Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1----3Gal epitope in primates.
Anti-Gal is a natural antibody, which constitutes as much as 1% of circulating IgG in humans and displays a distinct specificity for the structure Gal alpha 1----3Gal. This glycosidic structure has been found on various tissues of many nonprimate mammals. A comparative study of the occurrence of anti-Gal versus the expression of the Gal alpha 1----3Gal epitope was performed in primates, and a distinct evolutionary pattern was observed. Whereas anti-Gal was found to be present in Old World monkeys and apes in titers comparable to those in humans, its corresponding antigenic epitope is abundantly expressed on erythrocytes of New World monkeys. Immunostaining with anti-Gal of glycolipids from New World monkey erythrocytes indicated that the molecules to which anti-Gal binds are similar to those found in rabbit and bovine erythrocytes. These findings indicate that there is an evolutionary reciprocity between New World and Old World primates in the production of the Gal alpha 1----3Gal structure and the antibody that recognizes it. The expression of the Gal alpha 1----3Gal epitope was evolutionarily conserved in New World monkeys, but it was suppressed in ancestral lineages of Old World primates. The suppression of this epitope was accompanied by the production of anti-Gal. The observed in vivo binding of anti-Gal to human normal senescent and some pathologic erythrocytes implies that the Gal alpha 1----3Gal epitope is present in man in a cryptic form.


Species variants of cathepsin L and their immunological identification.
Cathepsin L variants purified from sheep and ox liver are shown to have similar catalytic properties to those from rat, rabbit and man with regard to activity against the substrate benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumarylamide and inhibition by benzyloxycarbonyl-Phe-Phe-diazomethane, thus identifying cathepsin L in these species for the first time. All five variants of cathepsin L are shown to be immunologically related by their interaction with antibodies raised to the human enzyme. Sheep liver was found to yield more enzyme than any other species, suggesting that this tissue is a good source of cathepsin L. Cathepsin S, a closely related enzyme, could not be detected in livers of any of these species.


Qualitative and Semiquantitative Elastography for the Diagnosis of Intermediate Suspicious Thyroid Nodules Based on the 2015 American Thyroid Association Guidelines.
To evaluate qualitative and semiquantitative elastography for the diagnosis of intermediate suspicious thyroid nodules based on the 2015 American Thyroid Association (ATA) guidelines. Through a retrospective search of our institutional database, 746 solid thyroid nodules found on grayscale ultrasonography, strain elastography, and ultrasound-guided fine-needle aspiration between June and November 2009 were collected. Among them, 80 nodules from 80 patients with an intermediate suspicion of malignancy based on the 2015 ATA guidelines that were 10 mm or larger were recruited as the final study nodules. Elastographic findings were categorized according to the criteria of Rago et al (J Clin Endocrinol Metab 2007; 92:2917-2922) and Asteria et al (Thyroid 2008; 18:523-531), and strain ratio values were calculated and recorded. The independent 2-sample t test and χ2 test (or Fisher exact test) were used to evaluate differences in clinical parameters between benign and malignant thyroid nodules. All variables were compared by univariate and multivariate logistic regression analyses, and odds ratios with 95% confidence intervals were calculated. Of the 80 nodules, 6 (7.5%) were malignant, and 74 (92.5%) were benign. No significant differences were observed in age, sex, nodule size, elasticity score, and strain ratio between benign and malignant nodules. No variables significantly predicted thyroid malignancy on the univariate analysis. On the multivariate logistic regression analysis, there were no independent variables associated with thyroid malignancy, including the elasticity score and strain ratio (all P > .05). Elastographic analysis using the elasticity score and strain ratio has limited ability to characterize the benignity or malignancy of thyroid nodules with an intermediate suspicion of malignancy based on the 2015 ATA guidelines.


Focus groups in nursing research.
The literature suggests that prior to the 1950s, focus groups were almost unknown within the social sciences. Today research studies using focus groups are gaining appeal in academic journals. Likewise, they are being used quite extensively outside academic environments. The aim of this paper by Elizabeth Ann Curtis and Richard Redmond is threefold. Firstly, it introduces the background and main characteristics of focus groups, outlines their uses, and discusses the planning and preparation of focus groups. Secondly it discusses the benefits and limitations associated with the use of focus groups. Thirdly it provides an example of how one of the authors applied focus groups in their own research studies.


[Solitary fibrous tumors of the pleura].
Solitary fibrous tumors of the pleura (SFTP) are very rare neoplasms. The majority of these tumors are benign, but about 10-20 % fulfill the criteria of malignancy. The clinical presentation varies according to the size and intrathoracic localization. In early stages, often asymptomatic, the tumors may grow to an enormous size and then cause symptoms such as cough, chest pain and dyspnea, but also paraneoplastic syndromes such as hypoglycemia or digital clubbing. Between 1981 and June 1998 we treated in our institution 16 SFTP in 14 patients (4 M, 10 F, average age at first operation 58 years). Eight patients showed symptoms, whereas in the other cases the tumors were found on routine chest X-rays. The usually pedunculated SFTP were completely resected without complications. Two patients developed malignant recurrences, which infiltrated the right upper lung lobe and the diaphragm respectively. In these cases the tumor was resected together with the adjacent structures. Since late recurrences are more often malignant than primary SFTPs long-term follow-up is mandatory even in benign lesions.


Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo.
Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5⁻0.6 OD/mg) and MPO (0.1⁻0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4⁻45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0⁻1.8 μM/mL) and decrease in SH levels (124.7⁻19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.


Effect of overlaid luminance contrast on perceived color contrast: Shadows enhance, borders suppress.
Natural scenes contain both color and luminance variations at different sizes and orientations that are sometimes spatially overlaid and sometimes not. Here, we explore visual interactions between overlaid color and luminance contrast that are both suprathreshold and highly visible. We used a color-luminance plaid in which the perception of the color contrast and luminance contrast components were measured separately using a method of constant stimuli, to reveal how overlaid cross-oriented luminance contrast affects perceived color contrast, and how color contrast affects perceived luminance contrast. Binocular, monocular, and dichoptic viewing conditions were used for different spatial frequencies (0.375-1.5 cpd, 2 Hz) and base contrasts. We find that overlaid, cross-oriented luminance contrast enhances perceived color contrast by an average of 32% (monocularly and binocularly) across a wide range of luminance contrasts, but interocularly suppresses color contrast. For the reverse condition, we found no effect of color contrast on perceived luminance contrast. If, however, the cross-oriented arrangement is changed to co-oriented, specifically with the color and luminance borders aligned and in-phase, the color enhancement disappears and becomes mild suppression. Likewise, if the phase of the co-aligned components is varied, color enhancement returns once the color and luminance borders are misaligned and out of phase. Thus the relative position of the color and luminance borders is a crucial factor in determining the type of interaction, with color suppression occurring when the luminance and color borders coincide, as when demarcating an object boundary, and color enhancement when they do not coincide, as occurs in shadows and shading.


Psychological functioning in Parkinson's disease post-deep brain stimulation: Self-regulation and executive functioning.
Parkinson's disease (PD) is a neurodegenerative disorder involving the basal ganglia, resulting in motor and extra-motor deficits. These extra-motor deficits may be reflective of a self-regulatory deficit impacting patients' ability to regulate cognitive processes, thoughts, behaviors, and emotions. There is a need to further examine the prevalence and range of self-regulation (SR) and executive functioning (EF) impairments in PD. This study sought to do so in a sample of patients with PD (N = 31) who underwent deep brain stimulation (DBS) surgery for motor symptom treatment. Patients completed measures indicative of SR and EF including neurocognitive tests, heart rate variability (HRV), and self-report questionnaires to examine these constructs in PD. The highest prevalence of impairments were observed for total impulse control disorder (ICD) symptoms (74%), depressive symptoms (48%), verbal fluency (phonemic: 39%; semantic: 36%), mental flexibility (32%), and self-reported SR impairments (Metacognition: 32%; Behavioral Regulation: 29%). Correlations among theoretically related constructs (i.e., SR, EF) were modest and variable; challenging the idea that SR is a unitary construct for which different domains depend on a common resource. In patients with PD post-DBS, higher resting HRV, thought to be indicative of better autonomic functioning, was linked to better EF in some instances but not others and not significantly associated with self-report SR. Overall, patients with PD exhibit various extra-motor deficits, ranging from subtle to severe. Health care professionals working with patients with PD should recognize the presence of extra-motor deficits, particularly ICDs, and obstacles that might arise from such impairments in patients' daily lives.


Unified fitness report for the workplace.
Fitness statements often are required of physicians by patients, employers, governmental agencies, and insurance providers to determine if the patient is fit for duty. Physicians making these ability statements are legally obligated to carefully justify them when placing or excluding individuals from the workplace. The Americans with Disabilities Act (ADA) mandates that medical providers use justifiable criteria and rational thought when determining the capability and risk of an individual. This chapter reviews the legal requirements of the ADA for employers and physicians and presents a uniform methodology that both can use to determine the performance capability of an individual with a temporary or permanent impairment or disability.


