Improving the Reliability Between the BODE Index and the BODS Index in Which the 6-Min Walk Test Was Replaced with the Five-Repetition Sit-to-Stand Test.
The BODS index has been confirmed to have predictive properties similar to the original BODE index for mortality in COPD. We evaluated the agreement between the BODS index and the BODE and explored with an updated BODS how this agreement could be improved and its ability to correctly discriminate individual participants' mortality in a prospective cohort study. We included prospectively a consecutive sample of 137 patients with COPD, between 40 and 80 years, during 2014 and followed for 5 years (2014-2019) in the Pneumology section of a public university hospital in Spain. They participated in the baseline data collection, which included BODE- and BODS-related measurements and prognostic factors, and were followed up for 5-year mortality. We used Bland-Altman plots and the kappa coefficient to analyze the agreement between both the original and updated BODS and the BODE index, and we used the areas under ROC curves (AUC) to compare their discriminative abilities for 5-year all-cause mortality. The original BODS index scores and quartiles had weak agreement with the BODE index, and our updated BODS strengthened these agreements (a small, statistically nonsignificant mean bias [<0.03] with LoAs<2 points, and a substantial Kappa coefficient [k =0.63; IC 95%: 0.53-0.73]). In addition, the updated BODS index scores had better summarized ability than the BODS index in discriminating participants' mortality during the following 5 years (AUC: 0.768 versus 0.736; p=0.04). The updated BODS index scores and quartiles may provide prognostic information similar to that provided by the BODE index in COPD. Future research should focus on index improvement through external validation, as well as the assessment of safety and effectiveness in clinical practice by means of impact studies.


Medical students' use of Facebook for educational purposes.
Medical students use Facebook to interact with one another both socially and educationally. This study investigates how medical students in a UK medical school use Facebook to support their learning. In particular, it identifies the nature of their educational activities, and details their experiences of using an educational Facebook group. Twenty-four medical students who self-identified as being Facebook users were invited to focus groups to attain a general overview of Facebook use within an educational context. A textual analysis was then conducted on a small group of intercalating medical students who used a self-created Facebook group to supplement their learning. Five of these students participated in semi-structured interviews. Six common themes were generated. These included 'collaborative learning', 'strategic uses for the preparation for assessment', 'sharing experiences and providing support', 'creating and maintaining connections', 'personal planning and practical organization' and 'sharing and evaluating educational resources'. Evidence from this study shows that medical students are using Facebook informally to enhance their learning and undergraduate lives. Facebook has enabled students to create a supportive learning community amongst their peers. Medical educators wishing to capitalize on Facebook, as a platform for formal educational initiatives, should remain cautious of intruding on this peer online learning community.


Perceived Risk of Harm Mediates the Effects of Primary Care Alcohol Use Screening and Brief Advice in Adolescents.
A previous trial found lower alcohol use risk during follow-up among adolescent primary care patients receiving computer-facilitated Screening and provider Brief Advice (cSBA) compared to treatment-as-usual (TAU). We tested whether the effect was mediated by alcohol-related perceived risk of harm (PRoH). We analyzed data from the cSBA trial on 12- to 18-year-old patients at 9 New England practices (n = 2,096, 58% females). The trial used a quasi-experimental pre-post design with practices being their own controls (TAU followed by cSBA). Because prior alcohol experience could modify effects, we stratified analyses by baseline past 12-month drinking. Among baseline nondrinkers, we tested baseline to 3-month trajectories in PRoH of "trying alcohol" as an effect mediator for drinking at 3- and 12-month follow-up. Similarly, among those with prior drinking, we examined baseline to 3-month trajectories in PRoH of "weekly binge drinking" as an effect mediator for drinking and binge drinking. We used the Hayes product of coefficients mediation approach. Among baseline nondrinkers (n = 1,449), cSBA had higher PRoH compared to TAU for "trying alcohol," and higher PRoH in turn was associated with lower follow-up drinking risk. PRoH mediated their cSBA effect at 12 months, but not 3 months. Among adolescents with prior drinking (n = 647), cSBA had higher PRoH for "weekly binge drinking," which was associated with lower drinking risk at both follow-ups, and lower binge drinking risk at 3 months. PRoH mediated their cSBA effect on drinking at both follow-ups, and binge drinking at 3 months. A computer-facilitated primary care intervention enhanced adolescents' perceived alcohol risks which in turn was associated with lower drinking risk.


Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison.
The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either fondaparinux 2.5 mg or placebo s.c. for 5-9 days, starting 6-8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9-87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving fondaparinux and five (0.8%) receiving placebo had died. In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo.


Lung Cancer Screening in People With HIV: A Mixed-Methods Study of Patient and Provider Perspectives.
People with HIV are at higher risk of lung cancer; however, there is limited research on attitudes, barriers, and facilitators to lung cancer screening in people with HIV. The objective of this study was to understand the perspectives on lung cancer screening among people with HIV and their providers. Surveys of people with HIV and HIV-care providers were complemented by qualitative focus groups and interviews designed to understand the determinants of lung cancer screening in people with HIV. Participants were recruited through an academic HIV clinic in Seattle, WA. Qualitative guides were developed by integrating the Consolidated Framework for Implementation Research and the Tailored Implementation of Chronic Diseases checklist. Themes that emerged from thematic analyses of qualitative data were compared with surveys in joint displays. All study components were conducted between 2021 and 2022. Sixty-four people with HIV completed surveys, and 43 participated in focus groups. Eleven providers completed surveys, and 10 were interviewed for the study. Themes from joint displays show overall enthusiasm for lung cancer screening among people with HIV and their providers, particularly with a tailored and evidence-based approach. Facilitators in this population may include longstanding engagement with providers and health systems and an emphasis on survivorship through preventive healthcare interventions. People with HIV may also face barriers acknowledged by providers, including a high level of medical comorbidities and competing issues such as substance abuse, mental health concerns, and economic instability. This study reveals that people with HIV and their providers have overall enthusiasm toward screening. However, tailored interventions may be needed to overcome specific barriers, including complex decision making in the setting of medical comorbidity and patient competing issues.


One-bag-fiber muscle spindles in tenuissimus muscles of the cat.
Over 150 complete and 139 incomplete single muscle spindles were examined in serial transverse sections of cat tenuissimus muscles in search for spindles lacking one of the two types of nuclear bag intrafusal fiber. Several histochemical reactions were used to type the intrafusal muscle fibers and assess the spindle motor and sensory innervation. One complete spindle lacked a bag1 fiber, and another spindle lacked a bag2 fiber. Several incomplete spindles also lacked bag1 fibers. In addition, ten double tandem spindles contained one capsular unit each that lacked the bag1 fiber, and one triple tandem spindle had two such capsules. All one-bag-fiber spindles had primary sensory innervation, but none had secondary sensory innervation. Their motor innervation was similar to that of the usual two-bag-fiber spindles in the number and disposition of intrafusal motor endings. It is unclear whether the one-bag fiber spindles, either single or tandem-linked, are products of an aberrant spindle development or represent a true anatomical and functional subcategory of the cat muscle spindle.


Increasing soft tissue depth is associated with stalling of magnetically controlled growing rods.
Magnetically controlled growing rods (MCGR) represent the most used implant for the treatment of early onset scoliosis (EOS). These implants lengthen through the application of a remote magnetic field but distraction force generation has been negatively correlated with increasing soft tissue depth. Given the high rate of MCGR stalling, we proposed to investigate the impact of preoperative soft tissue depth on the rate of MCGR stalling at a minimum of 2 years following implantation. A single-center, retrospective review of prospectively enrolled children with EOS treated with MCGR was performed. Children were included if they had a minimum of 2-years follow-up after implantation and underwent advanced spinal imaging (MRI or CT) preoperatively within a year of implantation. The primary outcome was the development of MCGR stall. Additional measures included radiographic deformity parameters and gain in MCGR actuator length. About 55 patients were identified with 18 having preoperative advanced imaging allowing tissue depth measurement (Mean 5.99 ± 1.9 years, 83.3% female, mean Cobb 68.6 ± 13.8°). At a mean follow-up of 46.1 ± 11.9 months, 7 patients (38.9%) experienced stalling. MCGR stalling was associated with increased preoperative soft tissue depth (21.5 ± 4.4 mm vs. 16.5 ± 4.1 mm; p = .025) and increased BMI (16.3 ± 1.6 vs. 14.5 ± 0.9; p = .007). Greater preoperative soft tissue depth and BMI were associated with the development of MCGR stalling. This data supports previous studies showing that the distraction capacity of MCGR diminishes with increased soft tissue depth. Further research is needed to validate these findings and their implications on the indications for MCGR implantation.


Plasma levels of C19 steroid glucuronides in pre-menopausal women with non-classical congenital adrenal hyperplasia.
Recent reports have thrown doubt on the role of measurements of plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG) as a marker of peripheral androgen metabolism in women with polycystic ovarian syndrome and idiopathic hirsutism. It has been suggested that a plasma profile of C19 steroid glucuronides may be more informative. While preliminary data indicates that both 3 alpha-diolG and androsterone G (ADTG) may arise from adrenal steroid precursors, there have been no reports of C19 steroid glucuronides in women with non-classical, or late-onset congenital adrenal hyperplasia (NC-CAH), who constitute a significant proportion of the hirsute female population. We therefore measured plasma levels of 3 alpha-diolG, ADTG and dihydrotestosterone G (DHTG) before and following a standard Cortrosyn test in 15 symptomatic and 3 asymptomatic NC-CAH patients, 5 heterozygote carriers for 21-hydroxylase deficiency (NCHETS) and 18 normal women. The effects of chronic glucocorticoid (GCR) therapy (greater than 3 months) on the C19 steroid glucuronide profile in the symptomatic patients was also investigated. Baseline plasma levels of all 3 glucuronides were significantly (P less than 0.001) higher in symptomatic patients compared with either normals or NCHETS. However, the order of discrimination was ADTG greater than 3 alpha-diolG greater than DHTG. There were no significant differences between steroid glucuronide levels for NCHET and normal women and the C19 steroid glucuronide concentrations for the asymptomatic NC-CAH patients were greater than 2 SD above the normal means. Moderate clinical improvement was observed in all patients receiving oral GCR therapy and was accompanied by approx. 80% suppression of the plasma levels of all 3 C19 steroid glucuronides. This contrasts with a mean suppression of androstenedione of only 50%. However, plasma levels of the C19 steroid glucuronides were not significantly increased in response to a short ACTH stimulation test. This may be explained by the fact that the androgen glucuronides are thought to be peripherally formed metabolites derived from unconjugated glandular secreted androgen precursors and thus their synthesis at 60 min following adrenal stimulation may lag substantially behind that of their respective precursors. There were significant linear correlations between the levels of all 3 glucuronides, but neither correlated with Ferriman-Gallway scores, body mass index or 17-hydroxyprogesterone levels.(ABSTRACT TRUNCATED AT 400 WORDS)


