Otosclerosis surgery: Assessment of patient comfort.
To evaluate operative comfort and stress in patients undergoing stapedotomy for otosclerosis under local versus general anesthesia. Consecutive otosclerosis patients managed over a 9-month period responded to 3 validated questionnaires to assess peri- and post-operative comfort: Glasgow Benefit Inventory, Cohen's Perceived Stress Scale and the Posttraumatic Stress Disorder Checklist Scale. These results and audiometric data were compared between local and general anesthesia groups. Twenty-one patients were included in the local anesthesia group and 7 in the general anesthesia group, after exclusion of patients with history of otosclerosis surgery. There was no significant inter-group difference on Glasgow Benefit Inventory (P=0.38) or Posttraumatic Stress Disorder Checklist Scale (P=0.86). Perceived Stress Scale scores were higher in the general anesthesia group (P=0.038). In total, 67% of patients reported no discomfort under local anesthesia, and 86% were ready to undergo the procedure under local anesthesia again. There were no significant differences in postoperative symptoms, or in air-bone gap≤10dB (local anesthesia 81%, general anesthesia 71%; P=0.156). Local anesthesia in otosclerosis surgery did not increase stress or postoperative symptoms compared to general anesthesia. Audiometric results were not affected by type of anesthesia.


[Continuous internal splinting of the small intestine for prevention of postoperative ileus (author's transl)].
This procedure was mostly performed in cases of recurrent ileus. The high mortality rate is due to the severe underlying diseases or postoperative complications.


Systematic review and meta-analysis of the role of Faecalibacterium prausnitzii alteration in inflammatory bowel disease.
We comprehensively carry out a systematic review and meta-analysis of previous studies to determine the association between intestinal Faecalibacterium prausnitzii (F. prausnitzii) and inflammatory bowel disease (IBD) in human studies. A systematic literature search of PubMed, Embase, and the Cochrane Library database was conducted until April 1, 2020. Inclusion criteria were studies involving patients with Crohn's disease (CD) or ulcerative colitis (UC) with abundance of F. prausnitzii. The quality of the studies was assessed by the modified Newcastle-Ottawa scale. A total of 1669 subjects (427 CD patients, 560 UC patients, and 682 healthy controls) were enrolled from 16 studies. Both CD (standardized mean difference [SMD]: -1.36; 95% CI, -1.74 to -0.98; P < 0.00001) and UC patients (SMD: -0.81; 95% CI, -1.21 to -0.42; P < 0.0001) had a lower abundance of F. prausnitzii than the healthy controls. Compared with the IBD remission patients, the IBD active patients had lower levels of F. prausnitzii (SMD: -0.56; 95% CI, -0.91 to -0.21; P = 0.002). In the subgroup analyses, the abundance of F. prausnitzii was reduced in both active CD patients (SMD: -0.78; 95% CI, -1.51 to -0.04; P = 0.04) and active UC patients (SMD:-0.44; 95%CI, -0.81 to -0.07; P = 0.02) when compared with the patients with CD or UC in remission, respectively. A negative association between abundance of F. prausnitzii and IBD activity is observed, but a cut-off level of F. prausnitzii to diagnose and/or to start treating IBD is not determined.


Swallowing and pharyngo-esophageal manometry in obstructive sleep apnea.
Upper airway nerve and muscle damage associated with obstructive sleep apnea may impair the strength and dynamics of pharyngeal and esophageal contractions during swallowing. To evaluate the presence of alterations in pharyngoesophageal manometry in patients with obstructive sleep apnea with and without oropharyngeal dysphagia. This study prospectively evaluated 22 patients with obstructive sleep apnea without spontaneous complaints of dysphagia, using a questionnaire, fiberoptic endoscopic evaluation of swallowing, and pharyngoesophageal manometry, including measurement of the upper and lower esophageal sphincter pressures and mean pharyngeal pressures at three levels during swallowing. The dysphagia group consisted of 17 patients (77.3%) in whom swallowing abnormalities were detected on fiberoptic endoscopic evaluation of swallowing (n=15; 68.2%) and/or in the questionnaire (n=7; 31.8%). The five remaining cases comprised a control group without oropharyngeal dysphagia. In all cases of abnormalities on fiberoptic endoscopic evaluation of swallowing, there was premature bolus leakage into the pharynx. There was no statistically significant difference between the groups regarding any of the pharyngoesophageal manometry measurements, age, or severity of obstructive sleep apnea. Pharyngoesophageal manometry detected no statistically significant difference between the groups with and without oropharyngeal dysphagia.


Classification of hysteroscopical images using texture and vessel descriptors.
In recent years, hysteroscopy, used as an outpatient office procedure, in combination with endometrial biopsy, has demonstrated its great potential as the method of first choice in the diagnosis of various gynecological abnormalities including abnormal uterine bleeding (AUB) and endometrial cancer (CA). In patients suffering with AUB, the blood vessels of the endometrium are hypertrophic, whereas in the case of CA vascularization is irregular or anarchic. In this paper, a methodology for the classification of hysteroscopical images of endometrium using vessel and texture features is presented. A total of 28 patients with abnormal uterine bleeding, 10 patients with endometrial cancer and 39 subjects with no pathological condition were imaged. 16 of the patients with AUB were premenopausal and 12 postmenopausal, all with CA were postmenopausal, and all with no pathological condition were premenopausal. All images were examined for the appearance of endometrial vessels and non-vascular structures. For each image, 167 texture and vessel's features were initially extracted, which were reduced after feature selection in only 4 features. The images were classified into three categories using artificial neural networks and the reported classification accuracy was 91.2 %, while the specificity and sensitivity were 83.8 and 93.6 % respectively.


Enhanced efficacy of formoterol-montelukast salt in relieving asthma features and in preserving β2-agonists rescue therapy.
Adrenergic β2-agonists represent a mainstay in asthma management. Their chronic use has been associated with decreased bronchoprotection and rebound hyperresponsiveness. Here we investigate on the possible therapeutic advantage of a pharmacological association of β2-agonists with montelukast, a highly selective leukotriene receptor antagonist, in modulating bronchial reactivity and controlling asthma features. The study has been conducted in vitro and in vivo and also takes advantage of the synthesis of a salt that gave us the possibility to simultaneously administer in vivo formoterol and montelukast (MFS). In vitro studies demonstrate that montelukast (1) preserves β2-agonist response in isolated bronchi by preventing homologous β2-adrenoceptor desensitization; (2) reduces desensitization by modulating β2-receptor translocation in bronchial epithelial cells. In vivo studies demonstrate that sensitized mice receiving formoterol or montelukast display a significant reduction in airway hyperresponsiveness, but the β2-agonist relaxing response is still impaired. Allergen challenge causes β2 heterologous desensitization that is further increased by treatment in vivo with formoterol. Conversely MFS not only inhibits airway hyperresponsiveness but it rescues the β2-agonist response. Histological analysis confirms the functional data, demonstrating an enhanced therapeutic efficiency of MSF in controlling also pulmonary metaplasia and lung inflammation. MFS is efficacious also when sensitized mice received the drug by local administration. In conclusion, the data obtained evidenced a therapeutic advantage in the association of β2-agonists with montelukast in the control of asthma-like features and a better rescue bronchodilation response to β2-agonists.


Propofol depresses the hypoxic ventilatory response during conscious sedation and isohypercapnia.
Propofol infusion at subanesthetic doses provides reliable conscious sedation. However, the ventilatory effects of sedative doses of propofol have not been established. The current study was conducted to determine the effects of propofol sedation on the hypoxic ventilatory response. Eight healthy, male volunteers received 1 mg.kg-1 propofol followed by a propofol infusion adjusted to maintain a constant, subanesthetic level of sedation. Hypoxic ventilatory response was measured using an isocapnic rebreathing technique: while keeping PETCO2 constant (approximately 6 mmHg above prestudy baseline), the authors continuously recorded minute ventilation and tidal volume, as oxygen saturation (SpO2) decreased from 98 to 70%. Hypoxic response determinations were performed before and during propofol infusion, as well as 30 and 60 min after termination of the propofol infusion. The slope of the hypoxic ventilatory response curve (VE vs. SpO2) decreased from 0.88 +/- 0.15 to 0.17 +/- 0.03 l.min-1.%SpO2 -1 during propofol sedation (mean +/- SE). Thirty minutes after discontinuation of the propofol infusion, slope returned to its prepropofol value. In addition, minute ventilation at SpO2 = 90% decreased during propofol sedation, from 16.1 +/- 0.8 to 8.7 +/- 0.4 l.min-1, accompanied by a similar decrease in tidal volume at SpO2 = 90%, from 1,099 +/- 87 to 523 +/- 21 ml. Thirty minutes after discontinuation of the propofol infusion, these variables also returned to their prepropofol values. The authors concluded that propofol infusion for conscious sedation significantly decreases the slope and causes a downward shift of the hypoxic ventilatory response curve measured during isohypercapnia.


[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence].
Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.


Validity and reliability of the Cataract TyPE Spec: an instrument for measuring outcomes of cataract extraction.
To design and validate a survey instrument that measures vision-related functional status, which is appropriate for self-administration in a clinical practice and mail survey setting. Observational, validation study in sequential patients. A prototype visual function instrument (the Cataract TyPE Spec) was developed based on focus group input and then validated in an outcomes study conducted among 1,823 patients who underwent cataract extraction performed by 22 surgeons at six centers in the United States. Reliability was determined by calculating Cronbach alpha for different types of administration (self-administration at the site of care and mailed survey) and across race and gender. Criterion validity was determined by correlating scores on the TyPE Spec with baseline measures and changes in visual acuity, overall rating of vision, and general quality of life. The instrument was internally valid (Chronbach alpha = 0.94), both on self-administration in the patient care setting and upon mailed survey administration and across patient race and gender. The TyPE Spec score was highly correlated with overall rating of vision (r =.54, P <.0001) and moderately correlated with Snellen acuity (r =.32, P <.0001), rating of vision in the better eye (r =.42, P <.0001), and quality of life, as measured by the physical component summary score of the SF-36 (r =.27, P <.001). Change in TyPE Spec similarly correlated with change in rating of vision overall, change in best-corrected Snellen acuity, and change in rating of vision in the operated eye. The cataract TyPE Spec instrument was found to be equally valid and internally consistent when administered in the patient care setting and by mail survey.


