Minimally invasive tricuspid valve surgery in patients at high risk.
Reports of minimally invasive tricuspid valve operations are rare, and results are often contradictory. This study analyzes our 5-year experience with minimally invasive tricuspid valve operations in high-risk patients. Between November 2005 and December 2011, tricuspid valve surgery using a nonsternotomy minimally invasive technique was performed in 64 patients (19 male, 45 female; mean age, 63.2 ± 12.8 years). Mean preoperative European System for Cardiac Operative Risk Evaluation was 7.3 ± 2.9, and predicted mortality was 11.6% ± 11.7%. Tricuspid valve regurgitation cause was functional in 36 patients (56.2%), endocarditis in 2 patients (3.1%), and rheumatic in 24 patients (37.5%). Two patients (3.1%) showed prosthesis dysfunction. Forty patients (62.5%) had undergone previous cardiac surgery. Tricuspid valve repair was performed in 35 patients (54.7%). Tricuspid valve replacement with bioprosthesis was performed in 27 patients (42.2%), and the remaining 2 patients (3.1%) underwent bioprosthetic replacement. Concomitant procedures (48) included mitral valve surgery (42 patients), atrial septal defect closure (5 patients), and myxoma exeresis (1 patient). Conversion to sternotomy occurred in 1 patient (1.6%). Overall hospital mortality was 7.9%. Stroke occurred in 1 patient (1.6%), and 5 patients underwent reoperation for bleeding (7.8%). Mean follow-up time was 21 ± 16 months (range, 1-59 months) and 100% completed. Cumulative Kaplan-Meier estimated 5-year survival was 81.3%, and 5-year freedom from reoperation was 100%. The heart-port-based minimally invasive approach seems to be safe, feasible, and reproducible in case of tricuspid valve operations. It ensures low perioperative morbidity, moderate to low rates of tricuspid regurgitation recurrence, and low late mortality. It also seems to have an added value in case of reoperative procedures.


Measuring shoulder external and internal rotation strength and range of motion: comprehensive intra-rater and inter-rater reliability study of several testing protocols.
Shoulder range of motion (ROM) and strength measurements are imperative in the clinical assessment of the patient's status and progression over time. The method and type of assessment varies among clinicians and institutions. No comprehensive study to date has examined the reliability of a variety of procedures based on different testing equipment and specific patient or shoulder position. The purpose of this study was to establish absolute and relative reliability for several procedures measuring the rotational shoulder ROM and strength into internal (IR) and external (ER) rotation strength. Thirty healthy individuals (15 male, 15 female), with a mean age of 22.1 ± 1.4 years, were examined by 2 examiners who measured ROM with a goniometer and inclinometer and isometric strength with a hand-held dynamometer (HHD) in different patient and shoulder positions. Relative reliability was determined by intraclass correlation coefficients (ICC). Absolute reliability was quantified by standard error of measurement (SEM) and minimal detectable change (MDC). Systematic differences across trials or between testers, as well as differences among similar measurements under different testing circumstances, were analyzed with dependent t tests or repeated-measures analysis of variance in case of 2 or more than 2 conditions, respectively. Reliability was good to excellent for IR and ER ROM and isometric strength measurements, regardless of patient or shoulder position or equipment used (ICC, 0.85-0.99). For some of the measurements, systematic differences were found across trials or between testers. The patient's position and the equipment used resulted in different outcome measures. All procedures examined showed acceptable reliability for clinical use. However, patient position and equipment might influence the results.


Polyarteritis nodosa revisited.
Polyarteritis nodosa (PAN), the prototype of systemic vasculitis, is a rare condition characterized by necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules. Signs and symptoms of this disease are primarily attributable to diffuse vascular inflammation and ischemia of affected organs. Virtually any organ with the exception of the lungs may be affected, with peripheral neuropathy and symptoms from osteoarticular, renal artery, and gastrointestinal tract involvement being the most frequent clinical manifestations. A clear distinction between limited versus systemic disease and idiopathic versus hepatitis B related PAN should be done because there are differences in the implicated pathogenetic mechanisms, their treatment, and prognosis. Currently, corticosteroids plus cyclophosphamide is the standard of care for idiopathic PAN, in particular for patients with adverse prognostic factors (more severe disease), in whom this combination prolonged survival. In contrast for hepatitis B related PAN treatment consists of schemes that include plasmapheresis and antiviral agents.


Prognostic implication of NQO1 overexpression in hepatocellular carcinoma.
To explore the role of NQO1 overexpression for prognostic implication in hepatocellular carcinoma (HCC), NQO1 mRNA levels were detected in HCC fresh tissue samples of HCC and nontumor tissues, respectively. One hundred fifty-six cases of HCC meeting strict follow-up criteria were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological features of HCC were evaluated using χ2 tests, survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient 5-year survival was analyzed using Cox proportional hazards analysis. In results, the levels of NQO1 mRNA were significantly up-regulated in 14 fresh tissue samples of HCC. Immunohistochemical analysis showed that the NQO1 expression and overexpression rates were significantly higher in HCC samples compared with either adjacent nontumor tissues or normal liver tissues. NQO1 overexpression correlated to tumor size, venous infiltration and late pTNM stage of HCC. NQO1 overexpression was also related to low disease-free survival and 5-year survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with NQO1 overexpression were significantly lower than those of patients without NQO1 expression. Further analysis using a Cox proportional hazards regression model revealed that NQO1 expression emerged as a significant independent hazard factor for the 5-year survival rate of patients with HCC. Therefore, NQO1 plays an important role in the progression of HCC. NQO1 may potentially be used as an independent biomarker for prognostic evaluation of HCC.


Occupational lead exposure on genome-wide DNA methylation and DNA damage.
Lead (Pb) exposure can induce DNA damage and alter DNA methylation but their inter-relationships have not been adequately determined. Our overall aims were to explore such relationships and to evaluate underlying epigenetic mechanisms of Pb-induced genotoxicity in Chinese workers. Blood Pb levels (BLLs) were determined and used as individual's Pb-exposure dose and the Comet assay (i.e., % tail DNA) was conducted to evaluate DNA damage. In the screening assay, 850 K BeadChip sequencing was performed on peripheral blood from 10 controls (BLLs ≤100 μg/L) and 20 exposed workers (i.e., 10 DNA-damaged and 10 DNA-undamaged workers). Using the technique, differentially methylated positions (DMPs) between the controls and the exposed workers were identified. In addition, DMPs were identified between the DNA-undamaged and DNA-damaged workers (% tail DNA >2.14%). In our validation assay, methylation levels of four candidate genes were measured by pyrosequencing in an independent sample set (n = 305), including RRAGC (Ras related GTP binding C), USP1 (Ubiquitin specific protease 1), COPS7B (COP9 signalosome subunit 7 B) and CHEK1 (Checkpoint kinase 1). The result of comparisons between the controls and the Pb-exposed workers show that DMPs were significantly enriched in genes related to nerve conduction and cell cycle. Between DNA-damaged group and DNA-undamaged group, differentially methylated genes were enriched in the pathways related to cell cycle and DNA integrity checkpoints. Additionally, methylation levels of RRAGC and USP1 were negatively associated with BLLs (P < 0.05), and the former mediated 19.40% of the effect of Pb on the % tail DNA. These findings collectively indicated that Pb-induced DNA damage was closely related to methylation of genes in cell cycle regulation, and methylation levels of RRAGC were involved in Pb-induced genotoxicity.


BCL6 encodes a sequence-specific DNA-binding protein.
Chromosomal rearrangements of BCL6 are commonly associated with diffuse large-cell lymphomas. We set out to determine the DNA-binding site of a glutathione-S-transferase fusion protein containing the BCL6 zinc finger region by employing cyclic amplification and selection of targets (CASTing). From oligonucleotides containing 16 central random bases, sequences binding to the protein on glutathione-coated beads were repeatedly selected and amplified by polymerase chain reaction (PCR). The binding sites were cloned and sequenced. A consensus, TTTNNNGNNATNCTTT, was obtained. Protein binding studies of double-stranded oligomers containing point mutations within the 3' CTTT confirmed the binding specificity of this part of the consensus. In addition, evidence indicated that some of the base pairs held constant in the oligonucleotides used for CASTing also contributed to binding.


Highly Efficient Thermally Activated Delayed Fluorescence from Pyrazine-Fused Carbene Au(I) Emitters.
Metal-based thermally activated delayed fluorescence (TADF) is conceived to inherit the advantages of both phosphorescent metal complexes and purely organic TADF compounds for high-performance electroluminescence. Herein a panel of new TADF Au(I) emitters has been designed and synthesized by using carbazole and pyrazine-fused nitrogen-heterocyclic carbene (NHC) as the donor and acceptor ligands, respectively. Single-crystal X-ray structures show linear molecular shape and coplanar arrangement of the donor and acceptor with small dihedral angles of <6.5°. The coplanar orientation and appropriate separation of the HOMO and LUMO in this type of molecules favour the formation of charge-transfer excited state with appreciable oscillator strength. Together with a minor but essential heavy atom effect of Au ion, the complexes in doped films exhibit highly efficient (Φ∼0.9) and short-lived (<1 μs) green emissions via TADF. Computational studies on this class of emitters have been performed to decipher the key reverse intersystem crossing (RISC) pathway. In addition to a small energy splitting between the lowest singlet and triplet excited states (ΔEST ), the spin-orbit coupling (SOC) effect is found to be larger at a specific torsion angle between the donor and acceptor planes which favours the RISC process the most. This work provides an alternative molecular design to TADF Au(I) carbene emitters for OLED application.


