Cystic fibrosis carrier screening: knowledge and attitudes of prenatal care providers.
We are conducting a trial of population carrier screening for cystic fibrosis (CF), targeting pregnant and nonpregnant patients of prenatal care providers. We first enlisted providers by presenting a description of the trial to the obstetrical staffs of the five Rochester, New York, hospitals having delivery services. Of the 124 prenatal care providers (111 obstetricians and 13 family practitioners) with delivery privileges at the five hospitals, only 81 (65%) attended one of our presentations. Providers who attended lacked knowledge about CF screening and counseling and expressed divergent attitudes about prenatal diagnosis for carrier women having test-negative partners. Of the 79 providers completing an attitude questionnaire, 68 (86%) were willing to offer carrier screening to all their patients if educational materials, testing, and counseling were all provided without charge. After visiting participating physicians' offices to orient their staff, we reached two additional conclusions. First, in considering whether to offer CF carrier screening to their patients, prenatal care providers are less concerned about imperfect test sensitivity, false reassurance of those testing negative, or discrimination against those testing positive than about time required to answer patients' questions if they screen and about legal liability if they do not. Second, some providers are more resistant to offering screening to nonpregnant patients than to pregnant patients, not because they believe that the timing is less appropriate, but because nonpregnant patients do not routinely receive an advance mailing, have phlebotomy, or return for follow-up. Our experience raises concerns about the willingness and capability of prenatal care providers to translate advances in molecular medicine into prenatal screening services.


Destructive Aorto-Mitral Endocarditis: Two Valves for One Annulus.
Surgery for endocarditis of the aorto-mitral continuity can be a challenge in case of extensive tissue destruction. We report two cases of a modified monobloc reconstruction of the aortic and mitral valves and of the aorto-mitral fibrous body. Two valve bioprostheses were sutured to each other and implanted as a composite graft. A pericardial patch sutured to the valves was employed to reconstruct both the noncoronary sinus and the left atrial roof. This technical adjustment allows adaptation to variable anatomical conditions in these particularly difficult cases.


Actions of somatostatin on excitatory and inhibitory nerves in the intestine.
Isolated segments from the guinea-pig ileum and colon were used to investigate the sites of action of somatostatin on intestinal nerves and muscle. Somatostatin reduced the amplitude of the contraction caused by stimulation of cholinergic nerves in the ileum, without antagonizing receptors for acetylcholine on the muscle, which indicates that somatostatin inhibits the release of transmitter from the cholinergic nerves. Somatostatin caused the intestinal muscle to relax. The relaxation was blocked by tetrodotoxin but not by guanethidine, indicating that somatostatin stimulates enteric non-adrenergic inhibitory nerves. The threshold of concentration for these actions of somatostatin was low (2 to 6 X 10(-10) M). At higher concentrations, somatostatin caused a transient inhibition of peristaltic reflexes and it also stimulated cholinergic nerves. No evidence was obtained for a direct action of somatostatin on intestinal muscle. It is concluded that somatostatin is possibly a neurotransmitter in the intestine that is released at neuro-neuronal junctions and causes an inhibition of intestinal movements.


Effects of human chorionic gonadotropin on the last day of a 5-day CIDR Synch protocol and 5 days later on circulating progesterone concentrations and luteal area in Holstein heifers.
The objective was to determine the effect of replacing GnRH with human chorionic gonadotropin (hCG) on the last day of a 5-d CIDR Synch protocol (d 0) and inducing accessory corpus luteum (CL) formation with hCG 5 d later (d 5) on serum progesterone (P4) concentrations and luteal dynamics in dairy heifers. Holstein heifers (n = 207) were synchronized with a 5-d controlled internal drug release (CIDR) Synch protocol (d -8: used CIDR inserted; d -3: CIDR removed and PGF2α). Heifers were randomly assigned to 1 of 4 treatments on d 0: control (G; n = 55), H (n = 50), GH (n = 53), and HH (n = 49). Heifers in G were treated with 100 μg of GnRH on d 0, while H heifers received hCG (3,300 IU) on d 0. Heifers enrolled in GH were treated with GnRH on d 0 and hCG on d 5, while HH received hCG on d 0 and 5. Ovaries were scanned by ultrasound on d 0, 5, and 12, and blood was collected on d 0, 5, 7, and 12. Heifers that ovulated before or after the hCG or GnRH d 0 treatment and had P4 ≤ 0.50 ng/mL on d 0 were considered as synchronized. Overall protocol synchronization response was 93.8%, with no differences among treatments. Only synchronized heifers (n = 193) were included in the analyses of luteal dynamics after d 0. Serum P4 concentration and original CL luteal area on d 5 in heifers treated with hCG on d 0 (H + HH) were greater than in heifers treated with GnRH on d 0 (G + GH). Almost all heifers treated with hCG on d 5 had ≥2 CL on d 12 (98.6%). Ovulatory response for d 5 hCG treatment did not differ for GH versus HH (97.2 vs. 94.7%). Heifers in HH had the highest serum P4 on d 7, and G had the lowest serum P4 on d 7 and 12. In contrast, serum P4 on d 7 did not differ for H versus GH. On d 12, serum P4 and total luteal area were not different for GH versus HH. In summary, heifers that received hCG on d 0 had a larger total luteal area and greater serum P4 concentration on d 5 than heifers treated with GnRH on d 0. Moreover, hCG on d 5 promoted a greater proportion of heifers with ≥2 CL on d 12 and a larger luteal area of the original CL, which resulted in a larger total luteal area on d 12. The HH treatment successfully increased serum P4 concentrations in heifers on d 7 compared with the other treatments.


Use of high-flow nasal oxygen for pregnant women with COVID-19 in the labour ward setting.
The presentation and management of SARS-CoV-2 (COVID-19) infection in the obstetric population is affected by the hormonal and mechanical changes of pregnancy. The increased oxygen demands in pregnancy in the face of conventional oxygen therapy, risks of tracheal intubation and discomfort from non-invasive positive pressure ventilation all support the use of high-flow nasal oxygen (HFNO) as an alternative therapy. The lack of published guidance for the use of HFNO has led to the development of local-level guidance based on expert consensus. More evidence exploring the use of HFNO therapy in the pregnant population is required to assist in developing clinical guidelines.


[Optimization of the loading in therapeutic physical exercise for patients with initial cerebral atherosclerosis].
A technique is described of muscular load optimization in the course of therapeutic physical training for rehabilitation of patients with early cerebral atherosclerosis aged 40-59.


Discrimination between worry and anxiety among cancer patients: development of a Brief Cancer-Related Worry Inventory.
A psychometric scale for assessing cancer-related worry among cancer patients, called the Brief Cancer-Related Worry Inventory (BCWI), was developed. A cross-sectional questionnaire survey for item development was conducted of 112 Japanese patients diagnosed with breast cancer, and test-retest validation analysis was conducted using the data from another prospective study of 20 lung cancer patients. The questionnaire contained 15 newly developed items for cancer-related worry, the Hospital Anxiety and Depression Scale, The Impact of Event Scale Revised, and the Medical Outcomes Study Short Form-8. Exploratory factor analysis of the 15 items yielded a 3-factor structure including (1) future prospects, (2) physical and symptomatic problems and (3) social and interpersonal problems. A second-order confirmatory factor analysis identified a second-order factor called cancer-related worry and confirmed the factor structure with an acceptable fit (chi-square (df=87)=160.16, P=0.001; GFI=0.83; CFI=0.92; RMSEA=0.09). The internal consistency and test-retest reliability were confirmed with the lung cancer sample. Multidimensional scaling found that cancer-related worry is separate from anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms. Our study succeeded in developing and confirming the validity and reliability of a BCWI. The study also confirmed the discriminable aspects of cancer-related worry from anxiety, depression, and PTSD symptoms.


A recognizable pattern of the midface of retinoblastoma patients with interstitial deletion of 13q.
In our study, we found a recognizable pattern of the midface in three retinoblastoma patients with interstitial deletion of chromosome 13 in lymphocytes. Further photographs of patients reported by other authors confirmed our conclusion that the midface in children with interstitial deletion of 13q from q12 to q22, always involving q14, is characterized by prominent eyebrows, broad nasal bridge, bulbous tip of the nose, a large mouth with a thin upper lip, and a long philtrum. This midface pattern could not be recognized in patients with normal karyotypes, suggesting that the critical segment for the midface phenotype as well as for retinoblastoma may exist in band 13q14.


Studies on the activity of phorbol myrystate acetate on the human polymorphonuclear leukocytes.
Phorbol myrystate acetate (PMA) activates nitroblue tetrazolium reduction in human polymorphs. The activation is inhibited by dibutyryl cyclic AMP, theophylline and phenylbutazone, but is not influenced by hydrocortisone in vitro, nor is it inhibited by leukocytes from patients treated with prednisone. Peptide analogues of Tuftsin also had no effect on this stimulatory activity. We conclude that the action of PMA on the nitroblue tetrazolium reduction is mediated through cyclic nucleotides.


Prediabetes and COVID-19 severity, an underestimated risk factor: A systematic review and meta-analysis.
The novel coronavirus disease 2019 (COVID-19) has rapidly spread through the whole globe. Since the beginning of the outbreak, some individuals were more likely to manifest more severe outcomes. Diabetic patients were of that sort; however, the severity of COVID-19 in prediabetic ones remained less identified. This study aimed to systematically review and conduct a meta-analysis of the previously published observational studies investigating the severity of COVID-19 in prediabetic patients. Medline/PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and google scholar databases were queried to identify relevant studies concerning prediabetes and serious COVID-19 outcomes. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the likelihood of severe presentations in prediabetic patients. A total of 3027 patients were included in the meta-analysis. A random-effects model was used regarding the high heterogeneity (I2 = 55%). Prediabetes was significantly associated with adverse outcomes of COVID-19 with an OR of 2.58 (95%CI, 1.46-4.56). Prediabetes could act as a risk factor for the severity of COVID-19. Early detection of prediabetic patients might be helpful to adopt preventive and protective strategies to improve the prognosis of the infected individuals.


