Gonadal transcriptomic analysis and differentially expressed genes in the testis and ovary of the Pacific white shrimp (Litopenaeus vannamei).
The Pacific white shrimp (Litopenaeus vannamei) is the world's most prevalent cultured crustacean species. However, the supply of high-quality broodstocks is limited and baseline information related to its reproductive activity and molecular issues related to gonad development are scarce. In this study, we performed transcriptome sequencing on the gonads of adult male and female L. vannamei to identify sex-related genes. A total of 25.16 gigabases (Gb) of sequences were generated from four L. vannamei gonadal tissue libraries. After quality control, 24.11 Gb of clean reads were selected from the gonadal libraries. De-novo assembly of all the clean reads generated a total of 65,218 unigenes with a mean size of 1021 bp and a N50 of 2000 bp. A search of all-unigene against Nr, SwissProt, KEGG, COG and NT databases resulted in 26,482, 23,062, 20,659, 11,935 and 14,626 annotations, respectively, providing a total of 30,304 annotated unigenes. Among annotated unigenes, 12,320 unigenes were assigned to gene ontology categories and 20,659 unigenes were mapped to 258 KEGG pathways. By comparing the ovary and testis libraries, 19,279 testicular up-regulated and 3,529 ovarian up-regulated unigenes were identified. Enrichment analysis of differentially expressed unigenes resulted in 1060 significantly enriched GO terms and 34 significantly enriched KEGG pathways. Nine ovary-specific, 6 testis-specific, 45 testicular up-regulated and 39 ovarian up-regulated unigenes were then confirmed by semi-quantitative PCR and quantitative real-time PCR. In addition, using all-unigenes as a reference, a total of 13,233 simple sequence repeats (SSRs) were identified in 10,411 unigene sequences. The present study depicts the first large-scale RNA sequencing of shrimp gonads. We have identified many important sex-related functional genes, GO terms and pathways, all of which will facilitate future research into the reproductive biology of shrimp. We expect that the SSRs detected in this study can then be used as genetic markers for germplasm evaluation of breeding and imported populations.


Color Doppler imaging of the eye and orbit.
Since the development of A- and B-scan ultrasound technique in the 1950s, significant progress in ophthalmic ultrasound has appeared. As the technology advances and ultrasound systems improve their ability to acquire and detect ultrasonic signals and to analyze them in terms of a spatial resolution and frequency distribution, there is no doubt that the extent of clinical applications will expand accordingly. Nevertheless, the fundamental physical restrictions of ultrasonography and Doppler will always remain the same. For ophthalmology, we hope that less expensive color Doppler systems with specifically designed probes, improved two-dimensional resolution, and Doppler spectrum acquisition will become more widely available. Because CDI allows for the first time a noninvasive assessment of the retrobulbar vasculature, we feel that many applications of this technology will develop for ophthalmology.


Bevacizumab in recurrent WHO grades II-III glioma.
The management of recurrent WHO grades II-III (rGII-III) glioma is not well established. This study describes the clinical outcomes in patients who received bevacizumab as rescue treatment. In this retrospective study, the main inclusion criteria were as follows: adult patients with histologicaly proved rGII-III glioma according 2016 WHO classification treated with bevacizumab from 2011 to 2019, T1 contrast enhancement on MRI. Efficacy was assessed using the high-grade glioma 2017 Response Assessment in Neuro-Oncology criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Eighty-one patients were included (M/F ratio: 1.7, median age at diagnosis: 38 years) among whom 46 (56.8%) had an initial diagnosis of grade II glioma. Previous treatments included at least one surgical intervention, radiotherapy (98.8%), and ≥ 2 chemotherapy lines (64.2%). After bevacizumab initiation, partial response, stable disease, and progressive disease were observed in 27.2%, 22.2%, and 50.6% of patients. The median PFS and OS were 4.9 months (95% confidence interval [CI] 3.7-6.1) and 7.6 months (95% CI 5.5-9.9). Bevacizumab severe toxicity occurred in 12.3%. Twenty-four (29.6%) patients discontinued bevacizumab without radiological progression. Oligodendroglioma and age ≥ 38 years at diagnosis were more frequent in this subgroup (odds ratio = 0.24, 95% CI 0.07-0.84, p = 0.023 and 0.36, 95% CI 0.13-0.99, p = 0.042). Ten of these 24 patients were alive at 12 months and two patients at 8 years after bevacizumab initiation, without any subsequent treatment. Bevacizumab can be an option for heavily pretreated patients with rGII-III glioma with contrast enhancement. In our study, bevacizumab displayed prolonged activity in a subgroup of patients.


Diastereoselective Synthesis of Fluorine-Containing Pyrrolizidines via Triphenylcarbenium Tetrafluoroborate-Promoted Carbofluorination of N-3-Arylpropargylpyrrolidine-Tethered Tertiary Allylic Alcohols.
Inexpensive and air stable triphenylcarbenium tetrafluoroborate efficiently promoted the carbofluorination of N-arylpropargylpyrrolidines bearing a tertiary allylic alcohol tether at the 2-position of the pyrrolidine ring to provide 1-isobutenyl-2-(fluoro(phenyl)methylenylhexahydro-1H-pyrrolizidines in a stereoselective fashion. When subjected to bis(trifluoromethane)sulfonamide, the same substrates underwent cycloisomerization reaction within minutes to generate 1-isobutenyl-2-benzoylhexahydro-1H-pyrrolizidines with excellent stereoselectivity.


Molecular mobility and the glass transition in amorphous glucose, maltose, and maltotriose.
We have used measurements of the phosphorescence intensity decay of the triplet probe erythrosin B, dispersed in amorphous glucose, maltose, and maltotriose at probe:sugar mole ratios of approximately 1:10(4), to monitor the molecular mobility of the sugar matrix in the glass and melt around the glass-transition temperature (Tg). Intensity decays were well fit using a stretched-exponential decay model in which the Kohlrausch-Williams-Watts lifetime tau and the stretching exponent beta are the physically meaningful parameters. When normalized to the glass-transition temperature, the erythrosin lifetime decreased in the order glucose>maltose>maltotriose. Analysis of the lifetime provided an estimate of the collisional quenching constant for deexcitation of the triplet state (kTS0); kTS0 increased in the order glucose<maltose<maltotriose over the range of T-Tg from about -40 to 50 degrees C. Although approximately constant in the glass, the magnitude of beta decreased around Tg in the order glucose>maltose>maltotriose, indicating that the lifetime heterogeneity increased in the order glucose<maltose<maltotriose. These data demonstrate that both the average rate of matrix molecular mobility and the width of the distribution of matrix mobility rates around the glass transition increase with an increase in the molecular size of the sugar in this homologous series.


Effectiveness of drug tests in outpatients starting opioid substitution therapy.
We aimed to assess the effectiveness of drug tests for treatment retention in outpatients starting opioid substitution therapy. A retrospective cohort was created from the data of the French health insurance system database for the Midi-Pyrenees region. Patients starting opioid substitution treatment (OST) were included and followed for 18 to 30 months. Two groups of patients were defined: the drug test group (at least one drug test reimbursement) and a control group (no drug test reimbursement). The cohort included 1507 patients. During follow-up, 39 subjects (2.6%) had at least one drug test reimbursement. Mean treatment retention was 207 days in the control group and 411 days in the drug test group (p < 0.001). With a multivariate Cox model, drug tests were associated with treatment retention: hazard ratio 0.55 (95% CI: 0.38-0.80). Use of a drug test in follow-up of opioid substitution treatment, although rarely prescribed, significantly improved treatment retention.


Risk factors for onset and remission of atopy, wheeze, and airway hyperresponsiveness.
Although many children with asthma may have a remission as they grow and other children who did not have asthma may develop asthma in adult life, knowledge about the factors that influence the onset and prognosis of asthma during adolescence and young adulthood is very limited. A cohort of 8-10 year old children (n=718) living in Belmont, New South Wales, Australia were surveyed six times at 2 yearly intervals from 1982 to 1992, and then again 5 years later in 1997. From this cohort, 498 subjects had between three and seven assessments and were included in the analysis. Atopy, airway hyperresponsiveness (AHR), and wheeze in the last 12 months were measured at each survey. Late onset, remission, and persistence were defined based on characteristics at the initial survey and the changes in characteristics at the follow up surveys. The proportion of subjects with late onset atopy (13.7%) and wheeze (12.4%) was greater than the proportion with remission of atopy (3.2%) and wheeze (5.6%). Having atopy at age 8-12 years (OR 2.8, 95% CI 1.5 to 5.1) and having a parental history of asthma (OR 2.0, 95% CI 1.02 to 4.13) were significant risk factors for the onset of wheeze. Having AHR at age 8-12 years was a significant risk factor for the persistence of wheeze (OR 4.3, 95% CI 1.3 to 15.0). Female sex (OR 1.9, 95% CI 1.01 to 3.60) was a significant risk factor for late onset AHR whereas male sex (OR 1.9, 95% CI 1.1 to 2.8) was a significant risk factor for late onset atopy. The onset of AHR is uncommon during adolescence, but the risk of acquiring atopy and recent wheeze for the first time continues during this period. Atopy, particularly present at the age of 8-10 years, predicts the subsequent onset of wheeze.


Pandemic portfolio choice.
COVID-19 has taught us that a pandemic can significantly increase biometric risk and at the same time trigger crashes of the stock market. Taking these potential co-movements of financial and non-financial risks into account, we study the portfolio problem of an agent who is aware that a future pandemic can affect her health and personal finances. The corresponding stochastic dynamic optimization problem is complex: It is characterized by a system of Hamilton-Jacobi-Bellman equations which are coupled with optimality conditions that are only given implicitly. We prove that the agent's value function and optimal policies are determined by the unique global solution to a system of non-linear ordinary differential equations. We show that the optimal portfolio strategy is significantly affected by the mere threat of a potential pandemic.