Treatment Outcome of Repaired Root Perforation: A Systematic Review and Meta-analysis.
This study aimed to review systematically the reported treatment outcome of repaired root perforation and to identify any preoperative factors that may influence the outcome of such repair. A comprehensive search was conducted by using 4 electronic databases, as well as manual search of cited references, to identify reports related to root perforation. Clinical studies published from 1950 to mid-2014 that evaluated the outcome of repaired root perforations were identified. Studies were further screened for similar characteristics for pooling of data for meta-analysis. Seventeen studies were included for systematic review and 12 suitable for meta-analysis. An overall pooled success rate of 72.5% (confidence interval, 61.9%-81.0%) was estimated for nonsurgical repair of root perforations. The use of mineral trioxide aggregate appeared to enhance the success rate to 80.9% (confidence interval, 67.1%-89.8%), but the difference was not statistically significant. The presence of pre-existing radiolucency adjacent to the perforation site fared a lower chance of success after repair (P < .05). Maxillary teeth demonstrated a significantly higher success rate compared with their mandibular counterpart (P < .05). Within the limitations of this study, it may be concluded that nonsurgical repair of root perforation results in a success rate of more than 70%. Teeth in the maxillary arch and absence of preoperative radiolucency adjacent to the perforation are favorable preoperative factors for healing after perforation repair. In view of the relatively high rate of clinical success, nonsurgical repair may be considered as the preferred treatment to handle this complication that arises during root canal therapy.


Perioperative blood transfusion and solid tumour recurrence.
Evidence regarding the association of blood transfusions with recurrence of solid tumours is largely conflicting. This is perhaps unsurprising given the retrospective nature of the studies performed to date, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, new data demonstrating that transfusions of whole blood, as opposed to red cell concentrates, are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences include earlier cancer recurrence and increased susceptibility to infection with bacteria and viruses. The questions raised in this review can be answered conclusively only by controlled prospective studies. For the present the prudent clinician will select red blood cells rather than whole blood for transfusion, employ autologous transfusions whenever feasible, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks.


Survival After Minimally Invasive Surgery in Older Women With Endometrial Carcinoma.
To analyze the impact of minimally invasive surgery for endometrial cancer on overall survival among age >65. We examined women who underwent hysterectomy from 2010 to 2015 from the U.S. National Cancer Data Base (NCDB). We evaluated the impact of surgical approach on survival. Of 243,601 endometrial cancer cases, 42,458 met the inclusion criteria. Laparoscopic approach was associated with improved survival by 14% (HR=0.86; 95%CI=0.80-0.92; p<0.001) and robotic approach was associated with improved survival by 12% (HR=0.88; 95%CI=0.83-0.93; p<0.0001), compared to the open approach. Similarly, the weighted adjusted 5-year overall survival was 73.1% (95%CI=72%-74.2%), 76.4% (95%CI=75.1-77.7%), and 75.5% (95%CI=74.7-76.4%) for open, laparoscopic, and robotic approaches, respectively (p<0.001). Minimally invasive surgery improved overall survival in women over 65 years with endometrial cancer.


Levels of cesium-137 in seawater and fish from the Brazilian coast.
Considering environmental pollution problems and their impact on man, we have developed a research programme on environment monitoring. The aim of this work was to develop and to apply radiochemical methods for the analysis of cesium-137 in marine samples, such as seawater and fish. Cesium-137 levels in surface seawater from the coastal region of São Paulo State range from 1.7 to 1.9 Bq.m-3. Samples of the five species of fish most consumed by local population were taken for the analysis of cesium-137. Levels for fish varied from 0.1 to 0.3 Bq.kg-1 of edible part. Data were used to calculate dose assessment.


Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.
The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation. Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki-67, bcl-2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p-values (Fisher's exact test, two-tailed) and positive/negative likelihood ratios (+LR/-LR) were calculated. Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (-LR < 0.01). Significant differences were also seen with bcl-2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl-2-positive and cytokeratin 10-negative. Cytokeratin 10-negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, -LR < 0.01). The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl-2 expression, absence of crowding and of mitoses.


Nuclear actin dynamics in gene expression and genome organization.
Although best known from its functions in the cytoplasm, actin also localizes to the cell nucleus, where it has been linked to many essential functions from regulation of gene expression to maintenance of genomic integrity. While majority of cytoplasmic functions of actin depend on controlled actin polymerization, in the nucleus both actin monomers and filaments have their own specific roles. Actin monomers are core components of several chromatin remodeling and modifying complexes and can also regulate the activity of specific transcription factors, while actin filaments have been linked to DNA damage response and cell cycle progression. Consequently the balance between monomeric and filamentous actin must be precise controlled also in the nucleus, since their effects are dynamically coupled. In this review, we discuss the recent data on how actin dynamics is regulated within the nucleus and how this influences the different nuclear processes dependent on actin.


Recent advances in impacts of microplastics on nitrogen cycling in the environment: A review.
Nitrogen cycling plays a decisive role in biogeochemistry, and largely depends on microbial driven nitrogen transformation. The environmental problems caused by microplastics are becoming more serious, and the analysis and control of its pollution in the environment have become a research hotspot in the field. The nitrogen transformation and nitrogen cycling in the environment are mainly driven by microorganisms in the environment, and the existence of microplastics can affect the microbial population, abundance and type, thus affecting the transformation of nitrogen. The effect of microplastics on microorganisms involved in nitrogen transformation is briefly described. This paper mainly reviews the research progress on the impacts of microplastics on nitrogen transformation and nitrogen cycling in water, soil, sediment and sewage sludge. Microplastic type, size and concentration can cause obvious difference in the impacts of microplastics on nitrogen transformation. Then, response and mechanism of microplastics to microorganism mediated nitrogen transformation and nitrogen cycling are introduced. Processes of nitrogen transformation are affected by interfering with microorganism diversity and structure, enzyme activities and related coding genes and oxygen flux. Additionally, additives released from microplastics can also affect the microbial activity. However, mechanisms of microplastics on environmental nitrogen transformation and nitrogen cycling are not fully understood due to the lack of relevant research. There are effective strategies to evaluate complex environmental systems, prolong action time, strengthen multi factor and multi-level research, and assist molecular biology and stable isotope technology. This review article can provide valuable insights into the impact of microplastics on microorganisms mediated nitrogen transformation processes and evaluate the impact on ecological and environmental health.


An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloproteinase-1 (Timp-1) Serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients.
The progression of COVID-19 has different clinical presentations, which raises a number of immunological questions. This study aimed to investigate MMP-9 and TIMP-1 levels in patients diagnosed with COVID-19 and whether the MMP-9/TIMP-1 ratio is associated with lung involvement in COVID-19. This study was conducted with 192 patients and 45 healthy controls. ELISA was used to measure the MMP-9 and TIMP-1. The MMP-9 and TIMP-1 levels of the patients were found to be higher than those of the controls. MMP-9 and TIMP-1 were detected more in patients with lung involvement on chest CT scans than in those with no lung involvement on chest CT scans. A comparison of lung involvement levels revealed no difference was found between the groups. The MMP-9/TIMP-1 ratio was 5.8 in the group with lung involvement on chest CT scans and 6.1 in the group without lung involvement on chest CT scans. No difference was found between the two groups. A comparison with respect to lung involvement levels showed that the MMP-9/TIMP-1 ratio difference was found between the groups. Diagnostic and treatment methods targeting MMP-9 activity or neutrophil activation may be important in predicting lung involvement in COVID-19 and directing clinical outcomes.


Heme levels are increased in human failing hearts.
The goal of this study was to characterize the regulation of heme and non-heme iron in human failing hearts. Iron is an essential molecule for cellular physiology, but in excess it facilitates oxidative stress. Mitochondria are the key regulators of iron homeostasis through heme and iron-sulfur cluster synthesis. Because mitochondrial function is depressed in failing hearts and iron accumulation can lead to oxidative stress, we hypothesized that iron regulation may also be impaired in heart failure (HF). We measured mitochondrial and cytosolic heme and non-heme iron levels in failing human hearts retrieved during cardiac transplantation surgery. In addition, we examined the expression of genes regulating cellular iron homeostasis, the heme biosynthetic pathway, and micro-RNAs that may potentially target iron regulatory networks. Although cytosolic non-heme iron levels were reduced in HF, mitochondrial iron content was maintained. Moreover, we observed a significant increase in heme levels in failing hearts, with corresponding feedback inhibition of the heme synthetic enzymes and no change in heme degradation. The rate-limiting enzyme in heme synthesis, delta-aminolevulinic acid synthase 2 (ALAS2), was significantly upregulated in HF. Overexpression of ALAS2 in H9c2 cardiac myoblasts resulted in increased heme levels, and hypoxia and erythropoietin treatment increased heme production through upregulation of ALAS2. Finally, increased heme levels in cardiac myoblasts were associated with excess production of reactive oxygen species and cell death, suggesting a maladaptive role for increased heme in HF. Despite global mitochondrial dysfunction, heme levels are maintained above baseline in human failing hearts.


Catching the Worm Early: An Atypical Case of Bancroftian Filarial Nephropathy.
Filarial glomerular disease has been attributed to circulating immune complex deposition. We report here a rare manifestation of filarial nephropathy with microfilariae documented in glomerular capillaries in addition to immune complex glomerulonephritis, thus suggesting that direct toxicity may also contribute to the pathogenesis of this entity.


DNA damage response: multilevel proteomics gains momentum.
In this issue of Molecular Cell, Beli et al. (2012) introduce a multilevel proteomics approach for parallel quantification of protein phosphorylation, acetylation, and abundance and apply this to the complex signaling network of the DNA damage response.


