Use of the melolabial flap in intraoral reconstruction.
Functional reconstruction of the oral cavity after tumor ablation is challenging. A variety of methods are available for reconstruction including primary closure, skin grafts, local cutaneous flaps, musculocutaneous flaps, and free flaps. Appropriate reconstruction addresses the size, location, and tissue needs of the defect. The melolabial flap allows for reliable and effective intraoral reconstruction with minimal donor morbidity, making it ideal for select defects. From 1989 to 1993 16 patients aged 51 to 81 years underwent reconstruction of intraoral defects with 24 melolabial flaps. Twenty-two flaps survived without complication and two flaps failed, for success rate of 91.7%. The two failed flaps occurred in the same patient. Of the remaining patients 8 had prior radiation therapy and 11 had prior or concomitant neck dissections. The flaps were used to reconstruct 13 floor-of-mouth, 1 buccal mucosa, 1 retromolar trigone, and 1 gingival defect. We conclude that the melolabial flap is ideal for select intraoral defects.


Current concepts review: septic arthritis of the knee pathophysiology, diagnostics, and therapy.
Treatments for bacterial arthritis of the knee joint are arthroscopic irrigation and debridement with systemic antibiotic medication. This article summarizes the relevant data of pathophysiology, stage of infection, symptoms, and diagnostics as well as stage-dependent treatment of bacterial arthritis of the knee joint. The major treatment principles are joint decompression, elimination of the causative organisms by intensive irrigation of the joint with elimination of proteolytic and lysosomal enzymes. Debridement of necrotic soft tissues with the aim of preserving the synovial membrane as an immune-competent structure, and a natural barrier, is recommended. Good results in treating knee infections have been achieved with arthroscopic joint revision and stage-dependent surgical therapy. The infection staging I-IV suggested by Gächter was used most commonly, which mainly reflects the pathophysiologic infection stages. For stages I-III, arthroscopic joint decompression with joint irrigation and debridement is effective and can be repeated in cases of persisting infection. The incidence of repeated arthroscopic joint irrigation depends on the initial stage of the infection and varies between 0 and 41% of the cases. For stage IV infections, the open revision is needed or in seldom cases of therapy failure under initial or repeated arthroscopic joint revision. The success rate of healing infections by arthroscopic irrigation was high with 90-100%.


Beyond journal publications - a new format for the publication of clinical trials.
Journal publications are the major route to communicate methods and results of clinical trials. However, the shortcomings of this format are well known, including insufficient quality of the information provided as well as publication and outcome reporting bias. Attempts to improve the situation via peer review, reporting guidelines or study registration did not solve the problem. Currently, new ways of data presentation in electronic databases, increased access to previously confidential documents, and the potential use of anonymized individual patient data from clinical trials beyond the individual trial, have led to discussions about new publication formats for clinical trials. The current paper describes the components required for full information on a clinical trial and discusses a new format to provide this information.


Hypervalent Iodine Compounds as Versatile Reagents for Extremely Efficient and Reversible Patterning of Graphene with Nanoscale Precision.
Rational patterning and tailoring of graphene relies on the disclosure of suitable reagents for structuring the target functionalities on the 2D-carbon network. Here, a series of hypervalent iodine compounds, namely, 1-chloro-1,2-benziodoxol-3(1H)-one, 1,3-dihydro-1-hydroxy-3,3-dimethyl-1,2-benziodoxole, and 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole is reported to be extremely efficient for a diversified graphene patterning. The decomposition of these compounds generates highly reactive Cl, OH, and CF3 radicals exclusively in the irradiated areas, which subsequently attach onto the graphene leading to locally controlled chlorination, hydroxylation, and trifluoromethylation, respectively. This is the first realization of a patterned hydroxylation of graphene, and the degrees of functionalization of the patterned chlorination and trifluoromethylation are both unprecedented. The usage of these mild reagents here is reasonably facile compared to the reported methods using hazardous Cl2 or ICl and allows for sophisticated pattern designs with nanoscale precision, promising for arbitrary nanomanipulation of graphene's properties like hydrophilicity and conductivity by the three distinct functionalities (Cl, OH, and CF3 ). Moreover, the attachment of functional entities to these highly functionalized graphene nanoarchitectures is fully reversible upon thermal annealing, enabling a full writing/storing/reading/erasing control over the chemical information stored within graphene. This work provides an exciting clue for target 2D functionalization and modulation of graphene by using suitable hypervalent iodine compounds.


Easy prognostic assessment of concomitant organ failure in critically ill patients undergoing mechanical ventilation.
Acute respiratory distress syndrome (ARDS) is a life-threatening disease. We evaluated the prognostic utility of Model for End-stage Liver Disease excluding INR (MELD-XI) score for predicting mortality in a cohort of critically ill patients on mechanical ventilation. In total, 11,091 mechanically ventilated patients were included in our post-hoc retrospective analysis, a subgroup of the VENTILA study (NCT02731898). Evaluation of associations with mortality was done by logistic and Cox regression analysis, an optimal cut-off was calculated using the Youden Index. We divided the cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12 score points). Peak-, plateau- and positive end-expiratory pressure were higher in patients with MELD-XI>12. Patients with MELD-XI>12 had higher driving pressures (14 ± 6 cmH2O versus 13 ± 6; p < 0.001). MELD-XI was associated with 28-day mortality after correction for relevant cofounders including SAPS II and ventilation pressures (HR 1.04 95%CI 1.03-1.05; p < 0.001. Patients with MELD-XI>12 evidenced both increased hospital (46% versus 27%; p < 0.001) and 28-day mortality (39% versus 22%). MELD-XI is independently associated with mortality and constitutes a useful and easily applicable tool for risk stratification in critically ill patients receiving mechanical ventilation. NCT02731898, registered 4 April 2016.


A new pericentric inv(8) in acute nonlymphocytic leukemia.
Chromosome studies were carried out on unstimulated bone marrow cells from a patient with a diagnosis of acute nonlymphocytic leukemia (FAB M6 ANLL). Cytogenetic analysis revealed a mosaic chromosome pattern 46,XX/46,XX,inv(8)(p21q24). This pericentric inversion has not been previously described in ANLL. Because, fragile sites, zinc finger gene loci, and the MYC protooncogene have been localized to band 8q24, a putative role for these sites and genes could be considered.


Analysis of Dendrobium huoshanense transcriptome unveils putative genes associated with active ingredients synthesis.
Dendrobium huoshanense C.Z. Tang et S.J. Cheng is a traditional Chinese herbal medicine with high medicinal value in China. Polysaccharides and alkaloids are its main active ingredients. To understand the difference of main active ingredients in different tissues, we determined the contents of polysaccharides and alkaloids in the roots, stems and leaves of D. huoshanense. In order to explore the reasons for the differences of active ingredients at the level of transcription, we selected roots, stems and leaves of D. huoshanenese for transcriptome sequencing and pathway mining. The contents of polysaccharides and alkaloids of D. huoshanense were determined and it was found that there were significant differences in different tissues. A total of 716,634,006 clean reads were obtained and 478,361 unigenes were assembled by the Illumina platform sequencing. We identified 1407 carbohydrate-active related unigenes against CAZy database including 447 glycosyltransferase genes (GTs), 818 glycoside hydrolases (GHs), 60 carbohydrate esterases (CEs), 62 carbohydrate-binding modules (CBMs), and 20 polysaccharide lyases (PLs). In the glycosyltransferases (GTs) family, 315 differential expression genes (DEGs) were identified. In total, 124 and 58 DEGs were associated with the biosynthesis of alkaloids in Dh_L vs. Dh_S and Dh_R vs. Dh_L, respectively. A total of 62 DEGs associated with the terpenoid pathway were identified between Dh_R and Dh_S. Five key enzyme genes involved in the terpenoids pathway were identified, and their expression patterns in different tissues was validated using quantitative real-time PCR. In summary, our study presents a transcriptome profile of D. huoshanense. These data contribute to our deeper relevant researches on active ingredients and provide useful insights into the molecular mechanisms regulating polysaccharides and alkaloids in Dendrobium.


Ultrasonic actuation of a fine-needle improves biopsy yield.
Despite the ubiquitous use over the past 150 years, the functions of the current medical needle are facilitated only by mechanical shear and cutting by the needle tip, i.e. the lancet. In this study, we demonstrate how nonlinear ultrasonics (NLU) extends the functionality of the medical needle far beyond its present capability. The NLU actions were found to be localized to the proximity of the needle tip, the SonoLancet, but the effects extend to several millimeters from the physical needle boundary. The observed nonlinear phenomena, transient cavitation, fluid streams, translation of micro- and nanoparticles and atomization, were quantitatively characterized. In the fine-needle biopsy application, the SonoLancet contributed to obtaining tissue cores with an increase in tissue yield by 3-6× in different tissue types compared to conventional needle biopsy technique using the same 21G needle. In conclusion, the SonoLancet could be of interest to several other medical applications, including drug or gene delivery, cell modulation, and minimally invasive surgical procedures.


Effect of statin treatment in obese selenium-supplemented mice lacking selenocysteine lyase.
People with obesity are often dyslipidemic and prescribed statins to prevent cardiovascular events. A common side effect of statin use is myopathy. This could potentially be caused by the reduction of selenoproteins that curb oxidative stress, in turn, affecting creatine metabolism. We determined if statins regulate hepatic and muscular selenoprotein expression, oxidative stress and creatine metabolism. Mice lacking selenocysteine lyase (Scly KO), a selenium-provider enzyme for selenoprotein synthesis, were fed a high-fat, Se-supplemented diet and treated with simvastatin. Statin improved creatine metabolism in females and oxidative responses in both sexes. Male Scly KO mice were heavier than females after statin treatment. Hepatic selenoproteins were unaffected by statin and genotype in females. Statin upregulated muscular Gpx1 in females but not males, while Scly loss downregulated muscular Gpx1 in males and Selenon in females. Osgin1 was reduced in statin-treated Scly KO males after AmpliSeq analysis. These results refine our understanding of the sex-dependent role of selenium in statin responses.


