Assessment of postoperative opioid stewardship using a novel electronic-based automated text and phone messaging platform.
Practices of opioid prescribing vary widely across general surgery providers. The goal of this study was to use a text-based platform to assess postdischarge opioid utilization. A prospective, cohort study enrolled adult patients undergoing operations across the following 3 general surgery sections: minimally invasive surgery, colorectal, and surgical oncology. Using Epharmix, an electronic text-based platform, short message service text messages were sent to enrolled patients on postdischarge days 1 to 7, 14, 2, and 28 inquiring about the number of opioid pills taken since discharge and pain medication refills. A total of 253 patients enrolled and completed the intervention. Patient participation was robust, with 80% of patients responded to >50% of all text-based questions, and 64% responded to >80% of all questions. Patients undergoing bariatric surgery were prescribed the most narcotic pain medications (average milligram of morphine equivalents: 250.8), and those undergoing endocrine neck surgery the least (average milligram of morphine equivalent: 53.5). All surgical categories studied consumed ≤25% of their total prescribed milligram of morphine equivalents. Only 8 patients (3.2%) requested an opioid refill by postdischarge days 28. A text-based platform can track reliably patients' opioid usage postdischarge. Such platforms may facilitate the development of data-driven, standardized practices of opioid prescribing matched to patients' anticipated opioid usage postdischarge.


Multiple partition Markov model for B.1.1.7, B.1.351, B.1.617.2, and P.1 variants of SARS-CoV 2 virus.
With tools originating from Markov processes, we investigate the similarities and differences between genomic sequences in FASTA format coming from four variants of the SARS-CoV 2 virus, B.1.1.7 (UK), B.1.351 (South Africa), B.1.617.2 (India), and P.1 (Brazil). We treat the virus' sequences as samples of finite memory Markov processes acting in A = { a , c , g , t } . We model each sequence, revealing some heterogeneity between sequences belonging to the same variant. We identified the five most representative sequences for each variant using a robust notion of classification, see Fernández et al. (Math Methods Appl Sci 43(13):7537-7549. 10.1002/mma.5705 ). Using a notion derived from a metric between processes, see García et al. (Appl Stoch Models Bus Ind 34(6):868-878. 10.1002/asmb.2346), we identify four groups, each group representing a variant. It is also detected, by this metric, global proximity between the variants B.1.351 and B.1.1.7. With the selected sequences, we assemble a multiple partition model, see Cordeiro et al. (Math Methods Appl Sci 43(13):7677-7691. 10.1002/mma.6079), revealing in which states of the state space the variants differ, concerning the mechanisms for choosing the next element in A. Through this model, we identify that the variants differ in their transition probabilities in eleven states out of a total of 256 states. For these eleven states, we reveal how the transition probabilities change from variant (group of variants) to variant (group of variants). In other words, we indicate precisely the stochastic reasons for the discrepancies.


Expression of TS, RRM1, ERCC1, TUBB3 and STMN1 Genes in Tissues of Non-small Cell Lung Cancer and its Significance in Guiding Postoperative Adjuvant Chemotherapy.
To explore the expression of TS, RRM, ERCC1, TUBB3 and STMN1 genes in the tissues of patients with non-small cell lung cancer (NSCLC) and its significance in guiding the postoperative adjuvant chemotherapy. Real time polymerase chain reaction (PCR) was applied to detect the expression of TS, RRM, ERCC1, TUBB3 and STMN1 genes in the tissues of NSCLC patients so as to analyze the relationship between the expression of each gene and the clinical characteristics and to guide the postoperative individualized chemotherapy according to the detection results of NSCLC patients. Expression of TS gene was evidently higher in patients with adenocarcinoma than those with non-adenocarcinoma (P=0.013) and so was the expression of ERCC1 (P=0.003). The expression of TUBB3 gene was obviously higher in NSCLC patients in phases I/II and IV than those in phase III (P1=0.021; P2=0.004), and it was also markedly higher in patients without lymph node metastasis than those with (P=0.008). The expression of STMN1 gene was apparently higher in patients in phase I/II than those in phase IV (P=0.002). There was no significant difference between the rest gene expression and the clinical characteristics of NSCLC patients (P>0.05). Additionally, the disease- free survival (DFS) was significantly longer in patients receiving gene detections than those without (P=0.021). The selection of chemotherapeutic protocols based singly on patients' clinical characteristics has certain blindness. However, the detection of tumor-susceptible genes can guide the postoperative adjuvant chemotherapy and prolong the DFS of NSCLC patients.


The treatment of benign thyroid disease.
The treatment of benign forms of thyroid disease is reviewed. Endemic goiter is a public health problem preventable by the addition of iodine to the food or water supply. Endemic and familial goiters are treated with replacement doses of I-thyroxine, as are sporadic colloid goiters and goiters resulting from chronic thyroiditis. Hyperfunctioning autionomous nodules without thyrotoxicosis and cystic nodules require no specific therapy. Prophylaxis against diffuse or nodular goiter after radiation to the head or neck for therapeutic purposes with thyroxine replacement therapy is debatable. All forms of hypothyroidism, including incipient types, require replacement thyroxine therapy, but this should be undertaken cautiously in older patients and in those with evidence of ischemic myocardial disease. Myxedema coma requires vigorous treatment and detailed supervision because of dismal mortality rates. Iodine 131 is the treatment of choice in diffuse toxic goiter, but alternative forms.


Simazine perturbs the maturational competency of mouse oocyte through inducing oxidative stress and DNA damage.
Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.


Botulinum toxin (DYSPORT) in tension-type headaches.
Botulinum toxin type A is effective in the reduction of muscle tenderness and pain in many diseases associated with myofascial pain. Since increased muscle tension may contribute to tension-type headaches, injections of botulinum toxin could be of therapeutic value. Results of own investigations are presented, in particular a double-blind, placebo-controlled study with 21 patients fulfilling the International Headache Society criteria for tension-type hedaches. Participants were randomly assigned to verum (pericranial injection of 10 x 20 MU DYSPORT) or placebo condition (injection of isotonic saline in the same manner). After 4, 8, and 12 weeks no significant differences between placebo and verum could be observed. Nevertheless, both groups significantly improved. The findings strongly suggest that higher doses or other injection sites might be necessary to achieve therapeutic effects of botulinum toxin in tension-type headaches. Actually, we are participating in a multi-center study using 500 MU of DYSPORT. Besides dose-finding problems, another explanation could be that peripheral mechanisms--such as increased pericranial muscle tension--only play a minor role in the pathogenesis of tension-type headaches.


Is parental socio-economic status related to the initiation of substance abuse by young people in an English city? An event history analysis.
This paper aims to examine the relationship between parental socio-economic status (SES) and adolescent substance use. The central question posed in the title is approached in two stages. First, theoretical and empirical research in this area is reviewed. Second, data from an ongoing longitudinal study of young people in England (the Peterborough Adolescent and Young Adult Development Study--PADS+) are used to highlight the nature of this relationship in one city. Results from discrete-time event history analyses show that when examining what predicts initiation of substance use, familial and demographic factors emerge as important predictors, but SES does not appear to be relevant. The concluding discussion focuses on whether support is found for hypotheses derived from the existing literature and implications for future research.


American Cancer Society--National Prostate Cancer Detection Project. Results from multiple examinations using transrectal ultrasound, digital rectal examination, and prostate specific antigen.
The American Cancer Society-National Prostate Cancer Detection Project is a prospective study of the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). Two thousand nine hundred ninety-nine men not previously suspected of having prostate cancer have been entered on study in ten participating clinical centers. The study protocol requires these men to undergo testing with the three detection methods under investigation on an annual basis for up to 5 years. Data currently are available on 1972 men who have completed protocol requirements for two sequential series of examinations. At the first visit, it was recommended that 16.5% of subjects undergo biopsy based on the TRUS and/or DRE findings. Seventy-three (3.7%) men were found to have cancer after the first series of examinations. When the 1899 men who did not have cancer were reexamined, in 11.4%, a biopsy was recommended, and an additional 33 (1.7%) cancers were detected. Cancer detection rates were higher in older men, and the sensitivity of TRUS was higher than that of DRE at both examinations. The positive predictive values (PPV) of TRUS and DRE varied significantly depending on the PSA level; PPV decreased at the second examination. Positive findings during the second examination were associated with elevated PSA levels during the earlier visit and rising PSA levels between examinations. Analyses of the 106 cancers detected currently showed a preponderance of early-stage cancer and low Gleason scores. It may be possible to increase the early detection of prostate cancer by periodic examination by a combination of detection modalities.


Partial trisomy of 3q detected by chromosome painting in a case of juvenile chronic myelomonocytic leukemia.
Juvenile chronic myelomonocytic leukemia (JCMMoL) is a rare disease with no specific type of chromosome aberration yet delineated. We report a 2-year-old boy who had in his leukemic bone marrow (BM) and peripheral blood (PB) cells the 46,XY,der(15)t(3;15)(q13.1;q26) karyotype. Phytohemagglutinin (PHA)-stimulated lymphocytes of peripheral blood had a normal 46,XY karyotype. The origin of the duplicated part of 3q was proved by fluorescence in situ hybridization (FISH) with the pHSR(sat III 15p) DNA probe and a chromosome 3-specific DNA library (i.e., chromosome painting). The chromosome finding in our case provides further proof of the close relationship between the rearrangement in region 3q13-->3q26 and the pathogenesis of acute myeloid leukemia (AML). Our patient has transformed into erythroleukemia [M6 according to the French-American-British (FAB) classification] during the course of the disease.


