Comparison between stimulated in-vitro fertilization and stimulated intrauterine insemination for the treatment of unexplained and mild male factor infertility.
A prospective trial was undertaken to evaluate the efficacy of stimulated in-vitro fertilization (SIVF) and stimulated intrauterine insemination (SIUI) in couples with unexplained and mild male factor infertility. In all, 80 couples were allocated to treatment with SIVF or SIUI, both treatments following the same protocol [clomiphene citrate and follicle stimulating hormone (FSH) injection], except that higher doses of FSH were used in the SIVF treatment cycles. Initially, 41 couples were allocated to and started treatment with SIVF but eight cases were eventually converted to SIUI because of under-response. Similarly, although 39 couples were initially allocated to SIUI treatment, five of these converted to SIVF because of over-response. The treatment cycles that were converted either to SIUI or to SIVF were not considered as treatment failures but as treatment changes and so were included in the analyses. Of the final 38 SIVF cycles, four were cancelled (dysfunctional response), failed fertilization occurred in five cycles and 29 subjects reached embryo transfer. There were two biochemical pregnancies [positive human chorionic gonadotrophin (HCG) only], two clinical abortions and seven live births. Of the final 42 SIUI cycles, only two were cancelled, insemination being performed in the remaining 40 cases. The result was one clinical abortion, three ectopics and eight live births. The proportion of cycles with positive HCG was identical (28.9% per cycle treated for SIVF and 28.6% for SIUI) and the livebirth rates were also not different (18.4% per cycle treated for SIVF and 19.0% for SIUI). The cost per maternity of SIUI was approximately half that of SIVF (Pounds Sterling 1923 versus Pounds Sterling 4611) and so we conclude that, as SIUI had an efficacy that was not significantly different from SIVF (using similar protocols) but was more cost-effective, it must be considered the more appropriate form of management for the treatment of unexplained and mild male factor infertility. Indeed, it is hard to justify the routine use of IVF, as a first approach, in unexplained infertility.


Expression patterns of ubiquitin conjugating enzyme UbcM2 during mouse embryonic development.
Ubiquitin conjugating enzyme UbcM2 (Ubiquitin-conjugating enzymes from Mice, the number reveals the identification order) has been implicated in many critical processes, such like growth-inhibiting, mediating cell proliferation and regulation of some transcription factor, but the expression profile during mouse embryo development remains unclear. Hereby, during mid-later embryonic stage, the expression patterns of UbcM2 were examined using in situ hybridization and quantitative real-time PCR (qRT-PCR). The signals were significantly intense in central nervous system and skeletal system, weak in tongue, heart, lung, liver, and kidney. In the central nervous system, UbcM2 was principally expressed in thalamus, external germinal layer of cerebellum (EGL), mitral cell layer of olfactory bulb, hippocampus, marginal zone and ventricular zone of cerebral cortex, and spinal cord. In the skeletal system, UbcM2 was primarily expressed in proliferating cartilage. Furthermore, qRT-PCR analysis displayed that the expression of UbcM2 was ubiquitous at E15.5, most prominent in brain, weaker in lung liver and kidney, accompanied by the lowest level in tongue and heart. During brain development, the expression level of UbcM2 first ascended and then decreased from E12.5 to E18.5, the peak of which sustained starting at E14.5 until E16.5. Together, these results suggest that UbcM2 may play potential roles in the development of mouse diverse tissues and organs, particularly in the development of brain and skeleton.


[Primary adenocarcinoma of the ureter. Case report].
Primary ureteral adenocarcinoma is an infrequent histological type of urinary neoplasm. Many authors consider intestinal metaplasia the pivotal event of the pathogenetic process, whether it occurs on a pre-existing urothelial carcinoma or on a normal urothelium. Diagnosis is essentially based on case history and clinical findings (hematuria and pain) and on diagnostic imaging. Treatment is surgical and the ideal procedure is nephroureterectomy with excision of a bladder margin adjacent to the ureteral opening and ispilateral para-aortoiliac lymphadenectomy. A 76-year-old man with primary adenocarcinoma of the ureter case is reported.


Virus replication and localization of varicella-zoster virus antigens in human embryonic fibroblast cells infected with cell-free virus.
When human embryonic fibroblast cells were infected with cell-free varicella-zoster virus, virus replication began between 8 and 14 h postinfection, and 4 more h werp required for the virus to infect neighboring cells. Virus-specific antigens were traced by the anticomplement immunofluorescent antibody technique. Virus antigen was first detectable 2 h postinfection in the cytoplasma, and diffuse fluorescence was observed in the nucleus as early as 4 h after infection. The nuclear fluorescence got brighter and cytoplasmic fluorescence was observed at 14 h postinfection. The spread of virus to the neighboring cells was recognized in 18 h postinfection. In the period of 24 to 48 h, antigens were seen at the nuclear membrane region and in the cytoplasma. Very strong fluorescence was restricted mainly to the nucleus, when phosphonoacetic acid or cytosine arabinoside was added to the infected cultures and the cells were incubated for 48 h.


Use of a minimally invasive fasciotomy technique for treatment of antebrachial compartment syndrome in two horses.
An 18-year-old Paint stallion (horse 1) and a 17-year-old Morgan gelding (horse 2) were evaluated because of an acute onset of severe unilateral forelimb lameness. Both horses were unable to bear weight on the affected forelimb and had a dropped elbow appearance. Radial nerve paralysis, triceps myopathy, and fractures of the humerus and ulna were ruled out. The caudal aspect of the affected antebrachium of each horse was very firm to palpation and became firmer when weight was shifted onto the limb. Ultrasonographic examination revealed swelling and suspected intramuscular hemorrhage of the caudal antebrachial muscles. On the basis of clinical examination and diagnostic imaging findings, both horses had antebrachial compartment syndrome diagnosed. Lameness did not substantially improve with medical treatment in either horse. Caudal antebrachial fasciotomy was performed in each horse. Following sedation and local anesthetic administration, a bistoury knife was inserted through small incisions to perform fasciotomy. Horses remained standing throughout the procedure and were immediately able to bear weight on the affected limb without signs of discomfort. Horse 1 developed colitis and horse 2 developed a mild incisional infection, but both fully recovered and returned to their previous activities. Antebrachial compartment syndrome is a rare cause of severe unilateral forelimb lameness and should be considered as a differential diagnosis in horses with a dropped elbow appearance. Both horses of this report had a successful outcome following antebrachial fasciotomy.


Conjugation of RTHLVFFARK to human lysozyme creates a potent multifunctional modulator for Cu2+-mediated amyloid β-protein aggregation and cytotoxicity.
Amyloid β-peptide (Aβ) aggregation induced by metal ions such as Cu2+ has been recognized as a crucial step in the pathogenesis of Alzheimer's disease (AD), so development of multifunctional agents that are able to inhibit Aβ aggregation and modulate Cu2+-Aβ species is considered as a promising strategy for fighting against AD. Our recent work proved that basification of human lysozyme (hLys) is in favor of enhancing the inhibition of Aβ aggregation. Based on the finding, we have herein designed R-hLys, a conjugate of bifunctional alkaline decapeptide (RTHLVFFARK, RK10) coupled onto hLys via reaction with the carboxyl groups on hLys. The design created an even more basic protein than hLys, thus increasing the potency of hLys on inhibiting Aβ fibrillation. Moreover, the RK10 conjugation onto hLys introduced a specific Cu2+-chelator and an additional peptide inhibitor (LVFFARK). Thus, a multifunctional modulator on Cu2+-mediated Aβ aggregation and cytotoxicity was developed. The multifunctional effects of R-hLys were systematically investigated on Aβ aggregation, Cu2+-mediated Aβ aggregation, ROS production, and remodeling mature Aβ species by comparison to its counterparts. The results revealed the following: (1) R-hLys possesses high potency on inhibiting Aβ fibrillogenesis; R-hLys at 1/5 to 1/4 of hLys concentration works similarly to hLys. (2) R-hLys exhibits high performance on inhibiting Cu2+-induced Aβ aggregation and cytotoxicity; it increased the cell viability from 48.9% to 86.1% at an equimolar concentration to Aβ. (3) R-hLys arrests the production of reactive oxygen species catalyzed by Cu2+ or Cu2+-Aβ42 species. (4) R-hLys remodels mature Aβ42 fibrils and Cu2+-Aβ42 aggregates into small amorphous aggregates of lower cytotoxicity; by co-incubation with R-hLys, the cytotoxicities of mature Aβ42 fibrils and Cu2+-Aβ42 aggregates are reduced from 31.4% to 14.2% and 48.1% to 10.4%, respectively. Taken together, R-hLys is a potent multifunctional modulator for inhibiting Aβ/Cu2+-mediated-Aβ aggregation, suppressing ROS production and remodeling mature Aβ42/Cu2+-Aβ42 species.


Secondary hypertension in patients with saccular intracranial aneurysm disease: A population based study.
Secondary hypertension is a serious form of hypertension, involving 5% to 10% of all hypertension patients. Hypertension is a risk factor of the saccular intracranial aneurysm (sIA) disease and subarachnoid hemorrhage from ruptured sIA (aSAH), but the impact of secondary hypertension on sIA disease is poorly known. In a defined Eastern Finnish sIA population we studied the prevalence of secondary hypertension and its impact on sIA disease phenotype. We included 2704 consecutive sIA patients first admitted to Kuopio University Hospital from 1995 to 2014. Their clinical data from Kuopio Intracranial Aneurysm patient and Family Database was fused with prescription drug usage data, hospital diagnoses and causes of death, retrieved from nationwide registries. Medical records of hypertensive sIA patients were reviewed to confirm or exclude secondary hypertension. Prevalence of secondary hypertension and associated diagnoses were calculated. Logistic regression was used to identify clinical characteristics of sIA disease that associated with secondary hypertension. We identified 2029 (75%) sIA patients with hypertension and 208 (10%) of them had secondary hypertension. Most frequent conditions associated with secondary hypertension were kidney and renovascular diseases (45%), sleep apnea (27%) and hypothyroidism (19%); 46 (22%) of the 208 patients had more than one such condition. In multivariate logistic regression analyses of 1561 aSAH patients, secondary hypertension significantly associated with the number of sIAs (p = 0.003; OR 1.32; 95% CI 1.10-1.58) and male gender (p = 0.034; OR 1.59; 95% CI 1.04-2.43). Secodary hypertension was relatively common (10%) among hypertensive sIA patients. Secondary causes for hypertension should be taken into account in hypertensive sIA patients, especially in aSAH patients with multiple intracranial aneurysms. Further research is indicated to evaluate the impact of secondary hypertension on the long-term rupture risk of unruptured sIA carriers and long-term outcome after aSAH.


