An exploration of the reach of the #MakeSpace4Research hashtag.
Use of social media to communicate with and engage health professionals is increasing. A communications campaign at Newcastle upon Tyne Hospitals NHS Foundation Trust used a Twitter hashtag to improve the visibility of nursing, midwifery and allied health professionals research. This study aimed to explore the reach of the #MakeSpace4Research campaign during its first 12 months. Between November 2018 and 2019, data on all tweets containing #MakeSpace4Research were examined using an online analytical tool. The studied variables were: total reach; total impressions; unique authors; total retweets; total mentions; and top tweeters. All these were collated using two separate variables: matching tweets and impact. #MakeSpace4Research appeared in 6884 tweets, involving 1085 individual Twitter accounts, resulting in more than 16 million impressions. Mentions and impressions both increased threefold, and unique authors more than doubled over the 12-month period. A spike in activity was noted after the campaign was launched at a nursing, midwifery and allied health professionals research conference in May 2019. The #MakeSpace4Research campaign has the potential to connect online communities of research-interested nurses, midwives and allied health professionals.


Preexistence of chronic tubular damage in cases of renal cell cancer after long and high exposure to trichloroethylene.
Substantially more cases of tubular damage were found among renal cell carcinoma patients who had been exposed to high levels of trichloroethylene over many years than among renal cell carcinoma patients who had not been exposed to trichloroethylene. This supports the hypothesis (Goeptar et al. 1995) that chronic tubular damage may be regarded as a necessary precondition for trichloroethylene to exert a nephrocarcinogenic effect. The findings also indicate that the urine protein patterns identified with SDS-PAGE may represent a valuable parameter for effect biomonitoring of persons exposed to high levels of trichloroethylene over many years.


Spinal hydatid disease.
Review article on spinal involvement of hydatid disease. A better understanding of this rare but clinically challenging disease is intended. An overview of the epidemiology, pathogenesis, presentation and diagnosis of spinal hydatid disease is provided. Management problems and frequent pitfalls are discussed as well as current therapeutic options, results and outcome. Thirty-seven reports of spinal hydatid disease published between 1964 and 2000 were reviewed. Most of the reported cases of spinal hydatid disease presented with spinal cord compression syndrome. Due to the relative rarity of the problem the diagnosis was frequently made during surgery. Surgical intervention by decompressive laminectomy was the most frequent first management. Reports of anterior procedures as well as spinal stabilization exist. Intraoperative prophylaxis to reduce spillage as well as pharmacotherapy were usually instituted. Results of surgery were generally reported to be poor. Progressive neurological and mechanical deterioration over the years was the most frequently reported disease course. Anecdotal reports of alternative management strategies exist. Spinal hydatid disease should be considered in the differential diagnosis of spinal cord compression syndrome in endemic countries and sought after with imaging and serology. Treatment is based on surgical decompression. Despite therapy the disease frequently relapses with progressive destruction of the vertebral column and neurological deterioration. Retention of spinal stability is the major long term concern. Overall outcome is poor with few reports of disease-free long term survival.


Nerve growth factor-inducible, large external (NILE) glycoprotein in developing rat cerebral cells in culture.
Fetal rat cerebral cells underwent neuronal differentiation in culture. This process was accompanied by distinct changes in the cellular glycoprotein pattern. The incorporation of [3H]-fucose into two proteins of apparent molecular weights of 30,000 and 60,000 daltons was significantly decreased and specific developmental changes were observed in a group of glycoproteins with high molecular weights (150,000-250,000 dalton). By means of indirect immunoprecipitation one of them was identified as NILE gp (nerve growth factor-inducible large external) glycoprotein (200,000 dalton), a marker of central and peripheral neurons. Its developmental expression on neurons of dissociated rat cerebral cultures was studied using the indirect immunofluorescence technique and compared to the fluorescent-labeling pattern of other neuronal markers. Neurons expressing NILE gp were detected as early as after one day in culture. No preferential staining of neurites versus cell bodies was observed. Two classes of NILE gp-positive cell-type, whereas the other group was represented by larger, more spindle-shaped neurons with a limited number of neuritic processes. In most cases one of these neuritic processes was preferentially labeled. Astroglia cells, as identified by immunolabeling with antisera against the glial acidic fibrillary protein, were observed to develop and mature after the first week in culture. NILE-positive neurons were found to be positioned in close association with glial cell processes.


Fiberoptic endoscopic evaluation of swallowing.
Fiberoptic endoscopic evaluation of swallowing is a technique that allows for the assessment of pharyngeal dysphagia and the implementation of rehabilitation interventions with the goal of promoting safe and efficient swallowing. An overview of the equipment needed for the laryngoscopic evaluation, how to conduct the examination, what can be visualized endoscopically, diagnostic parameters, the implementation of therapeutic strategies, and suggestions for future research are discussed herein.


Below-knee amputation: a modern approach.
Immediate and long-term results of 113 below-knee amputations in 103 patients are presented to justify a comprehensive program of management that includes an objective method for determining amputation level with xenon 133 clearance, precise surgical technic, immediate postoperative prosthesis, and an aggressive program of rehabilitaion. Prediction of healing of the last 30 below-knee amputations was 100% successful, showing the value of 133Xe clearance for determination of amputation level. Zero per cent thirty-day mortality and 100% prosthetic rehabilitation of patients on below-knee prostheses justifies the use of immediate postoperative prosthesis. Long-term follow-up of our patients demonstrates that the five year survival rate of diabetic patients is poor (39%) compared with the nondiabetic amputee (75%) who approached the survival of the normal, age-adjusted male population (85%). The fact that 75% of patients were alive after five years and were still independently ambulatory on their prostheses is final testimony to the value of the program.


Complications of laparoscopic pyeloplasty.
With the development of new video-endoscopic techniques like endopyelotomy, laparoscopy and retroperitoneoscopy the treatment of UPJO has become less invasive. The complications and learning curve of laparoscopic pyeloplasty are presented together with recommendations for adequate management. Based on the personal experience with 189 cases of retroperitoneoscopic pyeloplasty, a literature review (PubMed) was performed focussing on complication and success rates of the procedure. Intraoperative incidents were analysed using the Satava-classification, postoperative complications according to the Clavien-classification. The meta-analysis focussed on the experience of the 3 largest and 2 smaller series representing a cohort of 601 patients. Intraoperative incidents ranged from 2.0 to 2.3% in large series, mostly without consequences for the patient including ligation of lower pole artery, loss of needle, hyperkapnia, cutting of DJ-stent, colonic injury, and port site bleeding. The conversion rate was mainly due to inability to access UPJ or to accomplish the anastomosis ranging between 0.5 and 5.5%. Postoperative complications occured between 12.9 and 15.8% in large series. A total of 5.4-10% represented Grade III-complications, such as urine leakage, haematoma, colonic lesion, and stone formation. Recurrent UPJ-stenosis requiring reintervention was seen in 3.5-4.8%. In all three large series, complications were part of the learning curve. Laparoscopic pyeloplasty has been proven safe and effective with comparable results to open surgery. The experience of pioneering centres with incidence and management of complications will be used by next generations of laparoscopic urologic surgeons to shorten their learning curve.


Atypical xanthoastrocytoma presenting as a meningioma.
A 15-year-old boy was admitted to excision of a large exophytic right parietal tumor, which, on computed tomography scans and angiograms, revealed marked contrast-medium enhancement in infusion studies. Angiographic studies showed meningeal feeders, which suggested a meningioma. Computed tomography scans demonstrated extensive erosion of the skull, which indicated a slowly growing process. Pathologically it shared many features with pleomorphic xanthoastrocytomas, suggesting that neoplasia of the glia limitans may have a wide range of clinicopathological manifestations, including a favorable long-term prognosis.


Ribonucleotide reductase and deoxyribonucleotide pools.
Ribonucleotide reductase plays a crucial role in the maintenance of dNTP pools. A molecular model for the allosteric regulation of the enzyme is substantiated by the effects of nucleosides or inhibitors on pool sizes in intact cells as well as by manifestations of mutations of the reductase and other enzymes involved in deoxynucleoside metabolism. Studies of the dynamics of dNTP pools in 3T6 cells suggest compartmentation of dCTP pools, with perferential DNA synthesis from a pool labeled from cytidine. In contrast, no kinetic evidence for more than one dTTP pool was obtained. Our experiments also suggest that all dTTP formed in growing 3T6 cells is used up for DNA synthesis.


Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers.
Alcohol-a risk factor for atrial fibrillation (AF)-is metabolized by aldehyde dehydrogenase 2 (ALDH2). Dysfunctional alleles of ALDH2 (ALDH2-deficient variants) are prevalent among East Asians. Because the prevalence of AF is estimated to be high in ALDH2-deficient variant carriers, we investigated the correlation between AF and ALDH2-deficient variant carriers, including the association with habitual alcohol consumption. A total of 656 consecutive patients were included in this investigation. ALDH2 genotypes were divided into ALDH2 homozygous wild-type (∗1/∗1), ALDH2 heterozygous-deficient allele (∗1/∗2), and ALDH2 homozygous-deficient allele (∗2/∗2). Multivariate analyses were applied to determine the correlation between ALDH2 genotype and AF. ALDH2∗1/∗2 and ALDH2∗2/∗2 carriers who were ALDH2-deficient variant carriers comprised 199 (30.3%) and 27 (4.1%) patients, respectively. Among these patients, the proportions of habitual alcohol consumption were 26.1% and 0%, respectively. Multivariate analysis revealed that ALDH2∗1/∗2 itself was not a risk factor for AF (odds ratio [OR]: 1.28; P = 0.21). However, habitual alcohol consumption in ALDH2∗1/∗2 carriers was an independent risk factor of AF (OR: 4.13; P = 0.001). Contrary to expectations, ALDH2∗2/∗2 itself had a lower incidence of AF among other risk factors (OR: 0.37; P = 0.03). Although the ALDH2∗1/∗2 itself was not associated with AF, ALDH2∗1/∗2 carriers with habitual alcohol consumption could experience AF because of slow alcohol metabolism. In contrast, ALDH2∗2/∗2 itself had a lower incidence of AF. This might be related to the absence to habitual alcohol consumption in ALDH2∗2/∗2 carriers because of the negligible activity of ALDH2. Thus, abstaining from alcohol consumption might prevent the development of AF in patients who are ALDH2∗1/∗2 carriers.