Relationship between equilibration times and the presence of cumulus cells, and effect of taxol treatment for vitrification of in vitro matured porcine oocytes.
The effects of the presence or absence of cumulus cells and equilibration times (1 and 4 min) with cryoprotectant, and Taxol treatment before vitrification (0.5-5.0 microM) on development of in vitro matured porcine oocytes after vitrification were examined. Ethylene glycol (30%) and sucrose (0.5M) was used as a vitrification solution (39 degrees C), and cryotop was used for cryo-container. There was a significant relationship (F value: 6.077, P<0.05) in the rate of morphologically normal oocytes after vitrification between the equilibration times and the presence or absence of cumulus cells. The blastocyst rates were not significantly different between Taxol (1.4-5.5%) and non-treated control (8.8%). The results show that the optimal exposure time to achieve survival after vitrification depends on the presence or absence of cumulus cells, and that Taxol has no positive effect on the developmental capacity of vitrified, in vitro matured porcine oocytes.


Nutrition for Infant Feeding.
It has long been demonstrated that nutrition in the first 1000 days of life can affect health outcomes later in life [...].


The dependence of EGFR oligomerization on environment and structure: A camera-based N&B study.
Number and brightness (N&B) analysis is a fluorescence spectroscopy technique to quantify oligomerization of the mobile fraction of proteins. Accurate results, however, rely on a good knowledge of nonfluorescent states of the fluorescent labels, especially of fluorescent proteins, which are widely used in biology. Fluorescent proteins have been characterized for confocal, but not camera-based, N&B, which allows, in principle, faster measurements over larger areas. Here, we calibrate camera-based N&B implemented on a total internal reflection fluorescence microscope for various fluorescent proteins by determining their propensity to be fluorescent. We then apply camera-based N&B in live CHO-K1 cells to determine the oligomerization state of the epidermal growth factor receptor (EGFR), a transmembrane receptor tyrosine kinase that is a crucial regulator of cell proliferation and survival with implications in many cancers. EGFR oligomerization in resting cells and its regulation by the plasma membrane microenvironment are still under debate. Therefore, we investigate the effects of extrinsic factors, including membrane organization, cytoskeletal structure, and ligand stimulation, and intrinsic factors, including mutations in various EGFR domains, on the receptor's oligomerization. Our results demonstrate that EGFR oligomerization increases with removal of cholesterol or sphingolipids or the disruption of GM3-EGFR interactions, indicating raft association. However, oligomerization is not significantly influenced by the cytoskeleton. Mutations in either I706/V948 residues or E685/E687/E690 residues in the kinase and juxtamembrane domains, respectively, lead to a decrease in oligomerization, indicating their necessity for EGFR dimerization. Finally, EGFR phosphorylation is oligomerization dependent, involving the extracellular domain (550-580 residues). Coupled with biochemical investigations, camera-based N&B indicates that EGFR oligomerization and phosphorylation are the outcomes of several molecular interactions involving the lipid content and structure of the cell membrane and multiple residues in the kinase, juxtamembrane, and extracellular domains.


Arthroscopic ulnar nerve decompression in the setting of elbow osteoarthritis.
To present the technique and outcomes of arthroscopic ulnar nerve decompression at the elbow in a series of patients with associated osteoarthritis. A retrospective chart review identified all patients with symptomatic ulnar compression neuropathy and osteoarthritis at the elbow treated with arthroscopic decompression between March 2002 and June 2007. Information regarding preoperative symptom severity and function, associated arthritis and other disorders of the involved extremity, postoperative symptoms and function, complications, and reoperations were reviewed from the medical record. All patients were followed up for at least 12 months, and data collection included clinical evaluations and survey correspondence. Thirteen patients (15 elbows) were available for review. The series consisted of patients with an average age of 51 years (range, 20-75 y). All patients had arthroscopic ulnar nerve decompression, osteophyte resection, and capsulectomy during the same procedure. An average postoperative follow-up of 47 months revealed 7 excellent, 5 good, 1 fair, and 2 poor results. Three patients had reoperations because of persistent or recurrent symptoms. These 3 patients had severe (Dellon classification) symptoms including muscular wasting on presentation. This technique appears to be a useful procedure for treatment of cubital tunnel syndrome at the time of elbow arthroscopic debridement arthroplasty. Additional follow-up and prospective comparative studies are indicated to further evaluate this technique. Therapeutic IV.


Mass spectrometric identification of immunogenic SARS-CoV-2 epitopes and cognate TCRs.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections elicit both humoral and cellular immune responses. For the prevention and treatment of COVID-19, the disease caused by SARS-CoV-2, it has become increasingly apparent that T cell responses are equally if not more important than humoral responses in mediating recovery and immune protection. One major challenge in developing T cell-based therapies for infectious and malignant diseases has been the identification of immunogenic epitopes that can elicit a meaningful T cell response. Traditionally, this has been achieved using sophisticated in silico methods to predict putative epitopes deduced from binding affinities. Our studies find that, in contrast to current convention, "immunodominant" SARS-CoV-2 peptides defined by such in silico methods often fail to elicit T cell responses recognizing naturally presented SARS-CoV-2 epitopes. We postulated that immunogenic epitopes for SARS-CoV-2 are best defined empirically by directly analyzing peptides eluted from the naturally processed peptide-major histocompatibility complex (MHC) and then validating immunogenicity by determining whether such peptides can elicit T cells recognizing SARS-CoV-2 antigen-expressing cells. Using a tandem mass spectrometry approach, we identified epitopes derived from not only structural but also nonstructural genes in regions highly conserved among SARS-CoV-2 strains, including recently recognized variants. Finally, there are no reported T cell receptor-engineered T cell technology that can redirect T cell specificity to recognize and kill SARS-CoV-2 target cells. We report here several SARS-CoV-2 epitopes defined by mass spectrometric analysis of MHC-eluted peptides, provide empiric evidence for their immunogenicity, and demonstrate engineered TCR-redirected killing.


Dietary Behavior and Urinary Gallic Acid Concentrations in Older Minority Residents of East Harlem, New York City.
In this multidisciplinary study, we explored relationships between demographic factors, dietary habits, and gallic acid, a polyphenolic biomarker that correlates with self-reported dietary behaviors and negatively correlates with the incidence of cancer. Thirty-three (33) participants were recruited from a senior center in East Harlem, New York City, a racially diverse and underserved community. A National Institute of Health (NIH)-validated survey questionnaire was used to gather dietary behavior data, alongside demographic and cancer history information. Urine samples were obtained from participants for analyzing gallic acid content level. All 33 recruited participants completed the survey and 25 of them provided urine samples for gallic acid analysis. Associations between demographic factors and intake of certain foods were observed. Specifically, age was negatively associated with French fries/fried potatoes, cooked dried beans, and tomato soup intake (p < 0.05), and Black/African American race was associated with increased consumption of fruits and vegetables in comparison to Hispanic/Latino ethnicity (p < 0.05). No associations between urinary gallic acid levels and demographic information was observed. However, French fries/fried potatoes intake was significantly associated with urinary gallic acid concentration (p < 0.01). The small sample size limited the execution of meaningful statistical analysis. However, this study provided preliminary findings about the dietary behavior of older adults in East Harlem, New York City, which will serve as a basis for a future larger study to investigate nutrition/dietary education intervention on cancer prevention among diverse elderly residents in New York City.


Water sources are associated with childhood diarrhoea prevalence in rural east-central Mali.
Water supply improvements generally reduce the incidence of diarrhoea. However, populations with limited access to a safe water supply may continue to draw water from unimproved sources, thereby increasing their risk of diarrhoea. Furthermore, young children who are not breastfed may be even more susceptible to water-borne diarrhoeal pathogens. Our study explored the interactive protective effects against diarrhoea of exclusively using improved water sources and breastfeeding among children in rural Mali. Interviews were conducted with parents or guardians of children under 7 years of age in seven villages with access to a variety of water supplies. Water sources used, breastfeeding status, demographics and recent diarrhoea symptoms were determined for 1117 children. The cross-sectional findings were used to compare diarrhoea prevalence among exclusive and non-exclusive users of improved water sources. Variation in prevalence by age and exclusive breastfeeding status was evaluated using chi-square and multivariate analyses. Children whose water was drawn exclusively from wells had a significantly lower prevalence of diarrhoea as compared with children whose water was drawn from a spring or stream (5.9% vs. 8.7%; P=0.04). The exclusive use of improved water sources had no impact on diarrhoea prevalence among children who were exclusively breastfed. Similarly, the strongest protective effect was observed among children who were not exclusively breastfed. Our results indicate that using surface water as a primary or secondary water source exposes children to greater risk of diarrhoeal disease than using only improved sources such as wells. It is particularly beneficial for young children who are not exclusively breastfed to be supplied with water drawn from improved sources.


5-Fluorouracil preferentially sensitizes mutant KRAS non-small cell lung carcinoma cells to TRAIL-induced apoptosis.
Mutations in the KRAS gene are very common in non-small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL-based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. Current research has focused on selecting a subpopulation of cancer patients who may benefit from TRAIL-based therapy and identifying best drugs to work with TRAIL. In the current study, we found that NSCLC cells with a KRAS mutation were highly sensitive to treatment with TRAIL and 5-fluorouracil (5FU). Compared with other chemotherapeutic agents, 5FU displayed the highest synergy with TRAIL in inducing apoptosis in mutant KRAS NSCLC cells. We also found that, on a mechanistic level, 5FU preferentially repressed survivin expression and induced expression of TRAIL death receptor 5 to sensitize NSCLC cells to TRAIL. The combination of low-dose 5FU and TRAIL strongly inhibited xenograft tumor growth in mice. Our results suggest that the combination of TRAIL and 5FU may be beneficial for patients with mutant KRAS NSCLC.


