Solid neuroendocrine carcinomas of the breast: metastases or primary tumors?
Neuroendocrine breast carcinomas are rare but may represent either metastatic or primary lesions. So far, clinical and preoperative histopathological examinations do not distinguish properly between a primary or metastatic breast tumor. Due to any possible consequences following an appropriate treatment, markers which may be helpful for such a distinguishment are needed. We addressed this study in order to evaluate the immunohistochemical expression of GCDFP-15 and mammaglobin in a subset of pure neuroendocrine breast carcinomas (n = 9) and compared the expression profile with a cohort of non-mammary neuroendocrine tumors (n = 99). We observed in our study that solid neuroendocrine breast carcinomas are characterized by the expression of estrogen and progesterone receptors as well as GCDFP-15 and/or mammaglobin. GCDFP-15 was expressed in 6 out of 9 cases, mammaglobin was positive in 4 out of 9 tumors. In contrast, neuroendocrine tumors of the non-mammary cohort expressed neither GCDFP-15 nor mammaglobin. We conclude that mammaglobin and GCDFP-15 as markers of epithelial breast origin may work as a new and reliable diagnostic tool to distinguish primary endocrine tumors of the breast from a metastatic neuroendocrine disease. This is of utmost importance, especially for surgical management.


Mapping antigenic sites on the major outer membrane protein of Chlamydia trachomatis with synthetic peptides.
The antigenicity of the major outer membrane protein (MOMP) of Chlamydia trachomatis was comprehensively evaluated by using overlapping hexapeptide homologs of serovar B MOMP and polyclonal rabbit antisera in a peptide enzyme-linked immunosorbent assay. Of 367 hexapeptides, 152 showed reactivities with at least one antiserum. Seven hexapeptides located within variable domain (VD) IV (residues 288 to 316) were found to be most reactive in terms of their binding titer and frequency, suggesting that VD IV is the immunodominant region within the MOMP as detected by this assay. Peptide-reactive antibodies could also recognize corresponding epitopes on either viable or acetone-permeabilized organisms. The antigenic specificity and immunoaccessibility of epitopes located in VD IV were resolved by absorbing antisera with chlamydial elementary bodies. Six antigenic sites were found in this region and included a B-type-specific site (S1), four subserogroup-specific sites (S2 and S4 to 6), and one species-specific site (S3), each displaying varying degrees of surface exposures on elementary bodies from different C. trachomatis serovars.


Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.
To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs). This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis. Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, P = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, P = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively. The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.


A double-blind randomized-controlled trial comparing the desensitizing efficacy of a new dentifrice containing carbonate/hydroxyapatite nanocrystals and a sodium fluoride/potassium nitrate dentifrice.
Several dentifrices have shown to be effective in reducing dentine hypersensitivity (DH), but more effective products are needed. The aim of the study was to evaluate the desensitizing efficacy of a new dentifrice based on zinc-carbonate hydroxyapatite (CHA) nanocrystals. Using a double-blind, randomized design, the new dentifrice was compared with potassium nitrate/fluoride dentifrice (active control). The participant's DH was evaluated at baseline and after 4 and 8 weeks using airblast (primary outcome), tactile, cold water and subjective tests (secondary outcomes). The final sample consisted of 70 subjects with baseline DH; 36 received the new dentifrice and 34 the control one. Both dentifrices were largely effective; the percentage of score reduction from baseline to 8 weeks was greater than 28% for all tests (and greater than 55% for the cold water test) in both groups. As compared with controls, experimental subjects had a significantly greater improvement in the airblast test score (mean percentage of reduction of 46.0%versus 29.4% in controls) and the subjective test score (47.5%versus 28.1%, respectively), with both differences already being significant after 4 weeks. In contrast, there was no significant difference between groups for either the tactile or cold water tests at any time point and with any outcome. This study documented that the new dentifrice containing zinc-CHA nanocrystals significantly reduced dentinal hypersensitivity after 4 and 8 weeks, supporting its utility in clinical practice.


Manipulation of host behaviour by Toxoplasma gondii: what is the minimum a proposed proximate mechanism should explain?
The behavioural manipulation hypothesis posits that parasites can change the behaviour of hosts to increase the reproductive fitness of the parasite. The protozoan parasite Toxoplasma gondii fits this description well. Sexual reproduction occurs in the cat intestine, from which highly stable oocysts are excreted in faeces. Grazing animals, including rodents, can then ingest these oocysts. The parasite has evolved the capacity to abolish the innate fear that rodents have of the odours of cats, and to convert that fear into an attraction. This presumably increases the likelihood of the rodent being predated, thereby completing the parasite's life cycle. The behavioural syndrome produced by T. gondii does not have any precedent in neuroscience research. This is not a case where the normal functioning of fear system have been altered. This is not even the case of the altering of fear towards predator odours, while leaving other kinds of fear intact. This is an unprecedented example of one component of the fear being eliminated (and replaced by a novel attraction), while appearing to leave other domains unchanged. An understanding of the neurobiological effects of T. gondii is beginning to emerge. One possibility is T. gondii's preferential localisation to, and effects within the amygdala; this is particularly intriguing, given the role of this brain structure in the normal fear response. Obviously, far more must be understood, and the unique behavioural effects of T. gondii put very demanding constraints on any hypothesis we formulate to explain proximate neurobiological mechanisms.


First impressions: making up your mind after a 100-ms exposure to a face.
People often draw trait inferences from the facial appearance of other people. We investigated the minimal conditions under which people make such inferences. In five experiments, each focusing on a specific trait judgment, we manipulated the exposure time of unfamiliar faces. Judgments made after a 100-ms exposure correlated highly with judgments made in the absence of time constraints, suggesting that this exposure time was sufficient for participants to form an impression. In fact, for all judgments-attractiveness, likeability, trustworthiness, competence, and aggressiveness-increased exposure time did not significantly increase the correlations. When exposure time increased from 100 to 500 ms, participants' judgments became more negative, response times for judgments decreased, and confidence in judgments increased. When exposure time increased from 500 to 1,000 ms, trait judgments and response times did not change significantly (with one exception), but confidence increased for some of the judgments; this result suggests that additional time may simply boost confidence in judgments. However, increased exposure time led to more differentiated person impressions.


Modeling the formation of TiO2 ultra-small nanoparticles.
The structures of TiO2 ultra-small nanoparticles (USNPs) at the atomistic level have been predicted because of their potential importance in catalytic, environmental, biological and energy applications. Low energy (TiO2)n clusters and USNPs (n up to 80 at the B3LYP/DZVP2 level, and up to 384 at the PM6 level) were found using a novel bottom-up global optimization approach that is based on all-atom real-space calculations. These structures include USNPs that belong to 1-D, 2-D and 3-D USNP series where all the members share the same fragment types and local translational symmetries. Most of the metastable 2-D and 3-D USNPs contain tubular building blocks similar to the 1-D USNPs. The 3-D USNPs that resemble the bulk anatase are predicted to be energetically favorable structures for 64 ≤ n ≤ 384. A fragment-based model was developed to relate the energy with geometry for the 1-D, 2-D and 3-D USNPs. Surface energy densities were predicted for surface fragments at the different positions of the USNPs using this new model. Based on the predicted surface energy densities and the partial density of states, the most catalytically active sites for the anatase-like 3-D USNPs were predicted to be the kink sites on Face-x surfaces consisting of an octahedral-Ti, the step (edge) sites between the Face-x and Face-y surfaces consisting of a square pyramidal-Ti (on Face-x), and the step sites consisting of a trigonal bipyramidal Ti on the Face-y surfaces.


Identification of a loss-of-function mutation in Ube2l6 associated with obesity resistance.
We previously mapped a locus on BALB/c chromosome 2 associated with protection from leptin-deficiency-induced obesity. Here, we generated the corresponding congenic mouse strain by introgression of a segment of C57BL/6J chromosome 2 to the BALB/c background to confirm the genotype-phenotype associations. We found that the BALB/c alleles decreased fat mass expansion by limiting adipocyte hyperplasia and adipocyte hypertrophy. This was concomitant to an increase in adipocyte triglyceride lipase (ATGL)-mediated triglyceride breakdown and prolongation of ATGL half-life in adipose tissue. In addition, BALB/c alleles on chromosome 2 exerted a cell-autonomous role in restraining the adipogenic potential of preadipocytes. Within a 9.8-Mb critical interval, we identified a nonsynonymous coding single nucleotide polymorphism in the gene coding for the ubiquitin-conjugating enzyme E2L6 (Ube2l6, also known as Ubch8) and showed that the BALB/c allele of Ube2l6 is a hypomorph leading to the lack of UBE2L6 protein expression. Ube2l6 knockdown in 3T3-L1 adipocytes repressed adipogenesis. Thus, altered adipogenic potential caused by Ube2l6 knockdown is likely critically involved in BALB/c obesity resistance by inhibiting adipogenesis and reducing adipocyte numbers. Overall, we have identified a loss-of-function mutation in Ube2l6 that contributes to the chromosome 2 obesity quantitative trait locus.


Delayed-onset dementia after stroke or transient ischemic attack.
Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.