RNA chain length and stoichiometry govern surface tension and stability of protein-RNA condensates.
Proteomic studies have shown that cellular condensates are frequently enriched in diverse RNA molecules, which is suggestive of mechanistic links between phase separation and transcriptional activities. Here, we report a systematic experimental and computational study of thermodynamic landscapes and interfacial properties of protein-RNA condensates. We have studied the affinity of protein-RNA condensation as a function of variable RNA sequence length and RNA-protein stoichiometry under different ionic environments and external crowding. We have chosen the PolyU sequences for RNA and arginine/glycine-rich intrinsically disordered peptide (RGG) for proteins as a model system of RNA-protein condensates, which we then investigate through in vitro microscopy measurements and coarse-grained molecular dynamics simulations. We find that crowding and RNA chain length can have a major stabilizing effect on the condensation. We also find that the RNA-protein charge ratio is a crucial variable controlling stability, interfacial properties, and the reentrant phase behavior of RGG-RNA mixtures.


Advanced Studies on Rhizoma Dioscoreae Collettii.
Rhizoma Dioscoreae Collettii, is known as Huang Dioscorea collettii, Rhizoma Coptidis Brevisepalae or yellow ginger. It is neutral in nature and bitter in taste which is described to Gan (Liver) meridian, Wei (Stomach) meridian and Pangguang (Bladder) meridian. It was often used in the treatment of chyloid stranguria, gonorrhea, leucorrhagia, rheumatism arthralgia pain, joints disable, and lumbar knee pain syndrome in clinical.


Some characteristics of hydroxylapatite powder particles after plasma spraying.
We have studied the particles of hydroxylapatite (HA) powder, the particles after plasma spraying, their distribution on substrate surface and their condition after transfer through the plasma torch. Mean particle size of HA powders was as follows: HA-A: 3.8 microm, HA-B 88.2 microm. The area of HA coating after plasma spraying, when the torch had a constant position against the substrate surface, shows two characteristic zones: the central part of coating formed mainly from deformed particles and the marginal part of coating with small non-deformed particles. These small non-deformed particles can be found in all zones of the coating and together with greater non-deformed particles and partially deformed particles will unfavourably affect the adhesive and cohesive strength of the coating and its porosity. The maximum diameter of the molten (spherical) particles in the conditions of Ar + H2 plasma, output P = 24 kW was: DA = 25 microm (HA-A) and DB = 65 microm (HA-B). The intervals of dimensions in which most of molten particles occurred were HA-A: 0-15 microm (98%), HA-B: 5-35 microm (84%). From comparison of HA-A and HA-B powders it can be concluded that the transport of HA-A powder was not continuous, the amount of molten HA-A particles was considerably greater (90%) than that of HA-B powder (63%). Phase decomposition and also solubility of HA-A powder (at in vitro tests) was greater. If we consider transport of particles, their melting, splitting and spraying efficiency, the suitable size of HA powder particles for the given spraying conditions is somewhere between the size of HA-A and HA-B particles--let us say--in the interval from 20 to 60 microm.


The deuce-ace of Lassa Fever, Ebola virus disease and COVID-19 simultaneous infections and epidemics in West Africa: clinical and public health implications.
Globally, the prevailing COVID-19 pandemic has caused unprecedented clinical and public health concerns with increasing morbidity and mortality. Unfortunately, the burden of COVID-19 in Africa has been further exacerbated by the simultaneous epidemics of Ebola virus disease (EVD) and Lassa Fever (LF) which has created a huge burden on African healthcare systems. As Africa struggles to contain the spread of the second (and third) waves of the COVID-19 pandemic, the number of reported cases of LF is also increasing, and recently, new outbreaks of EVD. Before the pandemic, many of Africa's frail healthcare systems were already overburdened due to resource limitations in staffing and infrastructure, and also, multiple endemic tropical diseases. However, the shared epidemiological and pathophysiological features of COVID-19, EVD and LF as well their simultaneous occurrence in Africa may result in misdiagnosis at the onset of infection, an increased possibility of co-infection, and rapid and silent community spread of the virus(es). Other challenges include high population mobility across porous borders, risk of human-to-animal transmission and reverse zoonotic spread, and other public health concerns. This review highlights some major clinical and public health challenges toward responses to the COVID-19 pandemic amidst the deuce-ace of recurrent LF and EVD epidemics in Africa. Applying the One Health approach in infectious disease surveillance and preparedness is essential in mitigating emerging and re-emerging (co-)epidemics in Africa and beyond.


Felt stigma proportion in people living with epilepsy: A systematic review.
Numerous inventories to identify felt stigma (FS) in people living with epilepsy (PLWE) have been developed. Past studies have mainly focused on the relationship between FS scores and clinical factors, making it challenging to delineate FS proportions and compare FS between groups. We aimed to integrate FS proportions in PLWE and compare them by continent. We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, and Scopus. Among the identified studies, we chose the ones providing an FS proportion measured by Jacoby's Stigma Scale (JSS) and its revised version (JSS-R) in PLWE. We applied the random-effects model. A total of 63 datasets from 47 studies were included. There were 29,924 PLWE, with 14,323 of them experiencing FS. The overall FS proportion was 48.4%. Of these datasets, 51 used JSS, and 12 used JSS-R. The FS proportions were 44.9% for the former and 62.1% for the latter, with significant heterogeneity. In the intercontinental comparison with 51 datasets employing JSS, the difference in FS proportions was insignificant: 51.2% in Africa, 47.2% in Europe, 35.4% in Asia, and 28.8% in the Middle East. Furthermore, the meta-regression revealed that the year of each primary study did not influence the FS proportion. Among PLWE, FS proportions depended on the choice of a measurement tool. When measured using JSS, the FS proportion was 44.9%, while it was 62.1% when evaluated with JSS-R. Even though the FS proportions were integrated differently, no substantial differences were observed between continents.


The seroepidemiology of Chlamydiae in Finland over the period 1971 to 1987.
The seroepidemiology of chlamydial infections in the Finnish population was studied by analysing the prevalence of chlamydial complement fixing (CF) antibodies in patients sera sent for virus serological screening tests over 17 years from 1971 to 1987. The total number of sera studied was over 160,000. In the early 1970s, the prevalence of chlamydial CF antibodies (CF titres greater than or equal to 8) was low (less than 2%), but later the proportion of seropositive cases rose, and in 1976, 18% of sera contained antibodies. In 1984, the seropositivity rate was over 31%. The prevalence of high chlamydial CF titres (titres greater than or equal to 64) also showed annual variation. In general, under 1% of sera contained chlamydial CF antibodies in high titre, but in 1979 and 1984, distinct peaks occurred when 1.3% and 1.4% of sera, respectively, had titres greater than or equal to 64. The age-related antibody positivity rate showed a decline during early infancy, an increase in childhood and adolescence, and a stable level in adulthood when approximately 20% of the sera contained antibodies. The chlamydial antigen used in this survey was genus-specific, i.e. it detects antibodies against all chlamydial species. Epidemiological data support the hypothesis that infections due to a novel chlamydial species, TWAR chlamydia, are the most likely explanation for the relatively frequent occurrence of chlamydial CF antibodies and for the variation in CF antibody prevalence.


Plasma levels of catechols after fasting in intact or adrenal-demedullated rats.
We compared arterial plasma levels of catechols after a 24-h fast with levels after 24 h of an ad libitum diet in conscious rats. Epinephrine concentrations were significantly decreased after the fast; levels of norepinephrine, dopa, and dihydroxyphenylglycol were unaffected. Adrenal-demedullated rats had decreased levels of dopa regardless of dietary intake and lower levels of norepinephrine after fasting than during the usual diet. The results indicate that fasting decreases adrenomedullary activity in intact animals, with little or no effect on sympathoneural activity.


Long-term treatment with metformin in the prevention of fatty liver in Zucker diabetic fatty rats.
Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats. Male ZDF rats and Zucker lean rats aged 4-8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed. Data demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats. These results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.


Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis.
The Notch ligand Delta1 (Dll1) is expressed in human interfollicular epidermis (IFE) and regulates differentiation and adhesion of cultured human keratinocytes. However, the consequences of deleting Dll1 in mouse epidermis have not been examined. Here, we report that in embryonic mouse skin Dll1 is expressed by patches of keratinocytes in the basal layer of the IFE and in the dermal papilla and hair bulb. In a Dll1 hypomorph mutant that survives until birth, hair follicles formed normally but proliferation and thickness of the IFE were increased. Deletion of Dll1 using Cre recombinase expressed under the control of the keratin-5 (K5) promoter resulted in a delay in the first postnatal anagen, but subsequent hair cycles were normal. As in the hypomorph, IFE proliferation was stimulated and expression of K10 and K17 was disturbed. Older mice developed tumors with elements of IFE differentiation. Keratinocytes cultured from K5Cre x Dll1(flox/flox) epidermis showed a transient increase in proliferation, with a subsequent decrease in integrin expression and increased terminal differentiation. These results demonstrate that Dll1 contributes to the control of proliferation and differentiation in IFE, whereas Jagged1 regulates hair follicle differentiation.