Circ_0091579 exerts an oncogenic role in hepatocellular carcinoma via mediating miR-136-5p/TRIM27.
Circular RNAs (circRNAs) act as crucial regulators in tumorigenesis. In this study, the working mechanism of circ_0091579 in hepatocellular carcinoma (HCC) progression was investigated. The expression of RNA and protein was measured via RT-qPCR and Western blot assay. Cell proliferation ability was analyzed via CCK8, EdU and colony formation assays. Cell migration and invasion abilities were detected via transwell assays. Flow cytometry was applied to assess cell cycle and apoptosis. The target relation between miR-136-5p and circ_0091579 or tripartite motif containing 27 (TRIM27) was certified using dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0091579 in tumor growth in vivo. The protein level of Ki67 in tumor tissues was analyzed by immunohistochemistry (IHC) assay. Circ_0091579 expression was elevated in HCC tissues and cell lines. HCC patients with high circ_0091579 expression displayed low survival rate. Circ_0091579 knockdown suppressed the proliferation, migration, invasion, cell cycle progression and epithelial-mesenchymal transition (EMT) and induced apoptosis of HCC cells. Circ_0091579 acted as a molecular sponge for miR-136-5p, and circ_0091579 silencing-mediated effects were largely overturned by the knockdown of miR-136-5p in HCC cells. MiR-136-5p interacted with the 3' untranslated region (3'UTR) of TRIM27, and TRIM27 overexpression largely counteracted miR-136-5p overexpression-induced influences in HCC cells. Circ_0091579 sponged miR-136-5p to up-regulate TRIM27 expression in HCC cells. Circ_0091579 silencing suppressed xenograft tumor growth in vivo. Circ_0091579 exhibited an oncogenic role to enhance the malignant potential of HCC cells through mediating miR-136-5p/TRIM27 axis in vitro and in vivo.


A tug of war between DCC and ROBO1 signaling during commissural axon guidance.
Dynamic and coordinated axonal responses to changing environments are critical for establishing neural connections. As commissural axons migrate across the CNS midline, they are suggested to switch from being attracted to being repelled in order to approach and to subsequently leave the midline. A molecular mechanism that is hypothesized to underlie this switch in axonal responses is the silencing of Netrin1/Deleted in Colorectal Carcinoma (DCC)-mediated attraction by the repulsive SLIT/ROBO1 signaling. Using in vivo approaches including CRISPR-Cas9-engineered mouse models of distinct Dcc splice isoforms, we show here that commissural axons maintain responsiveness to both Netrin and SLIT during midline crossing, although likely at quantitatively different levels. In addition, full-length DCC in collaboration with ROBO3 can antagonize ROBO1 repulsion in vivo. We propose that commissural axons integrate and balance the opposing DCC and Roundabout (ROBO) signaling to ensure proper guidance decisions during midline entry and exit.


The application of open intramedullary fixation in the treatment of pediatric radial and ulnar shaft fractures.
This retrospective review evaluates the efficiency of standard intramedullary Kirschner wires for the treatment of unstable diaphyseal forearm fractures in children. Retrospective review. Large teaching and research hospital in Turkey. Thirty-one patients with diaphyseal forearm fractures were treated by surgical method between 1988 and 1998. The mean age was 12.3 years (range 7 to 17 years). The mean follow-up period was 4.2 years (1 to 6.2 years). The method of treatment of each forearm fracture was open reduction and intramedullary Kirschner wire fixation using a mini-incision. Fracture union, growth disturbance of the forearm, and complications were evaluated. Union was obtained in all cases except two (6.4 percent). No forearm inequality was observed. Intramedullary fixation is a useful technique for unstable shaft fractures of the forearm in children that can not be treated by closed manipulation.


Risk of sudden cardiac arrest and ventricular arrhythmia with sulfonylureas: An experience with conceptual replication in two independent populations.
Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardiac arrest (SCA) or ventricular arrhythmia (VA). We assessed the comparative real-world risk of SCA/VA among users of second-generation sulfonylureas: glimepiride, glyburide, and glipizide. We conducted two incident user cohort studies using five-state Medicaid claims (1999-2012) and Optum Clinformatics commercial claims (2000-2016). Outcomes were SCA/VA events precipitating hospital presentation. We used Cox proportional hazards models, adjusted for high-dimensional propensity scores, to generate adjusted hazard ratios (aHR). We identified 624,406 and 491,940 sulfonylurea users, and 714 and 385 SCA/VA events, in Medicaid and Optum, respectively. Dataset-specific associations with SCA/VA for both glimepiride and glyburide (vs. glipizide) were on opposite sides of and could not exclude the null (glimepiride: aHRMedicaid 1.17, 95% CI 0.96-1.42; aHROptum 0.84, 0.65-1.08; glyburide: aHRMedicaid 0.87, 0.74-1.03; aHROptum 1.11, 0.86-1.42). Database differences in data availability, populations, and documentation completeness may have contributed to the incongruous results. Emphasis should be placed on assessing potential causes of discrepancies between conflicting studies evaluating the same research question.


Neighbourhood socioeconomic status and overweight/obesity: a systematic review and meta-analysis of epidemiological studies.
Low neighbourhood socioeconomic status (NSES) has been linked to a higher risk of overweight/obesity, irrespective of the individual's own socioeconomic status. No meta-analysis study has been done on the association. Thus, this study was done to synthesise the existing evidence on the association of NSES with overweight, obesity and body mass index (BMI). Systematic review and meta-analysis. PubMed, Embase, Scopus, Cochrane Library, Web of Sciences and Google Scholar databases were searched for articles published until 25 September 2019. Epidemiological studies, both longitudinal and cross-sectional ones, which examined the link of NSES to overweight, obesity or BMI, were included. Data extraction was done by two reviewers, working independently. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale for the observational studies. The summary estimates of the relationships of NSES with overweight, obesity and BMI statuses were calculated with random-effects meta-analysis models. Heterogeneity was assessed by Cochran's Q and I2 statistics. Subgroup analyses were done by age categories, continents, study designs and NSES measures. Publication bias was assessed by visual inspection of funnel plots and Egger's regression test. A total of 21 observational studies, covering 1 244 438 individuals, were included in this meta-analysis. Low NSES, compared with high NSES, was found to be associated with a 31% higher odds of overweight (pooled OR 1.31, 95% CI 1.16 to 1.47, p<0.001), a 45% higher odds of obesity (pooled OR 1.45, 95% CI 1.21 to 1.74, p<0.001) and a 1.09 kg/m2 increase in mean BMI (pooled beta=1.09, 95% CI 0.67 to 1.50, p<0.001). NSES disparity might be contributing to the burden of overweight/obesity. Further studies are warranted, including whether addressing NSES disparity could reduce the risk of overweight/obesity. CRD42017063889.


Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization.
An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood. We utilized holographic and fluorescent microscopy to assess the contribution of ATP synthase and adenine nucleotide translocator (ANT) toward PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. In wild-type cells, calcium-induced CSA-sensitive depolarization preceded opening of PTP, which occurred only after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high-conductance PTP but not depolarization, which presumably occurs through activation of the low-conductance PT, which has a molecular nature that is different from both complexes.


Springtime macronutrient intake of Alaska natives of the Bering Straits Region: the Alaska Siberia Project.
The diet of Alaska Natives is a complicated mix of native and imported foods. Dietary intake, which may have changed considerably in the past several decades, has important implications for risk of chronic disease. The objective of this study was to add to the knowledge of dietary intake of Alaska Natives of the Bering Straits Region by describing the macronutrient intake of adults. Observational study of dietary intake. A 24-hour dietary recall was administered among all consenting, non-pregnant residents of four villages, aged 25 years, or more. Data are presented for 209 men and 225 women, who represent 48% of eligible participants. Dietary intake was higher in proportion of energy from protein and lower in proportion of carbohydrate than non-Hispanic white Americans overall. Higher energy and protein intakes were reported for men. Comparisons were also made among Alaskan ethnic groups and previous Alaskan surveys. This study of diet among Alaska Natives demonstrates consistency with other recent work. Differences in diet from earlier 20th century observations, such as higher carbohydrate and lower protein intake, are consistent with documented acculturation in Alaska and other circumpolar regions.


Description of a new species of Oligosita Walker (Chalcidoidea: Trichogrammatidae), egg parasitoid of Balclutha brevis Lindberg (Homoptera: Cicadellidae) living on Pennisetum setaceum, from Italy.
A new species of Oligosita Walker (Chalcidoidea: Trichogrammatidae), O. balcluthae Viggiani et Laudonia n. sp., is described as a parasitoid of the eggs of Balclutha brevis Lindberg (Homoptera: Cicadellidae) associated with crimson fountain grass, Pennisetum setaceum (Poaceae) in Italy. Morphological features and biology of the new species are discussed and illustrated. The 28S-D2 and ITS2 regions were successfully amplified and sequenced.


A viral activator of gene expression functions via the ubiquitin-proteasome pathway.
The ability of herpes simplex virus type 1 (HSV-1) to attain a latent state in sensory neurones and reactivate periodically is crucial for its biological and clinical properties. The active transcription of the entire 152 kb viral genome during lytic replication contrasts with the latent state, which is characterized by the production of a single set of nuclear-retained transcripts. Reactivation of latent genomes to re-initiate the lytic cycle therefore involves a profound change in viral transcriptional activity, but the mechanisms by which this fundamentally important process occurs are yet to be well understood. In this report we show that the stimulation of the onset of viral lytic infection mediated by the viral immediate-early (IE) protein Vmw110 is strikingly inhibited by inactivation of the ubiquitin-proteasome pathway. Similarly, the Vmw110-dependent reactivation of quiescent viral genomes in cultured cells is also dependent on proteasome activity. These results constitute the first demonstration that the transcriptional activity of a viral genome can be regulated by protein stability control pathways.


