Heterogeneity and organization of the ribosomal RNA genes of Cucurbita maxima.
Thirty-six clones were recovered from Cucurbita maxima genomic DNA which had been enriched for rDNA and cleaved at the unique repeat unit Hind III site. Twenty-nine of these, which contain complete rDNA units, were compared to a standard whose intergenic spacer (IGS) nucleotide sequence has been determined. Twenty-one are identical in length and restriction site pattern. Eight which differ from the standard in length do so because of addition or deletion of varying numbers of IGS subrepetitive units of two different classes, with four of the length variants being different in both of these classes. Seven clones were isolated which contain incomplete repeat units, six of which are composites of rDNA and non-rDNA material. They have been cleaved at the unique rDNA Hind III site at one end and at a non-rDNA Hind III site at the other. We consider it most likely that these are derived from the termini of repeat unit tandem arrays, although other explanations are possible. Twelve individual plants of two different cultivars were examined for heterogeneity of IGS length distribution. They all appear to be identical in this regard.


Maintenance of resting energy expenditure after weight loss in premenopausal women: potential benefits of a high-protein, reduced-calorie diet.
The number of contemporary diet plans promoting high protein intakes for weight management has increased dramatically. Complementing this dietary approach with increased physical activity has proven to be beneficial. Recent studies have suggested that protein intakes in excess of the current Recommended Dietary Allowance (0.8 g/kg) may be of metabolic benefit during weight loss. This investigation assessed changes in resting energy expenditure and substrate oxidation in overweight and obese premenopausal women in response to a weight loss intervention that combined a high-protein, reduced-calorie diet with increased physical activity. Thirty-nine overweight and obese premenopausal women (age, 30.9 +/- 1.5 years; body mass index, 30.2 +/- 0.5 kg/m2) participated in a 10-week weight loss program in which they ate a reduced-calorie diet for which protein provided 30% of total energy and approximated 1.4 g/kg. Subjects incrementally increased physical activity (ie, steps walking) throughout the diet intervention period. Resting energy expenditure, substrate oxidation, and body composition were assessed before (PRE) and after (POST) the 10-week weight loss program. Subjects experienced a 5% decrease in body weight, with significant decreases in both fat mass (PRE, 35.5 +/- 1.2 kg; POST, 32.4 +/- 1.1 kg; P < .0001) and fat-free mass (PRE, 44.6 +/- 0.7 kg; POST, 43.6 +/- 0.7 kg; P < .0001). Changes in body weight or body composition did not alter resting energy expenditure. Protein oxidation increased (PRE, 18% +/- 1%; POST, 20% +/- 1%; P < .05) and fat oxidation decreased (PRE, 37% +/- 3%; POST, 30% +/- 3%; P < .05) after the 10-week intervention. These findings illustrate that a weight loss intervention combining consumption of a high-protein, reduced-calorie diet with increased physical activity promotes weight loss without negatively impacting resting energy expenditure in this population of women.


Studies on Xenopus immunoglobulins using monoclonal antibodies.
Monoclonal antibodies raised against Xenopus Ig recognize antigenic determinants on IgM and low mol. wt Ig (LMW Ig or IgY ). On SDS-PAGE two forms of mu were distinguished in the supernatant and cell lysate of tunicamycin-treated spleen cell culture. The two bands of v observed in serum appear to be the result of carbohydrate heterogeneity. The light chains resolved into two distinct bands which differed in peptide maps; the more slowly migrating band of light chain was preferentially associated with v. Patterns of cross-reactivity between the immunoglobulins of 11 species of Xenopus and three subspecies of Xenopus laevis were obtained; the polymorphism of mu and v antigenic determinants and its implications for species divergence are discussed.


Resistant starch modulates in vivo colonic butyrate uptake and its oxidation in rats with dextran sulfate sodium-induced colitis.
We previously demonstrated improvements of colonic lesions due to dextran sulfate sodium (DSS) in rats after 7 d of supplementation with resistant starch (RS) type 3, a substrate yielding high levels of butyrate (C(4)), a colonic cell fuel source. In the present study, we hypothesized that if inflammation is related to decreased C(4) utilization by the colonic mucosa, RS supplementation should restore C(4) use simultaneously with an increase in the amount of C(4) present in the digestive tract. Hence, we compared, in vivo, the cecocolonic uptake of C(4) and its oxidation into CO(2) and ketone bodies in control and DSS-treated rats fed a fiber-free basal diet (BD) or a RS-supplemented diet. Sprague-Dawley rats (n = 60) were used. DSS treatment was performed to induce acute colitis and then to maintain chronic colitis. After cecal infusion of [1-(13)C]-C(4) (20 micro mol in 1 h), concentrations and (13)C-enrichment of C(4), ketone bodies, and CO(2) were quantified in the abdominal aorta and portal vein. Portal blood flow was recorded. During acute colitis, (13)C(4) uptake and (13)CO(2) production were lower in DSS rats than in controls. During chronic colitis, DSS rats did not differ from controls. After 7 d of chronic colitis, RS-DSS rats exhibited the same C(4) uptake as BD-DSS rats in spite of higher C(4) cecocolonic disposal. After 14 d, C(4) uptake was higher in RS-DSS than in BD-DSS rats. Thus, the increased utilization of C(4) by the mucosa is subsequent to evidence of healing and appears to be a consequence rather than a cause of this RS healing effect.


The Impact of Preoperative Immune Modulating Nutrition on Outcomes in Patients Undergoing Surgery for Gastrointestinal Cancer: A Systematic Review and Meta-analysis.
To define the influence of preoperative immune modulating nutrition (IMN) on postoperative outcomes in patients undergoing surgery for gastrointestinal cancer. Although studies have shown that perioperative IMN may reduce postoperative infectious complications, many of these have included patients with benign and malignant disease, and the optimal timing of such an intervention is not clear. The Embase, Medline, and Cochrane databases were searched from 2000 to 2018, for prospective randomized controlled trials evaluating preoperative oral or enteral IMN in patients undergoing surgery for gastrointestinal cancer. The primary endpoint was the development of postoperative infectious complications. Secondary endpoints included postoperative noninfectious complications, length of stay, and up to 30-day mortality. The analysis was performed using RevMan v5.3 software. Sixteen studies reporting on 1387 patients (715 IMN group, 672 control group) were included. Six of the included studies reported on a mixed population of patients undergoing all gastrointestinal cancer surgery. Of the remaining, 4 investigated IMN in colorectal cancer surgery, 2 in pancreatic surgery, and another 2 in patients undergoing surgery for gastric cancer. There was 1 study each on liver and esophageal cancer. The formulation of nutrition used in all studies in the treated patients was Impact (Novartis/Nestlé), which contains ω-3 fatty acids, arginine, and nucleotides. Preoperative IMN in patients undergoing surgery for gastrointestinal cancer reduced infectious complications [odds ratio (OR) 0.52, 95% confidence interval (CI) 0.38-0.71, P < 0.0001, I = 16%, n = 1387] and length of hospital stay (weighted mean difference -1.57 days, 95% CI -2.48 to -0.66, P = 0.0007, I = 34%, n = 995) when compared with control (isocaloric isonitrogeneous feed or normal diet). It, however, did not affect noninfectious complications (OR 0.98, 95% CI 0.73-1.33, P = 0.91, I = 0%, n = 1303) or mortality (OR 0.55, 95% CI 0.18-1.68, P = 0.29, I = 0%, n = 955). Given the significant impact on infectious complications and a tendency to shorten length of stay, preoperative IMN should be encouraged in routine practice in patients undergoing surgery for gastrointestinal cancer.


Discrimination of the toxic potential of chemically differing topical glucocorticoids using a neutral red release assay with human keratinocytes and fibroblasts.
In inflammatory skin disease, hydrocortisone and prednisolone double esters are about equipotent to conventional medium potency topical glucocorticoids, such as betamethasone valerate. Local adverse effects, in particular skin atrophy, are a potential problem with topical glucocorticoids. Recently, cell cultures have shown promise as a means of assessing local tolerance. To investigate the toxic potential of hydrocortisone, hydrocortisone-17-butyrate, hydrocortisone aceponate, prednicarbate, triamcinolone acetonide, betamethasone valerate and desoximethasone, human keratinocytes and fibroblasts were exposed to these agents in vitro, using a modified neutral red release assay. In addition, the morphology of these cells was assessed by light microscopy. Although all the topical glucocorticoids tested proved toxic to both cell types, there were major differences between glucocorticoids in their effect on fibroblasts. Hydrocortisone and the non-halogenated double-ester-type glucocorticoids were less toxic than the conventional medium potency topical glucocorticoids tested (betamethasone valerate and desoximethasone). In particular, hydrocortisone aceponate was less toxic than betamethasone valerate (P < or = 0.05). In general, the effect of topical glucocorticoids on the cells, based on neutral red release, was more marked with keratinocytes than with fibroblasts. Although the ranking order with respect to the toxic potential was similar, a clear-cut difference was not observed between non-halogenated double-ester-type glucocorticoids and betamethasone valerate. Morphological changes due to glucocorticoid exposure followed the same pattern with both keratinocytes and fibroblasts. The neutral red release assay is able to discriminate between the cytotoxic effects of chemically differing topical glucocorticoids on human keratinocytes and fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)


[Analgesic effect and gastro-intestinal motility inhibitory action of 3-hydroxy-4-methoxy-acetophenone from Cynanchum paniculatum (Bunge) Kitagawa].
3-Hydroxy-4-methoxy-acetophenone (HMA) isolated from Cynanchum paniculatum was found to have analgesic effect and inhibitory action on the gastro-intestinal motility. The effect and action were equivalent to that of paeonol, HMA displayed a very low degree of antibacterial activity against Escherichia coli and Shigella flexneri.


