Willingness to take a screening test for colorectal cancer: a community-based survey in Malaysia.
The aims of the study were (i) to determine the knowledge and perceptions of colorectal cancer (CRC), (ii) to explore the willingness of the study population to take a screening test for CRC, and (iii) to identify factors affecting the willingness to take a screening test for CRC. A cross-sectional survey was carried out in a semiurban town in Malaysia using a pretested structured questionnaire. Descriptive statistics were determined for all important variables. A binary logistic regression model was introduced to identify independent predictors of the willingness to take a screening test. Factors influencing willingness were explored according to the constructs of the health belief model. Of the 256 respondents who had heard about CRC, the majority were aware of altered bowel habits (67.3%) or the presence of blood in stool or rectal bleeding (63.4%) as the warning symptoms. Although 38% of the respondents knew of colonoscopy as the screening test, 22% were not aware of any screening test for CRC. A majority (77.4%) showed willingness to take a screening test for CRC. In the multivariate analysis, 'having family or friends with history of CRC' and 'self-perceived risk' were the two significant variables for predicting the acceptance of CRC screening among the study population. Findings suggested that the respondents' knowledge of the CRC screening test was inadequate, albeit a high proportion expressed their intention to take screening tests. Health education on the CRC addressing available screening tests and the benefits of early screening for CRC should be scaled up.


[The middle meningeal blood supply to the posterior fossa (author's transl)].
The middle meningeal artery can sometimes supply the complete vascularisation of the posterior fossa, i.e., the dura mater of the cerebellar fossa and the tentorium cerebelli. The authors present an anatomic and radiologic correlative study based upon an unusual case where the middle meningeal artery arose from the ascending pharyngeal artery and vascularised the entire posterior cerebellar fossa.


Allogeneic bone marrow transplantation in 24 patients with multiple myeloma reported to the EBMT registry.
Twenty-four patients with multiple myeloma received an allogeneic bone-marrow graft from HLA-compatible sibling donors (n = 23), or a twin donor (n = 1). Eighteen patients are alive, 1-36 months post bone-marrow transplantation (median 14 months). Ten of these patients had no signs of multiple myeloma as judged by immunoglobulins in serum, light chains in urine, or the percentage of plasma-cells in bone-marrow aspirate. Bone lesions on X-ray were mainly unchanged. Six patients died from transplant-related complications 3 weeks to 5 months post transplantation. One of these patients had severe acute graft-versus-host disease (aGVHD). In other patients aGVHD was a minor problem. Allogeneic bone-marrow transplantation appears to be a promising method for treatment of a selected group of patients with multiple myeloma.


TLR9 stability and signaling are regulated by phosphorylation and cell stress.
Innate sensing of pathogens elicits protective immune responses through pattern recognition receptors, including Toll-like receptors. Although signaling by Toll-like receptors is regulated at multiple steps, including localization, trafficking, proteolytic cleavage, and phosphorylation, the significance of post-translational modifications and cellular stress response on Toll-like receptor stability and signaling is still largely unknown. In the present study, we investigated the role of cytoplasmic tyrosine motifs in Toll-like receptor-9 stability, proteolytic cleavage, and signaling. We demonstrated that tyrosine phosphorylation is essential for mouse Toll-like receptor-9 protein stability and signaling. Upon inhibition of tyrosine kinases with piceatannol, Toll-like receptor-9 tyrosine phosphorylation induced by CpG deoxyribonucleic acid was inhibited, which correlated with decreased signaling. Furthermore, inhibition of Src kinases with 1-tert-Butyl-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine also inhibited response to CpG deoxyribonucleic acid. Toll-like receptor-9 protein stability was also sensitive to autophagy, the cellular stress response pathway, and infection by a deoxyribonucleic acid virus. Whereas autophagy induced by rapamycin or low serum levels caused a preferential loss of the mature p80 proteolytic cleavage product, infection with herpes simplex virus-1 and induction of cell stress with tunicamycin caused preferential loss of full-length Toll-like receptor-9, which is localized to the endoplasmic reticulum. Our data reveal new information about the stability and signaling of Toll-like receptor-9 and suggest that immune evasion mechanisms may involve targeted loss of innate sensing receptors.


Erotic and disgust-inducing pictures--differences in the hemodynamic responses of the brain.
The aim of this fMRI study was to explore brain structures that are involved in the processing of erotic and disgust-inducing pictures. The stimuli were chosen to trigger approach and withdrawal tendencies, respectively. By adding sadomasochistic (SM) scenes to the design and examining 12 subjects with and 12 subjects without sadomasochistic preferences, we introduced a picture category that induced erotic pleasure in one sample and disgust in the other sample. Since we also presented neutral pictures, all subjects viewed pictures of four different categories: neutral, disgust-inducing, erotic, and SM erotic pictures. The analysis indicated that several brain structures are commonly involved in the processing of disgust-inducing and erotic pictures (occipital cortex, hippocampus, thalamus, and the amygdala). The ventral striatum was specifically activated when subjects saw highly sexually arousing pictures. This indicates the involvement of the human reward system during the processing of visual erotica.


Biogeographical ancestry, variable selection, and PLS-DA method: a new panel to assess ancestry in forensic samples via MPS technology.
As evidenced by the large number of articles recently published in the literature, forensic scientists are making great efforts to infer externally visible features and biogeographical ancestry (BGA) from DNA analysis. Just as phenotypic, ancestry information obtained from DNA can provide investigative leads to identify the victims (missing/unidentified persons, crime/armed conflict/mass disaster victims) or trace their perpetrators when no matches were found with the reference profile or in the database. Recently, the advent of Massively Parallel Sequencing technologies associated with the possibility of harnessing high-throughput genetic data allowed us to investigate the associations between phenotypic and genomic variations in worldwide human populations and develop new BGA forensic tools capable of simultaneously analyzing up to millions of markers if for example the ancient DNA approach of hybridization capture was adopted to target SNPs of interest. In the present study, a selection of more than 3000 SNPs was performed to create a new BGA panel and the accuracy of the new panel to infer ancestry from unknown samples was evaluated by the PLS-DA method. Subsequently, the panel created was assessed using three variable selection techniques (Backward variable elimination, Genetic Algorithm and Regularized elimination procedure), and the best SNPs in terms of inferring bio-geographical ancestry at inter- and intra-continental level were selected to obtain panels to predict BGA with a reduced number of selected markers to be applied in routine forensic cases where PCR amplification is the best choice to target SNPs.


Nitrate and a nitrate-reducing Rothia aeria strain as potential prebiotic or synbiotic treatments for periodontitis.
A few studies indicate that nitrate can reduce dysbiosis from a periodontitis point of view. However, these experiments were performed on samples from healthy individuals, and it is unknown if nitrate will be effective in periodontal patients, where the presence of nitrate-reducing bacteria is clearly reduced. The aim of this study was to test the effect of nitrate and a nitrate-reducing R. aeria (Ra9) on subgingival biofilms of patients with periodontitis. For this, subgingival plaque was incubated with 5 mM nitrate for 7 h (n = 20) or 50 mM nitrate for 12 h (n = 10), achieving a ~50% of nitrate reduction in each case. Additionally, Ra9 was combined with 5 mM nitrate (n = 11), increasing the nitrate reduced and nitrite produced (both p < 0.05). The addition of nitrate to periodontitis communities decreased biofilm mass (50 mM > 5 mM, both p < 0.05). Five millimolar nitrate, 50 mM nitrate and 5 mM nitrate + Ra9 led to 3, 28 and 20 significant changes in species abundance, respectively, which were mostly decreases in periodontitis-associated species. These changes led to a respective 15%, 63% (both p < 0.05) and 6% (not significant) decrease in the dysbiosis index. Using a 10-species biofilm model, decreases in periodontitis-associated species in the presence of nitrate were confirmed by qPCR (all p < 0.05). In conclusion, nitrate metabolism can reduce dysbiosis and biofilm growth of periodontitis communities. Five millimolar nitrate (which can be found in saliva after vegetable intake) was sufficient, while increasing this concentration to 50 mM (which could be achieved by topical applications such as a periodontal gel) increased the positive effects. Ra9 increased the nitrate metabolism of periodontitis communities and should be tested in vivo.


Rapid screening of DOM's metal-binding ability using a fluorescence-based microplate assay.
This note describes the development of a method to rapidly quantify the metal-binding ability of low-volume DOM samples based on their fluorescence properties. The method uses 96-well microplates to screen the fluorescence quenching observed when increasing concentrations of various metals are added to the pH-buffered DOM sample. Only 1.6 mL of DOM sample is required to quantify the binding affinity for each metal and the result is obtained in a few minutes. This study presents results for a surface soil DOM sample for which binding was assessed for Cu2+, Fe2+, Ni2+ at pH 5 and 9.


Mid-infrared ChG-on-MgF2 waveguide gas sensor based on wavelength modulation spectroscopy: publisher's note.
This publisher's note contains corrections to Opt. Lett.46, 4797 (2021)OPLEDP0146-959210.1364/OL.440361.


Inhibition of the development of Q-bands on human chromosomes by netropsin.
Netropsin, an oligopeptide-type basic antibiotic, having exclusively A-T-specific DNA-binding affinity and situating itself into the minor groove of the double helix, represses the development of Q-bands if human chromosome preparations are treated with it before quinacrine mustard staining. The most probable interpretation of this effect is that netropsin interferes with the intercalation of the dye molecules. It is assumed this phenomenon supports the hypothesis that quinacrine mustard binds preferentially to A-T-rich sequences of DNA in the metaphase chromosomes.


