[The effect of hypertonic solutions on contracture of a tonic muscle fiber].
Effect of glycerol, sucrose and NaC1 hypertonic solutions exerted on potassium contracture and resting membrane potential in isolated frog tonic muscle fibres were studied. Sucrose and NaC1 hypertonic solutions induce a stable depolarization and depress potassium contracture, while glycerol results in a transient depolarization followed by recovery of resting membrane potential and contracture reactions. The removal of 400 mM glycerol induces an insignificant depolarization and disappearance of contracture reactions, however, after the removal of sucrose of NaC1 hypertonicity both the parameters tend to restore. The isolated phasic and tonic fibres lose irreversibly potassium contracture reactions after the removal of 100 mM and 400 mM glycerol, respectively, the latter being more resistant to this procedure. Nevertheless it is concluded that the T-system is equally important for excitation--contraction coupling in tonic and in phasic fibres.


Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats.
Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in females. Obesity and mechanical injuries caused by OA are attributed to joint loading, cartilage disintegration, and bone loss, as well as inflammation. Pharmacological and non-pharmacological treatments can be used for OA. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on rats with diet-induced obesity. OA was induced by an anterior cruciate ligament transection and a partial medial meniscectomy (ACLT + MMx). The male SD rats were fed with a high-fat diet (HFD) for 4 weeks to induce obesity before causing ACLT + MMx to induce OA. The OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with an HFD. We observed that the swelling in the knee joint was alleviated and the hind paw weight distribution was rectified after feeding them with fucoidan and that there was no significant effect on the weight gain and feed intake. Fucoidan administration indicated no significant variation on the high-density lipoprotein (HDL)-Cholesterol level, but it did indicate reduced plasma triglycerides and low-density lipoprotein (LDL)-Cholesterol levels. In addition, the weight-bearing tests showed an improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.


Mallory-Weiss tear during gastric endoscopic submucosal dissection.
A 78-year-old woman was referred to our department for treatment of an early gastric cancer. Esophagogastroduodenoscopy (EGD) demonstrated a flat elevated lesion and a polypoid lesion on the greater curvature of the antrum. Histological analysis of, endoscopic biopsy samples taken from these lesions revealed an adenocarcinoma and a hyperplastic polyp, respectively. ESD was conducted for removal of the lesions. Carbon dioxide (CO(2)) instead of room air was used for insufflation, and the patient was adequately sedated without struggling or vomiting during the treatment. No significant bleeding from the lesion was observed during ESD, but fresh blood was identified endoscopically. Surprisingly, a Mallory-Weiss tear with active bleeding was detected on the lesser curvature of the gastric corpus. A total of eight hemoclips were applied for hemostasis. Both lesions were completely removed en bloc, and no bleeding or perforation developed after ESD. Histologically, the first lesion was a papillary carcinoma limited to the mucosal layer and without lymphovascular invasion or involvement of the surgical margins, while the second lesion was a benign hyperplastic polyp.


Efficacy of ciprofloxacin-clarithromycin combination against drug-resistant Pseudomonas aeruginosa mature biofilm using in vitro experimental model.
Pseudomonas aeruginosa is the main cause of mortality in cystic fibrosis patients and eradication of its biofilm represents a substantial problem clinically. In this study, biofilm of a cystic fibrosis strain P. aeruginosa PACI22 was established and confocal laser scanning microscopy was utilized for biofilm visualization. A quantitative time-kill biofilm model was implemented in vitro to assess the biocidal effect of ciprofloxacin, clarithromycin, and their combination at concentration levels ranged from 0.5× to 64× minimum biofilm inhibitory concentrations (MBIC) against the biofilm and the mean log bacterial densities (Log CFU/ml) retrieved from the biofilm were monitored by frequent sampling at 0, 3, 6, 9, 12, and 24 hr throughout the experiment. The results revealed that none of the tested antibiotics alone could completely eradicate the biofilm-ensconced bacteria at 0.5-64× MBIC values after 24 hr of treatment. Conversely, ciprofloxacin-clarithromycin combination at 32-64× MBIC entirely exterminated the biofilm. Furthermore, a substantial in vitro synergism between ciprofloxacin and clarithromycin against the biofilm was experimentally verified. This promising synergism affords scientific rationale for further in vivo investigations to evaluate the therapeutic potential of this combination for treatment of chronic pulmonary infections caused by P. aeruginosa biofilms.


Terrabacter aerolatus sp. nov., isolated from an air sample.
A Gram-positive, strictly aerobic, motile, rod- or coccoid-shaped bacterium, strain 5516J-36(T), was isolated from an air sample from Jeju region, Korea, and its taxonomic position was investigated by a polyphasic approach. The organism grew optimally at 30 degrees C and pH 7.0-8.0. Comparative 16S rRNA gene sequencing studies demonstrated that this strain was highly related phylogenetically to Terrabacter terrae PPLB(T) and Terrabacter tumescens DSM 20308(T), showing 98.9 % sequence similarity to both strains. However, the DNA-DNA reassociation values between 5516J-36(T) and the type strains of Terrabacter terrae and Terrabacter tumescens were low (51 and 48 %, respectively). The peptidoglycan type was A3gamma, the predominant menaquinone was MK-8(H(4)), the polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol and an unidentified phosphoglycolipid and the whole-cell sugars were glucose, ribose, rhamnose, xylose and galactose. Mycolic acids were absent. The major fatty acids (>5 % of total fatty acids) were iso-C(15 : 0), iso-C(16 : 0), iso-C(14 : 0), iso-C(17 : 0) and anteiso-C(15 : 0). The DNA G+C content was 71.7 mol%. On the basis of the above data, it is proposed that strain 5516J-36(T) represents a novel species, Terrabacter aerolatus sp. nov. The type strain of Terrabacter aerolatus is 5516J-36(T) (=KACC 20556(T) =DSM 18562(T)).


Parental history of depression or anxiety and the cortisol awakening response.
It is unclear whether altered hypothalamic-pituitary-adrenal (HPA) axis regulation, which frequently accompanies depression and anxiety disorders, represents a trait rather than a state factor. To examine whether HPA axis dysregulation represents a biological vulnerability for these disorders, we compared cortisol levels in unaffected people with and without a parental history of depressive or anxiety disorders. We additionally examined whether possible HPA axis dysregulations resemble those observed in participants with depression or anxiety disorders. Data were from the Netherlands Study of Depression and Anxiety. Within the participants without a lifetime diagnoses of depression or anxiety disorders, three groups were distinguished: 180 people without parental history, 114 with self-reported parental history and 74 with CIDI-diagnosed parental history. These groups were additionally compared with people with major depressive disorder or panic disorder with agoraphobia (n = 1262). Salivary cortisol samples were obtained upon awakening, and 30, 45 and 60 min later. As compared with unaffected participants without parental history, unaffected individuals with diagnosed parental history of depression or anxiety showed a significantly higher cortisol awakening curve (effect size (d) = 0.50), which was similar to that observed in the participants with depression or anxiety disorders. Unaffected people with self-reported parental history did not differ in awakening cortisol levels from unaffected people without parental history. Unaffected individuals with parental history of depression or anxiety showed a higher cortisol awakening curve, similar to that of the participants with depression or anxiety disorders. This suggests that a higher cortisol awakening curve reflects a trait marker, indicating an underlying biological vulnerability for the development of depressive and anxiety disorders.


The role of ΔfosB in the medial preoptic area: Differential effects of mating and cocaine history.
The transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35-37-kDa isoform of ΔFosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase ΔFosB-ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing ΔFosB, its dominant negative antagonist ΔJunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. ΔFosB overexpression impaired copulation and promoted female-directed aggression, compared to ΔJunD and control males. These data suggest that ΔFosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression. (PsycINFO Database Record


NF-Y associates with H3-H4 tetramers and octamers by multiple mechanisms.
NF-Y is a CCAAT-binding trimer with two histonic subunits, NF-YB and NF-YC, resembling H2A-H2B. We previously showed that the short conserved domains of NF-Y efficiently bind to the major histocompatibility complex class II Ea Y box in DNA nucleosomized with purified chicken histones. Using wild-type NF-Y and recombinant histones, we find that NF-Y associates with H3-H4 early during nucleosome assembly, under conditions in which binding to naked DNA is not observed. In such assays, the NF-YB-NF-YC dimer forms complexes with H3-H4, for whose formation the CCAAT box is not required. We investigated whether they represent octamer-like structures, using DNase I, micrococcal nuclease, and exonuclease III, and found a highly positioned nucleosome on Ea, whose boundaries were mapped; addition of NF-YB-NF-YC does not lead to the formation of octameric structures, but changes in the digestion patterns are observed. NF-YA can bind to such preformed DNA complexes in a CCAAT-dependent way. In the absence of DNA, NF-YB-NF-YC subunits bind to H3-H4, but not to H2A-H2B, through the NF-YB histone fold. These results indicate that (i) the NF-Y histone fold dimer can efficiently associate DNA during nucleosome formation; (ii) it has an intrinsic affinity for H3-H4 but does not form octamers; and (iii) the interactions between NF-YA, NF-YB-NF-YC, and H3-H4 or nucleosomes are not mutually exclusive. Thus, NF-Y can intervene at different steps during nucleosome formation, and this scenario might be paradigmatic for other histone fold proteins involved in gene regulation.