Association of -308 TNF-α promoter polymorphism with clinical aggressiveness in patients with head and neck squamous cell carcinoma.
Genetic polymorphisms in the promoter region of the tumour necrosis factor-α (TNF-α) gene are involved in the regulation of the expression levels of its cytokine. Besides, these polymorphisms have been associated with the clinical behaviour of cancer. We investigated the -308 promoter region polymorphisms of the TNF-α gene and its association with the clinicopathological factors of a head and neck squamous cell carcinoma (HNSCC) sample. Furthermore, we analysed the impact of all the variables on the overall survival of patients. A sample of HNSCC (n=89) was evaluated. Clinicopathological factors and overall survival data were gathered. The TNF-α gene was analysed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data analyses were performed by using bivariate and multivariate statistical tests. Significance was set at p<0.05. HNSCC subjects carrying the A allele (GA/AA) exhibited associations with poor performance status (OR=2.82, p=0.039), lesions located on posterior areas (OR=4.02, p=0.002), and large-size tumours (OR=2.91, p=0.015). Subjects carrying only AA genotype exhibited association with poor performance status (OR=6.667, p=0.007). A worse overall survival was noted in subjects with large tumours (OR=4.87, p=0.005) and locoregional metastatic disease (OR=2.50, p=0.018). Our data suggests that the presence of the A allele/AA haplotype in HNSCC individuals might contribute to the higher clinical aggressiveness of malignant disease.


Non-Equilibrium Polymerization of Cross-β Amyloid Peptides for Temporal Control of Electronic Properties.
Hydrophobic collapse plays crucial roles in protein functions, from accessing the complex three-dimensional structures of native enzymes to the dynamic polymerization of non-equilibrium microtubules. However, hydrophobic collapse can also lead to the thermodynamically downhill aggregation of aberrant proteins, which has interestingly led to the development of a unique class of soft nanomaterials. There remain critical gaps in the understanding of the mechanisms of how hydrophobic collapse can regulate such aggregation. Demonstrated herein is a methodology for non-equilibrium amyloid polymerization through mutations of the core sequence of Aβ peptides by a thermodynamically activated moiety. An out of equilibrium state is realized because of the negative feedback from the transiently formed cross-β amyloid networks. Such non-equilibrium amyloid nanostructures were utilized to access temporal control over its electronic properties.


Transcutaneous electrical stimulation in treatment of postoperative pain.
Transcutaneous electrical stimulation as a means of relieving acute pain was evaluated in 100 patients who underwent abdominal or thoracic operative procedures. Transcutaneous electrical stimulation proveded pain relief in 77 per cent of test patients as opposed to 17 per cent of control patients. Transcutaneous electrical stimulation is an effective method of treatment that has many advantages over analgesic drugs.


Characterization and properties of non-granular thermoplastic starch-Clay biocomposite films.
Biocomposite films were prepared using as raw materials non-granular normal maize starch plasticized with glycerol and Na-montmorillonite clay particles in various concentrations. The physicochemical properties of films were studied, and their structure and morphology were investigated using XRD analysis, Thermal analysis, Scanning Electron Microscopy combined with Element Microanalysis. The mechanical characteristics were investigated through tensile test. The results indicated that the presence of clay particles in the starch matrix reduced the water absorption rate of films in comparison to starch films containing glycerol but not clay particles. The biocomposite films exhibited enhanced tensile properties at low glycerol and high clay contents. Best results were obtained for films containing 20 wt% glycerol and 10-20 wt% clay content. It is suggested that the non-granular maize starch, is a suitable raw material for the preparation of biocomposite films with improved structural and mechanical characteristics in comparison to films prepared using granular starch.


Recurrent respiratory papillomatosis: A state-of-the-art review.
Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aero-digestive tract caused by human papillomavirus (HPV) infection, which affects children and young adults. The aim of this review is to describe the main etiological, epidemiological, clinical, diagnostic, and treatment aspects of RRP. Most infections in children occur at birth, during passage through the birth canals of contaminated mothers. In adults, HPV is transmitted sexually. Papillomas usually appear as exophytic nodules, primarily in the larynx, but occasionally involving the nasopharynx, tracheobronchial tree, and pulmonary parenchyma. The disease course is unpredictable, ranging from spontaneous remission to aggressive persistent or recurrent disease. Although it occurs rarely, RRP has the potential for malignant transformation to squamous cell carcinoma. Clinically, RRP usually presents with nonspecific symptoms of airway involvement, including chronic cough, hoarseness, wheezing, voice change, stridor, and chronic dyspnea. Helical computed tomography (CT) is highly accurate for the identification and characterization of focal or diffuse airway narrowing caused by nodular vegetant lesions. The typical CT pattern of lung papillomatosis consists of numerous multilobulated nodular lesions of various sizes, frequently cavitated, scattered throughout the lungs. Bronchoscopy is the most reliable method for the diagnosis of RRP; it enables direct visualization of lesions in the central airways and collection of biopsy samples for histopathological diagnosis, and is also useful for therapeutic planning. The definitive diagnosis of RRP is based on histopathological analysis. Currently, no definitive curative treatment for RRP is available; despite the availability of adjunctive treatments, surgery remains the mainstay of treatment.


Survival and Long-Term Outcomes of Children Who Survived after End-of-Life Decisions in a Neonatal Intensive Care Unit.
To investigate long-term outcomes of infants who survive despite life-and-death discussions with families and a decision to withdraw or withhold life-sustaining interventions (WWLST) in one neonatal intensive care unit. Medical records for neonatal intensive care unit admissions from 2012 to 2017 were reviewed for presence of WWLST discussions or decisions, as well as the 2-year outcome of all children who survived. WWLST discussions were prospectively recorded in a specific book; follow-up to age 2 years was determined by retrospective chart review. WWLST discussions occurred for 266 of 5251 infants (5%): 151 (57%) were born at term and 115 (43%) were born preterm. Among these discussions, 164 led to a WWLST decision (62%) and 130 were followed by the infant's death (79%). Of the 34 children (21%) surviving to discharge after WWLST decisions, 10 (29%) died before 2 years of age and 11 (32%) required frequent medical follow-up. Major functional limitations were common among survivors, but 8 were classified as functionally normal or with mild-to-moderate functional limitations. When a WWLST decision was made in our cohort, 21% of the infants survived to discharge. By 2 years of age, the majority of these infants had died or had major functional limitations. This highlights the uncertainty of WWLST decisions during neonatal intensive care and the importance of ensuring that parents are informed of all possibilities. Additional studies including longer-term follow-up and ascertaining the family's views will be important.


Smoking cessation intervention in parents of young children: a randomised controlled trial.
To examine whether telephone counselling based on the stages of change component of Transtheoretical model of behaviour change together with educational materials could help non-motivated smoking parents of young children to cease. Randomised controlled trial. Hong Kong Special Administrative Region, PR China. 952 smoker fathers and mothers of Chinese children aged 5 years. Participants were randomly allocated into two groups: the intervention group received printed self-help materials and three-session telephone-based smoking cessation counselling delivered by trained counsellors; the control group received printed self-help materials only. A structured questionnaire was used for data collection at baseline and at 1, 3 and 6 month follow up. The main outcome is 7 day point prevalence quit rate at 6 months (defined as not smoking during the 7 days preceding the 6 month follow up) determined by self reports. Other secondary outcomes were self reported 24 h point prevalence quit rate and self-reported continuous quit rate and bio-chemically validated quit rate at 6 months. A total of 952 smoker fathers and mothers were randomized to the intervention (n = 467) and control (n = 485) groups. Most were daily smokers (92.4%) and the mean number of cigarettes smoked per day was 14.5 (SD = 8.9). By using intention-to-treat analysis, the 7 day point prevalence quit rate at 6 month follow up was significantly greater in the intervention group (15.3%; 68/444) than the control group (7.4%; 34/459) (P < 0.001). The absolute risk reduction was 7.9% (95% confidence interval: 3.78% to 12.01%). The number needed to treat to get one additional smoker to quit was 13 (95% CI: 8-26). The crude odds ratio of quitting was 2.3(95% CI: 1.5-3.5). The adjusted odds ratio was 2.1 (95% CI: 1.4-3.4) (adjusted for age, number of years smoked, and alcohol dependency). Proactive telephone counselling is an effective aid to promote smoking cessation among parents of young children.


Late-onset peritoneal recurrence of advanced gastric cancer 20 years after primary resection.
Late onset of peritoneal recurrence of gastric cancer more than 10 years after surgery is extremely rare, and only three cases have been reported. We present the case of a 61-year-old man who was diagnosed finally with peritoneal recurrence of gastric cancer 20 years after primary curative resection. As a result of small-bowel obstruction caused by peritoneal recurrence, diverting ileostomy with partial ileal resection was performed. The resected specimen revealed tubular adenocarcinoma that resembled the primary gastric cancer. The clinical course after the second operation was unfavorable and systemic chemotherapy had no effect. He died at 62 years of age, 21 years and 7 months after initial gastrectomy. Immunohistochemical analysis using antibodies against proliferating cell nuclear antigen (PCNA), Ki-67, and p53 was performed to investigate the phenotype of primary and recurrence cancer. Protein expression of proliferation markers such as PCNA and Ki-67 was down-regulated, but p53 was overexpressed at the site of recurrence. These data suggest that late peritoneal recurrence has a low proliferation rate and is resistant to chemoradiotherapy. In conclusion, we present late onset of peritoneal recurrence of gastric cancer more than 20 years after primary surgery, and speculate on the mechanism of late-onset recurrence in our case.


Effect of dietary restriction on cholesterol biosynthesis in the liver and the intestine of cholesterol-fed rabbits.
The effect of dietary restriction (half of the control ration) on cholesterol biosynthesis was investigated in rabbits fed either standard or cholesterol-rich diets. Accompanying the amplification of hypercholesterolemia, additional disturbances of cholesterol metabolism were observed when cholesterol feeding was associated with dietary restriction. In the intestine, underfed rabbits showed a more marked inhibition of duodenal cholesterol biosynthesis from [14C]acetate following cholesterol feeding than rabbits on normal caloric ration. In contrast liver cholesterogenesis was equally suppressed in both groups receiving cholesterol-rich diets. Cholesterol biosynthesis from [14C]mevalonate was also inhibited by cholesterol feeding particularly in the duodenum of underfed rabbits. In addition cholesterol feeding induced a marked increase of the labeled esterified: free cholesterol ratio in the liver, demonstrating intensive esterification, this was enhanced by dietary restriction. The additional cholesterol which accumulates in the plasma and in various tissues in underfed rabbits is of dietary origin since the feedback control of cholesterogenesis by exogenous cholesterol was shown to be very effective in these animals.