A new electrocardiographic algorithm to differentiate upper loop re-entry from reverse typical atrial flutter.
This study was performed to differentiate upper loop re-entry (ULR) from reverse typical atrial flutter (AFL). Right atrial ULR and reverse typical AFL have different mechanisms and ablation strategies, but similar electrocardiographic characteristics. This study included 26 patients with reverse typical AFL and 20 patients with ULR. The noncontact mapping system (EnSite-3000, Endocardial Solutions, St. Paul, Minnesota) was used to confirm diagnosis and guide successful radiofrequency ablation. Flutter wave polarity and amplitude in the 12-lead surface electrocardiogram were determined by two independent electrophysiologists. The flutter wave polarity in leads I and aVL was significantly different between the reverse typical AFL and ULR groups (p < or = 0.001). Voltage measurement revealed significant differences between reverse typical AFL and ULR in leads I, II, aVR, aVF, V1, and V2 (p < 0.001). A new diagnostic algorithm based on negative or isoelectric/flat flutter wave polarity and amplitude < or =0.07 mV in lead I was useful for diagnosis of ULR, with an accuracy of 90% to 97%, a sensitivity of 82% to 100%, and a specificity of 95%. Polarity and voltage measurement of flutter wave in lead I can differentiate reverse typical AFL from ULR.


Biochemical correlates of phenotypic reversion in interferon-treated mouse cells transformed by a human oncogene.
Mouse interferon (IFN) induced a phenotypic reversion in RS 485, a clonal line of NIH 3T3 oncogenically transformed by a human c-Ha-rasl gene activated by Ha-MuSV long terminal repeats (LTRs). Transfected c-Ha-ras DNA, unchanged in quantity and distribution, as compared to the parental RS 485 transformed cells, was still present in these revertants; however, there was a significant reduction in the amount of c-Ha-ras specific mRNA and of c-Ha-ras specified p21 protein.


Heat shock induces the transcriptional activation of c-fos protooncogene.
Treatment of murine 3T3 fibroblasts with mild elevated temperature (43 degrees C for 45 minutes) followed by recovery at 37 degrees C induced high levels of c-fos mRNA. The maximal c-fos induction was found after recovery at 37 degrees C for 15 minutes. Sodium arsenite induced both hsp 70 and c-fos transcripts. Induction of hsp 70 and c-fos by heat shock did not require intact protein synthesis. c-fos mRNA induced by heat shock was more stable (T1/2 greater than 90 minutes) than that induced by phorbol esters (t1/2 approximately 30 minutes). Northern blot analysis in the presence of actinomycin D and nuclear run off experiments demonstrated that heat shock augmented the transcription rate of c-fos protooncogene. Human growth hormone under the control of a murine genomic c-fos fragment spanning 770 bp 5' from the start of transcription is induced in transfected cells in response to heat shock. These data indicate that heat shock induces c-fos protooncogene acting at both transcriptional and post-transcriptional (i.e. via stabilization of transcripts) levels.


The aqueduct echo method applied to brain stem tumours.
Echoencephalography of the posterior fossa was performed in nine cases of brain stem lesion. In all instances a dorsal displacement of the cerebral aqueduct was disclosed by means of the aqueduct echo method. The quantitative displacement was expressed by the A:B ratio method and found to agree well with calculations from corresponding pneumoencephalography.


Persistence of fungicide Euparen on strawberry and/or in some canned products of strawberry.
There was studied the persistence of Euparen(dichlofluanid) on strawberry and in some canned products of strawberry, respectively. The rate of decrease of dichlofluanid residues on the leaves of strawberry is proceeding according to the first-order reaction kinetics in the initial 21 days. The content of dichlofluanid residues on strawberry treated twice with fungicide varies from 0.5 to 1.0 ppm, for strawberry sprayed three times from 1.0 to 2.0 ppm, respectively. The significant decay of dichlofluanid residues occurs during the technological procedures applied. The sensoric analysis of strawberry has proved the negative influence of the third spray of fungicide in the initial days. No significance differences between strawberry treated with fungicide and control has been found in flavor and taste of the canned products investigated.


Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents.
In recent years, cell cycle and checkpoint pathways regulation are offering new therapeutic approaches against cancer. Isatin, is a well exploited scaffold in the anticancer domain. Accordingly, the current work describes the design and synthesis of two series of (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)hydrazinylidene)-thiazolidin-4-ones, 4(a-s) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene)hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-s). The structures of the synthesized molecules were confirmed by spectral and elemental methods of analyses. Pure diastereomers were further identified with 1H-1H-NOESY and confirmed with X-ray crystallography. The target compounds were tested in vitro for their cytotoxicity against three human epithelial cell lines, liver (HepG2), breast (MCF-7), and colon (HT-29) in addition to the diploid human normal cells (WI-38) compared to doxorubicin as a reference drug. Variable cytotoxic effects (IC50 3.29-100 µmol) were reported on the three cancer cell lines with pronounced selectivity compared to the normal one WI-38. The potency of the most active compounds, 4o, 4s, 5e, 5f, 5l, 5m and 5o (IC50 3.29-9.92 µmol), in both series associated with the (Z) configurations of N = thiazolidin/ene or one, however, the configuration of the N = isatin moiety seemed to be of no importance to the activity. The tested compounds were grouped for their possible mechanism of action into 4 categories. Compound 4o with no apparent effect on all genes examined. Compounds 4s and 5o affected all genes investigated and seem to have multiple cellular targets; induced the expression of p53 and caspases, and downregulated that of CDK1. Compounds 5l and 5m directly elevated the expression of initiator and effector caspases without going through p53 pathway. Finally, compounds 5e and 5f elevated the expression of p53 and inhibited CDK1. Compounds 4s, 5e, 5f, 5l, 5m, and 5o caused a significant elevation in the activity of cleaved caspase 3 as well. Docking studies on CDK1 revealed that the active molecules bind to the tested enzyme by the same manner of the co-crystallized ligands and the isatin-thiazoldinone/ene scaffold is essential for binding of these molecules.


Multiple changes in chromatin structure precede the transcriptional activation of the human growth hormone locus in placental cells.
In addition to the growth hormone gene (hGH-N) itself, the human growth hormone (hGH) locus contains four related genes, namely hGH-V and hCS-L, -A and -B, which have appeared very recently in evolution and are specifically expressed in placenta. With the aim of identifying the regulatory elements responsible for this placental-specific expression, we have mapped the DNaseI hypersensitive sites present at the hGH gene cluster in a placental cell line (BeWo) that expresses the hGH-V and hCS genes. Our results reveal a complex pattern of hypersensitive sites distributed along the hGH locus, most of which appear to be cell type-specific. Thus, we have identified placental-specific hypersensitive sites within the first intron of the hGH-N and hGH-V genes, but not in the equivalent regions of the hCS genes. In addition, we have found several placental-specific hypersensitive sites downstream of the hCS-L and hCS-A genes, which might reflect the presence of enhancer elements similar to that located downstream of the hCS-B gene (Walker et al. (1990) J. Biol. Chem. 265, 12940). Comparison of BeWo cells with a placental cell line (JEG-3) which does not express the hGH-V and hCS genes revealed a very similar pattern of hypersensitive sites, suggesting that the sites detected are established before the onset of transcription. Our results indicate that the transition to an active hGH locus in placental cells requires multiple alterations in chromatin structure, and provide a framework for the molecular analysis of the regulatory elements and mechanisms mediating such processes.


Association of the major coat protein of fd bacteriophage with phospholipid vesicles.
The association of the major coat protein of fd bacteriophage with a phospholipid bilayer was investigated by analyzing the protein's susceptibility to proteolysis and its circular dichroism spectrum when incorporated into single-walled phospholipid vesicles. In the limits tested, this association appeared to be independent of the mass ratio of protein to lipid and of vesicle size, phospholipid composition, and method of preparation. The circular dichroism data are consistent with a similar "membrane-bound" conformation for all cases of vesicle-associated coat protein and for deoxycholate micelle-associated coat protein. Proteolysis of coat protein associated with deoxycholate micelles and with phospholipid vesicles defined the central hydrophobic core presumed to represent that portion of the protein which associates with membrane bilayers in vivo. The isolated core, which assumed a predominantly beta-type conformation in detergent solution, maintained a beta conformation when associated with a vesicle phospholipid bilayer.


Family income and young adolescents' perceived social position: associations with self-esteem and life satisfaction in the UK Millennium Cohort Study.
Self-esteem and life satisfaction are important aspects of positive mental health in young people, and both are socially distributed. However, the majority of evidence is based on socioeconomic characteristics of the family. As children enter adolescence and gain independence, perceptions of their own social position are likely to influence mental health. Using data on 11-year-olds from the UK Millennium Cohort Study, we investigated associations of both family income and young adolescents' perception of their social position with self-esteem and life satisfaction. We hypothesised that there would be differences in the impact of perceived social position on positive mental health when investigating the full scale scoring distribution or the bottom of the distribution. Therefore, we estimated proportional odds for having greater positive mental health (across the distribution of scores) and ORs for poor outcomes (lowest 10% scores). The likelihood of greater self-esteem and life satisfaction increased with income; similarly, the risk of having poor self-esteem and life satisfaction increased as income decreased. Young adolescents who perceived their family as poorer than their friends (instead of about the same) were less likely to have greater self-esteem and life satisfaction and were more likely to have poor outcomes. Young adolescents who perceived their family as richer were more likely to have poor self-esteem, but were not less likely to have greater self-esteem. For life satisfaction, young adolescents who perceived their families as richer were less likely to have greater and more likely to have poor life satisfaction. Policies to redistribute income in families with children are likely to benefit the mental health of young people. However, it is also important to consider the impact of social comparison on young people's mental health as they enter adolescence.