[Conditions for developing mental disorders in myocardial infarction].
Conditions for mental disorders formation at different stages of the underlying disease have been specified as a result of clinico-psychopathological, clinico-catamnestic and experimental psychological studies carried out in 55 patients with myocardial infarction. The authors show an important role of the clinical features of myocardial infarction in the formation of asthenic symptomatology and affective pathology in the acute period of myocardial infarction. In the subacute period of the illness, the premorbid characteristics and psychotraumatic factors preceding the disease exert a noticeable effect on the development of depressive and ++astheno-hypochondriac disorders. In the clinical picture of acute myocardial infarction, a less significant role is played by age-associated factor. At the outpatient stage of myocardial infarction treatment, the psychotraumatic factors due to chronic disease and related situations assume a particular significance in the formation of depressive hypochondriac symptomatology.


Effect of demographic and injury etiologic factors on intensive care unit mortality after severe head injury in a low middle income country.
Low- and middle-income countries bear the mortality burden of head injury compared with high-income countries. Not much has been studied about predictors of poor outcome after head injury in these countries. This study describes and quantifies the effect of demographics and injury causative factors on mortality in a cohort managed in a Nigerian tertiary hospital intensive care. A retrospective study was undertaken of all patients admitted into intensive care with severe head injury at the University of Port Harcourt Teaching Hospital, Nigeria between 1 st January, 1997 and 31 st December, 2006. Logistic regression analysis was performed to examine the effect of age, gender and injury etiology on risk of intensive care unit (ICU) mortality. The number of ICU admission for severe head injury was 231 patients with a male to female ratio of 2.8:1. Patients' mean age and standard deviation was 31.2 ± 15.5 years. The mortality rate was 52.8%. Road traffic injury was the most common etiologic factor (84%). Logistic regression analysis indicated a 56% increase in the risk of ICU mortality between the ages of 21 and 40 years. The effect of age was found to be nonlinear (likelihood ratio P = 0.033). On multivariable analysis, patient's gender (odds ratio 1.07; 95% confidence interval: 0.56-1.97) and etiology of injury were not significantly associated with risk of mortality. Gender was not a modifier of the effect of age (P = 0.218). The study indicated a strong prognostic effect of age. Gender and etiology of injury had no effect on ICU mortality among study cohort.


Decolorization of textile dyes in an air-lift bioreactor inoculated with Bjerkandera adusta OBR105.
A new decolorizing white-rot fungus, OBR105, was isolated from Mount Odae in South Korea and identified by the morphological characterization of its fruit body and spores and partial 18s rDNA sequences. The ligninolytic enzyme activity of OBR105 was studied to characterize their decolorizing mechanism using a spectrophotometric enzyme assay. For the evaluation of the decolorization capacity of OBR105, the isolate was incubated in an erlenmeyer flask and in an airlifte bioreator with potato dextrose broth (PDB) medium supplemented with each dye. In addition, the decolorization efficiency of real textile wastewater was evaluated in an airlift bioreactor inoculated with the isolate. The isolate was identified as Bjerkandera adusta and had ligninolytic enzymes such as laccase, lignin peroxidase (LiP), and Mn-dependent peroxidase (MnP). Its LiP activity was higher than its MnP and laccase activities. B. adusta OBR105 successfully decolorized reactive dyes (red 120, blue 4, orange 16, and black 5) and acid dyes (red 114, blue 62, orange 7, and black 172). B. adusta OBR105 decolorized 91-99% of 200 mg L-1 of each dye (except acid orange 7) within 3 days in a PDB medium at 28°C, pH 5, and 150 rpm. This fungus decolorized only 45% of 200 mg L-1 acid orange 7 (single azo-type dye) within 3 days, and the decolorization efficiency did not increase by prolonging the cultivation time. In the air-lift bioreactor, B. adusta OBR105 displayed a high decolorization capacity, greater than 90%, for 3 acid dyes (red 114, blue 62, and black 172) and 1 reactive dye (blue 4) within 10-15 h of treatment. B. adusta OBR105 could decolorize real textile wastewater in the air-lift bioreactor. This result suggests that an air-lift reactor employing B. adusta OBR105 is a promising bioreactor for the treatment of dye wastewater.


Current and future molecular diagnostics of gastric cancer.
Introduction: Gastric cancer (GC) is the fifth most common cancer and confers the second-highest mortality among other cancers. Improving the survival rates of GC patients requires prompt and accurate diagnosis and effective treatment which is often preceded by the poorly understood pathogenic mechanisms. Area covered: This literature review aims to summarize current understanding of genetic and molecular alterations that promote carcinogenesis including (1) activation of oncogenes, (2) overexpression of growth factors, receptors and matrix metalloproteinases, (3) inactivation of tumor suppressor genes, DNA repair genes, and cell adhesion molecules and (4) alterations of cell-cycle regulators that regulate biological characteristics of cancer cells. Moreover, the significance of molecular biomarkers such as micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) and advanced molecular techniques including droplet digital polymerase chain reaction (ddPCR), quantitative PCR (qPCR) and next-generation sequencing (NGS) are also discussed. Expert opinion: A GC-specific panel of biomarkers based on the NGS or ddPCR has the potential for diagnosis, prognosis, and monitoring treatment response in GC patients. Despite the requirements for validation in larger population in clinical studies, race-specific differences in the gene panel have also to be examined by performing the clinical trials in subjects with different races.


How streamlining telecommunications can cut IT expense.
Hospitals and health systems can save IT expenses by implementing more efficient processes in accordance with the principles of effective telecommunications expense management. This approach involves three primary steps: Inventory of existing infrastructure. Charge verification. Optimization of rates and design for continual improvement.


Responses of persons with dementia to challenges in daily activities: a synthesis of findings from empirical studies.
The purpose of this study was to obtain a better understanding of strategies initiated and used in response to problems in performing daily occupations by persons with dementia in a mild to moderate stage. The results from seven in-depth, qualitative studies conducted by the author and coworkers, describing such response strategies were analyzed and synthesized using aggregated analysis. Synthesized categories describing different types of response behavior were identified and the variations within them investigated. In general, the strategies used by persons with mild to moderate dementia were intuitively employed and characterized as "common sense behavior." The main goal of the strategies was understood as retaining a sense of control and mastery over everyday life matters. It is argued that the users implicitly or explicitly experienced a need to adapt; further exploration of how awareness of ability and disability in daily life occupation may be experienced and expressed in persons with dementia seems important. Findings suggest that therapists and caregivers be open to detecting and supporting the response strategies used by persons with dementia as long as they appear to be useful from the perspective of the individual rather than strictly from an efficacy point of view.


Centrally administered naloxone blocks reflex natriuresis after acute unilateral nephrectomy.
Acute unilateral nephrectomy (AUN) leads to a natriuresis and kaliuresis by the remaining kidney through reflex mechanisms involving opiate receptors. To determine whether the opiate receptors mediating these responses are located in the central nervous system, we carried out AUN in anesthetized rats undergoing continuous ventriculocisternal perfusion (VCP) with artificial cerebrospinal fluid (CSF). AUN caused large increases in both Na (UNaV) and K (UKV) excretion without changes in glomerular filtration rate or arterial blood pressure. When the opiate receptor antagonist naloxone was added to the perfusate to achieve a perfusion rate of 32 micrograms X kg-1 X h-1, AUN failed to increase either UNaV or UKV by the remaining kidney. This dose of naloxone, however, was without effect when infused intravenously. Addition of thyrotropin-releasing hormone (TRH) to the artificial CSF to achieve a VCP rate of 50 micrograms X kg-1 X h-1 also blocked the expected increase in UNaV and UKV by the remaining kidney after AUN. Infusion of TRH intravenously at the same rate did not interfere with the postnephrectomy natriuresis or kaliuresis. Higher intravenous infusion rates of TRH (1 and 2 mg X kg-1h-1) prevented the postnephrectomy natriuresis without affecting the kaliuresis. These results indicate that the effect of naloxone to block the reflex natriuresis and kaliuresis after AUN resides largely in the central nervous system. The blockade by naloxone of the postnephrectomy natriuresis is duplicated by centrally administered TRH, providing another example of the interaction of this hormone with the endogenous opioid system. Large intravenous infusions of TRH also block the postnephrectomy natriuresis but not the kaliuresis.


Premedication with diclofenac and prednisolone to prevent postoperative pain and swelling after third molar removal.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and steroid are able to effectively reduce the postoperative sequelae after impacted third molar removal. However, few studies have evaluated the activity of the combined effects of these two drugs. The purpose of this study was to evaluate whether a single dose of prednisolone, taken orally before operation, would increase the effects of diclofenac in preventing pain and swelling after surgical removal of impacted third molars. Thirty healthy patients requiring surgical removal of four third molars were randomly assigned to two groups. In group A, patients were preoperatively given 50 mg of either diclofenac or placebo when impacted teeth were removed on each side. In group B, in addition to 50 mg of diclofenac, 10 mg of prednisolone or placebo was administered. Postoperative pain, swelling and range of mouth opening were recorded. Preoperative administration of 50 mg of diclofenac could relieve pain and swelling more than the placebo. Additional 10 mg of prednisolone could further reduce swelling. The combination of diclofenac and prednisolone has a better analgesic and anti-inflammatory effect.


Web-based weight management programs in an integrated health care setting: a randomized, controlled trial.
To assess the efficacy of a Web-based tailored behavioral weight management program compared with Web-based information-only weight management materials. Participants, 2862 eligible overweight and obese (BMI = 27 to 40 kg/m2) members from four regions of Kaiser Permanente's integrated health care delivery system, were randomized to receive either a tailored expert system or information-only Web-based weight management materials. Weight change and program satisfaction were assessed by self-report through an Internet-based survey at 3- and 6-month follow-up periods. Significantly greater weight loss at follow-up was found among participants assigned to the tailored expert system than among those assigned to the information-only condition. Subjects in the tailored expert system lost a mean of 3 +/- 0.3% of their baseline weight, whereas subjects in the information-only condition lost a mean of 1.2 +/- 0.4% (p < 0.0004). Participants were also more likely to report that the tailored expert system was personally relevant, helpful, and easy to understand. Notably, 36% of enrollees were African-American, with enrollment rates higher than the general proportion of African Americans in any of the study regions. The results of this large, randomized control trial show the potential benefit of the Web-based tailored expert system for weight management compared with a Web-based information-only weight management program.


