Type IX Ehlers-Danlos syndrome and Menkes syndrome: the decrease in lysyl oxidase activity is associated with a corresponding deficiency in the enzyme protein.
Type IX of the Ehlers-Danlos syndrome (E-D IX) and the Menkes syndrome are X-linked recessively inherited disorders characterized by abnormalities in copper metabolism. These abnormalities are associated with a severe reduction in the activity of lysyl oxidase, the extracellular copper enzyme that initiates crosslinking of collagens and elastin. No increase in this deficient enzyme activity was obtained when culture media from fibroblasts of patients with E-D IX or the Menkes syndrome were incubated with copper under various conditions in vitro. A distinct, although small, increase in lysyl oxidase activity was obtained, however, when copper-supplemented media were used during culturing of the fibroblasts, although even under these conditions, the enzyme activity in the media from the affected cells remained markedly below that of the controls. Immunoprecipitation, dot-blotting, and immunoperoxidase staining experiments with antisera to human lysyl oxidase indicated that fibroblasts from patients with E-D IX or the Menkes syndrome do not secrete into their medium, or contain inside the cell, any significant amounts of a copper-deficient, catalytically inactive lysyl oxidase protein. These findings appear to be consistent with the hypothesis that synthesis of the lysyl oxidase protein itself is impaired. The possibility is not excluded, however, that a copper-deficient enzyme protein may be synthesized in normal amounts but become degraded very rapidly inside the cell. The failure to obtain any large increase in the deficient lysyl oxidase activity upon various forms of copper administration suggests that it may not be possible to obtain any significant improvement in the connective tissue manifestations of these disorders by copper therapy.


[Low-reactive free radicals inhibiting nonbranched chain processes of addition].
The kinetics of inhibition of nonbranched chain processes of addition of reactive free radicals at double bonds O=O, C=O, and C=C of molecules in liquid homogeneous binar systems from saturated and unsaturated components by low-reactive free radicals (o-CH3C6H4CH2O*4, HO*4; HC=O; CH2=C(CH3)CH2, and CH2=CHCHOH) was studied. It was assumed that as the concentration of the unsaturated component (as a source of low-reactive free radicals) increases (after the optimum concentration is attained, which corresponds to the maximum rate of the process) the phenomena of increasing inhibition of these processes may act as the elements of self-regulation of similar processes in nature, which returns them into the stationary state. The energetics of the key radical-molecular gas phase reactions was analyzed. The thermal effects of total dissociation reactions of simple alkylperoxyl (exo effect) and alkoxyl (endo effect) reactive free radicals in the gas phase were compared. The kinetic equations (with one to three parameters being directly determined), obtained by the quasi-steady-state treatment, are presented, which make it possible to describe nonmonotonic (with a maximum) dependencies of the rates of formation of molecular 1:1-adducts on the concentration of the unsaturated component.


The doctor's role in rural health care.
A new pattern of health care in developing countries promises to meet the needs of rural people and still provide reasonable gratification for health workers. The service must have mutually strengthening linkages between all levels of the health care system. Reallocating roles in the health team requires turning routine medical care over to auxiliaries so that professionals can concentrate on more complex problems, such as community diagnosis and therapy. Young doctors are reasonable and willing to undertake a rural rotation early in their medical careers. This will help to identify those few who will provide leadership in improving rural services.


Marine peptides in breast cancer: Therapeutic and mechanistic understanding.
Breast cancer is the most prevalent invasive form of cancer in females and posing a great challenge for overcoming disease burden. The growth in global cancer deaths mandates the discovery of new efficacious natural anti-tumor treatments. In this regard, aquatic species offer a rich supply of possible drugs. Studies have shown that several marine peptides damage cancer cells by a broad range of pathways, including apoptosis, microtubule balance disturbances, and suppression of angiogenesis. Traditional chemotherapeutic agents are characterized by a plethora of side effects, including immune response suppression. The discovery of novel putative anti-cancer peptides with lesser toxicity is therefore necessary and timely, especially those able to thwart multi drug resistance (MDR). This review addresses marine anti-cancer peptides for the treatment of breast cancer.


Low frequency of the ADH2*2 allele among Atayal natives of Taiwan with alcohol use disorders.
Genetic variation at two polymorphic alcohol dehydrogenase loci, ADH2 and ADH3, and at the polymorphic mitochondrial aldehyde dehydrogenase locus, ALDH2, may influence the risk of developing alcoholism by modulating the rate of elimination of ethanol and the rate of formation and elimination of acetaldehyde. Populations differ in allele frequencies at these loci. We determined the genotypes at all three of these loci in Atayal natives of Taiwan. The frequencies of ADH2*2, ADH3*1, and ALDH2*1 alleles (0.91, 0.99, and 0.95, respectively) were significantly higher among the Atayal than among a predominantly Han Chinese population from Taiwan. Among the Atayal, the group with alcohol use disorders (alcohol dependence and alcohol abuse) had a significantly lower frequency of the ADH2*2 allele (0.82) than those without alcohol use disorders (0.91). The ADH2*2 allele encodes the beta 2 subunit; isozymes containing beta 2 subunits oxidize alcohol faster in vitro than the beta 1 beta 1 isozyme encoded by ADH2*1. Thus, the simplest explanation for these data is that individuals with a beta 2 isozymes have a higher rate of ethanol oxidation, which is a deterrent to alcohol abuse and dependence in some individuals. The Atayal with alcohol use disorders also had a lower frequency of ALDH2*2 than the controls; this allele is known to be responsible for the alcohol-flush reaction among Asians, and thereby deters drinking.


The process of change in cognitive therapy for depression: predictors of early inter-session symptom gains.
Although cognitive therapy for depression is an efficacious treatment, questions about the aspects of the therapy that are most critical to successful implementation remain. In a sample of 60 cognitive therapy patients with moderate to severe depression, we examined three aspects of therapists' adherence to cognitive therapy techniques, the patients' facilitation or inhibition of these techniques, and the therapeutic alliance as predictors of session-to-session symptom improvement across the first five therapy sessions. Two elements of therapist adherence (viz., cognitive methods and negotiating content/structuring sessions) emerged as the strongest predictors of symptom improvement. Patient facilitation or inhibition of therapist adherence also predicted subsequent symptom change. Neither adherence to behavioral methods/homework nor the therapeutic alliance was a significant predictor in parallel analyses. Although alliance scores did not predict subsequent symptom change, they were significantly predicted by prior symptom change. These findings support the model of change that motivates cognitive therapy for depression, and they highlight the potential role of patient facilitation of therapists' adherence in treatment response.


[Influence of digital subtraction cerebral angiography on blood flow in the middle cerebral artery].
The aim. Despite adhibition of new, improved enhancing agents some subjective signs during cerebral angiography are notified. This suggests that cerebral blood flow might be influenced by this procedure. The validity of transcranial color doppler sonography (TCCS) in cerebral blood flow evaluation is already proved and this method was selected for blood flow parameters estimation before and after cerebral angiography. 33 subjects (17 female and 16 male) aged 50 +/- 13 were diagnosed by cerebral angiography. Before and immediately after angiographic examination cerebral blood flow parameters were evaluated in middle cerebral arteries by transcranial, sektor 2.5 MHz probe of Toshiba Aplio SSA 770A system. In comparison to pre-angiographic TCCS examination middle cerebral artery systolic velocity decreased about 3 cm/s (p<0.05). Mean and end-diastolic velocity in MCA insignificantly increased about 1 and 2 cm/s respectively (p>0.05). Impedance index values significantly decreased (Wilcoxon test, p<0.05) after angiography. Change of flow parameters in the middle cerebral artery prove increase of cerebral blood flow after diagnostic angiography.


Treatment satisfaction in postmenopausal women suboptimally adherent to bisphosphonates who transitioned to denosumab compared with risedronate or ibandronate.
For many patients, adhering to postmenopausal osteoporosis treatment is a challenge. Higher treatment satisfaction is associated with greater persistence with these therapies, which is associated with better outcomes. This study aimed to evaluate the change in treatment satisfaction in postmenopausal women who were suboptimally adherent to daily or weekly oral bisphosphonates and who transitioned to denosumab vs a monthly oral bisphosphonate. Pooled data of outpatients from two international, multicenter, randomized, open-label studies were analyzed. Postmenopausal women (n = 1703) age 55 years or greater with low bone mineral density who were suboptimally adherent with prior oral bisphosphonate therapy, as assessed by the Osteoporosis-Specific Morisky Medication Adherence Scale, were included in the study. Patients received denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B ligand, 60 mg s.c. every 6 months vs the oral bisphosphonates ibandronate or risedronate, 150 mg once monthly for 12 months. Change in treatment satisfaction scores from baseline to months 6 and 12 were measured using the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM is a validated tool that measures perception of four domains of treatment satisfaction: effectiveness, side effects, convenience, and global satisfaction. Patients in both treatment groups showed improvement from baseline for all four TSQM domains at 6 and 12 months. However, the denosumab group had significantly (all P < .001) greater improvements among all four TSQM domains at 6 and 12 months compared with the oral bisphosphonate group. Women with low adherence to oral bisphosphonates reported greater treatment satisfaction when transitioned to denosumab vs switching to a monthly oral bisphosphonate.


Carcinoma of the rectum with a single penile metastasis.
Metastatic disease of colon and rectal carcinoma accounts for a high proportion of cancer related deaths. The common organs involved in metastatic diseases include liver, lung, brain and bone. Although, theoretically possible, metastasis to the other organs are rare. We report the first case of carcinoma of the rectum with a solitary metastasis to the glans penis.


