Local immunostimulation of the bovine mammary gland with interleukin-2.
One day after drying off, miniosmotic pumps releasing interleukin-2 were implanted into teat cisterns of six Jersey cows. Each cow had two quarters with (sensitized) and without (unsensitized) chronic Staphylococcus aureus infection. At 1 and 3 wk after implantation, three cows were sacrificed and mammary tissues processed to examine the cytological response to interleukin-2. Concentrations of lymphoid cells were determined in tissues lining teat and gland cistern linings, and plasma cells were characterized by Ig class. For total lymphoid cell and IgG1 and IgG2 plasma cell concentrations, sensitized placebo quarters and unsensitized interleukin-2 quarters were similar, indicating interleukin-2 stimulated a cellular immune response equal to that of quarters infected with S. aureus. Greatest response was observed in sensitized interleukin-2 quarters, suggesting that the cytokine was more effective in quarters with prior exposure to S. aureus antigens. Greater numbers of lymphocytes and macrophages were found in secretions of interleukin-2 quarters than in secretion of control quarters. Local interleukin-2 immunostimulation may supplement immunization procedures and enhance protection against natural S. aureus challenge.


[Treatment and prevention of venous thromboembolic events: present and future antithrombotic agents].
Two new classes of anticoagulants are actually developed which would change in the near future our strategies for the prevention and the treatment of venous thromboembolic events. These two classes are the anti-factor Xa and anti-factor IIa (direct antithrombin) agents. Among the anti factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux is a synthetic form of the natural pentasaccharide, its pharmacokinetics allows one s.c. administration/24 hours. It is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade with a limited use due to several drawback. More recently synthetic direct antithrombins modified to allow oral route have been developed, the most advanced in development, melagatran, is active in the prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Melagatran is also active in the prevention of arterial thromboembolic events on atrial fibrillation. But other molecular forms of synthetic orally active direct antithrombin are also in development. Besides these important changes in our therapeutics which should appear in a near future, molecules aimed at other target are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis. These new drugs at our disposal to treat venous thromboembolism should modify completely our handling of the patients. But additionally the numerous clinical trials necessary to prove the efficacy of the drugs, modify our understanding in the implication of the coagulation and in the physiopathogeny of thrombotic events.


Development of a recumbent isometric yoga program for patients with severe chronic fatigue syndrome/myalgic encephalomyelitis: A pilot study to assess feasibility and efficacy.
Our previous randomized controlled trial demonstrated that isometric yoga in a sitting position reduces fatigue in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). However, some patients experience difficulties sitting or practicing isometric yoga in a sitting position for long periods. To date, therapeutic interventions for patients with severe symptoms have not been established. Therefore, we developed a recumbent isometric yoga program, which takes approximately 20 min to complete, designed to reduce fatigue in patients with severe CFS/ME. The aim of this pilot study was to assess the feasibility, safety, and usefulness of this program. This pilot study included 12 adult patients with CFS/ME. Six patients were reluctant to practice isometric yoga in a sitting position because of the severity of their fatigue (group 1). The remaining six patients had previously practiced isometric yoga in a sitting position (group 2). For 3 months, the patients of both groups practiced recumbent isometric yoga every 2 to 4 weeks with a yoga instructor and at home on other days if they could. The short-term effects of isometric yoga on fatigue were assessed using the Profile of Mood Status (POMS) questionnaire immediately before and after their final session with the yoga instructor. The long-term effects of isometric yoga on fatigue were assessed using the Chalder Fatigue Scale (FS) questionnaire before and after the intervention period. Adverse events, satisfaction with the program, and preference of yoga position (sitting or recumbent) were also recorded. All subjects completed the intervention. In both groups, the POMS fatigue score was significantly decreased after practicing the 20-min yoga program and the Chalder FS score was decreased significantly after the 3-month intervention period. There were no serious adverse events. All subjects in group 2 preferred the recumbent isometric yoga program over a sitting yoga program. This study suggests that recumbent isometric yoga is a feasible and acceptable treatment for patients with CFS/ME, even for patients who experience difficulty practicing isometric yoga in the sitting position.


CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway.
The progression of cancer is accelerated by increased proliferation, angiogenesis, and inflammation. These processes are mediated by leukotrienes. Several cancer cell lines overexpress 5-lipoxygenase, an enzyme that converts arachidonic acid into leukotrienes. An early inhibitor of the 5-lipoxygenase pathway is Rev-5901, which, however, lacks in in vivo efficacy, as it is rapidly metabolized. We investigated the introduction of carboranes as highly hydrophobic and metabolically stable pharmacophores into lipoxygenase inhibitors. Carboranes are icosahedral boron clusters that are remarkably stable and used to increase the metabolic stability of unstable pharmaceutics without changing their biological activity. By introduction of meta-carborane into Rev-5901, the first carborane-based inhibitor of the 5-lipoxygenase pathway was obtained. We report the synthesis and inhibitory and cytotoxic behavior of these compounds toward several melanoma and colon cancer cell lines and their related anticancer mechanisms.


β blockers switched to first-line therapy in hypertension.
In their recent guidelines, the European Society of Hypertension upgraded β blockers, putting them on equal footing with thiazide diuretics, renin-angiotensin system blockers (eg, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and calcium channel blockers. The reason offered for upgrading β blockers was the observation that they are often used for many other clinical conditions commonly encountered with hypertension. This upgrade would allow for the treatment of two conditions with a single drug (a so-called twofer). In most current national and international hypertension guidelines, β blockers are only considered to be an alternative when there are specific indications. Compared with the other first-line antihypertensive drug classes, β blockers are significantly less effective in preventing stroke and cardiovascular mortality. To relegate β blockers to an inferiority status as previous guidelines have done was based on the evidence in aggregate, and still stands. No new evidence supports the switch of β blockers back to first-line therapy. We are concerned that this move might lead to widespread harm because of inferior stroke protection.


Therapeutic influence as a function of therapist attire and the seating arrangement in an initial interview.
Investigated the impact of therapist attire and seating arrangement on observers' perceptions of a therapist's attractiveness, expertise, and trustworthiness in an initial interview analogue. Each of 233 undergraduates listened to an audiotaped interview segment while viewing a synchronized slide presentation of a male therapist in one of four conditions cross-matched on attire formality (coat and tie vs. sports shirt) and seating arrangement (behind desk vs. no desk). Significant effects emerged for therapist attire, seating arrangement, and S gender. The casual attire/no desk setting elicited the highest attraction ratings, and the effects of the seating arrangement were mediated by the S gender. Females responded to the behind-desk arrangement with lower ratings of the therapist across all measures. Initial impressions, which were influenced by the therapist's attire and seating arrangement, were correlated highly with Ss' willingness to see this therapist for consultation.


The DcMaster Transposon Display maps polymorphic insertion sites in the carrot (Daucus carota L.) genome.
DcMaster is a family of PIF/Harbinger-like class II transposable elements identified in carrot. We present a modified Transposon Display molecular marker system allowing amplification of genomic regions containing DcMaster elements. We scored 77 DcMaster Transposon Display (DcMTD) amplicons, of which 54 (70%) were segregating in the F(2) progeny from the cross between wild and cultivated carrot. Segregating amplicons were incorporated into a previously developed molecular linkage map of carrot. Twenty-eight markers were attributed to the wild parent, 23 originated from the cultivated parent, and three markers remained unlinked. The markers were evenly distributed among the nine linkage groups. However, differences in the distribution pattern of DcMaster insertion sites in the genomes of the wild and cultivated parent were observed. Specificity of the obtained amplicons was confirmed by sequencing and three putative DcMaster subfamilies, differing in the sequence of their terminal inverted repeats, were revealed.


Genetic Mechanism Revealed of Age-Related Macular Degeneration Based on Fusion of Statistics and Machine Learning Method.
Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world which affects the quality of life for millions of elderly individuals worldwide. Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to AMD. To better understand the disease pathogenesis and identify causal genes for AMD, we applied random walk (RW) and support vector machine (SVM) to identify AMD-related genes based on gene interaction relationship and significance of genes. Our model achieved 0.927 of area under the curve (AUC), and 65 novel genes have been identified as AMD-related genes. To verify our results, a statistics method called summary data-based Mendelian randomization (SMR) has been implemented to integrate GWAS data and transcriptome data to verify AMD susceptibility-related genes. We found 45 genes are related to AMD by SMR. Among these genes, 37 genes overlap with those found by SVM-RW. Finally, we revealed the biological process of genetic mutations leading to changes in gene expression leading to AMD. Our results reveal the genetic pathogenic factors and related mechanisms of AMD.


FACTORS INFLUENCING UNINTENDED PREGNANCY AND ABORTION AMONG UNMARRIED YOUTH IN VIETNAM: A LITERATURE REVIEW.
Unintended pregnancy and abortion among unmarried youths arepublic health issues in Vietnam. This review aims to analyse factors influencing unintended pregnancy and abortion among unmarried youths using published and unpublished literatures. An ecological model was used as the conceptual framework with five levels of factors to guide the analysis. The intrapersonal factors include increasing permissive attitudes and practices of premarital sex, lack of knowledge on contraception, andlow self-efficacy among females. The interpersonal factors include poor communication among partners and between parents and youths on sexuality-related issues, and peer-influence. The organizational factors include inadequate sexuality education and sexual and reproductive health (SRH) services for youths. The contextual factors include gender inequality, cultural norms, and migration. The final level is lack of separate policy on youth SRH. The findings point out four major determinants of unintended pregnancy and abortion among unmarried youths, including: 1) cultural norms, which consider premarital sex is a taboo; 2) lack and inadequate quality of sexuality education in the schools; 3) lack of youth-friendly SRH services; and 4) no separate policy addressing youth SRH.