Surgical outcomes and transfusion of minimal amounts of blood in the operating room.
To examine outcomes in patients who receive small amounts of intraoperative blood transfusion. Longitudinal, uncontrolled observational study evaluating results of intraoperative transfusion in patients entered into the American College of Surgeons National Surgical Quality Improvement Program database. We made propensity-matched comparisons between patients who received and did not receive intraoperative transfusion to minimize confounding when estimating the effect of intraoperative transfusion on postoperative outcomes. We queried the American College of Surgeons National Surgical Quality Improvement Program database for patients undergoing operations between January 1, 2005, and December 31, 2009. A large sample of surgical patients from 173 hospitals throughout the United States. Operative mortality and serious perioperative morbidity (≥1 of 20 complications). After exclusions, 941,496 operations were analyzed in patients from 173 hospitals. Most patients (893,205 patients [94.9%]) did not receive intraoperative transfusions. Patients who received intraoperative infusion of 1 unit of packed red blood cells (15,186 patients [1.6%]) had higher unadjusted rates of mortality and more serious morbidity. These rates further increased with intraoperative transfusion of more than 1 unit of packed red blood cells in a dose-dependent manner. After propensity matching to adjust for multiple preoperative risks, transfusion of a single unit of packed red blood cells increased the multivariate risk of mortality, wound problems, pulmonary complications, postoperative renal dysfunction, systemic sepsis, composite morbidity, and postoperative length of stay compared with propensity-matched patients who did not receive intraoperative transfusion. There is a dose-dependent adverse effect of intraoperative blood transfusion. It is likely that a small, possibly discretionary amount of intraoperative transfusion leads to increased mortality, morbidity, and resource use, suggesting that caution should be used with intraoperative transfusions for mildly hypovolemic or anemic patients.


Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender.
Droplet-based single-cell assays, including single-cell RNA sequencing (scRNA-seq), single-nucleus RNA sequencing (snRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), generate considerable background noise counts, the hallmark of which is nonzero counts in cell-free droplets and off-target gene expression in unexpected cell types. Such systematic background noise can lead to batch effects and spurious differential gene expression results. Here we develop a deep generative model based on the phenomenology of noise generation in droplet-based assays. The proposed model accurately distinguishes cell-containing droplets from cell-free droplets, learns the background noise profile and provides noise-free quantification in an end-to-end fashion. We implement this approach in the scalable and robust open-source software package CellBender. Analysis of simulated data demonstrates that CellBender operates near the theoretically optimal denoising limit. Extensive evaluations using real datasets and experimental benchmarks highlight enhanced concordance between droplet-based single-cell data and established gene expression patterns, while the learned background noise profile provides evidence of degraded or uncaptured cell types.


Association of terminal chromosome 1 deletion with sertoli cell-only syndrome.
We report on del(1)(q44), developmental delay, cryptorchidism, and seizure disorder in a 19-year-old man. Endocrinologic evaluation showed delayed puberty and elevated gonadotropins. Testicular biopsy was consistent with Sertoli cell-only syndrome. The case illustrates a previously an unreported manifestation in males with del(1)(q44), and suggests a link between the development of germinal epithelium and genes in the 1q44 area.


The ultra-thin bronchoscope in management of the difficult paediatric airway.
The use of an ultra-thin flexible fiberoptic bronchoscope with a single lumen diameter of 2.7 mm at the distal tip to assist intubation of paediatric patients with a difficult airway is reported. Two patients (ages 30 months and 18 months) with mandibular hypoplasia and one patient (three months) with the Pierre-Robin syndrome are reported. In each case two fiberoptic bronchoscopes were used. The first allowed introduction of topical local anaesthetic while the second and smaller one was used for tube placement.


Coordination and hydrogen bonded network structures of Cu(II) with mixed ligands: a hybrid hydrogen bonded material, an infinite sandwich arrangement, and a 3-D net.
Mixed-ligand Cu(II) complexes with deprotonated trimesic acid and phenanthroline-type ligands were synthesised by solvothermal methods to form 2-D infinite hexagonal hydrogen bonded structures with additional trimesic acid (H3tma) molecules. The complex [Cu(phendione)2(H2tma)2].2(H3tma).1.65(CF3CH2OH).2.5(H2O), where phendione = 1,10-phenanthroline-5,6-dione, has hydrogen bonded networks of [Cu(phendione)2(H2tma)2] complexes interspersed with layers of H3tma with a topologically identical hydrogen bonding network. Whereas in [Cu(1,10-phenanthroline)(H2tma)2]2.2(H3tma), a dimeric Cu(II) complex hydrogen bonds directly to additional H3tma molecules to form a three-layered 2-D network resembling an infinite sandwich. The synthesis and structures of simple Cu(II) complexes of the phendione ligand are also reported. One of these, [Cu(phendione)2Br2] shows a particularly polar packing arrangement.


Arthroscopic treatment of femoroacetabular impingement shows persistent clinical improvement in the mid-term.
The concept of femoroacetabular impingement (FAI) and the indication for surgical intervention have been established in the last decade. Despite promising short-term results and emerging arthroscopic techniques, it remains unclear whether patients benefit from surgical correction in the mid- to long-term and whether progressive joint degeneration can be prevented. A retrospective study of our first 50 consecutive patients who underwent arthroscopic correction for FAI was conducted. The modified Harris hip score (mHHS) was assessed preoperatively and at final follow-up. In addition, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and a subjective hip value (SHV) were added at final follow-up. Degenerative changes according to Kellgren and Lawrence scale and the α angle were analyzed preoperatively and on the most recent radiograph. Of a total of 50 patients, 44 (24 male, 20 female) with a mean age of 34.3 years (17-65) were available with complete follow-up. Of these 44 patients, 39 were treated with correction of the femoral offset for isolated cam deformity, 5 with additional focal pincer correction and partial labral resection. After a mean follow-up of 66.3 ± 14.5 months the mHHS had improved significantly from 67.2 ± 6.4 preoperatively to 86.4 ± 13.5 (p < 0.001). The WOMAC score (converted to 0 = best/100 = worst) resulted in mean indices for the subcategories pain, stiffness and function of 11.8 ± 16.5, 12.2 ± 17.8 and 9.1 ± 16.1. The SHV was reported with a mean of 77.7 ± 21.8 % at final follow-up. The α angle was reduced significantly from 57.2° ± 10.1° to 46.3° ± 7.4° (p < 0.001). The Kellgren and Lawrence score showed a non-significant trend from 2.0 ± 0.8 preoperatively to 2.2 ± 0.9 in the most recent radiograph (p = 0.46). 5 patients had been converted to a total hip arthroplasty a mean of 28 ± 7.1 months postoperatively. These patients were significantly (p < 0.01) older with a mean age of 49.8 ± 7.8 years and showed significantly higher present osteoarthritic changes with an average Kellgren and Lawrence score of 2.6 ± 2.5 before FAI correction (p < 0.01). Arthroscopic correction of femoroacetabular impingement results in a persistent clinical improvement without significant progression of degenerative changes in the majority of patients. The indication for surgery should be established cautiously when degenerative changes are present. Level IV, Case series with no comparison group.


Virtual conferences: results of an international survey on radiologist preferences and perspectives.
We explored perceptions and preferences regarding the conversion of in-person to virtual conferences as necessitated by travel and in-person meeting restrictions. A 16-question online survey to assess preferences regarding virtual conferences during the COVID-19 pandemic and future perspectives on this subject was disseminated internationally online between June and August 2020. A total of 508 responses were received from 73 countries. The largest number of responses came from Italy and the USA. The majority of respondents had already attended a virtual conference (80%) and would like to attend future virtual meetings (97%). The ideal duration of such an event was 2-3 days (42%). The preferred time format was a 2-4-h session (43%). Most respondents also noted that they would like a significant fee reduction and the possibility to attend a conference partly in-person and partly online. Respondents indicated educational sessions as the most valuable sections of virtual meetings. The reported positive factor of the virtual meeting format is the ability to re-watch lectures on demand. On the other hand, the absence of networking and human contact was recognized as a significant loss. In the future, people expressed a preference to attend conferences in person for networking purposes, but only in safer conditions. Respondents appreciated the opportunity to attend the main radiological congresses online and found it a good opportunity to stay updated without having to travel. However, in general, they would prefer these conferences to be structured differently. The lack of networking opportunities was the main reason for preferring an in-person meeting. • Respondents appreciated the opportunity to attend the main radiological meetings online, considering it a good opportunity to stay updated without having to travel. • In the future, it is likely for congresses to offer attendance options both in person and online, making them more accessible to a larger audience. • Respondents indicated that networking represents the most valuable advantage of in-person conferences compared to online ones.


Aegle marmelos fruit pectin for food and pharmaceuticals: Physico-chemical, rheological and functional performance.
Pectin is used in a number of foods as a gelling agent, thickener, texturizer, emulsifier and stabilizer. Bael fruit, obtained from Aegle marmelos, is a rich source of pectin. Bael fruit pectin (BFP) was extracted from ripe Bael fruits. The process yielded 15% (w/w) pure BFP. The swelling index decreased in the following order: water>pH 7.4>pH 6.8>pH 1.2>HCl (0.1N). Galacturonic acid content of 87.8%, degree of esterification of 47.2%, 17.3% methoxy groups, 0.29% acetyl groups and equivalent weight of 1209.5, indicate it to be a good gelling agent and easily amenable to derivatization. BFP exhibited a significant concentration-dependent prolongation of prothrombin time. The absence of hemagglutinating activity and antinutritional factors coupled with the activity to confer better emulsion capacity, stability and antimicrobial activity gives BFP a clear edge over commercial citrus pectin (CP) for exploitation as an additive in food and pharmaceuticals.