Relationships between certification and job perceptions of oncology nurses.
To explore relationships between oncology nursing certification and oncology nurses' job perceptions. Descriptive, correlational. Questionnaire mailed to homes of Oncology Nursing Society (ONS) members. 703 certified and 514 noncertified ONS members (N = 1,217; 50% response rate). Data were collected using survey methods and grouped by respondents' certification status for statistical analysis. Certification, group cohesion, organizational commitment, and job satisfaction. Certification was weakly correlated with cohesion, commitment, and satisfaction. Work setting, rather than certification, accounted for differences in job perceptions. Job perceptions were most positive in settings characterized by a high percentage of patients with cancer (> 75%), a high percentage of RNs (> or = 80%), and monetary support for continuing education. The hypothesis that oncology nurses' certification status is associated with job perceptions that are valued by employers was not supported. Nurses' job perceptions have been linked to control over nursing practice and participation in organizational and clinical decision making. Managerial strategies that empower certified nurses to practice with more autonomy and participate in decisions that affect patient care should be emphasized.


Angular dependence of the reflectance from an isotropic polydomain medium: the influence of absorption.
The angular dependence of the reflectance from an absorbing randomly oriented polydomain medium consisting of domains either small or large compared with the wavelength is investigated. Besides the two conventional cases, where the refractive index of the incidence medium is either smaller or larger than the averaged index of refraction (small-domain limit) or every principal index of refraction of the domains (large-domain limit), we also discuss a third principal case, which exists only in the large-domain limit. In this third case, only one of the principal indices of refraction is larger than that of the incidence medium, while the averaged index of refraction is smaller. Thus, in contrast to the small-domain limit, total reflection is completely suppressed even in the absence of absorption. A characteristic property of such a polydomain medium is its ability to considerably depolarize linear polarized light in spite of being optically isotropic. Additionally, the parallel polarized reflectance Rp can exceed the perpendicular polarized reflectance Rs over certain angle of incidence ranges. Absorption decreases these domain-size-dependent properties, even under the assumption of constant anisotropy. Nevertheless, for materials with low absorption indices, these effects can affect the optical properties significantly.


Frequency analysis of gut EMG.
The EMG of the gut smooth muscle plays an important role in the regulation of gastrointestinal motility in health and disease. The EMG in general consists of an omnipresent oscillatory electrical control activity (ECA) and spikes or other potentials that result in contractions of the smooth muscle. This paper addresses the question of how the ECA signals can best be processed and how inappropriate transformations of such signals may produce misleading results. The various factors affecting the composition of the gut EMG, in time and space along the gut, are discussed briefly. The need for the analysis of the ECA for its oscillatory nature is mentioned together with details regarding the widely used visual, period, and Fourier analysis techniques. Fourier analysis techniques have been applied with increasing frequency to gut EMG; the various features of Fourier analysis and considerations for their implementation on the computer are discussed. The visual, period, and Fourier analysis approaches as well as their uses and limitations in application to a variety of ECAs of the stomach and of the colon in dogs and humans are illustrated. This study indicates that period analysis techniques are well suited for the study of the visibly oscillatory upper gut EMG, while smoothed spectral analysis is more appropriate for the study of colonic EMG.


In search of the genetic footprints of Sumerians: a survey of Y-chromosome and mtDNA variation in the Marsh Arabs of Iraq.
For millennia, the southern part of the Mesopotamia has been a wetland region generated by the Tigris and Euphrates rivers before flowing into the Gulf. This area has been occupied by human communities since ancient times and the present-day inhabitants, the Marsh Arabs, are considered the population with the strongest link to ancient Sumerians. Popular tradition, however, considers the Marsh Arabs as a foreign group, of unknown origin, which arrived in the marshlands when the rearing of water buffalo was introduced to the region. To shed some light on the paternal and maternal origin of this population, Y chromosome and mitochondrial DNA (mtDNA) variation was surveyed in 143 Marsh Arabs and in a large sample of Iraqi controls. Analyses of the haplogroups and sub-haplogroups observed in the Marsh Arabs revealed a prevalent autochthonous Middle Eastern component for both male and female gene pools, with weak South-West Asian and African contributions, more evident in mtDNA. A higher male than female homogeneity is characteristic of the Marsh Arab gene pool, likely due to a strong male genetic drift determined by socio-cultural factors (patrilocality, polygamy, unequal male and female migration rates). Evidence of genetic stratification ascribable to the Sumerian development was provided by the Y-chromosome data where the J1-Page08 branch reveals a local expansion, almost contemporary with the Sumerian City State period that characterized Southern Mesopotamia. On the other hand, a more ancient background shared with Northern Mesopotamia is revealed by the less represented Y-chromosome lineage J1-M267*. Overall our results indicate that the introduction of water buffalo breeding and rice farming, most likely from the Indian sub-continent, only marginally affected the gene pool of autochthonous people of the region. Furthermore, a prevalent Middle Eastern ancestry of the modern population of the marshes of southern Iraq implies that if the Marsh Arabs are descendants of the ancient Sumerians, also the Sumerians were most likely autochthonous and not of Indian or South Asian ancestry.


Soluble TREM2 is elevated in Parkinson's disease subgroups with increased CSF tau.
Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease and affects 1% of the population above 60 years old. Although Parkinson's disease commonly manifests with motor symptoms, a majority of patients with Parkinson's disease subsequently develop cognitive impairment, which often progresses to dementia, a major cause of morbidity and disability. Parkinson's disease is characterized by α-synuclein accumulation that frequently associates with amyloid-β and tau fibrils, the hallmarks of Alzheimer's disease neuropathological changes; this co-occurrence suggests that onset of cognitive decline in Parkinson's disease may be associated with appearance of pathological amyloid-β and/or tau. Recent studies have highlighted the appearance of the soluble form of the triggering receptor expressed on myeloid cells 2 (sTREM2) receptor in CSF during development of Alzheimer's disease. Given the known association of microglial activation with advancing Parkinson's disease, we investigated whether CSF and/or plasma sTREM2 differed between CSF biomarker-defined Parkinson's disease participant subgroups. In this cross-sectional study, we examined 165 participants consisting of 17 cognitively normal elderly subjects, 45 patients with Parkinson's disease with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF amyloid-β and tau levels revealed that CSF sTREM2 concentrations were elevated in Parkinson's disease subgroups with a positive tau CSF biomarker signature, but not in Parkinson's disease subgroups with a positive CSF amyloid-β biomarker signature. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in Parkinson's disease.


Deteriorated and unchanged patients in psychological treatment in Swedish primary care and psychiatry.
Despite substantial effect sizes for psychological therapy among different diagnosis groups and in different treatment contexts, many studies show that a large proportion of patients do not attain reliable improvement and a substantial portion are worse off after treatment. Previous studies suggest that patients in psychiatry may have worse outcome than patients in primary care. In this practice-based study of psychological treatment in Swedish primary care and adult psychiatry, the proportions of patients who did not improve and who deteriorated were assessed. Proportions of reliably improved, unchanged, and reliably deteriorated patients among 840 patients in primary care and 317 patients in specialist psychiatry were assessed by self-ratings using the Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM). More than half of the patients did not change reliably. About 2% of the patients in primary care and 7% in psychiatry deteriorated. Multilevel analyses of the data from primary care indicated that there were no therapist effects. The results emphasize the importance of monitoring treatment continuously in order to increase results for patients who do not improve.


Hepatitis B virus core protein stimulates the proteasome-mediated degradation of viral X protein.
Hepatitis B virus (HBV) X protein (HBx) plays an essential role in viral replication and in the development of hepatocellular carcinoma. HBx has the ability to transactivate the expression of all HBV proteins, including the viral core protein HBc. Consistent with its regulatory role, HBx is relatively unstable and is present at low levels in the cell. We report here that the level of HBx was significantly reduced by the coexpression of HBc in cultured human hepatoma cells, whereas the level of HBx mRNA was unaffected. The repression of HBx by HBc was relieved by treating cells with the proteasome inhibitor MG132, indicating that HBc acts by stimulating the proteasome-mediated degradation of HBx. Moreover, the inhibitory effect of HBc was specific to HBx and did not affect other proteins, including p53, a known target of the proteasome. Although no direct physical interaction between HBc and HBx could be demonstrated, mutational analysis indicated that the C-terminal half of HBc is responsible for its inhibitory effect. These results suggest that HBc functions as a novel regulator of the HBV life cycle and of hepatocellular carcinogenesis through control of the HBx level via an inhibitory feedback type of mechanism.