PCR amplification, cloning, and sequencing of ancient DNA.
PCR amplification of DNA is routine in modern molecular biology. However, the application of PCR to ancient DNA (aDNA) experiments often requires significant modification to standard protocols. The degraded nature of most aDNA fragments requires targeting shorter fragments, performing replicate amplifications, incorporating multiple negative controls, combating PCR inhibition, using specific DNA polymerases to deal with damaged bases, working in a separate aDNA facility, and modifying the PCR recipe to deal with damaged and low copy-number target DNA. In this chapter, we describe how and why these procedures are implemented, discuss aDNA-specific troubleshooting methodology, and suggest modifications to commercial cloning and sequencing procedures to reduce the expense of PCR product cloning.


Effect of Dextran 40 and aprotinin on experimental acute pancreatitis.
This study examines and compares the prophylactic role of aprotinin and Dextran 40 in acute pancreatitis. Experimental acute pancreatitis was induced in 70 male Wistar rats using the closed-duodenal-loop technique. The rats were randomly divided into four groups; sham operation, untreated acute pancreatitis, and therapy with aprotinin or Dextran 40. Samples of blood and urine were collected at the beginning and at the end of the 24-hr period for measurement of amylase and creatinine which allowed calculation of the amylase-creatinine clearance ratio (ACCR). Mortality in the aprotinin group was the same as the untreated rats (20%). Dextran 40 therapy was associated with a lower mortality rate (6.7%). Light microscopic examination confirmed that the histologic changes of acute pancreatitis were less severe in both the aprotinin- and Dextran 40-treated rats. The ACCR was elevated after Dextran 40 therapy, which was due mainly to high urinary amylase levels. These results suggest that Dextran 40 may have a prophylactic role in acute experimental pancreatitis but again emphasizes the high false-positive rate of the ACCR determination.


Somatic and germline ATM variants in non-small-cell lung cancer: Therapeutic implications.
ATM is an apical kinase of the DNA damage response involved in the repair of DNA double-strand breaks. Germline ATM variants (gATM) have been associated with an increased risk of developing lung adenocarcinoma (LUAD), and approximately 9% of LUAD tumors harbor somatic ATM mutations (sATM). Biallelic carriers of pathogenic gATM exhibit a plethora of immunological abnormalities, but few studies have evaluated the contribution of immune dysfunction to lung cancer susceptibility. Indeed, little is known about the clinicopathological characteristics of lung cancer patients with sATM or gATM alterations. The introduction of targeted therapies and immunotherapies, and the increasing number of clinical trials evaluating treatment combinations, warrants a careful reexamination of the benefits and harms that different therapeutic approaches have had in lung cancer patients with sATM or gATM. This review will discuss the role of ATM in the pathogenesis of lung cancer, highlighting potential therapeutic approaches to manage ATM-deficient lung cancers.


A survey of root canal treatment of molar teeth by general dental practitioners in private practice in Saudi Arabia.
The purpose of this study was to evaluate the practice and depth of knowledge of root canal treatment by general dental practitioners working in private dental centers in different cities within the Kingdom of Saudi Arabia. A questionnaire was distributed to 400 general dental practitioners. Completed questionnaires were analyzed in term of simple summary statistics. A total of 252 (63%) practitioners responded. The majority of the respondents were Syrians (59%) and Egyptians (32%). Ninety-one per cent of the respondents indicated that they performed root canal treatment. Amongst those who carried out root canal treatment, only seven practitioners (3%) used rubber dam for isolation. More than half of the respondents (55%) used saline to irrigate canals during treatment. Forty-six per cent of practitioners used formocresol as an inter appointment medicament. The standardized and step-back preparation techniques were the method of choice for the majority of the respondents (91%). Ninety-seven per cent of the practitioners used stainless steel hand instruments to prepare root canals and the majority (92%) used gutta-percha for obturation. Seventy-four per cent of the respondent used cold lateral condensation. The average number of radiographs routinely taken for root canal treatment was four. Ninety-three per cent indicated that they usually completed a root canal treatment of molar teeth in three or more visits. Eighty-eight per cent of the practitioners preferred waiting for 1 or 2 weeks to restore the teeth permanently. Results of this study confirm that many general dental practitioners are not following quality guidelines for endodontic treatment.


Clonidine suppresses methylxanthine induced quasi-morphine withdrawal syndrome.
The effects of the alpha-2 adrenergic agonist, clonidine, on the "quasi-morphine withdrawal syndrome" (QMWS) were examined in drug naive rats. The QMWS was induced by combined systemic administration of iso-butyl-methylxanthine (IBMX: 15 mg/kg, IP) and naloxone (1 mg/kg, IP). Pretreatment with clonidine (50 micrograms/kg, IP) significantly decreased the incidence of 11 out of 16 withdrawal signs. Since clonidine suppresses signs and symptoms of true morphine withdrawal, the suppression of methylxanthine effects demonstrates an additional similarity of the QMWS to true morphine withdrawal. These results suggest that a significant common neural mechanism of both the QMWS and true morphine withdrawal is affected by clonidine.


Narrative accounts of illness in schizophrenia: association of different forms of awareness with neurocognition and social function over time.
Awareness of illness in schizophrenia reflects complex storied understanding of the impact of the disorder upon one's life. Individuals may be aware of their illness in different ways and this may be related to their functioning. A total of 76 adults with schizophrenia were assessed for their awareness of illness, neurocognition, social cognition, and social function concurrently and social function was also assessed at three later time points. A cluster analysis revealed 3 groups: generally full awareness, generally limited awareness, and superficial awareness. Comparisons between these profiles revealed the superficial group had poorer executive function, emotion recognition ability, and capacity for social relationships than the full awareness group, yet had better verbal memory and more social contacts than the limited awareness group. These results suggest assessing the narrative qualities of awareness of illness may reveal unique links with cognition and function, and this may have implications for interventions.


Genetic and environmental aetiology of the dimensions of Callous-Unemotional traits.
A Callous-Unemotional trait specifier (termed 'Limited Prosocial Emotions') was added to the diagnosis of conduct disorder in DSM-5. The Inventory of Callous-Unemotional Traits (ICU) is a comprehensive measure of these traits assessing three distinct, yet correlated dimensions--Callousness, Uncaring, and Unemotional--all thought to reflect the general Callous-Unemotional construct. The present study was the first to examine the degree to which the aetiology of these dimensions is shared v. independent. Parent-reported ICU data from 5092 16-year-old twin pairs from the Twins Early Development Study were subjected to confirmatory factor analysis. Multivariate genetic modelling was applied to the best-fitting structure. A general-specific structure, retaining a general factor and two uncorrelated specific factors (Callousness-Uncaring, Unemotional), provided the best fit to the data. The general factor was substantially heritable (h2 = 0.58, 95% CI 0.51-0.65). Unusually, shared environmental influences were also important in accounting for this general factor (c2 = 0.26, 95% CI 0.22-0.31), in addition to non-shared environmental influences. The Unemotional dimension appeared phenotypically and genetically distinct as shown by the substantial loadings of unemotional items on a separate dimension and a low genetic correlation between Unemotional and Callousness-Uncaring. A general factor, indicative of a shared phenotypic structure across the dimensions of the ICU was under substantial common genetic and more modest shared environment influences. Our findings also suggest that the relevance of the Unemotional dimension as part of a comprehensive assessment of CU traits should be investigated further.


Altmetric: Top 50 dental articles in 2014.
Introduction Altmetrics is a new and emerging scholarly tool that measures online attention surrounding journal articles. Altmetric data resources include: policy documents, news outlets, blogs, online reference managers (eg Mendeley and CiteULike), post-publication peer-review forums (eg PubPeer and Publons), social media (eg Twitter, Facebook, Weibo, Google(+), Pinterest, Reddit), Wikipedia, sites running Stack Exchange (Q&A), and reviews on F1000 and YouTube.Methods To identify the top 50 dental articles in 2014, PubMed was searched using the following query "("2014/1/1"[PDAT]:"2014/12/31"[PDAT]) and jsubsetd[text]" in December, 2015. Consequently, all PubMed records were extracted and sent to Altmetric LLP (London, UK) as a CSV file for examination. Data were analysed by Microsoft Office Excel 2010 using descriptive statistics and charts.Results Using PubMed searches,15,132 dental articles were found in 2014. The mean Altmetric score of 50 top dental articles in 2014 was 69.5 ± 73.3 (95% CI: -74.14 to 213.14). The British Dental Journal (48%) and Journal of Dental Research (16%) had the maximum number of top articles. Twitter (67.13%), Mendeley (15.89%) and news outlets (10.92%) were the most popular altmetric data resources.Discussion Altmetrics are intended to supplement bibliometrics, not replace them. Altmetrics is a fresh and emerging arena for the dental research community. We believe that dental clinical practitioners, research scientists, research directors and journal editors must pay more attention to altmetrics as a new and rapid tool to measure the social impact of scholarly articles.


Screening and brief intervention for alcohol problems in an underserved population: development of baseline data via patient exit interviews.
This case reports the implementation of post-care patient interviews to determine whether or not patients received screening and brief intervention (when needed) for alcohol problems.


The use of fluorescamine as a detection reagent in protein microcharacterization.
With recent advances in protein microchemistry, compatible methods for the preparation and quantitation of proteins and peptides are required. Fluorescamine, a reagent which reacts with primary amino groups has been used successfully to detect amino acids, peptides, and proteins in various micromethods. This article discusses these methods which include (1) amino acid analysis of protein and peptide hydrolysates with postcolumn fluorescamine derivatization; (2) purification and characterization of proteins and peptides by reversed-phase HPLC with postcolumn fluorescamine derivatization; (3) purification of peptides by two-dimensional chromatography and electrophoresis on thin-layer cellulose with fluorescamine staining; and (4) electroblotting of protein bands from SDS-PAGE to glass fiber filters and polyvinylidene difluoride (PVDF) membranes with fluorescamine staining. In addition, this article also compares a postcolumn fluorescamine detection system with a UV detection system in the applications of amino acid analysis and reversed-phase HPLC protein/peptide analysis.