Natural Communities of Carotenogenic Chlorophyte Haematococcus lacustris and Bacteria from the White Sea Coastal Rock Ponds.
Haematococcus lacustris is a biotechnologically important green unicellular alga producing widely used keta-karotenoid astaxanthin. In natural habitats, it exists in the form of algal-bacterial community, and under laboratory conditions, it is also accompanied by bacteria. The issue of the bacterial composition of industrial algal cultures is widely recognized as important. However, there is a dearth of information about bacterial composition of H. lacustris communities. In current work, we analyze the composition of natural H. lacustris communities from the White Sea coastal temporal rock ponds. For the first time, a 16S rRNA gene-based metagenome of natural H. lacustris bacterial communities has been generated. Main results of its analysis are as follow. Bacterial families Comamonadaceae, Cytophagaceae, Xanthomonadaceae, Acetobacteraceae, Rhodobacteraceae, and Rhodocyclaceae were observed in all studied H. lacustris natural communities. They also contained genera Hydrogenophaga and Cytophaga. Bacteria from the Hydrogenophaga genus were present in H. lacustris cultures after their isolation under the conditions of laboratory cultivation. Similar to other planktonic microalgae, H. lacustris forms a phycosphere around the cells. In this zone, bacteria attached to the algal surface. The contact between H. lacustris and bacteria is maintained even after sample drying. The study provides information about possible members of H. lacustris core microbiome, which can be presented in the industrial and laboratory cultures of the microalga.


Intrathoracic gastric emptying of solid food after esophagectomy for esophageal cancer.
Information on the function of the intrathoracic stomach after esophageal resection for esophageal cancer is limited. This study evaluated the factors affecting intrathoracic gastric emptying of solid food in patients who had undergone this surgery. Between February 2003 and August 2003, intrathoracic gastric emptying of solid food was evaluated by radioisotope in 56 of the patients who underwent esophageal replacement surgery with the stomach for esophageal cancer. The 50% gastric emptying time was categorized into three ranges: over 180 minutes was defined as delayed, within 180 minutes as intermediate, and when all the radioisotopes were dumped into the jejunum as rapid. The factors affecting the gastric emptying were analyzed. In 6 out of 56 (10.7%) patients the radioisotope removal was too rapid to check the gastric-emptying time, and hence the analysis was performed in 50 patients. Twenty-one (37.5%) patients showed significantly delayed gastric emptying. The 50% gastric emptying time calculated by an exponential fitting method was 422 and 109 minutes in the delayed and intermediate groups, respectively. Age, the method of gastric drainage, and the stomach shape used did not affect the intrathoracic gastric emptying. Only the follow-up interval after surgery was a significant factor on gastric emptying (p = 0.024). The intrathoracic gastric emptying of solid food was more and more increased over time after surgery by regression analysis (p = 0.03). The use of the intrathoracic stomach as an esophageal substitute had a significant effect on gastric emptying, with intrathoracic gastric emptying of solid foods immediately after esophagectomy being markedly prolonged in about 50% of patients. However, the intrathoracic gastric emptying significantly increased over time. Research is required into improving intrathoracic gastric emptying in the early period after esophagectomy.


Postoperative, But Not Preoperative Coronavirus Disease 2019 (COVID-19), Is Associated With an Increased Rate of Medical Adverse Events Following Arthroscopic Procedures.
To characterize how severe acute respiratory syndrome coronavirus 2 infection in the perioperative period affects the medical adverse event (MAE) rates in arthroscopic sports medicine procedures. The Mariner coronavirus disease 2019 (COVID-19) database was queried for all shoulder, hip, or knee arthroscopies, 2010 to 2020. Patients with COVID-19 in the 3 months before to 3 months after their surgery were matched by age, sex, and Charlson Comorbidity Index to patients with an arthroscopy but no perioperative COVID-19 infection, or a COVID-19 infection but no arthroscopic procedure. MAEs in the 3 months after surgery or illness were compared between groups. The final cohort consisted of 1,299 matched patients in 3 groups: COVID-19 alone, arthroscopy and perioperative COVID-19, and arthroscopy alone. There were 265 MAEs if a patient had COVID-19 alone (20.4%), 200 MAEs if a patient had arthroscopy with COVID-19 (15.4%), and 71 (5.5%) MAEs if a patient had arthroscopy alone (P < .01). If a patient had an arthroscopy, having COVID-19 was associated with 3.1-fold elevated odds (95% confidence interval [CI] 2.9-3.4, P < .01) of MAE. Among patients with an arthroscopy, MAEs were more common if a patient acquired COVID-19 in the 3 months after their surgery (pooled odds ratio 7.39, 95% CI 5.49-9.95, P < .01) but not if a patient had preoperative COVID-19 (pooled odds ratio 0.66, 95% CI 0.42-1.03, P = .07). Having COVID-19 during the postoperative period appears to confer a 7-fold elevated risk of MAEs after shoulder, hip, and knee arthroscopy compared with matched patients with arthroscopy and no perioperative COVID-19 but equivalent to that of patients with COVID-19 and no arthroscopy. However, there was no increase in postoperative MAEs if a patient had COVID-19 during the 3 months preceding surgery. Therefore, it appears safe to conduct an arthroscopic procedure shortly after recovery from COVID-19 without an increase in acute medical complication rates. Level III, retrospective cohort study.


γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection.
African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.


Plasma sprayed hydroxyapatite coatings on titanium substrates. Part 2: optimisation of coating properties.
Heat treatment and the introduction of a Ti bond coat have been applied to hydroxyapatite (HA) coatings sprayed using different plasma powers and gas mixtures. Attempts were made in this way to achieve optimal coating properties for orthopaedic implants. In particular, the effects on the degree of crystallinity, the adhesion, the OH ion content and the purity were evaluated. Heat treatment at 700 C for 1 h in air proved to be effective in increasing the crystallinity, regaining the OH- ion and removing other non-HA compounds, although it caused a significant decrease in the degree of adhesion (interfacial fracture toughness) for those specimens sprayed at high powers. This heat treatment was found to induce significant transformation of amorphous HA to the crystalline form, while not detrimentally changing the properties of the underlying Ti-6Al-4V substrates. Precoating with a 100 microm Ti layer increased the adhesion of the HA coatings on Ti-6Al-4V substrates, primarily by providing a rougher surface and promoting better mechanical interlocking. Changes in coating properties during immersion in biological fluids were also studied and were found to depend critically on the chemical composition of the fluids. Small precipitates formed on the coating surfaces when immersed in Ringers solution. These might account for the apparent drop in the degree of crystallinity when measured using X-ray diffraction. A significant drop in the interfacial adhesion was found for those coatings sprayed at high powers. This could be offset by prior precoating with a titanium bond coat and suitable heat treatment. In summary, the following processing sequence is suggested in order to achieve optimum coating properties: precoating the substrate with a layer of Ti (approximately 100 microm), spraying HA at a sufficiently high-power level (depending on particle size and gas mixture) and heat treatment at 700 degrees C for 1 h in air.


Integrity of the cortico-spinal tract is associated with physical activity.
Background and purpose: Despite the primary motor efferent role of the cortico-spinal tract (CST), it is hardly understood whether the amount of physical activity is associated with the integrity of the CST.Materials and methods: We examined the association between the amount of physical activity and the integrity of the CST, using Diffusion Tensor Imaging (DTI) data from 465 individuals. The CST was segmented by probabilistic tractography and the association of the fractional anisotropy (FA) within was tested against physical activity (PA) assessed by moderate-intensity physical activity of the International Physical Activity Questionnaire.Results: The FA and PA showed a positive association. Post-hoc analyses showed that the radial diffusivity (RD) of the CST was negatively associated with PA, suggesting a potential association with preserved myelination with PA.Conclusion: This study shows that the integrity of the CST is associated with its traffic in the general population.


A novel delins (c.773_819+47delinsAA) mutation of the PCCA gene associated with neonatal-onset propionic acidemia: a case report.
Propionic acidemia (PA)(OMIM#606054) is an inborn error of branched-chain amino acid metabolism, caused by defects in the propionyl-CoA carboxylase (PCC) enzyme which encoded by the PCCA and PCCB genes. Here we report a Chinese neonate diagnosed with suspected PA based on the clinical symptoms, gas chromatography-mass spectrometry (GC/MS), and brain imaging tests. Targeted next-generation sequencing (NGS) was performed on the proband. We detected only one heterozygous recurrent nonsense variant (c.937C > T, p.Arg313Ter) in the PCCA gene. When we manually checked the binary alignment map (BAM) diagram of PCCA gene, we found a heterozygous deletion chr13:100915039-100915132delinsAA (c.773_819 + 47delinsAA) (GRCh37.p13) inside the exon 10 in the PCCA gene. The results were validated by Sanger sequencing and qPCR method in the family: the variant (c.937C > T, p.Arg313Ter) was in the maternal allele, and the delins was in the paternal allele. When the mother was pregnant again, prenatal diagnosis was carried out through amniocentesis at 18 weeks gestation, the fetus carried neither of the two mutations. After birth, newborn screening was undertaken, the result was negative. We identified a recurrent c.937C > T and a novel c.773_819 + 47delinsAA mutations in the PCCA gene, which may be the genetic cause of the phenotype of this patient. Our findings expanded the spectrum of causative genotype-phenotype of the PCCA gene. For the cases, the NGS results revealed only a heterozygous mutation in autosomal recessive disease when the gene is associated with phenotypes, it is necessary to manually check the BAM diagram to improve the detection rate. Targeted NGS is an effective technique to detect the various genetic lesions responsible for the PA in one step. Genetic testing is essential for genetic counselling and prenatal diagnosis in the family to avoid birth defects.