Prostaglandin d2 as a potential antithrombotic agent.
Prostaglandin D2 was found to be a potent inhibitor of platelet aggregation. Aggregation of human platelets by ADP, collagen and prostaglandin G2 was inhibited more strongly by PGD2 than by PGE1. Although ADP-induced aggregation of rabbit platelets was inhibited more strongly by PGE1 than by PGD2 the latter prostaglandin gave a more long-lasting inhibitory effect on platelet aggregation following intravenous or oral administration. These results coupled with the finding that PGD2 has less hypotensive effects on the cardiovascular system than PGE1 suggest the possible use of PGD2 as an antithrombotic agent.


Potent HIV-1 protease inhibitors with antiviral activities in vitro.
A series of novel difluoroketones with low molecular weight (less than 600 m.u.) and which are potent inhibitors of the HIV-1 protease (IC50 = 1.0 to 21 nM) were synthesized. These compounds also exhibited antiviral activity by inhibition of the cytopathic effect of HIV-1(3)B in MT-4 cells in vitro.


Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia.
Components of insulin/IGF-1 receptor-mediated signaling pathways in pancreatic beta-cells have been implicated in the development of diabetes, in part through the regulation of beta-cell mass in vivo. Studies in vitro have shown that the protein Ras homolog enriched in brain (Rheb) plays a key role as a positive upstream regulator of the mammalian target of rapamycin complex 1 (mTORC1) pathway in integrating inputs from nutrients and growth factors for cell growth. Our objective was to investigate the role of the mTORC1 pathway in the regulation of beta-cell mass in vivo. We generated transgenic mice that overexpress Rheb in beta-cells. We examined the activation of the mTORC1 pathway and its effects on beta-cell mass, on glucose metabolism, and on protection against hyperglycemia. Immunoblots of islet extracts revealed that the phosphorylation levels of ribosomal protein S6 and eukaryotic initiation factor 4E binding protein 1, downstream effectors for mTORC1, were upregulated in transgenic beta-cells. Immunostaining of the pancreatic sections with anti-phospho-S6 antibody confirmed upregulation of the mTORC1 pathway in beta-cells in vivo. The mice showed improved glucose tolerance with higher insulin secretion. This arose from increased beta-cell mass accompanied by increased cell size. The mice also exhibited resistance to hyperglycemia induced by streptozotocin and obesity. Activation of the mTORC1 pathway by Rheb led to increased beta-cell mass in this mouse model without producing obvious unfavorable effects, giving a potential approach for the treatment of beta-cell failure and diabetes.


Prognostic and therapeutic implications of immunologic test results in rheumatic disease.
In systemic lupus erythematosus, some immunologic tests quantify disease activity, enable prediction of higher risk patterns of disease, and serve as therapeutic guides. In rheumatoid arthritis, serologic phenomena are significantly associated with more severe and sustained joint disease and with visceral manifestations (vasculitides and granulomas), but they have not been useful in monitoring the course of disease or response to therapy. In other rheumatic syndromes, a variety of antinuclear specificities show promise as marker antibodies, but their prognostic and therapeutic implications remain largely unexplored.


Prednisolone reduces the interferon response to AAV in cynomolgus macaques and may increase liver gene expression.
Ornithine transcarbamylase deficiency is a rare X-linked genetic urea cycle disorder leading to episodes of acute hyperammonemia, adverse cognitive and neurological effects, hospitalizations, and in some cases death. DTX301, a non-replicating, recombinant self-complimentary adeno-associated virus vector serotype 8 (scAAV8)-encoding human ornithine transcarbamylase, is a promising gene therapy for ornithine transcarbamylase deficiency; however, the impact of sex and prophylactic immunosuppression on ornithine transcarbamylase gene therapy outcomes is not well characterized. This study sought to describe the impact of sex and immunosuppression in adult, sexually mature female and male cynomolgus macaques through day 140 after DTX301 administration. Four study groups (n = 3/group) were included: male non-immunosuppressed; male immunosuppressed; female non-immunosuppressed; and female immunosuppressed. DTX301 was well tolerated with and without immunosuppression; no notable differences were observed between female and male groups across outcome measures. Prednisolone-treated animals exhibited a trend toward greater vector genome and transgene expression, although the differences were not statistically significant. The hepatic interferon gene signature was significantly decreased in prednisolone-treated animals, and a significant inverse relationship was observed between interferon gene signature levels and hepatic vector DNA and transgene RNA. These observations were not sustained upon immunosuppression withdrawal. Further studies may determine whether the observed effect can be prolonged.


Fos-tau-LacZ mice expose light-activated pathways in the visual system.
We have employed fos-tau-LacZ (FTL) transgenic mice to examine functional activation in the visual areas of the nervous system. The FTL mice express the marker gene lacZ in neurons and their processes following many different stimuli, and allow the imaging of activation from the level of the entire brain surface through individual neurons and their projections. Analysis of FTL expression in the retinas of mice following diurnal exposure to light shows that bipolar cells, specific classes of amacrine cells, ganglion cells, and a dense network of processes in the inner plexiform layer are functionally activated. In animals deprived of light, there is almost no activity in the retina. In the lateral geniculate nucleus (LGN), light exposure appears responsible for FTL expression in dorsal nuclei, but not for expression in the ventral nuclei or the intergeniculate leaflet. In the superficial layers of the superior colliculus, FTL expression is highly dependent on light exposure. Similarly, light exposure is required for FTL expression in primary visual cortex (area 17), but some expression remains in area 18 of dark-adapted animals. Finally, using mice with one or both eyes missing, we have determined which parts of the visual system are dependent on the presence of a functional connectivity from the eye. These data demonstrate the usefulness of the FTL mice to map functional activation within the entire visual system. Furthermore, we can capture visual activation in a conscious animal. Our findings give an insight into the architecture of activity within the retina and throughout the visual system.


Drosha processing controls the specificity and efficiency of global microRNA expression.
microRNAs (miRNAs) are a large family of approximately 22-nucleotide-long RNAs that regulate gene expression. They are first transcribed as long, primary transcripts, which then undergo a series of processing steps to generate the single-stranded, mature miRNAs. Here, we showed that Drosha cleaved hundreds of human primary miRNA transcript substrates with different efficiencies in vitro. The differential Drosha susceptibility of the primary miRNA transcripts significantly correlated with the expression of the corresponding, mature miRNAs in vivo. Conserved miRNAs were more efficiently expressed in vivo, and their primary transcripts were also better Drosha substrates in vitro. Combining secondary structure prediction and statistical analyses, we identified features in human primary miRNA transcripts that predisposed miRNAs to efficient Drosha processing in vitro as well as to better expression in vivo. We propose that the selectivity of Drosha action contributes greatly to the specificity and efficiency of miRNA biogenesis. Moreover, this study serves as an example of substrate specificity of a biochemical reaction regulating gene expression at a global scale in vivo. This article is part of a Special Issue entitled: MicroRNA's in viral gene regulation.


Fetal overgrowth in pregnancies complicated by diabetes: development of a clinical prediction index.
To develop an index to predict fetal overgrowth in pregnancies complicated by diabetes. Data were derived from a cohort of 275 women with singleton gestations in a collaborative diabetes in pregnancy program. Regression analysis incorporated clinical factors available in the first 20-30 weeks of pregnancy that were assigned beta-coefficient-based weights, the sum of which yielded a fetal overgrowth index (composite score). Fifty-one (18.5%) pregnancies were complicated by fetal overgrowth. The derived index included five clinical factors: age ≤ 30, history of macrosomia, excessive gestational weight gain, enlarged fetal abdominal circumference, and fasting hyperglycemia. Area under the curve (AUC) for the index is 0.88 [95% confidence interval (CI) 0.82-0.92]. Cut-points were selected to identify "high-risk" and "low-risk" ranges (≥ 8 and ≤ 3) that have positive and negative predictive values of 84% (95% CI 70-98%) and 95% (95% CI 92-98%), respectively. The majority of women in our cohort (n = 182, 66%) had a "low-risk" index while 9% (n = 25) had a "high-risk" index. Sub-analyses of nulliparous women and women with gestational and pre-gestational diabetes revealed that the overgrowth index was equally or more predictive when applied separately to each of these groups. This fetal overgrowth index that incorporates five clinical factors provides a means of predicting fetal overgrowth and thereby serves as a tool for targeting the allocation of healthcare resources and treatment individualization.


Aptamer selection and aptasensor construction for bone density biomarkers.
Osteoporosis (OP) is a bone disease involved in dysregulation of one of the bone metabolism arms, formation, or desorption cause a porous bone. Osteocalcin (OC) and beta-crosslap (BC), are the well-known markers for OP, which are connected to bone formation and desorption, respectively. In addition to the OP biomarker, BC is also used as an estrogen replacement therapeutic monitoring. ELISA and other antibody-based detection methods are routinely used for measuring OC and BC. These methods have limitations that include thermostability, sensitivity, sacrificing animals, and cost of production. However, aptamer-based-assays are of interest to overcome these drawbacks and achieve the most specific and robust application. Herein, specific aptamers for OC and BC were selected by the systematic evolution of ligands by exponential enrichment (SELEX) method from the pool of ssDNA library with 60 random sequences. The binding affinity (Kd) of the selected aptamers were evaluated against the respective biomarkers. The high-affinity aptamers of OC and BC showed the Kd values of 59 and 55 nM respectively. A graphene oxide-based aptasensors were fabricated from the high-affinity aptamers, and the detection limits of OC and BC were found to be 0.4 pg/ml and 0.21 pg/ml, respectively. These aptasensors have been tested with OC and BC spiked buffer samples and validated using serum samples collected from osteoporotic rats.