Self-aggregation of triadin in the sarcoplasmic reticulum of rabbit skeletal muscle.
The 95 kDa transmembrane glycoprotein triadin is believed to be an essential component of excitation-contraction coupling in the junctional sarcoplasmic reticulum of skeletal muscle fibers. It is debatable whether triadin mediates intraluminal interactions between calsequestrin and the ryanodine receptor exclusively or whether this junctional protein provides also a cytoplasmic linkage between the Ca2+-release channel and the dihydropyridine receptor. Here, we could show that native triadin exists as disulfide-linked homo-polymers of above 3000 kDa. Under non-reducing conditions, protein bands representing the alpha1-dihydropyridine receptor and calsequestrin did not show an immunodecorative overlap with the extremely high-molecular-mass triadin clusters. Following chemical crosslinking, the ryanodine receptor and triadin exhibited a similarly decreased electrophoretic mobility. However, immunoblotting of diagonal non-reducing/reducing two-dimensional gels clearly demonstrated a lack of overlap between the immunodecorated bands representing triadin, the alpha1-dihydropyridine receptor, the ryanodine receptor and calsequestrin. Thus, in native membranes triadin appears to form large self-aggregates primarily. Although triadin exists in a close neighborhood relationship to the Ca2+-release channel tetramers, it does not seem to be directly linked to the other main triad components implicated in the regulation of the excitation-contraction-relaxation cycle and Ca2+-homeostasis. This agrees with a proposed role of triadin in the maintenance of overall triad architecture.


Research in training clinics: a bridge between science and practice.
Clinics associated with psychology training programs have potential to generate important research data. The expectation that research be experimental in nature has limited the pursuit of research in training clinics. This type of efficacy study is not feasible in most clinics, where too much variation occurs as a result of training and administrative demands. Numerous process-outcome studies have been effectively conducted in training clinics. This article reviews some of these studies, identifies problems related to research in training clinics, and makes recommendations for the development of an enhanced research agenda for training clinics.


Perception of safety is a prerequisite for the association between neighbourhood green qualities and physical activity: Results from a cross-sectional study in Sweden.
In this study, we assess how the Scania Green Score (SGS5), and the five distinct perceived neighbourhood green dimensions within this area-aggregated index (1km2 squares), is associated with self-reported physical activity and general health, and if perceived safety and social coherence has a moderating effect. Two independent surveys, both conducted in Scania, Sweden, was used for data on SGS5 and health outcomes (N=28 198 and N=23 693), respectively. SGS5 was more clearly associated with physical activity (OR 1.06; 95% CI 1.02-1.10) than with general health (OR 1.02; 95% CI 1.00-1.04). This association was moderated by safety (p for interaction <0.001); SGS5 was positively associated with physical activity only among individuals who perceived high safety in their neighbourhood (OR 1.07; 95% CI 1.02-1.11). No moderating effect was seen for social coherence. Among specific dimensions, cultural history was positively associated with both physical activity and general health. Our results suggest that perception of safety is a prerequisite for the positive effects of neighbourhood green qualities.


[A case of severe involvement of the motor neuron system accompanied with cerebellar ataxia].
Here we report a sporadic case of severe involvement of the motor neuron system accompanied with cerebellar ataxia. A 55-year-old Japanese woman was admitted to our hospital because of unstable gait and clumsiness of hands. Since she had prominent ataxia, she was initially diagnosed as late onset cortical cerebellar atrophy (LCCA). However, mild muscular weakness and atrophy were pointed out. Weakness in extremities progressed slowly and she became unable to walk in two years. On the second admission, in addition to cerebellar ataxia, she had moderate to severe muscular weakness and atrophy with fasciculation in extremities. Although she had no sensory impairment, micturitional disturbance nor orthostatic hypotension, she had impaired skin sweating response. MRI imaging revealed moderate cerebellar and brain stem atrophy. Neurophysiological examination revealed upper and lower motor neuron damage. Beta-D-N acetylglucosaminidase activity was normal and SCA1, DRPLA and Machado-Joseph disease were excluded by DNA studies. Combination of motor neuron disease and cerebellar degeneration has been very rare. Only two cases similar to our case were reported before. Our patient had anti GM1-ganglioside antibody in her serum, suggesting that motor neuron disease and cerebellar degeneration may occur with the same pathophysiological mechanism.


CT in spontaneous adrenal gland rupture. A case report.
To report on an exceptional case of spontaneous, idiopathic, unilateral adrenal gland rupture that caused massive retroperitoneal hemorrhage. US and CT were performed in a patient who presented with acute abdominal pain. Urgent adrenalectomy was required to prevent the blood loss from continuing. The CT findings were correlated with the histological findings. CT proved to be an accurate imaging modality by which to diagnose adrenal hemorrhage. The absence of irregular tissue enhancement showed that neoplasia was not the underlying cause of the hematoma.


Prenatal fasudil exposure alleviates fetal growth but programs hyperphagia and overweight in the adult male rat.
Numerous data indicate that Rho kinase inhibitors, such as Fasudil, may constitute a novel therapy for cardiovascular and metabolic diseases. We evaluated long-term effects of exposure to Fasudil during late gestation (10 mg/day) in male rat offspring from birth until 9 months. We also analyzed its effects in offspring from hypertensive mothers treated with a nitric oxide synthesis inhibitor (L-NAME; 50 mg/day). Prenatal exposure to Fasudil did not affect birth weight, but increased body weight from postnatal day 7 (P7) to 9 months. In intrauterine growth-restricted (IUGR) fetuses exposed to L-NAME, maternal Fasudil treatment increased birth weight. At P42 and P180, rats exposed to Fasudil and L-NAME showed alterations of their food intake as well as an increased basal glycemia associated with mild glucose intolerance at 6 months which was also observed in Fasudil-exposed rats. In 9 month-old rats, exposure to Fasudil increased the daily food intake as well as hypothalamic mRNA level of the orexigenic NPY peptide without modulation of the anorexigenic POMC gene expression. Altogether, our data suggest that prenatal Fasudil exposure alleviates fetal growth in IUGR rats, but programs long-term metabolic disturbances including transient perturbations of glucose metabolism, a persistent increase of body weight gain, hyperphagia and an augmented expression of hypothalamic NPY orexigenic gene. We postulate that Fasudil treatment during perinatal periods may predispose individuals to the development of metabolic disorders.


Intracranial bleeding in haemophilia beyond the neonatal period--the role of CT imaging in suspected intracranial bleeding.
We conducted a review of a single institutional experience of patients with haemophilia presenting with suspected intracranial haemorrhage (ICH) who underwent computed tomographic (CT) neuro-imaging. We found that over a 9-year period (1996-2004) 43 patients with haemophilia presented 73 times with suspected ICH: 10 presented multiple times (range: 2-9 times). The median age at presentation was 3.5 years (range: 0.5-17). Preceding trauma occurred in most (62/73; 85%) episodes. ICH was confirmed in 11 of the 73 (16%) episodes in eight patients. Patients with severe haemophilia accounted for a disproportionate number of episodes of suspected (60/73; 82%) and of confirmed ICH (10/11; 91%). All ICH occurred in patients not on prophylaxis; five occurred in three inhibitor-positive patients. Altered consciousness at presentation was present in 10/11 (91%) cases of confirmed ICH but only in 5/62 (8%) (ICH-negative) episodes. The positive and negative predictive values of altered consciousness to predict/rule out an ICH was 67% and 98%, respectively. The following were associated with an increased risk of presenting with suspected ICH and of having a confirmed ICH: (i) having severe haemophilia; (ii) not being on prophylaxis; (iii) having an inhibitor; and (iv) presenting with an altered level of consciousness. Patients without any of these features may not need to undergo CT imaging when presenting with suspected ICH. Ideally a prospective study to evaluate this hypothesis should be conducted.


Incidence and Prevalence of Diagnosed Vitiligo According to Race and Ethnicity, Age, and Sex in the US.
Vitiligo has substantial psychosocial consequences. Yet its burden is poorly established. To estimate incidence and prevalence of diagnosed vitiligo across age, sex, and racial and ethnic subgroups in the US. This analysis comprising a cohort study and cross-sectional study included electronic health records for health care-seeking children, adolescents, and adults across 4 US census regions. Data for the incidence analysis were obtained from January 1, 2015, through December 31, 2019, and data for the prevalence analysis were obtained from January 1 through December 31, 2019. Data were analyzed from December 13, 2022, to June 8, 2023. The main outcomes were incidence (per 100 000 person-years [PY]) and prevalence of diagnosed vitiligo overall and by age, race and ethnicity, and sex. A total of 2 980 778 patients with vitiligo were included in the incidence analysis (mean [SD] age, 41.5 [24.0] years; 57.0% female; 1.4% Asian American; 12.9% Black; 1.5% Hispanic/Latino; 77.3% White; 6.9% other or multiracial) and 1 057 534 in the prevalence analysis (mean [SD] age, 43.4 [24.7] years; 57.5% female; 1.7% Asian American, 14.7% Black, 1.4% Hispanic/Latino; 75.7% White; 6.6% other or multiracial). Age- and sex-adjusted overall incidence rate (IR) of diagnosed vitiligo was 22.6 per 100 000 PY (95% CI, 21.5-23.8 per 100 000 PY), and prevalence was 0.16% (95% CI, 0.15%-0.17%). Sex-adjusted IR was highest among patients aged 60 to 69 years (25.3 per 100 000 PY; 95% CI, 22.2-28.6 per 100 000 PY), and prevalence was highest among patients aged 70 years or older (0.21%; 95% CI, 0.19%-0.23%). The highest age-adjusted IR was observed among Asian American patients (41.2 per 100 000 PY; 95% CI, 28.2-58.2 per 100 000 PY), followed by Hispanic/Latino patients (37.3 per 100 000 PY; 95% CI, 25.7-52.4 per 100 000 PY), patients reporting other or multiple races (31.1 per 100 000 PY; 95% CI, 25.9-37.1 per 100 000 PY), Black patients (29.6 per 100 000 PY; 95% CI, 26.0-33.6 per 100 000 PY), and White patients (18.7 per 100 000 PY; 95% CI, 17.5-20.0 per 100 000 PY). The highest age-adjusted prevalence was observed among Hispanic/Latino patients (0.29%; 95% CI, 0.20%-0.39%), followed by Asian American patients (0.27%; 95% CI, 0.19%-0.35%), patients reporting other or multiple races (0.24%; 95% CI, 0.20%-0.28%), Black patients (0.22%; 95% CI, 0.19%-0.24%), and White patients (0.13%; 95% CI, 0.12%-0.14%). This cross-sectional study found that vitiligo diagnosis was more common in older patients, Hispanic/Latino patients, and Asian American patients.