Rapid genotyping of known mutations and polymorphisms in beta-globin gene based on the DHPLC profile patterns of homoduplexes and heteroduplexes.
Beta-thalassemia represents a great heterogeneity as over 200 mutations have been identified for the beta-globin gene responsible for this disease. A rapid genotyping test with high accuracy, selectivity, and reproducibility suitable for the determination of known mutations is needed for prenatal screening and post-natal diagnosis of this disease in clinical setting. We have performed the validation of a DHPLC assay for direct genotyping of known causative mutations in beta-globin gene using the chromatographic pattern-based strategy under partially-denaturing conditions. DHPLC assay was established based on the analysis of 795 DNA samples from a group of various genotypes for the 20 mutations and 8 polymorphisms in beta-globin gene then validated on 319 tests in a blind study. The results obtained with this assay were in concordance with the results obtained by DNA sequence analysis. This simple method can meet the requirements of direct genotyping of known beta-thalassemia mutations and/or polymorphisms in the clinical setting for Chinese and in general as a model for other populations.


Superior vena caval obstruction by lipomatous hypertrophy of the right atrium.
A structural abnormality was suspected when passage of a Swan-Ganz catheter was obstructed at the distal superior vena cava (SVC). At autopsy, lipomatous hypertrophy of the right atrium markedly narrowed the lumen at the SVC-right atrial junction.


Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period.
the incidence and prevalence of patients with advanced heart failure is increasing worldwide and the number of cardiac transplantations remains limited. it was the aim of the study to describe our experience with the increasing number of available medical, interventional and cardiac surgery options, and to assess heart failure survival score predictability in an academic heart failure center within a 1-year follow-up. in all patients who were referred for cardiac transplant evaluation within a 12-month period between April 1998 and March 1999 at our Interdisciplinary Heart Failure and Transplant Program, our team assessed all medical interventions as well as interventional and surgical treatment options that were available, based on the clinical profile on initial presentation. In 92% of the 120 patients referred for cardiac transplantation evaluation, drug therapy could be optimized. A considerable number of patients could be subjected to an organ-preserving intervention or surgery, either PTCA (n=11), CABG (n=4), valve repair (n=7), multisite pacing (n=7), or partial ventricular resection (n=5). Only a small group of patients with the worst heart failure survival score were listed for heart transplantation (n=17) or received a ventricular assist device (n=3). within a contemporary cohort of advanced heart failure patients, only a small number of patients will undergo cardiac transplantation, which is predictable by the heart failure survival score. Most patients will undergo optimized medical therapy and a considerable number will be subjected to interventional or surgical treatment options.


The influence of cochlear temperature on the electrical travelling wave pattern in the guinea pig cochlea.
Cochlear microphonics (CM) were recorded in the guinea pig using differential recording from the first and third cochlear turns as well as by using a 10-electrode array inserted in the scala tympani of the basal turn. The excitation profile as represented by the CM was quantified by amplitude and phase data, and was measured at normal temperature (38 degrees C) and a 10 degrees lower cochlear temperature. It appears that the CM pattern shifts toward the base of the cochlea as a result of cooling. This is explained on the basis of an increased compliance of the basilar membrane with an optional influence of increased viscosity of the perilymph.


A Novel Lumbar Motion Segment Classification to Predict Changes in Segmental Sagittal Alignment After Lateral Interbody Fixation.
Retrospective cohort study. Lateral interbody fixation is being increasingly used for the correction of segmental sagittal parameters. One factor that affects postoperative correction is the resistance afforded by posterior hypertrophic facet joints in the degenerative lumbar spine. In this article, we describe a novel preoperative motion segment classification system to predict postoperative correction of segmental sagittal alignment after lateral lumbar interbody fusion. Preoperative computed tomography scans were analyzed for segmental facet osseous anatomy for all patients undergoing lateral lumbar interbody fusion at 3 institutions. Each facet was assigned a facet grade (min = 0, max = 2), and the sum of the bilateral facet grades was the final motion segment grade (MSG; min = 0, max = 4). Preoperative and postoperative segmental lordosis was measured on standing lateral radiographs. Postoperative segmental lordosis was also conveyed as a percentage of the implanted graft lordosis (%GL). Simple linear regression was conducted to predict the postoperative segmental %GL according to MSG. A total of 36 patients with 59 operated levels were identified. There were 19 levels with MSG 0, 14 levels with MSG 1, 13 levels with MSG 2, 8 levels with MSG 3, and 5 levels with MSG 4. Mean %GL was 115%, 90%, 77%, 43%, and 5% for MSG 0 to 4, respectively. MSG significantly predicted postoperative %GL (P < .01). Each increase in MSG was associated with a 28% decrease in %GL. We propose a novel facet-based motion segment classification system that significantly predicted postoperative segmental lordosis after lateral lumbar interbody fusion.


DNA methylation. Inhibition of de novo and maintenance methylation in vitro by RNA and synthetic polynucleotides.
A partially purified HeLa cell DNA methylase will methylate a totally unmethylated DNA (de novo methylation) at about 3-4% the rate it will methylate a hemimethylated DNA template (maintenance methylation). Our evidence suggests that many, if not most, dCpdG sequences in a natural or synthetic DNA can be methylated by the enzyme. There is a powerful inhibitor of DNA methylase activity in crude extracts which has been identified as RNA. The inhibition of DNA methylase by RNA may indicate that this enzyme is regulated in vivo by the presence of RNA at specific chromosomal sites. The pattern of binding of RNA to DNA in the nucleosome structure and the DNA replication complex may determine specific sites of DNA methylation. An even more potent inhibition of DNA methylase activity is observed with poly(G), but not poly(C), poly(A), or poly(U). The only other synthetic polynucleotides studied which inhibit DNA methylation as well as poly(G) are the homopolymers poly(dC).poly(dG) and poly (dA).poly(dT). These results point out the unique importance of the guanine residue itself in the binding of the DNA methylase to dCpdG, the site of cytosine methylation. The surprising inhibition of the methylation reaction by poly(dA).poly(dT), which is itself not methylated by the enzyme, suggests the possible involvement of adjacent A and T residues in influencing the choice of sites of methylation by the enzyme.


Artificial intelligence-based measurement outperforms current methods for colorectal polyp size measurement.
An accurate polyp size estimation during colonoscopy is crucial to determine the surveillance interval and predict the risk of malignant progression. However, there is a high degree of subjectivity in estimating polyp size among endoscopists in clinical practice. We aimed to assess the efficacy of a novel method that uses artificial intelligence (AI) to measure the size of colon polyps and compare it with current approaches. Using the W-Net model for vessel segmentation and based on retinal image datasets (DRIVE, STARE, CHASE-DB, and HRF) and colonoscopy images, we developed the bifurcation-to-bifurcation (BtoB) distance measuring method and applied it to endoscopic images. Measurements were compared with those obtained by eight endoscopists (four expert and four trainees). Diagnostic ability and reliability were evaluated using Lin's concordance correlation coefficients (CCCs) and Bland-Altman analyses. For both experts and trainees, visually estimated sizes of the same polyp were significantly inconsistent depending on the camera view used (P < 0.001). Bland-Altman analyses showed that there was a trend toward underestimation of the sizes of the polyps in both groups, especially for polyps larger than 10 mm. The new technique was highly accurate and reliable in measuring the size of colon polyp (CCC, 0.961; confidence interval 0.926-0.979), clearly outperforming the visual estimation and open biopsy forceps methods. The new AI measurement method improved the accuracy and reliability of polyp size measurements in colonoscopy images. Incorporating AI might be particularly important to improve the efficiency of trainees at estimating polyp size during colonoscopy.


Histiocytosis X: a seven-year experience at a children's hospital.
Thirty-two patients with histiocytosis X were evaluated and treated at Children's Memorial Hospital, Chicago, during the years 1978 to 1984. Twelve patients (38%) had solitary or multifocal bone lesions, three (9%) had bone lesions and diabetes insipidus, and seventeen (53%) had cutaneous and/or multisystem involvement. Age at diagnosis ranged from 2 days to 15 years. Fifteen patients were 2 years of age or younger at the time of diagnosis. Sixteen patients (50%) had skin infiltrates, of whom seven (43%) had cutaneous lesions documented at birth. Cutaneous lesions included vesicopustules, erythematous papules, nodules, eczematous dermatitis, granulomatous ulcerative lesions, petechiae, and hemorrhagic lesions. Xanthomas and nail dystrophy were not observed. The therapeutic regimen chosen was based on extent of involvement and location of infiltrates. Only two of the thirty-two patients died; both had multisystem disease.


Surgical simulation training for escharotomy: A novel course, improving candidate's confidence in a time critical procedure.
Circumferential deep burns on the limb lead to a constrictive, tourniquet-like effect causing critical limb ischaemia. The treatment, escharotomy, is a time-critical procedure that sometimes is required before the patient arrives at a burn centre. At present, no practical method of teaching this procedure is incorporated into formal educational courses. The feasibility of a comprehensive education package to teach upper limb escharotomy was assessed in a group of plastic and general surgery trainees in Wales. Small group workshops focused on the clinical presentation of patients requiring escharotomy. Participants then executed this on a custom-made high-fidelity simulation upper limb model. The articulated limb has subcutaneous silicone fat which bulges upon decompression and a finger-tip which turns pink indicating satisfactory reperfusion. A before and after five-point Likert scale was used to evaluate changes in participants' self-assessed confidence in the surgical management of escharotomy. Statistical significance between scores was assessed using the Wilcoxon signed-rank test. A total of 34 participants took part. Following completion of the course, general surgery trainees' confidence in executing the procedure increased from a median score of 1.00 "not confident at all" (IQR 1.00-2.00) to 4.00 "fairly confident" (IQR 4.00-5.00, p < 0.01). Plastic surgery trainees' confidence increased from a median score of was 3.00 "somewhat confident" (IQR 1.75-4.00) to 4.00 "fairly confident" (IQR 3.00-4.25, p < 0.01). We developed a comprehensive simulator course that has been demonstrated to improve candidate's confidence in performing escharotomy. The next stage in the course development is to confirm the results in a larger cohort. By developing this simulator course we aim to improve emergency burn care education in the UK and globally.


[Carcinogenic effect of N-methyl-N-nitro-N-nitrosoguanidine on male rats of different inbred lines].
Rats reveal distinct variations in response to carcinogenic action. The highest frequency of stomach tumors (69.6%) and the shortest period of their development (54.7 weeks) were registered in noninbred rats. Multiple lesions of the gastrointestinal tract were relatively frequent, too. Augustus and Penguin rats responded with a high frequency of tumor development. However, tumors arose in them later than in noninbred rats. Wistar rats appeared to be relatively resistant to MNNG action.