Salt-tolerant plant moderates the effect of salinity on soil organic carbon mineralization in a subtropical tidal wetland.
Although salinization is widely known to affect cycling of soil carbon (C) in tidal freshwater wetlands, the role of the presence or absence of plants in mediating the responses of soil organic carbon (SOC) mineralization to salinization is poorly understood. In this study, we translocated soils collected from a tidal freshwater wetland to sites with varying salinities along a subtropical estuarine gradient and established unplanted and planted (with the salt-tolerant plant Cyperus malaccensis Lam.) mesocosms at each site. We simultaneously investigated cumulative soil CO2 emissions, C-acquiring enzyme activities, availability of labile organic C (LOC), and structures of bacterial and fungal communities. Overall, in the planted mesocosm, the soil LOC content and the activities of β-1,4-glucosidase, cellobiohydrolase, phenol oxidase, and peroxidase increased with salinization. However, in the unplanted mesocosm, soil LOC content decreased with increasing salinity, whereas all the C-acquiring enzyme activities did not change. In addition, salinization favored the dominance of bacterial and fungal copiotrophs (e.g., γ-Proteobacteria, Bacteroidetes, Firmicutes, and Ascomycota) in the planted mesocosms. Contrarily, in the unplanted mesocosms salinization favored bacterial and fungal oligotrophs (e.g., α-Proteobacteria, Chloroflexi, Acidobacteria, and Basidiomycota). In both planted and unplanted mesocosms, cumulative soil CO2 emissions were affected by soil LOC content, activities of C-acquiring enzymes, and microbial C-use trophic strategies. Overall, cumulative soil CO2 emissions increased by 35% with increasing salinity in the planted mesocosm but decreased by 37% as salinity increased in the unplanted mesocosm. Our results demonstrate that the presence or absence of salt-tolerant plants can moderate the effect of salinity on SOC mineralization in tidal wetland soils. Future C prediction models should embed both planted and unplanted modules to accurately simulate cycling of soil C in tidal wetlands under sea level rise.


Characterization of inverted coaxial 76 Ge detectors in GERDA for future double- β decay experiments.
Neutrinoless double- β decay of 76 Ge is searched for with germanium detectors where source and detector of the decay are identical. For the success of future experiments it is important to increase the mass of the detectors. We report here on the characterization and testing of five prototype detectors manufactured in inverted coaxial (IC) geometry from material enriched to 88% in 76 Ge. IC detectors combine the large mass of the traditional semi-coaxial Ge detectors with the superior resolution and pulse shape discrimination power of point contact detectors which exhibited so far much lower mass. Their performance has been found to be satisfactory both when operated in vacuum cryostat and bare in liquid argon within the Gerda setup. The measured resolutions at the Q-value for double- β decay of 76 Ge ( Q β β = 2039 keV) are about 2.1 keV full width at half maximum in vacuum cryostat. After 18 months of operation within the ultra-low background environment of the GERmanium Detector Array (Gerda) experiment and an accumulated exposure of 8.5 kg · year, the background index after analysis cuts is measured to be 4 . 9 - 3.4 + 7.3 × 10 - 4 counts / ( keV · kg · year ) around Q β β . This work confirms the feasibility of IC detectors for the next-generation experiment Legend.


A Supplement with Bromelain, Lentinula edodes, and Quercetin: Antioxidant Capacity and Effects on Morphofunctional and Fecal Parameters (Calprotectin, Cortisol, and Intestinal Fermentation Products) in Kennel Dogs.
Oxidative stress causes several pathological conditions in humans and animals, including gastrointestinal disorders. The aim of this study was to analyze the antioxidant capacity of three natural powdered raw materials containing quercetin, bromelain, and Lentinula edodes and develop a new feed supplement for dogs using a combination of them. The total phenolic content (TPC), antioxidant activity, DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) of the extracts, either individually or in combination, were evaluated colorimetrically. The effects of this supplement on healthy adult dogs' nutritional, inflammatory, and stress status were evaluated. American Staffordshire Terrier adult female dogs (n = 30) were randomly assigned to a control (n = 15) or a treated (n = 15) group. The supplement was added as powder to the food of the treated dogs once daily for 28 days. There was no significant difference in the body weight and body condition scores between the initial and final phases of the experiment. At the end of our study, a significant decrease in fecal calprotectin, cortisol, indole/skatole, and N-methylhistamine and a significant increase in short-chain fatty acids were observed as compared to the control group. In conclusion, this natural feed supplement can be used to improve gastrointestinal health and psycho-physical conditions in dogs.


Surgical treatment of vascular malformations of the extremities in children and adolescents.
The treatment of vascular malformations (VM) of the extremities is controversial. Six patients with large, localized, symptomatic VMs of the extremities underwent surgical excision. In five cases abnormal vessels were apparent under the skin; in two of these there was also red discoloration of the skin secondary to skin involvement. Magnetic resonance imaging was the most helpful imaging modality in evaluating these patients. Subfascial resection was performed in five cases. Muscle was involved in four patients and was removed in all four cases. At follow-up, there was improvement in symptoms and function with no clinically apparent recurrence an average of 30 months following the operation. There was improvement in pain intensity from an average of 4.3 on a scale of 1 to 10 before surgery to 1.3 after surgery. Surgical excision of localized VMs that are extensive and include fascia and muscle, as appropriate, can successfully improve pain and function without evidence of recurrence at 1 to 5 years of follow-up.


Analysis of the regulation of penicillin biosynthesis in Aspergillus nidulans by targeted disruption of the acvA gene.
To analyse the regulation of the biosynthesis of the secondary metabolite penicillin in Aspergillus nidulans, a strain with an inactivated acvA gene produced by targeted disruption was used. acvA encodes delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), which catalyses the first step in the penicillin biosynthetic pathway. To study the effect of the inactivated acvA gene on the expression of acvA and the second gene, ipnA, which encodes isopenicillin N synthase (IPNS), A. nidulans strain XEPD, with the acvA disruption, was crossed with strain AXB4A carrying acvA-uidA and ipnA-lacZ fusion genes. Ascospores with the predicted non-penicillin producing phenotype and a hybridization pattern indicating the presence of the disrupted acvA gene, and the fusion genes integrated in single copy at the chromosomal argB locus were identified. Both fusion genes were expressed at the same level as in the non-disrupted strain. Western blot analysis (immunoblotting) revealed that similar amounts of IPNS enzyme were present in both strains from 24 to 68 h of a fermentation run. In the acvA disrupted strain, IPNS and acyl-CoA: 6-aminopenicillanic acid acyltransferase (ACT) specific activities were detected, excluding a sequential induction mechanism of regulation of the penicillin biosynthesis gene ipnA and the third gene aat.


Atrial branch coronary artery stenosis as a mechanism for atrial fibrillation.
The etiology of atrial fibrillation (AF) is multifactorial and incompletely understood. The purpose of this study was to evaluate the association between coronary artery disease (CAD) affecting atrial tissue and AF. Patients from a single center with obstructive CAD during cardiac catheterization (January 1, 2007, through December 1, 2013) were included in a matched case-control analysis on the basis of the presence or absence of new-onset AF within 12 months of catheterization. Quantitative measurements of stenosis severity were performed for the sinoatrial nodal artery, atrioventricular (AV) nodal artery, and right intermediate atrial artery (RIAA) as well as the right coronary, left circumflex, and left anterior descending proximal to the takeoff for each atrial level artery. A multivariable logistic regression model identified factors associated with AF. Of 1794 patients, 115 (6%) developed AF within 1 year of catheterization. The matched cohort included 110 patients with and 110 patients without AF within 12 months of catheterization. Higher odds of AF at 1 year were associated with increasing lesion stenosis severity in the RIAA (odds ratio [OR] 1.41 per 10% increase in lesion severity above 50%; 95% confidence interval [CI] 1.01-1.97; P = .047) and AV nodal artery (OR 1.58 per 10% increase in lesion severity above 50%; 95% CI 1.00-2.49; P = .050). Odds of AF diagnosis during the year after catheterization increased with the number of atrial arteries with >50% lesion (OR 1.53 for each additional artery; 95% CI 1.08-2.15; P = .015). In patients with obstructive CAD, disease of the AV nodal artery and RIAA as well as a higher burden of CAD within all arteries supplying blood flow to the atrial myocardium were associated with higher odds of new-onset AF at 1 year.


Comparison Of Surgical Outcomes Between Excisional Goniotomy Using The Kahook Dual Blade And iStent Trabecular Micro-Bypass Stent In Combination With Phacoemulsification.
To compare 6-month surgical outcomes of patients who underwent phacoemulsification (Phaco) combined with iStent implantation (iStent) versus excisional goniotomy using Kahook Dual Blade (KDB). Retrospective comparative case series of 58 iStent-Phaco eyes and 44 KDB-Phaco eyes operated upon by a single surgeon between 2016 and 2018. Preoperative, intraoperative, and postoperative intraocular pressure (IOP) and IOP-lowering medication data were collected. The primary outcome was the proportion of eyes using ≥1 fewer IOP-lowering medication at Month 6 while maintaining IOP ≤ 18 mmHg. Baseline IOP was 17.2 (standard error 0.7) in the KDB-Phaco group using a mean of 1.9 (0.2) medications; at Month 6, mean IOP was 14.8 mmHg P=0.002) on 1.0 (0.2) medications (P<0.002). Baseline IOP was 16.7 (0.4) in the iStent-Phaco group using a mean of 1.4 (0.1) medications; at Month 6, mean IOP was 14.2 mmHg (P<0.002) on 1.4 (0.1) medications P=0.374). Changes in IOP and medications were not significantly different between groups (P>0.05). Significantly more KDB-Phaco eyes than iStent-Phaco eyes (43.2% vs 17.2%, P=0.004) were using ≥1 fewer medications while maintaining IOP ≤18 mmHg at Month 6. Adverse events were uncommon and similar in nature and frequency between groups with the exception that more KDB-Phaco eyes than iStent-Phaco eyes (8 [18.2%] versus 1 [1.7%]) experienced an IOP elevation presumed to be related to steroid use. KDB-Phaco and iStent-Phaco provided comparable IOP and medication reductions. The proportion of eyes able to discontinue 1 or more medications while maintaining IOP ≤ 18 mmHg was significantly greater in eyes undergoing KDB-Phaco.


A case of myasthenia gravis accompanied by invasive thymoma, alopecia areata and dry mouth.
We report a 43-year-old man suffering from myasthenia gravis with invasive thymoma accompanied with alopecia areata and dry mouth. These complications are extremely rare and the pathogenetic etiology of these complications was thought to depend on a generalized immunological disturbance.


