Human behavior and performance in deep space exploration: next challenges and research gaps.
As space exploration missions move from low orbit to distant destinations, including the Moon and Mars, new psychological, behavioral, and team challenges will arise. This manuscript represents an up-to-date white paper developed by European experts invited by the European Space Agency (ESA), mapping unfilled research gaps related to the psychology of space exploration, considering the incoming human missions, and accounting for the available scientific knowledge. ESA created the expert team and facilitated its work, but the team was completely independent in terms of contents. The white paper considers basic issues of adaptation, pre-, during-, and post-mission experiences, and possible countermeasures to be developed and tested. The resulting integrative map provides a guide for researchers that are interested in conducting research in the support of future space exploration endeavors.


Trigenic Synthetic Genetic Array (τ-SGA) Technique for Complex Interaction Analysis.
Complex genetic interactions occur when mutant alleles of multiple genes combine to elicit an unexpected phenotype, which could not be predicted given the expectation based on the combination of phenotypes associated with individual mutant alleles. Trigenic Synthetic Genetic Array (τ-SGA) methodology was developed for the systematic analysis of complex interactions involving combinations of three gene perturbations. With a series of replica pinning steps of the τ-SGA procedure, haploid triple mutants are constructed through automated mating and meiotic recombination. For example, a double-mutant query strain carrying two mutant alleles of interest, such as a deletion allele of a nonessential gene and a conditional temperature-sensitive allele of an essential gene, is crossed to an input array of yeast mutants, such as the diagnostic array set of ~1200 mutants, to generate an output array of triple mutants. The colony-size measurements of the resulting triple mutants are used to estimate cellular fitness and quantify trigenic interactions by incorporating corresponding single- and double-mutant fitness estimates. Trigenic interaction networks can be further analyzed for functional modules using various clustering and enrichment analysis tools. Complex genetic interactions are rich in functional information and provide insight into the genotype-to-phenotype relationship, genome size, and speciation.


Chlorhexidine inactivation by saliva.
Chlorhexidine mouth rinsing is commonly used for oral flora reduction. Indigenous microorganisms (viridans streptococci) are significantly suppressed, while "hospital-acquired" gram-negative bacilli are not affected in vivo. To explain the discrepancies between good in vitro and poor in vivo activity of chlorhexidine, minimum bactericidal concentration values for 120 isolates were studied by means of a standard dilution method in fresh whole saliva, broth, and glucose 5%. Both saliva and broth significantly reduced the bactericidal activity of chlorhexidine against all microorganisms tested as compared to glucose 5% (p less than 0.01). Minimum bactericidal concentrations for indigenous flora were significantly lower than the values obtained for the "hospital-acquired" microorganisms (p less than 0.05). These observations of chlorhexidine inactivation by saliva may explain why chlorhexidine mouth rinsing is of limited value in decontaminating the oral cavity.


Damage to epithelial basement membrane by thermokeratoplasty.
To determine the effects of thermokeratoplasty (TKP) on the basement membrane complexes of the corneal epithelium, transmission electron microscopy was performed on the corneal buttons of five patients with failed TKP and on two normal corneas and five corneas with keratoconus that were immediately treated by TKP (acute TKP). The consistent findings of thermal dissolution of basement membrane after acute TKP and persistent defects of basement membrane complexes many months after therapeutic thermokeratoplasty were significant. Given the potentially damaging effects of thermokeratoplasty on the epithelial basement membrane, faulty epithelial adhesion should be anticipated after thermokeratoplasty and should be treated aggressively, possibly with careful prophylactic use of bandage hydrophilic contact lenses.


Free groin flap in hemifacial volume reconstruction.
Use of the free groin flap, one of the first microvascular free flaps described, has been neglected recently because it has a short pedicle and varies anatomically. However, we have found its anatomical features and type of tissue ideal for volumetric enhancement in severe hemifacial asymmetry. We present a retrospective review of a consecutive series of 14 patients who had hemifacial augmentation with a free groin flap (mean age at operation 17 years, range 10-42) since 2001, and discuss the surgical technique. The most common cause of asymmetry was hemifacial microsomia (n=6). Anatomical variation of the vessels in the groin did not cause problems. Arterial anastomosis was to the facial artery in 13 patients; 12 patients had simultaneous hard tissue procedures. No flaps failed. The free groin flap is a useful adjunct in the management of hemifacial deficits in volume when free fat grafts will not provide enough bulk. Although the operation can take longer than non-vascularised grafts, little tissue is lost so long-term results may be more predictable. We have found the anatomy fairly consistent and the short pedicle caused no problems.


The use of a battery of strains of mice in a factorial design to study the induction of dominant lethal mutations.
The induction of dominant lethality following oral dosing of males with 200 mg/kg of cyclophosphamide was investigated using a factorial experimental design. Males from 3 genotypes, BALB/c, CBA/Ca and CBA/Ca X C57BL/6JF1 hybrid (CBB6F1) were mated to 6 females of the same genotype as the males over 3 weeks. Cyclophosphamide reduced the mating frequency of the BALB/c and CBA/Ca males. The total number of implants/female was reduced in all 3 genotypes with the greatest effect in the first 2 weeks after the males were treated. The proportion of early deaths/litter was significantly increased in CBA/Ca and CBB6F1 but the increase was smaller and non-significant with BALB/c. There was a high incidence (29.8%) of early deaths in the control BALB/c females. Statistical analysis of the ratio of early deaths to total implants in a litter using either the Freeman-Tukey binomial or the arc-sine transformation gave similar and satisfactory results. Analysis of early death data rather then the ratio of early deaths: total implants would have led to misleading conclusions. The implications of the use of a factorial design in dominant lethal assays for the detection of strain variation in mutagenic response without an increase in animal usage is discussed.


DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma.
Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival. DKN-01 is a humanized monoclonal antibody with DKK1 neutralizing activity that may provide clinical benefit to patients whose tumors have overexpression of DKK1 or Wnt genetic alterations. We conducted an open-label, Phase 2 basket study with 2-stage design in patients with endometrial carcinoma (EC) and platinum-resistant/refractory epithelial ovarian cancer. DKN-01 was administered either as monotherapy or in combination with weekly paclitaxel at investigator's discretion. All patients underwent NGS testing prior to enrollment; tumor tissue was also tested for DKK1 expression by RNAscope pre-treatment and after cycle 1 if available. At least 50% of patients were required to have a Wnt signaling alteration either directly or tangentially. This publication reports results from the EC population overall and by DKK1-expression. DKN-01 monotherapy and in combination with paclitaxel was more effective in patients with high DKK1-expressing tumors compared to low-expressing tumors. DKN-01 monotherapy demonstrated an objective response rate [ORR] of 25.0% vs. 0%; disease control rate [DCR] of 62.5% vs. 6.7%; median progression-free survival [PFS] was 4.3 vs. 1.8 months, and overall survival [OS] was 11.0 vs. 8.2 months in DKK1-high vs DKK1-low patients. Similarly, DKN-01 in combination with paclitaxel demonstrated greater clinical activity in patients with DKK1-high tumors compared to DKK1-low tumors: DCR was 55% vs. 44%; median PFS was 5.4 vs. 1.8 months; and OS was 19.1 vs. 10.1 months. Wnt activating mutations correlated with higher DKK1 expression. DKN-01 was well tolerated as a monotherapy and in combination with paclitaxel. Collectively, data demonstrates promising clinical activity of a well-tolerated drug, DKN-01, in EC patients with high tumoral DKK1 expression which frequently corresponded to the presence of a Wnt activating mutation. Future development will focus on using DKN-01 in DKK1-high EC patients in combination with immunotherapy.


Structural consequences of sequence patterns in the fingerprint region of the nucleotide binding fold. Implications for nucleotide specificity.
The dinucleotide binding beta alpha beta motif in the crystal structures of seven different enzymes has been analysed in terms of their three-dimensional structures and primary sequences. We have identified that the hydrogen bonding of the adenine ribose to the glycine-rich turn containing the fingerprint sequence GXGXXG/A occurs via a direct or indirect mechanism, depending on the nature of the fingerprint sequence but independent of coenzyme specificity. The major determinant of the type of interaction is the nature of the residue occupying the last position of the above fingerprint. In the NAD(+)-linked dehydrogenases, an acidic residue is commonly used to form important hydrogen bonds to the adenine ribose hydroxyls and, hitherto, this residue has been thought to be an indicator of NAD+ specificity. However, on the basis of the three-dimensional structure of the NAD(+)-linked glutamate dehydrogenase (GDH) from Clostridium symbiosum we have demonstrated that this residue is not a universal requirement for the construction of an NAD+ binding site. Furthermore, considerations of sequence homology unambiguously identify an equivalent acidic residue in both NADP+ and dual specificity glutamate dehydrogenases. The conservation of this residue in these enzymes, coupled to its close proximity to the 2' phosphate implied by the necessary similarity in three-dimensional structure to C. symbiosum GDH, implicates this residue in the recognition of the 2' phosphate either via water-mediated or direct hydrogen-bonding schemes. Analysis of the latter has led us to suggest that two patterns of recognition for the 2' phosphate group of NADP(+)-binding enzymes may exist, which are distinguished by the ionization state of the 2' phosphate.


Psychological distress and associated factors among kidney transplant recipients and living kidney donors during COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic has caused significant psychological distress globally. Our study assessed the prevalence of psychological distress and associated factors during COVID-19 pandemic among kidney transplant recipients and kidney donors. A cross-sectional survey of 497 participants (325 recipients and 172 donors) was conducted from 1st May to 30th June 2020 in Singapore. The survey questionnaire assessed knowledge levels of COVID-19, socio-demographic data, health status, psychosocial impact of COVID-19, and precautionary behaviors during the pandemic. Psychological distress was defined as having anxiety, depression, or stress measured by the validated Depression, Anxiety and Stress Scale-21. Linear regression analyses were used to assess factors associated with higher psychological distress. The prevalence of psychological distress was 14.3% (95% confidence interval: 11.5-17.6%) in the overall population; it was 12.8% (9.79-16.6%) in recipients and 13.4% (9.08-19.6%) in donors with no significant difference (P = 0.67). Younger age (21-49 vs. ≥50 years), unmarried status, non-Singapore citizen, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. No interactions were observed between recipients and donors. At least one in ten recipients and donors suffer from psychological distress during COVID-19 pandemic. Focused health education to younger adults, unmarried individuals, non-Singapore citizens, and those with poor health status could potentially prevent psychological distress in recipients and donors.