A comparison of women with fibromyalgia syndrome to criterion fitness standards: a pilot study.
To compare fitness of women with fibromyalgia syndrome (FMS) aged 50+ with performance standards associated with functional independence in late life. Data came from a longitudinal study tracking physical and cognitive function of 93 women with FMS and included the most recent symptoms, activity levels, and fitness assessments. Most women performed below criterion-referenced fitness standards for all measures. Nearly 90% percent of those < 70 years scored below the standard for lower body strength. Only ~20% of respondents < 70 years old met the criteria for aerobic endurance. A third of those aged over 70 met the standard in agility and dynamic balance. Physical activity was positively associated with fitness performance, while pain and depression symptoms were negatively associated. High proportions of women with FMS do not meet fitness standards recommended for maintaining physical independence in late life, indicating a risk for disability. Regular fitness assessments and targeted exercise interventions are warranted.


Navigating the Intersection between Genomic Research and Clinical Practice.
The Risk Assessment Program (RAP) at Fox Chase Cancer Center (Philadelphia, PA) is a multi-generational prospective cohort, enhanced for personal and family history of cancer, consisting of over 10,000 individuals for whom data on personal and family history of cancer, risk factors, genetic and genomic data, health behaviors, and biospecimens are available. The RAP has a broad research agenda including the characterization of genes with known or potential relevance to cancer, gene-gene and gene-environment interactions, and their contribution to clinically useful risk assessment and risk reduction strategies. Increasingly, this body of research is identifying genetic changes which may have clinical significance for RAP research participants, leading us to confront the issue of whether to return genetic results emerging from research laboratories. This review will describe some of the important fundamental points that must be debated as we develop a paradigm for return of research results. The key issues to address as the scientific community moves toward adopting a policy of return of research results include the best criteria for determining which results to offer, the consent document components necessary to ensure that the participant makes a truly informed decision about receiving their results, and associated logistical and cost challenges.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.


Enantioselective Determination of Polycyclic Musks in River and Wastewater by GC/MS/MS.
The separation of chiral compounds is an interesting and challenging topic in analytical chemistry, especially in environmental fields. Enantioselective degradation or bioaccumulation has been observed for several chiral pollutants. Polycyclic musks are chiral and are widely used as fragrances in a variety of personal care products such as soaps, shampoos, cosmetics and perfumes. In this study, the gas chromatographic separation of chiral polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclo-penta-γ-2-benzopyrane (HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetra-hydronaphthalene (AHTN), 6-acetyl-1,1,2,3,3,5-hexamethylindane (AHDI), 5-acetyl-1,1,2,6-tetramethyl-3-iso-propylindane (ATII), and 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)-indanone (DPMI) was achieved on modified cyclodextrin stationary phase (heptakis (2,3-di-O-methyl-6-O-tert-butyl-dimethylsilyl-β-CD in DV-1701)). Separation techniques are coupled to tandem mass spectrometry (MS-MS), as it provides the sensitivity and selectivity needed. River and wastewaters (influents and effluents of wastewater treatment plants (WWTPs)) in the Nakdong River were investigated with regard to the concentrations and the enantiomeric ratios of polycyclic musks. HHCB was most frequently detected in river and wastewaters, and an enantiomeric enrichment was observed in the effluents of one of the investigated wastewater treatment plants (WWTPs). We reported the contamination of river and wastewaters in Korea by chiral polycyclic musks. The results of this investigation suggest that enantioselective transformation may occur during wastewater treatment.


Cantor dust zone plates.
In this paper we use the Cantor Dust to design zone plates based on a two-dimensional fractal for the first time. The pupil function that defines the coined Cantor Dust Zone Plates (CDZPs) can be written as a combination of rectangle functions. Thus CDZPs can be considered as photon sieves with rectangular holes. The axial irradiances produced by CDZPs of different fractal orders are obtained analitically and experimentally, analyzing the influence of the fractality. The transverse irradiance patterns generated by this kind of zone plates has been also investigated.


Multicultural long-term care nurses' perceptions of factors influencing patient dignity at the end of life.
The goal of this mixed-methods study was to characterize the perceptions of multicultural long-term care nurses about patient dignity at the end-of-life (EOL). The study was conducted in a large, urban, long-term care (LTC) facility. Participants were 45 long-term care nurses and 26 terminally ill nursing home residents. Nurses completed an openended interview about their perceptions of the concept of dying with dignity, and the data were analyzed using grounded theory methods. Main themes identified as promoting resident dignity at the EOL included treating them with respect, helping them prepare for the EOL, promoting shared decision-making, and providing high-quality care. The nurses' cultural and religious backgrounds influenced their perceptions of what constitutes dignity-conserving care. Foreign-born nurses stressed the need for EOL rituals, but this was strikingly absent in the statements of U.S.-born nurses. Foreign-born Catholic nurses stated that the dying experience should not be altered using analgesics to relieve suffering or by attempts to hasten death by forgoing curative therapy or by other means. Nurses and terminally ill individuals completed the Dignity Card-sort Tool (DCT). A comparison of the DCT responses of the LTC nurses cohort with those of the terminally ill participants revealed that the nurses felt patient dignity was eroded when patient wishes were not followed and when they were treated without respect. In contrast, dying LTC residents felt that poor medical care and loss of ability to choose care options were the most important factors leading to erosion of dignity.


Induction of Autophagy by Baicalin Through the AMPK-mTOR Pathway Protects Human Skin Fibroblasts from Ultraviolet B Radiation-Induced Apoptosis.
Baicalin, a natural product isolated from Scutellaria radix, has been reported to exert anti-oxidant and anti-apoptotic effects on skin, but the underlying mechanism remains poorly understood. This study aimed to investigate the possible mechanism of anti-UVB effect of baicalin in human skin fibroblasts. Cell proliferation was estimated by CCK-8 Kit. Apoptotic incidence was detected by flow cytometry with Annexin V-PE/PI apoptosis detection kit. Autophagy was determined by the evaluation of fluorescent LC3 puncta and Western blotting. Cell signalling was analysed by Western blotting. Baicalin exerted cytoprotective effects in UVB-induced HSFs. Moreover, baicalin increased autophagy and suppressed UVB-induced apoptosis of HSFs. Pretreatment with 3-MA, an autophagy inhibitor, attenuated baicalin-induced HSFs autophagy and promoted apoptosis. Baicalin activated AMPK, which leads to suppression of basal mTOR activity in cultured HSFs. Administration of compound C, an AMPK inhibitor, abrogated AMPK phosphorylation and increased mTOR phosphorylation and apoptosis compared with baicalin alone. Taken together, these results indicate the important role of mTOR inhibition in UVB protection by baicalin and provide a new target and strategy for better prevention of UV-induced skin disorders.


Effects of dietary selenium and vitamin E on boar performance and tissue responses, semen quality, and subsequent fertilization rates in mature gilts.
Three experiments involving 192 crossbred boars evaluated the effects of dietary Se (0 or .5 ppm) and vitamin E (0 or 220 IU/kg) on growth, tissue Se, and alpha-tocopherol concentrations, and on semen quality and its subsequent effect on fertilization rate in mature gilts. Diets formulated used torula yeast and dextrose or cornstarch as the basal feedstuffs and were provided from weaning through sexual maturity. The basal diets averaged .063 ppm Se and 3.46 mg alpha-tocopherol/kg diet. Experiment 1 was a 2 x 2 factorial and conducted as a randomized complete block design in six replicates. Boars were allotted at weaning (initial BW 7.7 kg) with growth and feed performance determined to 145 kg BW. Five boars were killed at weaning and three from each treatment group at periodic intervals to 145 kg BW. Serum and tissue Se and alpha-tocopherol concentration and glutathione peroxidase (GSH-Px) activity were subsequently determined. No performance benefit from either nutrient was demonstrated. Tissue (serum, liver, and testis) GSH-Px activity and Se and alpha-tocopherol concentrations were higher (P < .01) at each period when that respective nutrient fortified the diet. Testis GSH-Px activity increased from weaning to 145 kg BW even when Se was not added to the diet. Experiment 2 was conducted after training three boars from each treatment group of Exp. 1 for semen collection. From 9 mo of age and for a 16-wk period, semen was collected three times weekly and the volume, sperm concentration, motility, and percentage of normal and abnormal sperm were determined. Boars fed either the nonfortified Se or vitamin E diets had sperm with lower motilities (P < .01) and a higher percentage of sperm cells with bent and shoehook tails (P < .01). Diets low in added Se seemed to have a greater detrimental effect on the percentage of motile and abnormal sperm than diets inadequate in vitamin E. Sperm cells had a high concentration of Se and alpha-tocopherol, and a high GSH-Px activity. Experiment 3 was conducted using the boars from Exp. 2; 34 mature gilts were inseminated at 12 and 24 h after estrus. Gilts were killed 5 to 7 d postcoitum and the reproductive tracts were recovered. The semen from boars fed the nonfortified Se diet had a lower fertilization rate of oocytes with fewer accessory sperm penetrating the zona pellucida. The results from these experiments indicate that dietary Se and vitamin E can affect boar semen quality, but the greater effect seemed to be from Se.


Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth.
To evaluate the association between HIV infection and sexual maturation, and mediation of this association by HIV effects on growth. Pooled data were analyzed from two longitudinal cohort studies, the International Maternal Pediatric Adolescent AIDS Clinical Trials P219/219C Study (1993-2007) and the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (2007-2015), including perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youths. We evaluated age at sexual maturity among 2539 PHIV and PHEU adolescents based on annual physician-assessed pubertal staging measures. Interval-censored regression models were used to evaluate associations of HIV infection with age at maturity. Mediation analyses accounting for height and BMI Z-scores at specific ages were used to estimate direct and indirect effects of HIV infection on age at sexual maturity. Mean ages at sexual maturity for PHIV girls (n = 1032) were 15.5 years for both female breast and pubic hair and 15.9 and 15.8 years for PHIV boys (n = 1054) for genitalia and pubic hair, respectively. PHIV youths matured approximately 6 months later on average than PHEU (n = 221 girls and 232 boys), and this difference persisted after adjustment for race/ethnicity and birth cohort. BMI and height Z-scores mediated the association between HIV infection and later maturation in girls, accounting for up to 74% of the total HIV effect. Only height Z-scores mediated the effect of HIV on male age at maturity, accounting for up to 98% of the HIV effect. PHIV youths attain sexual maturity later on average than PHEU youths. Much of this difference may be attributable to deficient growth, suggesting directions for future interventions.