More than just a number of publications: Unity Index, an alternative "ranking" for bibliometric analyses.
This paper presents the unity index- an index designed in response to the call to find a more holistic way to assess scientific production. In this case, the scientific production is understood from a multivariate perspective using existing measurements, such as the number of publications, the number of, and the H-Index. It can be used especially when generating or assessing production in bibliometric studies. The index consists of a 3-part point system where points are assigned to the authors based on their position in the rank of the 3 traditional indicators for production, acceptance and impact. The index is calculated by attributing 1 point to the author with most published articles and increasing the number of points attributed by 1 to all the subsequent authors. The same point attribution is done to the remaining 2 indicators, acceptance -citations- and impact -h-index-. In the presented method, 3 different means of calculation are shared. Finally, the method is validated and different ways to analyze the results and generate insights are suggested.•The Unity Index offers a new way to assess scientific production from a multivariate perspective.•The index can be calculated easily using MS Excel formulas, but automatic ways of calculation are also easily available.•Bibliometric studies can profit from a less linear way to analyze the information and generate more insightful information and guide the research.


On some Moroccan Pamphagidae, with the description of a new species of Euryparyphes (Orthoptera: Caelifera).
An update to the distribution records of the Moroccan Pamphagidae is presented. One new species to science, Euryparyphes minor sp. n., is described, and one new combination is proposed.


The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.
The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.


Spatially regulated activation of membrane fusogenic peptides with chaperone-like ionic copolymers.
Controlled or targeted membrane lysis induced by cascades of assembly and activation of biomolecules on membrane surfaces is important in programmed cell death and host defense systems. In a previous study, we reported that an ionic graft copolymer with a polycation backbone and water-soluble graft chains, poly(allylamine)-graft-dextran (PAA-g-Dex) chaperoned folding and assembly of E5, a membrane-destructive peptide derived from influenza hemagglutinin, to its increase membrane-disruptive activity. In this study, we modified the copolymer with long acyl chains, which resulted in delivery of the copolymer to membrane surfaces of liposomes and living cells. The liposomes with PAA-g-Dex functionalized with stearic acid (PAA-g-Dex-SA) on their surfaces underwent vesicle-to-sheet conversion upon addition of E5, whereas control liposomes did not. E5 also induced selective lysis of cells incubated with PAA-g-Dex-SA. The spatially specific activation of E5 on target membrane surfaces driven by self-assembly of copolymer and activation of E5 should find application in lipid-based delivery devices and cell-based therapeutics.


Radiotherapy or surgery for T2N0M0 glottic carcinoma? A decision-analytic approach.
Decision analysis was used to evaluate the results of treatment of T2N0M0 glottic carcinoma as presented in the literature. Based on mean values for recurrence, salvage eligibility after recurrence and salvage success, the 5-year survival after radiotherapy and surgery proved to be almost identical, 85 and 86%. If the recurrence rates and the salvage rates were varied, a marginal advantage for surgery in small tumours (T2a) and a major advantage in more extended (T2b) tumours was seen if only survival is considered. To take the quality of speech into account, a utility analysis was performed. A utility scale was defined ranging from 0.0 as the value for death, to 1.0 for a successfully irradiated patient with preservation of normal speech. A utility of 0.99 or less for the laryngectomized patient would favour radiotherapy over surgery for all T2 tumours. In patients with T2b tumours and in extreme circumstances, e.g. if failure rates of radiotherapy are extremely high or if recurrence rates after surgery are extremely low, an exact assessment of patient utilities may be pivotal. Under normal circumstances radiotherapy is preferred for T2N0M0 glottic carcinoma if both survival and the quality of speech are taken into account.


Caffeine contracture and iodoacetate rigor in frog skeletal muscle. A comparison.
Frog sartorius muscle treated with 5.0 mM or greater caffeine exhibits stiffness similar to that obtained from muscle in iodoacetate rigor. The data provide quantitative evidence that suggests that caffeine at irreversible contracture-producing concentrations somehow induces a rigor or rigorlike state in skeletal muscle.


Olfactory input to the lateral hypothalamus of the old world monkey.
Responses of lateral hypothalamic neurons to 8 odors were studied in chronic unanesthetized old world monkeys (Macaca irus). Many neurons (54.5%) responded to a single odor only, and the number of neurons responding to 2, 3 and 4 odors decreased successively. No neuron responded to as many as 5 odors. Thus, the presence of olfactory input and a highly discriminative ability for odors were found in the lateral hypothalamic area (LHA). Neuronal responses to the same odors were also studied in the septum (Spt). In anesthetized old world monkeys, evoked potentials were recorded in the LHA and in areas of the Spt and the nucleus accumbens (Acc) during stimulation of the olfactory bulb (OB). When the Spt (and probably the Acc with it) was subsequently destroyed, OB-evoked potentials in the LHA disappeared. Next, by injecting horseradish peroxidase (HRP) into the LHA, an olfactory pathway to the LHA was examined. Labeled neurons were found mainly in the Spt and the Acc, and only partly in other areas. However, labeled neurons were scarcely found in the prepyriform (PPF)-entorhinal (ER) area or in the olfactory tubercle (OT). The present study thus shows that an olfactory pathway to the LHA passes through the Spt and probably also the Acc, but not through the PPF-ER areas nor through the OT in the old world monkey.


Bone transport techniques in posttraumatic bone defects.
The treatment of posttraumatic diaphyseal bone defects (BD) calls on a number of techniques including bone transport techniques: isolated shortening, compression-distraction at the fracture site, shortening followed by lengthening in a corticotomy distant from the site and segmental bone transport. The multicenter retrospective study combined 38 cases: 22 cases of initial diaphyseal bone defect and 16 cases of secondary diaphyseal BD, sometimes associated with metaphyseal or metaphyseal-epiphyseal BD, involving the humerus, the forearm, the femur and the tibia. These techniques were mainly used on the lower extremity (33 cases), for the most part on the tibia (22 cases) in young men. Bone healing was acquired in 37 cases out of 38 after a mean 14.9 months (range, 6-62 months). A mean 4.3 secondary interventions were required to obtain final union; most notably, a bone graft was necessary at the docking site for the segmental bone transport procedures. Many reconstruction techniques can be proposed to treat posttraumatic BD. None responds to all situations. Bone transport techniques have their place and their indications. Isolated shortening is intended for bone loss not exceeding 3cm, notably in the humerus and to a lesser degree in the lower extremity. Shortening associated with lengthening is valuable in the femur and the tibia for bone loss up to 6cm. Segmental bone transport is the only technique that can treat bone defects associated with shortening in the lower limb. For substantial bone loss beyond 10cm, segmental bone transport is particularly indicated. However, these cases of substantial bone loss tend to be resolved by a hybridization of the procedures. The distraction gap of a bone segment can, for example, be prepared using an induced-membrane technique. Level IV. Retrospective study.


Histopathological survey of pathogens and commensals of white-clawed crayfish (Austropotamobius pallipes) in England and Wales.
A histopathological survey of white-clawed crayfish (Austropotamobius pallipes) from six rivers in England and Wales was conducted between November 2007 and September 2011. A. pallipes bacilliform virus (ApBV) was present in four samples; infected crayfish showed pathological responses ranging from mild hypertrophy of infected nuclei and emargination of chromatin through to loss of architecture of the hepatopancreatic cells. Crayfish were found to be hosts to two different ciliate species, mites, nematodes, digeneans and the microsporidian Thelohania contejeani. The variation in disease presence between populations highlights the importance of conducting appropriate surveys of native crayfish prior to movement of animals to refugia sites for relocation, restocking or breeding programmes.


A longitudinal faculty development program: supporting a culture of teaching.
Recent trends in faculty development demonstrate a shift from short term to long-term programs; formal to informal learning in the workplace; individual to group settings; and from individual support to institutional support. The purpose of this study was to develop and evaluate a one-year Clinical Teaching Fellowship (CTF) program designed to equip early career medical practitioners and basic scientists with necessary skills to facilitate Team-based learning (TBL). The CTF program provided formal training, a choice of informal professional development activities, and practical co-teaching opportunities in TBL. Of the 40 registrants, 31 (78%) completed the program. Data were collected via questionnaire and focus group. Data were analysed using descriptive statistics and framework analysis. Participants considered the CTF program as relevant to their needs and useful to their career. Learning was enriched through the combination of training, practical teaching experience alongside senior clinical teachers, the multi-disciplinary context of training and co-teaching in TBLs; and the sense of community. Competing clinical responsibilities made it difficult to attend training and TBL teaching. The CTF program provided a longitudinal faculty development framework promoting preparation, practice and development of teaching skills. Securing institutional support to invest in the growth and development of early career teachers is essential to sustained innovation and excellence in teaching.


[Registration and cost estimation of clinical and outpatient activities of patients with HIV infection].
The implications of AIDS for health care are unknown. Precise data about the extent to which patients appeal to hospital health care facilities and resulting costs are not available, mainly due to the absence of suitable methods for the registration of demographic, medical and financial data on individual patients in hospitals. In this paper we present the preliminary results of application of a new system which allows such a detailed collection and analysis of data. By evaluating patients with HIV infections treated in the University Hospital Utrecht between January 1, 1987 and July 1, 1988, the mean yearly costs of in- and outpatient treatment of a patient with AIDS (CDC-IV) were found to be Dfl. 40,267.-; those of treatment of patients with other HIV infections ranged from Dfl. 3,629.-(CDC-III) to Dfl. 5,115.-(CDC-II). Comparison of the mean costs for patients who died in that period with those for patients who did not, reveals that patients dead of AIDS would have cost Dfl. 75,289.-yearly and those with AIDS who were alive at July 1, 1988 Dfl. 27,308.-.


Transitioning to Adulthood from Foster Care.
Transitional age foster youth do not typically receive the types of family supports their nonfoster peers enjoy. Many foster youth experience multiple adversities and often fare worse than nonfoster peers on long-term functional outcomes. Governments increasingly recognize their responsibility to act as parents for state dependents transitioning to adulthood and the need to provide services to address social/emotional supports, living skills, finances, housing, education, employment, and physical and mental health. More research is needed to inform the development of effective programs. Transitional age foster youth benefit from policies promoting a developmentally appropriate, comprehensive, and integrated transition system of care.