Preliminary evidence that endoscopic gastroplication reduces food reward.
Morbidly obese patients are most successfully treated with bariatric surgery. Although restrictive gastric surgery physically limits food intake, it is also suggested that eating behavior and food-reward mechanisms are affected. Therefore, eating behavior and food-reward were assessed in ten patients that underwent gastric volume reduction by endoscopic gastroplication. Patients participated in test days before and one, three and twelve months after the procedure. Weight loss, food intake, appetite, gastric emptying rate, food-reward (i.e. liking and wanting) and eating behavior were assessed. Body mass index decreased from 38.3 (37.6-42.6) to 33.9 (31.0-35.9) kg/m2 after one year. Ad libitum food intake decreased significantly after one month, but not after one year. Gastric emptying rate did not change. AUC of VAS scores for desire to eat, quantity, fullness, hunger, snacking and satiety changed after one month, but not all remained significantly changed after one year. Thirst did not change. Liking scores of food items decreased significantly in the fasted as well as the satiated state after the procedure. Wanting scores did not change. Uncontrolled eating decreased significantly after three and twelve months; emotional eating was only significantly decreased after three months. The results show that food intake decreases, while VAS scores for appetite and eating behavior change accordingly. Liking, but not wanting of food items changed to benefit the weight losing patient. The effects were stronger at one-month follow-up than at 12 months, which may be a risk of relapse after initial successful weight loss. The effects of new bariatric procedures on food-reward should be studied in future randomized trials to further elucidate their impact. REGISTERED AT CLINICALTRIALS. GOV: NCT02381340.


Development and validation of a Markov microsimulation model for the economic evaluation of treatments in osteoporosis.
Markov models are increasingly used in economic evaluations of treatments for osteoporosis. Most of the existing evaluations are cohort-based Markov models missing comprehensive memory management and versatility. In this article, we describe and validate an original Markov microsimulation model to accurately assess the cost-effectiveness of prevention and treatment of osteoporosis. We developed a Markov microsimulation model with a lifetime horizon and a direct health-care cost perspective. The patient history was recorded and was used in calculations of transition probabilities, utilities, and costs. To test the internal consistency of the model, we carried out an example calculation for alendronate therapy. Then, external consistency was investigated by comparing absolute lifetime risk of fracture estimates with epidemiologic data. For women at age 70 years, with a twofold increase in the fracture risk of the average population, the costs per quality-adjusted life-year gained for alendronate therapy versus no treatment were estimated at €9105 and €15,325, respectively, under full and realistic adherence assumptions. All the sensitivity analyses in terms of model parameters and modeling assumptions were coherent with expected conclusions and absolute lifetime risk of fracture estimates were within the range of previous estimates, which confirmed both internal and external consistency of the model. Microsimulation models present some major advantages over cohort-based models, increasing the reliability of the results and being largely compatible with the existing state of the art, evidence-based literature. The developed model appears to be a valid model for use in economic evaluations in osteoporosis.


Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study.
Patients with relapsed malignant glioma have a poor prognosis. We developed a strategy of vaccination using autologous mature dendritic cells loaded with autologous tumour homogenate. In total, 12 patients with a median age of 36 years (range: 11-78) were treated. All had relapsing malignant glioma. After surgery, vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5 (range: 2-7) vaccines was given. There were no serious adverse events except in one patient with gross residual tumour prior to vaccination, who repetitively developed vaccine-related peritumoral oedema. Minor toxicities were recorded in four out of 12 patients. In six patients with postoperative residual tumour, vaccination induced one stable disease during 8 weeks, and one partial response. Two of six patients with complete resection are in CCR for 3 years. Tumour vaccination for patients with relapsed malignant glioma is feasible and likely beneficial for patients with minimal residual tumour burden.


Cardiac valve surgery in patients with poor left ventricular function.
Of 316 patients who underwent operation for valvular heart disease at the Toronto Western Hospital, between January 1978 and December 1981, 41 (31 men, 10 women), ranging in age from 24 to 74 years, had severely impaired left ventricular function (ejection fraction less than 40% and left ventricular end-diastolic pressure more than 18 mm Hg). All 41 patients were in New York Heart Association (NYHA) class III or IV. Fourteen patients had disease of the aortic valve, 13 of the mitral valve and 14 of both aortic and mitral valves. Twenty-two patients also had serious coronary artery disease. The valve dysfunction was corrected in all patients by replacement or repair and all severe coronary artery stenoses were bypassed with saphenous vein grafts. There were three hospital deaths and five late deaths during a mean follow-up of 26 months (range from 6 to 48 months). All patients improved symptomatically by a least one functional NYHA class. The actuarial survival including operative deaths was 79%.


Correlation between Cardiopulmonary Indices and Running Performance in a 14.5 km Endurance Running Event.
Running is a common recreational activity, and the number of long-distance-race participants is continuously growing. It is well-established that regular physical activity can prevent and manage non-communicable diseases and benefit public health. Training for a long-distance race requires development of specific aerobic abilities and should generate the desired race performance. The purpose of this study was to support the training design and motivation of recreational endurance runners, by investigating whether a 14.5 km race performance of long-distance runners correlates with their cardiopulmonary indices measured in the laboratory. To examine the relationships of a 14.5 km running performance with the cardiopulmonary parameters of amateur runners, a cross-sectional study design was applied. Fifteen (eleven men and four women) recreational long-distance runners (aged 41.3 ± 9.2 years) from Northern Greece were included in the study and were evaluated in the laboratory within one week before an endurance running race-the 14.5 km Philip Road race, in Greece. The laboratory-based examinations of the athletes consisted of a comprehensive medical pre-participation screening and maximal cardiopulmonary exercise testing. The results showed that the 14.5 km race performance time (73.8 ± 9.7 min) significantly correlated with the cardiopulmonary-exercise-testing speed-related indices at specific submaximal and maximal workloads (p < 0.01, p < 0.05), while the cardiopulmonary indices of oxygen uptake did not reliably predict race running time (p > 0.05). There is a better correlation of the 14.5 km running performance of recreational long-distance runners with the cardiopulmonary-exercise-testing speed-related indices at specific workloads than with the indices of oxygen uptake, running economy or respiratory economy. When preparing a training strategy, amateur long-distance runners should mostly rely on specific running-speed-related laboratory data rather than on oxygen-uptake values.


Outcomes of Renal Transplant Recipients after Percutaneous Coronary Intervention.
Renal transplantation (RT) can improve life expectancy in hemodialysis (HD) patients. However, little is known about the outcomes of renal transplant recipients after percutaneous coronary intervention (PCI). This study aimed to elucidate the effect of RT on clinical outcomes after PCI. Renal transplant recipients who underwent PCI from 2002 to 2017 were enrolled. To evaluate the effectiveness of RT, we retrospectively reviewed HD patients who underwent PCI. Propensity-score matching was performed using logistic regression to control for differences in baseline characteristics. The primary outcome was the incidence of major adverse cardiac events. After propensity matching, patients were classified into the RT (n = 50) group and HD (n = 50) group. Kaplan-Meier analysis revealed that the incidence of major adverse cardiac events was significantly lower in the RT group than in the HD group (p < 0.0001). Moreover, RT was associated with a lower risk for all-cause death (odds ratio 0.04; 95% confidence interval 0.002 to 0.03; p = 0.0054) and target vessel revascularization (OR 0.27; 95% CI 0.07 to 0.79; p = 0.015). RT may improve clinical outcomes after PCI, and it is encouraged for HD patients to increase life expectancy and reduce the occurrence of adverse events after PCI. Further research would be warranted to support this finding.


Reduced hearing, ownership, and use of hearing aids in elderly people in the UK--the MRC Trial of the Assessment and Management of Older People in the Community: a cross-sectional survey.
Reduced hearing in elderly people is important because it is disabling and potentially treatable. We aimed to assess the prevalence of reduced hearing in elderly people and levels of ownership of hearing aids and use. We have done a cross-sectional survey of people aged at least 75 years in 106 family practices in the UK. We obtained self-reported data on hearing difficulties for 32,656 people and gave 14,877 a whispered voice test (response rate 78%). 2537 (8%) of 32,656 participants reported a lot of difficulty hearing and 13,630 (42%) a little or a lot of difficulty. 3795 (26%) of 14877 participants who completed the whispered voice test (95% CI 23-29) failed the test, the proportion rising sharply with age. Following wax removal, 343 passed a retest, leaving 3452 (23%, 20-26) who failed the test, even after wax removal if present. 998 (46%) of 2180 people wearing a hearing aid at the time of testing failed the whispered voice test. More than half the people who failed the test did not own a hearing aid. 2200 (60%) of 3846 people who owned a hearing aid said they used it regularly. Level of use was strongly related to perceived benefit. Reduced hearing is common and provision of hearing aids inadequate in elderly people. Many people who own a hearing aid do not use it regularly, and even when wearing their aid many still have socially disabling levels of hearing loss. A major source of morbidity in elderly people could be alleviated by improvements in detection and management of reduced hearing.