The Impact of FOXP3 Polymorphism on the Risk of Allergic Rhinitis: A Meta-Analysis.
Polymorphisms of several genes were reported to be associated with the risk of allergic rhinitis. Here, we first conducted a meta-analysis to evaluate the potential genetic association between the polymorphisms of the FOXP3 (Forkhead Box P3) gene and the susceptibility to allergic rhinitis. A total of 2671 relevant articles were initially retrieved from the databases of PubMed, Web of Science, Embase, WANFANG/CNKI and Scopus, and six eligible case-control studies were finally enrolled in our meta-analysis, according to our strict inclusion/exclusion criteria. Based on the extracted data, Mantel-Haenszel statistic, Cochrane's Q statistic, I2 test, subgroup meta-analysis, Begg's test, Egger's test and sensitivity analysis were performed via Stata/SE 12.0 software. The results of the Mantel-Haenszel statistic regarding rs3761548 showed that no significant difference was observed in the allergic rhinitis case and population-based control group under the genetic models of A versus C, AA versus CC, CA+AA versus CC, AA versus CC+CA and carrier A versus C (all P-value of Association Test, PA > 0.05), apart from CA versus CC (PA = 0.020). The similar results were obtained in the subgroup analysis of Asian. In addition, we did not obtain the positive result in the meta-analysis of rs2232365 (all PA > 0.05). We also excluded the presence of large publication bias through Begg's test and Egger's test, and we confirmed the stability of data by sensitivity analysis. In summary, no significant association between rs3761548, rs2232365 polymorphisms of the FOXP3 gene, and an increased susceptibility to allergic rhinitis was identified based on the published data; however, this conclusion should be confirmed by more studies with increased sample sizes.


Spatial patterns of Anopheles freeborni and Culex tarsalis (Diptera: Culicidae) larvae in California rice fields.
Spatial patterns of Anopheles freeborni Aitken and Culex tarsalis Coquillett larvae were studied during summer by sampling with a standard mosquito dipper in 104 rice fields in northern California. Culex tarsalis larval abundance was highest initially, then decreased and remained low through late summer. An. freeborni larval abundance was low initially, increased steadily, and peaked in mid-August. The degree of aggregation for both species as measured using Taylor's power law and Iwao's Patchiness Regression was highest among the first instars and then decreased as the larvae aged. Seasonal peaks in the degree of aggregation were observed. Analysis of covariance showed that for Taylor's model both instar and time effects were statistically significant, with instar showing the largest effect. In comparison, all slopes resulting from Iwao's model were significantly different, indicating that this model was affected by specific combinations of instar, week, and location and, thus, was less useful in developing an area-wide sampling plan. Optimal sample size was estimated using two methods. One method calculated the number of dips needed to estimate population abundance at three fixed-precision levels. The second calculated the minimum number of dips needed to collect at least one larva. The latter requires a substantially smaller sample size and may provide an effective method for monitoring larval mosquito abundance for control purposes.


Therapeutic plasma exchange for mechanical red cell hemolysis: A case series.
We present three cases of severely elevated plasma free hemoglobin (PFH) in pediatric patients on mechanical circulatory support devices at a tertiary pediatric care center. Due to severe levels of PFH in the setting of critical illness with the inability to pursue immediate mechanical device exchange, membrane filtration therapeutic plasma exchange (TPE) was performed, which resulted in a lowering of PFH levels. However, long-term outcomes were heterogeneous across the cases. This case series reviews patient presentation, organ function before and after TPE, and the overall role of TPE as an effective treatment option to decrease severely elevated PFH levels. In doing so, we hope to add to what is known about the use of TPE for mechanical red cell hemolysis and provide guidance on its use in critically ill patients.


[Peritoneal hydatidosis in children. Report of a historical case].
Peritoneal hydatidosis is a rare localisation of hydatic disease, most often secondary to a hydatic cyst of the liver. Its primitive form is considered due to a haematogenous diffusion through arterial vessels. We report a historical case of peritoneal hydatidosis concomitant to a hepatic localisation, in a 13-year-old girl. Diagnosis was performed by ultrasounds and CT scan, and a strong positive serology. Surgical cure has been completed by pharmacologic treatment with the aim of avoiding a relapse. A brief reminder of the therapeutic management of the disease is provided.


Blastocyst Transfer: A Risk Factor for Gestational Diabetes Mellitus in Women Undergoing In Vitro Fertilization.
The risk of developing gestational diabetes mellitus (GDM) is higher in women undergoing assisted reproductive treatment than in women conceiving spontaneously. To determine whether the GDM risk after day-3 embryo transfer differs from the GDM risk after day-5 blastocyst transfer. Prospective observational study in women becoming pregnant after first fresh embryo or blastocyst transfer. A total of 1579 women got pregnant and had live birth; 1300 women got day-3 embryo transfer only, whereas 279 women received at least 1 blastocyst. Of 1579 women, 252 developed GDM. Age, body mass index, baseline estradiol, baseline high-density lipoprotein, and progesterone on the day of human chorionic gonadotropin injection were not different in women receiving day-3 embryos only vs women receiving at least 1 blastocyst. The number and quality of retrieved oocytes were not different in women receiving day-3 embryo transfer from those receiving blastocysts. Our study confirmed already established GDM risk factors such as age and body mass index, baseline estradiol, and high-density lipoprotein, as well as progesterone after ovarian stimulation. We furthermore demonstrate that the GDM incidence in women receiving day-5 blastocyst transfer was significantly higher than those who received day-3 embryo transfer (21.15% vs 14.85%; P = 0.009). Considering confounding factors, we likewise saw that blastocyst transfer was an independent procedure-related GDM risk factor [P = 0.009, Exp (B): 1.56, 95% CI: 1.12-2.18]. Blastocyst transfer after in vitro fertilization/intracytoplasmic sperm injection increases the risk of developing GDM.


Purification and characterisation of an extracellular beta-glucosidase with transglycosylation and exo-glucosidase activities from Fusarium oxysporum.
An extracellular beta-glucosidase from Fusarium oxysporum was purified to homogeneity by gel-filtration and ion-exchange chromatographies. The enzyme, a monomeric protein of 110 kDa, was maximally active at pH 5.0-6.0 and at 60 degrees C. It hydrolysed 1-->4-linked aryl-beta-glucosides and 1-->4-linked, 1-->3-linked and 1-->6-linked beta-glucosides. The apparent Km and kcat values for p-nitrophenyl beta-D-glucopyranoside (4-NpGlcp) and cellobiose were 0.093 (Km), 1.07 mM (kcat) and 1802 (Km), 461.5 min-1 (kcat), respectively. Glucose and gluconolactone inhibited the enzyme competitively with Ki values of 2.05 mM and 3.03 microM, respectively. Alcohols activated the enzyme; butanol showed maximum effect (2.2-fold at 0.5 M) while methanol increased the activity by 1.4-fold at 1 M. The enzyme catalysed the synthesis of methylglucosides, ethylglucoside and propylglucosides, as well as trisaccharides in the presence of different alcohols and disaccharides, respectively. In addition, the enzyme hydrolysed the unsubstituted and methylumbelliferyl cello-oligosaccharides [MeUmb(Glc)n] but the rate of hydrolysis decreased with increasing chain length. Analysis of products released from MeUmb(Glc)n as a function of time revealed that the enzyme attacked these substrates in a stepwise manner and from both ends. Thus, beta-glucosidase from F. oxysporum, with the above interesting properties, could be of commercial interest.


Equality in health care: Christian engagement with a secular obsession.
A frenetic search for equality lies at the center of much secular and even "Christian" bioethics. In a secular world, if one does not believe in God, if this life is one's whole existence, it would seem that one could not settle for less than equal approbation, especially equality before the risks of suffering and death, which medicine promises to ameliorate. Yet, the concern for equality in health care is puzzling. After a modest level of access to health care there is little difference in average life expectancy. Are concerns for equality in health care even vaguely Christian? The pursuit of Christian perfection has never been correctly equated with state-imposed egalitarianism. Furthermore, an all-encompassing, secular, egalitarian health care system may provide equal access to significantly immoral medical treatments. In contrast to secular thought, the call of Christianity is a call to holiness, not a call to an egalitarianism that superficially resonates with certain elements of Christian thought.


Incidence, risk factors and outcomes of new-onset atrial fibrillation in patients with sepsis: a systematic review.
Critically ill patients with sepsis are prone to develop cardiac dysrhythmias, most commonly atrial fibrillation (AF). Systemic inflammation, circulating stress hormones, autonomic dysfunction, and volume shifts are all possible triggers for AF in this setting. We conducted a systematic review to describe the incidence, risk factors and outcomes of new-onset AF in patients with sepsis. MEDLINE, EMBASE and Web Of Science were searched for studies reporting the incidence of new-onset AF, atrial flutter or supraventricular tachycardia in patients with sepsis admitted to an intensive care unit, excluding studies that primarily focused on postcardiotomy patients. Studies were assessed for methodological quality using the GRADE system. Risk factors were considered to have a high level of evidence if they were reported in ≥ 2 studies using multivariable analyses at a P value <0.05. Subsequently, the strength of association was classified as strong, moderate or weak, based on the reported odds ratios. Eleven studies were included. Overall quality was low to moderate. The weighted mean incidence of new-onset AF was 8% (range 0 to 14%), 10% (4 to 23%) and 23% (6 to 46%) in critically ill patients with sepsis, severe sepsis and septic shock, respectively. Independent risk factors with a high level of evidence included advanced age (weak strength of association), white race (moderate association), presence of a respiratory tract infection (weak association), organ failure (moderate association), and pulmonary artery catheter use (moderate association). Protective factors were a history of diabetes mellitus (weak association) and the presence of a urinary tract infection (weak association). New-onset AF was associated with increased short-term mortality in five studies (crude relative effect estimates ranging from 1.96 to 3.32; adjusted effects 1.07 to 3.28). Three studies reported a significantly increased length of stay in the ICU (weighted mean difference 9 days, range 5 to 13 days), whereas an increased risk of ischemic stroke was reported in the single study that looked at this outcome. New-onset AF is a common consequence of sepsis and is independently associated with poor outcome. Early risk stratification of patients may allow for pharmacological interventions to prevent this complication.


Torquetenovirus infection among northeastern Thai blood donors.
Semi-nested polymerase chain reaction technique was used to detect Torquetenovirus (TTV) DNA in 234 healthy blood donors in northeast Thailand. The incidence of TTV was 28% in 101 healthy blood donors negative for HBsAg and anti-HCV antibody, 25% in 71 HBsAg carriers and 29% among 62 with anti-HCV antibody. No association of TTV infection was found with gender, age, and HBV or HCV infection.