[Reconstructive osteoplastic operations after amputation of the shoulder increasing the functional ability for prosthesis].
The article presents 3 methods of operative reconstruction of the shoulder stump for improving the conditions of prosthesis without fixation of the prosthesis at the level of the shoulder joint. The methods were used in 42 patients and gave good functional results.


Quality of life and motivation to change in eating disorders. Perception patient-psychiatrist.
To assess motivation to change (Mch) of patients with an eating disorder (ED) and its relationship with quality-of-life (QoL) by comparing patient and psychiatrist perceptions. Patients (n=358) with an ED completed the disease-specific Health-Related Quality of Life for Eating Disorders (HeRQoLED) questionnaire, the Eating Attitudes Test (EAT-26) and the Short-Form Health Survey (SF-12) at baseline; 273 completed them after 1 year of treatment. The relationship between health-related quality of life (HRQoL) and the Mch stage was assessed using analysis of variance. Chi-square and Kappa statistical analysis assessed congruence in motivational change perception of the patients and psychiatrists. Higher patient-reported Mch was associated with higher HRQoL at the study beginning and end but not using the patient Mch as perceived by the psychiatrist. Initially, the patient and psychiatrist perceptions of Mch differed (kappa coefficient, -0.01); after 1 year they tended to converge (k=0.34). Higher Mch and higher QoL are positively associated. However, patient and psychiatrist perceptions of Mch and the relationship with QoL differ. After 1 year of treatment, these differences decreased.


Lack of Enteral Feeding Associated with Mortality in Prematurity and Necrotizing Enterocolitis.
Necrotizing Enterocolitis (NEC) remains a significant cause of morbidity and mortality. Recently, there has been an increased recognition of the importance of intestinal immunity and the associations with antibiotics and enteral feeds in the pathophysiology of NEC. The primary purpose of this study is to examine the association of enteral feeds on the survival of premature neonates with NEC. A retrospective review using the Vermont Oxford Network for a Level IV NICU from January 1, 2013 through December 31, 2019 was performed. All neonates had a gestational age between 22 to 29 weeks, weighed at least 300 grams (n = 653), had a reported enteral feed status and were treated for NEC (n = 43). Data analysis utilized two-tailed t-tests for NEC and infection rates then Fisher's exact tests for survival status. The incidence of NEC in the population was 6.6% (43/653). Of the 43 neonates treated for NEC, 27 were enterally fed, while the other 16 were not. All 27 neonates with NEC that were able to achieve enteral feeds survived and had an infection rate of 22.2%. Meanwhile, all 16 neonates with NEC that were unable to achieve enteral feeds died and had an infection rate of 62.5%. There is a significant association between enteral feeds and NEC, survival, and infection rates in premature neonates. These findings support the importance of intestinal immunity and the microbiota in NEC. Given the limitations of the retrospective review, the profound survival advantage with enteral feeds reinforces the need for further study.


The effect of TURP on prognosis in prostatic carcinoma.
Of 553 patients definitively irradiated for biopsy proven prostatic adenocarcinoma from January 1976 to March 1986, 287 patients with a minimum follow-up of 4 years were studied. One hundred sixty-two patients had transurethral prostatic resection (TURP); one hundred twenty-five patients did not. When subdivided by stage and histologic grade, those patients with poorly differentiated tumors who underwent TURP had a noticeably higher, but not statistically different, incidence of bony metastasis as compared to those who did not have TURP. Survival at 5 years also appeared to be better in patients with poorly differentiated and stage C disease without TURP. However, local tumor recurrence in poorly differentiated tumor with TURP was 42% as compared to 20% in the NO TURP group, p = .04. Moreover, when the incidence of osseous metastasis was assessed by local tumor status, 20% of the TURP patients with local tumor control developed metastases as compared to 66% of those with local failure. Similarly, within the NO TURP group, the incidence of bony metastasis was 16% for those with local control and 50% for those with local recurrence, p = .005 in both cases. Survival was likewise affected by local tumor control, regardless of whether or not TURP was performed. In patients with local tumor control, survival was 80% at 5 years with TURP and 86% without TURP (p greater than 0.1). In contrast, only 14% of patients with local recurrence and TURP were alive at 5 years which was not statistically different from the 32% survival in those with local recurrence but NO TURP. It seems, therefore, that comparing prognosis by TURP alone overlooks the inherent characteristics of the tumor and the extent of the disease.


Influence of somatostatin on blood pressure and plasma renin activity in the rat.
In the anaesthetized rat synthetic somatostatin can interfere with the renin-angiotensin system by increasing plasma renin activity and decreasing normal blood pressure or counteracting several types of experimental hypertension.


Astrocytic phosphorylation of PDK1 on Tyr9 following an excitotoxic lesion in the mouse hippocampus.
3-phosphoinositide-dependent kinase-1 (PDK1) is suggested to play important roles in the regulation of synaptic plasticity and neuronal cell survival in the mature CNS. Although few studies have investigated the roles of PDK1, little is known about PDK1 changes in glial cells under neuropathological conditions. In current report, phosphorylation of PDK1 was monitored specially on tyrosine residues, following the induction of an excitotoxic lesion in rat brain by using kainic acid administration. In injured hippocampal CA3 region, Tyr9 phosphorylation of PDK1 was increased from 4h until 3 day post-injection. Double immunohistochemistry further evaluated that these phosphorylated forms of PDK1 were localized in astrocytes not other cells. Overexpression of unphosphorylatable mutant, PDK1-Y9F leads to inhibit Protein kinase B (PKB/Akt) activation and cAMP responsive element binding protein (CREB) phosphorylation. In conclusion, our results suggested for the first time that tyrosine phosphorylation of PDK1 is required for PKB and CREB activation in KA-mediated excitotoxic lesion in mouse brain.


Humoral immune response to Dipylidium caninum infection of stray dogs in Taiwan.
Two kinds of homogeneous proglottid, mature and gravid, of Dipylidium caninum were used as the antigens for immunodiagnosis of canine dipylidiosis in stray dogs in Tainan, Taiwan. The ELISA was performed on 30 serum samples; 24 from dipylidiosis, four from ancylostomosis and two from toxocariosis. The ELISA have specificity and sensitive of 100 and 50% for mature proglottid extract, and 75 and 100%, respectively, for gravid proglottid extract. EITB technique showed two major peptide bands of 94.8 and 97.9kDa were recognized in the sera pool of infected dogs.


The effect of kinship on spacing among female red-backed voles, Clethrionomys rufocanus bedfordiae.
I examined the effect of relatedness on spatial organization and reproduction in enclosed populations of red-backed voles (Clethrionomys rufocanus bedfordiae) in 1984 and 1985. Enclosures with low and high coefficients of relatedness among females were established, and the proximity and overlap of the home ranges of these females were recorded before and after the introduction of males. The following conclusion were reached: 1. The number of females that established home ranges and gave birth to young did not differ significantly among the enclosures. 2. Before males were introduced, sisters had home ranges in closer proximity than non-sibling females. After males were introduced, some sibling females still remained close to each other but occupied exclusive home ranges near those of their sisters. Other sibling groups, particularly in 1985, dispersed after the males' introduction. 3. The overlap or proximity between neighboring females decreased after the males' introduction, but the trend was more pronounced for kin than for non-kin. 4. A female was better able to acquire an exclusive home range when the neighboring female was a sister than when the neighbor was not a sister. 5. The tendency for female littermates to disperse was non-random. The difference in body weight between dispersers and residents was significant within the sibling groups but not within the non-siblings groups introduced at the same locations.


Measurement of the kinetics of DNA repair synthesis after uv irradiation using immunochemical staining of incorporated 5-bromo-2'-deoxyuridine and flow cytometry.
The kinetics of unscheduled DNA synthesis in normal human fibroblasts was characterized by flow cytometry utilizing the immunofluorescent detection of 5-bromo-2'-deoxyuridine (BrdUrd) incorporated into cellular DNA during the repair process. Quiescent normal human fibroblasts were irradiated with ultraviolet light and incubated in the presence of BrdUrd during a postirradiation repair period. The amount of unscheduled DNA synthesis was then quantified in the quiescent cells by immunofluorescence staining using monoclonal antibodies against BrdUrd incorporated into the DNA. Significant amounts of unscheduled DNA synthesis were measured after doses as low as 0.1 J/m2 and for time periods as short as 15 min. The initial repair rate was found to be linear with time at all doses tested until repair neared completion. Interestingly, the initial repair rate was constant for doses over the range of 5 to 40 J/m2, whereas the time to completion of repair was dose dependent. These results suggest that above 5 J/m2 in normal human fibroblasts, the repair process is saturated but continues to function until all available regions are repaired. Using this methodology for measuring unscheduled DNA synthesis in combination with second and third flow markers, it is now possible to measure unscheduled DNA synthesis in heterogeneous mixtures of cells.


Gas chromatography/tandem mass spectrometry detection of extracellular kynurenine and related metabolites in normal and lesioned rat brain.
We describe here a gas chromatography-tandem mass spectrometry (GC/MS/MS) method for the sensitive and concurrent determination of extracellular tryptophan and the kynurenine pathway metabolites kynurenine, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) in rat brain. This metabolic cascade is increasingly linked to the pathophysiology of several neurological and psychiatric diseases. Methodological refinements, including optimization of MS conditions and the addition of deuterated standards, resulted in assay linearity to the low nanomolar range. Measured in samples obtained by striatal microdialysis in vivo, basal levels of tryptophan, kynurenine, and QUIN were 415, 89, and 8 nM, respectively, but 3-HK levels were below the limit of detection (<2 nM). Systemic injection of kynurenine (100 mg/kg, i.p.) did not affect extracellular tryptophan but produced detectable levels of extracellular 3-HK (peak after 2-3 h: ~50 nM) and raised extracellular QUIN levels (peak after 2h: ~105 nM). The effect of this treatment on QUIN, but not on 3-HK, was potentiated in the N-methyl-D-aspartate (NMDA)-lesioned striatum. Our results indicate that the novel methodology, which allowed the measurement of extracellular kynurenine and 3-HK in the brain in vivo, will facilitate studies of brain kynurenines and of the interplay between peripheral and central kynurenine pathway functions under physiological and pathological conditions.