Global differences in blood pressure control and clinical outcomes in the INternational VErapamil SR-Trandolapril STudy (INVEST).
The INternational VErapamil SR-Trandolapril Study (INVEST), a prospective, randomized, antihypertensive trial, found that two different medication regimens produced similar blood pressure (BP) control with equivalent cardiovascular (CV) outcomes (death from any cause, nonfatal myocardial infarction [MI], or nonfatal stroke). The study was undertaken to investigate whether differences exist by global regions in demographics, treatment, and outcomes in the INVEST trial. Data were analyzed for 22,576 patients with stable coronary artery disease (CAD) enrolled in INVEST. We investigated differences in patient characteristics, treatment approaches, BP control, and clinical outcomes by creating three global regions based on geographical location: Northern Americas (NA), Caribbean (CA), and Eurasia (EA). We observed significant regional differences in patient characteristics, treatment patterns, BP control, and CV outcomes. At baseline, patients from NA were older and had greater body mass index, higher rates of diabetes, peripheral vascular disease, and coronary revascularization, but lower rates of MI or left ventricular hypertrophy than patients in CA and EA. At 24 months, there were regional differences in both study and nonstudy antihypertensive drug use. Despite having higher mean baseline BP, patients from CA and EA achieved lower mean systolic BP throughout study follow-up. Furthermore, patients from both CA and EA had lower rates of all-cause mortality, fatal or nonfatal MI, fatal or nonfatal stroke, and newly diagnosed diabetes than patients from NA. In INVEST, regional differences in medication utilization, BP control, and CV outcomes were identified. These disparities warrant further investigation to define appropriate care for patients with hypertension and stable CAD from an international public health perspective.


Human semen quality as affected by SARS-CoV-2 infection: An up-to-date review.
Revealing the effect of SARS-CoV-2 infection on semen quality is a dynamic priority for many healthcare providers in the field as well as subfertile patients. Therefore, the collective summary in this research approach is still highly needed, especially with the continuous increase in original publications. Here, we provide an up-to-date review and discussion to collectively reveal the effect of SARS-CoV-2 infection on human semen quality. To do this, we reviewed all articles and abstracts published in Scopus and PubMed using the keywords 'SARS-CoV-2' and 'COVID' versus 'sperm' and 'semen'. In summary, it can be revealed that, at both symptomatic and recovery stages of infection, no investigational evidence of SARS-CoV-2 shedding in human semen. Also, the mainstream of the up-to-date published work reveals a negative impact of SARS-CoV-2 infection on semen quality parameters, particularly sperm count and motility. However, long-term post-recovery comparative studies seem very important in this particular setting.


Microanatomy of the palatal mucosa of the semiaquatic malayan box turtle, Cuora amboinensis, and functional implications.
Scanning Electron Microscopy (SEM) revealed that the palate of Cuora amboinensis has a flat surface with keratinized and non-keratinized regions. Keratinization is reflected in disc-shaped keratinized dead cells with rough microplicae on the surface, and is concentrated close to the rhamphotheca. The surface of the non-keratinized hexagonal epithelial cells is dotted with microvilli and sometimes with cilia. Taste buds are present both in lightly keratinized and non-keratinized regions and exhibit a crater-like shape. Light microscopy shows the different tissue layers of the oral mucosa and the different epithelial structures. In keratinized regions, keratinocytes mature from basal to superficial, where they build up keratin layers of varying thickness. In non-keratinized regions, the epithelial cells are arranged in a stratified fashion, and cuboidal to cylindric cells form a superficial layer. Goblet cells appear to be diffusely distributed, but are often organized in goblet cell fields which can be folded into crypts. Taste buds consist of slender epithelial cells, exhibit the typical barrel-like shape and are specially concentrated in the anterior, praechoanal palate. This anterior concentration of taste buds is shown by kinematographic analysis to correlate with the food prehension mode in Cuora amboinensis. The lamina propria of the palatal mucosa consists of loose connective tissue with inflammatory cells between capillaries. All these structures of the oral mucosa act as a functional entity and help determine how successfully an organism adapts ecologically to the environment.


Endometriosis and Sexual Functioning: How Much Do Cognitive and Psycho-Emotional Factors Matter?
Women with endometriosis often suffer from genito-pelvic pain. The objective of the present study was to analyze the relationship between cognitive and psycho-emotional factors and sexual functioning of women with endometriosis, comparing women with and without endometriosis. A total of 87 women with endometriosis (EG) and 100 women without endometriosis (CG) completed a socio-demographic questionnaire; the short-form of McGill Pain Questionnaire (SF-MPQ); the Female Sexual Functioning Index (FSFI); the Sexual Distress Scale (SDS); the Symptoms Checklist (SCL-90-R); the Toronto Alexithymia Scale (TAS-20); the Positive and Negative Affects Scale (PANAS); the Sexual Dysfunctional Belief Questionnaire (SDBQ); the Sexual Modes Questionnaire (SMQ); and the Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC). EG obtained worse scores than CG in SF-MPQ, Pain subscale of FSFI, and SDS. EG reached higher scores than CG on almost all scales of SCL-90-R and lower scores in the "Identifying Feelings" scale of TAS-20. Furthermore, EG reported more negative emotions toward sexuality than CG (PANAS) higher scores on the "Affection Primacy" scale of SDBQ and the "Helpless" sexual cognitive schema of QCSASC than CG. No significant differences were found in SMQ. Sexual health professionals should address psychological, emotional, and cognitive factors since they seem involved in patients' sexual experiences.


Pustular lesions in the neonate: Focused diagnostic approach based on clinical clues.
Pustules in a neonate can be due to various causes. Though the majority of conditions causing pustules in a neonate are benign, it is essential to clearly differentiate these from serious ones. A systematic approach based on detailed history and clinical examination of the neonate along with basic laboratory evaluation narrows down diagnostic possibilities and aids in the correct diagnosis. This review outlines a step-by-step approach so as to avoid clinical dilemmas and unnecessary intervention.


One Health compartment analysis of ESBL-producing Escherichia coli reveals multiple transmission events in a rural area of Madagascar.
ESBL-producing Escherichia coli (ESBL-Ec) is considered a key indicator for antimicrobial resistance (AMR) epidemiological surveillance in animal, human and environment compartments. There is likelihood of ESBL-Ec animal-human transmission but proof of cross-compartment transmission is still unclear. To characterize ESBL-Ec genetic similarity in various compartments (humans, animals and environment) from a rural area of Madagascar. We collected ESBL-Ec isolates prospectively from humans, animals and the environment (water) between April and October 2018. These isolates were subject to WGS and analysed with cutting-edge phylogenomic methods to characterize population genetic structure and infer putative transmission events among compartments. Of the 1454 samples collected, 512 tested positive for ESBL-Ec. We successfully sequenced 510 samples, and a phylogenomic tree based on 179 365 SNPs was produced. Phylogenetic distances between and amongst compartments were indistinguishable, and 104 clusters of recent transmission events between compartments were highlighted. Amongst a large diversity of ESBL-Ec genotypes, no lineage host specificity was observed, indicating the regular occurrence of ESBL-Ec transfer among compartments in rural Madagascar. Our findings stress the importance of using a phylogenomic approach on ESBL-Ec samples in various putative compartments to obtain a clear baseline of AMR transmissions in rural settings, where one wants to identify risk factors associated with transmission or to measure the effect of 'One Health' interventions in low- and middle-income countries.


Integration of autophagy and anoikis resistance in solid tumors.
Macroautophagy or autophagy is a lysosome-dependent process in which enzymatic degradation and recycling of cytosolic components occurred due to stressful conditions. This cellular arrangement imparts anoikis resistance in solid tumors. Anoikis, a special form of apoptosis occurring when cells detach from the extracellular matrix, is a critical mechanism in maintaining tissue homeostasis and development. Anoikis resistance facilitates tumorigenesis and metastasis. However, the complexity of the role of autophagy in tumor is underscored by evidence that autophagy can function as both a pro-survival or pro-death depending on the context and the stimuli, which are likely exploitable for tumor therapy. This review focuses on recent progress in understanding anoikis resistance and autophagy signaling, paying particular attention to its relevance in solid tumor metastasis.


Total hip arthroplasty in acute acetabulum fractures: a systematic review.
The incidence of acetabular fractures has increased significantly in recent years due to demographic change. It can be divided into high-energy acetabular fractures primarily seen in adult patients versus geriatric patients mostly suffering from low-energy trauma. Historically, acetabular fractures have been treated either non-operatively or surgically following open reduction and internal fixation (ORIF), whereas nowadays total hip arthroplasty (THA) provides a true alternative. Aim of this study was to perform a systematic review on the outcome following THA in acute acetabulum fractures. PubMed/MEDLINE, Cochrane and Google databases were systematically searched on December 9, 2021. The key terms were [acetabular fracture] AND [[arthroplasty] OR [fixation]]. All retrospective and prospective original studies in English and German were analyzed the outcome following THA in acute acetabulum fractures were included. A total of 2459 studies were screened, which includes 15 studies that met the inclusion criteria with a total of 590 patients at a mean age of 61.3 years (SD 11.48). Most studies described good to excellent results. Especially, THA allows elderly patients quicker mobilization and rehabilitation as well as symptomatic relief, as compared to ORIF or non-operative treatment. Patients who underwent non-operative treatment showed better results compared to those who underwent ORIF initially. In acetabulum fractures, THA provides a good alternative with very good results when patients are carefully selected. Good to excellent outcomes are reported for both acute and delayed use of THA in elderly patients. Level 2, systematic review.


Nursing assessment of the incontinent geriatric outpatient population.
The key to effective management of urinary incontinence is a comprehensive evaluation that accurately characterizes the type of incontinence and, if possible, identifies the underlying etiology. The nurse has a vital role in the initial assessment of the incontinent elderly individual in the outpatient setting. By obtaining a thorough history and physical examination, a voiding diary, and simple laboratory tests, the nurse can make a preliminary diagnosis of the type of incontinence. In simple, uncomplicated cases, the nurse might initiate a trial of behavioral treatment prior to further evaluation. In complex cases, referral for further gynecologic or urologic evaluation may be initiated.