Effect of GnRH down-regulation on cumulus cell viability and apoptosis as measured by fluorescence-activated cell sorting.
To determine whether gonadotropin releasing hormone (GnRH)-agonist or -antagonist induces higher percentages of cumulus cell apoptosis and if the use of either is detrimental to ART outcomes. Women in a private facility under treatment for IVF had their cumulus cells isolated and analyzed by flow cytometry. Viable, apoptotic, and dead cumulus cell rates related to ovarian stimulation by GnRH-agonist or -antagonist were measured and compared with fertilization and implantation rates. Treatment with GnRH-agonist produced a greater number of follicles than treatment with GnRH-antagonist. No differences in implantation and pregnancy rates were found. While cumulus cell (CC) apoptosis was positively correlated with estradiol on the day of hCG administration, no significant difference in the percentage of apoptotic cells between treatments was detectable. Additionally, implantation rate and the average follicular estradiol production on the day of hCG administration were no different between treatments. GnRH-agonist or -antagonist treatment protocols induce similar levels of apoptosis in CCs and are not detrimental to ART outcomes.


A morphological study of the effect of the Cavitron ultrasonic surgical aspirator system near human peripheral nerves.
The Cavitron ultrasonic surgical aspirator system was used to clear superficial tissue from the greater auricular nerve in four human subjects. Following stimulation, the nerves were removed together with an untreated section and processed for examination by light microscopy. Significant damage had been sustained by these nerves, which was not apparent in the control sections. Disruption of the perineurium, intraneural hemorrhage, endoneural edema, and degenerative changes of the myelinated nerve fibers were seen. Damage to neural tissue was evident 0.5 to 1.5 mm in advance of the point of contact with the cutting tip.


Effect of Indocyanine Green Fluorescence Angiography on Anastomotic Leakage in Patients Undergoing Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials and Propensity-Score-Matched Studies.
Meta-analyses have demonstrated that indocyanine green (ICG) can effectively prevent anastomotic leakage (AL) after colorectal surgery. However, recent evidence from large randomized controlled trial (RCT) has suggested that ICG fluorescence angiography does not reduce the incidence of AL in colorectal surgery. This study was conducted to evaluate the value of ICG for the prevention of AL following colorectal surgery. Up to September 16, 2021, PubMed, Embase, China National Knowledge Infrastructure, Web of Science, Scopus, Cochrane Library, and VIP databases were searched for RCTs and propensity-score matched (PSM) studies evaluating the use of ICG for prevention of AL after colorectal surgery. Mean differences (MDs) or odds ratios (ORs) and 95% confidence intervals (CI) were calculated. Twenty studies (5 RCTs and 15 PSM studies) with a total of 5,125 patients were included. ICG did not reduce the reoperation rate (OR, 0.71; 95% CI, 0.38, 1.30), conversion rates (OR, 1.34; 95% CI, 0.65, 2.78), or mortality (OR, 0.50; 95% CI, 0.13, 1.85), but ICG did reduce the incidence of AL (OR, 0.46; 95% CI, 0.36, 0.59) and symptomatic AL (OR, 0.48; 95% CI, 0.33, 0.71), and reduced the length of hospital stay (MD,-1.21; 95% CI,-2.06,-0.35) and intraoperative blood loss (MD,-9.13; 95% CI,-17.52,-0.74). In addition, ICG use did not increase the incidence of total postoperative complications (OR, 0.93; 95% CI, 0.64, 1.35), postoperative ileus (OR, 1.26; 95% CI, 0.53, 2.97), wound infection (OR, 0.76; 95% CI, 0.44, 1.32), urinary tract infection (OR, 0.87; 95% CI, 0.30, 2.59), pulmonary infection (OR, 0.23; 95% CI, 0.04, 1.45), urinary retention (OR, 1.08; 95% CI, 0.23, 5.04), anastomotic bleeding (OR, 1.53; 95% CI, 0.27, 8.60), anastomotic stricture (OR, 0.74; 95% CI, 0.24, 2.29), or operative time (MD,-9.64; 95% CI,-20.28, 1.01). ICG can effectively reduce the incidence of AL, without prolonging the operation time or increasing postoperative complications in colorectal surgery. www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021279064.


Metazoans evolved by taking domains from soluble proteins to expand intercellular communication network.
A central question in animal evolution is how multicellular animals evolved from unicellular ancestors. We hypothesize that membrane proteins must be key players in the development of multicellularity because they are well positioned to form the cell-cell contacts and to provide the intercellular communication required for the creation of complex organisms. Here we find that a major mechanism for the necessary increase in membrane protein complexity in the transition from non-metazoan to metazoan life was the new incorporation of domains from soluble proteins. The membrane proteins that have incorporated soluble domains in metazoans are enriched in many of the functions unique to multicellular organisms such as cell-cell adhesion, signaling, immune defense and developmental processes. They also show enhanced protein-protein interaction (PPI) network complexity and centrality, suggesting an important role in the cellular diversification found in complex organisms. Our results expose an evolutionary mechanism that contributed to the development of higher life forms.


beta-Carboline binding to deoxycholate solubilized benzodiazepine receptors from calf cerebral cortex.
The beta-carbolines harmane and norharmane competitively inhibit [3H]flunitrazepam ([3H]FNZ) binding to deoxycholate-solubilized benzodiazepine receptors from calf cerebral cortex, with Ki in the micromolar range [3H]Propyl-beta-carboline-3-carboxylate ([3H]PrCC) binds to the soluble receptors with an affinity similar to its binding to particulate receptors (0.41 nM vs 0.48 nM, respectively). The component that binds [3H]PrCC displays a sedimentation profile on sucrose gradient centrifugation similar to that of [3H]FNZ binding component (sedimentation coefficient about 11S).


A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis.
To compare the genetic regulation of collagen-induced arthritis (CIA) with that of pristane-induced arthritis (PIA) in rats. A genome-wide linkage analysis of an (E3 x DA)DA backcross of rats with CIA (n = 364 male rats; the same strain combinations as previously used to determine the genetic control of PIA) was performed. The strongest loci in both CIA and PIA (i.e., Cia12/Pia4 and Cia13/Pia7) were isolated in congenic strains. Susceptibility in both congenic strains was tested in rats with CIA and in rats with PIA. We found a striking, although not complete, similarity of the arthritis-controlling loci in CIA and in PIA, as well as the previously defined loci associated with cartilage destruction, antibody production, and the acute-phase response. All major PIA quantitative trait loci (QTLs) identified in early severe arthritis were also strong regulators of CIA. The 2 strongest QTLs, Cia12/Pia4 on chromosome 12 and Cia13/Pia7 on chromosome 4, were also analyzed in congenic strains with DA or E3 as the background genome. Consistent with the results of linkage analysis, the congenic strain experiments showed that the chromosome 4 locus was more penetrant in CIA than in PIA, while the chromosome 12 locus almost completely dominated the control of PIA severity. The underlying genetic control of CIA was found to have many, but not all, pathogenic mechanisms in common with PIA, despite the use of a cartilage-specific antigen (type II collagen) to induce CIA but not PIA.


Endocrine complications after solid-organ transplant in cystic fibrosis.
In individuals with cystic fibrosis (CF), severe pulmonary or liver disease is frequently addressed with lung or liver transplant, respectively. Specific endocrine co-morbidities including diabetes mellitus, osteoporosis, and adrenal insufficiency accompany solid organ transplant and may be particularly problematic in individuals with CF, who are already at increased risk of diabetes and compromised bone health. Diabetes and osteoporosis screening and initiation of appropriate preventive measures are recommended prior to transplant. We review the existing data to provide practitioners with guidance regarding management of these endocrine conditions post-transplant. Further studies are needed to establish appropriate screening strategies and treatment regimens for endocrine complications of solid organ transplant in patients with CF.


The regulation of hypoxanthine guanine phosphoribosyl transferase activity through transfer of PRPP by metabolic cooperation.
We have developed a method of relating changes in hypoxanthine guanine phosphoribosyl transferase (HGPRTase) activity to the rate of phosphoribosyl pyrophosphate (PRPP) synthesis in isolated cell lines and in co-cultures of different cell lines. Using this approach, we have determined the response of the HGPRTase activity of communication-competent and communication-incompetent cells to changes in PRPP content. The HGPRTase activity of HGPRT+ communication-competent NS cells responds to changes of their own PRPP level, as well as to changes of the PRPP level of HGPRT- cells with which they are co-cultured. In contrast, the HGPRTase activity of the HGPRT+, but communication-incompetent L929 cells responds to changes of their own PRPP content but not to changes of the PRPP content of the cocultured HGPRT- cells. These and other experiments show that PRPP is freely exchangeable between communication-competent cells and that the intracellular activity of HGPRTase in one cell can be regulated by changes in the levels of its substrate in another cell through metabolic cooperation. The results also indicate that HGPRTase normally functions at a small fraction of its total activity, and that this can be greatly increased by raising the intracellular PRPP levels. Furthermore, it is found that when communication-competent cells establish intercellular communication, they share a common pool of PRPP and of purine nucleotides. This approach can be used as the basis of a biochemical method for the quantitation of metabolic cooperation between cells.


