Differential effects of gonadectomy on thymic stromal cells in promoting T cell differentiation in mice.
Twenty-six week-old BDF1 mice were gonadectomized and grafted with thymus from irradiated (8.5 Gy) newborn, 6-week-old, or 26-week-old mice. One month later, grafted thymuses were recovered and examined in terms of thymocyte numbers, subpopulations and proliferative responses to Concananavlin A (Con A). The growth of the irradiated thymus was significantly higher in gonadectomized (Gx) than in sham-operated (Sham) mice and the magnitude of thymic growth was apparently age-dependent, as it was greater for newborns than for older mice. Con A response of thymocytes was also significantly higher in Gx mice than in Sham mice, and the magnitude of the response declined with advancing age of the thymus donors. Flow cytometric analysis revealed that a significant increase in the percentage of CD4+CD8- was observed in thymus grafts showing high Con A responses. However, this effect of Gx on the thymus graft was dependent on age of the thymus donor. Namely, newborn thymus grafts could grow equally well in both Gx and Sham recipients, whereas thymus grafts from 6- and 26-week-old mice could grow well only in Gx, but not in Sham recipients. The number of thymocytes was comparable in thymus grafts from 6- and 26-week-old mice, but the proliferative response to Con A was higher in the former than in the latter graft. Collectively, Gx appeared to promote immigration of thymocyte precursors into the thymus and to enhance proliferation and differentiation of thymocytes towards CD4+CD8- T cells, in an age-related manner.


Muscle relaxant action of phenobarbitone in genetically spastic rats: an electromyographic study.
The muscle relaxant effect of phenobarbitone was studied in genetically spastic rats which exhibit spontaneous tonic activity in the electromyogram (EMG) of the gastrocnemius muscle. Phenobarbitone, 10-30 mg/kg i.p., reduced the tonic activity in the EMG of the gastrocnemius muscle of such rats in a dose- and time-dependent manner. The GABA antagonists bicuculline, 2 mg/kg i.p., and picrotoxin, 2 and 3 mg/kg i.p., reduced the muscle relaxant effect of phenobarbitone, 20 and 30 mg/kg. The benzodiazepine receptor antagonists, Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg (doses which do not affect tonic activity in the EMG), failed to alter the depressant effect of phenobarbitone 30 mg/kg, in the EMG. Beta-Carboline-3-carboxylic acid methylester (beta-CCM), 2 mg/kg i.p., while not affecting the tonic activity in the EMG, reversed the depressant effect of phenobarbitone, 30 mg/kg. Both Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg, prevented the reversal of the depressant action of phenobarbitone, 30 mg/kg, produced by beta-CCM, 2 mg/kg. The results indicate that the muscle relaxant action of phenobarbitone in genetically spastic rats is mediated via GABA-related mechanisms and add further support to the hypothesis that both Ro 15-1788 and CGS 8216 are specific antagonists at benzodiazepine receptors, devoid of intrinsic activity at moderate doses. The results also suggest that reversal of the muscle relaxant action of phenobarbitone by beta-CCM is mediated via a GABA/benzodiazepine receptor/chloride ionophore complex.


Struggling with the basics: food and housing insecurity among college students across twenty-two colleges and universities.
To quantify the number and type of students failing to secure basic needs. Students attending 22 postsecondary schools in the United States in Fall 2019. The Adult Food Security Module and part of the #RealCollege Survey were used to measure food and housing insecurity, respectively. Logistic and linear regression models were used to assess the relationship between selected factors and basic needs insecurities. Participants (n = 22,153) were classified as 44.1% and 52.3% food insecure and housing insecure, respectively. Homeless students or those who experienced childhood food insecurity were at the greatest odds of college food insecurity. Year in school was the largest contributor to being housing insecure, with PhD or EdD students being 1,157% more likely to experience housing insecurity compared to freshmen. High prevalence of basic needs insecurities remain. Current campus initiatives may be insufficient, calling for a more holistic approach at the campus, state, and national levels.


Quantitative analysis of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) gene expression in calf and adult bovine ovaries.
It has been reported that calf oocytes are less developmentally competent than oocytes obtained from adult cows. Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) play critical roles in folliculogenesis, follicular development and ovulation in mammalian ovaries. In the present study, we attempted to compare the expression patterns of BMP15 and GDF9 in the cells of calf and cow ovaries to determine a relationship between the level of these genes and the low developmental competence of calf oocytes. Bovine tissues were collected from 9-11 months-old calves and from 4-6 years-old cows. We characterized the gene expression of BMP15 and GDF9 in calf and adult bovine oocytes and cumulus cells using quantitative real-time reverse transcriptase polymerase chain reaction (QPCR) and in situ hybridization. Immunohistochemical analysis was also performed. The expression of BMP15 and GDF9 in cumulus cells of adult ovaries was significantly higher than that in calf ovaries, as revealed by QPCR. GDF9 expression in the oocytes of calf ovaries was significantly higher than in those of the adult ovaries. In contrast, BMP15 expression in the oocytes of calf and adult ovaries was not significantly different. The localization of gene expression and protein were ascertained by histochemistry. Our result showed for the first time BMP15 and GDF9 expression in bovine cumulus cells. BMP15 and GDF9 mRNA expression in oocytes and cumulus cells was different in calves and cows.


Killing of preimplantation mouse embryos by main ingredients of cleansers AS and LAS.
When main ingredients of cleansers, alcohol sulfate (AS) and linear alkylbenzene sulfonate (LAS), were applied to the dorsal skin of pregnant JCL:ICR mice during preimplantation period (days 0-2), significant numbers of embryos collected from the oviducts and uteri on day 3 showed severe deformity or remained at the morula stage. Most of abnormal embryos were fragmented or remained at the 1-8 cell stages, and they were either dead or dying. Even when these abnormal embryos were cultivated in the detergent-free medium, they were not recovered, while most growth-retarded embryos (morula) could grow and hatch with one or two days lag by the further in vitro cultivation. Similar results were observed with commercially obtained kitchen detergent and hair shampoo, although such embryocidal effects were not detected with natural soap and distilled water. Fertilized eggs may be specifically sensitive to synthetic detergents. Very low doses of X-rays also induced significant yields of abnormal embryos. Major difference between X-rays and detergents was that X-ray-induced abnormality appeared at the morula or blastocyst stage, while detergent-induced one did at the earlier stages.


[Urodynamic profile of voiding disorders persisting after treatment of posterior urethral valve].
Posterior urethral valves (PUV) are the most common cause of bladder outlet obstruction in infancy that impairs renal and bladder function. We realize a retrospective study and examined 35 boys with urinary disorders post-treatment of PUV, seen at the urodynamic consultation. The mean age: 7.56 years, urinary problems are dominated by recurrent urinary tract infections and urinary leakage, morphological assessment is marked by the constant expansion of the urinary tract and bladder, 18 children have end-stage renal disease of which 8 are candidates for transplantation. About urodynamic, the uroflowmetry with measure of post-void urine residue: dysuria with significant residual urine in 14 children; for cystometry, 20 children with bladder hyperactivity, 9 bladders are hypotonic hypoactive with high capacity, 6 explorations are normal. Urodynamic explorations are all interest when voiding symptoms persist after endoscopic section valves and despite a good radiological result.


What strategies do desk-based workers choose to reduce sitting time and how well do they work? Findings from a cluster randomised controlled trial.
Large amounts of sitting at work have been identified as an emerging occupational health risk, and findings from intervention trials have been reported. However, few such reports have examined participant-selected strategies and their relationships with behaviour change. The Stand Up Victoria cluster-randomised controlled trial was a workplace-delivered intervention comprising organisational, environmental and individual level behaviour change strategies aimed at reducing sitting time in desk-based workers. Sit-stand workstations were provided, and participants (n = 134; intervention group only) were guided by health coaches to identify strategies for the 'Stand Up', 'Sit Less', and 'Move More' intervention targets, including how long they would stand using the workstation. Three-month workplace sitting and activity changes (activPAL3-assessed total sitting, prolonged sitting (i.e., sitting ≥30 min continuously) and purposeful walking) were evaluated in relation to the number (regression analysis) and types of strategies (decision-tree analysis). Over 80 different strategies were nominated by participants. Each additional strategy nominated for the 'Stand Up' intervention target (i.e. number of strategies) was associated with a reduction in prolonged sitting of 27.6 min/8-h workday (95% CI: -53.1, - 2.1, p = 0.034). Types of strategies were categorised into 13 distinct categories. Strategies that were task-based and phone-based were common across all three targets. The decision tree models did not select any specific strategy category as predicting changes in prolonged sitting ('Stand Up'), however four strategy categories were identified as important for total sitting time ('Sit Less') and three strategy categories for purposeful walking ('Moving More'). The uppermost nodes (foremost predictors) were nominating > 3 h/day of workstation standing (reducing total workplace sitting) and choosing a 'Move More' task-based strategy (purposeful walking). Workers chose a wide range of strategies, with both strategy choice and strategy quantity appearing relevant to behavioural improvement. Findings support a tailored and pragmatic approach to encourage a change in sitting and activity in the workplace. Evaluating participant-selected strategies in the context of a successful intervention serves to highlight options that may prove feasible and effective in other desk-based workplace environments. This trial was prospectively registered with the Australian New Zealand Clinical Trials register ( ACTRN12611000742976 ) on 15 July 2011.


Shining a light on species delimitation in the tree genus Engelhardia Leschenault ex Blume (Juglandaceae).
Enhanced efficacy in species delimitation is critically important in biology given the pending biodiversity crisis under global warming and anthropogenic activity. In particular, delineation of traditional classifications in view of the complexity of species requires an integrative approach to effectively define species boundaries, and this is a major focus of systematic biology. Here, we explored species delimitation of Engelhardia in tropical and subtropical Asia. In total, 716 individuals in 71 populations were genotyped using five chloroplast regions, one nuclear DNA region (nrITS), and 11 nuclear simple sequence repeats (nSSR). Phylogenetic trees were constructed and relationships among species were assessed. Molecular analyses were then combined with 14 morphological characteristics of 720 specimens to further explore the species boundaries of Engelhardia. Integrating phylogenetic and morphological clusters provided well-resolved relationships to delineate seven species. The results suggested that: first, that E. fenzelii, E. roxburghiana, E. hainanensis, E. apoensis, and E. serrata are distinct species; second, E. spicata var. spicata, E. spicata var. aceriflora, E. spicata var. colebrookeana, and E. rigida should be combined under E. spicata and treated as a species complex; third, E. serrata var. cambodica should be raised to species level and named E. villosa. We illuminated that bias thresholds determining the cluster number for delimiting species boundaries were substantially reduced when morphological data were incorporated. Our results urge caution when using the concepts of subspecies and varieties in order to prevent confusion, particularly with respect to species delimitation for tropical and subtropical species. In some cases, re-ranking or combining subspecies and/or varieties may enable more accurate species delimitation.