A novel ultrasensitive and fast aptamer biosensor of SEB based on AuNPs-assisted metal-enhanced fluorescence.
A fluorescent biosensor strategy was developed in combination with immunomagnetic separation for rapid and sensitive detection of staphylococcal enterotoxin B (SEB). Magnetic nanoparticles (MNPs) modified with aptamer of SEB could capture the SEB. Then the gold nanoparticles (AuNPs) fluorescent probe was added and a "sandwich structure" was formed between AuNPs, SEB and MNPs. The MNPs-SEB-AuNPs structure could be separated with an additional magnetic field, which resulted the lower signals of AuNPs fluorescent probe. In optimal conditions, the current method displayed a broad quantitative range from 100 to 107 fg/mL and the limit of detection was 3.43 fg/mL. The recovery of SEB-spiked milk samples ranged from 92.00 to 119.00 %, which revealed that the developed method had great accuracy. Furthermore, the method was fast and economical for ultrasensitive detection. Therefore, the fluorescent biosensor based on MNPs-AuNPs is promising for the detection of other environmental and food pollutants.


CD8+ T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy.
While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs. with allergic reactions upon food challenge after a withdrawal period; n = 21 vs. 30 respectively among total 120 intent-to-treat participants). Lower frequencies of naïve CD8+ T cells and terminally differentiated CD57+CD8+ T cell subsets at baseline (pre-OIT) are associated with SU. Frequency of naïve CD8+ T cells shows a significant positive correlation with peanut-specific and Ara h 2-specific IgE levels at baseline. Higher frequencies of IL-4+ and IFNγ+ CD4+ T cells post-OIT are negatively correlated with SU. Our findings provide evidence that an immune signature consisting of certain CD8+ T cell subset frequencies is potentially predictive of SU following OIT.


A Stereoselective Synthesis of Fused Carbocycles with a cis-1,2-Diol Moiety by Desymmetrization: SmI2-Mediated Pinacol Coupling of meso-Cyclic 1,3-Diones.
Samarium diiodide (SmI2)-mediated desymmetrization of a meso-cyclic 1,3-dione pinacol coupling is described. The reaction proceeds with high stereoselectivity to provide fused carbocyclic compounds with three contiguous stereogenic centers featuring an all-carbon quaternary center and a cis-1,2-diol moiety.


Hemodynamic, platelet and clinical responses to prostacyclin in unstable angina pectoris.
The hemodynamic and platelet effects of prostacyclin (PGI2) were investigated in 27 patients with unstable angina (14 treated patients; 13 control subjects) given a 72-hour infusion (5 ng/kg/min) or placebo. This randomized study was double-blind and conducted as a substudy of a multicenter trial testing the clinical efficacy of PGI2. The clinical and angiographic features were identical in the 2 groups. Blood pressure and heart rate were not modified significantly by PGI2. A recurrence of angina during infusion occurred in 8 treated patients (57.1%) and in 8 control subjects (61.5%). Two patients receiving PGI2 and none in the control group developed a myocardial infarction. Levels of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, increased from baseline values (less than 20 pg/ml) to 605 +/- 41 pg/ml during infusion. Levels of fibrinopeptide A, beta-thromboglobulin, platelet factor 4, thromboxane B2 and the platelet aggregates ratio in blood were similar between the 2 groups before, during and after PGI2 infusion. Prostacyclin reduced ex vivo platelet aggregation to adenosine diphosphate and thromboxane B2 generation by approximately 50% during the infusion period with return of aggregation to baseline and platelet thromboxane B2 production to above baseline after the discontinuation of PGI2. Thus, despite favorable effects of PGI2 upon platelet aggregation and systemic hemodynamics, the prostanoid failed to improve the clinical evolution of unstable angina.


Medication Education for Dosing Safety: A Randomized Controlled Trial.
This study sought to determine whether a brief intervention at the time of emergency department (ED) discharge can improve safe dosing of liquid acetaminophen and ibuprofen by parents or guardians. We performed a randomized controlled trial in the ED of parents and guardians of children 90 days to 11.9 years of age who were discharged with acetaminophen or ibuprofen, or both. Families were randomized to standard care or a teaching intervention combining lay language, simplified handouts, provision of an unmarked dosing syringe, and teach-back to confirm correct dosing. Participants were called 48 to 72 hours and 5 to 7 days after ED discharge to assess understanding of correct dosing. The primary outcome was defined as parent or guardian report of safe dosing at the time of first follow-up call. Our primary hypothesis was that the intervention would decrease the rate of error from 30% to 10% at 48- to 72-hour follow-up. We enrolled 149 of 259 (58%) eligible subjects; 97 of 149 (65%) were reached at first follow-up call, of whom 35 of 97 (36%) received the intervention. Among those participants receiving the intervention, 25 of 35 (71%) were able to identify a safe dose for their child at the time of the first call compared with 28 of 62 (45%) of those in the control arm. The difference in proportions was 26% (95% confidence interval [CI] 7% to 46%). There was a 58% increase in reporting safe dosing in the intervention group compared with the control roup (relative risk 1.58; 95% CI 1.12 to 2.24), and it remained significant after adjustment for health literacy and language (adjusted relative risk 1.50; 95% CI 1.06 to 2.13). A multifaceted intervention at the time of ED discharge-consisting of a simplified dosing handout, a teaching session, teach-back, and provision of a standardized dosing device-can improve parents' knowledge of safe dosing of liquid medications at 48 to 72 hours.


How cells clean house.
Inside the cytoplasm of a living cell, organelles called autophagosomes continually engulf bits of cytoplasm, along with damaged cell parts and invading bacteria and viruses. The "sweepings" are carried to digestive organelles for breakup and recycling. The process is called autophagy. Cell biologists are learning about autophagy in great detail by tracing the protein signals that drive and control the process. A fuller understanding of autophagy is opening up new options for treating cancer, infectious disease, immune disorders and dementia, and it may one day even help to slow down aging.


Assessment of return to sport and functional outcomes following distal femoral, double level and high tibial osteotomies for active patients with symptomatic varus malalignment.
This study indicated the outcomes of three surgical techniques for the treatment of symptomatic unicompartmental knee osteoarthritis (UKOA) with varus malalignment in younger, active patients: distal femoral osteotomy (DFO), double-level osteotomy (DLO) and high tibial osteotomy (HTO). The outcomes measured included the return to sport, sport activity and functional scores. A total of 103 patients (19 DFO, 43 DLO, 41 HTO) were enrolled in the study and were divided into three groups based on their oriented deformity, each undergoing one of the three surgical techniques. All patients underwent pre- and post-operative evaluations including X-rays, physical exams and functional assessments. All three surgical techniques were effective in treating UKOA with constitutional malalignment. The average time to return to sport was similar among the three groups (DFO: 6.4 ± 0.3 [5.8-7] months, DLO: 4.9 ± 0.2 [4.5-5.3] months, HTO: 5.6 ± 0.2 [5.2-6] months). The sport activity and functional scores improved significantly for all three groups, with no significant differences observed among the groups. Various knee osteotomy procedures, DFO, DLO, and HTO, result in high RTS rates and quick RTS times with satisfactory functional scores. Despite pre- to post-operative improvements in sport activities following DFO and DLO, pre-symptom levels were not reached following all evaluated procedures. Retrospective case-control study, Level III.


The effect of alcohol availability on marijuana use: evidence from the minimum legal drinking age.
This paper exploits the discontinuity created by the minimum legal drinking age of 21 years to estimate the causal effect of increased alcohol availability on marijuana use. We find that consumption of marijuana decreases sharply at age 21, while consumption of alcohol increases, suggesting that marijuana and alcohol are substitutes. We further find that the substitution effect between alcohol and marijuana is stronger for women than for men. Our results suggest that policies designed to limit alcohol use have the unintended consequence of increasing marijuana use.


Characterization and Anti-Aging Activity of Polysaccharides from Akebia trifoliata Fruit Separated by an Aqueous Two-Phase System.
Bioactive polysaccharides have numerous pharmacological effects that are beneficial to human health. Akebia trifoliata (Thunb.) Koidz. has great development prospects as a food resource with medicinal value. The polysaccharides (ATFP) were extracted from A. trifoliata fruit by an aqueous two-phase system. ATFP-3, purified with DEAE-52 and Sephadex G-200 from ATFP, was mainly composed of glucose (47.55%) and galactose (20.39%). Its hydroxyl radical scavenging rate was 89.30% at 1.60 mg/mL and its IC50 was 0.29 mg/mL. ATFP-3 significantly enhanced the survival rate of Caenorhabditis elegans under thermal or oxidative stress. Furthermore, ATFP-3 could prolong the lifespan of C. elegans and improve the activities of the antioxidant enzyme, while also decrease the accumulation of lipofuscin and the level of malondialdehyde (MDA) in aging worms. Thus, ATFP-3 has application potential in health benefits for humans.


C(h)AR-ting a new course in incurable lymphomas: CAR T cells for mantle cell and follicular lymphomas.
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has transformed the natural history of relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell non-Hodgkin lymphoma. Based on these results, CD19 CAR T cells have since been tested in largely incurable lymphomas, including mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma, with promising early results that raise the question of whether this cellular immunotherapy could have curative potential and change the natural history of these diseases. This article reviews these results and this hypothesis.


Inhibition of mitochondrial complex II alters striatal expression of genes involved in glutamatergic and dopaminergic signaling: possible implications for Huntington's disease.
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor abnormalities and cognitive impairment. The irreversible succinate dehydrogenase (SD) inhibitor 3-nitropropionic acid (3NP) causes neurodegeration in the striatum resembling HD when administered to rodents or primates. Using corticostriatal brain slice preparations, we analyzed the pattern of gene expression following 3NP application utilizing cDNA microarrays. Acute 3NP treatment modulates the expression of several genes involved in dopaminergic and glutamatergic signaling in corticostriatal brain slices, and unbalances the downstream serine/threonine protein kinase and phosphatase network affecting the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). Our data provide new information about the molecular events possibly underlying neurodegeneration induced by this mitochondrial toxin.