Catheter thrombosis and superior/inferior vena cava syndrome are rare complications of long term parenteral nutrition.
The objective of this study was to determine the incidence of catheter thrombosis and superior/inferior vena cava (SVC IVC ) syndrome in a large population of patients receiving home total parenteral nutrition (TPN), using retrospective data collection and analysis. 527 patients including 138 children who were discharged on home TPN and followed in the UCLA home TPN program for a minimum of one week between April, 1973 and October, 1991. There was a total of 1154 years of patients follow-up, including 241 years in children. Fifty-seven patients (11%) developed 81 episodes of catheter thrombosis excluding SVC IVC syndrome with an incidence of 0.07 episodes per catheter year. The median catheter duration prior to thrombosis was 7 months. Twenty-one thromboses occured in children with an incidence of 0.09 per catheter year. Eleven percent of thrombotic episodes were associated with catheter sepsis. Thirty-nine percent of patients had a PTT less than control values. Twenty-two patients including 6 children developed SVC IVC syndrome with an incidence of 0.02 per catheter year. SVC IVC syndrome was not associated with catheter sepsis in any patient. Sixty-eight percent of patients had catheter thrombosis at some point prior to developing SVC IVC syndrome. It is concluded that catheter-related thrombotic events are rare complications of home TPN and are uncommonly associated with infection. However, we recommend warfarin anticoagulation following an initial thrombotic event, in the absence of catheter malposition, for all such patients as long as they maintain a central venous catheter.


Validation of a methodology to quantify macro, micro, and potentially toxic elements in food matrices.
To routinely assess whether consumed food meets international guidelines, a single analytical method able to quantify minerals and potentially toxic elements (PTEs) in real food matrices is required. This work validated a simple and efficient method to quantify nine elements in different food matrices by ICP-MS. Samples from local markets (chicken, mussels, fish, rice, and seaweed) and certified reference materials were digested with HNO3 68 % and H2O2 30 %. All performance criteria (working range, linearity, LOD, LOQ, selectivity, repeatability, and trueness) met the requirements of the Portuguese Association of Accredited Laboratories. Comparison between raw and cooked food showed significant changes in most element levels, and PTEs contents complied with the maximum permissible values (EC N° 1881/2006). The minimum and maximum amounts of the foods studied, alone or in combination, raw or cooked, that can be daily consumed to meet EFSA and WHO nutritional and safety requirements were analysed.


Fibrous hamartoma of infancy: imaging findings.
Fibrous hamartoma of infancy is a benign tumor that typically arises within the first 2 years of life in the subcutaneous and lower dermal layers. Diagnosis can be challenging as it is a rare tumor, and the imaging appearance is not well known. To describe the imaging features in 4 cases of fibrous hamartoma of infancy focusing on ultrasound (US) and magnetic resonance (MR) findings. In this retrospective IRB-approved study, informed consent was waived. We searched patient charts for histopathology-confirmed fibrous hamartoma of infancy diagnosis between November 2013 and November 2022. We found four cases, three boys and one girl, and the mean age was 1.4 years (5 months-3 years). The lesions were located in the axilla, posterior elbow, posterior neck, and lower back. All four patients underwent ultrasound evaluation of the lesion, and two patients also underwent MRI evaluation. The imaging findings were reviewed by consensus by two pediatric radiologists. US imaging revealed subcutaneous lesions with variably defined hyperechoic regions and intervening hypoechoic bands resulting in a linear "serpentine" pattern or a "multiple semicircle" pattern. MR imaging evidenced heterogeneous soft tissue masses, localized in the subcutaneous fat, and showed hyperintense fat interspersed with hypointense septations on both T1- and T2-weighted images. Fibrous hamartoma of infancy has a suggestive appearance on US with heterogeneous, echogenic subcutaneous lesions with intervening hypoechoic portions, in parallel or circumferential arrangement that can be seen as a serpentine or semicircular pattern. On MRI, interspersed macroscopic fatty components show high signal intensity on T1- and T2-weighted images and reduced signal on fat-suppressed inversion recovery images, with irregular peripheral enhancement.


A relaxin-like gonad-stimulating peptide from the starfish Aphelasterias japonica.
Relaxin-like gonad-stimulating peptide (RGP) in starfish is the first identified invertebrate gonadotropin responsible for final gamete maturation. In this study, a new ortholog RGP was identified from Aphelasterias japonica. The DNA sequence encoding A. japonica RGP (AjaRGP) consists of 342 base pairs with an open reading frame encoding a peptide of 113 amino acids (aa), including a signal peptide (26aa), B-chain (20aa), C-peptide (42aa), and A-chain (25aa). AjaRGP is a heterodimeric peptide with disulfide cross-linkages. Comparing with Asterias amurensis RGP (AamRGP) and Patiria (=Asterina) pectinifera RGP (PpeRGP), the amino acid identity levels of AjaRGP with respect to AamRGP and PpeRGP are 84% and 58% for the A-chain and 90% and 68% for the B-chain, respectively. This suggests that AjaRGP is closer to AmaRGP rather than PpeRGP. Although chemical synthetic AjaRGP can induce gamete spawning and oocyte maturation in ovarian fragments of A. japonica, the ovary of P. pectinifera fails to respond to AjaRGP. This suggests that AjaRGP acts species-specifically.


Time is of the essence: an application of a relational event model for animal social networks.
Understanding how animal social relationships are created, maintained and severed has ecological and evolutionary significance. Animal social relationships are inferred from observations of interactions between animals; the pattern of interaction over time indicates the existence (or absence) of a social relationship. Autonomous behavioural recording technologies are increasingly being used to collect continuous interaction data on animal associations. However, continuous data sequences are typically aggregated to represent a relationship as part of one (or several) pictures of the network of relations among animals, in a way that parallels human social networks. This transformation entails loss of information about interaction timing and sequence, which are particularly important to understand the formation of relationships or their disruption. Here, we describe a new statistical model, termed the relational event model, that enables the analysis of fine-grained animal association data as a continuous time sequence without requiring aggregation of the data. We apply the model to a unique data set of interaction between familiar and unfamiliar steers during a series of 36 experiments to investigate the process of social disruption and relationship formation. We show how the model provides key insights into animal behaviour in terms of relationship building, the integration process of unfamiliar animals and group building dynamics. The relational event model is well suited to data structures that are common to animal behavioural studies and can therefore be applied to a range of social interaction data to understand animal social dynamics.


Cross-reactivity between enteric adenoviruses and adenovirus type 4: analysis of epitopes by solid-phase immune electron microscopy.
The immunological relationships between the two newly discovered serotypes of enteric adenoviruses, Ad40 and Ad41, and antisera to human adenoviruses representing all subgroups were studied by solid-phase immune electron microscopy. A pronounced two-way cross-reaction was seen between Ad40 (subgroup F) and Ad41 (subgroup G). Furthermore, a distinct one-way cross-reaction was noted between adenovirus type 4 antiserum (subgroup E) and virions of Ad40.


Influence of waking and sleep stages on the inter-ictal paroxysmal activity in partial epilepsy with complex seizures.
Twenty-six patients suffering from partial epilepsy with complex seizures underwent polysomnographic recording. Paroxysmal activity (PA) densities in waking and sleep stages were assessed. Total PA densities of one night were found to be an increasing function of the seizure frequency in the previous period. Nineteen patients had more PA during sleep, 5 others in the waking state and the two remaining patients exhibited no differences in PA densities between sleep and waking. Nocturnal seizures were reported by patients showing the sleep PA increase pattern; they also used more anti-convulsants than patients showing the waking PA increase pattern. Differences in PA densities between these two groups were more pronounced in the more desynchronized (waking) and the more synchronized (stages 3 + 4) cortical states. The modulation by slow wave sleep stages was independent of, and superimposed on, the sleep/waking one.


Maternal resistance exercise promotes changes in neuroplastic and epigenetic marks of offspring's hippocampus during adult life.
Studies indicate that gestational exercise practice positively impacts the offspring's cognition. Nevertheless, the influence of maternal resistance exercise, different periods of exercise practice, and the inter- and transgenerational effects involved in these responses are not known. This study sought to report the influence of the maternal practice of resistance exercise on offspring's cognitive function, exploring behavior, and neuroplastic and epigenetic marks in the hippocampus. Female Wistar rats were divided into four groups: sedentary (SS), exercised during pregnancy (SE), exercised before pregnancy (ES), and exercised before and during pregnancy (EE). Exercised rats were submitted to a resistance exercise protocol (vertical ladder climbing). Between postnatal days (P)81 and P85, male offspring were submitted to the Morris water maze test. At P85, the following analyses were performed in offspring's hippocampus: expression of IGF-1 and BrdU+ cells, global DNA methylation, H3/H4 acetylation, and HDAC2 amount. Only the offspring of SE mothers presented subtly better performance on learning and memory tasks, associated with lower HDAC2 amount. Offspring from ES mothers presented an overexpression of hippocampal neuroplastic marks (BrdU+ and IGF-1), as well as a decrease of DNA methylation and an increase in H4 acetylation. Offspring from EE mothers (continuously exercised) did not present modifications in plasticity or epigenetic parameters. This is the first study to observe the influence of maternal resistance exercise on offspring's brains. The findings provide evidence that offspring's hippocampus plasticity is influenced by exercise performed in isolated periods (pre- or gestationally) more than that performed continually.


Usefulness of TAO model to predict and manage the transformation in soil of carbon and nitrogen forms from West-Africa urban solid wastes.
The TAO model of Transformation of Added Organic materials (AOM) calibrated on AOMs and substrates of temperate areas was used to assess the transformations in soil of carbon and nitrogen forms of AOMs: raw materials, selected mixtures and composts from Ouagadougou urban wastes. AOMs were studied in terms of chemical and biochemical contents and for their C and N mineralization during incubations in a typical Ferric Lixisol of the sub-urban agriculture of Ouagadougou. The TAO model was used to predict the transformations of C (very labile, resistant and stable organic C) and N (very labile, resistant and stable organic N, produced and immobilized inorganic N) forms driven by AOM biochemical data. Without any change in calibration formulae, TAO predicted accurately the C transformations and inorganic N production of most of the tested AOMs, with a tendency to slightly overestimate C mineralization of previously well-composted materials and re-mineralization of immobilized N. Complementary adjustments using more complete data from laboratory experiments are suggested, but the model agrees with other data collected in the field and appears as a promising tool to optimise the management of urban wastes in the tropical area as well as for agro industrial organic fertilizers of the temperate zone. This application suggests ways to improve the management of urban wastes aiming to optimize agricultural yields, system sustainability and C sequestration in soil.