Venous thromboembolism prophylaxis in gynecologic oncology: a prospective, controlled trial of low-dose heparin.
One hundred eighty-five patients undergoing operation for gynecologic malignancy participated in a randomized controlled trial of low-dose heparin prophylaxis. Prospective surveillance for deep venous thrombosis was performed with daily fibrinogen 125I counting in the legs and impedance plethysmography. Twelve of 97 (12.4%) patients in the control group and 13 of 88 (14.8%) patients in the low-dose heparin group developed a venous thromboembolic complication. There was no statistical difference in the incidence of proximal deep vein thrombosis, calf vein thrombosis, or pulmonary emboli between the control and low-dose heparin groups. Low-dose heparin does not afford any prophylactic benefit to patients undergoing major pelvic operative procedures for gynecologic malignancy.


Complete Genome and Methylome Sequences of Salmonella enterica subsp. enterica Serovars Typhimurium, Saintpaul, and Stanleyville from the SARA/SARB Collection.
In this announcement, we report the complete genome and methylome sequences of three Salmonella enterica strains from the SARA and SARB collection: S. enterica subsp. enterica serovar Typhimurium (SARA13), S. enterica subsp. enterica serovar Saintpaul (SARA26), and S. enterica subsp. enterica serovar Stanleyville (SARB61).


A shear stress analysis of the bonding of porcelain veneers to enamel.
This study demonstrated the relative strengths of the composite resin bond to etched enamel and the composite resin bond to surface-treated porcelain with similar conditions. It also compared the strength of a combined porcelain/composite/enamel bond with the strengths of porcelain/composite resin and enamel/composite resin bonds and evaluated the effectiveness of silane treatment of the etched porcelain. The influence of thermocycling was also investigated. There were 20 samples for each five categories: (1) composite resin/etched porcelain; (2) composite resin/etched and silane-treated porcelain; (3) composite resin/acid-etched enamel; (4) etched porcelain/composite resin/acid-etched enamel; and (5) etched and silane-treated porcelain/composite resin/acid-etched enamel. Half in each category were subjected to thermocycling. Shear testing and microscopic examination of the fracture sites resulted in the following: (1) Shear testing a combined enamel/composite/porcelain bond resulted in significantly different values from testing individual enamel/composite resin and porcelain/composite resin bond strengths. (2) Silane treatment of the etched porcelain recorded a significantly greater shear strength to the merely etched samples. (3) Thermocycling did not significantly dilute the effects of silane treatment of the etched porcelain surface.


[Short communications on cases of eye, larynx, trachea and skin disease].
A freefloating iris cyst in a dog, the congenitally attached apex of the epiglottis in a cat, spontaneous healing of Filaroides osleri in a dog and dermoid sinus in a Ridgeback crossbreed are discussed.


Measurement of operative femoral anteversion during cementless total hip arthroplasty and influencing factors for using neck-adjustable femoral stem.
Placement of femoral stem in excessive anteversion or retroversion can cause reduced range of motion, prosthetic impingement, and dislocation. The aim of this study was to assess the operative femoral anteversion in patients treated with total hip arthroplasty (THA) and analyze the need of adjusting stem anteversion. We retrospectively included 101 patients (126 hips) who underwent cementless THA with a manual goniometer to determine the femoral anteversion between October 2017 and December 2018. The operative femoral anteversion we measured was recorded during THA. We further divided those hips into three subgroups based on the range of operative femoral anteversion: group 1 (<10°), group 2 (10-30°), and group 3 (>30°) and compared the differences of their demographic data. Univariate and multivariate logistic regression were used to identify the influencing factors for the need of neck-adjustable femoral stem. The clinical and radiographic outcomes were also assessed. Perioperative complications were recorded. After THA, the Harris hip scores improved from 52.87 ± 15.30 preoperatively to 90.04 ± 3.31 at the last follow-up (p < 0.001). No implant loosening, stem subsidence, and radiolucent lines were observed on radiographs. No severe complications occurred and no components needed revision at the latest follow-up. The mean operative femoral anteversion was 14.21° ± 11.80° (range, -9 to 60°). Patients with femoral anteversion more than 30° were about 10 years younger than others. Femoral anteversion >30° was more common in patients with developmental dysplasia of the hip (DDH). There were totally 14 hips treated with the neck-adjustable femoral stem. From the univariate analysis, we can observe that female sex, diagnosis of DDH (compared with osteonecrosis), and higher operative femoral anteversion and its value >30° (compared with <10°) are associated with higher rates of using the neck-adjustable femoral stem. However, all these factors were no longer considered as independent influencing factors when mixed with other factors. This study highlighted the significance of operative femoral anteversion. Identification of abnormal femoral anteversion could assist in adjusting stem anteversion and reduce the risk of dislocation after THA.


A new fibrillization mechanism of β-lactoglobulin in glycine solutions.
Even though amyloid aggregates were discovered many years ago the mechanism of their formation is still a mystery. Because of their connection to many of untreatable neurodegenerative diseases the motivation for finding a common aggregation path is high. We report a new high heat induced fibrillization path of a model protein β-lactoglobulin (BLG) when incubated in glycine instead of water at pH 2. By combining atomic force microscopy (AFM), transmission emission microscopy (TEM), dynamic light scattering (DLS) and circular dichroism (CD) we predict that the basic building blocks of fibrils made in glycine are not peptides, but rather spheroid oligomers of different height that form by stacking of ring-like structures. Spheroid oligomers linearly align to form fibrils by opening up and combining. We suspect that glycine acts as an hydrolysation inhibitor which consequently promotes a different fibrillization path. By combining the known data on fibrillization in water with our experimental conclusions we come up with a new fibrillization scheme for BLG. We show that by changing the fibrillization conditions just by small changes in buffer composition can dramatically change the aggregation pathway and the effect of buffer shouldn't be neglected. Fibrils seen in our study are also gaining more and more attention because of their pore-like structure and a possible cytotoxic mechanism by forming pernicious ion-channels. By preparing them in a simple model system as BLG we opened a new way to study their formation.


Ectopic Pax-3 activates MyoD and Myf-5 expression in embryonic mesoderm and neural tissue.
To understand how the skeletal muscle lineage is induced during vertebrate embryogenesis, we have sought to identify the regulatory molecules that mediate induction of the myogenic regulatory factors MyoD and Myf-5. In this work, we demonstrate that either signals from the overlying ectoderm or Wnt and Sonic hedgehog signals can induce somitic expression of the paired box transcription factors, Pax-3 and Pax-7, concomitant with expression of Myf-5 and prior to that of MyoD. Moreover, infection of embryonic tissues in vitro with a retrovirus encoding Pax-3 is sufficient to induce expression of MyoD, Myf-5, and myogenin in both paraxial and lateral plate mesoderm in the absence of inducing tissues as well as in the neural tube. Together, these findings imply that Pax-3 may mediate activation of MyoD and Myf-5 in response to muscle-inducing signals from either the axial tissues or overlying ectoderm and identify Pax-3 as a key regulator of somitic myogenesis.


Epistasis Analysis: Classification Through Machine Learning Methods.
Complex disease is different from Mendelian disorders. Its development usually involves the interaction of multiple genes or the interaction between genes and the environment (i.e. epistasis). Although the high-throughput sequencing technologies for complex diseases have produced a large amount of data, it is extremely difficult to analyze the data due to the high feature dimension and the combination in the epistasis analysis. In this work, we introduce machine learning methods to effectively reduce the gene dimensionality, retain the key epistatic effects, and effectively characterize the relationship between epistatic effects and complex diseases.


White paint dot-like lesions of the scrotum: Microsporum gypseum infection.
A 29-year-old renal transplant patient taking mycophenolate mofetil 1 g b.i.d., cyclosporine 100 mg b.i.d. and prednisone 10 mg q.d. presented with white paint, dot-like incrustations on the skin of his right scrotum. A 10% potassium hydroxide preparation of scrapings from the lesions showed septate hyphae and Microsporum gypseum was cultured. Topical bifonazole 1% cream cleared the lesions within 2 weeks. At the 2-month follow up there was no relapse.


[Frequency of Chlamydia trachomatis in the cervix of pregnant women during prenatal examinations].
From February 1993 to October 1995, 80 endocervical samples taken from 80 pregnant patients in pre-natal control were examined in private practice at the Hospital Angeles del Pedregal in Mexico City for purposes of detecting Chlamydia trachomatis by direct inmunoflorecency. Gestational ages ranged from 20 to 39 week. A positive reaction to Chlamydia trachomatis was observed in 10% (8 patients) of the participating patients. Taking into account this frequency it is suggested that this study be a part of prenatal control.


Endoscopic dilation of colonic postoperative strictures.
After the use of surgical staplers had become widespread, the number of colonic postoperative stenoses was observed to have increased. Nevertheless, the clinical relevance of this observation is minimal since only 2-5% of the patients complain of chronic constipation or obstruction symptoms. In such cases medical therapy is somewhat troublesome, and surgical treatment always implies a major operation. Endoscopic dilation has proved to be a reliable, simple, and safe therapeutic alternative. Forty-two patients with evidence of stenosis of either colocolic or colorectal anastomosis underwent mechanical or pneumatic dilation in our unit: 19 patients with a temporary diverting stoma were dilated before the colostomy was removed; in the remaining 23 cases, treatment was given according to the patients' symptoms or because it was not possible to pass the anastomosis with an endoscope. The overall failure rate was 2.4%, and no morbidity or mortality was found. When the percentages of patients successfully treated in one session alone were compared (76.9% versus 51.8%), balloon dilation was found to be more effective than bougienage. In our opinion, endoscopic dilation represents the mainstay of treatment of colonic anastomotic strictures, with surgery being reserved for the rare failures, when recurrence of cancer should be suspected.