Rational engineering of cofactor specificity of glutamate dehydrogenase for poly-γ-glutamic acid synthesis in Bacillus licheniformis.
Poly-γ-glutamic acid (γ-PGA) is a multifunctional biopolymer mainly produced by Bacillus. The cofactor specificity of enzymes plays a critical role in regulating metabolic process and metabolite production. Here, we present a novel approach for switching cofactor specificity of glutamate dehydrogenase RocG from nicotinamide adenine dinucleotide phosphate (NADPH) to nicotinamide adenine dinucleotide (NADH) to improve γ-PGA production. Firstly, 3D structural modeling and molecular docking were performed to predict the binding modes of NADH and NADPH. Several site-specific mutants based on the conventional and Random Accelerated Molecular Dynamics simulations were obtained to alter cofactor specificity. Then, the effects of RocG variants overexpressions on γ-PGA production were evaluated. Compared to the wild-type, the mutant RocGD276E showed highest increase in γ-PGA yield, increased by 40.50%. Meanwhile, yields of main by-products acetoin and 2,3-butandieol were decreased by 21.70% and 16.53%, respectively. Finally, the results of enzymatic properties confirmed that glutamate dehydrogenase mutant RocGD276E exhibited the higher affinity for NADH, caused a shift in coenzyme preference from NADPH to NADH, with a catalytic efficiency comparable with NADPH-dependent RocG. Taken together, this research demonstrated that switching the cofactor preference of glutamate dehydrogenase via rational design was an effective strategy for high-level production of γ-PGA in Bacillus licheniformis.


Immunomodulatory and immunoregulatory nanomedicines for autoimmunity.
Autoimmune diseases, caused by cellularly and molecularly complex immune responses against self-antigens, are largely treated with broad-acting, non-disease-specific anti-inflammatory drugs. These compounds can attenuate autoimmune inflammation, but tend to impair normal immunity against infection and cancer, cannot restore normal immune homeostasis and are not curative. Nanoparticle (NP)- and microparticle (MP)-based delivery of immunotherapeutic agents affords a unique opportunity to not only increase the specificity and potency of broad-acting immunomodulators, but also to elicit the formation of organ-specific immunoregulatory cell networks capable of inducing bystander immunoregulation. Here, we review the various NP/MP-based strategies that have so far been tested in models of experimental and/or spontaneous autoimmunity, with a focus on mechanisms of action.


Translation of glucocorticoid receptor mRNA in vitro yields a nonactivated protein.
The glucocorticoid receptor is present in cytosol prepared from cell extracts of nonhormone-treated cells as a large nonactivated (i.e. non-DNA binding) 9 S heteromeric complex which contains the Mr approximately 90,000 heat shock protein, hsp90. hsp90 is expressed under physiological conditions in mammalian cells and is also present in reticulocyte lysate, as assessed by Western immunoblotting using specific anti-hsp90 antibodies. We have translated glucocorticoid receptor mRNA in reticulocyte lysates. The receptor synthesized under cell-free conditions also interacts with hsp90 both in the presence and absence of ligand, as determined by sucrose gradient centrifugation. The in vitro synthesized glucocorticoid receptor does not bind to DNA-cellulose but can be converted to a DNA binding form following labeling with dexamethasone and heat treatment. Thus, the glucocorticoid receptor is synthesized in a nonactivated form under cell-free conditions. These data indicate that the 9 S glucocorticoid receptor complex found in cytosol does not represent an artifact due to cell homogenization and supports the existence in vivo of the glucocorticoid receptor-hsp90 complex.


Persisting signs of disease activity at Magnetic Resonance Enterocolonography predict clinical relapse and disease progression in quiescent Crohn's disease.
Deep remission including clinical remission and tissue healing has been advocated as the therapeutic target in Crohn's disease. Yet, the definition of deep remission remains unclear. The aim of this study was to assess the persisting lesions at magnetic resonance enterocolonography (MREC) in clinically quiescent Crohn's disease as well as their relapse predictive value. we performed a prospective monocentre cohort study. We included patients with clinical remission. At baseline, these patients had blood tests, the measurement of fecal calprotectin and underwent a MREC. They were then followed up clinically for a minimum of 1 year. A relapse was defined by a HBI > 4 with an increase of at least 3 points. Correlations between clinical, demographic, biological parameters and MREC signs were assessed as well as the time-to-relapse predictive value of the studied variables. Twenty seven patients were recruited. Fourteen out of 27 had persisting disease activity at MREC. MREC signs only partly correlated with biomarkers. Ten out of 27 patients relapsed over a median follow up of 25 months. In univariate analysis, relative contrast enhancement of the most affected segment (HR: 2.56; P = 0.046), ulcers (HR: 12.5; P = 0.039), fistulas (HR: 14.1; P = 0.009) and target sign (HR: 3.63; P = 0.049) were associated with relapse. In multivariate analysis, fistula was the only one. Half of the patients with clinically quiescent Crohn's disease had persisting signs of disease activity at MREC. These signs predicted time-to-relapse.


Antimicrobial photodynamic therapy in dentistry using an oil-in-water microemulsion with curcumin as a mouthwash.
Antimicrobial photodynamic therapy (PDT) has emerged as an alternative therapeutic strategy to conventional procedures using antibiotics. A mouthwash based on a microemulsion with curcumin for disinfecting the oral cavity in combination with PDT was developed. A pseudo-ternary phase diagram was constructed to select the microemulsion, and a physicochemical characterization of the selected formulation was performed. Curcumin was quantified using spectrophotometry. The stability of the formulation with curcumin was evaluated after storage for 60 days at 40 °C, and the in vitro effectiveness of the formulation associated with PDT was evaluated using a light-emitting diode at 430 nm (blue) with two irradiation times (10 and 30 min) on biofilms of Candida albicans, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. The formulation registered a pH of 6.24, apparent viscosity of 1.64 cP, Newtonian rheological behavior, droplet size of 14 ± 1 nm, polydispersity index of 0.151, and zeta potential of -7.7 mV. The preparation remained stable after storage for 60 days. There was a significant CFU. mL-1 reduction in all tested microorganisms after treatment combining PDT and curcumin microemulsion (30 or 60 μg.mL-1), and the largest reductions were 5.6175 log10 CFU. mL-1 in E. coli (10' and 30', both with 30 μg.mL-1); 5.181 log10 CFU. mL-1 in MRSA (30' and 30 μg.mL-1); and 3.497 log10 CFU. mL-1 in C. albicans (30' and 60 μg.mL-1). The formulation containing curcumin in combination with antimicrobial PDT showed promising results in vitro, and this potential formulation awaits further evaluation in clinical trials.


Carbon monoxide (CO) derived from the CO-releasing molecule CORM-2 reduces peritoneal adhesion formation in a rat model.
Although low-dose carbon monoxide (CO) administration has been shown to have an anti-fibrotic effect in various fibrotic diseases, its effects on peritoneal adhesion (PA), one of the postoperative complications, are not elucidated. In this study, the effect of CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2) administration on the formation of PA and the underlying factors of its potential effect were investigated. After the induction of PA, rats were divided into four groups with 8 rats in each group. The rats received either (i) dimethyl sulfoxide:saline solution (1:10) as a vehicle, (ii) 2.5 mg/kg CORM-2, (iii) 5 mg/kg CORM-2, or (iv) inactive (i) CORM (iCORM) intragastrically every day for a duration of 7 days. PA was not induced in rats (n = 8) designated as sham controls. Gross, histological, immunohistochemical and quantitative real-time polymerase chain reaction analyses were performed to evaluate the effectiveness of CORM-2 administration. Gross analysis showed that CORM-2 administration reduced PA formation compared to rats treated with vehicle. Histological and immunohistochemical examinations showed that increased collagen deposition, myofibroblast accumulation, microvessel density, and M1 macrophage count in the peritoneal fibrosis area of vehicle-treated rats decreased following CORM-2 treatments. PCR analyses showed that CORM-2 treatments decreased hypoxia-induced Hif1a, profibrotic Tgfb1, ECM components Col1a1 and Col3a1, collagen degradation suppressor Timp1, fibrinolysis inhibitor Serpine1, and pro-inflammatory Tnf mRNA expressions, while increasing the M2 macrophage marker Arg1 mRNA expression. These results suggested that CORM-2 administration reduces PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis and fibrogenesis.


Micro/Nanoengineered α-Fe2 O3 Nanoaggregate Conformably Enclosed by Ultrathin N-Doped Carbon Shell for Ultrastable Lithium Storage and Insight into Phase Evolution Mechanism.
The Fe-based transition metal oxides are promising anode candidates for lithium storage considering their high specific capacity, low cost, and environmental compatibility. However, the poor electron/ion conductivity and significant volume stress limit their cycle and rate performances. Furthermore, the phenomena of capacity rise and sudden decay for α-Fe2 O3 have appeared in most reports. Here, a uniform micro/nano α-Fe2 O3 nanoaggregate conformably enclosed in an ultrathin N-doped carbon network (denoted as M/N-α-Fe2 O3 @NC) is designed. The M/N porous balls combine the merits of secondary nanoparticles to shorten the Li+ transportation pathways as well as alleviating volume expansion, and primary microballs to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors fast electron transfer and protects the electrode from electrolyte corrosion. Therefore, the M/N-α-Fe2 O3 @NC electrode delivers an excellent reversible capacity of 901 mA h g-1 with capacity retention up to 94.0 % after 200 cycles at 0.2 A g-1 . Notably, the capacity rise does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex situ XRD and HRTEM experiments. It is verified that the reversible phase transformation of α↔γ occurs during the first cycle, whereas only the α-Fe2 O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2 O3 electrodes.


Value of DCE-MRI for staging and response evaluation in rectal cancer: A systematic review.
Aim was to perform a systematic review to evaluate the clinical value of dynamic contrast-enhanced (DCE) MRI in rectal cancer. A systematic search was performed on Pubmed, Embase and the Cochrane library. Studies that evaluated DCE-MRI for tumour aggressiveness, primary staging and restaging after chemoradiation (CRT) were included. Information on population, DCE technique, DCE parameters and outcome (angiogenesis, staging and response) were extracted. 19 studies were identified; 10 evaluated quantitative analyses, 6 semiquantitative analyses and 3 evaluated both. 8 studies evaluated correlation between DCE-parameters and angiogenesis or tumour aggressiveness, 11 studies evaluated response prediction pre- and post-CRT. Semiquantitative washin parameters showed a significantly positive correlation with angiogenesis, while for quantitative analyses conflicting results were found. Conflicting results were also reported for the correlation between DCE parameters and tumour aggressiveness: both higher and lower vascularity in more aggressive tumours are reported, while some studies report no correlation. Six studies showed a predictive value of Ktrans for response. A high Ktrans pre-CRT was significantly correlated with a complete/good response, but the reported pre-CRT Ktrans varied substantially (0.36-1.93). After CRT a reduction in Ktrans of 32%-36% was significantly associated with response. For semiquantitative analyses pre-CRT late slope was reported to be significantly lower in good responders, however only few studies exist on semiquantitative analyses of post-CRT DCE-MRI. DCE-MRI in rectal cancer is promising mainly for prediction and assessment of response to CRT, where a high pre-CRT Ktrans and a decrease in Ktrans are significantly predictive for response.


