Mycoremediation of Benzo[a]pyrene by Pleurotus ostreatus in the presence of heavy metals and mediators.
Benzo[a]pyrene is considered as a priority pollutant because of its carcinogenic, teratogenic and mutagenic effects. The highly recalcitrant nature of Benzo[a]pyrene poses a major problem for its degradation. White-rot fungi such as Pleurotus ostreatus can degrade Benzo[a]pyrene by enzymes like laccase and manganese peroxidase. The present investigation was carried out to determine the extent of Benzo[a]pyrene degradation by the PO-3, a native isolate of P. ostreatus, in the presence of heavy metals and ligninolytic enzyme mediators. Modified mineral salt medium was supplemented with 5 mM concentration of different heavy metal salts and ethylenediaminetetraacetic acid. Vanillin and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (1 and 5 mM) were used to study the effect of mediators. Results indicated that P. ostreatus PO-3 degraded 71.2 % of Benzo[a]pyrene in the presence of copper ions. Moderate degradation was observed in the presence of zinc and manganese. Both biomass formation and degradation were severely affected in the presence of all other heavy metal salts used in the study. Copper at 15 mM concentration supported the best degradation (74.2 %), beyond which the degradation progressively reduced. Among the mediators, 1 mM 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) supported 78.7 % degradation and 83.6 % degradation was observed under the influence of 5 mM vanillin. Thus, metal ion like copper is essential for better biodegradation of Benzo[a]pyrene. Compared to synthetic laccase mediator like 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate), natural mediator such as vanillin may play a significant role in the degradation of aromatic compounds by white-rot fungi.


Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency.
The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.


Radiation safety and education in the applicants of the final test for the expert of pain medicine.
The C-arm fluoroscope is known as the most important equipment in pain interventions. This study was conducted to investigate the completion rate of education on radiation safety, the knowledge of radiation exposure, the use of radiation protection, and so on. Unsigned questionnaires were collected from the 27 pain physicians who applied for the final test to become an expert in pain medicine in 2011. The survey was composed of 12 questions about the position of the hospital, the kind of hospital, the use of C-arm fluoroscopy, radiation safety education, knowledge of annual permissible radiation dose, use of radiation protection, and efforts to reduce radiation exposure. In this study, although most respondents (93%) had used C-arm fluoroscopy, only 33% of the physicians completed radiation safety education. Even though nine (33%) had received education on radiation safety, none of the physicians knew the annual permissible radiation dose. In comparing the radiation safety education group and the no-education group, the rate of wearing radiation-protective glasses or goggles and the use of radiation badges or dosimeters were significantly higher in the education group. However, in the use of other protective equipment, knowledge of radiation safety, and efforts to reduce radiation exposure, there were no statistical differences between the two groups. The respondents knew very little about radiation safety and had low interest in their radiation exposure. To make the use of fluoroscopy safer, additional education, as well as attention to and knowledge of practices of radiation safety are required for pain physicians.


Emergency Department Visits Due to Dyspnea: Association with Inhalation Therapy in COPD and Cases with Adverse Drug Reactions.
Dyspnea is a leading symptom of COPD that causes presentations in emergency departments or negatively impacts on them. Guideline-based inhalation therapies are intended to reduce dyspnea in COPD patients. This study analyzed how common guideline recommended inhalation therapy regimens are occurring in clinical practice among COPD patients presenting to emergency departments due to adverse drug reactions in polytherapy using data of the German ADRED database. In total, 269 COPD cases were identified. In a further analysis, all cases were analyzed for documented GOLD stage and guideline-recommended inhalation therapy for COPD. Dyspnea and other symptoms identified during ED presentation were analyzed and compared between patients who did and did not receive the guideline's recommended inhalation therapy. In this observation, 41% (n = 46) of all 112 cases with a documented COPD and GOLD stage received an underdosed therapy according to current guidelines. Dyspnea was the most common identified symptom (32%, n = 36) in this cohort and occurred more often in patients who received an underdosage of inhalation therapy (p < 0.01). Patients with COPD presenting to ED with ADRs show a high rate of non-guideline-recommended inhalation therapy and present more often with dyspnea compared to those COPD patients who received an adequate dosing of inhalation therapy.


Scanning the visual field without eye movements--a sex difference.
Subjects identified the location of a briefly exposed target pattern in the presence of five other patterns. Right-handed females, but not males, exhibited a significantly higher error rate in correctly localizing the target pattern when it was in the left visual field, particularly for the left parafoveal region. This unexpected distribution of errors as a function of target location can be accounted for by a sequential (serial) mechanism which scans the visual field. Since the exposure time was too brief for eye movements to have occurred, the results must reflect an internal scan of the neural representation of the information retained in the visual system following the brief stimulus presentation.


Identification and sequence analysis of the E1 genomic region of a porcine adenovirus.
The complete nucleotide sequence of the putative early transcriptional region 1 (E1) of the genome of NADC-1, a porcine adenovirus, was determined. The E1 region of NADC-1 was found to be 3658 bp and located between 0 and 11.2 map units. Twelve potential open reading frames (ORFs) and five polyadenylation signals were identified in the r strand. The nucleotide sequence and each predicted amino acid sequence were compared to sequences available on a number of databases by a BLAST search and comparison. A single region of nucleotide sequence similarity was identified with the sequence of human adenovirus 5. Only 2 of the 12 potential ORFs encode polypeptides that have homology to known adenovirus polypeptides. For these predicted proteins, similarities were found with a number of adenovirus proteins. The strongest homology was found to potential E1 products of bovine adenovirus 3.


Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 1. Protein staining.
The isoelectric points and the molecular weights of the major components of the eight Thoroughbred protease inhibitor (Pi) types have been determined by polyacrylamide gel isoelectric focusing and polyacrylamide gel pore gradient (ISO-DALT) electrophoresis respectively. The major Pi proteins focus in the range pH 3.74-4.43 and have molecular weights ranging from 55 000-72 000 daltons. Using the ISO-DALT method of electrophoresis, protein maps for the eight Thoroughbred Pi types have been presented for the first time. None of the homozygous Pi types are identical except for the types S1 and S2 which show partial identity. The results do not necessarily support Juneja et al.'s (1979) contention of two closely linked alpha 1 Pi systems based on molecular weight differences. It is suggested that the traditional nomenclature originally proposed by Braend (1970) be maintained to describe the eight Pi alleles in Thoroughbred horse plasma. The ISO-DALT method provides a sensitive technique which is superior to existing techniques for the analysis of the horse Pi system.


A nonrandomized controlled trial of individualized exercise prescription combined with remote exercise management in patients who are overweight or obese.
Between 2012 and 2020, the obesity rate increased among Chinese people aged 18 years and above, along with blood pressure, fasting blood glucose, serum total cholesterol, and triglycerides. Our objective was to compare the effects of a combined intervention, including individualized exercise prescription plus remote management versus individualized exercise prescription only, on cardiovascular risk factors in patients who are overweight or obese, with the aim of establishing a more effective remote model of health management than self-management. This nonrandomized controlled trial (ChiCTR2100046307) studied patients who are overweight or obese at model labor health management centers from January 2019 to December 2019, including 55 people in the experimental group and 34 in the control group. The relevant indexes of all the research objects from both experimental group and control group were examined. Participants in the experimental group were given individualized exercise prescription combined with remote exercise management over a period of 3 months. The control group was prescribed exercise only at time of enrollment and taught about exercise once, followed by voluntary exercise and self-management for 3 months. After adjusting for baseline differences, the changes in weight (-2.72 ± 4.03 kg versus 0.32 ± 2.50 kg, P < 0.0001), body mass index (-0.99 ± 1.44 kg/m2 versus 0.11 ± 0.92 kg/m2, P < 0.0001), waist circumference (-2.98 ± 6.29 cm versus 0.60 ± 5.33 cm, P < 0.0001), visceral fat area (-9.75 ± 19.68 cm2 versus -1.31 ± 12.37 cm2, P = 0.028), body fat (- 2.65 ± 3.52 kg versus 0.54 ± 2.67 kg, P < 0.0001), body fat rate (-2.50 ± 3.32% versus 0.21 ± 3.30%, P < 0.0001), uric acid (-9.75 ± 19.68 µmol/L versus -1.31 ± 12.37 µmol/L, P = 0.028), serum total cholesterol (-0.11 ± 0.40 mmol/L versus -0.11 ± 0.59 mmol/L, P = 0.004), fasting insulin (- 2.36 ± 5.20 μU/mL versus 1.22 ± 7.34 μU/mL, P = 0.009), and homeostatic model assessment of insulin resistance (-0.62 ± 1.25 versus 0.14 ± 1.83, P = 0.022) were significantly better in the experimental group than in the control group after intervention. Individualized exercise prescription combined with remote management in patients who are obese or overweight facilitated weight and fat loss, lowered blood pressure and serum total cholesterol, improved glucose metabolism and insulin resistance, and reduced cardiovascular risk factors. The intervention was superior to conventional education in terms of weight loss, fat reduction, total cholesterol reduction, fasting insulin reduction, and amelioration of insulin resistance.


Upregulation of p27 cyclin-dependent kinase inhibitor and a C-terminus truncated form of p27 contributes to G1 phase arrest.
Potent anti-cancer compounds FR901464 and its methyl-ketal derivative spliceostatin A (SSA) inhibit cell cycle progression at G1 and G2/M phases. These compounds bind to the spliceosome and inhibit the splicing reaction. However, the molecular mechanism underlying G1 arrest after SSA treatment remains unknown. In this study, we found that ~90% of SSA-treated cells arrested at G1 phase after cell cycle synchronization. SSA treatment caused upregulation of the p27 cyclin-dependent kinase inhibitor both at mRNA and protein levels. In addition to p27, we observed expression of p27*, a C-terminal truncated form of p27 that is translated from CDKN1B (p27) pre-mRNA accumulated after splicing inhibition. Overexpression of p27 or p27* inhibited the exit from G1 phase after a double thymidine block. Conversely, knocking down of p27 by siRNA partially suppressed the G1 phase arrest caused by SSA treatment. There results suggest that G1 arrest in SSA-treated cells is caused, at least in part, by upregulation of p27 and p27*.