Prediction of convection-enhanced drug delivery to the human brain.
The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes an engineering approach for the systematic design of targeted drug delivery into the human brain. The proposed method predicts achievable volumes of distribution for therapeutic agents based on first principles transport and chemical kinetics models as well as accurate reconstruction of the brain geometry from patient-specific diffusion tensor magnetic resonance imaging. The predictive capabilities of the methodology will be demonstrated for invasive intraparenchymal drug administration. A systematic procedure to determine the optimal infusion and catheter design parameters to maximize penetration depth and volumes of distribution in the target area will be discussed. The computational results are validated with agarose gel phantom experiments. The methodology integrates interdisciplinary expertise from medical imaging and engineering. This approach will allow physicians and scientists to design and optimize drug administration in a systematic fashion.


Persistent spreading of ligament cells on osteopontin/bone sialoprotein-I or collagen enhances tolerance to heat shock.
Fibronectin (FN), bone sialoprotein-I (BSP-I), Type I collagen, and a number of synthetic peptides containing the integrin attachment sequence (RDG) were evaluated for their ability to affect stress tolerance in osteo-ligament cells (OL). The attachment and spreading of OL cells was determined by the method of Klebe (1974) and Akiyama et al. (1986). Survival from heat shock was evaluated after the methods of Gerner et al. (1976). These studies showed that FN, BSP-I, and synthetic RGD peptides enhance attachment of OL cells. Increased survival from heat was limited to cells spread on fibronectin, BSP-I, and Type I collagen. OL cells that persistently spread on BSP-I and Type I collagen had more survivors than cells demonstrating transient spreading on FN. These studies indicate that (a) cell spreading is a prerequisite for stress tolerance and (b) enhanced stress tolerance is mediated by protein sequences other than those immediately surrounding the RGD sites in native proteins.


Crystal structure of tetra-aqua-bis-(thio-cyanato-κN)nickel(II)-2,5-di-methyl-pyrazine (1/4).
In the crystal structure of the title compound, [Ni(NCS)2(H2O)4]·4C6H8N2, the Ni(II) cations are coordinated by four water ligands and two trans-coordinated terminally N-bonded thio-cyanate anions in a slightly distorted octa-hedral geometry. The asymmetric unit consists of a Ni(2+) cation located on a centre of inversion, two water mol-ecules and one thio-cyanate ligand, as well as two uncoordinated 2,5-di-methyl-pyrazine ligands in general positions. In the crystal, discrete complex mol-ecules are linked into a three-dimensional network by O-H⋯N hydrogen bonding between the water H atoms and the 2,5-di-methyl-pyrazine N atoms.


China's low-carbon economic transition: Provincial analysis from 2002 to 2012.
As the largest energy consumer and CO2-emitting country, China is committed to achieving a low-carbon economy (LCE). This study seeks to understand the spatial evolution of China's LCE provinces and determine which sectors could promote the formation of LCE provinces. Multiregional input-output (MRIO) analysis is applied to filter the LCE provinces and the sectoral structure changes behind the LCE in China from 2002 to 2012. The result shows that approximately 30% of the provinces (i.e., Tianjin, Zhejiang, Jiangsu and Chongqing) become LCE provinces faster than other provinces from 2002 to 2012, and the location of the LCE provinces gradually shifts from coastal to inland regions after 2007. Some sectors (i.e., nonmetal mining, chemical industry and nonmetal manufacturing) gradually become LCE sectors from 2002 to 2012, and these sectors promote the formation and development of LCE provinces. On this basis, this study proposes policy implications regarding the benchmarking of sectors and a sectoral structure that can promote the formation of LCE provinces.


Long-term survival after resection for bronchogenic carcinoma.
Of 915 resections for bronchogenic carcinoma over a 25-year period (1945-1969), 249 patients survived over 5 years; 127 of the patients eligible survived over 10 years, 61 over 15 years, and 22 over 20 years. The case material was divided into three time periods: 1945-49, 1950-59 and 1960-69, as well as by extent of resection. Lobectomy became the operation of choice, pneumonectomy being reserved for the more extensive lesions. Observed survival rates at 5, 10 and 15 years for 561 patients in the lobetomy series were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19% in the 1960-69 period. Observed rates for 354 patients having pneumonectomies were similar for three time periods, being 16, 8 and 6% at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10 and 15 years rose from 33, 28 and 26%, repectively, in the 1950-59 period to 50, 39 and 35% in the last time period, becoming a near horizontal curve segment after 5 years. Dominant factors in survival were extent of the lesion and stage of nodal involvement, histologic type and location being less significant.


Many-body Tunneling and Nonequilibrium Dynamics of Doublons in Strongly Correlated Quantum Dots.
Quantum tunneling dominates coherent transport at low temperatures in many systems of great interest. In this work we report a many-body tunneling (MBT), by nonperturbatively solving the Anderson multi-impurity model, and identify it a fundamental tunneling process on top of the well-acknowledged sequential tunneling and cotunneling. We show that the MBT involves the dynamics of doublons in strongly correlated systems. Proportional to the numbers of dynamical doublons, the MBT can dominate the off-resonant transport in the strongly correlated regime. A T 3/2-dependence of the MBT current on temperature is uncovered and can be identified as a fingerprint of the MBT in experiments. We also prove that the MBT can support the coherent long-range tunneling of doublons, which is well consistent with recent experiments on ultracold atoms. As a fundamental physical process, the MBT is expected to play important roles in general quantum systems.


Changes in pontine muscarinic receptor binding during sleep-waking states in the rat.
Number and affinity of pontine muscarinic receptors were examined in rats sacrificed during polygraphically defined wakefulness (W), synchronized sleep (S) and desynchronized sleep (D). Saturation binding assays with (-)-[3H]quinuclidinyl benzilate [( 3H]QNB) showed that muscarinic receptor levels were higher in W and D than in S. These findings indicate that brain receptor levels may change in relation to sleep-waking states. The significance of such changes in relation to the time course of sleep-waking states, as well as the possibility that the number of pontine muscarinic receptors plays a role in the triggering of D are discussed.


A national study of postoperative thyroid hormone supplementation rates after thyroid lobectomy.
The American Thyroid Association updated guidelines in 2015 to allow lobectomy for low-risk thyroid cancers. The objectives of this study were (1) to determine thyroid hormone supplementation rates after lobectomy and (2) to evaluate the effect of the American Thyroid Association guideline change on lobectomy and hormone supplementation rates among thyroid cancer patients. The Merative MarketScan Databases was used to identify adult (≥age 18) patients who underwent thyroidectomy for benign nodules or thyroid cancer. The association between indication for surgery and postoperative thyroid hormone supplementation was examined using χ2 analyses and multivariable logistic regression models. Among patients with thyroid cancer, lobectomy and hormone supplementation rates were compared in the periods before (2008-2015) and after the guideline change (2016-2019). Of the 81,926 patients identified, 33,756 (41.2%) underwent thyroid lobectomy, 45,104 (55.1%) underwent total thyroidectomy, and 3,066 (3.7%) underwent completion thyroidectomy. Patients who underwent lobectomy for malignancy were significantly more likely to require hormone supplementation (59.3% vs 39.4% [P < .001], adjusted odds ratio 2.34 [95% confidence interval 2.20-2.48]) compared to those with benign disease. Compared to the 2008 to 2015 period, the proportion of patients who underwent lobectomy for thyroid cancer was higher in the 2016 to 2019 period (34.3% vs 30.3%, P < .001), with fewer patients requiring completion thyroidectomy (25.6% vs 29.8%, P < .001) and thyroid hormone supplementation (56.9% vs 60.1%, P = .04). The postoperative thyroid hormone supplementation rate was significantly higher in patients who had thyroid cancers compared to benign diseases. After the American Thyroid Association guidelines changed, lobectomy rates increased significantly without a concomitant increase in the completion of thyroidectomy.


Laparoscopic pancreaticoduodenectomy in the porcine model.
Minimally invasive techniques offer theoretical advantages for treating resectable periampullary neoplasms. Laparoscopic pancreaticoduodenectomy (LPD) was first reported in 1992 and has been performed clinically despite lack of animal data to support the operation. The purpose of this study was to develop LPD in an acute porcine model and to assess safety and efficacy before considering clinical trials. LPD was initiated in six domestic pigs under general anesthesia. Once pneumoperitoneum was created, five 10-mm access ports were placed (one central and two in each flank). After cholecystectomy, the duodenum was mobilized and the proximal jejunum was divided distal to the ligament of Treitz. The neck of the pancreas was separated from the superior mesenteric vein, and the midstomach was divided by a stapler. Pancreaticojejunostomy (PJ), choledochojejunostomy (CDJ), and gastrojejunostomy (GJ) were performed using interrupted sutures. The animals were immediately sacrificed and the operative site was examined. LPD was aborted in three animals due to complications: intestinal perforation with fecal contamination (one) and prolonged resection time >/= 2.5 h (two). LPD was completed in three animals (operative time ranged from 5.0 to 7.5 h, blood loss < 200 cc); however, at sacrifice one PJ and two CDJs had small posterior leaks. The efferent loop of the GJ was narrowed by the staple line in one pig. All animals had extensive ecchymosis of the jejunal serosa due to excessive manipulation. Despite a significant number of anastomotic leaks in the immediate postoperative period, laparoscopic pancreaticoduodenectomy is feasible in a porcine model. Further studies and technical development are necessary before laparoscopic pancreatic resection can be performed on a more widespread basis.


[Limits of outpatient rheumatology care].
In recent years outpatient rheumatology has developed into one of the most important pillars of rheumatological care. The better diagnostic possibilities, the well-founded training of rheumatologists and the diverse guidelines have led to increasingly more patients being diagnosed as outpatients and can be treated by the most modern options as outpatients. Nevertheless, limits have also been set for outpatient rheumatology. This article aims to highlight what the limits of outpatient rheumatology currently are and who sets the limits. The presentation of the limitations should help all participants in the healthcare system to avoid false expectations and frustration; however, limits can also be relocated or overcome by appropriate motivation. The long-term target should be a further improvement in the interaction between outpatient and inpatient rheumatology and therefore the rheumatological care of patients. The medical limits of outpatient rheumatology are relatively clear and predominantly uncontroversial, the unjustified referral to the inpatient section is, for example, relatively rarely a problem. Some theoretically possible outpatient interventions are carried out in the inpatient sector more due to logistical problems. The healthcare political and legal limitations of outpatient rheumatological institutions are greater. Despite further limitations of outpatient rheumatology this discipline and the outpatient activity still represents an exciting, modern and last but not least a very satisfying activity, which is promoted here.