Gold(I)-promoted heterocyclization of internal alkynes: a comparative study of direct metallate 5-endo-dig cyclization versus a stepwise cyclization.
With cationic gold catalysts, internal alkynes bearing both propargylic acyloxy groups and tosylamide pronucleophiles were found to cyclize to give either five- or six-membered ring nitrogen heterocycles. A wide variety of gold catalysts, counterions, and solvents were examined to elucidate their effect on product distribution. In most cases, the direct 5-endo-dig cyclization was found to be the major pathway leading to good yields of dehydropyrrolidine products. Alkyne substrates bearing additional normal alkyl substituents at the propargylic position gave dehydropiperidines as the major product. This pathway is thought to proceed by way of a 1,2- Rautenstrauch rearrangement to produce a vinyl gold(I) carbene, which undergoes conjugate addition by the nitrogen pronucleophile. Structural and electronic factors were studied in the nitrogen pronucleophile and in the migrating acyloxy group. Each was found to have a minor effect on the product ratio.


A Web-Based Communication Tool for Postoperative Follow-up and Pain Assessment at Home After Primary Knee Arthroplasty: Feasibility and Usability Study.
We report the use of an electronic tool, Eir (Eir Solutions AS, Norway), for symptom registration at home after knee arthroplasty. This electronic tool was used in a randomized controlled trial (RCT) comparing 3 different analgesic regimens with respect to postoperative pain and side effects. The aim of this substudy was to investigate this electronic tool for symptom registrations at home with respect to usability (ie, how easy it was to use) and feasibility (ie, how well the tool served its purpose). To assess the tool's usability, all participants were invited to fill out the 10-item System Usability Scale (SUS) after using the tool for 8 days. To assess feasibility, data regarding the participants' ability to use the tool with or without assistance or reminders were collected qualitatively on a daily basis during the study period. A total of 134 patients completed the RCT. Data concerning feasibility of the web-based tool were collected from all 134 patients. The SUS was completed by 119 of the 134 patients; 70.2% (94/134) of the patients managed to use the tool at home without any technical support. All technical challenges were related to the login procedure or internet access. The mean SUS score was 89.6 (median 92.5; range 22.5-100). This study showed high feasibility and high usability of the Eir web tool. The received reports gave the necessary information needed for both research data and clinical follow-up. ClinicalTrials.gov NCT02604446; https://www.clinicaltrials.gov/ct2/show/NCT02604446.


In vitro activity of 12 antimicrobial peptides against Mycobacterium tuberculosis and Mycobacterium avium clinical isolates.
Tuberculosis (TB) remains a major threat to human health worldwide. The increasing incidence of non-tuberculous mycobacterial infections and particularly those produced by Mycobacterium avium has emphasized the need to develop new drugs. Additionally, high levels of natural drug resistance in non-tuberculous mycobacteria (NTM) and the emergence of multidrug-resistant (MDR) TB is of great concern. Antimicrobial peptides (AMPs) are antibiotics with broad-spectrum antimicrobial activity. The objective was to assess the activity of AMPs against Mycobacterium tuberculosis and M. avium clinical isolates. MICs were determined using microtitre plates and the resazurin assay. Mastoparan and melittin showed the greatest activity against M. tuberculosis, while indolicidin had the lowest MIC against M. avium. In conclusion, AMPs could be alternatives for the treatment of mycobacterial infections. Further investigation of AMPs' activity in combination and associated with conventional antibiotics and their loading into drug-delivery systems could lead to their use in clinical practice.


Syntheses optimization, structural and thermoelectric properties of 1/1 Tsai-type quasicrystal approximants in RE-Au-SM systems (RE=Yb, Gd and SM=Si, Ge).
Yb-Cd (Tsai-type) quasicrystals constitute the largest icosahedral quasicrystal family where Yb can be replaced by other rare earth elements (RE) and Cd by pairs of p- and d-block elements. YbCd6 is a prototype 1/1 Tsai-type approximant phase which has a similar local structure to the Yb-Cd quasicrystal. In this study, the syntheses of Yb15.78Au65.22Ge19.00, Gd14.34Au67.16Ge18.5 and Gd14.19Au69.87Si15.94 Tsai-type 1/1 quasicrystal approximants are optimized using the self-flux technique. The crystal structures of the compounds are refined by collecting single crystal x-ray diffraction data. The structural refinements indicated that the compounds are essentially isostructural with some differences at their cluster centers. The basic polyhedral cluster unit in all the three compounds can be described by concentric shells of icosahedra symmetry and of disordered tetrahedra and/or a rare earth atom at the cluster center. Furthermore, the thermoelectric properties of the compounds are probed and their dimensionless figures of merit are calculated at different temperatures. A significant difference is observed in their thermoelectric properties, which could arise due to the slight difference in their crystal structure and chemical composition, as we move from Ge to Si and/or Gd to Yb. Therefore, this study shows the systematic effect of the chemical substitution of structurally similar materials on their thermoelectric properties.


Assessment of implant surface and instrument insert changes due to instrumentation with different tips for ultrasonic-driven debridement.
To assess the changes of implant surfaces of different roughness after instrumentation with ultrasonic-driven scaler tips of different materials. Experiments were performed on two moderately rough surfaces (I-Inicell® and II-SLA®), one surface without pre-treatment (III) and one smooth machined surface (IV). Scaler tips made of steel (A), PEEK (B), titanium (C), carbon (D) and resin (E) were used for instrumentation with a standardized pressure of 100 g for ten seconds and under continuous automatic motion. Each combination of scaler tip and implant surface was performed three times on 8 titanium discs. After instrumentation roughness was assessed by profilometry, morphological changes were assessed by scanning electron microscopy, and element distribution on the utmost surface by energy dispersive X-ray spectroscopy. The surface roughness of discs I and II were significantly reduced by instrumentation with all tips except E. For disc III and IV roughness was enhanced by tip A and C and, only for IV, by tip D. Instrumentation with tips B, D and E left extensive residuals on surface I, II and III. The element analysis of these deposits proved consistent with the elemental composition of the respective tip materials. All ultrasonic instruments led to microscopic alterations of all types of implants surfaces assessed in the present study. The least change of implant surfaces might result from resin or carbon tips on machined surfaces.


Long-term results of the subclavian flap repair for coarctation of the aorta in infants.
Coarctation is a congenital narrowing of the aorta that often requires repair during infancy. The subclavian flap aortoplasty was once widely favored for its avoidance of a circumferential suture line and low incidence of recoarctation. The aim of this study is to report the long-term results of the subclavian flap repair for coarctation of the aorta in infants. Our operative database was queried for infants with coarctation who underwent subclavian flap aortoplasty from 1966 to 1991. Medical records were reviewed for patient characteristics and outcomes. Survivors were identified for additional phone interview. Fifty-five patients met the inclusion criteria. There were 7 early deaths (in hospital), 11 late deaths, 5 patients lost to follow-up, and 32 known long-term survivors with a mean follow-up of 22.0 years (range 2.4-34.9). Hospital mortality was not associated with patient characteristics but was associated with earlier year of surgery (P = .015). A trend toward decreased overall survival was seen in patients with coarctation with associated cardiac defects (P = .072). Reintervention for recoarctation was required in 3 (6.6%) patients and was not related to the patient characteristics. There were no apparent complications related to subclavian artery sacrifice. Subclavian flap aortoplasty provides excellent long-term results for the repair of coarctation in infants. The incidence of recoarctation requiring reintervention is low and compares favorably with other techniques. Compromise of growth or function of the left arm was not appreciated. The subclavian flap technique remains a viable surgical option for the repair of coarctation in infants.


Cardiac Pathophysiology and the Future of Cardiac Therapies in Duchenne Muscular Dystrophy.
Duchenne muscular dystrophy (DMD) is a devastating disease featuring skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. Historically, respiratory failure has been the leading cause of mortality in DMD, but recent improvements in symptomatic respiratory management have extended the life expectancy of DMD patients. With increased longevity, the clinical relevance of heart disease in DMD is growing, as virtually all DMD patients over 18 year of age display signs of cardiomyopathy. This review will focus on the pathophysiological basis of DMD in the heart and discuss the therapeutic approaches currently in use and those in development to treat dystrophic cardiomyopathy. The first section will describe the aspects of the DMD that result in the loss of cardiac tissue and accumulation of fibrosis. The second section will discuss cardiac small molecule therapies currently used to treat heart disease in DMD, with a focus on the evidence supporting the use of each drug in dystrophic patients. The final section will outline the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, or repair. There are several new and promising therapeutic approaches that may protect the dystrophic heart, but their limitations suggest that future management of dystrophic cardiomyopathy may benefit from combining gene-targeted therapies with small molecule therapies. Understanding the mechanistic basis of dystrophic heart disease and the effects of current and emerging therapies will be critical for their success in the treatment of patients with DMD.