A new display technique for computer-processed digital scans.
This article presents a new approach for presenting scintigraphic images. The technique combines the conventional plotting the contour lines and the highlighting, by means of hatching, of the concavities (or convexities) of the 'surface' representative of radioactive distribution. The search for the surface features is achieved generally by the method of normal curvatures. An example with a phantom demonstrates the utility of this representation method.


Malignancy arising in cystic ovarian teratomas. A report of 24 cases.
Twenty-four cases with a malignant change involving one of the elements of an ovarian dermoid cyst are reported. The patients were older than those with benign ovarian dermoid cysts. Squamous carcinoma was most frequent with adenocarcinoma, undifferentiated carcinoma and a fibrosarcoma also occurring. Survival time after diagnosis was less than 1 year in 75% of the cases.


The homeobox factor Irx3 maintains adipogenic identity.
Inhibition of Irx3 and Irx5 has been shown to reduce body weight and white adipose tissue (WAT) mass through cell-autonomous and sympathetic-induced increases in adipocyte beiging and thermogenesis in mice and humans. However, the underlying mechanisms of the Irx control over beiging are still largely unknown, as illustrated by recent reports showing divergent effects of Irx3 on adipocyte metabolism and function. Here, we investigated the role of Irx3 in controlling beige preadipocyte function and differentiation. Stable knock out of Irx3 in ME3 mouse preadipocytes capable of beiging was performed using a CRISPR-Cas9 system, and the effect on cell differentiation was assessed by qPCR, RNA-seq, Oil-red-O lipid staining and Alcian Blue staining of proteoglycans. Changes in cell identities were validated using cell type enrichment analysis from RNA-seq data. Proliferation and cell cycle progression in undifferentiated cells were measured by WST-1 and flow cytometry, reactive oxygen species (ROS) generation was determined by fluorescence spectrometry and mitochondrial respiration was investigated by Seahorse assay. Irx3 was found to be essential for the identity, function and adipogenic differentiation of beige adipocyte precursors. Irx3-KO impaired proliferation, ROS generation and mitochondrial respiration in the preadipocytes. We further observed profound changes in numerous genes during both early and late stages of adipogenic differentiation, including genes important for adipocyte differentiation, cell cycle progression, oxidative phosphorylation (OXPHOS) and morphogenesis. Irx3-KO cells failed to accumulate lipids following adipogenic stimuli, and cell enrichment analysis revealed a loss of preadipocyte identity and a gain of chondrocyte-like identity in Irx3-KO cells during early differentiation. Finally, unlike the control cells, the Irx3-KO cells readily responded to chondrogenic stimuli. Irx3 is required for preadipocyte identity and differentiation capacity. Our findings suggest that, while inhibition of Irx3 may be beneficial during later developmental stages to modulate adipogenesis in the beige direction, constitutive and complete absence of Irx3 in the embryonic fibroblast stage leads to detrimental loss of adipogenic differentiation capacity.


{N-[(4-Meth-oxy-2-oxidophen-yl)(phen-yl)methyl-idene]glycinato}di-phenyl-silicon(IV).
The title compound, C28H23NO4Si, crystallizes in the monoclinic space group P21/c. The silicon complex consists of a tridentate dinegative Schiff base ligand bound to a di-phenyl-silyl unit. The coordination geometry of the penta-coordinate silicon atom is a distorted trigonal bipyramid.


Applications of high-resolution recycling liquid chromatography: From small to large molecules.
A twin-column recycling separation process (TCRSP) is assembled and used to generate higher speed and/or higher resolution levels than those of the usual non-recycling process at the same back pressure. It enables the users to solve very challenging separation problems caused by too small selectivity factors and/or too low column efficiencies. The relative gain in speed-resolution performance increases with increasing the number of cycles in the TCRSP, decreasing the maximum allowable pressure imposed by the LC system, decreasing the column permeability, and with reducing the separation speed. TCRSP is then particularly attractive for conventional LC systems (5000psi maximum) and columns packed with sub-2μm to 3.5μm particles. The performance of the real TCRSP was compared to that of the ideal TCRSP for which the retention factor is strictly pressure-independent. A broad range of separation problems encountered in conventional non-recycling chromatography can be easily solved by using a TCRSP assembly based on two 15cm long columns. Under adsorption conditions, the TCRSP enables the full baseline separation of polycyclic aromatic hydrocarbon (PAH) isomers (benzo[a]anthracene and chrysene) on a 3.5μm XSelect-HSS T3 phase, the complete or improved resolution of racemic mixtures (4-phenylbutanol and bromacil) using the same 2.5μm cellulose-1 chiral stationary phase, and the full resolution of isotopic compounds (benzene/1,3,5-benzene-d3/benzene-d6) on a 2.7μm Cortecs-C18 phase. Under non-adsorption conditions or in size-exclusion chromatography (SEC), the fractionation of a polystyrene standard mixture (molecular weights of 35, 66, 130, 277, 552, 1210, and 2500kDa) was completed after only 8 cycles on a 1.7μm BEH 200Åphase. Similarly, a mixture of intact proteins with molecular weights of 16.7, 66.4, 150, 660, and 1320kDa was fully resolved on a 2.5μm BEH 450Åphase after only 6 cycles. Finally, TCRSP enables the complete separation of a few high-molecular-weight species (monoclonal antibody aggregates, small relative abundance of 1 for 250) from the intact monomeric monoclonal antibody (Vectibix).


Evaluation of cutaneous surface parameters in psoriatic patients.
The purpose of this study was to compare cutaneous surface parameters in lesional and non-lesional skin of psoriatic patients and in corresponding areas of control subjects. Sixty-six psoriatic patients (of any grade of severity, with or without arthritis, without any therapy other than systemic biologic drugs) and 28 healthy controls were enrolled in this observational, case-control study. Exclusion criteria were current or past sebo-psoriasis and seborrheic dermatitis, pustular or erithrodermic psoriasis; treatment with immune-suppressive agents, retinoids, or ultraviolet phototherapy in the last 6 months; topical treatment in the last 2 weeks. Corneometry, sebumetry, and pHmetry were evaluated on non-lesional skin of forehead, cheek, chin and volar region of forearm, and on a psoriatic plaque (on elbow or neighboring areas); in controls, the same areas were considered. Corneometry values were significantly lower in psoriatic plaques vs. elbows of controls. Sebumetry showed significantly higher values in non-lesional forearm skin and plaques of psoriatic patients vs. corresponding areas of controls. pH was significantly lower in all areas in psoriasis. No differences were found between patients treated or not with biologics and with or without arthritis. Evaluating surface skin parameters in psoriasis is useful to better understand the etiopathogenic mechanism and could suggest new therapeutic approaches.


Comprehensive Reform and Greater Equity in Applying to Residency-Trainees' Mixed Responses to a Pass/Fail USMLE Step 1.
Pass/fail USMLE Step 1 score reporting may have varying implications for trainees of different demographic and training backgrounds. To characterize the perspectives of a diverse cohort of trainees on the impact of pass/fail Step 1 score reporting. In 2020, 197 US and international medical school deans and 822 designated institutional officials were invited to distribute anonymous electronic surveys among their trainees. Separate surveys for medical students and residents/fellows were developed based on the authors' prior work surveying program directors on this topic. Underrepresented in medicine (UiM) was defined in accordance with AAMC definitions. Descriptive and comparative analyses were performed, and results were considered statistically significant with P < .05. A total of 11 633 trainees responded (4379 medical students and 7254 residents/fellows; 3.3% of an estimated 285 000 US trainees). More students favored the score reporting change than residents/fellows (43% vs 31%; P < .001; 95% CI 0-24). Trainees identifying as UiM were more likely to favor the change (50% vs 34%; P < .001; 95% CI 0-32) and to agree it would decrease socioeconomic disparities (44% vs 25%; P < .001; 95% CI 0-38) relative to non-UiM trainees. Nearly twice as many osteopathic and international medical graduate students felt they would be disadvantaged compared to MD students because of pass/fail score reporting (61% vs 31%; P < .001; 95% CI 0-60). Trainee perspectives regarding USMLE Step 1 score reporting are mixed. UiM trainees were more likely to favor the score reporting change, while osteopathic and international medical students were less in favor of the change.


Conceptual and numerical modeling of radionuclide transport and retention in near-surface systems.
Scenarios of barrier failure and radionuclide release to the near-surface environment are important to consider within performance and safety assessments of repositories for nuclear waste. A geological repository for spent nuclear fuel is planned at Forsmark, Sweden. Conceptual and numerical reactive transport models were developed in order to assess the retention capacity of the Quaternary till and clay deposits for selected radionuclides, in the event of an activity release from the repository. The elements considered were carbon (C), chlorine (Cl), cesium (Cs), iodine (I), molybdenum (Mo), niobium (Nb), nickel (Ni), radium (Ra), selenium (Se), strontium (Sr), technetium (Tc), thorium (Th), and uranium (U). According to the numerical predictions, the repository-derived nuclides that would be most significantly retained are Th, Ni, and Cs, mainly through sorption onto clays, followed by U, C, Sr, and Ra, trapped by sorption and/or incorporation into mineral phases.


