The microsomal metabolism of pentachlorophenol and its covalent binding to protein and DNA.
The microsomal metabolism of pentachlorophenol (PCP) was investigated, with special attention to the conversion dependent covalent binding to protein and DNA. The two metabolites detected were tetrachloro-1,2- and tetrachloro-1,4-hydroquinone. Microsomes from isosafrole (ISF)-induced rats were by far the most effective in catalyzing the reaction: the rate of conversion was increased 7-fold over control microsomes. All other inducers tested (hexachlorobenzene (HCB), phenobarbital (PB) and 3-methylcholanthrene (3MC) gave 2--3-fold increases over control. There are indications that the 1,2- and 1,4-isomers are produced in different ratio's by various cytochrome P-450 isoenzymes: Microsomes from PB- and HCB-treated rats produced the tetrachloro-1,4- and tetrachloro-1,2-hydroquinone in a ratio of about 2, while microsomes from rats induced with 3 MC and ISF showed a ratio of about 1.3. When PCP was incubated with microsomes from rats treated with HCB, a mixed type inducer of P-450, the ratio between formation of the 1,4- and 1,2-isomers decreased with increasing concentration of PCP, suggesting the involvement of at least two P-450 isoenzymes with different Km-values. The overall apparent Km-value for HCB-microsomes was 13 microM both for the formation of the soluble metabolites and the covalent binding to microsomal protein, suggesting both stem from the same reaction. The covalent binding could be inhibited by ascorbic acid and this inhibition was accompanied by an increase in formation of tetrachlorohydroquinones (TCHQ). Although a large variation was observed in rates of conversion between microsomes treated with different (or no) inducers, the rate of covalent binding to microsomal protein was remarkably constant. A conversion-dependent covalent binding to DNA was observed in incubations with added DNA which was 0.2 times the amount of binding to protein (37 pmol/mg DNA).


Comparison between two clones of Daphnia magna: effects of multigenerational cadmium exposure on toxicity, individual fitness, and biokinetics.
We investigated the effects of genotype (two different clones) and multigenerational Cd-exposure history on Cd toxicity, individual fitness, and biokinetics in populations of a freshwater cladoceran Daphnia magna. The adults of the tolerant (T) clone had longer mean-survival-time than the sensitive (S) clone in both control groups (without Cd-exposure) and continuous Cd-exposure groups, but the two clones showed comparable resistances to acute Cd stress in the recovery groups. The body concentration of metallothionein (MT) played a critical role in handling Cd stress, which mainly accounted for the significant difference between the two clones in terms of survival distribution. High comparability of these two clones in individual fitness parameters and biokinetics suggested that these parameters are unlikely driven by genetic variation. For each specific clone, continuous Cd-exposure inhibited the animal growth, elevated the MT induction, and increased the Cd uptake rate (ingestion rate, assimilation efficiency from dietary phase, and uptake rate from dissolved phase), all of which enhanced the weight-specific Cd accumulation in daphnids' bodies. The strong dependence of biokinetic parameters on environmental factors (e.g., food concentrations, pH, dissolved or dietary metal concentration, and metal exposure histories) rather than on genotypes implied the great potential of using biokinetics in inter-lab comparisons and environmental risk assessments.


Ultrasound-Guided Suprapectoral Tenodesis of the Long Head of the Biceps Brachii.
When the long head of the biceps tendon is diseased, tenodesis is an appropriate treatment strategy. The specific technique used is dependent on visualization, fixation method and hardware, and tenodesis location. For suprapectoral tenodesis techniques, those that fix the tendon within or below the bicipital groove can be challenging owing to the transverse humeral ligament covering the groove. To accurately identify the biceps tendon in this area, the ligament often requires resection. Ultrasound provides surgeons with a safe and noninvasive tool to visualize the biceps tendon as it exits the bicipital groove, negating the need for unroofing and other pitfalls associated with traditional techniques. This technical note describes an ultrasound-guided suprapectoral biceps tenodesis procedure.


Fine structural localization of glucose-6-phosphatase activity in the pancreatic islets of two amphibian species (Salamandra salamandra L. and Rana esculenta L.).
The ultrastructural distribution of glucose-6-phosphatase activity has been investigated in the salamander and frog pancreas. In the pancreas of salamander the enzyme was located in the A-cells, while in frog it occurred in all main types of islet cells B-, A-, and D-cells). As a rule, the reaction intensity was higher in the frog islet cells. No reaction was recorded in the exocrine pancreatic tissue of both species. The glucose-6-phosphatase activity was constantly detected in the lumen of rough endoplasmic reticulum and between the nuclear envelopes. Other enzyme localizations, observed especially in the A-cells of the salamander pancreas, were considered possible diffusion artifacts ro remnants of other phosphatase activity. The enzyme distribution in different types of islet cells, as well as its functional significance are discussed in relation to the findings of other authors.


Vitamin D deficiency in critically ill COVID-19 ARDS patients.
Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.


Tissue response to bioerodible, subcutaneous drug implants: a possible determinant of drug absorption kinetics.
The fibrous tissue compartments that develop in response to the subcutaneous implantation of bioerodible heat-fused rods of norethindrone and cholesterol (85 and 15%, respectively) were studied by light and electron microscopy at various intervals after implantation to determine whether the biological inflammatory response may play a role in drug absorption. Thirty-five regularly menstruating, sterilized (tubal ligation), healthy females each received four Annuelle rods. The microanatomy of seven of the largest implants (135 mg norethindrone) was studied. A dense fibrous biological compartment was found to surround each rod. By light microscopy no abnormal tissue response was revealed. Scanning and transmission electron microscopy showed that the surfaces of the rods were covered by a cellular matrix of mononuclear cells. The fibrous compartment was composed of a loose cellular bed immediately surrounding the norethindrone rod, a dense fibrous connective tissue envelope containing blood and lymphatic vessels, and an outer fatty connective tissue layer. Transmission electron microscopy confirmed that the cellular tissue immediately surrounding the rods was composed mainly of lipid laden macrophages. Norethindrone levels in tissue capsules at 3 and 10.5 months were 0.05 and 8.4% by weight, respectively. These observations suggest that the local inflammatory response plays a role in the active processing of this delivery system. This picture is qualitatively different from the general view of the fibrous capsule as a simple rate limiting membrane. The effects observed in this study suggest that a more complex, functional biological system develops in response to the subcutaneous introduction of a drug delivery device.


miR‑205‑3p promotes lung cancer progression by targeting APBB2.
Non‑small cell lung cancer (NSCLC), a leading cause of cancer‑associated mortality, has resulted in low survival rates and a high mortality worldwide. Accumulating evidence has suggested that microRNAs (miRs) play critical roles in the regulation of cancer progression and the present study aimed to explore the underlying mechanism of miR‑205 in NSCLC. Reverse transcription‑quantitative PCR was performed, which determined that miR‑205 expression was upregulated in NSCLC, and the present study detected the upregulation of miR‑205‑3p in a number of NSCLC cell lines and NSCLC tissues. In addition, the mediation of amyloid β precursor protein‑binding family B member 2 (APBB2) by miR‑205‑3p was demonstrated. Moreover, miR‑205‑3p was predicted to directly target the 3'untranslated region of APBB2, which was confirmed using a dual‑luciferase reporter assay. It was found that lentivirus mediated‑APBB2 knockdown could promote cellular viability and suppress apoptosis in NSCLC cells, as determined via MTT, TUNEL and flow cytometry assays. Thus, the current findings highlighted the potential promotive impact of miR‑205‑3p on NSCLC processes and may provide theoretical evidence for miR‑205‑3p as a potential clinical gene therapy target.


A study of post-traumatic stress disorder in schizophrenic patients 35 years after experiencing the Tangshan earthquake.
This study aimed to investigate the relationship between dissociative experiences, post-traumatic stress disorder (PTSD), and psychiatric symptoms exhibited by schizophrenic patients 35 years after the Tangshan earthquake. Seventy-one schizophrenic patients who had experienced the Tangshan earthquake were selected and evaluated by the Post-traumatic Dissociative Experience Questionnaire (PDEQ), thPTSD Checklist-Civilian Version (PCL-C), and the Positive and Negative Symptom Scale (PANSS). The score of Group B (re-experiencing symptoms) in PCL-C was significantly positively correlated with age and significantly negatively correlated with the course of schizophrenia. Both gender and marriage were significantly positively correlated with the score of PCL-C Group D (irritability symptoms caused by hyperarousal). The PDEQ score was negatively correlated with thecourse of schizophrenia and positively correlated with the presence of sleep difficulties. Significant differences were found between the PCL-C scores of the positive and negative symptoms of the three core symptom groups; the positive rate of Group B was significantly higher than that of Group D, and the positive rate of Group C was significantly higher than that of Group D. The PCL-C total score was positively correlated with the negative symptom factor score of PANSS; Group C's symptoms were significantly negativelycorrelated with the positive factor score of PNASS; andGroup D's' symptoms were significantly negatively correlated with the PANSS total score and the positive factor score. When consiering patients with schizophrenia post the Tangshan earthquake, age, gender, and marital status were all positively correlated with PTSD. The course of schizophrenia was negatively associated with PTSD and dissociative experiences. PTSD was positively correlated with the negative symptoms of schizophrenia and negatively correlated with the positive symptoms of schizophrenia. Thus, the conditions and symptoms of PTSD may interact with those of schizophrenia.