Marmesin is a novel angiogenesis inhibitor: Regulatory effect and molecular mechanism on endothelial cell fate and angiogenesis.
In the present study, we investigated the effects and molecular mechanism of marmesin, a coumarin compound isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-induced endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. Marmesin treatment inhibited VEGF-A-stimulated endothelial cell proliferation through down-regulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. In addition, marmesin treatment abrogated VEGF-A-induced endothelial cell migration, invasion and capillary-like structure formation in vitro as well as angiogenic sprouting ex vivo. These anti-angiogenic activities of marmesin were mediated through inactivation of VEGF-A-stimulated signaling pathways, and down-regulation of cell surface signaling molecules including VEGF receptor-2, human epidermal growth factor receptor-2, integrin β1 and integrin-liked kinase. Taken together, these findings clearly support the pharmacological roles of marmesin in regulating angiogenesis, and warrant further evaluation and development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.


Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome.
Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle and its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription and replication of HBV genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes its task by hijacking Spindlin1, an epigenetic reader comprising three consecutive Tudor domains. Our biochemical and structural studies have revealed that the highly conserved N-terminal 2-21 segment of HBx (HBx2-21) associates intimately with Tudor 3 of Spindlin1, enhancing histone H3 "K4me3-K9me3" readout by Tudors 2 and 1. Functionally, Spindlin1-HBx engagement promotes gene expression from the chromatinized cccDNA, accompanied by an epigenetic switch from an H3K9me3-enriched repressive state to an H3K4me3-marked active state, as well as a conformational switch of HBx that may occur in coordination with other HBx-binding factors, such as DDB1. Despite a proposed transrepression activity of HBx2-21, our study reveals a key role of Spindlin1 in derepressing this conserved motif, thereby promoting HBV transcription from its chromatinized genome.


Effects of cubic ecological restoration of mining wasteland and the preferred restoration scheme.
In view of the strong acidity and high heavy metal contents of the soil, the low vegetation cover, and strong soil erosion caused by mining activities, the reasonable determination of the cubic restoration mode is the key to determining the good or bad ecological restoration effects on mining wasteland. In this study, based on field experiments, a combined cubic ecological restoration scheme for soil improvement-vegetation reconstruction was constructed. Using analysis of variance, a regression model, and the Mantel test, the differences in soil properties and the biodiversity were analyzed under different restoration schemes, the entropy-weighted-TOPSIS method was used to optimize the best ecological restoration model. The results revealed that compared with the pre-restoration state, the restoration significantly increased the soil pH (p < 0.05) by 4.07-5.73, regulated the strong acidic environment of the soil, increased the organic matter content by 5.35-11.21 times, and improved the soil fertility. The available contents of Pb and Cd were reduced by 67.15-75.58 % and 64.15-88.68 %, respectively compared with the background values. Biodiversity improved significantly, and the available content of Cd was an important factor in the biodiversity recovery. The evaluation of the effect of the restoration scheme showed that the combination of mixed soil amendments of rice husks and chicken manure (10 kg/m2), bacterial fertilizer (1.8 kg/m2), biochar (1.3 kg/m2), lime (8.3 kg/m2), and soil conditioner (1.0 kg/m2) and tolerant plants (Pinus elliottii, Lagerstroemia indica, and Plantago asiatica) are the optimal cubic ecological restoration scheme for the study area, with a plant survival rate of > 90 %, eight families and 10 species of plants, and a coverage rate of 100 %. These research results provide a scientific basis and technical support for reasonable artificial intervention in ecological restoration of mining waste sites in Nanling, northern Guangdong.


ENdovascular Versus SUrgical Treatment for All-comer Patients With PROsthetic Bypass Graft Occlusion: The Multicentre ENSUPRO Study.
Bypass surgery plays a key role in complex lower limb lesions. However, there is a lack of evidence regarding the management of symptomatic prosthetic bypass graft (PBG) occlusion. This study aimed to report outcomes following open, hybrid, or endovascular management of patients presenting with symptomatic PBG occlusion. A multicentre, retrospective cohort study was conducted, including patients presenting with PBG occlusion between January 2014 and December 2021 from 18 centres. It assessed the comparative value of treatment strategies, including (1) recanalisation of native vessels, (2) endovascular treatment of the failed PBG, (3) hybrid treatment, and (4) open surgery. The primary outcome measure was amputation free survival (AFS, time to major amputation and/or death), whereas all-cause mortality, major amputation, PBG re-occlusion, target lesion revascularisation (TLR), and Rutherford category (RC) improvement during follow up were deemed as secondary endpoints. Of 260 patients with occluded PBGs, 108 (41.5%) were treated endovascularly (24 [22.2%] by recanalisation of native vessels and 84 [77.7%] by PBG reopening), 57 (21.9%) underwent hybrid revascularisation, and 58 (22.3%) had surgery. In addition, 27 (10.4%) were treated conservatively and 10 (3.8%) received systemic thrombolysis. With a median follow up of 1.4 (0.6 - 3.0) years, AFS was 95.5%, 76.4%, 45.5%, and 37.1%, respectively in Groups 1 - 4 (p = .007). Older age and non-endovascular treatment (HR 1.05 and 1.70; p < .01 for both) were independent predictors of poor AFS. Endovascular treatment was associated with lower rates of major amputation (p = .04), PBG re-occlusion (p < .001), and TLR (p = .04), and higher RC improvements (p < .001), whereas all-cause mortality was comparable between treatment groups (p = .21). Endovascular treatment is associated with higher rates of AFS and RC improvement and lower rates of PBG re-occlusion and TLR in patients with PBG occlusion.


Macrocystic pancreatic lesions: differentiation of benign from premalignant and malignant cysts by CT.
To assess useful CT features for differentiating benign from premalignant and malignant macrocystic pancreatic lesions. Seventy-four patients with pathologically proven macrocystic pancreatic lesions were enrolled: 17 benign cysts (macrocystic serous cystadenoma, n=12; congenital cyst; n=5) and 57 premalignant and malignant cysts (mucinous cystic neoplasm, n=28; intraductal papillary mucinous neoplasm of branch duct type, n=20; tumor with cystic change, n=9). Size, location, shape (lobulated, round or oval, or complex cystic with tubular cyst), wall thickness (thin, < or =1mm; thick, >1mm), internal surface (smooth or irregular), and other findings were analyzed with multiphasic CT with thin-section (2.5-3mm) images. CT features between two groups were compared using univariate and multivariate stepwise logistic regression analyses. On univariate analysis, the differences for the shape (p=0.007), wall thickness (p=0.011), and internal surface (p=0.012) between benign and premalignant and malignant cysts were significant. A lobulated shape, a thin wall and a smooth internal surface were more frequent in benign cysts, whereas a round or oval shape or a complex cystic shape with tubular cyst, a thick wall and an irregular internal surface were more frequent in premalignant and malignant cysts. On multivariate analysis, the shape (p=0.002) and wall thickness (p=0.025) were significant CT features for differentiating benign from premalignant and malignant cysts. Shape and wall thickness are the main CT features for differentiating benign from premalignant and malignant macrocystic pancreatic lesions.


An active-learning assignment using nonprescription medicines.
To create and implement a web-based written assignment to evaluate student's abilities to select appropriate nonprescription medications and recommend therapy. Each student developed a patient case study from an assigned condition, made treatment recommendations, and provided patient counseling information using at least 2 nonprescription medicines. The active-learning exercise required students to apply information previously presented in a large classroom setting. Cases most commonly submitted included therapy for burns, acne, conjunctivitis, lacerations, and poison ivy. One-hundred five students completed a 5-item questionnaire regarding the assignment. The majority of the respondents (51.9%) felt the assignment helped to reinforce course content and 58.1% felt it made them more comfortable with making product recommendations. The Personal Pharmacy assignment was an effective learning activity for enhancing student's understanding and appropriate selection of nonprescription medicines.


[The cytotoxic effect of a low density lipoprotein delivered aclarubicin on leukemia cells].
To investigate the feasibility and effectiveness of low density lipoprotein (LDL) particles as a carrier of a lipophilic anthracycline drug aclarubicin (ACR) for targeting delivery to an acute monocytic leukemia cell line THP-1. LDL-ACR complex was prepared by incubating LDL with ACR. The intracellular ACR content was assayed fluorometrically. Cytotoxicity was studied by cell protein measurement and 3H-TdR incorporation test. Intracellular accumulation of LDL-ACR was reduced when THP-1 cells were incubated in the presence of native LDL, but methylated LDL had no effect on the cellular LDL-ACR accumulation. The LDL-ACR complex caused a greater inhibition of the growth of THP-1 cells than that of normal bone marrow nucleated cells. The cellular accumulation of LDL-ACR complex was much more than that of free ACR. The 3H-TdR incorporation test showed that the complex was more effective in the inhibition of DNA synthesis than that of the free drug. The potency of ACR to tumor cells increased and its toxicity to normal cells decreased when LDL was used as a carrier.


Multi-method evaluation of a 2-(1,3,4-thiadiazole-2-yl)pyrrolidine corrosion inhibitor for mild steel in HCl: combining gravimetric, electrochemical, and DFT approaches.
The corrosion inhibition properties of 2-(1,3,4-thiadiazole-2-yl)pyrrolidine (2-TP) on mild steel in a 1 M HCl solution were investigated using weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and open circuit potential (OCP) measurements. In addition, DFT calculations were performed on 2-TP. The polarization curves revealed that 2-TP is a mixed-type inhibitor. The results indicate that 2-TP is an effective inhibitor for mild steel corrosion in a 1.0 M HCl solution, with an inhibition efficiency of 94.6% at 0.5 mM 2-TP. The study also examined the impact of temperature, revealing that the inhibition efficiency increases with an increasing concentration of 2-TP and decreases with a rise in temperature. The adsorption of the inhibitor on the mild steel surface followed the Langmuir adsorption isotherm, and the free energy value indicated that the adsorption of 2-TP is a spontaneous process that involves both physical and chemical adsorption mechanisms. The DFT calculations showed that the adsorption of 2-TP on the mild steel surface is mainly through the interaction of the lone pair of electrons on the nitrogen atom of the thiadiazole ring with the metal surface. The results obtained from the weight loss, potentiodynamic polarization, EIS and OCP measurements were in good agreement with each other and confirmed the effectiveness of 2-TP as a corrosion inhibitor for mild steel in 1.0 M HCl solution. Overall, the study demonstrates the potential use of 2-TP as a corrosion inhibitor in acid environments.