Surgical risk factors for recurrence of inverted papilloma.
To identify variations in surgical technique that impact the recurrence of inverted papilloma following endoscopic excision. Retrospective cohort. Data from 127 consecutive patients who underwent endoscopic excision of inverted papilloma and oncocytic papilloma at a tertiary care medical center from 1998 to 2011 were reviewed. Patient demographics, comorbidities, tumor stage, and intraoperative details, including tumor location and management of the base, were evaluated to identify factors associated with tumor recurrence. Recurrence of papilloma occurred in 16 patients (12.6%). Mean time to recurrence was 31.0 months (range, 5.2-110.0 months). Mucosal stripping alone was associated with a recurrence rate of 52.2% (12/23 patients), compared to 4.9% (3/61 patients) when the tumor base was drilled, 4.7% (1/21 patients) when it was cauterized, and 0.0% (0/22 patients) when it was completely excised (P = .001). Increased recurrence rate was associated with tumors located in the maxillary sinus (P = .03), as well as the performance of endoscopic medial maxillectomy (P = .001) and external frontal approaches (P = .02). Drilling, cauterizing, or completely excising the bone underlying the tumor base during endoscopic resection reduces the recurrence rate of inverted and oncocytic papilloma, when compared to mucosal stripping alone. Surgeons who perform endoscopic resection of these tumors should consider utilization of these techniques when possible. 4.


Influence of acute and chronic administration of benzylamine on glucose tolerance in diabetic and obese mice fed on very high-fat diet.
The combination of vanadate plus benzylamine has been reported to stimulate glucose transport in rodent adipocytes and to mimic other insulin actions in diverse studies. However, benzylamine alone activates glucose uptake in human fat cells and increases glucose tolerance in rabbits. The aim of this work was to unravel the benzylamine antihyperglycemic action and to test whether its chronic oral administration could restore the defective glucose handling of mice rendered slightly obese and diabetic by very high-fat diet (VHFD). When VHFD mice were i.p. injected with benzylamine at 0.7 to 700 micromol/kg before glucose tolerance test, they exhibited reduced hyperglycemic response without alteration of insulin secretion. Whole body glucose turnover, as assessed by the glucose isotopic dilution technique, was unchanged in mice perfused with benzylamine (total dose of 75 micromol/kg). However, their in vivo glycogen synthesis rate was increased. Benzylamine appeared therefore to directly facilitate glucose utilisation in peripheral tissues. When given chronically at 2000 or 4000 micromol/kg/d in drinking water, benzylamine elicited a slight reduction of water consumption but did not change body weight or adiposity and did not modify oxidative stress markers. Benzylamine treatment improved glucose tolerance but failed to normalize the elevated glucose fasting plasma levels of VHFD mice. There was no influence of benzylamine ingestion on lipolytic activity, basal and insulin-stimulated glucose uptake, and on inflammatory adipokine expression in adipocytes. The improvement of glucose tolerance and the lack of adverse effects on adipocyte metabolism, reported here in VHFD mice allow to consider orally given benzylamine as a potential antidiabetic strategy which deserves to be further studied in other diabetic models.


Financial technology, industrial ecology and energy efficiency.
To achieve peak carbon neutrality, it is necessary to transform energy structures, promote industrial ecology, and enhance energy efficiency. Employing provincial panel data from 2011-2020, we empirically investigate the impact of financial technology on energy efficiency and the role of industrial ecology in the development of financial technology to enhance energy efficiency. The findings reveal that financial technology can significantly enhance energy efficiency and promote it by improving industrial ecology. Furthermore, industrial ecology can act as a crucial channel for financial technology to promote energy efficiency. Specifically, an increase of one standard deviation in financial technology is associated with a 33.1% surge in energy efficiency on average. Financial technology has made a significant contribution to the improvement of energy efficiency in all regions, albeit with regional heterogeneity. Under different threshold variables, financial technology exerts a facilitating effect on the enhancement of energy efficiency; the impact of financial technology on energy efficiency remains heterogeneous.


Factors influencing adolescent girls and young women's uptake of community-based PrEP services following home-based HIV testing in Eastern Cape, South Africa: a qualitative study.
Home-based service delivery has been used to improve access to HIV testing and antiretroviral initiation across sub-Saharan Africa, but it has yet to be leveraged to improve pre-exposure prophylaxis (PrEP) uptake. We interviewed 37 adolescent girls and young women (AGYW) in Eastern Cape, South Africa to explore why they chose to initiate PrEP or not following home-based HIV testing and referral for PrEP, and what influenced time to PrEP initiation. Participants reported that home visits provided a source of trusted information and a way to involve family members in their PrEP initiation decisions, motivating some to start PrEP. AGYW who initiated PrEP were more likely to qualitatively perceive themselves to be at high risk for HIV compared with those who never initiated PrEP. Integrating home-based HIV testing with PrEP education and referral may be a valuable way to reduce familial barriers and boost PrEP uptake among AGYW in South Africa. Trial registration: NCT03977181. Retrospectively registered on June 6, 2019.


Hospital workers' opinions on the predisposing factors to blood-related work accidents in Central Hospital, Benin City, Edo State, Nigeria.
Hospital workers are prone to accidental injuries during their day-to-day activities at work. These accidental injuries are of importance because many of these predispose the workers to blood-borne infections. A total of 242 hospital workers at Central Hospital, Benin City, Edo State participated in a cross-sectional study carried out between June and August 1999 aimed at finding out the predisposing factors to blood-related work accidents. The study group consisted of 53 doctors, 34 laboratory workers and 155 nurses. All doctors and laboratory workers at Central Hospital were involved in the study, while 50% of the nursing population were involved in the study. The nurses were selected using a stratified random sampling method. The respondents completed a pretested self-administered questionnaire. The results showed that the four main factors responsible for accidents among the hospital workers were: non-availability of protective measures; desire to hasten the procedure; type of procedure; and use of inadequate/inappropriate equipment. The major factor responsible for accidents at work among hospital workers was non-availability of protective measures. It is therefore recommended that adequate materials and equipment should be provided. This study could be further validated using a qualitative study design (focus group discussions).


Puerarin alleviates cadmium-induced rat neurocyte injury by alleviating Nrf2-mediated oxidative stress and inhibiting mitochondrial unfolded protein response.
Cadmium (Cd) is a highly neurotoxic environmental pollutant. Puerarin (Pur) is a natural antioxidant isolated from Kudzu root that exhibits a powerful neuroprotective effect. Herein, we illustrated the mechanism underlying the protective effect of Pur on Cd-induced rat neurocyte injury in an in vivo rat model as well as in vitro using PC12 cells and primary rat cerebral cortical neurons. First, the results showed that Pur alleviated Cd-induced cerebral cortical pathological damage and decreased the viability of neurocytes. Furthermore, Cd activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which plays a negative role in Cd-induced rat neurocyte injury. In addition, Pur alleviated Cd-induced oxidative stress by enhancing antioxidant defense, reducing reactive oxygen species (ROS) accumulation and lipid peroxidation, and inhibiting activation of the Nrf2 signaling pathway in rat neurocytes. Moreover, Pur inhibited the Cd-induced mitochondrial unfolded protein response (UPRmt) in rat neurocytes. Overall, Pur alleviated Cd-induced rat neurocyte injury by alleviating Nrf2-mediated oxidative stress and inhibiting UPRmt.


Element distribution is altered in a zone surrounding human glioblastoma multiforme.
Recent data indicate that A(1) adenosine receptor (A(1)AR) density is increased in a zone surrounding human and experimental gliomas. On the contrary, tumor tissue and adjacent brain tissue show low to intermediate A(1)AR densities. In order to assess whether changes in A(1)AR expression are indicating further processes of a chemical reorganization of the peritumoral zone, we investigated element concentrations and distribution patterns of copper and zinc in six human glioblastoma multiforme (GBM) specimens by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Uranium and lead were used as external standards. Copper and zinc levels were increased in a peritumoral zone corresponding to the region of elevated A(1)AR density. They showed a lower density in the solid tumor in comparison to surrounding brain tissue, although the cellular density was higher within GBM. Our findings suggest that the immediate vicinity of GBM is characterized by increased levels of copper and zinc supporting the view that higher A(1)AR density surrounding GBM is not an isolated alteration of peritumoral tissue but an indicator of complex changes in the vicinity of infiltrative tumors. Further research is needed to explore the pathophysiological consequences of altered peritumoral element distribution.


Rapid FLASH NMR imaging.
Nuclear magnetic resonance (NMR) spectroscopy and imaging provide new tools for non-invasive investigations of living systems. Recent developments in rapid NMR imaging now offer considerable improvements for both scientific applications and medical diagnosis. Using fast imaging sequences cross-sectional images may be recorded within seconds and, therefore, become free from motional artifacts due to breathing or peristalsis. New functional imaging experiments include dynamic studies of the application of paramagnetic contrast agents or ECG-synchronized recordings of cardiac NMR movies. Superior anatomical information is achieved by three-dimensional NMR imaging with measuring times of minutes rather than hours.


Multimodal imaging in multiple evanescent white dot syndrome and new insights in pathogenesis.
To report the multimodal imaging in multiple evanescent white dot syndrome (MEWDS) during the acute and convalescent stages in order to better understand the focus of the inflammatory process. Retrospective cohort study of 4 patients with MEWDS. Each patient underwent: enhanced depth imaging-optical coherence tomography (EDI-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA) and en-face OCT and OCT angiography (OCT-A). Choroidal subfoveal thickness (CST) was measured manually. All patients were studied in the acute stage and convalescent stage after disappearance of OCT abnormalities and resolution of visual symptoms. Four MEWDS patients with a mean age of 23.5years were studied (range: 16-33years). Two patients were women. Initial mean visual acuity (VA) was 80.25 ETDRS. Final mean VA was 84.25 ETDRS. OCT imaging showed disruption of the ellipsoid zone and a slightly elevated RPE layer with overlying hyperreflective material, all of which corresponded to hyperautofluorescent FAF lesions. FA revealed multiple hyperautofluorescent lesions, correlated with hypocyanescent spots on the late ICGA. OCT-A showed normal superficial and deep retinal capillary plexus as well as choriocapillaris. The disease was self-limited in all the cases, with a mean time of 9weeks to resolution (range: 4-16). The pathophysiology of MEWDS is still debated. We believe that there is still not enough evidence to implicate the outer retina as the primary cause. For now, we suggest that this transient disease is the consequence of choriocapillaris hypoperfusion, but further studies are required to elucidate this hypothesis.