Clostridium Difficile infections in patients with AML or MDS undergoing allogeneic hematopoietic stem cell transplantation identify high risk for adverse outcome.
Clostridium difficile (CD) infection is the main cause of nosocomial enterocolitis in western countries and in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). Recipients of alloHCT are at high risk for CD infection but large studies in this population are rare and conflicting results have been reported. We analyzed 727 patients with AML or MDS undergoing alloHCT in our center from 2004 to 2015. Ninety-six patients (13%) had CD infection and 103 patients (14%) were identified as asymptomatic carriers by screening at admission and once a week during aplasia. Patients with CD infection had a shorter median overall survival of 8 months (95% CI, 6-36 months) compared with 25 months (95% CI, 17-35 months) for patients without CD infection, (HR 1.4, p = 0.04). CD positive patients were less likely to develop acute graft-versus-host disease (aGvHD; HR 0.6, p = 0.004) compared with CD-negative patients, but did not show differences in gastrointestinal aGvHD (HR 0.9, p = 0.5). Symptomatic patients developed gastrointestinal aGvHD (HR 2.5, p = 0.02) more often compared with asymptomatic CD positive patients. This analysis demonstrates a high prevalence for CD infection in patients undergoing alloHCT. A significant lower overall survival for patients with CD infection could be demonstrated.


The delta 12-desaturase from the house cricket, Acheta domesticus (Orthoptera: Gryllidae): characterization and form of the substrate.
A novel delta 12-desaturase from animals, which converts oleic acid (18:1n-9) to linoleic acid (18:2n-6), was characterized in the house cricket, Acheta domesticus. The delta 12-desaturase product, linoleic acid, was determined by silver nitrate thin-layer chromatography, radio-gas-liquid chromatography and radio-high-performance liquid chromatography with the latter being used for routine analyses. Enzyme activity was located in the microsomal fraction of whole insect homogenates. NADPH or NADH was required for activity, with NADPH being the more efficient electron donor. In short incubation times with oleoyl-CoA as substrate, the highest amount of product, linoleic acid, was found as linoleoyl-CoA. With longer incubation periods, most of the linoleic acid was recovered in the polar lipid fraction containing phospholipid. Preincubation of the microsomal preparation in the absence of NADPH, which allowed 90% of the oleoyl moiety to be transacylated into complex lipid, resulted in no detectable desaturation upon addition of NADPH. These data indicate that the oleic acid moiety used as substrate was in the form of a CoA derivative and not in the form of a phospholipid, as it is for the plant delta 12-desaturase. This is the first characterization of a delta 12-desaturase from an animal system and the first report of a delta 12-desaturase that uses oleoyl-CoA as substrate.


Inflated prediction accuracy of neuropsychiatric biomarkers caused by data leakage in feature selection.
In recent years, machine learning techniques have been frequently applied to uncovering neuropsychiatric biomarkers with the aim of accurately diagnosing neuropsychiatric diseases and predicting treatment prognosis. However, many studies did not perform cross validation (CV) when using machine learning techniques, or others performed CV in an incorrect manner, leading to significantly biased results due to overfitting problem. The aim of this study is to investigate the impact of CV on the prediction performance of neuropsychiatric biomarkers, in particular, for feature selection performed with high-dimensional features. To this end, we evaluated prediction performances using both simulation data and actual electroencephalography (EEG) data. The overall prediction accuracies of the feature selection method performed outside of CV were considerably higher than those of the feature selection method performed within CV for both the simulation and actual EEG data. The differences between the prediction accuracies of the two feature selection approaches can be thought of as the amount of overfitting due to selection bias. Our results indicate the importance of correctly using CV to avoid biased results of prediction performance of neuropsychiatric biomarkers.


A Stepwise Approach to the Surgical Management of Hemorrhagic Choroidal Detachments.
This work describes a stepwise surgical approach to draining choroidal detachments and 2 cases for which this approach was used. The first step involves insertion of an anterior chamber maintainer and a nonvalved 23- or 25-gauge trocar cannula at the highest peak of hemorrhagic choroidal detachment (as determined using B-scan ultrasonography), 6 to 8 mm from and angled 20° to 30° toward the limbus. The second step involves removal of the trocar to expose the sclerotomy. Alternatively, the second step can be insertion of a second trocar. The third step involves the creation of a small focal peritomy around the preexisting sclerotomy and enlargement of the preexisting sclerotomy into a radial sclerotomy. Progression between steps only occurs if prior steps did not provide adequate drainage. Two cases of appositional hemorrhagic choroidal detachments in hypotonic eyes were successfully resolved by this stepwise approach. In case 1, a choroidal detachment developed after a corneal ulcer perforation. The hemorrhagic choroidal detachment in case 1 was resolved with steps 1 and 2, and an unnecessary scleral cutdown was avoided. In case 2, a choroidal detachment developed after a trabeculectomy. The detachment in case 2 required progression to step 3, extension of the trocar insertion site into a radial sclerotomy. This stepwise approach should be considered to reduce excessive manipulation of the globe and conjunctiva in hemorrhagic and serous choroidal detachments that warrant surgical intervention.


Lipid peroxidation and protective enzymes during myocardial infarction.
Fasting blood taken from 34 patients with myocardial infarction, 19 with unstable angina and 40 healthy controls, was analysed for malondialdehyde and erythrocyte detoxification enzymes, superoxide dismutase and glutathione peroxidase. Malondialdehyde concentration was raised in the patients with myocardial infarction during the initial 48 h after an attack, and correlated with the severity of the attack. 12 days after the infarct, malondialdehyde concentrations were lower but still raised. Superoxide dismutase activity was below normal during the initial 48 h post infarct and raised twelve days after. Glutathione peroxidase was reduced after 12 days. Similar, but less marked changes were seen in the patients unstable angina.


The outcome of COVID-19 in children with chronic lung disease: Systematic review and meta-analyses.
Few studies have examined the impact of Coronavirus disease 2019 (COVID-19) infection on children with chronic lung disease (CLD). To perform a systematic review and meta-analysis to determine the prevalence, risk factors for contracting COVID-19, and complications of COVID-19, in children with CLD. This systematic review was based on articles published between January 1, 2020 and July 25, 2022. Children under 18 years old, with any CLD and infected with COVID-19 were included. Ten articles involving children with asthma and four involving children with cystic fibrosis (CF) were included in the analyses. The prevalence of COVID-19 in children with asthma varied between 0.14% and 19.1%. The use of inhaled corticosteroids (ICS) was associated with reduced risk for COVID-19 (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.40-0.90). Uncontrolled asthma, younger age, AND moderate-severe asthma were not significant risk factors for contracting COVID-19. Children with asthma had an increased risk for hospitalization (RR: 1.62, 95% CI: 1.07-2.45) but were not more likely to require assisted ventilation (RR: 0.51, 95% CI: 0.14-1.90). The risk of COVID-19 infection among children with CF was <1%. Posttransplant and cystic fibrosis-related diabetes mellitus (CFRDM) patients were at an increased risk for hospitalization and intensive care treatment. Hospitalizations were higher in children with asthma with COVID-19 infection. However, using ICS reduced the risk of COVID-19 infection. As for CF, postlung transplantation and CFRDM were risk factors for severe disease.


Photobiotin-labeled DNA and RNA hybridization probes.
Nucleic acid hybridization, the formation of a duplex between two complementary nucleotide sequences, is being increasingly utilized in the research laboratory and for the routine diagnosis of disease. Biotin-labeled nucleic acid hybridization probes have advantages over radioactively labeled probes in terms of stability, safety, and time of detection. The hybridization of a biotin-labeled probe to a target nucleic acid is carried out on a nitrocellulose or nylon filter; the bound probe is usually detected by the binding of an avidin-enzyme conjugate or a streptavidin-enzyme complex (both avidin and streptavidin have a high affinity for biotin), followed by a colorimetric reaction in which the bound enzyme converts a colorless substrate into a colored product.


Simple and Efficient Pressure Ulcer Reconstruction via Primary Closure Combined with Closed-Incision Negative Pressure Wound Therapy (CiNPWT)-Experience of a Single Surgeon.
In this study, we aimed to analyze the clinical efficacy of closed-incision negative pressure wound therapy (CiNPWT) when combined with primary closure (PC) in a patient with pressure ulcers, based on one single surgeon's experience at our medical center. We retrospectively reviewed the data of patients with stage III or IV pressure ulcers who underwent reconstruction surgery. Patient characteristics, including age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, application of CiNPWT to reconstructed wounds, duration of hospital stay, and wound complications were analyzed. Operation time (38.16 ± 14.02 vs. 84.73 ± 48.55 min) and duration of hospitalization (36.78 ± 26.92 vs. 56.70 ± 58.43 days) were shorter in the PC + CiNPWT group than in the traditional group. The frequency of debridement (2.13 ± 0.98 vs. 2.76 ± 2.20 times) was also lower in the PC + CiNPWT group than in the traditional group. The average reconstructed wound size did not significantly differ between the groups (63.47 ± 42.70 vs. 62.85 ± 49.94 cm2), and there were no significant differences in wound healing (81.25% vs. 75.38%), minor complications (18.75% vs. 21.54%), major complications (0% vs. 3.85%), or mortality (6.25% vs. 10.00%) between the groups. Our findings indicate that PC combined with CiNPWT represents an alternative reconstruction option for patients with pressure ulcers, especially in those for whom prolonged anesthesia is unsuitable.