Does biventricular pacing improve hemodynamics in children undergoing routine congenital heart surgery?
Biventricular (BiV) pacing or cardiac resynchronization therapy (CRT) is an established therapy for heart failure in adults. In children, cardiac dyssynchrony occurs most commonly following repair of congenital heart disease (CHD) where multisite pacing has been shown to improve both hemodynamics and ventricular function. Determining which patient types would specifically benefit has not yet been established. A prospective, repeated measures design was undertaken to evaluate BiV pacing in a cohort of children undergoing biventricular repair for correction of their CHD. Hemodynamics, arterial blood gas, electrocardiographic (ECG), and echocardiographic data were collected. Pacing protocol was undertaken prior to the patient's extubation with 20 min of conventional right ventricular (RV) or BiV pacing, preceded and followed by 10 min of recovery time. Multivariate statistics were used to analyze the data with p values <0.05 considered significant. Twenty-five (14 female) patients underwent surgery at a median (range) age of 5.2 (0.1-37.4) months with no early mortality. The Risk-adjusted classification for Congenital Heart Surgery (RACHS) scores were 2 in 14 patients, 3 in eight patients, and 4 in three patients. None had pre-existing arrhythmias, dyssynchrony, or required pacing pre-operatively. No patient required implantation of a permanent pacemaker post-operatively. The median cardio-pulmonary bypass time was 96 (55-236) min. RV and BiV pacing did not improve cardiac index from baseline (3.23 vs. 3.42 vs. 3.39 L/min/m2; p > 0.05). The QRS duration was not changed with pacing (100 vs. 80 vs. 80 ms; p > 0.05). On echocardiography, the time-to-peak velocity difference between the septal and posterior walls (synchrony) during pacing was similar to baseline and was also not statistically significant. BiV pacing did not improve cardiac output when compared to intrinsic sinus rhythm or RV pacing in this cohort of patients. Our study has shown that BiV pacing is not indicated in children who have undergone routine BiV congenital heart surgery. Further prospective studies are needed to assess the role of multisite pacing in children with ventricular dyssynchrony such as those with single ventricles, those undergoing reoperation or those with high RACHS scores.


Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.
Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations, morphological features, and clinical behavior.


Sentinel lymph node biopsy in node-negative squamous cell carcinoma of the oral cavity and oropharynx.
Considerable controversy exists regarding the merits of elective neck dissection in patients with early stage oral cavity and oropharyngeal squamous cell carcinoma. It is highly desirable to have a method of identifying those patients who would benefit from further treatment of the neck when they are clinically node-negative. The purpose of the present study was to examine the use of sentinel lymph node biopsy in identifying occult neck disease in a cohort of patients with node-negative oral cavity and oropharyngeal squamous cell carcinoma. We evaluated a total of 13 patients with oral cavity and oropharyngeal cancer who were clinically and radiologically node-negative. A sentinel lymph node was found in all 13 patients, revealing metastatic disease in five patients, four of whom had one or more positive sentinel lymph nodes. There was one false negative result, in which the sentinel lymph node was negative for tumour whereas histological examination of the neck dissection specimen showed occult disease. In view of these findings, we would recommend the use of sentinel lymph node biopsy in cases of oral cavity and oropharyngeal squamous cell carcinoma, in order to aid the differentiation of those patients whose necks are harbouring occult disease and who require further treatment.


Postpartum anxiety, depression and social health: findings from a population-based survey of Australian women.
Whilst the prevalence and correlates of postpartum depression are well established, far less is known about postpartum anxiety. Studies have described the association between socio-demographic factors and postpartum depression, yet few have explored the association between stressors in women's lives around the time of having a baby and maternal psychological morbidity. This study aimed to describe the population prevalence of postpartum depression, anxiety, co-morbid anxiety and depression and social health issues; and to examine the association between postpartum psychological and social health issues experienced in the six months following birth. Population-based survey of all women who gave birth in Victoria and South Australia in September/October 2007. Women were mailed the survey questionnaire six months following birth. Anxiety and depression were measured using the Depression Anxiety Stress Scales (DASS-21). Questionnaires were completed by 4,366 women. At six months postpartum the proportion of women scoring above the 'normal' range on the DASS-21 was 12.7% for anxiety,17.4% for depression, and 8.1% for co-morbid depression and anxiety. Nearly half the sample reported experiencing stressful life events or social health issues in the six months following birth, with 38.3% reporting one to two and 8.8% reporting three or more social health issues. Women reporting three or more social health issues were significantly more likely to experience postnatal anxiety (Adj OR = 4.12, 95% CI 3.0-5.5) or depression (Adj OR = 5.11, 95% CI = 3.9-6.7) and co-morbid anxiety and depression (Adj OR = 5.41, 95% CI 3.8-7.6) than women who did not report social health issues. Health care providers including midwives, nurses, medical practitioners and community health workers need to be alert to women's social circumstances and life events experienced in the perinatal period and the interplay between social and emotional health. Usual management for postpartum mental health issues including Cognitive Behavioural Therapy and pharmacological approaches may not be effective if social health issues are not addressed. Coordinated and integrated perinatal care that is responsive to women's social health may lead to improvements in women's emotional wellbeing following birth.


Hippocampal motor memory network reorganization depends on familiarity, not time.
There is debate as to whether a time-dependent transformation of the episodic-like memory network is observed for nonepisodic tasks, including procedural motor memory. To determine how motor memory networks reorganize with time and practice, mice performed a motor task in a straight alley maze for 1 d (recent), 20 d of continuous training (continuous), or testing 20 d after the original training (remote), and then regional c-Fos expression was assessed. Elevated hippocampal c-Fos accompanied remote, but not continuous, motor task retrieval after 20 d, suggesting that the hippocampus remains engaged for nonhabitual remote motor memory retrieval.


Investigation of the Correlation between Androgen Receptor and ZEB1 and its Value in Progression of Gastric Cancer.
Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription factor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). It is well-known that ZEB1 mRNA expression is directly induced by both Estrogen Receptor (ER) and Progesterone Receptor (PR). Moreover, Androgen Receptor (AR) and PR could bind to the same regulatory element. Since it has been shown that AR overexpresses in Gastric Cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate whether AR could regulate ZEB1 expression in GC. The expression profile of ZEB1 in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimens was assessed by qRT-PCR, and the association of ZEB1 expression with clinicopathological features was investigated. Furthermore, possible correlation between ZEB1 and AR was evaluated to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Finally, molecular interaction of ZEB1 and AR was assessed using a potent AR antagonist in GC cells. Among GC patients, 70.2% (40/57) overexpressed ZEB1 and 64.91% (37/57) overexpressed AR relative to normal gastric tissues. ZEB1 overexpression was significantly correlated with the AR overexpression in GC patients. Moreover, ZEB1 overexpression was remarkably associated with lower overall survival; however, it was not an independent prognostic factor. Evidence shows that simultaneous evaluation of ZEB1 and AR expression could independently predict survival of GC patients (HR= 2.193, p=0.047). These findings have clinical importance suggesting simultaneous evaluation of ZEB1 and AR expression as a potential prognostic marker. Moreover, AR may regulate ZEB1 expression in GC cells proposing a possible promising targeted therapy for GC patients.


Dipyridamole-induced myocardial ischemia.
Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary "steal" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.


[The effect of the physico-chemical properties of suture materials and the surface structure on adherence of tumor cells].
Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastigmatic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.


Effect of aluminum phosphate gel on prevention of early rebleeding after ligation of esophageal variceal hemorrhage.
Liver cirrhosis is the main cause of portal hypertension. The leading cause of death in patients with liver cirrhosis is its most common complication, esophageal variceal bleeding (EVB). Endoscopic variceal ligation (EVL) is recommended by many guidelines to treat EVB and prevent rebleeding; however, esophageal ulcers occur after treatment. Delayed healing of ulcers and unhealed ulcers lead to high rebleeding and mortality rates. Thus, the prevention of early postoperative rebleeding is of great significance in improving the quality of life and prognosis of patients. To evaluate the efficacy of aluminum phosphate gel (APG) plus a proton pump inhibitor (PPI) in the prevention of early rebleeding after EVL in patients with EVB. The medical records of 792 patients who were diagnosed with EVB and in whom bleeding was successfully stopped by EVL at Shenzhen People's Hospital, Guangdong Province, China from January 2015 to December 2020 were collected. According to the study inclusion and exclusion criteria, 401 cases were included in a PPI-monotherapy group (PPI group), and 377 cases were included in a PPI and APG combination therapy (PPI + APG) group. We compared the incidence rates of early rebleeding and other complications within 6 wk after treatment between the two groups. The two-sample t-test, Wilcoxon rank-sum test, and chi-squared test were adopted for statistical analyses. No significant differences in age, sex, model for end-stage liver disease score, coagulation function, serum albumin level, or hemoglobin level were found between the two groups. The incidence of early rebleeding in the PPI + APG group (9/337; 2.39%) was significantly lower than that in the PPI group (30/401; 7.48%) (P = 0.001). Causes of early rebleeding in the PPI group were esophageal ulcer (3.99%, 16/401) and esophageal varices (3.49%, 14/401), while those in the PPI + APG group were also esophageal ulcers (5/377; 1.33%) and esophageal varices (4/377; 1.06%); such causes were significantly less frequent in the PPI + APG group than in the PPI group (P = 0.022 and 0.024, respectively). The early mortality rate within 6 wk in both groups was 0%, which was correlated with the timely rehospitalization of all patients with rebleeding and the conduct of emergency endoscopic therapy. The incidence of adverse events other than early bleeding in the PPI + APG group (28/377; 7.43%) was significantly lower than that in the PPI group (63/401; 15.71%) (P < 0.001). The incidence of chest pain in the PPI + APG group (9/377; 2.39%) was significantly lower than that in the PPI group (56/401; 13.97%) (P < 0.001). The incidence of constipation in the PPI + APG group (16/377; 4.24%) was significantly higher than that in the PPI group (3/401; 0.75%) (P = 0.002) but constipation was relieved after patients drank more water or took lactulose. In the PPI and PPI + APG groups, the incidence rates of spontaneous peritonitis within 6 wk after discharge were 0.50% (2/401) and 0.53% (2/377), respectively, and those of hepatic encephalopathy were 0.50% (2/401) and 0.27% (1/377), respectively, presenting no significant difference (P > 0.999). PPI + APG combination therapy significantly reduces the incidence of early rebleeding and chest pain in patients with EVB after EVL.