The effects of critical illness on intestinal glucose sensing, transporters, and absorption.
Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice. Prospective observational study in humans and mice. ICU and university-affiliated research laboratory. Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied. Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection. Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcripts were reduced by 55% (p < 0.001), 50% (p = 0.002), and 69% (p = 0.004). Critical illness is characterized by markedly diminished glucose absorption, associated with reduced intestinal expression of glucose transporters (sodium-dependent glucose transporter-1 and glucose transporter-2) and sweet taste receptor transcripts. These changes are paralleled in cecal ligation and puncture mice.


Perennials on rock islands: testing for patterns of colonization and competition.
The density and presence of 18 saxicolous (occurring among rocks) perennial plant species were measured on 61 habitat islands in Baja California. These data were compared with a random colonization simulation that placed species on islands in direct proportion to species densities and island areas. The initial simulation placed too many species on the islands. This problem was rectified by introducing the effects of within island seed dispersal. Both the data and the simulations showed patterns of density compensation. Density compensation is usually perceived as being evidence of interspecific competition; however, it could be caused by other factors, such as lack of predators or habitat differences between the islands. Since the simulation included no differences between the species in their competitive ability, I used the deviations of the simulations from the data as a measure of relative competitive ability. A conservative requirement for demonstrating that competition affects the densities of these species is finding an ecological tradeoff between colonizing and competitive ability. There was no evidence for a tradeoff between competitive and colonizing ability. The dispersal method of the plants (either animal or wind) had a larger but nonsignificant effect on the deviations. Thus there is no evidence for competition affecting the deviations in density and occurrence of these species from the simulations. Random colonization including the effects of both multiple source pools and perhaps the dispersal method of the species is the most parsimonious explanation for the density and diversity patterns.


[Clinical experiences with digital video image analysis procedures in the assessment of endoscopic ENT video findings].
Recent developments in data processing enable digital information to be obtained from video frames, leading to the possibility of computerised analysis of endoscopic ENT videos (e.g. in laryngology). Two simple pilot systems ("Genlock Computer with Superimposer" and "Videodigitizer") are presented, as basis for a discussion of the advantages and disadvantages of these methods.


A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival.
Postnatal cardiac remodeling is characterized by a marked decrease in the insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) expression. The underlying mechanism remains unexplored. This study examined the role of microRNAs in postnatal cardiac remodeling. By expression profiling, we observed a 10-fold increase in miR-378 expression in 1-week-old neonatal mouse hearts compared with 16-day-old fetal hearts. There was also a 4-6-fold induction in expression of miR-378 in older (10 months) compared with younger (1 month) hearts. Interestingly, tissue distribution analysis identified miR-378 to be highly abundant in heart and skeletal muscles. In the heart, specific expression was observed in cardiac myocytes, which was inducible by a variety of stressors. Overexpression of miR-378 enhanced apoptosis of cardiomyocytes by direct targeting of IGF1R and reduced signaling in Akt cascade. The inhibition of miR-378 by its anti-miR protected cardiomyocytes against H(2)O(2) and hypoxia reoxygenation-induced cell death by promoting IGF1R expression and downstream Akt signaling cascade. Additionally, our data show that miR-378 expression is inhibited by IGF1 in cardiomyocytes. In tissues such as fibroblasts and fetal hearts, where IGF1 levels are high, we found either absent or significantly low miR-378 levels, suggesting an inverse relationship between these two factors. Our study identifies miR-378 as a new cardioabundant microRNA that targets IGF1R. We also demonstrate the existence of a negative feedback loop between miR-378, IGF1R, and IGF1 that is associated with postnatal cardiac remodeling and with the regulation of cardiomyocyte survival during stress.


Cognitive-behavioral therapy and urge urinary incontinence in women. A systematic review.
UUI co-exists with numerous health conditions, having a substantial negative impact on health-related quality of life and mental health. Cognitive-behavioral therapy (CBT) could help patients manage these problems by changing the way they think and behave. We carried out a systematic review of the literature assessing the modalities and effects of CBT as a stand-alone strategy, without adding PFMT, on symptoms and clinical signs, in women with UUI. Our secondary objective was to report modalities and effects of CBT on health-related quality of life, psychological symptoms and patient-reported satisfaction. The PRISMA methodology was used to carry out this systematic review. A literature search was conducted in PubMed, PEDro, Web of Science and Cochrane Library databases from inception to December 2020. The PICO approach was used to determine the eligibility criteria. Twelve papers were included in the present review which showed beneficial effects on both symptom severity (p < 0.05) and more subjective areas such as quality of life, psychological symptoms or patient satisfaction level (p < 0.05), respectively). However, results on the effectiveness of CBT on clinical signs remains conflicting. Based on the available literature, this review suggested a high level of evidence for the effectiveness of CBT on symptom severity and a moderate level of evidence for the effectiveness of CBT on quality of life, psychological symptoms and patient satisfaction. However, we highlighted no evidence for the effects of CBT on clinical signs.


Reduction of rapid eye movement (REM) sleep by glucose alone or glucose and insulin in rats.
Administration of a high dose of glucose (2.5 g/kg, i.p.) that is known to produce severe hyperglycemia in euglycemic rats suppressed rapid eye movement (REM) sleep time significantly during the first three hours of 8 hr total electroencephalogram (EEG) recording period. Co-administration of glucose (2.5 g/kg, i.p.) and a non-convulsive dose of insulin (1.0 I.U./kg, i.p.) produced a significant reduction in REM sleep time during 1st through 5th hour and an increase in slow-wave sleep (NREM) time in the 3rd and 4th hour of 8 hr total EEG recording period. However, awake, NREM and REM sleep time in the 8 hr total EEG recording period were unaffected by either glucose alone or glucose plus insulin treatments. These results strongly suggest that the insulin's effects on the sleep-awake cycle i.e. reduction in REM and a slight increase in NREM sleep times of rats is not due to indirect effects of insulin on the central nervous system via hypoglycemia as reported by us previously, but could possibly be due to its direct effects on brain chemistry of neurotransmitters such as serotonin, catecholamines and acetylcholine which are believed to modulate the sleep-awake cycle pattern in rats.


Intranodal Glue Embolization for the Management of Postsurgical Groin Lymphocele and Lymphorrhea.
This report describes intranodal lymphatic embolization for treatment of groin lymphatic leaks following surgery or percutaneous vascular interventions. In 10 consecutive patients with groin lymphatic leak between 2015 and 2017, lymphangiography with embolization was performed by intranodal injection with dilute N-butyl cyanoacrylate (NBCA). Mean volume of dilute NBCA (1:3 with ethiodized oil) injected was 1 mL. Clinical success rate was 80%. Median time to resolution was 7 days. Intranodal lymphatic embolization for treatment of groin lymphatic leaks is a safe and effective treatment alternative to surgery resulting in a rapid time to resolution.


Antimicrobial and in silico studies of the triterpenoids of Dichapetalum albidum.
Here we report a new polyhydroxylated triterpene, 2β,6β,21α-trihydroxyfriedelan-3-one (4) isolated from the root and stem bark of Dichapetalum albidum A. Chev (Dichapetalaceae), along with six known triterpenoids (1-3, 5, 6, 8), sitosterol-3β-O-D-glucopyranoside (9), a dipeptide (7), and a tyramine derivative of coumaric acid (10). Friedelan-3-one (2) showed an antimicrobial activity (IC50) of 11.40 μg/mL against Bacillus cereus, while friedelan-3α-ol (1) gave an IC50 of 13.07 μg/mL against Staphylococcus aureus with ampicillin reference standard of 19.52 μg/mL and 0.30 μg/mL respectively. 3β-Acetyl tormentic acid (5) showed an IC50 of 12.50 μg/mL against Trypanosoma brucei brucei and sitosterol-3β-O-d-glucopyranoside (9) showed an IC50 of 5.06 μg/mL against Leishmania donovani with respective reference standards of IC50 5.02 μg/mL for suramin and IC50 0.27 μg/mL for amphotericin B. Molecular docking of the isolated compounds on the enzyme glucose-6-phosphate dehydrogenase (G6PDH) suggested 3β-acetyl tormentic acid (5) and sitosterol-3β-O-D-glucopyranoside (9) as plausible inhibitors of the enzyme in accordance with the experimental biological results observed.


Offering-level strategy formulation in health service organizations.
One of six different strategies must be selected for a health service offering to provide consumers with distinctive value and achieve sustainable competitive advantage in a market or market segment. Decisions must be made regarding objectives sought, market segmentation, market scope, and the customer-value proposition that will be pursued.


Quantification of the human lateral geniculate nucleus in vivo using MR imaging based on morphometry: volume loss with age.
Because it is a small subcortical structure, the precise measurement of the human LGN is still a technical challenge. In this article, we identify the LGN in vivo, measure its volume based on high-resolution MR imaging, and then relate its volume to subject age to evaluate the potential clinical application. A semiautomatic LGN isolation method was developed on scans obtained with 1.5T MR imaging, which involves highlighting the surrounding landmarks, obtaining candidate LGN voxels with a region-growing algorithm, and isolating the LGN from the ventral diencephalon. The method was accessed with a test-retest reliability on the results from 55 healthy subjects at different ages. This method showed high test-retest within-subject reliability (ICC, 0.950 and 0.948 in left and right hemispheres, respectively) among 3 independent measurements in each subject. The unilateral volume was highly variable, ranging from 52 to 102 mm(3) in the left and 66 to 105 mm(3) in the right hemisphere, with significantly larger volumes on the right (86 mm(3)) than on the left (77 mm(3)). The combined bilateral volumes (controlled for ICV) significantly decreased in size with progressing age from 20 to 65 years (r = -0.512, P = .000). There was no sex difference in bilateral LGN volumes (male/female: 163.1 ± 18.2/162.2 ± 21.4 mm(3)). Using our new technique, we were able to reliably determine the human LGN volume in vivo, which was found to decline with age. The volumes obtained by our method corresponded well with previously reported postmortem values, so our method may be considered to be superior for investigating the pathology of LGN.


