Prevalence of new maternal alloantibodies after intrauterine transfusion for severe Rhesus disease.
Limited information is published on the frequency of new maternal alloantibodies found in patients treated for isoimmunization. The purpose of this study was to determine the prevalence of additional maternal red cell alloantibodies, found after the initiation of treatment for Rhesus (Rh) disease. A retrospective review of all patients treated for severe Rh disease was undertaken. Rh disease requiring intrauterine blood transfusion was defined as severe. Gravidas with alloantibodies in addition to Rh were included, but those without Rh antibodies were excluded. New alloantibodies were defined as antibodies absent in previous pregnancies and on initial pregnancy screening, and found after the onset of invasive treatment. There were a total of 84 intrauterine blood transfusions performed in 31 gravidas with severe Rh disease. Seven patients (23%) were found to develop additional red cell alloantibodies after treatment during the pregnancy. Induction of additional maternal red cell alloantibodies after treatment for severe Rh disease is relatively common. This may have significant implications for future pregnancies in this high-risk population.


[Ethmoidectomy and orbital decompression in endocrine ophthalmopathy].
23 orbita decompression operations were performed in patients suffering from endocrine exophthalmos (Grave's disease) after normalization of thyroid metabolism and systemic corticoid therapy remained unsuccessful. We developed a modification of an external ethmoidectomy. The lamina of the middle nasal concha is carefully preserved, any opening to the nasal cavity is closed. Flap door incisions of the periorbita complete this procedure. Results are good and were followed up for a period of 30 months. The operation resulted in prompt restitution of normal eye position with fast normalization of visual acuity and field. Squint surgery was done in addition.


Use of key feature questions in summative assessment of veterinary medicine students.
To prove the hypothesis that procedural knowledge might be tested using Key Feature (KF) questions in written exams, the University of Veterinary Medicine Hannover Foundation (TiHo) pioneered this format in summative assessment of veterinary medicine students. Exams in veterinary medicine are either tested orally, practically, in written form or digitally in written form. The only question formats which were previously used in the written e-exams were Type A Single-choice Questions, Image Analysis and Short Answer Questions. E-exams are held at the TiHo using the electronic exam system Q [kju:] by CODIPLAN GmbH. In order to examine less factual knowledge and more procedural knowledge and thus the decision-making skills of the students, a new question format was integrated into the exam regulations by the TiHo and some examiner used this for the first time in the computer based assessment. Following a successful pilot phase in formative e-exams for students, KF questions were also introduced in summative exams. A number of multiple choice questions were replaced by KF questions in four computer based assessment in veterinary medicine. The subjects were internal medicine, surgery, reproductive medicine and dairy science. The integration and linking of KF questions into the computer based assessment system Q [kju:] went without any complications. The new question format was well received both by the students and the teaching staff who formulated the questions. The hypothesis could be proven that Key Feature questions represent a practicable addition to the existing e-exam question formats for testing procedural knowledge. The number of KF questions will be therefore further increased in examinations in veterinary medicine at the TiHo.


Perchlorate reduction by autotrophic bacteria attached to zerovalent iron in a flow-through reactor.
Biological reduction of perchlorate by autotrophic microorganisms attached to zerovalent iron (ZVI) was studied in flow-through columns. The effects of pH, flow rate, and influent perchlorate and nitrate concentrations on perchlorate reduction were investigated. Excellent perchlorate removal performance (> or = 99%) was achieved at empty bed residence times (EBRTs) ranging from 0.3 to 63 h and an influent perchlorate concentration of 40-600 microg L(-1). At the longest liquid residence times, when the influent pH was above 7.5, a significant increase of the effluent pH was observed (pH > 10.0), which led to a decrease of perchlorate removal. Experiments at short residence times revealed that the ZVI column inoculated with local soil (Colton, CA) containing a mixed culture of denitrifiers exhibited much better performance than the columns inoculated with Dechloromonas sp. HZ for reduction of both perchlorate and nitrate. As the flow rate was varied between 2 and 50 mL min(-1), corresponding to empty bed contact times of 0.15-3.8 h, a maximum perchlorate elimination capacity of 3.0 +/- 0.7 g m(-3) h(-1) was obtained in a soil-inoculated column. At an EBRT of 0.3 h and an influent perchlorate concentration of 30 microg L(-1), breakthrough (> 6 ppb) of perchlorate in the effluent did not occur until the nitrate concentration in the influent was 1500 times (molar) greater than that of perchlorate. The mass of microorganisms attached on the solid ZVI/sand was found to be 3 orders of magnitude greater than that in the pore liquid, indicating that perchlorate was primarily reduced by bacteria attached to ZVI. Overall, the process appears to be a promising alternative for perchlorate remediation.