Using Health Education to Address Student Physical Activity and Nutrition: Evidence and Implications to Advance Practice.
School-based health education can provide students with learning experiences that improve knowledge, attitudes, and perceptions (KAP) and behaviors regarding physical activity and nutrition. We conducted a 2-phase systematic review. Phase 1 was a review of reviews (ie, systematic reviews or meta-analyses) that were published 2010-2018. Phase 2 was a search for individual articles published 2010-2020 addressing topics relevant to our review; we searched for articles that had not been part of a sufficiently relevant or recent review or that had been part of a review that concluded that too few articles were available to assert sufficient evidence. Forty-three studies were assessed: 20 randomized controlled trials and 23 quasi-experimental designs. Collectively, interventions had a favorable impact on students' PA and nutrition KAP, but behavioral and secondary outcome results (eg, body mass index) were mixed. Using the evidence-based health education strategies identified in this review can help contribute to improvements in students' KAP and behaviors.


[Sports as therapy].
Over the last 2 decades the clinical application of physical exercise as a therapeutic strategy has developed from rehabilitation to prevention and treatment of cardiovascular diseases. This shift in clinical application was accompanied by a more systematic research approach of the involved mechanisms and the objective clinical assessment of sport interventions using prospective randomized clinical trials. This ongoing process established physical exercise as an evidence-based and guideline-oriented treatment option. In stable coronary artery disease (CAD), exercise therapy has long been used for rehabilitation purposes following an acute myocardial infarction. A recent meta-analysis revealed a significant 27% reduction of total mortality among training patients. Four mechanisms are considered important mediators of the reduced cardiac event rate: improvement of endothelial function, reduced progression of coronary lesions, reduced thrombogenic risk, and improved collateralization. The therapeutic benefit of regular physical exercise has also been confirmed in direct comparison with an interventional strategy: a 12-month exercise therapy in stable CAD patients was associated with a higher event-free survival as compared to conventional percutaneous coronary intervention. In stable chronic heart failure (CHF), physical activity was traditionally discouraged-with negative consequences for the patients: exercise intolerance worsened, the progression of disease-related muscular atrophy accelerated. A carefully designed exercise program at 50-70% of the maximal oxygen uptake was effective in improving exercise capacity by 12-32%. In a recent meta-analysis, exercise therapy reduced the relative risk of CHF mortality by 35% and CHF-related hospitalizations by 28%. Considering the growing body of evidence in favor of sport as a therapy, training interventions should be considered additional/alternative therapeutic strategies as compared with established pharmacological/interventional options.


A new technique for cranial bone osteofixation: use of bioabsorbable tacks and plates to fix parietal bone split grafts used for reconstruction of a posttraumatic frontal bone defect.
Recent advances in bioabsorbable devices have introduced tacks that do not require tapping. This may help to reduce operative time and, consequently, costs. The goal of this study was to demonstrate the feasibility of a new method of cranial bone osteofixation using novel bioabsorbable tacks and plates instead of screws. A 36-year-old man presented for elective cranioplasty to reconstruct a large frontal cranial bone defect that followed a decompression operation performed because of a head injury sustained 6 months previously. Cranioplasty was performed using split parietal bone grafts to reconstruct the defect. Bone grafts were fixed together and to the skull using self-reinforced (SR) poly(L/DL)lactide [SR-poly(L/DL)lactide] (70/30) (Biosorb FX) plates (n = 10) and tacks (n = 98). The plates were 0.6 mm thick, 102 mm long, and 12 mm wide. The tacks had a maximum thread diameter of 2 mm and a length of 6 mm. The tacks used did not require any tapping procedure, and they were applied using a special applicator gun. Stable and secure fixation was obtained during surgery. The postoperative period was uneventful, except for delayed epithelialization of a small area (1 x 0.5 cm) over the frontal skin that healed later. One year after surgery, the cosmetic result was excellent, and no complications were detected. Stabilization of large cranial bone pieces can be achieved using bioabsorbable SR-poly(L/DL)lactide plates and tacks, with excellent cosmetic results. The method is thought to be reliable and may help to reduce operative time.


Evaluation of CAAX prenyl protease II of Leishmania donovani as potential drug target: Infectivity and growth of the parasite is significantly lowered after the gene knockout.
Prenylation pathway is responsible for post translational modification of various signal proteins, including proteins of Ras superfamily. CAAX prenyl proteases are known to be key players in prenylation pathway. In the current study, we have evaluated CAAX prenyl protease II as a possible drug target against Leishmania donovani parasite, the causative agent of visceral leishmaniasis. Gene knockout strategy was employed to target CAAX prenyl protease II and subsequent effects were studied. CAAX prenyl protease II knockout resulted in significant decrease in growth and infectivity.


Parameters guiding selection of best embryos for transfer after cryopreservation: a reappraisal.
The purpose of this study was to evaluate the respective influences of blastomere survival and resumption of mitosis on the outcome of frozen-thawed embryos. A retrospective analysis was performed in our centre on 363 thawing cycles, involving 4-cell day 2 grade 1 embryos with <10% fragmentation. A higher implantation rate per transferred embryo was observed when all transferred embryos were characterized by fully intact blastomeres (100% blastomere survival) as compared with damaged embryos (50 or 75% blastomere survival) (22.0 versus 7.2%; P < 0.0001). Moreover, the implantation rate per transferred embryo was significantly higher for cleaved embryos compared with uncleaved embryos (19.7 versus 3%; P < 0.0001). Transfer of fully intact, cleaved embryos resulted in the highest implantation rates compared with transfer of damaged and uncleaved embryos (27.4 versus 0%; P < 0.0001). Intermediate implantation rates were observed when only one of the two criteria was fulfilled (13 versus 11% respectively; P > 0.05). Multivariate analysis showed that the clinical pregnancy rate was influenced by both criteria (odds ratio = 3.4 for transfer of embryos with six or more cells versus embryos with less than six cells. The results of our study suggest that the most important factor to predict further embryo development is the total number of blastomeres in transferred embryos, however they are obtained (good survival and/or resumption of mitosis).


Attitudes Toward Juvenile Sex Offender Legislation: The Influence of Case-Specific Information.
This study examined attitudes toward the application of adult sex offender legislation to juvenile sex offenders. Participants were randomly assigned to one of nine conditions. In the generic condition, the participants were asked to envision a generic juvenile sex offender, whereas in the manipulated conditions, participants read a vignette with three manipulated variables: offense type, victim age, and victim gender. Afterward, all participants (n = 978) completed questionnaires assessing perceptions of juvenile sex offenders and juvenile sex offender legislation. Overall, participants in the generic juvenile sex offender condition rated the perpetrator as more dangerous and more likely to reoffend than participants in the experimental conditions. Moreover, participants in the generic juvenile sex offender condition were more likely to endorse more punitive punishments and viewed perpetrators as "superpredators." When examining differences between the experimental conditions, participants reading vignettes with younger victims and male victims as well as vignettes with contact offenses were more likely to view the perpetrator as dangerous, likely to recidivate, as a "superpredator," and deserving of more punitive punishments. Implications for public policy as well as future research directions are discussed.


SGLT inhibitors for improving Healthspan and lifespan.
Sodium-glucose cotransporter inhibitor/inhibition (SGLTi), initially approved as a glucose-lowering therapy for type 2 diabetes, is associated with decreased risks for many of the most common conditions of aging, including heart failure, chronic kidney disease, all-cause hospitalization, atrial fibrillation, cancer, gout, emphysema, neurodegenerative disease/dementia, emphysema, non-alcoholic fatty liver disease, atherosclerotic disease, and infections. Studies also show that SGLTi improves overall life expectancy and reduces risks of cardiovascular death and cancer death. These wide-ranging health benefits are largely unexplained by the SGLTi's modest improvements in standard risk factors. SGLTi produces upregulation of nutrient deprivation signaling and downregulation of nutrient surplus signaling. This in turn promotes autophagy, which helps to optimize cellular integrity and prevent apoptotic cell death. SGLTi decreases oxidative stress and endoplasmic reticulum stress, restores of mitochondrial health, stimulates mitochondrial biogenesis, and diminishes proinflammatory and profibrotic pathways. These actions help to revitalize senescent cells, tissues, and organs. In summary, SGLTi appears to slow aging, prevent disease, and improve life expectancy, and its mechanisms of action lend strong biological plausibility to this hypothesis. Further randomized trials are warranted to test whether SGLTi, a safe and well-tolerated, once-daily pill, might improve healthspan and lifespan.