Insights from a dataset on behavioral intentions in learning information flow diagram capability for software design.
Developing complex software may be difficult for students or those with less technical expertise in software design due to the large number of diagrams and the complexity of their relationships. Unified modeling language (UML) provides conceptual software design as a system's blueprints, including programming statements, software processes, software components, deployment, design, and development, whereas database schemas use UML for an object-oriented database and entity relation model (ERD) for a relational database. An information flow diagram (IFD) is a technical tool for designing software that includes Infrastructure, data and information, and processing flow. IFD can benefit from examining a new paradigm that facilitates a more practical and rapid understanding of information designs. This data set contains the results of an investigation into the factors affecting the acceptance of IFD for software design by college students. Google forms are used to collect information from undergraduate and graduate computer science, IT, and software engineering students. The extended technology acceptance model (TAM) will focus on studying factors affecting acceptance or decision to use IFD, which includes the ability to create information flow diagrams, satisfaction with software design, and business requirement expectations. This study was carried out at four Thai universities. Research data collection for software design and development courses spanned the academic year 2021. Concerning the use of IFD in software design, 537 respondents were questioned regarding their perceptions, behavioral intentions, information flow diagram capability, software design satisfaction, and business requirement expectations. All students completed the survey. To ensure that participation was voluntary, each participant gave informed consent. Any collected information was rendered anonymous. The participants were given the information solely for research purposes. Ethical values, respect, autonomy, compassion, and confidentiality were guaranteed. The survey's primary questions correspond to the acceptance model's independent variables. Online distribution of the questionnaire yielded 537 valid responses. The dataset consists of 1) student demographics and 2) student perspectives on the factors influencing their intent to learn and apply IFD to software design. Partial Least Squares - Structural Equation Modelling was utilized to analyze the data (PLS-SEM). With the help of these data, researchers, software developers, and educators in various settings can use and analyze alternative software designs and validate models used to study and predict the acceptance of behaviors and factors.


Risk factors and screening techniques in 500 patients with benign and malignant colon polyps. An urban community experience.
The authors have reviewed 13 years of experience with 500 patients who had 1240 polypoid lesions identified at colonoscopy. An analysis of these patients' symptoms, signs, and past histories prior to initial colonoscopy were collated by computer in order to provide useful information to help in early identification of patients with polyps and to define specific risk factors in patients with polypoid cancers (71 patients with 79 cancers). This study shows that the 500 patients with colon polyps, with and without cancer, are similar in all parameters measured. Their symptoms correlated poorly with the pathology or location of the polyp. Frequently unrelated symptoms brought the patient to the attention of their private physician. A significant high-risk group of patients identified were those with prior colon polyps and cancer. A positive family history of colon cancer was not common. Barium enema, the most common examination, was performed in 90 percent of patients and was the first test to diagnose polyps in 54 percent. Flexible sigmoidoscopy, only more recently available and performed in 20 percent of the patients, established a diagnosis of polypoid disease 96 percent of the time. This study supports screening for all adults above 40 years of age with flexible sigmoidoscopy and stool occult blood.


Audit--a cause for TMJ dysfunction.
The last few years have seen those of us in hospital practice confronted by clinical audit and unit budgeting. We have recently been advised, by our unit general manager, that in the next financial year we must make a 1% saving, followed by 2% the subsequent year. Of course, clinical budgeting is nothing new for our colleagues in general practice. They have been working within its confines almost since the inception of the Health Service, in the guise of item of service payment. However, for those of us in hospital practice who have hitherto been relatively cushioned from economic realities, this can come as quite a shock.


Angiotensin-induced thirst: effects of third ventricle obstruction and periventricular ablation.
The role of periventricular tissue surrounding the anteroventral third ventricle (AV3V) in mediating drinking behavior induced by angiotensin II was investigated rats. Electrolytic lesions which bilaterally destroyed preoptic-hypothalamic periventricular tissue surrounding AV3V abolished drinking responses normally elicited by intracerebral injections of angiotensin. In another experiment, ventricular obstruction in AV3V had no effect on drinking of a palatable sweet milk solution while the drinking responses induced by peripheral versus central administration of angiotensin were dissociated. Drinking normally induced by lateral preoptic injections of angiotensin was no longer observed when AV3V obstruction prevented drug distribution via cerebrospinal fluid circulation to AV3V periventricular tissue; the drinking response induced by subcutaneous injection of angiotensin was enhanced, however, after placement of the ventricular obstruction. These results, coupled with the earlier observation that AV3V lesions also abolish drinking induced by subcutaneous angiotensin injectin, suggest that, after central or peripheral administration, angiotensin acts on AV3V periventricular tissue to arouse drinking. In contrast to centrally injected angiotensin, peripherally administered angiotensin does not contact receptors by entry and spread in cerebrospinal fluid. After peripheral injection angiotensin may contact sensitive AV3V tissue directly from blood, perhaps via the organum vasculosum of the lamina terminalis, a highly vascularized circumventricular organ within the AV3V which lacks a blood-brain barrier.


A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma.
Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pyrimidine biosynthesis pathway. A clinical stage inhibitor of DHODH (rate-limiting enzyme in the de novo pathway) diminishes uridine-5'-phosphate (UMP) pools, generates DNA damage, and induces apoptosis through suppression of replication forks-an "on-target" effect, as shown by uridine rescue. Matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in the brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.


Feasibility of percutaneous cryoablation of vertebral metastases under local anaesthesia in ASAIII patients.
spine metastases are common concern from several primary neoplasms, modern management include percutaneous techniques such as ablation and cementoplasty. This research aims to evaluate the treatment under local anaesthesia in high-risk patients (ASA III). from January 2013 up to September 2016 we treated via percutaneous cryoablation 11 advanced oncological patients classified as ASA III, then retrospectively a review of their clinical history has been performed. Interventions were managed under local anaesthesia, injecting low doses of bupivacaine 2,5mg/ml (from10 to 30ml). Cryoprobes of 17G were introduced under CT guidance. VAS scores were evaluated pre, intra and post operative up to the 3rd month and further, statistical analyses were obtained using T student test. thirteen spinal metastases were cryoablated in 11 patients (6W, 5M; mean age of 53 years, range 52-81). Tumour location was: sacrum (n=6), lumbar spine (n=3), thoracic spine (n=2). The average VAS value during the procedure was 5,27 (standard deviation 0,90). There were statistically significant decreases in the median numeric VAS scale score at 1-week, 1-month, and 3-month time points (P<.001 for all). Technical success was achieved in all cases. Among patients with neurological deficit, some clinical improvement was assessed. cryoablation with or without subsequent cement injection can be safely performed with local anaesthesia for pain relief also in patients with high ASA score with higher risk of complications, in the absence of any other suitable treatment.


Analysis of the incidence and influencing factors associated with binary restenosis of target lesions after drug-coated balloon angioplasty for patients with in-stent restenosis.
Drug-coated balloon (DCB) is a novel and effective device for coronary artery disease patients with in-stent restenosis (ISR). However, the incidence and possible influencing factors associated with binary restenosis have not yet been adequately assessed. The data are extracted from a prospective, multicenter, randomized controlled trial. A total of 211 patients with ISR were enrolled at 13 centers from August 2017 to October 2018 and treated with DCB. At the 9-month coronary angiographic follow-up, patients were divided into restenosis and non-restenosis groups, and demographic data, lesion features, and laboratory tests were retrospectively reviewed. Furthermore, logistic regression analysis was used to identify possible influencing factors. All patients successfully underwent treatment, and 166 patients with 190 lesions took part in angiography follow-ups at 9 months. Of these, 41 patients with 44 target lesions developed restenosis following treatment, and the incidence of ISR was 24.7%. There were significant differences in the average length of target lesions and the number of multivessel lesions and fasting plasma glucose (FBG) between the two groups (p < 0.05). Demographic data, cardiac risk factors, left ventricular ejection fractions (LVEF), blood routine tests, biochemical tests, and other features of devices and lesions showed no difference. Logistic regression analyses showed that FBG > 6.1 mmol/L (OR: 7.185 95% CI: 2.939-17.567 P < 0.001) and length of lesion (OR:1.046 95% CI: 1.001-1.093 P = 0.046) were associated risk factors. The longer length of lesions, more target lesions and FBG > 6.1 mmol/L per individual may be characteristics of patients showing ISR following treatment. Studies with larger sample size, and more complete follow-up data are needed in the future to expend on these findings. No.: NCT04213378, first posted date (30/12/2019).


Noncontiguous finished genome sequence and description of Nocardioides massiliensis sp. nov. GD13(T).
Nocardioides massiliensis sp. nov strain GD13(T) is the type strain of N. massiliensis sp. nov., a new species within the genus Nocardioides. This strain was isolated from the faeces of a 62-year-old man admitted to intensive care for Guillain-Barré syndrome. Nocardioides massiliensis is a strictly aerobic Gram-positive rod. Herein we describe the features of this bacterium, together with the complete genome sequence and annotation. The 4 006 620 bp long genome contains 4132 protein-coding and 47 RNA genes.