Neonatal suppurative parotitis over the last 4 decades: report of three new cases and review.
Neonatal suppurative parotitis is a rare disease. Only 32 cases were reported in the English-language literature between 1970 and 2004. We searched Medline for acute, neonatal, bacterial, suppurative, parotitis, facial, preauricular swelling starting from 1970, limiting our search to the English-language literature. We reviewed all the reported cases together with three more managed in our department. We identified nine new cases since 2004. The total number of patients reviewed was 44, including our patients. Most of them were male (77%). The majority developed unilateral inflamed parotid swelling (77%) and exuded pus from the ipsilateral Stensen duct. Fever was seen in fewer than half of them (47%). Premature babies constituted a third of the patients. Staphylococcus aureus was the leading causative agent (61%). Most patients responded well to conservative treatment with antibiotics (77%). The most frequently used combination of antibiotics was an anti-staphylococcal agent with either an aminoglycoside or a third-generation cephalosporin. A minority required surgical drainage. No deaths were reported in the group studied after 1970. Neonatal suppurative parotitis is rare but easy to diagnose and if readily treated with appropriate antibiotics the outcome is excellent.


31P-NMR studies of glucose and glutamine metabolism in cultured mammalian cells.
31P-NMR measurements of the concentrations of phosphorus-containing metabolites in mammalian cells immobilised and perifused with glucose and glutamine as sole carbon source have shown that the intracellular Pi concentration is significantly higher in cells perifused with glutamine than with glucose. The data are consistent with the proposal that the rate of glutamine utilisation may be controlled by the activity of phosphate-activated glutaminase.


Effect of RU-486 and related compounds on the proliferation of cultured macrophages.
Macrophages are implicated in the pathophysiology of endometriosis and are influenced by anti-inflammatory steroids as well as anti-oxidants. We tested the effect of RU-486, an antiprogesterone, antiglucocorticoid and an antioxidant, on the proliferation of RAW macrophages. The incorporation of 3H-thymidine was significantly inhibited by both progesterone and RU-486. Progesterone and RU-486, in combination, synergistically inhibited macrophage growth. In contrast, dexamethasone-stimulated growth was antagonized by RU-486 in a dose dependent manner. ZK 112,993 which is structurally related to RU-486 but lacks antioxidant properties, also inhibited thymidine incorporation. The synergistic effect of RU-486 and ZK 112,993 with progesterone implicate a mechanism of action separate from receptor bound antagonists. A cell permeable antioxidant, pyrrolidine dithiocarbamate was very effective in inhibiting the incorporation of 3H-thymidine into cells. These results suggest novel therapeutic modalities in the management of endometriosis via antiglucocorticoid as well as antioxidant mechanisms.


Cardiac response to norepinephrine and sympathetic nerve stimulation following experimental subarachnoid hemorrhage.
This study aimed to investigate the cardiac response to sympathetic stimulation and norepinephrine exposure following subarachnoid hemorrhage (SAH). Cardiac functional response was assessed 3 days following an injection of 300 microl of homologous blood in the cisterna magna using an in situ perfused, innervated rat heart model. Sympathetic nervous activity was indirectly assessed from measurements of arterial plasma and tissue norepinephrine concentration and cardiac beta-receptor density. In in situ perfused hearts, sympathetic nerve stimulation (2, 4 and 8 Hz, 1 min duration) induced a frequency-dependent increase in left ventricular pressure (VP), with the response being more pronounced in the SAH group of animals at the higher frequency (P<0.05). However, the concomitant release of norepinephrine was identical in the two groups of animals. Increasing doses of norepinephrine (10(-9) to 10(-5) M) added to the perfusate induced a dose-dependent increase in VP and its first derivative (dP/dt). Both responses were greater in the SAH animals compared to the sham rats (P<0.01). ECG recordings from SAH animals presented a higher incidence of different types of arrhythmias, both at rest and when submitted to electrical stimulation or norepinephrine exposure. No difference was found between groups in left ventricle norepinephrine content, plasma norepinephrine nor left ventricle beta-receptor density. In conclusion, hearts from animals following acute experimental SAH exhibit enhanced sensitivity to norepinephrine infusion and sympathetic nerve stimulation, and are more prone to develop arrhythmias. However, hypersensitivity of the heart may not be explained by changes in norepinephrine release or by beta-receptor density.


Very Early Progression of an In-Stent Calcified Nodule 2 Weeks After Drug-Eluting Stent Implantation in the Calcified Lesion.
In-stent calcified nodules (CNs) are one of the mechanisms of in-stent restenosis, but their underlying cause has not been elucidated. We report a case of a patient with early stent thrombosis due to an in-stent CN only 2 weeks after drug-eluting stent implantation. The fact that the in-stent CN was detected only 2 weeks after the initial percutaneous coronary intervention means that the underlying mechanism was the progression of the CN, indicating that in-stent CNs can occur even in the subacute phase. After percutaneous coronary intervention for a severe calcified lesion, very early progression of CNs can occur, and they require close follow-up and intensive antiplatelet therapy.


Preliminary Results of Femtosecond Laser-assisted Cataract Surgery in a Private Clinic in Iran.
To report the preliminary results of femtosecond laser-assisted cataract surgery in Iranian patients. This prospective case series included 21 eyes of 21 patients with cataract. Mean patient age was 66.7 ± 10 years. The patients underwent femtosecond-laser assisted cataract surgery (VICTUS Femtosecond Laser Platform: Bausch + Lomb) and intraocular lens (IOL) implementation in Bina Eye Hospital, Tehran, Iran between May and October, 2014. Visual outcomes, intraocular pressure (IOP), and complications were evaluated three months after surgery. Mean preoperative best-spectacle corrected visual acuity (BSCVA) was 0.40 ± 0.21 logMAR which significantly improved to 0.02 ± 0.03 logMAR three months postoperatively (P < 0.001). Mean preoperative IOP was 17.88 ± 2.70 mmHg which significantly decreased to 12.5 ± 1.51 mmHg three months after operation (P < 0.001). Mean duration of operation for these patients was 29.30 ± 8 minutes and mean femtosecond laser process time was 4.20 ± 2 minutes. In terms of complications, 9 patients developed fine subconjunctival hemorrhage and eye redness and 2 patients had mild corneal edema which all subsided within less than 7 days. Serious complications such as anterior or posterior capsule tears were not encountered. Femtosecond laser-assisted cataract surgery is a relatively new method of cataract.


In vitro collagen fibril alignment via incorporation of nanocrystalline cellulose.
This study demonstrates a method for producing ordered collagen fibrils on a similar length scale to those in the cornea, using a one-pot liquid-phase synthesis. The alignment persists throughout samples on the mm scale. The addition of nanocrystalline cellulose (NCC), a biocompatible and widely available material, to collagen prior to gelation causes the fibrils to align and achieve a narrow size distribution (36±8nm). The effects of NCC loading in the composites on microstructure, transparency and biocompatibility are studied by scanning electron microscopy, ultraviolet-visible spectroscopy and cell growth experiments. A 2% loading of NCC increases the transparency of collagen while producing an ordered microstructure. A mechanism is proposed for the ordering behavior on the basis of enhanced hydrogen bonding during collagen gel formation.


The effect of serum creatinine method choice on estimated glomerular filtration rate determined by the abbreviated MDRD formula.
The aim of this study was to measure the variability in estimated glomerular filtration rate (eGFR) calculated by laboratories in Northern Ireland where creatinine assays other than the Beckman CX3 assay used to derive the Modification of Diet in Renal Disease (MDRD) are utilized. Fifty patient samples were analysed for serum creatinine by kinetic Jaffe assays on the Roche modular P-800 (compensated assay), the Beckman LX20 and the Abbott Aeroset analysers. The median (interquartile range) eGFR calculated by the abbreviated MDRD equation using the creatinine results obtained by each method were 45.4 (31.7-66.6), 49.2 (35.4-78.1) and 50.0 (35.1-71.2) mL/min/1.73 m2 for Beckman, Roche (compensated) and Abbott assays, respectively. Following mathematical alignment of creatinine methods to the Beckman method the median (interquartile range) eGFR for the Roche and Abbott methods were 44.0 (32.0-67.6) and 45.6 (31.2-64.8) mL/min/1.73 m2, respectively. The regression equations published in this study can be used to align creatinine methods. However, method-related biases in eGFR of up to 10% are minimal in the context of the magnitude of variance reflected in the 90% confidence intervals.


Lactating mouse mammary cell uptake of 59Fe-transferrin. The effect of KCN, 2,4-dinitrophenol, ethanol and ATP.
1. Amounts of KCN of 0.2, 1.0 and 2.0 X 10(-11) mol in a probe do not prevent the uptake of transferrin iron from lactating mouse mammary gland cells. 2. The effect of 5, 10 and 100 X 10(-11) mol in a probe 2,4-dinitrophenol dissolved in 20% ethanol is also negative on the iron-transferrin uptake from the cell. 3. There is a statistically significant decrease of uptake of transferrin-iron under the influence of 20% ethanol in the incubation mixture (25, 50 and 100 microliters). The effect of ethanol is diminished by 2,4-dinitrophenol in the solution. 4. The uptake of 59Fe-transferrin from cells of lactating gland was blocked by ATP (in amounts 0.5, 1.0 and 10.0 X 10(-11) mol per probe) while other concentrations have no effect. It seems that ATP does not release 59Fe from transferrin, nor help the iron uptake from the cells. 5. All evidence indicates that the uptake of transferrin-iron from lactating mammary gland cells is not an energy dependent process.