Altered GABAergic effects on kainic acid-induced seizures in the presence of hippocampal sclerosis in rats.
Although deficient inhibitory action of GABAergic neurons is frequently implicated in the pathogenesis of epileptic seizures, their exact contribution to the epileptogenicity is still controversial. In the present study, we investigated the effects of GABAergic action on kainic acid (KA)-induced hippocampal seizure in rats with or without hippocampal sclerosis (HS). HS was produced by pretreatment of KA (12 mg/kg i.p.) 3 weeks prior to induction of acute KA seizure (8 mg/kg i.p.). After development of epileptiform activity in the hippocampus, either muscimol (50 ng/microliters, 1.0 microliter) or vehicle (phosphate buffer solution, 1.0 microliter) was applied locally in the left dorsal hippocampus through a cannula and electrobehavioral observation was performed continuously for 6 h. The seizures were divided into four stages according to their severity. 7 days after the induction of acute seizure, the rats were sacrificed and subjected to histological examinations. In the rats without HS, muscimol reduced the seizure severity as well as neuronal damage, whereas muscimol facilitated the severity of both indicators in the presence of HS. Muscimol accelerated the propagation of epileptiform activity and the onset of more advanced seizure stages regardless of presence or absence of HS. Our study suggest that the GABAa function has dual effects on the final severity of KA-induced seizure depending on the presence or absence of HS and that it accelerates the rate of seizure development in either condition. The altered GABAa function in the presence of HS would probably modify seizure activity.


Evaluation and clinical interpretation of hypergammaglobulinemia E: differentiating atopy from immunodeficiency.
Increases in total serum IgE levels can be observed in many diverse conditions, from infection to atopy to primary immunodeficiency. The differentiation of atopy from immunodeficiency most often is made on a clinical basis, after taking findings from history, physical examination, and laboratory studies into consideration. However, total IgE level is neither a sensitive nor a specific diagnostic marker for any particular disease and, therefore, should not be relied on to establish a diagnosis of either atopy or primary immunodeficiency.


Explaining own and others' behavior in a controversial issue: animal experimentation.
The authors investigated how 2 groups with different attitudes toward animal experimentation-researchers who conducted animal experiments and members of animal welfare organizations who protested against animal experiments--made attributions for the behavior of the opposing group. The 2 groups showed an actor--observer effect, mentioning more internal causes for the opponents' behavior and more external causes for their own behavior. Both groups were able to take the other's perspective, resulting in a reversed actor-observer effect. The less involved participants followed the pattern of ratings of the group whose attitudes corresponded to their own. In particular, the participants with a negative attitude toward animal experimentation rated researchers' behavior as more internally caused than did those with a positive attitude. The results illustrated how the participants formed and defended attitudes in a social context.


The granuloma pouch: an in vivo model for pharmacokinetic and chemotherapeutic investigations. II. Microbiological characterization.
In this paper we have described the microbiology of the granuloma pouch model in rats. We studied the biochemical parameters of pouch exudates infected with Escherichia coli. Data revealed that the inflammatory response increased during the course of infection since lactate dehydrogenase levels as well as alpha 2 and gamma-globulin fractions were increased in comparison to uninfected controls. Infection of the pouches did not spread. We also monitored the growth characteristics of four different E. coli strains. In vitro incubation of these strains in human and rat serum as well as in pouch exudate, and the in vivo growth rate in infected pouches revealed that the degree of serum sensitivity was clearly related to viability in vivo. Serum-resistant strains grew well in pouch exudate, whereas serum-sensitive strains were eliminated from the infected pouches. Since elimination of these strains was dependent on the challenge dose, we concluded that cellular and/or humoral host defense mechanisms became locally exhausted or inactivated. Thus, the granuloma pouch represents a local bacterial infection of a poorly defended, inflamed body cavity.


Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration.
Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer's disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.


Method for removal of the St. Jude valve.
A method is presented for removal of the St. Jude Medical valve when it must be replaced with another prosthesis. The sewing ring is transected in the radial direction, freeing the rigid portion of the valve. This is then removed, allowing the remainder of the sewing ring to be excised under direct vision. This method simplifies and increases the safety of this procedure.


Haematologic complications from human babesiosis: a case report.
Formerly known as Nantucket fever, babesiosis is increasing in incidence across the Northeastern United States. Because of its emerging health risk globally, it is important to be aware of its various presenting manifestations. We present the case of a middle-aged man with haemolytic anaemia from Babesia microti infection.


A trade based view on casino taxation: market conditions.
This article presents a trade based theory of casino taxation along with empirical evidence found from Macao as a typical tourism resort. We prove that there is a unique optimum gaming tax in a particular market for casino gambling, argue that any change in this tax is engendered by external demand shifts, and suggest that the economic rent from gambling legalization should be shared through such optimal tax between the public and private sectors. Our work also studies the tradeoff between economic benefits and social costs arising from casino tourism, and provides some policy recommendations for the sustainable development of gaming-led economies. The theoretical arguments in this article turn out to be consistent with empirical observations on Macao realities over the recent decade.


Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients.
To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients. A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated. Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001) and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain. In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI.


Donor versus recipient preferences for aid allocation: A systematic review of stated-preference studies.
As Official Development Assistance (ODA) tops 180 billion USD per year, there is a need to understand the mechanisms underlying aid effectiveness. Over the past decade we have seen some low- and middle-income countries become developed nations with record economic growth. Others remain in development purgatory, unable to provide their citizens with access to essential services. In an effort to improve aid effectiveness, the prescriptive nature of aid, where (typically) Western countries allocate funds based on perceived need or the strategic priorities of donors is being reconsidered in favour of locally-led development, whereby recipient governments and sometimes citizens are involved in the allocation and delivery of development aid. Meeting the preferences of donors (both governments and citizens) has been a longstanding priority for international development organisations and democratically governed societies. Understanding how these donor preferences relate to recipient preferences is a more recent consideration. This systematic review analysed 58 stated preference studies to summarise the evidence around donor and recipient preferences for aid and, to the extent possible, draw conclusions on where donor and recipient preferences diverge. While the different approaches, methods, and attributes specified by included studies led to difficulties drawing comparisons, we found that donors had a stronger preference than recipients for aid to the health sector, and that aid effectiveness could be more important to donors than recipients when deciding how to allocate aid. Importantly, our review identifies a paucity of literature assessing recipient perspectives for aid using stated preference methods. The dearth of studies conducted from the recipient perspective is perplexing after more than 30 years of 'alignment with recipient preferences', 'local ownership of aid', 'locally-led development' and 'decolonisation of aid'. Our work points to a need for further research describing preferences for aid across a consistent set of attributes in both donor and recipient populations.


Current surgical management of ovarian cancer.
Surgical management of ovarian cancer requires excellent judgment and mastery of a wide array of procedures. Involvement of a gynecologic oncologist improves outcomes. Staging of apparent stage I disease is important. Minimally invasive techniques provide advantages. Primary debulking surgery provides the best long-term survival of any strategy in advanced ovarian cancer. Aggressive surgical paradigms have the greatest success. Further cytoreductive surgery may be appropriate. Most relapsed patients require management of bowel obstruction at some point. Palliative intervention can enhance quality of life. Surgical correction may extend survival. For end-stage patients with progressive disease, the treating gynecologic oncologist must manage expectations.


Hemocholecyst caused by accidental injury associated with radiofrequency ablation for hepatocellular carcinoma: A case report.
Radiofrequency ablation (RFA) is an effective and safe treatment for hepatocellular carcinoma that features a lower incidence of serious complications than surgical resection. Hemocholecyst caused by RFA is a rare complication of secondary damage to the intrahepatic bile duct that results in hemobilia. Here we report on a case of a hemocholecyst caused by accidental injury during RFA that induced hematemesis and melena. Digital subtraction angiography revealed no gallbladder arterial injuries. After conservative treatment and transcatheter arterial chemoembolization, the patient's condition stabilized, and she was discharged 1 wk later. Therefore, when performing interventional procedures such as RFA, clinicians must be vigilant because even minor injuries can lead to serious complications such as hemocholecyst.


Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial.
EndoPredict (EP) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) who are being treated with adjuvant endocrine therapy. Herein we report the prospective-retrospective clinical validation of EP in the node-positive, chemotherapy-treated, ER+/HER2- BC patients in the GEICAM 9906 trial. The patients (N = 1,246) were treated either with six cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) or with four cycles of FEC followed by eight weekly courses of paclitaxel (FEC-P), as well as with endocrine therapy if they had hormone receptor-positive disease. The patients were assigned to EP risk categories (low or high) according to prespecified cutoff levels. The primary endpoint in the clinical validation of EP was distant metastasis-free survival (MFS). Metastasis rates were estimated using the Kaplan-Meier method, and multivariate analysis was performed using Cox regression. The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2- tumors from the 800 available samples in the GEICAM 9906 trial. On the basis of the EP, 25% of patients (n = 141) were classified as low risk. MFS was 93% in the low-risk group and 70% in the high-risk group (absolute risk reduction = 23%, hazard ratio (HR) = 4.8, 95% confidence interval (CI) = 2.5 to 9.5; P < 0.0001). Multivariate analysis showed that, in this ER+/HER2- cohort, EP results are an independent prognostic parameter after adjustment for age, grade, lymph node status, tumor size, treatment arm, ER and progesterone receptor (PR) status and proliferation index (Ki67). Using the predefined EPclin score, 13% of patients (n = 74) were assigned to the low-risk group, who had excellent outcomes and no distant recurrence events (absolute risk reduction vs high-risk group = 28%; P < 0.0001). Furthermore, EP was prognostic in premenopausal patients (HR = 6.7, 95% CI = 2.4 to 18.3; P = 0.0002) and postmenopausal patients (HR = 3.3, 95% CI = 1.3 to 8.5; P = 0.0109). There were no statistically significant differences in MFS between treatment arms (FEC vs FEC-P) in either the high- or low-risk groups. The interaction test results between the chemotherapy arm and the EP score were not significant. EP is an independent prognostic parameter in node-positive, ER+/HER2- BC patients treated with adjuvant chemotherapy followed by hormone therapy. EP did not predict a greater efficacy of FEC-P compared to FEC alone.


Accelerated ventricular rhythm in childhood.
Four patients, aged 6 to 14 years, with accelerated ventricular rhythm were studied from June 1976 to June 1978. Three were asymptomatic and had no evidence of cardiac disease. One patient had equivocal evidence of myocarditis. All four patients are well without therapy. The benign nature of this rhythm and the importance of its differentiation from ventricular tachycardia is stressed.