Degradation of Methyl 2-Aminobenzoate (Methyl Anthranilate) by H₂O₂/UV: Effect of Inorganic Anions and Derived Radicals.
This study shows that methyl 2-aminobenzoate (also known as methyl anthranilate, hereafter MA) undergoes direct photolysis under UVC and UVB irradiation and that its photodegradation is further accelerated in the presence of H₂O₂. Hydrogen peroxide acts as a source of hydroxyl radicals (·OH) under photochemical conditions and yields MA hydroxyderivatives. The trend of MA photodegradation rate vs. H₂O₂ concentration reaches a plateau because of the combined effects of H₂O₂ absorption saturation and ·OH scavenging by H₂O₂. The addition of chloride ions causes scavenging of ·OH, yielding Cl₂·- as the most likely reactive species, and it increases the MA photodegradation rate at high H₂O₂ concentration values. The reaction between Cl₂·- and MA, which has second-order rate constant k C l 2 • - + M A = (4.0 ± 0.3) × 10⁸ M-1·s-1 (determined by laser flash photolysis), appears to be more selective than the ·OH process in the presence of H₂O₂, because Cl₂·- undergoes more limited scavenging by H₂O₂ compared to ·OH. While the addition of carbonate causes ·OH scavenging to produce CO₃·- ( k C O 3 • - + M A = (3.1 ± 0.2) × 10⁸ M-1·s-1), carbonate considerably inhibits the photodegradation of MA. A possible explanation is that the elevated pH values of the carbonate solutions make H₂O₂ to partially occur as HO₂-, which reacts very quickly with either ·OH or CO₃·- to produce O₂·-. The superoxide anion could reduce partially oxidised MA back to the initial substrate, with consequent inhibition of MA photodegradation. Fast MA photodegradation is also observed in the presence of persulphate/UV, which yields SO₄·- that reacts effectively with MA ( k S O 4 • - + M A = (5.6 ± 0.4) × 10⁸ M-1·s-1). Irradiated H₂O₂ is effective in photodegrading MA, but the resulting MA hydroxyderivatives are predicted to be about as toxic as the parent compound for aquatic organisms (most notably, fish and crustaceans).


Characterization of Fischer rat embryo (CREF) cells transformed by bovine papillomavirus type 1.
Transformation of an established Fischer rat embryo (CREF) cell line by bovine papillomavirus type 1 (BPV-1), in contrast to transformation by type 5 adenovirus or the T24 (Ha-ras) oncogene, resulted in transformants which did not exhibit a major increase in saturation density or a decrease in 125I-epidermal growth factor binding. BPV-1-transformed CREF clones did, however, grow in agar suspension culture and were tumorigenic in both nude mice and Fischer rats. The majority of transformed clones contained multiple extrachromosomal copies of BPV DNA. One transformed CREF clone contained integrated BPV-1 DNA which underwent sequence rearrangements following tumor formation in a Fischer rat and reestablishment in cell culture. BPV copy number varied in subclones of transformants isolated from the same monolayer focus, in agar-derived subclones of the same transformed focus, in tumors and in tumor-derived BPV-transformed CREF subclones. The degree of expression of specific transformation-related phenotypes, i.e., saturation density, growth in agar, and tumorigenicity, was not correlated with BPV copy number in transformed clones. Analysis of the biological properties of tumor-derived BPV-1-transformed CREF subclones indicated that certain transformants developed a stable increase in expression of transformation-related properties, a process termed "progression." TPA did not enhance the frequency of BPV-1 transformation or BPV DNA copy number in transformed CREF cells. The present study demonstrates that the CREF- transformation system can be utilized to study the molecular basis of BPV-1 transformation and should prove useful in studying the role of specific BPV-1 transforming proteins in regulating expression of the transformed phenotype and the mechanism by which transformed cells undergo progression of the transformed state.


Remineralization potential of phosphorylated chitosan and silver diamine fluoride in comparison to sodium fluoride varnish: invitro study.
The purpose of this study was to evaluate and compare the remineralization potential of phosphorylated chitosan nanoparticles (Pchi) and silver diamine fluoride (SDF) compared to sodium fluoride varnish (NaF) on microhardness of artificial carious lesions in a biomimetic minimally invasive approach that is being regarded as the future of preventive dentistry. The sample size included 40 intact extracted maxillary anterior human teeth. Baseline microhardness was recorded using Vickers hardness test and energy-dispersive X-ray spectroscopy (EDX). Artificial caries-like lesions were created on the exposed enamel by suspending all teeth in demineralizing solution for 10 days in a temperature of 37 °C and then the hardness and EDX were remeasured. Samples were then divided into four main groups: Group A (positive control group) n = 10, treated with NaF, Group B n = 10, treated with SDF, Group C n = 10, treated with Pchi and Group D (negative control group) n = 10 that received no treatment. After treatment, samples were incubated in artificial saliva solution at 37 °C in for 10 days and then reassessed. Data were then recorded, tabulated, and statistically analyzed using Kruskal-Wallis test and Wilcoxon signed test. Scanning electron microscope (SEM) was used to analyze the morphological changes of enamel surface after treatment. Groups B and C showed the highest calcium (Ca) and phosphate (P) content as well as hardness values, while group B had the highest percentage of fluoride. SEM revealed a smooth layer of mineral formed on the surface of enamel for both groups. Pchi and SDF showed the highest increase in enamel microhardness and remineralization potential. The minimally invasive approach for remineralization could be enhanced using SDF and Pchi.


Adenocarcinoma below stapled ileoanal anastomosis after restorative proctocolectomy for ulcerative colitis.
A case of adenocarcinoma arising in a 39-year-old patient after restorative proctocolectomy is reported. The patient underwent an ileal pouch-anal anastomosis with double-stapled technique for severe ulcerative colitis 18 years earlier, without evidence of associated neoplasm or dysplasia in operative specimen. After endoscopic diagnosis of adenocarcinoma, the patient was submitted to excision of the pouch and permanent ileostomy, followed by combined radiotherapy and chemotherapy. Pathology showed an AJCC stage III moderately differentiated mucinous adenocarcinoma. The patient died 24 months after the operation, due to cancer progression. There are 50 reported cases in the indexed medical literature of carcinoma arisen after ileal pouch-anal anastomosis for ulcerative colitis. Twenty-five out of these arose after mucosectomy and hand-sewn anastomosis, and 25 after stapling technique. Furthermore, in 48% of the patients, dysplasia or cancer was already present at the time of the colectomy. The increase of reported cases suggests a routine long-term endoscopic surveillance in patients with long-standing ileal pouches, especially in presence of dysplasia or cancer in the proctocolectomy specimen.


Process-based modeling to assess the nutrient removal efficiency of two endangered hydrophytes: Linking nutrient-cycle with a multiple-quotas approach.
Hydrophytes have been widely used to reduce nutrient levels in aquatic ecosystems, but only limited species with high nutrient removal efficiencies have been implemented. Thus, it is necessary to continually explore new candidate species with high nutrient removal efficiencies. To effectively explore the nutrient removal ability of hydrophytes, a new process-based model combining the multiple-quotas approach and nutrient-cycle model was developed. The multiple-quotas approach provides a theoretical framework to conceptually explain the uptake and response of autotrophs to multiple nutrients. The developed process-based model was validated using observational data from microcosm experiments with two emergent hydrophytes, Menyanthes trifoliata and Cicuta virosa. The results showed that both M. trifoliata and C. virosa effectively reduced nitrogen (N) and phosphorus (P) in both water and sediment layers, but M. trifoliata showed a higher removal efficiency for both nutrients than C. virosa, particularly for total ammonia + ammonium-nitrogen (NHx-N) and nitrate-nitrogen (NO3-N) in the sediment layer (M. trifoliata: 0.579-0.976 for NHx-N, 0.567-0.702 for NO3-N; C. virosa: 0.212-0.501 for NHx-N, 0.466-0.560 for NO3-N). In addition, M. trifoliata achieved the maximum removal efficiency for N and P at higher nutrient exposure levels than C. virosa (M. trifoliata: exposure level of 0.725-0.775; C. virosa: exposure level of 0.550-0.575). The developed model well simulated the species-specific growth patterns of hydrophytes depending on the nutrient exposure level as well as the N and P dynamics in the water and sediment layers. The approach adopted in this study provides a useful tool for discovering candidate species to improve hydrophyte diversity and effectively remove nutrients from aquatic ecosystems.


Different modes of intraocular pressure reduction after three different nonfiltering surgeries and trabeculectomy.
To study the mode of intraocular pressure (IOP) reduction based on correlation with the preoperative IOP after filtering and nonfiltering surgeries. Pre- and postsurgical IOPs at 6 months were compared in one eye of each of 789 subjects with primary open-angle glaucoma, pseudoexfoliation glaucoma, or ocular hypertension who underwent trabeculectomy with adjunctive mitomycin C alone (Lectomy-MMC) (n = 145), phaco-viscocanalostomy (Phaco-VCS) (n = 320), phaco-trabeculotomy ab externo (Phaco-lotomy) (n = 116), or phacoemulsification aspiration and intraocular lens implantation alone (PEA+IOL) (n = 208). The correlation between the preoperative and 6-month postoperative IOP was not significant in eyes that underwent Lectomy MMC (r = -0.026, P = 0.7552, IOP reduction 51.9%), but was significant in eyes treated by Phaco-VCS (r = 0.409; IOP reduction, 24.8%) or PEA+IOL alone (r = 0.294; IOP reduction, 9.9%), and was marginal in eyes treated by Phaco-lotomy (P = 0.062; r = 0.174; IOP reduction, 24.1%). Among the four cohorts studied, the variation in the 6-month postoperative IOP was the largest after Lectomy-MMC. After glaucoma surgery, there are two modes of IOP reduction. The postoperative IOP after Lectomy MMC did not correlate with the preoperative IOP, whereas the postoperative IOP levels after Phaco-VCS, Phaco-Lotomy, and PEA+IOL correlated with preoperative IOP levels. We may be able to predict postsurgical IOP after nonfiltering surgery.