Angiogenesis in pre-malignant conditions.
Evidence from human studies suggests that angiogenesis commences during the pre-malignant stages of cancer. Inhibiting angiogenesis may, therefore, be of potential value in preventing progression to invasive cancer. Understanding the mechanisms inducing angiogenesis in these lesions and identification of those important in human tumourigenesis are necessary to develop translational strategies that will help realise the goal of angioprevention.


Analyzing the functions of Rab11-effector proteins during cell division.
Recycling endosomes recently have emerged as major regulators of cytokinesis and abscission steps of cell division. Rab11-endosomes in particular were shown to transport proteins to the mitotic ingression furrow and play a key role in establishing the abscission site. Rab11 GTPase functions by binding and activating various effector proteins, such as Rab11 family interacting proteins (FIPs). FIPs appear to be at the core of many Rab11 functions, with FIP3 playing a role in targeting of the Rab11-endosomes during mitosis. Here we summarize the newest finding regarding the roles and regulation of FIP3 and Rab11 complex, as well as describe the methods developed to analyze membrane and cytoskeleton dynamics during abscission step of cytokinesis.


Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration.
In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF-differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G0/G1 phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells.


Evidence for a serotonergic mechanism of the learned helplessness phenomenon.
The present experiments examined the role of the serotonergic system in the learned helplessness phenomenon. In Experiment 1, a 200 mg/kg dose of 1-tryptophan injected 30 min prior to testing disrupted acquisition of Fixed Ratio 2 shuttle escape behavior. In Experiment 2, a 100 mg/kg dose of 5-HTP produced interference with the acquisition of the escape response. Furthermore, this interference was prevented by treatment with the serotonergic antagonist methysergide. In Experiment 3, animals were pretreated with a subeffective dose of 1-tryptophan in combination with subeffective exposure to inescapable shock. These animals showed a deficit in the acquisition of FR-2 shuttle escape. In Experiment 4, combined exposure to a subeffective dose of 5-HTP and inescapable shock (40 trials) resulted in an acquisition deficit. This deficit was reversed by methysergide. Experiment 5 showed that the detrimental effects of exposure to prolonged (80 trials) of inescapable shock can be prevented by treatment with methysergide. These studies implicate the serotonergic system as a possible mediator of the learned helplessness phenomenon.


[Development of loneliness in old age in times of COVID-19].
The article investigates the development of loneliness before and in the first months of the Covid-19 pandemic against the background of the socio-economic situation of older people. For this purpose, variance analyses are carried out with data from Lower Austria utilizing two surveys (pre-pandemic, peri-pandemic). The analyses show that older people are not a homogeneous group, i.e. the level of loneliness was already divergent before the pandemic and these existing differences were largely maintained at a somewhat higher level during the pandemic with little variation.


NPC-14686 (Fmoc-l-homophenylalanine)-induced CaCa2+ increases and death in human prostate cancer cells.
The effect of NPC-14686, a potential anti-inflammatory drug, on cytosolic free Ca2+ levels ([Ca2+]i) and growth in PC3 human prostate cancer cells was examined by using fura-2 as a fluorescent Ca2+ indicator and WST-1 as a fluorescent growth dye. NPC-14686 at concentrations above 10 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 100 microM. NPC-14686-induced Ca2+ influx was confirmed by Mn2+ quench of fura-2 fluorescence. The Ca2+ signal was also reduced by removing extracellular Ca2+. Pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+ nearly abolished 200 microM NPC-14686-induced Ca2+ release; and conversely pretreatment with NPC-14686 completely inhibited thapsigargin-induced Ca2+ release. The Ca2+ release induced by 200 microM NPC-14686 was not affected by inhibiting phospholipase C with 2 microM U73122. Overnight treatment with 1-500 microM NPC-14686 decreased cell viability in a concentration-dependent manner. These findings suggest that in human PC3 prostate cancer cells, NPC-14686 increases [Ca2+]i by evoking extracellular Ca2+ influx and releasing intracellular Ca2+ from the endoplasmic reticulum via a phospholiase C-independent manner. NPC-14686 may be cytotoxic to prostate cancer cells.


Evaluation of Transbronchial Lung Cryobiopsy Freezing Time, Biopsy Size, Histological Quality, and Incidence of Complication: A Prospective Clinical Trial.
Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.


Geochemistry of organic carbon and nitrogen in surface sediments of coastal Bohai Bay inferred from their ratios and stable isotopic signatures.
Total organic carbon (TOC), total nitrogen (TN) and their δ(13)C and δ(15)N values were determined for 42 surface sediments from coastal Bohai Bay in order to determine the concentration and identify the source of organic matter. The sampling sites covered both the marine region of coastal Bohai Bay and the major rivers it connects with. More abundant TOC and TN in sediments from rivers than from the marine region reflect the situation that most of the terrestrial organic matter is deposited before it meets the sea. The spatial variation in δ(13)C and δ(15)N signatures implies that the input of organic matter from anthropogenic activities has a more significant influence on its distribution than that from natural processes. Taking the area as a whole, surface sediments in the marine region of coastal Bohai Bay are dominated by marine derived organic carbon, which on average accounts for 62±11% of TOC.


Role of cardiovascular magnetic resonance in acute and chronic ischemic heart disease.
Cardiovascular magnetic resonance (CMR) is a multi-parametric, multi-planar, non-invasive imaging technique, which allows accurate determination of biventricular function and precise myocardial tissue characterization in a one-stop-shop technique, free from the use of ionizing radiations. Though CMR has been increasingly applied over the last two decades in every-day clinical practice, its widest application has been in the assessment of ischemic cardiomyopathy.


How common is isolated dysphasia among patients with stroke treated with intravenous thrombolysis, and what is their outcome? Results from the SITS-ISTR.
To describe the frequency and outcome of isolated dysphasia among patients treated with intravenous thrombolysis (IVT). Patients registered in the SITS International Stroke Thrombolysis Register (SITS-ISTR). Patients with stroke (N=58,293) treated with IVT between December 2002 and December 2012. A multinational, prospective, observational monitoring register. Isolated dysphasia and modified Rankin Scale (mRS). We identified patients presenting with isolated dysphasia by reviewing items within the baseline National Institutes of Health Stroke Scale (NIHSS). We performed descriptive statistics for baseline and demographic data, and reported patients' characteristics, radiological data and changes in their NIHSS score within 7 days and mRS score at 3 months. We also reported corresponding data from the general SITS-ISTR cohort. We found isolated dysphasia at baseline in 1.14% (663/58,293) of all patients treated with IVT patients. Patients with isolated dysphasia had a longer onset to treatment time, lower proportion of visible infarctions on admission imaging scan and atrial fibrillation, and were less often classified as having large vessels causing strokes, in comparison with the rest of the SITS-ISTR. Symptomatic intracerebral haemorrhage occurred in 2.3% of patients per SITS-MOST definition and fatal outcome in 5.5%. At 7 days, 50% of patients with isolated dysphasia recovered completely and at 3 months, 86.3% patients were functionally independent (mRS score 0-2), 71.7% had an excellent outcome (mRS score 0-1) and 45.5% had an mRS score of 0. A low proportion of patients with isolated dysphasia are treated with IVT. Half of these patients were fully recovered at 7 days.


Identification and quantification of 5-hydroxypipecolic acid and hydroxyproline in mammalian brain and blood by selected ion monitoring.
A method for the analysis of 5-hydroxypipecolic acid and 4-hydroxyproline in mammalian brain and blood is reported. The identification and quantification of the two hydroxyimino acids were accomplished with gas chromatography/mass spectrometry including a selected ion-monitoring technique following HPLC prepurification. The lower limit of detection for the method is 2 to 10 pmol. The amounts of 5-hydroxypipecolic acid and 4-hydroxyproline in blood were 20 to 30 pmol/ml and 3 to 6 nmol/ml, respectively. Their concentrations in the rabbit whole brain were determined to be 5 and 120 pmol/g, respectively.


The use of indium-111-labeled leukocytes for abscess detection.
A case is reported in which a labeled white cell scan was helpful in the diagnosis of a periappendiceal abscess. The method of labeling is described and the usefulness of the technique discussed.


Neonatal extra-corporeal life support: indications and limitations.
Cardiac extra-corporeal life support is used more frequently in the current era of complex, high-risk neonatal heart surgery. Although outcome for neonates with complex heart disease has improved in the last decade, thanks to advances in surgery and intensive care, survival in the subset that require extra-corporeal support remains unchanged at below 40%. Neonatal cardiac extra-corporeal support is a technically challenging therapy that is applied in a range of contexts including: post-operative low cardiac output syndrome, cardiac arrest, high-risk interventional catheterisation or as a bridge to recovery from dysrhythmia and myocarditis. Extra-corporeal life support has increased in particular for neonates with single ventricle disease in the last 5 years, mainly achieving similar results to biventricular patients. Further research is required in order to determine the optimal methods for patient selection and to establish important predictors of outcome including the longterm neurological development of survivors.