Elastic nailing of tibia shaft fractures in young children up to 10 years of age.
Although tibia shaft fractures in children usually have satisfactory results after closed reduction and casting, there are several surgical indications, including associated fractures and soft tissue injuries such as open fractures. Titanium elastic nails (TENs) are often used for pediatric tibia fractures, and have the advantage of preserving the open physis. However, complications such as delayed union or nonunion are not uncommon in older children or open fractures. In the present study, we evaluated children up to 10 years of age with closed or open tibial shaft fractures treated with elastic nailing technique. A total of 16 tibia shaft fractures treated by elastic nailing from 2001 to 2013 were reviewed. The mean patient age at operation was 7 years (range: 5-10 years). Thirteen of 16 cases were open fractures (grade I: 4, grade II: 6, grade IIIA: 3 cases); the other cases had associated fractures that necessitated operative treatments. Closed, antegrade intramedullary nailing was used to insert two nails through the proximal tibial metaphysis. All patients were followed up for at least one year after the injury. Outcomes were evaluated using modified Flynn's criteria, including union, alignment, leg length discrepancies, and complications. All fractures achieved union a mean of 16.1 weeks after surgery (range: 11-26 weeks). No patient reported knee pain or experienced any loss of knee or ankle motion. There was a case of superficial infection in a patient with grade III open fracture. Three patients reported soft tissue discomfort due to prominent TEN tips at the proximal insertion site, which required cutting the tip before union or removing the nail after union. At the last follow-up, there were no angular or rotational deformities over 10° in either the sagittal or coronal planes. With the exception of one case with an overgrowth of 15 mm, no patient showed shortening or overgrowth exceeding 10mm. Among final outcomes, 15 were excellent and 1 was satisfactory. Even with open fractures or soft tissue injuries, elastic nailing can achieve satisfactory results in young children, with minimal complications of delayed bone healing, or infection.


Health hazards for terrestrial vertebrates from toxic cyanobacteria in surface water ecosystems.
Toxigenic cyanobacteria are photosynthetic prokaryotes that are most often recognized in marine and freshwater systems, such as lakes, ponds, rivers, and estuaries. When environmental conditions (such as light, nutrients, water column stability, etc.) are suitable for their growth, cyanobacteria may proliferate and form toxic blooms in the upper, sunlit layers. The biology and ecology of cyanobacteria have been extensively studied throughout the world during the last two decades, but we still know little about the factors and processes involved in regulating toxin production for many cyanobacterial species. In this minireview, we discuss these microorganisms, and more especially the toxins they produce, as a potential and important health risk for wild and domestic animals.


The advisability of the prudent diet in adolescence.
Risk factor status for cardiovascular disease is affected by life style. Adolescence is a time during which long term life-style habits, including dietary habits, are established. Physicians who treat adolescent patients have a responsibility to be aware of the scientific evidence on the diet-heart question so that they can provide their patients with sound dietary advice. The American Heart Association has recommended that Americans consume a "prudent diet" in which daily consumption of cholesterol is no more than 300 mg with up to 30-35% of calories derived from fat, and less than 10% of calories derived from saturated fat and less than 10% from polyunsaturated fat. This paper reviews this recommendation with particular reference to studies of adolescents. This review centers around four main issues: 1) the estimated effect on serum cholesterol levels of a switch from the usual American diet to the prudent diet; 2) the effect of a predicted decrease in serum cholesterol on the risk of developing cardiovascular disease; 3) evaluation of the evidence of possible adverse effects of the prudent diet; 4) feasibility of the prudent diet. Based on a review of these four issues, the authors feel that the American Heart Association's prudent diet should be strongly recommended for all healthy adolescents.


Dopamine neurons release transmitter via a flickering fusion pore.
A key question in understanding mechanisms of neurotransmitter release is whether the fusion pore of a synaptic vesicle regulates the amount of transmitter released during exocytosis. We measured dopamine release from small synaptic vesicles of rat cultured ventral midbrain neurons using carbon fiber amperometry. Our data indicate that small synaptic vesicle fusion pores flicker either once or multiple times in rapid succession, with each flicker releasing approximately 25-30% of vesicular dopamine. The incidence of events with multiple flickers was reciprocally regulated by phorbol esters and staurosporine. Thus, dopamine neurons regulate the amount of neurotransmitter released by small synaptic vesicles by controlling the number of fusion pore flickers per exocytotic event. This mode of exocytosis is a potential mechanism whereby neurons can rapidly reuse vesicles without undergoing the comparatively slow process of recycling.


Technical Feasibility and Early Clinical Outcome of Biportal Endoscopic Transforaminal Lumbar Interbody Fusion Using Larger Cage.
Transforaminal lumbar interbody fusion with biportal endoscopic guidance (BE-TLIF) has been previously reported with promising clinical results. However, complications such as delayed union or subsidence occurred as with open surgery. We assumed using larger cages would result in less occurrence of such complications. We aimed to analyze the clinical outcome and technical feasibility of BE-TLIF using larger cages, initially designed for oblique lumbar interbody fusion. We enrolled cases that underwent single-level BE-TLIF between January 2021 and January 2022. Polyetheretherketone cages that were larger than the conventional size were used. Diagnoses were degenerative spondylolisthesis or isthmic spondylolisthesis. Visual analog scale scores of the back and leg and Oswestry Disability Index were collected perioperatively. Modified Macnab criteria were used to evaluate the patients at the final follow-up. Radiologic outcome of interbody fusion rate and perioperative complications were analyzed. A total of 35 cases were included in this study. The mean age was 67.5 ± 8.4 and consisted of 13 male patients, and the mean follow-up duration was 18.3 ± 3.7 months. The majority (32/35, 91.3%) of the index level was located within the lower lumbar region, L4-S1. Oswestry Disability Index scores improved from 65.4 ± 5.4 preoperatively to 15.4 ± 6.1 at the final follow-up (P < 0.001). Visual analog scale scores of the leg decreased from 7.9 ± 1.5 to 1.7 ± 1.5 at the final follow-up (P < 0.001). Per the modified Macnab criteria on the final follow-up, 94% of the patients reported good/excellent. Most (94.2%) of the patients showed fusion grade I and II at the 1-year follow-up. No patient showed subsidence or other postoperative complication. BE-TLIF using a larger cage was safely performed without risk of subsidence during the 1-year follow-up. A cage with a larger footprint may be advantageous in BE-TLIF in the aspect of interbody fusion and subsidence.


Maximinus Daia, a Roman emperor who may have had Graves' disease and died of a thyrotoxic crisis.
Evidence is presented that the Roman emperor Maximinus Daia had Graves' disease and died of severe thyrotoxicosis. The information about this emperor's terminal illness is drawn from the writings of the 4th century writers Eusebius and Lactantius. An existing statue indicates that the emperor had bilateral Graves' ophthalmopathy.


More stage A prostatic cancers, less surgery for benign hypertrophy in smokers.
Records were reviewed of 396 men less than 75 years old with a history of transurethral prostatectomies, known smoking habits, height, weight and no prostate malignancy more advanced than stage A. The 51 men with stage A cancer included more current smokers than the 345 without malignancy (45.1% versus 22.3%, odds ratio 2.9, confidence interval 1.6 to 4.5, p < 0.001). Prostatectomy specimens from smokers were smaller than those from nonsmokers (21.4 versus 26.9 gm., p < 0.005) and those from cancer patients were smaller than those from men without cancer. Small adenomas included more cancers per kilogram than large adenomas in smokers and nonsmokers. Men with a history of prostatectomy were less often current smokers than 128 men with newly diagnosed colon cancer (22.3% versus 42.2%, odds ratio 0.49, confidence interval 0.27 to 0.77), and less often ever smokers than 325 men from a general internist's office (46.5% versus 55.4%, odds ratio 0.70, confidence interval 0.52 to 0.94). These data suggest smoking as a risk factor for stage A prostatic cancer and confirm smoking abstinence as a risk factor for prostatic hypertrophy requiring surgery.


Defensive strategies of soft corals (Coelenterata: Octocorallia) of the Great Barrier Reef : III. The relationship between ichthyotoxicity and morphology.
The relationship between ichthyotoxicity and predation-related defensive functional morphology was examined in alcyonacean soft corals of the central and northern regions of the Great Barrier Reef (GBR), Australia. Approximately 170 specimens were assessed encompassing a number of genera within three families: 1) the Alcyoniidae (Lobophytum, Sarcophytum, Sinularia, Cladiella, Parerythropodium, and Alcyonium); 2) Neptheidae (Lemnalia, Paralemnalia, Capnella, Lithophyton, Nephthea, Dendronephthya, Scleronephthya, and Stereonephthya), and 3) Xeniidae (Anthelia, Efflatounaria, Cespitularia, Heteroxenia, and Xenia). Ichthyotoxicity data were derived from earlier studies which used Gambusia affinis Baird and Girard (Vertebrata, Pisces) as a test organism. These data were compared to morphological data collected from specimens in the field and laboratory. Three sets of statistical analyses were performed, each considering a progressively narrower group of taxa. The first included 68 specimens and considered 16 morphological characters in each, falling into the general categories of gross colony form, colony texture, presence of mucus, colony color, polyp retractility, and sclerite morphology and distribution. These were tested for independence against ichthyotoxicity data. The second set of analyses involved a more restricted morphological data set derived from 28 species of Sinularia in combination with 28 species within the Nephtheidae, comparing them to their respective toxicity ranks. The third analysis considered the previous two taxonomic groups separately in relation to their toxicity levels.The attempt to consider many morphological characters in a taxonomically diverse collection did not reveal any general association in the Alcyonacea between defensive morphology and toxicity, and those associations which did emerge were clearly erroneous. The second analysis, considering only Sinularia spp. and nephtheids, demonstrated a negative association between ichthyotoxicity and the morphological characters of a) polypary armament, b) microarmament of the individual polyp, and c) strong mineralization of the coenenchyme. The third analysis revealed that the negative association found between toxicity and the first two characters was derived entirely from the nephtheids while the association detected between toxicity and the third character was restricted to Sinularia. It is concluded that a relationship between toxicity and morphology can be demonstrated, but it is heavily dependent upon which specific morphological characters are being considered and at what level of taxonomic resolution the analysis is being performed. An approach utilizing many characters over many taxa is unlikely to yield significant, reliable, or meaningful results.


