Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells.
The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture. In this study, we generated mouse proliferating myeloid cells (pMC) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DC) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80, and CD86. In addition, exposure to maturation stimuli induced the production of TNFα and IL12p70, and enhanced the expression of MHC-II, CD40, and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow-derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2K(b)-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs.


Human histologic evaluation of a bone graft combined with GTR in the treatment of osseous dehiscence defects: a case report.
There are many possible goals and outcomes of periodontal surgical therapy, but the ultimate goal is regeneration. Since the definition of periodontal regeneration is histologic, it is difficult to document. The purpose of this study was to evaluate a technique that combined a bone graft and guided tissue regeneration (GTR) to see if regeneration occurred. Four teeth with dehiscence-type osseous defects that were scheduled for extraction were treated with bone grafts and GTR. During the surgical procedure, a notch was placed into the root at the apical extent of the calculus. The teeth were extracted with conservative block sections 7 months after the treatment. They were processed, sectioned, stained, and evaluated histologically. The results revealed that regeneration did not occur in any of the teeth treated. In 2 of the teeth new connective tissue attachment was formed. In these 2 teeth cementum could be seen in the notch with connective tissue fibers inserting into the cementum. In one of the teeth the junctional epithelium extended apical to the notch, while in 3 cases the epithelium stopped at or coronal to the notch. In this case report, no regeneration could be documented, but new attachment could be seen in 2 of the 4 teeth treated.


A Classic Pattern of Type 1 Brugada Syndrome on ECG: A Case Report.
Brugada syndrome is an inherited disorder characterized by a channelopathy of cardiac sodium, potassium, and calcium channel. The pathophysiology of this disorder is not completely elucidated yet, however, most of the reported cases are caused by a pathogenic alteration in the SCN5A gene, leading to the malfunction of cardiac sodium channels. Several stressors are well known to unmask this pathology including fever and electrolytes imbalance. Three ECG patterns are frequently described in the literature, type 1, type 2, and type 3. However, only the type 1 pattern is considered diagnostic of Brugada syndrome in the appropriate clinical context. Therapeutic strategies can range from conservative medical management with antiarrhythmic medications to Automatic Implantable Cardioverter Defibrillator (AICD) placement. Prompt recognition is of utmost importance since this pathology can rapidly evolve into life-threatening arrhythmias and sudden cardiac death. Here we present a case of a 22-year-old male who presented after a syncopal episode and was found to have Brugada syndrome in the setting of Influenza A infection.


Evidence of postprandial absorption of olive oil phenols in humans.
Olive oil phenols are potent antioxidants in vitro. If this were to be also demonstrated in vivo, it would help to explain the beneficial effects of this typical ingredient of the Mediterranean diet. This study was designed to determine the presence in lipoprotein fractions of two phenolic compounds peculiar to extra virgin olive oil, namely tyrosol and OH-tyrosol, and whether their absorption induces an antioxidant effect in vivo. Two trials were performed. In the first (Long-term), 14 healthy volunteers followed two diets, each for one month. The only difference between the diets was that the first supplied 50 g of extra virgin olive oil per day, where-as the second one supplied 50 g of refined olive oil with no simple phenols, as demonstrated by GC-MS analysis. There were no changes in LDL oxidizability and tyrosol and OH-tyrosol were not recovered in lipoproteins and plasma from fasting samples drawn at the end of each diet period. In the second study (Postprandial), eight healthy volunteers received an oral fat load consisting of 100 g of extra virgin olive oil. Blood was drawn at times 0', 30', 60', 120', 240', 360', and major plasma lipoprotein classes were separated. The concentration of tyrosol, OH-tyrosol and vitamin E was determined in lipoprotein fractions. Plasma antioxidant capacity was measured by a crocin-bleaching test and expressed as mM Trolox C equivalents. Tyrosol and OH-tyrosol were recovered in all lipoprotein fractions, except VLDL, with concentrations peaking between 60' and 120'. However, a very high variability in tyrosol and OH-tyrosol absorption was observed among subjects. Vitamin E content of LDL and HDL did not vary significantly throughout the study. Plasma antioxidant capacity increased significantly at time 120' (baseline 0.96 mM Trolox; 120' 1.19 mM Trolox; p = 0.02), and then returned almost to baseline values after 360' (1.1 mM Trolox). These findings suggest that phenolic compounds in olive oil are absorbed from the intestine, though not through a pathway dependent on chylomicron formation, and may exert a significant antioxidant effect in vivo, probably in the postprandial phase.


A qualitative exploration of smokers' views regarding aspects of a community-based mobile stop smoking service in the United Kingdom.
Developing more accessible stop smoking services (SSS) is important, particularly for reaching smokers from socio-economically deprived groups who are more likely to smoke and less likely to quit in comparison to their more affluent counterparts. A drop-in mobile SSS (MSSS) was piloted across 13 locations in socio-economically deprived areas of Nottingham. Semi-structured telephone interviews were conducted to explore the views of 40 smokers who registered with the MSSS. The MSSS appeared to trigger quit attempts. For some of the participants the attempt was totally unplanned; for others, it built on pre-existing thoughts about quitting which had not yet been acted upon. Smokers interested in quitting were comfortable about approaching the MSSS, whilst acknowledging that they did not feel pressured to register with the service. The drop-in format of the MSSS was found to be more appealing than making an appointment. In addition, several participants articulated that they may not have utilised other SSS had they not come across the MSSS. A MSSS may be an effective way to prompt quit attempts for smokers not planning to quit and also reach smokers who would not engage with SSS.


An educational intervention to improve data recording in the management of ischaemic heart disease in primary care.
Gaps in computerized medical records and a lack of a systematic approach to data recording make progress towards achieving quality standards in primary care difficult to demonstrate. The aim of this study was to examine the effect of an educational intervention on data quality in primary care. A before-and-after study of key data quality measures was carried out in 87 general practices in eight primary care organizations in England in phase 1 and 84 general practices in phase 2. The subjects were 19,470 patients with ischaemic heart disease in phase 1 and 19,784 patients in phase 2. The main outcome measures were improvement in the completeness and quality of the computerized medical record. Anonymized data were extracted from clinical information systems and processed to produce comparative information on each practice. Data quality workshops were arranged, in which reflection can take place, backed up by summary statistics. Practice visits provided training and personalized feedback of patients needing intervention. In the patients with heart disease, nearly 16,000 new clinical entries were made in the key improvement areas. The percentage of patients advised to quit smoking increased by 49.3 per cent, from 23.6 per cent to 61.9 per cent. There were also significant improvements in many other aspects of management. Focused interventions that provide targeted and relevant clinical information can be implemented in primary care. Such interventions can lead to a rise in data quality in primary care, but their effectiveness needs to be further tested in more rigorous research settings such as randomized controlled trials.


Regional variation in health care intensity and treatment practices for end-stage renal disease in older adults.
An increasing number of older adults are being treated for end-stage renal disease (ESRD) with long-term dialysis. To determine how ESRD treatment practices for older adults vary across regions with differing end-of-life intensity of care. Retrospective observational study using a national ESRD registry to identify a cohort of 41,420 adults (of white or black race), aged 65 years or older, who started long-term dialysis or received a kidney transplant between June 1, 2005, and May 31, 2006. Regional end-of-life intensity of care was defined using an index from the Dartmouth Atlas of Healthcare. Incidence of treated ESRD (dialysis or transplant), preparedness for ESRD (under the care of a nephrologist, having a fistula [vs graft or catheter] at time of hemodialysis initiation), and end-of-life care practices. Among whites, the incidence of ESRD was progressively higher in regions with greater intensity of care and this trend was most pronounced at older ages. Among blacks, a similar relationship was present only at advanced ages (men aged > or = 80 years and women aged > or = 85 years). Patients living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to be under the care of a nephrologist before the onset of ESRD (62.3% [95% confidence interval {CI}, 61.3%-63.3%] vs 71.1% [95% CI, 69.9%-72.2%], respectively) and less likely to have a fistula (vs graft or catheter) at the time of hemodialysis initiation (11.2% [95% CI, 10.6%-11.8%] vs 16.9% [95% CI, 15.9%-17.8%]). Among patients who died within 2 years of ESRD onset (n = 21,190), those living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to have discontinued dialysis before death (22.2% [95% CI, 21.1%-23.4%] vs 44.3% [95% CI, 42.5%-46.1%], respectively), less likely to have received hospice care (20.7% [95% CI, 19.5%-21.9%] vs 33.5% [95% CI, 31.7%-35.4%]), and more likely to have died in the hospital (67.8% [95% CI, 66.5%-69.1%] vs 50.3% [95% CI, 48.5%-52.1%]). These differences persisted in adjusted analyses. There are pronounced regional differences in treatment practices for ESRD in older adults that are not explained by differences in patient characteristics.


Empowering individuals to self-manage chemotherapy side effects.
Providing concise, consistent, and individually relevant patient education is critical. At one institution, patients and families attended a chemotherapy education class consisting of an 11-minute DVD and an oncology nurse-facilitated group discussion. Postclass and eight-week follow-up surveys assessing understanding of treatment side effects, self-care management, and confidence in managing side effects were administered. Quantitative and qualitative data suggested the DVD and oncology nurse-facilitated group discussion provided consistent information, flexibility, and expert knowledge in empowering patients and families to self-manage chemotherapy side effects.


Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent.
Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment.