Fludeoxyglucose positron emission tomography-computed tomography scan showing polyarthritis in a patient with an atypical presentation of Henoch-Schönlein vasculitis without clinical signs of arthritis: a case report.
Henoch-Schönlein vasculitis is the most common systemic vasculitis in children. Arthritis or arthralgia occurs in 80 % of patients. We believe this to be the first case report to describe the finding of polyarthritis in a fludeoxyglucose positron emission tomography-computed tomography scan in a patient with Henoch-Schönlein vasculitis without clinical signs of arthritis. A 4.5-year-old Caucasian boy presented with fever of 4 days' duration followed by debilitating migratory arthralgia and inflammation. He underwent a fludeoxyglucose positron emission tomography-computed tomography scan to exclude a possible malignant cause or to detect any infectious or autoimmune focus of his symptoms. Fludeoxyglucose uptake was observed in multiple large joints and in multiple tendons. These findings suggested active polyarthritis and polytendinitis. However, physical and ultrasound evaluations did not show any signs of arthritis in our patient, despite his evident arthralgia. Fludeoxyglucose positron emission tomography-computed tomography might be able to detect inflammatory activity in painful joints that cannot yet be detected clinically or with ultrasound evaluation in a patient with Henoch-Schönlein vasculitis. Therefore, fludeoxyglucose positron emission tomography-computed tomography can be of additional value in the diagnostic workup of patients with an unresolved diagnosis of suspected autoimmune disease, especially in patients with unresolved arthralgia and fever of unknown cause.


Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model.
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-β 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-β1, IL-1β, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-β1, IL-1β, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone.


[Endogamy index and its changes with time in some populations of the Volga-Ural region].
Data on several populations of Russia have been used to demonstrate that the change in the endogamy index detected in the second half of the 20th century is not global. Migration activity remains high in populations with relatively low endogamy indices, and their endogamy does not change with time. In regions with medium and high endogamy indices, these values also tend to remain stable. The endogamy indices of urban populations are increasing, and those of rural populations are decreasing.


Mycorrhizal diversity and specificity in Lecanorchis (Orchidaceae).
Lecanorchis is a nonphotosynthetic plant genus in Vanilloideae, Orchidaceae. Because of the distribution of many Lecanorchis taxa in various climate conditions, we hypothesized that mycorrhizal diversity and specificity are different among the different taxa of Lecanorchis. In the present study, identities of mycorrhizal fungi were examined for 90 individuals of 10 Lecanorchis taxa at 26 sites from Niigata to Okinawa Prefectures in Japan. Phylogenetic analyses of Lecanorchis taxa based on the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA gene (rDNA) divided the examined Lecanorchis taxa into three groups, groups A, B, and C. ITS rDNA sequences suggested that fungi associating with Lecanorchis were ectomycorrhiza-forming fungi in Lactarius, Russula, Atheliaceae, and Sebacina, with Lactarius and Russula dominant. Our results suggested some degree of mycorrhizal specialization among Lecanorchis taxa. Interestingly, the Lecanorchis group C had some specific relationships with Lactarius, whereas less specificity was found in the relationships with Russula. However, observed specificity results may be biased by geographic opportunity, and we suggest further research to assess whether Lecanorchis species are limited to the associations we observed.


Distribution of pediatric hand fractures: age- and bone maturation-dependent differences.
To investigate the distribution and characteristics of fractures of bones of the hand on radiographs with respect to age and skeletal maturity of the fractured bone, and to identify predictors of surgery. This cross-sectional, retrospective study included children (≤ 18 years) with hand fractures who underwent radiographic examinations (2019-2021). Fracture location, presence of displacement (≥ 2 mm), angulation (≥ 10°), articular extension, and if skeletally immature, then physeal involvement and Salter-Harris grade were recorded. Mann-Whitney U, Kruskal-Wallis, Fisher's exact, and chi-square tests as well as logistic regression analyses were used. Study group of 508 (350 boys, 158 girls; median age, 11.9 years) included 575 (63% phalangeal, 37% metacarpal, and 0.3% carpal) fractures. Younger children were more likely to sustain phalangeal and older children carpal and metacarpal fractures (median ages: 10.8 vs 12.3 and 13.8 years, p < 0.001); and fractures of the small finger accounted for 50% of metacarpal and 43% of phalangeal fractures. Fracture displacement (12% vs 22%, p = 0.02) and angulation (25% vs 49%, p < 0.001) were more common with mature than immature bones. A third of immature bones had physeal involvement and the most common pattern was Salter-Harris type II (89%). Surgical intervention was uncommon (11%) and independent predictors were displacement (OR = 3.99, 95% CI 1.95-8.19, p < 0.001) and articular extension (OR = 5.11, 95% CI 2.00-13.07, p < 0.001). While younger children were more likely to sustain phalangeal than metacarpal fractures and less likely to have displacement and angulation when compared to older children; only displacement and articular extension were significant independent predictors of surgery.


Genetic diversity of two color morphs of Northern snakehead (Channa argus) unveiled by the mitochondrial DNA D-loop region.
To analyze the genetic background of 'white' type Northern snakehead (Channa argus), and provide atheoretical basis for breeding of C. argus, the investigation of genetic diversity and population structure were investigated based on the complete sequences of mitochondrial DNA D-loop region for three cultured 'white' type C. argus populations, and four 'bicolor' type C. argus populations were used to compare with them; 28 mutation loci and 30 haplotypes were found in the D-loop sequence of all individuals with a total length of 907 bp. The highest haplotype diversity (Hd ) and nucleotide diversity (Pi ) in the 'white' type C. argus populations were 0.505 and 0.00057, respectively, which lower than those in the 'bicolor' type C. argus populations (Hd = 0.911, Pi = 0.00326). Population differentiation values (F ST) show that the four 'bicolor' type C. argus populations had obvious genetic differentiation (Fst: 0.21902-0.49428. p < 0.01), but not in the three 'white' type C. argus populations (Fst: -0.00571 to 0.07261. p > 0.05). The phylogenetic tree and Median Joining (MJ) network showed that the genetic distance among 'white' type C. argus populations is very close. Therefore, much attention should be paid to protecting population genetic diversity and avoiding inbreeding in the breeding of 'white' type C. argus.


Giardiasis.
Giardia spp. are common, yet frequently overlooked, parasites of small animals. These parasites may cause chronic diarrhea in dogs and cats. This article discusses the clinical signs of giardiasis, and its diagnosis, treatment, and control.


Adverse outcome of T3-predominant maternal Grave's disease during pregnancy in the mother and the offspring.
Note required for Clinical Vignette.


Minor head injury in children younger than two years of age: description, prevalence and management in the emergency room of the pediatric university hospital.
In children less than two years old, minor head trauma can result in intracranial injury. No known studies exist that determine the number of children younger than two years old who visit the emergency room (ER) due to minor head injury in Puerto Rico. To determine the prevalence of children with minor head trauma and describe related issues. Information was gathered from the medical records of children 0 to 2 years old who visited the University Pediatric Hospital ER from 2004-2006. Several factors were analyzed. From our 136 subjects, there was a male prevalence of 59%. The predominant reason for head injury was a fall (86%). There was abuse in 7% of the subjects. Eighty-five percent (85%) of injuries occurred at home. The most common etiology of head trauma was a fall at home. The prevalence of abuse in 7% of these children should alert physicians.


Serum parathyroid hormone and alkaline phosphatase as predictors of calcium requirements after total parathyroidectomy for hypocalcemia in secondary hyperparathyroidism.
To prevent hypocalcemia, this study examined the efficiency of a calcium supplement formula guided by predicted calcium requirement in patients with renal failure after parathyroidectomy with autotransplantation. In the first phase, a protocol was followed whereby intravenous calcium gluconate was repeatedly titrated based on serum calcium levels in 22 patients with parathyroidectomy with autotransplantation. In the second phase, the first equation protocol was applied in 74 patients with parathyroidectomy with autotransplantation and revised. There is a significant correlation between the postoperative amount of calcium requirement and preoperative serum alkaline phosphatase level (r = 0.442; P < .001) and parathyroid hormone level (PTH; r = 0.889; P < .001). For prediction of insufficient calcium supplement, the cutoff point of PTH and alkaline phosphatase level values were calculated by receiver operating characteristic (ROC) curve analysis and modified equations were developed by regression analysis. The preoperative PTH and alkaline phosphatase levels can predict postoperative calcium requirements, such that equations of calcium supplement allow the management of hypocalcemia efficiently in patients on dialysis after parathyroidectomy with autotransplantation.


Determining the Suitability of Registries for Embedding Clinical Trials in the United States: A Project of the Clinical Trials Transformation Initiative.
Patient registries are organized systems that use observational methods to collect uniform data on specified outcomes in a population defined by a particular disease, condition, or exposure. Data collected in registries often coincide with data that could support clinical trials. Integrating clinical trials within registries to create registry-embedded clinical trials offers opportunities to reduce duplicative data collection, identify and recruit patients more efficiently, decrease time to database lock, accelerate time to regulatory decision-making, and reduce clinical trial costs. This article describes a project of the Clinical Trials Transformation Initiative (CTTI) intended to help clinical trials researchers determine when a registry could potentially serve as the platform for the conduct of a clinical trial. Through a review of registry-embedded clinical trials and commentaries, semi-structured interviews with experts, and a multi-stakeholder expert meeting, the project team addressed how to identify and describe essential registry characteristics, practices, and processes required to for conducting embedded clinical trials intended for regulatory submissions in the United States. Recommendations, suggested practices, and decision trees that facilitate the assessment of whether a registry is suitable for embedding clinical trials were developed, as well as considerations for the design of new registries. Essential registry characteristics include relevancy, robustness, reliability, and assurance of patient protections. The project identifies a clear role for registries in creating a sustainable and reusable infrastructure to conduct clinical trials. Adoption of these recommendations will facilitate the ability to perform high-quality and efficient prospective registry-based clinical trials.