Formation of tRNA Wobble Inosine in Humans Is Disrupted by a Millennia-Old Mutation Causing Intellectual Disability.
The formation of inosine at the wobble position of eukaryotic tRNAs is an essential modification catalyzed by the ADAT2/ADAT3 complex. In humans, a valine-to-methionine mutation (V144M) in ADAT3 that originated ∼1,600 years ago is the most common cause of autosomal recessive intellectual disability (ID) in Arabia. While the mutation is predicted to affect protein structure, the molecular and cellular effects of the V144M mutation are unknown. Here, we show that cell lines derived from ID-affected individuals expressing only ADAT3-V144M exhibit decreased wobble inosine in certain tRNAs. Moreover, extracts from the same cell lines of ID-affected individuals display a severe reduction in tRNA deaminase activity. While ADAT3-V144M maintains interactions with ADAT2, the purified ADAT2/3-V144M complexes exhibit defects in activity. Notably, ADAT3-V144M exhibits an increased propensity to form aggregates associated with cytoplasmic chaperonins that can be suppressed by ADAT2 overexpression. These results identify a key role for ADAT2-dependent folding of ADAT3 in wobble inosine modification and indicate that proper formation of an active ADAT2/3 complex is crucial for proper neurodevelopment.


Alternative dental casting alloys.
The diversity of alloys available to the dental practitioner has never been more extensive. We now have the opportunity to select alloys based on the individual patient's specific biologic, functional, and economic requirements. There is no one alloy suitable for all applications, because in metallurgy there is a constant trade-off in properties as changes in formulations are made. To make optimal use of the choices available, and for ethical and medicolegal considerations, it is incumbent upon the practitioner to be aware of the identity and composition of the alloys prescribed.


A preliminary study of the bioactivity of vegetative proteins extracted from Malaysian Bacillus thuringiensis isolates.
Vegetative proteins from Malaysian strains of Bacillus thuringiensis israelensis strains (Bt 11, Bt 12, Bt 15, Bt 16, Bt 17, Bt 21 and Bt 22) and Bacillus sphaericus H-25 strains (Bs 1 and Bs 2) were screened for haemolytic, cytotoxic and larvicidal activity. SDS-PAGE profiles of the Bacillus thuringiensis strains studied consistently showed major bands of 33-37 kDa and 47 kDa. Bt 16 also showed two bands of 66 kDa and 45 kDa similar to the previously reported binary vegetative protein, Vip1Ac (66 kDa) and Vip 2Ac (45 kDa). Both the Bacillus sphaericus strains showed a 35 kDa band that was similiar to a previously reported vegetative protein, the Mtx2 protein. Bs 2 also contains a 37 kDa band, similar to another vegetative protein, the Mtx 3 protein. With the exception of Bt 17 and Bt 21, vegetative proteins from all Bacillus thuringiensis and Bacillus sphaericus strains were highly haemolytic to human erythrocytes, causing more than 75% haemolysis at the highest concentration of 200 microg/ml. High haemolytic activity was associated with high cytotoxic activity with most of the haemolytic strains being indiscriminately cytotoxic to both CEM-SS (human T lymphoblastoid) and HeLa (human uterus cervical cancer) cell lines. Interestingly, the less haemolytic vegetative proteins from Bt 17 and Bt 21 demonstrated cytotoxic activity comparable to that of the highly haemolytic vegetative proteins. Bt 21 displayed toxicity towards both cell lines while Bt 17 was more toxic towards CEM-SS cells. Bioassay against Aedes aegypti and Culex quinquefasciatus larvae revealed that vegetative proteins from the Bacillus thuringiensis strains had activity against both species of larvae but vegetative proteins from Bacillus sphaericus were weakly larvicidal towards Cx. quinquefasciatus only.


Parental caregivers of children with developmental disabilities mount a poor antibody response to pneumococcal vaccination.
In older populations, caregiving for a spouse with dementia has been associated with a poor antibody response to vaccination. The present study examined whether younger caregivers, specifically the parents of children with developmental disabilities, would also show a diminished antibody response to vaccination. At baseline assessment, 30 parents of children with developmental disabilities and 29 parents of typically developing children completed standard measures of depression, perceived stress, social support, caregiver burden, and child problem behaviours. They also provided a blood sample and were then vaccinated with a pneumococcal polysaccharide vaccine. Further blood samples were taken at 1- and 6-month follow-ups. Caregivers mounted a poorer antibody response to vaccination than control parents at both follow-ups. This effect withstood adjustment for a number of possible confounders and appeared to be, at least in part, mediated by child problem behaviours. The negative impact of caregiving on antibody response to vaccination is not restricted to older spousal caregivers, but is also evident in younger parents caring for children with developmental disabilities. The behavioural characteristics of the care recipients may be a key consideration in whether or not immunity is compromised in this context.


Modulus and chemical mapping of multilayer coatings.
Thermoplastic olefins (TPOs) are polymeric materials utilized for interior and exterior automotive parts. These materials are often painted to protect and enhance their appearance. TPO materials possess a low surface energy because of the aliphatic backbone, and adhesion promoters (APs), such as chlorinated polyolefins, are used to increase paint adhesion and improve paint performance. The impact of the AP structure and processing conditions on the mechanical properties and degree of interpenetration was investigated on cross sectioned coatings. The AP structure was varied by the chlorine content and molecular weight for the same TPO and polyester acrylic, melamine-cured paint system. Two different processing conditions were investigated. Mechanical properties were measured using depth-sensing indentation. Long-range diffusion of coating components across each interface was verified with confocal Raman microscopy. The AP interfaces, AP/base coat and AP/TPO, were chemically and mechanically sharp at the 1 mum lateral resolution of both techniques. Depth-sensing indentation measured a modulus gradient across the top coating cross section. The free air surface of the top coat had a higher modulus than the interior. Processing conditions and polishing to prepare the cross section for measurements were found to affect only the control AP.


Survey datasets on the externalizing behaviors of primary school pupils and secondary school students in some selected schools in Ogun State, Nigeria.
This data article contains the partial analysis (descriptive statistics) of data obtained from 1770 primary school pupils and secondary school students in three Local Government Areas of Ogun State, Nigeria. The schools are either privately owned or public (government owned) schools. The aim of the field survey is to measure the level and patterns of externalizing behavior of the respondents. The data was collected using a standardized questionnaire. The questionnaire is a modification of Achenbach manual for Child behavior checklist (Achenbach, 2001) [1] and manual for Youth self-report (Achenbach and Rescorla, 2001) [2]. The questionnaire was designed to suit the demographic and socio-cultural nature of the target population. Analysis of the data can provide useful insights to the patterns of externalizing behavior of primary school pupils and secondary school students.


Workplace Exposures and Cognitive Function During Adulthood: Evidence From National Survey of Midlife Development and the O*NET.
Expand understanding of the role of selected workplace exposures (ie, occupational complexity, conflict in the workplace, pace of work, and physical hazards) in adults' cognitive function. Cross-sectional data (n = 1991) from the second wave of the Midlife in the United States (MIDUS) study; restricted to participants who completed telephone-based cognitive assessments of episodic memory, executive functioning, and self-perceived memory. Occupational exposure data were harvested from the ONET Release 6.0. Greater complexity was associated with better self-perceived memory among women and men, and better episodic memory and executive functioning among women. Greater physical hazards were independently associated with poorer episodic memory and executive functioning. Objective assessments of physical and psychosocial exposures in the workplace are independently associated with cognitive outcomes in adulthood, with psychosocial exposures being particularly pronounced among women.


Tubular Structure Segmentation via Multi-Scale Reverse Attention Sparse Convolution.
Cerebrovascular and airway structures are tubular structures used for transporting blood and gases, respectively, providing essential support for the normal activities of the human body. Accurately segmenting these tubular structures is the basis of morphology research and pathological detection. Nevertheless, accurately segmenting these structures from images presents great challenges due to their complex morphological and topological characteristics. To address this challenge, this paper proposes a framework UARAI based on the U-Net multi-scale reverse attention network and sparse convolution network. The framework utilizes a multi-scale structure to effectively extract the global and deep detail features of vessels and airways. Further, it enhances the extraction ability of fine-edged features by a joint reverse attention module. In addition, the sparse convolution structure is introduced to improve the features' expression ability without increasing the model's complexity. Finally, the proposed training sample cropping strategy reduces the influence of block boundaries on the accuracy of tubular structure segmentation. The experimental findings demonstrate that the UARAI-based metrics, namely Dice and IoU, achieve impressive scores of 90.31% and 82.33% for cerebrovascular segmentation and 93.34% and 87.51% for airway segmentation, respectively. Compared to commonly employed segmentation techniques, the proposed method exhibits remarkable accuracy and robustness in delineating tubular structures such as cerebrovascular and airway structures. These results hold significant promise in facilitating medical image analysis and clinical diagnosis, offering invaluable support to healthcare professionals.


Participation in a farmers' market fruit and vegetable prescription program at a federally qualified health center improves hemoglobin A1C in low income uncontrolled diabetics.
Fruit and vegetable prescription programs have been shown to increase consumption of fresh produce, but whether they have an impact on medical outcomes is unknown. The purpose of this study was to examine the role of participation in a farmers' market and fruit and vegetable prescription program on changes in hemoglobin A1C (HbA1C), blood pressure (BP) and weight in patients with uncontrolled type 2 diabetes at a federally qualified health center (FQHC) in Detroit, MI. The 13-week Fresh Prescription program (June 2015-October 2015) was designed to improve access and consumption of produce among low-income patients with uncontrolled type 2 diabetes. The program allotted up to $40 ($10 per week for up to four weeks) for purchase of produce from a FQHC located farmers' market. Adult, non-pregnant patients with a history of type 2 diabetes that had an elevated HbA1C > 6.5 within three months before Fresh Prescription program were eligible to participate. HgA1c, BP and weight were collected within three months of program start and within three months of completion. There were 65 eligible participants with complete biometric data. A statistically significant (p = 0.001) decrease in HbA1C was found (9.54% to 8.83%). However, weight (208.3 lbs. to 209.0 lbs.) and BP (135.1/79.3 mm Hg to 135.8/77.6 mm Hg) did not change from pre- to post-study (p > 0.05). Access to a fruit and vegetable prescription program over a 13-week period led to decreased HbA1C concentrations in uncontrolled type 2 diabetic patients living in an urban area of predominately-lower socioeconomic status.