Development of an Artificial Intelligence-Based Support Technology for Urethral and Ureteral Stricture Surgery.
This paper proposes a technological system that uses artificial intelligence to recognize and guide the operator to the exact stenosis area during endoscopic surgery in patients with urethral or ureteral strictures. The aim of this technological solution was to increase surgical efficiency. The proposed system utilizes the ResNet-50 algorithm, an artificial intelligence technology, and analyzes images entering the endoscope during surgery to detect the stenosis location accurately and provide intraoperative clinical assistance. The ResNet-50 algorithm was chosen to facilitate accurate detection of the stenosis site. The high recognition accuracy of the system was confirmed by an average final sensitivity value of 0.96. Since sensitivity is a measure of the probability of a true-positive test, this finding confirms that the system provided accurate guidance to the stenosis area when used for support in actual surgery. The proposed method supports surgery for patients with urethral or ureteral strictures by applying the ResNet-50 algorithm. The system analyzes images entering the endoscope during surgery and accurately detects stenosis, thereby assisting in surgery. In future research, we intend to provide both conservative and flexible boundaries of the strictures.


Comparative physiological and soil microbial community structural analysis revealed that selenium alleviates cadmium stress in Perilla frutescens.
Cadmium (Cd) toxicity not only affects plant growth and development, but also affects human health through the food chain. Several studies have demonstrated that Selenium (Se) alleviates Cd stress in plants; however, whether and how Se-alleviated Cd stress by regulating the structure of soil microbial community remain largely unclear. Here, we investigated the alleviating effects of exogenous applied Se (foliar spraying or root application) on plant growth under Cd stress in perilla (Perilla frutescens L.) by measuring the biomass, photosynthetic fluorescence parameters, root cell wall components and soil microbial community structure and diversity. Under Cd stress, perilla seedlings supplemented with Se increased chlorophyll content. Foliar spraying Se increased the levels of relative chlorophyll content (ΦII), photosynthetic system II (ΦPSII) and electron transport rate (ETR) in perilla leaves under Cd stress; while, root application of Se increased the levels of photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), water use efficiency (WUE) and stomatal limitation value (Ls) under Cd stress. Compared with Cd toxicity alone, root application of Se increased the contents of hemicellulosic 1 and hemicellulosic 2 in the cell wall of perilla roots. Cd toxicity or root application of Se did not affect soil bacterial community diversity. Root application of Se increased the relative abundance of Proteobacteria, Bacteroidetes, Fibrobacteres, Sphingomonas and Nitrosospira in Cd-contaminated soil, and thereby improving soil microbial community structure, finally promoting the growth of perilla seedlings.


Staff Perspectives of Barriers to Access and Delivery of Palliative Care for Persons With Dementia in Long-Term Care.
Dementia is a syndrome that is progressive, degenerative, and terminal. The palliative care philosophy aims to maximize quality of life for the dying individual and is both beneficial for and underused with persons dying with dementia. The purpose of this study was to investigate the experiences of long-term care staff delivering palliative care to individuals with dementia to determine how care was delivered, to learn which guidelines were used, and whether policies affected the delivery of palliative care. Twenty-two staff participants were interviewed. Their experiences were interpreted using phenomenological methodology. Findings yielded 3 key themes: confusion, resource shortages, and communication difficulties. Implications for practice include clarification of terminology surrounding palliative care, education of families about dementia and palliative care, better resource management, and the need to address when palliative care best fits within the dementia process.


Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies.
The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1-10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%.


Hydrogen sulfide inhibits plasma renin activity.
The development of renovascular hypertension depends on the release of renin from the juxtaglomerular (JG) cells, a process regulated by intracellular cAMP. Hydrogen sulfide (H2S) downregulates cAMP production in some cell types by inhibiting adenylyl cyclase, suggesting the possibility that it may modulate renin release. Here, we investigated the effect of H2S on plasma renin activity and BP in rat models of renovascular hypertension. In the two-kidney-one-clip (2K1C) model of renovascular hypertension, the H2S donor NaHS prevented and treated hypertension. Compared with vehicle, NaHS significantly attenuated the elevation in plasma renin activity and angiotensin II levels but did not affect plasma angiotensin-converting enzyme activity. Furthermore, NaHS inhibited the upregulation of renin mRNA and protein levels in the clipped kidneys of 2K1C rats. In primary cultures of renin-rich kidney cells, NaHS markedly suppressed forskolin-stimulated renin activity in the medium and the intracellular increase in cAMP. In contrast, NaHS did not affect BP or plasma renin activity in normal or one-kidney-one-clip (1K1C) rats, both of which had normal plasma renin activity. In conclusion, these results demonstrate that H2S may inhibit renin activity by decreasing the synthesis and release of renin, suggesting its potential therapeutic value for renovascular hypertension.


Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort.
The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up. The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244-566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80-6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05-3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43-20.39). Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five-year mortality.


Connectivity and variability of related cognitive subregions lead to different stages of progression toward Alzheimer's disease.
Single modality MRI data is not enough to depict and discern the cause of the underlying brain pathology of Alzheimer's disease (AD). Most existing studies do not perform well with multi-group classification. To reveal the structural, functional connectivity and functional topological relationships among different stages of mild cognitive impairment (MCI) and AD, a novel method was proposed in this paper for the analysis of regional importance with an improved deep learning model. Obvious drift of related cognitive regions can be observed in the prefrontal lobe and surrounding the cingulate area in the right hemisphere when comparing AD and healthy controls (HC) based on absolute weights in the classification mode. Alterations of these regions being responsible for cognitive impairment have been previously reported. Different parcellation atlases of the human cerebral cortex were compared, and the fine-grained multimodal parcellation HCPMMP performed the best with 180 cortical areas per hemisphere. In multi-group classification, the highest accuracy achieved was 96.86% with the utilization of structural and functional topological modalities as input to the training model. Weights in the trained model with perfect discriminating ability quantify the importance of each cortical region. This is the first time such a phenomenon is discovered and weights in cortical areas are precisely described in AD and its prodromal stages to the best of our knowledge. Our findings can establish other study models to differentiate the patterns in various diseases with cognitive impairments and help to identify the underlying pathology.


Improved BM3D image denoising using SSIM-optimized Wiener filter.
Image denoising is considered a salient pre-processing step in sophisticated imaging applications. Over the decades, numerous studies have been conducted in denoising. Recently proposed Block matching and 3D (BM3D) filtering added a new dimension to the study of denoising. BM3D is the current state-of-the-art of denoising and is capable of achieving better denoising as compared to any other existing method. However, there is room to improve BM3D to achieve high-quality denoising. In this study, to improve BM3D, we first attempted to improve the Wiener filter (the core of BM3D) by maximizing the structural similarity (SSIM) between the true and the estimated image, instead of minimizing the mean square error (MSE) between them. Moreover, for the DC-only BM3D profile, we introduced a 3D zigzag thresholding. Experimental results demonstrate that regardless of the type of the image, our proposed method achieves better denoising performance than that of BM3D.


Effect of Saturation Pressure Difference on Metal-Silicide Nanopowder Formation in Thermal Plasma Fabrication.
A computational investigation using a unique model and a solution algorithm was conducted, changing only the saturation pressure of one material artificially during nanopowder formation in thermal plasma fabrication, to highlight the effects of the saturation pressure difference between a metal and silicon. The model can not only express any profile of particle size-composition distribution for a metal-silicide nanopowder even with widely ranging sizes from sub-nanometers to a few hundred nanometers, but it can also simulate the entire growth process involving binary homogeneous nucleation, binary heterogeneous co-condensation, and coagulation among nanoparticles with different compositions. Greater differences in saturation pressures cause a greater time lag for co-condensation of two material vapors during the collective growth of the metal-silicide nanopowder. The greater time lag for co-condensation results in a wider range of composition of the mature nanopowder.


The use of social media and online communications in times of pandemic COVID-19.
The use of social media as a tool for professional communication and education in healthcare has been increasing; pros and cons of such platforms were extensively debated in recent years with mixed results. During the COVID-19 pandemic, social media use has accelerated to the point of becoming a ubiquitous part of modern healthcare systems. As with any tool in healthcare, its risks and benefits need to be carefully considered. In this article, we review the use of social media in the current pandemic. Importantly, we will illustrate this using experiences from the perspective of large medical organisations and also identify the common pitfalls.