Amino acid biases in the N- and C-termini of proteins are evolutionarily conserved and are conserved between functionally related proteins.
Analysis of the Arabidopsis thaliana, Saccharomyces cerevisiae, Mus musculus, Escherichia coli, Bacillus subtilis, Thermoplasma acidophilum, and Sulfolobus tokodaii genomes demonstrate that many amino acid biases occur at the N- and C-termini of proteins, a statistically significant number of these biases are evolutionarily conserved, and these biases occur in amino acids beyond the first and last five amino acids. Analyses designed to shed light on the mechanism causing amino acid biases suggest that in at least some cases the bias is caused by forces acting at the nucleic acid level. It is also demonstrated that in E. coli functionally related proteins show similar biases at the N- and C-termini suggesting that the mechanisms causing the biases are complex and in some cases are related to function.


The reactivity of phenancyl bromide under β-cyclodextrin as supramolecular catalyst: a computational survey.
Phenacyl bromide as one starting material in multicomponent reactions (MCRs) with β-cyclodextrin (β-CD) as catalyst can get an excellent yield in short reaction times. The interaction of β-CD with phenacyl bromide plays an important role in this process. This paper studies the complex of β-CD with phenacyl bromide using density functional theory (DFT) method. Energy is investigated to find out the lowest energy of two possible complexation models. Hydrogen bonds are researched on the basis of natural bonding orbital (NBO) analysis. The relative position between phenacyl bromide and β-CD is confirmed by (1)H nuclear magnetic resonance ((1)HNMR). The results of frontier molecular orbitals and charge distribution reveal that β-CD catalyst improves the reactivity and electrophilicity of phenacyl bromide, meanwhile, the carbonyl group of phenacyl bromide more easily gives a carbocationic intermediate in the presence of β-CD as catalyst. The reactivity of phenancyl bromide under β-CD as supramolecular catalysis is improved.


[Antiemetic and antinauseant effect of alizapride in patients subjected to antiblastic infusion chemotherapy in a day-hospital regime].
A study about alizapride in out patients with nausea and vomiting during infusional antiblastic chemotherapy.


Comparison of the antiviral effects of 5-methoxymethyldeoxyuridine-5'-monophosphate with adenine arabinoside-5'-monophosphate.
Methoxymethyldeoxyuridine-5'-monophosphate (MMUdR-MP) and arabinofuranosyladenine-5'-monophosphate (Ara-AMP) had significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in RK-13 and Vero cells. MMUdR-MP and Ara-AMP were more potent than methoxymethyldeoxyuridine (MMUdR) and arabinofuranosyladenine (Ara-A) against the MS strain of HSV-2. MMUdR-MP inhibited replication of HSV-1r (mutant resistant to MMUdR). MMUdR in combination with Ara-AMP showed additive activity; whereas the MMUdR-MP and Ara-AMP combination was antagonistic against herpes viruses. MMUdR in combination with Ara-A was synergistic in reducing the log virus yield. Cytotoxicity (microscopic lesions) was observed on exposure to MMUdR-MP and Ara-AMP at 450 and 90 microM, respectively. Rapidly proliferating RK-13 cells exposed to Ara-AMP (64 microM) were killed. In the same system, the cells surviving after incubation with MMUdR-MP (650 microM), multiplied at an almost normal rate.


Unresectable nonmetastatic squamous cell carcinoma of the esophagus managed by sequential chemotherapy (cisplatin and bleomycin) and radiation therapy.
For patients with unresectable nonmetastatic squamous cell carcinoma of the esophagus (SCCE), the conventional treatment has been radiation therapy (RT). Because RT alone is unsatisfactory, there has been increasing interest in including chemotherapy (CT) in the management of these patients. Twenty-five previously untreated patients with unresectable nonmetastatic SCCE were treated with sequential CT and RT. CT consisted of cisplatin 35 mg/m2/day for 3 days plus bleomycin 15 mg/day for 3 days as an 18-hour infusion every 3 weeks. After three courses of CT, RT was administered (dose, 200 rads/day with a planned total dose of 50-60 Gy). Nineteen tumors were T3; six were T2 and larger than 7 cm. Fifteen patients (60%) had severe dysphagia that required placement of nasogastric tubes in 14 and gastrostomy in 1. All patients were evaluable for response. Thirteen patients (52%) had a partial response to CT. After combined treatment, four patients had complete responses (16%), and nine had partial responses (36%; overall response rate, 52%). The median survival was 8 months; 20% were alive at 1 year, and 8% lived more than 4 years. The median survival for responders to CT was 8 months compared with 5 months for nonresponders (P = 0.005). Combined treatment improved dysphagia in 16 patients (64%) with complete resolution in 13. Toxicity was mild. The use of sequential CT (cisplatin and bleomycin) and RT in this group of patients is feasible; there is little additional toxicity, and good palliative effects can be achieved. The patient's response to CT is a good prognostic factor. The development of more effective combinations that induce more durable responses and higher rates of complete response are required.


Risk differences between children and adults in road traffic injuries: a descriptive study from a tertiary-care hospital in a low-income country.
Our study attempted to describe the differences in circumstances, risk groups, and severity of road traffic injuries (RTIs) among injured children (1-15 years) and adults (≥16 years) coming to the tertiary-care hospital, Karachi, Pakistan. Past medical records from June 2006 to May 2007 of injured patients coming to the Emergency Department of the Aga Khan University Hospital, Karachi were reviewed. Data were recorded regarding the basic epidemiological features, hospital stay, body parts that are injured, and severity of injuries. Of 411 RTI patients, males outnumbered females by a ratio of 4 : 1 accounting for 81% (n = 333) of injured. Among pedestrians (82; 20%), females were injured more than males (38 vs. 16%; P < 0.01). When compared with adults, injured children were mostly pedestrians (18 vs. 36%; P = 0.01) and presented with severe Glasgow Coma Scale (GCS) (9 vs. 18%; P = 0.02). Among adults, most RTIs were caused by two wheelers crashing with four wheelers (16 vs. 19%; P = 0.01). Motor vehicle occupants (adjusted odds ratio: 3.04; 95% confidence interval: 1.382-6.668) were more likely to have severe GCS (GCS < 8) even after adjusting for injury severity. The study may assist local authorities in Karachi to prioritize interventions to address common injuries among those who are at a high risk for RTIs. Further quantitative and qualitative studies are needed to assess the factors leading to RTIs among pedestrians in Karachi.


Compton and proximity imaging of 225Ac in vivo with a CZT gamma camera: a proof of principle with simulations.
In vivo imaging of 225Ac is a major challenge in the development of targeted alpha therapy radiopharmaceuticals due to the extremely low injected doses. In this paper, we present the design of a multi-modality gamma camera that integrates both proximity and Compton imaging in order to achieve the demanding sensitivities required to image 225Ac with good image quality. We consider a dual-head camera, each of the heads consisting of two planar cadmium zinc telluride detectors acting as scatterer and absorber for Compton imaging, and with the scatterer practically in contact with the subject to allow for proximity imaging. We optimize the detector's design and characterize the detector's performance using Monte Carlo simulations. We show that Compton imaging can resolve features of up to 1.5 mm for hot rod phantoms with an activity of 1 μCi, and can reconstruct 3D images of a mouse injected with 0.5 μCi after a 15 minutes exposure and with a single bed position, for both 221Fr and 213Bi. Proximity imaging is able to resolve two 1 mm-radius sources of less than 0.1 μCi separated by 1 cm and at 1 mm from the detector, as well as it can provide planar images of 221Fr and 213Bi biodistributions of the mouse phantom in 5 minutes.


Complementation of the xeroderma pigmentosum DNA repair defect in cell-free extracts.
Soluble extracts from human lymphoid cell lines that perform repair synthesis on covalently closed circular DNA containing pyrimidine dimers or psoralen adducts are described. Short patches of nucleotides are introduced by excision repair of damaged DNA in an ATP-dependent reaction. Extracts from xeroderma pigmentosum cell lines fail to act on damaged circular DNA, but are proficient in repair synthesis of ultraviolet-irradiated DNA containing incisions generated by Micrococcus luteus pyrimidine dimer-DNA glycosylase. Repair is defective in extracts from all xeroderma pigmentosum cell lines investigated, representing the genetic complementation groups A, B, C, D, H, and V. Mixing of cell extracts of group A and C origin leads to reconstitution of the DNA repair activity.


Prophylactic nipple-sparing mastectomy in young previvors: Examining decision-making, reconstructive outcomes, and patient satisfaction in BRCA+ patients under 30.
Bilateral prophylactic mastectomies (BPM) in young previvors with high-risk mutations are rising; however, little data on management, therapy timing, and outcomes exist. BRCA+ patients under 30 undergoing BPM from 2006 to 2018 were reviewed. Twenty-two patients aged 23-29 underwent mastectomy 4.2 years after genetic diagnosis. Twelve patients completed surveys, most often citing personal decisions (50%) for undergoing mastectomy and plastic surgeons' recommendations (83.3%) for reconstruction. About 73% of patients completely understood risks/benefits of mastectomy and 63.6% of reconstruction. Patients reported high BREAST-Q Satisfaction and Well-Being scores. Continued educational resource development will optimize shared decision-making in the reconstructive process.


Oral colonization of Acinetobacter baumannii in intensive care units: Risk factors, incidence, molecular epidemiology, association with the occur of pneumonia and sepsis, and infection control measures.
Oral colonization of Acinetobacter baumannii can lead to infections such as pneumonia and sepsis. We aimed to evaluate oral colonization of hospitalized patients in ICUs and to examine risk factors for oral colonization, molecular epidemiology, and incidence of pneumonia and sepsis. The study began in February 2021. Oral cultures were taken. The microorganisms were identified by a Maldi-tof MS mass spectrometry device. Colistin resistance genes were investigated by polymerase chain reaction. Clonal relationships were determined by pulsed-field gel electrophoresis. A. baumannii was found in 21 of 96 patients' oral cultures. Pneumonia and sepsis due to A. baumannii were detected in 14 and 5 patients, respectively. The mean growth time of A. baumannii from oral cultures was 11.8 days, and the meantime for the occurrence of pneumonia after oral growth was 5.2 days. We determined a plasmid mediated mcr-2 colistin resistance gene in a colistin susceptible A. baumannii strain. It is the first report of the plasmid mediated mcr-2 colistin resistance gene in our country. In total, fourteen different A. baumannii genotypes were determined in PFGE. It was determined that the effects of antibiotic use, oral motor dysfunction, mechanical ventilation, intubation, orogastric tube use, and total parenteral nutrition intake on oral colonization were statistically significant. Oral colonization of A. baumannii is a significant concern in ICUs. We believe that it is important to take oral cultures and follow the risk factors and take infection control measures to prevent oral colonization of resistant isolates in ICUs.