To whom do psychiatrists offer smoking-cessation counseling?
Individuals with mental illness have high rates of tobacco dependence; however, little is known about what influences a psychiatrist's decision to offer smoking-cessation counseling to smoking patients. Using the National Ambulatory Medical Care Survey, the authors identified 1,610 psychiatric office visits for patients who smoke. They investigated the relationship between patient and visit characteristics and smoking-cessation counseling with logistic regression. Psychiatrists offered cessation counseling at 12.4% of the visits for smoking patients. The adjusted probability of receiving smoking-cessation counseling was significantly higher for those older than 50; for those with a medical diagnosis of obesity, hypertension, or diabetes mellitus; for those in a rural location; and for those having an initial visit. Those with bipolar affective disorder were more likely to receive smoking-cessation counseling than those with depression. Psychiatrists may be missing opportunities to offer smoking-cessation counseling to patients who smoke.


The effect of antisera to insulin, 2-deoxyglucose-induced hyperglycemia, and starvation on wound healing in normal mice.
Wound healing was examined in normal C57BL/6 male mice treated with antiserum to insulin or 2-deoxyglucose (2-DG) and in mice starved for 33 h. Hyperglycemia was induced after antiserum or 2-DG treatment; the blood glucose was lowered in the starved mice when compared with controls. Small dermal wounds were made in the ears of the mice 1 h after the initial injection of antisera or 2-DG. The starved group were wounded after 25 h of fasting. All animals were biopsied 8 h later. The wounds were examined by light microscopy and wound components (capillaries, fibroblasts, PMNs, collagen, and edema) were quantitated by lineal point analysis. Mice treated with antisera to insulin and mice starved for 33 h had an impaired healing response; the mice treated with 2-DG had a response similar to controls. These results suggest that hyperglycemia, per se, or the production of any toxic metabolites from high blood glucose levels could not alone induce the poor healing response. The depressed response in the antiserum-treated and starved mice may be due to the decreased availability of insulin to the wound tissues. These data support the hypotheses that insulin is a necessary component for an adequate wound healing response. In addition to a role in glucose transport and metabolism, insulin may also promote cellular growth.


Characterization of a novel porcine parvovirus tentatively designated PPV5.
A new porcine parvovirus (PPV), provisionally designated as PPV5, was identified in U.S. pigs. Cloning and sequencing from a circular or head-to-tail concatemeric array revealed that the PPV5 possesses the typical genomic organization of parvoviruses with two major predicted open reading frames (ORF1 and ORF2), and is most closely related to PPV4 with overall genomic identities of 64.1-67.3%. The amino acid identities between PPV5 and PPV4 were 84.6%-85.1% for ORF1 and 54.0%-54.3% for ORF2. Unlike PPV4, but similar to bovine parvovirus 2 (BPV2), PPV5 lacks the additional ORF3 and has a much longer ORF2. Moreover, the amino acid sequences of ORF1 and ORF2 of BPV2 showed higher homologies to PPV5 than to PPV4. The conserved motifs of the Ca(2+) binding loop (YXGXG) and the catalytic center (HDXXY) of phospholipase A2 (PLA2) were identified in VP1 (ORF2) of PPV5, as well as in BPV2, but were not present in PPV4. Phylogenetic analyses revealed that PPV5, PPV4 and BPV2 form a separate clade different from the genera Parvovirus and Bocavirus. Further epidemiologic investigations of PPV4 and PPV5 in U.S. pigs of different ages indicated a slightly higher prevalence for PPV5 (6.6%; 32/483) compared to PPV4 (4.1%; 20/483), with detection of concurrent PPV4 and PPV5 in 15.6% (7/45) of lungs of infected pigs. Evidence for potential vertical transmission or association with reproductive failure was minimal for both PPV4 and PPV5. The high similarity to PPV4 and the lack of ORF3 may suggest PPV5 is an intermediate of PPV4 during the evolution of parvoviruses in pigs.


Ribosomal protein S27-like is a physiological regulator of p53 that suppresses genomic instability and tumorigenesis.
Cell-based studies showed that several Mdm2-binding ribosomal proteins, upon overexpression, stabilize and activate p53. In contrast, here we show in a mouse knockout study that Mdm2-binding ribosomal protein S27-like (Rps27l), upon disruption, activates p53. Germline inactivation of Rps27l triggers ribosomal stress to stabilize Mdm2, which degrades Mdm4 to reduce Mdm2-Mdm4 E3 ligase towards p53, leading to p53-dependent apoptotic depletion of hematopoietic stem cells and postnatal death, which is rescued by Trp53 deletion. Paradoxically, while increased p53 is expected to inhibit tumorigenesis, Rps27l⁻/⁻;Trp53⁺/⁻ mice develop lymphomas at higher incidence with p53 loss-of-heterozygosity and severe genome aneuploidy, suggesting that Rps27l disruption impose a selection pressure against p53. Thus, Rps27l has dual functions in p53 regulation: under Trp53⁺/⁺ background, Rps27l disruption triggers ribosomal stress to induce p53 and apoptosis, whereas under Trp53⁺/⁻ background, Rps27l disruption triggers genomic instability and Trp53 deletion to promote tumorigenesis. Our study provides a new paradigm of p53 regulation.


Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients.
Cutaneous vasculitis (CV), a condition characterized by palpable purpura and nonspecific histopathologic findings, presents a diagnostic and therapeutic challenge because it may be a primary disorder or it may be a cutaneous manifestation of another entity, such as systemic necrotizing vasculitis, connective tissue disease, systemic bacterial infection, or malignancy. We studied 303 unselected patients (172 adults and 131 children) with CV to assess the disease associations and etiologic factors, to identify the frequency of primary and secondary CV in different age-groups, and to characterize features that help to distinguish between primary and secondary CV. Of the 131 children, 130 had primary CV: Henoch-Schönlein purpura (HSP) in 116 and hypersensitivity vasculitis (HV) in 14. In contrast, of the 172 adults, only 120 had primary CV: HSP in 39, HV in 70, and essential mixed cryoglobulinemia in 11. CV was a manifestation of systemic necrotizing vasculitis in 23 adults (polyarteritis nodosa in 17, Wegener granulomatosis in 4, and Churg-Strauss syndrome in 2). CV was secondary to other processes in 29 adults: in 20 patients CV was associated with connective tissue disease or another autoimmune or rheumatic disease, in 5 patients CV was a manifestation of severe bacterial infection, especially bacterial endocarditis (4 cases), and in the other 4 patients CV was the presenting symptom of an underlying malignancy. The patients for whom CV was a manifestation of systemic necrotizing vasculitis or secondary to a connective tissue disease, severe bacterial infection, or malignancy had clinical and laboratory data suggestive of the associated disorder. The clinical picture and outcome of primary CV in both children and adults were benign. By contrast, the prognosis of patients with CV in the context of systemic necrotizing vasculitis or secondary to other entities depended on the primary process. Given the different disease association in children and adults, we propose a simple diagnostic workup in children with CV. By contrast the diagnostic approach in adults with CV should be more cautious and the workup more extensive. The early differentiation between primary CV, secondary CV, and CV presenting as a symptom of systemic necrotizing vasculitis, especially in adults, is of paramount importance for an adequate diagnosis and appropriate treatment.


Mohs surgery of basal cell carcinoma--a critical review.
Mohs surgery for basal cell carcinoma (BCC) of the skin attempts to ensure complete tumour removal by histological examination of the entire excision margin and further excision of involved sites. Advocates recommend its use in recurrent or incompletely excised tumours, poorly defined, histologically aggressive or large primary tumours and BCCs situated at high risk or cosmetically important sites. The claimed advantages over other surgical therapies are that it provides a better chance of cure and since less normal tissue is removed the simpler surgical repair ensures a superior cosmetic result. This review examines the published evidence that supports the enthusiasm for the use of Mohs surgery in the treatment of BCC, contrasting cure rates and cosmetic outcome with results achieved by attempted single complete excision and examines the 2 principles upon which Mohs surgery is based, namely that BCCs spread by contiguous growth and that all tumour cells have to be destroyed to achieve a cure.


School finance: fifty years of expansion.
Since 1949-50, per-pupil expenditures in public elementary and secondary schools have more than quadrupled, even after adjusting for inflation. This article discusses some of the reasons. A significant share of the increase is the result of an 86% inflation-adjusted increase in teachers' salaries between 1949-50 and 1971-72, although teachers' salaries have changed little in the following 25 years. The ratio of students to school employees has dropped by half since 1949-50 as a result of declining class sizes and the hiring of more nonteaching school employees, which significantly affects costs. Even maintaining class size at a constant level will cause school budgets to grow at a rate greater than that of inflation because schools must compete in a labor market against other employers who are able to produce more with fewer employees. A substantial part of the increase in per-pupil spending is a result of expansions in services provided by the schools. More expensive, specialized classes for high school students, compensatory education for students from disadvantaged backgrounds, special education and related services for students with disabilities, and desegregation efforts all contribute to higher costs. Efforts to improve funding equity have led to increased expenditures: rather than take funding from wealthier districts, most states prefer to raise the funding available to schools at the bottom and the middle of the scale, increasing total spending. Finally, a share of the total increase must be attributed to the workings of the political system governing schools.