Parent and Provider Preferences for Parenting Intervention Delivery in Rural Appalachia: A Qualitative Analysis Guiding Adaptation.
The public health impact of behavioral parent training (BPT) is limited, especially in underserved communities such as rural central Appalachia. To improve access to BPT in this region, we completed the first two steps of the ADAPT-ITT framework for systematic adaptation of evidence-based interventions: (1) assessing community perspectives about BPT delivery, and (2) deciding upon a specific intervention and adaptations needed to increase its acceptability and accessibility in rural central Appalachian counties. Guided by a community advisory board, we conducted key informant interviews with parents (N = 21) and three focus groups with child service providers to elicit stakeholders' perspectives about child behavior problems in their communities; existing resources; and preferences regarding four characteristics of BPT delivery: interventionist, modality, dose, and location. Results of directed content analysis led to the selection of local, trusted community health workers to deliver a brief, tailored BPT with flexibility in modality and location.


Which dietary components modulate longitudinal growth?
Linear growth in children is sensitive to nutritional status; the growth of the human skeleton requires many different nutritional factors for energy and building blocks: proteins, lipids, carbohydrates and micronutrients. However, what are the specific nutritional factors that are required for proper growth and what is the composition that will be most beneficial is still not known. Recent findings indicate that macro and micronutrients are required as building blocks and as cofactors for important enzymes. In addition, they stimulate linear growth by acting as regulatory factors and also affect gut microbiome. Some interesting studies regarding the effect of proteins and amino acids are presented. Most studies investigated the effect of replacing a single micronutrient that was deficient; however, in real life, deficiency of one nutritional element is commonly associated with other deficiencies. Therefore, it is a reasonable clinical approach, both in developing and developed countries, to use a mixture of both macro and micronutrients to support growth. How much of each of the components and what is the best composition are still open questions that require more research.


On the detection of simple points in higher dimensions using cubical homology.
Simple point detection is an important task for several problems in discrete geometry, such as topology preserving thinning in image processing to compute discrete skeletons. In this paper, the approach to simple point detection is based on techniques from cubical homology, a framework ideally suited for problems in image processing. A (d-dimensional) unitary cube (for a d-dimensional digital image) is associated with every discrete picture element, instead of a point in epsilon(d) (the d-dimensional Euclidean space) as has been done previously. A simple point in this setting then refers to the removal of a unitary cube without changing the topology of the cubical complex induced by the digital image. The main result is a characterization of a simple point p (i.e., simple unitary cube) in terms of the homology groups of the (3d - 1) neighborhood of p for arbitrary, finite dimensions


[Absorption spectra and magnetic circular dichroism of heme-containing proteins in nonequilibrium states. VI. Cytochrome c-oxidase].
Low temperature (77 degrees K) absorption spectra of nonequilibrium states of cytochrome c oxidase produced by reduction of oxidases form protein by thermolysed electrons at 77 degrees K was studied. During reduction of cytochrome oxidase water-glycerol solution by thermolysed electrons at 77 degrees K a nonequilibrium reduced protein is formed. Low temperature (77 degrees K) absorption spectra of the nonequilibrium cytochrome oxidase differs from those reduced by ditionite. It was shown that the oxidation state of cytochrome a3 or addition of cytochrom c have no influence on these spectral changes. It is assumed, that the observed effects are conditioned by structural differences of reduced and oxidased cytochrome oxidase active center. Similar spectral changes were observed for cytochrome oxidase, bound to the mitochondrial membrane. At temperature increasing the low temperature reduced protein is relaxed to a corresponding equilibrium state. The spectral properties of bacterial cytochrome oxidase M. lysodeicticus do not depend on the way of reduction (by dytionite or thermolysed electrons at 77 degrees K).


Framework for the Design of Cannabis-Mediated Phase I Drug-Drug Interaction Studies.
Cannabis has become legal in much of the United States similar to many other countries, for either recreational or medical use. The use of cannabis products is rapidly increasing while the body of knowledge of its myriad of effects still lags. In vitro and clinical data show that cannabis' main constituents, delta-9-tetrahydrocannabinol and cannabidiol, can affect pharmacokinetics (PK), safety, and pharmacodynamics (PD) of other drugs. Within the context of clinical drug development, the widespread and frequent use of cannabis products has essentially created another special population: the cannabis user. We propose that all clinical drug development programs include a Phase 1 study to assess the drug-drug interaction potential of cannabis as a precipitant on the PK, safety, and if applicable, the PD of all new molecular entities (NMEs) in a combination of healthy adult subjects as well as frequent and infrequent cannabis users. This data should be required to inform drug labeling and aid health care providers in treating any patient, as cannabis has quickly become another common concomitant medication and cannabis users, a new special population.


Direct synthesis of aryl-annulated [c]carbazoles by gold(i)-catalysed cascade reaction of azide-diynes and arenes.
The gold-catalysed annulation of conjugated alkynes bearing an azido group with arenes gave annulated [c]carbazoles. Using benzene, pyrrole, and indole derivatives as the nucleophiles, benzo[c]-, pyrrolo[2,3-c]-, and indolo[2,3-c]carbazoles were produced, respectively. The reaction proceeded through pyrrole and benzene ring construction accompanied by the formation of two carbon-carbon and one carbon-nitrogen bond and the cleavage of two aromatic C-H bonds. The mechanism of the reaction with pyrrole was investigated by density functional theory calculations. N,N'-dimethylated indolo[2,3-c]carbazole showed dual ultraviolet-visible-near-infrared and fluorescence spectral changes upon electrolysis.


Evaluating the impact of in-patient bed reduction and community nurse increases in one English Mental Healthcare Trust.
This Mental Health Task Force funded project was designed to evaluate the impact of organizational changes in Northampton, a traditional English Mental Healthcare Trust. Services in Northampton were typically provided by a large 'watertower' Victorian hospital on the outskirts of the town. The hospital had been, over a period of some years, reducing the use of in-patient beds. In February 1995 a further 10 beds were withdrawn enabling the closure of a complete building and the re-deployment of some staff into the community. By reducing in-patient beds, and increasing the number of community staff it was hoped that there would be a significant effect upon both hospital admissions, length of stay with resultant cost savings, and an increase in community nurse-patient contacts. To establish baselines quantitative data were gathered about pre-existing acute and community services, with comparisons made from qualitative and quantitative data gathered during the initial change period. Information was collected concerning in-patient admissions within the acute services, community psychiatric nurse (CPN) caseloads including new admissions, care delivery costs and interviews with service managers. The project found that changes in the general patient profile could not be attributed solely to the reduction in available beds but there did appear to be a direct correlation between bed reduction, increase in percentage bed occupancy and more demanding CPN caseloads. Concern was expressed about the ability of community staff to meet the needs of an increasingly female (age 20-39 years) user group. Savings to the Trust were estimated at Pounds 300,000 per annum. The paper concludes with recommendations for future changes.


Matching target dose to target organ.
In vitro assays have become a mainstay of modern approaches to toxicology with the promise of replacing or reducing the number of in vivo tests required to establish benchmark doses, as well as increasing mechanistic understanding. However, matching target dose to target organ is an often overlooked aspect of in vitro assays, and the calibration of in vitro exposure against in vivo benchmark doses is often ignored, inadvertently or otherwise. An example of this was recently published in Environmental Health Perspectives by Wagner et al (2016), where neural stems cells were used to model the molecular toxicity of lead. On closer examination of the in vitro work, the doses used in media reflected in vivo lead doses that would be at the highest end of lead toxicity, perhaps even lethal. Here we discuss the doses used and suggest more realistic doses for future work with stem cells or other neuronal cell lines.


The contribution of foveal activation to the oculomotor gap effect.
Saccade initiation is facilitated when there is no physical stimulus at the start position of the saccade. There have been numerous explanations for this 'gap effect', the most prominent one being the facilitated release from active fixation when no visual information is present. Attributed to potential fixation sensitive neurons in the superior colliculus, previous research has suggested the gap effect to be a foveal specific effect. The aim of the present study was to investigate whether the gap effect is strictly a foveal effect by using a gaze-contingent eccentric fixation adaptation of the fixation offset paradigm. Results show that, although the gap effect is diminished under eccentric viewing conditions, it is still significantly present. This suggests that the gap effect is mediated by more than foveal specific factors alone. We argue that lateral interactions in the superior colliculus may also contribute to the gap effect.


Investigating the impacts of COVID-19 among LGBTQ2S youth experiencing homelessness.
LGBTQ2S youth are overrepresented among youth experiencing homelessness and experience significantly higher rates of mental health issues compared to heterosexual and cisgender youth. COVID-19 related challenges for LGBTQ2S youth experiencing homelessness remain unknown. To address this gap, this study aimed to understand the impacts of the COVID-19 pandemic on LGBTQ2S youth at risk of, and experiencing, homelessness in the Greater Toronto Area, Ontario, Canada and surrounding areas. Utilizing a mixed-methods convergent parallel design, LGBTQ2S youth experiencing homelessness were recruited to participate in virtual surveys and in-depth one-on-one interviews. Surveys included standardized measures and were administered to measure mental health outcomes and collect information on demographic characteristics, and health service use. Survey data were analyzed with descriptive statistics and statistical tests for difference of proportions. Interviews were analyzed using an iterative thematic content approach. Sixty-one youth completed surveys and 20 youth participated in one-on-one interviews. Quantitative and qualitative data showed that youth have been significantly impacted by the COVID-19 pandemic in various ways, including experiencing poor mental health, such as suicidality, depression, anxiety, and increased substance use, and lack of access to health and social support services. Our study highlights the need for LGBTQ2S inclusive and affirming health care and support services for precariously housed adolescents to address the pre-existing social and health issues that have been exacerbated by the pandemic.