Aluminium toxicokinetics after intramuscular, subcutaneous, and intravenous injection of Al citrate solution in rats.
Knowledge of dose linearity, plasma clearance, rate and extent of subcutaneous (SC) and intramuscular (IM) absorption of soluble aluminium (Al) citrate is considered a prerequisite for evaluation of toxicokinetic data obtained from SC or IM administration of Al adjuvants in medicinal products. Therefore, total Al plasma kinetics was investigated after SC, IM, and IV administration of single Al doses (36 and 360 µg/kg IM or SC; 30 and 300 µg/kg IV) given as citrate solution in rats. Control groups receiving vehicle (saline) were run in parallel to monitor background plasma Al levels over time resulting from dietary intake. Evaluation of Al plasma profiles was done by both non-compartmental analysis of baseline-corrected data and simultaneous model fitting to the raw data using a population kinetics approach. High and dose-independent total plasma clearance (6.6 mL/min/kg) was observed after IV administration corresponding to 60-82% of normal rat GFR. This supports the previous assumptions that parenterally administered Al citrate is more rapidly cleared from plasma than other Al species (e.g., chloride or lactate). Furthermore, plasma exposure of Al (Cmax and AUC0-inf) increased dose-proportionally at all administration routes. Fast and complete absorption of Al was observed at each dose level after both SC and IM administration (bioavailability estimates: 88 and 110%). Estimates for the first-order absorption rate constant ka correspond to absorption half-lives of 36 min (SC) and ≤ 13 min (IM). There was no increase in tissue Al content (whole bone and brain) after 36 µg/kg IM compared to control rats.


Pre-treatment with N-acetylcysteine upregulates superoxide dismutase 2 and catalase genes in cadmium-induced oxidative stress in the chick omphalocele model.
In the chick embryo, administration of the heavy metal Cadmium (Cd) induces omphalocele phenotype. Cd is a potent inhibitor of antioxidant enzymes and causes accumulation of reactive oxygen species (ROSs) such as hydrogen peroxide. Previous work with the Cd chick model has demonstrated that increased levels of MDA, as a marker for oxidative stress, 24 h post Cd treatment (24H) are identical in chick embryos exposed to Cd. Furthermore, of the several antioxidants assessed, only N-acetylcysteine (NAC) has been shown to reduce MDA levels to control values in the Cd-treated chick embryo. However, the molecular mechanisms by which NAC acts to maintain oxidative stress in the Cd-induced ventral body wall defect chick model remains to be unclear. We designed this study to investigate the hypothesis that gene expression levels of antioxidant enzymes are downregulated in malformed embryos exposed to Cd compared to controls and to determine the effect of pre-treatment with NAC on the expression levels of genes encoding antioxidant enzymes. After 60 h incubation, chick embryos were pre-treated with NAC and exposed to either chick saline or Cd. Chicks were then harvested at 24H and divided into five groups: control, Cd group without malformation [Cd(-)], Cd group with malformation [Cd(+)], NAC + Cd(-) and NAC + Cd(+). Real-time PCR was performed to evaluate the relative mRNA expression levels of antioxidant enzymes, including superoxide dismutase (SOD)-1, SOD2, catalase (CAT) and glutathione peroxidase (GPX)-4. Differences between five groups were tested by Tukey-Kramer post-hoc test following one-way ANOVA. Statistical significance was accepted at p < 0.05. Immunohistochemistry was also performed to evaluate protein expression. The mRNA expression levels of SOD2 and CAT were significantly decreased in Cd(+) as compared to controls, whereas there was no significant difference between controls and Cd(-) (p < 0.05 vs. controls). In addition, gene expression levels of SOD2 and CAT were significantly increased in NAC + Cd(-) as compared to Cd(+) and NAC + Cd(+) (p < 0.05 vs. controls). However, there were no significant differences in the expression levels of SOD1 and GPX4 among any groups. Increased immunoreactivity of SOD2 and CAT was also observed in NAC + Cd(-) as compared to Cd(+) and NAC + Cd(+). Our results suggest that SOD2 and CAT may play an important role in preventing Cd-induced teratogenesis. Prenatal treatment with drugs which can upregulate SOD2 and CAT transcripts may have a therapeutic potential in preventing omphalocele phenotype.


Role of natriuretic peptides in the cardiovascular-adipose communication: a tale of two organs.
Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in the energy metabolism of several substrates in humans and animals, thus interrelating the heart, as an endocrine organ, with various insulin-sensitive tissues and organs such as adipose tissue, muscle skeletal, and liver. Adipose tissue dysfunction is associated with altered regulation of the natriuretic peptide system, also indicated as a natriuretic disability. Evidence points to a contribution of this natriuretic disability to the development of obesity, type 2 diabetes mellitus, and cardiometabolic complications; although the causal relationship is not fully understood at present. However, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on the current literature on the metabolic functions of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Natriuretic peptide system alterations could be proposed as one of the linking mechanisms between adipose tissue dysfunction and cardiovascular disease.


Localization of ENaC subunit mRNAs in adult bullfrog skin.
Adult amphibian skin has served as a model for the investigation of Na(+)-transporting epithelia, such as mammalian renal tubules. The amiloride-blockable epithelial Na(+) channel (ENaC), which is located in the apical membrane of the outer living cell layer, regulates Na(+) transport across the epithelium. ENaC is thought to develop during the terminal differentiation of epidermal cells, but the details are unclear. Here, we used in situ hybridization to examine the localization of the ENaC subunit mRNAs in skin of adult bullfrogs, to clarify the development of ENaC. We found that α-ENaC mRNA was expressed within the cells of the Stratum granulosum, the Stratum spinosum, and the Stratum germinativum, while β-ENaC mRNA was expressed within the cells of the S. granulosum and the S. spinosum. However, we could not detect expression of γ-ENaC mRNA, possibly for technical reasons. α- and β-ENaC mRNAs, at least, were present in the sub-apical cells, in which ENaC protein is not necessary for amphibian skin to possess its Na(+)-transport function. Our results may mean that the sub-apical cells are already producing the ENaC subunit mRNAs prior to the final step in their differentiation.


Telehealth medication management and health care spending in a Medicare Accountable Care Organization.
BACKGROUND: Value-based care is an opportunity for medication optimization services to improve medication management and reduce health care spending. The reach of these services may be extended through telehealth. However, as health care systems and payers grapple with the long-term financing of telehealth, real-world assessments are needed to evaluate the potential economic impact of pharmacy-driven telehealth services. OBJECTIVE: To evaluate the impact of a scalable pharmacist-driven telehealth intervention to improve medication management on health care spending for clinically complex patients who were enrolled in a Medicare Next Generation Accountable Care Organization. METHODS: Data for this pretest-posttest nonequivalent group design study came from Medicare claims from 2015 to 2020 and linked pharmacist care activity data derived from the electronic medical record. Patients in the intervention group were identified as those who received the telehealth medication management service. Patients in the control group were offered the service and refused or could not be contacted. The primary outcome was total medical spending over a 6-month period, and impact was assessed using a covariate-adjusted difference-in-difference model. RESULTS: There were 581 patients who received the intervention and 1,765 who served as controls. The telehealth intervention reduced total medical spending by $2,331.85 per patient over the first 6 months of the service ($388.50 per month; P = 0.0261). Across a range of estimates for the cost of service delivery, we find a return on investment of 3.6:1 to 5.2:1. CONCLUSIONS: The $388.50 monthly savings found in this study represent a substantial reduction in health care spending and emphasize the opportunity for telehealth delivery of medication management services to improve value as a part of alternative payment models. DISCLOSURES: This study was funded by the UNC Health Care Department of Pharmacy. Dr Urick has received personal fees from Pharmacy Quality Solutions and Cardinal Health. Drs Peters, Vest, Colmenares, Foushee, and DeFalco are employees of UNC Health Care Department of Pharmacy. Mr Easter received a Co-PI grant from NACDS Foundation to implement Community-based Value Care Initiative (CVCI) in a community pharmacy setting. He also received a grant to Eshelman School of Pharmacy. He has an individual consulting agreement with digital health company Truentity Health to provide go to market strategy for medication management services. He also has stock options from Truentity Health as a component of the consulting agreement. Dr Foushee has a leadership or fiduciary role at Member-At-Large and the Ambulatory Care Academy of the North Carolina Association of Pharmacists. At the time this work was conducted, Dr Urick, Dr Pathak, and Dr Blanchard were all employees of the UNC Eshelman School of Pharmacy.


The activity and selectivity of catalytic peroxide oxidation of chlorophenols over Cu-Al hydrotalcite/clay composite.
Liquid phase catalytic oxidation of chlorophenols (CPs) was carried out over Cu-Al hydrotalcite/clay composite at ambient temperature and pressure using hydrogen peroxide as oxidant. The results showed that the catalyst had high catalytic activity, with complete oxidation of 4-CP within 40 min at 40 °C. The content and position of chlorine on the aromatic ring had significantly different effects on the oxidation rate of CPs, with the rate sequence of phenol > monochlorophenol (MCP) > dichlorophenol (DCP) > trichlorophenol (TCP), 3-CP > 2-CP > 4-CP, and 3,5-DCP > 3,4-DCP > 2,5-DCP > 2,4-DCP > 2,6-DCP. This was ascribed to the interactions among σ-electron withdrawing conductive effect, π-electron donating conjugative effect, and steric hindrance effect of chlorine. It was evidenced that the catalytic peroxide oxidation of CPs in the first step was selective and rate-limiting, where chlorinated 1,4-benzoquinones formed.


A bigger picture: cause and cognition in relation to differing scientific frameworks.
The exchange between Lee (1992) and Hawkins (1992) on the one hand and Bandura (present volume) on the other represents a far more fundamental disagreement than whether behavior-analytic or cognitive accounts of self-efficacy are more persuasive. The deeper disagreement is really a conflict between equally legitimate but incompatible world views and, thus, it is both ontological and epistemological in nature. The present paper argues that the disagreement can be traced to differences between mechanistic and contextual or relational scientific frameworks and involves such issues as basic scientific objectives, units of analysis, and differing perspectives on causation and explanation. These differences are briefly described.


Management of Descemet's membrane detachment.
Detachment of Descemet's membrane is a rare but serious complication of cataract surgery. Most surgeons attempt to reposition the membrane by injecting air, slow-reabsorbing gases, or viscoelastic substances into the anterior chamber. We describe five cases of subtotal detachment without rolled scroll. These cases recovered spontaneously after two to three months. We believe that conservative treatment in such cases is indicated and has a good chance of favorable outcome.