Mistreatment of women during childbirth in Abuja, Nigeria: a qualitative study on perceptions and experiences of women and healthcare providers.
Global efforts have increased facility-based childbirth, but substantial barriers remain in some settings. In Nigeria, women report that poor provider attitudes influence their use of maternal health services. Evidence also suggests that women in Nigeria may experience mistreatment during childbirth; however, there is limited understanding of how and why mistreatment this occurs. This study uses qualitative methods to explore women and providers' experiences and perceptions of mistreatment during childbirth in two health facilities and catchment areas in Abuja, Nigeria. In-depth interviews (IDIs) and focus group discussions (FGDs) were used with a purposive sample of women of reproductive age, midwives, doctors and facility administrators. Instruments were semi-structured discussion guides. Participants were asked about their experiences and perceptions of, and perceived factors influencing mistreatment during childbirth. Thematic analysis was used to synthesize findings into meaningful sub-themes, narrative text and illustrative quotations, which were interpreted within the context of this study and an existing typology of mistreatment during childbirth. Women and providers reported experiencing or witnessing physical abuse including slapping, physical restraint to a delivery bed, and detainment in the hospital and verbal abuse, such as shouting and threatening women with physical abuse. Women sometimes overcame tremendous barriers to reach a hospital, only to give birth on the floor, unattended by a provider. Participants identified three main factors contributing to mistreatment: poor provider attitudes, women's behavior, and health systems constraints. Moving forward, findings from this study must be communicated to key stakeholders at the study facilities. Measurement tools to assess how often mistreatment occurs and in what manner must be developed for monitoring and evaluation. Any intervention to prevent mistreatment will need to be multifaceted, and implementers should consider lessons learned from related interventions, such as increasing audit and feedback including from women, promoting labor companionship and encouraging stress-coping training for providers.


Fulminant group A streptococcal infection without gangrene in the extremities: Analysis of five autopsy cases.
Five autopsy cases of fulminant group A streptococcal infection without gangrene in the extremities are presented. Clinical course of the fulminant illness was short (2-4 days). One pathological autopsy case was aged (86-years-old), and hemorrhagic cystitis was observed. The other four forensic autopsy cases were young (24-38 years-old) with the mean age of 32, and the primary infective lesions were located in the postpartum endometrium, tonsil and bronchus (2 cases). Systemic coccal dissemination with poor neutrophilic reaction was seen in two of five cases. Bilateral renal cortical necrosis was noted in three cases (including two with bacterial embolism). Hemophagocytosis, probably resulting from hypercytokinemia, was characteristic in three cases without bacterial embolism. Gram-positive cocci colonizing the hemorrhagic and necrotizing lesions were consistently immunoreactive for streptococcal antigens and Strep A (a carbohydrate antigen on group A streptococci). Neutrophilic reaction was mild in the primary infected foci. Clinicians should note that fulminant streptococcal infection (streptococcal toxic shock syndrome) in young and immunocompetent patients may not be associated with gangrene in the extremities. Autopsy prosecutors (diagnostic and forensic pathologists) must recognize the difficulty in making an appropriate autopsy diagnosis, particularly when bacterial embolism is not associated.


Physiology of female sexual function: animal models.
Data concerning the physiology of desire, arousal, and orgasm in women are limited because of ethical constraints. Aim. To gain knowledge of physiology of female sexual function through animal models. To provide state-of-the-art knowledge concerning female sexual function in animal models, representing the opinions of seven experts from five countries developed in a consensus process over a 2-year period. Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. Sexual desire may be considered as the presence of desire for, and fantasy about, sexual activity. Desire in animals can be inferred from certain appetitive behaviors that occur during copulation and from certain unconditioned copulatory measures. Proceptive behaviors are dependent in part on estrogen, progesterone, and drugs that bind to D1 dopamine receptors, adrenergic receptors, oxytocin receptors, opioid receptors, or gamma-amino butyric acid receptors. Peripheral arousal states are dependent on regulation of genital smooth muscle tone. Multiple neurotransmitters/mediators are involved including adrenergic, and nonadrenergic, noncholinergic agents such as vasoactive intestinal polypeptide, nitric oxide, neuropeptide Y, calcitonin gene-related peptide, and substance P. Sex steroid hormones, estrogens and androgens, are critical for structure and function of genital tissues including modulation of genital blood flow, lubrication, neurotransmitter function, smooth muscle contractility, mucification, and sex steroid receptor expression in genital tissues. Orgasm may be investigated by urethrogenital (UG) reflex, in which genital stimulation results in rhythmic contractions of striated perineal muscles and contractions of vagina, anus, and uterine smooth muscle. The UG reflex is generated by a multisegmental spinal pattern generator involving the coordination of sympathetic, parasympathetic, and somatic efferents innervating the genital organs. Serotonin and dopamine may modulate UG reflex activity. More research is needed in animal models in the physiology of female sexual function.


Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population.
Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥ 60 years) (OR 2.38, p(c)7.4 × 10(-5)). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, p(c) 4.71 × 10(-4)), a finding not previously described. No significant association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG.


Serum Neurofilament Light Chain Levels Are Related to Small Vessel Disease Burden.
Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment. Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]). Serum NfL levels were elevated in both SVD samples (P<1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R2=0.52, P=1.2e-09; sporadic SVD, R2=0.21, P<1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R2=0.27, P=7.6e-05; sporadic SVD, R2=0.06, P=4.8e-08), focal neurological symptoms (CADASIL, NIHSS, P=4.2e-05) and disability (CADASIL, mRS, P=3.0e-06). We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.


A Monte Carlo evaluation of three Compton camera absorbers.
We present a quantitative study on the performance of cadmium zinc telluride (CZT), thallium-doped sodium iodide (NaI(Tl)) and germanium (Ge) detectors as potential Compton camera absorbers. The GEANT4 toolkit was used to model the performance of these materials over the nuclear medicine energy range. CZT and Ge demonstrate the highest and lowest efficiencies respectively. Although the best spatial resolution was attained for Ge, its lowest ratio of single photoelectric to multiple interactions suggests that it is most prone to inter-pixel cross-talk. In contrast, CZT, which demonstrates the least positioning error due to multiple interactions, has a comparable spatial resolution with Ge. Therefore, we modelled a Compton camera system based on silicon (Si) and CZT as the scatterer and absorber respectively. The effects of the detector parameters of our proposed system on image resolution were evaluated and our results show good agreement with previous studies. Interestingly, spatial resolution which accounted for the least image degradation at 140.5 keV became the dominant degrading factor at 511 keV, indicating that the absorber parameters play some key roles at higher energies. The results of this study have validated the predictions by An et al. which state that the use of a higher energy gamma source together with reduction of the absorber segmentation to sub-millimetre could achieve the image resolution of 5 mm required in medical imaging.


Effect of ciliary-muscle contraction force on trapezius muscle activity during computer mouse work.
The present study aimed to identify whether or not an increase in ciliary-muscle contraction force, when the eye-lens is adjusted for viewing at a near distance, results in an increase in trapezius muscle activity, while performing a natural work task. Twelve participants, ranging in age from 21 to 32 years, performed a computer-mouse work task during free gaze conditions. A moving visual target was tracked with a computer mouse on a screen placed at two different distances from the eyes, 25 cm and 50 cm. Tracking performance, eye accommodation, and bilateral trapezius muscle activity were measured continuously. Ciliary-muscle contraction force was computed according to a formula which takes into account the age-dependent, non-linear relationship between the contraction force of the ciliary muscle and the produced level of eye accommodation. Generalized estimating equations analyses were performed. On the dominant hand side and for the nearest screen distance, there was a significant effect of ciliary-muscle contraction force on the trapezius muscle activity (p < 0.001). No other effects were significant (p > 0.05). The results support the hypothesis that high visual demands, during computer mouse work, increase ciliary muscle contraction force and contribute to a raise of the sustained level of trapezius muscle activity. The current study specifically clarifies the validity of the relationship between ciliary-muscle contraction force and trapezius muscle activity and demonstrates that this relationship is not due to a general personality trait. We conclude that a high level of ciliary muscle contraction force can contribute to a development of musculoskeletal complaints in the neck-shoulder area.


Different structural changes occur in blue- and green-proteorhodopsins during the primary photoreaction.
We examine the structural changes during the primary photoreaction in blue-absorbing proteorhodopsin (BPR), a light-driven retinylidene proton pump, using low-temperature FTIR difference spectroscopy. Comparison of the light-induced BPR difference spectrum recorded at 80 K to that of green-absorbing proteorhodopsin (GPR) reveals that there are several differences in the BPR and GPR primary photoreactions despite the similar structure of the retinal chromophore and all-trans --> 13-cis isomerization. Strong bands near 1700 cm(-1) assigned previously to a change in hydrogen bonding of Asn230 in GPR are still present in BPR. However, additional bands in the same region are assigned on the basis of site-directed mutagenesis to changes occurring in Gln105. In the amide II region, bands are assigned on the basis of total (15)N labeling to structural changes of the protein backbone, although no such bands were previously observed for GPR. A band at 3642 cm(-1) in BPR, assigned to the OH stretching mode of a water molecule on the basis of H2(18)O substitution, appears at a different frequency than a band at 3626 cm(-1) previously assigned to a water molecule in GPR. However, the substitution of Gln105 for Leu105 in BPR leads to the appearance of both bands at 3642 and 3626 cm(-1), indicating the waters assigned in BPR and GPR exist in separate distinct locations and can coexist in the GPR-like Q105L mutant of BPR. These results indicate that there exist significant differences in the conformational changes occurring in these two types proteorhodopsin during the initial photoreaction despite their similar chromophore structures, which might reflect a different arrangement of water in the active site as well as substitution of a hydrophilic for hydrophobic residue at residue 105.


Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice.
Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder characterized by persistent intrusive thoughts (obsessions) and repetitive actions (compulsions). Dysfunction of cortico-striato-thalamo-cortical circuitry is implicated in OCD, although the underlying pathogenic mechanisms are unknown. SAP90/PSD95-associated protein 3 (SAPAP3; also known as DLGAP3) is a postsynaptic scaffolding protein at excitatory synapses that is highly expressed in the striatum. Here we show that mice with genetic deletion of Sapap3 exhibit increased anxiety and compulsive grooming behaviour leading to facial hair loss and skin lesions; both behaviours are alleviated by a selective serotonin reuptake inhibitor. Electrophysiological, structural and biochemical studies of Sapap3-mutant mice reveal defects in cortico-striatal synapses. Furthermore, lentiviral-mediated selective expression of Sapap3 in the striatum rescues the synaptic and behavioural defects of Sapap3-mutant mice. These findings demonstrate a critical role for SAPAP3 at cortico-striatal synapses and emphasize the importance of cortico-striatal circuitry in OCD-like behaviours.


Aspergilloma in the paracavernous region--two case reports.
A 30-year-old male and a 40-year-old female presented with Aspergillus fungal granuloma in the cerebral locations involving the gasserian-ganglion and its divisions in one case and was densely adherent to the lateral dural wall of the cavernous sinus in the other. Both patients were otherwise healthy with no evidence of immuno-suppression. The lesions resembled benign tumor on preoperative imaging and intraoperative consistency and vascularity. The lesions were successfully and completely resected. Both patients developed major cerebral arterial territory infarcts in the postoperative phase, remote from the site of operation, leading to crippling neurological deficits in one patient and death in the other. The unusual location and the unusual and similar clinical course suggests that awareness of the possibility of ischemic complications after surgical resection of intracranial aspergillomas is necessary.


Simulation in vascular access surgery training.
Rapidly growing technical developments and working time constraints call for changes in trainee formation. In reality, trainees spend fewer hours in the hospital and face more difficulties in acquiring the required qualifications in order to work independently as a specialist. Simulation-based training is a potential solution. It offers the possibility to learn basic technical skills, repeatedly perform key steps in procedures and simulate challenging scenarios in team training. Patients are not at risk and learning curves can be shortened. Advanced learners are able to train rare complications. Senior faculty member's presence is key to assess and debrief effective simulation training. In the field of vascular access surgery, simulation models are available for open as well as endovascular procedures. In this narrative review, we describe the theory of simulation, present simulation models in vascular (access) surgery, discuss the possible benefits for patient safety and the difficulties of implementing simulation in training.


Population-based assessment of the outcomes in patients with postcolonoscopy colorectal cancers.
The potential for cancers to not be detected on colonoscopy is increasingly recognised, but little is known about patient outcomes. The objective of this study was to assess the outcomes of patients diagnosed with postcolonoscopy colorectal cancers (PCCRCs). We conducted a population-based retrospective cohort study, including all patients diagnosed with colorectal cancer (CRC) in Ontario, Canada from 2003 to 2009. Patients were categorised into three groups: DETECTED (diagnosed within 6 months of first colonoscopy), PCCRC (diagnosed 6-36 months after first colonoscopy) or NOSCOPE (no colonoscopy within 36 months of diagnosis). Univariate and multivariable analyses were conducted to study overall survival, surgical treatment, emergency presentation and surgical complications. Overall, 45 104 patients were included, with 2804 being classified as having a PCCRC. Compared with the DETECTED group, PCCRC was associated with a significantly higher likelihood of stage IV disease (17.2% vs 12.9%), worse overall survival (5 year OS: 60.8% vs 68.3%, p<0.0001; adjusted HR: 1.25, 95% CI 1.17 to 1.32, p<0.0001), a higher likelihood of emergency presentation (OR: 2.86, 95% CI 2.56 to 3.13, p<0.001) and lower likelihood of surgical resection (OR: 0.61, 95% CI 0.55 to 0.67, p<0.001). However, patients with PCCRC had significantly better outcomes than those in the NOSCOPE group (stage IV: 37.1%, 5 year OS: 38.9%) Compared with CRC detected by colonoscopy, PCCRCs are associated with a higher risk of emergent presentation, a lower likelihood of surgical resection and most notably, significantly worse oncological outcomes. However, they have better outcomes than patients with no recent colonoscopy.


Identification of a second T-cell antigen receptor in human and mouse by an anti-peptide gamma-chain-specific monoclonal antibody.
We developed a monoclonal antibody (mAb) (9D7) against a synthetic peptide (P13K) selected from the deduced amino acid sequence of the constant region of the gamma chain of the murine T-cell antigen receptor (TCR) (amino acids 118-130). Using this mAb, we identified a putative second TCR expressed on peripheral blood lymphocytes from a patient with severe combined immunodeficiency (SCID) that were propagated in culture with recombinant interleukin 2 (rIL-2) and Con A. This mAb immunoprecipitated two polypeptide chains of 40 and 58 kDa under nonreducing conditions and of 40 and 56 kDa under reducing conditions from 125I-labeled denatured lysates of T3+ WT31- lymphocytes expanded in culture from a SCID patient. These polypeptide chains were not disulfide linked and were not present on human peripheral blood lymphocytes from normal donors cultured for 5 days with phytohemagglutinin or for 2 weeks with rIL-2 and polyclonal activators or on cells of the Jurkat lymphoblastoid human T-cell line. Chemical crosslinking of 125I-labeled cells followed by immunoprecipitation with anti-Leu-4 mAb under nonreducing or reducing conditions revealed that the 40- and 56-kDa polypeptide chains were associated with the T3 differentiation antigen. These results were confirmed by sequential immunoprecipitation with anti-Leu-4 mAb followed by 9D7 anti-P13K mAb. The 9D7 anti-P13K mAb immunoprecipitated two polypeptide chains of 43 and 64 kDa from denatured lysates of lymphocytes from a patient with severe common variable immunodeficiency (CVI) that were expanded in culture with rIL-2 and Con A. Thus, this second TCR may be composed of two polypeptide chains (gamma gamma'), both of which appear to be the product of the gamma-chain gene. These experiments were done with polyclonal cell populations. Cloned T3+ WT31- cell populations are required to determine whether this TCR contains two gamma polypeptide chains. In contrast, only one polypeptide chain of 56 kDa was immunoprecipitated by the 9D7 anti-P13K mAb from peripheral blood lymphocytes from a patient with mild CVI expanded in culture with rIL-2 and polyclonal activators. Using the same 9D7 anti-P13K mAb and immunoblotting analysis, we identified a 35 kDa gamma-chain polypeptide under reducing conditions expressed on purified L3T4- Lyt2- BALB/c mouse thymocytes. This gamma-chain TCR is disulfide linked and has a molecular mass of 80 kDa under nonreducing conditions.


Impact of mothers' employment on infant feeding and care: a qualitative study of the experiences of mothers employed through the Mahatma Gandhi National Rural Employment Guarantee Act.
To explore the experiences of mothers employed through the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) using focus group discussions (FGDs) to understand the impact of mothers' employment on infant feeding and care. The effects of mothers' employment on nutritional status of children could be variable. It could lead to increased household income, but could also compromise child care and feeding. The study was undertaken in the Dungarpur district of Rajasthan, India. Mothers of infants <12 months of age. Ten FGDs, two in each of the five administrative blocks of the study district were conducted. The groups were composed of a minimum of 5 and maximum of 8 participants, giving a total of 62 mothers. Thematic analysis was conducted to assess patterns and generate emergent themes. Four major themes were identified-'mothers' employment compromises infant feeding and care', 'caregivers' inability to substitute mothers' care', 'compromises related to childcare and feeding outweigh benefits from MGNREGA' and 'employment as disempowering'. Mothers felt that the comprises to infant care and feeding due to long hours of work, lack of alternative adequate care arrangements, low wages and delayed payments outweighed the benefits from the scheme. This study provides an account of the trade-off between mothers' employment and child care. It provides an understanding of the household power relationships, societal and cultural factors that modulate the effects of mothers' employment. From the perspective of mothers, it helps to understand the benefits and problems related to providing employment to women with infants in the MGNREGA scheme and make a case to pursue policy changes to improve their working conditions.


N1 responses to images of hands in occipito-temporal event-related potentials.
Hands, much like faces, convey social information, instructions and intentions to an observer. While the neural processes of face perception have been widely studied, it was only recently that fMRI identified occipito-temporal areas sensitive to static images of hands as body parts. To complement these studies with fine-grained timing information, we measured event-related EEG potentials (ERPs) from 33 subjects who were presented with static images of hands versus faces, whole bodies, and inanimate objects as controls. Already at N1 latency, ~ 170ms, hand-related ERP patterns were manifest in two results: (1) significant differences in amplitudes for images of hands versus bodies in occipito-temporal N1 responses; (2) left lateralization of responses to images of hands, and also of the difference waveforms (hands minus bodies), quantifying hand-related responses. In line with fMRI studies of hand-sensitive areas distinct from extrastriate body area (EBA), the current findings provide electrophysiological evidence for hand-sensitive brain activation, occurring at a similarly early latency as N1 responses to faces.