Vulnerability and protection talk: systemic therapy process with people with intellectual disability.
Vulnerability and protection are key concepts within the literature relating to systemic therapy for people with an intellectual disability (ID). This paper explores the processes by which these concepts were discussed in systemic therapy sessions. Four videotapes of systemic therapy sessions were evaluated using a qualitative design, incorporating thematic and conversation analysis. The videotapes were drawn from systemic therapy sessions with 3 families with an adult with ID. Vulnerability and protection themes were identified within the content of therapeutic conversations, including protection from the disability and its consequences; protection from peers, siblings, and the world at large; and protection from emotionally sensitive topics. Protective strategies were also used by all system members through the process of therapy. Key strategies were topic switch and reversals. Protection is a key issue. Clinical practice could be enhanced if therapists reflect on the strategies they employ in addressing protection effectively.


A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma.
The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival.


Effects of oral UFT combined with or without zoledronic acid on bone metastasis in the 4T1/luc mouse breast cancer.
Bone metastasis is one of the major causes of increased morbidity and eventual mortality in breast cancer patients. Therefore, intervention of bone metastases is one of the important targets in the management of breast cancer. In the present study, we examined the effects of the orally administrable chemotherapeutic agent UFT (a combination of tegafur and uracil at a molar ratio of 1:4) on bone metastases using an animal model of the 4T1/luc mouse breast cancer. The 4T1/luc cells developed spontaneous metastases to bone following orthotopic cell inoculation. Oral daily administration of UFT (20 mg/kg/day) significantly reduced the orthotopic tumor burden; however, the lower dose (15 mg/kg/day) did not. In contrast, histologic examination showed that both doses of UFT significantly suppressed bone metastases in a dose-dependent manner. Since clinical studies have demonstrated that bisphosphonates (BPs), specific inhibitors of osteoclastic bone resorption, are beneficial for breast cancer patients with bone metastases, we next examined the effects of UFT combined with the BP zoledronic acid (ZOL) on established bone metastases. The combination of UFT (20 mg/kg/day) with ZOL (250 microg/kg) caused an enhanced reduction of bone metastases compared with UFT alone. In vitro studies showed that 5-fluorouracil (5-FU), an active metabolite of UFT, and ZOL increased apoptosis in 4T1/luc cells and inhibited osteoclast-like cell formation in an additive fashion. Our results suggest that oral UFT is an effective chemotherapeutic agent for advanced breast cancer accompanying bone metastases and that the combination with BP increases its benefits for bone metastases.


Angiotensin IV is induced in experimental autoimmune encephalomyelitis but fails to influence the disease.
In multiple sclerosis (MS) and its corresponding animal models, over-activity of the renin-angiotensin system (RAS) has been reported and pharmacological RAS blockade exerts beneficial effects. The RAS generates a number of bioactive angiotensins, thereby primarily regulating the body's sodium homeostasis and blood pressure. In this regard, angiotensin IV (AngIV), a metabolite of the RAS has been shown to modulate inflammatory responses. Here we studied potential implications of AngIV signalling in myelin oligodendrocyte glycoprotein (MOG) peptide induced murine experimental autoimmune encephalomyelitis (EAE), a close-to-MS animal model. Mass spectrometry revealed elevated plasma levels of AngIV in EAE. Expression of cognate AT4 receptors was detected in macrophages and T cells as major drivers of pathology in EAE. Yet, AngIV did not modulate macrophage or T cell functions in vitro or displayed detectable effects on neuroantigen specific immune responses in vivo. The data argue against a major contribution of AngIV signalling in the immunopathogenesis of MOG-EAE.


Can sexual outcomes be enhanced after cancer using online technology?
The impact that cancer and its treatments can have on sexual functioning, sexual desire, and sexual arousal can be profound and many patients report significant unmet needs in relation to managing sexual difficulties. We reviewed the literature to understand the application of Internet-based technology in the delivery of psychosexual interventions, information provision, and support. Ten studies were identified that utilized Internet-based technology to deliver information, support, or psychosexual interventions designed to improve sexual outcomes, sexual distress, and quality of life of cancer survivors. The intensity of intervention, approach, and complexity differed substantially across platforms. The review identified a range of intervention types designed to enhance sexual outcomes following the challenges that many individuals face after cancer diagnosis and treatment. It is evident that the use of online technology in improving sexual outcomes in cancer care is still in its infancy; however, there is emerging evidence to support the delivery of psychosexual care using the online environment. Further research, using larger, more well controlled methodologies, is required to confirm that sexual outcomes can be improved through the use of online interventions.


Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus.
The human cell surface antigen 4F2 is a disulfide-linked heterodimer consisting of a glycosylated heavy chain and a nonglycosylated light chain. The antigen is ubiquitously expressed on proliferating cells but only in resting cells from certain tissues. Its function has been proposed to relate to cellular Ca2+/Na+ exchange. We describe the molecular cloning of the 4F2 heavy chain gene and cDNA by a gene transfer approach. Part of the gene was isolated from a genomic lambda library constructed with DNA of a secondary transfectant L cell line that expresses 4F2 antigen. A gene-specific probe derived from the phage inserts was used to isolate two full length cDNA clones. Both cDNA clones directed the expression of 4F2 antigen in transfected mouse L cells. The 4F2 antigen heavy chain gene specifies a 2.1-kilobase mRNA with an open reading frame coding for a 529-residue protein of 58 kDa. The protein lacks an NH2-terminal signal peptide but contains an internal transmembrane-spanning region and four potential glycosylation sites in its COOH-terminal domain. We predict that the 4F2 antigen heavy chain is a transmembrane protein with a cytoplasmic NH2 terminus of 81 amino acids. The antigen shows no homology to known protein sequences.


The association between human milk fatty acid composition in mothers with an elevated body mass index and infant growth changes.
Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life. Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age. We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted β = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories.


Favorable effects of myo-inositol, selenomethionine or their combination on the hydrogen peroxide-induced oxidative stress of peripheral mononuclear cells from patients with Hashimoto's thyroiditis: preliminary in vitro studies.
The aim of this study was to assess whether blood mononuclear cells (PBMC) from Hashimoto's thyroiditis (HT) and control women, were protected from in vitro H2O2-induced oxidative stress after addition of antioxidants. PBMC, from 8 HT women and 3 healthy women (controls), were cultured in the presence of 200 µM H2O2 alone, with subsequent addition of myo-inositol (Myo) (0.25, 0.5, 1.0 µM), selenomethionine (SelMet) (0.25, 0.5, 1.0 µM), or their combination (0.25+0.25, 0.5+0.5, 1.0+1.0 µM). PBMC proliferation, vitality, genotoxicity (Comet score) and secretion in the medium of the chemokines CXCL10 [IP10], CCL2 e CXCL9 [MIG] were the indices measured. PBMC proliferation was decreased by H2O2 alone, and it decreased further and dose-dependently in either group (greatest decrease with Myo+SelMet in HT). H2O2 alone decreased vitality by 5% in controls and 10% in the HT group, but vitality was rescued by the three additions. The addition of H2O2 alone increased the Comet score at +505% above baseline in controls and +707% in HT women. In either group, each addition dose-dependently contrasted genotoxicity. Concentrations of chemokines in the medium were increased by H2O2 alone, and in HT women more than in controls. Each addition dose-dependently decreased these concentrations in either group, and often below baseline levels, with Myo+SelMet being the most potent addition (up to approximately -80% of baseline). The tested antioxidants exert beneficial effects on PBMC exposed in vitro to H2O2-induced oxidative stress in both control and HT women. Particularly, the association Myo+SelMet is the most effective. After the demonstration of a favorable in vitro outcomes in a large cohort of HT patients, we could predict favorable in vivo outcomes given by the same supplement. Thus, one can select HT patients with a high chance of benefit from supplementation.


Self-harm in young offenders.
The prevalence and correlates of self-harm and suicidal behavior in 515 young offenders (mean age 17.3 years, SD = 1.7) serving community-based orders (CBOs; n = 242) or custodial sentences (n = 273) in Victoria, Australia, are described. Results from structured interviews showed that 83 (16.1%) participants reported self-harming in the previous 6 months, and this was more common among those serving custodial sentences than those serving CBOs (19.4% vs. 12.4%; OR 3.10, 95% CI: 1.74-5.55). Multiple incidents were more common in females and 24% (95% CI: 19-39) of participants who had self-harmed reported having done so with suicidal intent. Self-harm was associated with recent bullying victimization, expulsion from school, past year violent victimization, cannabis dependence, and risk-taking behavior in the preceding year. The epidemiological profile of self-harm in this population appears to be distinct from that seen in the general population. Young offenders who self-harm are a vulnerable group with high rates of psychiatric morbidity, substance misuse problems, and social risk factors. They may benefit from targeted psychological interventions designed specifically to address impulsivity, delivered both within-and during the transition from-the youth justice system.