The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 2: Oropharyngeal residue, swallow and cough response, and pneumonia.
Dysphagia is a well-known complication of acute stroke. Given the complexity of cerebral swallowing control it is still difficult to predict which patients are likely to develop swallowing dysfunction based on their neuroimaging. In Part 2 of a comprehensive voxel-based imaging study, whether the location of a stroke lesion can be correlated with further dysfunctional swallowing patterns, pulmonary protective reflexes and pneumonia was evaluated. In all, 200 acute stroke cases were investigated applying flexible endoscopic evaluation of swallowing within 96 h from admission. Lesions were mapped using patients' computed tomography/magnetic resonance images and these were registered to a standard space. The percentage of lesioned volume of 137 anatomically defined brain regions was determined on a voxel basis (FSL5.0). Region-specific odds ratios (ORs) were calculated with respect to the presence of oropharyngeal residue, delayed swallow response, insufficient cough reflex and occurrence of pneumonia during hospital stay. Colour-coded lesion location maps of brain regions with significant ORs were created (P < 0.05). Lesion maps for residue and impaired swallow response depicted parietal-temporal areas of the right hemisphere. Limbic structures in the right hemisphere and sensory regions on the left were associated with cough reflex disturbance. There was no overlap of lesion maps for impaired swallow response and insufficient cough reflex or pneumonia, but substantial overlap between the last two conditions. This study gives new insights on the cortical representation of single components of swallowing and airway protection behaviours. The lesion model may help to risk-stratify patients for dysphagia and pneumonia based on their brain scan.


Bacterial Polyglucuronic Acid/Alginate/Carbon Nanofibers Hydrogel Nanocomposite as a Potential Scaffold for Bone Tissue Engineering.
3D nanocomposite scaffolds have attracted significant attention in bone tissue engineering applications. In the current study, we fabricated a 3D nanocomposite scaffold based on a bacterial polyglucuronic acid (PGU) and sodium alginate (Alg) composite with carbon nanofibers (CNFs) as the bone tissue engineering scaffold. The CNFs were obtained from electrospun polyacrylonitrile nanofibers through heat treatment. The fabricated CNFs were incorporated into a PGU/Alg polymeric solution, which was physically cross-linked using CaCl2 solution. The fabricated nanocomposites were characterized to evaluate the internal structure, porosity, swelling kinetics, hemocompatibility, and cytocompatibility. The characterizations indicated that the nanocomposites have a porous structure with interconnected pores architecture, proper water absorption, and retention characteristics. The in vitro studies revealed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability assessment showed that the nanocomposites were biocompatible and supported bone cell growth. These results indicated that the fabricated bacterial PGU/Alg/CNFs hydrogel nanocomposite exhibited appropriate properties and can be considered a new biomaterial for bone tissue engineering scaffolds.


Retinitis pigmentosa, ataxia, and peripheral neuropathy.
The clinical features of four patients with retinitis pigmentosa, ataxia and peripheral neuropathy but with no increase in serum phytanic acid are reported. Three patients also had sensorineural deafness and radiological evidence of cerebellar atrophy. Nerve conduction studies revealed abnormalities of sensory conduction and normal or only mild slowing of motor conduction velocity. Sural nerve biopsy demonstrated a reduction in the density of myelinated fibres. There were no onion bulb formations. These cases clinically resemble Refsum's disease, but differ in having no detectable biochemical abnormality, and a peripheral neuropathy which is not hypertrophic in type. They may represent unusual cases of spinocerebellar degeneration.


Polyarylisocyanides Derived from an Alkyne-Pd(II) Catalyst as Robust Alignment Media with Excellent Enantiodiscimination.
The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.


Platelet kinetics in patients with bone marrow hypoplasia: evidence for a fixed platelet requirement.
We have studied 16 normal subjects and 27 patients with stable, untreated thrombocytopenia secondary to bone marrow failure and platelet counts ranging from 12,000 to 70,000/microL. Autologous platelets were labeled with 51Cr for measurement of mean platelet life span in the normal subjects and in 20 patients. Labeled donor cells were used in the remaining subjects. Platelet survival, as determined with both autologous and homologous platelets, correlated directly with platelet count in the thrombocytopenic patients. Platelet life span was only modestly reduced in patients having counts in the range of 50,000 to 100,000/microL (7.0 +/- 1.5 days v 9.6 +/- 0.6; P less than .01) but was markedly reduced when the count fell below 50,000/microL (5.1 +/- 1.9 days, P less than .001). The recovery of donor platelets in severely thrombocytopenic recipients (60% +/- 15%) was equivalent to control values (66% +/- 8%; P greater than .2). The recovery of autologous platelets was normal when the platelet count exceeded 50,000/microL (74% +/- 15%) but was reduced in patients with lower counts (50% +/- 22%; P less than .01). All patient and normal data were well correlated by a model predicting a maximum platelet life span of 10 1/2 days and a fixed requirement for 7,100 platelets per microliter of blood per day, or about 18% of the normal rate of platelet turnover, which averaged 41,200 platelets per microliter per day. We conclude that although relatively few platelets are used to support vascular integrity, this requirement is reflected by a reduced platelet life span in marrow hypoplasia and may contribute to the shortening of platelet survival observed in other thrombocytopenias.


The visual hull of smooth curved objects.
The visual hull is a geometric entity that relates the shape of an object to its silhouettes or shadows. This paper develops the theory of the visual hull of generic smooth objects. We show that the visual hull can be constructed using surfaces which partition the viewpoint space of the aspect graph of the object. The surfaces are those generated by the visual events tangent crossing and triple point. An analysis based on the shape of the object at the tangency points of these surfaces allows pruning away many surfaces and patches not relevant to the construction. An algorithm for computing the visual hull is outlined.


High-performance perovskite photodetectors based on CH3NH3PbBr3 quantum dot/TiO2 heterojunction.
Organo-lead halide perovskite materials have opened up a great opportunity to develop high performance photodetectors because of their superior optoelectronic properties. The main issue with perovskite-only photodetector is severe carrier recombination. Integration of perovskite with high-conductive materials such as graphene or transition metal sulfides certainly improved the photoresponsivity. However, achieving high overall performance remains a challenge. Here, an improved photodetector is constructed by perovskite quantum dots (QDs) and atomic layer deposited ultrathin TiO2 films. The designed CH3NH3PbBr3 QD/TiO2 bilayer device displays inclusive performance with on/off ratio of 6.3 × 102, responsivity of 85 A W-1, and rise/decay time of 0.09/0.11 s. Furthermore, we demonstrate that interface plays a crucial role in determining the device current and enhance the overall performance of heterostructure photodetector through interface engineering. We believe that this work can provide a strategy to accelerate development of high-performance solution-processed perovskite photodetectors.


BRAF V600E/V600K Mutations versus Nonstandard Alterations: Prognostic Implications and Therapeutic Outcomes.
BRAF and MEK inhibitors are standard of care for BRAF V600E/K-mutated melanoma, but the benefit of BRAF and/or MEK inhibitors for nonstandard BRAF alterations for melanoma and other cancers is unclear. Patients with diverse malignancies whose cancers had undergone next-generation sequencing were screened for BRAF alterations. Demographics, treatment with BRAF and/or MEK inhibitors, clinical response, progression-free survival (PFS), and overall survival (OS) were determined from review of the electronic medical records for patients with standard BRAF V600E/K versus nonstandard BRAF alterations. A total of 213 patients with BRAF alterations (87 with nonstandard alterations) were identified; OS from diagnosis was significantly worse with nonstandard BRAF versus standard alterations, regardless of therapy [HR (95% confidence interval), 0.58 (0.38-0.88); P = 0.01]. Overall, 45 patients received BRAF/MEK-directed therapy (eight with nonstandard alterations); there were no significant differences in clinical benefit rate [stable disease ≥6 months/partial/complete response (74% vs. 63%; P = 0.39) or PFS (P = 0.24; BRAF V600E/K vs. others)]. In conclusion, patients with nonstandard versus standard BRAF alterations (BRAF V600E/K) have a worse prognosis with shorter survival from diagnosis. Even so, 63% of patients with nonstandard BRAF alterations achieved clinical benefit with BRAF/MEK inhibitors. Larger prospective studies are warranted to better understand the prognostic versus predictive implication of standard versus nonstandard BRAF alterations.


[Mediastinal large B-cell lymphoma].
The group of mediastinal B-cell lymphomas from large cells includes such pathogenic-connected diseases as diffuse large-cell B-cell lymphoma, primary mediastinal large-cell B-cell lymphoma, and recently separated rare nosological form--mediastinal lymphoma of grey zone and classical Hodgkin's lymphoma. Comparative characteristics of these tumors allow revealing many similarities, which in some cases creates significant difficulties for differential diagnosis. Wherein the members of the group differ by their clinical and epidemiological features, prognosis and require different treatment.


Fibrinopeptide A in urine from patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis--evidence for dephosphorylation and carboxyterminal degradation of the peptide by the kidney.
Urinary fibrinopeptide A immunoreactivity was determined by radioimmunoassay using two anti-fibrinopeptide A sera with a different specificity in patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis. Elevated levels were frequently observed with both sera, and intravenous administration of heparin in patients with a thromboembolic disorder resulted in a decline of urinary fibrinopeptide A (FPA) concentrations to normal or nearly normal values. For both sera significant correlations with plasma levels were found although one of the sera reacted significantly better with the material in urine samples from these patients than the other (p less than 0.0001, n = 73). Analysis of urinary fibrinopeptide A immunoreactivity by high performance liquid chromatography (HPLC) provided evidence that A peptide material present in this body fluid was heterogeneous. In view of the characteristics of the antisera used in this study, data suggest that urinary FPA immunoreactivity consists to a large extent of carboxyterminally degraded FPA. Excretion of circulating FPA immunoreactive material through the kidneys apparently involves dephosphorylation and carboxyterminal breakdown of the A peptide. Since both synthetic and native phosphorylated or unphosphorylated fibrinopeptide A appeared to be stable in urine in vitro, an active role of the kidney in degrading the A peptide is likely.