Prevalence of signs and symptoms related to temporomandibular disorders and orofacial pain in patients indicated for orthognathic surgery: a meta-analysis.
To evaluate the prevalence of signs and symptoms related to temporomandibular disorders (TMD) and orofacial pain in patients with indication for orthognathic surgery. The search was carried out in seven electronic databases and gray literature. Studies that evaluated the frequency of signs and symptoms related to TMD and orofacial pain were included. The risk of bias was assessed using the Joanna Briggs Critical Appraisal tool. A meta-analysis of proportions with a random effect model was performed and the GRADE tool judged the certainty of evidence. After searching the databases, 1859 references were retrieved, 18 of which were selected for synthesis. The prevalence of individuals with at least one TMD symptom was 51% [CI95% = 44-58%], and 44% of the subjects had temporomandibular joint click/crepitus [CI95% = 37-52%]. Additionally, 28% exhibited symptoms related to muscle disorders [CI95% = 22-35%], 34% had disc displacement with or without reduction [CI95% = 25-44%], and 24% had inflammatory joint disorders [CI95% = 13-36%]. The prevalence of headache was 26% [CI95% = 8-51%]. The certainty of evidence was considered very low. Approximately 1 in 2 patients with dentofacial deformity presents some sign and symptom related to TMD. Myofascial pain and headache may be present in approximately a quarter of patients with dentofacial deformity. A multidisciplinary treatment is necessary for these patients, involving a professional with expertise in the management of TMD.


[Adaptation of a dementia test for use in visually handicapped persons exemplified by SIDAM (Structured Interview for the Diagnosis of Alzheimer disease, Multi-Infarct Dementia and Dementias of other Etiology)].
In epidemiological field studies on the prevalence and incidence of dementia, the problem of cognitive testing of visually impaired individuals is rarely discussed. In the Leipzig Longitudinal Study of the Aged (LEILA 75+) a version of the SIDAM (SIDAM-Structured Interview for the Diagnosis of dementia of the Alzheimer type, Multi-infarct dementia and dementias of other etiology) for the visually impaired was employed from which all items requiring image processing had been omitted (SIDAM-blind). In order to be able to interpret the test results, the final scores for the full SIDAM were estimated by linear transformation of the scores in the blind-version. The method of linear transformation is based on certain theoretical assumptions which are examined in this paper. Linear transformation of scores has proved to be a valid procedure only for individuals with high cognitive performances. Thus, an evaluation of estimated scores based on the norms for the original SIDAM has limitations. Consequently, age-specific norms for the SIDAM-blind are presented. Sensitivities and specificities for different cut-off points used to discriminate between demented and non-demented vision-impaired individuals are given.


Interleukin-10-1082A/G polymorphism and inflammatory bowel disease susceptibility: a meta-analysis based on 17,585 subjects.
A large number of studies have shown that the interleukin-10 (IL-10)-1082A/G polymorphism is implicated in susceptibility to inflammatory bowel disease (IBD). However, the results are inconsistent. We performed this meta-analysis to estimate the association between -1082A/G polymorphism in the IL-10 gene and IBD susceptibility. A total number of 18 case-control studies including 17,585 subjects were identified. No association was found between -1082A/G polymorphism and ulcerative colitis (UC) susceptibility. However, increased risk of Crohn's disease (CD) was associated with -1082A/G polymorphism in the dominant genetic model (GG+GA vs. AA: OR=1.22, 95% CI: 1.02-1.46, P=0.028) and the heterozygote comparison (GA vs. AA: OR=1.28, 95% CI: 1.05-1.55, P=0.015). The results of this meta-analysis provide evidence for the association between IL-10-1082A/G polymorphism and susceptibility of CD. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future.


Noncardiac surgical procedures in patient supported with long-term implantable left ventricular assist device.
Left ventricular assist devices (LVADs) are increasingly used as bridges to transplantation or as destination therapy. As sicker and older patients are more frequently considered for mechanical support, general surgical problems are expected to increase in these patients. Anesthesia records and clinical charts were reviewed for 11 recipients of LVADs undergoing 12 general surgical procedures between January 1988 and March 2007. Eight patients underwent major surgical procedures: 1 intracranial hematoma drainage, 1 right hemicolectomy with ileocolostomy, 1 splenectomy, 1 surgical repair of an iliac-femoral artery pseudoaneurysm, 2 cholecystectomies, 1 pyelolithotomy, and 1 coil embolization of a femoral side-branch disruption. Four patients underwent minor surgical procedures. The mean duration of LVAD support before surgery was 58.7 +/- 45.6 days. All patients survived the procedures. Noncardiac surgery in LVAD recipients is feasible, without significant morbidity or mortality. Intraoperative coagulation management has a key role in safely performing these procedures.


Determination of thiols following their separation by CZE with amperometric detection at a carbon electrode.
The amperometric detection (AD) employing a carbon disk electrode as a working electrode to determine the thiol compounds, including cysteine (CYS), glutathione (GSH), 6-thiopurine (TP), and methimazole (MMI), following their separation by capillary zone electrophoresis (CZE) is described in this paper. The detection potential was chosen at +1100 mV and all analytes exhibit good response at this potential on the carbon disk electrode. The reproducibility, linearity, and recovery were evaluated under the optimum conditions. The four analytes can be baseline resolved within 20 min and the detection limits reached about 10(-6) mol/l of magnitude. The method was applied to the separation and determination of the actual thiol samples and the analytical results were satisfactory.


Bentall operation in a patient with an anomalous left circumflex artery: Case report and review.
Anomalous origin of a left circumflex artery from the right coronary sinus represents a technical challenge in patients who require aortic valve/root procedures. This case report describes a patient who presented with bicuspid aortic valve, anomalous origin of the circumflex artery, severe aortic regurgitation, and aneurysm of the ascending aorta as well as aortic root that was safely managed following the Bentall procedure with the combined button technique.


The complexities of consumer empowerment in the modern consumption environment.
The modern consumption environment has significantly expanded opportunities for consumer empowerment, yet such empowerment hinges on specific conditions and contexts. We discuss the complexities of consumer empowerment in the modern consumption environment across four domains of empowerment: consumer choice, access to marketplace information, consumer voice, and consumer experience. Through this lens, we examine how and when evolving marketplace offerings (e.g., sharing economy, consumer co-creation), technologies (e.g., product customization, artificial intelligence, augmented reality, virtual reality), communication platforms (e.g., user-generated content, social media, on-line word of mouth), and consumption trends (e.g., multitasking) may have beneficial or detrimental effects on consumer empowerment.


The impact of cultural evolution on the ego ideal, depression, psychosis, and suicide: a South India community study of the widow.
Cultural factors have a significant impact on the manifestation of psychiatric illness and the development of the ego ideal. The evolution of the widow's cultural role in a South India village provides insight on the ego ideal through several generations. As treatment of widows changed so that their appearance became indistinguishable from other women, they no longer became objects of revulsion. A case study approach documents the interrelationship of changes in the cultural ego ideal on psychiatric illness among widows in a South India village over a period of more than four decades.


Studies of Jak/STAT3 expression and signalling in psoriasis identifies STAT3-Ser727 phosphorylation as a modulator of transcriptional activity.
Jak/Tyk proteins have recently aroused as possible therapeutic targets for the treatment of psoriasis. In psoriasis, these proteins signal through STAT molecules including STAT3, and STAT3 expression and activation has been shown augmented in psoriatic lesions. Here, we characterized the expression of Jak/Tyk proteins in lesional compared with non-lesional psoriatic skin. Jak1, Jak2 mRNA and protein and Tyk2 mRNA appeared to be downregulated, whereas Jak3 mRNA expression was increased. Moreover, STAT3 expression and activation was examined in psoriasis. STAT3 is activated at two phosphorylation sites: Tyr705 and Ser727. Both phosphorylation sites were phosphorylated in lesional psoriatic skin. The activation of STAT3 by Jak/Tyk proteins was studied in cultured normal human keratinocytes. Tyr705 phosphorylation was induced by IL-6 and IL-20 in a Jak2-dependent manner, and moreover, phosphorylation of Tyr705 produced a strong increase in STAT3 transcriptional activity. TNFα, 12-O-Tetradecanoylphorbol 13-acetate (TPA) and UVB irradiation induced Ser727 phosphorylation of STAT3 in an ERK1/2- and p38 MAPK-dependent manner, which resulted in a modulatory effect on STAT3 transcriptional activity. Our results demonstrate how different signalling pathways can integrate and lead to regulation of STAT3 transcriptional activity.


Application of the TGx-28.65 transcriptomic biomarker to classify genotoxic and non-genotoxic chemicals in human TK6 cells in the presence of rat liver S9.
In vitro transcriptional signatures that predict toxicities can facilitate chemical screening. We previously developed a transcriptomic biomarker (known as TGx-28.65) for classifying agents as genotoxic (DNA damaging) and non-genotoxic in human lymphoblastoid TK6 cells. Because TK6 cells do not express cytochrome P450s, we confirmed accurate classification by the biomarker in cells co-exposed to 1% 5,6 benzoflavone/phenobarbital-induced rat liver S9 for metabolic activation. However, chemicals may require different types of S9 for activation. Here we investigated the response of TK6 cells to higher percentages of Aroclor-, benzoflavone/phenobarbital-, or ethanol-induced rat liver S9 to expand TGx-28.65 biomarker applicability. Transcriptional profiles were derived 3 to 4 hr following a 4 hr co-exposure of TK6 cells to test chemicals and S9. Preliminary studies established that 10% Aroclor- and 5% ethanol-induced S9 alone did not induce the TGx-28.65 biomarker genes. Seven genotoxic and two non-genotoxic chemicals (and concurrent solvent and positive controls) were then tested with one of the S9s (selected based on cell survival and micronucleus induction). Relative survival and micronucleus frequency was assessed by flow cytometry in cells 20 hr post-exposure. Genotoxic/non-genotoxic chemicals were accurately classified using the different S9s. One technical replicate of cells co-treated with dexamethasone and 10% Aroclor-induced S9 was falsely classified as genotoxic, suggesting caution in using high S9 concentrations. Even low concentrations of genotoxic chemicals (those not causing cytotoxicity) were correctly classified, demonstrating that TGx-28.65 is a sensitive biomarker of genotoxicity. A meta-analysis of datasets from 13 chemicals supports that different S9s can be used in TK6 cells, without impairing classification using the TGx-28.65 biomarker.