Wilson's disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance.
To determine the phenotypes and predominant disease-causing mutations in Lebanese patients with Wilson's disease, as compared to regional non-European data. The clinical profile of 36 patients diagnosed in Lebanon was studied and their mutations were determined by molecular testing. All patients underwent full physical exam, including ophthalmologic slit-lamp examination ultrasound imaging of the liver, as well as measurement of serum ceruloplasmin and 24-h urinary-Cu levels. In addition, genetic screening using PCR followed by sequencing to determine disease-causing mutations and polymorphisms in the ATP7B gene was carried on extracted DNA from patients and immediate family members. Our phenotypic-genotypic findings were then compared to reported mutations in Wilson's disease patients from regional Arab and non-European countries. Patients belonged to extended consanguineous families. The majority were homozygous for the disease-causing mutation, with no predominant mutation identified. The most common mutation, detected in 4 out of 13 families, involved the ATP hinge region and was present in patients from Lebanon, Egypt, Iran and Turkey. Otherwise, mutations in Lebanese patients and those of the region were scattered over 17 exons of ATP7B. While the homozygous exon 12 mutation Trp939Cys was only detected in patients from Lebanon but none from the regional countries, the worldwide common mutation H1069Q was not present in the Lebanese and was rare in the region. Pure hepatic phenotype was predominant in patients from both Lebanon and the region (25%-65%). Furthermore, the majority of patients, including those who were asymptomatic, had evidence of some hepatic dysfunction. Pure neurologic phenotype was rare. Findings do not support presence of a founder effect. Clinical and genetic screening is recommended for family members with index patients and unexplained hepatic dysfunction.


A reassessment of vascular factors in relation to intravascular coagulation.
Sural nerve biopsy was performed in twenty-four diabetic patients, with clinical and electrophysiological evidence of diabetic neuropathy. Material from an autopsy case was also examined. Vessels plugged with fibrin were seen within nerve in nine cases. In three cases fibrin was observed tracking into the vessel wall and in four, older thrombus was observed in vessels. Areas of necrosis in nerve bundles were seen in two of the latter. In two patients there had been a preceding episode of intravascular coagulation. Fibrin deposition within small vessels could well play a part in damaging the diabetic nerve and a disturbance of the balance between deposition and removal by fibrinolysis could explain phasic variation in the symptoms of neuropathy.


Horizontal Ridge Augmentation Under a Removable Partial Denture and Implant Placement.
Implant planning has moved in recent years to virtual planning with a CBCT scan and fabrication of a surgical guide based on that virtual planning. Unfortunately, positioning based on prosthetics is typically missing from the CBCT scan. Use of a diagnostic guide fabricated in office permits information from ideal prosthetic positioning to improve virtual planning and subsequent fabricated of a corrected surgical guide. This becomes more important when insufficiencies in the ridges horizontal aspects (width) will require ridge augmentation to allow later implant placement. This article discusses a case with insufficient ridge width and determination of where augmentation is required to house implants in ideal prosthetic positions, the subsequent grafting, implant placement and restoration.


Bisphenol A aggravate selenium deficiency-induced apoptosis via miR-215-3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial.
Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR-215-3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR-215-3p was detected by qRT-PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH-DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis-related genes were detected by qRT-PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR-215-3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR-215-3p and Dio1 in vitro, and found that overexpression of miR-215-3p and knockout of Dio1 can induce apoptosis. Interestingly, miR-215-3p-Inhibitor and N-acetyl- l-cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR-215-3p/Dio1. The miR-215-3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.


A comparative study on image-based snake identification using machine learning.
Automated snake image identification is important from different points of view, most importantly, snake bite management. Auto-identification of snake images might help the avoidance of venomous snakes and also providing better treatment for patients. In this study, for the first time, it's been attempted to compare the accuracy of a series of state-of-the-art machine learning methods, ranging from the holistic to neural network algorithms. The study is performed on six snake species in Lar National Park, Tehran Province, Iran. In this research, the holistic methods [k-nearest neighbors (kNN), support vector machine (SVM) and logistic regression (LR)] are used in combination with a dimension reduction approach [principle component analysis (PCA) and linear discriminant analysis (LDA)] as the feature extractor. In holistic methods (kNN, SVM, LR), the classifier in combination with PCA does not yield an accuracy of more than 50%, But the use of LDA to extract the important features significantly improves the performance of the classifier. A combination of LDA and SVM (kernel = 'rbf') is achieved to a test accuracy of 84%. Compared to holistic methods, convolutional neural networks show similar to better performance, and accuracy reaches 93.16% using MobileNetV2. Visualizing intermediate activation layers in VGG model reveals that just in deep activation layers, the color pattern and the shape of the snake contribute to the discrimination of snake species. This study presents MobileNetV2 as a powerful deep convolutional neural network algorithm for snake image classification that could be used even on mobile devices. This finding pave the road for generating mobile applications for snake image identification.


The improved survival rate and cost-effectiveness of a 7-day continuous subcutaneous insulin infusion set.
The purpose of this article is to compare the insulin cost-savings of the Medtronic Extended Infusion Set (or EIS, a.k.a. Extended Wear Infusion Set) designed and labeled for up to 7-day use with rapid-acting insulins to the current standard of care, 2- to 3-day infusion sets. There are three major improvements (reducing insulin waste, plastic waste, and adverse events) with the extended duration of infusion set wear. This analysis focuses on cost savings from reduced insulin wastage during set changes. Studies published on insulin infusion set survival and EIS clinical trial data (NCT04113694) were used to estimate device lifetime performance using a Markov chain Monte Carlo model, including the assessment of adverse effects and device failure. Total costs associated with infusion set change or failure were systematically found in published literature or estimated based on physical usage, and the direct impact on insulin costs was calculated. Based on the model and clinical data, EIS users can expect to change their infusion sets about 75 fewer times than standard set users each year. The costs related to unrecoverable insulin during an infusion set and reservoir change in the US were estimated to range from $19.79 to $22.48, resulting in approximately $1324 to $1677 in annual cost-savings for the typical user from minimizing insulin wastage. The study only assessed devices used within a monitored setting, that is, clinical trials. In addition, the variability associated with healthcare standards and costs and individual treatment variability including insulin dosages, contribute to the uncertainties with the calculations. Our analysis demonstrates that by extending the duration of infusion set wear, there may be substantial cost savings by reducing insulin wastage.


Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis.
Clinical and genetic findings are presented in 18 patients, from 7 pedigrees with different types of spinal muscular atrophy (SMA). The SMA diagnosis was based on EMG and muscle biopsy findings. All 7 pedigrees show an unusual genetic pattern, not consistent with simple autosomal recessive inheritance. Furthermore, in 6 of the 7 pedigrees different types of SMA were present within each pedigree. Our findings can be explained by an extension of a multiple alleles hypothesis originally described by Becker in 1964.


ILC3-like ILC2 subset increases in minimal persistent inflammation after acute type II inflammation of allergic rhinitis and inhibited by Biminkang: Plasticity of ILC2 in minimal persistent inflammation.
Minimal persistent inflammation (MPI), the local inflammation that occurs after an acute type II immune response in patients with allergic rhinitis (AR), is responsible for airway hyperreactivity and the recurrence of AR. Innate lymphoid cells (ILCs) play a crucial role in mucosal immune homeostasis, but the changes of ILC subsets in the MPI stage remain unclear. In this study, the levels of ILC-secreting cytokines in nasal lavages were analyzed from 19 AR patients and 8 healthy volunteers. AR and MPI model mice were established to study the ILC subsets. The results showed that IL-17A was significantly increased in nasal lavage of AR patients in the MPI stage by MSD technology. When compared with the AR model mice, the frequency of IL-13+ ILC2 in the nasal mucosa and lungs decreased, while IL-5+ ILC2 remain high in MPI model mice. A part of the IL-5+ ILC2 subset displayed ILC3-like characteristics with elevated RORγt, IL-17A and IL-23R expression. Especially, these ILC3-like ILC2 exhibited up-regulation of GATA3+ RORγt+ were increased in MPI model mice. After the treatment of Biminkang, the frequencies of IL-5+ ILC2, IL-17A+ ILC3, and GATA3+ RORγt+ ILC3-like ILC2 were significantly reduced, and IL-23R expression was also decreased on ILC3-like-ILC2 subset. These results suggested that the elevated IL-17A in the MPI stage has been related to or at least partly due to the increased of ILC3-like ILC2. Biminkang could effectively decrease IL-17A+ ILC3 and inhibit ILC3-like ILC2 subset in the MPI stage. Biminkang is effective in administrating MPI by regulating airway ILC homeostasis.


Dosimetric benefits of dynamic conformal arc therapy-combined with active breath-hold in lung stereotactic body radiotherapy.
To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.


Terminal component of complement (C9) in the cerebrospinal fluid of patients with multiple sclerosis and neurologic controls.
We measured the concentration of C9 in the CSF and plasma of 93 consecutive patients referred for CSF examination in an outpatient multispecialty clinic. We noted no differences in CSF C9 or C9 index between patients with multiple sclerosis and neurologic controls.