Aligned nanogold assisted one step sensing and removal of heavy metal ions.
We depict a novel strategy exploiting the chemistry of metal ion adsorption for detection and sequestration of toxic heavy metal from processed water using gold nanoparticles capped with 4-aminothiophenol. The interaction between 4-aminothiophenol capped gold nanoparticles and heavy metal ions was studied as a function of time and concentration using TEM, HRTEM, SEM, EDS, and I-V characterization. Experiments confirmed that pH is one of the crucial controlling parameters. Adsorption capacity was monitored using AAS, UV-vis spectroscopy and I-V measurement. In the absence of any alloy formation between Au and heavy metal ions, the desorption of the heavy metal ions from 4-aminothiophenol capped gold nanoparticles surface by pH modulation serves as a mean of collection of heavy metal ions. Experiments revealed that the concentration of heavy metal ions in processed water after adsorption is below the maximum permissible limit set by the WHO.


Demonstration of a wavelength monitor comprised of racetrack-ring resonators with defect mediated photodiodes operating in the C-band.
A CMOS compatible wavelength monitor comprised of two thermally tuned racetrack-ring resonators with defect mediated photodiode structures is experimentally demonstrated in monolithic silicon. Each resonator is independently tuned so as to determine an unknown input wavelength by tuning the resonance peak locations until there is overlap between the two comb spectra. The presence of two of these resonator/heater components, each with a different free spectral range, increases the unambiguous measurement range when compared to one component used on its own.


Gastric Activity and Gut Peptides in Patients With Functional Dyspepsia: Postprandial Distress Syndrome Versus Epigastric Pain Syndrome.
The goals of the study were to investigate in both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) the gastric electrical activity and the gastric emptying (GE) time together with the circulating concentrations of motilin, somatostatin, corticotrophin-releasing factor, and neurotensin, and to establish whether the genetic variability in the neurotensin system genes differs between these 2 categories of functional dyspepsia (FD). The current FD classification is based on symptoms and it has been proven not to be completely satisfying because of a high degree of symptom overlap between subgroups. Gastric electrical activity was evaluated by cutaneous electrogastrography: the GE time by C-octanoic acid breast test. Circulating concentrations of gut peptides were measured by a radioimmunoassay. NTS 479 A/G and NTSR1 rs6090453 SNPs were evaluated by PCR and endonuclease digestion. Fifty-four FD patients (50 female/4 male) were studied. Using a symptom questionnaire, 42 patients were classified as PDS and 12 as EPS, although an overlap between the symptom profiles of the 2 subgroups was recorded. The electrogastrographic parameters (the postprandial instability coefficient of dominant frequency, the dominant power, and the power ratio) were significantly different between the subgroups, whereas the GE time did not differ significantly. In addition, EPS was characterized by a different gut peptide profile compared with PDS. Finally, neurotensin polymorphism was shown to be associated with neurotensin levels. This evidence deserves further studies in consideration of an analgesic role of neurotensin. Analysis of gut peptide profiles could represent an interesting tool to enhance FD diagnosis and overcome limitations due to a distinction based solely on symptoms.


Learning metrics on spectrotemporal modulations reveals the perception of musical instrument timbre.
Humans excel at using sounds to make judgements about their immediate environment. In particular, timbre is an auditory attribute that conveys crucial information about the identity of a sound source, especially for music. While timbre has been primarily considered to occupy a multidimensional space, unravelling the acoustic correlates of timbre remains a challenge. Here we re-analyse 17 datasets from published studies between 1977 and 2016 and observe that original results are only partially replicable. We use a data-driven computational account to reveal the acoustic correlates of timbre. Human dissimilarity ratings are simulated with metrics learned on acoustic spectrotemporal modulation models inspired by cortical processing. We observe that timbre has both generic and experiment-specific acoustic correlates. These findings provide a broad overview of former studies on musical timbre and identify its relevant acoustic substrates according to biologically inspired models.


Ontogenetic and spatiotemporal variability in anchoveta Engraulis ringens diet off Peru.
In this study, historical data available since 1954 were used to get new insight to ontogenetic and spatiotemporal variability in Peruvian anchovy or anchoveta Engraulis ringens diet. Whatever the period, E. ringens foraged mainly on macrozooplankton and the importance of euphausiids in E. ringens diet appears directly related to euphausiids abundance. This bottom-up effect is also observed at smaller scale because the euphausiids fraction increased with E. ringens total length and euphausiids accessibility. Selecting the largest prey, the euphausiids, provides an energetic advantage for E. ringens in its ecosystem where oxygen depletion imposes strong metabolic constraints on pelagic fishes. This study illustrates the plasticity of E. ringens that allows it to cope with its highly variable environment.


Frequency of dissociative identity disorder in the general population in Turkey.
This study attempted to determine the prevalence of dissociative identity disorder in the general population. The Dissociative Experiences Scale (DES) was administered to 994 subjects in 500 homes who constituted a representative sample of the population of Sivas City, Turkey. The mean DES score was 6.7+/-6.1 (mean +/- SD). Of the 62 respondents who scored above 17 on the DES, 32 (51.6%) could be contacted during the second phase of the study. They were matched for age and gender with a group of respondents who scored below 10 on the scale, and the Dissociative Disorders Interview Schedule (DDIS) was then administered to both groups. Seventeen subjects (1.7%) received a diagnosis of dissociative disorder according to the structured interview. In the third phase, eight of 17 subjects who had a dissociative disorder on the structured interview could be contacted for a clinical evaluation. They were matched with a nondissociative control group and interviewed by a clinician blind to the structured interview diagnosis. Four of eight subjects were diagnosed clinically with dissociative identity disorder, yielding a minimum prevalence of 0.4%. Dissociative identity disorder is not rare in the general population. Self-rating instruments and structured interviews can be used successfully for screening these cases. Our data, derived from a population with no public awareness about dissociative identity disorder and no exposure to systematic psychotherapy, suggest that dissociative identity disorder cannot be considered simply an iatrogenic artifact, a culture-bound syndrome, or a phenomenon induced by media influences.


[Specific prophylaxis of influenza with inactivated split vaccine Vaxigrip].
Influenza remains a serious health problem, annually causing epidemics embracing up to 10% of the population of the world, and at the periods of pandemics this number may rise 4- to 6-fold. In the overwhelming majority of the countries the prophylaxis of influenza is carried out at present out with the use of inactivated vaccines. One of such vaccines is the highly purified split vaccine Vaxigrip (Aventis-Pasteur, France), permitted for use in Russia since 1992. The article contains the review of the data of literature, as well as the materials provided by the authors, which indicate that the preparation has low reactogenicity (also for children starting from the age of 6 months) and high reactogenic properties, leading to antibody formation at protective levels with respect to all three components of the vaccine. The vaccine has been found to ensure pronounced prophylactic efficacy for 70-90% of vaccinees and a decrease in influenza morbidity even in case of using the preparation a week before the onset of the epidemic. This shows the advantage of Vaxigrip in comparison with other inactivated vaccines.


Nasolabial appearance after two palatoplasty types in cleft lip and palate.
Facial appearance is important for normal psychosocial development in children with cleft lip and palate (CLP). There is conflicting evidence on how deficient maxillary growth may affect nasolabial esthetics. We retrospectively investigated nasolabial appearance in two groups, the Langenback (35 children; mean age 11.1 years; range: 7.9-13.6) and Vomerplasty (58 children; mean age 10.8 years; range: 7.8-14), who received unilateral CLP surgery by the same surgeon. The hard palate repair technique differed between the two groups. In the Langenback group, palatal bone on the non-cleft side only was left denuded, inducing scar formation and inhibiting maxillary growth. In the Vomerplasty group, a vomerplasty with tight closure of the soft tissues on the palate was applied. Thirteen lay judges rated nasolabial esthetics on photographs using a modified Asher-McDade's index. Nasolabial esthetics in both groups was comparable (p > 0.1 for each nasolabial component). Inferior view was judged as the least esthetic component and demonstrated mean scores 3.18 (SD = 0.63) and 3.13 (SD = 0.47) in the Langenback and Vomerplasty groups, respectively. Mean scores for other components were from 2.52 (SD = 0.63) to 2.81 (SD = 0.62). Regression analysis showed that vomerplasty is related with slight improvement in the nasal profile only (coefficient B = -0.287; p = 0.043; R(2 ) = 0.096). This study demonstrates that the use of vomerplasty instead of the Langenbeck technique is weakly associated with the nasolabial appearance among pre-adolescent patients with UCLP.


In situ aquaculture methods for Dysidea avara (Demospongiae, Porifera) in the northwestern Mediterranean.
Marine sponges produce secondary metabolites that can be used as a natural source for the design of new drugs and cosmetics. There is, however, a supply problem with these natural substances for research and eventual commercialisation of the products. In situ sponge aquaculture is nowadays one of the most reliable methods to supply pharmaceutical companies with sufficient quantities of the target compound. In this study, we focus on the aquaculture of the sponge Dysidea avara (Schmidt, 1862), which produces avarol, a sterol with interesting pharmaceutical attributes. The soft consistency of this species makes the traditional culture method based on holding explants on ropes unsuitable. We have tested alternative culture methods for D. avara and optimized the underwater structures to hold the sponges to be used in aquaculture. Explants of this sponge were mounted on horizontal ropes, inside small cages or glued to substrates. Culture efficiency was evaluated by determination of sponge survival, growth rates, and bioactivity (as an indication of production of the target metabolite). While the cage method was the best method for explant survival, the glue method was the best one for explant growth and the rope method for bioactivity.


Occurrence, characteristics, and outcome of patients hospitalized with a diagnosis of acute myocardial infarction who do not fulfill traditional criteria.
The diagnosis of acute myocardial infarction (AMI) is traditionally based on clinical history, elevation of serum enzyme activity, and typical changes in the electrocardiogram (ECG); however, not all patients who develop AMI fulfill these criteria on discharge from hospital. The aim of the study was to evaluate (1) the frequency with which the traditional criteria for AMI are not fulfilled among patients diagnosed with AMI on discharge, and (2) whether patients with and without these criteria differ in terms of characteristics, treatment, and outcome. All patients aged < 75 years and hospitalized in the municipality of Göteborg with a discharge diagnosis of AMI were included. Fulfillment criteria for AMI were two of the following three points: (1) chest pain, (2) increase in cardiac enzymes, and (3) development of Q waves. In all, 1,188 admitted patients, 27% of whom were women, were included in the analysis. Of these, 193 (16%) did not fulfill the traditional criteria for AMI. These patients had an in-hospital mortality rate of 48%; of these, 59% died a sudden death, and of those who were autopsied (62%), 96% showed signs of a fresh AMI. The most common symptom on admission to hospital in patients who did not fulfill the traditional criteria was chest pain (34%), followed by dyspnea (27%) and fatigue (14%). Of those who died suddenly, fewer than half had been admitted to the coronary care unit. Patients diagnosed with AMI who do not fulfill the traditional diagnosis criteria have high mortality. On admission to hospital, the initial suspicion of AMI is often vague. Measures for earlier detection of life-threatening coronary artery disease among these patients are warranted.