['It is not in our heads'. The management and psychiatric referral of children with somatically-unexplained abdominal pain].
Two patients, girls aged 9 and 10 years, were admitted to the paediatric ward due to somatically-unexplained debilitating abdominal pain. Both they and their parents expressed resistance to psychiatric examination before and after admission. After conversations with a psychiatrist and an activation programme, one of the girls recovered and the other family broke the medical contact after having enforced a lot of somatic investigations; when followed up, they stated that the complaints had disappeared. The management of somatically-unexplained abdominal pain in children is not always easy. It is essential to introduce the psychiatrist as an expert in treating the consequences of the complaints rather than an expert in searching for psychiatric causes. Associated impaired functioning is a sign of severe symptoms, which require referral to a psychiatrist or a psychologist.


Costs and cost-effectiveness analyses of mCARE strategies for promoting care seeking of maternal and newborn health services in rural Bangladesh.
We examined the incremental cost-effectiveness between two mHealth programs, implemented from 2011 to 2015 in rural Bangladesh: (1) Comprehensive mCARE package as an intervention group and (2) Basic mCARE package as a control group. Both programs included a core package of census enumeration and pregnancy surveillance provided by an established cadre of digitally enabled community health workers (CHWs). In the comprehensive mCARE package, short message service (SMS) and home visit reminders were additionally sent to pregnant women (n = 610) and CHWs (n = 70) to promote the pregnant women's care-seeking of essential maternal and newborn care services. Economic costs were assessed from a program perspective inclusive of development, start-up, and implementation phases. Effects were calculated as disability adjusted life years (DALYs) and the number of newborn deaths averted. For comparative purposes, we normalized our evaluation to estimate total costs and total newborn deaths averted per 1 million people in a community for both groups. Uncertainty was assessed using probabilistic sensitivity analyses with Monte Carlo simulation. The addition of SMS and home visit reminders based on a mobile phone-facilitated pregnancy surveillance system was highly cost effective at a cost per DALY averted of $31 (95% uncertainty range: $19-81). The comprehensive mCARE program had at least 88% probability of being highly cost-effective as compared to the basic mCARE program based on the threshold of Bangladesh's GDP per capita. mHealth strategies such as SMS and home visit reminders on a well-established pregnancy surveillance system may improve service utilization and program cost-effectiveness in low-resource settings.


Exploring the use of mobile phone technology for the enhancement of the prevention of mother-to-child transmission of HIV program in Nyanza, Kenya: a qualitative study.
Community-based mobile phone programs can complement gaps in clinical services for prevention of mother-to-child transmission (PMTCT) of HIV in areas with poor infrastructure and personnel shortages. However, community and health worker perceptions on optimal mobile phone communication for PMTCT are underexplored. This study examined what specific content and forms of mobile communication are acceptable to support PMTCT. Qualitative methods using focus groups and in-depth interviews were conducted in two district hospitals in Nyanza Province, Kenya. A total of 45 participants were purposefully selected, including HIV-positive women enrolled in PMTCT, their male partners, community health workers, and nurses. Semi-structured discussion guides were used to elicit participants' current mobile phone uses for PMTCT and their perceived benefits and challenges. We also examined participants' views on platform design and gender-tailored short message service (SMS) messages designed to improve PMTCT communication and male involvement. Most participants had access to a mobile phone and prior experience receiving and sending SMS, although phone sharing was common among couples. Mobile phones were used for several health-related purposes, primarily as voice calls rather than texts. The perceived benefits of mobile phones for PMTCT included linking with health workers, protecting confidentiality, and receiving information and reminders. Men and women considered the gender-tailored SMS as a catalyst for improving PMTCT male involvement and couples' communication. However, informative messaging relayed safely to the intended recipient was critical. In addition, health workers emphasized the continual need for in-person counseling coupled with, rather than replaced by, mobile phone reinforcement. For all participants, integrated and neutral text messaging provided antenatally and postnatally was most preferred, although not all topics or text formats were equally acceptable. Given the ubiquity of mobile phones in Kenya and current health-related uses of mobile phones, a PMTCT mobile communications platform holds considerable potential. This pre-intervention assessment of community and health worker preferences yielded valuable information on the complexities of design and implementation. An effective PMTCT mobile platform engaging men and women will need to address contexts of non-disclosure, phone sharing, and linkages with existing community and facility-based services.


Brachmann-de Lange syndrome (BDLS) with asymmetry and skin pigmentary anomalies: a result of mosaicism for a putative bdls gene mutation?
Brachmann-de Lange syndrome (BDLS, OMIM 122470) is a rare malformation syndrome characterized by mental retardation, short stature, limb abnormalities, and a distinctive craniofacial appearance. There is wide clinical variability and mildly affected patients are common. The genetic basis of BDLS and the reasons for its phenotypical variability are still unknown. We report on a patient with mild BDLS and the unusual findings of asymmetric growth of one body half and irregularly shaped pigmentary anomalies of the skin. These two traits have not been previously described in BDLS but have been associated with phenomena of genetic mosaicism in other conditions. We suggest that this patient's phenotype could be the result of mosaicism for a mutation or submicroscopic deletion affecting one or several genes responsible for BDLS.


[Factors associated with access to health services prior to pregnancy by pregnant adolescents].
To assess determinants of access to primary care services prior to pregnancy by pregnant adolescents. Theory-based cross-sectional study conducted to examine access to heath services at five dimensions: geographic, economic, administrative, psychosocial and information. There were included in the study 200 first-time pregnant adolescents (aged 10 to 19 years) who attended a primary care unit in the municipality of Indaiatuba, Southeastern Brazil, in 2003. Data was collected using a semi-structured questionnaire applied in face-to-face interviews conducted just before their first pre-natal care visit. Data analyses were performed through Person's chi-square or Fisher's exact test, and by a multivariate logistic regression model including all five dimensions of access. More than half (63.7%) of the adolescents utilized some gynecological care service. Information (43.8%) or psychosocial feelings of embarrassment or fear (37.0%) barriers were the most frequent reasons given for not having sought care before. The main barrier to health service access was related to the psychosocial dimension, reported by 77.0% of the adolescents studied. Among all barriers to health service access, the most important were those related to the psychosocial dimension. There is a need for new strategies to facilitate access to health services by adolescents, including actions to reduce gender-based barriers taking into consideration sociodemographic characteristics of this population and the relationship they have with their partners.


Mandibular Fractures Admitted to the Emergency Department: Data Analysis from a Swiss Level One Trauma Centre.
Mandibular fracture is a common occurrence in emergency medicine and belongs to the most frequent facial fractures. Historically road traffic injuries (RTIs) have played a prominent role as a cause for mandibular fractures. We extracted data from all patients between August 2012 and February 2015 with "lower jaw fracture" or "mandibular fracture" from the routine database from the emergency department. We conducted a descriptive analysis at a Swiss level one trauma centre. 144 patients were admitted with suspected mandibular fractures. The majority underwent CT diagnostic (83%). In 7% suspected mandibular fracture was not confirmed. More than half of all patients suffered two or more fractures. The fractures were median or paramedian in 77/144 patients (53%) and in other parts (corpus, mandibular angle, ramus mandibularis, collum, and temporomandibular joint) in 100/144 (69%). Male to female ratio was 3 : 1 up to 59 years of age; 69% were younger than 40 years. 72% of all patients presented during daytime, 69% had to be hospitalized, and 31% could be discharged from the ED after treatment. Most fractures were due to fall (44%), followed by interpersonal violence (25%) and sport activities (12%). Falls were a dominant cause of fracture in all age groups while violence and sport activities were common only in younger patients. Comparisons to other studies were difficult due to lack of standardization of causes contributing to the injuries. In the observed time period and setting RTIs have played a minor role compared to falls, interpersonal violence, and sports. In the future, standardized documentation as well as categorization of causes for analytic purposes is urgently needed to facilitate international comparison of studies.


Quantitative Analyses for Early Tempo-spatial Patterning of Differentiated Human Induced Pluripotent Stem Cells on Micropatterns using Time-lapse Bright-field Microscopy Images.
Three germ layer formation on micropatterns are extremely useful for quantitative analysis of hiPSC (human induced pluripotent stem cells) pluripotency. Spatial patterns of stem cells differentiated on the micropatterns will be formed from about 24 hours after differentiation induction and usually quantitated near 48 hours. To delineate the germ layer formation process, temporal changes in spatial patterning of germ layers should be analyzed by noninvasive microscopy. This study proposed a series of image processing methods combined with a U-net automatic segmentation to segment differentiated hiPSCs captured by bright-field microscopy. High segmentation accuracy (83.3%) for the test bright-field images compared with their concurrent Hoechst images (85%) was achieved. Tempo-spatial patterning and formation process of germ layers on the micropatterns can be visualized and quantified by segmenting time-lapse bright-field microscopy images using our method.