Repeat self-harm among Chinese adolescents: 1-year incidence and psychosocial predictors.
Self-harm in adolescents is prevalent and is the most significant predictor of future self-harm and suicide. Longitudinal data on the incidence and predictors of repeat self-harm in the general population of adolescents are limited. This study investigated 1-year incidence and psychosocial predictors of repeat self-harm in Chinese adolescents. Shandong Adolescent Behavior and Health Cohort is a longitudinal study of behavior and health in adolescents in Shandong Province, China. Of 7072 participants who were assessed in 2015 and again 1 year later in 2016, 1879 reported a history of self-harm at the baseline survey and were included for this analysis. A self-administered structured questionnaire was used to assess behavioral and emotional problems, sleep, life stress, previous history of self-harm and suicidal thought, and family factors at baseline and self-harm at 1-year follow-up. Mean age of the sample was 14.86 (SD 1.36) years and 54.6% were female. At 1-year follow-up, 22.1% participants engaged in repeat self-harm. Multiple logistic regression analyses showed that female gender (OR 1.45, 95% CI 1.11-1.89), alcohol use (OR 1.95, 95% CI 1.48-2.57), frequent nightmares (OR 1.61, 95% CI 1.14-2.28), elevated depression score (OR 1.59, 95% CI 1.05-2.42), and prior suicidal thought (OR 1.79, 95% CI 1.37-2.34) were independently and significantly associated with an increased risk of repeat self-harm. More than one in five Chinese adolescents who had a history of self-harm engaged in self-harm at 1-year follow-up. Multiple psychosocial factors including female gender, alcohol use, frequent nightmares, depression, and prior suicidal thought appeared to be significant predictors of repeat self-harm. Our findings highlight the importance of comprehensive psychosocial assessment and intervention of repeat self-harm in adolescents.


Estimation of surgical risk in the elderly: a correlative review.
Age continues to be a risk factor for overall mortality in elective and emergency surgical procedures. Postoperative pneumonias, life-threatening cardiac complications, and malignancy-related complications account for most deaths. Heart disease, dementia, and diabetes confer an additional surgical risk for elderly patients. Careful preoperative assessment, however, can categorize elderly patients into groups that are at no additional risk. Factors other than age should be considered in estimating surgical risk in the elderly.


Laryngopharyngeal reflux mimicking limited wegener granulomatosis.
We present a case of subglottic stenosis (SGS) in a young patient with positive ANCA but a wrong diagnosis of Wegener granulomatosis (WG). Instead, she was diagnosed as having laryngopharyngeal reflux (LPR). Pitfalls of ANCA testing in this scenario, the route to diagnosis of LPR and the contribution of this entity to subglottic stenosis (SGS) in WG are discussed. Caution when interpreting ANCA results is mandatory to avoid improper management.


Anterior interosseous nerve compression syndrome: is there a role for endoscopy?
Anterior interosseous nerve syndrome is characterized by paralysis of the flexor digitorum profundus, the flexor pollicis longus and the pronator quadratus muscles without sensory loss. Extended exploration of the anterior interosseous nerve is the surgical treatment of choice. The present study evaluates the feasibility of an endoscopic approach for nerve decompression. Preparation of the anterior interosseous nerve was performed in ten human cadaver arms. Subsequently, one female patient suffering from anterior interosseous nerve syndrome was endoscopically operated on. A skin incision of 3-4 cm in the proximal direction was made at the forearm, and the median nerve was visualized between the pronator teres muscle and the flexor digitorum superficialis. Subsequently, the anterior interosseus nerve branch was identified, followed distally and decompressed under endoscopic view. The procedure could be accomplished in all cases under endoscopic view. Due to the very steep surgical angle, a branch of the anterior interosseus nerve was injured in one cadaver case. In all other cases, no adverse effects were observed. In the clinical case, the anterior interosseus nerve was endoscopically identified and decompressed, but a skin incision of 5 cm was required. The results demonstrate that an endoscopic decompression of the anterior interosseus nerve is possible. Several difficulties occurred: Due to the depth of the surgical approach, especially in case of bulky muscles and very small skin incisions, the view is limited, harboring a higher risk of nerve injury. With more experience and specially designed endoscopes, application of this technique in anterior interosseus nerve compression syndrome might become more feasible.


Association Between Dementia Care Programs in Assisted Living Facilities and Transitions to Nursing Homes in Ontario, Canada: A Population-Based Cohort Study.
We investigate whether older adults who were newly diagnosed with dementia (severity unspecified) and resided in an assisted living facility that offered a dementia care program had a lower rate of transition to a nursing home, compared to those who resided in an assisted living facility without such a program. Population-based retrospective cohort study. Linked, person-level health system administrative data on older adults who were newly diagnosed with dementia and resided in an assisted living facility in Ontario, Canada, from 2014 to 2019 (n = 977). Access to a dementia care program in an assisted living facility (n = 57) was examined. Multivariable Cox proportional hazards regression with robust standard errors clustered on the assisted living facility was used to model the time to transition to a nursing home from the new dementia diagnosis. There were 11.8 transitions to a nursing home per 100 person-years among older adults who resided in an assisted living facility with a dementia care program, compared with 20.5 transitions to a nursing home per 100 person-years among older adults who resided in an assisted living facility without a dementia care program. After adjustment for relevant characteristics at baseline, older adults who resided in an assisted living facility with a dementia care program had a 40% lower rate of transition to a nursing home (hazard ratio 0.60, 95% confidence interval 0.44, 0.81), compared with those in an assisted living facility without such a program at any point during the follow-up period. The rate of transition to a nursing home was significantly lower among older adults who resided in an assisted living facility that offered a dementia care program. These findings support the expansion of dementia care programs in assisted living facilities.


Utilization of waste fish oil and glycerol as carbon sources for polyhydroxyalkanoate production by Salinivibrio sp. M318.
A moderately halophilic bacterium isolated from fermenting shrimp paste, Salinivibrio sp. M318 was found capable of using fish sauce and mixtures of waste fish oil and glycerol as nitrogen and carbon sources, respectively, for poly(3-hydroxybutyrate) (PHB) production. A cell dry weight (CDW) of up to 10 g/L and PHB content of 51.7 wt% were obtained after 48 h of cultivation in flask experiment. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] was synthesized when 1,4-butanediol, γ-butyrolactone, or sodium 4-hydroxybutyrate was added as precursors to the culture medium. The biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] was achieved by supplying precursors such as sodium valerate, sodium propionate, and sodium heptanoate. Salinivibrio sp. M318 was able to accumulate the above mentioned PHAs during the growth phase. High CDW of 69.1 g/L and PHB content of 51.5 wt% were obtained by strain Salinivibrio sp. M318 after 78 h of cultivation in fed-batch culture. The results demonstrate Salinivibrio sp. M318 to be a promising wild-type bacterium for the production of PHA from aquaculture residues.


Biological monitoring for exposure to deltamethrin: a human oral dosing study and background levels in the UK general population.
An oral dose of the pyrethroid insecticide deltamethrin was administered to five volunteers at the acceptable daily intake (ADI, 0.01 mg/kg). Total urine was collected from the volunteers at timed intervals for 60h post-exposure. The metabolites 3-(2,2-dibromovinyl)-2,2-dimethyl-(1-cyclopropane)carboxylic acid (DBVA) and 3-phenoxybenzoic acid (3-PBA) were quantified in hydrolysed urine using GC-MS analysis. Both metabolites exhibited rapid elimination half-lives of 3.6 and 7.1h, respectively. Levels of DBVA quantified in urine were approximately 5 times greater than 3-PBA. Mean metabolite levels found in 24h total urine collections, normalised for a 70 kg individual, were 42.8 μmol DBVA/mol creatinine (range 34.6-63.2; CV=28%) and 8.7 μmol 3-PBA/mol creatinine (range 6.6-12.7; CV=31%). We calculate that a 70 kg person receiving a dose of deltamethrin at the ADI would be expected to have a 24-h total urine collection level of 32-53 μmol DBVA/mol creatinine (95% confidence interval). Analysis of 336 samples from adult UK residents with no known exposure to deltamethrin derives an upper reference value (95th percentile) of 0.5 μmol DBVA/mol creatinine (maximum 4.2 μmol DBVA/mol creatinine), demonstrating that general population exposure to deltamethrin in the UK is very low and well within levels expected at the ADI.


Safety and authenticity risks in heritage food preparation at different types of food service establishments: A case study of Saudi Arabia.
In Saudi Arabia, tourism is becoming increasingly popular, and forms an essential element of Vision 2030. Accordingly, food service establishments (FSEs) including hotels, ordinary restaurants, heritage restaurants and productive families (i.e., home-based catering) provide heritage cuisine to tourists. This study aimed to assess the authenticity and safety risks associated with the production of heritage food dishes in different FSEs. An online questionnaire was administered in Saudi Arabia, and a total of 85 culinary professionals from different FSEs responded. The culinary professionals were requested to provide opinions on the frequency of food safety and authenticity risk situations at their FSEs, using a five-point Likert scale. The results indicate that most food safety risk situations occur less frequently in hotels because of strict food safety management systems. In contrast, food safety risk situations are more frequent in ordinary and heritage restaurants, particularly in the absence of personal hygiene requirements. In productive families, most food safety risk situations occur because there are no control systems or inspections. Authenticity risks occur less frequently in productive families and heritage restaurants than in other FSEs. Hotels often/always face authenticity risk situations, such as cooking of heritage dishes by non-Saudi culinary professionals and the use of modern equipment. Ordinary restaurants face the highest risk, mostly because of the limited knowledge and skills of the cooks. Overall, this study provides the first insight into the occurrence of possible safety and authenticity risk situations during the preparation of heritage dishes; this information may contribute to improve the production of safe and authentic heritage dishes in the hospitality industry for tourists and local people.