Persistent proliferation of normal hepatocytes and promotion of preneoplastic development by N-nitrosodibenzylamine in rats.
In a traditional long-term study N-nitrosodibenzylamine (NDBzA) was proven to be noncarcinogenic, but recently the substance was found to produce genotoxic lesions in hepatocytes. Our own experiments have shown that relatively low single doses of NDBzA cause liver hypertrophy and additive proliferation of hepatocytes in rats. Both effects are known from well-documented promoters and non-genotoxic carcinogens, respectively, in rodents. Investigation of NDBzA in an initiation-promotion assay (IP assay) showed it to cause an increase in the number and size of preneoplastic liver cell foci. This occurred only after initiation with diethylnitrosamine, but not when 2-acetylaminofluorene was used. Another property of NDBzA is its sustained mitotic stimulation of extrafocal hepatocytes. This is inconsistent with their adaptive loss of susceptibility to mitogens in IP assays using other promoters of hepatocarcinogenesis. The following conclusions can be drawn. First, "differential inhibition" of the proliferation of extrafocal hepatocytes, in contrast to the selective mitostimulation of preneoplastic cells, is obviously no prerequisite for cancer development. Second, primary mitogenicity of a compound in short-term studies can be a useful indicator for tumorigenic potential. In the case of NDBzA the data available at present are still insufficient to classify it unequivocally in terms of genotoxic or nongenotoxic carcinogenicity.


The pattern of cervical penetration and the effect of topical treatment with prostaglandin and/or FSH and oxytocin on the depth of cervical penetration in the ewe during the peri-ovulatory period.
Artificial insemination in sheep has two major limiting factors: the poor quality of frozen-thawed ram semen and the convoluted anatomy of the sheep cervix that does not allow transcervical passage of an inseminating catheter. It has been demonstrated that in the ewe during estrus, there is a degree of cervical relaxation mediated by ovarian and possibly gonadotrohic hormones, and we set out to investigate factors that might enhance cervical relaxation. Five experiments were conducted on ewes of different breeds to determine: 1) the pattern of cervical penetration during the periovulatory period in ewes of several breeds (Welsh Mountain, Île-de-France, Vendéenne, Romanov and Sarda); 2) the effect of the "ram effect" a socio-sexual stimulus, on cervical penetration; and 3) the effects of the intracervical administration of follicle-stimulating hormone (FSH), oxytocin and a prostaglandin E agonist (misoprostol) on the depth of cervical penetration during the periovulatory period. The results showed that during the periovulatory period in all breeds examined, there was increased penetration of the cervical canal (P<0.05) by an inseminating catheter. Cervical penetration increased to a maximum 54 h after the removal of progestagen sponges and then gradually declined. Furthermore, the depth of cervical penetration but not its pattern, was affected (P<0.05) by the breed of ewe. The maximum depth of cervical penetration was lower (P<0.05) in the Vendéenne breed compared to the Île-de-France and Romanov breeds, which did not differ from one another. In the presence of rams, the depth of cervical penetration was increased at 48 and 54 h after removal of sponges (P<0.05) and reduced at 72 h (P<0.05). The local administration of hormones FSH, misoprostol (a PGE agonist) and oxytocin alone and in various combinations did not have any significant effect on the depth of cervical penetration during the periovulatory period. In conclusion, the natural relaxation of the cervix observed in ewes of several breeds occurs at a time during estrus, 54 h after the removal of progestagen sponges, which is the most suitable for artificial insemination. The effect was enhanced by the presence of a ram but not by the local intracervical administration of FSH, misoprostol and oxytocin even though oxytocin and PGE2 are involved in cervical function. The time of maximum cervical penetration in the preovulatory period (54 h) coincides with high LH and estradiol concentrations suggesting they might be responsible for the relaxation of the cervix probably through an oxytocin-PGE mediated pathway.


Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events.
While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/μL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/μL, a CD8 count ≥1500 cells/μL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/μL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.


Predicting the hand, foot, and mouth disease incidence using search engine query data and climate variables: an ecological study in Guangdong, China.
Hand, foot, and mouth disease (HFMD) has caused a substantial burden in China, especially in Guangdong Province. Based on the enhanced surveillance system, we aimed to explore whether the addition of temperate and search engine query data improves the risk prediction of HFMD. Ecological study. Information on the confirmed cases of HFMD, climate parameters and search engine query logs was collected. A total of 1.36 million HFMD cases were identified from the surveillance system during 2011-2014. Analyses were conducted at aggregate level and no confidential information was involved. A seasonal autoregressive integrated moving average (ARIMA) model with external variables (ARIMAX) was used to predict the HFMD incidence from 2011 to 2014, taking into account temperature and search engine query data (Baidu Index, BDI). Statistics of goodness-of-fit and precision of prediction were used to compare models (1) based on surveillance data only, and with the addition of (2) temperature, (3) BDI, and (4) both temperature and BDI. A high correlation between HFMD incidence and BDI (r=0.794, p<0.001) or temperature (r=0.657, p<0.001) was observed using both time series plot and correlation matrix. A linear effect of BDI (without lag) and non-linear effect of temperature (1 week lag) on HFMD incidence were found in a distributed lag non-linear model. Compared with the model based on surveillance data only, the ARIMAX model including BDI reached the best goodness-of-fit with an Akaike information criterion (AIC) value of -345.332, whereas the model including both BDI and temperature had the most accurate prediction in terms of the mean absolute percentage error (MAPE) of 101.745%. An ARIMAX model incorporating search engine query data significantly improved the prediction of HFMD. Further studies are warranted to examine whether including search engine query data also improves the prediction of other infectious diseases in other settings.


Automated measurement of spatial preference in the open field test with transmitted lighting.
New modification of the open field was designed to improve automation of the test. The main innovations were: (1) transmitted lighting and (2) estimation of probability to find pixels associated with an animal in the selected region of arena as an objective index of spatial preference. Transmitted (inverted) lighting significantly ameliorated the contrast between an animal and arena and allowed to track white animals with similar efficacy as colored ones. Probability as a measure of preference of selected region was mathematically proved and experimentally verified. A good correlation between probability and classic indices of spatial preference (number of region entries and time spent therein) was shown. The algorithm of calculation of probability to find pixels associated with an animal in the selected region was implemented in the EthoStudio software. Significant interstrain differences in locomotion and the central zone preference (index of anxiety) were shown using the inverted lighting and the EthoStudio software in mice of six inbred strains. The effects of arena shape (circle or square) and a novel object presence in the center of arena on the open field behavior in mice were studied.


Roles of Bacillus endospores in the environment.
The occurrence and diverse roles of Bacillus spp. and their endospores in the environment is reviewed, with particular emphasis on soil ecology, host-symbiont and host-parasite interactions, and human exploitation of spores as biological control agents and probiotics.


A severe case of myopotential interference in a patient with a respiratory-dependent rate modulated pacemaker.
Symptomatic myopotential interference was observed in a patient with a respiratory-dependent rate modulated pacemaker (RDP3). During treadmill exercise, prolonged interference suspended the rate responsive function and resulted in reversion to the interference mode with the pacing rate falling back to the basic frequency during the interference. This loss of rate response resulted in severe impairment of exercise tolerance and reduction in cardiac output during exercise. The unit was replaced with a bipolar activity sensing rate modulated pacemaker.


Evolution and structure of research fields driven by crises and environmental threats: the COVID-19 research.
Evolution of science and behavior of new research fields emerging under conditions of crisis are new topics hardly known in social studies of science and scientometrics. In particular, the ecosystem and dynamics of research fields during crisis are vital aspects for explaining and planning the scientific development, and allocating resources efficaciously toward positive societal impact. This study here endeavors to analyze the evolution and structure of COVID-19 (Coronavirus Disease 2019) research, a new research field emerged and driven by a global pandemic crisis. The dynamics and structure of this research field are compared to related fields concerning respiratory disorders that are not guided by pandemic crisis, such as chronic obstructive pulmonary disease and lung cancer, to explain similarities and differences. Results suggest that a crisis-driven research field is characterized by an unparalleled velocity of scientific production equal to about 1.2% daily, based on notes and short papers mainly open access that support scientific advances and discoveries in research arena over a short period of time, such as the development of innovative drugs given by novel vaccines and new antiviral COVID-19 treatments. Findings are generalized in properties that clarify the evolution and structure of new research fields and their research behavior in a period of crisis for guiding decisions of policymakers to support scientific and technological progress in human society in the presence of environmental threats.


Biodegradation of di-n-butyl phthalate by an isolated Gordonia sp. strain QH-11: Genetic identification and degradation kinetics.
Di-n-butyl phthalate (DBP) is one of the most widely used phthalic acid esters (PAEs), which have shown increasing environmental concerns worldwide. A bacterial strain designated as QH-11, was isolated from activated sludge and found to be capable of utilizing DBP as carbon and energy sources for growth. 16S rRNA and gyrb gene sequence analysis revealed that strain QH-11 was most closely related to Gordonia sp. Kinetics studies of DBP degradation by the strain QH-11 revealed that DBP depletion curves fit with the modified Gompertz model (R(2)>0.98). Meanwhile, substrate utilization tests showed that strain QH-11 could utilize other common PAEs and also the main intermediate product phthalic acid (PA). A gene encoding the large subunit of the phthalate dioxygenase, which is responsible for PA degradation, was successfully detected in strain QH-11. Furthermore, the results of reverse transcription quantitative PCR demonstrate that mRNA expression level of phthalate dioxygenase increased significantly after strain QH-11 was induced by DBP and PA.


Changes in Blood Profile from Steady State in Patients with Sickle Cell Anemia Admitted for Vaso-occlusive Crisis and Acute Chest Syndrome.
Close to half of all patients with sickle cell disease (SCD) will have at least one episode of acute chest syndrome (ACS) during their lifetime. Multiple cells and molecules involved with the inflammatory cascade play a role in the development of ACS. We found that patients with SCD who developed ACS as a complication of a vaso-occlusive crisis (VOC) had a significant increase in leukocytes and decrease in platelets from their steady state when compared with a separate admission for VOC without ACS development. No significant change from steady state hemoglobin or reticulocyte count was noted between the two admissions. These results indicate that trending laboratory markers may be useful to predict patients at risk for ACS development.