FAT4 functions as a tumour suppressor in gastric cancer by modulating Wnt/β-catenin signalling.
FAT4, a cadherin-related protein, was shown to function as a tumour suppressor; however, its role in human gastric cancer remains largely unknown. Here, we investigated the role of FAT4 in gastric cancer and examined the underlying molecular mechanisms. The expression of FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of gastric cancer patients. The effects of FAT4 silencing on cell proliferation, migration, and invasion were assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay, and migration and invasion assays in gastric cancer cell lines in vitro and in a mouse xenograft model in vivo. Downregulation of FAT4 expression in gastric cancer tissues compared with adjacent normal tissues was correlated with lymph-node metastasis and poor survival. Knockdown of FAT4 promoted the growth and invasion of gastric cancer cells via the activation of Wnt/β-catenin signalling, and induced epithelial-to-mesenchymal transition (EMT) in gastric cancer cells, as demonstrated by the upregulation and downregulation of mesenchymal and epithelial markers. Silencing of FAT4 promoted tumour growth and metastasis in a gastric cancer xenograft model in vivo. FAT4 has a tumour suppressor role mediated by the modulation of Wnt/β-catenin signalling, providing potential novel targets for the treatment of gastric cancer.


Primary structure of common carp prolactins.
The complete amino acid sequence of common carp (Cyprinus carpio) prolactin (PRL) has been determined. One milligram of carp PRL was reduced, carboxymethylated, and then cleaved with cyanogen bromide and several enzymes. Another milligram of carp PRL was digested with lysyl endopeptidase. The resulting fragments were separated by reverse-phase high-performance liquid chromatography and subjected to sequence analysis by the automatic Edman method with a gas-liquid sequencer and the manual DNS-Edman method. The carp PRL consists of 186 amino acid residues with two disulfide linkages formed between residues 46-160 and 177-186. In addition, it lacks the linkage in the amino-terminal portion of mammalian prolactins, as do salmon and tilapia PRLs, and shows 77% sequence identity with salmon PRL and 36% identity with mammalian PRLs. The sequence comparison has been performed with 190 alignment positions. Four conserved segments of the alignment positions 1-32, 46-66, 71-94, and 155-182 that were found between salmon and mammalian PRLs are further confirmed in carp PRL. Variant residues are clustered in the region of residues 98-143 which has 48% sequence identity with salmon PRL and only 2% with mammalian PRL.


Alterations in Ca2+-dependent and cAMP-dependent signaling pathways affect neurogenesis and melanogenesis of quail neural crest cells in vitro.
Trunk neural crest cells primarily form neurons, nerve supportive cells of the peripheral nervous system and melanocytes. We are interested in signal transduction pathways that affect the production of peripheral neurons or melanocytes. Quail neural crest cell cultures were treated with a variety of drugs that affect components of protein kinase A- (PKA-), protein kinase C- (PKC-) and inositol-3-phosphate- (I3P-) dependent pathways. Forskolin, a drug that increases cAMP levels, augmented melanocyte populations and reduced neuronal populations in our cultures. H8 and H89, two drugs that inhibit PKA, reduced melanocyte populations well below control levels. Down regulation of PKC with a phorbol ester, PMA, or with calphostin C inhibited neurogenesis. PMA also enhanced melanogenesis. Increasing intracellular calcium levels (with A23187 or thapsigargin) resulted in cultures with few melanocytes but many neurons, compared to untreated controls. An antagonist of the I3P pathway, wortmannin, prevented the appearance of neurons but did not affect melanocyte populations. In summary, molecules that altered the PKA-dependent pathway affected melanogenesis. Manipulations of the I3P and/or PKC-dependent pathways influenced neurogenesis. Stimulation of one pathway often inhibited appearance of cells associated with the alternative pathway.


Response of a human head-neck model to transient saggital plane loading.
A reproducible, synthetic replica of the human head and neck system utilizing a water-filled cadaver skull mounted on fiberglass-reinforced resin vertebrae and supported by passive silicone rubber muscle and ligament elements has been constructed. Contact force, head accelerations, disk pressures and intracranial pressure responses to conditions of transient saggital plane pendulum loading have been ascertained. Front and rear head impacts as well as excitation of the entire system through its rigid base were effected. Input energies ranging from 0.0089 N m to 4.63 N m were employed resulting in head accelerations up to 180 g.


Synergistic interactions of Desulfovibrio and Petrimonas for sulfate-reduction coupling polycyclic aromatic hydrocarbon degradation.
Microbial sulfate-reduction coupling polycyclic aromatic hydrocarbon (PAH) degradation is an important process for the remediation of contaminated sediments. However, little is known about core players and their mechanisms in this process due to the complexity of PAH degradation and the large number of microorganisms involved. Here we analyzed potential core players in a black-odorous sediment using gradient-dilution culturing, isolation and genomic/metagenomic approaches. Along the dilution gradient, microbial PAH degradation and sulfate consumption were not decreased, and even a significant (p = 0.003) increase was observed in the degradation of phenanthrene although the microbial diversity declined. Two species, affiliated with Desulfovibrio and Petrimonas, were commonly present in all of the gradients as keystone taxa and showed as the dominant microorganisms in the single colony (SB8) isolated from the highest dilution culture with 93.49% and 4.73% of the microbial community, respectively. Desulfovibrio sp. SB8 and Petrimonas sp. SB8 could serve together as core players for sulfate-reduction coupling PAH degradation, in which Desulfovibrio sp. SB8 could degrade PAHs to hexahydro-2-naphthoyl through the carboxylation pathway while Petrimonas sp. SB8 might degrade intermediate metabolites of PAHs. This study provides new insights into the microbial sulfate-reduction coupling PAH degradation in black-odorous sediments.


Interpretive analysis of online teaching labs constructed using moodle during the pandemic period.
The Algerian Ministry of Higher Education announced the closure of universities and switched to distance teaching due to the strong and rapid spread of COVID-19. The pandemic that forced this change created many obstacles to pedagogy. In fact, many related issues had to be resolved and other alternative teaching strategies examined. This article defines a strategy that ensures the pedagogical continuity of laboratory practical work of computer graphics course in a COVID- 19 context. It also includes data analysis of student satisfaction questionnaire on the lab work strategy quality. As a result of this research, the success rates in the graphics design course reached 91,79% and students' grades ranged from 4.33/20 to 18.17/20. This result is consistent with the combined-type graphical representation of COLLES. Guidelines and best practices are provided for performing online learning labs, including the university's online learning platform as well as different teaching scenarios, tutoring and peer assessment techniques. Computer science instructors can use this innovative strategy to develop content-specific courses, establish recommended skills, and deploy technology to improve their teaching methods.


Spray drying of budesonide, formoterol fumarate and their composites-II. Statistical factorial design and in vitro deposition properties.
The aim of this study was to investigate the effect of changing spray drying parameters on the production of a budesonide/formoterol fumarate 100:6 (w/w) composite. The systems were spray dried as solutions from 95% ethanol/5% water (v/v) using a Büchi 191-Mini Spray Dryer. A 2(5-1) factorial design study was undertaken to assess the consequence of altering spray drying processing variables on particle characteristics. The processing parameters that were studied were inlet temperature, spray drier airflow rate, pump rate, aspirator setting and feed concentration. Each batch of the resulting powder was characterised in terms of thermal and micromeritic properties as well as an in vitro deposition by twin impinger analysis. Overall, the parameter that had the greatest influence on each response investigated was production yield - airflow (higher airflow giving greater yields), median particle size - airflow (higher airflow giving smaller particle sizes) and Carr's compressibility index - feed concentration (lower feed concentration giving smaller Carr's indices). A six- to seven-fold difference in respirable fraction can be observed by changing the spray drying process parameters. The co-spray dried composite system which displayed best in vitro deposition characteristics, showed a 2.6-fold increase in respirable fraction in the twin impinger experiments and better dose uniformity compared with the physical mix of micronised powders.


More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance.
Following the discovery in 1998 of γ-H2AX, the first histone modification induced by DNA damage, interest in the changes to chromatin induced by DNA damage has exploded, and a vast amount of information has been generated. However, there has been a discrepancy between our rapidly advancing knowledge of how chromatin responds to DNA damage and the understanding of why cells mobilize large segments of chromatin to protect the genome against destabilizing effects posed by tiny DNA lesions. Recent research has provided insights into these issues and suggests that chromatin responses induced by DNA damage are not simply the accumulation of 'nuclear foci' but are mechanisms required to guard genome integrity.


The role of left inferior frontal cortex during audiovisual speech perception in infants.
In the first year of life, infants' speech perception attunes to their native language. While the behavioral changes associated with native language attunement are fairly well mapped, the underlying mechanisms and neural processes are still only poorly understood. Using fNIRS and eye tracking, the current study investigated 6-month-old infants' processing of audiovisual speech that contained matching or mismatching auditory and visual speech cues. Our results revealed that infants' speech-sensitive brain responses in inferior frontal brain regions were lateralized to the left hemisphere. Critically, our results further revealed that speech-sensitive left inferior frontal regions showed enhanced responses to matching when compared to mismatching audiovisual speech, and that infants with a preference to look at the speaker's mouth showed an enhanced left inferior frontal response to speech compared to infants with a preference to look at the speaker's eyes. These results suggest that left inferior frontal regions play a crucial role in associating information from different modalities during native language attunement, fostering the formation of multimodal phonological categories.


Overexpression of NSAID-activated gene product in prostate cancer.
NSAID-activated gene (NAG-1) protein was previously identified by microarray analysis as overexpressed in prostate cancer. We performed immunohistochemistry and Western blotting with rabbit polyclonal antibody to NAG-1. Fifty malignant tissues obtained by prostatectomy and 17 from benign cases were compiled. Cancer tissues included Gleason scores 3-6, 3+4=7, 4+3=7, and 8-10. Cancer and high-grade prostatic intraepithelial neoplasia (PIN) consistently showed moderate to intense cytoplasmic reactivity in 95-100% of epithelium. Staining intensity inversely correlated with preoperative serum prostate-specific antigen (PSA) (p=0.005) and with grade, averaging (on a 0 to 3+ scale) 2.3 +/- 0.6 in the lowest grade group, and 2.0 +/- 0.7, 1.8 +/- 0.5, and 1.5 +/- 0.6 as grade increased (p<0.008). Benign epithelium was nonreactive in 17/17 specimens without concurrent cancer (11 transurethral resection, 2 enucleation, 4 biopsy, p=0.002). Decreased NAG-1 expression in higher grade cancer is consistent with its known antitumorigenic, proapoptotic activities.