Comprehensive analysis of gluten in processed foods using a new extraction method and a competitive ELISA based on the R5 antibody.
The only treatment for coeliac disease is to follow a strict, life-long gluten-free diet. It is therefore essential to use a highly sensitive, specific technique for gluten analysis in foods. Nowadays, the usual method for determining gluten content in gluten-free foods, internationally accepted by the Codex Alimentarius Commission, is the R5 antibody-based sandwich ELISA, combined with the cocktail-extraction solution. This technique requires at least two epitopes in the protein, but in hydrolysed foods, proteins are fragmented during food processing and converted into peptides in which only one toxic epitope may appear. Consequently, it was necessary to develop a new competitive immunoassay that, together with a reliable, compatible extraction solution, would provide a complete gluten analysis in any kind of food. We analysed commercial foods and home-made maize breads spiked with a known amount of gliadins using the sandwich R5 ELISA and the new competitive R5 ELISA that has been developed. These foods had previously been extracted with 60% ethanol/water, the cocktail solution or the new extracting solution called UPEX (universal prolamin and glutelin extractant solution). The complementary SDS-PAGE and western blot techniques were also used to confirm the gluten content. The limits of detection and quantification of the competitive R5 ELISA were 0.36 and 1.22 ng/ml of gliadins, respectively. The intra- and inter-assay precisions based on two samples were, respectively, 7.3% and 5.4% for the first sample and 9.9% and 6.3% for the second. This new assay was a better technique than the sandwich R5 ELISA for detecting gliadins quantitatively in hydrolysed foods. Regarding the extraction procedure, we did not find any significant interference from components of the UPEX solution at the concentration used. In addition, the UPEX solution extraction was compatible with the R5 western blot and mass spectrometry techniques. The competitive R5 ELISA we developed, combined with the UPEX solution described here, is a very useful tool for detecting and quantifying gluten in any kind of food samples, including heat-treated and/or hydrolysed ones.


Using Computer Vision and Depth Sensing to Measure Healthcare Worker-Patient Contacts and Personal Protective Equipment Adherence Within Hospital Rooms.
Background. We determined the feasibility of using computer vision and depth sensing to detect healthcare worker (HCW)-patient contacts to estimate both hand hygiene (HH) opportunities and personal protective equipment (PPE) adherence. Methods. We used multiple Microsoft Kinects to track the 3-dimensional movement of HCWs and their hands within hospital rooms. We applied computer vision techniques to recognize and determine the position of fiducial markers attached to the patient's bed to determine the location of the HCW's hands with respect to the bed. To measure our system's ability to detect HCW-patient contacts, we counted each time a HCW's hands entered a virtual rectangular box aligned with a patient bed. To measure PPE adherence, we identified the hands, torso, and face of each HCW on room entry, determined the color of each body area, and compared it with the color of gloves, gowns, and face masks. We independently examined a ground truth video recording and compared it with our system's results. Results. Overall, for touch detection, the sensitivity was 99.7%, with a positive predictive value of 98.7%. For gowned entrances, sensitivity was 100.0% and specificity was 98.15%. For masked entrances, sensitivity was 100.0% and specificity was 98.75%; for gloved entrances, the sensitivity was 86.21% and specificity was 98.28%. Conclusions. Using computer vision and depth sensing, we can estimate potential HH opportunities at the bedside and also estimate adherence to PPE. Our fine-grained estimates of how and how often HCWs interact directly with patients can inform a wide range of patient-safety research.


[Clinical picture and localization of foci of softening in the brain following vertebral artery thrombosis].
The authors conducted a clinico-anatomical analysis of 45 observations with thrombosis of the vertebral arteries. In the majority of cases thrombosis of the vertebral arteries was isolated. In 5 observations it was combined--with thrombosis of the carotid artery (2 cases), with the middle brain artery (2 cases) and with the posterior cerebellum artery (1 case). In one observation thrombosis of the right innominate, subclavian, general carotid and vertebral arteries was diagnosed clinically and angiographically. Thrombosis of the vertebral arteries occurs in the presence of expressed atherosclerotic changes in the brain vessels with acute stenosis.


Uterine Lipoleiomyoma: A Case Report and Review of Literature.
Uterine lipoleiomyoma is a rare benign neoplasm that falls under the umbrella of uterine leiomyoma. Upon histological examination, leiomyoma is primarily composed of smooth muscle cells of the uterus. Whereas, lipoleiomyoma reveals a characteristic pattern of mature adipocytes interspersed in uterine smooth muscles. This paper is discussing a case of a 60-year-old postmenopausal grand multiparous woman who presented with postmenopausal bleeding. A primary diagnosis of leiomyoma was made, however, histopathological diagnosis revealed its rare variant, lipoleiomyoma.


Listening to a walking human activates the temporal biological motion area.
A vivid perception of a moving human can be evoked when viewing a few point-lights on the joints of an invisible walker. This special visual ability for biological motion perception has been found to involve the posterior superior temporal sulcus (STSp). However, in everyday life, human motion can also be recognized using acoustic cues. In the present study, we investigated the neural substrate of human motion perception when listening to footsteps, by means of a sparse sampling functional MRI design. We first showed an auditory attentional network that shares frontal and parietal areas previously found in visual attention paradigms. Second, an activation was observed in the auditory cortex (Heschl's gyrus and planum temporale), likely to be related to low-level sound processing. Most strikingly, another activation was evidenced in a STSp region overlapping the temporal biological motion area previously reported using visual input. We thus propose that a part of the STSp region might be a supramodal area involved in human motion recognition, irrespective of the sensory modality input.


The use of forearm free fillet flap in traumatic upper extremity amputations.
Complete traumatic upper extremity avulsions are an infrequent but devastating injury. These injuries are usually the result of massive blunt trauma to the upper limb. Intact issue from amputated or nonsalvageable limbs may be transferred for reconstruction of complex defects resulting from trauma when the indications for replantation are not met. This strategy allows preservation of stump length or coverage of exposed joints, and provides free flap harvest for reconstruction without additional donor-site morbidity. A retrospective review at São João Hospital was performed on seven patients who had undergone immediate reconstruction with forearm free fillet flaps between 1992 and 2007. There were six men and one woman, with patient age ranging from 17 to 74 years (mean, 41 years). Amputation sites were at the humeral neck (n = 1), at the humeral shaft (n = 5), and below the elbow (n = 1). The area of the forearm free fillet flap skin paddle was 352.14 +/- 145.48 cm (mean +/- SD). The two major complications were the flap loss and the patient death on postoperative day 3 in other case. The postoperative course in the remaining five cases was uneventful with good healing of the wounds. Minor complications included two small residual defects treated by split-thickness skin grafting and one wound infection requiring drainage and revision. The forearm free fillet flap harvested from the amputated limb provides reliable and robust tissue for reconstruction of large defects of the residual limb without additional donor-site morbidity. Microsurgical free fillet flap transfer to amputation sites is valuable for achieving wound closure, improving stump durability, and maximizing function via preservation of length.


Secondary School Athletic Trainers' Experiences With Organizational Conflict: A Comparison Across Employment Models.
Athletic training is a multifaceted profession characterized by interpersonal relationships and a team approach to care. Collaborative relationships, by nature, open the door to conflict, which has been reported frequently in the collegiate athletic setting. However, secondary school athletic trainers' (ATs') experiences with conflict and pressure in their role are not readily understood. To measure the extent and sources of stress, pressure, and conflict within the secondary school athletic training setting and determine if differences exist across employment characteristics. Cross-sectional study. Secondary school athletics. Secondary school ATs (n = 725, age = 39.8 ± 10.5 years, years certified = 16.7 ± 9.7, years in current role = 10.6 ± 7.8). Participants were asked to reply to an online questionnaire with quantitative measures pertaining to organizational conflict and workplace dynamic. Employment type (school district employee, school district teacher, medical or university facility, independent contractor) and status (full time, part time) served as independent variables. Likert-scale scores (1 = strongly agree to 5 = strongly disagree; 1 = always to 5 = never) and perceived sources of stress, pressure, and conflict were the dependent variables. Analyses consisted of Kruskal-Wallis tests with Mann-Whitney U post hoc tests and odds ratios to assess associations between variables of interest. We obtained a 15.3% response rate (725/4745). Although the ATs reported experiencing conflict and pressure, these experiences were relatively infrequent and not universal. Compared with part-time ATs, full-time ATs described higher ratings of strong relationships with coaches (P = .003) and principals (P = .002). The most frequently identified sources of conflict were parents (59%) and coaches (53.9%), followed by athletes (32.6%). Full-time ATs were 1.6 times more likely to report experiencing conflict with a coach than part-time ATs (odds ratio = 1.550, 95% CI = 1.037, 2.317; P = .040). Secondary school ATs' experiences regarding organizational conflict were relatively positive. Instances of pressure and conflict were noted, though relatively infrequently, and these experiences were largely uninfluenced by employment type.


[Simultaneous determination of geniposide, baicalin and berberine hydrochloride in Angong Niuhuang pill by RP-HPLC].
A new method for the simultaneous quantitative determination of geniposide, baicalin and berberine hydrochloride in Angong Niuhuang pill using reversed phase high performance liquid chromatographic method had been developed. The optimum chromatographic conditions were as follows: Agilent Zorbax SB - C18 column (4.6 mm 250 mm, 5 m), acetonitrile-H2O (containing 6 mmol L(-1) KH2PO4, pH 4.6) gradient elution; as a detection wavelength of 343 nm. The calibration curves of geniposide, baicalin and berberine were linear at the ranges of 4.50-110.00, 5.00-153.00, 6.40-191.00 mg L(-1), respectively. The limits of detection of the method were 0.77 ng for geniposide, 1.53 ng for baicalin and 1.43 ng for berberine hydrochloride. The recoveries of the method were 104.44% (RSD 1.79% ) for geniposide, 96.98% (RSD 1.76%) for baicalin, 101.08% (RSD 3.1%) for berberine hydrochloride. This method had been successfully applied to determine the content of geniposide, baicalin and berberine hydrochloride in Angong Niuhuang pill.


Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column derivatization RP-HPLC and application to drug-protein binding in human plasma.
A stereoselective reversed-phase high-performance liquid chromatography (HPLC) assay to determine the enantiomers of flurbiprofen, ketoprofen and etodolac in human plasma was developed. Chiral drug enantiomers were extracted from human plasma with liquid-liquid extraction. Then flurbiprofen and ketoprofen enantiomers reacted with the acylation reagent thionyl chloride and pre-column chiral derivatization reagent (S)-(-)-alpha-(1-naphthyl)ethylamine (S-NEA), and etodolac enantiomers reacted with S-NEA using 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBT) as coupling agents. The derivatized products were separated on an Agilent Zorbax C18 (4.6 mm x 250 mm, 5 microm) column with a mixture of acetonitrile-0.01 mol.L(-1) phosphate buffer (pH 4.5) (70:30, v/v) for flurbiprofen enantiomers, acetonitrile-0.01 mol.L(-1) phosphate buffer (pH 4.5) (60:40, v/v) for ketoprofen enantiomers and methonal-0.01 mol.L(-1) potassium dihydrogen phosphate buffer (pH 4.5) (88:12, v/v) for etodolac enantiomers as mobile phase. The flow of mobile phase was set at 0.8 mL.min(-1) and the detection wavelength of UV detector was set at 250 nm for flurbiprofen and ketoprofen enantiomers and 278 nm for etodolac enantiomers. The assay was linear from 0.5 to 50 microg.mL(-1) for each enantiomer. The inter- and intra-day precision (R.S.D.) was less than 10% and the average extraction recovery was more than 87% for each enantiomer. The limit of quantification for the method was 0.5 microg.mL(-1) (R.S.D.<10%, n=5). The method developed was used to study the drug-protein binding of flurbiprofen, ketoprofen and etodolac enantiomers in human plasma. The results showed that the stereoselective binding of etodolac enantiomer was observed and flurbiprofen and ketoprofen enantiomers were not.


Outcome of Patients With Severe Aortic Stenosis and Normal Coronary Arteries Undergoing Transcatheter Aortic Valve Implantation.
Coronary artery disease and severe aortic stenosis (AS) often coexist. This study sought to investigate the impact of normal coronary arteries as negative risk marker in patients undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI were dichotomized according to the presence or absence of normal coronary arteries, defined as absence of coronary lesions with diameter stenosis ≥30% in vessels ≥1.5 mm in diameter on coronary angiogram in patients without prior coronary revascularization. The primary end point was 1-year mortality. Out of 987 patients with severe AS undergoing TAVI, 258 (26%) patients had normal coronary arteries. These patients were younger, more likely women, and had lower EuroSCORE II and STS risk scores. Although mortality at 30 days was similar in the normal coronary artery and the coronary atherosclerosis groups (3.1% vs 5.6%, p = 0.11), it was lower in those with normal coronary arteries at 1 year (8.9% vs 17%, p = 0.003). In multivariable analysis, the presence of normal coronary arteries on coronary angiogram independently predicted 1-year mortality (adjusted HR 0.57, 95% CI 0.37 to 0.90, p = 0.02). In conclusion, this study defined normal coronary arteries as negative risk marker in patients with severe AS undergoing TAVI.


Erythrocyte biochemistry of the grey-headed fruit bat (Pteropus poliocephalus).
1. Several haematological and biochemical parameters were measured in the erythrocytes of the grey-headed fruit bat. 2. The level of 2,3-diphosphoglycerate was almost twice that found in human erythrocytes. Similarly pyruvate kinase activity was more than twice that of man. 3. The activities of other enzymes of the glycolytic pathway were similar to those found in man. 4. The level of reduced glutathione (GSH) and the GSH regeneration rate in the erythrocytes of the bat were comparable to those found in man.


V79 Chinese hamster cells deacetylate trans-N-acetoxy-4-acetylaminostilbene and trans-N-hydroxy-4-acetylaminostilbene to mutagenic and cytotoxic metabolites.
The N-acetoxy and N-hydroxy derivatives of trans-4-acetylaminostilbene (AAS) were demonstrated to induce gene mutations at the hgprt locus and to be cytotoxic in V79 cells. These cells deacetylated AAS. Paraoxon inhibited the deacetylation of AAS by more than 99% and reduced the mutagenicity and cytotoxicity of N-hydroxy-AAS and N-acetoxy-AAS to about one-tenth. Hence, deacetylated metabolites, formed by the target cells, were important for the observed biological effects.


Fixed reconstructions in partially edentulous patients using two-part ITI implants (Bonefit) as abutments.
Fixed reconstructions on implant abutments may be a welcome modality in the treatment of partially edentulous patients following the principles of a prophylactically oriented comprehensive care. The option to create artificial tissue integrated abutments widens the range of indications for fixed reconstructions. Risky long-span bridges as well as the preparation of intact teeth for bridge abutments may frequently be avoided. Never should the contours of the prosthesis interfere with the patient's performance of optimal plaque control. Furthermore, supportive periodontal therapy with regular maintenance visits must be provided to optimize a long-term prognosis of the dention as well as the tissue-integrated artificial abutments.


Office ultrasound should be the first-line investigation for confirmation of correct ESSURE placement.
Hysteroscopic options for permanent birth control (PBC), such as the ESSURE device, are becoming increasingly popular as an alternative to laparoscopic tubal ligation. The success of the technique hinges upon correct device placement within the intramural portion of the fallopian tube. To determine the utility of office ultrasound for confirming correct ESSURE PBC device placement at the 3-month check in a general gynaecology practice. The first 99 patients in a single centre following ESSURE PBC device placement. Prospective cohort study. Clinical data was reviewed from patient records, both from the time of the initial procedure and from the follow-up at 3 months. All women underwent an ultrasound at the 3-month check. The ESSURE PBC devices were placed successfully in 84.8% of cases. Of those cases with apparently successful placement, office ultrasound alone confirmed correct device placement at the 3-month check in 94% of cases. Further imaging was needed in only 6% of cases. Office ultrasound performed by the general gynaecologist at the 3-month check is more convenient for the patient, and is sufficient to confirm ESSURE PBC device placement in the vast majority of cases. We propose that the protocol for ESSURE PBC device follow-up should be altered to replace X-ray with ultrasound as the first-line investigation.


A review of nasolabial flaps for intra-oral defects.
The nasolabial flap has been used in 23 patients for reconstruction of moderate size intra-oral defects. Versatility in design of the flap is allowed by the numerous blood vessels supplying the nasolabial skin. Flap vascularity was reliable, there being no cases of total loss and three cases (12%) of partial necrosis. Recurrence of tumour occurred in 8.7% of cases and in those operated in the first instance for recurrence, there was no further local disease. There were minor problems of intra-oral hair growth, donor site distortion and obstructive sialadenopathy. However, because of its simple elevation, proximity to the defect and versatility, we believe that the nasolabial skin flap is a useful procedure for closure of selected intra-oral defects.


mTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters.
Chemotherapy can eradicate a majority of cancer cells. However, a small population of tumor cells often survives drug treatments through genetic and/or non-genetic mechanisms, leading to tumor recurrence. Here we report a reversible chemoresistance phenotype regulated by the mTOR pathway. Through a genome-wide CRISPR knockout library screen in pancreatic cancer cells treated with chemotherapeutic agents, we have identified the mTOR pathway as a prominent determinant of chemosensitivity. Pharmacological suppression of mTOR activity in cancer cells from diverse tissue origins leads to the persistence of a reversibly resistant population, which is otherwise eliminated by chemotherapeutic agents. Conversely, activation of the mTOR pathway increases chemosensitivity in vitro and in vivo and predicts better survival among various human cancers. Persister cells display a senescence phenotype. Inhibition of mTOR does not induce cellular senescence per se, but rather promotes the survival of senescent cells through regulation of autophagy and G2/M cell cycle arrest, as revealed by a small-molecule chemical library screen. Thus, mTOR plays a causal yet paradoxical role in regulating chemotherapeutic response; inhibition of the mTOR pathway, while suppressing tumor expansion, facilitates the development of a reversible drug-tolerant senescence state.


Hyperglycemia and downregulation of caveolin-1 enhance neuregulin-induced demyelination.
Neuregulins (NRGs) are growth factors which bind to Erb receptor tyrosine kinases that localize to Schwann cells (SCs). Although NRGs can promote cell survival, mitogenesis, and myelination in undifferentiated SCs, they also induce demyelination of myelinated co-cultures of SCs and dorsal root ganglion (DRG) neurons. We have shown previously that Erb B2 activity increased in premyelinating SCs in response to hyperglycemia, and that this correlated with the downregulation of the protein caveolin-1 (Cav-1). As myelinated SCs undergo substantial degeneration in diabetic neuropathy, we used myelinated SC/DRG neuron co-cultures to determine if hyperglycemia and changes in Cav-1 expression could enhance NRG-induced demyelination. In basal glucose, NRG1 caused a 2.4-fold increase in the number of damaged myelin segments. This damage reached 3.8-fold under hyperglycemic conditions, and was also associated with a robust decrease in the expression of Cav-1 and compact myelin proteins. The loss of Cav-1 and compact myelin proteins following hyperglycemia and NRG treatment was not due to neuronal loss, since the axons remained intact and there was no loss of PGP 9.5, an axonal marker protein. To examine if changes in Cav-1 were sufficient to alter the extent of NRG-induced demyelination, SC/DRG neurons co-cultures were infected with antisense or dominant-negative Cav-1(P132L) adenoviruses. Either antisense-mediated downregulation or mis-localization of endogenous Cav-1 by Cav-1(P132L) resulted in a 1.5- to 2.4-fold increase in NRG-induced degeneration compared to that present in control cultures. These data support that hyperglycemia and changes in Cav-1 are sufficient to sensitize myelinated SC/DRG co-cultures to NRG-induced demyelination.