Integrative analyses of transcriptomics and metabolomics in Raphidocelis subcapitata treated with clarithromycin.
As a macrolide antibiotic, clarithromycin (CLA) has a high detection rate in surface water and sewage treatment plant effluents worldwide, posing a considerably high ecological risk to aquatic ecosystem. However, algal transcriptome and metabolome in response to CLA remains largely unknown. In this study, a model alga Raphidocelis subcapitata (R. subcapitata), was exposed to CLA at the concentrations of 0, 3, 10, and 15 μg L-1. Transcriptomic analysis was performed for all the treatment groups, whereas metabolomics was merely applied to 0, 3, and 10 μg L-1 groups because of the limited amount of algal biomass. After 7 d cultivation, the growth of R. subcapitata was significantly hindered at the concentrations above 10 μg L-1. A total of 115, 1833, 2911 genes were differentially expressed in 3, 10, and 15 μg L-1 groups, respectively; meanwhile, 134 and 84 differentially accumulated metabolites (DAMs) were found in the 3 and 10 μg L-1 groups. Specifically, expression levels of DEGs and DAMs related to xenobiotic metabolism, electron transport and energy synthesis were dysregulated, leading to the produced reactive oxygen species (ROS). To confront the CLA-induced injury, the biosynthesis of unsaturated fatty acids and carotenoids of R. subcapitata in 3 μg L-1 were up-regulated; although the photosynthesis was up-regulated in both 10 μg L-1 and 15 μg L-1 groups, the energy synthesis and the ability to resist ROS in these two groups were down-regulated. Overall, this study shed light on the mechanism underlying the inhibitory effects of macrolide antibiotics in algae.


Rapid evolution of the trophoblast kunitz domain proteins (TKDPs)-a multigene family in ruminant ungulates.
The trophoblast Kunitz domain proteins (TKDPs) are products of the outer cells (trophoblasts) of the placenta of cattle, sheep, and related species. Most are expressed abundantly for only a few days during the time at which the ruminant conceptus is first establishing intimate contacts with the uterine lining. The TKDPs are secretory proteins that possess a carboxyl-terminal peptidase inhibitory domain related to the Kunitz family of serine peptidase inhibitors. On the amino-terminal end are one or more highly unusual regions that are unique to the TKDP genes and have no apparent similarity to any other known sequences. The TKDPs are a rather divergent family that exhibits a good deal of variation among the members. To better understand the reason for such variation, the rates of synonymous (dS) and nonsynonymous (dN), as well as radical (pNR) and conservative (pNC), substitutions were assessed. Phylogenetic trees revealed that the Kunitz domains represented three related groups, whereas the amino-terminal domains formed four groupings. Pairwise comparisons between Kunitz and amino-terminal domain groups demonstrated that dN was consistently greater than dS. In addition, nonsynonymous substitutions in the Kunitz domains tended to be radical (changing charge or polarity), while those in the amino-terminal domains exhibited neither a preponderance of conservative nor radical substitution rates. In summary, the rapid evolution of the TKDPs, coupled with their restricted temporal expression during development, likely reflects the establishment of protein-protein interactions that have evolved to serve the unusual synepitheliochorial placenta of ruminant ungulates.


Phenotypes and Genotypes in Five Children with Congenital Insensitivity to Pain with Anhidrosis.
Congenital insensitivity to pain with anhidrosis is an extremely rare hereditary disorder linked to variants in NTRK1. Our goal was to characterize the clinical features and the genetic basis of the disorder in Chinese patients. Patients were enrolled via social networking. Clinical features were investigated by interview, chart review, and physical examination. DNA was extracted from peripheral blood to genotype NTRK1 in patients and their parents. Variants identified were checked against a control cohort by high-throughput sequencing, and the effects of these variants were assessed in silico. Clinical features in five patients were cataloged, and six loss-of-function NTRK1 variants were identified, including a frameshift variant c.963delG, a nonsense variant c.1804C>T, an intron variant c.851-33T>A, and three missense variants c.1802T>G, c.2074C>T, and c.2311C>T. The results expand the spectrum of clinical and genetic features of congenital insensitivity to pain with anhidrosis and will help facilitate analysis of genotype-phenotype association in the future.


Analysis of body composition in individuals with high bone mass reveals a marked increase in fat mass in women but not men.
High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear. To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover. We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. A total of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls. We measured fat mass, by DXA, and bone turnover markers. Among women, fat mass was inversely related to age in controls (P = .01), but not in HBM cases (P = .96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P < .001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P < .002); however, lean mass increases were less marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P < .001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5] μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P < .001). HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover.


The ability of salbutamol and theophylline to suppress immediate allergic conjunctivitis in the guinea pig.
Topically administered salbutamol was extremely effective in suppressing immediate allergic conjunctivitis in the guinea pig; a dose as low as 0.1% elicited 98% inhibition. Topical pretreatment with 1% propranolol completely blocked the suppressant action of 0.1% salbutamol. This was also the case after systemic propranolol (1 mg/kg SC); the beta-adrenoceptor antagonist itself has no effect on antigen-induced inflammation. The effect of 0.1% salbutamol was unaltered by pretreatment with the specific beta 1-adrenoceptor antagonist betaxolol (1 mg/kg SC). In marked contrast, the suppressant action of 0.1% salbutamol was profoundly inhibited by pretreatment with the selective beta 2-adrenoceptor antagonist ICI-118,551 (0.5 mg/kg SC). The experiments employing beta-adrenoceptor antagonists unequivocally demonstrate that the salbutamol suppression of immediate allergic conjunctivitis in the guinea pig is mediated via the activation of beta 2-adrenoceptors. The methylxanthine phosphodiesterase inhibitor theophylline was active after oral administration, 50 mg/kg eliciting an 80% inhibition. Theophylline was inactive topically at 1% and 5%, but this could be due to the fact that the compound was insoluble at these concentrations. Thus, procedures that elevate cyclic-AMP levels suppress immediate hypersensitivity reactions in the guinea pig conjunctiva. Whether or nor this offers an alternative approach to treat allergic conjunctivitis in humans remains to be determined.


Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination.
Ku70-Ku80 heterodimers promote the non-homologous end-joining (NHEJ) of DNA breaks and, as shown here, the fusion of dysfunctional telomeres. Paradoxically, this heterodimer is also located at functional mammalian telomeres and interacts with components of shelterin, the protein complex that protects telomeres. To determine whether Ku contributes to telomere protection, we analysed Ku70(-/-) mouse cells. Telomeres of Ku70(-/-) cells had a normal DNA structure and did not activate a DNA damage signal. However, Ku70 repressed exchanges between sister telomeres - a form of homologous recombination implicated in the alternative lengthening of telomeres (ALT) pathway. Sister telomere exchanges occurred at approximately 15% of the chromosome ends when Ku70 and the telomeric protein TRF2 were absent. Combined deficiency of TRF2 and another NHEJ factor, DNA ligase IV, did not elicit this phenotype. Sister telomere exchanges were not elevated at telomeres with functional TRF2, indicating that TRF2 and Ku70 act in parallel to repress recombination. We conclude that mammalian chromosome ends are highly susceptible to homologous recombination, which can endanger cell viability if an unequal exchange generates a critically shortened telomere. Therefore, Ku- and TRF2-mediated repression of homologous recombination is an important aspect of telomere protection.


Oral Glucose Tolerance Testing Using Candy: A Sweet Solution to Improve Screening in Children with Cystic Fibrosis?
Oral glucose tolerance testing is recommended for all children with CF older than 9 years, yet compliance remains poor across centers. We performed a small pilot study assessing the glycemic curves and participant satisfaction in seven children and adolescents. We chose a dextrose-based candy (Nerds®) free of any fat, fiber, gelatin, or corn syrup and performed the candy OGTT 1-4 days following the standard oral dextrose solution OGTT. Glucose values at 120 min were similar between the candy and oral dextrose solution (p = 0.8986). Our small pilot suggests that a carefully selected candy alternative may result in similar glycemic OGTT when compared to the standard oral dextrose solution. However, some participants preferred the oral dextrose solution to candy due to having to consume a large volume in a short period of time. This may have significant implications as centers consider candy alternatives to increase OGTT adherence rates.


Combined liver-kidney transplant for the management of methylmalonic aciduria: a case report and review of the literature.
Over 27 cases of liver transplant, kidney transplant and combined liver-kidney transplant have been reported for the treatment of methylmalonic aciduria. We describe a case of a 5-year-old boy who underwent combined liver-kidney transplant (CLKT) for phenotypic mut0 disease. His history was notable for more than 30 hospitalizations for severe acidosis, metabolic strokes, liver disease, pancreatic disease, chronic renal insufficiency with interstitial nephritis, and decreased quality of life. Post-CLKT, there was a marked reduction in serum (80%) and urine MMA levels (90%) as well as a cessation of metabolic decompensations. Neurologic deterioration continued post-CKLT manifested as a cerebellar stroke. The clinical details and therapeutic implications of solid organ transplant for methylmalonic aciduria are discussed.


Effect of second messenger systems on oxalate uptake in renal epithelial cells.
The oxalate transport system along with protein phosphorylation appears to be deranged in stone formers. This study was undertaken to characterize in LLC-PK1 cells in culture the effect of altering specific intracellular second messenger systems on oxalate uptake. Cellular uptake experiments were performed at 37 degrees C in buffer [265 mM mannitol, 5 mM NaOH, 5 mM KOH, 10 mM Ca-EGTA, 25 mM HEPES/TRIS, pH = 7.4 or in Hank's balanced salt solution (HBSS)] containing 200 microM labeled oxalate (1-14C, 0.3 microCi). Cells were preincubated with DAG (final concentration of 100 microM), phorbol myristate acetate (10 microM), forskolin (50 microM), 8-bromo-cyclic AMP (50 microM), trifluoroperazine (20 microM) and low molecular weight heparin (1 mg/ml) for 10 min in the presence and absence of the anion transport inhibitor DIDS (100 microM) and the effect(s) on oxalate uptake at 10, 25 and 45 min incubation were determined. Chemicals (DAG, forskolin, TPA and 8-bromo-cAMP) which stimulate protein kinase A or C activity resulted in an increased uptake of oxalate while inhibitors of these systems (trifluoroperazine and low molecular weight heparin) resulted in decreased oxalate uptake. The results demonstrate that oxalate uptake in renal tubular cells is modulated by protein kinase C and A dependent mechanisms.