Examination of the efficacy and safety of intraoperative gastroscopic testing of the gastrojejunal anastomosis in laparoscopic Roux Y gastric bypass surgery.
The laparoscopic Roux Y gastric bypass (LRYGB) is one of the most often performed bariatric surgical intervention. Intraoperative gastroscopy (IOG) seems to be reliable to decrease the leakage rate of gastrojejunal anastomosis (GJA) and of gastric pouch (GP). Our aim was to test the efficacy and the safety of this method. Two hundred fifty-two LRYGB operations were performed in our institution between 1 January 2008 and 1 January 2010. IOG is routinely made to test the integrity of GJA and of GP. Patients' dates were retrospectively analysed. The intragastric pressure developed during gastroscopy in humans was measured and compared with pressure values led to destruction (positive air test) of the GJA and/or GP in animal models (hybrid pigs). Stomach and bowel wall samples from the test animals without pressure strain, with pressure strain developed at gastroscopy in humans and with pressure strains led to destruction of GJA and/or GP were histologically examined. IOG resulted in six of our cases (2.3%) positive air test. There was no anastomosis insufficiency in postoperative period. Mean pressure during IOG was 32 mmHg, mean time of examination was 3.8 min and mean maximal pressure was 43 mmHg in humans. The mean pressure leading to positive air test in pigs was 150 mmHg. We could not detect any microscopical difference between stomach and jejunum samples without pressure strain and after pressure strain developed in humans during the gastroscopy. We conclude that intraoperative gastroscopy is an effective and safe method to test the integrity of GJA and GP in LRYGB surgery.


Easy stereoselective synthesis of 5α-estrane-3β,17α-diol, the major metabolite of nandrolone in the horse.
5α-Estrane-3β,17α-diol is the major metabolite of nandrolone in horse urine. The presence of 5α-estrane-3β,17α-diol in female and gelding urines is prohibited by Racing Rules and its natural presence in male urine led regulation authorities to establish a concentration threshold of 45 ng/mL. This paper describes a rapid, simple and stereoselective synthesis of 5α-estrane-3β,17α-diol, providing horseracing laboratories with an essential reference material for their antidoping performance.


Regions of cerebral ischemia located by pyridine nucleotide fluorescence.
The fluorescence of the reduced form of the endogenous pyridine nucleotide nicotinamide adenine dinucleotide was used to map regions of ischemia in cat brain. A remarkably microheterogeneous pattern of increased fluorescence resulted from a critical level of incomplete cerebral ischemia. The fluorescence pattern suggests that ischemia occurs initially in microwatershed zones between penetrating cerebral arteries.


DNA in non Hodgkin-lymphoma--a cytophotometric study.
Cytophotometric DNA determinations on 26 cases of non-Hodgkin's lymphoma yielded the following findings: 1. Follicular centrocytic/centroblastic lymphomas (M. Brill-Symmers) and diffuse centrocytic lymphomas (lymphocytic lymphosarcoma) have a diploid DNA stem line. Diploid DNA values are observed in benign tumors, so that the assignment of these lymphomas to the group of "low grade malignancies" appears justified. 2. Lymphoblastic sarcomas show an aneuploid DNA stem line, as do 96% of all malignant tumors. 3. Lymphoid cells, plasma cells, and immunoblasts seen in immunocytomas are aneuploid. Thus these lymphomas must belong to the group of "high-grade malignant lymphomas" as regards their DNA distribution. 4. Immunoblastic sarcomas have aneuploid DNA stem lines (1 case tetraploid), in which both the lymphoid cells and the plasma cells from those immunoblastic sarcomas arising from immunocytomas show atypical DNTA distribution patterns. 5. In two cases of angioimmunoblastic lymphadenopathy, the lymphoid cells, plasma cells, and immunoblasts are aneuploid. They are thus regarded as "high grade malignancy" lymphomas. The results are discussed with respect to clinical course and prognosis. Measurements on a larger series of cases and correlation to clinical data are needed to support these results. Ultrafast DNA measurements made by flow-through cytophotometry can perhaps be helpful in the future for making the decision between a "low" or "high" grade malignant lymphoma.


The impact of an educational forum intervention on East African mothers' HPV vaccine-related knowledge, attitudes, and intentions to vaccinate their adolescent children.
HPV vaccine uptake in U.S. East African adolescents is low. We developed and evaluated a culturally-targeted interactive educational intervention for East African immigrant mothers to increase HPV-vaccine-related knowledge, attitudes, and intentions to vaccinate adolescent children. Eligible mothers had ≥ 1 11-17-year-old child and reported all children's HPV vaccination status as unvaccinated or unknown. The intervention was delivered via 10 dinners in the Seattle metropolitan area (8 with the Somali community, 2 with the Ethiopian community). Educational presentations and pre/post-tests on knowledge, attitudes, and intentions were conducted in the participants' native language by a co-ethnic physician. Pre/post differences in responses were evaluated with McNemar's tests and GEE models. HPV vaccination uptake 6-months post-intervention was evaluated using state immunization registry data. Of 115 participating mothers, most (84%) were Somali and < 40 years of age (60%). Median years of formal education was 8 (range 0-16), and 61% reported a household income <$25,000. Knowledge of HPV/HPV-vaccines was low pre-intervention, with correct responses ranging from 4% to 39% (61%-91% of responses were "not sure"); correct post-intervention responses ranged from 29% to 97%. Pre-intervention, only 12% of mothers thought they had enough information to make a decision about vaccination, compared to 90% post-intervention. Pre-intervention, only 16% of mothers reported that they were somewhat or very likely to vaccinate their child, compared to 83% post-intervention. All pre/post comparisons were statistically significantly different (p < 0.0001). Although mothers were more likely to report correct HPV-related knowledge and positive vaccine attitudes and intentions post-intervention, only two mothers' children initiated HPV vaccination within 6 months after the intervention. Results illustrate that a culturally targeted educational intervention effectively increased East African mothers' HPV vaccine-related knowledge, attitudes, and intentions to vaccinate their adolescent children. Future research should identify additional intervention components that can bridge the gap between intention and behavior to facilitate HPV vaccine uptake.


Comparative evaluation of proliferative potential and replicative senescence associated changes in mesenchymal stem cells derived from dental pulp and umbilical cord.
Mesenchymal stem cells (MSC) have been widely studied for tissue regeneration and cell-based therapy. MSC can be isolated from different body tissues while several biological waste sources like dental pulp, umbilical cord, cord derived blood, amniotic fluid or urine have also emerged as potential sources of MSCs. Specifically, isolation of MSCs from such non-conventional sources show promising outcomes due to the non-invasiveness of the extraction process and high proliferation capacity of the isolated MSC. However, these stem cells also exhibit the limitation of replicative senescence in long-term culture condition. Inter-cellular reactive oxygen species is an important contributor for inducing cellular senescence under long-term culture conditions. For translational application, it becomes imperative to compare the stem cells isolated from these sources for their senescence and proliferative properties. In this study, MSC were extracted from two different sources of biological waste materials-dental pulp and umbilical cord, and compared for their proliferation capacity and replicative senescence at different passage numbers (i.e. P2 and P6). Intracellular ROS production was significantly (p < 0.001) less in dental pulp stem cells culture in comparison to umbilical cord-derived stem cells at P6. The β-gal expression also showed significantly (p < 0.001) low expression in DPSC culture compared to that of UCSC at P6. The study indicates the source of stem cells influences the proliferation capacity as well as replicative senescence of MSCs. This study will thus pave the path of future research in selecting appropriate stem cell source for regenerative medicine application.


Circular lipectomy with lateral thigh-buttock lift.
Patients with body contour deformities amongst the challenges that plastic surgeons most frequently face. Through the years, many surgical procedures have been developed that attempt to solve many forms of body contour deformities while optimizing the number of surgical stages within safety limits. In one stage, circular lipectomy with lateral thigh and buttock lift and trochanteric liposuction corrects deformities of the abdomen, the lateral thighs, the buttocks, the supra-gluteal area, the lateral supra-gluteal area, leaving only one circular scar that can be covered with a thong. It is performed under epidural anesthesia, requires one or two units of autologous blood, one night in a hospital, and two or three weeks off work. Thirty-nine patients were operated on without any major complications. Results were consistently good and superior to patients' expectations.


Psychosocial interventions for late-life major depression: evidence-based treatments, predictors of treatment outcomes, and moderators of treatment effects.
This systematic review evaluates the efficacy of psychosocial interventions for the acute treatment of late-life depression and identifies predictors of treatment outcomes and moderators of treatment effects. Problem-solving therapy, cognitive behavioral therapy, and treatment initiation and participation program have supportive evidence of efficacy, pending replication. Although the data on predictors of treatment outcomes and moderators of treatment effects are preliminary, it appears that baseline anxiety and stress level, personality disorders, endogenous depression, and reduced self-rated health predict worse depression outcomes. Future research may examine the moderating effects of baseline depression severity and identify other clinical or demographic moderators.


Impact of visceral fat accumulation on the prognosis of patients with cirrhosis.
The impact of obesity, evaluated using body mass index (BMI), on mortality in patients with cirrhosis is controversial. The prognostic impact of visceral fat accumulation, which is recommended as an indicator of obesity-related mortality, is still unknown. This study aimed to clarify the impact of visceral fat accumulation on mortality in patients with cirrhosis. A total of 335 cirrhotic patients without hepatocellular carcinoma were retrospectively evaluated. The impact of obesity, defined as a visceral fat area ≥100 cm2 at the umbilical level or BMI ≥25 kg/m2 on mortality, was evaluated using competing risk analysis. Of 355 patients, visceral fat accumulation was seen in 147 patients. During the observation period (1340 ± 980 days), 84 patients died, and 17 received liver transplantation. Visceral fat accumulation was not found to be associated with mortality (hazard ratio [HR] 1.423, P = 0.180) in any of the patients. After stratification of the patients, visceral fat accumulation was observed to be associated with a poor prognosis in patients with skeletal muscle depletion (HR 3.804, P = 0.003), but not in those without (HR 1.147, P = 0.660). On the other hand, obesity defined by BMI ≥25 kg/m2 was not found to be associated with mortality in patients with (HR 0.341, P = 0.390) or without skeletal muscle depletion (HR 1.227, P = 0.500). Visceral fat accumulation is a useful index for evaluating obesity and aggravates mortality in cirrhotic patients with skeletal muscle depletion, but not in those without.