Electronic thermography of normal facial structures: a pilot study.
New electronic thermographic instruments capable of routine clinical examination need to be evaluated for their potential as a diagnostic aid in dentistry. This study assessed thermal symmetry of the face and neck in 20 normal subjects with the use of frontal and lateral views, at 1.0 degree C and 0.5 degree C sensitivity, under controlled conditions. Electronic thermographic images were analyzed for thermal symmetry, by means of a grid matching technique, in 12 anatomic regions and the overall face. Results indicated that thermal symmetry for the entire face was high (70.2%). The 12 specific facial areas demonstrated varying levels of thermal symmetry. Regions of high symmetry on frontal projections included the anterior portion of the neck (82.0%), the TMJ (80.0%), the lower lip (78.6%), and the upper lip (77.3%). The temporal region (46.7%) was found to be of relatively low thermal symmetry. Regions of high symmetry on lateral projections included the nasal region (69.5%) and the inframandibular region (67.0%). The posterior neck region (44.2%) was found to be of relatively low thermal symmetry. In general, normal subjects demonstrated high levels of thermal symmetry over most regions of the face. This pilot investigation is an early step in the evaluation of electronic thermography for future use in dentistry.


Cardiac image registration of the left atrium and pulmonary veins.
Cardiac image registration, in the context of the left atrium, is intermodal, with the acquired image and the real-time reference image residing in different image spaces, and involves optimization, where one image space is transformed into the other. Geometry-based methods, which include using fiducial points and/or surface-based techniques, are usually used for cardiac image registration. During fiducial point registration, fiducial points are either external skin markers or manually determined by marking anatomical landmarks using mapping catheters. Usually, a minimum of three noncollinear points is needed for optimal registration. During surface registration, each of the images' surfaces are characterized to determine the best transformation between them. Unlike the rigid body registration used extensively in the study of the brain, cardiac image registration is unique and challenging. In addition to the errors inherent in intermodal registration, errors due to respiration and cardiac motion during the cardiac cycle are specific to cardiac image registration. This review addresses the basic principles of registration and the inherent registration errors as they relate to cardiac imaging and registration.


Does successful smoking cessation reduce anxious arousal among treatment-seeking smokers?
There is limited work that has examined the effect of quitting smoking on anxious arousal, an underlying dimension of anxiety symptoms and psychopathology. Smokers (n=185, 54.1% female) enrolled in a smoking cessation treatment trial were monitored post-cessation in terms of abstinence status (biochemically verified; at Weeks 1, 2, and Month 1 post-quit) and severity of panic-relevant symptoms (self-reported; at Month 1 and 3 post-quit). Structural equation models were conducted, adjusting for participant sex, age, treatment condition, and pre-cessation nicotine dependence, presence of depressive/anxiety disorders, anxious arousal, and anxiety sensitivity. After adjusting for covariates, participants who remained abstinent for one month (n=80; 43.2%) relative to those who did not (n=105; 56.8%) demonstrated significant reductions in anxious arousal at Month 1 (β=-.26, p=.04) and Month 3 post-quit (β=-.36, p=.006); abstinence status had a non-significant effect on anxious arousal severity at Month 3 after controlling for Month 1 anxious arousal (β=-.18, p=.09). Findings align with theoretical models of smoking-anxiety interplay and suggest that smoking cessation can result in reductions in anxious arousal.


Perceptions of inpatient rehabilitation changes after the Centers for Medicare and Medicaid Service 2010 regulatory updates contrasted with actual performance.
To compare and contrast subjective perceptions with objective compliance of the impact of the 2010 Centers for Medicare and Medicaid Service updates of the Medicare Benefit Policy Manual. Cross-sectional survey. An electronic survey was sent by the Uniform Data System for Medical Rehabilitation to all enrolled inpatient rehabilitation facility subscribers (n = 817). The survey was sent April 15, 2011, and responses were tabulated if they were received by May 15, 2011. Comparing and contrasting of the subjective perception to objective evaluation and/or compliance with the Medicare Benefit Policy Manual on case mix index, length of stay, admissions by diagnostic category as well as perception of preadmission screening, postadmission evaluation, plan of care, and interdisciplinary conferencing. Twenty-five percent of the 817 facilities responded, for a total of 209 responses. Complete data were present in 148 of the respondents. For most diagnostic categories, perception of change did not mirror reality of change; neither did the perception between change in case mix index and length of stay. Perception did match reality in stroke and multiple trauma cases; respondents perceived an increase in admissions for the 2 impairments, and there was an overall increase in reality. Comparison with actual data identified that gaps exist between diagnostic category perceptions and actual diagnostic category admission performance. Regulations such as the 75%-60% rule and audit focus on non-neurologic conditions as well as actual inpatient rehabilitation facility program payment reports may have influenced respondents perceptions to change associated with the Medicare Benefit Policy Manual modifications. This disparity between perception and actual data may have implications for programmatic planning, forecasting, and resource allocation.


Central non-NMDA receptors of a honey bee with hereditary kynurenine deficiency.
Pharmacological characteristics of non-NMDA receptors involved in associative learning were studied in wild honey bees (normal) and carriers of snow laranja mutation (kynurenine deficiency) by pharmacological analysis and behavioral criteria. The effects of systemic injections of non-NMDA receptor agonists (AMPA, kainic, quisqualic, and domoic acids), AMPA receptor antagonist (NS257-HCl), and AMPA receptor modulator (cyclothiaside) on retention of conditioned reflexes in short-term memory (1 min after the end of learning) were studied. The pharmacological characteristics of non-NMDA receptors were changed in snow laranja mutants with kynurenine deficiency.


Modularity of Conifer Diterpene Resin Acid Biosynthesis: P450 Enzymes of Different CYP720B Clades Use Alternative Substrates and Converge on the Same Products.
Cytochrome P450 enzymes of the CYP720B subfamily play a central role in the biosynthesis of diterpene resin acids (DRAs), which are a major component of the conifer oleoresin defense system. CYP720Bs exist in families of up to a dozen different members in conifer genomes and fall into four different clades (I-IV). Only two CYP720B members, loblolly pine (Pinus taeda) PtCYP720B1 and Sitka spruce (Picea sitchensis) PsCYP720B4, have been characterized previously. Both are multisubstrate and multifunctional clade III enzymes, which catalyze consecutive three-step oxidations in the conversion of diterpene olefins to DRAs. These reactions resemble the sequential diterpene oxidations affording ent-kaurenoic acid from ent-kaurene in gibberellin biosynthesis. Here, we functionally characterized the CYP720B clade I enzymes CYP720B2 and CYP720B12 in three different conifer species, Sitka spruce, lodgepole pine (Pinus contorta), and jack pine (Pinus banksiana), and compared their activities with those of the clade III enzymes CYP720B1 and CYP720B4 of the same species. Unlike the clade III enzymes, clade I enzymes were ultimately found not to be active with diterpene olefins but converted the recently discovered, unstable diterpene synthase product 13-hydroxy-8(14)-abietene. Through alternative routes, CYP720B enzymes of both clades produce some of the same profiles of conifer oleoresin DRAs (abietic acid, neoabietic acid, levopimaric acid, and palustric acid), while clade III enzymes also function in the formation of pimaric acid, isopimaric acid, and sandaracopimaric acid. These results highlight the modularity of the specialized (i.e. secondary) diterpene metabolism, which produces conifer defense metabolites through variable combinations of different diterpene synthase and CYP720B enzymes.


Solvatochromic study of excited state dipole moments of some biologically active indoles and tryptamines.
Absorption and fluorescence spectra of some biologically active indole and tryptamine derivatives have been recorded at room temperature in solvents of different polarities. The interest in the photophysical properties of these molecules arises mainly from their utility in medicinal chemistry as neurotransmitter and hallucination/hallucinic agents. Excited-state dipole moments of these molecules have been estimated from solvent-dependent Stokes shift data using a solvatochromic method based on a microscopic solvent polarity parameter (ETN). All indoles show a substantial increase in the dipole moment upon excitation to the emitting state. These results are generally consistent with the Parametric Method 3 (PM3) calculations, and are found to be quite reliable in view of the fact that the correlation of the solvatochromic Stokes shifts with the microscopic solvent polarity parameter (ETN) is superior to that obtained using bulk solvent polarity functions.


Release-activity: a long way from phenomenon to new drugs.
Multiple dilutions of the original substance release its peculiar activity referred to as "release-activity". Although this activity originates from the initial substance, it does not depend on its negligible concentration in extreme dilutions. Thus, the terms "dose", "ultralow dose", and "homeopathic dose", do not correctly describe the release-active solutions, since the concept of dose implies the presence of some part of the original substance in a dilution with its intrinsic therapeutic potency. The data are reported on the molecular and cellular mechanisms of the mode of action of the release-active agents, some of which being introduced into clinical practice.


Photodynamic inactivation of Staphylococcus aureus in the system of titanium dioxide nanoparticles sensitized by hypocrellin B and its application in food preservation.
Staphylococcus aureus (S. aureus) is a foodborne pathogen that endangers human health worldwide. Antimicrobial photodynamic inactivation (aPDI), mediated by titanium dioxide nanoparticles (TiO2NP), was recently used to control the growth of S. aureus, however, UV illumination had to be offered to initiate the photodynamic reaction. To overcome this drawback, a dual-photon system was established here based on TiO2NP and hypocrellin B (HB), a natural pigment with photocatalyst activity. Irradiated at the visible light (9 J/cm2) at the wavelength of 460 nm, the joint use of both photosensitizers (PS) caused a substantial decline of staphylococcal survival, reaching a maximum decrease of 4 ∼ 5 logs. When 10 nM HB and 100 µM TiO2NP were applied, a synergistic photokilling effect was achieved, only in the mixed phase of anatase/rutile, Degussa P25. Regarding the antimicrobial mechanisms, it was found that the membrane integrity of S. aureus was heavily disrupted, surface morphology was altered, intracellular substances like potassium and DNA were leaked, and biofilm formation was significantly circumvented due to the excitation of sensitized PS. In terms of antioxidant responsiveness of S. aureus, qPCR results showed that a series of genes encoding the membrane-associated cell death effectors were deregulated. Among them, LrgA was recognized as a key responsive element, due that the mutant strain harboring a constitutively-expressed LrgA strengthened the bactericidal effect of aPDI. Finally, the dual-photon strategy lowered the microbial contamination in the tested apple with its quality maintained, under the condition of visible light. Taken together, a new dual-photon system based on TiO2NP and HB was constructed and validated in photokilling S. aureus, providing a well-adapted technique to maintain food safety.