Effect of Chemotherapy on the Gut Microbiome of Breast Cancer Patients During the First Year of Treatment.
There is accumulating information of the effects of chemotherapy and weight changes on the gut microbiome of breast cancer patients. In this 1-year follow-up study, we investigated gut microbiome of 33 breast cancer patients who donated fecal samples at baseline and after completion of treatment. We compared alpha diversity and mean taxa abundance at baseline and absolute taxa abundance changes (final-baseline) by treatment (16 neoadjuvant [neoADJ], 13 adjuvant [ADJ], 4 no chemotherapy [noC]) and specific chemotherapy agent using Wilcoxon rank sum and negative binomial mixed model (NBMM) analysis. All four gut alpha diversity measures changed in association with chemotherapy treatment; they increased in the neoADJ (+16.4% OTU p = 0.03; +51.6% Chao1 p = 0.03; +7.0% Shannon index p = 0.02; +11.0% PD whole tree p = 0.09) but not in the ADJ and noC group (ADJ+noC). The difference in Chao1 index change between groups was statistically significant (pneoADJ vs. ADJ+noC=0.04). Wilcoxon p values of 0.03-0.003 were observed for five taxa. In NBMM analysis, changes in taxa abundance differed (Bonferroni-adjusted p ≤ 0.0007) for two Bacteroidetes taxa (g_Alistipes, f_S24-7) and two Firmicutes taxa (g_Catenibacterium, g_Eubacterium). NBMM analysis results remained unchanged with adjustment for weight changes. Alpha diversity changes were also found by receipt of chemotherapy agents. Consistent increases in alpha diversity were observed among those treated with TCHP (OTU p = 0.009; Chao1 p = 0.02; Shannon p = 0.02; PD whole tree p = 0.05) but not AC, Taxol or Herceptin. Those treated with TCHP or Herceptin showed increases in Verrucomicrobia (g_Akkermansia) but decreases of Bacteroidetes(g_Alistipes); the differences in changes in taxa abundance were statistically significant. Results from this pilot longitudinal study support an effect of chemotherapy, particularly neoADJ on the gut microbiome of breast cancer patients even after adjustment for weight changes. Further investigations are needed to confirm these findings in larger studies and with longer follow-up and to assess the impact of these microbiome changes on patient outcome.


Health sciences library building projects: 1995 survey.
The Medical Library Association's fifth annual survey of recent health sciences library building projects identified twenty-five libraries planning, expanding, or constructing new library facilities. None of the fifteen new library projects are free standing structures; however, several occupy a major portion of the project space. Ten projects involve renovation of or addition to existing space. Information regarding size, cost of project, type of construction, completion date, and other factual data was provided for twelve projects. The remaining identified projects are in pre-design or early-design stages, or are awaiting funding approval. Library building projects for three hospital libraries, three academic medical libraries, and an association library are described. Each illustrates how considerations of economics and technology are changing the traditional library model from a centrally stored information depository housing a wide range of information under one roof where users come to the information, into an electronic model gradually shifting from investment in the physical presence of resources to investment in creating work space for creditible information specialists who help in-house and distanced users to obtain information electronically from any place and at any time. This new model includes a highly skilled library team to manage, filter, and package the information to users trained by these resident experts.


Gender Differences in Homicide of Neonates, Infants, and Children under 5 y in South Africa: Results from the Cross-Sectional 2009 National Child Homicide Study.
Homicide of children is a global problem. The under-5-y age group is the second largest homicide age group after 15-19 y olds, but has received little research attention. Understanding age and gender patterns is important for assisting with developing prevention interventions. Here we present an age and gender analysis of homicides among children under 5 y in South Africa from a national study that included a focus on neonaticide and infanticide. A retrospective national cross-sectional study was conducted using a random sample of 38 medico-legal laboratories operating in 2009 to identify homicides of children under 5 y. Child data were abstracted from the mortuary files and autopsy reports, and both child and perpetrator data data were collected from police interviews. We erred towards applying a conservative definition of homicide and excluded sudden infant death syndrome cases. We estimated that 454 (95% CI 366, 541) children under the age of 5 y were killed in South Africa in 2009. More than half (53.2%; 95% CI 46.7%, 59.5%) were neonates (0-28 d), and 74.4% (95% CI 69.3%, 78.9%) were infants (under 1 y), giving a neonaticide rate of 19.6 per 100,000 live births and an infanticide rate of 28.4 per 100,000 live births. The majority of the neonates died in the early neonatal period (0-6 d), and abandonment accounted for 84.9% (95% CI 81.5%, 87.8%) of all the neonates killed. Distinct age and gender patterns were found, with significantly fewer boy children killed in rural settings compared to urban settings (odds ratio 0.6; 95% CI 0.4, 0.9; p = 0.015). Abuse-related killings and evidence of sexual assault were more common among older girls than in all other age and gender groups. Mothers were identified as the perpetrators in all of the neonaticides and were the most common perpetrators overall (71.0%; 95% CI 63.9%, 77.2%). Abandoned neonates were mainly term babies, with a mean gestational age of 38 wk. We did not have information on abandonment motives for all newborns and did not know if babies were abandoned with the intention that they would die or with the hope that they would be found alive. We therefore considered all abandoned babies as homicides. Homicide of children is an extreme form or consequence of violence against children. This national study provides one of the first analyses of neonaticide and infanticide by age and gender and shows the failure of reproductive and mental health and social services to identify and help vulnerable mothers. Multi-sectoral prevention strategies are needed.


Mediofrontal event-related potentials in response to positive, negative and unsigned prediction errors.
Reinforcement learning models make use of reward prediction errors (RPEs), the difference between an expected and obtained reward. There is evidence that the brain computes RPEs, but an outstanding question is whether positive RPEs ("better than expected") and negative RPEs ("worse than expected") are represented in a single integrated system. An electrophysiological component, feedback related negativity, has been claimed to encode an RPE but its relative sensitivity to the utility of positive and negative RPEs remains unclear. This study explored the question by varying the utility of positive and negative RPEs in a design that controlled for other closely related properties of feedback and could distinguish utility from salience. It revealed a mediofrontal sensitivity to utility, for positive RPEs at 275-310ms and for negative RPEs at 310-390ms. These effects were preceded and succeeded by a response consistent with an unsigned prediction error, or "salience" coding.


Low bone mineral density is two to three times more prevalent in non-athletic premenopausal women than in elite athletes: a comprehensive controlled study.
To compare bone mineral density (BMD), investigate factors associated with BMD, and examine the prevalence of low BMD in athletes and non-athletic controls. The study included a questionnaire (part I), measurement of BMD (part II), and a clinical interview (part III). All Norwegian female athletes on national teams (n = 938) and an aged matched random sample of non-athletic controls (n = 900) were invited to participate. The questionnaire was completed by 88% of athletes and 70% of controls. A random sample of these athletes (n = 300) and controls (n = 300) was invited to participate in parts II and III. All parts were completed by 186 athletes (62%) and 145 controls (48%). Mean (standard deviation) total body (TB) BMD was higher (p<0.001) in athletes (1.21 (0.09) g/cm2) than in controls (1.18 (0.08) g/cm2), and higher (p<0.001) in high impact (HI) sports athletes than in medium impact (MI) and low impact (LI) sports athletes. In athletes, body weight and impact loading sports were positively associated, and percent body fat and eating disorders were negatively associated with TB BMD. Body weight and weight bearing activities were positively associated and menstrual dysfunction was negatively associated with TB BMD in controls. A higher percentage of controls (28.3%) than athletes (10.7%) had low BMD (p<0.001). Female elite athletes have 3-20% higher BMD than non-athletic controls and HI sports athletes have 3-22% higher BMD compared with MI and LI sports athletes. Low BMD is two to three times more common in non-athletic premenopausal women than in elite athletes.


Snap-through buckling of initially curved microbeam subject to an electrostatic force.
In this paper, the snap-through buckling of an initially curved microbeam subject to an electrostatic force, accounting for fringing field effect, is investigated. The general governing equations of the curved microbeam are developed using Euler-Bernoulli beam theory and used to develop a new criterion for the snap-through buckling of that beam. The size effect of the microbeam is accounted for using the modified couple stress theory, and intermolecular effects, such as van der Waals and Casimir forces, are also included in our snap-through formulations. The snap-through governing equations are solved using Galerkin decomposition of the deflection. The results of our work enable us to carefully characterize the snap-through behaviour of the initially curved microbeam. They further reveal the significant effect of the beam size, and to a much lesser extent, the effect of fringing field and intermolecular forces, upon the snap-through criterion for the curved beam.


The Arabidopsis dwarf1 mutant is defective in the conversion of 24-methylenecholesterol to campesterol in brassinosteroid biosynthesis.
Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism.