Actor-partner association of work-family conflict and parental depressive symptoms during COVID-19 in China: Does coparenting matter?
Parental depressive symptoms and their related factors have not been widely examined during the COVID-19 pandemic. Therefore, the current study examined the actor and partner associations of work-family conflict and parental depressive symptoms. Considering the new demands and challenges for families during the COVID-19 pandemic, we further explored the moderation effect of coparenting. A cross-sectional online survey with 985 paired fathers and mothers was conducted in Mainland China. In 11.6% of families, only mothers reported moderate to severe depressive symptoms; in 10.6% families, only fathers reported moderate to severe depressive symptoms; in 9.5% families, the mother and father reported mild to moderate depressive symptoms. Results of the actor-partner interdependence model showed that parental family-to-work conflict was negatively associated with their own depressive symptoms. The negative actor association of maternal family-to-work conflict and depressive symptoms was moderated by undermining coparenting. The partner effects of maternal family-to-work and work-to-family conflicts on paternal depressive symptoms were moderated by undermining coparenting. Moreover, supportive coparenting moderated the actor association of work-to-family conflict and the depressive symptoms of fathers. Results highlight the importance of family-to-work conflict and family function for parental depressive symptoms. These findings can help promote parental well-being during the COVID-19 pandemic.


Not so simple: a quasi-experimental study of how researchers adjudicate genetic research results.
Ethicists contend that researchers are obliged to report genetic research findings to individual study participants when they are clinically significant, that is, when they are clinically useful or personally meaningful to participants. Yet whether such standards are well understood and can be consistently applied remains unknown. We conducted an international, cross-sectional survey of cystic fibrosis (CF) and autism genetics researchers using a quasi-experimental design to explore factors influencing researchers' judgments. Eighty percent of researchers agreed, in principle, that clinically significant findings should be reported to individual participants. Yet judgments about when a specific finding was considered clinically significant or warranted reporting varied by scientific factors (replication, robustness, intentionality, and disease context), capacity of the research team to explain the results, and type of research ethics guidance. Further, judgments were influenced by the researchers' disease community (autism or CF), their primary role (clinical, molecular, statistical) and their beliefs regarding a general reporting obligation. In sum, judgments about the clinical significance of genetic research results, and about whether they should be reported, are influenced by scientific parameters as well as contextual factors related to the specific research project and the individual researcher. These findings call into question the assumption that the conditions under which an obligation to disclose arises are uniformly understood and actionable. Adjudicating the clinical readiness of provisional data may be a responsibility better suited to evaluative experts at arms' length of the provisional data in question, rather than a responsibility imposed upon researchers themselves.


A survey of Streptococcus pneumoniae, Streptococcus zooepidemicus, Salmonella spp., Bordetella bronchiseptica and Sendai virus in guinea pig colonies in Japan.
S. pneumoniae, S. zooepidemicus, Salmonella spp., B. bronchiseptica and Sendai virus were examined in a total of 45 guinea pig colonies (17 institutional and 28 breeder's colonies) of Hartley strain, and found to be positive in 6, 3, 5, 20 and 14 colonies, respectively. Sendai virus was highly prevalent among guinea pigs, showing so high rates positive as 80 to 100% of animals obtained from 11 of the 14 contaminated colonies. B. bronchiseptica was also shown to be prevalent within contaminated colonies by indication of rates positive more than 40% of animals examined in 14 of the 20 colonies. Infection rates of other 3 pathogens, however, ranged from lower than 20% to higher than 80% according to colonies. All strains of Salmonella isolated in this survey were identified as S. typhimurium and those of S. pneumoniae as serotype 19F.


Equine Gastric Ulcer Syndrome: An Update on Current Knowledge.
Equine Gastric Ulcer Syndrome (EGUS) is a term that has been used since 1999, initially being used to describe all gastric mucosal disease in horses. Since this time, the identification of two distinct main disease entities of the equine gastric mucosa have been described under the umbrella of EGUS; these are Equine Squamous Gastric Disease (ESGD) and Equine Glandular Gastric Disease (EGGD). In 2015 the European College of Equine Internal Medicine (ECEIM) released a consensus statement defining these disease entities. This document highlighted the lack of evidence surrounding EGGD compared to ESGD, and identified knowledge gaps for further research to be directed. Subsequently, many studies on EGGD have been published, especially on pathophysiology, diagnosis, and treatment. This article updates current knowledge on both ESGD and EGGD as understanding has evolved since the last large-scale review.


Cost-effectiveness of COVID-19 vaccination in Latin America and the Caribbean: an analysis in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru.
Our study analyzes the cost-effectiveness of the COVID-19 vaccination campaigns in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru. Using a previously published SVEIR model, we analyzed the impact of a vaccination campaign (2021) from a national healthcare perspective. The primary outcomes were quality adjusted life years (QALYs) lost and total costs. Other outcomes included COVID-19 cases, hospitalizations, deaths, and life years. We applied a discount rate of 3% for health outcomes. We modeled a realistic vaccination campaign in each country (the realistic country-specific campaign). Additionally, we assessed a standard campaign (similar, "typical" for all countries), and an optimized campaign (similar in all countries with higher but plausible population coverage). One-way deterministic sensitivity analyses were performed. Vaccination was health improving as well as cost-saving in almost all countries and scenarios. Our analysis shows that vaccination in this group of countries prevented 573,141 deaths (508,826 standard; 685,442 optimized) and gained 5.07 million QALYs (4.53 standard; 6.03 optimized). Despite the incremental costs of vaccination campaigns, they had a total net cost saving to the health system of US$16.29 billion (US$16.47 standard; US$18.58 optimized). The realistic (base case) vaccination campaign in Chile was the only scenario, which was not cost saving, but it was still highly cost-effective with an ICER of US$22 per QALY gained. Main findings were robust in the sensitivity analyses. The COVID-19 vaccination campaign in seven Latin American and Caribbean countries -that comprise nearly 80% of the region- was beneficial for population health and was also cost-saving or highly cost-effective.


Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma.
Dual-targeting nanoparticle drug delivery system was developed by conjugating Angiopep with PEG-PCL nanoparticles (ANG-NP) through bifunctional PEG to overcome the limitations of low transport of chemotherapeutics across the Blood-brain barrier (BBB) and poor penetration into tumor tissue. ANG-NP can target the low-density lipoprotein receptor-related protein (LRP) which is over-expressed on the BBB and glioma cells. Compared with non-targeting nanoparticles, a significantly higher amount of rhodamine isothiocyanate-labeled dual-targeting nanoparticles were endocytosed by U87 MG cells. The antiproliferative and cell apoptosis assay of paclitaxel-loaded ANG-NP (ANG-NP-PTX) demonstrated that ANG-NP-PTX resulted in enhanced inhibitory effects to U87 MG glioma cells. The transport ratios across the BBB model in vitro were significantly increased and the cell viability of U87 MG glioma cells after crossing the BBB was obviously decreased by ANG-NP-PTX. Enhanced accumulation of ANG-NP in the glioma bed and infiltrating margin of intracranial U87 MG glioma tumor-bearing in vivo model were observed by real time fluorescence image. In conclusion, Angiopep-conjugated PEG-PCL nanoparticles were prospective in dual-targeting drug delivery system for targeting therapy of brain glioma.


Immunosuppression impact on long-term cardiovascular complications after liver transplantation.
With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed. The objective of this study is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation. Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were >/=18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx. At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group. Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease.


Sleep apnea and pulmonary hypertension: A riddle waiting to be solved.
Obstructive sleep apnea (OSA) is an under-recognized yet highly prevalent disease that has major implications to cardiovascular health. Pulmonary hypertension (pH) is less common but none the less a fatal condition. The association of OSA and PH is a known but not well understood phenomenon. Furthermore, the relationship appears to be bi-directional with limited understanding of the mechanism(s) driving the processes. PH in OSA has real time consequences as it has been shown to increase mortality. Limited data suggests that treatment with continuous positive pressure therapy may be beneficial and reduce pulmonary pressure. In this review, we discuss current data on prevalence of PH in OSA and vice versa. We also explore the pathophysiology of this relationship and a proposed mechanism for their connection. Finally, we address the treatment of OSA with CPAP and its impact on pulmonary pressures. Gaps in knowledge and future research potential are illustrated and discoursed.


The Appraisal Approach to Aging and Emotion: An Integrative Theoretical Framework.
To advance our understanding of how emotional experience changes across the adult life span, we propose an integrative theoretical framework: the appraisal approach to aging and emotion (AAAE). AAAE posits that (a) age-related cognitive, motivational, and physical changes fundamentally change the appraisal system in certain ways, and that (b) older adults often deploy appraisal processes in different ways relative to their younger counterparts. As such, we hypothesize that these age-related changes to the appraisal process underlie the finding that older and younger adults tend to experience different emotions. In this paper we integrate findings from the aging literature with appraisal theory, grounding AAAE in theoretical and empirical work relevant to the relationship between aging and appraisal processes. Using our theoretical framework, it is possible to identify critical points of investigation for aging and emotion researchers to further develop our understanding of the proximal-level determinants of age differences in emotion.


Awareness towards an increasing concern during pregnancy: maternal and perinatal outcomes of women with cancer.
Increased incidence of cancer in women of childbearing age and improvements on treatment for preserving fertility have led to higher frequency of pregnancy during or after cancer treatment. This study aimed to describe maternal and perinatal outcomes associated with cancer and pregnancy and, as a secondary analysis, to compare outcomes of women with active disease and with remission before pregnancy. We performed a retrospective study of women followed up at a referral center owing to a history of cancer or cancer diagnosed during pregnancy. Data on sociodemographic information, obstetrical history, types of neoplasia, treatments offered, antenatal follow-up, and maternal and perinatal outcomes were retrieved from medical chart review. A descriptive analysis was performed and a comparison among women with active and nonactive disease was performed using Student t-test and chi-square test. A total of 66 women were included in a 5-year period. The most frequent types of cancer were breast (33%), hematologic (21%), brain (11%), cervical (9%), and ovarian (5%) cancers. There were 39 participants (59%) who had active disease and 26 who received oncological treatment during pregnancy, and 23 (34.8%) had a vaginal delivery. There were 4 women who needed intensive care unit admission postpartum. A total of 18 (29.5%) deliveries were at term, most newborns (59%) with adequate weight for gestational age and only 1 had Apgar score lower than 7 in the fifth minute of life. There was 1 stillbirth. The active invasive cancer during pregnancy group showed a higher rate of preterm birth and lower birthweight with significant statistical difference (P=.03 and P<.01, respectively). Breast cancer was the most frequent type of cancer in our cohort. Most deliveries were preterm, with adequate birthweight. Women with active cancer are more likely to have a preterm childbirth and newborns with lower birthweight.