Risk factors and peripartum outcomes of failed epidural: a prospective cohort study.
Awareness to rate, risk factors, and the associated peripartum outcomes of failed epidural analgesia (FEA) may improve expectations and labor management. We aimed to identify risk factors for FEA and to examine peripartum outcomes associated with failure. A prospective cohort study conducted between March 2015 and August 2015, at a single university medical center. Laboring women at ≥34 weeks, receiving epidural analgesia, were eligible. Pain was evaluated using a 0-10 cm visual analogue scale (VAS). FEA was defined as VAS score ≥5, 30 min after the loading dose. The primary outcome was to identify risk factors for FEA. In addition, second-stage duration and operative vaginal delivery rate were also examined. Univariate logistic regression and stepwise multivariate logistic regression were performed to estimate the predictors for FEA. Of all 414 women included, 35 (8.5%) had FEA. Multivariate stepwise logistic regression revealed that fetal head station 1 cm above the ischial spines (p = 0.002, adjusted OR 5.4, 95% CI 1.9-16.0), oxytocin use (p = 0.026, adjusted OR 2.8, 95% CI 1.1-6.8), and seniority of the anesthesiologist (p = 0.046, adjusted OR 0.97, 95% CI 0.93-0.99) at epidural insertion were found as significant variables associated with FEA. Second-stage duration and operative vaginal delivery rate did not differ significantly between women with failed and successful epidural. Higher fetal head station and oxytocin use may be associated with higher failure rate. Labor outcomes related to epidural use, occurred at comparable rates, among women with failed and successful epidural.


Lessons from common markers of tumor-initiating cells in solid cancers.
Tumor-initiating cells (TICs) have emerged as the driving force of carcinomas, which appear as hierarchically structured. TICs as opposed to the tumor bulk display tumor forming potential, which is linked to a certain degree of self-renewal and differentiation, both major features of stem cells. Markers such as CD44, CD133, CD24, EpCAM, CD166, Lgr5, CD47, and ALDH have been described, which allow for the prospective enrichment of TICs. It is conspicuous that the same markers allow for an enrichment of TICs in various entities and, on the other hand, that different combinations of these markers were independently reported for the same tumor entity. Potential functions of these markers in the regulation of TIC phenotypes remained somewhat neglected although they might give insights in common molecular themes of TICs. The present review discusses major TIC markers with respect to their function and potential contributions to the tumorigenic phenotype of TICs.


Intra-operative nerve monitoring and recurrent laryngeal nerve injury during thyroid surgery: a network meta-analysis of prospective studies.
Recurrent laryngeal nerve (RLN) injury is a feared complication of thyroid surgery occurring in 1-5% of cases. The present approaches to RLN preservation include RLN visualization with no nerve monitoring (No-NM), intermittent intra-operative nerve monitoring (I-IONM) and continuous intra-operative nerve monitoring (C-IONM). There is ambiguity as to which of these strategies should be the preferred method of RLN preservation. A systematic review of the PubMed, Embase and the Cochrane Collaboration databases was undertaken with network meta-analysis (NMA) performed according to the PRISMA and Cochrane Collaboration guidelines. A Bayesian NMA was conducted using R packages netmeta with outcomes expressed as odds ratios (ORs) with 95% credible intervals (CrI). Only prospective studies were included. Eighteen studies met inclusion criteria, including 22,080 patients and 40,642 nerves at risk (NAR). Overall, 23,364 NARs (57.5%) underwent I-IONM, 17,176 (42.3%) No-NM and 98 (0.2%) underwent C-IONM. There were no significant differences between groups regarding the incidence of permanent RLN injury following thyroid surgery (I-IONM vs.No-NM, OR 0.84, 95% CrI 0.55-1.19; C-IONM vs. No-NM, OR 0.44, 95% CrI 0.02-5.00). Pooled analysis showed that IONM (I-IONM or C-IONM) demonstrated a protective effect versus No-NM in reducing the incidence of transient RLN injury (OR 0.75, 95% CI 0.59-0.97, p = 0.03). IONM strategies did not significantly reduce the incidence of permanent RLN injury following thyroid surgery. However, the small number of C-IONM NARs limits conclusions that may be drawn. Further well-designed prospective studies will be required to definitively assess the utility of C-IONM.


An International Consensus List of Potentially Clinically Significant Drug-Drug Interactions in Older People.
We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies.


Extraskeletal myxoid chondrosarcoma: Clinicopathological features and outcomes from the United States sarcoma collaborative database.
This investigation described clinicopathological features and outcomes of extraskeletal myxoid chondrosarcoma (EMC) patients. EMC patients were identified from the United States Sarcoma Collaborative database between 2000 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and prognostic factors were analyzed. Sixty individuals with a mean age of 55 years were included, and 65.0% (n = 39) were male. 73.3% (n = 44) had a primary tumor. A total of 41.6% (n = 25) developed tumor relapse following resection. The locoregional recurrence rate was 30.0% (n = 18/60), and mean follow-up was 42.7 months. The 5-year OS was 71.0%, while the 5-year RFS was 41.4%. On multivariate analysis for all EMC, chemotherapy (hazard ratio [HR], 6.054; 95% confidence interval [CI], 1.33-27.7; p = 0.020) and radiation (HR, 5.07, 95% CI, 1.3-20.1; p = 0.021) were independently predictive of a worse RFS. Among patients with primary EMC only, the 5-year OS was 85.3%, with a 30.0% (n = 12) locoregional recurrence rate, though no significant prognostic factors were identified. Long-term survival with EMC is probable, however there exists a high incidence of locoregional recurrence. While chemotherapy and radiation were associated with a worse RFS, these findings were likely confounded by recurrent disease as significance was lost in the primary EMC-only subset.


Morphological Variation and Its Environmental Correlates in the Taihangshan Swelled-Vented Frog across the Qinling Mountains.
The Taihangshan swelled-vented frog (Feirana taihangnica), an endemic species to the Qinling Mountains, central China, has experienced a dramatic population decline over the last few decades. The aim of this work was to quantify morphological variation in F. taihangnica across the Qinling Mountains and examine environmental correlates of this variation of morphological traits. We implemented a hierarchical partitioning to estimate the independent contribution of each environmental variable on morphological variations. Temperature seasonality was the greatest contributor in variations of snout-vent length (SVL) and head width, and ultraviolet-B (UV-B) radiation of the lowest month was the most influential on both thigh length and tibia width. Then, we used generalized additive models to analyze the relationship between each environmental factor and morphological trait variations. Along the increasing of annual mean temperature, SVL decreased firstly and then increased, indicating no support for Bergmann's rule. Furthermore, SVL was negatively correlated with annual precipitation, while positively with temperature seasonality. The mean UV-B of the highest and lowest months was positively and negatively correlated with head width, thigh length and tibia width, respectively. The results of this study help us to understand adaptive potential of this mountain frog species via morphological variations in the light of environmental changes.


Distinct microbial community along the chronic oil pollution continuum of the Persian Gulf converge with oil spill accidents.
The Persian Gulf, hosting ca. 48% of the world's oil reserves, has been chronically exposed to natural oil seepage. Oil spill studies show a shift in microbial community composition in response to oil pollution; however, the influence of chronic oil exposure on the microbial community remains unknown. We performed genome-resolved comparative analyses of the water and sediment samples along Persian Gulf's pollution continuum (Strait of Hormuz, Asalouyeh, and Khark Island). Continuous exposure to trace amounts of pollution primed the intrinsic and rare marine oil-degrading microbes such as Oceanospirillales, Flavobacteriales, Alteromonadales, and Rhodobacterales to bloom in response to oil pollution in Asalouyeh and Khark samples. Comparative analysis of the Persian Gulf samples with 106 oil-polluted marine samples reveals that the hydrocarbon type, exposure time, and sediment depth are the main determinants of microbial response to pollution. High aliphatic content of the pollution enriched for Oceanospirillales, Alteromonadales, and Pseudomonadales whereas, Alteromonadales, Cellvibrionales, Flavobacteriales, and Rhodobacterales dominate polyaromatic polluted samples. In chronic exposure and oil spill events, the community composition converges towards higher dominance of oil-degrading constituents while promoting the division of labor for successful bioremediation.


Are periprosthetic osteolytic lesions in ankle worth bone grafting?
We retrospectively evaluated the medium-term follow-up of bone grafting due to periprosthetic osteolytic lesions in ankles. 34 ankles (32 patients) with total ankle arthroplasty (TAA) underwent re operation. Indications were large periprosthetic osteolytic lesions or continuous growing of the lesions. The osteolytic lesions were imaged by CT before reoperation and once a year after that. The mean CT follow-up after re operation was 3.8 years (range, 2-6.2 years). Patient's clinical outcome was also monitored. Osteolysis continued to progress in 44 bone grafted lesions (68%) in CT follow-up. Pain (p=0.04) and location of the lesion (p=0.03) were associated with progression of osteolysis. In 18 bone grafted osteolytic lesions (28%) the radiological survival remained excellent. 25 out of 34 ankles showed improvement of the function after bone grafting. There is no established treatment protocol for osteolysis around TAA. Bone grafting is one alternative in the treatment of osteolytic lesions.


Premature mortality in poor health and low income adults with epilepsy.
To examine mortality and causes of death (CODs) in socioeconomically disadvantaged persons with epilepsy (PWEs) in the United States. We performed a retrospective open cohort analysis using Ohio Medicaid claims data between 1992 and 2008 to assess mortality and COD in 68,785 adult Medicaid beneficiaries with epilepsy. Case fatality (CF), mortality rates (MRs), standardized mortality ratios (SMRs), and years of potential life lost (YPLLs) were calculated. The SMRs were estimated to compare risk of death in PWEs with that in the general Medicaid population with and without disabilities. Proportionate mortality ratios (PMRs), YPLLs, and SMRs for specific COD were also obtained. There were 12,630 deaths in PWEs. CF was 18.4%, the age-race-sex adjusted MR was 18.6/1,000 person-years (95% confidence interval [CI], 18.3-18.9). The SMR was 1.8 (95% CI, 1.8-1.9) when compared to the general Medicaid population, and was 1.4 (95% CI, 1.3-1.6) when compared to those with disabilities. The average YPLL was 16.9 years (range 1-47 years). Both epilepsy and comorbid conditions significantly contributed to premature mortality in PWEs. Cardiovascular diseases, cancer, and unintentional injuries were the most common COD and account for a large proportion of YPLLs. Deaths from epilepsy-related causes occurred in about 10% of the cases. Socioeconomically deprived PWEs, especially young adults, experience high mortality and die 17 years prematurely. The high mortality in Medicaid beneficiaries with epilepsy affirms that comorbid conditions and epilepsy play a crucial role in premature death. Management of comorbid conditions is, at a minimum, as important as epilepsy management, and therefore deserves more attention from physicians, particularly those who care for Medicaid beneficiaries with epilepsy.