Neoadjuvant Treatment with HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.
This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety. A network meta-analysis was applied to estimate the risk ratios along with 95% confidence intervals (CIs) for pathological complete response (pCR) and serious adverse events (SAE). A mixed-effect parametric survival analysis was conducted to assess the disease-free survival (DFS) between treatments. Twenty-one RCTs with eleven regimens of neoadjuvant anti-HER2 therapy (i.e., trastuzumab + chemotherapy (TC), lapatinib + chemotherapy (LC), pertuzumab + chemotherapy (PC), pertuzumab + trastuzumab (PT), trastuzumab emtansine + pertuzumab (T-DM1P), pertuzumab + trastuzumab + chemotherapy (PTC), lapatinib + trastuzumab + chemotherapy (LTC), trastuzumab emtansine + lapatinib + chemotherapy (T-DM1LC), trastuzumab emtansine + pertuzumab + chemotherapy(T-DM1PC), PTC followed by T-DM1P (PTC_T-DM1P), and trastuzumab emtansine (T-DM1)) and chemotherapy alone were included. When compared to TC, only PTC had a significantly higher DFS with a hazard ratio (95% CI) of 0.54 (0.32-0.91). The surface under the cumulative ranking curve (SUCRA) suggested that T-DM1LC (91.9%) was ranked first in achieving pCR, followed by the PTC_T-DM1P (90.5%), PTC (74.8%), and T-DM1PC (73.5%) regimens. For SAEs, LTC, LC, and T-DM1LC presented with the highest risks (SUCRA = 10.7%, 16.8%, and 20.8%), while PT (99.2%), T-DM1P (88%), and T-DM1 (83.9%) were the safest regimens. The T-DM1PC (73.5% vs. 71.6%), T-DM1 (70.5% vs. 83.9%), and PTC_T-DM1P (90.5% vs. 47.3%) regimens offered the optimal balance between pCR and SAE. The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen. However, these results were based on a small number of studies, and additional RCTs assessing the efficacy of regimens with T-DM1 are still needed to confirm these findings.


Reorganizing the History of Present Illness to Improve Verbal Case Presenting and Clinical Diagnostic Reasoning Skills of Medical Students: The All-Inclusive History of Present Illness.
The Institute of Medicine states that most diagnostic errors are caused by flaws in clinician diagnostic thinking. Accurately inferring the correct diagnosis from the patient history is the best way to improve diagnostic accuracy and efficiency. Such an improvement is contingent upon training early phase medical learners how to organize data from a patient history to arrive at the most likely diagnosis of the patient's chief health concern (CC). We describe how organizing the traditional history of present illness into what our trainees have come to call the "All-Inclusive History of Present Illness" (AIHPI) by applying the Bayesian statistical concepts of chronologically sequencing, as suggested by Skeff, both relevant historical risks and known medical events generate a series of pre-event probabilities of the most likely disease causing a patient's CC. Our trainees have enthusiastically recognized that the AIHPI organization process helps them improve both their ability to deliver well-organized, succinct verbal case presentations and the efficiency of generating and communicating what they think is the most likely disease causing a patient's CC.


Dry-Season Snow Cover Losses in the Andes (18°-40°S) driven by Changes in Large-Scale Climate Modes.
The Andean snowpack is the primary source of water for many communities in South America. We have used Landsat imagery over the period 1986-2018 in order to assess the changes in the snow cover extent across a north-south transect of approximately 2,500 km (18°-40°S). Despite the significant interannual variability, here we show that the dry-season snow cover extent declined across the entire study area at an average rate of about -12% per decade. We also show that this decreasing trend is mainly driven by changes in the El Niño Southern Oscillation (ENSO), especially at latitudes lower than 34°S. At higher latitudes (34°-40°S), where the El Niño signal is weaker, snow cover losses appear to be also influenced by the poleward migration of the westerly winds associated with the positive trend in the Southern Annular Mode (SAM).


Inhibition of IL-6 overproduction by steroid treatment before transsternal thymectomy for myasthenia gravis: does it help stabilize perioperative condition?
Overproduction of interleukin (IL)-6 plays an important role in the pathophysiology of myasthenia gravis (MG), and thymectomy can cause myasthenic crisis because of surgically induced overproduction of IL-6. Preoperative steroid therapy is beneficial in preventing MG crisis during the perioperative period. The purpose of this study was to clarify the effect of preoperative steroid therapy on proinflammatory mediators during the perioperative period of transsternal thymectomy for MG. The study group comprised 20 consecutive MG patients undergoing transsternal thymectomy during the period March 2002 through March 2004. Seventeen of these patients received dose-escalated steroid therapy before thymectomy (steroid treatment group) and three did not (non-steroid treatment group). Serum concentrations of C-reactive protein (CRP) and IL-6 were determined during the perioperative period; clinical outcomes were reviewed, and the results were compared between the two groups. Peak serum IL-6 and CRP concentrations were significantly lower in the steroid treatment group than in the non-steroid treatment group. Amongst perioperative variables subjected to multiple regression analysis, preoperative steroid treatment were found to be the most significant independent predictor of inhibited IL-6 production on postoperative day 1. No postoperative respiratory failure occurred in the steroid treatment group, but it did occur in the non-steroid treatment group. Preoperative steroid therapy can ameliorate IL-6 overproduction and may help stabilize the patient's postoperative condition.


A promising QTL QSns.sau-MC-3D.1 likely superior to WAPO1 for the number of spikelets per spike of wheat shows no adverse effects on yield-related traits.
A likely new locus QSns.sau-MC-3D.1 associated with SNS showing no negative effect on yield-related traits compared to WAPO1 was identified and validated in various genetic populations under multiple environments. The number of spikelets per spike (SNS) is one of the crucial factors determining wheat yield. Thus, improving our understanding of the genes that regulate SNS could help develop wheat varieties with higher yield. In this study, a recombinant inbred line (RIL) population (MC) containing 198 lines derived from a cross between msf and Chuannong 16 (CN16) was used to construct a genetic linkage map using the GenoBaits Wheat 16 K Panel. The genetic map contained 5,991 polymorphic SNP markers spanning 2,813.25 cM. A total of twelve QTL for SNS were detected, and two of them, i.e., QSns.sau-MC-3D.1 and QSns.sau-MC-7A, were stably expressed. QSns.sau-MC-3D.1 had high LOD values ranging from 4.99 to 11.06 and explained 9.71-16.75% of the phenotypic variation. Comparison of QSns.sau-MC-3D.1 with previously reported SNS QTL suggested that it is likely a novel one, and two kompetitive allele-specific PCR (KASP) markers were further developed. The positive effect of QSns.sau-MC-3D.1 was also validated in three biparental populations and a diverse panel containing 388 Chinese wheat accessions. Genetic analysis indicated that WHEAT ORTHOLOG OFAPO1 (WAPO1) was a candidate gene for QSns.sau-MC-7A. Pyramiding of QSns.sau-MC-3D.1 and WAP01 had a great additive effect increasing SNS by 7.10%. Correlation analysis suggested that QSns.sau-MC-3D.1 was likely independent of effective tiller number, plant height, spike length, anthesis date, and thousand kernel weight. However, the H2 haplotype of WAPO1 may affect effective tiller number and plant height. These results indicated that utilization of QSns.sau-MC-3D.1 should be given priority for wheat breeding. Geographical distribution analysis showed that the positive allele of QSns.nsau-MC-3D.1 was dominant in most wheat-producing regions of China, and it has been positively selected among modern cultivars released in China since the 1940s. Gene prediction, qRT-PCR analysis, and sequence alignment suggested that TraesCS3D03G0216800 may be the candidate gene of QSns.nsau-MC-3D.1. Taken together, these results enrich our understanding of the genetic basis of wheat SNS and will be useful for fine mapping and cloning of the gene underlying QSns.sau-MC-3D.1.


Clinical Benefit of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves.
The use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and bioprosthetic heart valve is still controversial. The aim of this study was to compare the tolerability and effectiveness of treatment with DOACs versus vitamin K antagonists (VKAs) in patients with AF and a bioprosthetic heart valve in clinical practice. Data for this study were sourced from the multicenter, prospectively maintained AF Research Database (NCT03760874), which includes all patients with AF undergoing follow-up at participating centers through outpatient visits every 3-6 months. The rates of occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism), major bleed, and intracranial hemorrhage (ICH) were assessed. These data were used for quantifying the net clinical benefit (NCB) of DOACs versus VKAs, in accordance with the following formula: (Thromboembolic events incidence rate with VKAs - Thromboembolic events incidence rate with DOACs) - Weighting factor × (ICH rate with DOACs - ICH incidence rate with VKAs). The database was retrospectively queried for patients with AF who were prescribed a DOAC or VKA and had a history of bioprosthetic heart valve replacement. A total of 434 patients with AF (DOACs, n = 211; VKAs, n = 223) were identified. Propensity score matching identified 130 patients prescribed DOACs (apixaban, 55.4%; rivaroxaban, 30.0%; dabigatran, 13.1%; edoxaban, 1.4%) and the same number of VKA recipients (warfarin, 89.2%; acenocoumarol, 10.8%). The mean (SD) duration of follow-up was 26.8 (2.3) months. The incidence rates of thromboembolic events were 1.3 per 100 person-years in the DOAC group versus 2.0 per 100 person-years in the VKA group (P = 0.14). The incidence rates of major bleed events were 2.6 per 100 person-years in the DOAC group versus 4.9 per 100 person-years in the VKA group (P = 0.47). The incidence rates of ICH were 0.38 per 100 person-years in the DOAC group versus 1.16 in the VKA group (hazard ratio = 0.33; 95% CI, 0.05-2.34; P = 0.3). A positive NCB of DOACs over VKAs of +1.87 was found. According to these data from clinical practice, DOACs seem to be associated with a greater NCB versus VKAs in patients with AF with a bioprosthetic heart valve, primarily due to lower rates of both major bleeds and thromboembolic events.


TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels.
OSCA/TMEM63s form mechanically activated (MA) ion channels in plants and animals, respectively. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. Here, we uncover an unanticipated monomeric configuration of TMEM63 proteins. Structures of TMEM63A and TMEM63B (referred to as TMEM63s) revealed a single highly restricted pore. Functional analyses demonstrated that TMEM63s are bona fide mechanosensitive ion channels, characterized by small conductance and high thresholds. TMEM63s possess evolutionary variations in the intracellular linker IL2, which mediates dimerization in OSCAs. Replacement of OSCA1.2 IL2 with TMEM63A IL2 or mutations to key variable residues resulted in monomeric OSCA1.2 and MA currents with significantly higher thresholds. Structural analyses revealed substantial conformational differences in the mechano-sensing domain IL2 and gating helix TM6 between TMEM63s and OSCA1.2. Our studies reveal that mechanosensitivity in OSCA/TMEM63 channels is affected by oligomerization and suggest gating mechanisms that may be shared by OSCA/TMEM63, TMEM16, and TMC channels.