E2F7-EZH2 axis regulates PTEN/AKT/mTOR signalling and glioblastoma progression.
E2F transcription factors are considered to be important drivers of tumour growth. E2F7 is an atypical E2F factor, and its role in glioblastoma remains undefined. E2F7 expression was examined in patients by IHC and qRT-PCR. The overall survival probability was determined by statistical analyses. MTT assay, colony formation, cell-cycle assay, cell metastasis and the in vivo model were employed to determine the functional role of E2F7 in glioblastoma. Chromatin immunoprecipitation, luciferase assay and western blot were used to explore the underlying mechanisms. E2F7 was found to be up-regulated in glioblastoma patients, and high E2F7 expression was associated with poor overall survival in glioblastoma patients. Functional studies showed that E2F7 promoted cell proliferation, cell-cycle progression, cell metastasis and tumorigenicity abilities in vitro and in vivo. E2F7 promoted the transcription of EZH2 by binding to its promoter and increased H3K27me3 level. EZH2 recruited H3K27me3 to the promoter of PTEN and inhibited PTEN expression, and then activated the AKT/mTOR signalling pathway. In addition, restored expression of EZH2 recovered the abilities of cell proliferation and metastasis in E2F7-silencing cells. Collectively, our findings indicate that E2F7 promotes cell proliferation, cell metastasis and tumorigenesis via EZH2-mediated PTEN/AKT/mTOR pathway in glioblastoma.


Reverse total shoulder arthroplasty for the treatment of proximal humeral fractures: patterns of use among newly trained orthopedic surgeons.
This study compared the use of reverse and hemishoulder arthroplasty for the treatment of proximal humeral fractures among orthopedic surgeons taking part II of the American Board of Orthopaedic Surgery board examination. We hypothesized that the use of reverse shoulder arthroplasty for fractures in the elderly is increasing amongst newly trained orthopedic surgeons. We queried the American Board of Orthopaedic Surgery database for the cases of proximal humeral fractures treated with arthroplasty submitted between 2005 and 2012. We evaluated the prosthesis used, patient-specific factors, complications, and the difference in use by shoulder fellowship-trained surgeons. From 2005 to 2012, 5395 board-eligible orthopedic surgeons submitted cases to the database. Of these, 435 (mean, 54 per year) were proximal humeral fractures treated with arthroplasty. The overall incidence of reverse shoulder arthroplasty for fracture increased from 2% to 4% during 2005 to 2007 to 38% in 2012. Shoulder surgeons treated 5 times more proximal humeral fractures with shoulder arthroplasty and were also more than 20 times more likely to use a reverse implant (P < .0001). The difference in complication rates between reverse and hemishoulder arthroplasty was not significant (P = .49). Patients who received a hemiarthroplasty tended to be younger (mean age, 70.8 vs 75.7 years; P = .0015). Overall, the use of a hemiarthroplasty for fracture is still more common (62% in 2012), although the relative proportion of reverse implants is rising. Among shoulder surgeons, more than 50% of the arthroplasties performed for fractures during the past 3 years (2010-2012) have been reverse arthroplasties.


The emerging role of epigenetics in human autoimmune disorders.
Epigenetic pathways play a pivotal role in the development and function of the immune system. Over the last decade, a growing body of studies has been published out seeking to explain a correlation between epigenetic modifications and the development of autoimmune disorders. Epigenetic changes, such as DNA methylation, histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by regulating gene expression. This paper reviews the importance of epigenetic alterations during the development of the most prevalent human autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), Sjogren's syndrome (SS), autoimmune thyroid diseases (AITD), and type 1 diabetes (T1D), aiming to provide new insights in the pathogenesis of autoimmune diseases and the possibility to develop novel therapeutic approaches targeting the epigenome.


Protective methylation of immunoglobulin and T cell receptor (TcR) gene loci prior to induction of class switch and TcR recombination.
Methylation of the S gamma 1 switch region and C gamma 1 constant region gene from the immunoglobulin heavy chain locus and of the J beta 2 and C beta regions from the T cell receptor beta chain (TcR beta) locus is compared here in murine germ-line cells, nonlymphoid cells and lymphocytes. In germ-line cells and in lymphocytes prior to recombination all four regions show strong methylation, i.e. most Msp I sites are methylated. After activation of lymphocytes, demethylation is observed for those regions which are activated for recombination, at specific sites 5' of S gamma 1 in B cells activated with bacterial lipopolysaccharide and interleukin 4, and for J beta 2 in thymocytes. In nonlymphoid cells, where these regions cannot be used for recombination, considerable demethylation is observed for all four regions analyzed as compared to lymphocytes. The result implies an important role for methylation of recombinatorial regions. Methylation may be involved in protecting them from uninduced recombination, thus allowing regulated expression of distinct genes in lymphocyte ontogeny.


Internal iliac artery transposition for vascular reconstruction in a patient with life-threatening iatrogenic common iliac artery injury.
Major vascular injury during surgery is life threatening and can be a nightmare for any surgeon.We share our experience of a 42-year-old woman where right common iliac artery and both common iliac veins were accidentally injured during lumbar discectomy leading to haemorrhagic shock. Patient was resuscitated and explored. A 4 cm segment of right common iliac artery was found lacerated along with perforations of both iliac veins. Proximal segment of internal iliac artery was mobilised quickly and vascular continuity was restored by end-to-end anastomosis of this segment to the proximal segment of common iliac artery after excising the damaged segment. Iliac veins were repaired primarily. Patient made an uneventful recovery. We share this technique as it was found expeditious and effective and may benefit surgeons working in this field.


Using manganese-enhanced MRI to understand BOLD.
The 1990s were designated "The Decade of the Brain" by U.S. Congress, perhaps in great anticipation of the impact that functional neuroimaging techniques would have on advancing our understanding of how the brain is functionally organized. While it is impossible to overestimate the impact of functional MRI in neuroscience, many aspects of the blood oxygenation level-dependent (BOLD) contrast remain poorly understood, in great part due to the complex relationship between neural activity and hemodynamic changes. To better understand such relationship, it is important to probe neural activity independently. Manganese-enhanced MRI (MEMRI), when used to monitor neural activity, is a technique that uses the divalent manganese ion, Mn(2+), as a surrogate measure of calcium influx. A major advantage of using Mn(2+) as a functional marker is that the contrast obtained is directly related to the accumulation of the ion in excitable cells in an activity dependent manner. As such, the contrast in MEMRI is more directly related to neural activity then hemodynamic-based fMRI techniques. In the present work, the early conceptualization of MEMRI is reviewed, and the comparative experiments that have helped provide a better understanding of the spatial specificity of BOLD signal changes in the cortex is discussed.


Elderly female ultra-marathoners reduced the gap to male ultra-marathoners in Swiss running races.
Recent studies showed that female runners reduced the performance gap to male runners in endurance running with increasing age and race distance. However, the investigated samples were generally small. To investigate this further, the present study examined sex differences by age across various race distances (5, 10 km, half-marathon, marathon, and ultra-marathon) using a large dataset of over 1,100,000 race records from Switzerland over two decades (1999-2019). The study explored performance and participation disparities between male and female runners by employing diverse methods, such as descriptive statistics, histograms, scatter and line plots, correlations, and a predictive machine learning model. The results showed that female runners were more prevalent in shorter races (5, 10 km, half-marathon) and outnumbered male runners in 5 km races. However, as the race distance increased, the male-to-female ratio declined. Notably, the performance gap between sexes reduced with age until 70 years, after which it varied depending on the race distance. Among participants over 75 years old, ultra-marathon running exhibited the smallest sex difference in performance. Elderly female ultra-marathoners (75 years and older) displayed a performance difference of less than 4% compared to male ultra-marathoners, which may be attributed to the presence of highly selected outstanding female performers.


A case-control study of oral contraceptive use in women with adenocarcinoma of the uterine cervix.
To evaluate oral contraceptive (OC) use as a possible cause of the changed ratio between adenocarcinoma and squamous cell carcinoma of the uterine cervix a case-control study was performed. The OC use among 23 women with adenocarcinoma of the uterine cervix was compared with that of a matched group of 46 women with squamous cell carcinoma. No differences in percentage of OC use, duration of such use or period of OC use in relation to diagnosis could be demonstrated between the two groups compared.


The gasdermins, a protein family executing cell death and inflammation.
The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. Gasdermins contain a cytotoxic N-terminal domain and a C-terminal repressor domain connected by a flexible linker. Proteolytic cleavage between these two domains releases the intramolecular inhibition on the cytotoxic domain, allowing it to insert into cell membranes and form large oligomeric pores, which disrupts ion homeostasis and induces cell death. Gasdermin-induced pyroptosis plays a prominent role in many hereditary diseases and (auto)inflammatory disorders as well as in cancer. In this Review, we discuss recent developments in gasdermin research with a focus on mechanisms that control gasdermin activation, pore formation and functional consequences of gasdermin-induced membrane permeabilization.


The current status of robotic colorectal surgery training programmes.
Robotic-assisted colorectal surgery (RACS) is steadily increasing in popularity with an annual growth in the number of colorectal procedures undertaken robotically. Further upscaling of RACS requires structured and standardised robotic training to safeguard high-quality clinical outcomes. The aims of this systematic review were to assess the structure and assessment metrics of currently established RACS training programmes. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines was performed. Searches were performed of the Ovid Medline, Embase and Web of Science databases between 2000 and 27th November 2021 to identify studies reporting on training curricula in RACS. Core components of training programmes and their relevant outcome assessment metrics were extracted. Thirteen studies were identified, with all training programmes designed for the da Vinci platform (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Common elements of multimodal programmes included theoretical knowledge (76.9%), case observation (53.8%), simulation (100%) and proctored training (76.9%). Robotic skills acquisition was assessed primarily during the simulation phase (n = 4, 30.1%) and proctoring phase (n = 10, 76.9%). Performance metrics, consisting of time or assessment scores for VR simulation were only mandated in four (30.1%) studies. Objective assessment following proctored training was variably reported and employed a range of assessment metrics, including direct feedback (n = 3, 23.1%) or video feedback (n = 8, 61.5%). Five (38.4%) training programmes used the Global Assessment Score (GAS) forms. There is a broad consensus on the core multimodal components across current RACS training programmes; however, validated objective assessment is limited and needs to be appropriately standardised to ensure reproducible progression criteria and competency-based metrics are produced to robustly assess progression and competence.