Remote cognitive rehabilitation in patients post-cerebrovascular accident: an experience report.
Aiming to contribute to the reduction of cognitive impairment, as well as to improve the quality of life of patients affected by stroke, it was proposed to carry out a cognitive rehabilitation focused on attentional aspects (sustained, alternate, selective and divided attention). Due to the new Coronavirus pandemic and the need for social isolation, the rehabilitation was adapted to the remote model. The rehabilitation was designed and carried out with six patients, coming from a public neurology outpatient service, who had suffered a stroke within a period of up to one year before the start of rehabilitation. Fifteen sessions of cognitive rehabilitation were carried out, lasting approximately 50 minutes, once a week, for four months. In all functions, the four types of attention were worked on. In addition, there were also unassisted activities performed by the patients after each session. The protocol was carried out by Psychology and Medicine students, who elaborated and adapted all activities to be performed by video call. The adaptations were made based on the knowledge and effectiveness of face-to-face rehabilitation for this population. Patients and family members collaborated in the activities, but the emergency adaptation to the remote model also had limitations, such as the withdrawal of some patients due to difficulty access or unstable internet connection. However, there were also positive results, such as the possibility of participation by people from other cities and people with mobility difficulties. This experience allowed students to develop skills in interacting with patients, as well as strategies to deal with the challenges of remote care. Thus, it was not necessary to interrupt the students´ education, moreover, the skills developed are important for the e-health context, which is an increasingly present demand in today's world. Remote cognitive rehabilitation is a possibility for patients who have suffered cognitive impairment due to stroke. Despite the difficulties arising from the pandemic, it was an important experience, with significant value for academic training, which stimulated the skills needed to care for patients, in addition to creativity and adaptation in the face of adversity.


Extranodal natural killer/T-cell lymphoma, nasal type: 'midline lethal granuloma.' A case report.
Extranodal natural killer/T cell lymphoma, nasal type, is a non-Hodgkin lymphoma, most commonly affecting the nasal cavity, paranasal sinuses and nasopharynx. Clinically it is characterised by destruction of facial tissues, commencing in the midline. In most cases it arises from malignant transformation of natural killer cells (NK); sometimes from malignant transformation of cytotoxic T cells.Extranodal NK/T cell lymphoma, nasal type, is rare, but even more rare in black persons. The purpose of this article is to report a severe case of extranodal NK/T cell lymphoma, nasal type, in an elderly black male.


Catalytic and thermodynamic properties of the urocanate hydratase reaction.
Urocanate hydratase (4-imidazolone-5-propionate hydro-lyase, EC 220.127.116.11) isolated from Pseudomonas putida contains covalently bound alpha-ketobutyrate as its cofactor. In the process of examining the mechanism by which alpha-ketobutyrate serves in this capacity, various thermodynamic parameters and temperature effects on urocanate hydratase activity were determined. As the equilibrium constant at 15 degrees C for imidazooone propionate formation from urocanate is approximately 69, regardless of whether urocanic acid or chemically synthesized imidazolone propionate is used as the initial substrate, it is concluded that the reaction is freely reversible. DeltaG degrees ', deltaH degrees ' and deltaS degrees ' were --2.5 kcal/mole, +5.2 kcal/mole and +26 cal/deg mole, respectively. Measurement of first-order reaction rates at various temperatures, in order to calculate the Arrhenius activation energy, showed a sharp break in the Arrhenius plot at 29 degrees C. Further examination of this phenomenon by determining s20,w values of urocanate hydratase as a function of temperature revealed a dramatic change at 31 degrees C. Since the enzyme in both experiments reverts to its original state when the temperature is lowered back below the transition point, it is proposed that urocanate hydratase undergoes a reversible conformational change or partial dissociation which affects its catalytic properties in the range of 29--31 degrees C.


A prognostic value of CA 19-9 but not of CEA in patients with gastric cancer.
The diagnostic and prognostic value of tumour markers CEA and CA 19-9 was studied in patients with gastric cancer. Pre-operative serum concentrations of CEA and CA 19-9 were determined in 100 gastric cancer patients and in 77 patients with relevant benign diseases. The sensitivity of both CEA (cut-off level 3 ng/ml) and CA 19-9 (cut-off level 37 U/ml) for gastric cancer was 30%. The specificities were 73% and 87%, respectively. There was a significant difference in prognosis, for both CEA (cut-off level 3 ng/ml, P < 0.05) and CA 19-9 (cut-off level 37 U/ml, P < 0.01), between patients with high vs low pre-operative serum levels. The overall 5-year survival was 26% and that of patients with low marker levels was 30% (CEA) and 35% (CA 19-9) compared with 15% (CEA) and 0% (CA 19-9) for patients with high marker levels. To evaluate whether the high vs low serum marker level was an independent prognostic factor, the patients were compared within the same stage of disease. There was still a significant difference in 5-year survival in stages II, III and IV between patients with high vs low pre-operative serum levels for CA 19-9 (P < 0.05), but not for CEA. In stage I, no differences in survival could be found for either marker. In conclusion, high pre-operative serum levels of CEA seem to predict higher stage of disease, whereas CA 19-9 might have an independent prognostic value in patients within the stage of II, III or IV gastric cancer. The diagnostic value of both CEA and CA 19-9 is limited.


Impact of Pre-Analytical and Analytical Variables Associated with Sample Preparation on Flow Cytometric Stainings Obtained with EuroFlow Panels.
Objective interpretation of FC results may still be hampered by limited technical standardization. The EuroFlow consortium conducted a series of experiments to determine the impact of different variables on the relative distribution and the median fluorescence intensity (MFI) of markers stained on different cell populations, from both healthy donors and patients' samples with distinct hematological malignancies. The use of different anticoagulants; the time interval between sample collection, preparation, and acquisition; pH of washing buffers; and the use of cell surface membrane-only (SM) vs. cell surface plus intracytoplasmic (SM+CY) staining protocols, were evaluated. Our results showed that only monocytes were represented at higher percentages in EDTA- vs. heparin-anticoagulated samples. Application of SM or SM+CY protocols resulted in slight differences in the percentage of neutrophils and debris determined only with particular antibody combinations. In turn, storage of samples for 24 h at RT was associated with greater percentage of debris and cell doublets when the plasma cell disorder panel was used. Furthermore, 24 h storage of stained cells at RT was selectively detrimental for MFI levels of CD19 and CD45 on mature B- and T-cells (but not on leukemic blasts, clonal B- and plasma cells, neutrophils, and NK cells). The obtained results showed that the variables evaluated might need to be tailored for sample and cell type(s) as well as to the specific markers compared; however, defining of well-balanced boundaries for storage time, staining-to-acquisition delay, and pH of washing buffer would be a valid recommendation for most applications and circumstances described herein.


Local Shwartzman-like phenomenon prepared with haptoglobin-hemoglobin complex and provoked with prostaglandin.
Intradermal injection of haptoglobin-hemoglobin (Hp-Hb) complex followed by intravenous injection of prostaglandin (PG) F2a or E2 produced a local Shwartzman-like phenomenon (LSLP) in rabbits, whereas PGE1 has no provoking action. Intradermal injection of hemoglobin or erythrocytes also produced LSLP when provoked with endotoxin or PGF2alpha. The provoking action of endotoxin in the local shwartzman reaction may not be entirely mediated through PGs.


Evolution of endoscopic extraperitoneal radical prostatectomy (EERPE)--technical improvements and development of a nerve-sparing, potency-preserving approach.
During the last decade, laparoscopy has become a standard technique in the armoury of the urologist due to constant technological advances and refinements. Laparoscopic radical prostatectomy (LRPE), although technically demanding and associated with a considerable learning curve, has become the surgical procedure of choice in selected and specialized urological centers around the globe for patients with clinically localized prostate cancer. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal prostate. The principal disadvantages of LRPE are potential intraperitoneal complications, such as bowel injury, ileus, intraperitoneal bleeding, intraperitoneal urinary leakage, intraperitoneal adhesion formation and concomitant small bowel obstruction. Endoscopic extraperitoneal radical prostatectomy (EERPE) is a further advancement of minimal invasive surgery as it overcomes the limitations of LRPE by the strictly extraperitoneal route of access combining the advantages of minimal invasive surgery with those of an extraperitoneal procedure. Based on our growing experience with this procedure, we have introduced several technical modifications, improvements and refinements including a nerve-sparing, potency-preserving approach (nEERPE) in an effort to further improve this minimally invasive procedure.


Hypothyroidism is associated with higher testosterone levels in postmenopausal women with Hashimoto's thyroiditis.
There are few data about possible interaction of sex hormones and thyroid autoimmunity and function in women with Hashimoto's thyroiditis (HT) after menopause. Therefore, our aim was to investigate sex hormone levels in euthyroid (EuHT) and hypothyroid (HypoHT) postmenopausal women with HT. We performed a prospective observational clinical study that included 55 women with HT (AllHT) and 18 healthy subjects (HS) after menopause matched by age, body mass index, follicle-stimulating hormone, and menopause duration. According to their thyrotropin (TSH) level, the AllHT patients were divided into two subgroups: EuHT with TSH in the range 0.35-5.5 mU/L and HypoHT with TSH above 5.5 mU/L. Total and free testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E2), and progesterone (P) were measured in all subjects. Values are presented as mean ± SD. The Mann-Whitney U test was used for comparison of values between the groups. Correlations were tested using Kendall's tau test. In the HypoHT group, significantly higher free T levels were found in comparison to the HS group (7.89 ± 3.55 pmol/L and 7.13 ± 3.03 pmol/L, p < 0.05). Furthermore, in HypoHT, free T was significantly higher than in EuHT (7.19 ± 5.65 pmol/L, p < 0.05). SHBG was significantly lower in HypoHT compared with HS (45.4 ± 17.4 nmol/L and 60.09 ± 19.51 nmol/L, p < 0.05). No significant correlation was found between sex hormone levels and thyroglobulin and thyroid peroxidase antibodies. We report significantly higher free and total T levels in hypothyroid postmenopausal women with HT. To our knowledge, this is the first study of sex hormone levels in postmenopausal women with HT.