5-HT uptake blockade prevents the increasing effect of K(ATP) channel blockers on electrically evoked [3H]-5-HT release in rat and mouse neocortical slices.
To explore if prolonged--as opposed to acute--5-HT uptake blockade can lead to changes in the function of ATP-dependent potassium (K(ATP)) channels, we investigated in rat and mouse neocortical slices the effects of K(ATP) channel blockers on electrically evoked [3H]-serotonin ([3H]-5-HT) release after short- and long-term exposure to 5-HT uptake blockers. Glibenclamide (1 microM), a K(ATP) channel blocker, enhanced the electrically evoked [3H]-5-HT release by 66 and by 77%, respectively, in rat and in mouse neocortex slices. This effect was confirmed in the rat by tolbutamide (1 microM), another K(ATP) channel antagonist. After short-term blockade (45 min) of 5-HT uptake, glibenclamide still increased the release of [3H]-5-HT in the rat. Glibenclamide, however, failed to enhance [3H]-5-HT release after long-term uptake blockade (210 min). In the mouse, however, both short- and long-term inhibition of 5-HT reuptake by citalopram (1 microM) prevented the facilitatory effect of glibenclamide. The Na(+)/K(+)-ATPase inhibitor ouabain (3.2 microM) abolished the glibenclamide-induced increase in [3H]-5-HT release in both rat and mouse, suggesting that an operative Na(+)/K(+)-ATPase is a prerequisite for activation of K(ATP) channels. The terminal 5-HT(1B) autoreceptor-mediated feedback control was involved in the glibenclamide-induced increase in [(3)H]-5-HT release only in mouse neocortical tissue, as evident from the use of the 5-HT(1B) autoreceptor ligands metitepin (1 microM) and cyanopindolol (1 microM). These results suggest that in the rat long-term uptake blockade leads to an impaired activity of the Na(+)/K(+)-ATPase, which increases intracellular ATP and consequently closes K(ATP) channels. In the mouse, however, short-term uptake blockade seems to already reduce the activity of the Na(+)/K(+)-ATPase and thereby the consumption of ATP. Blockade of 5-HT transporters thus may close K(ATP) channels through increased intracellular ATP. The following slight depolarisation seems to facilitate 5-HT release. These results may contribute to a better understanding of the mechanisms involved in the clinical time latency of antidepressant efficacy of monoamine uptake blockers.


Discriminative stimulus properties of tianeptine.
In view of the difficulties in using antidepressant agents as training drugs in drug discrimination research, it was reasoned that tianeptine, because of its short duration of action and its lack of toxicity associated with long-term administration, would be well-suited to establish a discriminative stimulus cue in rats and, hence, a valuable tool in the investigation of the neural basis of depression. A drug discrimination procedure was used to determine whether tianeptine was associated with a specific discriminative stimulus effect, and substitution tests were conducted to determine whether this effect was mediated by serotonergic mechanisms. Rats were trained to discriminate 10 mg/kg tianeptine from saline and were tested with fluoxetine, a selective serotonin (5-HT) reuptake inhibitor; venlafaxine, a 5-HT/noradrenaline reuptake inhibitor; 8-hydroxy-(2-di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist; and caffeine, a nonselective antagonist of adenosine receptors. Tianeptine induced a specific, robust, and sustained discriminative stimulus in rats. Fluoxetine and 8-OH-DPAT partially substituted for tianeptine by producing >50% of tianeptine-appropriate lever responding. In contrast, venlafaxine and caffeine induced responding on a saline-associated lever. The discriminative stimulus effect of tianeptine is mediated by serotonergic mechanisms, but what is surprising is that this mechanism seems to be, at least partially, enhanced by serotonergic transmission.


Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity.
Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.


Folate and iron metabolism in patients with tumors and inflammations.
Reduced serum concentrations of nutrients like iron, zinc and folates and of albumin and cholesterol are found, as well as emaciation, both in malnutrition and in cancer. In patients with leukemia, a depletion of intracellular potassium and hypo-potassemia are found in addition. The use of hyperalimentation in cancer was originally based on the concept that too little food is the cause of these disturbances in the nutrition state. However, there is also a disturbed metabolism of nutrients in patients with tumors and inflammatory disease. In the case of folic acid, the disturbed metabolism could not be normalized by hyperalimentation. The more advanced the disease, the more pronounced is the disturbed nutrient metabolism, and this disturbance is related to the macrophage activity. It is not self-evident, therefore, that hyperalimentation can normalize the nutritional state in cancer. Emaciation in cancer patients is not caused exclusively by malnutrition.


Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition.
Mycobacterium tuberculosis, the causative agent of tuberculosis, is a growing threat to global health, with recent efforts towards its eradication being reversed in the wake of the COVID-19 pandemic. Increasing resistance to gyrase-targeting second-line fluoroquinolone antibiotics indicates the necessity to develop both novel therapeutics and our understanding of M. tuberculosis growth during infection. ParDE toxin-antitoxin systems also target gyrase and are regulated in response to both host-associated and drug-induced stress during infection. Here, we present microbiological, biochemical, structural, and biophysical analyses exploring the ParDE1 and ParDE2 systems of M. tuberculosis H37Rv. The structures reveal conserved modes of toxin-antitoxin recognition, with complex-specific interactions. ParDE1 forms a novel heterohexameric ParDE complex, supported by antitoxin chains taking on two distinct folds. Curiously, ParDE1 exists in solution as a dynamic equilibrium between heterotetrameric and heterohexameric complexes. Conditional remodelling into higher order complexes can be thermally driven in vitro. Remodelling induces toxin release, tracked through concomitant inhibition and poisoning of gyrase activity. Our work aids our understanding of gyrase inhibition, allowing wider exploration of toxin-antitoxin systems as inspiration for potential therapeutic agents.


Performances of antibiotic resistance genes profile upon the action of biochar-activated peroxydisulfate in composting.
In this study, the amendment of biochar-activated peroxydisulfate during composting to remove antibiotic resistance genes (ARGs) by direct (microbial community succession) and indirect methods (physicochemical factors) was analyzed. When implementing indirect methods, the synergistic effect of peroxydisulfate with biochar optimized the physicochemical habitat of compost, maintaining its moisture within a range of 62.95%-65.71%, and a pH of 6.87-7.73, and causing the compost to mature 18 days earlier than the control groups. The direct methods caused the optimized physicochemical habitat to adjust the microbial communities and reduce the abundance of most of the ARG host bacteria (Thermopolyspora, Thermobifida, and Saccharomonospora), thus inhibiting this substance's amplification. Heatmap analysis confirmed the necessary connection between physicochemical factors, microbial communities, and ARGs. Moreover, a mantel test confirmed the direct significant effect of the microbial communities on ARGs and the indirect significant effect of physicochemical factors on ARGs. The results showed that the abundance of more ARGs was down-regulated at the end of composting and regulated by biochar-activated peroxydisulfate, especially for the abundance of AbaF, tet(44), golS, and mryA, which was significantly decreased by 0.87-1.07 fold. These results provide new insights into the removal of ARGs during composting.


Identifying and quantifying potential super-spreaders in social networks.
Quantifying the nodal spreading abilities and identifying the potential influential spreaders has been one of the most engaging topics recently, which is essential and beneficial to facilitate information flow and ensure the stabilization operations of social networks. However, most of the existing algorithms just consider a fundamental quantification through combining a certain attribute of the nodes to measure the nodes' importance. Moreover, reaching a balance between the accuracy and the simplicity of these algorithms is difficult. In order to accurately identify the potential super-spreaders, the CumulativeRank algorithm is proposed in the present study. This algorithm combines the local and global performances of nodes for measuring the nodal spreading abilities. In local performances, the proposed algorithm considers both the direct influence from the node's neighbourhoods and the indirect influence from the nearest and the next nearest neighbours. On the other hand, in the global performances, the concept of the tenacity is introduced to assess the node's prominent position in maintaining the network connectivity. Extensive experiments carried out with the Susceptible-Infected-Recovered (SIR) model on real-world social networks demonstrate the accuracy and stability of the proposed algorithm. Furthermore, the comparison of the proposed algorithm with the existing well-known algorithms shows that the proposed algorithm has lower time complexity and can be applicable to large-scale networks.


Cutaneous leishmaniasis: A case report of a diagnostic dilemma.
Cutaneous leishmaniasis (CL) is the most prevalent clinical form of leishmaniasis and is caused by vector-borne protozoan parasite. Variation in diagnostic accuracy exists. A 54-year-old female farmer by occupation presented with lesion over right thigh for 8 months. Lesion evolved over period of 2-3 months and progressed to form ulcer with surrounding redness. On examination, solitary plaque with crateriform ulcer 3 * 2 cm in size roughly oval in shape was present. Ulcer floor was moist, smooth shiny with serous discharge, and well-defined raised erythematous margin was present. Biopsy was done which showed features suggestive of lupus vulgaris, for which anti-tubercular treatment (ATT) was started. There was persistence of ulcer despite 4 months of ATT, for which diagnosis was reconsidered and fine-needle aspiration cytology (FNAC) was performed. FNAC showed numerous intra- and extracellular amastigotes suggestive of leishmaniasis which was treated with complete disappearance of ulcer over 4 months.


