next-generation sequencing (NGS) has enabled gene analysis at a reasonable cost. Describe a collaboration between Cuban and Spanish researchers to identify candidate variants and investigate the molecular epidemiology of 106 Cuban haemophilia patients using NGS. The molecular analysis protocol included well-established LR-PCR procedures to detect F8 inversions, NGS with a 30-gene panel to sequence F8 and F9, and multiplex ligation-dependent probe amplification to identify large structural variants. One-hundred and thirty-one candidate variants were identified along F8, F9, and VWF; 72 were unique and 28 (39%) had not been previously recorded. Putative variants were identified in 105/106 patients. Molecular characterization enabled confirmation and reclassification of: 90 HA (85%), 15 HB (14%), and one type 2N VWD (1%). Null variants leading to non-production of FVIII or FIX were common in severe HA (64%), moderate HA (74%), and severe HB (60%), whereas missense variants were frequent in mild HA (57%) and moderate or mild HB (83%). Additional variants in VWF were identified in 16 patients. This is the first description of the molecular epidemiology of HA and HB in Cuba. Variants identified in index cases will be of value for local implementation of familial studies and prenatal diagnosis using the molecular approaches available in Cuba. The results of this protocolled genetic study improved the accuracy of the clinical diagnosis and will facilitate management of these patients.


Trends and factors associated with initial and recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections among HIV-infected persons: an 18-year study.
Factors associated with initial methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs) and their recurrence have not been fully elucidated among HIV-infected persons. We retrospectively evaluated a large cohort of HIV-infected patients from 1993 to 2010 for culture-proven MRSA SSTIs. Separate logistic regression models evaluated factors associated with initial and recurrent infections. Of the 794 patients, 63 (8%) developed an initial infection (19.8 infections/1000 person years [PY]); risk factors included CD4 count <500 cells/mm(3) and HIV RNA level ≥400 copies/mL (P < .01), US Centers for Disease Control and Prevention (CDC) stage C versus A/B (P < .01), and injection drug use (IDU, P < .01). In all, 27% developed recurrence (206 infections/1000 PY); risk factors included hospital admission (P = .02). Minocycline for treatment of the initial infection was associated with an 80% decreased odds for recurrence (P = .03). HIV control and avoidance of IDU may be useful in reducing rates of MRSA SSTIs among HIV-infected persons.


"Our best hope is a cure." Hope in the context of advance care planning.
Advance care planning (ACP) has the potential to enhance end-of-life care, yet often fails to live up to that potential. This qualitative interpretive study was designed to explore the process and outcomes of ACP using the patient-centered Advance Care Planning Interview (PC-ACP) developed by the Respecting Choices® program in Wisconsin. Patients diagnosed with advanced lung cancer and close family members were recruited. Nine family dyads participated in the PC-ACP interview, which was audio-recorded. Follow-up interviews took place 3 and 6 months after the PC-ACP interview and were also recorded. Thematic analysis was conducted on transcribed interviews using constant comparison. Analysis showed that hope was a significant theme in the ACP process and this article reports on that theme. Hope for a cure was one of many hopes that supported quality of life for the participant dyads. Three themes were identified: hope is multifaceted, hope for a cure is well considered, and hope is resilient and persistent. The seeming paradox of hoping for a cure of an incurable cancer did not interfere with the process of ACP. The dyads engaged in explicit discussions of end-of-life scenarios and preferences for care. ACP did not interfere with hope and hope for a cure did not interfere with ACP. Concerns about false hope are called into question. The principle of honoring hope is not necessarily in conflict with the principle of truthful communication. This is clinically significant, as the findings suggest we need not disrupt hope that we think of as "unrealistic" as long as it supports the family to live well. Further, ACP can be successful even in the context of hoping for a cure.