The instantaneous torque-angular velocity relation in plantar flexion during jumping.
Torques, angular velocities, and power of the ankle joint during plantar flexion were measured in jumping experiments in order to achieve insight into shape and magnitude of the instantaneous torque-angular velocity relation in a complex movement. Twelve trained subjects performed maximal vertical jumps from a semi-squatting position with 100 degrees of flexion in the knee joint. Ground reaction force measurements and film analyses were used to calculate instantaneous torques, angular velocities, and power outputs during plantar flexion. The shape of the instantaneous torque-angular velocity was different from the well-known hyperbolic force-velocity relation for isolated muscles. Maximal power output (2499 +/- 751 [SD] W) occurred at 60% of the mean maximal torque (301 +/- 62 N X m) and 80% of the mean maximal angular velocity (970 degrees/s). The maximal power output was six times larger than the power output reported in the literature for maximal isokinetic (monoarticular) plantar flexions. Influences like storage of energy in the series elastic component of Hill's muscle model and the role of polyarticular muscles in transporting energy from knee to ankle are discussed. It is concluded that many more selective studies will be necessary before it is possible to relate intrinsic muscle properties to the performance of muscles in poly-articular complex movements.


Mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats; accumulation of wax components; implications for risk assessment.
Female Fischer 344 rats were exposed to three MOSH mixtures: oils largely below and above C25 (S-C25 and L-C25) and a 1:1 mixture of L-C25 with a wax; doses of 400, 1000 and 4000mg/kg feed were administered during 120days. MOSH were determined by on-line HPLC-GC-FID in liver, spleen, adipose tissue and the carcass. The composition of the hydrocarbons accumulated in the tissues was further analyzed by comprehensive two-dimensional GC (GC×GC). MOSH in the mass range of C26-30 were more strongly accumulated than those between C20-25, which does not support the present classification of MOSH differentiating at n-C25 for risk assessment. Compared to the total of the MOSH, n-alkanes and n-alkyl monocyclic naphthenes were generally enriched in adipose tissue. In liver and spleen, n-alkanes up to C25 were eliminated, but strongly accumulated at around C30. Based on this profile, poor solubility and the melting points, it is hypothesized that crystallization protects these wax components against metabolism and elimination. In the liver, relative retention of n-alkanes decreased again beyond C30, accentuated at high exposure, suggesting reduced absorption. Compared to the animal data, accumulation of n-alkanes from food sources, such as apples, into human tissues seems low, perhaps because of low absorption due to their presence in crystalline form. A series of dominant isoalkanes, accumulated in all tissues analyzed, was characterized, though without proposing a structure. Implications on present regulation of white mineral oil products are discussed.


What do we actually know about the relationship between arterial hypertension and atrial fibrillation?
Arterial hypertension and atrial fibrillation (AF) are very prevalent cardiovascular diseases, commonly seen together. Considering the fact that frequency of these medical conditions is constantly increasing due to human life extension, AF will be one of the major risks of cardiovascular morbidity and mortality in the future. Several pathophysiological mechanisms have been proposed to explain the onset of AF in arterial hypertension, and there are numerous theories that explain the protective effect of renin-angiotensin-aldosterone system (RAAS) blockade on new-onset AF. However, the consensus on pathophysiology and the favorable effect of RAAS blockade on AF development is still missing. On the other hand, large clinical trials and meta-analyses demonstrated a positive effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on AF prevention, which is why these drugs are included in the current guidelines for arterial hypertension, and will probably be better positioned in the new guidelines, which will be published this year. The recent studies have also shown a preventive effect of other antihypertensive drugs on AF occurrence and demonstrated that aggressive approach to hypertensive patients with AF is very important not only for conversion into sinus rhythm, but also for sinus rhythm maintenance.


Seasonal variation and dissolved organic matter influence on the distribution, transformation, and environmental risk of pharmaceuticals and personal care products in coastal zone: A case study of Tianjin, China.
Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have raised urgent environmental issues. The dissolved organic matter (DOM) plays a pivotal role on PPCPs' migration and transformation. To obtain a comprehensive understanding of the occurrence and distribution of PPCPs, a seasonal sampling focused on the riverine system in coastal zone, Tianjin, Bohai Rim was conducted. The distribution and transformation of thirty-three PPCPs and their interaction with DOM were investigated, and their sources and ecological risks were further evaluated. The total concentration of PPCPs ranges from 0.01 to 197.20 μg/L, and such value is affected by regional temperature, DOM and land use types. PPCPs migration at soil-water interface is controlled by temperature, sunlight, water flow and DOM. PPCPs have a high affinity to the protein-like DOM, while the humus-like DOM plays a negative influence and facilitates PPCPs' degradation. It is also found that protein-like DOM can represent point source pollution, while humus-like substances indicate non-point source (NPS) emission. Specific PPCPs can be used as markers to trace the source of domestic discharge. Additionally, daily use PPCPs such as ketoprofen, caffeine and iopromide are estimated to be the main risk substances, and their ecological risk varies on space, season and river hydraulic condition.


Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody.
T-cell bispecific antibodies (TCBs) crosslink tumor and T-cells to induce tumor cell killing. While TCBs are very potent, on-target off-tumor toxicity remains a challenge when selecting targets. Here, we describe a protease-activated anti-folate receptor 1 TCB (Prot-FOLR1-TCB) equipped with an anti-idiotypic anti-CD3 mask connected to the anti-CD3 Fab through a tumor protease-cleavable linker. The potency of this Prot- FOLR1-TCB is recovered following protease-cleavage of the linker releasing the anti-idiotypic anti-CD3 scFv. In vivo, the Prot-FOLR1-TCB mediates antitumor efficacy comparable to the parental FOLR1-TCB whereas a noncleavable control Prot-FOLR1-TCB is inactive. In contrast, killing of bronchial epithelial and renal cortical cells with low FOLR1 expression is prevented compared to the parental FOLR1-TCB. The findings are confirmed for mesothelin as alternative tumor antigen. Thus, masking the anti-CD3 Fab fragment with an anti-idiotypic mask and cleavage of the mask by tumor-specific proteases can be applied to enhance specificity and safety of TCBs.


Imaging features and prognostic factors in fetal and postnatal torcular dural sinus malformations, part I: review of experience at Boston Children's Hospital.
Even for the most common dural sinus malformation (DSM), the torcular DSM (tDSM), generalizable statements about etiology and prognosis are difficult because neurosurgeons/neuroradiologists and obstetrical imagers have focused on different patient age groups, have reported different outcomes, and have offered differing pathophysiologic explanations. To examine the imaging features and outcomes of a local cohort of tDSMs across fetal-neonatal life for commonalities. Review of imaging and clinical outcome for a local cohort of 12 tDSM patients (9 fetal, 3 postnatal). All 12 tDSMs had similar imaging characteristics, including enlargement of the torcular and intraluminal thrombus early on, later evolving to peripheral scar tissue after treatment or spontaneous regression. Spontaneous decrease in size of the tDSM was observed in 6 prenatal and 1 postnatal case, and this decrease appeared to be irreversible once it occurred. One of 9 prenatal tDSMs was demonstrated to have arteriovenous fistulae in utero, while 2 of 3 postnatal diagnoses had arteriovenous fisutlae. All 6 prenatal tDSM diagnoses followed to term and all 3 postnatal diagnoses had a grossly normal neurologic outcome after a median of 12 months of age. Prenatal and postnatal tDSMs have overlapping imaging features suggesting a common etiology, and involution of a tDSM is a key imaging biomarker for a favorable outcome. While there is reason for concern with postnatally diagnosed tDSMs, good outcomes may still be achieved across the fetal-neonatal age spectrum of presentations. These findings are generalized in part II of this article.


A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.
In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse.


Third-generation cephalosporins for polymicrobial surgical sepsis.
During 31 months of study, 808 patients with polymicrobial surgical infection were randomized for antibiotic therapy between a third-generation cephalosporin (moxalactam disodium [149], cefotaxime sodium [125], and cefoperazone sodium [141]) and the combination of gentamicin sulfate plus clindamycin (393). Results based on antibiotic therapy included the following: cure in 83% given cephalosporin, 73% with antibiotic combination; control but recurrent sepsis in 7% and 15%; and failure in 4% and 8%, respectively. Such data support the tenet that third-generation cephalosporins are at least equal, if not superior, to the combination of gentamicin plus clindamycin for treatment of polymicrobial surgical sepsis.


Alcohol and the driver. Council on Scientific Affairs.
Scientific investigations have produced 50 years of accumulated evidence showing a direct relationship between increasing blood alcohol concentration (BAC) in drivers and increasing risk of a motor vehicle crash. There is scientific consensus that alcohol causes deterioration of driving skills beginning at 0.05% BAC or even lower, and progressively serious impairment at higher BACs. Drivers aged 16 to 24 years have the highest representation of all age groups in alcohol-related road crashes; young drivers involved in alcohol-related fatal crashes have lower average BACs than older drivers. Alcohol impairs driving skills by its effects on the central nervous system, acting like a general anesthetic. It renders slower and less efficient both information acquisition and information processing, making divided-attention tasks such as steering and braking more difficult to carry out without error. The influence of alcohol on emotions and attitudes may be a crash risk factor related to driving style in addition to driving skill. Biologic variability among humans produces substantial differences in alcohol influence and alcohol tolerance, making virtually useless any attempts to fix a "safe" drinking level for drivers. The American Medical Association supports a policy recommending (1) public education urging drivers not to drink, (2) adoption by all states of 0.05% BAC as per se evidence of alcohol-impaired driving, (3) 21 years as the legal drinking age in all states, (4) adoption by all states of administrative driver's license suspension in driving-under-the-influence cases, and (5) encouragement for the automobile industry to develop a safety module that thwarts operation of a motor vehicle by an intoxicated person.