The Asian Games, air pollution and birth outcomes in South China: An instrumental variable approach.
We estimate the effects of air-pollution exposure on low birthweight, birthweight, and prematurity risk in South China, for all expectant mothers and by maternal age group and child sex. We do so by exploiting exogenous improvement in air quality during the 2010 Guangzhou Asian Games, when strict regulations were mandated to assure better air quality. We use daily air-pollution levels collected from monitoring stations in Guangzhou, the Asian Games host city, and Shenzhen, a nearby control city, between 2009 and 2011. We first show that air quality during the Asian Games significantly improved in Guangzhou, relative to Shenzhen. Next, using birth-certificate data for both cities for 2009-2011 and using expected pregnancy overlap with the Asian Games as an instrumental variable, we study the effects of three pollutants (PM10, SO2, and NO2) on birth outcomes. Four main conclusions emerge: 1) air pollutants significantly reduce average birthweight and increase preterm risk; 2) for birthweight, late pregnancy is most sensitive to PM10 exposure, but there is not consistent evidence of a sensitive period for other pollutants and outcomes; 3) for birthweight, babies of mothers who are at least 35 years old show more vulnerability to all three air pollutants; and 4) male babies show more vulnerability than female babies to PM10 and SO2, but birthweights of female babies are more sensitive than those of male babies to NO2.


Technical reproducibility of genotyping SNP arrays used in genome-wide association studies.
During the last several years, high-density genotyping SNP arrays have facilitated genome-wide association studies (GWAS) that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the studied phenotypic trait. Moreover, discordance observed in results between independent GWAS indicates the potential for Type I and II errors. High reliability of genotyping technology is needed to have confidence in using SNP data and interpreting GWAS results. Therefore, reproducibility of two widely genotyping technology platforms from Affymetrix and Illumina was assessed by analyzing four technical replicates from each of the six individuals in five laboratories. Genotype concordance of 99.40% to 99.87% within a laboratory for the sample platform, 98.59% to 99.86% across laboratories for the same platform, and 98.80% across genotyping platforms was observed. Moreover, arrays with low quality data were detected when comparing genotyping data from technical replicates, but they could not be detected according to venders' quality control (QC) suggestions. Our results demonstrated the technical reliability of currently available genotyping platforms but also indicated the importance of incorporating some technical replicates for genotyping QC in order to improve the reliability of GWAS results. The impact of discordant genotypes on association analysis results was simulated and could explain, at least in part, the irreproducibility of some GWAS findings when the effect size (i.e. the odds ratio) and the minor allele frequencies are low.


Toward Growing Robots: A Historical Evolution from Cellular to Plant-Inspired Robotics.
This paper provides the very first definition of "growing robots": a category of robots that imitates biological growth by the incremental addition of material. Although this nomenclature is quite new, the concept of morphological evolution, which is behind growth, has been extensively addressed in engineering and robotics. In fact, the idea of reproducing processes that belong to living systems has always attracted scientists and engineers. The creation of systems that adapt reliably and effectively to the environment with their morphology and control would be beneficial for many different applications, including terrestrial and space exploration or the monitoring of disasters or dangerous environments. Different approaches have been proposed over the years for solving the morphological adaptation of artificial systems, e.g., self-assembly, self-reconfigurability, evolution of virtual creatures, plant inspiration. This work reviews the main milestones in relation to growing robots, starting from the original concept of a self-replicating automaton to the achievements obtained by plant inspiration, which provided an alternative solution to the challenges of creating robots with self-building capabilities. A selection of robots representative of growth functioning is also discussed, grouped by the natural element used as model: molecule, cell, or organism growth-inspired robots. Finally, the historical evolution of growing robots is outlined together with a discussion of the future challenges toward solutions that more faithfully can represent biological growth.


(2,3,5,6-Tetra-fluoro-phenolato-κO)(5,10,15,20-tetra-phenyl-porphyrinato)iron(III).
The title compound, [Fe(C44H28N4)(C6HF4O)], is a porphyrin complex with iron(III) in fivefold coordination with a tetra-fluoro-phenolate group as the axial ligand. The Fe atom and the phenolate ligand are disordered across the porphyrin ring with the two phenolates appearing to be roughly related by a center of symmetry. The occupancies of the two phenolate groups refined to 0.788 (3) for the major component and 0.212 (3) for the minor component. The structure shows extraordinary Fe displacements of 0.488 (4) (major) and 0.673 (4) Å (minor) from the 24-atom mean plane of the porphyrin. The Fe-Np distances range from 2.063 (4) to 2.187 (6) Å and the Fe-O distances are 1.903 (5) Å for major component and 1.87 (2) Å for minor component. The four phenyl groups attached to the porphyrin ring form dihedral angles of 63.4 (4), 49.6 (4), 62.4 (4), and 63.3 (4)° (in increasing numerical order) with the three nearest C atoms of the porphyrin ring. The major and minor component phenolate groups form dihedral angles of 24.9 (4)° and 24.8 (4)°, respectively, with the four porphyrin N atoms. The Fe⋯Fe distance between the two iron(III) atoms of adjacent porphyrin mol-ecules is 6.677 (3) Å. No close inter-molecular inter-action was observed. The crystal studied was twinned by inversion, with a major-minor component ratio of 0.53 (3):0.47 (3).


Turbulence and bias-induced flows in simple magnetized toroidal plasmas.
Turbulence and bias-induced flows in simple magnetized toroidal plasmas are explored with global three-dimensional fluid simulations, focusing on the parameters of the Helimak experiment. The simulations show that plasma turbulence and transport in the regime of interest are dominated by the ideal interchange instability. The application of a bias voltage alters the structure of the plasma potential, resulting in the equilibrium sheared flows.These bias-induced vertical flows located in the gradient region appear to reduce the radial extent of turbulent structures,and thereby lower the radial plasma transport on the low field side.


Visualizing the history of living spaces.
The technology available to building designers now makes it possible to monitor buildings on a very large scale. Video cameras and motion sensors are commonplace in practically every office space, and are slowly making their way into living spaces. The application of such technologies, in particular video cameras, while improving security, also violates privacy. On the other hand, motion sensors, while being privacy-conscious, typically do not provide enough information for a human operator to maintain the same degree of awareness about the space that can be achieved by using video cameras. We propose a novel approach in which we use a large number of simple motion sensors and a small set of video cameras to monitor a large office space. In our system we deployed 215 motion sensors and six video cameras to monitor the 3,000-square-meter office space occupied by 80 people for a period of about one year. The main problem in operating such systems is finding a way to present this highly multidimensional data, which includes both spatial and temporal components, to a human operator to allow browsing and searching recorded data in an efficient and intuitive way. In this paper we present our experiences and the solutions that we have developed in the course of our work on the system. We consider this work to be the first step in helping designers and managers of building systems gain access to information about occupants' behavior in the context of an entire building in a way that is only minimally intrusive to the occupants' privacy.


Hyperbaric oxygen reduces the progression and accelerates the regression of atherosclerosis in rabbits.
We studied the effect of hyperbaric oxygen (HBO) treatment on the extent of diet-induced accumulation of lipid oxidation products in rabbit plasma and tissues, on plasma paraoxonase activity, and on the extent of progression and regression of atherosclerotic lesions in the rabbit aorta. HBO treatment of cholesterol-fed rabbits dramatically reduces the development of arterial lesions despite having little or no effect on plasma or individual lipoprotein cholesterol concentrations. Compared with no treatment in cholesterol-fed animals, HBO treatment also substantially reduces the accumulation of lipid oxidation products (conjugated dienes, trienes, and thiobarbituric acid-reactive substances) in plasma, in the low density lipoprotein and high density lipoprotein fractions of plasma, in the liver, and in the aortic tissues. In addition, HBO treatment prevents the decrease in plasma paraoxonase activity observed in rabbits fed cholesterol-rich diets. Similarly, in regression studies, HBO treatment has no effect on the rate of plasma (or lipoprotein) cholesterol decline but significantly accelerates aortic lesion regression compared with no treatment. Direct measures of aortic cholesterol content support these morphological observations. On the basis of these results, we conclude that repeated, but relatively short, exposure to HBO induces an antioxidant defense mechanism(s) that is responsible for retarding the development or accelerating the regression of atherosclerotic lesions.


Glypican-1 as a Biomarker for Prostate Cancer: Isolation and Characterization.
Prostate cancer is the most frequently diagnosed male visceral cancer and the second leading cause of cancer death in the United States. Standard tests such as prostate-specific antigen (PSA) measurement have poor specificity (33%) resulting in a high number of false positive reports. Consequently there is a need for new biomarkers to address this problem. The MIL-38 antibody was first described nearly thirty years ago, however, until now, the identification of the target antigen remained elusive. By a series of molecular techniques and mass spectrometry, the MIL-38 antigen was identified to be the highly glycosylated proteoglycan Glypican-1 (GPC-1). This protein is present in two forms; a membrane bound core protein of 55-60 kDa and secreted soluble forms of 40 kDa and 52 kDa. GPC-1 identification was confirmed by immuno-precipitation, western blots and ELISA. An ELISA platform is currently being developed to assess the levels of GPC-1 in normal, benign prostatic hyperplasia (BPH) and prostate cancer patients to determine whether secreted GPC-1 may represent a clinically relevant biomarker for prostate cancer diagnosis.