Relevance of the Viborg Population Based Screening Programme (VISP) for Cardiovascular Conditions Among 67 Year Olds: Attendance Rate, Prevalence, and Proportion of Initiated Cardiovascular Medicines Stratified By Sex.
To report sex specific overall attendance rate, prevalence of screen detected cardiovascular conditions, proportion of unknown conditions before screening, and proportion initiating prophylactic medicine among 67 year olds in Denmark. Cross sectional cohort study. Since 2014, all 67 year olds in Viborg, Denmark, have been invited to screening for abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), carotid plaque (CP), hypertension, cardiac disease, and type 2 diabetes. Individuals with AAA, PAD, and or CP are recommended cardiovascular prophylaxis. Combining data with registries has facilitated estimation of unknown screen detected conditions. Up to August 2019, 5 505 had been invited; registry data were available for the first 4 826 who were invited. The attendance rate was 83.7%, without sex difference. Screen detected prevalence was significantly lower among women than men: AAA, 5 (0.3%) vs. 38 (1.9%) (p < .001); PAD, 90 (4.5%) vs. 134 (6.6%) (p = .011); CP, 641 (31.8%) vs. 907 (44.8%) (p < .001); arrhythmia, 26 (1.4%) vs. 77 (4.2%) (p < .001); blood pressure ≥ 160/100 mmHg, 277 (13.8%) vs. 346 (17.1%) (p = .004); and HbA1c ≥ 48 mmol/mol, 155 (7.7%) vs. 198 (9.8%) (p = .019), respectively. Pre-screening proportions of unknown conditions were particularly high for AAA (95.4%) and PAD (87.5%). AAA, PAD, and or CP were found in 1 623 (40.2%), of whom 470 (29.0%) received pre-screening antiplatelets and 743 (45.8%) lipid lowering therapy. Furthermore, 413 (25.5%) started antiplatelet therapy and 347 (21.4%) started lipid lowering therapy. Only smoking was significantly associated with all vascular conditions in multivariable analysis: odds ratios (ORs) for current smoking were AAA 8.11 (95% CI 2.27 - 28.97), PAD 5.60 (95% CI 3.61 - 8.67) and CP 3.64 (95% CI 2.95 - 4.47). The attendance rate signals public acceptability for attending cardiovascular screening. Men had more screen detected conditions than women, but prophylactic medicine was started equally frequently in both sexes. Sex specific cost effectiveness follow up is warranted.


Superior Sagittal Sinus Thrombosis in a Patient With Iatrogenic Intracranial Hypotension: A Case Report.
Cerebral venous thrombosis is a rarely reported complication of iatrogenic intracranial hypotension. We discuss a rare case of a 46-year-old woman presenting with a week-long history of severe orthostatic headaches two weeks following L4-L5 microscopic discectomy for symptomatic lumbar disc herniation. Computed tomography venography of the head revealed evidence of superior sagittal sinus thrombosis while contrast-enhanced magnetic resonance imaging of the brain revealed signs of intracranial hypotension consisting of pachymeningeal enhancement, bilateral subdural hygromas, enlarged pituitary gland, effacement of the basal ambient cisterns, and low-lying cerebellar tonsils. Additional lumbar spine imaging revealed the culprit to be a large epidural fluid collection extending from the epidural space to the superficial subcutaneous fat, suggestive of a cerebrospinal fluid leak. The patient was managed with admission, bed rest, isotonic intravenous fluids, caffeine, and therapeutic dosing of low molecular weight heparin. In such cases, clinical suspicion and early recognition and management are of paramount importance to prevent devastating consequences. Management, whether conservatively or with surgical intervention, should be made on a case-by-case basis.


Sodium chloride enhanced oligomerization of L-glutamic acid in aqueous solution.
The presence of NaCl was found to significantly enhance the formation of longer peptides in N,N'-carbonyldiimidazole induced oligomerization of L-glutamic acid in homogeneous aqueous solution. The enhancement was detected in the presence of as low as 0.01-M NaCl and the highest yield of longer oligomers was achieved in the presence of 1-M NaCl. The possible prebiotic relevance is discussed.


Optimized broadband wide-angle absorber structures.
By introducing the notion of wavelength- and angle-averaged absorptance, we assess in a systematic way the possibility of achieving wide-angle absorptance in a spectral range. We determine the optimum thicknesses for which this broadband wide-angle absorption occurs for a representative example of infrared detector.


A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.
To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays. The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF. SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution. The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.


Recovery mechanism of postural disturbance after vestibular neurectomy.
Sectioning of the unilateral vestibular nerve of the bull frog resulted in tilting of the head and the body. The angle of head tilt was periodically measured. The angle returned to 0 degree in an average of 7.3 weeks. A morphological study demonstrated normal structure of the sensory epithelia and a well-regenerated nerve bundle. Also, discrete action potentials could be recorded from the nerve centrally to the cut site of the vestibular nerve. These results indicate that recovery from the tilting involves two mechanisms, one being central compensation and the other reactivation of the sensory cell-nerve unit.


A new hemiterpene glycoside from the ripe tomatoes.
A new hemiterpene glycoside (1) was isolated from ripe tomatoes (the fruit of Lycopersicon esculentum, Solanaceae) along with eight known compounds. The chemical structure of 1 was determined to be 2-methylbutan-1-ol β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside, based on spectroscopic data as well as chemical evidence. In addition, the radical-scavenging activities of the isolated compounds on the free radical of 1,1-diphenyl-2-picrylhydrazyl were examined. Among the tested compounds, tryptophan, 4-O-β-d-glucopyranosyl caffeic acid and dihydro-p-coumaryl alcohol γ-O-β-d-glucopyranoside demonstrated 42.0%, 50.1% and 76.0% scavenging activities, respectively, at a concentration of 0.5 mM.


Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis.
The multifunctional growth factor scatter factor/hepatocyte growth factor (SF/HGF) and its receptor tyrosine kinase c-Met have emerged as key determinants of brain tumor growth and angiogenesis. SF/HGF and c-Met are expressed in brain tumors, the expression levels frequently correlating with tumor grade, tumor blood vessel density, and poor prognosis. Overexpression of SF/HGF and/or c-Met in brain tumor cells enhances their tumorigenicity, tumor growth, and tumor-associated angiogenesis. Conversely, inhibition of SF/HGF and c-Met in experimental tumor xenografts leads to inhibition of tumor growth and tumor angiogenesis. SF/HGF is expressed and secreted mainly by tumor cells and acts on c-Met receptors that are expressed in tumor cells and vascular endothelial cells. Activation of c-Met leads to induction of proliferation, migration, and invasion and to inhibition of apoptosis in tumor cells as well as in tumor vascular endothelial cells. Activation of tumor endothelial c-Met also induces extracellular matrix degradation, tubule formation, and angiogenesis in vivo. SF/HGF induces brain tumor angiogenesis directly through only partly known mechanisms and indirectly by regulating other angiogenic pathways such as VEGF. Different approaches to inhibiting SF/HGF and c-Met have been recently developed. These include receptor antagonism with SF/HGF fragments such as NK4, SF/HGF, and c-Met expression inhibition with U1snRNA/ribozymes; competitive ligand binding with soluble Met receptors; neutralizing antibodies to SF/HGF; and small molecular tyrosine kinase inhibitors. Use of these inhibitors in experimental tumor models leads to inhibition of tumor growth and angiogenesis. In this review, we summarize current knowledge of how the SF/HGF:c-Met pathway contributes to brain tumor malignancy with a focus on glioma angiogenesis.


Postextubation laryngeal edema: a review with consideration for home discharge.
Respiratory complications occurring in the immediate postoperative period are well known to the seasoned postanesthesia care unit nurse. The most common adverse respiratory events originating in this setting are airway obstruction, hypoventilation, hypoxemia, and pulmonary aspiration of gastric contents. The focus of this article details airway compromise secondary to edema of the larynx and adjacent structures as a consequence of translaryngeal intubation. Postextubation laryngeal edema is a relatively rare problem; however, severe episodes may have life-threatening ramifications. A review of pertinent airway anatomy and airflow dynamics as they relate to this compromised airway condition is presented. Risk factors for the development of postextubation laryngeal edema plus contemporary patient treatment strategies will be reinforced. Patient management issues are addressed, with emphasis placed on the ambulatory patient in which discharge to a remote location is anticipated.


Nondissipative diffusion of lattice solitons out of thermal equilibrium.
We perform Langevin dynamics simulations for pulse solitons on atomic chains with anharmonic nearest-neighbor interactions. After switching off noise and damping after a sufficiently long time, the solitons are only influenced by the thermal phonon bath which had been created by the noise. The soliton diffusion constant D is considerably smaller than before the switch-off, and it is proportional to the square of the temperature T , in contrast to the diffusion due to the noise which is proportional to T . We derive a diffusion equation for a soliton which is scattered elastically in an ensemble of phonons and derive general expressions for D and for the drift velocity v(d) . These expressions can be evaluated for the case of the Toda lattice for which the soliton shift due to the phonon scattering is known explicitly. D is indeed proportional to T2 and agrees well with the simulation results, while v(d) is much smaller than the soliton velocity and cannot be measured in the simulations due to the large fluctuations of the soliton position. We express D in terms of soliton characteristics which are known also for solitons on other anharmonic chains in the continuum limit: namely, velocity, amplitude, and width. The results agree well with the simulations if the soliton shape is the same as in the Toda case. If the shape is different, only an estimate of the order of magnitude can be given.