Analysis of Determinants of Postoperative Satisfaction After Rhinoplasty.
To analyze different variables that influence postrhinoplasty quality of life outcomes to ascertain the determinants of postoperative satisfaction. Prospective, observational study. This was a prospective, observational study where patients were divided into two groups based on the postoperative Rhinoplasty Outcome Evaluation (ROE) score: high satisfaction group, when postoperative ROE scores were >50, and low satisfaction group, when postoperative ROE scores were ≤50. Patients' general characteristics, Portuguese version of the Nasal Obstruction Symptom Evaluation (NOSE-p) score, the Body Dysmorphic Disorder Examination, nasal angles, and measures from the esthetic facial analysis of postoperative photographs were compared between the groups. Seventy-eight patients were included: 19 in the low satisfaction group and 58 in the high satisfaction group. The median reduction in the NOSE-p score was -45 (interquartile range [IIQ] -20 to -60) (P < .001) in the high satisfaction group and -10 (IIQ -10 to -30) in the low satisfaction group (P = .053). The high satisfaction group had a significantly higher reduction in NOSE-p scores. There was no significant difference between the groups in terms of the analyzed facial parameters, although a significant difference was found when comparing them with the ones established in the literature as a pattern. Previous rhinoplasty, preoperative crooked nose, and higher NOSE-p scores were significantly associated with lower ROE scores (P < .05) in the robust Poisson regression model. Functional results play an important role in satisfaction after rhinoplasty. Neoclassical canons were not fulfilled even in a group of patients with a high postoperative satisfaction evaluation. 3 Laryngoscope, 132:1569-1575, 2022.


[Association between adiposity and cardiovascular risk factors in prepubertal children].
To examine the relationships between of four measures of adiposity, namely waist circumference (WC), body mass index (BMI), and subscapular and abdominal skinfolds, with different cardiovascular risk factors in prepubertal children. Four hundred and ninety-four prepubertal children aged 6-10 years participated in this cross-sectional study. The subscapular and abdominal skinfolds, WC, and BMI were measured to assess adiposity, and cardiovascular risk factors (CVRFs) were assessed by measuring systolic (SBP) and diastolic blood pressures (DBP), glucose, triglycerides (TG), and high density (HDL-C) and low density lipoprotein cholesterol (LDL-C). Dichotomous variables were created based on whether or not the subjects were in the upper quartile (Q4) for the WC, BMI, and skinfold variables. No CVRF was found in 52.8% of children, 33.4% had one factor, and 10.9% and 2.8% had 2 and 3 factors respectively. An adjusted logistic regression analysis showed that being in Q4 of anthropometric variables and CVRFs was associated to TG levels ≥ 100 mg/dL. Glucose levels ≥ 96 mg/dL were associated to Q4 and abdominal fold. Presence of 2 or more CVRFs was significantly associated to Q4 in all anthropometric variables despite adjustment for age, gender, and calorie intake. The subscapular skinfold was the adiposity marker associated to the highest risk. Children with a more unfavorable adiposity profile tend to have a greater cardiovascular risk in the prepubertal stage.


ERCC1 is a potential biomarker for predicting prognosis, immunotherapy, chemotherapy efficacy, and expression validation in HER2 over-expressing breast cancer.
To investigate the relationship between Excision repair cross-complementation 1 (ERCC1) expression, clinicopathological features, and breast cancer prognosis in patients treated with trastuzumab. Further, we aim to explore the immune status of ERCC1 in breast cancer. The data were retrieved from publicly available databases like the Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression. The data was used to perform differential expression analyses between tumor and normal tissues in pan-cancers, immune-related analysis, homologous recombination deficiency (HRD), tumor mutation burden, and microsatellite instability. A total of 210 patients with HER2 over-expressing breast cancer from the Fourth Hospital of Hebei Medical University between January 2013 to December 2015 were enrolled in the study. Ten adjacent normal tissues were used to study the expression pattern of ERCC1 in normal tissues. Immunohistochemistry was performed to study ERCC1 expression and immune cell infiltration in different status of ERCC1 expression. Further, the correlation between ERCC1 expression, immune cell infiltration clinicopathological features, and the prognosis of patients with breast cancer was analyzed. The immune analysis revealed a significant correlation between CD8+ T cell, CD4+ T cell, T helper cell, macrophages, mast cells, and ERCC1 expression. Spearman analysis show that ERCC1 expression is related to macrophages and T cells. A close correlation was observed between increased ERCC1 expression and high tumor immune dysfunction and exclusion (TIDE) score as well as HRD. The results revealed a significant correlation among ERCC1, chemotherapy and estrogen receptor (ER; P < 0.05) expression. Univariate survival analysis revealed a significant correlation (P < 0.05) between that ERCC1 and ER expression, blood vessel invasion, and disease-free survival (DFS). ERCC1 and ER expression, tumor size, blood vessel invasion, pathological type, and lymph node metastases significantly correlated (P < 0.05) with overall survival in patients. Multivariate regression analysis revealed that ERCC1 expression and chemotherapy were independent factors that influence DFS. ERCC1 expression and vascular tumor thrombus were independent influencing factors that influence OS. A correlation was observed between high ERCC1 expression and poor patient prognosis. High ERCC1 expression also influences the efficacy of immunotherapy and chemotherapy.


[Lipid metabolic changes in rats with radiation sickness and a pronounced intestinal syndrome following the local irradiation of the abdominal area. The total lipid content of the blood serum and tissues].
Local X irradiation of rat abdomen causes pronounced hyperlipemia after 4 and 72 h and a considerable accumulation of phospholipids and triacylglycerides in the liver after 72 h. In the thymus, the content of the nonesterified fatty acids decreased 4 h and that of cholesterol increased 72 h after irradiation.


ELONGATA3 is required for shoot meristem cell cycle progression in Arabidopsis thaliana seedlings.
A key feature of the development of a higher plant is the continuous formation of new organs from the meristems. Originally patterned during embryogenesis, the meristems must activate cell division de novo at the time of germination, in order to initiate post-embryonic development. In a mutagenesis screen aimed at finding new players in early seedling cell division control, we identified ELONGATA3 (ELO3) as a key regulator of meristem cell cycle activation in Arabidopsis. Our results show that plants carrying a hypomorphic allele of ELO3 fail to activate cell division in the meristems following germination, which leads to seedling growth arrest and lethality. Further analyses suggest that this is due to a failure in DNA replication, followed by cell cycle arrest, in the meristematic tissue. Interestingly, the meristem cell cycle arrest in elo3 mutants, but not the later leaf developmental defects that have been linked to the loss of ELO3 activities, can be relieved by the addition of metabolic sugars in the growth medium. This finding points to a new role by which carbohydrate availability promotes meristem growth. Furthermore, growth arrested elo3 mutants suffer a partial loss of shoot meristem identity, which provides further evidence that cell cycle activities can influence the control of tissue identity.


Recycling nutrients in the beef supply chain through circular manuresheds: Data to assess tradeoffs.
Nutrient circularity can help supply chain participants meet sustainability targets. Across the segmented beef supply chain, opportunity exists to reinforce and introduce nutrient circularity by recycling surplus manure nutrients from cattle feedlots to lands where cattle feed is produced. We describe four datasets developed to evaluate options in U.S. and Canadian beef systems. The datasets delineate three "circular manuresheds," each encompassing a hay-grazing landscape where beef cattle are raised on grazingland and supplemented with hay grown nearby, and the distant feedlots where those cattle produce manure nutrients for potential import back to the hayfields. We selected the hay-grazing landscapes of New Mexico, USA; Florida, USA; and western Canada (Manitoba, Saskatchewan, Alberta, British Columbia) because of their significant grazingland production and potential to substitute feedlot manure for commercial fertilizer on hayfields. In each circular manureshed, the manure nutrients from major feedlot destinations could supply a considerable proportion of the P used by hay for grazing cattle: 34% of the P requirements in New Mexico, 36% in Florida, and 6% in western Canada. The average distance to return the resource was 647 km for New Mexico, 1,884 km for Florida, and 1,587 km for western Canada. These magnitudes and distances suggest that the New Mexico circular manureshed may be the most economically viable in the current agri-food system, but this reflects only part of a greater, multi-factor assessment of tradeoffs. The circular manureshed concept provides a platform for simultaneous consideration of competing factors for sustainability via circularity.


Valorization of Kappaphycus alvarezii through extraction of high-value compounds employing green approaches and assessment of the therapeutic potential of κ-carrageenan.
This study utilizes different emerging green extraction technologies to recover maximum value-added products from Kappaphycus alvarezii and evaluate their bio-functional properties. Using the supercritical fluid extraction (SFE) method, the total lipid yield of 0.21 ± 0.2 % was obtained from the biomass. Linoleic acid, eicosapentaenoic acid, arachidonic acid, γ-linolenic acid, and docosahexaenoic acid were present in higher concentrations (9.12 %) in the lipid extracted with SFE as compared to hexane (5.5 %). Using an ultrasonication assisted approach, ~56 % of κ-carrageenan was recovered from SFE residual biomass, which contains 28.5 ± 1.9 % sulfate content. It exhibited a monosaccharide content of 3,6-anhydrogalactose (~24 %) and galactose (~53 %), as well as rheological properties within FAO limitations that can be explored for food-grade applications. ~58 % of the total protein (12.5 %) from SFE residual biomass was recovered using subcritical water hydrolysis method. The effectiveness of κ-carrageenan in suppressing the 3CLpro of SARS-CoV-2 using in vitro and in silico approaches was investigated. κ-Carrageenan effectively inhibited the main protease by up to 93 % at 1.6 mg mL-1. In silico results revealed that κ-carrageenan successfully binds to the active site of the main protease while retaining the structural integrity and stability of protein-ligand complexes.