Enhanced production of carboxymethylcellulase of a marine microorganism, Bacillus subtilis subsp. subtilis A-53 in a pilot-scaled bioreactor by a recombinant Escherichia coli JM109/A-53 from rice bran.
A gene encoding the carboxymethylcellulase (CMCase) of a marine bacterium, Bacillus subtilis subsp. subtilis A-53, was cloned in Escherichia coli JMB109 and the recombinant strain was named as E. coli JMB109/A-53. The optimal conditions of rice bran, ammonium chloride, and initial pH of the medium for cell growth, extracted by Design Expert Software based on response surface methodology, were 100.0 g/l, 7.5 g/l, and 7.0, respectively, whereas those for production of CMCase were 100.0 g/l, 7.5 g/l, and 8.0. The optimal temperatures for cell growth and the production of CMCase by E. coli JM109/A-53 were found to be and 40 and 35 °C, respectively. The optimal agitation speed and aeration rate of a 7 l bioreactor for cell growth were 400 rpm and 1.5 vvm, whereas those for production of CMCase were 400 rpm and 0.5 vvm. The optimal inner pressure for cell growth was 0.06 MPa, which was the same as that for production of CMCase. The production of CMCase by E. coli JM109/A-53 under optimized conditions was 880.2 U/ml, which was 2.9 times higher than that before optimization. In this study, rice bran and ammonium chloride were developed as carbon and nitrogen source for production of CMCase by a recombinant E. coli JM109/A-53 and the productivity of E. coli JM109/A-53 was 5.9 times higher than that of B. subtilis subp. subtilis A-53.


Toxigenic C. difficile induced inflammatory marker expression by human intestinal epithelial cells is asymmetrical.
Clostridium difficile infection of the intestinal epithelium and consequent pseudomembranous colitis is an important cause of morbidity and mortality. Pathogenesis has been ascribed exclusively to toxin production. Using in vitro models of human intestinal epithelial layers, we show that exposure to toxigenic C. difficile upregulates epithelial expression of IL-8 and ICAM-1, two molecules important in neutrophil chemoattraction and adhesion and subsequent inflammation. IL-8 production was also stimulated by toxin-containing supernatants. C difficile induced IL-8 release was inhibited by specific antiserum. Increased ICAM-1 expression only occurred after basolateral exposure to C. difficile while apical exposure had no effect on ICAM-1 expression. However, transepithelial electrical resistance was impaired by apical exposure to bacterial suspensions. We suggest that apical exposure to C. difficile induces changes in epithelial layer integrity which allows the bacteria and/or the toxin access to the basolateral compartment where pathogenic inflammatory mechanisms are activated.


Production of innovative gluten-free breakfast cereals based on red and black rice by extrusion processing technology.
The transformation of black and red, broken or not, whole rice grains, into breakfast cereals is an interesting way to add value to these snacks for some reasons. Firstly, broken kernels hardly achieve a high market value; whole rice is healthy not only for their nutrient contents but also for their phytochemical profile, rich in phenolic compounds; breakfast cereals from pigmented rice are colored by themselves, and any additional colorant is unneeded; finally, rice is naturally gluten-free and suitable for those with conditions like celiac disease or gluten sensitivity. The objective of this study was to optimize some extrusion parameters that account for the physicochemical properties of extrudates by using response surface methodology. Feed moisture between 15 and 21% and the 4th barrel zone temperature between 110 and 160 °C were the independent variables. Specific features such as color, texture, water solubility and absorption, cold viscosity, expansion, specific volume, and compression force were evaluated. The trials have shown that moisture had a higher impact on the extrusion process than temperature. Less expanded, denser, harder, and darker products were obtained at higher moisture levels. The optimum points were defined at 15.5% and 16.0% of feed moisture and 159 °C and 150 °C of temperature for black and red rice extrudates, respectively. These conditions resulted in cereal breakfast balls with optimal water solubility, volume, texture, and good color. Additionally, cold viscosities and a low compression led to products with a potential high approval by consumers.


Adsorption of mycotoxins.
In vitro binding studies with different mycotoxins are often made to test various adsorbents for their ability to detoxify these toxins in animal feed. In this study different clays were investigated for their ability to bind aflatoxin B1, zearalenone, ochratoxin A and deoxynivalenol in two different buffer systems (pH 3 and pH 6.5). In addition chemical/physical properties like cation exchange capacity and the concentration of exchangeable Ca(2+), Na(+), Mg(2+) and K(+) ions in the adsorbents were determined to establish if there is a connection between these parameters and the capacity to bind mycotoxins. Most of the tested clays showed high adsorption rates for aflatoxin B1 in both buffer systems. Adsorption rates for ochratoxin A and zearalenone of the tested clays were in the range of 0-100%. None of the tested adsorbents had the ability to bind deoxynivalenol. In this study no correlation between the cation exchange capacity of the clays or the concentration of exchangeable Ca(2+), Na(+), Mg(2+) and K(+) ions and the ability to adsorb mycotoxins could be investigated.


Neonatal anterior cervical arachnoid cyst: case report and review of the literature.
Anterior cervical arachnoid cysts are rare in the pediatric population, with only 16 cases reported. We present the first case of an anterior cervical arachnoid cyst in a neonate and review the literature on pediatric cervical arachnoid cysts. A 16-day-old baby girl with a history of myelomeningocele repair progressively developed symptoms of upper extremity weakness over the course of 2 weeks. Magnetic resonance imaging (MRI) demonstrated a compressive arachnoid cyst extending from C2 to C7. The child was taken for posterior cervical laminoplasty and cyst fenestration. Intraoperatively, diffuse cervical arachnoiditis was noted. Rapid improvement in upper extremity paresis was noted within 24 h of surgery, and MRI confirmed decompression of the cyst. However, flaccid upper extremity paresis recurred within 2 weeks. MRI confirmed recurrence of the anterior cervical arachnoid cyst. The child was taken for a secondary fenestration and stenting of the cyst. Only partial improvement in arm function was noted by 1 month following reoperation. Arachnoid cysts can be effectively treated with surgical fenestration, shunting, and complete or partial excision. Rapid identification and treatment results in improvement in myelopathic symptoms; however, the most efficacious treatment modality remains unknown. Of the 17 cases of anterior cervical arachnoid cysts reported in the literature, 11 (65%) have had either prior myelomeningocele repair or a history of spinal trauma. Anterior cervical arachnoid cysts should be considered in the differential diagnosis of acute onset myelopathy in the pediatric population especially in cases with a history of spinal trauma or myelomeningocele repair.


Effects of noise exposure on neonatal auditory brainstem response thresholds in pregnant guinea pigs at different gestational periods.
Noise exposure during pregnancy has been reported to cause fetal hearing impairment. However, little is known about the effects of noise exposure during various gestational stages on postnatal hearing. In the present study, we investigated the effects of noise exposure on auditory brainstem response (ABR) at the early, mid-, and late gestational periods in newborn guinea pigs. Pregnant guinea pigs were exposed to 4-kHz pure tone at a 120-dB sound pressure level for 4 h. We divided the animals into four groups as follows: the control, early gestational exposure, mid-gestational exposure, and late gestational exposure groups. ABR thresholds and latencies in newborns were recorded using 1-, 2-, and 4-kHz tone burst on postnatal days 1, 7, 14, and 28. Changes in ABR thresholds and latencies were measured between the 4 × 4 and 4 × 3 factorial groups mentioned above (gestational periods × postnatal days, gestational periods × frequencies). The thresholds were low in the order of control group < early gestational exposure group < mid-gestational exposure group and late gestational exposure group. Noise exposure during pregnancy influenced ABR thresholds in neonatal guinea pigs. This is the first study to show that noise exposure during the early, mid-, and late gestational periods significantly elevated ABR thresholds in neonatal guinea pigs.


Childhood vitiligo.
Eighty-two children (ages 6 months to 12 years) with clinical and/or histopathologic diagnoses of vitiligo were evaluated; 35 were male and 47, female. Fifty-six were black, 25 white, and 3 classified as "other." Children were compared with control groups of children with other skin diseases and with adults with vitiligo. Children had an increased incidence of segmental vitiligo (p less than 0.01). Children had an increased incidence of autoimmune and/or endocrine disease and also of premature graying in their immediate and extended family members (p less than 0.001). Six of 33 children with vitiligo tested had positive organ-specific serum autoantibodies, which was a higher incidence than in the control group of children (p less than 0.05). Eighteen percent of children treated with topical psoralens and long-wave ultraviolet light (PUVA) therapy had an acceptable response, which was less than an adult group similarly treated. We have found childhood vitiligo to be a distinct subset of vitiligo, showing increased segmental presentation; strong autoimmune and/or endocrine disease background and high incidence of premature graying in the families of affected children; the presence of organ-specific serum autoantibodies and a poor response to topical PUVA therapy.


Surgical drainage of amoebic abscess of the liver.
45 cases of amoebic abscess of the liver which were managed, over a period of 17 years, by surgical drainage are reviewed. The clinical presentation, diagnostic procedures performed, and morbidity and mortality are presented. From the results the following indications for surgical intervention are recommended: presence of an obvious liver abscess; persistence or aggravation of symptoms and signs during or following medical treatment, or persistence of symptoms with an inconclusive result from diagnostic procedures.