Retinitis Pigmentosa in Onitsha, Nigeria.
Retinitis pigmentosa describes a heterogenous group of progressive hereditary degeneration of the photoreceptor-retinal pigment epithelium complex with varying clinical manifestations. Although studies on the epidemiology of blindness and visual impairment in Nigeria have documented the contribution of retinitis pigmentosa, detailed study of the prevalence, incidence, and pattern of retinitis pigmentosa in Nigeria are few. The aim of this study was to describe the relative frequency rate and pattern of retinitis pigmentosa among new patients at the Guinness Eye Center Onitsha Nigeria. Case files of new patients with clinical features of retinitis pigmentosa seen over a 6-year period were reviewed. Information on age, sex, and associated clinical features were extracted into a standard proforma and analyzed. Thirty-seven (0.6%) of 5876 new patients had retinitis pigmentosa. There were 25 (67.6%) males and 12 (32.4%) females with an age range of 4-76 years; the median age was 33 years. Family history suggested autosomal dominant inheritance in 15 (40.6%) patients, autosomal recessive inheritance 4 (10.8%), X-linked inheritance 9 (24.3%), and 9 (24.3%) sporadic. Six (16.2%) patients were blind (acuity <3/60) and 22 (59.5%) patients had visual impairment (acuity <6/18). Eight (21.6%) patients had coexistent deafness (syndromic retinitis pigmentosa) including two (5.4%) cases of Usher syndrome. The relative frequency rate of retinitis pigmentosa among new patients in our hospital is low but the associated visual and otologic incapacitation are enormous. A prospective study incorporating molecular genetics would more exactly determine the inheritance pattern and the common genes of retinitis pigmentosa in Nigerians.


Knowledge and feelings about colorectal cancer among the Jewish adult population in Israel: A mixed methods study.
Few previous studies found that people's knowledge of colorectal cancer (CRC) risk factors and symptoms is a predictor of high compliance with CRC screening. Feelings about CRC have rarely been examined. This mixed method study is aimed at examining knowledge and feelings about CRC among the Jewish adult population in Israel. One hundred and ninety six Jewish Israelis were interviewed using semi-structured face to face personal interviews. Clinical characteristics and knowledge about CRC were analyzed by quantitative methods. Feelings about CRC were analyzed by the qualitative constant comparative method. Most of the participants were at risk for developing CRC due to their native background as Jews of Eastern European origin. The most well known risk factor was family history of CRC, but only a third were aware of it. Screening for CRC by colonoscopy was known to about half the participants. CRC evoked negative feelings of fear of contracting an oncological disease, stress as a result of a new realty, sadness at the possibility of late discovery, disgust and embarrassment because of the involvement of an intimate area and the connection to body secretions. Positive feelings of optimistic faith and hope were found with regard to survival. The knowledge level of the participants about CRC symptoms, risk factors, and recommended screening was low to moderate. CRC evoked mainly negative feelings. Increasing knowledge about CRC and reducing negative feelings evoked by CRC are essential.


Human sperm cooperate to transit highly viscous regions on the competitive pathway to fertilization.
Human sperm compete for fertilization. Here, we find that human sperm, unexpectedly, cooperate under conditions mimicking the viscosity contrasts in the female reproductive tract. Sperm attach at the head region to migrate as a cooperative group upon transit into and through a high viscosity medium (15-100 cP) from low viscosity seminal fluid. Sperm groups benefit from higher swimming velocity, exceeding that of individual sperm by over 50%. We find that sperm associated with a group possess high DNA integrity (7% fragmentation index) - a stark contrast to individual sperm exhibiting low DNA integrity (> 50% fragmentation index) - and feature membrane decapacitation factors that mediate sperm attachment to form the group. Cooperative behaviour becomes less prevalent upon capacitation and groups tend to disband as the surrounding viscosity reduces. When sperm from different male sources are present, related sperm preferentially form groups and achieve greater swimming velocity, while unrelated sperm are slowed by their involvement in a group. These findings reveal cooperation as a selective mode of human sperm motion - sperm with high DNA integrity cooperate to transit the highly viscous regions in the female tract and outcompete rival sperm for fertilization - and provide insight into cooperation-based sperm selection strategies for assisted reproduction.


Kent bundles in the anterior septal space.
Kent bundles in the anterior septal area of the heart occupy a region of complex morphology. In this study, the anatomical characteristics of the area were reviewed by the dissection of 12 human hearts and then an analysis was done of the results of operation in 15 patients with Kent bundles in this location. One important anatomical finding was the relationship of the atrial septum, the right fibrous trigone, and the underlying membranous ventricular septum to the atrioventricular node and the His bundle. The normal components of the conduction system are protected from injury at operation by encasement in these structures. At operation, the accuracy with which retrograde endocardial mapping could identify the Kent bundle was demonstrated in 8 patients who had Kent bundles clearly shown to be within 2 to 5 mm of the His bundle. Kent bundle interruption in 13 patients was achieved by a precisely placed incision and dissection, and in 2 patients by cryothermia. In 1 of these 2 patients, both the His bundle and the Kent bundle were interrupted when cryothermia was used at a second operation. This study indicates that a Kent bundle and His bundle can be within 2 mm of each other, judging their positions by retrograde endocardial mapping. Final proof of the Kent bundle's location is demonstrated by interruption. With the protection afforded to the His bundle by encasement in the right fibrous trigone, surgical interruption of the adjacent Kent bundle can be accomplished without injury to the His bundle.


Proximal Hamstring Injuries: Management of Tendinopathy and Avulsion Injuries.
To outline the typical presentation, physical examination, diagnostic imaging, and therapeutic treatment options for proximal hamstring injuries to improve awareness, expedient diagnosis, and definitive management. Proximal hamstring tendinopathy and partial-thickness tears can often successfully be managed with a combination of non-operative modalities, including physiotherapy focused on eccentric strengthening, extracorporeal shock wave therapy, or peri-tendinous injections. Surgery is reserved for refractory cases, but can yield good outcomes. Contrastingly, non-operative treatment often leads to unsatisfactory outcomes in complete ruptures, with residual weakness and reduced function with poor return-to-sport rates. Instead, surgical repair can provide satisfactory outcomes, with good-to-excellent functional outcomes and strength, with acute treatment preferred over delayed, chronic repair. Hamstring tendinopathy and partial-thickness tears can be successfully treated non-operatively with good functional outcomes, with surgical repair reserved for refractory cases. Complete tears are best managed with surgical repair, allowing improved strength and functional outcomes.


Age variation in the minimum clinically important difference in SRS-22r after surgical treatment for adult spinal deformity - A single institution analysis in Japan.
The Scoliosis Research Society-22r (SRS-22r) has been shown to be reliable, valid and responsive to change in patients with adult spinal deformity (ASD) undergoing surgery. The minimum clinically important difference (MCID) quantifies a threshold value of improvement that is clinically relevant to the patient. Health-related quality of life scores depend on age. The purpose of this study was to assess MCID threshold values stratified by age for SRS-22r domains in patients with ASD undergoing surgical correction. We identified a consecutive series of 184 Japanese ASD patients who completed the SRS-22r and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) preoperatively and 1 year postoperatively. Effectiveness as measured on the JOABPEQ was used as the anchor to determine MCID for the Function, Pain, and Mental health domains using receiver-operating-characteristic (ROC) curve analysis. We performed MCID analysis stratified by age (<70 or ≥70). Mean preoperative SRS-22r Function score was 2.69 improving to 3.23 at postoperatively (p < 0.001). Mean preoperative SRS-22r Pain score was 3.04 improving to 3.78 at postoperatively (p < 0.001). Mean preoperative SRS-22r Mental health score was 2.72 improving to 3.25 at postoperatively (p < 0.001). There was a statistically difference in change in domain score between "not effective" and "effective" (p < 0.001). The ROC curve analysis methods yielded MCID values of 0.58 for Function, 0.55 for Pain, and 0.70 for Mental health domains. There was difference of MCID value for Function and Mental health domain between aged <70 and ≥70; 0.78 and 0.55 for Function; 0.70 and 0.48 for Mental health. Results of this study showed that MCID threshold values for SRS-22 Function and Mental health domains in older than 70 was lower than in younger than 70, potentially implying that older patients have lower expectation.


Implementation of a virtual learning from discrepancy meeting: a method to improve attendance and facilitate shared learning from radiological error.
To assess the effect on radiologist participation in learning from discrepancy meetings (LDMs) in a multisite radiology department by establishing virtual LDMs using OsiriX (Pixmeo). Sets of anonymised discrepancy cases were added to an OsiriX database available for viewing on iMacs in all radiology reporting rooms. Radiologists were given a 3-week period to review the cases and send their feedback to the LDM convenor. Group learning points and consensus feedback were added to each case before it was moved to a permanent digital LDM library. Participation was recorded and compared with that from the previous 4 years of conventional LDMs. Radiologist feedback comparing the two types of LDM was collected using an anonymous online questionnaire. Numbers of radiologists attending increased significantly from a mean of 12±2.9 for the conventional LDM to 32.7±7 for the virtual LDM (p<0.0001) and the percentage of radiologists achieving the UK standard of participation in at least 50% of LDMs annually rose from an average of 18% to 68%. The number of cases submitted per meeting rose significantly from an average of 11.1±3 for conventional LDMs to 15.9±5.9 for virtual LDMs (p<0.0097). Analysis of 35 returned questionnaires showed that radiologists welcomed being able to review cases at a time and place of their choosing and at their own pace. Introduction of virtual LDMs in a multisite radiology department improved radiologist participation in shared learning from radiological discrepancy and increased the number of submitted cases.


Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.
Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL.


A standard large wound of the corneal epithelium in the rabbit.
A method of iodine vapor cautery was applied to rabbit eyes. The cautery produces an approximately circular area denuded of epithelium of uniform size. The eye is not inflamed, and the very rapid mean healing rate of 1.42 mm2hr-1 was observed.