A multiresidue analytical method using solid-phase extraction and high-pressure liquid chromatography tandem mass spectrometry to measure pharmaceuticals of different therapeutic classes in urban wastewaters.
An analytical method with two extraction steps has been developed and validated for the simultaneous determination of 30 pharmaceuticals belonging to various therapeutic categories in urban wastewater. The aim was to boost the little available information on drugs' fates in sewage treatment plants (STPs) and in the receiving surface water. Aqueous samples were divided into two aliquots, each extracted by a different solid-phase extraction (SPE) method and analysed by reversed-phase liquid chromatography tandem mass spectrometry (HPLC-MS-MS). Recoveries of the pharmaceuticals were mostly greater than 70% and the overall variability of the method was below 8%. The instrumental quantification limit (IQL) varied between 30 and 400 pg injected, and the limits of quantification (LOQ) were in the low ng/L range. Nineteen pharmaceuticals were detected in concentrations between 0.5 and 2000 ng/L in effluents collected from several STPs in Italy. Atenolol, ciprofloxacin, furosemide, hydrochlorothiazide, ofloxacin, ranitidine and sulphamethoxazole were the most abundant compounds. The present analytical method was useful to check for pharmaceuticals in various Italian STPs and to identify the most abundant compounds.


The years of the monkey.
The fact that mammals are diploid sets a barrier to rapidly understand the function of non-coding and coding genes in the genome. Recently, Yang et al. reported successful derivation of monkey haploid embryonic stem cells from parthenotes, which provide an effective platform for studying mammalian gene function and enable reverse genetic screening of genes for recessive phenotypes in monkeys.


Statins and nitric oxide reduce C-reactive protein production while inflammatory conditions persist.
C-reactive protein (CRP) is made in liver and its serum concentration increases in inflammation. Measurement of serum CRP is recommended for use as an indicator of inflammation and predictor of atherosclerosis. Cholesterol-lowering drugs statins also lower CRP. To evaluate statin-mediated CRP reduction and to reassess clinical usefulness of CRP, we investigated regulation of CRP gene expression. Here, we show that pravastatin and simvastatin prevent the induction of CRP expression in human hepatoma Hep3B cells exposed to proinflammatory cytokines IL-6 and IL-1beta The nitric oxide (NO) donor, sodium nitroprusside, also prevented the induction of CRP expression while the CRP inducers IL-6 and IL-1beta were present with the cells. The effect of NO on CRP expression was at the level of transcription. These findings suggest that the decrease in CRP level in vivo after statin-treatment does not necessarily reflect absence of inflammation, and that NO-releasing drugs have the potential to reduce serum CRP levels. Thus, the measurement of serum CRP levels alone in individuals on statin/NO-therapy is not as useful as was imagined.


Evaluating diffusion-weighted magnetic resonance imaging for target volume delineation in head and neck radiotherapy.
Inter-observer variability (IOV) in target volume delineation is a source of error in head and neck radiotherapy. Diffusion-weighted imaging (DWI) has been shown to be useful in detecting recurrent head and neck cancer. This study aims to determine whether DWI improves target volume delineation and IOV. Four radiation oncologists delineated the gross tumour volume (GTV) for ten head and neck cancer patients. Delineation was performed on CT alone as well as fused image sets which incorporated fluorodeoxyglucose (FDG)-positron emission tomography (PET) and magnetic resonance imaging (MRI) in the form of CT/PET, CT/PET/T2W and CT/PET/T2W/DWI image sets. Analysis of the variability of contour volumes was completed by comparison to the simultaneous truth and performance level estimation (STAPLE) volumes. The DICE Similarity Coefficient (DSC) and other IOV metrics for each observer's contour were compared to the STAPLE for each patient and image dataset. A DWI usability scoresheet for delineation was completed. The CT/PET/T2W/DWI mean GTV volume of 13.37 (10.35-16.39)cm3 was shown to be different to the mean GTV of 10.92 (8.32-13.51)cm3 when using CT alone (P < 0.001). The GTV DSC amongst observers for CT alone was 0.72 (0.65-0.79), CT/PET was 0.73 (0.67-0.80), CT/PET/T2W was 0.71 (0.64-0.77) and CT/PET/T2W/DWI was 0.69 (0.61-0.75). Mean GTVs with the addition of DWI had slightly larger volumes compared to standard CT and CT/PET volumes. DWI may add supplemental visual information for GTV delineation while having a small impact on IOV, therefore potentially improving target volume delineation.


Role of oxidative stress in inactivation of Escherichia coli BW25113 by nanoscale zero-valent iron.
An Escherichia coli BW25113 wildtype strain and mutant strains lacking genes that protect against oxidative stress were examined at different growth phases for susceptibility to zero-valent iron (nZVI). Viability of cells was determined by the plate count method. All mutant strains were more susceptible than the wild type strain to nZVI; however, susceptibility differed among the mutant strains. Consistent with the role of rpoS as a global stress regulator, an rpoS gene knockout mutant exhibited the greatest susceptibility to nZVI under the majority of conditions tested (except exponential and declining phases at longer exposure time). Mutants lacking genes encoding the inducible and constitutively expressed cytosolic superoxide dismutases, sodA and sodB, respectively, were more susceptible to nZVI than a mutant lacking the gene encoding sodC, a periplasmic superoxide dismutase. This suggests that nZVI induces oxidative stress inside the cells via superoxide generation. Quantitative polymerase chain reaction was used to examine the expression of katG, a gene encoding the catalase-peroxidase enzyme, in nZVI-treated E. coli at different growth phases. Results showed that nZVI repressed the expression of katG in all but lag phases.


Implementation of Lung Cancer Screening in the United States: Changing Trends Based on a Survey of Society of Thoracic Radiology Members.
The aim of this study was to determine whether practices and protocols regarding low-dose CT (LDCT) screening for lung cancer have changed among Society of Thoracic Radiology (STR) members after the recent release of recommendations in favor of LDCT screening by organizations such as the US Preventive Services Task Force (USPSTF). We administered an online survey to members of the STR in 2013, before the release of the USPSTF recommendations, to determine the availability and attributes of screening programs at their institutions. Here we report results of a follow-up survey conducted using the same protocols but distributed in November 2014, after the release of the guidelines. We filtered returned surveys such that each institution was represented only once in the data. Of the 75 unique institutions represented in the 2014 survey, 62 (83%) had an active screening program, compared with 66% of institutions in the original 2013 survey. In addition, approximately half of the institutions reported >50 patients screened in the 12 months before administration of the 2014 survey compared with 28% in 2013. In 2014, most institutions without an active screening program were considering implementing one. Our follow-up survey showed several trends in the utilization of LDCT screening for lung cancer between 2013 and 2014: in 2014, an increased number of sites had active screening programs, increased numbers of patients were screened, and there was greater integration of smoking cessation counseling as part of the screening programs at individual institutions.


MDM2 antagonist Nutlin-3 enhances bortezomib-mediated mitochondrial apoptosis in TP53-mutated mantle cell lymphoma.
This study demonstrated a pronounced synergistic growth-inhibitory effect of an MDM2 inhibitor Nutlin-3 and a proteasome inhibitor bortezomib in mantle cell lymphoma (MCL) cells regardless of TP53 mutant status and innate bortezomib sensitivity. In the mutant TP53 MCL cells which are intrinsically resistant to bortezomib, the combination of Nutlin-3/bortezomib synergistically induced cytotoxicity through the mitochondrial apoptotic pathway mediated by transcription-independent upregulation of NOXA, sequestration of MCL-1, activation of BAX, BAK, caspase-9 and -3. In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. These findings indicate potential therapeutic efficacy of Nutlin-3/bortezomib combination for the treatment of chemorefractory MCL.


Poly-ADP-ribose polymerase: machinery for nuclear processes.
It is becoming increasingly clear that the nuclear protein, poly-ADP-ribose polymerase 1 (PARP1), plays essential roles in the cell, including DNA repair, translation, transcription, telomere maintenance, and chromatin remodeling. Despite the exciting progress made in understanding the ubiquitous role of poly-ADP-ribose metabolism, a basic mechanism of PARP's activity regulating multiple nuclear processes is yet to be outlined. This review offers a holistic perspective on activity of PARP1, based on empirically observable phenomena. Primary attention is given to mechanisms by which PARP1 regulates a broad range of essential nuclear events, including two complementary processes (1) regulation of protein-nucleic acid interactions by means of protein shuttling and (2) utilizing poly-ADP-ribose as an anionic matrix for trapping, recruiting, and scaffolding proteins.


Necrosectomy and postoperative local lavage in necrotizing pancreatitis.
Necrosectomy with postoperative continuous local lavage was performed in a prospective study involving 95 patients with necrotizing pancreatitis. In the same period 567 patients with oedematous-interstitial pancreatitis were treated non-operatively with a hospital mortality rate of 0.7 per cent. In patients with necrotizing pancreatitis the median Ranson criteria score was 4.5 points; operation was required at a median of 7 days after the onset of symptoms because of non-response to conservative treatment. In all, 59 per cent of the patients (56 out of 95) developed extended intrapancreatic parenchymal necrosis, 70 per cent had ascites, and 66 per cent had intra- and extrapancreatic necrosis; 42 per cent of the patients had bacterial infection of the necrotic tissue. For lavage a median of 8 l/24 h of fluid were instilled postoperatively for 25 days (median). The lavage fluid showed high levels of immunoreactive trypsin, phospholipase A2, and endotoxin in the early postoperative period. Hospital mortality rate was 8.4 per cent. Necrosectomy and continuous postoperative lavage can achieve high survival rates in patients with necrotizing pancreatitis. Postoperative local lavage allows the continuous non-operative evacuation of biologically active compounds and devitalized tissue, and avoids damage to remaining vital exocrine and endocrine pancreatic tissue.


Thyroid hormones and [14C] glucose metabolism in bacteria.
The effects of triiodothyronine and thyroxine on metabolism and growth of bacteria were studied. It was observed that over a certain range of concentration thyroxine and triiodothyronine produced increase in 14CO2 release from [14C]-labeled glucose and also stimulated bacteria growth.