EVALUATION OF UNDERWATER ENDOSCOPIC MUCOSAL RESECTION FOR COLORECTAL POLYPS IN AN OUTPATIENT CLINIC IN BRAZIL.
Since 2012, a new technique for resection of large polyps has been described, the underwater endoscopic mucosal resection (UEMR). Some advantages that emerge from it is the needless of injection in submucosal layer and a greater chance of complete capture of the polyp. There are few studies of UEMR in Brazil. The aim of this study is to evaluate the safety and efficacy of this technique in one Brazilian center. This case series was conducted from February to December of 2020. Colorectal polyps greater than 9 mm without features of deep submucosal invasion were resected using UEMR. Twenty-four large polyps were resected with the UEMR approach from 24 patients. The mean size of the polys was 19 mm, ranging from 12 to 35 mm. All lesions were successful resected and 66% (16/24) were resected en bloc. In histologic analyses, most of them were adenomas (70.8%) and only one had deep submucosal invasion. There were no cases of acute complications, such perforation or acute bleeding. The UEMR is a safe and feasible procedure. With the emerging data on the procedure, it seems to be a wonderful tool in preventing colorectal cancer and its applicability and scope should be encourage to surpass reference centers.


Fate of micronuclei and micronucleated cells.
The present review describes available evidence about the fate of micronuclei and micronucleated cells. Micronuclei are small, extranuclear chromatin bodies surrounded by a nuclear envelope. The mechanisms underlying the formation of micronuclei are well understood but not much is known about the potential fate of micronuclei and micronucleated cells. Many studies with different experimental approaches addressed the various aspects of the post-mitotic fate of micronuclei and micronucleated cells. These studies are reviewed here considering four basic possibilities for potential fates of micronuclei: degradation of the micronucleus or the micronucleated cell, reincorporation into the main nucleus, extrusion from the cell, and persistence in the cytoplasm. Two additional fates need to be considered: premature chromosome condensation/chromothripsis and the elimination of micronucleated cells by apoptosis, yielding six potential fates for micronuclei and/or micronucleated cells. The available data is still limited, but it can be concluded that degradation and extrusion of micronuclei might occur in rare cases under specific conditions, reincorporation during the next mitosis occurs more frequently, and the majority of the micronuclei persist without alteration at least until the next mitosis, possibly much longer. Overall, the consequences of micronucleus formation on the cellular level are still far from clear, but they should be investigated further because micronucleus formation may contribute to the initial and later steps of malignant cell transformation, by causing gain or loss of genetic material in the daughter cells and by the possibility of massive chromosome rearrangement in chromosomes entrapped within a micronucleus by the mechanisms of chromothripsis and chromoanagenesis.


[Evaluation of the effects of vibro-acoustic stimulation test on the fetus during labor under epidural analgesia and evidence of its safety by way of auditory brainstem response].
This study was undertaken to elucidate the effects of epidural analgesia on vibro-acoustic stimulation test (VAST) during normal labor and auditory brainstem response (ABR) in fifty full term parturients without any complication. The safety of VAST in relation to the ABR of neonates was also studied. The results were as follows, 1) There were some changes in CTG monitoring in five cases (10%) in the 10 minutes after epidural analgesia. However, these changes were not ominous signs but all related to the coiling of the cord, as previously reported. 2) The ABR latency-intensity curve (audio-function of the newborn infants) revealed no hazardous change in VAST-loaded infants or in the controls. The response threshold was 10dB in this study. The application of VAST to the parturients under epidural analgesia was therefore not only harmless to the fetuses but also a useful way to evaluate fetal well-being.


The Alu insertion in the CLCN5 gene of a patient with Dent's disease leads to exon 11 skipping.
Alu sequences are short, interspersed elements that have generated more than one million copies in the human genome. They propagate by transcription followed by reverse transcription and integration, causing mutations, recombination, and changes in pre-mRNA splicing. We have recently identified a 345-bp long Alu Ya5 element inserted in codon 650 within exon 11 of the chloride channel ClC-5 gene (CLCN5) of a patient with Dent's disease. A microsatellite pedigree analysis indicated that the insertion occurred in the germline of the maternal grandfather. Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and nephrocalcinosis. Here, we found, by RT-PCR amplification of RNA extracted from the patient's blood and subsequent DNA sequencing, that the Alu insertion led to an aberrant splicing of the CLCN5 pre-mRNA that skipped exon 11. Using the ESE finder and RESCUE-ESE Web interfaces, we identified two high-score exonic splicing enhancer (ESE) sequences in the site of insertion. The functional significance of these ESE motifs is suggested by our observation that these sequences are highly conserved among mammal CLCN5 genes. Therefore, we suggest that the Alu insertion causes exon skipping by interfering with splicing regulatory elements. The altered splicing would predict a truncated ClC-5 protein that lacks critical domains for sorting and chloride channel function.


Linkages between nursing and the quality of patient care: a 2-year comparison.
In 2005, the Robert Wood Johnson Foundation established the Interdisciplinary Nursing Quality Research Initiative (INQRI) program to produce rigorous evidence regarding linkages between nursing and quality of health care. The purpose of this paper is to describe scientific advances in understanding relationships between nursing, care processes, and the outcomes of the people supported by this discipline in 2004 (year before INQRI's launch) and in 2009 (5 years after INQRI was established). Comprehensive literature reviews for the years 2004 and 2009 were conducted using a conceptually based search strategy and multidisciplinary engines. The designs, methods, results, and conclusions of included papers were summarized, synthesized, and analyzed. The literature search identified 389 studies (161 in 2004; 228 in 2009), which examined the relationship between nursing and patient care quality. The number of published papers in all categories of study designs-nonexperimental (72 in 2004; 97 in 2009), quasi-experimental (55 in 2004; 80 in 2009) and experimental (34 in 2004; 51 in 2009)-increased between the years 2004 and 2009. This line of inquiry also has expanded its reach through publications in a greater diversity of journals and journals with higher impact ratings. The body of evidence regarding linkages between nursing and quality of care has increased in the nature and depth of science between 2004 and 2009, as seen in higher rates and quality of publications, enhanced methodological rigor, and evidence of stronger interdisciplinary collaboration. Although the unique contribution of INQRI to this expanded body of knowledge is unclear, the evidence supports the increased importance of INQRI's goal of measuring and enhancing nursing's contributions to the quality of patient care.


Birth order in homosexual versus heterosexual sex offenders against children, pubescents, and adults.
Homosexual men erotically attracted to physically mature partners typically have more older brothers than comparable heterosexual men. We investigated whether late fraternal birth positions also occur in homosexuals attracted to children or pubescents. Probands were 710 sex offenders from Gebhard et al.'s (1965) study of sexual offending. Homosexual offenders against adults and pubescents had later fraternal birth positions than heterosexual offenders against adults and pubescents, respectively; there was no difference between the homosexual and heterosexual offenders against children. Results provide some evidence that homosexuality in men attracted to immature males is etiologically related to homosexuality in men attracted to mature males.


Total Ankle Arthroplasty Using the Agility Stemmed Talar Revisional Component: Three to Eight Year Follow-Up.
Ankle fusion has been the traditional treatment of choice for failed total ankle arthroplasties or arthritic conditions that preclude the use of primary implants. A custom stemmed agility talar component was designed to be used in these conditions. The first 30 cases by a single surgeon were reviewed at two intervals. The study was a retrospective chart review with data including ankle diagnosis, deformity, bone loss and other factors that may have an impact on ankle arthroplasty. American Orthopedic Foot and Ankle Society (AOFAS) hindfoot clinical rating scale scores were recorded and this group of patients was reviewed post operatively at a mean of 19 months (6-52), and at a mean of 54 months (37-94). The design rational will be discussed, as well as a brief description of the surgical technique. Retention of the implant was 93 percent at a mean of 19 months and 88 percent at a mean of 54 months. AOFAS scores were improved from 55 to 71 at the latest review. Complications included two slow healing lateral incisions, one deep infection, one fractured stem, and one below knee amputation secondary to acute femoral artery occlusion. Our experience with this custom implant has allowed salvage of many complex and difficult talar sided problems that otherwise would have required a fusion.


Integrative microphysiological tissue systems of cancer metastasis to the liver.
The liver is the most commonly involved organ in metastases from a wide variety of solid tumors. The use of biologically and cellularly complex liver tissue systems have shown that tumor cell behavior and therapeutic responses are modulated within the liver microenvironment and in ways distinct from the behaviors in the primary locations. These microphysiological systems have provided unexpected and powerful insights into the tumor cell biology of metastasis. However, neither the tumor nor the liver exist in an isolated tissue situation, having to function within a complete body and respond to systemic events as well as those in other organs. To examine the influence of one organ on the function of other tissues, microphysiological systems are being linked. Herein, we discuss extending this concept to tumor metastases by integrating complex models of the primary tumor with the liver metastatic environment. In addition, inflammatory organs and the immune system can be incorporated into these multi-organ systems to probe the effects on tumor behavior and cancer treatments.


Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression leads to paracrine growth promotion of chronic myelogenous leukemia cells.
Galectin-3 is induced in chronic myelogenous leukemia (CML) cells by co-culture with bone marrow stromal cells, making paracrine growth promotion of CML cells in conditioned medium (CM) from galectin-3 overexpressing CML cells more potent. We used gel filtration chromatography to demonstrate that the bovine SERPINA1-fetal bovine serum albumin (BSA) complex was specifically suppressed in CM from galectin-3 overexpressing cells. The SERPINA1-BSA complex as well as human plasma SERPINA1 inhibited the growth of CML cells, while exogenous galectin-3 partly offset this effect. These findings suggest that galectin-3 overexpression promotes paracrine growth of CML cells by interfering with the action of the growth inhibitory SERPINA1-albumin complex.


Optimized extraction and molecular characterization of polysaccharides from Sophora alopecuroides L. seeds.
Optimized extraction of crude polysaccharides from Sophora alopecuroides L. seeds (CSAP) was firstly investigated, and the results were extraction time 4.15 h, extraction temperature 70.68°C and water/seed ratio 50.99:1 ml/g. At this proximal point, highest yield (10.88%) and relative viscosity (1.2952) were obtained for CSAP, which contained 78.40% sugar, 6.08% protein, 9.71% ash, 7.16% moisture and 1.88% uronic acid. Neutral fractions of F15, F25, F35 and F60 were further obtained via stepwise alcohol precipitation. Results of monosaccharide composition indicated that CSAP and its neutral fractions mainly consisted of mannose and galactose (79.45-97.52%) with M/G ratios of 0.94-1.48, typical for galactomannans, which were demonstrated by FT-IR. Weight-average molecular weight, radius of gyration and hydrodynamic radius were in the same order (F15>F25>F35>F60), whereas the highest intrinsic viscosity was observed for F25. Multiple analyses, including Mark-Houwink-Sakurada exponent (0.48-0.80), persistence length (1.45-3.93 nm), conformation zoning (random coil) and power-law exponent (b>1), showed flexible coils for all neutral fractions. Concerning viscometry, there were no aggregates (K″ 0.60) or coil overlaps ("master curve") of F25 in dilute solutions. Relatively weak surface activity of F25 was probably related to its particular chemical structure and proteinaceous moieties closely conjoined.