Hypothalamic and liver transcriptome from two crucial life-history stages in a migratory songbird.
What is the central question of this study? What are the molecular underpinnings of the seasonal adaptation in a latitudinal migratory songbird? What is the main finding and its importance? We found changes in mRNA levels after a photoperiod-induced alteration of seasonal state in a captive long-distance latitudinal avian migrant. The hypothalamus and liver transcriptomes revealed genes involved in the regulatory and functional pathways between non-migratory and migratory states. Our results provide insights into mechanisms underlying homeostasis during seasonal changes that are conserved across most species, including humans. Very little is understood about genetic mechanisms underlying the onset of spring migration in latitudinal avian migrants. To gain insight into the genetic architecture of the hypothalamus and liver tissues of a long-distance migrant, we examined and compared the transcriptome profile of captive night-migratory black-headed buntings (Emberiza melanocephala) between photoperiod-induced winter non-migratory (WnM) and spring migratory (SM) life-history states under short and long days, respectively. High-throughput 454 pyrosequenced transcripts were mapped initially with reference to the genome of two phylogenetically close species, Taeniopygia guttata and Ficedula albicollis. The F. albicollis genome gave higher annotation results and was used for further analysis. A total of 216 (78 in hypothalamus; 138 in liver) genes were found to be expressed differentially between the WnM and SM life-history states. These genes were enriched for physiological pathways that might be involved in the regulation of seasonal migrations in birds. For example, genes for the ATP binding pathway in the hypothalamus were expressed at a significantly higher level in SM than in the WnM life-history state. Likewise, upregulated genes associated with the myelin sheath and focal adhesion were enriched in the hypothalamus, and those with cell-to-cell junction, intracellular protein transport, calcium ion transport and small GTPase-mediated signal transduction were enriched in the liver. Many of these genes are a part of physiological pathways potentially involved in the regulation of seasonal migration in birds. These results show molecular changes at the regulatory and metabolic levels associated with seasonal transitions in a long-distance migrant and provide the basis for future studies aimed at unravelling the genetic control of migration in birds.


From organelle to protein gel: a 6-wk laboratory project on flagellar proteins.
Research suggests that undergraduate students learn more from lab experiences that involve longer-term projects. We have developed a one-semester laboratory sequence aimed at sophomore-level undergraduates. In designing this curriculum, we focused on several educational objectives: 1) giving students a feel for the scientific research process, 2) introducing them to commonly used lab techniques, and 3) building skills in both data analysis and scientific writing. Over the course of the semester, students carry out two project-based lab experiences and write two substantial lab reports modeled on primary literature. Student assessment data indicate that this lab curriculum achieved these objectives. This article describes the first of these projects, which uses the biflagellate alga Chlamydomonas reinhardtii to introduce students to the study of flagellar motility, protein synthesis, microtubule polymerization, organelle assembly, and protein isolation and characterization.


Changes in lung volume and (PAO2-PaO2) during anaesthesia.
The theory, that the decrease in lung volume which occurs after induction of general anaesthesia is the cause of the higher (PAO2-PaO2) during anaesthesia, was examined in 18 patients. Lung volume was increased during anaesthesia by changing the posture of the patient to 30 degrees head-up, but there was no improvement in (PAO2-PaO2). There were no correlations between change in (PAO2-PaO2) and in cardiac output between different postures. It is concluded that gas exchange is independent of change in lung volume during anaesthesia, at least over the range examined. It remains possible that restoration of lung volume to pre-anaesthetic values may not restore regional distribution of ventilation to pre-anaesthetic values.


Drug distribution and clinical safety in treating cystic craniopharyngiomas using intracavitary radiotherapy with phosphorus-32 colloid.
The present study evaluated drug distribution and clinical safety in treating patients with cystic craniopharyngioma (CP) with intracavitary radiotherapy using phosphorus-32 (32P) colloid. In total, 40 patients who were recently diagnosed with primary or recurrent cystic CP were enrolled into the study. Patients underwent stereotactic intracavitary therapy and were administered 32P colloid and iopamidol-300 (1:1 dilution). Head computed tomography (CT) scans were performed 2 h after surgery in order to assess drug distribution and leakage. Results obtained from the ophthalmic examination (visual acuity, visual field and fundus), enhanced head magnetic resonance imaging and/or CT scans, blood analysis, coagulation tests, electrolyte tests, pituitary hormone level analysis, and hepatic and renal function tests were compared between the 0.5, 1, 1.5 and 2 mCi groups. The 32P colloid per minute radioactive count was quantitatively measured in urine and blood samples using a CAPRAC well-type NaI γ counter at 1, 3 and 7 days post-surgery. In total, 6, 2 and 1 case(s) from the 2, 1.5 and 1 mCi groups, respectively, demonstrated heterogeneous drug distribution and intracavitary cerebrospinal fluid leakage. Furthermore, out of 24 patients, no significant differences were identified in blood analysis, blood biochemical measurements and pituitary hormone levels prior to and 7 days after surgery. Blood 32P deposition returned to normal levels within 3 days after surgery, whereas urine deposition returned to normal within 7 days after surgery. Methods utilized in the present study were advantageous in terms of convenience, speed and low cost, therefore, these techniques are suitable for continuous monitoring of patient 32P colloid deposition.


Phototunable surface interactions.
Photoresponsive polymer brushes constitute an attractive platform for tuning surface properties and functionality. Since the degree of photoconversion can be controlled by the light dose, functional states with intermediate properties between those of the nonexposed and fully exposed brushes are accessible. Here we investigate the light-modulated interfacial, adhesion, and frictional properties of photosensitive polymer brushes with a methacrylate backbone and ionizable -COOH side groups modified with the photoremovable group 6-nitroveratryloxycarbonyl (NVOC). The original brush (PNVOCMA) gradually changes into a charged poly(methacrylic acid) (PMAA) brush upon exposure to ultraviolet light due to the photoremoval of the chromophore and generation of free COOH groups. We show how the physical properties of the brush can be gradually tuned with the exposure dose using condensation microscopy, atomic force microscopy (AFM), force mapping, and friction force spectroscopy.


L-histidine inhibits the heat-induced gelation of actomyosin in a low ionic strength solution.
The heat-induced gelation of actomyosin plays a key role in meat processing. Our previous study showed that L-histidine could affect the characteristics of a heat-induced gel of myosin on a low ionic strength. To apply the specific effect of L-histidine to meat processing, the heat-induced gel properties of actomyosin in the presence of L-histidine were investigated. Actomyosin in a low ionic strength solution containing L-histidine did not form a gel upon heating. The dynamic rheological properties of actomyosin in low ionic strength solutions were distinct depending on the presence or absence of L-histidine. Electron microscopy showed that, heated at 50°C, actomyosin in a low ionic strength solution containing L-histidine remained a filamentous structure. The surface hydrophobicity of actomyosin was stable up to 50°C in a low ionic strength solution containing L-histidine. In conclusion, L-histidine might suppress the aggregation of actomyosin and inhibit heat-induced gelation in a low ionic strength solution.


The reconstruction of bilateral clefts using endosseous implants after bone grafting.
This article presents the orthodontic reconstruction of an adult bilateral cleft patient with a severe Class III malocclusion in which endosseous implants were inserted after secondary alveolar bone grafting. The patient was a 21-year-old Japanese male whose lateral incisors were congenitally missing and whose premaxilla was inclined lingually. The occlusion was classified as Angle Class III with an overjet of -8 mm. Orthodontic alignment was initiated to correct the position of the maxillary incisors before bone grafting. After the anterior occlusal relationship was corrected, bilateral alveolar clefts were reconstructed by bone grafting with autogenous particulate marrow and cancellous bone harvested from the iliac crest. ITI-SLA fixtures (Institute Straumann, Waldenburg, Switzerland) (length, 10 mm; diameter, 4.1 mm) were placed into the grafted bone for prosthetic restoration of the missing lateral incisors. The results illustrate that this protocol can be expected to provide an acceptable occlusion and good dentoalveolar stability in adult cleft patients.


Trochoidal Milling and Neural Networks Simulation of Magnesium Alloys.
This paper set out to investigate the effect of cutting speed vc and trochoidal step str modification on selected machinability parameters (the cutting force components and vibration). In addition, for a more detailed analysis, selected surface roughness parameters were investigated. The research was carried out for two grades of magnesium alloys-AZ91D and AZ31-and aimed to determine stable machining parameters and to investigate the dynamics of the milling process, i.e., the resulting change in the cutting force components and in vibration. The tests were performed for the specified range of cutting parameters: vc = 400-1200 m/min and str = 5-30%. The results demonstrate a significant effect of cutting data modification on the parameter under scrutiny-the increase in vc resulted in the reduction of the cutting force components and the displacement and level of vibration recorded in tests. Selected cutting parameters were modelled by means of Statistica Artificial Neural Networks (Radial Basis Function and Multilayered Perceptron), which, furthermore, confirmed the suitability of neural networks as a tool for prediction of the cutting force and vibration in milling of magnesium alloys.


Al-alkyls as acceptor dopant precursors for atomic-scale devices.
Atomically precise ultradoping of silicon is possible with atomic resists, area-selective surface chemistry, and a limited set of hydride and halide precursor molecules, in a process known as atomic precision advanced manufacturing (APAM). It is desirable to expand this set of precursors to include dopants with organic functional groups and here we consider aluminium alkyls, to expand the applicability of APAM. We explore the impurity content and selectivity that results from using trimethyl aluminium and triethyl aluminium precursors on Si(001) to ultradope with aluminium through a hydrogen mask. Comparison of the methylated and ethylated precursors helps us understand the impact of hydrocarbon ligand selection on incorporation surface chemistry. Combining scanning tunneling microscopy and density functional theory calculations, we assess the limitations of both classes of precursor and extract general principles relevant to each.


A conserved pathway that controls c-Myc protein stability through opposing phosphorylation events occurs in yeast.
The c-Myc transcription factor is a key regulator of cell proliferation and cell fate decisions. c-Myc overexpression is observed in a variety of human tumors, revealing the importance of maintaining normal levels of c-Myc protein. c-Myc protein stability in mammalian cells is controlled by interdependent and sequential phosphorylation and dephosphorylation events on two highly conserved residues, serine 62 and threonine 58. Here we show that these sequential phosphorylation and dephosphorylation events and their effect on c-Myc stability also occurs in the model system Saccharomyces cerevisiae. These results suggest the presence of a conserved pathway in yeast that controls protein turnover in response to a specific phospho-degron sequence. These findings have implications regarding conserved pathways for regulated protein degradation, and they validate the use of genetically tractable yeast for the study of the turnover of proteins such as c-Myc that contain this motif.