Hypothalamic monoamine contents in endotoxin fever of new-born guinea pigs and kittens.
In new-born guinea pigs and kittens Escherichia coli endotoxin did not significantly modify the hypothalamic level of either norepinephrine (NE) or 5-hydroxytryptamine (5-HT). The hypothalamic 5-hydroxyindoleacetic acid (5-HIAA) content was significantly elevated in endotoxin-treated animals, but this elevation was confined to a period following the endotoxin injections by about 60 min in guinea pigs and 75-90 min in kittens.


Minimally invasive, no hardware subtalar arthrodesis with autogenous posterior iliac bone graft.
Sixteen patients underwent minimally invasive subtalar arthrodesis through a mini-invasive approach with posterior iliac graft between 2004 and 2006. No hardware was used to transfix the arthrodesis and partial weight bearing was allowed immediately. The primary indication for surgery was the squeal of fracture os calcis in terms of subtalar joint arthritis, loss of heel height, malalignment of the hindfoot, and pain with weight bearing. There were 12 male and 4 female patients with a mean age of 30 (range 17-52). Patients were followed up for a period of 40.8 months (range 36-48 months). The mean interval from injury to fusion was 2 (+0.6) years ranging from 6 months to 6 years post fracture. The average clinical rating scale based on the American Orthopaedic Foot and Ankle Society (AOFAS) improved from 36 preoperatively to 78 at the latest follow-up (P < 0.05). Union rate was 94%. Radiographic evaluation revealed a mean increase in calcaneal inclination of 6.25 + 8.3 degrees (P < 0.07) and a mean increase in the lateral talocalcaneal angle of 7.42 + 10.2 degrees (P < 0.08). Complications were graft nonunion in 1 patient and transient tendoachilles tendinitis in another. This technique can be used to decrease the morbidity associated with the late complications of os calcis fractures by aligning the hindfoot, restoring the heel height and correcting calcaneal and talar inclination. It offers the advantage of early weight bearing while avoiding hardware complications.


Mapping of CRF-immunoreactive nerve fibers in the medulla oblongata and spinal cord of the rat.
By use of an antiserum raised against Corticotropin Releasing Factor (CRF 1-41), nerve fibers can be stained in the medulla oblongata and spinal cord of rats. A dense plexus of CRF-immunoreactive (CRFi) nerve fibers is present in the nucleus tractus spinalis nervi trigemini from which fiber bundles enter the tractus spinalis nervi trigemini. Large numbers of CRFi fibers are present in the substantia gelatinosa of the spinal cord, while the tractus solitarius, the nucleus tractus solitarius and the nucleus ambiguus contain a low number of CRFi fibers. In rats treated with colchicine, CRFi cell bodies are found in the hypothalamus and occasionally in the nucleus tractus solitarius and the nucleus olivaris inferior. Posterolateral deafferentation of the hypothalamus did not result in a disappearance of the CRFi fibers in the medulla oblongata and spinal cord 7 days after surgery. These results indicate that CRFi fibers present in the spinal cord and medulla oblongata are part of a novel peptidergic neuronal system, which is different from the hypothalamo-infundibular CRF system.


Assessment of Hepatotoxicity Induced by Aluminum Oxide Nanoparticles in Oreochromis niloticus Using Integrated Biomarkers: Exposure and Recovery.
The hepatotoxic impacts of 2, 4, and 8 mg/L of Al2O3 nanoparticles (31.4 ± 4.8 nm) were evaluated in Oreochromis niloticus after 7 days of exposure and 15 days of recovery periods. The biochemical analysis of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in plasma showed significant increases in both 4 and 8 mg/L Al2O3 NPs exposed groups. The antioxidant biomarkers showed concentration-dependent elevations in catalase, superoxide dismutase, glutathione peroxidase activities, and thiobarbituric acid reactive substances levels. Glutathione reduced contents showed significant reductions in both 4 and 8 mg/L Al2O3 nanoparticles exposed groups. Several hepatic histopathological alterations were recorded ranging from adaptive responses (e.g. melanomacrophages aggregation) to permanent damage (e.g. necrosis). The recovery period using toxicant-free water led to an obvious reduction in the Al content in liver, liver and antioxidant enzymes in addition to regressive histopathological alterations based on the frequency of alterations occurrence and the extent of affected areas.


Biodiesel classification by base stock type (vegetable oil) using near infrared spectroscopy data.
The use of biofuels, such as bioethanol or biodiesel, has rapidly increased in the last few years. Near infrared (near-IR, NIR, or NIRS) spectroscopy (>4000cm(-1)) has previously been reported as a cheap and fast alternative for biodiesel quality control when compared with infrared, Raman, or nuclear magnetic resonance (NMR) methods; in addition, NIR can easily be done in real time (on-line). In this proof-of-principle paper, we attempt to find a correlation between the near infrared spectrum of a biodiesel sample and its base stock. This correlation is used to classify fuel samples into 10 groups according to their origin (vegetable oil): sunflower, coconut, palm, soy/soya, cottonseed, castor, Jatropha, etc. Principal component analysis (PCA) is used for outlier detection and dimensionality reduction of the NIR spectral data. Four different multivariate data analysis techniques are used to solve the classification problem, including regularized discriminant analysis (RDA), partial least squares method/projection on latent structures (PLS-DA), K-nearest neighbors (KNN) technique, and support vector machines (SVMs). Classifying biodiesel by feedstock (base stock) type can be successfully solved with modern machine learning techniques and NIR spectroscopy data. KNN and SVM methods were found to be highly effective for biodiesel classification by feedstock oil type. A classification error (E) of less than 5% can be reached using an SVM-based approach. If computational time is an important consideration, the KNN technique (E=6.2%) can be recommended for practical (industrial) implementation. Comparison with gasoline and motor oil data shows the relative simplicity of this methodology for biodiesel classification.


Arthroscopic acromioplasty: extravasation of fluid into the deltoid muscle.
We studied 25 patients who underwent an arthroscopic examination of the shoulder and in whom 20 had an arthroscopic acromioplasty. In all patients there was extravasation of fluid due to the use of pressure irrigation. The pressures rose from a baseline of 12 mm up as high as 120 mm of mercury. Within 4 min of the procedure, the pressures had returned to the baseline. No patients showed evidence of muscle damage during electromyograms done at 4-6 weeks postoperatively. Pressure irrigation appears to be safe for subacromial decompression.


Viability of frozen allografts.
The use of meshed skin grafts allows an evaluation of the biologic properties of stored tissues such as skin. Frozen allograft may serve as an excellent biologic membrane, but it is not a satisfactory product for longer term allografting (intermediate allografting). The method of thawing (microwave oven versus water bath) appeared to have little effect on the ultimate viability and outcome of the frozen allograft.


Peer feedback as a medium to facilitate reflective practice among pharmacy students in a case-based learning environment.
The ability to reflect is a key element in preparing pharmacy professionals to meet the challenges of a dynamic health care environment. This mixed-methods study explored the pedagogical benefits of peer feedback by designing, developing, and implementing a peer feedback activity to facilitate reflective practice among pharmacy students. Twenty second-year doctor of pharmacy (PharmD) students in a required pharmacotherapy course participated in a systematic peer feedback activity and five of these students volunteered for semi-structured interviews. No significant correlation was found between perceived effectiveness of peer feedback and students' reflective thinking skills. Qualitative interview data revealed three major themes regarding PharmD students' perception of peer feedback as an instructional strategy to promote reflective practice: (1) the cognitive process of providing feedback, (2) the cognitive process after receiving peer feedback, and (3) perceptions of peer feedback as a tool to exercise reflective practice. Although limited in sample size, important lessons were learned on how to design, develop, and implement a peer feedback activity.


The orientation of the dorsal/ventral axis of zebrafish is influenced by gravitation.
Following fertilization of eggs of Brachydanio rerio a blastodisc is formed which, by cleavage divisions and epibolic movements, gives rise to a cell cap covering the yolk. When about half of the yolk is covered by the cells, a thickening appears at the progressing margin, the embryonic shield, which gives rise to the axial organs of the future embryo. Thereby, the dorsal/ventral axis can be recognized. Our experiments show that the blastodisc is formed at the position of the micropyle, the only site where the sperm can enter the egg and oocyte. Later the head appears at this position. We show that the position of the embryonic shield on the circumference of the cell cap is influenced by gravitation. We also demonstrate that there is no correlation between the orientation of the first or second cleavage plane and the position of the embryonic shield.