Perinatal and developmental outcome of infants exposed to methadone in-utero.
The purpose of this research is to delineate the effects of methadone exposure in-utero. Subjects were 141 infants born to drug dependent women maintained on methadone during pregnancy and 127 non-drug exposed comparison infants matched for race, maternal age, and socioeconomic status. Methadone exposed infants had smaller birth weights than comparison infants. Differences were also found in head circumference. However, this difference was not clinically significant but rather reflects the relationship between birth weight and head circumference. No difference was found between groups in mental development. One hundred and five methadone exposed infants and 63 comparison infants were evaluated with the Bayley Scale of Mental Development at 6 months of age. Mean Bayley Mental Development scores for methadone exposed infants and comparison infants were 103 and 105 respectively. These data suggest that while methadone exposure in-utero is associated with lower birth weight and head circumference, by six months of age, these infants do not exhibit any general developmental sequelae.


Future of outcomes measurement: impact on research in medical rehabilitation and neurologic populations.
The National Institutes of Health (NIH) has embraced the investigation and development of health-related patient-reported outcomes (PROs) for their potential use in clinical trials, as well as in examining health care reimbursements and regulatory affairs. The NIH has 3 major programs to address this topic: the Patient-Reported Outcomes Measurement Information System (PROMIS), NIH Toolbox for Assessment of Neurological and Behavioral Function, and Quality of Life in Neurological Disorders (Neuro-QOL), a health-related quality-of-life assessment tool for adults and children with neurologic disorders. These initiatives are focused on developing, validating, and measuring aspects of health by using assessment tools that bridge disease type. Given that rehabilitation takes place across a variety of environments with differing levels of specialized equipment and skilled personnel, PROs may provide consistent measures over time and therefore are anticipated to have substantial impacts on the medical rehabilitation community. Despite their advantages, the widespread use of PROs in rehabilitation faces significant and diverse challenges. This article describes the background behind the NIH PRO initiatives and illustrates both potential benefits and challenges to PRO use in the medical rehabilitation setting.


Efficacy and safety of Reyanning mixture in patients infected with SARS-CoV-2 Omicron variant: A prospective, open-label, randomized controlled trial.
A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p = 0.012), coughing (12.2% vs. 14.8%, p = 0.046), and expectoration (6.0% vs. 8.0%, p = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.


Developmental outcomes in Japanese preschool-age children conceived through assisted reproductive technology.
This study aimed to investigate the developmental outcomes of Japanese babies conceived through assisted reproductive technology (ART), born at ages 48 and 60 months. Data were collected from 725 children in a hospital-based cohort study conducted in Japan. The children's level of development was assessed using the Kinder Infant Development Scale, a parent-rated questionnaire that consists of nine developmental domains. We compared the development between children conceived through ART (N = 189) and those conceived naturally (N = 536) by conducting analyses of covariance. For the analyses, we controlled for the effects of maternal age, family income, parental education, and multiple births. At 48 months, no significant difference was found between children conceived through ART and those conceived naturally, except for the development of receptive language (F(1, 718) = 4.869, p = 0.028)), which was found only for boys. The mean developmental age of receptive language was 60.1 for the children conceived through ART and 57.5 for those conceived naturally. At 60 months, no significant difference was found between children conceived through ART and those conceived naturally, in all domains. At ages 48 and 60 months, no significant difference was found between the children conceived through ART and those conceived naturally in nine developmental domains, except for boys' receptive language at 48 months.


Use of individual containers for prostate biopsy samples: Do we gain diagnostic performance?
Prostate cores from transrectal biopsies are usually sent in separate vials for pathological processing. Although this is a common practice, there are controversial studies on its usefulness. We wanted to compare the rate of prostate cancer diagnosis between processing samples in 2 containers and processing them in individual containers to see if there are differences. Our secondary objective was to check the rate of diagnosis of various tumour subtypes in each of the 2 groups. A retrospective observational study was conducted of 2,601 cases of prostate biopsies. Ten cores were extracted in each biopsy. We divided the sample into 2 groups: biopsies sent in 2 containers to the department of pathology (left and right lobes) or sent in 10 (one for each cylinder), according to the different criteria used in our centre in the past. We then classified the cases according to the absence of neoplasia, insignificant tumour (involvement of just 1 cylinder, <5%, Gleason score<7), Gleason 6 or Gleason≥7. A bivariate statistical analysis was performed using the chi-squared test. A total of 1,777 participants were included in the 2-container group, and 824 were included in the 10-container group. We diagnosed a rate of 32.4% of cancers in the 2-container group and 40% in the 10-container group, a difference that was statistically significant (P<.001). The insignificant carcinomas were diagnosed more often in the 2-container group than in the 10-container group (6.4% vs. 4.3%, respectively; P=.03). Samples with a Gleason score of 6 were diagnosed more often in the 10-container group than in the 2-container group (11.9% vs. 8.1%, respectively; P=.002). The same occurred with the Gleason score≥7 (23.8% in the 10-container group vs. 17.9% in the 2-container group; P<.001). We diagnosed more prostate cancers when sending biopsied cores in individual containers. Once the procedure was conducted, we also observed in our series a reduction in the diagnoses of insignificant carcinoma to the detriment of an increased diagnosis of not insignificant carcinomas.


Hyaluronic acid hydrogel encapsulated BMP-14-modified ADSCs accelerate cartilage defect repair in rabbits.
Cartilage defect has a limited capacity to heal. In this context, we hypothesized that hyaluronic acid (HA) hydrogel encapsulated BMP-14-modified adipose-derived mesenchymal stem cells (ADSCs) could accelerate cartilage defect repair in rabbits. ADSCs were isolated and identified by flow cytometry. ADSCs were treated with adenovirus vector encoding BMP-14 (Ad-BMP-14) or adenovirus vector encoding control (Ad-ctrl). Real-time PCR (RT-PCR) and western blot assay was performed to verify the transfection efficacy and chondrogenic differentiation markers (ACAN, Collagen II and SOX9). Rabbit cartilage defect model was performed and randomly divided into following groups: control group, HA hydrogel + ADSCs, ADSCs, HA hydrogel + BMP-14 transfected ADSCs, HA hydrogel + BMP-14 transfected ADSCs. At 6, 9 and 12 weeks after surgery, scanning electron microscopy, hematoxylin-eosin, Safranin-O/Fast Green and immunohistochemical staining for Collagen II were performed to determine the role of HA hydrogel encapsulated BMP-14-modified ADSCs in cartilage repair in vivo. ADSCs were successfully isolated and positively expressed CD29, CD44 and CD90. Transfection efficacy of Ad-BMP-14 was verified by RT-PCR and western blot assay. Moreover, Ad-BMP-14 could significantly increased chondrogenic differentiation markers (ACAN, Collagen II and SOX9). The LV-BMP-14-ADSCs and HA hydrogel + LV-BMP-14-ADSCs groups revealed smoother surface cartilage repair that was level with the surrounding cartilage and almost complete border integration. HA hydrogel encapsulated BMP-14-modified ADSCs accelerate cartilage defect repair in rabbits. We need to further validate the specific mechanism of action of HA hydrogel encapsulated LV-BMP-14-ADSCs involved in the repairing cartilage damage in vivo.


Sexual dysfunction of male, after pelvic fracture.
Pelvic fractures are usually the result of high-energy trauma, and sexual dysfunction after a pelvic fracture is an often complication. Though organic pathologies can be the reason for sexual disorders, psychological factors following a trauma may also be linked to sexual problems. We aimed to evaluate the frequency of sexual dysfunction after pelvic fractures, and help these patients with their usually undisclosed sexual problems, and offer them support. During a 4-year period, between June 2008 and May 2012, 40 male patients (out of 57) with a mean age of 42.6 years (range 18-65 years) were evaluated retrospectively. Patients having organic pathologies (vascular, neural, and urogenital system pathologies) were excluded from the study. Patients were requested to complete the Arizona Sexual Experience Scale (ASEX), which is a 5-item self-evaluation scale. According to the results of the questionnaire, patients needing supportive treatment were referred to the psychiatry department. Twenty-two patients (55 %) scored 10 points or less in the ASEX questionnaire (normal). Eighteen patients (45 %) had 11 points or more (can be problematic). Four of these 18 patients had a score of 19 points or more (needing psychiatric evaluation). Patients with a score of ≥19 points, for any one item with a score of 5 or 6 points, or any three or more items with a score of 4 points were considered to have a high probability of sexual dysfunction after psychiatric evaluation. The frequency of sexual dysfunction in pelvic fractured patients was tested, and the need for investigating sexual disorders is stressed. This study attracts attention to sexual dysfunction after pelvic fractures and the necessity of referring these patients to the related clinics, for treatment. Retrospective case series.