The role of endothelial autocrine NRG1/ERBB4 signaling in cardiac remodeling.
Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (ECs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of erythroblastic leukemia viral oncogene homolog (ERBB)4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Here, we hypothesize that NRG1 autocrine signaling plays a role in cardiac remodeling. We generated EC-specific Erbb4 knockout mice to eliminate endothelial autocrine ERBB4 signaling without affecting paracrine NRG1/ERBB4 signaling in the heart. We first observed no basal cardiac phenotype in these mice up to 32 wk. We next studied these mice following transverse aortic constriction (TAC), exposure to angiotensin II (ANG II), or myocardial infarction in terms of cardiac performance, myocardial hypertrophy, myocardial fibrosis, and capillary density. In general, no major differences between EC-specific Erbb4 knockout mice and control littermates were observed. However, 8 wk following TAC both myocardial hypertrophy and fibrosis were attenuated by EC-specific Erbb4 deletion, albeit these responses were normalized after 20 wk. Similarly, 4 wk after ANG II treatment, myocardial fibrosis was less pronounced compared with control littermates. These observations were supported by RNA-sequencing experiments on cultured endothelial cells showing that NRG1 controls the expression of various hypertrophic and fibrotic pathways. Overall, this study shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling. This study contributes to understanding the spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury.NEW & NOTEWORTHY The role of NRG1/ERBB signaling in endothelial cells is not completely understood. Our study contributes to the understanding of spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury and shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling.


[Follicular lichenoid generalized granuloma annulare].
A follicular lichenoid generalized granuloma anulare in a 63 years old man with diabetes mellitus and sarcoidosis ( Mentoux -negative) is described. The histopathology revealed granuloma anulare localized around the hair follicles and the eccrine sweat gland ducts.


Social networks in cardiovascular disease management.
Cardiovascular disease remains the leading cause of death in the USA. Social networks have a positive association with obesity, smoking cessation and weight loss. This article summarizes studies evaluating the impact of social networks on the management of cardiovascular disease. The 35 studies included in the article describe the impact of social networks on a decreased incidence of cardiovascular disease, depression and mortality. In addition, having a large-sized social network is also associated with better outcomes and improved health. The role of pharmacists is beginning to play an important role in the patient-centered medical home, which needs to be incorporated into social networks. The patient-centered medical home can serve as an adaptive source for social network evolvement.


Test-potentiated learning: three independent replications, a disconfirmed hypothesis, and an unexpected boundary condition.
Arnold and McDermott [(2013). Test-potentiated learning: Distinguishing between direct and indirect effects of testing. Journal of Experimental Psychology: Learning, Memory, and Cognition, 39, 940-945] isolated the indirect effects of testing and concluded that encoding is enhanced to a greater extent following more versus fewer practice tests, referred to as test-potentiated learning. The current research provided further evidence for test-potentiated learning and evaluated the covert retrieval hypothesis as an alternative explanation for the observed effect. Learners initially studied foreign language word pairs and then completed either one or five practice tests before restudy occurred. Results of greatest interest concern performance on test trials following restudy for items that were not correctly recalled on the test trials that preceded restudy. Results replicate Arnold and McDermott (2013) by demonstrating that more versus fewer tests potentiate learning when trial time is limited. Results also provide strong evidence against the covert retrieval hypothesis concerning why the effect occurs (i.e., it does not reflect differential covert retrieval during pre-restudy trials). In addition, outcomes indicate that the magnitude of the test-potentiated learning effect decreases as trial length increases, revealing an unexpected boundary condition to test-potentiated learning.


Accelerated RNA secondary structure design using preselected sequences for helices and loops.
Nucleic acids can be designed to be nano-machines, pharmaceuticals, or probes. RNA secondary structures can form the basis of self-assembling nanostructures. There are only four natural RNA bases, therefore it can be difficult to design sequences that fold to a single, specified structure because many other structures are often possible for a given sequence. One approach taken by state-of-the-art sequence design methods is to select sequences that fold to the specified structure using stochastic, iterative refinement. The goal of this work is to accelerate design. Many existing iterative methods select and refine sequences one base pair and one unpaired nucleotide at a time. Here, the hypothesis that sequences can be preselected in order to accelerate design was tested. To this aim, a database was built of helix sequences that demonstrate thermodynamic features found in natural sequences and that also have little tendency to cross-hybridize. Additionally, a database was assembled of RNA loop sequences with low helix-formation propensity and little tendency to cross-hybridize with either the helices or other loops. These databases of preselected sequences accelerate the selection of sequences that fold with minimal ensemble defect by replacing some of the trial and error of current refinement approaches. When using the database of preselected sequences as compared to randomly chosen sequences, sequences for natural structures are designed 36 times faster, and random structures are designed six times faster. The sequences selected with the aid of the database have similar ensemble defect as those sequences selected at random. The sequence database is part of RNAstructure package at http://rna.urmc.rochester.edu/RNAstructure.html.


Insights into involuntary hospital admission procedures for psychiatric patients: A 3-year retrospective analysis of police records.
The procedure of involuntary hospitalization has been an ongoing subject of study. Its implementation requires the systematic co-ordination between the Justice and Health Care systems around the globe. In the case of Greece, the procedure under discussion is regulated by Law 2071/1992, which designates the Police as the agent that links the aforementioned systems together. The present study aims to shed light upon the procedure of involuntary hospitalizations, regarding the preparatory stage and the Police involvement up to the individuals' admission to the on-call hospital for a mental health assessment (MHA). The entry data of two police stations in Athens was recorded by the respective Duty Officer responsible for each case. The police records were retrospectively inspected and information on socio-demographic, clinical and parametric characteristics was extracted. The data collection took place between March and July 2020 and included 324 cases, 80.3% of which referred to involuntary hospitalizations; 17.6% of sample cases did not meet the criteria of the procedure, as opposed to 1.9% of the cases in which the patients eventually ended up being voluntarily admitted and afterwards hospitalized for treatment. There was a statistically comparison of socio-demographic, clinical and parametric variables in relation to the status of hospitalization groups (involuntary, voluntary and no hospitalization). Additionally, statistical comparisons were made between parametric and clinical variables in relation to the type of prosecution order (written: standard route, oral: emergency route). Acute mental health deterioration accounted for around 45% of the total data and it has been identified as the main factor for informing the Hearings Prosecutor office mainly by the patient's family and subsequently proceeding to the issuance of an order (in either written or oral form) to the Police. This enables the Police to escort the individuals and lead them to a psychiatric unit for mental health assessment (MHA) and based on this, for involuntary hospitalization if deemed necessary. In 87.9% of the cases, the individual was transported by police vehicles over a time span ranging from the very same day to 22 days. In total, the written prosecution orders (63.6%) outnumbered the oral ones (36.7%). The findings of the present study demonstrate that the Prosecution order type varies significantly depending on the causes that instigated the involuntary hospitalization procedure. The psychiatric decision whether there should be hospitalization or outpatient therapy also significantly varies depending on the diagnosis. Lastly, the results point out that the need for improvement and further clarification of the aforementioned Greek Law is absolutely essential.


[Evaluation of the influence of sex hormones on homocysteine concentration in pre- and postmenopausal women].
The aim of study was to evaluate the influence of sex hormones: estradiol (E), follicle-stimulating hormone (FSH), progesterone (P), testosterone (T), dehydroepiandrosterone (DHEA-S) and cortisol (F) on the serum homocysteine concentration (HCY) in 40 premenopausal (group M) and 80 postmenopausal (group K) women. The influence of E2 therapy (ET) on the serum HCY level in the women with surgical menopause was also estimated. The plasma HCY concentration in the group M was significantly higher that in group K. After ET serum HCY level decreased significantly. No correlations were found between serum HCY and E2 concentrations in the all groups. No correlations were observed between HCY and FSH, P, T and F concentrations in pre-and postmenopausal groups. There was a significant negative correlation between serum HCY and DHEA-S concentration in group K. This result may indicate, that high level of DHEA decreases HCY concentration. There was no correlation in group M, where the mean concentration of DHEA was lower than in group K. The results of study indicate, that menopause increases and ET decreases plasma HCY concentration. DHEA-S may inhibit plasma HCY concentration in premenopausal women. More studies are needed to elucidate these hypotheses.


Reducing the phase noise in diode lasers.
Diode lasers are widely used in atomic physics given their narrow linewidth and wavelength tunability. Nevertheless, although they present low noise for their intensity, excessive noise in the phase limits their application in quantum optics. Looking for reduction of this phase noise, we built and characterized a ring laser, using a semiconductor-tapered amplifier as the gain medium. We were able to reduce the phase noise of a diode laser to a factor of 10 above shot-noise level, bringing it closer to a useful coherent state for applications in quantum information.