Liver drains after surgery: what is the real practice? An international snapshot from the Li.DR.A.S. survey.
Despite current evidence, the use of drains in liver surgery is still controversial. We conducted an international survey to investigate the clinical use of drains in the E-AHPBA, A-HPBA and A-PHPBA communities. An open survey of 30 questions was prepared on Google-Form and distributed by email to all members. One hundred and ninety-one HPB surgeons responded to the survey. One hundred and twelve surgeons (58.6%) reported routine use of abdominal drains after liver resections. Eighty-eight (46.1%) responded that removal was driven by low volume and low bilirubin levels in the drains. For minor liver resection, 97 (50.8%) surgeons reported using drains selectively; in contrast, 134 (70.2%) surgeons prefer to use a drain always after major procedures. Among patients with cirrhosis, 87 (45.5%) surgeons reported routine drains placement, while 84 (44.0%) considered drains selectively. A no-drain policy was most prevalent among surgeons from North America (80%) versus Asian-Pacific (70.0%), European and African (60.8%), and South American (61.5%) surgeons. Among minimally invasive surgeons, 74.2% reported drain use only in selected cases versus 35.0% among surgeons who performed open surgery. The practice of draining after liver surgery is still highly variable among centers and surgeons around the world, with a high variability according to the underlying liver condition and planned surgical approach.


The relationship between early lexical and grammatical development in Spanish: evidence in children with different linguistic levels.
This study analyzes the relationship between lexical and grammatical development in Spanish children. The (European) Spanish version of the MacArthur-Bates CDI was used and administered to 593 Spanish-speaking children between the ages of 16 and 30-months-old. Regression analysis was applied to evaluate the relationship between age, vocabulary (total vocabulary, nouns, and verbs) and grammatical scores on two subsections of the Grammar Part. Total vocabulary explained a significantly greater proportion of variance in grammatical outcomes than age did. However, noun and verb vocabularies did not explain a greater proportion of variance in their respective morphologies than total vocabulary did. Additionally, the predictive relationship between vocabulary and grammar was found to be weaker for children whose scores were below the 10th percentile, although this could be due to the minor variability in this group and to extreme cases. We discuss the implications of these results in relation to the question of continuity between early vocabulary and grammar development in children.


Leiomyosarcoma of the Inferior Vena Cava Extending to the Right Atrium and Ventricle.
Primary tumors originating from the inferior vena cava (IVC), namely leiomyosarcoma, present significant challenges due to their poor prognostic features, including extensive extension and a substantial tumor burden. In this case, we present a 55-year-old female patient complaining of abdominal discomfort and vague abdominal pain. Additionally, we provide a comprehensive summary encompassing key aspects related to symptomatology, diagnostic approaches, treatment, and prognostic indicators. We also discuss the complexities involved in managing primary tumors of the inferior vena cava, emphasizing the critical significance of adopting a multidisciplinary team-based approach.


The effects of cognitive impairment on mortality among hospitalized patients with heart failure.
Cognitive impairment is a common, potentially reversible condition among older patients with heart failure. Because cerebral metabolic abnormalities have been associated with reduced survival in younger patients with advanced heart failure, we assessed the effect of cognitive impairment on the survival of older patients with heart failure. The association between cognitive dysfunction and in-hospital mortality was assessed in 1113 patients (mean [+/- SD] age, 78 +/- 9 years) who had been admitted for heart failure to 81 hospitals throughout Italy. One-year mortality was assessed in 968 patients with heart failure (age, 76 +/- 10 years) participating in the same study. Cognitive impairment was defined as a Hodkinson Abbreviated Mental Test score <7. In-hospital death occurred in 65 (18%) of the 357 participants with cognitive impairment and in 26 (3%) of the 756 patients with normal cognition (P <0.0001). Out-of-hospital mortality was 27% (51/191) among patients with cognitive impairment and 15% (115/777) among other participants (P <0.0001). In multivariate Cox regression models, decreasing levels of cognitive functioning were associated with increasing in-hospital mortality; cognitive impairment was associated with an almost fivefold increase in mortality (relative risk = 4.9; 95% confidence interval: 2.9 to 8.3) after adjusting for several potential confounders. Cognitive impairment is an independent prognostic marker in older patients with heart failure. Assessment of cognitive functioning, even by simple screening tests, should be part of the routine assessment of elderly patients with heart failure.


Improved clinical outcomes with abciximab therapy in acute myocardial infarction: a systematic overview of randomized clinical trials.
Investigations of glycoprotein (GP) IIb/IIIa inhibition in primary percutaneous coronary intervention (PCI) have suggested the efficacy of abciximab in improving clinical and angiographic outcomes, but sample-size limitations and variability in trial design preclude the ability to generalize these results to a broader patient population. Meta-analytic techniques were used to evaluate clinical outcomes from randomized trials comparing GP IIb/IIIa inhibition with placebo or control therapy in primary PCI for acute myocardial infarction (MI). In 3266 patients, treatment with abciximab significantly reduced the 30-day composite end point of death, reinfarction, or ischemic or urgent target-vessel revascularization (TVR; odds ratio [OR], 0.54; 95% CI, 0.40-0.72), with trends toward reduced 30-day death and death or reinfarction. Abciximab resulted in an increased likelihood of major bleeding (OR, 1.74; 95% CI, 1.11-2.72). By 6 months, abciximab significantly reduced the occurrence of death, reinfarction, or any TVR (OR, 0.80; 95% CI, 0.67-0.97), and there were positive trends favoring a decrease in mortality alone and the composite of death or reinfarction. Treatment with abciximab significantly reduces early adverse ischemic events, a clinical benefit that is maintained at 6-month follow-up. These findings support the use of adjunctive GP IIb/IIIa inhibition in primary PCI.


Slit-lamp studies of the rhesus monkey eye. I. Survey of the anterior segment.
Slit-lamp photographic studies of 144 caged rhesus monkeys, aged 2 months to 35 years, show age-related changes in anterior-chamber depth, lens thickness, anterior and posterior curvatures of the lens, and location of the posterior lens surface relative to the anterior corneal surface. For these parameters, as well as for those measured by other techniques, a difference in slope magnitude and (or) slope sign was found between the growth phase which lasts for 5-6 years, and the adult phase (greater than 5-6 years). Age-related changes in the adult rhesus eye are qualitatively similar in almost all aspects to those observed in the human eye, indicating that the rhesus is a good animal model for the study of human loss of accommodative amplitude.


Pharmacokinetic and pharmacodynamic consequences of stereoselective drug metabolism in man.
The examples discussed demonstrate the importance of stereoselective drug metabolism and raise the question of whether the therapeutic use of racemic drugs is still justified. There is no straightforward answer to this question. If only quantitative differences in therapeutic activity exist and the less active enantiomer is not predominantly responsible for side effects, the therapeutic benefit gained by using the more active enantiomer is only marginal and does not justify the substantial increase in costs involved in manufacturing such a drug preparation. However, if stereoselectivity in therapeutic activity is pronounced and adverse drug reactions are caused mainly by the less active isomer then an isomeric pure drug preparation should be used.


The complete genome sequences for three simian enteroviruses isolated from captive primates.
In a recent study, we used RT-PCR and partial genome sequencing to detect simian enteroviruses SV6, SV19 and SV46, as well as two new enterovirus types (EV92 and EV103) in fecal specimens from rhesus macaques (Macaca mulatta), pigtail macaques (M. nemestrina), and sooty mangabeys (Cercocebus atys) with diarrheal disease at a US primate center. The complete genome sequences of representative SV46, EV92, and EV103 strains, presented here, show that SV46 and EV92 are typical of the simian enteroviruses classified within the species Human enterovirus A, while EV103 appears to belong to an unclassified species that also contains SV6 and N125/N203.


Among patients with unhealthy alcohol use, those with HIV are less likely than those without to receive evidence-based alcohol-related care: A national VA study.
Alcohol use has important adverse effects on people living with HIV (PLWH). This study of patients with recognized unhealthy alcohol use estimated and compared rates of alcohol-related care received by PLWH and HIV- patients. Outpatients from the Veterans Health Administration who had one or more positive screen(s) for unhealthy alcohol use (AUDIT-C≥5) documented in their medical records 10/2009-5/2013 were eligible. Primary and secondary outcomes were brief intervention documented ≤14days after a positive alcohol screen, and a composite measure of any alcohol-related care (brief intervention, specialty addictions treatment or pharmacotherapy documented ≤365 days), respectively. Unadjusted and adjusted regression analyses compared alcohol-related care outcomes in PLWH and HIV- patients. The sample included 830,825 outpatients (3,514 PLWH), reflecting 1,172,606 positive screens (1-5 per patient). For PLWH, 57.0% (95% confidence interval 55.4-58.5%) of positive screens were followed by brief intervention, compared to 73.8% (73.7-73.9%) for HIV- patients [relative rate: 0.77 (0.75-0.79), p<0.001]. After adjustment, comparable proportions were 61.0% (59.3-62.6%) for PLWH and 73.7% (73.6-73.8%) for HIV- patients [adjusted RR=0.83 (0.80-0.85); p<0.001]. Secondary outcome results were similar: for PLWH and HIV- patients, 67.1% (65.7-68.6%) and 77.7% (95% CI 77.7-77.8%) of positive screens, respectively, were followed by any alcohol-related care after adjustment [adjusted RR=0.86 (0.85-0.88), p<0.001]. In this large national sample of VA outpatients with unhealthy alcohol use, PLWH were less likely to receive alcohol-related care than HIV- patients. Special efforts may be needed to ensure alcohol-related care reaches PLWH.