Should Exercises be Painful or not? Effects on Clinical and Experimental Pain in Individuals with Shoulder Pain.
Exercise can reduce pain, however the effect of painful versus non-painful exercises is uncertain. The primary aim of this randomized crossover study was to compare the effect of painful versus nonpainful isometric shoulder exercises on pain intensity after exercise in individuals with rotator cuff-related shoulder pain. Secondary exploratory aims were to describe the effects on pressure pain thresholds (PPTs), conditioned pain modulation (CPM) and muscle strength. On separate days, 35 individuals performed painful isometric shoulder exercises (external rotation; 20% above pain threshold), nonpainful isometric shoulder exercises (external rotation; 20% below pain threshold), and a rest condition, in randomised order. Shoulder pain intensity, PPTs, CPM, and external rotation strength were assessed before, immediately after and 45 minutes after conditions. No significant differences were observed between painful and nonpainful exercises. Visual analogue scale scores increased immediately after both painful and non-painful exercises compared with rest (P = .047, partial ƞ2 = .07), but were similar to preexercise levels after 45 minutes. No changes in PPTs, CPM, or muscle strength after exercises compared with rest were observed. Painful and non-painful isometric exercises caused a moderate but short-lasting increase in shoulder pain in individuals with RCRSP. Isometric exercises had no effect on pain sensitivity and shoulder muscle strength or CPM. PERSPECTIVE: This study evaluated for the first time in individuals with rotator cuff-related shoulder pain the effects of painful versus non-painful isometric exercises on different pain-related outcome measures. Both painful and non-painful isometric exercises caused a moderate but relatively short-lasting increase in shoulder pain in individuals with rotator cuff-related shoulder pain. Trial registration number: (ClinicalTrials.gov) NCT03675399.


Role of endoscopic papillary balloon dilation in patients with recurrent bile duct stones after endoscopic sphincterotomy.
Endoscopic sphincterotomy (ES) is an established treatment for patients with choledocholithiasis or common bile duct stones (CBDS), but further management of patients after ES with recurrent CBDS remains controversial. Endoscopic papillary large balloon dilation (EPLBD) has been used safely and effectively for stone removal in patients after ES with recurrent CBDS. The aim of this study was to evaluate the clinical efficacy of EPLBD in patients after complete ES with recurrent CBDS. Records of 891 patients with CBDS after complete ES from January 1991 to December 2008 were reviewed. Of 133 patients with recurrent CBDS, 122 had complete endoscopic bile duct clearance. Twenty-three patients (Group 1) underwent EPLBD and 99 (Group 2) underwent stone extraction without dilatation. Basic demographics and endoscopic findings at the first recurrence were recorded and analyzed. The primary end point was the second CBDS recurrence. No statistical differences were observed between the two groups, except for larger CBDS size in Group 1. The bile duct clearance rate was 96% in Group 1 and 91% in Group 2. No complications such as pancreatitis, perforation, and bleeding were noted in Group 1, and one patient in Group 2 suffered from bleeding after stone extraction. The rate of second recurrent CBDS after endoscopic clearance for the first recurrent CBDS was 17% in Group 1 and 60% in Group 2 (p < 0.001). There were two independent factors for the second recurrence, including cirrhosis (odds ratio 4.734, p = 0.023) and stone extraction directly without major papilla expansion (odds ratio 6.050, p = 0.003). EPLBD is a safe and effective endoscopic treatment for recurrent CBDS in patients after ES. It can also facilitate complete clearance of CBDS and prevent further CBDS recurrence.


Evaluating effects of primary defatting for flap thinning on the development of perfusion-related complications in free perforator flap reconstruction.
Primary defatting is suggested as an effective and appealing technique for achieving flap thinning. There has been a long-standing concern regarding its potential adverse effects on flap perfusion, for which limited clinical evidence exists. This study aimed to investigate whether primary defatting negatively influences the outcomes of free perforator flap reconstruction. Patients who underwent upper or lower extremity reconstruction using free perforator flaps between 2002 and 2020 were investigated. They were categorized into two groups according to whether they underwent primary defatting. The association of primary defatting with the development of perfusion-related complications was evaluated. A total of 421 patients were included in the analysis. Perfusion-related complications developed in 61 (14.5%) cases, including 12 cases (2.9%) of total flap loss. In total, 302 patients underwent primary defatting and 119 did not. The patients who underwent primary defatting had a higher body mass index (BMI), lower rate of comorbidities, and smaller harvested flaps than the controls. Both groups had similar rates of perfusion-related complications (13.9% vs. 16.0%, p = .589), including total flap loss (3.0% vs. 2.5%, p = .799). In the multivariate analyses, primary defatting was not associated with the development of perfusion-related complications (p = .957). In the subgroup analyses, the rate of perfusion-related complications did not differ between the two groups regardless of the BMI (≥25 or <25 kg/m2 ), comorbidities, and flap size (≥200, 100-200, or <100 cm2 ). Primary defatting does not appear to be associated with the development of perfusion-related complications in free perforator flap extremity reconstruction.


Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization.
Bacterial biofilms are formed on environmental surfaces and host tissues, and facilitate host colonization and antibiotic resistance by human pathogens. Bacteria often express multiple adhesive proteins (adhesins), but it is often unclear whether adhesins have specialized or redundant roles. Here, we show how the model biofilm-forming organism Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces. Both biofilm-specific adhesins Bap1 and RbmC function as a "double-sided tape": they share a β-propeller domain that binds to the biofilm matrix exopolysaccharide, but have distinct environment-facing domains. Bap1 adheres to lipids and abiotic surfaces, while RbmC mainly mediates binding to host surfaces. Furthermore, both adhesins contribute to adhesion in an enteroid monolayer colonization model. We expect that similar modular domains may be utilized by other pathogens, and this line of research can potentially lead to new biofilm-removal strategies and biofilm-inspired adhesives.


Correction to: CRISPR/Cas9-targeted mutagenesis of Os8N3 in rice to confer resistance to Xanthomonas oryzae pv. Oryzae.
It was highlighted that in the original article (Kim, 2019).


Predictors of Unintended Pregnancy Among Adolescent Girls During the Second Wave of COVID-19 Pandemic in Oyam District in Northern Uganda.
In Uganda, unintended pregnancies are responsible for one in three births with detrimental consequences, a situation that worsened during COVID-19. Thus, the present examined unplanned pregnancy and its associated risks in Oyam district, northern Uganda during the COVID-19 epidemic. This study employed a cross-sectional study among adolescent girls aged 15-19 years who had a pregnancy during the second phase of COVID-19 in Oyam district, northern Uganda in November 2022. A consecutive method was employed to recruit the participants attending health facilities. A structured questionnaire was utilized to collect data. For data analysis, both bivariate and multivariable regression methods with adjusted odds ratio and 95% CI were used. A p-value of 0.05 was used to determine the significance level. Of the total respondents, 292 (69.5%) were aged between 18 and 19 years of age, 295 (70.2%) lived in rural areas, and 222 (52.9%) had no formal education. The results also show that 293 (69.8%) of the respondents had unintended pregnancies during COVID-19. The results indicate that participants who lacked knowledge of the ovulation period (AOR: 0.242; 95% CI: 0156-0376; P<0.001), sex education during COVID-19 (AOR: 0.563; 95% CI:: 0.365-0.869; P=0.024) and lacked the freedom to discuss family planning-related issues with family members during COVID-19 (AOR: 0.228; 95% CI: 0.138-0.376; P<0.001) were more likely to have an unintended pregnancy compared to their counterparts. Our study shows that unwanted pregnancies among adolescent girls remain a public health issue in Oyam district with more than two-thirds of adolescents having unwanted pregnancies during the crisis of COVID-19. The major correlates of unwanted pregnancies among adolescent girls during COVID-19 pandemic were inadequate knowledge of the ovulation period, sex education, and lack of freedom to discuss family planning-related issues with family members. There is a need to prioritize interventions, especially in rural settings. Sex education to improve contraceptive use and delay sexual debut. In light of the possibility that social and cultural norms in the Oyam district prohibit parents and children from discussing sexual subjects, it is crucial to promote sexual health education through the mass media, including newspapers, television, radio, and social media.


Special considerations for research with pharmacologic agents.
As physical medicine and rehabilitation becomes more and more complicated, the medical rehabilitation research teams are often bewildered by the sweeping changes occurring in the application of therapeutic drugs for rehabilitation. Society, through the instrument of governmental regulations, dictates that all new treatments must be efficacious before "release."


[Use of three species of crustacea as test animals for the toxicity of two salts of heavy metals].
The utilization of marine amphipods Podocerus fulanus and Corophium acherusicum, and the marine isopod Paracerceis sculpta in heavy metal toxicity tests (Cd and Cu) demonstrated on the one hand, the value of these animals as tests subjects when exposed to various polluting agents and, on the other hand their tolerance to heavy metals in acute toxicity tests.


Injection of lipopolysaccharide induces the migration of splenic neutrophils to the T cell area of the white pulp: role of CD14 and CXC chemokines.
There is increasing evidence that neutrophils are involved in the regulation of adaptive immunity. We therefore tested whether these cells may colocalize with T lymphocytes in lymphoid organs. Our results demonstrate that administration of the microbial product LPS induces the migration of neutrophils in the spleen from the red pulp and the marginal zone to the area of the white pulp where T cells reside. This movement is CD14-dependent, whereas the recruitment of neutrophils in the peritoneal cavity is increased in the absence of CD14. Our data further suggest the involvement of the chemokine MIP-2 and keratinocyte-derived chemokine and their receptor CXCR2. We conclude that neutrophils may interact with naïve T cells upon infection/inflammation and that the migration of neutrophils in the lymphoid organs and in the periphery is regulated differently by a signal transduced by CD14.


[Treatment adherence: a key element].
A substantial percentage of patients fail to follow health professionals' recommendations, which affects the management of chronic diseases, reducing the effectiveness of therapeutic interventions and increasing the costs of the disease. Lack of adherence is a multidimensional phenomenon and is influenced by numerous factors that should be identified. A multiplicity of measures is available to improve adherence, such as simplifying treatment administration, but none of these measures is effective when used alone. One way of tackling lack of adherence is by identifying patients' barriers to medication and involving them in decision making. Ulcerative colitis (UC) poses a risk for lack of treatment adherence. In this disease, poor adherence correlates with poor disease control (drug effectiveness) and with higher costs. As in other chronic diseases, the causes associated with poor adherence are multiple, including psychosocial factors, the physician-patient relationship and patients' prejudices toward medication. A single dose of aminosalycylates (5-ASA) should be recommended, as this dose is as safe and effective as other regimens. However, by itself, this recommendation does not seem to improve adherence. Identifying the scale of the problem and developing strategies to involve the patient in decision making is crucial to improve treatment adherence.