Biodegradation of tert-butylphenyl diphenyl phosphate.
The biodegradation of tert-butylphenyl diphenyl phosphate (BPDP) was examined in microcosms containing sediment and water from five different ecosystems as part of our studies to elucidate the environmental fate of phosphate ester flame retardants. Biodegradation of [14C]BPDP was monitored in the environmental microcosms by measuring the evolution of 14CO2. Over 37% of BPDP was mineralized after 8 weeks in microcosms from an ecosystem which had chronic exposure to agricultural chemicals. In contrast, only 1.7% of BPDP was degraded to 14CO2 in samples collected from a noncontaminated site. The exposure concentration of BPDP affected the percentage which was degraded to 14CO2 in microcosms from the two most active ecosystems. Mineralization was highest at a concentration of 0.1 mg of BPDP and was inhibited with 10- and 100-fold higher concentrations of BPDP in these microcosms. Indigenous heterotrophic and BPDP-utilizing microbial populations and phosphoesterase enzyme activities were highest in sediments which had the highest biodegradation of BPDP. We observed adaptive increases in both microbial populations and phosphoesterase enzymes in some sediments acclimated to BPDP. Chemical analyses of the residues in the microcosms indicated undegraded BPDP and minor amounts of phenol, tert-butylphenol, diphenyl phosphate, and triphenyl phosphate as biodegradation products. These data suggest that the microbial degradation of BPDP results from at least three catabolic processes and is highest when low concentrations of BPDP are exposed to sediment microorganisms of eutrophic ecosystems which have high phosphotri- and diesterase activities and previous exposure to anthropogenic chemicals.


Survival analysis of 118 patients with systemic sclerosis.
Life-table analysis based on the survival statistics of 118 Hungarian patients with systemic sclerosis suggests that the presence of skin hypo- and/or hyperpigmentation indicates a poor prognosis. Furthermore, truncal skin involvement, lung, cardiac, and renal manifestations, older age at the onset of disease, anaemia, hand deformity, and elevated erythrocyte sedimentation rate values, predict an unfavourable prognosis, whilst patients with exposure to chemicals shows a relatively favourable disease outcome.


C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance.
C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE) in CRP transgenic mice by shifting CD4+ T cells away from the TH1 and toward the TH2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB), but did not require high levels of human CRP. Herein, we sought to determine if CRP's influence in EAE might be explained by CRP acting on dendritic cells (DC; antigen presenting cells known to express FcγRIIB). We found that CRP (50 µg/ml) reduced the yield of CD11c+ bone marrow-derived DCs (BMDCs) and CRP (≥5 μg/ml) prevented their full expression of major histocompatibility complex class II and the co-stimulatory molecules CD86 and CD40. CRP also decreased the ability of BMDCs to stimulate antigen-driven proliferation of T cells in vitro. Importantly, if the BMDCs were genetically deficient in mouse FcγRIIB then (i) the ability of CRP to alter BMDC surface phenotype and impair T cell proliferation was ablated and (ii) CD11c-driven expression of a human FCGR2B transgene rescued the CRP effect. Lastly, the protective influence of CRP in EAE was fully restored in mice with CD11c-driven human FcγRIIB expression. These findings add to the growing evidence that CRP has important biological effects even in the absence of an acute phase response, i.e., CRP acts as a tonic suppressor of the adaptive immune system. The ability of CRP to suppress development, maturation, and function of DCs implicates CRP in the maintenance of peripheral T cell tolerance.


The pituitary-testicular response to luteinising hormone releasing hormone administration to normal men.
The response of the pituitary and testis in normal men to the injection of LH-RH has been studied using single intravenous doses of either 25 mug or 100 mug. Serum LH levels rose with both doses but significant elevation of plasma testosterone was evident only following 100 mug of LH-RH. Though testosterone levels were elevated within 60 minutes, peak responses occurred from 4-12 hours post-injection. The rise in serum FSH levels was small or absent at 25 mug but was clearly present following 100 mug LH-RH, in general rising more slowly than LH levels but persisting for a longer period.


Assessing allele frequencies of single nucleotide polymorphisms in DNA pools by pyrosequencing technology.
Single nucleotide polymorphism (SNP) association studies searching for differences in allele frequencies between cases and controls have been widely used for genetic analysis. Individual genotyping is prohibitively expensive in large sample sizes. Pooling of samples provides the obvious advantage of higher throughput and lower cost. Here we report our results with the analysis of SNP allele frequencies in DNA pools using Pyrosequencing technology. For seven different SNPs, we observed a mean difference of 1.1 +/- 0.6% between allele frequencies determined in two different DNA pools (n = 150 cases and 150 controls) compared to individually genotyped samples.


Improvement of Thermosensitive Liposome Stability by Cerasome Forming Lipid with Si-O-Si Network Structure.
Liposomes have been widely used in gene transfection and drug delivery systems due to their excellent biocompatibility and encapsulation ability, especially, the ability to deliver the gene/drug into the cells via the membrane fusion. Thermosensitive liposomes have been proven to be a precise and effective method for cancer treatment in many preclinical studies. But the imperfect crystalline arrangement between grains occurred, resulting in planar defects at the boundaries of membranes, compromising the stability of thermosensitive liposomes. In the present study, we developed a facile method to improve the stability of ordinary thermosensitive liposomes by introducing organic-inorganic hybrid materials with local Si-O-Si net. A cerasome forming lipid, N, N-Dihxadecyl-N'- [(3-triethoxysilyl) propyl] urea, was synthesized and then introduced into the thermosensitive lipids to form the composite liposomes (named as cera-liposomes). The effects of the cerasome forming lipid on the cera-liposomes characteristics, including the morphology, drug loading, Zeta potential and stability of vesicles, were investigated. Cera-liposomes were thermosensitive, and they had a loading efficiency over 2 folds more than conventional thermosensitive liposomes. With the enhanced sustain of Si-O-Si, cera-liposomes were able to avoid collapsing and fusing during storage, and had a good resistance to nonionic surfactant. More than 80% drug was still retained after storage of 15 days at room temperature. The cerasome forming lipid showed potential in improving the stability of thermosensitive liposomes. This novel kind of cera-liposomes could be a stable and effective drug carrier for anticancer applications.


From sense of place to visualization of place: examining people-place relationships for insight on developing geovisualizations.
Effective resource planning incorporates people-place relationships, allowing these efforts to be inclusive of the different local beliefs, interests, activities and needs. 'Geovisualizations' can serve as potentially powerful tools for facilitating 'place-conscious' resource planning, as they can be developed with high degrees of realism and accuracy, allowing people to recognize and relate to them as 'real places'. However, little research has been done on this potential, and the place-based applications of these visual tools are poorly understood. This study takes steps toward addressing this gap by exploring the relationship between sense of place and 'visualization of place'. Residents of the Capital Regional District of BC, Canada, were surveyed about their relationship with local coastal places, concerns for the coast, and how they mentally visualize these places. Factor analysis identified four sense of place dimensions - nature protection values, community and economic well-being values, place identity and place dependence, and four coastal concerns dimensions - ecological, private opportunities, public space and boating impacts. Visualization data were coded and treated as dependent variables in a series of logistic regressions that used sense of place and coastal concerns dimensions as predictors. Results indicated that different aspects of sense of place and (to a lesser degree) concerns for places influence the types of elements people include in their mental visualization of place. In addition, sense of place influenced the position and perspective people assume in these visualizations. These findings suggest that key visual elements and perspectives speak to different place relationships, which has implications for developing and using geovisualizations in terms of what elements should be included in tools and (if appropriate) depicted as affected by potential management or development scenarios.


[Analysis of surgical treatment for Standford type A aortic dissection].
To summarize the surgical experience of type A aortic dissection. From January 2001 to December 2006, 54 cases were admitted for Standford type A aortic dissection, including 36 cases of acute aortic dissection and 18 cases of chronic. Thirty-five cases underwent emergence operation and 11 cases underwent selective/limited operation, while 8 cases received medical treatment According to the modus operandi of root of aorta, 9 cases underwent ascending aorta replacement merely, 11 cases for Bentall operation, 12 cases for Wheat operation and ascending aorta replacement, 14 cases for David operation and ascending aorta replacement. According to the modus operandi of aortic arch and descendens, 6 cases underwent right hemiarch replacement, 25 cases for total arch replacement with four branches aortic graft, 24 cases for stent-graft elephant trunk technique. One patient of coronary heart disease and 1 patient of right coronary fracture underwent coronary artery bypass grafting. Deep hyperthermic circulatory arrest and antegrade selective cerebral perfusion were applied with aortic arch operation. Surface cooling was applied with selective/limited operation. Four patients died in operation group (8.7%) and 8 died in non-operation group (75.0%). Postoperative complication included 1 mental symptom, 3 pleural/pericardial effusion, 1 hoarseness, 1 sternal rupture and poor wound healing. All the complication were cured. The operative out-hospital patients were followed up (13.0 +/- 14.2) months and the quality of life was satisfied. Standford type A aortic dissection should be operated aggressively. Expected outcome could be acquired with optimum modus operandi, proper cerebral protection and dealing with postoperative complication timely.


Shoulder kinematics is not influenced by external load during elevation in the scapular plane.
The current study aimed to compare the shoulder kinematics (3D scapular orientation, scapular angular displacement and scapulohumeral rhythm) of asymptomatic participants under unloaded and loaded conditions during unilateral shoulder elevation in the scapular plane. We used a repeated-measures design with a convenience sample. Eleven male participants with an age range of 21-28 years with no recent history of shoulder injury participated in the study. The participants performed isometric shoulder elevation from a neutral position to approximately 150 degrees of elevation in the scapular plane in intervals of approximately 30 degrees during unloaded and loaded conditions. Shoulder kinematic data were obtained with videogrammetry. During shoulder elevation, the scapula rotated upwardly and externally, and tilted posteriorly. The addition of an external load did not affect 3D scapular orientation, scapular angular displacement, or scapulohumeral rhythm throughout shoulder elevation (P > .05). In clinical practice, clinicians should expect to observe upward and external rotation and posterior tilt of the scapula during their assessments of shoulder elevation. Such behavior was not influenced by an external load normalized to 5% of body weight when performed in an asymptomatic population.