Reduction by beta-adrenoceptor blockade of hypoxia-induced right heart hypertrophy in the rat.
1. The study was undertaken to assess the role of beta-adrenoceptors in the induction of compensatory cardiac hypertrophy in an in vivo model. 2. In the rat, exposure to severe hypoxia (6% inspired oxygen for 8 h day) caused a 51% increase in right heart weight and a 75% increase in haematocrit. 3. The hypoxia-induced right ventricular hypertrophic response was reduced by 65% by oral treatment with a high dose of the non-selective beta-adrenoceptor antagonist, propranolol (80 mg kg-1 body weight); the drug treatment caused only a minor reduction (6%) in secondary polycythaemia. 4. With a less severe degree of hypoxia (7% inspired oxygen) there was only minimal secondary polycythaemia (+15%), and a lesser degree of compensatory right ventricular hypertrophy in untreated rats (+33%). 5. Treatment with the beta 1-adrenoceptor antagonist, atenolol, in a dose of 80 mg kg-1 body weight abolished right ventricular hypertrophy in response to 7% inspired oxygen, without affecting haematocrit and caused a small reduction in the ratio of heart weight to body weight in normoxic rats. 6. The results show that the effect of propranolol on hypoxic right ventricular hypertrophy is not secondary to any effect on secondary polycythaemia as has previously been suggested and that a marked reduction of compensatory cardiac hypertrophy can be obtained by a beta 1-selective adrenoceptor antagonist. Thus these findings support the view that noradrenaline released from cardiac sympathetic nerve terminals exerts a trophic effect on myocardial cells and demonstrates that in vivo, this trophic effect can be reduced by beta 1-adrenoceptor blockade.


Crystal nucleation in simple and complex fluids.
The application of density-functional methods from statistical mechanics to the nucleation of crystals from the melt is described. Simple fluids such as metals, with sizes comparable with the range of their attractive forces, are compared with complex fluids such as colloidal suspensions and proteins dissolved in solution. A different mechanism for crystal nucleation is proposed in the latter case, in which density (concentration) changes before periodic crystalline order appears. This leads to a theoretical foundation for empirical observations on the 'crystallization window' in protein crystallization. Comparisons are made with the results of computer simulation via molecular dynamics.


Rumor has it...: relay communication of stress cues in plants.
Recent evidence demonstrates that plants are able not only to perceive and adaptively respond to external information but also to anticipate forthcoming hazards and stresses. Here, we tested the hypothesis that unstressed plants are able to respond to stress cues emitted from their abiotically-stressed neighbors and in turn induce stress responses in additional unstressed plants located further away from the stressed plants. Pisum sativum plants were subjected to drought while neighboring rows of five unstressed plants on both sides, with which they could exchange different cue combinations. On one side, the stressed plant and its unstressed neighbors did not share their rooting volumes (UNSHARED) and thus were limited to shoot communication. On its other side, the stressed plant shared one of its rooting volumes with its nearest unstressed neighbor and all plants shared their rooting volumes with their immediate neighbors (SHARED), allowing both root and shoot communication. Fifteen minutes following drought induction, significant stomatal closure was observed in both the stressed plants and their nearest unstressed SHARED neighbors, and within one hour, all SHARED neighbors closed their stomata. Stomatal closure was not observed in the UNSHARED neighbors. The results demonstrate that unstressed plants are able to perceive and respond to stress cues emitted by the roots of their drought-stressed neighbors and, via 'relay cuing', elicit stress responses in further unstressed plants. Further work is underway to study the underlying mechanisms of this new mode of plant communication and its possible adaptive implications for the anticipation of forthcoming abiotic stresses by plants.


Comparing different methods for olefin quantification in pygas and plastic pyrolysis oils: Gas chromatography-vacuum ultraviolet detection versus comprehensive gas chromatography versus bromine number titration.
In steam cracking, upstream pyrolysis oil hydroprocessing, and in many downstream processes, olefinic content is key to assess process performance and process safety risk associated with highly exothermic reactions. When looking to plastic pyrolysis oils as a potential feedstock, as well as downstream products such as pyrolysis gasoline (pygas), these materials contain unsaturated hydrocarbons which are not present in fossil feedstocks. Pygas is a product of pyrolysis and exhibits a large number of chemical structural similarities with plastic pyrolysis oils, especially in terms of olefins structure. Quantification of the unsaturation content (olefins and di-olefins) is extremely important in industry, hence the focus of this manuscript. Detailed hydrocarbon analysis with flame ionization detection is inadequate to fully characterize the hydrocarbon composition of such samples, especially when peaks are closely eluting, or even co-eluting. In this study, the gas chromatography coupled to vacuum ultraviolet (GC-VUV) detection method previously described for the analysis of liquid hydrocarbon streams1 and plastic pyrolysis oils2 has been compared with comprehensive gas chromatography (GC × GC) and the industry standard for olefin quantification (i.e., bromine number titration). Although based on different methodologies, a correlation between the olefin content obtained from GC-VUV and the bromine number titration method is hereby presented.


Factors Influencing Willingness to Pay for Insecticidal Treated Bed Nets Among Rural Households of Bugina District North Wollo Zone, North-East Ethiopia.
Understanding potential demand and willingness to pay for the insecticide treated nets is important for sustainable insecticide-treated bed net intervention. However, there is limited evidence, and there is no study in this malarious area, so the study aimed to assess willingness to pay for insecticide-treated bed net and influencing factors. A multi-stage community-based cross-sectional study was conducted by using an interview administered questionnaire with a total sample size of 711H.H from March 01 to 30, 2020. The data were entered into EPI data version 4.6.0 and exported to STATA SE version 14 for further analysis. The mean price of willingness to pay was presented as mean and median. Bivariable and multivariable Tobit economical model was used to identify factors associated with willingness to pay. Regression coefficient (ß), 95% CI, t-value and p-value were used to measure the strength and presence of a statistical association. A total of 683 study participants with a response rate of 96.1% were included in the study. Sixty-four percent of respondents were willing to pay for three types of an insecticide-treated bed net, and the mean price for blue rectangular medium size ITN was 46 (±12.9) birr, for white circular medium size ITN was 44 (±12.3) birr and for blue circular medium size ITN was 43 (±11.8) birr. The factors influencing willingness to pay were sex, educational status, wealth status and knowledge toward malaria and ITN. This study revealed that in the Bugina district majority of the households were willing to pay for the three types of ITN with a mean price of 55.6 ETB. Sex, educational status, knowledge and wealth index are factors affecting willingness to pay for ITN; further awareness needs to be created regarding the severity of malaria and the demand of ITN.


Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: emerging translational approaches that bridge biology and behavior.
Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real-time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examine brain-based mechanisms of change, whereas others examine brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors.


Exonucleolysis is required for nuclear mRNA quality control in yeast THO mutants.
Production of aberrant messenger ribonucleoprotein particles (mRNPs) is subject to quality control (QC). In yeast strains carrying mutations of the THO complex, transcription induction triggers a number of interconnected QC phenotypes: (1) rapid degradation of several mRNAs; (2) retention of a fraction of THO-dependent mRNAs in transcription site-associated foci; and (3) formation of a high molecular weight DNA/protein complex in the 3'-ends of THO target genes. Here, we demonstrate that the 3'-5' exonucleolytic domain of the nuclear exosome factor Rrp6p is necessary for establishing all QC phenotypes associated with THO mutations. The N terminus of Rrp6p is also important presumably through its binding to the Rrp6p co-factor Rrp47p. Interestingly, the 3'-5' exonucleolytic activity of Dis3p, the only other active exonuclease of the nuclear exosome, can also contribute to RNA QC in THO mutants, while other nuclear 3'-5' exonucleases cannot. Our data show that exonucleolytic attack by the nuclear exosome is needed both for provoking mRNP QC and for its ensuing elimination of faulty RNA.


[Biogenesis of melanosomes - the chessboard of pigmentation].
Melanosomes are lysosome-related organelles in retinal pigment epithelial cells and epidermal melanocytes in which melanin pigments are synthesized and stored. Melanosomes are generated by multistep processes in which an immature unpigmented organelle forms and then subsequently matures. Such maturation requires inter-organellar transport of protein cargos required for pigment synthesis but also recruitment of effector proteins necessary for the correct transport of melanosomes to the cell periphery. Several studies have started to unravel the main pathways and mechanisms exploited by melanosomal proteins involved in melanosome structure and melanin synthesis. A major unexpected finding seen early in melanosome biogenesis showed the similarities between the fibrillar sheets of premelanosomes and amyloid fibrils. Late steps of melanosome formation are dependent on pathways regulated by proteins encoded by genes mutated in genetic diseases such as the Hermansky-Pudlak Syndrom (HPS) and different types of albinism. Altogether the findings from the past recent years have started to unravel how specialized cells integrate unique and ubiquitous molecular mechanisms in subverting the endosomal system to generate cell-type specific structures and their associated functions. Further dissection of the melanosomal system will likely shed light not only on the biogenesis of lysosome-related organelles but also on general aspects of vesicular transport in the endosomal system.


Comprehensive molecular analysis identifies RET alterations association with response of ICIs in multi-immunotherapy cohorts.
The RET gene, which is frequently mutated across many types of cancer, has been proven to be critically involved in tumorigenesis and tumour development; however, its prediction of the therapeutic efficacy of immune checkpoint inhibitor (ICI) therapy remains to be elucidated. The present research aims to investigate the association between RET mutations and the efficiency of ICI therapy. We analysed the role of RET mutations in predicting the prognosis of patients receiving ICIs therapy in the discovery cohort and validated it in the validation cohort. Then, multi-omics data from TCGA pan-cancer cohort was employed to propose the association between RET mutations and tumour inflamed anti-tumour immune response and tumour antigenicity. Our study revealed that among 606 cases and across five types of cancer, RET mutation was associated with better clinical outcomes for ICIs therapy, including elevated response rate, longer progression-free survival PFS, and longer overall survival OS. Multivariate analysis showed that RET mutation could independently predict the prognosis of patients treated with ICIs, after adjusting cancer types. The predictive value of RET status for the OS of patients treated with ICIs immunotherapy was further validated in the validation cohort (n = 1,409). Subgroup analysis suggested that only the monotherapy group showed significant differences in OS(P < 0.05) and PFS(P < 0.05) between RET-wildtype tumours and RET-mutant tumours. Multi-omics data analysis revealed potential anti-tumour immunity mechanisms of RET mutations, suggesting that RET-mutant tumours have enhanced immunogenicity, higher expression of immune checkpoints and chemokines, and higher immune cell infiltration than those observed in RET-wildtype tumours; thus, potentially indicating a more favourable response to immunotherapy. RET mutation may be a predictive biomarker of enhanced response to ICIs therapy. Extensive investigation of the underlying molecular mechanisms and prospective studies are needed in the future.