Opioid, NSAID, and OTC Analgesic Medications for Dental Procedures: PEARL Network Findings.
Dental treatment is often categorized as a moderately or severely painful experience; however, no clinical data reported by the patient and dentist currently exists to support this degree of pain. This has contributed possibly to the overprescribing of analgesics, in particular the opioid class of medications. The primary objective of the study was to document the dentists' postprocedural prescriptions and recommendations for analgesic medications and their effectiveness for a 5-day period. Medications prescribed or recommended in the patient-reported outcomes included: opioid, nonsteroidal anti-inflammatory drugs (NSAIDs), and over-the-counter (OTC) analgesics. Met hods : This study used both dentist and patient responses to evaluate the use of opioid, NSAID, and OTC recommended or prescribed analgesics following one of seven classes of dental procedures encompassing over 22 specific coded procedures thought to elicit pain. The patient-centered study included a 5-day postprocedural patient follow-up assessment of the medication's effectiveness in relieving pain. Baseline questionnaires were completed by 2765 (99.9%) of 2767 eligible patients, and 2381 (86%) patients responded to the Day 5 follow-up questionnaires. The data suggest NSAIDs, both OTC and prescribed dosages, may be a sufficient analgesic to treat most postoperative dental pain. Clinical judgment as to the use of an opioid should include the physiological principles related to the pharmacology of pain and inflammation and may include a central effect. ClinicalTrials.gov Identifier: NCT02929602.


Neuroanatomy of the subadult and fetal brain of the Atlantic white-sided dolphin (Lagenorhynchus acutus) from in situ magnetic resonance images.
This article provides the first anatomically labeled, magnetic resonance imaging (MRI) -based atlas of the subadult and fetal Atlantic white-sided dolphin (Lagenorhynchus acutus) brain. It differs from previous MRI-based atlases of cetaceans in that it was created from images of fresh, postmortem brains in situ rather than extracted, formalin-fixed brains. The in situ images displayed the classic hallmarks of odontocete brains: fore-shortened orbital lobes and pronounced temporal width. Olfactory structures were absent and auditory regions (e.g., temporal lobes and inferior colliculi) were enlarged. In the subadult and fetal postmortem MRI scans, the hippocampus was identifiable, despite the relatively small size of this structure in cetaceans. The white matter tracts of the fetal hindbrain and cerebellum were pronounced, but in the telencephalon, the white matter tracts were much less distinct, consistent with less myelin. The white matter tracts of the auditory pathways in the fetal brains were myelinated, as shown by the T2 hypointensity signals for the inferior colliculus, cochlear nuclei, and trapezoid bodies. This finding is consistent with hearing and auditory processing regions maturing in utero in L. acutus, as has been observed for most mammals. In situ MRI scanning of fresh, postmortem specimens can be used not only to study the evolution and developmental patterns of cetacean brains but also to investigate the impacts of natural toxins (such as domoic acid), anthropogenic chemicals (such as polychlorinated biphenyls, polybrominated diphenyl ethers, and their hydroxylated metabolites), biological agents (parasites), and noise on the central nervous system of marine mammal species.


Phenotype and genotype in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women and is characterized by hyperandrogenic chronic anovulation. The cause is unknown. PCOS is associated with significant insulin resistance as well as with defects in insulin secretion. These abnormalities place these women at substantial risk for developing type 2 diabetes mellitus. A defect in insulin-mediated receptor autophosphorylation has been found in a substantial proportion of PCOS women. Both PCOS and the insulin resistance that accompanies it appear to have major genetic components. Family studies of PCOS have supported this, although they suffer from incomplete phenotyping of probands and first-degree relatives. The phenotype in males and nonreproductive age females is uncertain. Despite the shortcomings of the family studies of PCOS, they have consistently indicated familial clustering and suggested that the mode of inheritance is dominant. Our initial studies of 50 families of PCOS probands indicate that 24% of sisters are affected with PCOS. There also appears to be an intermediate phenotype of sisters with regular menstrual cycles who are hyperandrogenic per se (22% of sisters). Additionally, there appears to be a major familial defect, with 50% of first-degree relatives having glucose intolerance (impaired glucose tolerance by oral glucose tolerance test or type 2 diabetes mellitus). These findings suggest that hyperandrogenism in females and glucose intolerance may be genetic traits in PCOS kindreds. Systematic phenotyping will allow assignment of affected status for eventual linkage analysis.


Learning smooth pattern transformation manifolds.
Manifold models provide low-dimensional representations that are useful for processing and analyzing data in a transformation-invariant way. In this paper, we study the problem of learning smooth pattern transformation manifolds from image sets that represent observations of geometrically transformed signals. To construct a manifold, we build a representative pattern whose transformations accurately fit various input images. We examine two objectives of the manifold-building problem, namely, approximation and classification. For the approximation problem, we propose a greedy method that constructs a representative pattern by selecting analytic atoms from a continuous dictionary manifold. We present a dc optimization scheme that is applicable to a wide range of transformation and dictionary models, and demonstrate its application to the transformation manifolds generated by the rotation, translation, and anisotropic scaling of a reference pattern. Then, we generalize this approach to a setting with multiple transformation manifolds, where each manifold represents a different class of signals. We present an iterative multiple-manifold-building algorithm such that the classification accuracy is promoted in the learning of the representative patterns. The experimental results suggest that the proposed methods yield high accuracy in the approximation and classification of data compared with some reference methods, while the invariance to geometric transformations is achieved because of the transformation manifold model.


Factors that correlate with the U.S. Medical Licensure Examination Step-2 scores in a diverse medical student population.
To assess factors that correlate with performance on U.S. Medical Licensure Examination (USMLE) Step-2 examination. Our hypothesis was that demographic factors, faculty assessments and other standardized test scores will correlate with students' performance on USMLE Step 2. A comparison of standardized examinations and demographic factors with USMLE Step-2 scores as the outcome variable was accomplished using the educational records of 171 medical students. Mean USMLE Step 2, USMLE Step 1, NBME-OB/GYN and MCAT scores, respectively, were 190.63, 194.53, 67.47 and 24.03. Positive correlations of USMLE Step 2 were: USMLE Step-1 scores (r=0.681, p=0.000); MCAT scores (r=0.524, p=0.000); NBME-OB/GYN scores (r=0.614, p=0.000); year of OB/GYN rotation (r=0.432, p=0.000); faculty grades (r=0.400, p=0.000); undergraduate GPA (r=0.287, p=0.000); and science GPA (r=0.255, p=0.002). Negative correlations of USMLE Step 2 were students' increasing age (r=-0.405, p=0.000), increasing number of MCAT attempts (r=-0.182, p=0.000) and increasing number of NBME-OB/GYN attempts (r=-0.310, p=0.000). There was no correlation with gender or race. Logistic regression analysis showed that a failing NBME-OB/GYN score (p=0.008), failing USMLE Step-1 score (p=0.01), failing faculty grade (p=0.029) and multiple MCAT attempts (p=0.033) independently increased the risk of failing USMLE Step 2. Premedical test-taking abilities (MCAT scores), results of preclinical standardized tests (USMLE Step 1) and performance on clinical rotations (NBME-OB/GYN score and faculty grade) correlate significantly with USMLE scores. These findings may assist educators in selecting medical students at risk of performing poorly on the USMLE Step-2 examinations.


Restoring rape survivors: justice, advocacy, and a call to action.
Rape results in mental and physical health, social, and legal consequences. For the latter, restorative justice-based programs might augment community response, but they generate controversy among advocates and policy makers. This article identifies survivors' needs and existing community responses to them. Survivors feel their legal needs are most poorly met due to justice system problems that can be summarized as attrition, retraumatization, and disparate treatment across gender, class, and ethnic lines. Empirical data support each problem and the conclusion that present justice options are inadequate. The article concludes by identifying common ground in advocacy and restorative justice goals and calls for a holistic approach to the needs of rape survivors that includes advocating for expanded justice alternatives. A call to action is issued to implement restorative alternatives to expand survivor choice and offender accountability. Conventional and restorative justice are often viewed as mutually exclusive whereas the author argues they are complementary.


Mechanisms regulating cilia growth and cilia function in endothelial cells.
The primary cilium is an important sensory organelle present in most mammalian cells. Our current studies aim at examining intracellular molecules that regulate cilia length and/or cilia function in vitro and ex vivo. For the first time, we show that intracellular cAMP and cAMP-dependent protein kinase (PKA) regulate both cilia length and function in vascular endothelial cells. Although calcium-dependent protein kinase modulates cilia length, it does not play a significant role in cilia function. Cilia length regulation also involves mitogen-activated protein kinase (MAPK), protein phosphatase-1 (PP-1), and cofilin. Furthermore, cofilin regulates cilia length through actin rearrangement. Overall, our study suggests that the molecular interactions between cilia function and length can be independent of one another. Although PKA regulates both cilia length and function, changes in cilia length by MAPK, PP-1, or cofilin do not have a direct correlation to changes in cilia function. We propose that cilia length and function are regulated by distinct, yet complex intertwined signaling pathways.