Infections and some other conditions affecting the skin and subcutis of the naso-ocular region of cats--clinical experience 1987-2003.
Infections of the skin or subcutis of the naso-ocular region develop through two mechanisms. Cases with lesions but without concomitant signs of nasal disease probably result from cat scratch injuries. Under certain circumstances, such lacerations result in the introduction of saprophytic microorganisms in such large numbers that host defence mechanisms are overwhelmed. This results in localised, variably invasive, disease in an otherwise immunocompetent host. An unpredictable range of organisms can give rise to such infections including a variety of fungal and bacterial genera. Causal organisms will likely vary from one geography to another as a result of differences in soil type and related environmental factors. Accordingly, procurement of appropriate tissue specimens for culture and susceptibility testing is essential to guide therapy, as these cases require medical and sometimes surgical intervention in order to effect a favourable outcome. In contrast, patients with naso-ocular lesions and concurrent signs of nasal disease have a different pathogenesis. Primary infection of the sinonasal region likely results from the inhalation of infectious propagules, with the infection subsequently penetrating overlying bones to invade the subcutaneous space. These lesions are typically the result of cryptococcosis or aspergillosis and must be distinguished from invasive nasal malignancies. An approach to the investigation and treatment of these patients is presented together with photographs of representative cases.


The rate of myocardial perfusion recovery after steroid therapy and its implication for cardiac events in cardiac sarcoidosis and primarily preserved left ventricular ejection fraction.
Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS. Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51-68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007). Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.


Inclusion of individuals with low IQ in drug development for autism spectrum disorder.
Although individuals with intellectual disability (ID) and/or limited language ability make up a significant proportion of those with autism spectrum disorder (ASD), they are routinely excluded from ASD research. As a result, this vulnerable population is prevented from participating in and deriving full benefit from research. In this commentary, we expand upon points made by McCracken and colleagues (this issue), who describe several opportunities for improvement in drug development for ASD related to the inclusion of individuals with ID and/or limited language ability.


Dietary models of insulin resistance.
Insulin resistance is a significant factor in the development of type 2 diabetes mellitus, however the connection between the Western diet and the development of insulin resistance has not been fully explained. Dietary macronutrient composition has been examined in a number of articles, and diets enriched in saturated fatty acids, and possibly in fructose, appear to be most consistently associated with the development of insulin resistance. However, mechanistic insights into the metabolic effects of such diets are lacking, and merit further study.


Materials swelling revealed through automated semantic segmentation of cavities in electron microscopy images.
Accurately quantifying swelling of alloys that have undergone irradiation is essential for understanding alloy performance in a nuclear reactor and critical for the safe and reliable operation of reactor facilities. However, typical practice is for radiation-induced defects in electron microscopy images of alloys to be manually quantified by domain-expert researchers. Here, we employ an end-to-end deep learning approach using the Mask Regional Convolutional Neural Network (Mask R-CNN) model to detect and quantify nanoscale cavities in irradiated alloys. We have assembled a database of labeled cavity images which includes 400 images, > 34 k discrete cavities, and numerous alloy compositions and irradiation conditions. We have evaluated both statistical (precision, recall, and F1 scores) and materials property-centric (cavity size, density, and swelling) metrics of model performance, and performed targeted analysis of materials swelling assessments. We find our model gives assessments of material swelling with an average (standard deviation) swelling mean absolute error based on random leave-out cross-validation of 0.30 (0.03) percent swelling. This result demonstrates our approach can accurately provide swelling metrics on a per-image and per-condition basis, which can provide helpful insight into material design (e.g., alloy refinement) and impact of service conditions (e.g., temperature, irradiation dose) on swelling. Finally, we find there are cases of test images with poor statistical metrics, but small errors in swelling, pointing to the need for moving beyond traditional classification-based metrics to evaluate object detection models in the context of materials domain applications.


Urinary tract infection in infants in spite of prenatal diagnosis of hydronephrosis.
The efficacy of preventing neonatal urinary infection in infants by diagnosing hydronephrosis in the fetus on obstetrical ultrasonography was studied. 426 infants had uroradiologic evaluation between 1984 and June 1991 because they had hydronephrosis detected in utero. Thirteen with posterior urethral valves were excluded. Of the remaining 413, 13 (3.1%) presented with urinary infection in the first 6 months of life. Ten of the 13 were boys and 7 were not circumcised. Eleven of the 13 infants less than 2 months old were formula-fed. The causes of hydronephrosis were reflux alone in 6, ureteropelvic junction obstruction in 6 (with coexisting ipsilateral reflux in 4), and primary megaureter in 1. Ultrasonography alone was insufficient to exclude reflux. Amoxicillin-resistant bacteria were the causative organisms in all 10 for whom bacteriology data was available. Four categories of management failure were identified: 1) failure of communication of the prenatal findings, 2) antibiotics not prescribed, 3) antibiotics prescribed but not administered, and 4) infection in spite of continuous antibiotic prophylaxis. Uncircumcised formula-fed male infants with reflux seemed to be at special risk for infection.


The cytosolic glycoprotein FP21 of Dictyostelium discoideum is encoded by two genes resulting in a polymorphism at a single amino acid position.
FP21 is a glycoprotein within the cytosolic compartment of Dictyostelium which carries an unusual carbohydrate modification(s) including the sugars fucose, galactose and N-acetylglucosamine. The soluble pool of FP21 from crude extracts resolves chromatographically into two fractions that differ in their glycosylation. Previous gene-mapping studies indicating the existence of two loci suggested that the FP21 fractions might be encoded by different genes. To address this issue, the two genes were cloned and sequenced, leading to the prediction that the protein products would differ by only a single amino acid, Ser or Ala, at codon 39. Protein sequence data on CNBr fragments of purified FP21 showed that both gene products are found in both fractions of the soluble pool. After further purification, the two fractions were no longer chromatographically resolvable, and there was no evidence for charge heterogeneity as determined by 2-D gel electrophoresis of whole cells. Thus, the initial separation of the different soluble subpopulations of this protein appears to be due to distinct molecular complexes, possibly related to differential glycosylation, and is not the result of the genetically-encoded amino acid polymorphism.


Association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy.
This study was to investigate the relation between the number of autophagosomes in podocytes and the syndromes of idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (sMN). The pathological changes in the kidney tissues of patients were detected with the hematoxylin and eosin staining, the periodic acid-Schiff reagent treatment, the Masson's trichrome staining and the immunofluorescence detection (IF). Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the IF assay pointing to LC3-II, an autophagic marker. Clinical data, including age, sex, edema, serum creatinine, estimated glomerular filtration rate, hematuria, urine protein excretion and serum albumin, were collected from in-patient medical records. Finally, the association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy was studied. Fewer autophagosomes were observed in podocytes of nephropathy group compared with the control group. Moreover, there was a significant difference in the autophagosome number between the two types of MN and each kind of nephropathy demonstrated distinct characteristics. Although the reduced autophagosome number in the IMN cases was not related to sex, this trend was exacerbated along with the progression from pathological stage I to II. In contrast, fewer autophagosomes were observed in class II and V LN patients compared with the controls, while greater numbers were detected in class III and IV LN patients. The results indicated that the autophagy participated in the podocyte injury in IMN and sMN and the number of autophagosomes in podocytes was related to the pathological classification.


Chronic Pleuritis and Recurrent Pleural Effusion After Atezolizumab for Small Cell Lung Cancer.
BACKGROUND As use of immune checkpoint inhibitors consistently grows, so does knowledge of immune-related adverse events. Pleural complications from PD-L1 inhibitors such as atezolizumab have never been reported. We describe the first reported case of biopsy-proven pleuritis manifesting as recurrent pleural effusion in a patient treated with atezolizumab. CASE REPORT A 66-year-old woman with history of extensive-stage small cell lung cancer presented with a new pleural effusion. She was previously treated with carboplatin, etoposide, and atezolizumab followed by atezolizumab maintenance, but this later was stopped due to pneumonitis. She had been on no systemic therapy for 6 months prior; radiation to the chest was completed 1 year earlier. Thoracentesis revealed an exudate with eosinophilia but no malignancy. She underwent medical thoracoscopy, which showed normal pleura with no evidence of radiation changes. Random pleural biopsies revealed only chronic pleuritis. Given normal-appearing pleura, radiation pleuritis was ruled out. It was felt that the chemotherapy had occurred too long ago to be a present cause of her pleuritis. As such, after extensive workup, the eosinophilic pleural effusion was felt to be due to pleuritis from atezolizumab. The effusion has ultimately recurred 5 times over 1 year, and cytology remains negative for malignancy. CONCLUSIONS Patients with prior cancer presenting with a new pleural effusion should undergo an extensive workup to evaluate for recurrence. When other causes have been ruled out, ongoing immune-related effects of immunotherapy should be considered. Pleural complications from PD-L1 inhibitors have not been reported; we present a possible case of chronic pleuritis and recurrent effusion due to atezolizumab.


Exo-Clinical Trials of Nutritional Supplements for Sexual Dysfunction: Precedents, Principles, and Protocols.
Care-seeking for sexual dysfunction is limited by embarrassment, efficacy/safety concerns, and cost. Nutritional supplements (NSs) are low-cost but unproven. To provide hypotheses on whether effective NS combinations for sexual dysfunction can be created following known pharmacology principles and tested with sufficient rigor in Internet-based "exo-clinical" trials (XCTs). PubMed and Google searches were conducted to review the feasibility of XCTs of NS combinations for sexual dysfunction. Findings were synthesized into recommendations for XCTs to treat the most common sexual problems. The hierarchy of references used for making recommendations was controlled clinical trials over uncontrolled trials. The frequency of sexual dysfunction was determined in population-representative national surveys. XCTs of cognitive behavioral therapy show conclusive efficacy for anxiety and depression. 5 small XCTs showed efficacy for female sexual dysfunction and erectile dysfunction (ED), and 2 XCTs of NS for other medical problems substantiated feasibility. To test the feasibility of XCTs for the most common forms of sexual dysfunction-ED, hypoactive sexual desire disorder (HSDD), and sexual performance anxiety-protocol outlines were generated for frugal XCTs; the total estimated subject time burden is ≤1 hour. An XCT is a cost-effective method of evaluating new treatments, including sexual dysfunction and common mental disorders, if compliance is maintained by regular outreach while minimizing the time burden on subjects and handling consent and privacy issues appropriately. NS combinations might expand the opportunities for relief of sexual dysfunction if formulated with pharmacologically active doses of NS with already supported efficacy and safety. The feasibility of XCTs of NS combinations for sexual dysfunction might be tested most productively in men with ED, in women with HSDD, and in men and women with sexual performance anxiety. Pyke RE. Exo-Clinical Trials of Nutritional Supplements for Sexual Dysfunction: Precedents, Principles, and Protocols. Sex Med Rev 2019;7:251-258.