Detection rate of Actinobacillus actinomycetemcomitans on the permanent 1st molars of primary school children in Taiwan by polymerase chain reaction.
Actinobacillus actinomycetemcomitans (Aa) has been implicated as the putative micro-organism for localized juvenile periodontitis (LJP). The most distinct clinical features of LJP include severe angular bony defects of the mesial sides of permanent first molars and the onset of disease during puberty. Currently, no large-scale studies have been performed which address the change in detection rates of Aa on the mesial sides of permanent 1st molars following eruption and up to puberty. In this study, subgingival plaque samples were taken from the mesial pockets of 2 randomly selected permanent 1st molars from 328 primary school children and 50 adult staff, and analyzed by polymerase chain reaction (PCR) to detect Aa. The results showed a 5.5% prevalence rate of Aa which increased after the eruption of 1st molars and peaked near puberty. There were no significant differences in the detection rates of Aa among different groups in terms of gender, plaque index (PII), and gingival index (GI); however, the higher detection rates of Aa were significantly associated with increased probing depths at p<0.05. PCR analysis of the subgingival plaques demonstrated a prevalence of Aa which peaked near puberty, suggesting that Aa may be important for LJP in Taiwan.


Arthrokinematics of the Distal Radioulnar Joint Measured Using Intercartilage Distance in an In Vitro Model.
Current techniques used to measure joint contact rely on invasive procedures and are limited to statically loaded positions. We sought to examine native distal radioulnar joint (DRUJ) contact mechanics using nondestructive imaging methods during simulated active and passive forearm rotation. Testing was performed using 8 fresh-frozen cadaveric specimens that were surgically prepared by isolating muscles involved in forearm rotation. A wrist simulator allowed for the evaluation of differences between active and passive forearm rotation. Three-dimensional cartilage surface reconstructions were created using volumetric data acquired from computed tomography. Using optically tracked motion data, the relative position of the cartilage models was rendered and used to measure DRUJ cartilage contact mechanics. The effects of forearm movement method and rotation angle on centroid coordinate data and DRUJ contact area were examined. The DRUJ contact area was maximal at 10° supination. There was more contact area in supination than pronation for both active and passive forearm rotation. The contact centroid moved volarly with supination, with magnitudes of 10.5 ± 2.6 mm volar for simulated active motion and 8.5 ± 2.6 mm volar for passive motion. Along the proximal-distal axis, the contact centroid moved 5.7 ± 2.4 mm proximal during simulated active motion. These findings were statistically significant. The contact centroid moved 0.2 ± 3.1 mm distal during passive motion (not significant). It is possible to examine cartilage contact mechanics of the DRUJ nondestructively while undergoing simulated, continuous active and passive forearm rotation. The contact centroid moved volarly and proximally with supination. There were higher contact area values in supination compared with pronation, with a peak value at 10° supination. This study documented normal DRUJ arthrokinematics using a nondestructive in vitro approach. It further reinforced the established biomechanical and clinical literature on contact patterns at the native DRUJ during forearm rotation.


Ultra-long-term outcome of surgically treated far-lateral, extraforaminal lumbar disc herniations: a single-center series.
Far-lateral extraforaminal lumbar disc herniation is an uncommon cause of nerve root entrapment, and studies addressing the long-term outcome of surgically treated patients are few. The purpose of this study was to analyze the ultra-long-term outcome of patients who were treated via a lateral approach. The medical reports of 138 consecutive patients were analyzed with regard to signs and symptoms, operative findings, complications, and short-term outcome (6 weeks). To assess long-term results, standardized telephone interviews were performed using a structured questionnaire. The patients were questioned about pain using the verbal rating scale and persisting symptoms, if any. Other queries were related to the Oswestry Disability Index. Subjective satisfaction with the result of surgery was classified as excellent (no pain), good (some pain), fair (moderate pain), and poor (unchanged or worse) based on MacNab classification. At short-term follow-up, major and moderate leg pain had decreased from 99.3 to 5.1% and low back pain from 97.8 to 2.8%. Sensory and motor deficits, however, were still present in the majority of patients. A total of 87 telephone interviews were conducted, and the mean follow-up was 146 months. As many as 49 patients (56.3%) reported complete relief of symptoms, 14 patients (16.1%) had minor ailments under physical stress, and 24 patients (27.6%) had permanent residual symptoms. The most common complaint was remaining sensory disturbance. Despite residual symptoms, the vast majority of patients expressed satisfaction with the result of surgery. The outcome was subjectively rated as follows: 75.9% excellent (66 patients), 18.4% good (16 patients), 4.6% fair (4 patients), and 1.1% poor (1 patient). The lateral approach is a minimally invasive and safe procedure with low complication rates. The profit from surgery is maintained beyond the usual postoperative observation periods. Thus, ultimate outcome at ultra-long-term follow-up is very gratifying in the vast majority of patients.


Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II.
In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn4CaO5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn4CaO5-cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn4CaO5-cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn4CaO5-cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.


Anti-inflammatory glycosylated flavonoids as therapeutic agents for treatment of diabetes-impaired wounds.
Diabetes is a chronic disease that affects more than 387 million people worldwide. About 20% of patients diagnosed with diabetes develop diabetic foot ulcerations (DFU). Standard treatment of DFU includes wound debridement, infection control, revascularization and, in general, the acceleration of the healing process. Topical ointments containing flavonoids exert beneficial effects in wound healing process. Flavonoids increase the migration and proliferation of fibroblasts and collagen synthesis. Furthermore, most flavonoids exert antibacterial and astringent activities that help in infection control. Additionally, flavonoids possess antioxidant and anti-inflammatory activities reducing the reactive oxygen species and modulating the inflammatory pathways, respectively. Bioactivity of flavonoids can vary according to source, chemical structure and glycosylation pattern. In summary, topical application of flavonoids reduces epithelialization and wound closure time of DFU in diabetic patients.


A history of opioid abuse: Why buprenorphine is superior for the management of opioid use disorder and pain.
Opioid abuse represents a public health crisis that has significant associated morbidity and mortality. Since beginning in the early 1990's, the opioid abuse epidemic has been difficult to control due to regulatory, economic, and psychosocial factors that have perpetuated its existence. This era of opioid abuse has been punctuated by three distinct rises in mortality, precipitated by unique public health problems that needed to be addressed. Patients affected by opioid abuse have been historically treated with either methadone or naltrexone. While these agents have clinical utility supported by robust literature, we the authors posit that buprenorphine is a superior therapy for both opioid use disorder (OUD) as well as pain. This primacy is due to the pharmacological properties of buprenorphine which render it unique among other opioid medications. One such property is buprenorphine's ceiling effect of respiratory depression, a common side effect and complicating factor in the administration of many classical opioid medications. This profile renders buprenorphine safer, while simultaneously retaining therapeutic utility in the medical practitioner's pharmacopeia for the treatment of opioid use disorder and pain.


The Tetraodon nigroviridis reference transcriptome: developmental transition, length retention and microsynteny of long non-coding RNAs in a compact vertebrate genome.
Pufferfish such as fugu and tetraodon carry the smallest genomes among all vertebrates and are ideal for studying genome evolution. However, comparative genomics using these species is hindered by the poor annotation of their genomes. We performed RNA sequencing during key stages of maternal to zygotic transition of Tetraodon nigroviridis and report its first developmental transcriptome. We assembled 61,033 transcripts (23,837 loci) representing 80% of the annotated gene models and 3816 novel coding transcripts from 2667 loci. We demonstrate the similarities of gene expression profiles between pufferfish and zebrafish during maternal to zygotic transition and annotated 1120 long non-coding RNAs (lncRNAs) many of which differentially expressed during development. The promoters for 60% of the assembled transcripts result validated by CAGE-seq. Despite the extreme compaction of the tetraodon genome and the dramatic loss of transposons, the length of lncRNA exons remain comparable to that of other vertebrates and a small set of lncRNAs appears enriched for transposable elements suggesting a selective pressure acting on lncRNAs length and composition. Finally, a set of lncRNAs are microsyntenic between teleost and vertebrates, which indicates potential regulatory interactions between lncRNAs and their flanking coding genes. Our work provides a fundamental molecular resource for vertebrate comparative genomics and embryogenesis studies.


Association of Fabry Disease with Hearing Loss, Tinnitus, and Sudden Hearing Loss: A Nationwide Population-Based Study.
Hearing loss and the related otologic manifestations are receiving increased scrutiny as significant causes of morbidity in Fabry disease. However, the relative risks of auditory deficits among patients with Fabry disease relative to the general population without a diagnosis of Fabry disease have not been studied. This study aims to explore the associations between Fabry disease and hearing-related manifestations using a nationwide population-based dataset. We identified study patients for this cross-sectional study from the 2015−2017 claims databases of the Taiwan Longitudinal Health Insurance Database 2005. We first identified 2312 patients aged over 20 years with a diagnosis of Fabry disease. We used propensity score matching to select five comparison patients per patient with Fabry disease and 11,560 comparison patients without Fabry disease. We used multivariable logistic regressions to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for tinnitus, hearing loss, and sudden deafness among Fabry disease patients vs. comparison patients. Chi-square tests showed statistically significant differences between patients with and without Fabry disease in the prevalence rates of tinnitus (16.7% vs. 11.7%, p < 0.001), hearing loss (7.5% vs. 6.2%, p = 0.014) and sudden deafness (1.7% vs. 1.0%, p = 0.005). Multiple logistic regression revealed that patients with Fabry disease were more likely to suffer from tinnitus, hearing loss and sudden deafness, with adjusted odds ratios of 1.513 (95% CI = 1.336−1.713), 1.246 (95% CI = 1.047−1.483), and 1.681 (95% CI = 1.166−2.423), respectively. We found that Fabry disease is significantly associated with certain auditory manifestations, including hearing loss, sudden deafness, and tinnitus.