Posttraumatic Stress Disorder and Death From Suicide.
This review summarizes the increasing public health concern about PTSD and suicide, and the population-based studies that have examined this association. Further, we discuss methodological issues that provide important context for the examination of this association. The majority of epidemiologic studies have shown that PTSD is associated with an increased risk of suicide; however, a notable minority of studies have documented a decreased risk of suicide among persons with PTSD. Methodological (e.g., sample size and misclassification) and etiologic issues (e.g., complicated psychiatric comorbidity) may explain the conflicting evidence. PTSD may be associated with an increased risk of suicide, but further research is needed. Increasing the use of appropriate methods (e.g., marginal structural models that can evaluate both confounding and effect modification, machine learning methods, quantification of systematic error) will strengthen the evidence base and advance our understanding.


The Study Centre of the German Surgical Society: current trials and results.
This article provides an overview of current and completed multicentre trials and systematic reviews performed by the Study Centre of the German Surgical Society (SDGC). The SDGC aims to transfer the concept of evidence-based medicine to surgery by planning, conducting and analyzing large national and international randomized multicentre trials concerning surgical issues. Every German surgeon may ask the SDGC for support to realize his clinical trial ideas. Another important task of the SDGC is the acquisition of trial funding from government institutions or industrial partners. Five multicentre randomized controlled trials (RCT) and 11 systematic reviews with meta-analyses have already been completed and published by the SDGC. Another seven RCTs are currently in the recruitment or follow up phase. A total of 2,500 patients in over 100 trial centres have participated so far.


CFTR transgene expression in primary DeltaF508 epithelial cell cultures from human nasal polyps following gene transfer with cationic phosphonolipids.
Cystic fibrosis (CF) is the most common autosomal lethal recessive disorder in the Caucasian population. The major cause of mortality is lung disease, owing to the failure of a functional protein from the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Today, even though the knowledge about the CFTR genomic is extensive, no efficient treatment has been developed yet. In this context, gene therapy represents a potential important advance on condition that it could develop efficient and safe transfection agents. Even though viral vectors have been used in most clinical trials owing to their high transfection efficiency, random integration and immunogenicity are still critical side effects. Consequently, all of these drawbacks brought forth the development of nonviral transfection systems. Although they engender few toxicity and immunogenicity problems, their low transfection efficiency is a hurdle that must be overcome. Over the past decade, we have developed an original family of monocationic lipids, cationic phosphonolipids, whose efficiency has been previously demonstrated both in vitro and in vivo. In this report, we observe that a new cationic phosphonolipid (KLN 30) can lead to the restoration of the CFTR protein following the ex vivo transfection of epithelial cells issuing from a F508 homozygous patient. The transgene expression and the cytotoxicity correlate with the charge ratio of the lipoplex. A kinetic study was performed, and a luminescent signal was detected until 35 d after transfection.


Influence of general anaesthesia on ano-rectal manometry in healthy children.
According to several investigations ano-rectal manometry is a valuable diagnostic test of Hirschsprung's disease. In order to yield accurate results it requires a quiet, calm child who cooperates. In the few instances when this is not possible, general anaesthesia may be desirable. Manometric recordings of the internal and sphincter activity were therefore performed in 15 healthy children when awake and during general anaesthesia. The tonic activity at rest was significantly reduced during anaesthesia. Relaxations of the internal sphincter in response to rectal distension were recorded in all children both when awake and during anaesthesia. They were, however, significantly less pronounced during anaesthesia. These findings strongly suggest that ano-rectal manometry in the diagnosis of Hirschsprung's disease may be performed with advantage during general anaesthesia if the child does not cooperate when awake.


Plasma alterations in cholinergic and serotonergic systems in early Alzheimer Disease: Diagnosis utility.
Alzheimer Disease (AD) is the most common cause of dementia and it involves a high social and economic cost worldwide, and the health system still does not count with an effective treatment. This may be explained by the lack of a reliable early diagnosis and the complex physiological mechanisms involved in the disease development. In this sense, the cholinergic and serotonergic systems may be altered in the disease course. In this study, metabolites from these pathways were determined in order to develop a non-invasive and early diagnosis model, as well as to advance in the knowledge of the physiopathological mechanisms of the disease. For this, plasma samples from mild cognitive impairment due to AD patients (MCI-AD, n = 25) and healthy controls (n = 25) were analysed. choline and tryptophan pathways were deregulated in MCI-AD. Therefore, a model based on betaine, cytidine, uridine, choline, acetylcholine, serotonin and tryptophan was developed, showing an AUC-ROC of 0.862, and sensitivity and specificity of 96% and 72%, respectively. Alterations in metabolites from these pathways are related to cognitive impairment and neurodegeneration, and they could be useful in AD diagnosis. Nevertheless, further research is required in order to validate this diagnosis model.


The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo.
Peripheral neuropathy is an important and disabling side-effect of cisplatin treatment. A new drug, Org 2766, has been found to prevent this neuropathy up to 1 month after treatment. A group of 18 patients with ovarian cancer, who participated in an earlier randomized study with placebo or Org 2766, together with cisplatin and cyclophophamide, were thereafter prospectively followed up to 2 years after discontinuation of treatment to monitor the development of neurological signs and symptoms and vibration perception threshold (VPT). Exploratory, descriptive data analysis shows that between 1 and 4 months after the last cycle the average sum score for neurological signs and symptoms and VPT had deteriorated compared with 1 month after treatment. Thereafter a gradual but incomplete improvement was seen between 4-12 and 12-24 months after treatment. These changes were seen in all patients regardless of previous treatment with Org 2766 or placebo, but deterioration was less pronounced in patients previously treated with Org 2766. These results suggests that treatment with Org 2766 to prevent a cisplatin-induced neuropathy should possibly be continued up to 4 months after the last cycle of cisplatin.


Choline and butyrate beneficially modulate the gut microbiome without affecting atherosclerosis in APOE*3-Leiden.CETP mice.
Choline has been shown to exert atherogenic effects in Apoe-/- and Ldlr-/- mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory and antiatherogenic properties, the aim of the present study was to investigate whether butyrate can alleviate choline-induced atherosclerosis. To this end, we used APOE*3-Leiden.CETP mice, a well-established atherosclerosis-prone model with human-like lipoprotein metabolism. Female APOE*3-Leiden.CETP mice were fed an atherogenic diet alone or supplemented with choline, butyrate or their combination for 16 weeks. Interestingly, choline protected against fat mass gain, increased the abundance of anti-inflammatory gut microbes, and increased the expression of gut microbial genes involved in TMA and TMAO degradation. Butyrate similarly attenuated fat mass gain and beneficially modulated the gut microbiome, as shown by increased abundance of anti-inflammatory and short chain fatty acid-producing microbes, and inhibited expression of gut microbial genes involved in lipopolysaccharide synthesis. Both choline and butyrate upregulated hepatic expression of flavin-containing monooxygenases, and their combination resulted in highest circulating TMAO levels. Nonetheless, choline, butyrate and their combination did not influence atherosclerosis development, and TMAO levels were not associated with atherosclerotic lesion size. While choline and butyrate have been reported to oppositely modulate atherosclerosis development in Apoe-/- and Ldlr-/- mice as related to changes in the gut microbiota, both dietary constituents did not affect atherosclerosis development while beneficially modulating the gut microbiome in APOE*3-Leiden.CETP mice.


Isolation of heat shock protein complexes.
Heat shock proteins (Hsp) are molecular chaperones with the capability to interact with a wide range of other proteins and are thus often found coupled with other heat shock and non-heat shock proteins. This can be an advantage to study specific interactions between a chaperone and other proteins and to generate an antitumoral immune response. In this chapter, we present two protocols to isolate Hsp. One involves column chromatography with hydroxyapatite and the other employs immunoprecipitation with antibodies coupled to magnetic beads. In both cases, we specifically want to isolate Hsp coupled with other proteins and use the Hsp complexes as intermediaries to present the coupled peptides/proteins to the immune system, or to explore the associations of a particular Hsp with other proteins.


Familial Exudative Vitreoretinopathy Imaged With Optical Coherence Tomography Angiography.
The authors present a case of a 29-year-old man who presented to the Department of Ophthalmology at their institution to complete a peripheral laser treatment in his left eye for familial exudative vitreoretinopathy complicated by tractional macular edema. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e112-e113.].


[Simultaneous determination of trace platinum, palladium and rhodium in environmental dust samples by ICP-MS after open-digestion].
A sensitive method for simultaneous determination of Pt, Pd and Rh in dust samples by ICP-MS after open-digestion was developed. The digestion method for the samples and conditions for measurement for ICP-MS were studied in detail. Aquaregia was proved to be a better solvent for the digestion of dust samples. Under the optimum conditions, the limits of detection of Pt, Pd and Rh were 0.48, 4.22 and 0.42 ng x g(-1), respectively. The proposed method was applied to the real sample analysis, and good recoveries were obtained. The recoveries of Pt, Pd and Rh were found to be between 87.6%-88%, 85.2%-87.8%, and 93%-95%, respectively.


Microhabitat factors affecting abundance and diversity of Conus on coral reefs.
Frequency and per cent cover of particular substratum types are shown to be important factors influencing abundance and diversity of mobile, predatory benthic invertebrates on spatially complex coral reef platforms. The most favorable portions of reefs for the gastropod Conus have <20% cover of algal-bound sand and <20% cover of living coral. The former microhabitat provides diurnal shelter for smaller Conus, harbors dense prey populations, and is typically interspersed with sand- and rubble-filled depressions in which many of the gastropods shelter during the day. In Micronesia and Australian Great Barrier Reef censuses, 39 1x10-m transects on favorable habitat supported an average of 7 Conus of 3 species. In striking contrast, portions of reef with >20% living coral are most unfavorable for Conus. Here density averaged 0.3 individual/10 m2, in 17 transects. Living coral harbors few suitable prey organisms, and contact with it elicits a strong avoidance response by Conus. Comparison of subtidal reef and intertidal bench habitats indicates that species diversity and population density are inversely related, but within both habitat types these attributes of Conus assemblages are positively associated.