A mechanically driven form of Kirigami as a route to 3D mesostructures in micro/nanomembranes.
Assembly of 3D micro/nanostructures in advanced functional materials has important implications across broad areas of technology. Existing approaches are compatible, however, only with narrow classes of materials and/or 3D geometries. This paper introduces ideas for a form of Kirigami that allows precise, mechanically driven assembly of 3D mesostructures of diverse materials from 2D micro/nanomembranes with strategically designed geometries and patterns of cuts. Theoretical and experimental studies demonstrate applicability of the methods across length scales from macro to nano, in materials ranging from monocrystalline silicon to plastic, with levels of topographical complexity that significantly exceed those that can be achieved using other approaches. A broad set of examples includes 3D silicon mesostructures and hybrid nanomembrane-nanoribbon systems, including heterogeneous combinations with polymers and metals, with critical dimensions that range from 100 nm to 30 mm. A 3D mechanically tunable optical transmission window provides an application example of this Kirigami process, enabled by theoretically guided design.


Purification and characterization of metallothionein-like cadmium binding protein from Asian periwinkle Littorina brevicula.
Although mussels and oysters in the ocean are known to act as bioconcentrators for contaminants such as heavy metals, their ability to survive in heavily polluted water is relatively limited. The Asian periwinkle, Littorina brevicula, is one species that can accumulate a variety of environmental heavy metals, and the expression of its metal binding protein (MBP) is induced by cadmium. To better characterize this protein and its detoxification mechanism against cadmium, the present work examined the induction of a cadmium binding protein (Cd-BP) in Littorina brevicula exposed to 400 microg/l CdCl(2) for 30 days. The induced Cd-BP was purified by chromatography from the supernatants of homogenized organs (digestive gland, gonad, gill and kidney). This Cd-BP was found to consist of 103 amino acids, was rich in Cys (21 residues), and partial C-terminal sequence obtained by MALDI-TOF MS analysis revealed a Cys-XXX-Cys motif, which resembles a typical feature of mollusc metallothionein (MT). The Cd-BP molecular weight of 9.8 kDa is a little larger than that of other MTs.


Common receptor for Bacillus thuringiensis toxins Cry1Ac, Cry1Fa, and Cry1Ja in Helicoverpa armigera, Helicoverpa zea, and Spodoptera exigua.
Binding studies using (125)I-Cry1Ac and biotinylated Cry1Fa toxins indicate the occurrence of a common receptor for Cry1Ac, Cry1Fa, and Cry1Ja in Helicoverpa armigera, Helicoverpa zea, and Spodoptera exigua. Our results, along with previous binding data and the observed cases of cross-resistance, suggest that this pattern seems to be widespread among lepidopteran species.


Heterogeneity in the Relationship of Substance Use to Risky Sexual Behavior Among Justice-Involved Youth: A Regression Mixture Modeling Approach.
Justice-involved adolescents engage in high levels of risky sexual behavior and substance use, and understanding potential relationships among these constructs is important for effective HIV/STI prevention. A regression mixture modeling approach was used to determine whether subgroups could be identified based on the regression of two indicators of sexual risk (condom use and frequency of intercourse) on three measures of substance use (alcohol, marijuana and hard drugs). Three classes were observed among n = 596 adolescents on probation: none of the substances predicted outcomes for approximately 18 % of the sample; alcohol and marijuana use were predictive for approximately 59 % of the sample, and marijuana use and hard drug use were predictive in approximately 23 % of the sample. Demographic, individual difference, and additional sexual and substance use risk variables were examined in relation to class membership. Findings are discussed in terms of understanding profiles of risk behavior among at-risk youth.


Changes in prenatal care and birth outcomes after federally qualified health center expansion.
To evaluate whether the expansion of Federally Qualified Health Centers (FQHCs) improved late prenatal care initiation, low birth weight, and preterm birth among Medicaid-covered or uninsured individuals. We identified all FQHCs in California using the Health Resources and Services Administration's Uniform Data System from 2000 to 2019. We used data from the U.S. Census American Community Survey to describe area characteristics. We measured outcomes in California birth certificate data from 2007 to 2019. We compared areas that received their first FQHC between 2011 and 2016 to areas that received it later or that had never had an FQHC. Specifically, we used a synthetic control with a staggered adoption approach to calculate non-parametric estimates of the average treatment effects on the treated areas. The key outcome variables were the rate of Medicaid or uninsured births with late prenatal care initiation (>3 months' gestation), with low birth weight (<2500 grams), or with preterm birth (<37 weeks' gestation). The analysis was limited to births covered by Medicaid or that were uninsured, as indicated on the birth certificate. The 55 areas in California that received their first FQHC in 2011-2016 were more populous; their residents were more likely to be covered by Medicaid, to be low-income, or to be Hispanic than residents of the 48 areas that did not have an FQHC by the end of the study period. We found no statistically significant impact of the first FQHC on rates of late prenatal care initiation (ATT: -10.4 [95% CI -38.1, 15.0]), low birth weight (ATT: 0.2 [95% CI -7.1, 5.4]), or preterm birth (ATT: -7.0 [95% CI -15.5, 2.3]). Our results from California suggest that access to primary and prenatal care may not be enough to improve these outcomes. Future work should evaluate the impact of ongoing initiatives to increase access to maternal health care at FQHCs through targeted workforce investments.


Pleural protein concentration and liquid volume in spontaneously hypertensive rats.
To determine the effect of systemic vascular hypertension on fluid balance in the pleural space, we studied the spontaneously hypertensive rat (SHR) and its genetic normotensive control, the Wistar-Kyoto rat (WKY). We measured arterial and venous pressures, total protein and albumin concentrations of pleural liquid and plasma, pleural space thickness, and pleural surface pressure in SHR and WKY that were matched for weight (260-300 g). Protein concentration was measured by a manual Biuret test and albumin concentration was measured by the bromcresol green colorimetric method. Pleural liquid thickness was measured in situ using light microscopy. Pleural surface pressure was assumed to equal pleural liquid pressure. In the SHR, total protein and albumin concentrations in pleural liquid were lower than in WKY, and pleural space thickness was larger in SHR than in WKY. These results are consistent with a higher capillary pressure and greater fluid filtration in SHR.


Tweet topics and sentiments relating to distance learning among Italian Twitter users.
The outbreak of COVID-19 forced a dramatic shift in education, from in-person learning to an increased use of distance learning over the past 2 years. Opinions and sentiments regarding this switch from traditional to remote classes can be tracked in real time in microblog messages promptly shared by Twitter users, who constitute a large and ever-increasing number of individuals today. Given this framework, the present study aims to investigate sentiments and topics related to distance learning in Italy from March 2020 to November 2021. A two-step sentiment analysis was performed using the VADER model and the syuzhet package to understand the overall sentiments and emotions. A dynamic latent Dirichlet allocation model (DLDA) was built to identify commonly discussed topics in tweets and their evolution over time. The results show a modest majority of negative opinions, which shifted over time until the trend reversed. Among the eight emotions of the syuzhet package, 'trust' was the most positive emotion observed in the tweets, while 'fear' and 'sadness' were the top negative emotions. Our analysis also identified three topics: (1) requests for support measures for distance learning, (2) concerns about distance learning and its application, and (3) anxiety about the government decrees introducing the red zones and the corresponding restrictions. People's attitudes changed over time. The concerns about distance learning and its future applications (topic 2) gained importance in the latter stages of 2021, while the first and third topics, which were ranked highly at first, started a steep descent in the last part of the period. The results indicate that even if current distance learning ends, the Italian people are concerned that any new emergency will bring distance learning back into use again.


3D Lithiophilic "Hairy" Si Nanowire Arrays @ Carbon Scaffold Favor a Flexible and Stable Lithium Composite Anode.
Lithium metal anode is considered to be a promising candidate for high-energy-density lithium-based batteries. However, the safety issue induced by uncontrollable dendrite growth hinders the commercialization of a Li anode. Herein, self-supported three-dimensional flexible carbon cloth covered with a lithiophilic silicon nanowire array is constructed as the host for loading of molten Li to achieve the C/SiNW/Li composite anode. The electrode component of the carbon cloth provides the flexible and conductive substrate to accommodate the volume change during the stripping/plating of Li and facilitate more efficient electron transport, while silicon nanowires improve the wettability of the carbon host to liquefied Li and render uniform Li deposition on the surface of the composite electrode. The as-prepared C/SiNW/Li composite anode exhibits enhanced cycling stability with a low hysteresis of 40 mV for more than 200 h and a better rate tolerance even at a current density of up to 5 mA cm-2. When coupling with the LiNi0.5Mn1.5O4 cathode, the full cells using the C/SiNW/Li composite anode demonstrate a remarkable electrochemical performance with an exceptional rate performance of up to 10 C and stable long-term cycling (the capacity retention of 62% at a 5 C rate over 2000 cycles), which is much higher than the cells with pure Li anode. This work provides a universal strategy to fabricate the flexible and stable carbon-based Li metal anode toward high-energy-density batteries.


SDS-PAGE technique as biomarker for fish toxicological studies.
Although many studies on the hematological and biochemical parameters in fishes have been done, still there are some shortage in the estimation and evaluation of the baseline's values of marine and freshwater fishes. Recently, the use of hematology and biochemistry of fishes in toxicology, aquaculture, environmental pollution, feeding, and antioxidants studies has been increased. In this study we introduced the importance of those parameters and their importance as biomarkers in fish toxicology from previous literature and as new findings. Hemato-biochemical parameters were widely used in fish toxicological studies. Many researches have used the protein electrophoresis as a valid tool to determining intra and inter-specific variation among species. Protein profile was extensively used in determining the health of fish, as indicators of anemia or other diseases provide information about the existence of the disease, and in the diagnosis of disease. So, to carry out the aim of this study, we reported one of the more advanced techniques used SDS-PAGE as molecular biomarker for protein profile analysis in fish with shedding the light on the importance of hematological and biochemical parameters in fish toxicological studies.