Microenviromental change after synthetic E-selectins interfere in ischemia-reperfusion in rats and its contribution to endogenetic/exogenous never stem cells.
To explore the special significances in advantages of using anti-inflammatory drugs, such as amelioration of growing conditions and the promotion of cell growth. Utilizing anti-adhesive effects of synthetic E-selectins, we observed the changes of inflammatory cytokines (TNF-α, IL-1β) contented in brain tissues and rat serums in rats hind cerebral ischemia-reperfusion models. Both growth and expression of endogenetic/exogenous neurological stem cells were detected after ameliorated local microenvironment. The contents of TNF-α and IL-1β were decreased in brain tissues and rat serums after applying synthetic E-selectins. Expression of exogenous neurological stem cells was enhanced. Animal neurological functions improved. Anti-inflammatory therapy in early stage could enhance proliferation of stem cells so that it has vital significations in treating cerebrovascular diseases.


CUG as a mutant start codon for cat-86 and xylE in Bacillus subtilis.
The cat-86 gene specifies chloramphenicol acetyltransferase (CAT). The cat-86 start codon is UUG, although related genes have AUG as the start codon. Changing the start codon to AUG increased expression of cat-86 by 36% in Bacillus subtilis. Changing the start codon to GUG and CUG decreased expression to 65% and 30%, respectively, of the level obtained when AUG was the start codon. CUG has not been previously shown to function as a start codon in B. subtilis. N-terminal sequencing of purified CAT protein specified by the CUG mutant, revealed that CUG was indeed the start codon and specified methionine. The gene xylE, which specifies catechol 2,3-dioxygenase, has AUG as its start codon. Changing the start codon for xylE to CUG decreased expression by 98%. However, when the ribosome-binding site sequence for xylE was optimized and the spacing between it and the start codon was increased to 8 nucleotides, xylE activity increased to 13% of the activity observed for AUG. CUG did not function efficiently as a start codon for cat-86 in Escherichia coli. These data suggest conditions under which CUG can function, with modest efficiency, as a start codon in B. subtilis.


A simple and economical chemical neutralization method for the destruction of sulfur mustard and its analogues.
A simple and economical chemical neutralization method is developed against highly toxic chemical warfare agent's viz. sulfur mustard (SM), sesquimustard, and their homologues/analogous. The method involves treatment of chemical warfare agents with sodium in inert solvents. This destruction method of sulfur mustards release innocuous products via desulfurization reactions. The products were characterized by GC-MS technique. The method is suitable in particular, for bulk destruction of heel of mustard stockpiles.


Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver.
Ezetimibe is a novel lipid-lowering agent that inhibits intestinal absorption of dietary and biliary cholesterol. The effects of ezetimibe on low-density lipoprotein (LDL)-cholesterol were found to generally consistent across all subgroups analyzed, including baseline lipid profile, hypertension, diabetes mellitus, and body mass index. Furthermore, recent clinical studies also revealed that co-administration of ezetimibe with on-going statins offered a well-tolerated and efficacious treatment to lower LDL-cholesterol levels in hypercholesterolemic patients with diabetes mellitus or the metabolic syndrome. Niemann-Pick C1 like 1 (NPC1L1) protein is recently found to be critical for intestinal cholesterol absorption, and is a target protein for ezetimibe. Human NPC1L1 protein is predominantly expressed in liver, whereas small intestine expression is only about 2-4% of that found in the liver. Thus, NPC1L1 does not function solely in the intestinal cholesterol absorption. Furthermore, loss of NPC1L1 expression has been shown to protect against diet-induced fatty liver. These observations let us to speculate that ezetimibe will become a new therapeutic approach for the treatment of non-alcoholic fatty liver, the hepatic manifestation of insulin resistant patients with the metabolic syndrome. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does ezetimibe treatment improve fatty liver in patients with hypercholesterolemia or the metabolic syndrome? If the answers are yes, are these beneficial effects of ezetimibe superior to those of other anti-hyperlipidemic resins with equihypolipidemic properties? (2) Does ezetimibe treatment improve insulin sensitivity in fatty liver patients with the metabolic syndrome? (3) How about the effects of ezetimibe treatment on serum levels of adiponectin, a key adipokine with insulin-sensitizing property? Large clinical trials will provide us with more definite information whether ezetimibe treatment can improve fatty liver and resultantly reduce the risk of progression of liver diseases in patients with the metabolic syndrome.


[Use of implants and ankylosed teeth in orthodontics. Review of the literature].
The clinical use of artificial implants or ankylosed teeth as orthodontic anchorage has been reported in the literature. The aim of this paper is to review the published material as a base for the development of the technique.


When to start cytotoxic therapy in asymptomatic patients with hormone refractory prostate cancer?
Until the publication of two pivotal trials, there were no treatment options available that did prolong the overall survival in men with hormone refractory prostate cancer (HRPC). Currently, docetaxel-based cytotoxic treatment is considered as a standard of care in all the patients with progressive metastatic HRPC. The use of this treatment regimen renders an equal survival benefit in all the subgroups of patients; however, there is a substantial difference in the overall survival between the subgroups. This review addresses the optimal timing of the cytotoxic treatment in asymptomatic patients with HRPC.


Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease.
There is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is associated with CAD, and the effects of testosterone on CAD as reported in literature have been considered as anti-atherosclerotic. The present study aimed to examine the possible association between serum GDF-15 and testosterone in male CAD patients. GDF-15 and testosterone concentrations were determined in blood samples of 426 male patients with CAD and 220 male controls. Serum concentrations of hs-CRP, and other baseline characteristics were also measured. Serum levels of GDF-15 were higher in CAD patients when compared to controls, and testosterone concentrations were lower (p < 0.001). Patients with low testosterone levels had higher concentrations of GDF-15 (p < 0.001). In stratified analyses, inverse relations between GDF-15 levels and testosterone were noted for almost all strata, stratified by categories of hs-CRP, leukocytes, neutrophils, neutrophil to lymphocyte ratio, glucose, HDL-c, and LDL-c, and whether had hypertension, diabetes, and underwent percutaneous coronary intervention (PCI). Furthermore, in the linear regression models with bootstrap resampling with 1000 replications, high GDF-15 levels were independently associated with testosterone deficiency in male patients with CAD. In male patients with CAD, high GDF-15 levels were associated with testosterone deficiency. These results support that upregulation of GDF-15 in the presence of low testosterone levels during CAD progression is a potential mechanism by which GDF-15 affects CAD.


Characterizing Regionalization of Inflammatory Bowel Disease Hospitalizations and Operations in Washington State.
Hospitalizations for inflammatory bowel disease (IBD) are a major contributor of healthcare utilization. We assessed IBD hospitalizations and surgical operations in Washington State to characterize regionalization patterns. We identified a cohort of hospitalizations for Crohn's disease (CD) or ulcerative colitis (UC) from 2008 to 2019 using Washington State's Comprehensive Hospital Abstract Reporting System (CHARS). Hospitalizations were characterized by emergent or elective acuity and whether an operation or endoscopic procedure was performed. Facility volume and distance travelled by patients were used to determine regionalization. There were 20,494 IBD-related hospitalizations at 95 hospitals: 13,585 (66.3%) with CD and 6,909 (33.7%) with UC. Emergencies accounted for 78.2% of all IBD-related hospitalizations and did not differ between CD (78.3%) and UC (77.9%) (p = 0.54). Surgery was performed during 10.3% and endoscopy during 30.6% of emergent hospitalizations. 72.0% of emergent hospitalizations occurred at 22 facilities, while 71.1% of elective hospitalizations were concentrated at 9 facilities. Operations were performed during 78.5% of elective hospitalizations, and five hospitals performed 69% of all elective surgery. Laparoscopic surgery increased in both emergent (17% to 52%, p < 0.001) and elective operations (18% to 42%, p < 0.001) from 2008 to 2019. In Washington State, most IBD hospitalizations were emergent, which were decentralized and typically non-operative. By contrast, most elective admissions involved surgery and were centralized at a few high-volume centers. Further understanding the drivers behind IBD hospitalizations may help optimize emergent medical and elective surgical care at a state level.


Ultrasmall 2 D Cox Zn2-x (Benzimidazole)4 Metal-Organic Framework Nanosheets and their Derived Co Nanodots@Co,N-Codoped Graphene for Efficient Oxygen Reduction Reaction.
The development of nonprecious metal-nitrogen-carbon (M-N-C) materials with efficient metal utilization and abundant active sites for the oxygen reduction reaction (ORR) is of great significance for fuel cells and metal-air batteries. Ultrasmall 2 D Cox Zn2-x (benzimidazole)4 [Cox Zn2-x (bim)4 ] bimetallic metal-organic framework (MOF) nanosheets (≈2 nm thick) are synthesized by a novel bottom-up strategy and then thermally converted into a core-shell structure of sub-5 nm Co nanodots (NDs) wrapped with 2 to 5 layers of Co,N-codoped graphene (Co@FLG). The size of the Co NDs in Co@FLG could be precisely controlled by the Co/Zn ratio in the Cox Zn2-x (bim)4 nanosheet. As an ORR electrocatalyst, the optimized Co@FLG exhibits an excellent half-wave potential of 0.841 V (vs. RHE), a high limiting current density of 6.42 mA cm-2 , and great stability in alkaline electrolyte. Co@FLG also has great ORR performance in neutral electrolyte, as well as in Mg-air batteries. The experimental studies and DFT calculations reveal that the high performance of Co@FLG is mainly attributed to its great O2 absorptivity, which is endowed by the abundant Co-Nx and pyridinic-N in the FLG shell and the strong electron-donating ability from the Co ND core to the FLG shell. This elevates the eg orbital energy of CoII and lowers the activation energy for breaking the O=O/O-O bonds. This work sheds light on the design and fabrication of 2 D MOFs and MOF-derived M-N-C materials for energy storage and conversion applications.