The psychosocial work environment and mental health of teachers: a comparative study between the United Kingdom and Hong Kong.
There is limited research on teachers' psychosocial work environment and mental health, and most has been conducted in predominantly Western countries that share a number of important common characteristics that distinguish them from countries in many other regions of the world. Within the framework of the effort-reward imbalance (ERI) theoretical model, the relationship between the psychosocial work environment and mental health of teachers in the United Kingdom (UK) and Hong Kong (HK) was investigated. Full-time qualified teachers from both the UK and HK (N = 259) participated in the research. They were asked to fill in a set of questionnaires that measured their perceived stress, mental health, psychosocial work environment and demographic information. Perceived stress was found to predict teachers' mental health. Overcommitment, the intrinsic component of the ERI model, predicted mental health among HK teachers. There were significant differences in the psychosocial variables between UK and HK teachers. The results showed support for the ERI model and in particular for the relationship between stress and mental health and demonstrated the role of overcommitment in the teaching profession. Some implications are discussed for combating cultural differences in managing the psychosocial work environment of teachers.


Feline ovarian neoplasms.
Primary ovarian neoplasms from 22 cats were described. A single cat had tumors of epithelial origin--bilateral cystadenomas. Seven animals had germ cell tumors--dysgerminomas or teratomas; two cats had bilateral tumors. Fourteen animals had neoplasms of sex cord-stromal origin--granulosa cell tumors and interstitial gland tumors. Four cats with granulosa cell tumors had clinical evidence of hormonal disturbance.


Rollover-free navigation for a mobile agent in an unstructured environment.
This paper introduces a navigation method for a teleoperated mobile agent (or robot) moving in an unstructured environment that includes unknown obstacles and uneven terrain, based on a guided-navigation algorithm (GNA) and a rollover-prevention algorithm (RPA). Although the mobile agent is primarily driven by an operator at a remote site, it reacts autonomously for avoiding collision with obstacles and for preventing rollover when it suspects/detects possible collision or rollover. The autonomous reactive motion is normally unexpected, thus there exists the inconsistency between the intended motion and the controlled motion of the agent from the operator. A force-reflection technique utilizing a force-feedback joystick is developed to manipulate this inconsistency. To verify the feasibility and effectiveness of the proposed navigation method, experiments with the Robot for Hazardous Application-Double Tracks (ROBHAZ-DT) (actual mobile agent) are successfully carried out.


Automatic attention cueing through eye movement in 2-year-old children with autism.
Automatic attention cueing by perceived changes in gaze direction was studied in 2-year-old children with autism and typically developing (TD) controls using a visual attention cueing paradigm. In Experiments 1 and 2 the cue consisted of an eye movement (Eyes) and a nonbiological movement (SimEyes), respectively. The results suggest that visual attention in children with autism and their TD counterparts is cued by perceived eye movement. Thus, although in naturalistic situations toddlers with autism do not follow the gaze of others, they are sensitive to directional cues inherent in eye movement. Cue-specific differences in performance related to the level of engagement and cue-processing time may suggest reliance on different underlying strategies for gaze processing in autism.


Respiratory training interventions improve health status of heart failure patients: A systematic review and network meta-analysis of randomized controlled trials.
Prior studies indicate that doing breathing exercises improves physical performance and quality of life (QoL) in heart failure patients. However, these effects remain unclear and contradictory. To determine the effects of machine-assisted and non-machine-assisted respiratory training on physical performance and QoL in heart failure patients. This was a systematic review and network meta-analysis study. A literature search of electronic databases was conducted for randomized controlled trials (RCTs) on heart failure. Respiratory training interventions were grouped as seven categories: IMT_Pn (inspiratory muscle training without pressure or < 10% maximal inspiratory pressure, MIP), IMT_Pl (inspiratory muscle training with low pressure, 10%-15% MIP), IMT_Pm (inspiratory muscle training with medium pressure, 30%-40% MIP), IMT_Ph (inspiratory muscle training with high pressure, 60% MIP or MIP plus aerobics), Aerobics (aerobic exercise or weight training), Qi_Ex (tai chi, yoga, and breathing exercise), and none. The four outcomes were heart rate, peak oxygen uptake (VO2 peak), 6-min walking distance test (6MWT), and Minnesota Living with Heart Failure QoL. The random-effects model, side-splitting model, and the surface under the cumulative ranking curve (SUCRA) were used to test and analyze the data. A total of 1499 subjects from 31 RCT studies were included. IMT_Ph had the highest effect sizes for VO2 peak and 6MWT, IMT_Pm highest for QoL, and Qi_Ex highest for heart rate. Aerobics had the second highest for VO2 peak, Qi_Ex second highest for 6MWT, and IMT_Ph second highest for heart rate and QoL. This study supports that high- and medium-intensity machine-assisted training improves exercise capacity and QoL in hospital-based heart failure patients. After hospital discharge, non-machine-assisted training continuously improves cardiac function.


Recent increases in efficiency in cigarette nicotine delivery: implications for tobacco control.
Recent increases in nicotine yield of cigarettes sold in the United States have been attributed by tobacco manufacturers to natural variation in agricultural products. We tested this assertion using data reported by the manufacturers. Data were collected from the annual reports filed with the Massachusetts Department of Public Health by 4 major manufacturers of cigarettes from 1997 to 2012. Reportable measures included nicotine yield (mg/cig) in smoke generated by a smoking machine based on the Massachusetts smoking regimen and nicotine content in the unburned tobacco per cigarette (mg/cig). We used multilevel linear mixed-effect models to examine temporal trends in and predictors of these measures, overall and by brand style and by brand family. While nicotine content remained relatively stable in the range of 12-14 mg/cig between 1998 and 2012, average nicotine yield increased significantly (p < .01) over time and ranged from the lowest level of 1.65 mg/cigarette in 1999 to the highest level of 1.89 mg/cigarette in 2011. Nicotine yield and yield-to-content ratio varied significantly among manufacturers and brand families. When controlling for market category and all available design features, the yield-to-content ratio of all manufacturers except Lorillard increased significantly over time. The data provided by tobacco manufacturers suggest that the increasing trend in yield is not related to variations in nicotine content but to the yield-to-content ratio, which contradicts their assertions of agricultural variations. Nicotine yield and yield-to-content ratio are controllable features of cigarettes, and they should be monitored and regulated by government agencies.


T-DNA gene 5 of Agrobacterium modulates auxin response by autoregulated synthesis of a growth hormone antagonist in plants.
Oncogenes carried by the transferred DNA (T-DNA) of Agrobacterium Ti plasmids encode the synthesis of plant growth factors, auxin and cytokinin, and induce tumour development in plants. Other T-DNA genes regulate the tumorous growth in ways that are not yet understood. To determine the function of T-DNA gene 5, its coding region was expressed in Escherichia coli. Synthesis of the gene 5 encoded protein (26 kDa) correlated with a 28-fold increase in conversion of tryptophan to indole-3-lactate (ILA), an auxin analogue. Expression of chimeric gene 5 constructs in transgenic tobacco resulted in overproduction of ILA that enhanced shoot formation in undifferentiated tissues and increased the tolerance of germinating seedlings to the inhibitory effect of externally supplied auxin. Promoter analysis of gene 5 in plants revealed that its expression was inducible by auxin and confined to the vascular phloem cells. cis-regulatory elements required for auxin regulation and phloem specific expression of gene 5 were mapped to a 90 bp promoter region that carried DNA sequence motifs common to several auxin induced plant promoters, as well as a binding site for a nuclear factor, Ax-1. ILA was found to inhibit the auxin induction of the gene 5 promoter and to compete with indole-3-acetic acid (IAA) for in vitro binding to purified cellular auxin binding proteins. It is suggested therefore that ILA autoregulates its own synthesis and thereby modulates a number of auxin responses in plants.


Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study.
This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd.


Effects of three-dimensional polymer networks in vertical alignment liquid crystal display controlled by in-plane field.
Polymer network in vertical alignment liquid crystal cell driven by in-plane field (VA-IPS) is formed in three dimensions to achieve fast response time and to keep the liquid crystal alignment even when an external pressure is applied to the cell. The network formed by UV irradiation to vertically aligned liquid crystal cell with reactive mesogen does not disturb a dark state while exhibiting very fast decaying response time less than 2ms in all grey scales and almost zero pooling mura. The proposed device has a strong potential to be applicable to field sequential display owing to super-fast response time and flexible display owing to polymer network in bulk which supports a gap between two substrates.