Echocardiography has low utility in cancer patients with Staphylococcus aureus bacteraemia: findings from a retrospective study.
To describe the incidence of infective endocarditis (IE) detected on echocardiography in cancer patients with confirmed Staphylococcus aureus bacteraemia (SAB). We retrospectively identified 95 cases of SAB in cancer patients from January 2007-March 2016. Echocardiography was ordered at the discretion of the treating team, and positive findings defined according to the Modified Duke Criteria. Complicated bacteraemia was defined by prolonged bacteraemia, presence of intracardiac device/prosthetic valve, or signs of metastatic infection. Major predisposing risk factors for IE (intracardiac device, prosthetic valve, valvular disease, diabetes mellitus, renal dialysis) were present in 27% of cases. Fifty-one of 95 (54%) had a central venous catheter and 17 (18%) patients had complicated bacteraemia. Echocardiography was performed in 75/95 (79%) episodes, with transthoracic echocardiography (TTE) alone in 56, transoesophageal echocardiography (TOE) alone in 4 and both in 15. Echocardiography was diagnostic for IE in 2 patients (1 TTE, 1 TOE), including one result that led to the diagnosis of IE in a clinically unsuspected case. Four further cases of IE were diagnosed on clinical findings, resulting in an overall rate of IE of 6% (6/95). Five of these cases occurred in patients with complicated bacteraemia or ≥ 1 risk factor for IE. No patient was readmitted due to IE. IE is infrequent in cancer patients with uncomplicated SAB and no risk factors for IE. Performing echocardiography routinely in all cancer patients with SAB rarely alters diagnosis or affects antibiotic management and therefore should be reserved for patients with specific risk factors.


Self-assembly of one- and two-dimensional hemoprotein systems by polymerization through heme-heme pocket interactions.
Supramolecular protein polymers: When a heme moiety was introduced to the surface of an apo-cytochrome b(562)(H63C) mutant, supramolecular polymers formed through noncovalent heme-heme pocket interactions. The incorporation of a heme triad as a pivot molecule in the protein polymer further led to a two-dimensional protein network structure, which was visualized by tapping-mode atomic force microscopy (see picture).


Small-molecule inducer of β cell proliferation identified by high-throughput screening.
The identification of factors that promote β cell proliferation could ultimately move type 1 diabetes treatment away from insulin injection therapy and toward a cure. We have performed high-throughput, cell-based screens using rodent β cell lines to identify molecules that induce proliferation of β cells. Herein we report the discovery and characterization of WS6, a novel small molecule that promotes β cell proliferation in rodent and human primary islets. In the RIP-DTA mouse model of β cell ablation, WS6 normalized blood glucose and induced concomitant increases in β cell proliferation and β cell number. Affinity pulldown and kinase profiling studies implicate Erb3 binding protein-1 and the IκB kinase pathway in the mechanism of action of WS6.


Treatment-Resistant Depression (TRD): Is the Opioid System Involved?
About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed.


Alkali-metal thiogermanates: sodium channels and variations on the La3CuSiS7 structure type.
Five new isotypic quaternary chalcogenides containing rare-earth metal atoms crystallizing in the hexagonal noncentrosymmetric space group P6(3) (No. 173) with the La(3)CuSiS(7) structure type have been synthesized by reacting the appropriate anhydrous rare-earth trichloride with sodium thiogermanate, Na(2)GeS(3). The reaction between LnCl(3) and Na(2)GeS(3) in an evacuated fused-silica ampule produced high yields of good-quality crystals of NaLn(3)GeS(7) [Ln = Ce (I), Nd (II), Sm (III), Gd (IV), and Yb (V)], while a similar reaction between EuCl(3) and Na(2)GeS(3) yielded a quinary chloride thiogermanate, Na(1.2)Eu(3.4)Cl(2)Ge(3)S(9) (VI), incorporating a cyclic trimeric Ge(3)S(9) building unit and adopting a structure related to La(3)CuSiS(7). The crystal structure of the compounds comprises a complex network of bicapped trigonal-prismatic LnS(8) and GeS(4) tetrahedra, which creates channels along the [001] direction. The Na(+) cations reside in these channels within trigonally distorted octahedral coordination environments, surrounded by six S atoms. For compounds III-V, the temperature dependence of the magnetic susceptibility indicates that these compounds are paramagnetic with μ(eff). = 1.86, 8.01, and 3.87 μ(B), for III-V, respectively. The experimental μ(eff) for IV is close to the theoretical value of 7.94 for free Gd(3+) ions, while μ(eff) values for III and V deviate from their theoretical values of 0.86 and 4.54 μ(B) for Sm(3+) and Yb(3+) ions, respectively. These compounds are semiconductors with optical band gaps of around 1.3 eV for III and V. Extended Hückel calculations suggest that the valence band comprises primarily S 3p and the bottom of the conduction band is dominated by empty rare-earth 5d orbitals. Compound VI exhibits a sharp optical absorption of around 2.18 eV, which is attributed to the f → d transition of Eu(II). The effective magnetic moment of 7.94 μ(B)/Eu is in excellent agreement with the theoretical value of 7.94 μ(B) for the free Eu(2+) ion.


Selective autophagy.
While starvation-induced autophagy is thought to randomly degrade cellular components, under certain circumstances autophagy selectively recognizes, sequesters, and degrades specific targets via autophagosomes. This process is called selective autophagy, and it contributes to cellular homeostasis by degrading specific soluble proteins, supramolecular complexes, liquid-liquid phase-separated droplets, abnormal or excess organelles, and pathogenic invasive bacteria. This means that autophagy, like the ubiquitin-proteasome system, strictly regulates diverse cellular functions through its selectivity. In this short review, we focus on the mechanism of "selective" autophagy, which is rapidly being elucidated.


Coupling Laser Diode Thermal Desorption with Acoustic Sample Deposition to Improve Throughput of Mass Spectrometry-Based Screening.
The move toward label-free screening in drug discovery has increased the demand for mass spectrometry (MS)-based analysis. Here we investigated the approach of coupling acoustic sample deposition (ASD) with laser diode thermal desorption (LDTD)-tandem mass spectrometry (MS/MS). We assessed its use in a cytochrome P450 (CYP) inhibition assay, where a decrease in metabolite formation signifies CYP inhibition. Metabolite levels for 3 CYP isoforms were measured as CYP3A4-1'-OH-midazolam, CYP2D6-dextrorphan, and CYP2C9-4'-OH-diclofenac. After incubation, samples (100 nL) were acoustically deposited onto a stainless steel 384-LazWell plate, then desorbed by an infrared laser directly from the plate surface into the gas phase, ionized by atmospheric pressure chemical ionization (APCI), and analyzed by MS/MS. Using this method, we achieved a sample analysis speed of 2.14 s/well, with bioanalytical performance comparable to the current online solid-phase extraction (SPE)-based MS method. An even faster readout speed was achieved when postreaction sample multiplexing was applied, where three reaction samples, one for each CYP, were transferred into the same well of the LazWell plate. In summary, LDTD coupled with acoustic sample deposition and multiplexing significantly decreased analysis time to 0.7 s/sample, making this MS-based approach feasible to support high-throughput screening (HTS) assays.


Ethnicity moderates outcome in family focused treatment for pediatric obsessive compulsive disorder.
This study examined predictors and moderators of treatment outcome in a randomized controlled trial (RCT) comparing two active interventions for pediatric obsessive compulsive disorder that differed with respect to the focus and format of family intervention. We had a particular interest in the role of race/ethnicity in shaping outcomes given our relatively diverse sample composition and the limited prior work in this area. A total of 62 youths (Mean age = 12.71 years; 57 % male; 34 % non-white) were assigned to either a standard cognitive behavioral therapy (CBT) family intervention (ST) or to a tailored intervention designed for cases of OCD complicated by poor family functioning (Enhanced Family Therapy; ET). Treatment in both arms involved 12 sessions of exposure therapy; the family interventions differed. Predictor and moderator variables were chosen based on the extant literature. Minority status did not predict outcome, suggesting that overall, white and non-white youth had comparable treatment response. Race/ethnicity did, however, moderate response with non-white youth faring better in the ET arm of the study. In particular, minority youth in ET had, on average, post-treatment CYBOCS scores consistent with clinical remission whereas their ST counterparts were left with symptoms considered moderately severe. There were no predictors of treatment outcome. Minority status predicts poorer response to standard CBT across disorders, suggesting the need for possible treatment adaptations. The present findings highlight one avenue for matching patients to treatments that might optimize outcomes and underscore the value of family involvement in OCD treatment.


High-dose methylprednisolone treatment for acute graft-versus-host disease after bone marrow transplantation in adults.
High-dose methylprednisolone (HDMP) was used to treat 18 episodes of severe (grades III and IV) acute graft-versus-host disease (GVHD) that developed after allogeneic bone marrow transplantation in 12 patients with acute leukemia and in 2 with aplastic anemia. Most of the patients showed rapid improvement in GVHD, with complete resolution of the skin and gut manifestations. However, the response of liver disease to the treatment was slow and incomplete. Complications seen were interstitial pneumonia and fungal and viral infections. Seven patients survived for more than two months following the treatment of acute GVHD. Five of these became long-term survivors with a median survival of 22+ months (range 11-38 months); all five long-term survivors developed chronic GVHD and are alive at the time of this report. It appears that HDMP is an effective treatment for severe acute GVHD. However, its true efficacy can only be ascertained in a randomized study comparing high-dose and conventional-dose methylprednisolone.


[Analysis of the results of 1221 colonoscopies in the hospitals of Burkina Faso, 1994-1997].
The authors report the results of 1221 colonoscopies. It appears from their analysis that whereas functional diseases of the colon remain predominant and topical, organic diseases appear to be increasing in frequency (polyps, polyposis, rectocolic cancer, parasitical colitis, diverticulis). Inflammatory bowel diseases are also beginning to be seen. The reported cases of Crohn's disease and ulcerative colitis are, so far as they know, the first in their country.


The Relationship Between Perceptions of Physical Self-Worth, Subdomain Importance, and Physical Fitness in Adolescents With Low Motor Competence: An Exploratory Study.
Purpose: Adolescent perceptions of their physical self-worth (PSW) and the component domains draw upon physical attributes, such as motor competence, physical fitness, and self-perceptions, which in turn enhance the desire to engage in physical activity. Whilst these relationships have been researched in populations with typical motor development, little is known of the interplay of these contributors to PSW with those with low motor competence (LMC). Even less is known of how importance placed on particular physical subdomains may be used by the adolescent with LMC to mitigate negative effects on their perceptions of PSW. Method: Thirty-four adolescents with low motor competence, 25 boys and 9 girls (Mage = 13.89 yrs, SD = 1.49), completed the McCarron Assessment of Neuromuscular Development (MAND), the Children's Physical Self-Perception Questionnaire (C-PSPP) and a range of physical fitness tests. Results: All self-perception subdomain score was lower than importance ratings. Physical fitness measures were also low but were not significantly associated with PSW. However, the higher importance scores relative to physical self-perceptions resulted in greater discrepancy scores in all subdomains. Conclusion: Adolescents with LMC have low PSW, and low self-perceptions relative to importance ratings for most physical self-subdomains. These discrepancies, rather than actual fitness, potentially reduce their motivation to be physically active.