Treatment of bladder cancer with interstitial iridium-192 implantation and external beam irradiation.
Although interstitial implantation of invasive carcinoma of the bladder has been shown to be an effective treatment in Europe, there has been little experience with this method in the U.S. During the past 6 years, 14 patients at the Hospital of the University of Pennsylvania with single bladder tumors less than 5 cm and no evidence of carcinoma in situ on random bladder biopsies have been treated by a combination of external beam radiation and iridium wire implant. The iridium wire is inserted by an afterloading technique following tumor exposure via suprapubic cystotomy. Following delivery of the prescribed dose, the sources are removed percutaneously. Three patients with recurrent or high grade T1 lesions and 11 patients with T2-T3A lesions have been treated. With a median follow-up of 22 months (range 17 to 65 months), 9 patients are currently NED, 4 patients have died of disease, and 1 patient has died of intercurrent disease. There have been two isolated bladder recurrences, both non-invasive, one having been treated with cystectomy and one being treated locally. In addition, one patient developed regional failure, two developed distant metastases only, and one developed local recurrence following distant failure. The 2-year actuarial local control rate is 84%, with an overall 2-year actuarial survival of 66%. Complications have been minimal. Bladder implantation by this method is technically simple and produces excellent local control with acceptable morbidity.


Effects of lentivirus-mediated ornithine decarboxylase gene on the proliferation and apoptosis of fibroblast-like synoviocytes in rats with arthritis.
This study aimed to explore the effects of lentivirus-mediated ornithine decarboxylase (ODC) gene on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) in rats with rheumatoid arthritis (RA). Twenty Lewis rats were randomized into control group (ten rats without processing) and RA group (ten rats of adjuvant-induced arthritis). The third-generation FLSs were randomized into test, control and blank groups. MTT assay and flow cytometry were employed to detect cell proliferation and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), and interleukin-2 (IL-2). Lewis rats in the RA group became ill from 11days on and got seriously ill 18days after modeling. However, rats in the control group had no obvious change. MTT assay showed that the test group had higher cell proliferation than the blank and control groups (P1<0.001; P2<0.001). Flow cytometry revealed that the apoptosis of FLSs in the test group was significantly lower than that in the blank and control groups (P1<0.001; P2<0.001). ELISA showed that the test group had higher TNF-α, IFN-γ and IL-2 level than the control and blank groups (all P<0.001), but no significant difference was found between the control and blank groups (all P>0.05). The results indicated that overexpression of ODC gene promotes the proliferation while suppressing apoptosis of FLSs in rats with RA.


Global research trends related to coronavirus disease 2019 and the aged: a bibliometric analysis.
A bibliometric analysis covering only the production of original studies or considering world production until 2022 has yet to be conducted. The creation and advancement of vaccines have also influenced research priorities, demonstrating the need for a new approach to this subject. To analyze worldwide scientific production related to coronavirus disease 2019 (COVID-19) and the aged and to describe what has already been produced. Bibliometric analysis with a quantitative approach. The search terms "COVID-19," "SARS-CoV-2," "Aged," and "Elderly" were used to retrieve articles from the Web of Science database. A total of 684 articles were included in the analysis. Data were imported into RStudio Desktop Software and linked to R Software. The Bibliometrix R package and VOSviewer software were used for analysis. Most articles were published in 2020. These were produced by 4,937 authors and published in 379 journals. The keyword most used by the authors was "COVID-19." Publications from 77 countries were obtained. China had the highest article production ranking, and Spain collaborated the most. The articles addressed the implications of the pandemic on the aged, the relationship between vaccination in the aged, and the implications for the disease itself. Further research should be conducted, mainly concerning vaccines and vaccination of the aged, owing to the need for and importance of immunization in this risk group, including assessing the long-term effects of vaccines.


Health-related lipids components of sardine muscle as affected by photooxidation.
The aim of this study was to evaluate the oxidative stability of sardine muscle lipids as related to the storage conditions. Whole sardines were stored at 4 °C for 4h under light exposure and at dark. The lowest levels of peroxide value (PV), thiobarbituric acid reactive substances (TBARs), cholesterol oxidation products (COPs) and the highest level of polyunsaturated fatty acids (PUFAs) content, especially PUFA n-3, were found in the untreated sardines (time zero). After light exposure, PUFA dramatically dropped (up to a 19% decrease) and a marked increase of PV (11.8 meq O₂/kg fat), TBARs (3.7 mg MDA/kg meat) and COPs (3.7 μg/g muscle) was observed; under darkness, the values of the oxidation parameters were similar to those found in untreated sardines. Although cholesterol oxidation rate did not exceed 0.9%, further research is required about toxicity levels of the single COPs, to better understand if the COPs levels found in untreated and photoxidized muscle (0.62-3.72 μg/g of muscle) do not represent a risk for human health.


Hibernoma: report of two cases.
Hibernomas are rare tumors of fat which are most often benign. Arteriographic fingings may be misleading with respect to the diagnosis of malignancy preoperatively. These uncommon tumors may be confused prior to surgery with lipomas, soft tissue sarcomas, and hemangiomas.


The cause of carbon isotope minimum events on glacial terminations.
The occurrence of carbon isotope minima at the beginning of glacial terminations is a common feature of planktic foraminifera carbon isotopic records from the Indo-Pacific, sub-Antarctic, and South Atlantic. We use the delta13C record of a thermocline-dwelling foraminifera, Neogloboquadrina dutertrei, and surface temperature estimates from the eastern equatorial Pacific to demonstrate that the onset of delta13C minimum events and the initiation of Southern Ocean warming occurred simultaneously. Timing agreement between the marine record and the delta13C minimum in an Antarctic atmospheric record suggests that the deglacial events were a response to the breakdown of surface water stratification, renewed Circumpolar Deep Water upwelling, and advection of low delta13C waters to the convergence zone at the sub-Antarctic front. On the basis of age agreement between the absolute delta13C minimum in surface records and the shift from low to high delta13C in the deep South Atlantic, we suggest that the delta13C rise that marks the end of the carbon isotope minima was due to the resumption of North Atlantic Deep Water influence in the Southern Ocean.


Three-dimensional printing in a patient with pulmonary artery pseudoaneurysm and complex congenital heart disease-A case report.
3D-printing is a powerful tool in patients with complex anatomy undergoing cardiac surgery.


Low-dose apixaban or rivaroxaban as secondary prophylaxis of upper extremity deep vein thrombosis.
Upper extremity deep vein thrombosis (UEDVT) may occur without inciting factor or may be secondary to malignancy, surgery, trauma, central venous catheter or related to thoracic outlet syndrome (TOS). International guidelines recommend anticoagulant treatment for at least three months, in particular the use of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). No data on extended anticoagulant therapy and reduced dose of DOACs have been reported in patients affected by UEDVT with persistent thrombotic risk (active cancer, major congenital thrombophilia) or without affected vein recanalization. In our retrospective observational study, including 43 patients, we treated secondary UEDVT with DOACs. In the acute phase of thrombosis (median time of 4 months), we used therapeutic dose of DOACs; the 32 patients with permanent thrombotic risk factors or without recanalization of the UEDVT were shifted to low-dose DOACs (apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily). During therapy with full-dose DOACs, 1 patient presented recurrence of thrombosis; no thromboembolic events were observed during treatment with low-dose DOACs. During full-dose treatment, 3 patients presented minor hemorrhagic complications; no hemorrhagic events were observed during DOACs at low dose. We think our preliminary data could support the indication to extend the anticoagulation with dose reduction of DOACs in patients affected by UEDVT and no-transient thrombotic risk. These data should be confirmed in randomized controlled prospective study.


Comparison of the actual amount of axial movement of 3 aspheric intraocular lenses using anterior segment optical coherence tomography.
To compare the mean effective lens position (ELP) and actual amount of axial movement of 3 aspheric intraocular lenses (IOLs) using anterior segment optical coherence tomography (AS-OCT). Department of Ophthalmology, Korea University College of Medicine, Seoul, South Korea. Retrospective comparative study. Consecutive patients had phacoemulsification with aspheric IOL implantation. The ELP measurements by AS-OCT were taken 1 week and 1, 3, and 6 months postoperatively. The ELPRMS was defined as the root mean square (RMS) of the change in ELP at each follow-up timepoint. An XL Stabi ZO 3-plate IOL was implanted in 30 eyes, an Acrysof IQ C-loop IOL in 22 eyes, and an Akreos MI-60 4-plate IOL in 17 eyes. The 4-plate IOL showed significant changes in the mean ELP from 1 week to 1 month and from 3 to 6 months postoperatively (P=.005 and P=.028, respectively). The changes of the other 2 IOLs were insignificant during the 3 postoperative visits. However, the mean ELPRMS of the C-loop IOL (0.06 mm ± 0.31 [SD]) was smaller than that of the 3-plate IOL (0.14 ± 0.28 mm) and the 4-plate IOL (0.20 ± 0.35 mm) (P=.014 and P=.023, respectively) during the 3 timepoints. An appropriate method based on the actual amount of axial IOL movement, such as the ELPRMS, is needed to assess the axial positional stability of IOLs. No author has a financial or proprietary interest in any material or method mentioned.