Occurrence of aflatoxins in nuts and peanut butter imported to UAE.
Nuts are an important food group that contributes to maintaining health; however, they can be a source of exposure to aflatoxins. This study was conducted from 2017 to 2021 to assess the incidence of aflatoxins in nuts and nut products imported to the UAE from 57 countries. Associations between container type and processing technique and aflatoxin levels were also analyzed. A total of 5401 samples of pistachios, peanuts, peanut butter, and mixed nuts were examined using HPLC-FLD analysis in conjunction with immunoaffinity cleanup. In nuts, non-conformity was detected in samples imported from 32 different countries. Mean aflatoxin values for the non-compliant samples ranged from 81.0 to 92.7 μg/kg in pistachios, peanuts, and mixed nuts. A significant difference (p < 0.05) was found between mean aflatoxin levels in samples of peanut butter (29.3 μg/kg) compared to the other types of nuts. Nuts packed in containers made of fabric material had the highest mean aflatoxin levels of 108.1 μg/kg, while 29.7 μg/kg was the lowest mean level and was detected in nuts packed in glass. Ground samples had the highest aflatoxin levels (158.9 μg/kg) among processed products. This report will be valuable as a reference document in developing approaches to control nut importation and for establishing procedures that prevent food safety risks due to aflatoxin exposure. A need was underlined for the regulating authority to audit companies importing nuts, ensure safe practices are in place, and establish standards to minimize contamination and prevent the need for product rejection at the border.


A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3-1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer.
Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m2 and subsequent doses 250 mg/m2, weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m2, Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4-6 cycles; patients who responded or remained stable received maintenance therapy with BTH1677/cetuximab (BTH1677 arm) or cetuximab (Control arm). Investigator and blinded central radiology reviews were conducted. Efficacy assessments included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, time-to-progression and overall survival (OS); safety was assessed by adverse events (AEs). Potential biomarker analysis for BTH1677 response was also conducted. Results Compared to control treatment, the addition of BTH1677 numerically increased ORR by both investigator (47.8% vs 23.1%; p=0.0468) and central (36.6% vs 23.1%; p=0.2895) reviews. No other endpoints differed between arms. PK was consistent with previous studies. BTH1677 was well tolerated, with AEs expected of the backbone therapy predominating. Biomarker-positive patients displayed better ORR and OS than negative patients. Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacy ClinicalTrials.gov Identifier: NCT00874848.


Parenteral antibiotics in elective colon surgery? A prospective, controlled clinical study.
The addition of perioperative gentamicin and clindamycin to an oral antibiotic bowel preparation was studied in a prospective, randomized, double-blind series of patients undergoing elective colectomy. Fifty-nine patients completed the study, with all receiving mechanical preparation of the colon and oral neomycin and erythromycin base. Thirty-one of these patients also received a preoperative and postoperative intravenous dose of gentamicin and clindamycin, while 28 received placebos. The two groups of patients were similar in age, both habitus, pathologic diagnosis, concomitant disease, operative procedures, operative time, blood loss, and adequacy of mechanical preparation of the colon. The incidence of infectious complications related to colectomy was 1% (three of 28) in the placebo group and 7% (two of 31) in the group receiving intravenous gentamicin and clindamycin. There were no wound infections directly related to colectomy in either group. There was no statistically significant reduction of infectious complications with the addition of intravenous gentamicin and clindamycin to oral neomycin and erythromycin-base bowel preparation.


Production of rotavirus-like particles in Spodoptera frugiperda larvae.
A strategy for the production of virus-like particles (VLPs) from simian rotavirus in larvae of the lepidopteran Spodoptera frugiperda is described. VP2 and VP6 coding sequences were co-expressed in larvae co-infected with recombinant baculovirus and these structural proteins self-assembled into VLPs that were secreted and accumulated in the haemolymph. Under electron microscopy, VLPs produced in larvae were indistinguishable from those produced in Sf9 insect cell cultures. The results showed that it is possible to obtain rotavirus VLPs in larvae reducing significantly the costs of production, making this approach an alternative for the manufacture of live rotavirus vaccines.


The Birth Plan Experience-A Pilot Qualitative Study in Southern Spain.
Healthcare systems advocate for quality care and humanized relations in routine birth care, and have therefore created the Birth Plan, a document available to pregnant women to state their preferences in relation to the birth process. This qualitative research with a phenomenological design was carried out to record the experiences of women who presented a Birth Plan. Sample selection was carried out using non-probabilistic, intentional and convenience sampling, selecting seven participants who were willing to participate and share their experiences. After analyzing the content of the interviews, four categories emerged: "respecting the woman's wishes: humanizing the birth process", "information and primary Care", "expectations regarding the care received" and "results of using the birth plan", with their corresponding subcategories. Women consider it beneficial to present a Birth Plan, because it informs them about the process and gives them the opportunity to have a better experience, which takes into account their preferences for making the delivery less instrumental. In addition, they state the importance of having trained professionals involved, and call for more attention to be paid to the birth process in general.


Differential risk factors for early and later hospital readmission of older patients.
This study aimed at analyzing rates and factors associated with early and later readmission (0-1 month and 2-3 months after discharge, respectively) of older people after index hospitalization. This prospective observational study was conducted in two teaching hospitals. People 70 years and over were interviewed within 48 h of emergency admission. Socio-demographic and medical factors were collected, together with functional factors including Activities of Daily Living (basis and instrumental), cognitive state, and geriatric syndromes. Medical diagnosis, length of stay, and destination were collected at discharge, and patients were followed up by phone 1 and 3 months after discharge. During these interviews, outcomes on readmission, institutionalization, need for help, and death were evaluated. The population of 625 patients had a mean age of 80.0 years. The rate of early readmission (01 month) was 10. 7% and the overall rate within 3 months was 23.1%. Logistic regression analysis showed that variables predicting early readmission were previous hospitalization within 3 months, a longer length of stay, and a discharge diagnosis in chapter 8 (respiratory system) and chapter 10 (genito-urinary system) of the ICD-9-CM. Variables predicting later readmission were previous hospitalization within 3 months, a discharge diagnosis in chapter 7 (circulatory system) of the ICD-9-CM, and a poor pre-admission IADL score. In a medicalized population of older people, several risk factors may be identified for 0-1 month and 2-3 month readmission. Besides severe morbidities at discharge, diagnoses and previous hospitalization, pre-admission IADL was an independent risk factor for 2-3 month readmission.


Starch inclusion complex for the encapsulation and controlled release of bioactive guest compounds.
The linear component of starch, especially amylose, is capable of forming inclusion complex (IC) with various small molecules. It could significantly modify the structure and properties of starch, and it could bring beneficial effects when bioactive compounds can be encapsulated. This review discusses the formation and characterization of the starch-guest IC and focuses on the recent developments in the use of starch ICs for the encapsulation and controlled release of bioactive guest compounds. A great number of guest compounds, such as lipids, aroma compounds, pharmaceuticals, and phytochemicals, were studied for their ability to be complexed with starch and/or amylose and some of the formed ICs were evaluated for the chemical stability improvement and the guest release regulation. Starch-guest ICs has a great potential to be a delivery system, as most existing studies demonstrated the enhancement on guest retention and the possibility of controlled release.


Evidence of Effect of Aerobic Exercise on Cognitive Intervention in Older Adults With Mild Cognitive Impairment.
This study aimed to evaluate the effectiveness of aerobic exercise as a cognitive intervention for older adults with mild cognitive impairment (MCI). The PubMed, EMBASE (Ovid), Cochrane Library, Web of Science, and Medline databases were searched from their inception until 30 April 2021. Randomized controlled trials (RCTs) examining the effects of aerobic exercise on global cognitive function in older adults with MCI were included. Ten eligible trials with acceptable methodological quality were identified. The meta-analysis results showed that aerobic exercise significantly improved the MMSE (N = 956, MD = 0.60, 95% CI: 0.28-0.92, p = 0.0003, I 2 = 31%, fixed effects model) and MoCA scores (N = 398, MD = 1.67, 95% CI. 1.18-2.15, p < 0.0001, I 2 = 37%, fixed-effects model) and overall cognitive performance in patients with MCI. The results of this study suggest that participation in regular aerobic exercise can improve cognitive function in older adults with MCI. These findings should be used with caution considering the limitations of the study.


Protocol to Reprogram Human Menstrual Blood-Derived Stromal Cells to Generate AOX15-iPSCs.
Cell reprogramming has revolutionized the fields of cell and regenerative biology. However, human induced pluripotent stem cell (iPSC) derivation remains inefficient and variable. Here, we present a protocol that uses human menstrual blood-derived stromal cells (MnSCs), which are susceptible to reprogramming, as a source of somatic cells. We describe an oocyte-based reprogramming combination to generate AOX15-iPSCs that can be used to study different states of pluripotency. For complete details on the use and execution of this protocol, please refer to Lopez-Caraballo et al. (2020).


Surgical management of soft tissue tumors of the abdominal wall: A retrospective study in a high-volume sarcoma center.
The aim of the study is to evaluate functional and oncological outcomes of patients undergoing abdominal wall soft tissue tumors (AWSTT) surgery. All consecutive patients that underwent surgery for malignant and intermediate AWSTT from 1999 to 2019 were retrospectively analyzed. Ninety-two patients were identified, 20 (22%) operated on for a desmoid tumor and 72 (78%) for a soft tissue sarcoma (STS). Fifty-two patients (57%) had in toto resection of the abdominal wall (from the skin to the peritoneum) and 9 (10%) required simultaneous visceral resection. The closure was direct in 28 patients (30%) and requiring a mesh, a flap or a combination of the two in respectively 42, 16, and 6 patients (47%, 17%, 6%). The postoperative complications rate was 26%. Thirteen patients (14%) developed an incisional hernia after a median delay of 27 months. After a median follow-up of 40 months, out of the 72 patients operated on for STS, 7 (10%) developed local recurrence and 11 (15%) distant recurrence. The median recurrence-free and overall survivals were 61 and 116, months respectively. Management of AWSTT requires extensive surgery but allows good local control with an acceptable rate of incisional hernia.


Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats.
The modulatory potential of noscapine, an opium alkaloid was assessed on the ethanol-induced changes in hepatic drug metabolizing enzyme systems, glutathione content and microsomal lipid peroxidation. Noscapine was administered orally to male Wistar rats at a dose level of 200 mg/kg bw alone as well as in combination with 50% ethanol (v/v) for 5 days. Noscapine administration was associated with a approximately 91% decrease in hepatic microsomal cytochrome P-450 content. A decline of approximately 36% was observed in the NADPH-cytochrome c reductase activity on noscapine administration. The lowering of cytochrome P-450 levels on noscapine administration was accompanied by a concomitant increase in heme oxygenase activity as well as serum bilirubin levels. Our results indicate that the combination dosage of noscapine and ethanol antagonised the ethanol-induced elevation of cytochrome P-450 levels. Noscapine fed rats had decreased glutathione (GSH) content and enhanced lipid peroxidation compared to control rats as indexed by MDA method. Further, noscapine and ethanol coexposure produced a more pronounced elevation in lipid peroxidation and the glutathione levels also decreased significantly. We speculate on the basis of our results that the significant enhancement of lipid peroxidation on combination dosage of noscapine and ethanol is a consequence of depletion of glutathione to certain critical levels. The inhibition of glutathione-S-transferase (GST) as well as lowering of cytochrome P-450 suggests that the biotransformation of noscapine and ethanol is significantly altered following acute coexposures.


Assessing the Usability of an Automated Continuous Temperature Monitoring Device (iThermonitor) in Pediatric Patients: Non-Randomized Pilot Study.
Fever is an important vital sign and often the first one to be assessed in a sick child. In acutely ill children, caregivers are expected to monitor a child's body temperature at home after an initial medical consult. Fever literacy of many caregivers is known to be poor, leading to fever phobia. In children with a serious illness, the responsibility of periodically monitoring temperature can add substantially to the already stressful experience of caring for a sick child. The objective of this pilot study was to assess the feasibility of using the iThermonitor, an automated temperature measurement device, for continuous temperature monitoring in postoperative and postchemotherapy pediatric patients. We recruited 25 patient-caregiver dyads from the Pediatric Surgery Department at the Massachusetts General Hospital (MGH) and the Pediatric Cancer Centers at the MGH and the Dana Farber Cancer Institute. Enrolled dyads were asked to use the iThermonitor device for continuous temperature monitoring over a 2-week period. Surveys were administered to caregivers at enrollment and at study closeout. Caregivers were also asked to complete a daily event-monitoring log. The Generalized Anxiety Disorder-7 item questionnaire was also used to assess caregiver anxiety at enrollment and closeout. Overall, 19 participant dyads completed the study. All 19 caregivers reported to have viewed temperature data on the study-provided iPad tablet at least once per day, and more than a third caregivers did so six or more times per day. Of all participants, 74% (14/19) reported experiencing an out-of-range temperature alert at least once during the study. Majority of caregivers reported that it was easy to learn how to use the device and that they felt confident about monitoring their child's temperature with it. Only 21% (4/9) of caregivers reported concurrently using a device other than the iThermonitor to monitor their child's temperature during the study. Continuous temperature monitoring was not associated with an increase in caregiver anxiety. The study results reveal that the iThermonitor is a highly feasible and easy-to-use device for continuous temperature monitoring in pediatric oncology and surgery patients. ClinicalTrials.gov NCT02410252; https://clinicaltrials.gov/ct2/show/NCT02410252 (Archived by WebCite at http://www.webcitation.org/73LnO7hel).


New designer drug of abuse: 3,4-Methylenedioxypyrovalerone (MDPV). Findings from apprehended drivers in Finland.
Starting in 2008 a new designer drug, 3,4-methylenedioxypyrovalerone (MDPV) appeared among users of illegal drugs in Finland. Since then there have been several seizures of MDPV by police and customs and it has been connected to many crimes of different types. In this study the incidence and impact of the use of MDPV in drivers suspected of being under the influence of drugs (DUID) in Finland was assessed. Since autumn 2009, blood samples from drivers suspected of DUID in Finland have been analysed for the presence of MDPV. A new LC-MS/MS method for the determination of MDPV in serum was established. In order to assess the impact of MDPV on driving performance, drug and alcohol findings of positive MDPV cases were compared with data from the clinical examination carried out while the suspect was under arrest. In a period of one year there were 259 positive MDPV cases from apprehended drivers (5.7% of all confirmed DUID cases). In 80% of the cases in which MDPV was found, amphetamine was also present. Benzodiazepines were also frequently found together with MDPV, which was to be expected since in Finland, in our experience, stimulants are very often used together with benzodiazepines. In most cases it remained unclear whether the observed psycho-physical achievement deficiency was induced by MDPV because the concentrations of other drugs, especially other stimulants, were often high. However, in some subjects, MDPV, or MDPV in combination with other substances was the most probable cause of the impairment. The concentrations of MDPV varied from 0.016mg/L to over 8.000mg/L. Little is known about the pharmacology of MDPV. However, based on our findings it is clear that MDPV has a serious impact on traffic safety in Finland.


Endoscopic Papillectomy for Ampullary Lesions of minor papilla.
Ampullary lesions (AL) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla but the role of EP for minor AL has not been accurately studied. We identified 20 patients with AL of minor duodenal papilla out of the multicentric database from the ESAP study that included 1422 EPs. We used the propensity score matching (nearest-neighbor method), to match these cases with ampullary lesions of the major duodenal papilla based on age, gender, histologic subtype and size of the lesion in a 1:2-ratio. Cohorts were compared by using Chi-square or Fisher's exact test as well as Mann-Whitney U test. Propensity-score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histological subtype of lesions of minor papilla was an ampullary adenoma in 12 Patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed non-neoplastic lesions. Invasive cancer (T1a), adenomyoma and neuroendocrine neoplasia each were found in one case. The rate of complete resection, en bloc resection and recurrences were comparable between both groups. There were no severe complications after EP of lesions of minor papilla. One patient had a delayed bleeding that could be treated by endoscopic hemostasis and two patients showed a recurrence in surveillance endoscopy after a median follow up of 21 months (IQR 12-50). EP is safe and effective in AL of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.


A new material platform of Si photonics for implementing architecture of dense wavelength division multiplexing on Si bulk wafer.
A new materials group to implement dense wavelength division multiplexing (DWDM) in Si photonics is proposed. A large thermo-optic (TO) coefficient of Si malfunctions multiplexer/demultiplexer (MUX/DEMUX) on a chip under thermal fluctuation, and thus DWDM implementation, has been one of the most challenging targets in Si photonics. The present study specifies an optical materials group for DWDM by a systematic survey of their TO coefficients and refractive indices. The group is classified as mid-index contrast optics (MiDex) materials, and non-stoichiometric silicon nitride (SiNx) is chosen to demonstrate its significant thermal stability. The TO coefficient of non-stoichiometric SiNx is precisely measured in the temperature range 24-76 °C using the SiNx rings prepared by two methods: chemical vapor deposition (CVD) and physical vapor deposition (PVD). The CVD-SiNx ring reveals nearly the same TO coefficient reported for stoichiometric CVD-Si3N4, while the value for the PVD-SiNx ring is slightly higher. Both SiNx rings lock their resonance frequencies within 100 GHz in this temperature range. Since CVD-SiNx needs a high temperature annealing to reduce N-H bond absorption, it is concluded that PVD-SiNx is suited as a MiDex material introduced in the CMOS back-end-of-line. Further stabilization is required, considering the crosstalk between two channels; a 'silicone' polymer is employed to compensate for the temperature fluctuation using its negative TO coefficient, called athermalization. This demonstrates that the resonance of these SiNx rings is locked within 50 GHz at the same temperature range in the wavelength range 1460-1620 nm (the so-called S, C, and L bands in optical fiber communication networks). A further survey on the MiDex materials strongly suggests that Al2O3, Ga2O3 Ta2O5, HfO2 and their alloys should provide even more stable platforms for DWDM implementation in MiDex photonics. It is discussed that the MiDex photonics will find various applications such as medical and environmental sensing and in-vehicle data-communication.


Combined common femoral artery endarterectomy with superficial femoral artery stenting plus Shuxuening Injection infusion for chronic lower extremity ischemia: 3-year results.
To investigate the efficacy and safety of combined common femoral artery (CFA) endarterectomy with superficial femoral artery (SFA) stenting plus Shuxuening Injection infusion in patients with complex multifocal arterial steno-obstructive lesions of the lower extremities. From March 2006 to March 2011, 104 lower limbs in 96 patients with multilevel peripheral arterial steno-occlusive disease, involving SFA as well as CFA and deep femoral artery (DFA) orifice, were treated by combined surgical with endovascular therapy, such as SFA stenting as an adjunct to CFA endarterectomy and patch angioplasty with the great saphenous vein. Before the end of the operation, 20 mL of Shuxuening Injection was infused through the catheter located in the treated artery. Technical and hemodynamic success, as well as primary and primary-assisted patency, was determined according to the Society for Vascular Surgery Guidelines. During follow-up, clinical status assessment, ankle-brachial index (ABI) test, and duplex Doppler ultrasound were administered every 6 months, and computed tomography angiography or magnetic resonance angiography was performed at 12, 24, and 36 months after discharge. All patients underwent successful combined CFA endarterectomy with SFA stenting treatment. The average ABI after the combination treatment increased from pretreatment of 0.32±0.21 to 0.82±0.24 (P<0.01). No perioperative death and major limb amputations occurred. The mean duration of follow-up for 104 limbs from 96 patients was 1,180 days (range, 196-2,064 days). During follow-up, 5 patients died due to myocardial infarction, cerebral infarction, or pneumonia, and 5 patients were lost to follow-up. There were 21 cases (21.4%) of restenosis, with 15 that occurred in-stent and 6 near the distal end of the stent. A total of 18 (18.3%) reinterventions were performed, including 6 balloon angioplasty, 8 restenting procedures, 2 bypass surgeries, and 2 major limb amputations. The primary patency rates were 92.2%, 76.8%, and 61.3% at 12, 24, and 36 months, respectively, while the primary-assisted patency rates were 94.4%, 83.2%, and 75.6% at 12, 24, and 36 months, respectively. The combined CFA endarterectomy with SFA stenting plus Shuxuening Injection infusion appears to offer a safe, less invasive, and effective treatment option to patients with chronic lower extremity ischemia due to complex multifocal peripheral artery disease.