Higher Hospitalization Rates in Children Born HIV-exposed Uninfected in British Columbia, Canada, Between 1990 and 2012.
Compared with children who are HIV-unexposed and uninfected (CHUU), children who are HIV-exposed and uninfected (CHEU) experience more clinical complications. We investigated hospitalizations among CHEU by antenatal antiretroviral therapy (ART) exposure, in British Columbia, Canada. This retrospective controlled cohort study used administrative health data from 1990 to 2012. CHEU and CHUU were matched 1:3 for age, sex and maternal geographical area of residence. We determined adjusted odds ratios (aORs) via conditional logistic regression, adjusting for maternal risk factors. A total of 446 CHEU and 1333 CHUU were included. Compared with CHUU, more CHEU experienced one or more lifetime hospitalization (47.3% vs. 29.8%), one or more neonatal hospitalization (40.4% vs. 27.6%), and any intensive care unit admission (28.5% vs. 9.2%). In adjusted analyses, CHEU experienced higher odds of any lifetime hospitalization (aOR 2.30, 95% confidence interval 1.81-2.91) and neonatal hospitalization (aOR 2.14, 95% confidence interval 1.68-2.73), compared with CHUU. There was, however, no difference in infection-related hospitalizations (9.0% vs. 7.5%), which were primarily respiratory tract infections among both CHEU and CHUU. CHEU whose mothers-initiated ART preconception showed lower odds of infection-related hospitalizations than children whose mothers initiated ART during pregnancy or received no ART. CHEU experienced increased odds of hospitalization relative to CHUU. A substantial number of CHEU hospitalizations occurred within the neonatal period and were ICU admissions. Initiating ART preconception may reduce the risk of infection-related hospitalizations. These findings reinforce the benefit of ART in pregnancy and the need for ongoing pediatric care to reduce hospitalizations.


3D CT protocol in the assessment of the esophageal neoplastic lesions: can it improve TNM staging?
The purpose of this prospective observational study was the evaluation of the usefulness of MPR reconstructions and virtual endoscopy in the study of the esophageal carcinoma. Thirty-nine patients with esophageal cancer proved by means of endoscopy, underwent preoperative TNM staging with dynamic CT of the chest and abdomen with the aid of 3D rendering. Twenty-six patients underwent surgery, and the CT results were compared with histopathologic findings. In staging the T parameter, the CT with 3D reconstructions and virtual endoscopy, showed a sensitivity of 92% and an accuracy of 88%. In staging lymph nodes, the sensitivity in our study was 85%, the specificity 58%, and the accuracy 69%. Our protocol of the study of the esophageal cancer with 3D CT and virtual endoscopy, demonstrated a high concordance with the surgical and pathologic findings. The 3D reconstructed images were very helpful to the surgeons regarding preoperative planning. We performed an observational enquiry, and although this was a small study, it has, however, confirmed that the 3D imaging of the esophagus represents a valuable advantage to conventional imaging. Further studies with a larger number of patients are needed to prove its superiority to traditional CT imaging of the esophagus.


Mutant mice reveal the molecular and cellular basis for specific sensory connections to inner ear epithelia and primary nuclei of the brain.
We review the in vivo evidence for afferent fiber guidance to the inner ear sensory epithelia and the central nuclei of termination. Specifically, we highlight our current molecular understanding for the role of hair cells and sensory epithelia in guiding afferents, how disruption of certain signals can alter fiber pathways, even in the presence of normal hair cells, and what role neurotrophins play in fiber guidance of sensory neurons to hair cells. The data suggest that the neurotrophin BDNF is the most important molecule known for inner ear afferent fiber guidance to hair cells in vivo. This suggestion is based on experiments on Ntf3 transgenic mice expressing BDNF under Ntf3 promoter that show deviations of fiber growth in the ear to areas that express BDNF but have no hair cells. However, fiber growth can occur in the absence of BDNF as demonstrated by double mutants for BDNF and Bax. We directly tested the significance of hair cells or sensory epithelia for fiber guidance in mutants that lose hair cells (Pou4f3) or do not form a posterior crista (Fgf10). While these data emphasize the role played by BDNF, normally released from hair cells, there is some limited capacity for directed growth even in the absence of hair cells, BDNF, or sensory epithelia. This directed growth may rely on semaphorins or other matrix proteins because targeted ablation of the sema3 docking site on the sema receptor Npn1 results in targeting errors of fibers even in the presence of hair cells and BDNF. Overall, our data support the notion that targeting of the afferent processes in the ear is molecularly distinct from targeting processes in the central nuclei. This conclusion is derived from data that show no recognizable central projection deviation, even if fibers are massively rerouted in the periphery, as in Ntf3(tgBDNF) mice in which vestibular fibers project to the cochlea.


New synthetic peptide with efficacy for heparin reversal and low toxicity and immunogenicity in comparison to protamine sulfate.
Protamine sulfate (PS), the only clinically approved antidote to unfractionated heparin (UFH), is widely used for cardiopulmonary surgery or other extracorporeal circulation situations. However, the applications of PS have accompanied various severe side-effects. In this study, we presented a novel synthesized peptide compound (RRRRR-RRRRR-RRRRR-sulfate, R15S) served as a safer UFH antidote. Comparison studies were conducted between PS and R15S on efficacy and safety, aided by heparin neutralization studies, drug toxicity studies and anaphylactic analysis. Our research demonstrated that R15S contained comparable UFH neutralization activity in vitro and in rats in vivo as to active partial thromboplastin time (APTT) and anti-FXa assays. There was no cytotoxicity for R15S at 60 μg mg(-1) or below and the median lethal dose (LD50) of R15S in mice was 35.4 mg kg(-1), both of which were similar to that of PS. Furthermore, R15S exhibited no immunogenicity while it was obvious in guinea pigs immunized with PS. The level of cross-reactivity to anti-PS antibodies of R15S was about 30%. Both of which indicated much safer properties of R15S than PS. In conclusion, we presented a promising candidate R15S for UFH reversal, which is effective in neutralizing UFH and potentially safer in use.


Untangling the Web of Lymphoma Somatic Mutations.
In this issue of Cell, Reddy et al. report integrative genetic characterization of diffuse large B cell lymphomas (DLBCL), including large-scale exome capture, transcriptomes, CRISPR screens, and integrative clinical biomarker studies. This provides the first comprehensive overview of DLBCL biology and the basis for future precision medicine approaches to this disease.


Management and treatment of decubital ulcers of an elderly population in the assisted sanitary residence of Futura-Viagrande (Catania, Sicily, Italy).
Decubital lesions indicate the gravity of the pathologies of the elderly patients, representing a serious cause of disability and of mortality. The present study was aimed at evaluating the decubital lesions during 1 year of treatment in an assisted sanitary residence (abbreviated as RSA from the Italian name), through observations of the assistential and therapeutical outcomes, aimed at improving the quality of life of the recovered elderly patients. We had 131 patients involved from a total of 308 recovered patients in the RSA. Their mean age was 83.4+/-1.3 years (74 women and 57 men). All cases were treated, considering the actual clinical stages, according to the advanced protocols on the basis of the guidelines of the National Pressure Ulcer Advisory Panel (NPUAP). All patients were evaluated by using the Braden-scale at the start and after 30 days for having a risk for the development of decubital ulcers and also for monitoring the modifications during the therapy, while the improvements were evaluated only clinically, establishing the reduction of the stage of the lesions. A precise analysis of the data revealed a higher prevalence of decubital lesions at the entrance to the RSA, particularly the advanced Grades III and IV (84 patients, 27% of all recovered subjects), compared to those with lower gravity Grades I and II (47 cases, 15% of all recovered subjects). Complete healing was observed only in a few cases (18.0%), mainly in the lower grades. Applying the therapeutic methods and protocols of NPUAP, most of the ulcers displayed an improving tendency. We had only a few mortal cases due to the ulcers (3 deaths of 131 patients), nevertheless, numerous death cases for other causes occurred among the patients, having advanced grades of ulcers (12%). Our data confirm the statement that the decubital ulcers represent the marker of severity of the polypathological state of the fragile elderly patients.


Single-stage repair of interrupted aortic arch type B with ventricular septal defect.
In this video tutorial, we present our surgical technique for single-stage complete repair of an interrupted aortic arch with ventricular septal defect. The key operative steps, which include dual cannulation, the arch repair, and the intra-cardiac repair, are clearly demonstrated.


Randomised clinical study of plaque removal efficacy of an electric toothbrush in primary and mixed dentition.
Clinical investigations of electric toothbrushes in young children are limited. To assess plaque reduction efficacy of an oscillating-rotating electric versus manual toothbrush in a paediatric population in primary and mixed dentitions. In this randomised, single-brushing, 2-treatment, 4-period, replicate-use crossover study, subjects were divided into 2 age groups (3-6 years; 7-9 years) and assigned to a treatment sequence involving an Oral-B Kids electric brush and a manual brush control. Plaque was assessed pre- and post-brushing (Turesky Modified Quigley-Hein Plaque Index). Parents brushed the teeth of their children aged 3-6 years, whereas children aged 7-9 years brushed their own teeth under supervision. Plaque removal scores were analysed for brush differences in each age group separately using an analysis of covariance for crossover design. Forty-one children (n = 20, 3-6 years; n = 21, 7-9 years) completed the study. For the primary dentition in children 3-6 years, the electric brush reduced 32.3% more plaque than the manual brush (P = .005). For the mixed dentition in children 7-9 years, the electric brush reduced 51.9% more plaque than the manual brush (P < .001). An electric toothbrush reduced significantly more plaque than a manual toothbrush in 2 paediatric age groups.