The evolution of human group B rotaviruses: correction and an update.
The Chinese adult diarrhea rotavirus (ADRV) and the Indian CAL strains of human group B rotaviruses were reported to be conserved in genes encoding structural proteins but divergent in NSP2 and NSP3 genes, raising the questions about the origin and the evolution of these strains. We repeated sequencing of the ADRV NSP2 and NSP3 genes and demonstrated high amino acid sequence identities with the CAL NSP2 and NSP3. Here we report the consequences of publishing and interpreting incorrect nucleotide sequences and provide evidence that the ADRV and CAL strains have evolved from a common ancestor.


Nitrogen reductions have decreased hypoxia in the Chesapeake Bay: Evidence from empirical and numerical modeling.
Seasonal hypoxia is a characteristic feature of the Chesapeake Bay due to anthropogenic nutrient input from agriculture and urbanization throughout the watershed. Although coordinated management efforts since 1985 have reduced nutrient inputs to the Bay, oxygen concentrations at depth in the summer still frequently fail to meet water quality standards that have been set to protect critical estuarine living resources. To quantify the impact of watershed nitrogen reductions on Bay hypoxia during a recent period including both average discharge and extremely wet years (2016-2019), this study employed both statistical and three-dimensional (3-D) numerical modeling analyses. Numerical model results suggest that if the nitrogen reductions since 1985 had not occurred, annual hypoxic volumes (O2 < 3 mg L-1) would have been ~50-120% greater during the average discharge years of 2016-2017 and ~20-50% greater during the wet years of 2018-2019. The effect was even greater for O2 < 1 mg L-1, where annual volumes would have been ~80-280% greater in 2016-2017 and ~30-100% greater in 2018-2019. These results were supported by statistical analysis of empirical data, though the magnitude of improvement due to nitrogen reductions was greater in the numerical modeling results than in the statistical analysis. This discrepancy is largely accounted for by warming in the Bay that has exacerbated hypoxia and offset roughly 6-34% of the improvement from nitrogen reductions. Although these results may reassure policymakers and stakeholders that their efforts to reduce hypoxia have improved ecosystem health in the Bay, they also indicate that greater reductions are needed to counteract the ever-increasing impacts of climate change.


MGAT2 inhibitor decreases liver fibrosis and inflammation in murine NASH models and reduces body weight in human adults with obesity.
Monoacylglycerol acyltransferase 2 (MGAT2) is an important enzyme highly expressed in the human small intestine and liver for the regulation of triglyceride absorption and homeostasis. We report that treatment with BMS-963272, a potent and selective MGAT2 inhibitor, decreased inflammation and fibrosis in CDAHFD and STAM, two murine nonalcoholic steatohepatitis (NASH) models. In high-fat-diet-treated cynomolgus monkeys, in contrast to a selective diacylglycerol acyltransferase 1 (DGAT1) inhibitor, BMS-963272 did not cause diarrhea. In a Phase 1 multiple-dose trial of healthy human adults with obesity (NCT04116632), BMS-963272 was safe and well tolerated with no treatment discontinuations due to adverse events. Consistent with the findings in rodent models, BMS-963272 elevated plasma long-chain dicarboxylic acid, indicating robust pharmacodynamic biomarker modulation; increased gut hormones GLP-1 and PYY; and decreased body weight in human subjects. These data suggest MGAT2 inhibition is a promising therapeutic opportunity for NASH, a disease with high unmet medical needs.


Unit activity in the cat visual cortex in the sleep--waking cycle.
Changes in spontaneous unit activity in the primary visual cortex during the sleep-waking cycle were studied in chronic experiments on dark-adapted cats. In the cell poulation studied activity in states of wakefulness and of paradoxical sleep did not differ significantly either in mean discharge frequency or in pattern. Activity of most cells in a state of slow sleep differed significantly from that in states of wakefulness and paradoxical sleep by the development of a "burst-pause" pattern in the unit discharges.


N -acetylcysteine is associated with reduction of postconcussive symptoms in elderly patients: A pilot study.
N -acetylcysteine (NAC) may be neuroprotective by minimizing postconcussion symptoms after mild traumatic brain injury (TBI), but limited data exist. This study evaluated the effects of NAC on postconcussion symptoms in elderly patients diagnosed with mild TBI. This prospective, quasirandomized, controlled trial enrolled patients 60 years or older who suffered mild TBI. Patients were excluded if cognitive function could not be assessed within 3-hours postinjury. Patients were allocated to receive NAC plus standard care, or standard care alone, based on the trauma center where they presented. The primary study outcome was the severity of concussive symptoms measured using the Rivermeade Postconcussion Symptoms Questionnaire (RPQ). Symptoms were evaluated on days 0, 7, and 30. The RPQ scores were compared both within and between treatment groups. There were 65 patients analyzed (NAC, n = 34; control, n = 31) with an average age of 76 ± 10 years. Baseline demographics and clinical variables were similar. No group differences in head Abbreviated Injury Scale score or Glasgow Coma Scale score were observed. Baseline RPQ scores (6 [0-20] vs. 11 [4-20], p = 0.300) were indistinguishable. The RPQ scores on day 7 (2 [0-8] vs. 10 [3-18], p = 0.004) and 30 (0 [0-4] vs. 4 [0-13], p = 0.021) were significantly lower in the NAC group. Within-group differences were significantly lower in the NAC ( p < 0.001) but not control group ( p = 0.319). N -acetylcysteine was associated with significant improvements in concussion symptoms in elderly patients with mild TBI. These results justify further research into using NAC to treat TBI. Therapeutic/Care Management; Level IV.


Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.
The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring.


Characterisation of a short, highly repeated and centromerically localised DNA sequence in crested and marbled newts of the genus Triturus.
A 32-33 bp highly repeated DNA sequence, TkS1, has been isolated from genomic DNA of the newt Triturus karelini digested with the restriction endonucleases HaeIII or AluI. TkS1 is known to be localised in the centromeric heterochromatin of all the chromosomes in T. karelini and the related species T. cristatus. TkS1 has been shown to be present in varying amounts in the genomic DNA of a range of species of Triturus, including representatives of the two main subgenera Triturus and Palaeotriton. A programme of sequencing of monomers, dimers and trimers of TkS1 was carried out in order to determine the level of conservation of the sequence within and between species of Triturus. Altogether 204 monomer (32/33 bp) clones were made of TkS1 from three individuals of T. karelini, and one individual each of T. cristatus, T. carnifex, T. dobrogicus and T. marmoratus, all members of the subgenus Triturus and the cristatus species group. A number of dimer (64 bp) and trimer (96 bp) clones were also made from DNA of a single specimen of T. karelini digested with HaeIII or AluI. Three distinct types of TkS1 were identified in all species examined, except for T. marmoratus where only two of the types were found. The types were distinguished on the basis of certain recurring divergent patterns in monomers sequenced from T. karelini. Type 1 is mainly characterised by the presence of an AluI site at positions 24-27 and type 3 mainly by the presence of an additional base (C) at position 14. Type 2 normally lacks the AluI site and the C at position 14, as well as having a number of other distinguishing features. TkS1 and its three types have remained remarkably constant in sequence since before the divergence of T. marmoratus from other species in the cristatus species group, about 10 million years ago. Examination of all 204 monomer clones and comparison with consensus sequences for the three types shows less than 5% divergence at any one position in the sequence. There is good evidence from examination of dimer and trimer clones of TkS1 that the different types are intermingled with each other, and all three types are likely to be present on all chromosomes. Dimeric (64 bp) TkS1 clones constructed from AluI fragments of T. karelini DNA show evidence of a trimeric (96 bp) "supertype" with the pattern type 1-type 3-type 1 that is much more common than would be expected on a random basis.(ABSTRACT TRUNCATED AT 400 WORDS)


An observation study of urinary biomarker exploratory in Alzheimer's disease using high-resolution mass spectrometry.
Alzheimer's disease (AD) is regarded as a progressive neurodegenerative dementia, characterized by degeneration of distinct neuronal populations. A case-control study was carried out using high-resolution mass spectrometry to explore AD-associated urinary metabolic biomarkers from 30 AD patients and 30 cognitively normal (CN) individuals. In total, 49 metabolites were determined and validated as known compounds using LC/MS analysis. Using the two-sample t-test statistical analysis (P < 0.05), 19 metabolites were shown to be significantly different from AD to CN. A diagnostic model of the receiver operating characteristic curve was constructed with a combination of nine molecules out of 19 metabolites, it yielded a separation with an area under the curve value of 0.976 between the two groups. This study indicated that urinary metabolites showed a significant expression between AD and CN. AD-related metabolites enable to satisfy the diagnostic power of disease discrimination. In addition, as a noninvasive approach, urine collection is done easily in clinical diagnosis of AD.