Equatorial pacific seismic reflectors as indicators of global oceanographic events.
The origin of a series of regionally correlatable seismic horizons in the Neogene sediments of the central equatorial Pacific is examined through seismic modeling and the detailed analyses of stratigraphic and physical property relationships in Deep Sea Drilling Project cores. These regionally traceable reflectors are synchronous; the younger reflectors are the direct result of carbonate dissolution events, the older ones of stratigraphically selective diagenetic processes. The changes in ocean chemistry associated with these events appear to be linked to global reorganizations of surface and bottom-water circulation patterns, the most dramatic of which are associated with reorganizations of North Atlantic bottom waters. These deepwater seismic horizons appear to correlate with the major events on the "relative sea-level" curve of Vail et al. for the Neogene.


Colobus type C virus: molecular cloning of unintegrated viral DNA and characterization of the endogenous viral genomes of Colobus.
The unintegrated viral DNA intermediates of colobus type C virus (CPC-1) were isolated from infected human cells that were permissive for viral growth. There were two major species of DNA, linear molecules with two copies of the long terminal repeat and relaxed circles containing only a single long terminal repeat. In addition, there was a minor species (approximately 10%) composed of relaxed circles with two copies of the long terminal repeat. A restriction endonuclease map of the unintegrated DNA was constructed. The three EcoRI fragments of circular CPC-1 DNA were cloned in the EcoRI site of lambda gtWES . lambda B and then subcloned in the EcoRI site of pBR322. Using these subgenomic fragments as probes, we have characterized the endogenous viral sequences found in colobus cellular DNA. They are not organized in tandem arrays, as is the case in some other gene families. The majority of sequences detected in cellular DNA have the same map as the CPC-1 unintegrated DNA at 17 of 18 restriction endonuclease sites. There are, however, other sequences that are present in multiple copies and do not correspond to the CPC-1 map. They do not contain CPC-1 sequences either in an altered form or fused to common nonviral sequences. Instead, they appear to be derived from a distinct family of sequences that is substantially diverged from the CPC-1 family. This second family of sequences, CPC-2, is also different from the sequences related to baboon endogenous type C virus that forms a third family of virus-related sequences in the colobus genome.


Functional conservation of subfamilies of putative UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases in Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of l(2)35Aa is essential in Drosophila.
The completed fruit fly genome was found to contain up to 15 putative UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) genes. Phylogenetic analysis of the putative catalytic domains of the large GalNAc-transferase enzyme families of Drosophila melanogaster (13 available), Caenorhabditis elegans (9 genes), and mammals (12 genes) indicated that distinct subfamilies of orthologous genes are conserved in each species. In support of this hypothesis, we provide evidence that distinctive functional properties of Drosophila and human GalNAc-transferase isoforms were exhibited by evolutionarily conserved members of two subfamilies (dGalNAc-T1 (l(2)35Aa) and GalNAc-T11; dGalNAc-T2 (CG6394) and GalNAc-T7). dGalNAc-T1 and novel human GalNAc-T11 were shown to encode functional GalNAc-transferases with the same polypeptide acceptor substrate specificity, and dGalNAc-T2 was shown to encode a GalNAc-transferase with similar GalNAc glycopeptide substrate specificity as GalNAc-T7. Previous data suggested that the putative GalNAc-transferase encoded by l(2)35Aa had a lethal phenotype (Flores, C., and Engels, W. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 2964-2969), and this was substantiated by sequencing of three lethal alleles l(2)35Aa(HG8), l(2)35Aa(SF12), and l(2)35Aa(SF32). The finding that subfamilies of GalNAc-transferases with distinct catalytic functions are evolutionarily conserved stresses that GalNAc-transferase isoforms may serve unique biological functions rather than providing functional redundancy, and this is further supported by the lethal phenotype of l(2)35Aa.


A case of gain-of-function mutation in calcium-sensing receptor: supplemental hydration is required for renal protection.
The calcium-sensing receptor (CaSR) regulates the extracellular calcium level, mainly by controlling parathyroid hormon secretion and renal calcium reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities increase CaSR activity leading to the development of such clinical manifestations as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case of CaSR gain-of-function mutation and represent a therapeutic intervention based on the functional characteristics of CaSR in renal tubule. DNA sequence analysis revealed a heterozygous G to T mutation identified in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal extracellular domain of the CaSR gene, one of the most important parts for the three-dimensional construction of the receptor, resulting in the substitution of phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide administration and supplemental hydration were started in addition to calcium supplementation. The combination therapy of thiazide and supplemental hydration markedly reduced both renal calcium excretion and urinary calcium concentration from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from 10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy stopped the progression of renal calcification during the follow-up period. Supplemental hydration should be considered essential for the following reasons: (1) calcium supplementation activates the CaSR in the kidney and suppresses renal urinary concentrating ability, (2) the thiazide has a diuretic effect, (3) as calcium supplementation increases renal calcium excretion, the supplemental hydration decreases urinary calcium concentration by increasing urinary volume, thereby diminishing the risk of intratubular crystallization of calcium ion.


Exocytosis and protein secretion in Trypanosoma.
Human African trypanosomiasis is a lethal disease caused by the extracellular parasite Trypanosoma brucei. The proteins secreted by T. brucei inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins. Overall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of T. brucei, but distinguished the secretome from published T. brucei whole proteome or glycosome. In addition, several proteins had not been previously described in Trypanosoma and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of Trypanosoma proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket. This study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of Trypanosoma as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing Trypanosoma to exchange proteins at least between parasites and/or to manipulate the host immune system.


Dynamic Akt/mTOR Signaling in Children with Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is a behaviorally defined disorder affecting 1 in 68 children. Currently, there is no known cause for the majority of ASD cases nor are there physiological diagnostic tools or biomarkers to aid behavioral diagnosis. Whole-genome linkage studies, genome-wide association studies, copy number variation screening, and SNP analyses have identified several ASD candidate genes, but which vary greatly among individuals and family clusters, suggesting that a variety of genetic mutations may result in a common pathology or alter a common mechanistic pathway. The Akt/mammalian target of rapamycin (mTOR) pathway is involved in many cellular processes including synaptic plasticity and immune function that can alter neurodevelopment. In this study, we examined the activity of the Akt/mTOR pathway in cells isolated from children with ASD and typically developing controls. We observed higher activity of mTOR, extracellular receptor kinase, and p70S6 kinase and lower activity of glycogen synthase kinase 3 (GSK3)α and tuberin (TSC2) in cells from children with ASD. These data suggest a phosphorylation pattern indicative of higher activity in the Akt/mTOR pathway in children with general/idiopathic ASD and may suggest a common pathological pathway of interest for ASD.


Length-weight relationships for 36 freshwater fish species from two tropical reservoirs: Ayamé I and Buyo, Côte d'Ivoire.
Nowadays, the successful management of small scale fisheries requires the use of biometric data collected in the field, in order to transform them into suitable indicators. The present study describes the length-weight relationships for 36 freshwater fish species from two tropical reservoirs Ayame I and Buyo, in Côte d'Ivoire. The main objective of the study was to provide a length weight key for a wide range of freshwater fish species from these tropical reservoirs exploited by the inland fisheries. The samplings were carried out at Buyo from July 1997 to August 1998, and from August 2004 to July 2005 in Ayame I. Fish specimens were collected from catches of artisanal fisheries using gill-nets, cast-nets, beach seines and bamboo traps. After landings, samples were identified, total weight for each specimen was recorded to the nearest gram and standard length was measured to the nearest millimetre. A total of 12 724 individuals belonging to 15 families and 24 genera were obtained in this study. The results indicated that the family with the highest number of species was Cichlidae with eight species. Six families were recorded with only one species per family. The value of the exponent b in the length weight relationships (W=aL(b)) ranged from 2.173 for Marcusenius furcidens to 3.472 for Polypterus endlicheri and the median of b was 2.756. The modal value of the exponent b equal to 2.70 indicates that most of the fish species in Ayame I and Buyo Reservoirs have negative allometric growth. The length weight parameters of the three species, Lates niloticus, Synodontis koensis and S. punctifer are described for the first time in these regions. The present length-weight key for 36 freshwater fish species could be used as a valuable tool for fishery managers, in order to improve the inland fisheries statistics largely based on hydropower reservoirs in Côte d'Ivoire.


Multiple scattering by random particulate media: exact 3D results.
We use the numerically exact superposition T-matrix method to perform extensive computations of electromagnetic scattering by a 3D volume filled with randomly distributed wavelength-sized particles. These computations are used to simulate and analyze the effect of randomness of particle positions as well as the onset and evolution of various multiple-scattering effects with increasing number of particles in a statistically homogeneous volume of discrete random medium. Our exact results illustrate and substantiate the methodology underlying the microphysical theories of radiative transfer and coherent backscattering. Furthermore, we show that even in densely packed media, the light multiply scattered along strings of widely separated particles still provides a significant contribution to the total scattered signal and thereby makes quite pronounced the classical radiative transfer and coherent backscattering effects.