Rhodium-catalysed hydroacylation or reductive aldol reactions: a ligand dependent switch of reactivity.
The pathway for the combination of enones and beta-S-substituted aldehydes using Rh-catalysis can be switched between a hydroacylation reaction or a reductive aldol reaction by simple choice of the phosphine ligand; this catalyst controlled switch allows access to new ketone hydroacylation products; useful 1,4-diketone intermediates for the synthesis of N-, S- and O-heterocycles.


Photoinductive activity of humic acid fractions with the presence of Fe(III): the role of aromaticity and oxygen groups involved in fractions.
Relationship between the photoinductive activity and the properties of humic acids (HA) fractions were investigated with and without Fe(III). Three fractions were separated based on the molecular weight (M(w)) and were obtained following the order of M(w): F(A)>F(B)>F(C). Compared to F(A) and F(B), photodegradation of atrazine under simulated sunlight was much faster in solution containing F(C), whose structure was dominated by greater aromaticity, more oxygen groups and fluorophores. The interaction of HA fractions and Fe(III) was studied using fluorescence spectrometry and F(C) had the largest quenching constant. The capacity of electron transfer, estimated from the amount of photoformed Fe(II), was also highest for F(C). Thus, the Fe(III)-F(C) complex was efficient in phototransformation of atrazine in nearly neutral aqueous solutions. These results suggest that the aromaticity and oxygen groups content of HA exert great influence on the binding ability of metals and on the fate of pollutants in natural waters.


Hybrid lamellar silica: combined template extraction and hydrophilic silanation.
The surface modification of lamellar silica prepared by liquid crystal templating has been investigated. Two hydrophilic surface modifier agents, 2-glycidoxypropyltrimethoxysilane and 2-[methoxy(polyethyleneoxy)propyl)]trimethoxysilane, have been tested. Characterizations of the modified silica include thermal analysis, (13)C and (29)Si solid state NMR, transmission electron microscopy (TEM) and X-ray diffraction (XRD). The different characterizations confirmed the preservation of the lamellar morphology and the successful surface modification with both silanes along with the template elimination. The results also indicate that the structure and length of the silanes influence the final lamellar organization as well as the grafting yields and mechanisms.


Glioblastoma models driven by different mutations converge to the proneural subtype.
The need of reliable syngeneic animal models for gliomas has been addressed in the last decades by reproducing genetic alterations typical of human glioblastoma in the mouse. Since different alterations underlie different molecular glioblastoma subtypes it is commonly expected that tumors induced by specific alterations represent models of the corresponding subtypes. We tested this assumption by a multilevel analysis ranging from a detailed histopathological analysis to a genome-wide expression profiling by microarray and RNA-seq on gliomas induced by two distinct molecular alterations: the overstimulation of the PDGF- and the EGF- pathways. These alterations are landmarks of proneural and classical glioblastoma subtypes respectively. However, our results consistently showed a strong similarity between the two glioma models. The expression profiles of both models converged toward a signature typical of oligodendrocyte progenitor cells, regardless the wide differentiative potential of the cell of origin. A classification based on similarity with human gliomas profiles revealed that both models belong to the proneural subtype. Our results highlight that reproducing a molecular alteration specific of a glioblastoma subtype not necessarily generates a tumor model recapitulating such subtype.


Complete 1H and 13C NMR spectral assignment of N-aralkylsulfonamides, N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and N-sulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepines. Conformational analysis of N-[((3',4'-dichlorophenyl)methyl)sulfonyl]-3-methyl-2,3,4,5-tetrahydro-1H-2-benzazepin.
The complete and unambiguous assignment of the 1H NMR and 13C NMR spectra of 26 N-aralkylsulfonamides, N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and N-sulfonylbenz[c]azepines was performed on the basis of APT, DEPT, homonuclear (gs-COSY) and 1H-detected heteronuclear one-bond (gs-HMQC) and long-range (gs-HMBC) correlation experiments. The methylated 2,3,4,5-tetrahydro-1H-2-benzazepine derivative 26 adopts a chair conformation as determined by 1H-1H coupling analysis and gamma-gauche effects. This is supported by a single-crystal X-ray structure analysis.


[Ovarian torsion during the postpartum period: about a case].
Ovarian torsion is a rare cause of pelvic pain during the postpartum period. The absence of specific clinical and radiological signs makes suspicion and preoperative diagnosis difficult. Delayed management can compromise ovarian viability. We report the case of a 24-year patient presenting to the Emergency Department five days after delivery with severe pelvic pain. The diagnosis of ovarian torsion associated with cystic mass was made on the basis of ultrasound images. The patients underwent cystectomy and a conservative treatment.


Early life indicators of first lactation milk yield and the effect of treatment for bovine respiratory disease on survivability and risk of pregnancy in Holstein dairy cattle.
The primary objective of this study was to evaluate the long-term effects of variables that could be measured early in life on first lactation milk production. The secondary objective was to evaluate the long-term effects of treatment for bovine respiratory disease (BRD), within the first 120 days of life, on survivability to 850 days and reproductive success. Data from Holstein heifer calves was collected from 1 October, 2015-31 January, 2020 and included milk consumption (MC; n = 10,431), bodyweight (BW; n = 9,825), average daily gain (ADG; n = 6,194), heifer conception age (n = 10,112), and 305-day first lactation milk production (305 M; n = 5,823), and treatment records for BRD (n = 12,485). Calves were fed pasteurized whole milk through an automated calf feeding system for 60 days (range, 48 - 126 days), with a 30% crude protein (CP) and 5% crude fat enhancer added at 20 g/L milk. Calves were weighed at birth, weaning, and several other times prior to 2 years of age. Daily BW were predicted for individual animals using a third order orthogonal polynomial to model individual BW regressions. Daily BW predictions were used to calculate ADG and BW predictions on specific days of interest. Season born, ADG (0-400 days), milk production potential, and heifer conception age had a significant impact on 305-day first lactation milk production (all P ≤ 0.05; r2 = 0.31). A retrospective cohort study was conducted utilizing data collected from a commercial farm with cohorts defined by BRD status. Calves treated for BRD from 61 to 120 days old had a significantly lower chance of survival to 850 days of age than animals not treated for BRD. Additionally, calves treated for BRD from 61 to 120 days old had reduced risk of pregnancy. The results show the impact of early life on future milk production, survivability, and pregnancy risk on a commercial dairy herd.


Sports Medicine Considerations When Caring for the Transgender Athlete.
Orthopaedic surgeons and other orthopaedic care providers have expressed a desire to care for transgender patients but have a self-perceived knowledge deficit. Transgender athletes experience many psychosocial barriers to sport that are useful for clinicians to understand. Medical and surgical gender-affirming care can impact musculoskeletal physiology and pathophysiology. Transgender women (TW) have demonstrated an increased risk of insufficiency fractures and thromboembolism in patients receiving exogenous estrogen therapy. The impact of gender-affirming care on sex-based differences in athletic injuries is less well studied.


In situ hybridization with digoxigenin-labelled DNA probes for the detection of human papillomavirus-induced focal epithelial hyperplasia among Venezuelans.
An in situ hybridization assay with digoxigenin-labelled probes was used to detect the presence of human papillomavirus (HPV) sequences in ten related Venezuelan patients with the diagnosis of focal epithelial hyperplasia. The samples displayed HPV sequences in all cases. Further restriction analysis in four of the patients suggested the presence of HPV-13 in oral lesions.


The social ecology of anxiety. Theoretical and quantitative perspectives.
Experience sampling is a relatively new research approach that captures relevant variations in experience and symptoms in the course of everyday life. In this paper, a socioecological frame of reference that integrates psychological, historical, cultural, and developmental theories about anxiety phenomena will be illustrated using quantitative descriptions of anxiety and avoidance behaviors gathered with the Experience-Sampling Method. The interaction between anxiety symptoms and the environment in which they occurred is explored in a case study that points to possibilities for future research and the establishment of therapeutic approaches that are optimally suited to the individual patient.


Spatial and seasonal variation and sources of deposition fluxes of polycyclic aromatic hydrocarbons (PAHs) in Shanghai.
Spatial and temporal variations of polycyclic aromatic hydrocarbons (PAHs) deposition fluxes and sources may significantly facilitate risk evaluation and pollution control of super megacity in China. A study on PAHs of wet and dry deposition in Shanghai was conducted from January to December of 2019. Seventeen sampling sites located in four functional areas were set, including the Baoshan iron and steel industry area (BS), Jinshan petrochemical industry area (JS), city center (CC), and Chongming agricultural area (CM). A total of 15 PAHs were determined by gas chromatography-mass spectrometry (GC-MS, Agilent 7890A/5975C). PAHs atmospheric deposition flux in winter was highest (3.12 ± 1.98 μg/(m2·day), mostly attributed to local emissions accumulation under adverse meteorological diffusion conditions, as well as pollutants transport from northern China during heating season. PAHs deposition fluxes in industrial area (BS and JS) were 3.75 ± 4.08 μg/(m2·day) and 3.18 ± 3.62 μg/(m2·day) respectively, which were greater than those in CC and CM, accounting for 1.91 ± 1.06 μg/(m2·day) and 1.41 ± 0.61 μg/(m2·day) respectively. Proportional composition and isomer ratios of PAHs indicated that the PAHs deposition in winter and spring samples were more homogeneous, whereas those of summer and autumn seemed to be more variable and dispersed. Positive matrix factorization model were employed to identify the potential sources of PAHs in specific functional areas. A dominance of contribution was attributed to coal combustion (46%) at BS, petroleum volatilization (48%) at JS, biomass burning (55%) at CM, and vehicle emission (49%) at CC. This study highlighted that local urbanization and industrialization have a significant contribution to PAHs deposition to specific functional regions in Shanghai.