Cardiac Protein Kinase D1 ablation alters the myocytes β-adrenergic response.
β-adrenergic (β-AR) signaling is essential for the adaptation of the heart to exercise and stress. Chronic stress leads to the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase D (PKD). Unlike CaMKII, the effects of PKD on excitation-contraction coupling (ECC) remain unclear. To elucidate the mechanisms of PKD-dependent ECC regulation, we used hearts from cardiac-specific PKD1 knockout (PKD1 cKO) mice and wild-type (WT) littermates. We measured calcium transients (CaT), Ca2+ sparks, contraction and L-type Ca2+ current in paced cardiomyocytes under acute β-AR stimulation with isoproterenol (ISO; 100 nM). Sarcoplasmic reticulum (SR) Ca2+ load was assessed by rapid caffeine (10 mM) induced Ca2+ release. Expression and phosphorylation of ECC proteins phospholambam (PLB), troponin I (TnI), ryanodine receptor (RyR), sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) were evaluated by western blotting. At baseline, CaT amplitude and decay tau, Ca2+ spark frequency, SR Ca2+ load, L-type Ca2+ current, contractility, and expression and phosphorylation of ECC protein were all similar in PKD1 cKO vs. WT. However, PKD1 cKO cardiomyocytes presented a diminished ISO response vs. WT with less increase in CaT amplitude, slower [Ca2+]i decline, lower Ca2+ spark rate and lower RyR phosphorylation, but with similar SR Ca2+ load, L-type Ca2+ current, contraction and phosphorylation of PLB and TnI. We infer that the presence of PKD1 allows full cardiomyocyte β-adrenergic responsiveness by allowing optimal enhancement in SR Ca2+ uptake and RyR sensitivity, but not altering L-type Ca2+ current, TnI phosphorylation or contractile response. Further studies are necessary to elucidate the specific mechanisms by which PKD1 is regulating RyR sensitivity. We conclude that the presence of basal PKD1 activity in cardiac ventricular myocytes contributes to normal β-adrenergic responses in Ca2+ handling.


Converting an implant-supported fixed prosthesis to an overdenture because of fixture loss: a case report.
A patient with a failed implant-supported prosthesis was treated with an immediate interim overdenture. After insertion of a bar modified from the prosthesis substructure, the patient was restored with an implant-supported overdenture. A bar soft liner retention system was used to aid retention and stability of the overdenture.


Emotional non-acceptance mediates the relationship between insecure attachment and specific psychopathology in women with eating disorders.
Insecure attachment is considered a general risk factor for eating disorders (ED). Emotion dysregulation has been proposed as one of the possible mechanisms by which attachment insecurity may affect ED psychopathology. Aim of the present study was to investigate whether difficulties in acceptance of emotions or emotional clarity may mediate the connection between insecure attachment and ED psychopathology. One hundred and twenty patients participated and completed the Italian version of Eating Disorder Inventory-2, Experience in Close Relationship questionnaire and Difficulties in Emotion Regulation Scale. A mediator path model was performed, in which insecure attachment dimensions were set as independent variables, ED specific psychopathology measures as dependent variables, and non-acceptance of emotion and lack of emotional clarity as mediators. The association between both attachment avoidance and anxiety and ED specific symptoms was mediated by emotional non-acceptance, but not by emotional clarity. This study showed the importance to address emotion regulation in individuals with ED, focussing on improving emotional acceptance. Exploring early developmental processes which lead to non-acceptance of emotions could improve this psychological trait in people with ED.


Development of human white matter fiber pathways: From newborn to adult ages.
Major long-range white matter pathways (cingulum, fornix, uncinate fasciculus [UF], inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], thalamocortical [TC], and corpus callosal [CC] pathways) were identified in eighty-three healthy humans ranging from newborn to adult ages. We tracked developmental changes using high-angular resolution diffusion MR tractography. Fractional anisotropy (FA), apparent diffusion coefficient, number, length, and volume were measured in pathways in each subject. Newborns had fewer, and more sparse, pathways than those of the older subjects. FA, number, length, and volume of pathways gradually increased with age and reached a plateau between 3 and 5 years of age. Data were further analyzed by normalizing with mean adult values as well as with each subject's whole brain values. Comparing subjects of 3 years old and under to those over 3 years old, the studied pathways showed differential growth patterns. The CC, bilateral cingulum, bilateral TC, and the left IFOF pathways showed significant growth both in volume and length, while the bilateral fornix, bilateral ILF and bilateral UF showed significant growth only in volume. The TC and CC took similar growth patterns with the whole brain. FA values of the cingulum and IFOF, and the length of ILF showed leftward asymmetry. The fornix, ILF and UF occupied decreased space compared to the whole brain during development with higher FA values, likely corresponding to extensive maturation of the pathways compared to the mean whole brain maturation. We believe that the outcome of this study will provide an important database for future reference.


Spontaneous epileptiform discharges in isolated human cortical slices from epileptic patients.
Human epileptic in vitro brain slices were obtained at ablative neurosurgical procedures and examined for spontaneous extracellular field potentials. Electrical events resembling interictal spikes and seizure discharges were observed in tissue from the electrocorticographic epileptic foci, but not in control tissue. It appears that important differences between the epileptic focus and normal tissue are maintained in vitro.


Wandering spleen in three children.
Three children with wandering spleen are presented. Liver-spleen technetium99m sulphur colloid scintigraphy is a helpful diagnostic tool that will demonstrate the abnormally located spleen or absent splenic activity when the blood supply is interrupted by a twisted pedicle. The diagnosis can also be made by angiography, but this relatively elaborate procedure is usually not necessary. Absence of the normal ligamentous attachments of the spleen associated with a long splenic pedicle may well be the cause of the wandering spleen and its torsion.


Doxorubicin-encapsulated thermosensitive liposomes modified with poly(N-isopropylacrylamide-co-acrylamide): drug release behavior and stability in the presence of serum.
In the field of the temperature sensitive drug delivery systems, we studied on the surface modification of liposomes by using poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAM) and polyethyleneglycol (PEG) to increase the release of doxorubicin (DOX) from liposomes and prolong the stability of liposomes in the presence of serum. The release of DOX from the PNIPAM-AAM/PEG modified liposomes is enhanced around the transition temperature of the polymer. In addition, the stability of the PNIPAM-AAM/PEG modified liposomes in serum shows a high level comparing with polymer unmodified liposomes. These results suggest that the modification on the surface of liposomes with both PNIPAM-AAM and PEG enhances the drug release from liposomes and reduces the protein adsorption in serum.


Remote monitoring of cardiovascular implantable devices in the pediatric population improves detection of adverse events.
With the exponential growth of cardiovascular implantable electronic devices (CIEDs) in pediatric patients, a new method of long-term surveillance, remote monitoring (RM), has become the standard of care. The purpose of this study was to determine the usefulness of RM as a monitoring tool in the pediatric population. A retrospective review was performed of 198 patients at the University of Iowa Children's Hospital who had CIEDs. Data transmitted by RM were analyzed. The following data were examined: patient demographics; median interval between transmissions; detection of adverse events requiring corrective measures, including detection of lead failure; detection of arrhythmias and device malfunctions independent of symptoms; time gained in the detection of events using RM versus standard practice; the validity of RM; and the impact of RM on data management. Of 198 patients, 162 submitted 615 RM transmissions. The median time between remote transmissions was 91 days. Of 615 total transmissions, 16 % had true adverse events with 11 % prompting clinical intervention. Of those events requiring clinical response, 61 % of patients reported symptoms. The median interval between last follow-up and occurrence of events detected by RM was 46 days, representing a gain of 134 days for patients followed-up at 6-month intervals and 44 days for patients followed-up at 3 month-intervals. The sensitivity and specificity of RM were found to be 99 and 72 %, respectively. The positive and negative predictive values were found to be 41 and 99 %, respectively. RM allows for early identification of arrhythmias and device malfunctions, thus prompting earlier corrective measures and improving care and safety in pediatric patients.


Effects of taxifolin on aspirin-induced gastric damage in rats: macroscopic and biochemical evaluation.
Taxifolin (dihydroquercetin) is a flavanonol isolated from various plants and has antioxidant effects. The aim of our study was to macroscopically and biochemically investigate the effects of taxifolin on aspirin-induced oxidative gastric damage in rats and to evaluate them by comparison with those of famotidine. Rats were divided into four drug administration groups: a healthy control group, an aspirin-only group (ASG), a taxifolin + aspirin group (TASG), and a famotidine + aspirin group (FASG). The results revealed that in light of the results that we obtained, 50 mg/kg taxifolin had anti-ulcer effects. At this dose, taxifolin was able to bring COX-1 activities to a level close to those seen in healthy rats with appropriate macroscopic, oxidant/antioxidant, and biochemical parameters. Based on these results, it can be said that taxifolin may be successfully used as a more potent alternative to famotidine, which is the currently accepted treatment for aspirin-induced ulcers.


Glutathione conjugates of ochratoxin A as biomarkers of exposure.
In the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity.


Endoscopic management of urethrovesical anastomotic obliteration following radical retropubic prostatectomy.
Urethrovesical anastomotic obliterative strictures are uncommonly reported sequelae of radical retropubic prostatectomy. We report a method to re-establish endoscopically continuity between the bladder and urethra after this complication.


Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase.
To analyze if oocytes can be obtained in all patients before cancer treatment within 2 weeks by initiating ovarian stimulation during the follicular or luteal phase. Prospective controlled multicenter trial. Four university-based centers. Forty cancer patients before chemotherapy. Twenty-eight patients were stimulated with gonadotropins in the follicular phase (group I). In 12 patients (group II), ovarian stimulation was initiated in the luteal phase, and these received GnRH antagonists and recombinant FSH. In 14 patients, 143 oocytes were further processed for fertilization by intracytoplasmic sperm injection (ICSI). Number of oocytes aspirated after ovarian stimulation, cumulative FSH/hMG dosage, viability and maturity of oocytes, and fertilization rate by ICSI. Patients in group I (age 27.6 +/- 4.9 yrs) were stimulated on average for 10.6 days, and patients in group II (age 31.2 +/- 5.7 yrs) for 11.4 days. Total amount of FSH was on average 2,255 IU (I) and 2,720 IU (II) per patient. Average and median numbers of aspirated oocytes were, respectively, 13.1 and 11.5 (I) versus 10.0 and 8.5 (II); 83.7% (I) and 80.4% (II) of the oocytes were mature and viable and could be treated by ICSI. Fertilization rate was 61.0% (I) versus 75.6% (II). This pilot study suggests that oocytes can be obtained before cancer treatment efficiently irrespective of the phase of the menstrual cycle.


Intraosseous capillary hemangioma of the frontal bone.
A 31-year-old woman with a history of slowly progressive proptosis associated with blepharoptosis was found radiographically to have a lytic lesion of the frontal bone. Complete surgical excision of the bony mass was performed. Histopathologically the tumor was a capillary hemangioma. Follow-up information two years later showed that the patient was alive and well, without clinical evidence of recurrence. Plain x-ray films appear to be more reliable for diagnosis than computed tomography exhibiting the characteristic sunburst pattern of intraosseous hemangiomas.