Lateral humeral condyle fractures in children: a comparison of two approaches to treatment.
The treatment of lateral condyle fractures in children remains controversial. This study investigates whether minimally displaced lateral condyle fractures should be treated surgically and compares different techniques of operative management. The authors retrospectively reviewed medical charts and radiographs of 97 children from two international centers whose therapeutic modalities differed, noting demographic data, fracture features, treatment modalities, complications, and clinical and radiographic results. Long-arm immobilization alone resulted in additional fracture displacement and a higher number of nonunions than did surgical management. The authors conclude that displaced fractures should be fixed surgically with two smooth or threaded Kirschner wires; they can pass through the ossific nucleus of the capitellum if necessary, but they must engage the far cortex. If patients are likely to be noncompliant with treatment, the wires should be buried under the skin to avoid the risk of infection, but this procedure necessitates a second surgery for removal of fixation.


Genetic analysis of petite mutants of Saccharomyces cerevisiae: transmissional types.
We have studied a number of petite [rho-] mutants of Saccharomyces cerevisiae induced in a wild-type strain of mitochondrial genotype [ome- CHL(R) ERY(S) OLI(S) (1, 2, 3) PAR(S)] by Berenil and ethidium bromide, all of which have retained two mitochondrial genetic markers, [CHL(R)] and [ERY(S)], but have lost all other known markers. Though stable in their ability to retain these markers in their genome, these mutants vary widely among themselves in suppressiveness and in the extent to which the markers are transmitted on crossing to a common wild-type tested strain. In appropriate crosses all of the strains examined in this study demonstrate mitochondrial polarity, and thus have also retained the [ome-] locus in a functional form; however, five different transmissional types were obtained, several of them quite unusual, particularly among the strains originally induced by Berenil. One of the most interesting types is the one that appears to reverse the parental genotypes with [CHL(R) ERY(S)] predominating over [CHL(S) ERY(R)] in the diploid [rho+] progeny, rather than the reverse, which is characteristic of analogous crosses with [rho+] or other petites. Mutants in this class also exhibited low or no suppressiveness. Since all of the petites reported here are derived from the same wild-type parent, and so have the same nuclear background, we have interpreted the transmissional differences as being due to different intramolecular arrangements of largely common retained sequences.


A multidimensional study of personality traits ad modum Sjöbring.
Three groups of epileptic out-patients (juvenile myoclonic epilepsy, psychomotor epilepsy, and cryptogenic grand mal) were studied. The groups were matched as closely as possible with each other with regard to sex, age, and treatment. Out-patients suffering from Menière's disease served as a control group; these patients were treated with placebo and matched with the epilepsy groups with regard to sex, duration of disease and social level. The Marke-Nyman inventory was used as a quantitative assessment of personality traits. This inventory is an operative definition of Sjöbring's neurophysiological model of personality, including the three dimensions: validity, stability and solidity. Our results showed that epileptic patients irrespective of the type of seizures were substable. Low validity was found in patients with juvenile myoclonic epilepsy and in patients with psychomotor epilepsy with temporal EEG focus. In those latter epilepsy groups a tendency to subsolidity was also observed. In Sjöbring's frame of reference these substable patients of low validity have a psychological vulnerability since they are unable to overcome the small concrete adversities of life. They adhere to problems, and being unable to solve them they tend to react in a mood of discontent or of maladjustment. In the usual psychiatric frame of reference substable patients of low validity are classified as psychoastenic patients with emotional instability.


The diagnostic value of H-index in S1 root compression.
The H-index was studied in 42 healthy subjects and in 20 patients showing unilateral S1 root compression. When compared to the normal subjects, all patients showed a decreased H-index, or an increased difference in H-index between the sides or both. These results indicate that both parameters are valuable in the diagnosis of S1 root impairment due to intervertebral disc protrusion.


Prognostic factors of poor surgical outcome after clitoral reconstruction in women with female genital mutilation/cutting.
Complications of surgical clitoral reconstruction for female genital mutilation/cutting (FGM/C) are a rare occurrence, but there has been reports of patients experiencing chronic pain or clitoral burial. This study aims to assess which factors are predictive of the occurrence of surgical complications in women who had surgical reconstruction for FGM/C (type 1, 2, or 3). This monocentric retrospective study was conducted among patients who underwent clitoral reconstruction after FGM/C from January 2016 to March 2020. Demographic and clinical data were abstracted from the medical records. The primary outcome was the occurrence of chronic pain (defined as occurrence or persistence of any clitoral pain >3 months after surgery), and the secondary outcome was the occurrence of clitoral burial. A total of 87 women were included in the analysis. Univariate analysis indicated significantly higher rates of a history of physical abuse in the group of women who experienced chronic pain after surgery (4 [100%] vs 2 [37.1%], P = .049). Patients with clitoral burial were significantly younger than the rest of the sample in univariate analysis (median [IQR], 29.6 years [24.6-30.2] vs 33.8 [28.2-37.9]; P = .049). Surgical treatment of women who underwent FGM/C should include the entire history of the patient and especially a record of experiencing physical abuse. The study stands out for its originality, the extensive sample size gathered over nearly 4 years, the surgical clitoral reconstructions conducted by an experienced surgeon, and the minimal amount of missing data. However, because the occurrence of these complications was rare, the number of patients in the subgroups was extremely low, preventing a valid multivariate analysis to be conducted. The study suggests that women with a history of physical abuse could be at greater risk for chronic pain after surgery and that younger women tend to experience more clitoral burial.


[Introduction to the study of peroxisomal disorders].
The peroxisome is an organelle found in all nucleated cells of mammalian. Its name is due to H2O2 formation as result of cell respiration catalyzed by oxidases and catalases and play and important role on myelination and neuronal migration. Peroxisomes are formed by assembling of membrane proteins (structural, receptors and transporters) into peroxisomal membrane. Peroxisomal proteins are encoded by nuclear genes, synthesized on cytosol ribosomes and imported into peroxisomal matrix, mediated by receptors and transporters membrane proteins. There are two main categories of peroxisomal disorders: disorder of peroxisome biogenesis exemplified by Zellweger syndrome, where multiple peroxisomal protein, functions are deficient and disorders which involves a single peroxisomal protein, exemplified by X-adrenoleukodystrophy, where the organelle is apparently intact.


Are genetic tests informative in predicting food allergy?
Food allergy is common among children and adults worldwide. Recent studies have improved our understanding of the genetic mechanism of food allergy and further studies may result in clinical application through genetic testing. Genetic factors are important in the development of food allergy. An increasing number of genes have been associated with food allergy in recent years. These include mutations and genetic variants in the filaggrin gene, the association of human leukocyte antigen DR and DQ regions with food allergy, copy number variation impacting CTNNA3 and RBFOX1, DNA methylation that partially mediates single nucleotide polymorphism association at the HLA-DR and DQ loci, as well as other genes. Several studies have implicated differences in gut microbiota composition in food allergy. With the advance of high-throughput genotyping and sequencing techniques together with improved analytical methods, the contributions of genetic and environmental factors in development of food allergy are being clarified. Yet much remains to be explored and more studies with larger sample sizes, better phenotyping, and improved quality control genomics methods are needed. The ultimate goal is the development of a panel of reliable markers for genetic testing in food allergy to improve overall patient care.


Hemispheric processing of landmark and geometric information in male and female domestic chicks (Gallus gallus).
A place learning paradigm was used to assess lateralisation and sex differences in domestic chicks dealing with global (geometric shape) and local (identity of a beacon) aspects of spatial encoding. Male and female domestic chicks were trained binocularly to localise food buried under sawdust in the centre of a square-shaped enclosure. They were then tested binocularly and monocularly (Experiment 1). Training in the same task was also carried out in the presence of a centrally placed visual beacon, so that chicks could then be tested in a number of transformed versions of the training arrangement: after removing the beacon (Experiment 2), after shifting the beacon to a corner (Experiment 3) and after simultaneously shifting the beacon to a corner and replacing it with a second, visually different, beacon (Experiment 4). Results show that the right hemisphere prevalently attends to the geometry of the environment in both male and female chicks. Males rely upon local information (beacon) more than females, also showing stronger encoding of this information in their left hemisphere than their right hemisphere.


Chronic myelogenous leukemia.
Chronic myelogenous leukemia involves clonal expansion of hematopoietic progenitor cells associated with the characteristic translocation between chromosomes 9 and 22, resulting in the generation of an aberrant bcr-abl protein with enhanced tyrosine kinase activity. The bcr-abl protein can induce cell proliferation, induce transformation of immature hematopoietic cells, and suppress apoptosis in vitro. Abnormalities of stromal cell and progenitor cell interaction may be central to the pathogenesis of the abnormal hematopoiesis in chronic myelogenous leukemia. Therapy with interferon alpha in chronic-phase chronic myelogenous leukemia can result in hematologic responses in up to 70% to 80% of patients and partial or complete cytogenetic responses in up to 50%; many studies show a significant overall survival advantage for patients treated with interferon. Allogeneic marrow transplantation can result in long-term survival for patients with chronic myelogenous leukemia, particularly younger patients undergoing transplantation early in the course of disease, and unrelated donor or autologous marrow transplantation may be an option for patients without a matched sibling donor. Future therapy will likely involve selection and expansion ex vivo of Ph- stem cells for reinfusion as part of a strategy for autologous marrow transplantation. Other areas of current investigation include in vitro assessment of the activity of antisense oligonucleotides and of the immunologic responses to chronic myelogenous leukemia cells.