The purified GABA/benzodiazepine/barbiturate receptor complex: four types of ligand-binding sites, and the interactions between them, are preserved in a single isolated protein complex.
A GABA/benzodiazepine/barbiturate receptor complex has been purified from bovine cerebral cortex by affinity chromatography on a benzodiazepine column. Depending on the detergent present during the isolation of the receptor (deoxycholate/Triton X-100 or CHAPS/Asolectin), and during the binding assays (Triton X-100 or CHAPS), the receptor displays different binding properties for the GABAA agonist [3H]muscimol and for the chloride ion channel blocking agent [35S]t-butylbicyclophosphorothionate (TBPS), whereas the binding properties for the benzodiazepine [3H]flunitrazepam are independent of isolation and assay conditions. Both methods of isolation yield a protein complex consisting of the same two subunits of Mr 53 000 and Mr 57 000. Therefore the different binding properties reflect different conformations of the isolated receptor protein. [3H]flunitrazepam binding to the CHAPS-purified receptor is stimulated by GABA and the barbiturate pentobarbital in a dose-dependent manner. Photo-affinity labeling of the purified receptor with [3H]flunitrazepam leads to incorporation of radioactivity into both subunits, but predominantly into the Mr 53 000 band, as shown by fluorography. Proteolytic degradation by trypsin of the isolated photo-affinity labeled receptor in detergent solution proceeds via a labeled Mr 48 000 polypeptide. Proteolytic destruction of the reversible [3H]flunitrazepam and [3H]muscimol binding activities requires greater than 100 fold higher concentrations of trypsin than the decomposition of the receptor polypeptides into fragments less than Mr 10 000.


Metabolic engineering of carotenoid biosynthesis in Escherichia coli by ordered gene assembly in Bacillus subtilis.
We attempted to optimize the production of zeaxanthin in Escherichia coli by reordering five biosynthetic genes in the natural carotenoid cluster of Pantoea ananatis. Newly designed operons for zeaxanthin production were constructed by the ordered gene assembly in Bacillus subtilis (OGAB) method, which can assemble multiple genes in one step using an intrinsic B. subtilis plasmid transformation system. The highest level of production of zeaxanthin in E. coli (820 microg/g [dry weight]) was observed in the transformant with a plasmid in which the gene order corresponds to the order of the zeaxanthin metabolic pathway (crtE-crtB-crtI-crtY-crtZ), among a series of plasmids with circularly permuted gene orders. Although two of five operons using intrinsic zeaxanthin promoters failed to assemble in B. subtilis, the full set of operons was obtained by repressing operon expression during OGAB assembly with a p(R) promoter-cI repressor system. This result suggests that repressing the expression of foreign genes in B. subtilis is important for their assembly by the OGAB method. For all tested operons, the abundance of mRNA decreased monotonically with the increasing distance of the gene from the promoter in E. coli, and this may influence the yield of zeaxanthin. Our results suggest that rearrangement of biosynthetic genes in the order of the metabolic pathway by the OGAB method could be a useful approach for metabolic engineering.


Progression and Resolution of Delirium in Elderly Patients Hospitalized for Acute Care.
The authors describe the clinical course of delirium in 325 elderly patients hospitalized for acute care. Of those patients who developed DSM-III delirium (n = 91), over two-thirds of patients (69.2%) experienced a prodromal period of at least 1 day prior to meeting full DSM-III criteria. Clinical evidence of delirium frequently persisted after hospital discharge although there was evidence of lessening of the extent of symptoms over time. These findings have implications for discharge planners concerned with providing appropriate supports for those still experiencing delirium symptoms at the time of hospital discharge.


Ethosuximide inducted changes in the gastro-intestinal tract.
Ethosuximide is an alternative medicament that is used for coupling of petit mal, especially in childhood. Some clinical observations show that it has secondary effects on the gastro intestinal tract (GIT). The present research tries to define the characteristics of Ethosuximide--the inducted secondary effects on the GIT, and to explain some of the possible mechanisms that cause them. The changes that occur in the GIT of patients cured with Ethosuximide are registered roentgenologically. The main change is the atony of the stomach and intestines and the reduced peristaltic activity. The influence of Ethosuximide is examined on smooth muscular samples of human stomach, taken in vitro using stomach resection. The medicament authoritatively reduce the spontaneous bioelectrical activity of the smooth muscular tissue, influences mainly it's components that have Ca+ nature. Together with that is indicated relaxation of the smooth muscular samples. In that research is expressed the thesis that this Ethosuximide reduction of the Ca(+)-influx in the smooth muscular cells and the related relaxation probably are one of the main reasons of the secondary effects on the GIT.


Novel technique of cytolithotripsy for large bladder stones.
We evaluated a minimally invasive surgical technique involving a single percutaneous access with a laparoscopic trocar under video-cystoscopic vision for managing large bladder stones. All patients were candidates for open surgery. Fourteen patients with bladder stones larger than 3 cm in diameter or multiple stones were treated with this technique. The procedure involved the percutaneous placement of a laparoscopic trocar under cystoscopic control and the introduction of a rigid nephroscope into the bladder. Stones were cleansed via fragmentation or direct removal. The technique was successful in all cases, resulting in controlled, stone-free bladders; there were no surgical complications. The mean operation time was comparable to that of standard management. All patients discharged uneventfully. None reported urethral stricture during the 24-month follow-up period. Percutaneous cystolithotripsy under endoscopic control is easy to perform and should be considered as an alternative for large or multiple bladder stones as it decreases the risk of urethral stricture.


Characterization of glutamate decarboxylase from Lactobacillus plantarum and its C-terminal function for the pH dependence of activity.
The gadB gene encoding glutamate decarboxylase (GAD) from Lactobacillus plantarum was cloned and expressed in Escherichia coli. The recombinant enzyme exhibited maximal activity at 40 °C and pH 5.0. The 3D model structure of L. plantarum GAD proposed that its C-terminal region (Ile454-Thr468) may play an important role in the pH dependence of catalysis. Accordingly, C-terminally truncated (Δ3 and Δ11 residues) mutants were generated and their enzyme activities compared with that of the wild-type enzyme at different pH values. Unlike the wild-type GAD, the mutants showed pronounced catalytic activity in a broad pH range of 4.0-8.0, suggesting that the C-terminal region is involved in the pH dependence of GAD activity. Therefore, this study may provide effective target regions for engineering pH dependence of GAD activity, thereby meeting industrial demands for the production of γ-aminobutyrate in a broad range of pH values.


Antigenic determinants of human C4, Rodgers and Chido.
The duplicated genes, C4A and C4B, are located within the major histocompatibility complex on chromosome 6 and each exhibits a high degree of polymorphism expressed as both electrophoretic and antigenic variation (Rg/Ch). Eight high-frequency antigens and one low-frequency antigen have been defined by immune human polyspecific antisera in haemagglutination inhibition assays. Close association exists between different C4 allotypes and the antigens they express. Normally, C4A expresses Rg and C4B has Ch but rare reverse associations exist. Nucleotide sequences of the C4d region from C4 allotypes of known antigenic status have demonstrated four polymorphic sites that correlate with the antigens, which, in a structural model, are seen to be conformational or sequential epitopes. The observed interrelationships of the antigens on C4 allotypes accommodated by the model suggest that the electrophoretic variation is located outside the C4d region. The molecular genetics of C4 are also considered as part of the polymorphism.


Integrative and Conjugative Elements (ICEs): What They Do and How They Work.
Horizontal gene transfer plays a major role in microbial evolution, allowing microbes to acquire new genes and phenotypes. Integrative and conjugative elements (ICEs, a.k.a. conjugative transposons) are modular mobile genetic elements integrated into a host genome and are passively propagated during chromosomal replication and cell division. Induction of ICE gene expression leads to excision, production of the conserved conjugation machinery (a type IV secretion system), and the potential to transfer DNA to appropriate recipients. ICEs typically contain cargo genes that are not usually related to the ICE life cycle and that confer phenotypes to host cells. We summarize the life cycle and discovery of ICEs, some of the regulatory mechanisms, and how the types of cargo have influenced our view of ICEs. We discuss how ICEs can acquire new cargo genes and describe challenges to the field and various perspectives on ICE biology.


[A new stage of development of gerontology and geriatrics in Russia: problems of creation of a geriatric care system. Part 1. Relevance, regulatory infrastructure].
This article is a 1st part of the analytical review, focused on a new step in development of geriatrics in Russia. Creation of state system geriatric care as important part of state politics in the area of enhancement of quality of life was proved. General aspects of improvement of social support of disable elderly persons in condition of restricted budget and interagency separation was presented. Establishment of unified system of medical social support and gerotechnologies for the elderly was substantiated, as a mechanism facilitated life activity and decreasing of demographic loading on economic status of regions of Russian Federation. Legislative and normative regulations of gerontology and geriatric development were observed as well. Accepted legislative and normative acts were analyzed for period since 1977 to 2014. The necessity of approaches to regulation modernization for elderly was demonstrated. Analytical review on number of legislative state documents issued after meeting of Presidium of State Council of the Russian Federation being in August 2014 was also presented. Applicability of these documents for realization new strategy of gerontology and geriatrics development in Russia was proved.


Clinical Features of Breast Cancer Patients with Human T-Cell Lymphotropic Virus Type-1 Infection.
Background: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATL), an aggressive form of T-cell malignancy. The relationship between HTLV-1 infection and cancer progression is controversial. HTLV-1 encodes oncogenic protein TAX1 and it is hypothesized that HTLV-1 infection is associated with breast cancer progression. In this study, we evaluated the relationship between HTLV-1 infection and clinicopathological factors in breast cancer patients. Methods: We retrospectively analyzed 610 patients with primary breast cancer who underwent surgical treatment without preoperative chemotherapy at Kagoshima University Hospital between January 2001 and January 2015. Results: When patients with and without HTLV-1 infection were compared, no differences in clinicopathological factors were observed, except for age. Disease-free survival and overall survival rates did not differ between groups. Conclusions: HTLV-1–positive patients were significantly older than HTLV-1–negative patients. It was supposed to be due to the fact that the HTLV-1 infection rate is decreasing. Any effect of HTLV-1 infection on breast cancer progression appears to be negligibly small.