Sediminihabitans luteus gen. nov., sp. nov., a new member of the family Cellulomonadaceae isolated from sea sediment.
Two novel Gram-positive actinobacteria, designated H97-3(T) and H83-5, were isolated from marine sediment samples and their taxonomic positions were investigated by a polyphasic approach. Both strains formed vegetative hyphae in the early phase of growth but the hyphae eventually fragmented into coccoid cells. The peptidoglycan type was found to be A4α. The predominant menaquinone was MK-9(H(4)), and the major fatty acids were anteiso-C(15:0), anteiso-C(17:0) and C(16:0). The DNA G+C content was 74.0-74.9 mol %. 16S rRNA gene sequencing analysis revealed that strains H97-3(T) and H83-5 represented novel members of the family Cellulomonadaceae. Their nearest phylogenetic neighbours were the members of the genus Oerskovia, with a similarity of 98.3-98.4 %. However, strains H97-3(T) and H83-5 were distinguishable from the members of the genus Oerskovia and the other genera of the family Cellulomonadaceae in terms of chemotaxonomic characteristics and phylogenetic relationship. The result of the DNA-DNA hybridization indicated that strains H97-3(T) and H83-5 belonged to the same species. Therefore, strains H97-3(T) and H83-5 represent a novel genus and species of the family Cellulomonadaceae, for which the name Sediminihabitans luteus gen. nov., sp. nov. is proposed. The type strain of S. lutes is H97-3(T) (=NBRC 108568(T) = DSM 25478(T)).


Mutations upstream of the ribosome-binding site affect translational efficiency.
The DNA coding for the major outer membrane lipoprotein of Escherichia coli has been fused to the coding region of the beta-galactosidase gene to measure the effect of various mutations on the efficiency of translation initiation. The various mutants were made by either inserting or deleting a small number of nucleotides into or from a region just upstream of the ribosome-binding site. These small mutations dramatically affect translation initiation as measured by the production of beta-galactosidase. We postulate that these mutations affect translation initiation by altering the secondary structure of the messenger RNA. In one case, we predict that a stem and loop just upstream of the Shine-Dalgarno sequence sterically hinders the binding of the ribosome to the mRNA.


Current progress in the development of the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin as carriers for the oral delivery of heterologous antigens and epitopes.
The development of non-living carrier systems for delivery of protective antigens or epitopes to the immune system represents both a fundamental and an applied aspect of vaccinology. A wide range of carrier systems, ranging from inert supports to proteins that exert direct immunomodulating effects on the immune response, are being studied. In this overview we describe the current progress in the development of the B-subunits of cholera toxin and Escherichia coli heat-labile enterotoxin as potential protein carriers for the oral delivery of chemically and genetically attached antigens and epitopes.


Experimental infection of cows with newly isolated Akabane virus strain (AKAV-7) causing encephalomyelitis.
Akabane virus (AKAV), an arthropod-transmitted bunyavirus, is a major cause of congenital abnormalities and encephalomyelitis in ruminants. In 2010, there was a major outbreak of encephalomyelitis in Korea and fifteen AKAV strains, including AKAV-7, were isolated from cows. To identify the neuropathogenicity of AKAV-7, we performed experimental infection of cows. Six-month-old female Korean Holstein dairy cattle were inoculated with AKAV-7 by various routes, including intracerebral (IC), intrasubarachnoid space (IS), subcutaneous (SC) and intravenous (IV); a separate group was vaccinated before intravenous infection. Five of the six cows in the IC group and two of the six cows in the IS group showed clinical signs such as locomotor ataxia and paralysis of the hind limbs. Three of six cows died after IC infection 9-12 days post infection (dpi). Histopathologic changes such as nonsuppurative encephalomyelitis were confirmed in various parts of the central nervous system in the IC, IS and SC groups. Early onset of neutralizing antibodies in the serum and lower viral mRNA levels in the peripheral blood mononuclear cells (PBMCs) and various tissues in the vaccinated group was noticeable compared to the unvaccinated group (IV group). We suggest that the AKAV vaccine currently used in Korea may be partially effective for protection against AKAV-7 in cows.


Nucleation and growth of cholesteric collagen tactoids: A time-series statistical analysis based on integration of direct numerical simulation (DNS) and long short-term memory recurrent neural network (LSTM-RNN).
Liquid-crystalline phase separation by nucleation and growth (NG) is a crucial step in the formation of collagen-based biomaterials. However, the fundamental mechanisms are not completely understood for chiral lyotropic colloidal mesogens such as collagen. To capture the dynamics of NG under a quenching process into the biphasic equilibrium zone, we use direct numerical simulation based on the time-dependent Ginzburg-Landau model allowing minimization of the total free energy comprised of five key contributions: phase separation (Flory-Huggins), ordering (Landau-de Gennes), chiral orientational elasticity (Frank-Oseen-Mermin), interfacial and coupling effects. LSTM-RNN is applied as a surrogate model to greatly enrich the results. Significant correlations are established using Symbolic Regression. We quantify the NG boundaries existing in the collagen phase diagram that has recently been developed and validated by our thermodynamic model (Khadem and Rey, 2019 [1]). We characterize the three NG stages (induction, nucleation, and coarsening) in terms of tactoids' shape, morphology, growth laws, and population across the NG zone. Wide-range generic correlations are developed, revealing the quench depth dependence of NG characteristics and connecting the sequential NG stages. We confirm experimental observations on time-dependent growth law exponent changes from an initial n≈0.5 for the mass transfer limited regime to n≈1 for the volume-driven phase ordering regime upon increasing quench depth during the nucleation period and having exclusively a value of n≈0.5 for the coarsening period regardless of quench depth. We lastly uncover the underlying physics behind the NG phenomena.


Complete genome sequence analysis of Narcissus yellow stripe virus infecting Narcissus tazetta in India.
The complete genome sequence of Narcissus yellow stripe potyvirus (NYSV) isolated from Narcissus tazetta cv. Paperwhite exhibiting leaf chlorotic stripe symptoms was determined for the first time from India. The viral genome sequence contained 9650 nucleotides that encode a large polyprotein (372.36 kDa) of 3103 amino acids. The comparison of the NYSV genome sequences with corresponding sequences of other potyviruses revealed 90-97% identities and closest phylogenetic relationships with NYSV-Zhangzhou-1 and -ZZ-2 isolates infecting N. tazetta reported from China. Therefore, the NYSV isolate understudy was considered as a new member of NYSV and designated as NYSV-NAR2.


Hybrid fiber coax networks: a viable option for telemedicine.
Cable companies have improved their networks to the degree that they are viable alternatives to currently deployed networks. A detailed look at these cable networks shows them to be superior in bandwidth (capacity), speed, flexibility, and ubiquity. The services that can be provided by these networks are ideal to numerous advanced applications, including telemedicine.


Small interfering RNA targeting nuclear factor kappa B to prevent vein graft stenosis in rat models.
Intimal hyperplasia plays an important role in vein graft stenosis. Inflammatory injury, especially nuclear factor kappaB (NF-κB) gene activation, is highly involved in stenosis progression. We examined whether neointimal hyperplasia and vein graft stenosis could be inhibited by silencing the NF-κB gene with small interference RNA (siRNA). Sixty adult male Sprague-Dawley rats were randomly divided into a normal vein group, a vein graft group, a scrambled siRNA group, and an NF-κB siRNA group. We performed reverse interpositional grafting of the autologous external jugular vein to the abdominal aorta. Vein grafts were treated with liposome and gel complexes containing NF-κB siRNA or scrambled siRNA. The levels of monocyte chemoattractant protein -1, tumor necrosis factor-α, and NF-κB p65 in vessel tissues were evaluated after surgery for content of proliferating cell nuclear antigen (PCNA) and vascular wall thickness. NF-κB siRNA treated vein graft showed less neointimal formation and fewer positive PCNA cells (P < .05). In addition there were lower levels of, NF-κB p65 protein and of inflammatory mediators (P < .05) compared with the vein graft group. Our study suggested that siRNA transfection suppressed NF-κB expression, reduced inflammatory factors, lessened neointimal proliferation, and suppressed PCNA.


Linking water environmental factors and the local watershed landscape to the chlorophyll a concentration in reservoir bays.
The frequency of harmful algal blooms caused by eutrophication is increasing globally, posing serious threats to human health and economic development. Reservoir bays, affected by water environment and local watershed landscape, are more prone to eutrophication and algal blooms. The chlorophyll a (Chl a) concentration is an important indicator for the degree of eutrophication and algal bloom. Exploring the complex relationships between water environment and landscape background, and Chl a concentration in the reservoir bays are crucial for ensuring high-quality drinking water from reservoirs. In this study, we monitored Chl a concentrations of 66 bays in Danjiangkou Reservoir and the related water quality parameters (e.g., water temperature, turbidity, nutrients) in waterbodies of these reservoir bays in the storage and discharge periods from 2015 to 2018. Partial least squares-structural equation modeling (PLS-SEM) was used to quantify the relationship between water environmental factors and watershed landscapes, and Chl a concentrations in reservoir bays. The results showed that mean Chl a concentration was higher in storage period than that in discharge period. Two optimal PLS-SEMs explained 66.8% and 53.6% of Chl a concentration variation in the storage and discharge periods, respectively. The net effect of water chemistry on Chl a concentration was more pronounced during the discharge period (total effect = 0.61, 37% of the total effect on Chl a), while the net effect of land-use composition on Chl a concentration was more significant during the storage period (total effect = 0.57, 30% of the total effect on Chl a). The landscape pattern had significant indirect effects on Chl a concentration, especially during the discharge period (indirect effect = -0.31, 19% of the total effect on Chl a). Our results provide valuable information for managers to make rational decisions, thereby contributing to the prevention of eutrophication and algal blooms in reservoir bays.