Use of multiplex PCR and PCR restriction enzyme analysis for detection and exploration of the variability in the free-living amoeba Naegleria in the environment.
A multiplex PCR was developed to simultaneously detect Naegleria fowleri and other Naegleria species in the environment. Multiplex PCR was also capable of identifying N. fowleri isolates with internal transcribed spacers of different sizes. In addition, restriction fragment length polymorphism analysis of the PCR product distinguished the main thermophilic Naegleria species from the sampling sites.


Anticoagulant treatment for venous thromboembolism: A pooled analysis and additional results of the XALIA and XALIA-LEA noninterventional studies.
The XALIA and XALIA-LEA prospective, noninterventional studies investigated the safety and effectiveness of rivaroxaban versus standard anticoagulation for venous thromboembolism (VTE) treatment in routine clinical practice across global regions. This pooled analysis combined their data to determine the incidence of thromboembolic and bleeding events in both treatment groups and addressed specific bleeding patterns in a broad range of patients. Patients with objectively confirmed VTE and an indication for ≥3 months' anticoagulation treatment received rivaroxaban or standard anticoagulation (eg, initial treatment with heparin/fondaparinux, followed by a vitamin K antagonist [VKA]). Treatment choice, dose, management, and duration were at the physician's discretion. Primary outcomes (major bleeding, recurrent VTE, and all-cause mortality) were compared between the two treatment groups. Propensity score stratification, and matching were used to reduce bias due to confounding variables. Overall, 7129 patients were enrolled from 36 countries; 6445 and 2714 patients were included in the propensity score-stratified and -matched analyses, respectively. Major bleeding and incidences of recurrent VTE were similar between treatment groups; all-cause mortality was lower with rivaroxaban than with standard anticoagulation. The incidences of genitourinary bleeding were higher with rivaroxaban than with standard anticoagulation therapy (46 and 23 events in the matched analysis, respectively). VKA management in real-world practice was suboptimal. XALIA and XALIA-LEA show similar safety and effectiveness profiles of rivaroxaban and standard anticoagulation for VTE treatment in routine practice in many parts of the world. The observations are consistent with results from the phase III EINSTEIN randomized controlled trials.


The immunology of renal cell carcinoma.
Renal cell carcinoma (RCC) is the most common type of kidney cancer and comprises several subtypes with unique characteristics. The most common subtype (~70% of cases) is clear-cell RCC. RCC is considered to be an immunogenic tumour but is known to mediate immune dysfunction in large part by eliciting the infiltration of immune-inhibitory cells, such as regulatory T cells and myeloid-derived suppressor cells, into the tumour microenvironment. Several possible mechanisms have been proposed to explain how these multiple tumour-infiltrating cell types block the development of an effective anti-tumour immune response, including inhibition of the activity of effector T cells and of antigen presenting cells via upregulation of suppressive factors such as checkpoint molecules. Targeting immune suppression using checkpoint inhibition has resulted in clinical responses in some patients with RCC and combinatorial approaches involving checkpoint blockade are now standard of care in patients with advanced RCC. However, a substantial proportion of patients do not benefit from checkpoint blockade. The identification of reliable biomarkers of response to checkpoint blockade is crucial to facilitate improvements in the clinical efficacy of these therapies. In addition, there is a need for the development of other immune-based strategies that address the shortcomings of checkpoint blockade, such as adoptive cell therapies.


The role of serum amyloid A staining of granulomatous tissues for the diagnosis of sarcoidosis.
Previous studies demonstrated that SAA staining of sarcoidosis granulomas was qualitatively and quantitatively different from other granulomatous diseases. These data suggest that positive SAA staining of granulomatous tissue may have adequate specificity to establish a diagnosis of sarcoidosis. Our objective was to determine the diagnostic specificity of SAA staining for sarcoidosis relative to other granulomatous disorders. Pathological specimens demonstrating granulomatous inflammation were retrospectively identified at one institution, plus 4 specimens were obtained from New York City firefighters with biopsy-confirmed World Trade Center "sarcoidosis-like" pulmonary disease. Specimens were analyzed if specific diagnoses related to the granulomatous inflammation were confirmed through medical record review. SAA staining was performed using previously developed methods. Two pathologists, blinded to each other and the diagnoses, determined if the stained material was SAA positive or negative. Discordant results were adjudicated by the two pathologists. 106 specimens were analyzed from 100 patients, with 36 biopsies (34%) from sarcoidosis tissues and 70 (66%) from other granulomatous disorders. The Cohen Kappa correlation between the two pathologists for SAA staining positivity was excellent (0.85, 0.73-0.98). The overall specificity of SAA staining for the diagnosis of sarcoidosis was 84% (59/70). The sensitivity was 44% (16/36). Although SAA staining of various granulomatous tissues was fairly specific for the diagnosis of sarcoidosis, the specificity was inadequate for SAA staining to be used as a diagnostic test for sarcoidosis in isolation. These data suggest that SAA production may not be a universal mechanism in the development of sarcoidosis.


Analysis of mouse germ-cell transcriptome at different stages of spermatogenesis by SAGE: biological significance.
The transcriptomes of mouse type A spermatogonia (Spga), pachytene spermatocytes (Spcy), and round spermatids (Sptd) were determined by sequencing the respective SAGE (Serial Analysis of Gene Expression) libraries. A total of 444,015 tags derived from one Spga, two Spcy, and one Sptd library were analyzed, and 34,619 different species of transcripts were identified, 5279 of which were novel. Results indicated the germ-cell transcriptome comprises of more than 30,000 transcripts. Virtual subtraction showed that cell-specific transcripts constitute 12-19.5% of the transcriptome. Components of the protein biosynthetic machinery are highly expressed in Spga. In Spcy transcription factors are abundantly expressed while transcripts encoding proteins involved in chromosome remodeling and testis-specific transcripts are prominent in Sptd. The databases generated by this work provide very useful resources for cellular localization of genes in silico. They are also extremely useful as sources for identification of splice variants of genes in germ cells.


Primary hypothyroidism presenting as pseudoacromegaly.
Pseudoacromegaly is a condition characterized by cutaneous manifestations of growth hormone excess but with normal growth hormone levels. This is described in patients with severe insulin resistance, pachydermoperiostitis, burnt out acromegaly and with intake of drugs like Minoxidil. Severe thyroid hormone deficiency rarely present with similar picture and the issue is further complicated in presence of pituitary hyperplasia. We report an unusual presentation of primary hypothyroidism with pseudoacromegaly and thyrotroph hyperplasia mimicking a pituitary macroadenoma. The thyrotroph hyperplasia resolved completely with levothyroxine therapy.


Clinically latent and autopsy-verified inflammatory disorders and malignant tumours in transplant patients.
The number of clinical autopsies decreases while the rate of missed relevant diagnoses is known to be 2%-20%. In this study, we focused on postmortem examinations of patients after transplantation of solid organs. A total of 122 cases were assessed for this study. Transplant organs included liver (LiTx; n=42/122, 34%), heart (n=8/122, 7%), lungs (n=32/122, 26%), kidney (KTx; n=38/122, 31%) and KTx+LiTx (n=2/122, 2%). The most frequent autopsy-verified causes of death were cardiac or respiratory failure (together n=85/122, 70%). The frequency of malignant tumours that were identified at autopsy was 5% (n=6/122). In 3% (n=4/122) of cases, Goldman class I discrepancies between clinical diagnosis and autopsy findings were identified. The rate of missed relevant diagnoses might be relatively low, but these cases nevertheless refute the contention that modern diagnostic techniques negate the need for autopsies in patients who died after transplantation.


[Preoperative evaluation of adult patients before elective, noncardiothoracic surgery : Joint recommendation of the German Society of Anesthesiology and Intensive Care Medicine, the German Society of Surgery, and the German Society of Internal Medicine].
Evaluation of the patient's medical history and a physical examination are the cornerstones of risk assessment prior to elective surgery and may help to optimize the patient's preoperative medical condition and to guide perioperative management. Whether the performance of additional technical tests (e. g. blood chemistry, ECG, spirometry, chest x‑ray) can contribute to a reduction of perioperative risk is often not very well known or is controversial. Similarly, there is considerable uncertainty among anesthesiologists, internists and surgeons with respect to the perioperative management of the patient's long-term medication. Therefore, the German Scientific Societies of Anesthesiology and Intensive Care Medicine (DGAI), Internal Medicine (DGIM) and Surgery (DGCH) have joined to elaborate recommendations on the preoperative evaluation of adult patients prior to elective, noncardiothoracic surgery, which were initially published in 2010. These recommendations have now been updated based on the current literature and existing international guidelines. In the first part the general principles of preoperative evaluation are described (part A). The current concepts for extended evaluation of patients with known or suspected major cardiovascular disease are presented in part B. Finally, the perioperative management of patients' long-term medication is discussed (part C). The concepts proposed in these interdisciplinary recommendations endorsed by the DGAI, DGIM and DGCH provide a common basis for a structured preoperative risk assessment and management. These recommendations aim to ensure that surgical patients undergo a rational preoperative assessment and at the same time to avoid unnecessary, costly and potentially dangerous testing. The joint recommendations reflect the current state-of-the-art knowledge as well as expert opinions because scientific-based evidence is not always available. These recommendations will be subject to regular re-evaluation and updating when new validated evidence becomes available.