Overuse of helicopter transport in the minimally injured: A health care system problem that should be corrected.
Mortality benefit has been demonstrated for trauma patients transported via helicopter but at great cost. This study identified patients who did not benefit from helicopter transport to our facility and demonstrates potential cost savings when transported instead by ground. We performed a 6-year (2007-2013) retrospective analysis of all trauma patients presenting to our center. Patients with a known mode of transfer were included in the study. Patients with missing data and those who were dead on arrival were excluded from the study. Patients were then dichotomized into helicopter transfer and ground transfer groups. A subanalysis was performed between minimally injured patients (ISS < 5) in both the groups after propensity score matching for demographics, injury severity parameters, and admission vital parameters. Groups were then compared for hospital and emergency department length of stay, early discharge, and mortality. Of 5,202 transferred patients, 18.9% (981) were transferred via helicopter and 76.7% (3,992) were transferred via ground transport. Helicopter-transferred patients had longer hospital (p = 0.001) and intensive care unit (p = 0.001) stays. There was no difference in mortality between the groups (p = 0.6).On subanalysis of minimally injured patients there was no difference in hospital length of stay (p = 0.1) and early discharge (p = 0.6) between the helicopter transfer and ground transfer group. Average helicopter transfer cost at our center was $18,000, totaling $4,860,000 for 270 minimally injured helicopter-transferred patients. Nearly one third of patients transported by helicopter were minimally injured. Policies to identify patients who do not benefit from helicopter transport should be developed. Significant reduction in transport cost can be made by judicious selection of patients. Education to physicians calling for transport and identification of alternate means of transportation would be both safe and financially beneficial to our system. Epidemiologic study, level III. Therapeutic study, level IV.


Overview of biliary tract cancer management practices in France: results of the ACABi national survey INTRODUCTION: Biliary tract cancers (BTC) are rare. Their management has evolved in recent years. ACABi conducted a survey on the management practices of CVB in France. METHODS: A questionnaire was developed by a multidisciplinary team and distributed (June-July 2021) by the French digestive oncology societies. The data were analyzed according to the type of practice center (group A: university hospital or cancer comprehensive center, group B: general hospital or private hospital) RESULTS: 172 physicians (hepato-gastroenterologists: 58.0%, oncologists: 19.5% and surgeons: 18.3%), representing all French regions, responded. Access to echo-endoscopy and endoscopic retrograde cholangio-pancreatography was identical between the groups (> 80%), unlike cholangioscopy (group A: 82.9%, group B: 63.6%). In the adjuvant setting, capecitabine was proposed in the majority (> 65%). For non-operable tumors, the most commonly used first-line chemotherapy was cisplatin/gemcitabine (CISGEM, 66.3%). In 38.5% of cases, it was not performed in the day hospital and only 13.6% proposed a break after a fixed number of courses. The most commonly used second-line treatment was 5FU/oxaliplatin (FOLFOX, 52.3%). Molecular profiling was performed in more than half of the patients for 41.1% of respondents in group A and 18.8% in group B. DISCUSSION: This survey shows the application of therapeutic standards but also certain practices diverging from the recommendations as well as disparities between centers.


Using membrane composition to fine-tune the pKa of an optical liposome pH sensor.
Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe pKa is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe pKa in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe pKa values by < 1 unit. The results show that rational modification of the membrane composition is a general non-covalent way to fine-tune the pKa of an optical liposome sensor for optimal pH sensing performance.


The role of traditional growing rods in the era of magnetically controlled growing rods for the treatment of early-onset scoliosis.
To describe the clinical and radiographic profile of early-onset scoliosis (EOS) patients treated with traditional growing rods (TGR) during the magnetically-controlled growing rod (MCGR) era. A US multicenter EOS database was reviewed to identify (1) patients who underwent TGR after MCGR surgery was introduced at their institution, (2) patients who underwent MCGR during the same time period. Of 19 centers, 8 met criteria with all EOS etiologies represented. Clinical notes were reviewed to determine the indication for TGR. Patient demographics and pre-operative radiographs were compared between groups. A total of 25 TGR and 127 MCGR patients were identified. The TGR patients were grouped by indication into the sagittal plane profile (n = 11), trunk height (n = 6), co-morbidities/need for MRI (n = 4), and other (ex: behavioral issues, remaining growth). Four patients had a combination of sagittal profile and short stature with sagittal profile listed as primary factor. The TGR short trunk group had a mean T1-S1 length of 192 mm vs 273 mm for the MCGR group (p = 0.0002). The TGR sagittal profile group, had a mean maximal kyphosis of 61° vs 55° for the MCGR group (p = 0.09). TGR continues to have a role in the MCGR era. In this study, the most commonly reported indications for TGR were sagittal plane profile and trunk height. These results suggest that TGR is indicated in patients of short stature with stiff hyperkyphotic curves. As further experience is gained with MCGR, the indications for TGR will likely be refined.


Neospora caninum in vitro: evidence that the destiny of a parasitophorous vacuole depends on the phenotype of the progenitor zoite.
We previously reported that Neospora caninum can be induced to express BAGI, a bradyzoite antigen, within 3 days of culture under stress conditions. The main goals of the present experiment were to increase the expression of BAGI in vitro (in part by extending cultures for 9 days), to observe parasitophorous vacuoles at various points of stage differentiation, and to test the ability of organisms produced in vitro to function like mature bradyzoites. Expression of BAG1 and of a tachyzoite antigen (NcSAGI) was monitored using a double-label immunofluorescence assay. For the purpose of this study, organisms expressing NcSAG1 were designated as tachyzoites, those expressing BAG1 were designated as bradyzoites, and those expressing both antigens were designated as intermediate zoites. The greatest percentage of intermediate zoites and bradyzoites (14%) occurred in bovine monocytes maintained for 9 days. These bradyzoites did not appear to be functionally mature; they did not induce patent infections in dogs. in contrast to bradyzoites that were produced in chronically infected mice. In vitro, large parasitophorous vacuoles contained either a pure population of tachyzoites or a mixture of tachyzoites and intermediate zoites, which is indicative of asynchronous stage conversion of organisms within a vacuole. Bradyzoites were first observed within small vacuoles on day 6. and bradyzoites never shared vacuoles with tachyzoites. This finding suggests that vacuoles containing bradyzoites may develop only if the cell is invaded by a zoite that has already begun bradyzoite differentiation. An alternative possibility is that cysts may develop if the establishing tachyzoite undergoes bradyzoite differentiation before multiplying. Cysts do not appear to arise from transformation of tachyzoites within large parasitophorous vacuoles.


Small Molecule Antagonists of NAADP-Induced Ca2+ Release in T-Lymphocytes Suggest Potential Therapeutic Agents for Autoimmune Disease.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+-releasing second messenger known to date, but the precise NAADP/Ca2+ signalling mechanisms are still controversial. We report the synthesis of small-molecule inhibitors of NAADP-induced Ca2+ release based upon the nicotinic acid motif. Alkylation of nicotinic acid with a series of bromoacetamides generated a diverse compound library. However, many members were only weakly active or had poor physicochemical properties. Structural optimisation produced the best inhibitors that interact specifically with the NAADP/Ca2+ release mechanism, having no effect on Ca2+ mobilized by the other well-known second messengers D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] or cyclic adenosine 5'-diphospho-ribose (cADPR). Lead compound (2) was an efficient antagonist of NAADP-evoked Ca2+ release in vitro in intact T lymphocytes and ameliorated clinical disease in vivo in a rat experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Compound (3) (also known as BZ194) was synthesized as its bromide salt, confirmed by crystallography, and was more membrane permeant than 2. The corresponding zwitterion (3a), was also prepared and studied by crystallography, but 3 had more desirable physicochemical properties. 3 Is potent in vitro and in vivo and has found widespread use as a tool to modulate NAADP effects in autoimmunity and cardiovascular applications. Taken together, data suggest that the NAADP/Ca2+ signalling mechanism may serve as a potential target for T cell- or cardiomyocyte-related diseases such as multiple sclerosis or arrhythmia. Further modification of these lead compounds may potentially result in drug candidates of clinical use.


Sex differences in the association between socioeconomic status and diabetes prevalence and incidence in China: cross-sectional and prospective studies of 0.5 million adults.
China has undergone rapid socioeconomic transition accompanied by lifestyle changes that are expected to have a profound impact on the health of its population. However, there is limited evidence from large nationwide studies about the relevance of socioeconomic status (SES) to risk of diabetes. We describe the associations of two key measures of SES with prevalent and incident diabetes in Chinese men and women. The China Kadoorie Biobank study included 0.5 million adults aged 30-79 years recruited from ten diverse areas in China during 2004-2008. SES was assessed using the highest educational level attained and annual household income. Prevalent diabetes was identified from self-report and plasma glucose measurements. Incident diabetes was identified from linkage to disease and death registries and national health insurance claim databases. We estimated adjusted ORs and HRs for prevalent and incident diabetes associated with SES using logistic and Cox regression models, respectively. At baseline, 30,066 (5.9%) participants had previously diagnosed (3.1%) or screen-detected (2.8%) diabetes among 510,219 participants included for cross-sectional analyses. There were 480,153 people without prevalent diabetes at baseline, of whom 9544 (2.0%) had new-onset diabetes during follow-up (median 7 years). Adjusted ORs (95% CIs) for prevalent diabetes, comparing highest vs lowest educational level, were 1.21 (1.09, 1.35) in men and 0.69 (0.63, 0.76) in women; for incident diabetes, the corresponding HRs were 1.27 (1.07, 1.51) and 0.80 (0.67, 0.95), respectively. For household income, the adjusted ORs for prevalent diabetes, comparing highest vs lowest categories, were 1.45 (1.34, 1.56) in men and 1.26 (1.19, 1.34) in women; for incident diabetes, the HRs were 1.36 (1.19, 1.55) and 1.06 (0.95, 1.17), respectively. Among Chinese adults, the associations between education and diabetes prevalence and incidence differed qualitatively between men and women, whereas higher household income was positively associated with diabetes prevalence and incidence in both sexes, with a stronger relationship in men than in women.