Trait gambling cognitions predict near-miss experiences and persistence in laboratory slot machine gambling.
'Near-miss' outcomes (i.e., unsuccessful outcomes close to the jackpot) have been shown to promote gambling persistence. Although there have been recent advances in understanding the neurobiological responses to gambling near-misses, the psychological mechanisms involved in these events remain unclear. The goal of this study was to explore whether trait-related gambling cognitions (e.g., beliefs that certain skills or rituals may help to win in games of chance) influence behavioural and subjective responses during laboratory gambling. Eighty-four individuals, who gambled at least monthly, performed a simplified slot machine task that delivered win, near-miss, and full-miss outcomes across 30 mandatory trials followed by a persistence phase in extinction. Participants completed the Gambling-Related Cognitions Scale (GRCS; Raylu & Oei, 2004), as well as measures of disordered gambling (South Oaks Gambling Screen [SOGS]; Lesieur & Blume, 1987) and social desirability bias (DS-36; Tournois, Mesnil, & Kop, 2000). Skill-oriented gambling cognitions (illusion of control, fostered by internal factors such as reappraisal of losses, or perceived outcome sequences), but not ritual-oriented gambling cognitions (illusion of control fostered by external factors such as luck or superstitions), predicted higher subjective ratings of desire to play after near-miss outcomes. In contrast, perceived lack of self-control predicted persistence on the slot machine task. These data indicate that the motivational impact of near-miss outcomes is related to specific gambling cognitions pertaining to skill acquisition, supporting the idea that gambling near-misses foster the illusion of control.


Application of polyimide films as a nuclear track detector (2): A latent track structure study with Fourier transform infrared spectroscopy.
This paper reports the relation between latent track structure and the detection threshold of etch pits formation in UPILEX-S® and Kapton. At the similar stopping power value, effective track core radii and G values for heavier ions are lower than those of lighter ions. These results would be due to the difference of the radial dose distribution for low- and high-velocity ions. The G value starts more rapidly rising above 600 and 1000 keV/μm for Kapton and UPILEX-S®, respectively. The detection threshold of UPILEX-S is 4000 keV/μm for Ar ions, at which effective track core radii of all functional groups are larger than 2 nm. Since the length of a molecule unit of UPILEX-S® is about 1.4 nm, at least more than two molecule units have to be damaged for the etch pit formation. A similar discussion is applicable to Kapton, whose detection threshold is significantly lower than UPILEX-S®.


Spontaneous Fracture of a Silicone Implant: A Delayed Complication of Rhinoplasty.
Silicone implants are commonly used alloplastic materials for rhinoplasty in Asia, as they are easy to manipulate, provide adequate volume augmentation, and exhibit excellent biocompatibility. However, they are associated with complications such as infection, displacement, and extrusion. Recently, we encountered an interesting complication in a 53-year-old woman presenting with palpable and visible stepping of the nasal dorsum. The patient had previously undergone rhinoplasty with an L-shaped silicone implant, and symptoms had been noticeable for approximately 1 year. Lateral nasal computed tomography revealed a fractured silicone implant. Because the patient reported no history of nasal trauma since rhinoplasty, we assumed that the silicone implant might have fractured spontaneously. The findings in this case suggest that spontaneous implant fracture can be a late complication of rhinoplasty with silicone implant.


Dendritic field development of retinal ganglion cells in the cat following neonatal damage to visual cortex: evidence for cell class specific interactions.
A well-known feature of the mammalian retina is the inverse relation that exists in central and peripheral retina between the density of retinal ganglion cells and their dendritic field sizes. Functionally, this inverse relation is thought to represent a means by which retinal coverage is maintained, despite significant changes in ganglion cell density. While it is generally agreed that the dendritic fields of mature retinal ganglion cells reflect, in part, competitive interactions that occur during development, the issue of whether these interactions are cell class specific remains unclear. In order to examine this question, we used intracellular staining techniques and an in vitro, living retina preparation to compare the soma and dendritic field sizes of alpha and beta ganglion cells from normal retinae with those of cells located in matched areas of retinae in which the density of beta ganglion cells had been reduced selectively by neonatal removal of visual cortex areas 17, 18, and 19. Our intracellular data show that while an early, selective, reduction in beta cell density has little or no effect on the cell body and dendritic field sizes of mature alpha cells, it results in a 13% increase in the mean soma area and an 83% increase in the mean dendritic field area of surviving beta cells. This differential effect suggests that the soma and dendritic field sizes of alpha and beta ganglion cells in the mature cat retina result primarily from competitive interactions during development that are cell class specific.


Chasing the landscape for intrahospital transmission and evolution of hypervirulent carbapenem-resistant Klebsiella pneumoniae.
The spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) is a global health concern. Here, we report the intrahospital colonization and spread of Hv-CRKP isolates in a tertiary hospital from 2017 to 2022. Analyses of 90 nonredundant CRKP isolates from 72 patients indicated that Hv-CRKP transferability relies on the dominant ST11-K64 clone. Whole-genome sequencing of 11 representative isolates gave 31 complete plasmid sequences, including 12 KPC-2 resistance carriers and 10 RmpA virulence vehicles. Apart from the binary vehicles, we detected two types of fusion plasmids, favoring the cotransfer of RmpA virulence and KPC-2 resistance. The detection of ancestry/relic plasmids enabled us to establish genetic mechanisms by which rare fusion plasmids form. Unexpectedly, we found a total of five rmpA promoter variants (P9T-P13T) exhibiting distinct activities and varying markedly in their geographic distributions. CRISPR/Cas9 manipulation confirmed that an active PT11-rmpA regulator is a biomarker for the "high-risk" ST11-K64/CRKP clone. These findings suggest clonal spread and clinical evolution of the prevalent ST11-K64/Hv-CRKP clones. Apart from improved public awareness of Hv-CRKP convergence, our findings might benefit the development of surveillance (and/or intervention) strategies for the dominant ST11-K64 lineage of the Hv-CRKP population in healthcare sectors.


[Engagement and academics results of the grade students].
The academic engagement is a three-feature psychological welfare (determination, knowledge absorptive capability and dedication) as an intrinsic commitment towards the studies. The main aim of this study is to know the motivational status in students and to compare this with their academic performance. For the purpose of this paper, it was carried out an observational, correlational, cross-sectional study. The target population is the students carrying out the clinical training in the University of Malaga as part of the Nursing Degree. According to the data achieved, the mean score are the followings: determination 3.46 out of 6 (ST 1.05), dedication 5.16 out of 6 (ST 0.97) and knowledge absorptive capability 3.59 out of 6 (ST 1.18). The engagement global mean score of the nursing students enrolled in this University School of Nursing is 4.1 out of 6. It is worthy to mention the levels for dedication, ranging from almost always and always, which involves a remarkable vocation towards their profession. The marks on Practicum II-III have evidenced an association with the engagement determination (p < 0.008), and knowledge absorption capability (p < 0.036). Marks on Practicum I have not evidenced any association.


A tale of two rivers: development, destruction, and despair in Ongata Rongai, Kenya.
Ongata Rongai is a rapidly growing peri-urban space in Nairobi Metropolitan, Kenya. The last 10 years have seen exponential population growth and building development leading to overcrowding and pressure on water and environmental resources. This original research sheds light on interactions among humans, animals, and this rapidly changing urban environment. It is therefore a quintessentially One Health study. Qualitative and ethnographically informed methods are employed to better understand the impact of rapid growth on the riparian environment and the effect of this on those who depend on it. The reflexive use of archival material and a historical ethnographic approach enabled in-depth narratives to address these issues within a longitudinal context, and the use of deliberate walking alongside visual methodologies and more traditional anthropological methods make this study novel both in terms of methodological approach and findings. This study finds that people cite high levels of pollution from solid waste and sewage have made the rivers almost unusable and a hazardous place for both humans and animals. Yet, in the past, these rivers played key roles in daily life. There is frustration with structural-level actors' moribund attitude to the environment. The poor health of the rivers and riparian environment leads to human and animal health challenges, increased pressure on water resources, and economic pressure due to a loss of livelihoods. The study contributes to what is currently a fairly small literature on urban riparian spaces globally, but one which is of growing and vital importance given the rapidly increasing percentage of humans who now reside in urban spaces. It contributes to WASH and urban clean water knowledge as well as One Health, public health, and urban growth narratives, and directly addresses challenges faced by SDG 6.


Saturating mutagenesis of an essential gene: a majority of the Neisseria gonorrhoeae major outer membrane porin (PorB) is mutable.
The major outer membrane porin (PorB) of Neisseria gonorrhoeae is an essential protein that mediates ion exchange between the organism and its environment and also plays multiple roles in human host pathogenesis. To facilitate structure-function studies of porin's multiple roles, we performed saturating mutagenesis at the porB locus and used deep sequencing to identify essential versus mutable residues. Random mutations in porB were generated in a plasmid vector, and mutant gene pools were transformed into N. gonorrhoeae to select for alleles that maintained bacterial viability. Deep sequencing of the input plasmid pools and the output N. gonorrhoeae genomic DNA pools identified mutations present in each, and the mutations in both pools were compared to determine which changes could be tolerated by the organism. We examined the mutability of 328 amino acids in the mature PorB protein and found that 308 of them were likely to be mutable and that 20 amino acids were likely to be nonmutable. A subset of these predictions was validated experimentally. This approach to identifying essential amino acids in a protein of interest introduces an additional application for next-generation sequencing technology and provides a template for future studies of both porin and other essential bacterial genes.