Parallel comparison of grip strength measures obtained with a MicroFET 4 and a Jamar dynamometer.
Repeated measures of grip strength obtained bilaterally with a Jamar and a MicroFET 4 dynamometer were compared. Measurements obtained with the MicroFET 4 tended to be slightly (2.2-3.1 lb.) higher but were highly correlated (r > or = .96) with those obtained with the Jamar. Parallel reliability for the two devices was excellent (intraclass correlation coefficient > or = .96). Although clinicians should be cautious about using the devices interchangeably, the MicroFET 4 appears to be a legitimate alternative to the Jamar dynamometer.


Heightened fearfulness as a developmental adaptation.
Although we find many merits to Grossmann's fearful ape hypothesis, unlike Grossmann, we see heightened fearfulness as an ontogenetic adaptation, signaling helplessness and fostering caregiving during infancy, which subsequently became exapted to promote cooperation. We also argue that, rather than being the "breeding ground" for enhanced infant fearfulness, cooperative care is more likely the evolved product of enhanced fearfulness.


Immunohistochemical analysis of the impact of ischemic change in benign prostatic hyperplasia.
We conducted experiments to elucidate the impact of ischemic change on benign prostatic hyperplasia (BPH) using immunohistochemistry. Medical records of consecutive patients over 60 years of age who underwent transurethral resection of the prostate for BPH between January 2009 and September 2012 were evaluated. As vascular risk factors, the presence or absence of diabetes mellitus, hypertension, current smoking, obesity, dyslipidemia, and diseases related to bladder function were investigated. As BPH-related factors, International Prostate Symptom Score, quality of life, maximal flow rate, postvoid residual volume, prostate-specific antigen, prostate volume, prostate calculi, and medication state for BPH were investigated. Immunohistochemistry was performed for hypoxia-inducible factor (HIF-1α), sex hormone receptors, and smooth muscle actin. Additionally, microvessel density (MVD) and diffuse fibrosis (DF) were evaluated. A total of 101 patients were included and HIF-1α expression in stroma and glands were observed in 56 (55.4%) and 34 (33.7%) cases, respectively. There was no significant association between HIF-1α expression and vascular risk factors or BPH-related variables. However, there was a significant correlation between the HIF-1α expression in stroma and higher MVD. HIF-1α expression in the stroma was also significantly correlated with higher expressions of the androgen and progesterone receptors in the stroma. DF was frequently found in cases with higher HIF-1α expression in the stroma than in those with lower HIF-1α expression. In patients with response to ischemic changes of the prostate, HIF-1α expression could be confirmed, and the expression of the androgen receptor was significantly lower in these patients. Chronic ischemic damage in the prostate can progress to a condition that is refractory to pharmacologic therapy. Chronic ischemic damage, which can progress to refractory phase to pharmacologic therapy, is correlated with the hormonal status of prostate.


Controlled Heterotypic Pseudo-Islet Assembly of Human β-Cells and Human Umbilical Vein Endothelial Cells Using Magnetic Levitation.
β-Cell functionality and survival are highly dependent on the cells' microenvironment and cell-cell interactions. Since the pancreas is a highly vascularized organ, the crosstalk between β-cells and endothelial cells (ECs) is vital to ensure proper function. To understand the interaction of pancreatic β-cells with vascular ECs, we sought to investigate the impact of the spatial distribution on the interaction of human cell line-based β-cells (EndoC-βH3) and human umbilical vein endothelial cells (HUVECs). We focused on the evaluation of three major spatial distributions, which can be found within human islets in vivo, in tissue-engineered heterotypic cell spheroids, so-called pseudo-islets, by controlling the aggregation process using magnetic levitation. We report that heterotypic spheroids formed by spontaneous aggregation cannot be maintained in culture due to HUVEC disassembly over time. In contrast, magnetic levitation allows the formation of stable heterotypic spheroids with defined spatial distribution and significantly facilitated HUVEC integration. To the best of our knowledge, this is the first study that introduces a human-only cell line-based in vitro test system composed of a coculture of β-cells and ECs with a successful stimulation of β-cell secretory function monitored by a glucose-stimulated insulin secretion assays. In addition, we systematically investigate the impact of the spatial distribution on cocultures of human β-cells and ECs, showing that the architecture of pseudo-islets significantly affects β-cell functionality. Impact statement Tissue engineering of coculture systems containing β-cells and endothelial cells (ECs) is a promising technique to stimulate β-cell functionality. In this study, we analyzed human pancreatic islet tissue and revealed three different native distributions of β-cells and ECs. We successfully recreated these distributions in vitro by employing magnetic levitation of human β-cells and ECs, forming controlled heterotypic pseudo-islets, which enabled us to identify a significant impact of the pseudo-islet architecture on insulin secretion.


Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer.
Enhancer of zeste homolog 2 (EZH2) is the histone lysine N-methyltransferase component of the Polycomb repressive complex 2 (PRC2), which, in conjunction with embryonic ectoderm development (EED) and suppressor of zeste 12 homolog, regulates cell lineage determination and homeostasis. Enzymatic hyperactivity has been linked to aberrant repression of tumor suppressor genes in diverse cancers. Here, we report the development of stabilized α-helix of EZH2 (SAH-EZH2) peptides that selectively inhibit H3 Lys27 trimethylation by dose-responsively disrupting the EZH2-EED complex and reducing EZH2 protein levels, a mechanism distinct from that reported for small-molecule EZH2 inhibitors targeting the enzyme catalytic domain. MLL-AF9 leukemia cells, which are dependent on PRC2, undergo growth arrest and monocyte-macrophage differentiation upon treatment with SAH-EZH2, consistent with observed changes in expression of PRC2-regulated, lineage-specific marker genes. Thus, by dissociating the EZH2-EED complex, we pharmacologically modulate an epigenetic 'writer' and suppress PRC2-dependent cancer cell growth.


Two jasmonate-responsive factors, TcERF12 and TcERF15, respectively act as repressor and activator of tasy gene of taxol biosynthesis in Taxus chinensis.
Methyl jasmonate (MeJA) is one of the most effective inducers of taxol biosynthetic genes, particularly the tasy gene. However, the mechanism underlying the regulation of tasy by MeJA is still unknown. In this study, a 550-bp 5'-flanking sequence was obtained and confirmed as the promoter of the tasy gene. Deletion analysis revealed that the fragment containing a GCC-box from -150 to -131 was the crucial jasmonate (JA)-responsive element, designated as JRE. Using JRE as bait, two binding proteins, namely TcERF12 and TcERF15, were discovered. Sequence alignment and phylogenetic analysis showed that TcERF12 was related to the repressor AtERF3, while TcERF15 was more related to the activator ORA59; these are typical GCC-box-binding ethylene-responsive factors. Both could significantly respond to MeJA for 10 and 4.5 times, respectively, in 0.5 h. When the two TcERFs were overexpressed in Taxus cells, tasy gene expression decreased by 2.1 times in TcERF12-overexpressing cells, but increased by 2.5 times in TcERF15-overexpressing cells. Results indicated that TcERF12 and TcERF15 were negative and positive regulators, respectively, in the JA signal transduction to the tasy gene by binding the GCC-box in the JRE of the tasy promoter. Our results promote further research on regulatory mechanisms of taxol biosynthesis.


Micro-punches versus micro-slices for serial sampling of human dentine: Striking a balance between improved temporal resolution and measuring additional isotope systems.
The last decade has seen a dramatic increase in the application of serial sampling of human dentine in archaeology. Rapid development in the field has provided many improvements in the methodology, in terms of both time resolution as well as the ability to integrate more isotope systems in the analysis. This study provides a comparison of two common sampling approaches, allowing researchers to select the most suitable approach for addressing specific research questions. Two common approaches for sequential sampling of human dentine (micro-punches and micro-slices) are compared in terms of viability and efficacy. Using archaeological deciduous second molars and permanent first molars, this study demonstrates how the two approaches capture aspects of the weaning process in different ways. In addition, different aspects related to the extraction protocols, such as the thickness of the central slide and the solubilisation step, are also evaluated. While both approaches show similar intra-tooth isotopic patterns, the micro-punches approach is preferable for research that requires a very fine temporal resolution, while the micro-slices approach is best for research where δ34 S values are needed, or when the samples are poorly preserved. In addition, the solubilisation step has a large effect on collagen yield, and, to a lesser extent, on isotopic compositions. Therefore, it is important to ensure that only samples that have undergone the same pre-treatment protocol are directly compared. We present the pros and cons of the two micro-sampling approaches and offer possible mitigation strategies to address some of the most important issues related to each approach.


Flavonoids suppresses the enhancing effect of beta-carotene on DNA damage induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A549 cells.
This study investigated the individual and combined effects of beta-carotene with a common flavonoid (naringin, quercetin or rutin) on DNA damage induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-related carcinogen in human. A human lung cancer cell line, A549, was pre-incubated with beta-carotene, a flavonoid, or both for 1h followed by incubation with NNK for 4 h. Then, we determined DNA strand breaks and the level of 7-methylguanine (7-mGua), a product of NNK metabolism by cytochrome P450 (CYP). We showed that beta-carotene at 20 microM significantly enhanced NNK-induced DNA strand breaks and 7-mGua levels by 90% (p < 0.05) and 70% (p < 0.05), respectively, and that the effect of beta-carotene was associated with an increased metabolism of NNK by CYP because the concomitant addition of 1-aminobenzotriazole, a CYP inhibitor, with beta-carotene to cells strongly inhibited NNK-induced DNA strand breaks. In contrast to beta-carotene, incubation of cells with naringin, quercetin or rutin added at 23 microM led to significant inhibition of NNK-induced DNA strand breaks, and the effect was in the order of quercetin > naringin > rutin. However, these flavonoids did not significantly affect the level of 7-mGua induced by NNK. Co-incubation of beta-carotene with any of these flavonoids significantly inhibited the enhancing effect of beta-carotene on NNK-induced DNA strand breaks; the effects of flavonoids were dose-dependent and were also in the order of quercetin > naringin > rutin. Co-incubation of beta-carotene with any of these flavonoids also significantly inhibited the loss of beta-carotene incorporated into the cells, and the effects of the flavonoids were also in the order of quercetin > naringin > rutin. The protective effects of these flavonoids may be attributed to their antioxidant activities because they significantly decreased intracellular ROS, and the effects were also in the order of quercetin > naringin > rutin. These in vitro results suggest that a combination of beta-carotene with naringin, rutin, or quercetin may increase the safety of beta-carotene.