Patterns of synaptic input on corticocortical and corticothalamic cells in the cat visual cortex. II. The axon initial segment.
In the present study we examined the synaptology of the axon initial segments (AISs) of three populations of retrogradely labeled pyramidal cells: callosal, corticothalamic, and ipsilateral corticocortical projecting cells. The cells were labeled by horseradish peroxidase injected into the contralateral visual cortex, the ipsilateral lateral geniculate nucleus, or area 19 of the ipsilateral hemisphere. The AISs of these cells were completely reconstructed from tracings of serial electron micrographs and the number and type of synapses ending on them determined. These data were compared with that described in the companion paper (Fariñas and DeFelipe, J Comp Neurol 1991; 304:53-69), in which the ultrastructure and synaptology of the somata of callosal and corticothalamic cells was investigated. Together, these data permit comparisons to be made between the somatic and axonic innervation of the same cells. Our results show that each population of efferent cells examined received a characteristic and rather homogeneous number (in comparison with the number of axosomatic synapses) of axoaxonic synapses: 16 to 23 for AISs of callosal cells, 22 to 28 for ipsilateral corticocortical cells, and 1 to 5 for corticothalamic cells. Since most axoaxonic synapses are likely to be GABAergic, it is concluded that each population of pyramidal cells receives a distinct GABAergic inhibitory synaptic profile.


Is bone mineral density advantage maintained long-term in previous weight lifters?
This cross-sectional study was done in order to ascertain whether there is a lifelong beneficial effect on bone mineral density (BMD) of early, long-lasting, and intense physical exercise. Forty-eight male ex-weight lifters, mean age 64 years (range 50-79) participated. They had followed a training program of an average of 10 hours/week (range 4-20) for an average of 13 years (range 1-34). They had all retired from competitive sport an average of 30 years (range 7-50) ago. Sixty-six age-matched volunteers served as controls. The bone mineral density (BMD, areal density, g/cm2) in the total body, spine, and hips and the fat content and lean body mass were measured with the LUNAR DPX bone mass scanner. In ex-weight lifters 50-64 years of age, the BMD was greater than in controls. After 65 years, no difference was found between the former weight lifters and their controls.


A new approach to the correction of involutional entropion by pretarsal orbicularis oculi muscle fixation.
A new surgical technique to repair involutional entropion involves fixation of a strip of dissected and displaced pretarsal orbicularis oculi muscle. In 112 patients followed up for an average of 14 months, this technique was successful. The procedure is easy to perform and complications were minimal.


The influence of load on the lifetime distribution.
This paper derives lifetime distributions for components that fail due to overloading. We introduce the notion of energy similarity. This makes it possible to use knowledge about how components behave under different loads in order to establish a probability model. To obtain parametric families, we consider two physically distinct cases: (1) components that function individually and (2) components that function as part of a system. The former leads to univariate and the latter to multivariate models. The results are particularly useful when little or no data is available.


Why not use the HbA1c as a criterion of dysglycemia in the new definition of the metabolic syndrome? Impact of the new criteria in the prevalence of the metabolic syndrome in a Mediterranean urban population from Southern Europe (IMAP study. Multidisciplinary intervention in primary care).
We analysed the prevalence of metabolic syndrome (MS) of the new diagnostic criteria and the HbA1c to diagnose dysglycemia. We studied 2006 adults without cardiovascular disease or diabetes. The use of the new criteria and the HbA1c resulted in an increase in the population prevalence of MS.


Peroxisome proliferator-activated receptor β/δ and γ agonists differentially affect prostaglandin E2 and cytokine synthesis and nutrient transporter expression in porcine trophoblast cells during implantation.
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-dependent transcription factors. PPARs have been shown to be important regulators of female reproductive functions, including conceptus development and placenta formation. This study examines the effect of PPARβ/δ and PPARγ agonists and antagonists on (1) the synthesis of prostaglandin (PG) E2, interleukin (IL) 6, interferon (IFN) γ, and tumor necrosis factor (TNF) α and (2) the mRNA expression of genes encoding nutrient transporters and/or binding proteins in Day 15 conceptus trophoblast cells. The study also examines whether PPAR agonist-modulated IL6, IFNγ, and TNFα secretion is mediated via mitogen-activated protein kinase (MAPK) pathways. Trophoblast cells were exposed to L-165,041 (a PPARβ/δ agonist) or rosiglitazone (a PPARγ agonist) in the presence or absence of GSK3787 (a PPARβ/δ antagonist) or GW9662 (a PPARγ antagonist) or in the presence or absence of U0126 (a MAPK inhibitor). Rosiglitazone stimulated PGE synthase and IFNG mRNA expression in trophoblast cells and enhanced PGE2 concentrations in the incubation medium. Moreover, cells treated with rosiglitazone exhibited increased abundance of the solute carrier organic anion transporter family member 2A1 (SLCO2A1, a PG transporter) and of fatty acid binding protein (FABP) 5 transcripts. All these effects were abolished by the addition of GW9662, which indicates that the action of rosiglitazone is PPARγ-dependent in the studied cells. L-165,041 inhibited TNFα synthesis and decreased the mRNA expression of FABP3 and IL6 in trophoblast cells. However, this effect was not abolished by the addition of GSK3787 into the incubation medium, suggesting that L-165,041 action is independent of PPARβ/δ. The inhibitory effect of L-165,041 on TNFα concentration and the stimulatory effect of rosiglitazone on IFNγ accumulation in the medium were not observed in the presence of the MAPK inhibitor, suggesting that the action of both agonists may be mediated by MAPKs. In conclusion, PPARβ/δ and PPARγ agonists are differentially involved in the trophoblast expression of genes related to conceptus development and implantation in pigs. Furthermore, L-165,041 and rosiglitazone may have PPAR-dependent and -independent effects in conceptus trophoblast cells.


Perspectives of service providers on aftercare service provision for persons with substance use disorders at a Rural District in South Africa.
Provision of aftercare services for persons with substance use disorders (PWSUD) within a rural context is typically met with various intersecting challenges, including unclear policy implications and lack of resources. In the South African context, service providers are expected to provide aftercare services that should successfully reintegrate persons with PWSUD into society, the workforce, family and community life as mandated by Act No. 70 of 2008, despite population diversity. Little has been established on the provision of aftercare services in South Africa and specifically within a rural context. This article explores service providers' perspectives in aftercare service provision for PWSUD in a rural district. A qualitative exploratory study design was conducted in a rural district in South Africa using semi-structured interviews and focus group discussions with forty-six service providers from governmental and non-governmental institutions, ranging from implementation to policy level of service provision. Data were analyzed thematically using a deductive approach. Codes were predetermined from the questions and the aims and objectives of the study used Beer's Viable Systems Model as a theoretical framework. NVivo Pro 12 qualitative data analysis software guided the organization and further analysis of the data. Four themes emanated from the data sets. Theme 1 on reflections of the interactional state of aftercare services and program content identified the successes and inadequacies of aftercare interventions including relevant recommendations for aftercare services. Themes 2, 3, and 4 demonstrate reflections of service provision from implementation to policy level, namely, identifying existing barriers to aftercare service provision, situating systemic enablers to aftercare service provision, and associated aftercare system recommendations. The intersecting systemic complexities of providing aftercare services in a rural context in South Africa was evident. There existed minimal enablers for service provision in this rural district. Service providers are confronted with numerous systemic barriers at all levels of service provision. To strengthen the aftercare system, policies with enforcement of aftercare services are required. Moreover, a model of aftercare that is integrated into the existing services, family centered, sensitive to the rural context and one that encourages the collaboration of stakeholders could also strengthen and sustain the aftercare system and service provision.


Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure.
Recently, there have been increasing reports that nano-sized component of particulate matter can reach the brain and may be associated with neurodegenerative diseases. Previously, our laboratory has studied the effect of intranasal instillation of nano-sized carbon black (CB) (14 nm and 95 nm) on brain cytokine and chemokine mRNA expressions and found that 14-nm CB increased IL-1 beta, TNF-alpha, CCL2 and CCL3 mRNA expressions in the olfactory bulb, not in the hippocampus of mice. To investigate the effect of a single administration of nanoparticles on neurotransmitters and proinflammatory cytokines in a mouse olfactory bulb, we performed in vivo microdialysis and real-time PCR methods. Ten-week-old male BALB/c mice were implanted with guide cannula in the right olfactory bulb and, 1 week later, were instilled vehicle or CB (14 nm, 250 microg) intranasally. Six hours after the nanoparticle instillation, the mice were intraperitoneally injected with normal saline or 50 mug of bacteria cell wall component lipoteichoic acid (LTA), which may potentiate CB-induced neurologic effect. Extracellular glutamate and glycine levels were significantly increased in the olfactory bulb of CB-instilled mice when compared with vehicle-instilled control mice. Moreover, we found that LTA further increased glutamate and glycine levels. However, no alteration of taurine and GABA levels was observed in the olfactory bulb of the same mice. We also detected immunological changes in the olfactory bulb 11 h after vehicle or CB instillation and found that IL-1 beta mRNA expression was significantly increased in CB- and LTA-treated mice when compared with control group. However, TNF-alpha mRNA expression was increased significantly in CB- and saline-treated mice when compared with control group. These findings suggest that nanoparticle CB may modulate the extracellular amino acid neurotransmitter levels and proinflammatory cytokine IL-1 beta mRNA expressions synergistically with LTA in the mice olfactory bulb.


Expression, Purification, and Solution-State NMR Analysis of the Two Human Single-Stranded DNA-Binding Proteins hSSB1 (NABP2/OBFC2B) and hSSB2 (NAPB1/OBFC2A).
Single-stranded DNA-binding proteins (SSBs) are essential to all living organisms as protectors and guardians of the genome. Apart from the well-characterized RPA, humans have also evolved two further SSBs, termed hSSB1 and hSSB2. Over the last few years, we have used NMR spectroscopy to determine the molecular and structural details of both hSSBs and their interactions with DNA and RNA. Here we provide a detailed overview of how to express and purify recombinant versions of these important human proteins for the purpose of detailed structural analysis by high-resolution solution-state NMR.


Nursing students' perception of medical errors: A cross-sectional study in a university.
To assess the perception of nursing students on medical errors. A descriptive cross-sectional survey. Data were collected from March-April 2019 in a university in Ghana from two hundred (200) students using simple random sampling and analysed with SPSS version 21. Mean age of respondents was 22.64 years. Medication error was perceived as the most common medical errors (MEs; 76%). Negligence was perceived as the most common cause of MEs (80.5%); nurses and doctors (84.5%-89.5%) were considered as staff who make most MEs. Respondents perceived that students commit MEs due to less knowledge about procedures (79%) and inadequate supervision (77%) in the clinical setting. Medication errors were observed as the most common of MEs that can affect patients' safety. Taking prudent measures in addressing this can reduce MEs in health facilities. Enhanced supervision and effective ways of teaching drug administration are recommended.