Outcomes of day case shoulder replacement surgery in a stand-alone day care unit in the United Kingdom.
This review aims to compare the outcomes for day case shoulder replacement with in-patient shoulder replacement surgery in a district general hospital. Seventy-three patients had 82 shoulder arthroplasty procedures. Forty-six procedures were undertaken in a dedicated stand-alone day-case unit and 36 were undertaken as in-patient cases. Patient were followed up at 6 weeks, 6 months and annually. There was no significant difference between the outcomes of shoulder arthroplasty procedures performed in the day case or in-patient settings making this a safe option for surgical care in a unit with an appropriate care pathway. Six complications in total were observed, three in each group. Operation time was statistically shorter for day cases by 25.1 min (95% CI - 36.5 to -13.7; d = -0.95, 95% CI -1.42 to 0.48). Estimated marginal means (EMM) revealed lower post-surgery oxford pain scores in day cases (EMM = 3.25, 95% CI 2.35, 4.16) compared with inpatients (EMM = 4.65, 95% CI 3.64 to 5.67). Constant shoulder scores were higher in day cases versus inpatients. Day case shoulder replacement is safe with comparable outcomes to routine inpatient care for patients up to ASA 3 classification with high satisfaction and excellent functional outcomes.


Medical resident's pursuing specialty and differences in clinical proficiency among medical residents in Japan: a nationwide cross-sectional study.
Standardized examinations assess both learners and training programs within the medical training system in Japan. However, it is unknown if there is an association between clinical proficiency as assessed by the General Medicine In-Training Examination (GM-ITE) and pursuing specialty. To determine the relative achievement of fundamental skills as assessed by the standardized GM-ITE based on pursuing career specialty among residents in the Japanese training system. Nationwide cross-sectional study. Medical residents in Japan who attempted the GM-ITE in their first or second year were surveyed. A total of 4,363 postgraduate years 1 and 2 residents who completed the GM-ITE were surveyed between January 18 and March 31, 2021. GM-ITE total scores and individual scores in each of four domains assessing clinical knowledge: 1) medical interview and professionalism, 2) symptomatology and clinical reasoning, 3) physical examination and treatment, and 4) detailed disease knowledge. When compared to the most pursued specialty, internal medicine, only those residents who chose general medicine achieved higher GM-ITE scores (coefficient 1.38, 95% CI 0.08 to 2.68, p = 0.038). Conversely, the nine specialties and "Other/Not decided" groups scored significantly lower. Higher scores were noted among residents entering general medicine, emergency medicine, and internal medicine and among those who trained in community hospitals with higher numbers of beds, were more advanced in their training, spent more time working and studying, and cared for a moderate but not an extreme number of patients at a time. Levels of basic skill achievement differed depending on respective chosen future specialties among residents in Japan. Scores were higher among those pursuing careers in general medical fields and lower among those pursuing highly specialized careers. Residents in training programs devoid of specialty-specific competition may not possess the same motivations as those in competitive systems.


Hosting the plant cells in vitro: recent trends in bioreactors.
Biotechnological production of high-value metabolites and therapeutic proteins by plant in vitro systems has been considered as an attractive alternative of classical technologies. Numerous proof-of-concept studies have illustrated the feasibility of scaling up plant in vitro system-based processes while keeping their biosynthetic potential. Moreover, several commercial processes have been established so far. Though the progress on the field is still limited, in the recent years several bioreactor configurations has been developed (e.g., so-called single-use bioreactors) and successfully adapted for growing plant cells in vitro. This review highlights recent progress and limitations in the bioreactors for plant cells and outlines future perspectives for wider industrialization of plant in vitro systems as "green cell factories" for sustainable production of value-added molecules.


Gel and anion exchange chromatographic properties of copper-containing metallothioneins.
Chromatographic properties of copper-binding proteins (copper-containing metallothioneins) induced in rat liver and kidney by the injection of either copper in the liver and kidney or cadmium in the kidney were compared with those of metallothioneins, with low or no copper content, induced by the injection of cadmium or zinc in the liver both on a Sephadex G-75 column and on a DEAE Sephadex A-25 column. The copper-containing metallothioneins were eluted at a slightly slower rate on a Sephadex G-75 column and at a higher buffer concentration on an anion exchange column than the metallothioneins with low or no copper content regardless of the inducing metals, copper or cadmium. The different chromatographic properties of the metallothioneins with high and low copper contents may be explained by the more compact conformation of the proteins with high copper contents than those with low or no copper contents and by the changes of electrostatic charge with coordination by copper.


DNA damage and repair in female C57BL/10 mice of different ages injected with the carcinogen benzo[a]pyrene-trans-7,8-diol.
Female C57BL/10 mice 2 and 14 months of age were killed 3, 6, 9, 12, 18 and 24 h after injection with 0.4 mg of benzo[a]pyrene-trans-7,8-dihydrodiol. The amount of carcinogen bound to DNA isolated from liver and kidney of each mouse was determined as benzo[a]pyrene-7,8,9,10-tetrol liberated upon acid hydrolysis of the DNA and measured by synchronous scanning fluorometry. Considerable variability was observed and a subset of animals in the middle-aged group failed to sustain appreciable damage upon injection of the carcinogen. Nevertheless, repair of DNA-bound carcinogen from both the liver and kidney of 2-month-old animals was clearly evident. In the subset of 14-month-old animals who sustained damage, evidence for removal of DNA-bound carcinogen was marginal.


Extracellular Ca2+ influences 1,2-diacylglycerol and inositol monophosphate formation in renal cortical slices stimulated with plasma obtained from uninephrectomized rats.
Formation of 1,2-diacylglycerol (DAG) and inositol phosphates was investigated in renal cortical slices after addition of plasma obtained 30 min after either uninephrectomy or sham operation. Plasma from uninephrectomized rats increased DAG concentration about 100% above control value during 5 min of incubation, but when extracellular Ca2+ had been chelated with 4 mM EGTA, the increase of DAG was only about 50% and the duration of the effect was 2 min only. Furthermore, chelation of extracellular Ca2+ did not affect the formation of InsP3 and InsP2 during 20 min of incubation, while the formation of InsP was significantly reduced. Results indicate that extracellular Ca2+ is needed for sustained increase in DAG concentration and increase in InsP radioactivity, suggesting phosphatidylinositol as their probable source.


Microspheres prepared with PLGA blends for delivery of dexamethasone for implantable medical devices.
To develop and characterize microspheres using poly (lactic-co-glycolic acid) (PLGA) blends (PLGA5050 (25 KD) and PLGA6535 (70 KD)) for dexamethasone delivery to prevent foreign body response to implantable biosensors. A single emulsion based oil/water solvent evaporation/extraction method was used to prepare microspheres. All the microspheres prepared exhibited the typical triphasic release profile, but with different initial burst release, lag phase and zero order release rates. The burst release was reduced when the two PLGA were mixed at a molecular level, whereas increase in burst release was observed when phase separation occurred. Microspheres prepared using PLGA blends had significantly shorter lag phase. The activation energy (Ea) of dexamethasone release from microspheres was similar to the Ea value of PLGA degradation. The release kinetics were significantly enhanced under accelerated conditions (45 and 53°C) without altering the release mechanism of the post-burst phase. A rank order correlation between accelerated and "real-time" release kinetics was observed. Polymer blends of PLGA can produce microspheres with reduced lag time. The accelerated release testing conditions investigated can discriminate the formulations and predict "real-time" release. Such accelerated release testing can be used as a rapid screening method to facilitate formulation development.


Sparklers, smoke bombs, and snakes, oh my! Effect of legislation on fireworks-related injuries in Minnesota, 1999-2005.
In 2002, Minnesota changed its law banning all fireworks and allowed for nonexplosive, nonaerial fireworks. This article reports that hospitals have seen a steady rise in the number of patients treated for injuries related to fireworks, including a 100% increase in the number of annual fireworks-related injuries between the years 1999 and 2005 based on hospital discharge data.


Selection and characterization of a variant of human melanoma cell line, A375 resistant to growth inhibitory effects of oncostatin M (OM): coresistant to interleukin 6 (IL-6).
Human melanoma cell line A375 is extremely sensitive to growth inhibitory effects of oncostatin M (OM). A375 cells resistant to the antiproliferative effect of OM were isolated by exposing OM-sensitive cells to ethyl methane sulfonate (EMS) for 24 h followed by continuous exposure to OM. An A375 subline resistant to OM-induced growth inhibition was selected by a limiting dilution technique and designated 4-1.10". The resistant cells were completely refractory to OM even up to a concentration of 500 ng/ml. Interestingly, the resistant cells were also nonresponsive to the growth inhibitory effects of interleukin-6 (IL-6). Other cytokines such as transforming growth factor beta (TGF-beta), interleukin-1 (IL-1), and tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) exhibited similar growth inhibitory effects on OM-sensitive or -resistant cells. OM-resistant cells were found to possess approximately 20% of OM receptors with the same affinities as compared to the parental OM-sensitive cells. However, the affinities and number of receptors for IL-6 were the same on both cell types. The OM treatment did not alter the cyclic AMP (cAMP) level of either the parental or the resistant cells. The OM-resistant cell line will be very useful in elucidating the mechanism of OM-elicited growth inhibition.


ALDH1A3-related congenital microphthalmia-8 due to a novel frameshift variant.
Microphthalmia (MCOP) is a group of rare developmental malformations of eye with often reduced size of the eyeball, leading to blindness. Affecting about 1 in 7000 live births, MCOP can occur due to either environmental or genetic factors. Isolated microphthalmia-8 (MCOP8) has been proved to be caused by autosomal recessive mutations of the ALDH1A3 gene (MIM*600463) encoding aldehyde dehydrogenase 1 family, member A3. Herein, we report an 8-year-old boy with vision problems since birth from a first-cousin consanguineous parents. The main symptoms of the patient included severe bilateral microphthalmia, cyst in the left eye and blindness. The child developed behavioral disorders at the age of 7. It should be noted that there is no family history of the disease. To identify the genetic factor underlying the pathogenesis in this case Whole Exome Sequencing (WES) was performed and followed by Sanger sequencing. A novel pathogenic variant, c.1441delA (p.M482Cfs*8), in the ALDH1A3 gene was detected by WES in the proband. Further prenatal diagnosis is highly suggested to the family for the future pregnancies.