Multivariate regression analysis on early mortality after orthotopic liver transplantation.
To identify the risk factors relating to early mortality after orthotopic liver transplantation. Clinical data of 37 adult patients undergoing liver transplantation were retrospectively collected and divided into two groups: the survived group and the death group (survival time<30 d). The relationship between multivariate risk factors and early mortality after orthotopic liver transplantation were analyzed by stepwise logistic regression. The survival rate was 73%. Early mortality rate was 27%. APACAE III, preoperative serum creatinine level and interoperative bleeding quantity had a significant independent association with early mortality. (R=0.1841, 0.2056 and 0.3738). APACHE III,preoperative serum creatinine level and interoperative bleeding quantity are significant risk factors relating to early mortality after orthotopic liver transplantation. To improve the recipient's preoperative critical condition and renal function and to reduce interoperative bleeding quantity could lower the early mortality after orthotopic liver transplantation.


Homoadenosylcobalamins as probes for exploring the active sites of coenzyme B12-dependent diol dehydratase and ethanolamine ammonia-lyase.
[Omega-(Adenosyl)alkyl]cobalamins (homoadenosylcobalamins) are useful analogues of adenosylcobalamin to get information about the distance between Co and C5', which is critical for Co-C bond activation. In order to use them as probes for exploring the active sites of enzymes, the coenzymic properties of homoadenosylcobalamins for diol dehydratase and ethanolamine ammonia-lyase were investigated. The kcat and kcat/Km values for adenosylmethylcobalamin were about 0.27% and 0.15% that for the regular coenzyme with diol dehydratase, respectively. The kcat/kinact value showed that the holoenzyme with this analogue becomes inactivated on average after about 3000 catalytic turnovers, indicating that the probability of inactivation during catalysis is almost 500 times higher than that for the regular holoenzyme. The kcat value for adenosylmethylcobalamin was about 0.13% that of the regular coenzyme for ethanolamine ammonia-lyase, as judged from the initial velocity, but the holoenzyme with this analogue underwent inactivation after on average about 50 catalytic turnovers. This probability of inactivation is 3800 times higher than that for the regular holoenzyme. When estimated from the spectra of reacting holoenzymes, the steady state concentration of cob(II)alamin intermediate from adenosylmethylcobalamin was very low with either diol dehydratase or ethanolamine ammonia-lyase, which is consistent with its extremely low coenzymic activity. In contrast, neither adenosylethylcobalamin nor adeninylpentylcobalamin served as active coenzyme for either enzyme and did not undergo Co-C bond cleavage upon binding to apoenzymes.


Wearable Technology To Reduce Sedentary Behavior And CVD Risk In Older Adults: A Pilot Randomized Clinical Trial.
Physical exercise is associated with decreased cardiovascular disease (CVD) risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk older adults. This pilot randomized clinical trial aimed to collect critical data on feasibility, safety, and protocol integrity necessary to design a fully powered randomized controlled trial (RCT) and evaluate the impact of combining structured exercise with an intervention designed to enhance non-exercise physical activity (EX+NEPA) compared to EX alone. Forty participants aged ≥60 years with moderate-to-high risk of coronary heart disease events were randomly assigned to either the EX+NEPA or EX groups and followed for 20 weeks. Both groups underwent a twice-weekly, 8-week center-based exercise intervention with aerobic and resistance exercises. EX+NEPA group also received a wearable activity tracking device along with behavioral monitoring and feedback throughout the study. Study outcomes were evaluated at 8 and 20 weeks. Data are presented as adjusted mean change of the differences over time with 95% confidence intervals at 20 weeks. Relative to EX, the change in steps/day at 20 weeks was 1994 (-40.27, 4028) higher for EX+NEPA. For sedentary time at close-out, the EX+NEPA group was -6.8 (-45.2, 31.6) min/day relative to EX. The between-group differences for systolic and diastolic blood pressure were -9.9 (-19.6, -0.3) and -1.8 (-6.9, 3.3) mmHg, respectively. The addition of wearable technology intervention appeared to positively influence daily activity patterns and changes in blood pressure - potentially improving risk factors for CVD. A fully powered randomized trial is needed to ultimately test this hypothesis.


Carboxylate polyanions accelerate inhibition of thrombin by heparin cofactor II.
The heparin cofactor II (HCII)/thrombin inhibition reaction is enhanced by various carboxylate polyanions. In the presence of polyaspartic acid, the HCII/thrombin reaction is accelerated more than 1000-fold with the second-order rate constant increasing from 3.2 x 10(4) M-1 min-1 (in the absence of polyAsp) to 3.6 x 10(7) M-1 min-1 as the polyAsp concentration is increased from 1 to 250 micrograms/ml. This accelerating effect was observed for HCII/thrombin, though to varying degrees, with other carboxylate polyanions. In contrast to HCII, the rate of antithrombin III inhibition of thrombin was decreased in the presence of polyAsp. The HCII/thrombin complex is rapidly formed in the presence of 10 micrograms/ml polyAsp when 125I-labeled-thrombin is incubated with plasma. It is possible that at physiological sites rich in carboxylate polyanions, thrombin may be preferentially inhibited by HCII.


Monoclonal antibodies reveal sagittal banding in the rodent cerebellar cortex.
We have produced two monoclonal antibodies against polypeptide-associated antigens of developing rat cerebellum. One antibody recognizes an antigen associated with synaptic vesicles and another binds to a polypeptide which is restricted to the cytoplasm of a subset of cerebellar Purkinje cells. Both antibodies reveal the biochemical differentiation of the rodent cerebellar cortex into antigenically distinct sagittal zones.


Establishment and evolution of a clinical pharmacy mental health hospital-in-the-home service: An autoethnography.
Hospital-in-the-Home (HiTH) services provide "inpatient-style" care for patients at home. While relatively well known in non-psychiatric settings, little is known about mental health (MH)-HiTH services, with even less known about the role of a clinical pharmacist (CP) within a MH-HiTH multidisciplinary team (MDT). The aim of this paper is to describe the evolution of the first MH-HiTH MDT in Western Australia and the various facets of the CP's role integrated within the service. The integration of a CP into a non-traditional practice setting represents a cultural change in the pharmacy profession. Hence, this paper utilised a descriptive-realistic style of the autoethnographic method, with the narrative written in the first-person point of view of the first author (M.F.). It specifically focused on the tasks performed by the team's CP. A narrative analysis approach was used to reflect on the reason these tasks are performed, the potential benefits and limitations of integrating a CP into the team and subsequent cultural influence on the pharmacy profession. The service commenced in 2014, consisting of an MDT of a consultant psychiatrist, a psychiatric registrar, clinical nurses, an occupational therapist, a social worker and a CP. Starting with 4 then 8 "virtual beds", it was gradually increased to 16 virtual beds. The MH-HiTH CP combined hospital clinical tasks - e.g. medication reconciliation and therapeutic drug monitoring - with home medication reviews as part of the MH-HiTH MDT. Lessons learnt include proactively integrating and flexibly adapting into a novel practice setting. There is scope to embed a CP within an MH-HiTH MDT; the major advantage is the inclusion of a comprehensive medication management service. While this is a promising new area where the pharmacy profession is becoming engaged, more studies are needed to quantify and confirm the stated benefits of such service.


A minireview on N-acetylcysteine: An old drug with new approaches.
N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of toxicity-induced by pesticides. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against oxidative stress caused by pesticide in many organs. The possible mechanisms of action may be associated to its antioxidant properties. The anti-oxidative activity of NAC has been attributed to the fast reaction with free radicals as well as the restitution of reduced glutathione (GSH).


Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine.
To monitor immune status during clinical trials and after vaccine registration, several assays have been developed to measure type-specific human papillomavirus (HPV) serum antibody levels. These include neutralization assays, single epitope-based inhibition immunoassays, and direct enzyme-linked immunosorbent assays (ELISAs). Neutralization assays based on multiple epitopes and independent of vaccine material are considered the 'gold standard' for unbiased assessment of the protective potential of vaccine-induced antibodies. However, their use in large clinical trials is challenging. Here, we compare both the direct ELISA and the single epitope-based inhibition ELISA with the pseudovirion-based neutralization assay (PBNA) for HPV-16/18 antibody responses in vaccinated women enrolled in trials of Cervarix, GSK's cervical cancer vaccine. The direct ELISA, which is based on multiple epitopes, was shown to have a higher degree of sensitivity and correlation with the PBNA when compared with the single epitope-based inhibition ELISA. Among double-positive results, high correlations were observed between the PBNA and the direct ELISA (0.70-0.88 for HPV-16 and 0.82-0.94 for HPV-18) and also with the single epitope-based inhibition ELISA (0.60-0.89 for HPV-16 and 0.57-0.96 for HPV-18) in women aged 15-25 years. The correlation persisted up to 6.4 years after primary vaccination. Similar levels of correlation were observed for adolescents aged 10-14 years and women aged 46-55 years. Therefore, the direct ELISA appears to be an excellent surrogate for neutralizing activity and can be used to evaluate antibody response induced by L1 virus-like particle-based cervical cancer vaccines, regardless of time elapsed after vaccination (up to 6.4 years) and the age of the vaccine recipient.