Increased telomerase activity in major depressive disorder with melancholic features: Possible role of pro-inflammatory cytokines and the brain-derived neurotrophic factor.
The biological mechanisms responsible for depression symptoms are not yet understood. For this reason, it is important to reveal the etiopathogenetic mechanisms in this disease. This study aims to compare the levels of pro-inflammatory cytokines, Brain-Derived Neurotrophic Factor (BDNF), and telomerase activity in patients with major depressive disorder (MDD) and healthy controls. Plasma BDNF, interleukin-6 (IL-6), IL-1beta, and Tumor Necrosis Factor-alpha (TNF-alpha) levels, and telomerase activity were measured in 39 patients with major depression and 39 healthy controls matched with patients in terms of age, gender, and education year. Plasma concentration of BDNF, IL-6 levels, and telomerase activity was significantly different between patients with MDD and healthy controls. Correlation analysis showed a positive trend between plasma BDNF levels and plasma IL-6 levels in patients with MDD with melancholic features. Furthermore, the path analysis results showed that the telomerase activity was indirectly affected by gender, IL-1β, IL-6, BDNF, and BMI, via the severity of depression and anxiety and MDD status as the mediators. Further studies are needed to examine the molecular mechanism of the telomerase activity and the role of BDNF and pro-inflammatory cytokines in the telomerase activation in MDD.


Glioma cell-derived placental growth factor induces regulatory B cells.
Tumor specific immune regulatory cells play an important role in the pathogenesis of glioma. The mechanisms have not been fully understood yet. It is suggested that placenta growth factor (PlGF) is involved in the generation of immune regulatory cells. This study aims to investigate the role of glioma cell-derived PlGF in the generation of regulatory B cells (Breg). Glioma cells were isolated from surgically removed glioma tissue. Cytokines were measured by enzyme-linked immunosorbent assay, quantitative real time RT-PCR and Western blotting. Immune suppressor functions of Bregs were assessed by T cell proliferation assay. The results showed that glioma cells expressed PlGF, which was increased after a non-specific activation. Naïve B cells captured the PlGF to differentiate into transforming growth factor-β positive Bregs. The Bregs were activated upon exposure to protein extracts of glioma tissue to suppress the CD8(+) T cell proliferation and the release of perforin and granzyme B. We conclude that glioma cell-released PlGF can induce Bregs to suppress CD8(+) T cell activities.


Effects of alpha-1 adrenergic blockade on the hormonal response to hypoglycaemic stress in normal man.
In order to evaluate the effect of alpha-1 adrenoreceptor regulation of ACTH release during insulin-induced hypoglycaemia, we studied the response to hypoglycaemia with and without prazosin premedication in eight normal men. Prazosin pretreatment did not affect basal or peak plasma ACTH, cortisol or GH during hypoglycaemic stress. However basal plasma levels of noradrenaline were increased (P less than 0.02) as were responses of AVP, angiotensin II (P less than 0.05) and noradrenaline (P less than 0.05) to hypoglycaemia after prazosin. Though it is possible that these augmented responses masked an inhibitory effect of prazosin, we were unable to demonstrate a major role for alpha-1 adrenergic receptors in mediating the ACTH response to hypoglycaemic stress in normal man.


Changed compounds of hydroxyzine in a human urine.
During a forensic toxicological GC/MS screening, changed compounds of hydroxyzine were found in a man's urine taken about 20 h after ingesting sake (Japanese liquor) and tranquilizers. The structures of those compounds were assigned to 4-chlorodiphenylmethane(I), p-chlorbenzophenone(III), norchlorcyclizine(IV), 7-(p-chloro-alpha-phenylbenzyl)-2-hydroxy-2H,3H-oxazolo-[3,2 -alpha] piperazine(V), 1-(p-chloro-alpha-phenylbenzyl)-4-methylpiperazine-3-one(VI), N-(p-chloro-alpha-phenylbenzyl)-N'-formylmethyl-N'- hydroxyethyl-1,2-ethenediamine(VII) and 1-(p-chloro-alpha-phenylbenzyl)-4-[2-ethoxy(2-ethoxy)-ethyl] piperazine(VIII) on the basis of the fragmentation patterns and relative retention times except VIII which was identified using the synthesized compound. I, V, VI, VII and VIII have not been reported previously, but the possibility of metabolites of hydroxyzine is still uncertain.


Direct ink writing of aloe vera/cellulose nanofibrils bio-hydrogels.
Direct-ink-writing (DIW) of hydrogels has become an attractive research area due to its capability to fabricate intricate, complex, and highly customizable structures at ambient conditions for various applications, including biomedical purposes. In the current study, cellulose nanofibrils reinforced aloe vera bio-hydrogels were utilized to develop 3D geometries through the DIW technique. The hydrogels revealed excellent viscoelastic properties enabled extruding thin filaments through a nozzle with a diameter of 630 μm. Accordingly, the lattice structures were printed precisely with a suitable resolution. The 3D-printed structures demonstrated significant wet stability due to the high aspect ratio of the nano- and microfibrils cellulose, reinforced the hydrogels, and protected the shape from extensive shrinkage upon drying. Furthermore, all printed samples had a porosity higher than 80% and a high-water uptake capacity of up to 46 g/g. Altogether, these fully bio-based, porous, and wet stable 3D structures might have an opportunity in biomedical fields.


By-design enantioselective self-amplification based on non-covalent product-catalyst interactions.
The synthesis of enantiomerically pure compounds is of great importance in pharmaceuticals, fragrances and biological applications, and functions as a key to many processes in nature. Asymmetric catalysis using enantiomerically pure catalysts represents an efficient synthetic method to achieve this goal. The enantiomeric excess of the reaction product correlates with the enantiomeric purity of the catalysts, except for nonlinear behaviour, therefore the use of stereochemically flexible catalysts seems to complicate the control of stereoselectivity. Self-amplifying catalytic reactions are attractive, but a general rational design is highly challenging. Here we show that product interaction with chiral recognition sites attached to structurally flexible phoshoramidite-type catalysts can sense the chirality and induce enantioselectivity in the catalyst. Structural flexibility along with sensing of the chirality of the product molecules results in a rapid increase of enantioselectivity of the dynamic catalysts (Δe.e. of up to 76%) and a shift out of equilibrium. In contrast to stereodynamic catalysts controlled with cleavable chiral auxiliaries, the enantioselectivity does not decrease.


IgE myeloma presenting with classical myeloma features.
A patient with IgE myeloma, presenting with bone lesions and modest anemia without plasma cell leukemia or hepatosplenomegaly, is described. The findings are compared with those of other patients with this and the more common forms of multiple myeloma.


The outcomes of nurse practitioner (NP)-Provided home visits: A systematic review.
With the shortage of primary care providers to provide home-based care to the growing number of homebound older adults in the U.S. Nurse Practitioners (NPs) are increasingly utilized to meet the growing demand for home-based care and are now the largest type of primary care providers delivering home-visits. The purpose of this study was to systematically examine the current state of the evidence on health and healthcare utilization outcomes associated with NP-home visits. Five Databases (PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library) were systematically searched to identify studies examining NP-home visits. The search focused on English language studies that were published before April 2019 and sought to describe the outcomes associated with NP-home visits. We included experimental and observational studies. Quality appraisal was performed with the Kmet, Lee & Cook tool, and results summarized qualitatively. The impact of NP-home visits on clinical (functional status, quality of life [QOL]), and healthcare utilization (hospitalization, Emergency department(ED) visits) outcomes was evaluated. A total of 566 citations were identified; 7 met eligibility criteria and were included in the review. The most commonly reported outcomes were emergency department (ED) visits and readmissions. Given the limited number of articles generated by our search and wide variation in intervention and outcomes measures. NP-home visits were associated with reductions in ED visits in 2 out of 3 studies and with reduction in readmissions in 2 out of 4 studies. Published studies evaluating the outcomes associated with NP-home visits are limited and of mixed quality. Limitations include small sample size, and variation in duration and frequency of NP-home visits. Future studies should investigate the independent effect of NP-home visits on the health outcomes of older adults using large and nationally representative data with more rigorous study design.


Mental disorders in individuals at risk for exercise addiction - A systematic review.
Exercise addiction is one of several behavioral addictions which has not yet been designated as an addictive disorder in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). This is in part due to a lack of clarity concerning co-occurring mental disorders of individuals at risk for exercise addiction. The aim of this review is to summarise the spectrum of psychopathology in populations at risk of exercise addiction. The MEDLINE, Web of Science and PsycINFO databases were searched. All studies from the date of database creation until February 2020 were considered eligible. Terms used were "exercise addiction" and other mental disorders mentioned in conjunction with substance-related and addictive disorders. Studies were included if they assessed risk for exercise addiction and at least one other mental disorder. Twenty studies were included. The disorders assessed were eating disorders (n = 14), depression (n = 6), anxiety (n = 4), other substance-related and addictive disorders (n = 5), and borderline personality disorder (n = 1). In thirteen of the studies, evidence was found for higher rates of at least one mental disorder (most commonly eating disorders, anxiety and other addictive disorders) in individuals at risk for exercise addiction, compared to those not at risk. Individuals at risk for exercise addiction show a broad range of mental disorders as assessed by self-report, which is in line with sufferers of other addictive disorders. Systematic psychological and clinical assessments in those at risk of exercise addiction are worthwhile, and will serve to characterize the mental health problems of individuals suffering from exercise addiction.


Recombining overlapping BACs into single large BACs.
BAC clones containing the entire genomic region of a gene including the long-range regulatory elements are very useful for gene functional analysis. However, large genes often span more than the insert of a BAC clone, and single BACs covering the entire region of interest are not available. Here, we describe a general system for linking two or more overlapping BACs into a single clone. Two rounds of homologous recombination are used. In the first, the BAC inserts are subcloned into the pBACLink vectors. In the second, the two BACs are combined together. Multiple BACs in a contig can be combined by alternating use of the pBACLInk vectors, resulting in several BAC clones containing as much of the genomic region of a gene as required. Such BACs can then be used in gene expression studies and/or gene therapy applications.