Superior Hypogastric Nerve Blockade for Uterine Artery Embolization: A Systematic Review.
Superior hypogastric nerve block (SHNB) has potential to reduce pain following uterine artery embolization (UAE). However, existing studies are limited by design, sample size, or conflicting results. A systematic review of the literature was performed. Outcomes included technical success, time to complete SHNB, time under fluoroscopy, procedure time, time to recovery, needle repositioning, same-day discharge, readmission, pain, analgesic consumption, and adverse events. Of 15 included studies, the same-day discharge rate was 98.8%, and readmission rate was 6.9%. The mean pain score was 3.4 in patients who received SHNB compared to 4.3 among controls. Of patients who received SHNB, 46.7% did not require further pain medication. Major adverse events occurred in 0.4% of patients. Early clinical studies suggest that SHNB appears to reduce pain and analgesic consumption in patients undergoing UAE. Additional randomized trials are needed to confirm these findings.


Common genetic variation modulating cardiac ECG parameters and susceptibility to sudden cardiac death.
Sudden cardiac death (SCD) is a prevalent cause of death in Western societies. Genome-wide association studies (GWAS) conducted over the last few years have uncovered common genetic variants modulating risk of SCD. Furthermore, GWAS studies uncovered several loci impacting on heart rate and ECG indices of conduction and repolarization, as measures of cardiac electrophysiological function and likely intermediate phenotypes of SCD risk. We here review these recent developments and their implications for the identification of novel molecular pathways underlying normal electrophysiological function and susceptibility to SCD.


Biodegradation of phthalate esters by two bacteria strains.
In this study two aerobic phthalic acid ester (PAE) degrading bacteria strains, DK4 and O18, were isolated from river sediment and petrochemical sludge, respectively. The two strains were found to rapidly degrade PAE with shorter alkyl-chains such diethyl phthalate (DEP), dipropyl phthalate (DPrP), di-n-butyl phthalate (DBP), benzylbutyl phthalate (BBP) and diphenyl phthalate (DPP) are very easily biodegraded, while PAE with longer alkyl-chains such as dicyclohexyl phthalate (DCP) and dihexyl phthalate (DHP) and di-(2-ethylhexyl) phthalate (DEHP) are poorly degraded. The degradation rates of the eight PAEs were higher for strain DK4 than for strain O18. In the simultaneous presence of strains DK4 and O18, the degradation rates of the eight PAEs examined were enhanced. When the eight PAEs were present simultaneously, degradation rates were also enhanced. We also found that PAE degradation was delayed by the addition of nonylphenol or selected polycyclic aromatic hydrocarbons (PAHs) at a concentration of 1 microg/g in the sediment. The bacteria strains isolated, DK4 and O18, were identified as Sphigomonas sp. and Corynebacterium sp., respectively.


Deterrent Effects of Essential Oils on Spotted-Wing Drosophila (Drosophila suzukii): Implications for Organic Management in Berry Crops.
Due to concerns about frequent applications of spinosad and other broad spectrum insecticides for managing spotted-wing drosophila (Drosophila suzukii Matsumura, SWD), we investigated the use of essential oils as an alternative to current insecticides. Essential oils from a number of plant species have been studied for their attraction and deterrence of SWD. However, these botanical products have not been thoroughly tested in the field. We conducted laboratory and field studies to determine the efficacy of botanical products, including lavender (Lavandula angustifolia Mill.) oil, catnip (Nepeta cataria L.) oil, KeyPlex Ecotrol® PLUS, and KeyPlex Sporan® EC2 on preventing SWD infestation in raspberry (Rubus idaeus L.) and blueberry (Vacciniumcorymbosum L.) crops. In a two-choice laboratory bioassay, lavender oil, Ecotrol, and Sporan treatments deterred SWD from a yeast-cornmeal-sugar based fly diet. In the field trials, raspberry fruit treated with Ecotrol had lower SWD infestation (6%), compared to the control (17%), and was comparable to spinosad (6%). No differences were seen in blueberry infestation. The combination of essential oils in Ecotrol may work to decrease SWD fruit infestation under certain conditions in the field, however more research is needed on the longevity of these products.