DNA marker technology for wildlife conservation.
Use of molecular markers for identification of protected species offers a greater promise in the field of conservation biology. The information on genetic diversity of wildlife is necessary to ascertain the genetically deteriorated populations so that better management plans can be established for their conservation. Accurate classification of these threatened species allows understanding of the species biology and identification of distinct populations that should be managed with utmost care. Molecular markers are versatile tools for identification of populations with genetic crisis by comparing genetic diversities that in turn helps to resolve taxonomic uncertainties and to establish management units within species. The genetic marker analysis also provides sensitive and useful tools for prevention of illegal hunting and poaching and for more effective implementation of the laws for protection of the endangered species. This review summarizes various tools of DNA markers technology for application in molecular diversity analysis with special emphasis on wildlife conservation.


The reliability and validity of a Japanese version of symptom checklist 90 revised.
To examine the validity and reliability of a Japanese version of the Symptom Checklist 90 Revised (SCL-90-R (J)). The English SCL-90-R was translated to Japanese and the Japanese version confirmed by back-translation. To determine the factor validity and internal consistency of the nine primary subscales, 460 people from the community completed SCL-90-R(J). Test-retest reliability was examined for 104 outpatients and 124 healthy undergraduate students. The convergent-discriminant validity was determined for 80 inpatients who replied to both SCL-90-R(J) and the Minnesota Multiphasic Personality Inventory (MMPI). The correlation coefficients between the nine primary subscales and items were .26 to .78. Cronbach's alpha coefficients were from .76 (Phobic Anxiety) to .86 (Interpersonal Sensitivity). Pearson's correlation coefficients between test-retest scores were from .81 (Psychoticism) to .90 (Somatization) for the outpatients and were from .64 (Phobic Anxiety) to .78 (Paranoid Ideation) for the students. Each of the nine primary subscales correlated well with their corresponding constructs in the MMPI. We confirmed the validity and reliability of SCL-90-R(J) for the measurement of individual distress. The nine primary subscales were consistent with the items of the original English version.


Tissue and regional distribution of cysteic acid decarboxylase. A new assay method.
A sensitive and rapid assay method method for cysteic acid decarboxylase was develped which combined the selectivity of ion exchange resin (a complete retention of the substrate, cysteic acid, and exclusion of the product, taurine) with the speed of a vacuum filtration. The synthesis and purification of 35S-labeled cysteic acid were described. The validity of the assay was established by the identification of the reaction product as taurine. With this new method, the decarboxylase activity was measured in discrete regions of bovine brain. Putamen had the highest activity, 172 pmol taurine formed/min/mg protein (100%), followed by caudate nucleus, 90%; cerebral cortex, 82%; hypothalamus, 81%; cerebellar cortex, 79%; cerebellar peduncle, 59%; thalamus, 42%; brain stem, 25%; pons, 10%; and corpus callosum, 3%. The decarboxylase activity in various mouse tissues was also determined as follows: liver, 403; brain, 145; kidney, 143; spinal cord, 59; lung, 21; and spleen, 10 pmol taurine formed/min/mg. No activity could be detected in skeleton muscle and heart, suggesting a different biosynthetic pathway for taurine synthesis in these tissues. The advantages and disadvantages of the new assay method are also discussed.


Peptide-enhanced tough, resilient and adhesive eutectogels for highly reliable strain/pressure sensing under extreme conditions.
Natural gels and biomimetic hydrogel materials have been able to achieve outstanding integrated mechanical properties due to the gain of natural biological structures. However, nearly every natural biological structure relies on water as solvents or carriers, which limits the possibility in extreme conditions, such as sub-zero temperatures and long-term application. Here, peptide-enhanced eutectic gels were synthesized by introducing α-helical "molecular spring" structure into deep eutectic solvent. The gel takes full advantage of the α-helical structure, achieving high tensile/compression, good resilience, superior fracture toughness, excellent fatigue resistance and strong adhesion, while it also inherits the benefits of the deep eutectic solvent and solves the problems of solvent volatilization and freezing. This enables unprecedentedly long and stable sensing of human motion or mechanical movement. The electrical signal shows almost no drift even after 10,000 deformations for 29 hours or in the -20 °C to 80 °C temperature range.


Pancreatic polypeptide and intestinal motility in dogs.
This study was designed to determine the potential role of endogenous PP in the control of intestinal motility by correlating plasma PP levels with motility patterns in fasted and fed dogs without and with administration of exogenous PP and rabbit PP antiserum. After an overnight fast, when the interdigestive myoelectric activity was recorded in each dog, mean basal PP at phase I averaged 35 +/- 7 pM with peaks of 52 +/- 5 pM coinciding with phase III (MMC) in duodenum. Postprandial rise in PP reached the peak level of 280 +/- 70 pM at the end of 1 hr after a meal when MMC was interrupted and replaced by fed-type motility pattern. Exogenous PP in a dose of 100 pmol/kg/hr infused when the phase III of the MMC passed mid-jejunum raised plasma PP to the level of 130 +/- 27 pM but failed to affect the spike activity or MMC periodicity. PP given in doses of 200 and 400 pmol/kg/hr, which raised plasma PP to 298 +/- 25 and 453 +/- 24 pM, respectively, increased dose dependently (but did not abolish) the MMC intervals and an overall spike activity due to the prolongation of phase II of the MMC. After termination of PP infusion, phase III-like activity appeared within 7-10 min. Injection of highly specific PP antiserum, which caused almost complete disappearance of plasma PP both in fasted and fed dogs, did not affect the MMC interval but increased spike activity in fasted animals and failed to affect significantly spike activity in fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of experimental spinal cord injury with magnetization transfer ratio histograms.
This study was designed to characterize the severity of tissue damage in experimental spinal cord injury using magnetization transfer (MT) histogram analysis. Seven Sprague-Dawley rats were subjected to laminectomy and standard weight-drop injury to the spinal cord (four rats at 15 cm drop-height and three rats at 2.5 cm). Three control animals underwent laminectomy without weight-drop. After sacrifice, the animals were scanned at 1.9 T with a pulsed off-resonance MT technique. Following magnetic resonance (MR) imaging, the cords were embedded in paraffin and sectioned into 5-microm sections for semiquantitative histopathological analysis. Composite histograms were generated using data spanning an axial distance of 3 cm centered on the injury site. MT histogram parameters, such as the amount of tissue with statistical correspondence to normal white matter, were highly predictive of histopathological results, including myelination state and neurofilament damage. Less correlation with edema was observed, suggesting that the technique was most sensitive to true tissue alteration.


Trastuzumab emtansine for patients with non-small cell lung cancer positive for human epidermal growth factor receptor 2 exon-20 insertion mutations.
Human epidermal growth factor receptor 2 (HER2) mutations are present in ∼3% of patients with non-small cell lung cancer (NSCLC), with exon-20 insertions accounting for ∼90% of such HER2 mutations and having been identified as driver oncogenic alterations. Antibody-cytotoxic drug conjugates including trastuzumab deruxtecan have shown an excellent efficacy for NSCLC with HER2 mutations. We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations. Eligible patients with HER2 exon-20 insertion mutations confirmed by next-generation sequencing or multiplex polymerase chain reaction platforms and a history of one or two lines of chemotherapy received T-DM1 (3.6 mg/kg) intravenously every 21 days. The primary end-point of the study was the objective response rate (ORR). Between February 2019 and July 2020, 22 patients were enrolled in the study. A775_G776insYVMA was the most frequent HER2 exon-20 insertion mutation, accounting for 19 (86.4%) of the 22 patients. The ORR was 38.1% (90% confidence interval, 23.0-55.9%), and the disease control rate was 52.4%. The median duration of response was 3.5 months, and the median progression-free survival and median overall survival were 2.8 and 8.1 months, respectively. Toxicity was mild, with the frequency of adverse events of grade ≥3 being low. T-DM1 is a potential treatment option for patients with NSCLC with HER2 exon-20 insertion mutations. Further investigation of biomarkers for T-DM1 is warranted to improve its efficacy for NSCLC with such mutations. JapicCTI-194620.


Specification of sense-organ identity by a Caenorhabditis elegans Pax-6 homologue.
The Pax-6 transcription-factor gene, containing a paired domain and a paired-type homeodomain, is conserved in structure and ubiquitously present among Metazoa. It is required for development of the central nervous system, and is mutated in human aniridia, mouse and rat small eye and Drosophila eyeless. We identified the Pax-6 gene of the nematode Caenorhabditis elegans in genetic studies of male tail morphology. C. elegans Pax-6 encodes at least two independent genetic functions. One, like other Pax-6 genes, contains paired and homeodomains; this constitutes the genetic locus vab-3. The other, described here, is expressed from an internal promoter and contains only the homeodomain portion; this constitutes the genetic locus mab-18. The mab-18 form of the gene is expressed in a peripheral sense organ and is necessary for specification of sense-organ identity. Its function in this context could be to regulate the expression of cell recognition and adhesion proteins required for sense-organ assembly.


The fibrous frame of the supraspinatus muscle. Correlations between anatomy and MRI findings.
30 MRI investigations of shoulders and 20 dissections of non embalmed cadaveric shoulders allowed us to demonstrate a particular organization of the supraspinatus muscle. In the anterior part of the muscle is an important fibrous frame with obliquely inserted muscle fibers. This organization suggests that this part of the supraspinatus muscle works as a "contractile tendon".


Dissemination of the fosfomycin resistance gene fosA3 with CTX-M β-lactamase genes and rmtB carried on IncFII plasmids among Escherichia coli isolates from pets in China.
The presence and characterization of plasmid-mediated fosfomycin resistance determinants among Escherichia coli isolates collected from pets in China between 2006 and 2010 were investigated. Twenty-nine isolates (9.0%) were positive for fosA3, and all of them were CTX-M producers. The fosA3 genes were flanked by IS26 and were localized on F2:A-:B- plasmids or on very similar F33:A-:B- plasmids carrying both bla(CTX-M-65) and rmtB. These findings indicate that the fosA3 gene may be coselected by antimicrobials other than fosfomycin.