Comparative hydrodynamic characterisation of two hydroxylated polymers based on α-pinene- or oleic acid-derived monomers for potential use as archaeological consolidants.
The Oseberg Viking ship burial is one of the most extensive collections of Viking wooden artefacts ever excavated in Norway. In the early twentieth century, many of these artefacts were treated with alum in order to preserve them, inadvertently leading to their current degraded state. It is therefore crucial to develop new bioinspired polymers which could be used to conserve these artefacts and prevent further disintegration. Two hydroxylated polymers were synthesised (TPA6 and TPA7), using α-pinene- and oleic acid-derived monomers functionalised with an acrylate moiety. Characterisation using biomolecular hydrodynamics (analytical ultracentrifugation and high precision viscometry) has shown that these polymers have properties which would potentially make them good wood consolidants. Conformation analyses with the viscosity increment (ν) universal hydrodynamic parameter and ELLIPS1 software showed that both polymers had extended conformations, facilitating in situ networking when applied to wood. SEDFIT-MSTAR analyses of sedimentation equilibrium data indicates a weight average molar mass Mw of (3.9 ± 0.8) kDa and (4.2 ± 0.2) kDa for TPA6 and TPA7 respectively. Analyses with SEDFIT (sedimentation velocity) and MultiSig however revealed that TPA7 had a much greater homogeneity and a lower proportion of aggregation. These studies suggest that both these polymers-particularly TPA7-have characteristics suitable for wood consolidation, such as an optimal molar mass, conformation and a hydroxylated nature, making them interesting leads for further research.


Three new high-prevalence antigens in the Cromer blood group system.
The Cromer blood group system consists of nine high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). This report describes three new Cromer high-prevalence antigens, named ZENA, CROV, and CRAM. Sequence analyses were performed on DNA from three probands whose serum samples each contained an alloantibody to a high-prevalence antigen in the Cromer blood group system. Polymerase chain reaction-restriction fragment length polymorphism analysis to detect the mutation encoding the CROV- phenotype was performed on 100 Croatian donors. To map the respective epitopes, DAF deletion mutants were tested by immunoblotting with eluates containing the antibodies. In each proband, sequence analysis revealed a single-nucleotide substitution in DAF: ZENA, 726T>G mutation, predicted change His242Gln; CROV, 466G>A mutation, predicted change Glu156Lys; and CRAM, 740A>G mutation, predicted change Gln247Arg. By analysis of DAF deletion mutants, the CROV antigenic determinant mapped to the complement control protein (CCP) domain 2, which is encoded by exon 3, whereas ZENA and CRAM mapped to CCP4, which is encoded by exon 6. This study describes three novel high-prevalence antigens in the Cromer blood group system each characterized by a predicted single-amino-acid substitution. The antigens have been assigned the following International Society of Blood Transfusion (ISBT) numbers: ZENA is CROM13, CROV is CROM14, and CRAM is CROM15.


Coordinative trapping of the boron β-diketiminato system [B(NMesCMe)2CH] via metal-templated synthesis.
A metal templated synthetic approach gives access to [Cp*Fe(CO)(2){B(NMesCMe)(2)CH}][BAr(f)(4)], and represents the first example of coordinative trapping of the elusive [B(NRCMe)(2)CH] fragment.


Characterization of a flavonol-rich antioxidant fraction from Spondias purpurea L. pulp and the effect of its incorporation on cellulose acetate-based film.
Active packaging containing natural flavonoid has recently emerged as a result of its potential to inhibit the oxidation of foods by interacting with it and/or its surrounding environment, with the aim of counteracting oxidation reactions and extending the shelf-life of foods. The plant Spondias purpurea L. is widely found in northeastern Brazil and is known to contain bioactive flavonoids. The present study aimed to obtain a flavonoid-rich fraction from the pulp of S. purpurea L. and incorporate it into the cellulose acetate film to obtain biodegradable films with antioxidant properties. The fractionation in SiO2 open-column chromatography of the S. purpurea pulp crude extract furnished an antioxidant active fraction containing the flavonols quercetin 3-O-rutinoside and kaempferol 3-O-rutinoside as the major compounds. This active fraction was incorporated (10, 20 and 30 g kg-1 ) into the substance produced with the casting method for cellulose acetate films. The films produced were characterized concerning mechanical properties, water vapor permeability (WVP) and antioxidant activity. The incorporation of the active flavonoid fraction from S. purpurea in the cellulose acetate films decreases WVP and elongation at break, at the same time as increasing antioxidant activity, tensile strength and elastic modulus. Thus, the S. purpurea pulps may be an alternative as a source of antioxidants for use in cellulose acetate films. © 2020 Society of Chemical Industry.


Post-Mastectomy Radiation Therapy for Invasive Lobular Carcinoma: A Comparative Utilization and Outcomes Study.
To date, there have been no analyses to assess factors that influence post-mastectomy radiation therapy (PMRT) utilization in invasive lobular carcinoma (ILC) or to quantify the benefit of PMRT in ILC as compared with invasive ductal carcinoma (IDC). We compared histology-specific utilization of PMRT by tumor and patient characteristics and estimated the effect of PMRT on overall and breast cancer-specific survival in ILC and IDC patients meeting American College of Radiology (ACR) criteria for PMRT. We used the Surveillance, Epidemiology, and End Results database to identify women diagnosed with ILC or IDC from 2004 to 2009 who underwent mastectomy. We assessed utilization of PMRT by T and N stage, analyzed factors associated with PMRT use, and quantified the histology-specific survival benefit of PMRT using log-rank tests and multivariate Cox regression analysis. We identified 86,098 IDC and 12,703 ILC patients. Within this cohort, 18.7% of IDC patients and 26.1% of ILC met ACR criteria for PMRT. Among patients with a definite indication, PMRT was more commonly employed in ILC than in IDC (59.6% vs. 56.3%; P = .0004). Among patients with a definite indication for PMRT, radiation improved 5-year breast cancer-specific survival from 71.4% to 77.0% for IDC (P < .0001) and from 80.9% to 84.7% for ILC (P = .0003). PMRT was used more commonly in ILC than in IDC. PMRT significantly improves 5-year overall survival and breast cancer-specific survival for ILC patients to a degree comparable with that seen in IDC. Moreover, among ILC and IDC patients who meet ACR criteria, PMRT appears to be significantly underutilized.


Risk of SARS-CoV-2 infection among contacts of individuals with COVID-19 in Hangzhou, China.
This study determined the rate of secondary infection among contacts of individuals with confirmed coronavirus disease 2019 (COVID-19) in Hangzhou according to the type of contacts, the intensity of contacts, and their relationship with the index patient. This is a retrospective cohort study. The analysis used the data of 2994 contacts of 144 individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The contacts were categorized according to the information source, type of contact, location, intensity of contact, and relationship with the index patient. The incidence of infection differed significantly according to contact type. Of the contacts, 186 (6.2%) developed symptoms, and 71 (2.4%) had confirmed SARS-CoV-2 infection. The main symptoms were cough and fever. Compared with those who had brief contact with the index case, those who had dined with the index case had 2.6 times higher risk of acquiring infection; those who had shared transport with, had visited, or had contact with the index case in a medical institution had 3.6 times higher risk of acquiring infection; and household contacts had 41.7 times higher risk of acquiring infection. Family members had 31.6 times higher risk of acquiring infection than healthcare providers or other patients exposed to an index case. The form and frequency of contact are the main factors affecting the risk of infection among contacts of individuals with COVID-19. Centralized isolation and observation of close contacts of individuals with confirmed SARS-CoV-2 infection, in addition to population-based control measures, can reduce the risk of secondary infections and curb the spread of the infection.


[Techniques and results of primary hip arthroplasty in geriatric acetabular fractures].
As a result of demographic changes, there is an increase in geriatric acetabular fractures [1, 2]. Geriatric patients often have comorbidities, such as pre-existing coxarthritis, reduced bone quality or limited compliance, which makes injury-adapted follow-up treatment difficult [3]. As a result joint-preserving interventions often fail at an early stage, so that hip arthroplasty is necessary in the short term. The 1‑year mortality after surgically stabilized acetabular fractures is 8.1%, a significant increase by a factor of 4 compared to the age group [4]. This illustrates that differentiated criteria for the indication of joint-preserving surgery versus arthroplasty are necessary to avoid reoperations and complications. Criteria for the indications for primary arthroplasty are fracture type, pre-existing coxarthritis, poor bone quality, limited compliance and patient age (> 75 years) [5, 6].In the following article, three treatment strategies for geriatric acetabular fractures and periprosthetic acetabular fractures are presented; the 1‑stage prosthesis implantation without osteosynthesis, the 1‑stage prosthesis implantation with osteosynthesis and the 2‑stage approach with limited osteosynthesis and early total arthroplasty. The advantages and disadvantages of these options are presented based on cases and the various aspects of the treatment. The treatment of geriatric acetabular fractures is an operative challenge for the surgeon and requires a high level of expertise in both special trauma surgery and revision arthroplasty and thus represents a special interface in the fields of orthopedics and trauma surgery.


A case of partial trisomy 20p resulting from meiotic recombination of a maternal pericentric inversion.
Here we report the cytogenetic and clinical manifestations observed in a patient with a rec(20)dup(20p)inv(20)(p11.2q13.3)mat. The patient was a full-term newborn girl with asymmetric intrauterine growth restriction and multiple congenital malformations, including a ventricular septal defect, pulmonary atresia, ambiguous genitalia, clinodactyly, and sacral dimpling. To our knowledge, this is the 4th report in the world and the 1st one in Korea of a patient with rec(20)dup(20p).


Urinary cross-linked carboxyterminal telopeptide, a bone resorption marker, decreases after vaso-occlusive crises in adults with sickle cell disease.
People with sickle cell disease often report severe bone pain with repeated bouts of vaso-occlusive crises, but the extent of skeletal injury incurred during these painful episodes remain unclear. We sought to quantify bone degradation by comparing urinary concentrations of carboxyterminal cross-linked telopeptide of type I collagen (CTX-1), a well-described marker of bone resorption, in a prospective cohort of 52 adults with sickle cell disease enrolled in the Sickle Cell Pain Markers Study. We also questioned if changes in urinary CTX-1 concentrations correlated with changes in hemolysis and inflammatory markers measured both during and after resolution of a painful vaso-occlusive episode. Thirty-one of the 52 adults enrolled in the study had paired urine samples for CTX-1 analysis. Urinary CTX-1, corrected for urine creatinine, significantly decreased from a mean of 3.45 μg/mmol during vaso-occlusive crises to 2.62 μg/mmol at recovery (p = 0.01). Thus, increased bone loss appears to correlate with acute vaso-occlusive crises in sickle cell disease. Our finding that urinary CTX-1 can be used to probe bone degradation in sickle cell disease provides an important new tool for diagnosing and monitoring response to therapy for people with sickle cell-related bone loss.