Changes in rural older adults' sedentary and physically-active behaviors between a non-snowfall and a snowfall season: compositional analysis from the NEIGE study.
Levels of physical activity change throughout the year. However, little is known to what extent activity levels can vary, based on accelerometer determined sedentary and physically-active time. The aim of this longitudinal study was to examine older adults' activity changes from a non-snowfall season to a subsequent snowfall season, with consideration of the co-dependence of domains of time use. Participants were 355 older Japanese adults (53.1% women, aged 65-84 years) living in a rural area of heavy snowfall who had valid accelerometer (Active style Pro HJA-750C) data during non-snowfall and snowfall seasons. Activity was classified as sedentary behavior (SB), light-intensity PA (LPA), and moderate-to-vigorous PA (MVPA). Compositional changes from the non-snowfall to the snowfall season were analyzed using Aitchison's perturbation method. The ratios of each component in the composition, such as [SBsnow/SBnon-snow, LPAsnow/LPAnon-snow, MVPAsnow/MVPAnon-snow] for seasonal changes, were calculated and were then divided by the sum of these ratios. In men, the percentages of time spent in each activity during the non-snowfall/snowfall seasons were 53.9/64.6 for SB; 40.8/31.6 for LPA; and 5.3/3.8 for MVPA; these corresponded to mean seasonal compositional changes (∆SB, ∆LPA, ∆MVPA) of 0.445, 0.287, and 0.268 respectively. In women, the percentages of time spent in each activity during the non-snowfall/snowfall seasons were 47.9/55.5 for SB; 47.9/41.0 for LPA; and 4.2/3.5 for MVPA; these corresponded to mean seasonal compositional changes (∆SB, ∆LPA, ∆MVPA) of 0.409, 0.302, and 0.289 respectively. The degree of seasonal change was greatest in men. In older adults, activity behaviors were changed unfavorably during snowfall season, particularly so for men. The degree of seasonal change was greatest for SB. Development of strategies to keep rural older adults active during the snowfall season may be needed for maintaining a consistently-active lifestyle for their health.


Expressions of Notch signalling pathway members during early pregnancy in mice.
Although pregnancy is initiated and maintained through highly complex mechanisms, it is essential to understand the events that occur before and during early pregnancy to understand a healthy implantation process. The Notch signal, thought to be involved in this process, is frequently the subject of research with its different aspects. To better understand the role of Notch signaling in the peri-implantation period of the mouse uterus, we investigated the state of expression and localization of Notch 3, Notch 4, Rbp-J, Hes1, Hes7, Hey2, HeyL, and Fbw7 in the uterus and implantation sites in early pregnancy. Balb/C mice were divided into groups D1, D4, D5, D6, and D8. For D5 and D6 groups, implantation sites were identified by intravenous injection of Chicago blue. IHC, WB, and QRT-PCR methods were used. Notch 3 was very strong positive on the 4th day of pregnancy. Notch 4 was highly expressed on days 4, 5, 6, and 8 of pregnancy when P4 levels were high. Hes 1 level was at the lowest on the 4th day of pregnancy. Hes 7 protein expression gradually increased from D1 to D8 in the uteri and implantation sites. Hey 2 expression was at the highest level on the 1st and 4th days. Hey L expression was on the apical of the glands. Fbxw7 that expression was high on the 1st and 4th days of pregnancy. Notch signaling may play an essential role in regulating endometrial receptivity. In addition, our Hes7 results are new to the literature.


A variant form of 2-methyl-3-hydroxybutyric and 2-methylacetoacetic aciduria.
A new case of assumed beta-ketothiolase deficiency, excreting 2-methyl-3-hydroxybutyrate and tiglylglycine is described in a 15-year-old boy. The patient presented with episodes of metabolic acidosis following intercurrent infections in the early childhood. After the age of 7 years he has had periods of headache, but no acidotic episodes have occurred even during infections. Systematic dietary treatment has not been instituted, and the patient is physically and mentally normal. This indicates a mild variant of the beta-ketothiolase deficiency. Diagnosis of the condition may be obscured by large quantities of ordinary ketone bodies, and requires gas chromatographic and mass spectrometric techniques.


Modest intracellular acidification suppresses death signaling in ouabain-treated cells.
The signaling cascade resulting in the death of several types of cells treated with ouabain or other cardiotonic steroids (CTS) remains poorly understood. Recently, we observed that ouabain kills epithelial and endothelial cells via its interaction with Na(+), K(+) -ATPase, but independently of inhibition of Na(+), K(+) -ATPase-mediated ion fluxes and inversion of the [Na(+)](i)/[K(+)](i) ratio. Here, we report that the death of ouabain-treated epithelial cells from the Madin-Darby canine kidney (C7-MDCK) and endothelial cells from porcine aortae is suppressed by acidification of medium from pH 7.4 to 7.0, i.e. under conditions when pH(i) was decreased from approximately 7.2 to 6.9. The rescue of ouabain-treated C7-MDCK cells was also detected under selective intracellular acidification caused by inhibition of Na(+)/H(+) exchanger. In these cells, neither Na(+), K(+) pump activity nor [(3)H]-ouabain binding was significantly affected by modest acidification. The death of ouabain-treated cells was independent of inhibition of RNA and protein synthesis with actinomycin D and cycloheximide. In contrast, both compounds sharply attenuated the protective action of acidified medium. Thus, our results show that very modest intracellular acidification is sufficient to inhibit the Na(+) (i)/K(+) (i)-independent death signal triggered in epithelial and endothelial cells by CTS. They also suggest that the protective action of acidification is mediated by de novo expression of genes involved in inhibition of the cell death machinery.


Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor-Positive/ERBB2-Positive Early Breast Cancer: The Neoadjuvant WSG-TP-II Randomized Clinical Trial.
Combination of chemotherapy with (dual) ERBB2 blockade is considered standard in hormone receptor (HR)-positive/ERBB2-positive early breast cancer (EBC). Despite some promising data on endocrine therapy (ET) combination with dual ERBB2 blockade in HR-positive/ERBB2-positive BC, to our knowledge, no prospective comparison of neoadjuvant chemotherapy vs ET plus ERBB2 blockade in particular with focus on molecular markers has yet been performed. To determine whether neoadjuvant de-escalated chemotherapy is superior to endocrine therapy, both in combination with pertuzumab and trastuzumab, in a highly heterogeneous HR-positive/ERBB2-positive EBC. This prospective, multicenter, neoadjuvant randomized clinical trial allocated 207 patients with centrally confirmed estrogen receptor-positive and/or progesterone receptor-positive (>1%) HR-positive/ERBB2-positive EBC to 12 weeks of standard ET (n = 100) vs paclitaxel (n = 107) plus trastuzumab and pertuzumab. A total of 186 patients were required to detect a statistically significant difference in pathological complete response (pCR) (assumptions: 19% absolute difference in pCR; power, ≥80%; 1-sided Fisher exact test, 2.5% significance level). Standard ET (aromatase inhibitor or tamoxifen) or paclitaxel, 80 mg/m2, weekly plus trastuzumab and pertuzumab every 21 days. The primary end point was pCR (ypT0/is, ypN0). Secondary end points included safety, translational research, and health-related quality of life. Omission of further chemotherapy was allowed in patients with pCR. PAM50 analysis was performed on baseline tumor biopsies. Of the 207 patients included (median [range] age, 53 [25-83] years), 121 (58%) had cT2 to cT4 tumors, and 58 (28%) had clinically node-positive EBC. The pCR rate in the ET plus trastuzumab and pertuzumab arm was 23.7% (95% CI, 15.7%-33.4%) vs 56.4% (95% CI, 46.2%-66.3%) in the paclitaxel plus trastuzumab and pertuzumab arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P < .001). Both immunohistochemical ERBB2 score of 3 or higher and ERBB2-enriched subtype were independent predictors for pCR in both arms. Paclitaxel was superior to ET only in the first through third quartiles but not in the highest ERBB2 quartile by messenger RNA. In contrast with the paclitaxel plus trastuzumab and pertuzumab arm, no decrease in health-related quality of life after 12 weeks was observed in the ET plus trastuzumab and pertuzumab arm. The WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing 2 neoadjuvant de-escalation treatments in HR-positive/ERBB2-positive EBC and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after ET plus trastuzumab and pertuzumab. ClinicalTrials.gov Identifier: NCT03272477.


Learning from history of natural disasters in the Sahel: a comprehensive analysis and lessons for future resilience.
One of the first environmental crises to attract interest in development initiatives and aid was the great drought of the 1970s in the Sahel. This study investigates the extent of damage caused by natural disasters from one of the most widely used databases-EM-DAT-with a sample size of 16 Sahelian countries over the period 1960-2020. These countries have been divided into three regions: Western Africa Sahel (WAS), Central Africa Sahel (CAS), and Eastern Africa Sahel (EAS). The analyses encompass four categories of natural hazards, namely, biological, climatological, hydrological, and meteorological. We used descriptive and test statistics to summarize the natural disaster records. Through this approach, we explore tendencies to identify the most frequently reported natural hazards; we examine their spatial distribution and evaluate their impacts in terms of socioeconomic damage and causalities. During the study period, a total of 1000 events were recorded in the database. The Western Africa Sahel (WAS) region had the highest number of disasters, with 476 events, followed by the Eastern Africa Sahel (EAS) region with 369 events. The most common hazards in the Sahel were hydrological (41.8%), mainly floods, and biological (39.5%) hazards. Approximately 300 million people in the Sahel were affected by natural hazards, with 59.17% in EAS, 36.48% in WAS, and 4.35% in CAS. Although droughts occurred less frequently (14%), they had a significant impact on the population, affecting 84% of those affected by natural hazards. In general, EAS experiences a higher impact from natural hazards, potentially influenced by the pastoral lifestyle of its population. However, WAS is also very vulnerable to natural hazards especially epidemics and nowadays floods. The uncontrolled urbanization in the area may contribute to this vulnerability.


Evidence for a specific regulation of recA gene transcription in Escherichia coli.
The kinetics of the recA, sfiA and umuDC genes transcription were studied during a double SOS-inducing treatment in Escherichia coli cells using several strains carrying lacZ gene fusions. A transient inhibition in recA, but not in sfiA or umuDC promoted beta-galactosidase synthesis was detected after successive UV-irradiations. Results obtained with a recA--lacZ fusion introduced in several DNA-repair mutants demonstrated that neither a lower LexA inactivation nor a decrease in the production of the inducing signal are the events through which the successive UV-irradiation promoted the arrest of recA transcription. On the contrary, a specific UV-dose-dependent delay appears to be the reason for the inhibition of the recA gene transcription in cells irradiated twice.