Enterobius vermicularis: a possible cause of symptoms resembling appendicitis.
The role of Enterobius vermicularis in appendicitis has been disputed. The aims of this retrospective study were to determine the prevalence of E. vermicularis in surgically removed appendices and to relate this to the age and sex of the patient, the time of the year, the presence of symptoms and the histological findings. The study included all appendices received in this laboratory during the 5 year period from 1984 through to 1988. There were 1867 appendices during this period of which 1108 were acutely inflamed and 759 were not inflamed (although 149 of these showed other pathological changes). The mean age distribution of all patients was 22.8 years. Enterobius vermicularis was identified in 63 appendices (3.4%). Infestation was more frequent in female (4.6%) than in male (1.9%) patients. The peak age was 12.8 years in females and 12.1 years in males. Of 63 patients who had E. vermicularis, 98% presented with symptoms of acute or recurrent appendicitis, yet 40 had no histological evidence of appendicitis or mucosal invasion by the parasite and only four had other possible explanations for abdominal pain. In an analysis of the subgroup of 147 patients who had incidental appendectomy at the time of laparotomy for other reasons, only one had E. vermicularis. It is concluded that E. vermicularis occurs more frequently in uninflamed appendices. It may be a cause of symptoms resembling acute appendicitis although the mechanism for this does not involve mucosal invasion by the parasite.


[Notch2 activation promotes osteoclastogenesis under high glucose concentration in vitro].
To study the effect of high glucose and mannitol (osmotic control) on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and Notch2 expression using bone marrow macrophages (BMMs) from mice. Furthermore, the effect of Notch2 activation on RANKL-induced osteoclastogenesis with high glucose concentration was explored. Preosteoclasts were cultured and exposed to sustained high glucose (0, 5, 10, 20, 40 mmol x L(-1)) levels to mimic diabetic conditions. Osteoclast formation was analyzed using tartrate resistant acid phosphatase (TRAP) assay. Expression of Notch2 gene was analyzed using real-time polymerase chain reaction. Constitutively over-expressed active Notch2, via stable transfection of exogenous ICN2 (intracellular fragment of Notch2) in preosteoclasts and the effect of Notch2 over expression on osteoclastogenesis was analyzed using Western blotting and TRAP staining. The osteoclast number with 20 mmol x L(-1) glucose (110.3 +/- 6.8) and 40 mmol x L(1) glucose (72.0 +/- 8.0) was significantly less than the group with 20mmol x L(-1) mannitol (152.7 +/- 7.0) and 40 mmol x L(-1) mannitol (157.0 +/- 12.5). The relative gene expression of Notch2 with 20 mmol x L(-1) glucose (1.65 +/- 0.23) and 40 mmol x L(-1) glucose (1.10 +/- 0.11) was significantly less than the group with 20 mmol x L(-1) mannitol (2.82 +/- 0.28) and 40 mmol x L(-1) mannitol (2.42 +/- 0.27) (P < 0.05). The osteoclast number after Notch2 activation (ICN2-OE) with 20 mmol x L(-1) glucose (206.7+/- 7.8) and 40 mmol x L(-1) glucose (178.3 +/- 11.5) was significantly more than the control group (EMPTY) (102.3 +/- 8.7 and 76.0 +/- 10.1 respectively) ( P < 0.05). Notch2 signaling activation may promote osteoclastogenesis under high glucose concentration.


Congenital factor XI deficiency with multiple tooth extractions (Case report).
Congenital factor XI deficiency (CFXI) is a rare blood disorder that occurs in one of every one million individuals. Given its rarity, there are very few reports of surgical procedures performed in the oral region CFXI patients. The present study reports the case of a 43-year-old man with CFXI who experienced multiple tooth extractions. It also conducted a review of the literature and treatment outline. We preoperatively administered fresh frozen plasma (FFP) before the tooth extraction and continued to transfuse FFP at the rate of 2 units per day from day 1 to 4 of admission. The extractions were divided into two parts, maxillary and mandibular and the teeth extracted on days 2 and 4 of admission. The patient was discharged on day 6 of admission because there was good progress and no postoperative bleeding. Therefore, it was possible to perform multiple tooth extractions without abnormal bleeding in the oral cavity; the chance of bleeding was reduced by administering FFP and increasing local hemostasis in CFXI patients.


The precautious nature of prestige: When leaders are hypervigilant to subtle signs of social disapproval.
Some group leaders exhibit hypervigilance to signs of social disapproval and that vigilance manifests at basic levels of social information processing such as visual attention and face perception. The current research tests hypotheses about when, why, and in whom such vigilance occurs. Across 2 pilot studies and 5 experiments (N = 1,667) we find that, when their social relationships are at stake, prestige-oriented leaders (but not dominance-oriented leaders) overperceive signs of social discontent and disapproval. When delivering public (but not private) critical feedback to subordinates, prestige-oriented leaders attended vigilantly to social cues, especially negative emotional expressions indicating social discontent (Experiment 1). When delivering public (but not private) critical feedback, prestige-oriented leaders were also biased toward perceiving smiles as disingenuous (Experiment 2). Experimental manipulations of prestige produced similar results, suggesting that an orientation toward prestige causes leaders to perceive smiles as disingenuous (Experiment 3), interpret neutral facial expressions as concealing negative, rather than positive, emotions (Experiment 4), and fixate their attention on social cues (Experiment 5). Consistent with error management theory, hypervigilance to signs of social discontent and disapproval may prompt prestige-oriented leaders to strengthen their social relationships and help them avoid losing the support of their group. These findings are among the first to illuminate basic cognitive processes underlying the psychology of prestige. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Changing social factors and their long-term implications for health.
This paper presents findings and arguments to show the power of social factors to affect health at the individual and at the national level. Social factors most strongly and negatively associated with health, at both levels, are those that indicate disorganisation and disruption, perceived helplessness and lack of support, low educational attainment, and poverty. Adverse changes in these social factors and their negative effects on health have been observed in many studies. When such adverse changes affect the lives and health of children, and those who will become parents, they affect the present and long-term future health of individuals because of the processes of biological programming described in this and other papers presented here. Such adverse changes in social factors also adversely affect the social circumstances of childhood, which in turn have a negative impact on health. Because changing social factors affect biological programming and social capitalisation, awareness of the health damaging effects of recent social change provides information on the future health of the population.


Pharmacokinetics of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules in De Novo Liver Transplant.
The pharmacokinetics of once-daily extended-release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open-label study, de novo liver transplant recipients were randomized to LCPT 0.07-0.13 mg/kg/day (taken once daily; n = 29) or twice-daily immediate-release tacrolimus capsules (IR-Tac) at 0.10-0.15 mg/kg/day (divided twice daily; n = 29). Subsequent doses of both drugs were adjusted to maintain tacrolimus trough concentrations of 5 to 20 ng/mL through day 90, and 5-15 ng/mL thereafter. Twenty-four-hour pharmacokinetic profiles were obtained on days 1, 7, and 14, with trough concentration and efficacy/safety monitoring through year 1. Similar proportions of patients in both groups achieved therapeutic trough concentrations on days 7 and 14 (day 7: LCPT = 78%, IR-Tac = 75%; day 14: LCPT = 86%, IR-Tac = 91%) as well as similar systemic and peak exposure. There was a robust correlation between drug concentration at time 0 and area under the concentration-time curve for both LCPT and IR-Tac (respectively, day 7: r = 0.86 and 0.79; day 14: r = 0.93 and 0.86; P < .0001 for all). Dose adjustments during days 1 to 14 were frequent. Thirty-five patients completed the extended-use period. No significant differences in adverse events were seen between groups. Incidence of biopsy-proven acute rejection (LCPT = 6 and IR-Tac = 4) was similar on day 360. Between formulations, overall exposure was similar at 1 week after transplant with the characteristic delayed-release pharmacokinetic profile of LCPT demonstrated in this novel population. These data support further investigation of the safety and efficacy of LCPT in de novo liver transplantation.


Real-time monitoring of intracellular redox changes in Methylococcus capsulatus (Bath) for efficient bioconversion of methane to methanol.
This study aimed to develop a novel method for real-time monitoring of the intracellular redox states in a methanotroph Methylococcus capsulatus, using Peredox as a genetically encoded fluorescent sensor of the NADH:NAD+ ratio. As expected, the fluorescence derived from the Peredox-expressing M. capsulatus transformant increased by supplementation of electron donor compounds (methane and formate), while it decreased by specifically inhibiting the methanol oxidation reaction. Electrochemical measurements confirmed that the Peredox fluorescence reliably represents the intracellular redox changes. This study is the first to construct a reliable redox-monitoring method for methanotrophs, which will facilitate to develop more efficient methane-to-methanol bioconversion processes.


Modelling the impact of blood flow on the temperature distribution in the human eye and the orbit: fixed heat transfer coefficients versus the Pennes bioheat model versus discrete blood vessels.
Prediction of the temperature distribution in the eye depends on how the impact of the blood flow is taken into account. Three methods will be compared: a simplified eye anatomy that applies a single heat transfer coefficient to describe all heat transport mechanisms between the sclera and the body core, a detailed eye anatomy in which the blood flow is accounted for either by the bioheat approach, or by including the discrete vasculature in the eye and the orbit. The comparison is done both for rabbit and human anatomies, normo-thermally and when exposed to homogeneous power densities. The first simplified model predicts much higher temperatures than the latter two. It was shown that the eye is very hard to heat when taking physiological perfusion correctly into account. It was concluded that the heat transfer coefficient describing the heat transport from the sclera to the body core reported in the literature for the first simplified model is too low. The bioheat approach is appropriate for a first-order approximation of the temperature distribution in the eye when exposed to a homogeneous power density, but the discrete vasculature down to 0.2 mm in diameter needs to be taken into account when the heterogeneity of the temperature distribution at a mm scale is of interest.