[Safety aspects during treatment with clozapine: : Adverse effects, titration, and therapeutic drug monitoring - a narrative review].
According to current guidelines, clozapine should be used as a third step in treatment resistant schizophrenia (TRS). In everyday clinical practice, however, it is frequently used at a much later stage, which leads to a significant deterioration of prognosis. The first part of this narrative overview focuses on the most frequent side effects of clozapine, on the relevance of slow titration, and on specific aspects of therapeutic drug monitoring (TDM). Medline, the Guideline for the use of clozapine 2013 of the Netherlands Clozapine Collaboration Group, and the S3 Guideline for Schizophrenia of the German Association for Psychiatry, Psychotherapy and Psychosomatics were searched for relevant literature, the last query dating from April 28th, 2023. Despite its unique efficacy clozapine is underused in clinical practice and prescription varies between and within countries. Next to hematological, metabolic, and vegetative side effects, clozapine induced inflammation manifesting in the form of pneumonia or myocarditis, which is mainly associated with rapid titration, represents a major clinical challenge with CRP monitoring being of particular relevance. In this context, it also has to be noted that sex, smoking behavior, and ethnic origin impact clozapine metabolism, thus requiring personalized dosing. Slow titration when possible, TDM, and CYP diagnostics when appropriate increase patient safety during treatment with clozapine and thus the likelihood of early prescription of this compound in TRS.


Dietary ceramide 2-aminoethylphosphonate, a marine sphingophosphonolipid, improves skin barrier function in hairless mice.
Sphingolipids are one of the major components of cell membranes and are ubiquitous in eukaryotic organisms. Ceramide 2-aminoethylphosphonate (CAEP) of marine origin is a unique and abundant sphingophosphonolipid with a C-P bond. Although molluscs such as squids and bivalves, containing CAEP, are consumed globally, the dietary efficacy of CAEP is not understood. We investigated the efficacy of marine sphingophosphonolipids by studying the effect of dietary CAEP on the improvement of the skin barrier function in hairless mice fed a diet that induces severely dry-skin condition. The disrupted skin barrier functions such as an increase in the transepidermal water loss (TEWL), a decrease in the skin hydration index, and epidermal hyperplasia were restored by CEAP dietary supplementation. Correspondingly, dietary CAEP significantly increased the content of covalently bound ω-hydroxyceramide, and the expression of its biosynthesis-related genes in the skin. These effects of dietary CAEP mimic those of dietary plant glucosylceramide. The novel observations from this study show an enhancement in the skin barrier function by dietary CAEP and the effects could be contributed by the upregulation of covalently bound ω-hydroxyceramide synthesis in the skin.


Lack of an association between CYP11B2 C-344T gene polymorphism and ischemic stroke: a meta-analysis of 7,710 subjects.
The association between aldosterone synthase (CYP11B2) C-344T gene polymorphism and ischemic stroke remains controversial and ambiguous. To better explain the association between CYP11B2 polymorphism and ischemic stroke risk, a meta-analysis was performed. Based on comprehensive searches of Medline, Embase, Web of Science, CNKI and CBM databases, we identified and abstracted outcome data from all articles to evaluate the association between CYP11B2 polymorphism and ischemic stroke. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed in all genetic models. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 12 studies including 3,620 ischemic stroke cases and 4,090 controls were identified. There was no statistical evidence of association between CYP11B2 C-344T polymorphism and ischemic stroke in all genetic models (allelic model: OR = 1.19, 95% CI = 0.95-1.49; additive model: OR = 1.43, 95% CI = 0.91-2.27; dominant model: OR = 1.30, 95% CI = 0.89-1.89; and recessive model: OR = 1.24, 95% CI = 0.96-1.60). On subgroup analysis by ethnicity, similarly results were found in both Asians and non-Asians. For Asians, the combined ORs and 95% CIs were (allelic model: OR = 1.07, 95% CI = 0.87-1.32; additive model: OR = 1.15, 95% CI = 0.77-1.71; dominant model: OR = 1.13, 95% CI = 0.92-1.38; and recessive model: OR = 1.09, 95% CI = 0.84-1.40). For none-Asians, the combined ORs and 95% CIs were (allelic model: OR = 1.58, 95% CI = 0.90-2.76; additive model: OR = 2.37, 95% CI = 0.79-7.05; dominant model: OR = 1.79, 95% CI = 0.77-4.19; and recessive model: OR = 1.80, 95% CI = 0.96-3.36). The present meta-analysis suggested that CYP11B2 C-344T polymorphism was unlikely contribute to ischemic stroke susceptibility.


Post-natal development of the retinal and cerebellar projections onto the lateral suprasylvian area in the cat.
1. Post-natal development of the retinal and cerebellar projections onto the medial bank of the lateral suprasylvian visual area was examined by using the field potential method and, additionally, by the orthograde horseradish peroxidase method. 2. Optic nerve stimulation elicited a surface-positive, depth-negative field potential in the medial bank of the lateral suprasylvian area of adult cats. By contrast, in kittens younger than 3 weeks old, a surface-negative, depth-positive field potential was evoked. The response grew adult-like by 1 month of age. Corticocortical response, activated by stimulation of cortical areas 17 and 18, underwent a similar developmental change. 3. Cerebellar stimulation evoked a surface-negative, depth-positive wave from birth up to adulthood. Thalamocortical afferents from the ventroanterior and ventrolateral nuclei of the thalamus to the medial bank of the lateral suprasylvian area, which is presumed to be responsible for this cerebellar response, terminate mostly in layer I in both new-born kittens and adult cats. 4. The present results, and our previous morphological findings on the projections from the extrageniculate visual thalamus and visual cortical areas 17 and 18 onto the medial bank of the lateral suprasylvian area, were correlated with reference to the maturation of the neuronal circuit in the cortex.


Goodness-of-fit test of the stratified mark-specific proportional hazards model with continuous mark.
Motivated by the need to assess HIV vaccine efficacy, previous studies proposed an extension of the discrete competing risks proportional hazards model, in which the cause of failure is replaced by a continuous mark only observed at the failure time. However the model assumptions may fail in several ways, and no diagnostic testing procedure for this situation has been proposed. A goodness-of-fit test procedure for the stratified mark-specific proportional hazards model in which the regression parameters depend nonparametrically on the mark and the baseline hazards depends nonparametrically on both time and the mark is proposed. The test statistics are constructed based on the weighted cumulative mark-specific martingale residuals. The critical values of the proposed test statistics are approximated using the Gaussian multiplier method. The performance of the proposed tests are examined extensively in simulations for a variety of the models under the null hypothesis and under different types of alternative models. An analysis of the 'Step' HIV vaccine efficacy trial using the proposed method is presented. The analysis suggests that the HIV vaccine candidate may increase susceptibility to HIV acquisition.


Adenocarcinoma mucinosum of extrophy bladder: A rare case report.
Bladder exstrophy is a rare congenital anomaly while, bladder adenocarcinoma mucinous type is a rare type of bladder cancer, with aggressive behavior and inadequate response to radiation and chemotherapy. In extremely rare cases, untreated bladder exstrophy could transform into bladder mucinous adenocarcinoma. We report a case of a 41-year-old male with untreated bladder exstrophy that transformed into mucinous adenocarcinoma. The patient also had epispadias and a right inguinal hernia. Joint procedures were conducted to perform radical cystectomy, total penectomy and W-Pouch continent urostomy, inguinal hernia repair, osteotomy, and keystone and scrotal flap by split-thickness skin graft (STSG) for wound closure. The patient progressed well after surgery, two months after initial procedure, nephrostomies were conducted due to pouches stenosis. Due to the government's limited transportation and lockdown policy, as the Covid-19 pandemic occurred, the patient could not come to the hospital for routine follow-up and died nine-month after surgery. Bladder exstrophy is one of the risk factors of bladder cancer. Transformation of bladder exstrophy into mucinous adenocarcinoma is extremely rare, as the case is the first case to be discovered in Indonesia. Surgery, followed with a strict follow-up regime, is mainstay of treatment in this type of malignancy. Adenocarcinoma of mucinous type is a scarce type of bladder exstrophy malignancies. A multidiscipline approach is mandatory in these cases. Strict and regular follow up are suggested for these cases.


A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols.
Availability of randomized controlled trial (RCT) protocols is essential for the interpretation of trial results and research transparency. In this study, we determined the availability of RCT protocols approved in Switzerland, Canada, Germany, and the United Kingdom in 2012. For these RCTs, we searched PubMed, Google Scholar, Scopus, and trial registries for publicly available protocols and corresponding full-text publications of results. We determined the proportion of RCTs with (1) publicly available protocols, (2) publications citing the protocol, and (3) registries providing a link to the protocol. A multivariable logistic regression model explored factors associated with protocol availability. Three hundred twenty-six RCTs were included, of which 118 (36.2%) made their protocol publicly available; 56 (47.6% 56 of 118) provided as a peer-reviewed publication and 48 (40.7%, 48 of 118) provided as supplementary material. A total of 90.9% (100 of 110) of the protocols were cited in the main publication, and 55.9% (66 of 118) were linked in the clinical trial registry. Larger sample size (>500; odds ratio [OR] = 5.90, 95% confidence interval [CI], 2.75-13.31) and investigator sponsorship (OR = 1.99, 95% CI, 1.11-3.59) were associated with increased protocol availability. Most protocols were made available shortly before the publication of the main results. RCT protocols should be made available at an early stage of the trial.


En_Línea. An online treatment to change lifestyle in overweight and obesity: study protocol for a randomized controlled trial.
Obesity has become a major public health problem. Innovative treatments are necessary. Internet and new technologies have been reported effective results in weight control programs, especially those with personalized feedback. This paper presents the protocol for a randomized controlled trial to test the effectiveness of an online weight control program, called en_línea, comparing with a standard group therapy and a control group. This is a randomized controlled trial with three intervention arms: en_línea, standard group therapy and control group. To perform this study, 305 adults (18-65 years) with overweight type II (27-29.9 kg/m2) or obesity type I (30-34.9 kg/m2) will be invited to participate. Interventions will last 17 weeks with follow-ups 1, 3, 6 and 12 months after the post-treatment appointment. The primary outcome will be post-treatment weight loss and the maintenance during the follow-ups. Secondary outcomes will be adherence rates, drop outs and quality of life. Participants will be assessed before randomization and they will be sign an inform consent. The future challenge is to design innovative obesity treatments. Internet could be a useful tool to improve traditional weight control programs. This new intervention format is appropriate for patients who prefer not to share their intimate problems with a group, and for the new generations who feel comfortable using new technologies. Besides, Internet allows reaching a large amount of people at the same time, even if they live far away. ClinicalTrials.gov NCT04127201. Retrospectively registered 15th October 2019.


[Prevalence and transferability of the plasmid lac+ character in "Klebsiella" sp. strains with "lac+-forte" phenotype].
36 strains of Klebsiella sp. showing a strong lactose-positive phenotype were examined for presence of R factors and for ability to promote the transfer of character lac+; 10 of the 13 R+ strains were able to transfer lac+ character and 4 showed the presence of R-lac factors. Transfer of R-lac factors from Klebsiella sp. strains to Salmonella typhi clinical isolates has also been obtained.