Assessing the effectiveness of a mammography screening service.
Trials have shown that mammography screening reduces mortality and probably decreases morbidity related to breast cancer. We assessed whether the major mammography service in Western Australia (BreastScreen WA) is likely to reduce mortality by comparing prognostic variables between screen-detected and other cases of breast cancer diagnosed in 1999. We assessed likely reductions in morbidity by comparing treatments received by these two groups. To confirm mortality and morbidity reduction, we also compared prognostic variables and treatments with targets. Information on demographic variables, tumour characteristics at presentation and treatments were collected from medical records for all incident cases of breast cancer in Western Australia in 1999. We matched cases with the Western Australian Cancer Registry records to determine which cases had been detected by BreastScreen WA. BreastScreen WA achieved the targets for mortality reduction. Tumours detected by BreastScreen WA were smaller in size, less likely to have vascular invasion, of lower histological grade and were more likely to be ductal carcinoma in situ alone without invasive carcinoma. Oestrogen receptor status was more likely to be positive, the difference in progesterone status was not significant, and lymph node involvement tended to be lower. BreastScreen WA patients were treated more often with local therapy and less often with systemic therapy, and the proportion of patients treated with breast-conserving surgery was close to the target for minimizing morbidity in breast cancer. Mammographic detection of breast cancer by BreastScreen WA is associated with reduced breast cancer morbidity and a more favourable prognosis.


Expression of growth-regulated oncogene beta in an endometrial epithelial cell line, HHUA, and cultured human endometrial cells.
It has been demonstrated that human endometrial epithelial cells (EEC) and stromal cells (ESC) produce a variety of chemokines in vivo and in vitro. Growth-regulated oncogene (GRO)beta, which belongs to the CXC chemokine family, is a potent chemoattractant for neutrophils. To evaluate the regulation of GRO beta expression in the endometrium, the production of GRO beta by an EEC line, HHUA, and cultured ESC stimulated with various inflammatory mediators was examined by using an enzyme-linked immunosorbent assay. Unstimulated HHUA and ESC constitutively secreted GRO beta. Interleukin-1 beta, tumor necrosis factor-alpha and interferon-gamma significantly stimulated the expression of GRO beta by HHUA and ESC. Lipopolysaccharide also stimulated the expression of GRO beta by ESC, but not by HHUA. It is suggested that, in the human endometrium, the regulation of GRO beta expression is distinct from that of other CXC chemokines expressed in the endometrium, such as GRO alpha and interleukin-8. The modulation of the GRO beta concentration in the endometrium by inflammatory mediators may contribute to the normal and pathological processes of human reproduction by regulating the trafficking of neutrophils into the endometrium.


Expression of hepatitis B virus x protein in hepatocytes suppresses CD8 T cell activity.
CD8(+) T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient CD8(+) T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect CD8(+) T cell activity. We analyzed the activation and apoptosis of CD8(+) T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Expression of HBx in hepatocytes induced low production of interferon-γ and apoptosis of CD8(+) T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Our results suggest that HBx may inhibit CD8(+) T cell response by regulation of interferon-γ production and apoptosis.


The relation between Helicobacter pylori and nonsteroidal anti-inflammatory drugs.
Both infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs (NSAIDs) can result in gastritis and ulcers. H. pylori has been identified as a major etiologic factor in the development of peptic ulcer disease; however, its relationship to NSAID-associated toxicity is less well characterized. Several studies have suggested that NSAID use does not increase susceptibility to H. pylori, and the converse has also been suggested, namely, that H. pylori does not exacerbate NSAID-associated injury. H. pylori itself may stimulate production of gastric prostaglandins, which may have a role in ulcer healing. More carefully controlled studies may be better able to elucidate the individual and synergistic mechanisms involved in ulceration induced by H. pylori and NSAIDs. Recent studies have suggested that elimination of H. pylori before NSAID treatment decreases ulcer occurrence. Therefore, at this time, eradication of H. pylori should be considered only in certain high-risk patients, i.e., those with a history of gastroduodenal ulcers.


Lepra reactions: A study of 130 cases from Pakistan.
To determine the occurrence and characteristics of lepra reactions in leprosy patients. The retrospective study was conducted at the Marie Adelaide Leprosy Centre, Karachi, and comprised data of patients admitted between January 1, 2013, and December 31, 2015, for the management of lepra reactions. Data was noted on a detailed proforma and was analysed using Microsoft Excel and applying chi-square test. Of the 130 cases, 95(73%) were males and 35(27%) were females. Mean age at onset of the first episode was 39±14 years. Borderline lepromatous was the most common classification 76(58%), with 40(53%) of them having type 1 reaction as the first episode and 36(47%) having a type 2 reaction Risk factors associated with recurrence were skin lesions, fever, lymphadenopathy and type of reaction (p<0.05). Healthcare providers need to be aware of the clinical manifestations of lepra reactions in order to diagnose them early.


Right Upper Extremity Idiopathic Primary Lymphedema in a 2-Year-Old Child.
Lymphedema of an extremity at birth can be an alarming finding. Our patient presented with difficulty breathing and productive cough and was found to have primary lymphedema of the right upper extremity since birth. Further testing was mostly unremarkable except for imaging that revealed many splenic lesions.


Vascular smooth muscle cells synthesize, secrete and express coagulation factor V.
Expression of cellular procoagulant activity may be one of the more important responses to vascular injury. Because factor V, a coagulation cofactor in the prothrombinase complex, catalyzes the conversion of prothrombin to thrombin, it may be a key to understanding this response. Therefore, we have investigated the synthesis, secretion and expression of factor V by vascular smooth muscle cells, which proliferate at sites of vascular injury. Cultured aortic vascular smooth muscle cells constitutively secreted Factor V activity, as determined by a functional assay. Labeled factor V was immunoprecipitated from conditioned medium of [35S]methionine-labeled cells, indicating that the secreted factor V was synthesized by vascular smooth muscle cells. Treatment of vascular smooth muscle cells with tunicamycin prevented secretion of factor V, suggesting that its secretion was dependent on the presence of N-linked carbohydrate. Factor V activity was also expressed on the vascular smooth muscle cell surface, as indicated by the ability of cultured cells to promote factor Xa-catalyzed prothrombin activation. These data suggest that the proliferation of smooth muscle cells in response to vascular injury may be one mechanism that links vascular disease with thrombosis.


Trocar-assisted sutureless intrascleral posterior chamber foldable intra-ocular lens fixation.
We report a novel technique characterized by sutureless scleral fixation of three-pieces foldable intraocular lens (IOL) using 25-gauge transconjunctival sutureless vitrectomy (TSV) trocars in patients with insufficient posterior capsule support. We performed this technique on the eight eyes of the seven patients. The scleral tunnels (STs) are prepared by insertion of the 25-gauge TSV microcannulas using the trocars, and anterior vitrectomy is performed through the clear corneal paracentesis with the aid of anterior chamber maintainer (ACM). Finally, the three-piece foldable IOL haptics are incarcerated into the prepared STs. The patients were followed up 5-8 months. None of the patients had complications such as postoperative endophthalmitis, glaucoma, IOL tilt or decentralization, and retinal detachment. Injection of a foldable IOL through a clear corneal small incision also contributes the less surgical-induced astigmatism. The presented novel sutureless scleral IOL fixation technique may provide minimal trauma to the surrounding tissues, good IOL stabilization decreasing the incidence of IOL tilt along with shorter operation time, and postoperative quiet eye.


Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature.
Background 11β-hydroxylase deficiency (11βOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5-8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11βOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11βOHD. Methods Clinical, biochemical and radiological data of patients with 11βOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11βOHD were identified (0.1-13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA-CA: 5.5 years, range 1.5-9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11βOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11βOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11βOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.


The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status.
BCL-2 protein plays a pivotal role in overriding programmed cell death (apoptosis), thus favouring a prolonged survival of normal and neoplastic cells. Expression of the bcl-2 gene has been documented in some human tumours (non-Hodgkin's lymphomas and prostatic adenocarcinomas), but findings in breast carcinomas have not been reported. We have used the monoclonal antibody 124 to investigate BCL-2 expression in 212 breast carcinomas, and to correlate it with the oestrogen (ER), progesterone (PR) and epidermal growth factor receptor (EGFR) status, and with other clinicopathological variables including tumour type, grade, stage, growth fraction (as evaluated by Ki-67 immunostaining), and p53 accumulation. Of the 212 carcinomas, 173 (81.6%) exhibited BCL-2 immunoreactivity in more than 25% of the neoplastic cells. BCL-2 immunoreactivity was strongly correlated with ER and PR expression (P < 0.00001), with the lobular type (P = 0.012) and with better differentiated neoplasms (P = 0.00003), whereas it was inversely correlated with EGFR (P < 0.00001), p53 (P = 0.0004) and Ki-67 (P = 0.0002) immunoreactivities. No association was found with tumour stage (T and N categories). We conclude that bcl-2 expression in breast cancers is related to the oestrogen-dependent transcription pathway.