Tanshinones and their Derivatives: Heterocyclic Ring-Fused Diterpenes of Biological Interest.
The available scientific literature regarding tanshinones is very abundant, and after its review, it is noticeable that most of the articles focus on the properties of tanshinone I, cryptotanshinone, tanshinone IIA, sodium tanshinone IIA sulfonate and the dried root extract of Salvia miltiorrhiza (Tan- Shen). However, although these products have demonstrated important biological properties in both in vitro and in vivo models, their poor solubility and bioavailability have limited their clinical applications. For these reasons, many studies have focused on the search for new pharmaceutical formulations for tanshinones, as well as the synthesis of new derivatives that improve their biological properties. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2015) on tanshinones in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we offer an update on the last five years of new research on these quinones, focusing on their synthesis, biological activity on noncommunicable diseases and drug delivery systems, to support future research on its clinical applications.


Application of medical cases in general genetics teaching in universities.
General genetics is a core course in life sciences, medicine, agriculture and other related fields. As one of the most fast-developing disciplines of life sciences in the 21th century, the influence of the genetics knowledge on daily life is expanding, especially on human health and reproduction. In order to make it easier for students to understand the profound principles of genetics and to better apply the theories to daily life, we have introduced appropriate medical cases in general genetics teaching and further extended them combined with theoretical basis of genetics. This approach will be beneficial to enhance students' abilities of genetic analysis and promote their enthusiasm to learn and master practical skills. In this paper, we enumerate medical cases related to the modern genetics teaching system to provide a reference for genetics teaching in general and normal universities.


Cardiac Emergency Response Planning for Schools: A Policy Statement.
A sudden cardiac arrest in school or at a school event is potentially devastating to families and communities. An appropriate response to such an event-as promoted by developing, implementing, and practicing a cardiac emergency response plan (CERP)-can increase survival rates. Understanding that a trained lay-responder team within the school can make a difference in the crucial minutes between the time when the victim collapses and when emergency medical services arrive empowers school staff and can save lives. In 2015, the American Heart Association convened a group of stakeholders to develop tools to assist schools in developing CERPs. This article reviews the critical components of a CERP and a CERP team, the factors that should be taken into account when implementing the CERP, and recommendations for policy makers to support CERPs in schools.


Homology modeling with low sequence identity.
The field of protein structure prediction is evolving rapidly and in the last few years a number of new methods have been developed and evaluated. However, comparative modeling, or modeling by homology, is still the method of choice when the unknown protein shares any significant sequence similarity with a protein of known structure. The accuracy of the method is highly dependent on the degree of similarity between the target protein and that used as a template. Nevertheless, careful consideration of all the steps performed in the modeling procedure allows useful information to be obtained also from a model based on very low sequence identity.


Synchrotron μCT imaging of bone, titanium implants and bone substitutes - a systematic review of the literature.
Today X-ray micro computer tomography (μCT) imaging is used to investigate bone microarchitecture. μCT imaging is obtained by polychromatic X-ray beams, resulting in images with beam hardening artifacts, resolution levels at 10 μm, geometrical blurring, and lack of contrasts. When μCT is coupled to synchrotron sources (SRμCT) a spatial resolution up to one tenth of a μm may be achieved. A review of the literature concerning SRμCT was performed to investigate its usability and its strength in visualizing fine bone structures, vessels, and microarchitecture of bone. Although mainly limited to in vitro examinations, SRμCT is considered as a gold standard to image trabecular bone microarchitecture since it is possible in a 3D manner to visualize fine structural elements within mineralized tissue such as osteon boundaries, rods and plates structures, cement lines, and differences in mineralization.


Patterns of smoking among Singaporeans.
In the mid-seventies, a few base-line survey showed an average of about 25% of adults (aged 15 years and above) were regular smokers. Males predominated (6-8:1), prevalence increased with age reaching peak after 40 years and cigarette consumption was 16/day in males and 10/day in females. Malays tended to have higher smoking rates, so were those with little or no education. In 1984, a repeat survey showed the overall rate at 19% and the age-specific rates had declined, especially in the group above 40 years (by up to 30%). Again, in 1987, another survey showed the overall rate at 13.6% and age-specific rates declined by another 30% from 1984. With the National Smoking Control Programme at full steam, there is every prospect that we will be able to achieve our goal of becoming a nation of non-smokers.


Cell based therapies as compared to autologous bone grafts for spinal arthrodesis.
Systematic review. To compare the clinical outcome of cell based grafts combined with bone extenders to autologous bone grafts. Alternative graft options that combine mesenchymal stem cells (MSCs) and bone marrow aspirate (BMA) with synthetic or allograft scaffolds have been recently used in several animal and clinical studies. This systematic review of the literature addresses the following key questions (KQs): (1) Does the use of MSCs or BMA combined with synthetic or allograft extenders contribute to thoracolumbar fusion rates that are comparable with the rates achieved by the use of iliac crest graft? (2) Are these fusion rates comparable with those of local bone graft (LBG)? (3) Does the addition of MSCs or BMA to iliac crest bone graft or LBG contribute to better throracolumbar fusion rates? (4) Are the cervical spine fusion outcomes achieved by the use of SCM or BMA with synthetic or allograft scaffolds comparable with the iliac crest bone graft or LBG outcomes? (5) Was there any difference in terms of fusion rates, when MSCs were compared with BMA? For KQ1, 4 level II, III studies used iliac crest bone graft as control. The results of these studies were inconsistent, and the overall body of evidence was found insufficient. Three, level II, III studies were identified for KQ2. Comparable fusion rates were demonstrated between LBG and BMA combined with calcium phosphate or collagen carrier. The overall body of evidence was found weak. For KQ3, one level III study was found. No significant difference was found in the fusion rates. No studies met the criteria for KQ4, 5. The currently available evidence is insufficient to support the use of MSCs or BMA combined with synthetic or allograft materials as a substitute or supplementary graft to autologous bone graft. 2.


Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-{gamma} in Huh-7 cells.
Hepatitis C virus (HCV) core protein genotype 3a induces the expression of suppressor of cytokine signalling protein 7 (SOCS-7), which is partially involved in the development of insulin resistance. The aim of the present study was to investigate the mechanism through which the core protein regulates SOCS-7 expression. We have explored, in the in vitro model of Huh-7 cells expressing the HCV core protein of genotype 3a, whether the expression of SOCS-7 as well as of other members of the SOCS family (SOCS-1 and SOCS-3) was activated by the STAT3 pathway, using immunoblotting and real-time PCR upon alpha interferon (IFN-alpha) treatment. We found that, whilst IFN-alpha treatment induced STAT3 activation and consequently SOCS-1 and SOCS-3 upregulation in HCV genotype 3a core-expressing Huh-7 cells, SOCS-7 mRNA expression was independent of STAT3 and seemed to be modulated by peroxisome proliferator-activated receptor gamma (PPAR-gamma) activity, as demonstrated by quantitative real-time PCR and immunoblot detection after treatment with the PPAR-gamma agonist rosiglitazone or the PPAR-gamma antagonist GW9262. In contrast to the other studied members of the SOCS family (1 and 3), which are regulated by STAT3 activation, SOCS-7 expression appears to be STAT3-independent and seems to be regulated instead by PPAR-gamma. This is the first report proposing a molecular mechanism through which the HCV core protein (genotype 3a) modulates SOCS-7 expression.


The Neurostimulation of the Brain in Depression Trial: Protocol for a Randomized Controlled Trial of Transcranial Direct Current Stimulation in Treatment-Resistant Depression.
Major depressive disorder (MDD) is the second highest cause of disability worldwide. Standard treatments for MDD include medicine and talk therapy; however, approximately 1 in 5 Canadians fail to respond to these approaches and must consider alternatives. Transcranial direct current stimulation (tDCS) is a safe, noninvasive method that uses electrical stimulation to change the activation pattern of different brain regions. By targeting those regions known to be affected in MDD, tDCS may be useful in ameliorating treatment-resistant depression. The objective of the Neurostimulation of the Brain in Depression trial is to compare the effectiveness of active versus sham tDCS in treating patients with ultraresistant MDD. The primary outcome will be the improvement in depressive symptoms, as measured by the change on the Mongtomery-Asberg Depression Rating Scale. Secondary outcomes will include changes in the Quick Inventory of Depressive Symptomatology Scale (subjective assessment), the World Health Organization Disability Assessment Schedule 2.0 (functional assessment), and the Screen for Cognitive Impairment in Psychiatry (cognitive assessment). Adverse events will be captured using the Young Mania Rating Scale; tDCS Adverse Events Questionnaire; Frequency, Intensity, and Burden of Side Effects Rating Scale; and Patient-Rated Inventory of Side Effects Scale. A parallel component of the study will involve assaying for baseline language function and the effect of treatment on language using an exploratory acoustic and semantic corpus analysis on recorded interviews. Participant accuracy and response latency on an auditory lexical decision task will also be evaluated. We will recruit inpatients and outpatients in the city of Edmonton, Alberta, and will deliver the study interventions at the Grey Nuns and University of Alberta Hospitals. Written informed consent will be obtained from all participants before enrollment. Eligible participants will be randomly assigned, in a double-blinded fashion, to receive active or sham tDCS, and they will continue receiving their usual pharmacotherapy and psychotherapy throughout the trial. In both groups, participants will receive 30 weekday stimulation sessions, each session being 30 minutes in length, with the anode over the left dorsolateral prefrontal cortex and the cathode over the right. Participants in the active group will be stimulated at 2 mA throughout, whereas the sham group will receive only a brief period of stimulation to mimic skin sensations felt in the active group. Measurements will be conducted at regular points throughout the trial and 30 days after trial completion. The trial has been approved by the University of Alberta Research Ethics Board and is scheduled to commence in June 2021. The target sample size is 60 participants. This is a protocol for a multicenter, double-blinded, randomized controlled superiority trial comparing active versus sham tDCS in patients with treatment-resistant MDD. ClinicalTrials.gov NCT04159012; http://clinicaltrials.gov/ct2/show/NCT04159012. PRR1-10.2196/22805.