Bridging dermatologists with patient advocacy organizations through smartphones.
Patient advocacy organizations seek to increase their benefits for patients with skin disease; low awareness and patient referrals among dermatologists have presented an obstacle to this. To determine whether the Skin Advocate iPhone App would increase awareness and referrals to patient advocacy organizations in the Coalition of Skin Diseases (CSD) among Texas dermatologists and dermatology residents and patient registrations among CSD member organizations. We present results of an institutional review board-exempted investigation conducted among member organizations of the CSD and among dermatologists and dermatology residents in Texas from April 1, 2011, through March 31, 2013. Effects were measured in a blinded fashion subjectively through pre-intervention and post-intervention surveys and objectively through internal analytics that tracked downloads and use of the iPhone app, as well as pre-intervention and post-intervention numbers of registrations for CSD member organizations. The Skin Advocate iPhone App. Awareness and referrals to patient advocacy organizations in the CSD among Texas dermatologists and dermatology residents and patient registrations among CSD member organizations. Throughout the study, mean app use ranged from 3.3 to 3.6 uses per user per month, maintaining the 3-fold improvement compared with self-reported referral for 90% of the study population and a 12-fold improvement for 64% of the study population. Our data revealed substantial improvement in self-reported physician awareness and referrals, and increased patient registrations for CSD organizations. The Skin Advocate iPhone App improved physician awareness and subsequent referrals to CSD member organizations.


The anal fistula plug versus the mucosal advancement flap for the treatment of anorectal fistula (PLUG trial).
Low transsphincteric fistulas less than 1/3 of the sphincter complex are easy to treat by fistulotomy with a high success rate. High transsphincteric fistulas remain a surgical challenge. Various surgical procedures are available, but recurrence rates of these techniques are disappointingly high. The mucosal flap advancement is considered the gold standard for the treatment of high perianal fistula of cryptoglandular origin by most colorectal surgeons. In the literature a recurrence rate between 0 and 63% is reported for the mucosal flap advancement. Recently Armstrong and colleagues reported on a new biologic anal fistula plug, a bioabsorbable xenograft made of lyophilized porcine intestinal submucosa. Their prospective series of 15 patients with high perianal fistula treated with the anal fistula plug showed promising results. The anal fistula plug trial is designed to compare the anal fistula plug with the mucosal flap advancement in the treatment of high perianal fistula in terms of success rate, continence, postoperative pain, and quality of life. The PLUG trial is a randomized controlled multicenter trial. Sixty patients with high perianal fistulas of cryptoglandular origin will be randomized to either the fistula plug or the mucosal advancement flap. Study parameters will be anorectal fistula closure-rate, continence, post-operative pain, and quality of life. Patients will be followed-up at two weeks, four weeks, and 16 weeks. At the final follow-up closure rate is determined by clinical examination by a surgeon blinded for the intervention. Before broadly implementing the anal fistula plug results of randomized trials using the plug should be awaited. This randomized controlled trial comparing the anal fistula plug and the mucosal advancement flap should provide evidence regarding the effectiveness of the anal fistula plug in the treatment of high perianal fistulas. ISRCTN: 97376902.


Aortic stiffness and kidney disease in an elderly population.
The causes of chronic kidney disease (CKD) in older people are not well understood. Aortic stiffness increases with age and results in the transmission of increased pulsatility into the kidney microvasculature, potentially contributing to CKD in older populations. We utilized data from the Age, Gene/Environment, Susceptibility-Reykjavik Study, a community-based prospective cohort study of cardiovascular disease (CVD) in Iceland. The relationship of carotid pulse pressure (CPP) and carotid-femoral pulse wave velocity (CFPWV) with estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and urine albumin-creatinine ratio (ACR) was assessed using linear regression, adjusting for demographics and CVD risk factors. 940 participants (mean (SD) age 75.8 (4.7) years, mean (SD) CFPWV 12.9 (4.2) m/s, mean (SD) CPP 69 (21) mm Hg, mean (SD) eGFR 68 (16) ml/min/1.73 m(2), and median (IQR) ACR 3 (2-6) mg/g) were included in this study. At CPP greater than 85 mm Hg, a higher CPP was associated with a lower eGFR in unadjusted analyses but not after adjustment. CPP was significantly associated with a higher ACR in fully adjusted models (β (95% CI) = 0.14 (0.03, 0.24) ln mg/g per SD). Higher CFPWV was associated with lower eGFR and higher ACR in unadjusted analyses but not after adjustment. Greater aortic stiffness may be associated with modestly higher levels of albuminuria in the elderly. The association between aortic stiffness and lower eGFR may be confounded by age and CVD risk factors.


Exploring the relationship between physical activity knowledge, health outcomes expectancies, and behavior.
Despite clear health benefits of physical activity, previous research has been limited in linking knowledge of physical activity recommendations to actual behavior. Using Expectancy Theory, we examined whether an individual's health outcome expectancies from physical activity might provide the missing link between knowledge and behavior. With data from a cross-sectional survey, we assessed differences between how much moderate physical activity people thought they needed for health benefits compared with what they thought experts recommended and the relationship of these differences to physical activity behaviors. Our hypothesis that people with positive health outcome expectancies would report more minutes of physical activity than those with neutral or negative health outcome expectancies was supported for all self-reported physical activity behaviors (P < .001). It appears that the health outcome expectancy of needing more physical activity than recommended by experts is correlated with achieving more physical activity, regardless of type. Future research should address health outcome expectancies as a way to impact physical activity.


Strict infection control leads to low incidence of methicillin-resistant Staphylococcus aureus bloodstream infection over 20 years.
Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide issue associated with significant morbidity and mortality. Multiple infection control (IC) approaches have been tested to control its spread; however, the success of the majority of trials has been short-lived and many efforts have failed. We report the long-term success of MRSA control from a prospective observational study over 20 years. University Hospital Basel is a large tertiary care center with a median bed capacity of 855 and 5 intensive care units (ICUs); currently, the facility has >32,000 admissions per year. The IC program at the University Hospital Basel was created in 1993, after 2 MRSA outbreaks. The program has included strict contact precautions with single rooms for MRSA-colonized or -infected patients, targeted admission screening of high-risk patients and healthcare workers at risk for carriage, molecular typing of all MRSA strains and routine decolonization of MRSA carriers including healthcare workers. We used the incidence of MRSA bloodstream infections (BSIs) to assess the effectiveness of this program. All MRSA cases were prospectively classified using a standardized case report form in nosocomial and nonnosocomial cases, based on CDC definitions. Between 1993 and 2012, 540,669 blood samples were cultured. The number of blood cultures increased from 865 per 10,000 patient days in 1993 to 1,568 per 10,000 patient days in 2012 (P<.001). We identified 1,268 episodes of S. aureus BSI from 1,204 patients. MRSA accounted for 34 episodes (2.7%) and 24 of these (1.9%) were nosocomial. MRSA BSI incidence varied between 0 and 0.27 per 10,000 patient days and remained stable with no significant variation throughout the study period (P=.882). Long-term control of MRSA is feasible when a bundle of IC precautions is strictly enforced over time.


Serum fetuin-A and arginase-1 in human obesity model: Is there any interaction between inflammatory status and arginine metabolism?
Obesity is a major risk factor for many chronic metabolic diseases such as inflammation, insulin resistance (IR) and fatty liver injury. It was reported that obesity causes some variations on the serum levels of fetuin-A and is associated with arginine metabolism, especially arginase-1 levels. The aim of our study was to evaluate, the interaction and possible changes of these liver over produced proteins, fetuin-A and arginase-1 levels in obesity-related inflammatory status. Study groups were composed of individuals aged between 19 and 63 (n = 62). The control group included healthy subjects with BMI < 25, obese group included obese patients with BMI > 30 and with no other chronic disease. Biochemical markers were determined by an auto-analyzer. Adiponectin, fetuin-A, arginase-1, asymmetric dimethylarginine (ADMA), arginine, Hexanoyl-lysine (HEL) and leptin levels were measured with commercial ELISA immunoassay kits. Nitrite and nitrate were determined with colorimetric assay kit in serum samples. High sensitive C-reactive protein (hsCRP) levels and liver function enzymes activities were higher in the obese group in respect to the control group. Serum fetuin-A, arginase-1 and leptin levels were increased but adiponectin levels were decreased in obese subjects. Fetuin-A levels showed significant correlations with arginase-1 and HOMA-IR. Consequently, we carried out an investigation about higher serum fetuin-A and arginase-1 levels may have an important role in obesity and obesity-related liver damage.


Treatment Adherence to Nucleos(t)ide Analogs in Chinese Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: A Single-Center Cross-Sectional Study.
Chronic hepatitis B virus (HBV) infection is a crucial risk factor in the occurrence and development of hepatocellular carcinoma (HCC). Antiviral therapy is very important for patients with HBV-related HCC. To maintain undetectable level of HBV DNA, patients must take nucleos(t)ide analogues (NUCs) appropriately and regularly. We explored the adherence of Chinese patients with HBV-related HCC to antiviral treatment. One-hundred and eighty-one patients were included in a cross-sectional study between August 2020 and February 2021. A structured questionnaire was used to interview patients, and a form was applied to collect data from electronic medical records. Medication adherence was measured using a visual analog scale. Data of the adherent group and non-adherent group were compared using Student's t-test and the chi-square test. Multivariate logistic regression analysis was employed to explore independent risk factors that affected adherence behavior. High adherence was reported in 46.4% of patients with HBV-related HCC. Patients with high adherence were more likely to be women (P = 0.02), shun alcohol (P = 0.01), take NUCs other than entecavir (P = 0.04), and pay attention to their titer of HBV DNA (P = 0.05). Sex, alcohol consumption, and taking entecavir were independent risk factors for low adherence (P < 0.05). The prevalence of virological breakthrough was lower in patients who adhered to NUC therapy than in those who did not, but the difference was not significant (P = 0.31). The adherence of patients with HBV-related HCC to NUC therapy was low. More attention should be paid to adherence of antiviral therapy in patients with HBV-related HCC.