Rectangular-Phase Tellurene on Ni(111) from Monolayer Films to Periodic Striped Patterns.
As an emerging member of monoelemental two-dimensional (2D) materials, 2D tellurium (tellurene) has recently attracted intensive attention due to its polymorphism arising from the multivalent nature and fascinating properties such as wide-range band gaps, high carrier mobilities, etc. Herein, we predict the formation of a rectangular-phase tellurene on Ni(111) by first-principles density functional theory (DFT) calculations and realize its direct syntheses and characterizations by molecular beam epitaxy (MBE) and scanning tunneling microscopy (STM). We reveal that the monolayer rectangular tellurene and underlying Ni(111) substrate are strongly coupled, along with good lattice registry along two mutually perpendicular directions, which serves as the key driving force for the tellurene formation. We also uncover the unique morphological transitions of Te/Ni(111) from rectangular tellurene monolayer, to uniform periodic striped patterns at the second layer, and then to thick striped patterns. This work should offer valuable insights for the substrate-mediated syntheses of monoelemental 2D materials, thus propelling their phase engineering and intriguing property explorations.


Coexisting pancreatic and breast adenocarcinomas: is there an association?
Two patients are reported with coexisting adenocarcinomas of pancreas and breast. One represents synchronous neoplasms, the other metachronous tumors diagnosed 7 years apart. The significance of these findings is discussed, including possible carcinogenic dietary factors common to both neoplasms. The potential problems associated with the histologic diagnosis of such coexisting tumors are stressed.


Factors associated with receiving hepatitis B vaccination among high-risk adults in the United States: an analysis of the National Health Interview Survey, 2000.
Although an effective vaccine against hepatitis B has been licensed in the United States since 1981, and successful childhood vaccination programs have been implemented, hepatitis B virus transmission continues to occur among high-risk adults. In this study, we identified factors associated with receipt of one or more doses of hepatitis B vaccine among adults at high risk for hepatitis B infection. We analyzed data from the 2000 National Health Interview Survey of selected adults ages 18-49 years who were at high risk for hepatitis B infection (n=1,036). Multivariable regression analysis was conducted to determine factors independently associated with vaccination. Although more than 80% (n=841) of high-risk adults reported previous visits to a clinician during the past year, only 30% (n=498) of men and 31% (n=538) of women reported having received a single dose of hepatitis B vaccine. Young age (18-29 years), never being married, past blood donation, and past human immunodeficiency virus (HIV) testing were independently associated with receiving vaccination for men. For women, young age (18-29 years) and previous vaccinations were significant factors associated with vaccination receipt. Additionally, having a primary care source (men) and seeing an obstetrician-gynecologist provider in the past year (women) were significantly associated with vaccination. Hepatitis B vaccination rates for high-risk adults are low, and missed opportunities are frequent. Additional strategies are needed to increase immunization rates of adults at high risk for hepatitis B.


Adherence to malaria treatment guidelines among health care workers in private health facilities in Kampala's informal settlements, Uganda.
Poor adherence to malaria treatment guidelines among healthcare workers (HCWs) is a major contribution to diagnostic challenges, treatment failure, and non-rational use of antimalarial medicines. However, there is limited information about adherence to malaria treatment guidelines among HCWs in private health facilities in informal settlements in Uganda. This study therefore assessed the level of adherence to malaria treatment guidelines and associated factors among HCWs in private health facilities in Kampala's informal settlements. A cross-sectional study was conducted among 339 HCWs from private health facilities in slums of 4 selected divisions in Kampala, Uganda. Quantitative data was collected using a semi-structured questionnaire, cleaned in MS Excel 2016 and analyzed using STATA 15.0 statistical software. Bivariate and multivariate analysis were conducted using a generalized linear model of modified Poisson regression to obtain factors associated with adherence to malaria treatment guidelines. The study revealed that majority of respondents 71.1%(241/339) were aged 30 years and below, and 50.1%(170/339) of the were female. Almost all of the respondents 98.8%(335/339) reported that they had malaria diagnostic equipment (microscopy or rapid diagnostic tests) at their facilities, 47.5%(161/339) had non-recommended anti-malarial drugs present in stock and 36.0% reported that they did not refer severely ill patients to higher health facilities in the previous 3 months. Although 92.6%(314/339) of the respondents had heard about the national malaria treatment guidelines, 63.1%(214/339) of them adhered to these guidelines. Having a bachelors degree (APR 1.54, (CI: 1.13-2.10)P 0.006), and having high levels of knowledge (APR 1.44, (CI: 1.13-1.60)P 0.001) were positively associated with high adherence to malaria treatment guidelines. In conclusion, adherence to malaria treatment guidelines was suboptimal and less than the national target of 90%. Enforcement, supervision, trainings, and continuous medical education should be enhanced in private healthcare facilities to improve adherence to malaria treatment guidelines in informal settlements.


[The principles of guaranteeing the quality of medical care for the wounded and ill].
The author states four main principles of maintenance of quality of the medical care to wounded and patients: a principle of conformity of preparation of the staff to soluble problems is provided by observance of the State educational standards of vocational training--carrying out the professiographic analysis of activity of the surgeons for creation of the models of the experts, perfection of the educational plans and programs; a principle of development of material base with sharp definition of priority spheres of its development for forthcoming year and use of material means for development of economic base of military-medical institutions; a principle of strict observance of modern medical technologies, based on the standards of equipment, outcomes (results of work of the medical institutions), medico-technological and medico-pharmaceutical; a principle of scientific quality management on the basis of estimation of staff-organizational structure of medical units and institutions, treatment-diagnostic technologies (processes) and the results of rendering of the medical care.


Selective oxidation of cysteine and methionine in normal and senile cataractous lenses.
The oxidation state of methionine and cysteine in normal and cataractous lenses is reported. In young lenses no oxidation was detected in any protein fraction examined. Only the intrinsic membrane fraction and membrane-related components showed evidence of oxidation in old (60-65 years of age) normal lenses. However, in a similar age group, with the development of cataract, progressive, dramatic changes were observed. With severe cataracts, 60% or more of the methionine in membrane-associated components was found in the methionine sulfoxide form, and methionine sulfone was observed in one case. Most of the cysteine was found oxidized to either the disulfide form or putative cysteic acid. Mixed disulfides with glutathione were observed. Oxidative changes in soluble components as illustrated by alpha-crystallin occurred more gradually. The data clearly support the viewpoint that extensive oxidation of lens proteins occurs with cataract and that it begins at the lens fiber membrane.


Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes.
Injection of rat atrial RNA into Xenopus oocytes resulted in the expression of guanine nucleotide binding (G) protein-activated K+ channel. Current through the channel could be activated by acetylcholine or, if RNA encoding a neuronal 5HT1A receptor was coinjected with atrial RNA, by serotonin (5HT). A 5HT-evoked current (I5HT) was observed in oocytes injected with ventricle RNA fractions (of 2.5-5.5 kb) and 5HT1A receptor RNA. I5HT displayed strong inward rectification with very little conductance above the K+ equilibrium potential, was highly selective for K+ over Na+, and was blocked by 5-300 microM Ba2+. I5HT was suppressed by intracellular injection of the nonhydrolyzable analog of GDP, guanosine 5'-[beta-thio]diphosphate, but not by treatment with pertussis toxin (PTX), suggesting coupling of the receptor to the G-protein-activated K+ channel via a PTX-insensitive G protein, possibly endogenously present in the oocyte. Coexpression of the alpha subunit of a PTX-sensitive G protein, G(i2), rendered I5HT sensitive to PTX inhibition. Native oocytes displayed a constitutively active inwardly rectifying K+ current with a lower sensitivity to Ba2+ block; expression of a similar current was also directed by atrial or ventricle RNA of 1.5-3 kb. Xenopus oocytes may be employed for cloning of the G-protein-activated K+ channel cDNA and for studying the coupling between this channel and G proteins.


Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice.
Influenza A virus replicates in the respiratory epithelium and induces an inflammatory infiltrate comprised of mononuclear cells and neutrophils. To understand the development of the cell-mediated immune response to influenza and how leukocyte trafficking to sites of inflammation is regulated, we examined the chemokine expression pattern in lung tissue from A/PR/8/34-infected C57BL/6 mice using an RNase protection assay. Monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-3alpha, regulated on activation, normal T expressed and secreted (RANTES), MIP-2, and interferon-inducible protein 10 (IP-10) mRNA expression was up-regulated between days 5 and 15 after infection, consistent with a role for these chemokines in leukocyte recruitment to the lung. Low levels of expression were detected for the CC chemokine receptors (CCR)2 and CCR5, whereas CXC chemokine receptor (CXCR)3 was significantly up-regulated by day 10 after infection, coinciding with peak inflammatory cell infiltration in the airways. As RANTES, IP-10, and their receptors were up-regulated during influenza virus infection, we investigated leukocyte recruitment and viral clearance in mice deficient in RANTES or CXCR3, the receptor for IP-10. Leukocyte recruitment and viral replication in influenza-infected RANTES knockout(-/-) mice were similar to that in control mice, showing that RANTES is not essential for the immune response to influenza infection. Similarly, leukocyte recruitment and viral replication in CXCR3-/- mice were identical to control mice, except at day 8 postinfection, where fewer lymphocytes, neutrophils, and eosinophils were detected in the bronchoalveolar lavage of CXCR3-/- mice. These studies suggest that although the chemokines detected may play a role in regulating leukocyte trafficking to the lung during influenza infection, some may be functionally redundant.