BID-induced structural changes in BAK promote apoptosis.
The BCL-2-family protein BAK is responsible for mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis. The BCL-2 homology 3 (BH3)-only protein BID activates BAK to perform this function. We report the NMR solution structure of the human BID BH3-BAK complex, which identified the activation site at the canonical BH3-binding groove of BAK. Mutating the BAK BH1 in the groove prevented activation and MOMP but not the binding of BID. BAK BH3 mutations allowed BID binding and activation but blunted function by blocking BAK oligomerization. BAK activation follows a 'hit-and-run' mechanism whereby BID dissociates from the trigger site, which allows BAK oligomerization at an overlapping interface. In contrast, the BH3-only proteins NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK. These findings provide insights into the early stages of BAK activation.


Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging.
Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlying molecular mechanism. Co-immunoprecipitation and proximal ligation assay results showed that TAGLN can interact with USP1. USP1 can be retained in the cytoplasm by TAGLN in UVA-induced cells, which inhibits the interaction between USP1/zinc finger E-box binding homeobox 1 (ZEB1), promote the ubiquitination degradation of ZEB1, and lead to photoaging. TAGLN knockdown can release USP1 retention and help human skin fibroblasts (HSFs) resist UVA-induced damage. The interactive interface inhibitors of TAGLN/USP1 were screened via virtual docking to search for small molecules that inhibit photoaging. Zerumbone (Zer), a natural product isolated from Zingiber zerumbet (L.) Smith, was screened out. Zer can competitively bind TAGLN to reduce the retention of USP1 in the cytoplasm and the degradation of ZEB1 ubiquitination in UV-induced HSFs. The poor solubility and permeability of Zer can be improved by preparing it as a nanoemulsion, which can effectively prevent skin photoaging caused by UVA in wild-type (WT) mice. Zer cannot effectively resist the photoaging caused by UVA in Tagln-/- mice because of target loss. The present results showed that the interaction of TAGLN and USP1 can promote ZEB1 ubiquitination degradation in UV-induced skin photoaging, and Zer can be used as an interactive interface inhibitor of TAGLN/USP1 to prevent photoaging.


Prediction of survival without morbidity for infants born at under 33 weeks gestational age: a user-friendly graphical tool.
To develop models and a graphical tool for predicting survival to discharge without major morbidity for infants with a gestational age (GA) at birth of 22-32 weeks using infant information at birth. Retrospective cohort study. Canadian Neonatal Network data for 2003-2008 were utilised. Neonates born between 22 and 32 weeks gestation admitted to neonatal intensive care units in Canada. Survival to discharge without major morbidity defined as survival without severe neurological injury (intraventricular haemorrhage grade 3 or 4 or periventricular leukomalacia), severe retinopathy (stage 3 or higher), necrotising enterocolitis (stage 2 or 3) or chronic lung disease. Of the 17 148 neonates who met the eligibility criteria, 65% survived without major morbidity. Sex and GA at birth were significant predictors. Birth weight (BW) had a significant but non-linear effect on survival without major morbidity. Although maternal information characteristics such as steroid use, improved the prediction of survival without major morbidity, sex, GA at birth and BW for GA predicted survival without major morbidity almost as accurately (area under the curve: 0.84). The graphical tool based on the models showed how the GA and BW for GA interact, to enable prediction of outcomes especially for small and large for GA infants. This graphical tool provides an improved and easily interpretable method to predict survival without major morbidity for very preterm infants at the time of birth. These curves are especially useful for small and large for GA infants.


Characterization of sub-watershed-scale stream chemistry regimes in an Appalachian mixed-land-use watershed.
An exploratory study was conducted in an urbanizing, mixed-land-use Appalachian watershed. Six study sites, characterized by contrasting land use/land cover, were instrumented to continuously monitor stream stage. Weekly grab samples were collected from each site and analyzed for elemental composition via spectrometric and spectrophotometric methods. Additional physico-chemical parameters were measured in situ. Data were analyzed using a suite of statistical methods, including hypothesis testing, correlation analysis, and principal components analysis (PCA). Significant differences (p < 0.05) between study sites were identified for every measured parameter except Co, Cu, Pb, and Ti concentrations. However, different parameters showed significant differences (p < 0.05) between site pairings. PCA results highlight consistent spatial differences between elemental composition and physico-chemical characteristics of streamwater samples. Results from correlation analyses indicated varying significant (p < 0.05) relationships between chemical parameters and hydroclimate metrics, with certain elements (e.g., Ca and Sr) and physico-chemical parameters (e.g., specific conductance) displaying greater sensitivity to hydroclimate at mixed-land-use sites, as compared to predominately urban, agricultural, or forest sites. Given the geological, topographical, and climatological similarities between the sites, and their close proximity, it was concluded that land use characteristics and associated hydrologic regime contrasts were the primary factors contributing to the observed results. Results comprise valuable information for land and water managers seeking to mitigate the impacts of land use practices on water resources and aquatic ecosystem health. The applied methodology can be used to more effectively target sub-watershed-scale remediation/restoration efforts within mixed-use watersheds, thereby improving the ultimate efficacy of management practices.


The effect of papaverine on local tissue PO2 and microflow in cat brain cortex.
The effect of intracarotid and intravenous administration of papaverine on local tissue PO2 and microflow in the cat's brain surface was studied. Local tissue PO2 was measured with a multiwire surface electrode polarographically, and microflow by local hydrogen clearance method. The intracarotid infusions were made for 1, 2 and 5 min with doses of 0.1, 0.2 and 0.5 mg/kg/min papaverine, and the intravenous ones for 5 min with doses of 0.2, 0.5 and 1 mg/kg/min. The continuous intracarotid infusions showed that papaverine in the doses used distinctly increased local tissue PO2 and microcirculation of the brain surface. With the doses applied, systemic arterial pressure (SAP) changed little. It slightly decreased only during the 5 min infusions containing 0.5 mg/kg/min. The duration of the effect increased with increases in the duration of the infusion and of the dose. The maximum duration was observed with 5 min infusions and lasted for 10--15 min after drug administration was discontinued. During the i.v. infusions, tissue PO2 and microflow rose less than with intracarotid ones. No redistribution of capillary flow was observed.


Validity and reliability of Spanish version of the EQ-i: YV[S] in Colombian children and youth.
Validity and reliability evaluations of the Emotional Quotient Inventory: Youth Version (EQ-i: YV[S]) with children and adolescents from different countries have shown variations in the structural model proposed by Bar-On. To examine the psychometric properties of EQ-i: YV[S] with a Colombian' sample. We randomly selected a sample of 1355 children and adolescents between 8 and 14 years old (Mage = 10.80; SD = 1.41). We conducted exploratory (n1 = 416) and confirmatory (n2 = 939) factor analyses (EFA, CFA), reliability, internal consistency, and predictive validity. The EFA explained 27.6% of the variance. The AFC indicated a multidimensional structure with four factors and 21 items obtained the best fit (χ2 = 334.358; df = 183; RMSEA=0.030; CFI=.951; TLI=944; NFI=.899) with acceptable internal consistency (ω = .57,.75). EQ-i: YV[S] factors explain 18.5% of the observed variance in problem-centered coping scores. The psychometric fit of the inventory supports evidence of its usefulness for screening processes in clinical or educational assessment.


Record linkage studies of drug-related deaths among adults who were released from prison to the community: a scoping review.
There are public health concerns about an increased risk of mortality after release from prison. The objectives of this scoping review were to investigate, map and summarise evidence from record linkage studies about drug-related deaths among former adult prisoners. MEDLINE, EMBASE, PsychINFO and Web of Science were searched for studies (January 2011- September 2021) using keywords/index headings. Two authors independently screened all titles and abstracts using inclusion and exclusion criteria and subsequently screened full publications. Discrepancies were discussed with a third author. One author extracted data from all included publications using a data charting form. A second author independently extracted data from approximately one-third of the publications. Data were entered into Microsoft Excel sheets and cleaned for analysis. Standardised mortality ratios (SMRs) were pooled (where possible) using a random-effects DerSimonian-Laird model in STATA. A total of 3680 publications were screened by title and abstract, and 109 publications were fully screened; 45 publications were included. The pooled drug-related SMR was 27.07 (95%CI 13.32- 55.02; I 2 = 93.99%) for the first two weeks (4 studies), 10.17 (95%CI 3.74-27.66; I 2 = 83.83%) for the first 3-4 weeks (3 studies) and 15.58 (95%CI 7.05-34.40; I 2 = 97.99%) for the first 1 year after release (3 studies) and 6.99 (95%CI 4.13-11.83; I 2 = 99.14%) for any time after release (5 studies). However, the estimates varied markedly between studies. There was considerable heterogeneity in terms of study design, study size, location, methodology and findings. Only four studies reported the use of a quality assessment checklist/technique. This scoping review found an increased risk of drug-related death after release from prison, particularly during the first two weeks after release, though drug-related mortality risk remained elevated for the first year among former prisoners. Evidence synthesis was limited as only a small number of studies were suitable for pooled analyses for SMRs due to inconsistencies in study design and methodology.


Information needs and preferences of recently diagnosed patients with inflammatory bowel disease.
The aim of this study was to assess the information needs and experiences of patients who were recently diagnosed with inflammatory bowel disease (IBD). Seventy-four patients, diagnosed with Crohn's disease or ulcerative colitis, 3-24 months previously were recruited from gastroenterology practices and completed the information needs survey. The most frequent sources of information in the first 2 months after diagnosis were the gastroenterologist and the Internet. In all, 24% of patients reported feeling dissatisfied with the information they were given at the time of their diagnosis, 31% were moderately satisfied, and 45% were very satisfied. There were many areas of information about the disease, its treatment, and self management that patients considered to be important and received little or no information about. When patients described how they would prefer to receive information if they were considering a new treatment in the future, 68% indicated that they preferred information from a medical specialist. Given the large number of topics judged by patients to be important and the complexity of the information required, it would be very difficult to communicate this information in oral discussion during typical consultation visits. Supplementing physician-patient consultations with well-designed written information or a Website recommendation may produce more effective communication and education. Patients rated these sources of information as having a high level of acceptability.