[About the need of restructuration of medical care of older than able-bodied population].
The article deals with the results of study of factual volumes of medical care according its main services provided to total population and to people older than able-bodied population in Nizhny Novgorod oblast. The study demonstrated that during last ten years, the character of organization and application of main volumes of medical care to people older than able-bodied population factually had no changes and does not correspond to the planned volumes of territorial program of public guarantees of free medical care. The increase of volume of emergency medical care in functioning of ambulance and emergency care service shortens possibilities of emergency medical care support and promote misallocation of financial resources. The level of medical care support of people older than able-bodied population in day-and-night hospitals is high at the same time it is lower in nursing departments and out-patient clinics. To provide the accessibility and quality of medical services to people older than able-bodied population the restructuration of medical care is needed to increase the volume of hospital-substituting types of medical care and to organize the service of specialized palliative care primarily for oncological patients.


STAM Prolongs Clear Cell Renal Cell Carcinoma Patients' Survival via Inhibiting Cell Growth and Invasion.
Background: Signal transducing adaptor molecule 1 (STAM1) was considered to mediate cell growth and be involved in multiple signaling pathways; however, no research on the role of STAM1 in any tumors has been published yet. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function. Methods: Data from The Cancer Genome Atlas (TCGA) in December 2019 were used to examine the role of STAM1 in indicating ccRCC patients' survival. A purchased tissue microarray (TM) and fresh ccRCC renal tissues were used for further validation. Then, STAM1 was overexpressed in human ccRCC cell lines for in vitro assays. Finally, bioinformatics was performed for STAM1 protein-protein interaction (PPI) network construction and functional analyses. Results: A total of 539 ccRCC and 72 control samples were included for the TCGA cohort, and 149 ccRCC and 29 control slices were included for the TM cohort. In the TCGA and TM cohorts, we found that STAM1 expression was lower in ccRCC compared with normal adjacent non-cancerous renal tissues (P < 0.0001 for both cohorts). STAM1 downregulation was also related to significantly shorter overall survival (OS) (P < 0.0001 for both cohorts). In the TCGA cohort, reduced STAM1 expression was also associated with aggressive features of the tumor. Under multivariate analyses, STAM1 was demonstrated to be an independent prognostic factor for ccRCC survival in both TCGA (HR = 0.52, 95% CI: 0.33-0.84, P = 0.007) and TM cohorts (HR = 0.12, 95% CI: 0.04-0.32, P < 0.001). Our in vitro experiments showed that STAM1 inhibited cell viability, invasion, and migration in ccRCC cell lines. In PPI network, 10 candidate genes categorized into five biological processes were found to be closely related to STAM1. Conclusion: STAM1 is a promising prognostic biomarker for predicting ccRCC survival outcomes. Preliminary pathogenesis is demonstrated by our in vitro experiments. Further pathological mechanisms of STAM1 in modulating ccRCC require comprehensive laboratory and clinical studies.


Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield: Results from a nationwide prospective cohort.
Approximately 5% of patients with colorectal cancer (CRC) have a Mendelian predisposition for the disease. Identification of the disease-causing genetic variant enables carrier testing and tailored cancer prevention within affected families. To determine the panorama and genetic variation of Mendelian CRC syndromes among referrals at the cancer genetics clinics in Sweden, 850 patients clinically selected for CRC genetic investigation were included in a prospective study that tested for all major hereditary polyposis and nonpolyposis CRC conditions. Genetically defined syndromes were diagnosed in 11% of the patients. Lynch syndrome was predominant (n = 73) followed by familial adenomatous polyposis (n = 12) and MUTYH-associated polyposis (n = 8); the latter of which two patients presented with CRC before polyposis was evident. One patient with a history of adolescent-onset CRC and polyposis had biallelic disease-causing variants diagnostic for constitutional mismatch repair deficiency syndrome. Post-study review of detected variants of unknown clinical significance (n = 129) resulted in the reclassification of variants as likely benign (n = 59) or as diagnostic for Lynch syndrome (n = 2). Our results reveal the panorama of Mendelian CRC syndromes at the cancer genetics clinics in Sweden and show that unified testing for polyposis and nonpolyposis CRC conditions as well as regular reexamination of sequence data improve the diagnostic yield.


Alcohol and mortality: Global alcohol-attributable deaths from cancer, liver cirrhosis, and injury in 2010.
Alcohol consumption has long been recognized as a risk factor for mortality. By combining data on alcohol per capita consumption, alcohol-drinking status and alcohol-drinking patterns, risk relationships, and mortality, the Comparative Risk Assessment Study estimated alcohol-attributable mortality for 1990 and 2010. Alcohol-attributable cancer, liver cirrhosis, and injury were responsible for the majority of the burden of alcohol-attributable mortality in 1990 and 2010. In 2010, alcohol-attributable cancer, liver cirrhosis, and injury caused 1,500,000 deaths (319,500 deaths among women and 1,180,500 deaths among men) and 51,898,400 potential years of life lost (PYLL) (9,214,300 PYLL among women and 42,684,100 PYLL among men). This represents 2.8 percent (1.3 percent for women and 4.1 percent for men) of all deaths and 3.0 percent (1.3 percent for women and 4.3 percent for men) of all PYLL in 2010. The absolute mortality burden of alcohol-attributable cancer, liver cirrhosis, and injury increased from 1990 to 2010 for both genders. In addition, the rates of deaths and PYLL per 100,000 people from alcohol-attributable cancer, liver cirrhosis, and injury increased from 1990 to 2010 (with the exception of liver cirrhosis rates for women). Results of this paper indicate that alcohol is a significant and increasing risk factor for the global burden of mortality.


The effects of psychotherapies: a study on patients' perception of results in an Italian public setting.
Enquiries centred on the perspective of users of psychiatric treatments and their families, has become an increasingly widespread method to improve the quality of treatments administered by health services. In this study, in particular, we examine the users' perception of the quality and variability of the effects of psychotherapies, the difficulties met, and the perceived help factors. The sample consists of 216 users of psychotherapy and 223 patients in psychiatric treatment with psychological support. They are outpatients, managed by the public health service. The questionnaires included closed ended, open-ended questions and scales that were previously tested on a sample of patients. The questionnaire for patients was anonymous and administered by researchers external to the medical staff. Irrespective of the diagnosis or of a concurrent pharmacological therapy, a high percentage of patients (75%), in both groups, feel improved. Improvement consist of the decrease of symptoms, a sense of feeling better, but also feeling grown up, more mature, having higher self-esteem and feeling more adequate in interpersonal relationships. This last type of result is significantly more frequent in the group of patients in psychotherapy. Besides these patients are faced with more difficulties and play more active a role while they are in treatment. The main difference between patients in psychotherapy and those in psychiatric management with psychological support is not indeed the identification of different perceived therapeutic factors, but rather the different evaluation of their relative importance. On the whole, the study seems to show that the effects of real psychotherapies include, beside an improvement of symptoms, the achievement of goals of personal growth and maturity, self-satisfaction and an increase in self-esteem, all in accordance with a conception of health as well-being and self-satisfaction rather than as absence of illness.


Do Patients Failing Return-to-Activity Criteria at 6 Months After Anterior Cruciate Ligament Reconstruction Continue Demonstrating Deficits at 2 Years?
The variability in outcomes after anterior cruciate ligament reconstruction (ACLR) might be related to the criteria that are used to determine athletes' readiness to return to their preinjury activity level. A battery of return-to-activity criteria (RTAC) that emphasize normal knee function and movement symmetry has been instituted to quantitatively determine athletes' readiness to return to preinjury activities. To investigate performance-based and patient-reported measures at 12 and 24 months after ACLR between patients who passed or failed RTAC at 6 months after ACLR. Cohort study; Level of evidence, 2. A total of 108 patients who had participated in International Knee Documentation Committee level 1 or 2 sports activities completed RTAC testing at 6, 12, and 24 months after surgery. The RTAC included the isometric quadriceps strength index (QI), 4 single-legged hop tests, the Knee Outcome Survey-activities of daily living subscale (KOS-ADLS), and the global rating scale of perceived function (GRS). Patients who scored ≥90% on all RTAC were classified as the pass group, and those who scored <90% on any RTAC were classified as the fail group. At 12- and 24-month follow-ups, patients were asked if they had returned to the same preinjury activity level. At the 6-month follow-up, there were 48 patients in the pass group and 47 in the fail group. At the 12-month follow-up, 31 patients (73.8%) from the pass group and 15 patients (39.5%) from the fail group passed RTAC, and at the 24-month follow-up, 25 patients (75.8%) from the pass group and 14 patients (51.9%) from the fail group passed RTAC. The rate of return to activities in the pass group was 81% and 84% at 12 and 24 months after ACLR, respectively, compared with only 44% and 46% in the fail group ( P ≤ .012), respectively; however, some patients in the fail group participated in preinjury activities without being cleared by their therapists. At 12 and 24 months, 60.5% and 48.1% of patients continued to fail again on the criteria, respectively. A statistically significant group × time interaction was found for the single hop and 6-m timed hop limb symmetry indices (LSIs) ( P ≤ .037), with only the fail group demonstrating a significant improvement over time. A main effect of group was detected for the QI and the crossover hop and triple hop LSIs ( P < .01), with patients in the pass group demonstrating higher performance. A main effect of time was detected for the crossover hop and triple hop LSIs and the GRS, with improvements seen in both groups ( P < .05). Patients who passed the RTAC early after ACLR were more likely to demonstrate normal knee function and movement symmetry at 12 and 24 months postoperatively, while patients who failed the RTAC early were more likely to demonstrate impaired knee function and movement asymmetry at 12- and 24-month follow-ups. Patients in the pass group had a higher rate of return to their preinjury activity level compared with those in the fail group. A group of patients chose to return to their preinjury activities, even though they were functionally not ready.