Transient receptor potential vanilloid-4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart.
Cardiovascular disease remains the greatest cause of mortality in Americans over 65. The stretch-activated transient receptor potential vanilloid-4 (TRPV4) ion channel is expressed in cardiomyocytes of the aged heart. This investigation tests the hypothesis that TRPV4 alters Ca2+ handling and cardiac function in response to increased ventricular preload and cardiomyocyte stretch. Left ventricular maximal pressure (PMax) was monitored in isolated working hearts of Aged (24-27 months) mice following preload elevation from 5 to 20mmHg, with and without TRPV4 antagonist HC067047 (HC, 1 µmol/L). In preload responsive hearts, PMax prior to and immediately following preload elevation (i.e. Frank-Starling response) was similar between Aged and Aged+HC. Within 1 min following preload elevation, Aged hearts demonstrated secondary PMax augmentation (Aged>Aged+HC) suggesting a role for stretch-activated TRPV4 in cardiac hypercontractility. However, after 20 min at 20 mmHg Aged exhibited depressed PMax (Aged<Aged+HC) suggestive of TRPV4-dependent contractile dysfunction with sustained stretch. To examine stretch-induced Ca2+ homeostasis at the single-cell level, isolated cardiomyocytes were stretched 10-15% of slack length while measuring intracellular Ca2+ with fura-2. Uniaxial longitudinal stretch increased intracellular Ca2+ levels and triggered Ca2+ overload and terminal cellular contracture in Aged, but not Aged+HC. Preload elevation in hearts of young/middle-age (3-12 months) mice produced an initial PMax increase (Frank-Starling response) without secondary PMax augmentation, and cardiomyocyte stretch did not affect intracellular Ca2+ levels. Hearts of transgenic mice with cardiac-specific TRPV4 expression exhibited PMax similar to 3- to 12-month control mice prior to and immediately following preload elevation but displayed secondary PMax augmentation. Cardiomyocytes of mice with transgenic TRPV4 expression were highly sensitive to mechanical stimulation and exhibited elevated Ca2+ levels, Ca2+ overload, and terminal contracture upon cellular attachment and stretch. TRPV4 contributes to a stretch-induced increase in cardiomyocyte Ca2+ and cardiac hypercontractility, yet sustained stretch leads to cardiomyocyte Ca2+ overload and contractile dysfunction in the aged heart.


The relationship between neurally mediated hypotension and the chronic fatigue syndrome.
To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome. Case-comparison study with mean (SD) follow-up of 24 (5) weeks. Tertiary care hospital. A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators' clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years). Each subject completed a symptom questionnaire and underwent a three-stage upright tilt-table test (stage 1, 45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension. Response to upright tilt and scores on symptom questionnaires prior to and during follow-up. An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension. We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.


Outpatient closure in a late colo-cutaneous postoperative anastomotic leak managed with EVAC in Bucaramanga, Colombia. Case report.
After Hartmann-type colostomy, the adequate selection of some patients allows reversal and closure of the colostomy, however, this reversal is not free of complications. Among complications, anastomotic leaks and fistulae can have functional, economic, and oncological consequences. Complications have been treated with surgery; yet, this management has changed considerably in recent years, moving towards less invasive therapies. This is the report of a 42-year-old man with a history of closed abdominal trauma with perforation of the sigmoid colon managed with a Hartmann-type colostomy. Six months later, he was admitted for a Hartmann reversal procedure without immediate complications. He was assessed again after 4 months observing a small area of erythema and periumbilical edema. EUS was performed without evidence of collections. Colonoscopy evidenced a 7-mm fistulous orifice in the colocolonic anastomosis. The Endo-VAC system was used, performing endoscopically exchanges twice a week following a low-residue diet. The procedure was performed on an outpatient basis and the closure of the leak hole in the colonic anastomosis was achieved in 30 days. Endoluminal vacuum therapy or EVAC, is an adaptation of the therapy used for negative pressure wound closure. This minimally invasive technique has been used for the treatment of gastrointestinal leaks and fistulae in selected patients and within a hospital setting. Our case presents the use of this technique in a late colocutaneous postoperative leak on an outpatient basis. To the best of our knowledge we report the first case of a late colocutaneous anastomotic leak managed with EVAC on an outpatient basis.


Translation and validation of the Dutch version of the Oxford 12-item knee questionnaire for knee arthroplasty.
In 1998, the Oxford 12-item knee questionnnaire was developed by Dawson et al. as a self-administered disease- and site-specific questionnaire, specifically developed for knee arthroplasty patients. Since then,it has proven to be an effective outcome questionnaire, and is widely used. Despite the positive psychometric properties for the Total Knee Arthroplasty (TKA) population, the 12-item knee questionnaire has only been translated into a few languages. We thus translated and validated the Oxford 12-item knee questionnaire for the Dutch population. After translation according to a forward/backward protocol, 174 knee arthroplasty patients were asked to answer the questionnaire together with an SF-36, an AKSS and a VAS. The reliability, validity, content validity and the sensitivity to change were all tested. Our Dutch version of the Oxford 12-item knee questionnaire achieved excellent scores in all of these properties. The Dutch Oxford 12-item knee questionnaire proved to be an excellent evaluation instrument for the Dutch orthopedic surgeon and can be used for all total knee arthroplasty patients.


Ethylenediaminediacetic acid bis(carbido amide chitosan): synthesis and evaluation as solid carrier to fabricate nanoemulsion.
We have optimized the synthesis of spray dried ethylenediaminediacetic acid bis(carbido amide chitosan) (ED-chitosan) microparticles employing 3(2) full factorial design. The ED-chitosan microparticles were characterized using FTIR-ATR, DSC analysis, oil adsorbing capacity, oil desorbing capacity, surface free energy and dynamic advancing contact angle. The ED-chitosan microparticles were found to have enhanced dispersive component of surface free energy as compared to Aerosil 200. However, they showed lower polar component. This was associated with similar oil adsorbing capacity but higher desorbing capacity. The SEM analysis supported ability of ED-chitosan microparticles to completely spread lipophillic drug over its surface. The reconstituted nanoemulsion generated from ED-chitosan was stable (neutral zeta potential), spherical shaped and 110 nm size (TEM analysis). Further, these nanoemulsions when prepared with primaquine were successfully enhanced in vitro dissolution and its ex vivo performance. Thus, the study showed new possibilities of industrial acceptance of ED-chitosan microparticles as a solid carrier for the fabrication of nanoemulsion.


Estimation of COVID-19 basic reproduction ratio in a large urban jail in the United States.
To estimate the basic reproduction ratio () of SARS-CoV-2 inside a correctional facility early in the COVID-19 pandemic. We developed a dynamic transmission model for a large, urban jail in the United States. We used the next generation method to determine the basic reproduction ratio We included anonymized data of incarcerated individuals and correctional staff with confirmed COVID-19 infections in our estimation of the basic reproduction ratio () of SARS-CoV-2. The estimated is 8.44 (95% Credible Interval (CrI): 5.00-13.13) for the entire jail. The high of SARS-CoV-2 in a large urban jail highlights the importance of including correctional facilities in public health strategies for COVID-19. In the absence of more aggressive mitigation strategies, correctional facilities will continue to contribute to community infections.


Molecular mechanisms of deoxynivalenol resistance in the yeastSaccharomyces cerevisiae.
The production of trichothecene toxins is a suspected virulence mechanism of several plant pathogenic fungi. This hypothesis has been confirmed forGibberella zeae (Fusarium graminearum) by gene disruption experiments, suggesting in turn, that resistance against the fungal toxin is a relevant component ofFusarium resistance of the host plant. Our goal is therefore to identify molecular mechanisms of trichothecene resistance. Using yeast as a model system we have found the following resistance mechanisms and genes: a) reduced uptake of deoxynivalenol (PDR5), b) toxin modification and reduction of toxicity (AYT1), and c) formation of a resistant toxin target (RPL3). Homologous plant genes exist and are attractive candidates forFusarium resistance genes.


Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway.
The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.


Flocculation in Saccharomyces cerevisiae is regulated by RNA/DNA helicase Sen1p.
The Nrd1-Nab3-Sen1 (NNS) complex terminates transcription of non-coding RNA genes and mediates degradation of the produced transcript by the nuclear exosome. The NNS complex also represses some stress response genes, by stimulating premature termination. A well-characterized stress response in yeast is flocculation, where cells aggregate to form flocs under expression of lectin-encoding genes designated as FLOs. In this study, we demonstrated the role of the NNS complex and Rrp6p in the expression of flocculation genes: FLO1, FLO5, FLO9, and FLO10. Furthermore, a deletion mutant of the RNA processing machinery (RNT1), and SEN1 mutants that are unable to interact with Rnt1p, exhibit a flocculation phenotype. In summary, we have identified a cooperative role of Rnt1p, Rrp6p and the NNS complex in the repression of FLO genes.


Complete Genome Sequences of the Two Strains Methylorubrum extorquens NBC_00036 and NBC_00404.
Here, we report the complete genome sequences of Methylorubrum extorquens NBC_00036 and Methylorubrum extorquens NBC_00404. The genomes were sequenced using the Oxford Nanopore Technologies MinION and Illumina NovaSeq systems. Both genomes are circular, with sizes of 5,661,342 bp and 5,869,086 bp, respectively.


3-Amino-3-deoxy-D-glucose: an antibiotic produced by a deep-sea bacterium.
Gram-positive bacteria isolated from deep-sea sediments of the Pacific basin showed considerable antibacterial activity. A Bacillus strain, isolated from a sediment sample collected at a depth of 4310 m, was shown to produce 3-amino-3-deoxy-D-glucose, a known antibiotic.