125I brachytherapy alone for recurrent or locally advanced adenoid cystic carcinoma of the oral and maxillofacial region.
This retrospective study was to evaluate the local control and survival of (125)I brachytherapy for recurrent and/or locally advanced adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. A total of 38 patients with recurrent and/or locally advanced ACC of the oral and maxillofacial region received (125)I brachytherapy alone from 2001-2010. Twenty-nine were recurrent cases following previous surgery and radiation therapy. The other 9 cases involved primary tumors. Overall, 12 tumors were located in the major salivary glands, 12 in the minor salivary glands, and 14 in the paranasal region, the nasal cavity or the skull base. The prescribed dose was 100-160 Gy. Patients were followed for 12-122 months (median 51 months). The 2-, 5-, and 10-year local tumor control rates were 86.3, 59, and 31.5 %, respectively. The 2-, 5-, and 10-year overall survival rates were 92.1, 65 and 34.1 %, respectively. Tumors > 6 cm had significantly lower local control and survival rates. No severe complications were observed during follow-up. (125)I brachytherapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent ACC.


Association between liver function and metabolic syndrome in Chinese men and women.
Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS.


Superior portosystemic collateral circulation estimated by azygos blood flow in patients with cirrhosis. Lack of correlation with oesophageal varices and gastrointestinal bleeding. Effect of propranolol.
In patients with cirrhosis, superior portosystemic collateral circulation was evaluated by the continuous thermodilution method in the azygos vein. Azygos blood flow was 5 times higher in a group of patients with cirrhosis (alcoholic in 27, cryptogenic in 8, post-hepatitic in 2 and primary biliary cirrhosis in 1), than in a group of patients without portal hypertension (steatosis in 2, granulomatous hepatitis in 2, persistent chronic hepatitis in 2 and Hodgkin's disease in 1). Azygos blood flow was not different in cirrhotic patients with no visible, in those with small-sized, and in those with large sized oesophageal varices. Azygos blood flow was not different in cirrhotic patients with and without a previous episode of gastrointestinal bleeding. Fifteen min after intravenous administration of 15 mg of propranolol, azygos blood flow significantly decreased whereas azygos blood flow did not change after placebo. The decrease in azygos blood flow was significantly more marked than the reduction in cardiac output. It is concluded that superior portosystemic collateral blood flow is elevated in patients with cirrhosis and that the reduction in this collateral circulation might explain the efficiency of propranolol in the prevention of recurrent gastrointestinal bleeding.


Facial defect augmentation with a dermal-fat graft.
The augmentation of facial soft-tissue defects can pose a difficult problem for the surgeon. Bone tends to resorb, giving unpredictable results, and alloplastic materials are firm to the touch and can migrate in the tissues. The dermal-fat graft provides a soft, natural-appearing augmentation. In the case reported here a 2-year follow-up shows excellent results obtained with the use of a dermal-fat graft to augment a soft-tissue defect over the mandible.


Characterization of kinetic parameters and the formation of volatile compounds during the tequila fermentation by wild yeasts isolated from agave juice.
The production of aroma compounds during tequila fermentation using four native yeast strains isolated from agave juice was quantified at controlled (35 degrees C) and uncontrolled temperatures (room temperature) by gas chromatography (FID). Three of the four strains were identified as Saccharomyces cerevisiae (MTLI 1, MALI 1 and MGLI 1) and one as Kloeckera apiculata (MALI 2). Among the aroma compounds produced, acetaldehyde has the highest accumulation at the controlled temperature and before 50% of sugar was consumed. The S. cerevisiae strains produced ethyl acetate in almost the same quantity at a concentration of 5 mg/L and the K. apiculata produced six-times more (30 mg/L) than the S. cerevisiae strains, independent of the fermentation temperature. The rate and amount of 1-propanol, amyl alcohols and isobutanol production were affected by the type of yeast used. The K. apiculate strain produced 50% less of the higher alcohols than the Saccharomyces strains. The results obtained showed that indigenous isolated yeasts play an important role in the tequila flavor and suggest that mixtures of these yeasts may be used to produce tequila with a unique and desirable aroma.


Tamoxifen's impact as a preventive agent in clinical practice and an update on the STAR trial.
Tamoxifen has long been an established adjuvant treatment in the management of advanced breast cancer. Studies carried out by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and other groups also established its use in the treatment of early breast cancer and subsequently as a risk-reducing agent for the development of contralateral breast cancer in breast cancer patients. The NSABP began its investigation of tamoxifen as a preventive agent in the early 1990s in women who had never had the disease with its Breast Cancer Prevention Trial (P-1). Its second prevention study, the STAR trial, is currently under way.


Effect of an Ayurvedic compound preparation on the ability of rat urine to influence mineral phase formation.
Rat urine could inhibit not only the in vitro initial precipitation of calcium and phosphate/oxalate ions as mineral phase but also the subsequent growth of the preformed mineral phase. Oral administration of the aqueous extract of a commercially available Ayurvedic compound preparation to rats, was found to significantly increase the ability of the urine samples to inhibit both the initial mineral phase formation and its subsequent growth.


Diagnostic value of an enzyme-linked immunospot assay for interferon-γ in genitourinary tuberculosis.
The aim of this study was to evaluate the diagnostic performance of an enzyme-linked immunospot (ELISPOT) assay for interferon-γ in patients with suspected genitourinary tuberculosis (TB). A total of 30 patients with suspected genitourinary TB at the National Taiwan University Hospital, Taipei, Taiwan, were prospectively enrolled from January 2007 to December 2009, and 12 of whom had positive urine culture for Mycobacterium tuberculosis. Frequency and dysuria were the most common symptoms noted in 6 (50.0%) and 4 (33.3%) patients, respectively. Pyuria was the most common finding of urinalysis noted in 11 (91.7%) patients. Six (50.0%) patients had positive acid-fast stain in urine. Among the 30 patients, 13 patients had positive ELISPOT assay. Eleven patients with positive ELISPOT assay had culture-confirmed TB, and the remaining 2 patients without evidence of active TB had positive ELISPOT assay. The overall sensitivity, specificity, positive predictive value, and negative predictive value for genitourinary TB diagnosis by the ELISPOT assay were 91.7% (95% confidence interval [CI], 59.8-99.6%), 88.9% (95% CI, 63.9-98.1%), 84.6% (95% CI, 53.7-97.3%), and 94.1% (95% CI, 69.2-96.7%), respectively. In conclusion, ELISPOT assay can provide useful support in diagnosing genitourinary TB.


Study of the sRNA RsmY involved in the genetic regulation of the synthesis of alginate and alkyl resorcinols in Azotobacter vinelandii.
Azotobacter vineladii is a Gram-negative bacterium that produces alginate and poly-hydroxybutyrate (PHB), two polymers of biotechnological interest. This bacterium has the ability to form desiccation-resistant cysts. In the cyst the membrane phospholipids are replaced with a family of phenolic lipids called alkylresorcinols (ARs). The alginate, PHB, and ARs are controlled by the GacS/A two-component system and the small regulatory RNA (sRNA) RsmZ1, belonging to the Rsm (Csr) regulatory system. The Rsm (Csr) systems usually possess two or more sRNAs, in this regard A. vinelandii is the bacterium with the highest number of rsm-sRNAs. Originally, the presence of two sRNAs of the RsmY family (RsmY1 and RsmY2) was reported, but in a subsequent work it was suggested that they conformed to a single sRNA. In this work we provide genetic evidence confirming that rsmY1 and rsmY2 constitute a single gene. Also, it was established that rsmY mutation decreased alginate and ARs production, but did not affect the PHB synthesis. Transcriptional studies showed that rsmY has its higher expression during the stationary growth phase, and in the absence of RsmZ1, rsmY increases its transcription. Interestingly, rsmY expression was influenced by the carbon source, but its expression did not correlate with alginate production.


FtsZ phosphorylation pleiotropically affects Z-ladder formation, antibiotic production, and morphogenesis in Streptomyces coelicolor.
The GTPase FtsZ forms the cell division scaffold in bacteria, which mediates the recruitment of the other components of the divisome. Streptomycetes undergo two different forms of cell division. Septa without detectable peptidoglycan divide the highly compartmentalised young hyphae during early vegetative growth, and cross-walls are formed that dissect the hyphae into long multinucleoid compartments in the substrate mycelium, while ladders of septa are formed in the aerial hyphae that lead to chains of uninucleoid spores. In a previous study, we analysed the phosphoproteome of Streptomyces coelicolor and showed that FtsZ is phosphorylated at Ser 317 and Ser389. Substituting Ser-Ser for either Glu-Glu (mimicking phosphorylation) or Ala-Ala (mimicking non-phosphorylation) hinted at changes in antibiotic production. Here we analyse development, colony morphology, spore resistance, and antibiotic production in FtsZ knockout mutants expressing FtsZ alleles mimicking Ser319 and Ser387 phosphorylation and non-phosphorylation: AA (no phosphorylation), AE, EA (mixed), and EE (double phosphorylation). The FtsZ-eGFP AE, EA and EE alleles were not able to form observable FtsZ-eGFP ladders when they were expressed in the S. coelicolor wild-type strain, whereas the AA allele could form apparently normal eGFP Z-ladders. The FtsZ mutant expressing the FtsZ EE or EA or AE alleles is able to sporulate indicating that the mutant alleles are able to form functional Z-rings leading to sporulation when the wild-type FtsZ gene is absent. The four mutants were pleiotropically affected in colony morphogenesis, antibiotic production, substrate mycelium differentiation and sporulation (sporulation timing and spore resistance) which may be an indirect result of the effect in sporulation Z-ladder formation. Each mutant showed a distinctive phenotype in antibiotic production, single colony morphology, and sporulation (sporulation timing and spore resistance) indicating that the different FtsZ phosphomimetic alleles led to different phenotypes. Taken together, our data provide evidence for a pleiotropic effect of FtsZ phosphorylation in colony morphology, antibiotic production, and sporulation.