Identification of key genes and construction of microRNA-mRNA regulatory networks in multiple myeloma by integrated multiple GEO datasets using bioinformatics analysis.
Multiple myeloma (MM) is a common hematological malignancy. To identify key genes and microRNAs in MM, we downloaded two gene expression profiles (GSE16558 and GSE47552) and two microRNA expression profiles (GSE17498 and GSE16558) from the Gene Expression Omnibus (GEO) database. A total of 596 differentially expressed genes (DEGs) and 39 differentially expressed microRNAs (DEMs) were screened out. Pathway analysis showed that upregulated genes were mainly enriched in the "B cell receptor signaling pathway", "Cell cycle" and "NF-kappa B signaling pathway", whereas downregulated genes were mainly enriched in the "Ribosome", "FoxO signaling pathway" and "p53 signaling pathway". We subsequently constructed a protein-protein interaction network of DEGs consisting of 277 genes and 563 interactions. In addition, 32 genes with high degrees in the network were identified as hub genes in MM, e.g. HDAC2, RBBP4, CREB1, and RB1. Additionally, we constructed a microRNA-mRNA regulatory network depicting interactions between DEMs and their targets, including the miR-135b-GADD45A and miR-148a-USPL1 pairs. In conclusion, the results of this data mining and integration help reveal the molecular basis of MM pathogenesis as well as potential biomarkers and therapeutic targets for MM diagnosis and treatment.


Microplastics in freshwater sediment: A review on methods, occurrence, and sources.
There is a rising concern regarding the accumulation of microplastics in the aquatic ecosystems. However, compared to the marine environment, the occurrence, transport, and diffusion of microplastics in freshwater sediment are still open questions. This paper summarizes and compares the methods used in previous studies and provides suggestions for sampling and analysis of microplastics in freshwater sediment. This paper also reviews the findings on microplastics in freshwater sediment, including abundance, morphological characteristics, polymer types, sources, and factors affecting the abundance of microplastics in freshwater sediment. The results show that microplastics are ubiquitous in the investigated sediment of rivers, lakes, and reservoirs, with an abundance of 2-5 orders of magnitude across different regions. Low microplastics concentration was observed in the Ciwalengke River with an average abundance of 30.3 ± 15.9 items/kg. In particular, an extremely high abundance of microplastics was recorded in the urban recipient in Norway reaching 12,000-200,000 items/kg. Fibers with particle size less than 1 mm are the dominant shape for microplastics in freshwater sediment. In addition, the most frequently recorded colors and types are white/transparent, and PE/PS, respectively. Finally, we conclude that the consistency of morphological characteristics and components of microplastics between the beach or marine sediments and freshwater sediments may be an indicator of these interlinkages and source-pathways. Microplastics in freshwater sediment need further research and exploration to identify its spatial and temporal variations and driving force through further field sampling and implementation of standard and uniform analytical methodologies.


Theorizing on neo public assistance: How do race and class impact resource uptake and behavior following disaster?
The consequences of environmental disasters and other ecologic and communal crises are frequently worst in racially/ethnically minoritized and low-income populations relative to other groups. This disproportionality may create or deepen patterns of governmental distrust and stoke health promotion disengagement in these groups. To date, there has been limited contextualization of how historically disenfranchised populations utilize government-administered or facilitated resources following such disasters. Focusing on the water crisis in Flint, Michigan, we examine and theorize on the usage of neo public assistance, free risk reduction resources that are provided to disaster survivors as a liminal means of redressing ills created and/or insufficiently mitigated by the state. We surveyed 331 Flint residents, evaluating their usage of four neo public assistance resources following the FWC, finding low to moderate uptake: 131 residents (39.6%) indicated that they obtained blood lead level (BLL) screenings, 216 (65.3%) had their tap water tested for lead (Pb) and other contaminants, 137 (41.4%) had their home water infrastructure replaced, and 293 (88.5%) had acquired bottled water at community distribution sites. Unemployment, receiving public benefits, and lacking reliable transportation and stable housing were associated with lower uptake of some resources. Compared to White and "Other" race individuals, Black residents were generally more likely to acquire/utilize these resources, suggesting heightened concerns and health promotion proclivities even in the face of observed macro and individual-level challenges. Potential reasons and implications are discussed.


Surgeon-performed ultrasound reliably predicts skin spacing and may decrease the rate of MammoSite balloon catheter explantation in patients undergoing brachytherapy for breast cancer.
The purpose of this study was to determine if the distance from the skin to the seroma cavity, as measured with ultrasound (US) before catheter placement, correlated with the distance from skin to MammoSite balloon catheter as measured on computerized axial tomography (CAT) after catheter placement. US was used to measure the distance from the skin to the seroma cavity, and then the MammoSite balloon catheter was inserted. Skin-to-balloon distance was then measured using CAT. Statistical analysis was performed to determine correlation between the 2 measurements. Our cohort consisted of 70 patients. US distance correlated with CAT distance (Pearson correlation coefficient .70). Mean US distance was 10.8 mm (SD 4.5 mm); mean CAT distance was 11.9 mm (SD 7.5 mm); and mean difference between the 2 measurements was -1.1 mm (SD 6.1 mm). A US measurement >/=7.6 mm predicted successful completion of MammoSite brachytherapy in 98% of patients. Patients with skin-to-seroma cavity distance <7.6 mm required explantation before treatment completion 39% of the time. Office-based US performed before insertion of the MammoSite balloon catheter statistically correlates with measurement by CAT. Patients with >/=7.6 mm skin-to-seroma cavity distance on US had a higher completion rate of MammoSite brachytherapy treatment.


Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease encompasses a spectrum of hepatic pathologies ranging from simple fatty liver to an inflammatory state known as nonalcoholic steatohepatitis (NASH). NASH is also characterized by severe hepatic oxidative stress. The goal of this study was to determine whether genes of the antioxidant response are induced in rodent models of nonalcoholic fatty liver disease. To simulate simple fatty liver and NASH, respectively, male Sprague-Dawley rats were fed a high-fat (HF) or a methionine and choline-deficient (MCD) diet for 8 weeks. Key marker genes of the antioxidant response that are known to undergo upregulation via activation of Nuclear Factor Erythroid 2-Related Factor 2 were measured using the branched DNA signal amplification assay. Messenger RNA levels of the antioxidant response, including NAD(P)H:quinone oxidoreductase-1 (Nqo1), Glutamate cysteine ligase catalytic (Gclc), and Heme oxygenase-1 (Ho-1), were significantly induced in MCD rat liver but not in HF rat liver. Furthermore, Nqo1 protein expression and activity underwent significant upregulation in MCD rat liver but not in HF rat liver. These data strongly indicate that the pathology induced by the MCD dietary model of NASH results in upregulation of the antioxidant response in rats.


Municipal solid waste incineration plant: A multi-step approach to the evaluation of an energy-recovery configuration.
This study proposes a multi-step approach to evaluating the environmental and economic aspects of a thermal treatment plant with an energy-recovery configuration. In order to validate the proposed approach, the Turin incineration plant was analyzed, and the potential of the incinerator and several different possible connections to the district heating network were then considered. Both local and global environmental balances were defined. The global-scale results provided information on carbon dioxide emissions, while the local-scale results were used as reference values for the implementation of a Gaussian model that could evaluate the actual concentrations of pollutants released into the atmosphere. The economic aspects were then analyzed, and a correspondence between the environmental and economic advantages defined. The results showed a high energy efficiency for the combined production of heat and electricity, and the opportunity to minimize environmental impacts by including cogeneration in a district heating scheme. This scheme showed an environmental advantage, whereas the electricity-only configuration showed an economic advantage. A change in the thermal energy price (specifically, to 40 €/MWh), however, would make it possible to obtain both environmental and economic advantages.


A single-center experience of late retransplantation of the liver.
Liver retransplantation is considered to carry a higher risk than primary transplantation. However, there are an increasing number of retransplant candidates, especially owing to late graft failure. The aim of this study was to analyze a single-center experience in late liver retransplantation. The overall rate of primary retransplantation was 11.4% (28 re-OLT out of 245 primary OLT); the 14 (52%) who underwent retransplantation at more than 3 months after the first transplant were analyzed by a medical record review. Causes of primary graft failure leading to retransplantation were chronic hepatic artery thombosis in five cases (36%); recurrent HCV cirrhosis in four cases (29%); chronic rejection in two cases (14%); veno-occlusive disease; hepatic vein thrombosis or idiopathic graft failure in one case each (7%). UNOS status at re-OLT was always 2A, all patients were hospitalized; three were intensive care unit bound. ICU and total hospital stay had been 7 +/- 5 and 28 +/- 16 days, respectively. One- and 2-year patient and graft survivals were 84% and 62% and 67% and 67%, respectively. Death occurred in four patients. Two out of the three recovered in ICU at the time of retransplantation, at a median interval of 15 +/- 9 days after retransplantation. The survival rate after late retransplantation is improving, and this option should be considered to be a efficient way to save lives, especially by defining the optimal timing for retransplantation.


Impact of the Regional Network for AMI in the Management of STEMI on Care Processes, Outcomes and Health Inequities in the Veneto Region, Italy.
Cardiovascular diseases are a leading cause of death in Europe. Outcomes in terms of mortality and health equity in the management of patients with ST-Elevation Myocardial Infarction (STEMI) are influenced by health care service organization. The main aim of the present study was to examine the impact of the new organizational model of the Veneto Region's network for Acute Myocardial Infarction (AMI) to facilitate primary percutaneous coronary intervention (PCI) on STEMI, and its efficacy in reducing health inequities. A retrospective cohort study was conducted on HDRs in the Veneto Region for the period 2007⁻2016, analyzing 65,261 hospitalizations for AMI. The proportion of patients with STEMI treated with PCI within 24 h increased significantly for men and women, and was statistically much higher for patients over 75 years of age (APC, 75⁻84: 9.8; >85: 12.5) than for younger patients (APC, <45: 3.3; 45⁻64: 4.9), with no difference relating to citizenship. The reduction in in-hospital, STEMI-related mortality was only statistically significant for patients aged 75⁻84 (APC: -3.0 [-4.5;-1.6]), and for Italians (APC: -1.9 [-3.2;-0.6]). Multivariate analyses confirmed a reduction in the disparities between socio-demographic categories. Although the new network improved the care process and reduced health care disparities in all subgroups, these efforts did not result in the expected survival benefit in all patient subgroups.