Scaffolding microdomains and beyond: the function of reggie/flotillin proteins.
Reggie/flotillin proteins are considered to be components of lipid rafts and are commonly used as marker proteins for lipid microdomains. Yet almost a decade after their discovery, the function of reggies/ flotillins is still enigmatic. In this review we summarize the present state of knowledge on reggie/flotillin structure, localization and function, and discuss the role of the proteins in development and disease. Based on insights into reggie/flotillin function and by comparison with related proteins of the so-called SPFH (Stomatin/Prohibitin/Flotillin/HflK/C) protein family, including stomatin, podocin and prohibitin, we propose the existence of specific types of protein-defined microdomains which are sculpt by the clustering of individual SPFH proteins. As 'specialized rafts' similar to caveolae, these membrane domains provide platforms for the recruitment of multiprotein complexes. Since, under certain circumstances, reggie-2/flotillin-1 translocates to the nucleus, reggie/ flotillin microdomains are not only stable scaffolds but also dynamic units with their own regulatory functions.


High-level ertapenem resistance in Klebsiella pneumoniae is due to RamA downregulation of ompK35 through micF.
An ertapenem-resistant Klebsiella pneumoniae clinical isolate (KP20) without carbapenemase and negative for the efflux pump inhibition test was resistant to ertapenem at a high level [minimum inhibitory concentration (MIC) = 64 mg/L] but susceptible to meropenem and imipenem. Second-generation sequencing was performed and a termination mutation was found in ramR. Complementation of ramR in KP20 reduced the ertapenem MIC by 128 times (from 64 mg/L to 0.5 mg/L). Overexpression of ramA and loss of OmpK35 were discovered in strain KP20 by quantitative reverse transcription PCR (RT-qPCR) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Furthermore, ramA deletion in strain KP20 resulted in a 128-fold decrease in the MIC of ertapenem (from 64 mg/L to 0.5 mg/L), and expression of OmpK35 was observed in KP20ΔramA by SDS-PAGE. Complementation of ramA in KP20ΔramA led to a 45.45-fold downregulation of ompK35. Complementation of ompK35 in KP20 could restore susceptibility to ertapenem (MIC reduced from 64 mg/L to 0.25 mg/L). Furthermore, results of the electrophoretic mobility shift assay showed that RamA could bind to the promoter of micF. These results showed that the termination mutation in ramR resulted in overexpression of ramA causing loss of OmpK35 expression through upregulation of micF, revealing the mechanism of ertapenem resistance only in K. pneumoniae.


In vitro induction of cecropin genes--an immune response in a Drosophila blood cell line.
The Drosophila melanogaster cell line mbn-2 was explored as a model system to study insect immune responses in vitro. This cell line is of blood cell origin, derived from larval hemocytes of the mutant lethal (2) malignant blood neoplasm (1(2)mbn). The mbn-2 cells respond to microbial substances by the activation of cecropin genes, coding for bactericidal peptides. The response is stronger than that previously described for SL2 cells, and four other tested Drosophila cell lines were totally unresponsive. Bacterial lipopolysaccharide, algal laminarin (a beta-1,3-glucan), and bacterial flagellin were strong inducers, bacterial peptidoglycan fragments gave a weaker response, whereas a formyl-methionine-containing peptide had no effect. Experiments with different drugs indicate that the response may be mediated by a G protein, but not by protein kinase C or eicosanoids, and that it requires a protein factor with a high rate of turnover.


Implementation and experiments for interactive lyrics transcreation system.
The evolution of the Internet has enabled us to enjoy the music created in various countries. But still, it is often difficult to understand the lyrics written in foreign languages. Professional translators have published many international songs with lyrics that fit the melody so that the ordinary people can enjoy the lyrics of such international songs. This paper discusses lyrics transcreation into the Japanese language. Also, the paper presents an interactive visual lyrics transcreation system and describes the details of its implementation. This system allows users to select temporary lyrics from a set of tentative translations and then freely modify the lyrics with a real-time visualization mechanism. We also propose a lyrics translation algorithm that solves an essential problem of lyrics translation into Japanese. In this study, we interviewed two experts regarding problems with lyrics translation and received reviews of our presented system. We also conducted preliminary experiments with 19 participants to determine the best combination of user interface components for our system. We performed additional user experiments inviting 12 participants to compare lyrics transcreation using the presented system to manual lyrics transcreation. Lyrics transcreation by the presented system brought better results against those of manual transcreation.


Clonality studies in giant cell tumor of bone.
Genetic studies including chromosome analysis, telomere reduction and telomere activity, DNA microsatellites and loss of heterozygosity (LOH) studies have been performed on giant cell tumor (GCT) of bone however whether this primary skeletal neoplasm represents a monoclonal or polyclonal proliferation is unknown. Utilizing a new assay to study the polymorphic human androgen receptor locus (HUMARA), the ratio of maternal inactive X-chromosome to the paternal inactive X (Lyon hypothesis) is determined via a methylation--specific polymerase chain reaction (PCR) technique to detect X-chromosome polymorphisms. Characterization of the genetic tumorigenesis of this unpredictable neoplasm may lend insight into its biological behavior and offer improvements in therapeutic intervention, as new information emerges regarding osteoclastic bone resorption. Seventeen female patients with giant cell tumor of bone had their DNA harvested and their X-chromosome inactivation pattern and polymorphisms determined and compared to control. A polyclonal proliferation pattern was identified in all informative samples studied.


Does quality stimulate customer satisfaction where perceived value mediates and the usage of social media moderates?
Customer is considered as the king in the world of business. The issue of customer satisfaction in electronics home appliances has received greater attention from academics and practitioners. In other words, customer satisfaction is a vital consideration in marketing. With the development of technology, new and innovative electronic home appliances are available in the market. Customers purchase and use the costly electronic home appliances where the satisfaction issue is an important concern. In Bangladesh, working families find the electronic home appliance very necessary. Companies offer state-of- the-art appliances for customers' household works. Therefore, the study intends to investigate the effect of product quality (PQ), quality of service (SQ) and perceived value on customer satisfaction (CS). In addition, this study also seeks this relationship shaped by customer's perceived value (CPV) as a key mechanism and interacted by social media usage. A total of 300 households were selected on a judgmental basis from Dhaka city in Bangladesh using a structured questionnaire. Collected data were CB-SEM (AMOS-v24) and SPSS. The findings showed PQ and SQ have positive effects on CS; SQ affects, but PQ does not affect CPV. CPV has a mixing mediating effect on SQ and CS relationship and PQ and CS relationship. Importantly, the positive impact of PQ, SQ and CPV is greater on customers who exhibit higher social media use. The conceptual framework was buttressed by EDT theory. The study contributed to contextual and theoretical knowledge in regards to home appliances. The practicing managers can collect an insight of customer satisfaction for their business.


Case report of osteomyelitis of the mandible in osteopetrosis and management considerations.
Osteopetrosis is a poorly known and probably underdiagnosed pathology. It is caused by various genetic abnormalities resulting in osteoclast dysfunction. Functional and aesthetic consequences have a major impact on the patient's quality of life. Ten percent of osteopetrosis cases develop osteomyelitis that usually involves the mandible. Management of this complication remains complex and often unsatisfactory. We report a case of a 62-year-old woman with osteopetrosis, complicated by mandibular osteomyelitis with intra-oral bone exposure and submental fistulas. Management was performed with antibiotic therapy and surgical necrotic resection. This cured the fistulas but the bone exposure persisted. This case report highlights the difficulty of achieving complete healing of osteomyelitis in osteopetrosis. Antibiotic therapy, surgical management, or even hyperbaric oxygen therapy are required, but must be adapted to the case. A free flap procedure is undesirable but, when it is necessary, a bone marrow transplant could be considered to restore osteoclast function. The management of mandibular osteomyelitis in patients with osteopetrosis must adapt to the situation and severity. To avoid most cases of osteomyelitic complications in patients suffering from osteopetrosis, we propose that a preventive strategy of better dental care should be considered.


Three-dimensional display of hepatic venous anatomy generated from spiral computed tomography data: preliminary results.
A new method is presented for generating three-dimensional images of the hepatic venous anatomy from helical computed tomography (CT) scans using volumetric rendering. The helical CT scans were obtained using peripheral injection of intravenous contrast via a power injector. Five patients with suspected liver tumors were studied from which one sample case was selected for illustration. Surgical planning of hepatic resection from three-dimensional images will soon become a practical part of patient care.


Type IV collagen in developing human lung: a comparison between normal and hypoplastic fetal lungs.
Human lung tissue obtained from 24 aborted fetuses of varying gestational ages (beyond 24 weeks) was examined for immunolocalisation of type IV collagen, using monoclonal antibody. Twelve cases of lung hypoplasia associated with oligohydramnios were compared with 12 normally developed lungs over the same gestational age range acting as control. Type IV collagen was located in alveolar septa and subepithelial basement membranes in all the lungs examined but showed less prominently in hypoplastic lungs than in control lungs of a similar gestational age. The findings suggest a potential role of type IV collagen in maturation of the developing human lung.