Fatigue experienced by patients receiving maintenance dialysis in hemodialysis units.
The fatigue that is observed in patients who are undergoing dialysis is usually associated with an impaired quality of life. The present cross-sectional study was conducted from January to April 2009 in three hemodialysis units in Kuala Lumpur, Malaysia. In this study, the Multidimensional Fatigue Inventory and Depression Anxiety and Stress Score 21 were used to determine the level of fatigue, depression, anxiety, and stress of patients who were undergoing dialysis. The data were obtained from a calculated sample of 116 and a total of 103 respondents participated in the study. A total of 56 (54.4%) and 47 (45.6%) respondents experienced a high level and a low level of fatigue, respectively. There was a significant relationship between the duration of treatment and the level of fatigue. The respondents who had been receiving treatment for > 2 years experienced more fatigue, compared to the respondents who had been undergoing hemodialysis for > 2 years. There was a significant difference in relation to the age of the participants regarding the level of fatigue. No significant relationship between the sex of the participants, anemia, depression, anxiety, stress, and the level of fatigue was observed. Special attention needs to be paid to both the younger and older adults who are receiving treatment. In addition, proper planning is needed for the patients regarding their daily activities in order to reduce fatigue. Nurses who work in hemodialysis units are recommended to provide exercise classes or group therapy in order to boost the energy levels among patients who are undergoing dialysis. Health professionals should provide appropriate treatment for patients who are experiencing fatigue in order to prevent any other complications that could arise.


Frequency of Stroke in Intermediate-Risk Patients in the Long-Term Undergoing TAVR vs SAVR: A Systematic Review and Meta-Analysis.
The aim of this research is to compare the long-term incidence of stroke in intermediate-risk patients who have undergone either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedures. The objective is to identify which method exhibits a higher propensity for stroke occurrence, potentially contributing to disability or stroke-related mortality. We conducted a systematic review and meta-analysis to evaluate the frequency of stroke post-TAVR and SAVR procedures. Data were compiled from a diverse array of research articles, retrieved from the Embase, Cochrane Library, and PubMed databases. Conclusions were derived from the comprehensive analysis of forest plots. The analysis indicates no significant reduction in stroke incidence among patients undergoing TAVR compared to those receiving SAVR. This conclusion, underscored by a P-value of 0.76 and a 95% confidence interval (CI) ranging from 0.80 to 1.17, arises from a careful review of multiple pertinent studies. The meta-analysis of pooled data does not reveal a significant decrease in stroke frequency associated with TAVR. For intermediate-risk patients, both TAVR and SAVR present similar stroke risks, indicating no procedure is inherently safer. Healthcare providers must take this into account when counseling patients, considering each procedure's benefits and drawbacks. This study focuses specifically on intermediate-risk individuals, so results may not apply universally. Further research across different risk categories is needed. This study emphasizes the need for individualized patient care and informed decision-making in aortic stenosis management.


Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information.
Compared to volumetric modulated arc therapy (VMAT), clinical benefits are anticipated when treating thoracic tumours with intensity-modulated proton therapy (IMPT). However, the current concern of plan robustness as a result of motion hampers its wide clinical implementation. To define an optimal protocol to treat lung and oesophageal cancers, we present a comprehensive evaluation of IMPT planning strategies, based on patient 4DCTs and machine log files. For ten lung and ten oesophageal cancer patients, a planning 4DCT and weekly repeated 4DCTs were collected. For these twenty patients, the CTV volume and motion were assessed based on the 4DCTs. In addition to clinical VMAT plans, layered rescanned 3D and 4D robust optimised IMPT plans (IMPT_3D and IMPT_4D respectively) were generated, and approved clinically, for all patients. The IMPT plans were then delivered in dry runs at our proton facility to obtain log files, and subsequently evaluated through our 4D robustness evaluation method (4DREM). With this method, for each evaluated plan, fourteen 4D accumulated scenario doses were obtained, representing 14 possible fractionated treatment courses. From VMAT to IMPT_3D, nominal Dmean(lungs-GTV) decreased 2.75 ± 0.56 GyRBE and 3.76 ± 0.92 GyRBE over all lung and oesophageal cancer patients, respectively. A more pronounced reduction was verified for Dmean(heart): 5.38 ± 7.36 GyRBE (lung cases) and 9.51 ± 2.25 GyRBE (oesophagus cases). Target coverage robustness of IMPT_3D was sufficient for 18/20 patients. Averaged dose in critical structures over all 4DREM scenarios changed only slightly for both IMPT_3D and IMPT_4D. Relative to IMPT_3D, no gain in IMPT_4D was observed. The dosimetric superiority of IMPT over VMAT has been established. For most thoracic tumours, our IMPT_3D planning protocol showed to be robust and clinically suitable. Nevertheless, accurate patient positioning and adapting to anatomical variations over the course of treatment remain compulsory.


Inhibition of apoptosis in human induced pluripotent stem cells during expansion in a defined culture using angiopoietin-1 derived peptide QHREDGS.
Adhesion molecule signaling is critical to human pluripotent stem cell (hPSC) survival, self-renewal, and differentiation. Thus, hPSCs are grown as clumps of cells on feeder cell layers or poorly defined extracellular matrices such as Matrigel. We sought to define a small molecule that would initiate adhesion-based signaling to serve as a basis for a defined substrate for hPSC culture. Soluble angiopoeitin-1 (Ang-1)-derived peptide QHREDGS added to defined serum-free media increased hPSC colony cell number and size during long- and short-term culture when grown on feeder cell layers or Matrigel, i.e. on standard substrates, without affecting hPSC morphology, growth rate or the ability to differentiate into multiple lineages both in vitro and in vivo. Importantly, QHREDGS treatment decreased hPSC apoptosis during routine passaging and single-cell dissociation. Mechanistically, the interaction of QHREDGS with β1-integrins increased expression of integrin-linked kinase (ILK), increased expression and activation of extracellular signal-regulated kinases 1/2 (ERK1/2), and decreased caspase-3/7 activity. QHREDGS immobilization to polyethylene glycol hydrogels significantly increased cell adhesion in a dose-dependent manner. We propose QHREDGS as a small molecule inhibitor of hPSC apoptosis and the basis of an affordable defined substrate for hPSC maintenance.


Serum cytokine concentrations, chorioamnionitis and the onset of bronchopulmonary dysplasia in premature infants.
To investigate the relationships between serum cytokine concentrations and chorioamnionitis (CAM) and CAM-related bronchopulmonary dysplasia (BPD) in premature infants. Serum was collected at 0 and 7 days after birth from 36 premature infants born at <32 weeks of gestation. We examined the relationships between 30 cytokine concentrations and CAM, BPD, and other perinatal factors. On day 0, GM-CSF, IL-15, IL-17, IL-2, IL-2R, VEGF, and MIG concentrations were significantly higher in the CAM group (n = 17) than in the non-CAM group (n = 19). These concentrations had decreased by day 7 and were similar in both groups. The IL-12p70 concentration on day 0 was significantly lower in the BPD group (n = 16) than in the non-BPD group (n = 15). BPD incidence was similar between the CAM and non-CAM groups. These data support the hypothesis that intrauterine inflammation is not a primary risk factor for BPD. The immunological environment at birth or soon after, rather than intrauterine fetal inflammation (e.g., CAM), is a primary risk factor for BPD onset in preterm infants. Decreased inflammatory responses are particularly relevant, as indicated by the relationship between BPD and low serum IL-12p70 concentrations on day 0.


Pathways of DNA unlinking: A story of stepwise simplification.
In Escherichia coli DNA replication yields interlinked chromosomes. Controlling topological changes associated with replication and returning the newly replicated chromosomes to an unlinked monomeric state is essential to cell survival. In the absence of the topoisomerase topoIV, the site-specific recombination complex XerCD- dif-FtsK can remove replication links by local reconnection. We previously showed mathematically that there is a unique minimal pathway of unlinking replication links by reconnection while stepwise reducing the topological complexity. However, the possibility that reconnection preserves or increases topological complexity is biologically plausible. In this case, are there other unlinking pathways? Which is the most probable? We consider these questions in an analytical and numerical study of minimal unlinking pathways. We use a Markov Chain Monte Carlo algorithm with Multiple Markov Chain sampling to model local reconnection on 491 different substrate topologies, 166 knots and 325 links, and distinguish between pathways connecting a total of 881 different topologies. We conclude that the minimal pathway of unlinking replication links that was found under more stringent assumptions is the most probable. We also present exact results on unlinking a 6-crossing replication link. These results point to a general process of topology simplification by local reconnection, with applications going beyond DNA.


Role of sex steroids in the regulation of bone morphology in men. The MINOS study.
In ageing men, skeletal fragility is associated with reduced cortical thickness and decreased bone density. To better understand the role of testosterone and 17beta-estradiol regarding these characteristics of skeletal fragility, we correlated their circulating levels with the estimates of mechanical bone properties derived from areal bone mineral density (aBMD) measured by DXA. External diameter and BMD were used to estimate cortical thickness, cross-sectional area (CSA), section modulus, buckling ratio and strength index of the femoral neck and distal radius on 760 men aged 40-85 years. The 17beta-estradiol level was an independent positive determinant of CSA, aBMD and estimated cortical thickness of both bones. In multivariate models adjusted for age, body weight, height, lean body mass and testosterone concentration, men in the lowest quartile of 17beta-estradiol had lower CSA at the femoral neck (4.8%, P<0.001) and distal radius (3.6%, P<0.01) compared with men in the highest quartile. They had also thinner cortical bone at the femoral neck and distal radius (4.8%, P<0.001 and 4.6%, P<0.001, respectively). Furthermore 17beta-estradiol had a negative association with indices of cortical instability (buckling ratio) and a positive association with bending strength (section modulus, strength index) both at femoral neck and radius. Men in the lowest quartile of 17beta-estradiol had higher buckling ratios (femoral neck 4.8%, P<0.002; radius 5.1%, P<0.005), lower strength index (femoral neck 8.5%, P<0.001, radius 6.1%, P<0.01) and greater section modulus at the femoral neck. However, there were no between-quartile differences in external diameter in any bone sites. Similar, even though somewhat smaller, between-quartile differences were found for bioavailable 17beta-estradiol. Neither total testosterone nor apparent free testosterone concentration was associated with any bone variables after adjusting for age, body weight, body height, and lean body mass and 17beta-estradiol level. In conclusion, in elderly men, low concentration of 17beta-estradiol (total and bioavailable) was associated with a decreased cortical thickness and with a deterioration of biomechanical parameters of long bones (lower section modulus and strength index, higher buckling ratio).