N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice.
The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (cocaine) is involved in regulating the development and expression of cocaine-conditioned reward and sensitization. We therefore hypothesized that drug-induced elevation in endocannabinoids (eCBs) and/or eCB-like molecules (eCB-Ls) may represent a protective mechanism against drug insult, and boosting their levels exogenously may strengthen their neuroprotective effects. Here, we determine the involvement of ECS in alcohol addiction. We first measured the eCBs and eCB-Ls levels in different brain reward system regions following chronic alcohol self-administration using LC-MS. We have found that following chronic intermittent alcohol consumption, N-oleoyl glycine (OlGly) levels were significantly elevated in the prefrontal cortex (PFC), and N-oleoyl alanine (OlAla) was significantly elevated in the PFC, nucleus accumbens (NAc) and ventral tegmental area (VTA) in a region-specific manner. We next tested whether exogenous administration of OlGly or OlAla would attenuate alcohol consumption and preference. We found that systemic administration of OlGly or OlAla (60 mg/kg, intraperitoneal) during intermittent alcohol consumption significantly reduced alcohol intake and preference without affecting the hedonic state. These findings suggest that the ECS negatively regulates alcohol consumption and boosting selective eCBs exogenously has beneficial effects against alcohol consumption and potentially in preventing relapse.


[Third-party funding and industrial sponsoring].
Due to sensational publications, media-effective proceedings and not least due to personal involvement in many cases the medical profession became aware of the potential criminal significance of third-party funding and industrial sponsoring in hospitals. It started with the so-called Heart-Valve-Affair ("Herzklappenskandal") in 1994. Since then, insecurity prevails which was further nourished by a new series of legal proceedings in spring 2002. Industrial sponsoring has been practised in hospitals for a long time. Research work at universities and colleges would hardly be possible without third-party funding, which is accepted de lege lata according to section sign 25 of the German Hochschulrahmengesetz (framework law on universities and colleges). In view of the course of action of the criminal prosecution authorities the question came up which precautions must be taken with regard to grants by the medical-pharmaceutical industry to avoid consequences from the point of view of criminal law.[nl]There are various facts and circumstances in relation with these benefits, such as providing financing of educational training, payments related to the participation in congresses, speaker's fees, consultancy agreements, clinical tests and application evaluation, provision of equipment and staff as well as providing financing thereof, donations to medical facilities and so-called Fördervereine (supporting associations), benefits for research projects, etc.


Local opinion leaders: effects on professional practice and health care outcomes.
Both the theory of diffusion of innovations and the social influences model of behaviour change suggest that using local opinion leaders to transmit norms and model appropriate behaviour may improve health professional practice. To assess the effects using local opinion leaders on the practice of health professionals or patient outcomes. We searched MEDLINE to May 1998, the Research and Development Resource Base in Continuing Medical Education, and reference lists of related systematic reviews and articles. Randomised trials of the use of local opinion leaders (defined as health professionals nominated by their colleagues as being educationally influential). The participants were health care professionals responsible for patient care. Two reviewers independently extracted data and assessed study quality. Eight studies were included involving more than 296 health professionals. A variety of patient problems were targeted, including acute myocardial infarction, cancer pain, osteoarthritis, rheumatoid arthritis, chronic lung disease, vaginal birth after caesarean section, labour and delivery, and urinary catheter care. Six of seven trials that measured health professional practice demonstrated some improvement for at least one outcome variable, and in two trials, the results were statistically significant and clinically important. In three trials that measured patient outcomes, only one achieved an impact upon practice that was of practical importance: local opinion leaders were effective in improving the rate of vaginal birth after previous caesarean section. Using local opinion leaders results in mixed effects on professional practice. However, it is not always clear what local opinion leaders do and replicable descriptions are needed. Further research is required to determine if opinion leaders can be identified and in which circumstances they are likely to influence the practice of their peers.


Full Phase Diagram of Active Brownian Disks: From Melting to Motility-Induced Phase Separation.
We establish the complete phase diagram of self-propelled hard disks in two spatial dimensions from the analysis of the equation of state and the statistics of local order parameters. The equilibrium melting scenario is maintained at small activities, with coexistence between active liquid and hexatic order, followed by a proper hexatic phase, and a further transition to an active solid. As activity increases, the emergence of hexatic and solid order is shifted towards higher densities. Above a critical activity and for a certain range of packing fractions, the system undergoes motility-induced phase separation and demixes into low and high density phases; the latter can be either disordered (liquid) or ordered (hexatic or solid) depending on the activity.


Excretion of HCO3- by the urinary bladder of Bufo marinus in metabolic alkalosis.
We studied the role of the urinary bladder of Bufo marinus in the excretion of bicarbonate into the urine. The toads were in metabolic alkalosis, produced by administering 120 mM NaHCO3 by stomach tube or by soaking the toads in 120 mM NaHCO3 solution for 48 to 72 hr. In vitro 10 cannulated whole bladders from toads in alkalosis transported bicarbonate from the serosal to mucosal medium. The average gradient created by this transport was 5.7 meq/1. In 15 whole bladders from toads in metabolic acidosis studied under identical conditions, there was no transport of bicarbonate into mucosal medium.


Testosterone signals through mTOR and androgen receptor to induce muscle hypertrophy.
The anabolic hormone testosterone induces muscle hypertrophy, but the intracellular mechanisms involved are poorly known. We addressed the question whether signal transduction pathways other than the androgen receptor (AR) are necessary to elicit hypertrophy in skeletal muscle myotubes. Cultured rat skeletal muscle myotubes were preincubated with inhibitors for ERK1/2 (PD98059), PI3K/Akt (LY294002 and Akt inhibitor VIII) or mTOR/S6K1 (rapamycin), and then stimulated with 100 nM testosterone. The expression of α-actin and the phosphorylation levels of ERK1/2, Akt and S6K1 (a downstream target for mTOR) were measured by Western blot. mRNA levels were evaluated by real time RT-PCR. Myotube size and sarcomerization were determined by confocal microscopy. Inhibition of AR was assessed by bicalutamide. Testosterone-induced myotube hypertrophy was assessed as increased myotube cross-sectional area (CSA) and increased α-actin mRNA and α-actin protein levels, with no changes in mRNA expression of atrogenes (MAFbx and MuRF-1). Morphological development of myotube sarcomeres was evident in testosterone-stimulated myotubes. Known hypertrophy signaling pathways were studied at short times: ERK1/2 and Akt showed an increase in phosphorylation status after testosterone stimulus at 5 and 15 min, respectively. S6K1 was phosphorylated at 60 min. This response was abolished by PI3K/Akt and mTOR inhibition but not by ERK1/2 inhibition. Similarly, the CSA increase at 12 h was abolished by inhibitors of the PI3K/Akt pathway as well as by AR inhibition. These results suggest a crosstalk between pathways involving fast intracellular signaling and the AR to explain testosterone-induced skeletal muscle hypertrophy.


High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.
To determine the short- and long-term efficacy and toxicity of the high-dose intravenous bolus interleukin 2 (IL-2) regimen in patients with metastatic melanoma. Two hundred seventy assessable patients were entered onto eight clinical trials conducted between 1985 and 1993. IL-2 (Proleukin [aldesleukin]; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical treatment cycle was scheduled after 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Data were analyzed through fall 1996. The overall objective response rate was 16% (95% confidence interval, 12% to 21%); there were 17 complete responses (CRs) (6%) and 26 partial responses (PRs) (10%). Responses occurred with all sites of disease and in patients with large tumor burdens. The median response duration for patients who achieved a CR has not been reached and was 5.9 months for those who achieved a PR. Twelve (28%) of the responding patients, including 10 (59%) of the patients who achieved a CR, remain progression-free. Disease did not progress in any patient responding for more than 30 months. Baseline performance status and whether patients had received prior systemic therapy were the only predictive prognostic factors for response to IL-2 therapy. Toxicities, although severe, generally reversed rapidly after therapy was completed. Six patients (2%) died from adverse events, all related to sepsis. High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.


Comparative efficacy of continuous and pulse dose terbinafine regimes in toenail dermatophytosis: A randomized double-blind trial.
Dermatophytes are the most frequently implicated agents in toenail onychomycosis and oral terbinafine has shown the best cure rates in this condition. The pharmacokinetics of terbinafine favors its efficacy in pulse dosing. To compare the efficacy of terbinafine in continuous and pulse dosing schedules in the treatment of toenail dermatophytosis. Seventy-six patients of potassium hydroxide (KOH) and culture positive dermatophyte toenail onychomycosis were randomly allocated to two treatment groups receiving either continuous terbinafine 250 mg daily for 12 weeks or 3 pulses of terbinafine (each of 500 mg daily for a week) repeated every 4 weeks. Patients were followed up at 4, 8 and 12 weeks during treatment and post-treatment at 24 weeks. At each visit, a KOH mount and culture were performed. In each patient, improvement in a target nail was assessed using a clinical score; total scores for all nails and global assessments by physician and patient were also recorded. Mycological, clinical and complete cure rates, clinical effectivity and treatment failure rates were then compared. The declines in target nail and total scores from baseline were significant at each follow-up visit in both the treatment groups. However, the inter-group difference was statistically insignificant. The same was true for global assessment indices, clinical effectivity as well as clinical, mycological, and complete cure rates. The short follow-up in our study may have led to lower cure rates being recorded. Terbinafine in pulse dosing is as effective as continuous dosing in the treatment of dermatophyte toenail onychomycosis.