Natural killer cell activity and distant metastasis in rectal cancers treated surgically with and without neoadjuvant chemoradiotherapy.
We investigated whether impaired preoperative natural killer (NK) cell activity correlates with asynchronous distant metastasis after curative surgery for rectal cancers. In addition, we examined if preoperative chemoradiotherapy for rectal cancers impairs NK cell activity and contributes to the induction of distant metastasis. Preoperative NK cell activity was examined in 174 rectal cancer patients. All patients were enrolled in this study and followed until asynchronous distant metastasis occurred. The mean NK activity in patients with stage IV disease (n = 20) was significantly lower than seen in other stages. There were no differences among stage I to stage III patients. In stage III patients, the cumulative distant metastasis-free rate after curative surgery was significantly lower in cases with NK activity of 25% or less than those with more than 25%. Preoperative chemoradiotherapy for stage I to III patients significantly impaired NK cell activity (n = 39), and the metastasis-positive ratio significantly increased among patients with stage II or stage III diseases (n = 30). Multivariate analysis indicated that dichotomized NK cell activity was a significant risk factor that is associated with distant metastasis as well as nodal involvement. In primary rectal cancers, NK cell activity is not necessarily impaired in accordance with the disease progression. It is considered an important background factor for developing asynchronous distant metastases in stage III rectal cancers. Neoadjuvant chemoradiotherapy impaired NK cell activity in selected patients, suggesting the necessity of concurrent immunotherapy for better outcomes.


Treatment outcomes among high-risk neuroblastoma patients receiving non-immunotherapy regimen: Multicenter study on behalf of the Thai Pediatric Oncology Group.
Neuroblastoma is the most common extracranial malignant solid tumor during childhood. Despite intensified treatment, patients with high-risk neuroblastoma (HR-NBL) still carry a dismal prognosis. The Thai Pediatric Oncology Group (ThaiPOG) proposed the use of a multimodality treatment to improve outcomes of HR-NBL in non-immunotherapy settings. Patients with HR-NBL undergoing ThaiPOG protocols (ThaiPOG-NB-13HR or -18HR) between 2013 and 2019 were retrospectively reviewed. Patient demographic data, treatment modalities, outcomes, and prognostic factors were evaluated and analyzed. A total of 183 patients with HR-NBL undergoing a topotecan containing induction regimen were enrolled in this study. During the consolidation phase (n = 169), 116 patients (68.6%) received conventional chemotherapy, while 53 patients (31.4%) underwent hematopoietic stem cell transplantation (HSCT). The 5-year overall survival (OS) and event-free survival (EFS) were 41.2% and 22.8%, respectively. Patients who underwent HSCT had more superior 5-year EFS (36%) than those who received chemotherapy (17.1%) (p = .041), although they both performed similarly in 5-year OS (48.7% vs. 39.8%, p = .17). The variation of survival outcomes was observed depending on the number of treatment modalities. HSCT combined with metaiodobenzylguanidine (MIBG) treatment and maintenance with 13-cis-retinoic acid (cis-RA) demonstrated a desirable 5-year OS and EFS of 65.6% and 58.3%, respectively. Poorly or undifferentiated tumor histology and cis-RA administration were independent factors associated with relapse and survival outcomes, respectively (p < .05). A combination of HSCT and cis-RA successfully improved the outcomes of patients with HR-NBL in immunotherapy inaccessible settings.


Differentiation of Hair Sheep Breeds Based on the Physiological and Blood Biochemical Changes in Response to Different Stressors Using Multivariate Analysis Techniques.
Physiological and blood measurement changes due to high heat load, restricted feed intake, and limited drinking water availability in 135 animals of three hair sheep breeds (Dorper, Katahdin, and St. Croix) were subjected to multivariate analysis techniques. The objective of this analysis was to evaluate the ability of these variables to separate individual hair sheep into groups based on adaptation characteristics in response to three physiological stressors and identify variables with greater discriminatory power. There were 16, 8, and 13 physiological and blood variables obtained from high heat load, restricted feed consumption, and water intake studies, respectively, for multivariate analysis. Physiological variables such as respiration rate, rectal and skin temperature, and panting score were measured only in the heat stress study. The results of the cluster and canonical discriminant analyses showed the presence of wide divergence (p < 0.05) between St. Croix and other breeds in their responses to high heat loads and restricted-feed- and -water-intake conditions. Dorper and Katahdin were grouped (p > 0.05) together based on the changes in physiological variables, which were separated (p < 0.05) from those of St. Croix as a resilient group. The stepwise discriminant analysis indicated that skin temperature, panting score, rectal temperature, respiration rate, and blood urea nitrogen and oxygen concentrations were the significant (p < 0.05) discriminating variables in clustering individual sheep into groups based on their responses to the high-heat-stress condition. Under the limited feed intake condition, the significant (p < 0.05) traits responsible for the separation of St. Croix from Dorper and Katahdin were blood triglyceride and cholesterol concentrations, whereas blood hemoglobin, osmolality, protein, and albumin were most important discriminating variables under the limited water intake condition. In conclusion, the results of the present study suggest that the stress responses of Dorper and Katahdin are similar and different from that of St. Croix. This finding can be useful information for future decisions in developing climate-resilient sheep through selective breeding.


Characteristics and survival prognosis of patients with pure squamous cell carcinoma of the gallbladder.
Pure squamous cell carcinoma (SCC) of the gallbladder is rare and often confused with the adenosquamous carcinoma (ASC) subtype in previous studies. The present study was attempted to differentiate SCC from ASC by resolving their characteristics and prognosis. The Surveillance, Epidemiology, and End Results database was queried for SCC and ASC of gallbladder cases from 1988 to 2015. Patients' clinicopathological characteristics and survival were analysed between the groups. Of the 709 patients with primary gallbladder cancer included in this study, 249 (35.1%) had pure SCC and the remaining 460 (64.9%) had ASC. It was found that pure SCC was associated with a larger median tumour size (58.0 versus 41.0 mm, P < 0.001), while ASC presented with a worse histological grade (47.4% versus 37.8% for grades III-IV, P = 0.019) and more lymph node invasion (27.4% versus 18.9%, P = 0.041). The 3-year overall survival and disease-specific survival rates in pure SCC were lower than those in ASC (7.5% versus 11.5% for overall survival, P < 0.001; 6.2% versus 10.9% for disease-specific survival, P < 0.001). Multivariate analysis showed that early Surveillance, Epidemiology, and End Results historic stage, treatment with surgery and chemotherapy were significant favourable prognostic factors for pure SCC, while tumour size, late study period, treatment with surgery and radiotherapy were significant predictors for ASC. There were significant differences in the clinicopathological characteristics and survival prognosis between pure SCC and ASC. Surgery combined with chemotherapy is the preferred treatment option for pure SCC.


The hyperlipidemia of pregnancy in normal and complicated pregnancies.
Alterations in the concentrations of the cholesterol and triglyceride moieties of lipoproteins separated by ultracentrifugation and precipitation methods were studied at frequent intervals throughout pregnancy and the puerperium in a group of 43 women. The plasma cholesterol concentration rose on the average by about 50 per cent, the major increase occurring in the second trimester. The plasma triglyceride concentration rose threefold, reaching its peak during the third trimester. All major lipoproteins participated in these changes: in very-low-density lipoproteins, both lipids rose in proportion to the ratio in nonpregnant women, but in low-density and high-density lipoproteins, the ratio of triglyceride to cholesterol rose. The triglyceride enrighment in low-density lipoproteins reflected the inclusion of intermediate-density lipoproteins (d 1.006 to 1.019). The occurrence of hypertension or pre-eclampsia led to a further increase in lipids in very-low-density lipoproteins. Hypercholesterolemia was greatest in women with pre-existing hypercholesterolemia, and women in the third pregnancy showed higher plasma cholesterol concentrations than women in the first pregnancy. Both cholesterol and triglyceride concentrations decreased significantly within 24 hours of delivery and this was reflected in all lipoproteins. However, while triglyceride levels continued to decrease rapidly returning to nonpregnant levels during the puerperium, cholesterol in low-density lipoprotein remained elevated for at least six to seven weeks post partum.


Hospitalizations and emergency department visits trends among elderly individuals in proximity to death: a retrospective population-based study.
Acute healthcare services are extremely important, particularly during the COVID-19 pandemic, as healthcare demand has rapidly intensified, and resources have become insufficient. Studies on specific prepandemic hospitalization and emergency department visit (EDV) trends in proximity to death are limited. We examined time-trend specificities based on sex, age, and cause of death in the last 2 years of life. Datasets containing all hospitalizations and EDVs of elderly residents in Friuli-Venezia Giulia, Italy (N = 411,812), who died between 2002 and 2014 at ≥ 65 years, have been collected. We performed subgroup change-point analysis of monthly trends in the 2 years preceding death according to sex, age at death (65-74, 75-84, 85-94, and ≥ 95 years), and main cause of death (cancer, cardiovascular, or respiratory disease). The proportion of decedents (N = 142,834) accessing acute healthcare services increased exponentially in proximity to death (hospitalizations = 4.7, EDVs = 3.9 months before death). This was inversely related to age, with changes among the youngest and eldest decedents at 6.6 and 3.5 months for hospitalizations and at 4.6 and 3.3 months for EDVs, respectively. Healthcare use among cancer patients intensified earlier in life (hospitalizations = 6.8, EDVs = 5.8 months before death). Decedents from respiratory diseases were most likely to access hospital-based services during the last month of life. No sex-based differences were found. The greater use of acute healthcare services among younger decedents and cancer patients suggests that policies potentiating primary care support targeting these at-risk groups may reduce pressure on hospital-based services.


Regional brain [Met]-enkephalin in alcohol-preferring and non-alcohol-preferring inbred strains of mice.
Scrutiny of the data from these studies reveals that the C58/J alcohol-preferring mice have significantly lower baseline methionine-enkephalin levels in both the corpus striatum and hypothalamus compared to C3H/CHRGL/2 non-alcohol-preferring mice. In other brain regions in these two strains, specifically, pituitary, amygdala, midbrain, and hippocampus, analysis of methionine-enkephalin levels did not show any significant differences. This suggests that the hypothalamus may indeed be a specific locus involved in the regulation of alcohol intake, via the molecular interaction between neuroamines, opioid peptides, as they are influenced by genetics and environment.