Age Estimation in Living Adults using 3D Volume Rendered CT Images of the Sternal Plastron and Lower Chest.
Age estimation is commonly of interest in a judicial context. In adults, it is less documented than in children. The aim of this study was to evaluate age estimation in adults using CT images of the sternal plastron with volume rendering technique (VRT). The evaluation criteria are derived from known methods used for age estimation and are applicable in living or dead subjects. The VRT images of 456 patients were analyzed. Two radiologists performed age estimation independently from an anterior view of the plastron. Interobserver agreement and correlation coefficients between each reader's classification and real age were calculated. The interobserver agreement was 0.86, and the correlation coefficients between readers classifications and real age classes were 0.60 and 0.65. Spearman correlation coefficients were, respectively, 0.89, 0.67, and 0.71. Analysis of the plastron using VRT allows age estimation in vivo quickly and with results similar than methods such as Iscan, Suchey-Brooks, and radiographs used to estimate the age of death.


Worst-point suicidal plans: a dimension of suicidality predictive of past suicide attempts and eventual death by suicide.
Among 440 psychiatric outpatients with current suicidal ideation, we examined the empirical distinction between the "plans" vs. "desire" dimensions of suicidality, focusing for conceptual and empirical reasons on a worst-point assessment strategy. Factor analyses were consistent with the distinction, but more importantly, among the current ideators included in this study, the worst-point "plans" dimension was the only predictor significantly related to both of two important indices, history of past attempt and eventual suicide. These findings bear on the trajectory of suicidal behavior over time, as well as inform the clinical assessment of suicidal patients.


IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis.
IL-23 is an important molecular driver of Th17 cells and has strong tumor-promoting proinflammatory activity postulated to occur via adaptive immunity. Conversely, more recently it has been reported that IL-17A elicits a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. Here we show the much broader impact of IL-23 in antagonizing antitumor immune responses primarily mediated by innate immunity. Furthermore, the majority of this impact was independent of IL-17A, which did not appear critical for many host responses to tumor initiation or metastases. IL-23-deficient mice were resistant to experimental tumor metastases in three models where host NK cells controlled disease. Immunotherapy with IL-2 was more effective in mice lacking IL-23, and again the protection afforded was NK cell mediated and independent of IL-17A. Further investigation revealed that loss of IL-23 promoted perforin and IFN-gamma antitumor effector function in both metastasis models examined. IL-23-deficiency also strikingly protected mice from tumor formation in two distinct mouse models of carcinogenesis where the dependence on host IL-12p40 and IL-17A was quite different. Notably, in the 3'-methylcholanthrene (MCA) induction of fibrosarcoma model, this protection was completely lost in the absence of NK cells. Overall, these data indicate the general role that IL-23 plays in suppressing natural or cytokine-induced innate immunity, promoting tumor development and metastases independently of IL-17A.


AIDS education for college students: review and proposal for a research-based curriculum.
The history of AIDS education for college students in the U.S. is reviewed. Wide agreement concerning the goals and overall content of the AIDS-education curriculum is found. However, the context and location of AIDS education within the curriculum vary considerably. Increased knowledge about AIDS is a frequent outcome, but improvements in attitude and reported sexual behaviors are more difficult to achieve. The conceptual frameworks used in AIDS education include the health belief model, social learning theory, and theory of reasoned action; each has contributed to the design of an AIDS-prevention curriculum. A proposed research-based AIDS-education curriculum would utilize the theory of planned behavior from attitude research, the elaboration likelihood model from persuasion research, and the conceptual change model from science education research.


Bone scintigraphy in testicular tumors.
Testicular tumors do not occur frequently. Primary treatment is surgical, and radiotherapy and chemotherapy can play important roles in cases of metastatic disease. Bone scintigraphy is used largely for early detection of skeletal metastases from several tumors, and conventional radiographic studies are less sensitive than the nuclear technique for such a purpose. The aim of this study was to identify the role of bone scintigraphy in cases of testicular tumors, regardless of the grade. The authors examined 28 patients (8 to 52 years old) with proved testicular tumors using Tc-99m MDP (750 MBq; 20 mCi) injected intravenously. Whole-body images were obtained 2 hours later, at 500,000 counts per image. Radiographic studies were obtained to investigate abnormal areas noted on scintigraphy. The results of bone scintigraphy were abnormal in seven cases, consisting of variable but diffuse uptake in the iliac bone on the same side as the affected testicle. MDP uptake was substantial in five of these patients (four seminomas, one nonseminoma; only two radiographic studies were abnormal), and the two other patients had moderate uptake of the radiopharmaceutical (two seminomas; radiographic studies were normal). Metastases were confirmed by biopsy in three cases. Early metastases from seminomas can occur through the lymphatic drainage toward the iliac lymph node chain. This could explain these findings. The scintigraphic aspects of the affected iliac bones seem characteristic. Early detection of metastases is very important to ensure the efficacy of radiotherapy and chemotherapy. Bone scintigraphy may play an important role in such cases and seems to be more sensitive than conventional radiography. Testicular tumor metastases should be considered when iliac involvement is observed. Paget's disease should be included in a differential diagnosis.


Enhancement of DNA vaccine potency by linkage of antigen gene to a gene encoding the extracellular domain of Fms-like tyrosine kinase 3-ligand.
Recently, Flt3 (Fms-like tyrosine kinase 3)-ligand has been identified as an important cytokine for the generation of professional antigen-presenting cells (APCs), particularly dendritic cells (DCs). A recombinant chimera of the extracellular domain of Flt3-ligand (FL) linked to a model antigen may potentially target the antigen to DCs and their precursor cells. Using human papillomavirus-16 E7 as a model antigen, we evaluated the effect of linkage to FL on the potency of antigen-specific immunity generated by naked DNA vaccines administered intradermally via gene gun. We found that vaccines containing chimeric FL-E7 fusion genes significantly increased the frequency of E7-specific CD8+ T cells relative to vaccines containing the wild-type E7 gene. In vitro studies indicated that cells transfected with FL-E7 DNA presented E7 antigen through the MHC class I pathway more efficiently than wild-type E7 DNA. Furthermore, bone marrow-derived DCs pulsed with cell lysates containing FL-E7 fusion protein presented E7 antigen through the MHC class I pathway more efficiently than DCs pulsed with cell lysates containing wild-type E7 protein. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The FL-E7 fusion vaccine mainly targeted CD8+ T cells, and antitumor effects were completely CD4 independent. These results indicate that fusion of a gene encoding the extracellular domain of FL to an antigen gene may greatly enhance the potency of DNA vaccines via CD8-dependent pathways.


A brief history of oxytocin and its role in modulating psychostimulant effects.
Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let-down reflex. Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia. In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity. We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes. Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects. Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents. Evidence also outlines a role for oxytocin in the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in both rodents and humans. Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated.


Age at the onset of tobacco smoking in South Africa: a discrete-time survival analysis of the prognostic factors.
While knowledge of onset of smoking tobacco, and associated risk factors can aid the formulation of evidence-based policy and interventions, such information is scarce in South Africa. We assessed age at onset of tobacco smoking in South Africa and identified its risk factors. We analysed data of 15,316 respondents aged 15-98 years from the 2012 South African National Health and Nutrition Examination Survey. Descriptive statistics and survival analysis techniques were used alongside weighted percentages. Overall lifetime prevalence of smoking was 20.5%. Among the 3360 ever-smoked respondents, the overall median age at smoking onset was 18 years (Inter-quartile range (IQR) =5) with 2% starting before age 10 while 60% had smoked before age 20. Likelihood of tobacco smoking was higher among adolescents (<=20 years) and those aged 20-29 years than those aged > = 60 years, thrice higher among males, 29% higher among urban dwellers and thrice higher in Western Cape and Free State than in North West Province. The onset of tobacco smoking was earlier among males, wealthier and "coloured" people from Northern and Eastern Capes. The onset of tobacco smoking peaked at 15-22 years and varied by province, sex, location, race and other characteristics. The age restrictions on smoking in South Africa has changed over time, coupled with the recent open and electronic advertisement of tobacco, and social media could have influenced the earlier onset of tobacco smoking in South Africa. Stricter regulations on tobacco-related advertisement and sales should be implemented.


Lycurim (R-74) in the therapy of chronic lymphocytic leukaemia.
Lycurim was used in the therapy of 41 CLL patients, in 34 a positive clinical effect was found. The effect was marked in cases of CLL associated with autoimmune haemolytic anaemia. The immunodepressive property of Lycurim was confirmed by immunological investigation. It has been shown that the levels of IgG, IgA and IgM fall after Lycurim treatment of CLL patients. At the same time the T-lymphocyte count decreases and a tendency for EAC rosette-forming B-lymphocyte decrease is marked.


Short-term studies of heart rate variability: comparison of two methods for recording.
Heart rate variability (HRV) is often analysed using short-term studies. Our objective was to compare two of them in a group of diabetic patients (reduced HRV) and in a control group. From the same 10 min surface electrocardiogram (ECG) two recordings were obtained. In one of them the whole signal was acquired through an A/D converter (post-event method). In the other (real-time method), an interface between the electrocardiograph and a parallel port of a computer was used to perform real-time processing of the ECG signal. The R-R intervals were measured after a visual validation in the post-event method. In the real-time method, the stored R-R intervals were automatically filtered. For both methods HRV indexes were calculated using the same software. The values of mean R-R intervals for each subject were almost identical regardless of the method. Accordingly, we found a high correlation between HRV indexes obtained from both methods (all Spearman values > or = 0.9441 and P < 0.0001). In addition, we found similar P values in the comparisons between the diabetic and control groups. We conclude that both methods are suitable for HRV analysis. Therefore, the selection of method can be based on other considerations such as the capability to store the ECG of the post-event method or the speed of analysis and lower cost of the real-time one.