Zinc induces hephaestin expression via a PI3K-CDX2 dependent mechanism to regulate iron transport in intestinal Caco-2 cells.
Zinc stimulates intestinal iron absorption via induction of divalent metal ion transporter (DMT1) and hephaestin (HEPH). While the increase in DMT1 is mediated via a PI3K/IPR2 axis, the mechanisms of Zn-induced HEPH expression downstream of PI3K remain elusive. In the current study we probed the role of Caudal-related homeobox transcription factor-2 (CDX2) on Zn-induced HEPH expression. Zn treatment of Caco-2 cells increased CDX2 phosphorylation and HEPH protein and mRNA expression. siRNA-silencing of CDX2 inhibited Zn-induced HEPH expression. LY294002, an antagonist of PI3K inhibited Zn-induced phosphorylation of CDX2, and downstream HEPH expression. These results suggest that increased expression of HEPH in intestinal cells following Zn treatment is mediated via a PI3K-CDX2 pathway.


The effect of death education course utilizing constructivist learning theory on first grade undergraduate nursing student attitudes and coping abilities towards death: A mixed study design.
Inadequate clinical preparation for palliative care is often reflected in inadequate education about death. Nursing students as nurses of the future, it is necessary to make them aware of death and overcome fear of it so that they can cope with their future careers and provide qualified and warmly care service. To determine the effect of death education course using constructivist learning theory on first grade undergraduate nursing student attitudes and coping abilities towards death. This study was designed using a mixed-methods design. Two campuses of a university school of nursing in China. First grade Bachelor of Nursing Science students (n = 191). Data collection includes questionnaires and reflective writing as after class task. Quantitative data were analyzed using descriptive statistics, the Wilcoxon Signed Rank test, and the Mann-Whitney U test. As for reflective writing, content analysis was hired to analysis. The intervention group's attitude towards death tended to be neutral acceptance. The intervention group's ability to deal with death (Z = -5.354, p < 0.001) and expression of thoughts about death (Z = -3.89 b, p < 0.001) greater than that of the control group. Four themes (Awareness of death before class, Knowledge, The meaning of palliative care, New cognition) were identified from reflecting writing. Compared with the conventional teaching, death education course utilizing constructivist learning theory was found to be a more effective method for developing students' death coping skills and reducing fear of death.


Melatonin attenuates repeated mild traumatic brain injury-induced cognitive deficits by inhibiting astrocyte reactivation.
Melatonin has been well documented for its neuroprotective role through inhibiting oxidative stress against traumatic brain injury (TBI). However, the specific role of melatonin and the exact effects on cell responses (neurons, astrocytes, and microglia) in different brain regions are unclear. Here, we subjected mice to closed head injury, to establish a repeated mild TBI model and detect neuronal activity and glial responses in cognition-related brain regions after melatonin administration. Melatonin only showed cognitive enhancement if administered during early pathological stages, but not in late (chronic) stages. Additionally, we observed a significant increase in neuronal activity and inhibition of astrocyte reactivation in medial prefrontal cortex and hippocampus, but not in other cognitive deficit related brain regions. Furthermore, by activating astrocytes in these brain regions, we found neuronal activity upregulation and cognitive improvement following melatonin treatment. Therefore, we concluded that melatonin administration during the early stages of TBI is necessary to inhibit astrocyte reactivation and to promote cognitive function. Our results provide evidence for use of melatonin for cognitive improvement after TBIs.


Transseptal use of high-density grid catheter for VT mapping and retrograde hemodynamic support with Impella pump in presence of Mitraclips.
We sought to establish the technical feasibility of VT-mapping with high-density catheters in patients with Mitraclips, requiring a hemodynamic support. A 73-year-old man with ischemic cardiomyopathy and reduced left ventricular ejection fraction (LVEF ~ 20%) was presented due to syncope and adequate shock of his ICD. Due to severe mitral valve regurgitation (MR), two Mitraclips were implanted earlier. The decision for catheter ablation was made in line with current guidelines. Given the increased PAAINESD score, the use of hemodynamic support was required. To employ an Impella pump via the retrograde transaortic approach, LV-mapping and VT-ablation were necessary to be performed via the transseptal approach, which was challenging due to the presence of Mitraclips. The MV passage with the steerable sheath was guided by a quadripolar catheter and 3D transoesophageal echo (TEE). After the 12F steerable sheath had passed the MV, the quadripolar catheter was exchanged by a high-density (HD) Grid® catheter. Hereafter, the Impella pump was placed retrogradely in the LV, and voltage-mapping of the LV and ablation was performed. At the end of the procedure, the Impella pump could be removed in stable hemodynamic conditions. The follow-up after 3, 6, and 12 months showed no new VT episodes. This case demonstrates the feasibility of the transseptal approach of VT mapping used HD Grid catheter and retrograde hemodynamic support with Impella Pump for VT treatment in patients after Mitraclips implantation. To avoid a damage of the MV and Mitraclips, 3D-TEE is advisable.


Gracilaria chorda subcritical water ameliorates hepatic lipid accumulation and regulates glucose homeostasis in a hepatic steatosis cell model and obese C57BL/6J mice.
Red seaweed, known as Rhodophyta, has a long history of use in traditional Asian medicine, including Traditional Chinese Medicine and Ayurveda. It is believed to have cooling and detoxification properties. Red seaweed species, such as Gracilaria, have been used in traditional remedies to address various conditions, such as inflammation, thyroid disorders, and digestive issues. Obesity is a risk factor of hepatic steatosis, a hallmark of non-alcoholic fatty liver disease (NAFLD) that affects nearly 25% of the worldwide population. Gracilaria chorda (GC) contains bioactive peptides that may be applicable in the prevention of metabolic syndrome diseases. This study investigated the effects of GC subcritical water extract at 210 °C (GCSW210) on preventing liver injury and lipid and glucose dysregulation in an oleic acid (OA)-induced hepatic steatosis cell model (HepG2) and high-fat diet (HFD)-induced obese animal model (C57BL/6J mice). Human hepatoma HepG2 cells were exposed to 0.1 mM OA for 24 h to induce hepatic steatosis and C57BL/6J mice were fed a HFD for 13 weeks. For lipid accumulation, triglyceride (TG) content was measured in both models, along with free fatty acid (FFA), plasma glucose, and insulin levels in HFD-fed mice. Protein expression of master regulators of adipogenesis and lipogenesis, as well as cholesterol and mitochondrial biosynthesis, was studied via western blotting in hepatic steatosis-induced in vitro and in vivo models. In addition, protein expression of the insulin signaling cascade in skeletal muscle tissues of HFD-fed mice was studied. GCSW210 significantly decreased lipid accumulation in HepG2 cells exposed to OA and suppressed the expression of lipogenic factors, such as sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase. In addition, GCSW210 abrogated transcription factors related to cholesterol biosynthesis, such as SREBP-2 and low-density lipoprotein receptor. Similarly, FFA, TG, serum glutamic acid, aspartate transaminase, alanine transferase, plasma glucose, and insulin levels were also significantly reduced in GCSW210-treated HFD-fed mice, which were comparable to the positive control mice treated with Garcinia cambogia extract. Additionally, GCSW210 enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase in the hepatic tissues of HFD-fed mice. Moreover, GCSW210 treatment improved insulin signal transduction by reducing insulin receptor substrate 1 Ser307 phosphorylation and elevated phosphatidylinositol 3-kinase/protein kinase B and glucose transporter type 4 protein expression in muscle tissue. 5-Hdroxymethylfufural (5-HMF) was confirmed to be active substances isolated from GCSW210 through LC-PDA and LC-MS. GCSW210 significantly regulated glucose metabolism, alleviated insulin resistance (IR) induced by high fatty acid synthesis and lipid accumulation, and elevated de novo lipogenesis by activating AMPK phosphorylation in both the liver and muscle tissues of HFD-fed mice. GCSW210 may be a potential functional food for preventing HFD-induced metabolic diseases, such as IR, NAFLD, and type 2 diabetes mellitus.


Analysis of aquaporins in Brassicaceae species reveals high-level of conservation and dynamic role against biotic and abiotic stress in canola.
Aquaporins (AQPs) are of vital importance in the cellular transport system of all living organisms. In this study, genome-wide identification, distribution, and characterization of AQPs were determined in Arabidopsis lyrata, Capsella grandiflora, C. rubella, Eutrema salsugineum, Brassica rapa, B. oleracea, and B. napus (canola). Classification and phylogeny of AQPs revealed the loss of XIPs and NIP-IIIs in all species. Characterization of distinctive AQP features showed a high level of conservation in spacing between NPA-domains, and selectivity filters. Interestingly, TIP3s were found to be highly expressed in developing seeds, suggesting their role in seed desiccation. Analysis of available RNA-seq data obtained under biotic and abiotic stresses led to the identification of AQPs involved in stress tolerance mechanisms in canola. In addition, analysis of the effect of ploidy level, and resulting gene dose effect performed with the different combinations of Brassica A and C genomes revealed that more than 70% of AQPs expression were dose-independent, thereby supporting their role in stress alleviation. This first in-depth characterization of Brassicaceae AQPs highlights transport mechanisms and related physiological processes that could be exploited in breeding programs of stress-tolerant cultivars.


Biosynthesis of non-melanin pigment by a divergent polyketide synthase in Metarhizium robertsii.
Fungal polyketide synthases (PKSs) and their related gene clusters are highly diversified at both inter- and intra-specific levels. The most well characterized PKS enzymes include those responsible for the biosynthesis of polyketide pigments such as melanins. The genome of the insect pathogenic fungus Metarhizium robertsii contains 20 type I PKSs but none has been functionally characterized. In this study, two PKS genes (designated as MrPks1 and MrPKs2) showing homologies to those counterparts for the biosynthesis of heptaketide pigments and dihydroxynaphthalene (DHN)-melanins, respectively, were deleted in two different strains of M. robertsii. The results indicated that disruption of MrPks1 but not MrPks2 impaired fungal culture pigmentation and cell wall structure. In addition to the negative effect of the DHN-melanin pathway inhibitor, it was postulated that DHN-melanin would not be produced by M. robertsii. Various assays revealed that the stress resistance abilities against ultraviolet radiation, heat shock and oxidants, as well as virulence against insects were not impaired in ΔMrPks1 and ΔMrPks2 isolates when compared with the wild-type strain. Thus, the non-melanin pigment(s) produced by the fungus do not contribute to cell damage protection and pathogenicity in M. robertsii. Physiological differences were evident in the two examined wild-type strains. The results from this study advance the understanding of functional divergence of fungal PKSs.