Nucleocytoplasmic export of type D simian retrovirus genomic RNA: identification of important genetic subregions and interacting cellular proteins.
The simian retrovirus (SRV) genome contains a constitutive transport element (CTE) within its 3' intergenic region (IR) that mediates the nuclear export of unspliced SRV RNA. The serogroup 2 SRV CTE is predicted to form a stable stem-loop structure containing two major internal loops exhibiting 180 degrees inverse symmetry, with loop face sequences A, A', B, and B' and additional minor internal and terminal loops. To begin the identification of potential CTE-interacting proteins and to assess structural requirements for protein interaction, we conducted RNA mobility shift assays using IR fragments that obliterated this region's known stable stem-loop structure. Using immunoblotting assays, we have determined that RNA helicase A, implicated in the nuclear export of unspliced SRV genomic RNA, does not appear to interact directly with either the complete serogroup 2 SRV 3' IR or the subregion RNAs and that formation of RNA-protein complexes is conferred by interaction with other novel proteins. UV crosslinking of RNA-protein complexes, coupled with RNase T1/A digestion, indicates that a novel protein of 120 kDa molecular weight interacts with the complete CTE or with individual subregion RNAs. Transfection analyses indicate that SRV recombinants containing A, A', B, or B' sequences forming the faces for two open loops undergo RNA export; only the complete sense CTE recombinant or a second recombinant containing two subregions in sense orientation that reconstitute the 3' two-thirds of the 3' IR, and contain only A' and B that form the faces for two terminal loops, are capable of SRV RNA export. These experiments indicate that secondary structural determinants of the 3' IR and multiple protein interactions may be important factors in the nuclear export of unspliced SRV RNA.


Diving Deep into the Data: A Review of Deep Learning Approaches and Potential Applications in Foodomics.
Deep learning is a trending field in bioinformatics; so far, mostly known for image processing and speech recognition, but it also shows promising possibilities for data processing in food analysis, especially, foodomics. Thus, more and more deep learning approaches are used. This review presents an introduction into deep learning in the context of metabolomics and proteomics, focusing on the prediction of shelf-life, food authenticity, and food quality. Apart from the direct food-related applications, this review summarizes deep learning for peptide sequencing and its context to food analysis. The review's focus further lays on MS (mass spectrometry)-based approaches. As a result of the constant development and improvement of analytical devices, as well as more complex holistic research questions, especially with the diverse and complex matrix food, there is a need for more effective methods for data processing. Deep learning might offer meeting this need and gives prospect to deal with the vast amount and complexity of data.


Regulation of haemopoiesis in long-term bone marrow cultures. IV. Glycosaminoglycan synthesis and the stimulation of haemopoiesis by beta-D-xylosides.
Sulfated glycosaminoglycans (GAGs) are distributed in consistent and distinctive patterns between the cell surface and the growth medium of haemopoietically active long-term bone marrow cultures. Heparan sulfate is the main cell surface component and chondroitin sulfate is the major sulfated species in the medium. When the cultures are supplemented with beta-D-xylosides a significant increase in chondroitin sulfate synthesis is observed but no stimulation of heparan sulfate synthesis occurs. The chondroitin sulfate accumulates in the culture medium in beta-D-xyloside-treated cultures but the composition of sulfated GAGs in cell-surface derived material is unaffected. beta-D-xylosides also stimulate the production of haemopoietic cells without any apparent alteration in the adherent stromal cells of the marrow cultures. Equivalent increases are obtained in cells at all stages of development so that a fivefold increase in pluripotent stem cells (CFU-S) is matched by fivefold increase in the granulocyte-macrophage progenitors (GM-CFC) and in mature granulocytes. The stimulation persists for many weeks in beta-D-xyloside-treated cultures. These results indicate that the sulfated GAGs may play an important role in the regulation of haemopoiesis.


Soft sensors for a sensing-actuation system with high bladder voiding efficiency.
Sensing-actuation systems can assist a bladder with lost sensation and weak muscle control. Here, we advance the relevant technology by integrating a soft and thin capacitive sensor with a shape memory alloy-based actuator to achieve a high-performance closed-loop configuration. In our design, sensors capable of continuous bladder volume detection and actuators with strong emptying force have been used. This integration has previously hindered performance due to large bladder volume changes. Our solution integrates sensing-actuation elements that are bladder compatible but do not interfere with one another, achieving real-time bladder management. The system attains a highly desirable voiding target of 71 to 100% of a rat's bladder with a volume sensitivity of 0.7 μF/liter. Our system represents an efficient voiding solution that avoids overfilling and represents a technological solution to bladder impairment treatment, serving as a model for similar soft sensor-actuator integration with other organs.


Corrosion and ion transfer from porous metallic alloys to tissues.
Investigations on porous and nonporous alloys currently available for surgical implant device stabilization through tissue ingrowth have shown microstructures that are characteristic of the thermal processing history of the device and alloy with differences between the nonporous and porous devices of the same nominal chemical analysis, in vitro corrosion potentials that are similar for porous and nonporous alloys and corrosion rates that are approximately proportional to the increases in relative surface areas (X 2 to X 10); local tissue interactions at the cellular level that are specific to the type and amount of elemental constituents present at the interface; and no direct correlations between the local cellular responses (fibroblasts) and the potential for hypersensitivity and other systemically mediated responses. Evaluations of the available published literature and available information on device retrievals and analyses support the opinion that no quantitative, statistically based epidemiologic studies have yet established significant correlations between selected metallic ions and major types of tissue lesions. However, with the changes in surface area and basic surface chemistry for existing alloy systems, research on the long-term tissue responses should be emphasized. In our opinion, biomaterial surface modifications are possible, whereby the relative quantities of released ions available to the environment could be significantly reduced.


Poor oral health and coronary heart disease.
A few recent studies have shown associations between poor oral health and coronary heart disease (CHD). The objective of this study was to examine the incidence of CHD in relation to number of teeth present and periodontal disease, and to explore potential mediators of this association, in a prospective cohort study. This study is a part of the ongoing Health Professionals Follow-Up Study (HPFS). Participants included a US national sample of 44,119 male health professionals (58% of whom were dentists), from 40 to 75 years of age, who reported no diagnosed CHD, cancer, or diabetes at baseline. We recorded 757 incident cases of CHD, including fatal and non-fatal myocardial infarction and sudden death, in six years of follow-up. Among men who reported pre-existing periodontal disease, those with 10 or fewer teeth were at increased risk of CHD compared with men with 25 or more teeth (relative risk = 1.67; 95% confidence interval, 1.03 to 2.71), after adjustment for standard CHD risk factors. Among men without pre-existing periodontal disease, no relationship was found (relative risk = 1.11; 95% confidence interval, 0.74 to 1.68). The associations were only slightly attenuated after we controlled for dietary factors. No overall associations were found between periodontal disease and coronary heart disease. Tooth loss may be associated with increased risk of CHD, primarily among those with a positive periodontal disease history; diet was only a small mediator of this association.


Effect of oral glucocorticoid treatment on serum inflammatory markers in acute asthma.
Acute asthma is associated with elevated serum concentrations of products of activated T cells and eosinophils. To compare the changes in concentrations of these products with disease severity and changes in lung function following oral prednisolone treatment. Twenty patients (mean age 8.7 years) were recruited on admission with acute asthma to a district general hospital. Disease severity was recorded before and after treatment with oral prednisolone using a validated pulmonary index score. Serum concentrations of interleukin (IL)-4, IL-5, soluble (s)CD25 (soluble IL-2 receptor), using a specific enzyme linked immunosorbent assay, and eosinophil cationic protein (ECP), using radioimmunoassay, were measured concomitantly. Non-asthmatic children (n = 6, mean age 9.2 years) undergoing elective surgery were recruited as controls, and serum samples were obtained on one occasion without treatment. Main outcome measures were changes in serum concentrations of cytokines and ECP, clinical asthma severity score, and peak expiratory flow rate. As expected, oral glucocorticoid treatment in the children with asthma was associated with clinical improvement and also with significant reductions in serum concentrations of IL-5 (mean 5.59 to 2.19 pg/ml, p = 0.0001), sCD25 (mean 2236 to 1772 pg/ml, p = 0.002), and ECP (mean 54.3 to 33. 1 pg/ml, p = 0.0001). Serum IL-4 concentrations, in most patients and all the controls, remained below the sensitivity of the assay. However, serum concentrations of IL-5, sCD25, and ECP remained significantly higher than in controls, even after treatment with oral glucocorticoids (p = 0.03). These data suggest that T cell mediated inflammation may persist in childhood asthma despite apparent clinical remission associated with conventional doses of prednisolone. The long term consequences of persistent inflammation after an apparently treated acute attack of asthma require clarification. Clinical assessment and pulmonary function are inadequate surrogates for airway inflammation.