An evaluation for the medium-term storage and viability of root cortex tissues stained with blue ink in the assessment of arbuscular mycorrhizal fungi.
Sheaffer blue ink is an effective method to stain arbuscular mycorrhizal (AM) fungi in a variety of plant species. It has, however, received criticism for its potential rapid degradation and short-term viability. The long and medium term storage and viability of stained samples has not, to date, been described for this particular staining method. This short communication reports on the viability of 730 samples stained with Sheaffer blue ink stored for the duration of 4 years in microscope slide boxes out of direct sunlight. There was no significant difference in micrograph image quality and presence of stain between years as indicated by the number of AM fungal structures quantified. In conclusion Sheaffer blue ink stain does not deteriorate in the medium term.


[Need for psychological correction in patients with pulmonary tuberculosis].
The paper presents the results of examination using a standardized multifactorial personality study schedule in patients with pulmonary tuberculosis, residents in the Samara Region, including 123 males and 55 females with first diagnosed tuberculosis, 152 males and 101 females with chronic pulmonary tuberculosis. Ninety-eight apparently healthy males and 142 females of the same age were examined as a control group. The type of a response in the psychotraumatic situation and psychological traits were identified. The leading type of a response (66%) was hyposthenic (an inhibitory response to stress) in males with first identified tuberculosis. Conflict somatization was peculiar to other males, as in 46% of the females. The behavioral type of dysadaptation and asocial and antisocial responses occur in 38.9% of the males with chronic pulmonary tuberculosis and in 25% of the females. 22.2% of the males and 50% of the females show a somatic response, which leads to the transition to the psychophysiological level, to the occurrence of psychosomatic diseases. Irrespective of the duration of the disease, all the patients, both males and females, need psychological correction.


Retention of surface structure causes lower density in atomic layer deposition of amorphous titanium oxide thin films.
Size effects and structural modifications in amorphous TiO2 films deposited by atomic layer deposition (ALD) were investigated. As with the previously investigated ALD-deposited Al2O3 system we found that the film's structure and properties are strongly dependent on its thickness, but here, besides the significant change in the density of the films there is also a change in their chemical state. The thin near-surface layer contained a significantly larger amount of Ti+3 species and oxygen vacancies relative to the sample's bulk. We attribute this change in chemistry to the ALD specific deposition process wherein each different atomic species is deposited in turn, thereby forming a "corundum-like" structure of the near-surface layer resembling that found in the Al2O3 system. This, combined with the fact that each deposited layer starts out as a surface layer and maintains the surface structure over the next several following deposition cycles, is responsible for the overall decrease in the film density. This is the first time this effect has been shown in detail for TiO2, expending the previously discovered phenomenon to a new system and demonstrating that while similar effects occur, they can present in different ways for oxide systems with different structures and symmetries.


The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study.
Microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. However, a recent Japanese trial showed that regorafenib plus nivolumab had encouraging anti-cancer activity in MSS or pMMR mCRCs. We retrospectively reviewed the efficacy and safety data of combination therapy with regorafenib plus anti-PD-1 antibody in patients with refractory MSS or pMMR mCRC in the medical centers of Shandong Province in China. Twenty-three patients with MSS or pMMR mCRC received regorafenib plus anti-PD-1 antibody. Eighteen (78.3%) patients experienced stable disease as best response, five (21.7%) patients had progressive disease, and no partial response was observed. The disease control rate (DCR) was 78.3% (18/23), and the median progression-free survival (PFS) was 3.1 months (95% CI, 2.32-3.89). Four of five (80.0%) patients with progressive disease had baseline liver metastasis, while nine of 18 (50.0%) patients with stable disease displayed no liver metastasis. One patient receiving radiofrequency ablation treatment for liver and abdominal wall metastases prior to combination treatment experienced a remarkably prolonged PFS of 9.2 months with SD. Neither liver metastasis status nor previous exposure to regorafenib was associated with treatment outcome. Treatment-related grade 3 toxicities were observed in 5/23 (21.7%) patients. No objective response was observed with the combination of regorafenib plus anti-PD-1 antibody, suggesting its little clinical activity in unselected Chinese patients with pMMR/MSS mCRC. Meanwhile, it exhibited some potential benefit in this cohort in terms of DCR and PFS. Adverse events were generally tolerable and manageable. Prospective studies with large sample sizes are needed to verify the findings. This combination strategy plus local ablative therapy might be worthy of further exploration.


Chemical speciation influences comparative activity of selenium-enriched garlic and yeast in mammary cancer prevention.
A recent human intervention trial showed that daily supplementation with selenized yeast (Se-yeast) led to a decrease in the overall cancer morbidity and mortality by nearly 50%; past research has also demonstrated that selenized garlic (Se-garlic) is very effective in mammary cancer chemoprevention in the rat model. The goal of this study was to compare certain biological activities of Se-garlic and Se-yeast and to elucidate the differences based on the chemical forms of selenium found in these two natural products. Characterization of organic selenium compounds in yeast (1922 microg/g Se) and garlic (296 microg/g Se) was carried out by high-performance liquid chromatography with inductively coupled plasma mass spectrometry or with electrospray mass spectrometry. Analytical speciation studies showed that the bulk of the selenium in Se-garlic and Se-yeast is in the form of gamma-glutamyl-Se-methylselenocysteine (73%) and selenomethionine (85%), respectively. The above methodology has the sensitivity and capability to account for >90% of total selenium. In the rat feeding studies, supplementation of Se-garlic in the diet at different levels consistently caused a lower total tissue selenium accumulation when compared to Se-yeast. On the other hand, Se-garlic was significantly more effective in suppressing the development of premalignant lesions and the formation of adenocarcinomas in the mammary gland of carcinogen-treated rats. Given the present finding on the identity of selenomethionine and gamma-glutamyl-Se-methylselenocysteine as the major form of selenium in Se-yeast and Se-garlic, respectively, the metabolism of these two compounds is discussed in an attempt to elucidate how their disposition in tissues might account for the differences in cancer chemopreventive activity.


A defensin from tomato with dual function in defense and development.
Defensins are antimicrobial peptides that are part of the innate immune system, contributing to the first line of defense against invading pathogens. Defensins and defensin-like peptides are functionally diverse, disrupting microbial membranes and acting as ligands for cellular recognition and signaling. Here we show that the tomato defensin DEF2 is expressed during early flower development. Defensin mRNA abundance, peptide expression and processing are differentially regulated in developing flowers. Antisense suppression or constitutive overexpression of DEF2 reduces pollen viability and seed production. Furthermore, overexpression of DEF2 pleiotropically alters the growth of various organs and enhances foliar resistance to the fungal pathogen Botrytis cinerea. Partially purified extracts from leaves of a DEF2-overexpressing line inhibited tip growth of B. cinerea. Besides providing insights into regulation of defensin expression, these data demonstrate that plant defensins, like their animal counterparts, can assume multiple functions related to defense and development.


Structural basis for the flexible recognition of α-glucan substrates by Bacteroides thetaiotaomicron SusG.
Bacteria that reside in the mammalian intestinal tract efficiently hydrolyze dietary carbohydrates, including starch, that escape digestion in the small intestine. Starch is an abundant dietary carbohydrate comprised of α1,4 and α1,6 linked glucose, yet mammalian intestinal glucoamylases cannot effectively hydrolyze starch that has frequent α1,6 branching as these structures hinder recognition and processing by α1,4-specific amylases. Here we present the structure of the cell surface amylase SusG from Bacteroides thetaiotaomicron complexed with a mixed linkage amylosaccharide generated from transglycosylation during crystallization. Although SusG is specific for α1,4 glucosidic bonds, binding of this new oligosaccharide at the active site demonstrates that SusG can accommodate α1,6 branch points at subsite -3 to -2, and also at subsite+1 adjacent to the site of hydrolysis, explaining how this enzyme may be able to process a wide range of limit dextrins in the intestinal environment. These data suggest that B. thetaiotaomicron and related organisms may have a selective advantage for amylosaccharide scavenging in the gut.


[Microbial spectrum of respiratory tract in patients with different pulmonary diseases].
To study microbial spectrum of respiratory tract in patients with pulmonary diseases. Culture of sputum/bronchial lavage fluid (S/BLF) and bronchoalveolar lavage fluid obtained from 36 HIV-negative patients with infiltrative pulmonary tuberculosis (IT), 18 patients with community-acquired pneumonia (CAP), 18 patients with lung cancer (LC) was performed on 5% blood agar using method of serial dilutions. Following concentrations of microorganisms were considered as diagnostic: 10(6) CFU/ml--in sputum, 10(4) CFU/ml--in bronchial lavage fluid, 10(3) CFU/ ml--in bronchoalveolar lavage fluid. Nonspecific microflora in S/BLF was isolated 94.4% of patients (34--IT, 17--CAP, and 17-LC), and in bronchoalveolar lavage fluid - in 69.4%, 61.1%, and 77.8% of patients respectively. Nonspecific microflora was presented as both monoculture and microbial associations. In group of patients with IT, the most frequent were associations of bacteria from Nesseriaceae family and streptococci, streptococci and staphylococci, streptococci and fungi from Candida genus. In group of patients with CAP, monocultures of microorganisms were detected rarely, whereas, in contrast, microbial associations were detected more frequently. In patients with LC, monocultures of microorganisms were isolated from S/ BLF in 2 cases and from broncoalveolar lavage fluid--in 9 cases; associations were detected in overwhelming majority of patients, more frequently--combination of streptococci and Neisseria, streptococci and yeast-like fungi. In patients with IT and CAP, Streptococcus pneumoniae was the most frequently detected microorganism, whereas non-fermenting bacteria predominated in lavage fluid. Diagnostic titers from bronchoalveolar lavage fluid in patients with CAP were detected only for Acinetobacter calcoaceticus, Citrobacterfreundii, and Escherichia coli. S.pneumoniae and Staphylococcus spp. were most frequently isolated from S/BLF in patients with LC, whereas in broncoalveolar lavage fluid of such patients S. pneumoniae, Pseudomonas aeruginosa, and non-fermenting bacteria were detected in titers exceeding diagnostic threshold. Species composition of nonspecific microflora during IT, CAP, and LC was virtually the same; microorganisms were detected in equal proportions.