Mayo Clinic experience with the AS800 artificial urinary sphincter for urinary incontinence after transurethral resection of prostate or open prostatectomy.
The model AS800 artificial urinary sphincter was implanted in 56 patients with urinary incontinence after transurethral resection of the prostate and in 8 patients after open prostatectomy. Their ages ranged from fifty-three to eighty-seven years (mean, 70 years). At presentation, 92 percent had total incontinence and 8 percent had distressing stress incontinence. Fifteen patients (23%) had had previous radiation therapy. Bulbous urethral cuffs were used in 60 (94%) patients and vesical neck cuffs in 4 (6%). Follow-up questionnaires were mailed to assess satisfaction rate and degree of continence. Continence was significantly improved in 90 percent, and 87 percent of the patients were satisfied with their sphincters. Surgical revisions were required in 14 patients (22%). Cuff compression was inadequate in 9 patients, and erosion led to revision in 3 patients. At follow-up, 3 patients had had at least one component of the AS800 removed (complete device in 2 and cuff in 1).


Personal and hospital factors associated with limited surgical resection for lung cancer, in-hospital mortality and complications in New York State.
Early stage lung cancer is generally treated with surgical resection. The objective of the study was to identify patient and hospital characteristics associated with the type of lung cancer surgical approach utilized in New York State (NYS), and to assess in-hospital adverse events. A total of 33 960 lung cancer patients who underwent limited resection (LR) or lobectomy (L) were selected from the NYS Statewide Planning and Research Cooperative System database (1995-2012). LR patients were more likely to be older (adjusted odds ratio ORadj and [95% confidence interval]: 1.01 [1.01-1.02]), female (ORadj : 1.11 [1.06-1.16]), Black (ORadj : 1.17 [1.08-1.27]), with comorbidities (ORadj : 1.08 [1.03-1.14]), and treated in more recent years than L patients. Length of stay and complications were significantly less after LR than L (ORadj : 0.56 [0.53-0.58] and 0.65 [0.62-0.69]); in-hospital mortality was similar (ORadj : 0.93 [0.81-1.07]), and was positively associated with age and urgent/emergency admission, but inversely associated with female gender, private insurance, recent admission year, and surgery volume. There was a growing trend toward LR, which was more likely to be performed in older patients with comorbidities. In-hospital outcomes were better after LR than L, and were affected by patient and hospital characteristics.


Repetitive Blunt Trauma and Arterial Injury in the Hand.
Arterial injury in the hand is most often due to repetitive blunt trauma. Although not always associated with significant impairment, it may cause serious ischemic damage or considerable disability. As a cause of digital ischemia, the frequency of this disorder is widely under appreciated. This study reviews the clinical and angiographic features of this condition. An extensive literature review combined with the authors experience with arterial injury in the hand due to repetitive blunt hand trauma is summarized with emphasis on mechanisms of injury and pathologic changes to explain the angiographic findings and clinical presentations. Angiographic findings are related to severity of injury and underlying changes in the arterial wall. The clinical presentation varies from asymptomatic to digital necrosis and gangrene, related to severity of arterial injury, collateral circulation, and the highly variable arterial anatomy in the hand. Early recognition is important because compared to many other causes of digital ischemia in the upper extremities, traumatic arterial injury is frequently readily treatable. Angiographic findings and clinical presentation are often characteristic. The diagnosis should not be based on a clear history of repetitive hand trauma since the patient may be unaware of this occurrence.


Chronic actinic damage of facial skin.
Chronic actinic damage of the skin manifests itself as extrinsic skin aging (photoaging) and photocarcinogenesis. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms of photoaging. DNA photodamage and ultraviolet-generated reactive oxygen species are the initial events that lead to most of the typical histologic and clinical manifestations of chronic photodamage of the skin. Chronic actinic damage affects all layers of the skin. Keratinocytes, melanocytes, fibroblasts, and endothelial cells are altered by ultraviolet radiation and can result in numerous changes in human skin, particularly the skin of fair-skinned individuals. These changes include actinic keratosis, thickening and wrinkling, elastosis, telengiectasia, solar comedones, diffuse or mottled hyperpigmentation, and skin cancers. There are many options in the treatment of changes caused by chronic actinic damage. The most effective measure of prevention of the photoaging and photocarcinogenesis is sun protection.


Influence of HLDF Differentiation Factor on Nonspecific Invasive Breast Carcinoma in vitro.
The study was carried out on samples of invasive breast carcinoma of no special type from 36 patients aged 48.0 to 62.8 years. The effect of HLDF on nonspecific invasive breast carcinoma was a decrease in the relative content of low-differentiated cells and an increase in the relative content of highly differentiated cells. HLDF did not have a cytotoxic effect leading to the death of low-differentiated cells but promoted promotes the acquisition of a higher degree of differentiation by them. A more pronounced effect of HLDF was observed in more aggressive metastasizing forms of neoplasia, which allows us to consider this differentiation factor as a candidate for use in the differentiation therapy of malignant neoplasms.


Mental health service needs and mental health of old adults living alone in urban and rural areas in China: The role of coping styles.
This study aimed to explore the level and relationship between the mental health service needs (MHSN), coping styles (CS), and mental health (MH) of old adults living alone in urban and rural, and to explore the moderating effects of coping styles. A cross-sectional study was conducted with 717 older adults living alone. The survey measured MHSN, CS, and MH. Data were analyzed using a structural equation and bootstrapping method. There were significant differences in the MHSN, CS, and MH between urban and rural old adults living alone (P < 0.05). The model of the impact of MHSN on MH in urban and rural old adults living alone showed a good fit. These findings highlighted the importance of high MHSN and positive CS as potential protective factors of mental health in old adults living alone. This provides a theoretical basis for psychological nursing for old adults living alone in the community.


Development of an integrated chronic obstructive pulmonary disease service model in an inner-city region in the UK: initial findings and 12-month results.
To improve the management of chronic obstructive pulmonary disease (COPD) in Salford, UK, and to evaluate the impact of an integrated service model after one year. A health needs analysis and benchmarking exercise was undertaken in 2007. These activities were used to develop an integrated service model in order to improve the diagnosis and management of COPD and reduce unscheduled hospital admissions and length of stay. Following implementation of the model, 811 further patients were diagnosed. Unscheduled hospital admissions for COPD fell from 935 to 840, length of stay was reduced from 8.3 to 7.7 days, and associated costs fell from £1,772, 865 to £1,528,080. The number of patients who completed pulmonary rehabilitation increased from 84 to 143. An integrated COPD service model was successful in increasing diagnosis, reducing hospital admissions and reducing length of hospital stay - in line with the proposed National Strategy for COPD Services in England. It also promoted management according to National Institute of Health and Clinical Excellence (NICE) guidelines.


miR-27b-3p Attenuates Muscle Atrophy by Targeting Cbl-b in Skeletal Muscles.
As it is well known, muscle atrophy is a process in which protein degradation increases and protein synthesis decreases. This process is regulated by a variety of links. Among them, microRNAs play an essential role in this process, which has attracted widespread attention. In this paper, we find that miR-27b-3p and Cbl-b genes are significantly differentially expressed in the induced atrophy model. The dual-luciferase experiment and Western blot analysis confirmed that miR-27b-3p could regulate the expression of Cbl-b. In C2C12-differentiated myotubes, the overexpression of the Cbl-b gene showed that Cbl-b could upregulate the expression of MuRF-1 and Atrogin-1, which are related marker genes of muscle atrophy, at both the mRNA and protein levels, indicating that the Cbl-b gene can specifically affect muscle atrophy. The knockdown of the Cbl-b gene after C2C12-differentiated myotubes induced atrophy treatment can downregulate the expression of muscle-atrophy-related genes, indicating that manual intervention to downregulate the expression of Cbl-b has a certain alleviating effect on muscle atrophy. These data suggest that miR-27b-3p can regulate the expression of the Cbl-b gene and then exert a particular influence on muscle atrophy through the Cbl-b gene.


Touch DNA collection - Performance of four different swabs.
A collaborative study conducted by three police forensic units, a DNA laboratory, and a forensic academic institute was undertaken in order to compare the performance of four different swabs in controlled and quasi-operational conditions. For this purpose, a reference swab (Prionics cardboard evidence collection kit) currently used within the police forensic units and 3 challenger swabs (COPAN 4N6FLOQSwabs™ (Genetics variety), Puritan FAB-MINI-AP and Sarstedt Forensic Swab) were used for collecting DNA traces from previously used items (referred as "touch DNA" in this article) including on 60 collars, 60 screwdrivers and 60 steering wheels obtained from volunteers. For each comparison, the surface considered was divided into two equal components; one was sampled with the reference swab and the other with one of the three challenger swabs. This lead to a total of 360 samples. Conclusions were consistent within the four operational partners. From a practical point of view, the COPAN 4N6FLOQSwabs™ (Genetics variety) was judged the most convenient to use. Furthermore, it allowed the recovery of significantly more DNA from collars (0.65 vs 0.13 ng/μL) and steering wheels (2.82 vs 1.77 ng/μL), and a similar amount of DNA from screwdrivers (0.032 vs 0.026 ng/μL) compared with the Prionics reference swab. The two other challenger swabs provided results that were not significantly different from the reference swab, except for the Puritan swab, whose performance was significantly lower for steering wheels (0.37 vs 0.58 ng/μL). As part of a conservation study, 50 μL of a blood dilution (1/4 with PBS) was deposited on a total of 105 COPAN (Genetics and Crime Scene varieties), Prionics and Sarstedt swabs. They were stored within a cupboard at room temperature. The integrity of the recovered DNA was evaluated with NGM SElect™ DNA profiles after different time-spans ranging from 1 day to 12 months by comparing the height difference of the peaks occurring at the shortest and longest loci, respectively. DNA seemed to remain stable, except when using the COPAN 4N6FLOQSwabs™ treated with an antimicrobial agent (Crime scene variety), which resulted in significant DNA degradation. Following these tests, the COPAN 4N6FLOQSwabs™ (Genetics variety), a model with a desiccant, was selected for further testing in fully operational conditions.