CMT-linked loss-of-function mutations in GDAP1 impair store-operated Ca2+ entry-stimulated respiration.
GDAP1 is an outer mitochondrial membrane protein involved in Charcot-Marie-Tooth (CMT) disease. Lack of GDAP1 gives rise to altered mitochondrial networks and endoplasmic reticulum (ER)-mitochondrial interactions resulting in a decreased ER-Ca2+ levels along with a defect on store-operated calcium entry (SOCE) related to a misallocation of mitochondria to subplasmalemmal sites. The defect on SOCE is mimicked by MCU silencing or mitochondrial depolarization, which prevent mitochondrial calcium uptake. Ca2+ release from de ER and Ca2+ inflow through SOCE in neuroblastoma cells result in a Ca2+-dependent upregulation of respiration which is blunted in GDAP1 silenced cells. Reduced SOCE in cells with CMT recessive missense mutations in the α-loop of GDAP1, but not dominant mutations, was associated with smaller SOCE-stimulated respiration. These cases of GDAP1 deficiency also resulted in a decreased ER-Ca2+ levels which may have pathological implications. The results suggest that CMT neurons may be under energetic constraints upon stimulation by Ca2+ mobilization agonists and point to a potential role of perturbed mitochondria-ER interaction related to energy metabolism in forms of CMT caused by some of the recessive or null mutations of GDAP1.


Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women.
The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response. We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003. BRCA1/2 testing of most prevalent mutations was mainly done using DNA isolate from formalin-fixed paraffin-embedded nontumor tissue. Survival estimates were derived using Cox regression and competing risk models. In 6478 breast cancer patients, we identified 3.2% BRCA1 and 1.2% BRCA2 mutation carriers. BRCA1 mutation carriers had a worse overall survival independent of clinico-pathological/treatment characteristics, compared with noncarriers (adjusted hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.97 to 1.47), though only statistically significant in the first five years of follow-up (adjusted HR = 1.40, 95% CI = 1.07 to 1.84). A large part of the worse survival was explained by incidence of ovarian cancers. Breast cancer-specific, disease-free, and metastasis-free survival results were less pronounced and mostly statistically nonsignificant but in the same direction with those of overall survival. Overall survival was worse, although not statistically significantly, within the ER-negative or ER-positive, grade 3, and small tumor subgroups. The worse survival was most pronounced in non-chemotherapy-treated patients (adjusted HR = 1.54, 95% CI = 1.08 to 2.19). Power for BRCA2 mutation carriers was limited; only after five years' follow-up overall survival was worse (adjusted HR = 1.47, 95% CI = 1.00 to 2.17). BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.


Post-primary school pupil's interest in physical education: age and gender differences.
Interest in Physical Education (PE) was studied in 3,344 11 to 18 year-old school children. Five aspects of educational importance (PE connotation, PE status, PE teacher, PE curriculum, and adolescent disturbances in relation to the PE lesson) were identified, and examined in relation to pupils' interest. For the younger age groups girls' interest in PE was significantly higher than that of the boys, while after the age of 14 the reverse was the case. The status of PE as a school subject was found to be the most important variable for interest in PE. The contribution of the PE teacher to pupils' level of interest was the least important of the factors examined. The results are discussed in terms of the differing importance for boys and girls of sport in social status systems for peer popularity. Suggestions for changes to PE lessons are offered.


Virologic therapy response significantly correlates with the number of active drugs as evaluated using a LiPA HIV-1 resistance scoring system.
Resistance testing is increasingly accepted as a tool in guiding the selection of human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy in HIV-1 infected individuals who fail their current regimen. To descriptively compare the correlation between virologic treatment response and results using three genotypic HIV-1 drug resistance interpretation systems: the VERSANT HIV-1 Resistance Assay (LiPA) system and two sequence-based interpretation systems. Specimens from 213 HIV-1-infected subjects, either starting (n=104) or switching to (n=109) a regimen of three or four antiretroviral drugs, were collected retrospectively at baseline and after 3 months of uninterrupted therapy. The correlation between viral load change and the number of predicted active drugs in the treatment regimen was assessed. An interpretation algorithm was recently developed to process VERSANT HIV-1 Resistance Assay (LiPA) data. The number of active drugs predicted using this algorithm was rank correlated with the viral load change over a 3-month treatment period. For comparison, a similar calculation was made using two sequence-based algorithms (REGA version 5.5 and VGI GuideLines Rules 4.0), both applied on the same sequences. Statistically significant (p<0.05) correlation coefficients for each of the three HIV-1 drug resistance interpretation systems were observed in the treatment-experienced subjects on a 3-drug regimen (-0.39, -0.38, and -0.42, respectively) as well as on a 4-drug regimen (-0.33, -0.31, and -0.37, respectively). However, no significant correlation was observed in treatment-naive subjects, probably due to the very low frequency of drug resistance in these subjects. All three genotypic drug resistance interpretation systems (LiPA version 1, REGA version 5.5, and VGI GuideLines Rules 4.0) were statistically significantly correlated with virologic therapy response as measured by viral load testing.


Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma.
Hepatocellular carcinomas (HCC) contain a subpopulation of cancer stem cells (CSCs), which exhibit stem cell-like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem-cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic-cell reprogramming. Here, we focused on the role played by the histone variant macroH2A1 as a potential epigenetic factor promoting CSC differentiation. In human HCC sections we uncovered a significant correlation between low frequencies of macroH2A1 staining and advanced, aggressive HCC subtypes with poorly differentiated tumor phenotypes. Using HCC cell lines, we found that short hairpin RNA-mediated macroH2A1 knockdown induces acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolysis. The loss of macroH2A1 increased expression of a panel of stemness-associated genes and drove hyperactivation of the nuclear factor kappa B p65 pathway. Blocking phosphorylation of nuclear factor kappa B p65 on Ser536 inhibited the emergence of CSC-like features in HCC cells knocked down for macroH2A1. Conclusion: The absence of histone variant macroH2A1 confers a CSC-like phenotype to HCC cells in vitro and in vivo that depends on Ser536 phosphorylation of nuclear factor kappa B p65; this pathway may hold valuable targets for the development of CSC-focused treatments for HCC. (Hepatology 2018;67:636-650).


National estimates of teenage sexual activity: evaluating the comparability of three national surveys.
In this article, we examine the reliability with which teenage sexual activity was reported in three recent national surveys. Unlike other study-effects analyses of objective demographic phenomena such as births and marriages, ours focuses on a more sensitive question--age at first intercourse as reported in three very different surveys. Specifically, we compare reports for the 1959-1963 cohort in the 1979 Kantner-Zelnik Study of Young Women, the 1982 National Survey of Family Growth, and the 1983 wave of the National Longitudinal Survey of Youth. For the ages when the majority of teens become sexually active (16-19), the three surveys provide comparable estimates of early sexual activity. For the younger teen ages, however, there is some disagreement among the estimates. Nevertheless, all three studies produce consistent estimates of the determinants of sexual activity throughout the teen years.


Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis.
We report the identification of the product of the Plasmodium falciparum Pf11-1 gene and demonstrate that it is a gametocyte-specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11-1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid-rich polypeptide. Our identification of the Pf11-1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which greater than 90% of the Pf11-1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR-based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11-1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11-1 gene-specific transcript (much greater than 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11-1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11-1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11-1 in erythrocyte rupture within the mosquito gut.


Decision and coordination of low-carbon supply chain considering technological spillover and environmental awareness.
We focus on the impacts of technological spillovers and environmental awareness in a two-echelon supply chain with one-single supplier and one-single manufacturer to reduce carbon emission. In this supply chain, carbon abatement investment becomes one of key factors of cutting costs and improving profits, which is reducing production costs in the components and products-the investment from players in supply chain. On the basis of optimality theory, the centralized and decentralized models are respectively established to investigate the optimal decisions and profits. Further, setting the players' profits of the decentralized scenario as the disagreement points, we propose a bargaining-coordination contract through revenue-cost sharing to enhance the performance. Finally, by theoretical comparison and numerical analysis, the results show that: (i) The optimal profits of players and supply chain improve as technological spillovers and environmental awareness increase, and the profits of them in the bargaining-coordination contract are higher than that in the decentralized scenario; (ii) Technological spillovers between the players amplify the impact of "free-ride" behavior, in which the supplier always incentives the manufacturer to improve carbon emission intensity, but the cooperation will achieves and the profits will improve only when technological spillovers and environmental awareness are great; (iii) The contract can effectively achieve coordinated supply chain, and improve carbon abatement investment.