MTFH: A Matrix Tri-Factorization Hashing Framework for Efficient Cross-Modal Retrieval.
Hashing has recently sparked a great revolution in cross-modal retrieval because of its low storage cost and high query speed. Recent cross-modal hashing methods often learn unified or equal-length hash codes to represent the multi-modal data and make them intuitively comparable. However, such unified or equal-length hash representations could inherently sacrifice their representation scalability because the data from different modalities may not have one-to-one correspondence and could be encoded more efficiently by different hash codes of unequal lengths. To mitigate these problems, this paper exploits a related and relatively unexplored problem: encode the heterogeneous data with varying hash lengths and generalize the cross-modal retrieval in various challenging scenarios. To this end, a generalized and flexible cross-modal hashing framework, termed Matrix Tri-Factorization Hashing (MTFH), is proposed to work seamlessly in various settings including paired or unpaired multi-modal data, and equal or varying hash length encoding scenarios. More specifically, MTFH exploits an efficient objective function to flexibly learn the modality-specific hash codes with different length settings, while synchronously learning two semantic correlation matrices to semantically correlate the different hash representations for heterogeneous data comparable. As a result, the derived hash codes are more semantically meaningful for various challenging cross-modal retrieval tasks. Extensive experiments evaluated on public benchmark datasets highlight the superiority of MTFH under various retrieval scenarios and show its competitive performance with the state-of-the-arts.


Early detection and treatment of postnatal depression in primary care.
Postnatal depression has a relatively high incidence and gives rise to considerable morbidity. There is sound evidence supporting the use of the Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal depression. This paper reports on a project developed by two health visitors and a community mental health nurse working in the United Kingdom. The aim of the project was to improve the early detection and treatment of postnatal depression in the population of the general practice to which they were attached. The health visitors screened for postnatal depression in the course of routine visits on four occasions during the first postpartum year. Women identified as likely to be suffering from postnatal depression were offered 'listening visits' as a first-line intervention, with referral on to the general practitioner and/or community mental health nurse if indicated. Data collected over 3 years showed that the project succeeded in its aim of enhancing early detection and treatment of postnatal depression. These findings replicate those of other studies. The data also showed that a substantial number of women were identified for the first time as likely to be suffering from postnatal depression at 12 months postpartum. Women screened for the first time at 12 months were at greater risk than those who had been screened earlier than this. Health visitors should screen for postnatal depression throughout the period of their contact with mothers, not solely in the immediate postnatal period. It is particularly important to screen women who, for whatever reason, were not screened when their child was younger. The knowledge and skills needed to use the Edinburgh Postnatal Depression Scale and provide first-line intervention and onward referral can be developed at practitioner level through close collaborative working.


The predatory mite, Pronematus ubiquitus, curbs Aculops lycopersici damage under greenhouse conditions.
The tomato russet mite, Aculops lycopersici, is a major worldwide pest infesting tomato crops for which only few control methods are available. At present, no commercialized beneficial organism has proven to be an effective biological control agent of the pest. As there is a strong need to develop alternatives to synthetic insecticides, we assessed the efficacy of an iolinid mite, Pronematus ubiquitus, as a preventive method against A. lycopersici in comparison with a curative treatment in a replicated experiment in the greenhouse. After pre-establishment of P. ubiquitus supplied with cattail pollen, followed by infestation of A. lycopersici, the predator was able to reduce pest populations by 98% as compared with control plants. Probably due to lack of food and high temperature, the number of P. ubiquitus decreased during the season and so the Eriophyid population rose, along with crop damage. The sulphur treatment could stop the progress of A. lycopersici, but their population levels remained high. Pronematus ubiquitus has a great potential to prevent the establishment of the tomato russet mite. Even if a curative treatment affects the pest mite, the use of a preventive method is preferable as such insecticides/acaricides are harmful for beneficials and are applied after symptom appearance, when the pest pressure is already high. Despite the need to optimise management of the predator throughout the season, P. ubiquitus proved to be able to establish successfully on tomato plants. This article is protected by copyright. All rights reserved.


pH-responsive dithiomaleimide-amphiphilic block copolymer for drug delivery and cellular imaging.
A drug delivery system that is integrated with fluorescent imaging is an emerging platform for tumor diagnostic and therapy. A pH-responsive fluorescent polymer that can respond to the surrounding medium is a desired component with which to construct an advanced drug delivery system with bioimaging characteristics and controllable drug releasing. In this work, we synthesized novel amphiphilic block copolymers of poly(ethylene glycol)-b-poly(2-(diisopropylamino) ethyl methacrylate-co-dithiomaleimide) (PEG-b-poly(DPA-co-DTM)) and poly(ethylene glycol)-b-poly(2-(dibutylamino) ethyl methacrylate-co-dithiomaleimide) (PEG-b-poly(DBA-co-DTM)) with pH-responsiveness and fluorescence. The block copolymers exhibited relatively stable fluorescence properties in different solvent and excitation-independent fluorescence behaviours. By copolymerizing the responsive segments in the molecule chain, the doxorubicin (DOX)-loaded micelles could be triggered to disassemble, thus releasing DOX at the corresponding pH values and yielding a pH-responsive drug release. Targeted deliveries of the drug within the cell were demonstrated by using the carrier responding to different pH values. The best antitumor effect was obtained by PEG-b-poly(DPA-co-DTM), which immediately released DOX as soon as it entered the tumor cells, as a result of responding to the regional pH level (pH = 6.3). The pH-responsive copolymers showed excellent biocompatibilities, as nearly 85% of cells with these fluorescent micelles survive when the testing concentration goes up to 200 μg mL-1. In all, these pH-responsive and dithiomaleimide-based fluorescent block copolymers hold great potential in future cancer diagnostic and therapeutic techniques.


Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation.
Tumor necrosis factor (TNF)-alpha controls T-cell activation and is a major inducer of human immunodeficiency virus (HIV)-1 replication in chronically infected cells. Therefore, we have investigated its role in primary cultures of HIV-infected human T lymphocytes by using neutralizing anti-TNF-alpha antibodies or TNF-alpha. Primary resting T lymphocytes produced TNF-alpha and supported HIV replication after T-cell receptor activation. Addition of neutralizing anti-TNF-alpha antibodies drastically reduced p24 antigen release and prevented CD4+ cell depletion associated with infection. Anti-TNF-alpha also prevented nuclear factor-kappa B (NF-kappa B) activation, and a good correlation between this inhibition and inhibition of HIV replication was observed. Moreover, supplementing the cultures with high doses of IL-2 reverted anti-TNF-alpha inhibition of cell proliferation but did not affect the inhibition of HIV p24 antigen release or NF-kappa B activation in the same cultures. Moreover, anti-TNF-alpha inhibited HIV-1 long terminal repeat (LTR)-driven transcription of a reporter gene in primary T cells in response to activation, either in the presence or the absence of HIV-1 Tat. Our results support an important role for autocrine TNF-alpha secretion in controlling HIV replication in primary T cells because of its ability to maintain NF-kappa B elevated in the nucleus of T cells.


[Impact of telemetric management on overall treatment costs and mortality rate among patients with chronic heart failure].
The rising prevalence of chronic heart failure (CHF) has led to an increase in total treatment expenditures. A medical care programme of telemetry was developed to reduce the number of patients with decompensated CHF, hospital admissions and overall treatment cost. As part of a prospective controlled study the body weight of 251 patients with CHF was monitored over one year. The supervising center contacted the patients whenever their body weight exceeded a threshold value. Patients were phoned by a designated personal adviser and received regular informative material and advice by specialist medical personnel. Patients' general practitioners had been involved in recruiting patients and by regularly sending them follow-up reports. Another group of 251 patients who had not received the described telemetric intervention served as control. The mean age of the patients was 71.7 years, lower than the 76.4 years of the control group. More patients in the intervention groups were in NYHA class III and IV than in the control group (52 % vs 36 %). After an average observation period of 12 months the duration of hospital stay had been reduced by 48 % (p = 0.01), the hospital costs by EUR 7128 per patient p = 0.01), while drug expenditure had increased by EUR 245 per patient (not significant). The total costs had thus fallen by EUR 6993 per patient (-39.5 %; p = 0.05). The mortality rate of 14.7 % in the intervention group was significantly lower than that of the control group of 27.1 % (p = 0.001). The reduction in costs and mortality rate was clearly greater for men than women. Total expenditure had been highest for patients who had died. The results indicate that total treatment costs and mortality rate can be reduced by telemetric monitoring of patients in CHF, especially in men.