Social Skill Outcomes Following Physical Activity-Based Interventions for Individuals on the Autism Spectrum: A Scoping Review Spanning Young Childhood Through Young Adulthood.
Researchers posit that physical activity (PA) settings may provide an increased opportunity for social interaction. However, little consensus exists regarding the construct of social skills. Moreover, little is known about what type or amount of PA is necessary for individuals on the autism spectrum to benefit from this increased interaction. Thus, this scoping review synthesized the components (e.g., design, participants, independent and dependent variables, etc.) and findings of PA-based interventions that included social skill components to identify how interventions have incorporated these skills in different settings. Based on a review of 25 articles, this review revealed a great deal of variability in the types of PA, social skills, and instruments studied, as well as the intensity of intervention delivery in the published findings. No longitudinal studies were identified as a part of the search. These results provide a foundation for the design of effective PA-based interventions that may have an increased impact on the social skills of individuals on the autism spectrum. Future research should employ longitudinal designs to capture the relationship between social skills and PA, as well as to increase the likelihood of capturing change.


Assessing the net effect of young maternal age on birthweight.
Pregnancy during adolescence presents an increased risk for low birthweight, which is attributed not only to physiologic immaturity but also to socioeconomic and behavioral risk factors associated with adolescence. The independent effect of maternal age on birthweight is difficult to ascertain because age is closely entangled with these risks. We first examined the effect of being an adolescent mother on these risk pathways and then estimated the net effect of maternal age on birthweight (weight in grams or low birthweight (<2500 g)) after controlling for these risks. We used data on 214 adolescent and 415 adult primiparae and their infants from the Cebu Longitudinal Health and Nutrition Survey, a community-based survey in Metro Cebu, Philippines. Consistent with findings from other studies, adolescents in this sample were more socioeconomically disadvantaged, had poorer nutritional status during pregnancy, and received less prenatal care than adults. Bivariate analyses showed that infants of adolescents had a lower mean birthweight and were more at risk of low birthweight compared to those born to older mothers. When socioeconomic, biological, and behavioral risk factors were controlled for, young maternal age ceased to have an effect on birthweight in grams but remained a significant predictor of low birthweight. The common pathways through which maternal age influenced both birthweight variables were through its effects on maternal height and weight-for-height during pregnancy. In the model predicting birthweight in grams the maternal age effect was further manifested through prenatal care utilization.


Molecular dynamics simulation of fractal aggregate diffusion.
The diffusion of fractal aggregates constructed with the method by Thouy and Jullien [J. Phys. A 27, 2953 (1994)] comprised of N(p) spherical primary particles was studied as a function of the aggregate mass and fractal dimension using molecular dynamics simulations. It is shown that finite-size effects have a strong impact on the apparent value of the diffusion coefficient (D), but these can be corrected by carrying out simulations using different simulation box sizes. Specifically, the diffusion coefficient is inversely proportional to the length of a cubic simulation box, and the constant of proportionality appears to be independent of the aggregate mass and fractal dimension. Using this result, it is possible to compute infinite dilution diffusion coefficients (D(o)) for aggregates of arbitrary size and fractal dimension, and it was found that D(o)∝N(p)(-1/df), as is often assumed by investigators simulating brownian aggregation of fractal aggregates. The ratio of hydrodynamic radius to radius of gyration is computed and shown to be independent of mass for aggregates of fixed fractal dimension, thus enabling an estimate of the diffusion coefficient for a fractal aggregate based on its radius of gyration.


Influence of feeding graded levels of canned sardines on the inflammatory markers and tissue fatty acid composition of Wistar rats.
Canned sardines are a ready-to-use fish product with excellent nutritional properties owing to its high n-3 long-chain PUFA content, mainly EPA (20 : 5n-3) and DHA (22 : 6n-3). The present study aimed to assess the effect of two dosages of canned sardines, recommended for the primary and secondary prevention of human CVD, on the inflammatory marker concentrations and fatty acid composition of erythrocytes and key metabolic tissues (liver, muscle, adipose tissue and brain) in the rat model. Wistar rats were fed a diet containing 11 % (w/w) of canned sardines (low-sardine (LS) diet) and a diet containing 22 % (w/w) of canned sardines (high-sardine (HS) diet) for 10 weeks. Daily food intake, weight gain, and organ and final body weights were not affected by the dietary treatments. The concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol decreased in both the LS and HS groups, while those of alanine aminotransferase and adiponectin increased. The concentrations of IL-1β increased only with the highest dosage of sardine. The dose-dependent influence of the graded levels of EPA+DHA was tissue specific. Compared with that of other tissues and erythrocytes, the fatty acid composition of the brain was less affected by the canned sardine-supplemented diets. In contrast, the retroperitoneal adipose tissue was highly responsive. The deposition ratios of EPA and DHA indicated that the LS diet was optimal for DHA deposition across the tissues, except in the retroperitoneal adipose tissue. Taken together, our findings indicate that a LS diet positively affects plasma lipid profiles and inflammatory mediators, whereas a HS diet has contradictory effects on IL-1β, which, in turn, is not associated with variations in the concentrations of other pro-inflammatory cytokines. This finding requires further investigation and pathophysiological understanding.


Atrial infarction is a unique and often unrecognized clinical entity.
A patient with heart failure and acute atrial fibrillation received the final diagnosis of atrial infarction associated with ventricular infarction based on clinical findings of ischemia in association with atrial fibrillation and heart failure (mechanisms probably involved: contractile dysfunction and loss of atrial contribution). Although a transesophageal echocardiography, which could refine the diagnosis of anatomic abnormalities, was not performed, all evidence led to the diagnosis of atrial involvement. Electrocardiographic findings were consistent with Liu's major criterion 3. Therapy with digitalis, quinidine and angiotensin-converting enzyme inhibitors was chosen, as the patient had acute pulmonary edema. The use of beta-blockers and verapamil was res-tricted. No other complications, such as thrombo-embolism or atrial rupture, were noted.


Coffee consumption and calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study.
While a recent meta-analysis of prospective studies reported that coffee consumption is associated with a lower risk of cardiovascular disease mortality, limited and inconsistent data are available on the relation of coffee intake with subclinical disease. Thus, the aim of the present study was to see the association of coffee consumption with the prevalence of atherosclerotic plaque in the coronary arteries in NHLBI Family Heart Study. In a cross-sectional design, we studied 1929 participants of the NHLBI Family Heart Study without known coronary heart disease. Coffee consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC as an Agatston score of ≥100 and used generalized estimating equations to calculate prevalence ratios of CAC as well as a sensitivity analysis at a range of cutpoints for CAC. Mean age was 56.7 years and 59% of the study subjects were female. In adjusted analysis for age, sex, BMI, smoking, alcohol, physical activity, field center, and energy intake, prevalence ratio (95% CI) for CAC was 1.0 (reference), 0.92 (0.57-1.49), 1.34 (0.86-2.08), 1.30 (0.84-2.02), and 0.99 (0.60-1.64) for coffee consumption of almost never, <1/day, 1/day, 2-3/day, and ≥4 cups/day, respectively. In a sensitivity analysis, there was no evidence of association between coffee consumption and prevalent CAC when CAC cut points of 0, 50, 150, 200, and 300 were used. These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women.


Interactions between COL5A1 Gene and Risk of the Anterior Cruciate Ligament Rupture.
Collagen alpha-1(V) chain, encoded by the COL5A1 gene, plays a crucial role in abundant fibrillar collagens supporting many tissues in the body containing type I collagen and appears to regulate the association between heterotypic fibers composed of both type I and type V collagen occurring among others in muscles, tendons and ligaments. Taking this fact into consideration we decided to examine the association between COL5A1 rs12722 and rs13946 polymorphisms, individually and as inferred haplotypes, with anterior cruciate ligament rupture risk (ACLR) in professional soccer players. A total of 134 male professional soccer players with surgically diagnosed primary anterior cruciate ligament ruptures and 211 apparently healthy male professional soccer players, who were without any self-reported history of ligament or tendon injury, were included in the study. Both the cases and the healthy controls were recruited from the same soccer teams, of a similar age category, and had a comparable level of exposure to anterior cruciate ligament injury. Genomic DNA was extracted from oral epithelial cells using GenElute Mammalian Genomic DNA MiniprepKit. All samples were genotyped for the rs12722 and rs13946 polymorphisms using a Rotor-Gene realtime polymerase chain reaction. Statistically significant differences in the genotype frequencies for the COL5A1 rs13946 polymorphisms in dominant modes of inheritance occurred (p = 0.039). Statistically significant differences were documented only in the dominant model under the representation tendency of the C-C haplotype in the ACLR group compared to controls (p = 0.038). Our results suggest that variation in the COL5A1 gene may be one of the non-modifiable factors associated with the ACL injury in professional soccer players. The C-C rs12722-rs13946 haplotype provides a protective effect against the ACL tear.