Noninvasive approaches to prenatal diagnosis of hemoglobinopathies using fetal DNA in maternal plasma.
Fetal DNA is present in the plasma of pregnant women and can be used for noninvasive prenatal diagnosis. Early work had focused on the detection of paternally inherited fetal mutations in maternal plasma. Recent advances in single-molecule counting approaches have allowed the mutation dosage of the fetus to be analyzed in maternal plasma. These developments have been demonstrated as feasible for noninvasive prenatal diagnosis of several hemoglobinopathies, including β-thalassemia and hemoglobin E disease.


Comments on health indicators: methodological perspectives.
This paper discusses several basic conceptual and methodological problems in the development and use of health indicators. We observe that two tendencies of the health indicators movement may deter progress toward producing informations of health status indexes and the tendency to conceptualize "health" in terms of expansive definitions should measure variables specified by a social system model and should be scaled according to units that are relevant to decision-making criteria.


Growth of Paracoccidioides brasiliensis yeast phase in a chemically defined culture medium.
A slight modification of the chemically defined medium of McVeigh and Morton resulted in an excellent substratum for the cultivation of Paracoccidioides brasiliensis yeast phase.


Continued symptomatic improvement three to five years after transmyocardial revascularization with CO(2) laser: a late clinical follow-up of the Norwegian Randomized trial with transmyocardial revascularization.
The goals of this study were to assess late clinical outcome and left ventricular ejection fraction (LVEF) after transmyocardial revascularization with CO(2) laser (TMR). During the 1990s TMR emerged as a treatment option for patients with refractory angina not eligible for conventional revascularization. Few reports exist on clinical effects and LVEF >3 years after TMR. One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized 1:1 to receive continued medical treatment or medical treatment combined with TMR. The patients were evaluated at baseline and after 3, 12 and 43 (range: 32 to 60) months with end points to angina, hospitalizations due to acute myocardial infarctions or unstable angina, heart failure and LVEF. Mortality was registered and MOS 36 Short-Form Health Survey answered at baseline and after 3, 6 and 12 months. Forty-three months after TMR, angina symptoms were still significantly improved, and unstable angina hospitalizations reduced by 55% (p < 0.001). Heart failure treatment (p < 0.01) increased, whereas the number of acute myocardial infarctions, LVEF and mortality was not affected. Quality of life was improved 3, 6 and 12 months after TMR. Forty-three months after TMR, angina symptoms and hospitalizations due to unstable angina were significantly reduced, heart failure treatment increased and LVEF and mortality were seemingly unaffected.


Simultaneous denitrification and desulfurization-S0 recovery of wastewater in trickling filters by bioaugmentation intervention based on avoiding collapse critical points.
In order to better achieve efficiently simultaneous desulfurization and denitrification/S0 recovery of wastewater, the intervention of sulfur oxidizing bacteria (SOB) and denitrifying bacteria (DNB) was employed to avoid the collapse critical points (the dramatically decrease of S/N removal efficiency) under the fluctuated load. With the assistance of DNB and SOB, collapse critical point of trickling filter (TF) was delayed from the P8 (105-114 d) to P10 stage (129-138 d). The treatment efficiency of nitrogen and sulfur was the highest with the S/N ratio of 3:1. The bioaugmentation of DNB and SOB at collapse critical point could effectively regulated collapse situation, which further increased the maximum system utilization/elimination capacity to 4.50 kg S m-3·h-1 and 0.90 kg N m-3·h-1 (increased by 56.89% and 65.56% in comparison to control). High-throughput sequencing analysis indicated that Proteobacteria (average 78.59%) and Bacteroidetes (average 9.30%) were dominant bacteria in the reactor at all stages. As the reaction proceeds, the microbial community was gradually dominated by some functional genera such as Chryseobacterium (average 2.97%), Halothiobacillus (average 22.71%), Rhodanobacter (average 14.02%), Thiobacillus (average 9.01%), Thiomonas (average 16.70%) and Metallibacterium (average 21.63%), which could remove nitrate or sulfide. Both of Principal Component Analysis (PCA) and Canonical Correlation Analysis (CCA) demonstrated the important role of DNB/SOB during the long-term run in the trickling filters (TFs).


Repair Bond Strength of High-viscosity Glass-ionomer Cements Using Resin Composite Bonded with Light- and Self-cured Adhesive Systems.
High-viscosity glass-ionomer cements (HVGICs) used with atraumatic restorative treatment can be repaired with light- or self-cured adhesive systems; however, the repair bond strength of two-step, self-etching and one-step adhesives in the light-cure mode surpass one-step self-cure adhesives. Working on a feasible self-cure approach in the absence of such in rural areas as well as in war zones is of prime importance.


Role of endometrial concentrations of heavy metals (cadmium, lead, mercury and arsenic) in the aetiology of unexplained infertility.
To determine the role of endometrial concentrations of heavy metals (cadmium, lead, mercury and arsenic) in the aetiology of unexplained infertility. Thirty-three women with unexplained infertility and 32 fertile women were recruited. Endometrial biopsies were collected during the putative window of implantation (cycle days 20-24). The concentrations of cadmium, lead, mercury and arsenic were measured in endometrial biopsy specimens using atomic absorption spectrometry. Cadmium was detected in 91% (30/33) of women with unexplained infertility, compared with 34% (11/32) of fertile women. The median endometrial cadmium concentration was 19.58 (interquartile range 1.46-30.23)μg/l in women with unexplained infertility, compared with 0.00 (interquartile range 0.00-0.40)μg/l in fertile women. Lead was detected in 15% (5/33) of women with unexplained infertility and 3% (1/32) of fertile women. Mercury and arsenic were not detected in any endometrial samples from either group. A significant difference in endometrial cadmium concentration was found between women with unexplained infertility and fertile women. This suggests that cadmium may be a contributing factor in the aetiology of unexplained infertility.


Disseminated cutaneous histoplasmosis in patients infected with human immunodeficiency virus.
In the pre-AIDS era disseminated histoplasmosis was rare and the cutaneous manifestations thereof were reported infrequently. A range of unusual clinical manifestations of disseminated cutaneous histoplasmosis (DCH) in AIDS patients has been documented, but the cutaneous histopathological descriptions are short and incomplete. In addition, the histopathological spectrum of AIDS-associated DCH is poorly recognized. This is a prospective 32-month study of all HIV positive patients diagnosed with histoplasmosis in the Departments of Anatomical Pathology and Dermatology, Nelson R. Mandela School of Medicine and King Edward VIII Hospital, Durban, South Africa. Clinical distribution and morphology of the individual skin lesions and CD4+ lymphocyte counts in the peripheral blood were analysed in relation to the histopathological features of biopsied lesional tissue. Ultrastructural examination of tissue retrieved from the wax blocks of three cases that exhibited dermal karyorrhexis and collagen necrosis was undertaken. Fungal culture of lesional skin tissue was undertaken in all patients. Twenty-one biopsies of papules (7), nodules (4), plaques (5), erythema multiforme-like lesions (2), vasculitic lesions (2) and exfoliative dermatitis (1) from 14 patients were examined. Of four biopsies (CD4 range: 120-128 cells/mm3) one and three demonstrated necrotizing and non-necrotizing granulomatous inflammation with a paucity of intrahistiocytic microorganisms. Seven biopsies (CD4 range: 2-56 cells/mm3) demonstrated diffuse dermal and intravascular accumulation of histiocytes densely parasitized by Histoplasma capsulatum var. capsulatum. Vasculitis, karyorrhexis or collagen necrosis was not present. Ten biopsies (CD4 range: 2-72 cells/mm3) demonstrated diffuse dermal karyorrhexis, collagen necrosis and interstitial, extracellular H. capsulatum var. capsulatum. Histiocytic disintegration and nuclear fragmentation and release of intact microorganisms and intact and ruptured lysosomes were identified ultrastructurally. Leucocytoclastic vasculitis was present in two biopsies of vasculitic clinical morphology. Microbiological culture confirmed histoplasmosis in all cases. Three patients died before treatment was commenced. Two patients died within the first two days of induction of therapy. Nine patients demonstrated dramatic healing of the cutaneous lesions. Despite the clinicopathological spectrum of DCH and the attendant host immunocompromise, timely and appropriate treatment of DCH may be lifesaving and allows rapid healing of skin lesions. A high index of clinical suspicion and skin biopsies and culture are crucial for accurate diagnosis.


[Peroral calcium administration test with free diet in idiopathic calcium nephrolithiasis--possibilities and limits].
Seventeen patients who recurrently formed idiopathic calcium kidney stones (SF) and 25 age- and sex-matched healthy blood donors (H) were challenged by an oral calcium load (1 g) after an overnight fast. Their usual diet was not changed before the test. Urine samples were taken before, 2 1/2, and 4 h after the calcium load. A blood sample was drawn 3 3/4 h after calcium loading. Before and 2 1/2 h after calcium dosage urinary measurements of calcium, magnesium, phosphate, oxalate, uric acid, and creatinine did not reveal any differences between SF and H. According to the calciuria after 4 h SF were separated in normocalciurics (NCSF) and hypercalciurics (HCSF). Nine-tenths of the NCSF had higher serum ionic calcium levels than H after calcium load (P less than 0.001), whereas HCSF were not different from H. Serum phosphate in SF was lower than in H (P less than 0.001). Carboxy-terminal parathormone, measured in 3 NCSF and 2 HCSF, was normal. Depending on the calciuria or calcemia 4 h after an oral calcium load, 16 of 17 SF showed a metabolic abnormality (hypercalcemia or hypercalciuria). It is concluded that intestinal calcium absorption in SF might be increased to variable rates.


ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway.
Lipid metabolic reprogramming plays a pivotal role in hepatocellular carcinoma (HCC) development, but the underlying mechanisms are incompletely characterized. Long chain acyl CoA synthetase 4 (ACSL4), a member of acyl-CoA synthetases (ACS) family, has been identified as a novel marker of alpha-fetoprotein-high subtype HCC and as an oncogene. Here, we identified a new function of ACSL4 in HCC lipid metabolism. ACSL4 can modulate de novo lipogenesis by accumulating intracellular triglycerides, cholesterols, and lipid droplets in HCC. Mechanistically, ACSL4 upregulates the master lipogenesis regulator sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes in HCC cells via c-Myc. Moreover, SREBP1 is crucial for ACSL4-mediated regulation of lipogenesis as well as HCC cell proliferation and metastasis, as SREBP1 overexpression rescues lipogenic deficiency and decreased oncogenic capabilities associated with ACSL4 suppression in vitro and in vivo. Clinically, our data showed that the expression of ACSL4 was positively correlated with that of SREBP1 in HCC patients, and the combinational biomarkers showed strong predictive value for HCC. Together, our findings uncover a new mechanism by which ACSL4 modulates aberrant lipid metabolism and promotes the progression of HCC.


Assessing the Prevalence and Associated Risk Factors for Presbylarynx in the Elderly Laryngology Population.
The primary objective of this study was to assess the prevalence of presbylarynx and its associated features in an elderly population representative of patients seen in a tertiary care laryngology practice. The secondary objective of this study was to compare laryngeal electromyography (LEMG) findings, coexisting VF conditions, medical history, surgical history, medication use, and other parameters between patients with and without presbylarynx. Adult voice patients aged 60 years and older who underwent strobovideolaryngoscopy were included in the study. Patients were assigned to one of two groups based on the majority (≥2/3) agreement of three blinded authors' (GA, KL, and HP) graded examinations of strobovideolaryngoscopy (SVL) videos for findings consistent with presbylarynx (atrophic vocal folds [VFA], vocal fold bowing [VFB], vocal process prominence [VPP] and anterior glottic insufficiency [GI]). Patient demographics, medical history, surgical history, medication use, laboratory results, and SVL videos were compiled. Statistical analysis was performed using SPSS 220.127.116.11 (IBM, Armonk, NY). All tests were performed two-tailed, and a P-value of less than 0.05 was considered statistically significant. One hundred sixty-four patients (84 female/80 male, mean age of 68.397 ± 4.947 years) were included in this study. The prevalence of presbylarynx was 52.4% (n = 86) in the study population. The mean age of patients in the presbylarynx group was significantly higher than the nonpresbylarynx group. Additionally, there were significantly more males than females in the presbylarynx group. The presbylarynx group also was found to have a higher proportion of ACE inhibitor (ACEi) use. Further, laboratory results revealed a significantly higher proportion of patients with elevated thyroid stimulating hormone (TSH) levels in the presbylarynx group. Conversely, patients in the nonpresbylarynx group were found to have a significantly higher rate of levothyroxine use. On SVL, patients in the nonpresbylarynx cohort were found to have a significantly higher proportion of benign vocal fold lesions and vocal fold paresis. However, LEMG testing revealed no statistically significant differences in muscle recruitment between groups. Men with presbylarynx were found to have a significantly higher proportion of VFB and VPP compared to women with presbylarynx. This retrospective study investigated the prevalence and risk factors associated with presbylarynx in patients representative of those treated by laryngologists. Signs consistent with presbylarynx are observable even in the presence of coexisting VF conditions. Older age, elevated TSH, the use of ACEi, and male gender was associated with signs of presbylarynx on SVL. Of those diagnosed with presbylarynx, males were identified as having higher proportions of VFB and VPP compared to females. More education regarding presbylarynx and further studies to improve standardization of the criteria for its diagnosis, as well as its relationship with other VF conditions, are encouraged to improve management of the aging voice.


New insights into the reduction of mitral valve systolic anterior motion after ventricular septal myectomy in hypertrophic obstructive cardiomyopathy.
To determine the mechanism of reduction of mitral valve systolic anterior motion by myectomy, we examined 33 patients with hypertrophic obstructive cardiomyopathy echocardiographically before and after myectomy. Measurements included outflow tract diameter, the direction of ejection streamline (the angle between the ejection flow and the mitral valve), midventricular fractional area change, and papillary muscle inward excursion in the short-axis image. After myectomy, the outflow tract was enlarged (from 1.2 +/- 0.3 cm to 2.1 +/- 0.4 cm; p < 0.001), and the ejection flow became more parallel to mitral leaflets (from 51 +/- 10 degrees to 28 +/- 8 degrees; p < 0.001), whereas hyperdynamic midventricular fractional area change was reduced (81% +/- 14% to 62% +/- 14%; p < 0.001), and papillary muscle excursion decreased (1.3 +/- 0.3 cm to 0.8 +/- 0.3 cm; p < 0.001). Outflow enlargement and reduced ventricular contraction would decrease the Venturi force. Change of ejection streamline and reduced contraction would decrease the drag force onto the mitral leaflets. Blunted papillary motion would increase the mitral leaflet tension and decrease the effect of drag force on both leaflets. Thus myectomy decreases Venturi and drag forces and appears to reduce systolic anterior motion of the mitral valve.


Contrast Material Injection Protocol With the Dose Determined According to Lean Body Weight at Hepatic Dynamic Computed Tomography: Comparison Among Patients With Different Body Mass Indices.
The objective of this study was to compare enhancement of the aorta and liver on hepatic dynamic computed tomography scans acquired with contrast material doses based on the lean body weight (LBW) or the total body weight (TBW). We randomly divided 529 patients (279 men, 250 women; median age, 66 years) scheduled for hepatic dynamic computed tomography into 2 groups. The LBW patients (n = 278) were injected with 679 mg iodine/kg (men) or 762 mg iodine/kg (women). The TBW group (n = 251) was injected with 600 mg iodine/kg TBW. Each group was subdivided into the 3 classes based on the body mass index (BMI; low, normal, high). Aortic enhancement during the hepatic arterial phase and hepatic enhancement during the portal venous phase was compared. The aortic and hepatic equivalence margins were 100 and 20 Hounsfield units, respectively. Comparison of the median iodine dose in patients with a normal or high BMI showed that it was significantly lower under the LBW protocol than the TBW protocol (558.2 and 507.0 mg iodine/kg, P < 0.001, respectively). However, in patients with a low BMI, the LBW protocol delivered a significantly higher dose than the TBW protocol (620.7 vs 600.0 mg iodine/kg, P < 0.001). The 95% confidence interval for the difference in aortic and hepatic enhancement between the 2 protocols was within the range of the predetermined equivalence margins in all BMI subgroups. Contrast enhancement was equivalent under both protocols. The LBW protocol can avoid iodine overdosing, especially in patients with a high BMI.


A novel partial de novo duplication of JARID2 gene causing a neurodevelopmental phenotype.
Deletions covering the entire or partial JARID2 gene as well as pathogenic single nucleotide variants leading to haploinsufficiency of JARID2 have recently been shown to cause a clinically distinct neurodevelopmental syndrome. Here, we present a previously undescribed partial de novo duplication of the JARID2 gene in a patient displaying features similar to those of patients with JARID2 loss-of-function variants. The index patient presents with abnormalities in gross motor skills and speech development as well as neuropsychiatric disorders. The patient has markedly dark infraorbital circles and slightly prominent supraorbital ridges.Whole-genome sequencing and array comparative genomic hybridization revealed a novel disease-causing variant type, a partial tandem duplication of JARID2, covering the exons 1-7. Furthermore, RNA sequencing validated the increased expression of these exons. Expression alterations were also detected in target genes of the PRC2 complex, in which JARID2 acts as an essential member. Our data add to the variety of different pathogenic variants associated with JARID2 neurodevelopmental syndrome.


Conventional and microwave-assisted SPPS approach: a comparative synthesis of PTHrP(1-34)NH(2).
Attracted by the possibility to optimize time and yield of the synthesis of difficult peptide sequences by MW irradiation, we compared Fmoc/tBu MW-assisted SPPS of 1-34 N-terminal fragment of parathyroid hormone-related peptide (PTHrP) with its conventional SPPS carried out at RT. MWs were applied in both coupling and deprotection steps of SPPS protocol. During the stepwise elongation of the resin-bound peptide, monitoring was conducted by performing MW-assisted mini-cleavages and analyzing them by UPLC-ESI-MS. Identification of some deletion sequences was helpful to recognize critical couplings and as such helped to guide the introduction of MW irradiations to these stages.


Formats for combinatorial synthesis: solid-phase, liquid-phase and surface.
Methods for combinatorial and parallel synthesis continue to evolve in order to meet the demands of modern synthetic organic chemistry. The nature of the support, while typically overlooked, is a key consideration for successful combinatorial organic synthesis. Developments in combinatorial synthesis technologies such as the 'lab-on-a-chip' concept and 96-well-plate-compatible resin plugs have been reported, which should contribute to meeting the increasing challenges of this field.


Protease Do is essential for survival of Escherichia coli at high temperatures: its identity with the htrA gene product.
The DNA encoding protease Do was isolated from an E. coli genomic DNA library in lambda gt11, and cloned into a Bluescript plasmid. The cells transformed with the recombinant plasmid were able to overproduce protease Do and grew normally. A mutant lacking the protease activity was also isolated by interrupting the chromosomal DNA with the kan gene. The mutant showed a prolonged lag period and reduced ability to degrade cell proteins as compared to its wild type. Moreover, they were unable to survive at high temperatures, similarly to the htrA mutants. These results suggest that protease Do may play an important role in the intracellular protein breakdown and is essential for survival at high temperatures. Identity of protease Do with the htrA gene product is discussed.


Prevalence, risk and protective factors of alcohol use disorder during the COVID-19 pandemic in U.S. military veterans.
There have been reports of increased alcohol consumption during the COVID-19 pandemic in the general population. However, little is known about the impact of the pandemic on the prevalence of alcohol use disorder (AUD), especially in high-risk samples such as U.S. military veterans. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative, prospective cohort of 3078 U.S. veterans. Pre-pandemic and 1-year peri-pandemic risk and protective factors associated with incident and chronic probable AUD were examined. A total of 6.9 % (n = 183) of veterans were classified as chronic probable AUD, 3.2 % (n = 85) as remitted from AUD, and 2.7 % (n = 71) as incident probable AUD during the pandemic; the prevalence of probable AUD in the full sample remained stable -10.1 % pre-pandemic and 9.6 % peri-pandemic. Younger age, greater pre-pandemic alcohol use severity, and COVID-related stressors were associated with incident AUD during the pandemic, whereas higher pre-pandemic household income was associated with lower risk of this outcome. Younger age, combat experience, lifetime substance use disorder, greater drug use severity, lower dispositional optimism, and more COVID-related worries and social restriction stress were associated with higher risk of chronic AUD. Nearly 1-in-10 US veterans screened positive for AUD 1-year into the pandemic; however, the pre- and 1-year peri-pandemic prevalence of probable AUD remained stable. Veterans who are younger, have served in combat roles, endorse more COVID-related stressors, and have fewer socioeconomic resources may be at higher risk for AUD during the pandemic.