Racial Disparities in Elementary School Disciplinary Actions: Findings From the ABCD Study.
Detentions and suspensions are common practices of school discipline, despite evidence that they are largely ineffective and disproportionately affect children from racial and ethnic minority backgrounds, particularly Black children, and children of lower socioeconomic status. However, few studies have examined suspension and detention rates among race, ethnicity, and family structure (single parent versus secondary caregiver) when controlling for typical behaviors associated with detention and suspension such as externalizing symptoms, age, sex, family income, family education, family conflict, and special education needs. Caregivers of 11,875 children between ages 9 and 10 years from the Adolescent Brain Cognitive Development (ABCD) study completed a questionnaire assessing their child's demographics, family information, emotions and behaviors, and past-year school discipline history. Data were analyzed with logistic regression, implemented with a generalized estimating equations model. 5.4% of children received a detention or suspension. Controlling for typical predictors of behaviors, Black and multiracial Black children had up to 3.5 times greater odds of receiving a detention or suspension than White children; there were no disciplinary differences for Hispanic or Asian children compared to White children. Children from single-parent households had 1.4 times the odds of receiving detentions or suspensions than children in homes with a secondary caregiver. Disciplinary actions that can impair typical childhood development, lead to academic failure and dropout, and cause significant emotional and psychological distress disproportionately affect Black children, multiracial Black children, and children from single-parent homes. Racism in elementary school discipline can perpetuate disparities in today's educational system.


Endoscopic Versus Microscopic Stapedotomy: A Single-Blinded Randomized Control Trial.
To demonstrate non-inferiority of endoscopic stapedotomy to microscopic stapedotomy for the treatment of otosclerosis. Single-blinded randomized control trial. Tertiary, academic otology-neurotology practice. Adult subjects with a diagnosis of otosclerosis and a preoperative air-bone gap (ABG) more than or equal to 20 dB undergoing primary stapedotomy. Endoscopic or microscopic stapedotomy. Primary audiometric outcome was postoperative ABG. Secondary audiometric outcomes included speech reception threshold (SRT), word recognition score (WRS), bone- and air-conduction pure tone averages (PTA), change in ABG, and ABG closure rates to less than or equal to 10 dB and less than or equal to 20 dB. Twenty-two patients were recruited. Eleven patients underwent endoscopic stapedotomy and 11 underwent microscopic stapedotomy. The endoscopic group was non-inferior to the microscopic group in terms of postoperative audiometric outcomes (endoscope versus microscope, p-value): ABG (8.1 dB versus 8.1 dB, <0.001), SRT (27.7 dB versus 25.9 dB, <0.001), WRS (92% at 65 dB versus 98% at 62 dB, <0.001), air-conduction PTA (33.5 dB versus 30.8 dB, <0.01), and change in ABG (23.0 dB versus 20.7 dB, <0.0001). ABG closure rates to less than or equal to 10 dB (72.7% versus 81.2%, p = 1.0) and less than or equal to 20 dB (90.9% versus 100%, p = 1.0) were not significantly different. There was no significant difference in operative time, necessity of scutum curettage, or postoperative dysgeusia. No patients required chorda tympani sacrifice. Preoperative tinnitus resolved in three patients in each group postoperatively. This study is the first randomized control trial to demonstrate non-inferiority of endoscopic to microscopic stapedotomy.


Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated.
The testis is known to be a site of corticosterone action, and testosterone production in Leydig cells is directly inhibited by glucocorticoids. Glucocorticoids bind to both glucocorticoid receptors (GRs) and to mineralocorticoid receptors (MRs). In Leydig cells, selective mineralocorticoid binding could result from oxidative inactivation of glucocorticoid by type 1 and/or 2 11beta-hydroxysteroid dehydrogenase (11betaHSD), as both isoforms are expressed. However, it remains unclear whether Leydig cells express MRs and respond directly to mineralocorticoid action. Therefore, the aims of the present study were to ascertain: (1) whether MR mRNA, protein and receptor binding are present in Leydig cells; and (2) if the mineralocorticoid modulates testosterone production. The mRNA encoding MR, as well as protein, and binding activity were each observed in adult rat Leydig cells. MR-ligand binding specificity within isolated Leydig cells was evaluated further by measuring displacement of MR binding to aldosterone by corticosterone in the presence and absence of carbenoxolone, an inhibitor of 11betaHSD1 and 2 that decreases conversion to biologically inert 11-dehydrocorticosterone. Carbenoxolone inhibited 11betaHSD oxidative activity, and reduced corticosterone-binding by 50%. Mineralocorticoid effects on steroidogenesis were assessed in the presence of aldosterone (0.01-10 nM) with or without the MR antagonist, RU28318. Aldosterone induced dose-dependent increases in both basal and luteinizing hormone-stimulated testosterone production. RU28318 eliminated the increase, indicating that these effects of aldosterone were mediated by the MR. The effects of aldosterone and luteinizing hormone (0.1 ng/ml) on testosterone production were synergistic, suggesting that the two hormones increased steroidogenesis through separate pathways. We conclude that Leydig cells express MRs and that testosterone production is subject to regulation by aldosterone.


Enhanced spectral shaping in steady-state free precession imaging.
Balanced steady-state free precession (SSFP) is hindered by the inherent off-resonance sensitivity and unwanted bright fat signal. Multiple-acquisition SSFP combination methods, where multiple datasets with different fixed RF phase increments are acquired, have been used for shaping the SSFP spectrum to solve both problems. We present a new combination method (weighted-combination SSFP or WC-SSFP) that preserves SSFP contrast and enables banding-reduction and fat-water separation. Methods addressing the banding artifact have focused on either getting robust banding-reduction (complex-sum SSFP) or improved SNR efficiency (sum-of-squares SSFP). The proposed method achieves both robust banding-reduction and an SNR efficiency close to that of the sum-of-squares method. A drawback of fat suppression methods that create a broad stop-band around the fat resonance is the wedge shape of the stop-band leading to imperfect suppression. WC-SSFP improves the suppression of the stop-band without affecting the pass-band performance, and prevents fat signal from obscuring the tissues of interest in the presence of considerable resonant frequency variations. The method further facilitates the use of SSFP imaging by providing a control parameter to adjust the level of banding-reduction or fat suppression to application-specific needs.


Suprapubic prostatectomy--combined technique.
Three hundred and fifty-one consecutive prostatectomies have been carried out using a combined suprapubic approach for the enucleation of the adenoma and a transurethral approach to control bleeding. Removal of any residual tissue in the prostatic fossa and removal of a wedge from the bladder neck are done with the resectoscope. The procedure is reserved for larger adenomas not suitable for transurethral resection.


Promoting informed choice of unsedated colonoscopy: patient-centered care for a subgroup of US Veterans.
In the United States, colonoscopy is usually performed under sedation. In practice, 2.3-7% actually requested unsedated colonoscopy and 1.4% received it because of no escorts. Efforts to increase usage would likely require increased patient counseling and education. We tested the hypothesis that knowledge conveyed by education-a key attribute of patient-centered care-is associated with acceptance of the "non-usual" option. After patients underwent discussions and expressed acceptance of sedated colonoscopy, the pros and cons of and local experience with unsedated colonoscopy were added. The patients who changed from accepting sedated to unsedated colonoscopy and outcomes of their examinations were recorded. From January to November 2006, 49 of 176 consecutive patients (28%) changed their choice from sedated to unsedated colonoscopy after being informed of the latter. Forty-eight had satisfactory bowel preparation. Cecal intubation rate was 93.7% (45 of 48). Thirty-six reported good experience and 43, likely to repeat. Cecal intubation, withdrawal, and discharge times were 23.0 +/- 1.4 min, 15.0 +/- 1.0 min, and 5.0 +/- 0.5 min, respectively (n = 45). Ability to communicate with the colonoscopist during and after the examination was the most frequently ranked reason for choosing unsedated colonoscopy. Our uncontrolled, non-randomized, single-site observational data revealed that for selected veterans, acceptance of unsedated colonoscopy coincides with knowledge of the option dispensed by patient counseling and education.


Rapid diagnosis of amniotic fluid embolism causing severe pulmonary failure.
We report an amniotic fluid embolism in a 28-year-old woman developing 8 h after elective cesarean section. She presented with severe respiratory distress syndrome. Amniotic cells were demonstrated in central venous blood and in the endotracheal aspirate.


Pharmacological management of Parkinson's disease motor symptoms: update and recommendations from an expert.
Parkinson's disease (PD) is a neurodegenerative multisystemic disorder that affects approximately 1% of the population over 55 years old, with the mean age of onset at 60 years old, and the prevalence of the disease constantly growing. PD is a progressive disease characterized by motor and non-motor symptoms that compromise patients' daily activities. It has a variable profile of onset and clinical evolution. Although currently available treatments have failed to clinically demonstrate neuroprotective properties, most motor symptoms are acceptably managed with dopaminergic medication. More than 50 years after launching levodopa, it remains the most effective treatment of motor symptoms in PD, able to provide sustained benefit throughout the entire course of the disease. Nevertheless, after two to three years of treatment, certain fluctuations start to appear in motor and non-motor responses to different doses of levodopa. Early identification and treatment of these fluctuations have a strong positive impact on the quality of life of the patient. Frequently accompanied by involuntary movements, proper control of fluctuations requires periodical adjustments of the medication and expert supplementation with dopaminergic and non-dopaminergic adjuvants. The main purpose of this work is to offer a practical, updated guideline for neurologists regarding the use of dopaminergic agents from the initial stages of PD. Special emphasis is placed on the critical period after the end of the 'honeymoon' phase when variations in the symptomatology presented by each patient appear, forcing re-adjustment of the medication to fit their individual needs.