Infection prevention knowledge, practice, and its associated factors among healthcare providers in primary healthcare unit of Wogdie District, Northeast Ethiopia, 2019: a cross-sectional study.
Adequate knowledge and safe practice of infection prevention among healthcare providers are vital to prevent nosocomial infections. Thus, this study aimed to assess the level of knowledge and practices of healthcare providers towards infection prevention and its associated factors in the health facilities of Wogdie District, Northern Ethiopia. Institution based cross-sectional study was conducted among 171 healthcare providers who were selected by a simple random sampling technique. Data were collected using interviewer-administered questionnaire. Multivariable logistic regression was performed to identify factors associated with knowledge and practice of infection prevention. About 70.8 and 55.0% of healthcare providers had adequate knowledge and safe practice of infection prevention respectively. Having infection prevention guideline (AOR = 3.65, 95% CI; 1.26, 10.54), taking infection prevention training (AOR = 2.2, 95% CI; 1.01, 4.75), having five years or more work experience (AOR = 1.52:95%CI; 1.13, 4.51), and working in maternity unit (AOR = 1.67:95%CI; 1.38-5.23) were positively associated with adequate knowledge of infection prevention. The odds of safe practice were higher in participants who received infection prevention training (AOR: 2.4; 95% CI; 1.01, 4.75) but lower among healthcare providers who are working in the facility which has no continuous water supply (AOR = 0.48:95% CI; 0.21, 0.83). A significant proportion of healthcare providers had inadequate knowledge and unsafe practice of infection prevention. To improve healthcare worker's knowledge of infection prevention, adequate pre-service as well as on job training should be given.


The influence of dipeptidyl peptidase-4 inhibitor on the progression of type B intramural hematoma.
Investigating whether dipeptidyl peptidase-4 inhibitors (DPP4i) could influence the progression of type B intramural hematoma (IMHB) in patients with diabetes mellitus (DM). Uncomplicated IMHB patients were matched by age, sex, and body mass index. Cox proportional hazard models were constructed to identify risk factors. A Kaplan-Meier survival analysis was used to estimate all-cause and aorta-related mortality. Ninety-six matched IMHB patients were divided into Group A (n = 32, IMHB patients without DM), Group B (n = 32, IMHB patients with DMreceiving oral antidiabetic drugs [without DPP4i]) and Group C (n = 32, IMHB patients with DM receiving oral antidiabetic drugs [with DPP4i]). Group C had the lowest rate of aorta-related adverse events (3.1%), aorta-related mortality (0.0%) and reintervention (3.1%). Cox proportional hazard models revealed that a lower eosinophil count (per 0.1, HR, 0.48; 95% CI, 0.29-0.79, P = 0.004) and a higher neutrophil to lymphocyte ratio (NLR) (HR, 1.13; 95% CI, 1.05-1.21, P = 0.001) were associated with higher occurrences of aorta-related adverse events. A lower eosinophil count (per 0.1, HR, 0.40; 95% CI, 0.18-0.89, P = 0.025) and a higher NLR (HR, 1.19; 95% CI, 1.08-1.32, P = 0.001) were also associated with increased aorta-related mortality. DPP4i administration in DM patients with IMHB was associated with lower aorta-related mortality and more benign progression than in those who did not receive DPP4i or those without DM. Furthermore, a higher eosinophil count and a lower NLR ratio are potential protective factors that may explain the potential therapeutic benefit of DPP4i.


The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing's syndrome.
In a cohort study of 182 consecutive patients with active endogenous Cushing's syndrome, the only predictor of fracture occurrence after adjustment for age, gender bone mineral density (BMD) and trabecular bone score (TBS) was 24-h urinary free cortisol (24hUFC) levels with a threshold of 1472 nmol/24 h (odds ratio, 3.00 (95% confidence interval (CI), 1.52-5.92); p = 0.002). The aim was to estimate the risk factors for fracture in subjects with endogenous Cushing's syndrome (CS) and to evaluate the value of the TBS in these patients. All enrolled patients with CS (n = 182) were interviewed in relation to low-traumatic fractures and underwent lateral X-ray imaging from T4 to L5. BMD measurements were performed using a DXA Prodigy device (GEHC Lunar, Madison, Wisconsin, USA). The TBS was derived retrospectively from existing BMD scans, blinded to clinical outcome, using TBS iNsight software v2.1 (Medimaps, Merignac, France). Urinary free cortisol (24hUFC) was measured by immunochemiluminescence assay (reference range, 60-413 nmol/24 h). Among enrolled patients with CS (149 females; 33 males; mean age, 37.8 years (95% confidence interval, 34.2-39.1); 24hUFC, 2370 nmol/24 h (2087-2632), fractures were confirmed in 81 (44.5%) patients, with 70 suffering from vertebral fractures, which were multiple in 53 cases; 24 patients reported non-vertebral fractures. The mean spine TBS was 1.207 (1.187-1.228), and TBS Z-score was -1.86 (-2.07 to -1.65); area under the curve (AUC) was used to predict fracture (mean spine TBS) = 0.548 (95% CI, 0.454-0.641)). In the final regression model, the only predictor of fracture occurrence was 24hUFC levels (p = 0.001), with an increase of 1.041 (95% CI, 1.019-1.063), calculated for every 100 nmol/24-h cortisol elevation (AUC (24hUFC) = 0.705 (95% CI, 0.629-0.782)). Young patients with CS have a low TBS. However, the only predictor of low traumatic fracture is the severity of the disease itself, indicated by high 24hUFC levels.


Factors Affecting the Job Satisfaction of U.S. Adult Endocrinologists: A Nationwide Survey.
Despite the increased demand and worsening burnout among U.S. endocrinologists, there is a paucity of data on job satisfaction and associated factors. This study examines the factors associated with job satisfaction among a nationally representative sample of U.S. endocrinologists. We conducted a cross-sectional survey of 1700 U.S. adult endocrinologists on the Facebook group "Endocrinologists." The survey was conducted over 4 weeks using an anonymous online questionnaire. The 45-question survey assessed job and salary satisfaction scores on a 5-point Likert scale along with multiple job-related variables. Univariate and multivariate analyses were conducted to identify the factors affecting job satisfaction. Out of 1700, 654 adult endocrinologists (504 women and 139 men) completed the survey. The mean job satisfaction score was 3.72 ± 0.86, with 67.5% having high job satisfaction. Comparatively, 339 (52.1%) had high salary satisfaction. There was a statistically significant relationship between the job and salary satisfaction scores (P < .01). Factors significantly associated with the job satisfaction score (P < .05) included the practice region, gender, number of medical assistants per endocrinologist, self-performance of thyroid ultrasound, and number of patients in the hospital per week. Multivariate analysis showed that full-time employment, along with high salary satisfaction, seeing fewer new patients per day, performing thyroid ultrasounds, and fewer patients in the hospital were associated with the highest job satisfaction. This study found about one-third of endocrinologists to have lower job satisfaction and identified multiple modifiable factors associated with endocrinologists' job satisfaction. Interventions focused on these potentially modifiable factors may improve job satisfaction among U.S. endocrinologists.


How does cirrhosis impact mortality, morbidity, and resource utilization in non-variceal upper gastrointestinal bleeding? A nationwide analysis.
Upper gastrointestinal bleeding is common in liver cirrhosis patients. Studies have described the prognostic impact of liver disease in non-variceal upper gastrointestinal bleeding (NVUGIB), but a direct subgroup comparison is lacking using a large database. To study the impact of NVUGIB on hospital-based outcomes in patients with cirrhosis. This is a retrospective study using Nationwide Inpatient Sample (NIS) employing International Classification of Diseases (ICD-10) codes for adult patients with a primary diagnosis of NVUGIB. Mortality, morbidity, and resource utilization were compared. Analyses were performed using STATA, proportions were compared using Fisher exact test, and continuous variables using Student's t-test. Confounding variables were adjusted using propensity matching, multivariate logistic, and linear regression analyses. Of 107,001,355 discharges, 957,719 had a diagnosis of NVUGIB. Of those, 92,439 had cirrhosis upon admission. NVUGIB patients with cirrhosis had higher adjusted odds of mortality and intensive care unit (ICU) admission than patients without cirrhosis (adjusted odds ratio (AOR) for mortality 1.31, p < 0.001, ICU admission AOR = 1.29, p < 0.001). NVUGIB patients with cirrhosis had shorter length of stay (LOS) by 0.44 days (p < 0.001), greater hospital costs per day ($3114 vs. $2810, p < 0.001), and lower odds of acute kidney injury (AOR = 0.81, p < 0.001). In addition, the cirrhotic patients had higher odds of receiving endoscopic therapy (AOR = 1.08, p < 0.001). There was no difference between the 2 groups' requirements of packed red blood cell transfusion, parenteral nutrition, hypovolaemic shock, and endotracheal intubation. We also identified novel independent predictors of mortality from NVUGIB in cirrhosis patients. Cirrhosis presents greater mortality and morbidity burden and greater healthcare resource utilization from NVUGIB.


National Enforcement of the FSPTCA at Point-of-Sale.
To describe patterns in the enforcement of the US Food and Drug Administration's current compliance check program. Data on retail violation rates (RVR) resulting from compliance checks were analyzed. Novel methods were developed to quantify violations and unify data on retail location and violation type. As of July 2013, 42 states and 3 US territories conducted compliance checks. Ninety-six percent of warning letters and 100% of Civil Monetary Penalties addressed sales to minors. RVRs varied significantly over time (OR = 1.15) and between states (ICC = 0.18). The compliance checks database makes it possible to examine how retail enforcement is unfolding over time and place. Results reveal an emphasis on youth access violations, presenting opportunities for research on regulations designed to reduce youth access.


Silencing the cochlear amplifier by immobilizing prestin.
Achieving the exquisite sensitivity and frequency selectivity of the mammalian ear requires active amplification of input sound. In this issue of Neuron, Dallos and colleagues demonstrate that the molecular motor prestin, which drives shape changes in the soma of mechanosensory hair cells, underlies mechanical feedback mechanisms for sound amplification in mammals.