Stereology of nerve cross sections.
Quantitative morphological data from nerve cross sections are of great value in experimental, developmental, and pathological studies. Efficient unbiased stereological techniques to estimate the total numbers and absolute size distributions of both myelinated and unmyelinated axons from a small sample of axons are described and evaluated. Axon numbers are estimated with the fractionator technique. Axon areas are estimated with the 2D-nucleator and the point counting technique for myelinated and unmyelinated axons, respectively. The axon perimeter is estimated by use of a line grid, and the myelin sheath thickness by direct orthogonal measurements in uniform, random locations. The empirically evaluated variance of the number estimates of myelinated axons was approximately approximately 0.05 when approximately 200 axons were counted. The empirical variance of area estimates obtained with a four-way 2D-nucleator was approximately 0.10 and contributed less than 0.5% to the observed total variance of axon areas within an animal. A light microscope modified for stereology with computer assisted stereological test systems and a motorised stage facilitate the acquisition of data for the myelinated axons, which is of primary interest in most studies. The unmyelinated axons are evaluated at the more time consuming electron microscopical level.


Nonparametric Bayesian inference of the fiber orientation distribution from diffusion-weighted MR images.
Diffusion MR imaging provides a unique tool to probe the microgeometry of nervous tissue and to explore the wiring diagram of the neural connections noninvasively. Generally, a forward model is established to map the intra-voxel fiber architecture onto the observable diffusion signals, which is reformulated in this article by adopting a measure-theoretic approach. However, the inverse problem, i.e., the spherical deconvolution of the fiber orientation density from noisy MR measurements, is ill-posed. We propose a nonparametric representation of the tangential distribution of the nerve fibers in terms of a Dirichlet process mixture. Given a second-order approximation of the impulse response of a fiber segment, the specified problem is solved by Bayesian statistics under a Rician noise model, using an adaptive reversible jump Markov chain Monte Carlo sampler. The density estimation framework is demonstrated by various experiments with a diffusion MR dataset featuring high angular resolution, uncovering the fiber orientation field in the cerebral white matter of the living human brain.


3,5-Disubstituted Isoxazole Derivatives: Potential Inhibitors of Inflammation and Cancer.
The products of arachidonic acid metabolism by lipoxygenase (LOX) and cyclooxygenase (COX) significantly contribute to inflammation and carcinogenesis. Particularly, overproduction of leukotrienes and prostaglandins contribute to tumor growth by inducing formation of new blood vessels that sustain tumor cell viability and growth. Hence, search for novel anticancer drug via inhibition of LOX and COX enzymes constitutes an impressive strategy till date. In this context, a series of isoxazole derivatives were synthesized and screened for their anti-inflammatory activity via LOX and COX inhibition. Among these, 3-(3-methylthiophen-2-yl)-5-(3,4,5-trimethoxyphenyl)isoxazole (2b) showed significant inhibitory activity toward LOX and COX-2. Additionally, 2b showed a good inhibition of tumor growth, peritoneal angiogenesis, and ascite formation in Ehrlich ascites carcinoma (EAC) cell mouse model. Further, the in silico molecular studies also revealed that the compound 2b binds to the catalytic domain of LOX and COX-1 and COX-2 strongly with high atomic contact energy (ACE) score compared to standard drug. These initial pharmacological data support the fact that the compound 2b serves as the basis in developing anti-inflammatory and anticancer agents.


Membrane anchoring of aminoacyl-tRNA synthetases by convergent acquisition of a novel protein domain.
Four distinct aminoacyl-tRNA synthetases (aaRSs) found in some cyanobacterial species contain a novel protein domain that bears two putative transmembrane helices. This CAAD domain is present in glutamyl-, isoleucyl-, leucyl-, and valyl-tRNA synthetases, the latter of which has probably recruited the domain more than once during evolution. Deleting the CAAD domain from the valyl-tRNA synthetase of Anabaena sp. PCC 7120 did not significantly modify the catalytic properties of this enzyme, suggesting that it does not participate in its canonical tRNA-charging function. Multiple lines of evidence suggest that the function of the CAAD domain is structural, mediating the membrane anchorage of the enzyme, although membrane localization of aaRSs has not previously been described in any living organism. Synthetases containing the CAAD domain were localized in the intracytoplasmic thylakoid membranes of cyanobacteria and were largely absent from the plasma membrane. The CAAD domain was necessary and apparently sufficient for protein targeting to membranes. Moreover, localization of aaRSs in thylakoids was important under nitrogen limiting conditions. In Anabaena, a multicellular filamentous cyanobacterium often used as a model for prokaryotic cell differentiation, valyl-tRNA synthetase underwent subcellular relocation at the cell poles during heterocyst differentiation, a process also dependent on the CAAD domain.


Association Between Antibiotic Redosing Before Incision and Risk of Incisional Site Infection in Children With Appendicitis.
To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis. Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing before incision. This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from July 2016 to June 2020 who received antibiotics upon diagnosis of appendicitis between 1 and 6 hours before incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within 1 hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events. A total of 3533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P <0.001) and iSSI rates were similar between groups [redosed: 1.2% vs non-redosed: 1.3%; odds ratio (OR) 0.84, (95%,CI, 0.39-1.83)]. In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs nonredosed: 2.5%; OR: 0.38, (95% CI, 0.17-0.84)], but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity. Redosing of antibiotics within 1 hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.


Magnetic nanoparticles incorporation into different substrates for dyes and heavy metals removal-A Review.
Substantial discharge of hazardous substances, especially dyes and heavy metal ions to the environment, has become a global concern due to many industries neglecting the environmental protocols in waste management. A massive discharge of contaminantsfrom different anthropogenic activities, can pose alarming threats to living species and adverse effect to the ecosystem stability. In the process of treating the polluted water, various methods and materials are used. Hybrid nanocomposites have attained numerous interest due to the combination of remarkable features of the organic and inorganic elements in a single material. In this regards, carbon and polymer based nanocomposites have gained particular interest because of their tremendous magnetic properties and stability. These nanocomposites can be fabricated using several approaches that include filling, template, hydrothermal, pulsed-laser irradiation, electro-spinning, detonation induced reaction, pyrolysis, ball milling, melt-blending, and many more. Moreover, carbon-based and polymer-based magnetic nanocomposites have been utilized for an extensive number of applications such as removal of heavy metal and dye adsorbents, magnetic resonance imaging, and drug delivery. This review emphasized mainly on the production of magnetic carbon and polymer nanocomposites employing various approaches and their applications in water and wastewater treatment. Furthermore, the future opportunities and challenges in applying magnetic nanocomposites for heavy metal ion and dye removal from water and wastewater treatment plant.


The Drosophila juvenile hormone receptor candidates methoprene-tolerant (MET) and germ cell-expressed (GCE) utilize a conserved LIXXL motif to bind the FTZ-F1 nuclear receptor.
Juvenile hormone (JH) has been implicated in many developmental processes in holometabolous insects, but its mechanism of signaling remains controversial. We previously found that in Drosophila Schneider 2 cells, the nuclear receptor FTZ-F1 is required for activation of the E75A gene by JH. Here, we utilized insect two-hybrid assays to show that FTZ-F1 interacts with two JH receptor candidates, the bHLH-PAS paralogs MET and GCE, in a JH-dependent manner. These interactions are severely reduced when helix 12 of the FTZ-F1 activation function 2 (AF2) is removed, implicating AF2 as an interacting site. Through homology modeling, we found that MET and GCE possess a C-terminal α-helix featuring a conserved motif LIXXL that represents a novel nuclear receptor (NR) box. Docking simulations supported by two-hybrid experiments revealed that FTZ-F1·MET and FTZ-F1·GCE heterodimer formation involves a typical NR box-AF2 interaction but does not require the canonical charge clamp residues of FTZ-F1 and relies primarily on hydrophobic contacts, including a unique interaction with helix 4. Moreover, we identified paralog-specific features, including a secondary interaction site found only in MET. Our findings suggest that a novel NR box enables MET and GCE to interact JH-dependently with the AF2 of FTZ-F1.


A pre-conditioning protocol of peripheral blood derived endothelial colony forming cells for endothelialization of tissue engineered constructs.
In regenerative medicine, autologous endothelial colony forming cells (ECFCs) bear the greatest potential to be used for surface endothelialization of tissue engineered constructs, as they are easily attainable and possess a high proliferation rate. The aim of this study was to develop a standardized pre-conditioning protocol under dynamic conditions simulating the physiology of human circulation to improve the formation of a flow resistant monolayer of ECFCs and to enhance the antithrombogenicity of the endothelial cells. The main focus of the study was to consequently compare the cellular behavior under a steady laminar flow against a pulsatile flow. Mononuclear cells were isolated out of peripheral blood (PB) buffy coats and plated on uncoated tissue culture flasks in anticipation of guidelines for Advanced Therapy Medicinal Products. ECFCs were identified by typical surface markers such as CD31, CD146 and VE-Cadherin. To explore the effects of dynamic cultivation, ECFCs and human umbilical vein endothelial cells were comparatively cultured under either laminar or pulsatile (1 Hz) flow conditions with different grades of shear stress (5 dyn/cm2versus 20 dyn/cm2). High shear stress of 20 dyn/cm2 led to a significant upregulation of the antithrombotic gene marker thrombomodulin in both cell types, but only ECFCs orientated and elongated significantly after shear stress application forming a confluent endothelial cell layer. The work therefore documents a suitable protocol to pre-condition PB-derived ECFCs for sustainable endothelialization of blood contacting surfaces and provides essential knowledge for future cultivations in bioreactor systems.