[National survey of transfusion practices in the neonatal period for the development of recommendations based on the "Haute Autorité de Santé methodology"].
Although transfusion practices have changed these last years, the neonatal period remains one period when the transfusion of blood components (in particular in red blood cells concentrates) is frequent, particularly for low birth weight premature babies. It is thus important to know well the pathophysiological characteristics specific to this age of life in order to reduce the risks of transfusion and to allow an optimal effectiveness of this treatment. Various studies on neonatal transfusion show that transfusion practices during the neonatal period are very heterogeneous from a team to another, and even within the same team. Therefore, we wanted to know the practices in France, by addressing a questionnaire to neonatology centres, in collaboration with the French Society Vigilance and Transfusion Therapy and the French Society of Neonatology (SFN). The results obtained confirm the heterogeneity of practices. To follow up on this study, we constituted a working group, in partnership with the SFN, the SFVTT and the EFS, with an aim of proposing good practice recommendations according to the methodology of the French "High Authority for Health", in order to homogenize at the national level transfusion practices of the new-born baby.


Interaction between Oenococcus oeni and Lactobacillus hilgardii isolated from wine. Modification of available nitrogen and biogenic amine production.
During the mixed culture of Lactobacillus hilgardii 5w, a common spoilage wine bacteria and Oenococcus oeni X(2)L, an amensalistic growth response of the malolactic bacteria was produced due to a competition for nitrogenous nutrients, mainly peptides. Arginine was fully consumed and peptide concentration diminished 60% with respect to both pure cultures at the end of exponential growth. Histamine release increased 34% with respect to L. hilgardii single culture. Under the poor nutritional conditions present during winemaking, L. hilgardii could increase histamine production and adversely affect malolactic fermentation conducted by O. oeni and hence the quality of the final product.


Study on temporal and spatial evolution law for dust pollution in double roadway ventilation system of short wall continuous mining face.
To explore the laws of variations in the evolution of dust pollution within a double tunnel ventilation system at a short wall continuous mining face, a numerical simulation of air flow movement was conducted in this study. Results showed that after the wind flowing in the supporting and heading tunnels reached the head, the wind sides returned at speeds of 6.5 and 10.3 m/s, respectively. Affected by the air volume and pressure differences between the two tunnels, part of the air flow entered the connecting tunnel at an average speed of 0.8 m/s and moved to the heading tunnel. Affected by the turbulence at the driving face, a high dust concentration zone with a maximum dust concentration of 1700 mg/m3 was formed in the tunnels at a distance of 15 m from the heading. Dust blocked by the shuttle car accumulated and settled near it and formed a dust zone with an approximate average concentration of 750 mg/m3 at a distance of 19-23 m from the heading. The dust produced by the bolt machine formed a dust mass with an average concentration of 900 mg/m3 at a distance of 0.5-4.5 m from the head. Quantitative analyses of the changes in dust concentration with time at the position of a driver of the continuous mining machine, shuttle car, and anchor bolt machine were conducted, and functional formulae for the quadratic distribution were obtained. Suggestions for dust control were then proposed.


NEXAFS imaging to characterize the physio-chemical composition of cuticle from African Flower Scarab Eudicella gralli.
The outermost surface of insect cuticle is a high-performance interface that provides wear protection, hydration, camouflage and sensing. The complex and inhomogeneous structure of insect cuticle imposes stringent requirements on approaches to elucidate its molecular structure and surface chemistry. Therefore, a molecular understanding and possible mimicry of the surface of insect cuticle has been a challenge. Conventional optical and electron microscopies as well as biochemical techniques provide information about morphology and chemistry but lack surface specificity. We here show that a near edge X-ray absorption fine structure microscope at the National Synchrotron Light Source can probe the surface chemistry of the curved and inhomogeneous cuticle of the African flower scarab. The analysis shows the distribution of organic and inorganic surface species while also hinting at the presence of aragonite at the dorsal protrusion region of the Eudicella gralli head, in line with its biological function.


Association of prenatal alcohol exposure with preadolescent alcohol sipping in the ABCD study®.
Early alcohol use initiation is one of the strongest predictors of alcohol use disorders. Identifying modifiable risk factors for problematic alcohol use can guide prevention initiatives. Globally, approximately 10% of women consume alcohol during pregnancy, however the impact of prenatal alcohol exposure (PAE) on offspring alcohol use patterns has been understudied. The aim of this study was to examine associations between PAE and preadolescent alcohol use behaviors. Cross-sectional data were utilized from 10,119 children aged 9.0-10.9 years (M = 9.9, SD = 0.6) enrolled in the Adolescent Brain Cognitive Development Study®, based in the United States. Linear mixed models tested associations between PAE and endorsement of non-religious alcohol sipping in offspring, when adjusting for confounding factors. In total, 2675 (26.4 %) youth were prenatally exposed to alcohol. Among PAE youth, total standard drinks consumed during pregnancy ranged from 0.4-90.0 drinks (M = 26.8, SD = 24.5). Compared to unexposed youth, those with any alcohol exposure during early pregnancy (∼0-7 weeks) were 1.7 times (95 % CI 1.4-2.0, p < .0001) more likely to endorse sipping alcohol by ages 9-10, while youth with low-level doses of alcohol throughout the entire pregnancy were 2.9 times (95 % CI 1.9-4.6, p < .0001) more likely to endorse sipping, when adjusting for confounding factors. A dose-dependent association between total standard drinks consumed during pregnancy and youth sipping endorsement was observed (β = 0.2, 95 % CI 0.1-0.2, p < .0001). This study shows that any alcohol use during pregnancy may play an important role in very early alcohol use experimentation among offspring by ages 9-10.


Disrupted serotonergic and sympathoadrenal systems in patients with chronic heart failure may serve as new therapeutic targets and novel biomarkers to assess severity, progression and response to treatment.
It is well established that the serotonergic system (SS) plays important roles in the pathogenesis of cardiovascular diseases. However, the impact of serotonin and its inter-relation with the sympathoadrenal system (SAS) in chronic heart failure (CHF) is poorly understood. Utilizing high-performance liquid chromatography with electrochemical detection, we determined blood plasma levels of serotonin (5-hydroxy-triptamine, [5-HT](p)), 5- hydroxy-indole-acetic acid ([5-HIAA](p)), epinephrine ([E](p)), norepinephrine ([NE](p)), 3,4-dihydroxy-L-phenyl-alanine ([DOPA](p)), dopamine ([DA](p)) and the platelet concentration of serotonin ([5-HT](pt)) in CHF patients with different morphofunctional alterations of myocardium. The morphofunctional alterations included diastolic dysfunction (DD), diastolic dysfunction with left ventricular hypertrophy (DD&LVH), and diastolic and systolic dysfunction (D&SD). All CHF groups showed significant rises of [5-HT](p) and [5-HT](pt). DD&LVH and D&SD individuals also had increased [5-HIAA](p). Levels of SAS blood biomarkers were also significantly changed. The correlation between SS and SAS was increased in CHF and corresponded with disease severity. These results clearly demonstrate that in CHF patients significant changes in SS and SAS occur, which are thought to relate to the morphofunctional alterations of myocardium. The observed changes in the levels of these biomarkers may serve as potential surrogates to monitor severity of disease, to evaluate response to drug treatment, and as a rational basis for new therapeutic approaches.


The effect of dietary grape pomace supplementation on epididymal sperm quality and testicular antioxidant ability in ram lambs.
Wine grape pomace (WGP) contains a rich source of polyphenols that can act as powerful antioxidants. The objective of this study was to investigate the effect of dietary WGP supplementation on antioxidative activity and epididymal sperm quality in rams. The rams were raised either under free-range or pen conditions, and the pen-raised rams were fed a WGP-containing diet (0, 5% and 10% of dry matter basis) for 74 days. An increase in the concentrations of reactive oxygen species (ROS, P < 0.05) and malondialdehyde (MDA, P < 0.05) were observed in the testes of rams subjected to restraint stress, and dietary WGP supplementation effectively decreased their contents (P < 0.05). Restraint stress reduced both weight and volume of testes, and impaired sperm quality. Dietary WGP supplementation increased testes weight, sperm concentration, motility and acrosomal integrity, and decreased sperm deformity in pen-raised animals (P < 0.05). The total antioxidative capacity (T-AOC) and catalase activity were decreased in the testes of pen-raised lambs (P < 0.05), and T-AOC, catalase, glutathione peroxidase 4 (GPx4) and superoxide dismutase (SOD) activity were increased when rams were fed the WGP-containing diet (P < 0.05). With the exception of SOD and GPx4, the mRNA contents of catalase and nuclear factor-like-2 factor (Nrf2) did not vary among the groups, and greater protein levels of SOD, catalase and GPx4 were observed in WGP-treated lambs (P < 0.05). Taken together, these results suggest that WGP can be used as a feed ingredient in rams to alleviate restraint induced oxidative stress and improve epididymal sperm quality.


Medical negligence law: 4. The patient's right to know: access to health records.
This article summarizes the main provisions of the Access to Health Records Act 1990 and considers its implications for the medical profession. It is the authors' view that although it is unlikely that the majority of patients will avail themselves of their rights under the Act, its provisions could have significant implications in the field of medical negligence.


From selective full-length genes isolation by TAR cloning in yeast to their expression from HAC vectors in human cells.
Transformation-associated recombination (TAR) cloning allows selective isolation of full-length genes and genomic loci as large circular Yeast Artificial Chromosomes (YACs) in yeast. The method has a broad application for structural and functional genomics, long-range haplotyping, characterization of chromosomal rearrangements, and evolutionary studies. In this paper, we describe a basic protocol for gene isolation by TAR as well as a method to convert TAR isolates into Bacterial Artificial Chromosomes (BACs) using a retrofitting vector. The retrofitting vector contains a 3' HPRT-loxP cassette to allow subsequent gene loading into a unique loxP site of the HAC-based (Human Artificial Chromosome) gene delivery vector. The benefit of combining the TAR gene cloning technology with the HAC gene delivery system for gene expression studies is discussed.