Optimised low-dose multidetector CT protocol for children with cranial deformity.
To present an optimised low-dose multidetector computed tomography (MDCT) protocol for the study of children with cranial deformity. Ninety-one consecutive MDCT studies were performed in 80 children. Studies were performed with either our standard head CT protocol (group 1, n = 20) or a low-dose cranial deformity protocol (groups 2 and 3). Group 2 (n = 38), initial, and group 3 (n = 33), final and more optimised. All studies were performed in the same 64-MDCT equipment. Cranial deformity protocol was gradationally optimised decreasing kVp, limiting mA range, using automatic exposure control (AEC) and increasing the noise index (NI). Image quality was assessed. Dose indicators such us CT dose index volume (CTDIvol), dose-length product (DLP) and effective dose (E) were used. The optimised low-dose protocol reached the following values: 80 kVp, mA range: 50-150 and NI = 23. We achieved a maximum dose reduction of 10-22 times in the 1- to 12-month-old cranium in regard to the 2004 European guidelines for MDCT. A low-dose MDCT protocol that may be used as the first diagnostic imaging option in clinically selected patients with skull abnormalities. • MDCT is a very useful tool in the study of skull lesions • Low-dose MDCT minimises child exposure to ionising radiation while maintaining image quality • Low-dose MDCT should be considered as the first imaging option in selected patients.


THEORIES AND METHODS IN DIFFERENT APPROACHES TO PHYLOGENETIC SYSTEMATICS.
Abstract- Systematic techniques may be viewed as symbolic languages which have both surface structure (measures of descriptive adequacy) and deep structure (measures of explanatory adequacy). Phylogenetic systematics is not theory-neutral because its deep structure embodies evolutionary assumptions. Pattern cladistics stands in relationship to phylogenetic systematics as a part to a whole and is indistinguishable from phylogenetic systematics unless an artificial dichotomy between surface structure and deep structure is maintained. Direct observation of ontogeny as a means of polarizing characters also stands as a part to a whole relative to outgroup comparisons. Direct observation of ontogeny does not resolve any cases that outgroup comparison fails to resolve, and outgroup comparison does resolve some cases where direct observation fails.


Surveillance for hepatitis B virus seroprevalence nearly 30 years after the implementation of a national vaccination program.
Hepatitis B virus (HBV) infection is associated with cirrhosis and hepatocellular carcinoma. Vaccination is one aspect of public health policy aimed at eliminating HBV infection. After the implementation of an HBV vaccination program for newborns in Thailand, the estimated residual infection rate was 3.5%. However, that study was conducted in only 5,964 participants in seven provinces and only 22 years after the start of the campaign. This study aimed to evaluate the HBV seroprevalence rate in Thailand in larger sample size and a longer duration after program implementation using HBV surveillance. This was a surveillance study conducted in 20 provinces in northeast Thailand. The study period was between July 2010 and November 2019. Rates of HBV seroprevalence in each province and overall were calculated. Participants were divided into two groups: those vaccinated under the national campaign and those who were not. Participants aged 0-20 years were used as references, while other age groups (intervals of 10 years) were comparators. Residual HBV seroprevalence after the vaccination program was calculated with odds ratio for HBV seroprevalence in each age group. There were 31,855 subjects who participated in the project. Of those, 1,805 (5.7%) had HBV. The HBV seroprevalence rate in the national HBV vaccination group was significantly lower than that in those not vaccinated under the national program (1.0% vs 5.9%; p<0.001). Seroprevalence was 1.0% in participants ≤20 years of age. Participants 31-40 years of age had the highest odds ratio (10.41), followed those 21-30 years of age (7.42). This real-world surveillance study showed that residual HBV infection was 1.0% after nearly 30 years of nationwide HBV vaccination.


Upregulation of caveolin-1 and its colocalization with cytokine receptors contributes to beta cell apoptosis.
Caveolin-1 (cav-1), the principal structural and signalling protein of caveolae, is implicated in various signalling events, including apoptotic cell death in type 2 diabetes. However, the precise role of beta cells in apoptosis has not been clearly defined. In this study, we investigated the involvement of cav-1 in cytokine-induced beta cell apoptosis and its underlying mechanisms in the rat beta cell line, INS-1 and isolated islets. Treatment of cytokine mixture (CM, TNFα + IL-1β) significantly increased the mRNA and protein expression of cav-1, and resulting in increased formation of caveolae. We found that IL-1 receptor 1 and TNF receptor localized to plasma membrane lipid rafts in the control cells and CM treatment recruited these receptors to the caveolae domain. After cav-1 siRNA transfection, CM-dependent NF-κB activation was reduced and consequently downregulated the mRNA expression of iNOS and IL-1β. Finally, decreased cell viability by CM treatment was ameliorated in both INS-1 cells and isolated islets treated with cav-1 siRNA. These results suggest that increased cav-1 expression and recruitment of cytokine receptors into caveolae contribute to CM-induced beta cell apoptosis.


Antibody neutralizing material of factor VII during the first weeks of life.
In a study on 66 newborns and infants, factor VII activity and factor VII related antigen were investigated on 110 occasions. A normal range was calculated by testing plasma from 12 healthy male volunteers at various dilutions. Most of the values in the newborns and infants fell within this range but 18.2% of the factor VII proteins showed a significantly different specific activity.


Synthetic Biology Toolkit for a New Species of Pseudomonas Promissory for Electricity Generation in Microbial Fuel Cells.
Microbial fuel cells (MFCs) offer sustainable solutions for various biotechnological applications and are a crucial area of research in biotechnology. MFCs can effectively treat various refuse, such as wastewater and biodiesel waste by decomposing organic matter and generating electricity. Certain Pseudomonas species possess extracellular electron transfer (EET) pathways, enabling them to transfer electrons from organic compounds to the MFC's anode. Moreover, Pseudomonas species can grow under low-oxygen conditions, which is advantageous considering that the electron transfer process in an MFC typically leads to reduced oxygen levels at the anode. This study focuses on evaluating MFCs inoculated with a new Pseudomonas species grown with 1 g.L-1 glycerol, a common byproduct of biodiesel production. Pseudomonas sp. BJa5 exhibited a maximum power density of 39 mW.m-2. Also, the observed voltammograms and genome analysis indicate the potential production of novel redox mediators by BJa5. Additionally, we investigated the bacterium's potential as a synthetic biology non-model chassis. Through testing various genetic parts, including constitutive promoters, replication origins and cargos using pSEVA vectors as a scaffold, we assessed the bacterium's suitability. Overall, our findings offer valuable insights into utilizing Pseudomonas spp. BJa5 as a novel chassis for MFCs. Synthetic biology approaches can further enhance the performance of this bacterium in MFCs, providing avenues for improvement.


Prenatal exposure to alcohol: effect on infant growth and morphologic characteristics.
In this prospective study of alcohol and other substance use during pregnancy, a cohort of 650 women was interviewed at each trimester of pregnancy. Data are presented concerning the status of 595 live singleton births. A relationship was demonstrated between prenatal maternal alcohol use and growth and morphologic abnormalities in the offspring. Low birth weight, decreased head circumference and length, and an increased rate of fetal alcohol effects were all found to be significantly correlated with exposure to alcohol during the first 2 months of the first trimester.


Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage.
This study investigated the effect of geldanamycin post-treatment on the development of secondary brain injury and neurological deficits in a mouse model of intracerebral hemorrhage. CD-1 mice received stereotactic injection of collagenase type VII into the right basal ganglia. Treatment groups were administered 1 mg/kg (low dose) or 10 mg/kg (high dose) of geldanamycin. Mice were euthanized at two time-points: 24 h or 72 h. Blood-brain-barrier permeability, brain edema, and neurobehavioral deficits were assessed. Additionally, the effects of geldanamycin on heat shock protein 27 and 72; tumor necrosis factor-alpha and interleukin 1 beta expressions were evaluated. High dose geldanamycin significantly attenuated blood-brain barrier disruption and brain edema after intracerebral hemorrhage. Neurobehavioral outcomes were significantly improved in some parameters by high dose treatment. Molecular results showed a marked increase in heat shock protein 72 expression in ipsilateral brain of geldanamycin treated groups with a reduction in the pro-inflammatory tumor necrosis factor-alpha. Geldanamycin post-treatment is neuroprotective in the mouse model of intracerebral hemorrhage. Geldanamycin administration results in reduction of inflammation, preservation of blood-brain-barrier and amelioration of neurobehavioral deficits after an insult possibly by upregulation of heat shock protein 72.


Effect of erythropoietin on the glucose transport of rat erythrocytes and bone marrow cells.
The effect of Ep on radioactive glucose and methyl-alpha-D-glucoside transport by rat erythrocytes and bone marrow cells were studied. There is initial linearity followed by saturation kinetics of [14C]glucose transport by the erythrocytes of starved and starved plus Ep-treated rats at different concentrations of glucose. Starvation caused slight inhibition of glucose transport which increased markedly on Ep administration to starved rats. Normal animals failed to show any significant change in glucose transport after Ep treatment. Methyl-alpha-D-glucoside inhibited the Ep-stimulated glucose transport significantly. Ep also stimulated the transport of radioactive methyl-alpha-D-glucoside which was competitively inhibited in presence of D-glucose. Glucose transport in erythrocytes was found to be sensitive to metabolic inhibitors like azide and DNP. A sulfhydryl reagent and ouabain also inhibited the transport process. Ep stimulated glucose and methyl-alpha-D-glucoside transport in the bone marrow cells of starved rats. The sugar analog competitively inhibited the glucose transport in bone marrow cells and vice versa.


Piroxicam therapy: a double blind, randomized, multicenter study comparing 2 versus 4 week treatment in patients with painful knee osteoarthritis with effusion.
To compare the efficacy and safety of piroxicam 20 mg once a day for 14 or 28 days in patients with knee osteoarthritis (OA) and synovial effusion. We conducted a multicenter, randomized, double blind study in 1905 outpatients. Efficacy was assessed by changes in synovial effusion, pain on a 100 mm visual analog scale (VAS), and impairment using Lequesne's functional index. Patients were classified at Day 28 as improved (defined as VAS and Lequesne index decrease of at least 30% from Day 14), worsened (defined as VAS and Lequesne index increase of at least 30% from Day 14), or unchanged. Safety was assessed on the basis of adverse events reported by the patients. After 14 days, changes in pain, synovial effusion, and functional impairment significantly decreased from baseline within each group (p < 0.001, respectively), but did not differ between the groups. Between 14 and 28 days, outcome measure changes were significantly better in the 28 day group, p = 0.01, 0.0001, and 0.0001, respectively. In the 28 day and 14 day groups, improvement with regard to pain was observed for 339 (52.4%) and 280 (29.4%) patients, respectively, (p < 0.0001), and with regard to functional impairment for 298 (31.5%) and 233 (24.3%) patients (p < 0.0001). Adverse events accounted for 7.5 and 6.7% of withdrawals in the 28 day and 14 day groups, respectively. When administration of piroxicam 20 mg is prolonged to 28 days, continuing benefit is observed for some patients with knee OA with painful synovial effusion without a significant difference in safety.