New insights to improve treatment adherence in asthma and COPD.
Chronic respiratory diseases such as asthma and COPD are typically managed by daily inhaled medication. However, the efficacy of an inhaled medication depends upon a patient's adherence to therapy, which refers to whether the medication is actually taken as prescribed. In patients with these diseases, higher adherence has been associated with better health outcomes, such as improved disease control and a reduction in severe and potentially costly exacerbations. Adherence is a multifaceted concept that includes medication-related, intentional, and unintentional reasons that patients may or may not take their medication as directed. The purpose of this integrative review is to present the individual patient factors that contribute to suboptimal adherence to inhaled therapies and the associated effects on health outcomes, while also highlighting evidence-based strategies for health care providers to improve adherence to such therapies in patients with asthma or COPD. Working closely with patients to establish a model of shared decision-making, which takes patient beliefs and preferences into account when choosing treatment options, has the potential to improve adherence and overall patient outcomes in the management of asthma and COPD.


Secretion of acetylcholine in response to graded depolarization of motor nerve terminals.
1. Depolarizing current pulses were used to elicit transmitter secretion from motor nerve terminals in mouse phrenic nerve-diaphragm preparations exposed to solutions containing tetrodotoxin and 4-aminopyridine. 2. The amplitude of end-plate potentials (e.p.p.s.) elicited by depolarizing pulses was depressed for several milliseconds following a hyperpolarizing pulse, and potentiated following a subthreshold depolarizing pulse. Recovery followed an exponential time-course with time constant of 1.5 to 2.5 ms. 3. The time constant of nerve terminals, calculated from strength-duration curves obtained with depolarizing current pulses that elicited transmitter secretion, ranged from 1.5 to 2.56 ms. 4. It was concluded that the nerve terminal time constant would explain the effects of conditioning polarizations if there were a presynaptic "threshold potential" for end-plate potentials. The decrease in latency of e.p.p.s. as stimulus strength was increased could be explained in the same way. 5. The amplitude of e.p.p.s. increased as depolarizing pulses were lengthened from 2 to 10 ms. When a brief depolarizing pulse was superimposed on a longer subthreshold pulse, e.p.p. amplitude could not be related to the maximum depolarization of the presynaptic terminal. Transmitter secretion appeared to depend on both the level and duration of the depolarization.


Attempts to transfer the resistance of Schistosoma mansoni-infected and irradiated cercaria-immunized mice by means of parabiosis.
Acquired resistance to Schistosoma mansoni infection was measured in S. mansoni-infected or irradiated cercaria-immunized mice, and in normal mice to which the former had been surgically joined. Such parabiotic partners were shown to freely exchange humoral and cellular blood constituents. There was no detectable transfer of resistance from mice infected for 8, 12, or 28 weeks to their uninfected partners, even if parabiosis was established before the initial infection and maintained to autopsy. In comparison with parabiosed controls, the number of adult worms surviving from a challenge infection was reduced by 51-96% in the previously infected mice but was not significantly reduced in their uninfected partners. In contrast, mice immunized with irradiated cercariae and their nonimmunized parabiotic partners showed similar levels of resistance. These data indicate that the resistance induced in mice by irradiated cercariae can be transferred, confirm that at least under some experimental conditions the resistance induced in mice by a previous S. mansoni infection is not readily transferred, and provide additional evidence that the resistance induced by normal infection and irradiated cercarial immunization differ in some fundamental way.


Calcination Enhances the Aflatoxin and Zearalenone Binding Efficiency of a Tunisian Clay.
Clays are known to have promising adsorbing characteristics, and are used as feed additives to overcome the negative effects of mycotoxicosis in livestock farming. Modification of clay minerals by heat treatment, also called calcination, can alter their adsorption characteristics. Little information, however, is available on the effect of calcination with respect to mycotoxin binding. The purpose of this study was to characterize a Tunisian clay before and after calcination (at 550 °C), and to investigate the effectiveness of the thermal treatment of this clay on its aflatoxin B1 (AFB1), G1 (AFG1), B2 (AFB2), G2 (AFG2), and zearalenone (ZEN) adsorption capacity. Firstly, the purified clay (CP) and calcined clay (CC) were characterized with X-ray Fluorescence (XRF), X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FTIR-IR), cation exchange capacity (CEC), specific surface area (SBET), and point of zero charge (pHPZC) measurements. Secondly, an in vitro model that simulated the pH conditions of the monogastric gastrointestinal tract was used to evaluate the binding efficiency of the tested clays when artificially mixed with aflatoxins and zearalenone. The tested clay consisted mainly of smectite and illite. Purified and calcined clay had similar chemical compositions. After heat treatment, however, some changes in the mineralogical and textural properties were observed. The calcination decreased the cation exchange capacity and the specific surface, whereas the pore size was increased. Both purified and calcined clay had a binding efficacy of over 90% for AFB1 under simulated poultry GI tract conditions. Heat treatment of the clay increased the adsorption of AFB2, AFG1, and AFG2 related to the increase in pore size of the clay by the calcination process. ZEN adsorption also increased by calcination, albeit to a more stable level at pH 3 rather than at pH 7. In conclusion, calcination of clay minerals enhanced the adsorption of aflatoxins and mostly of AFG1 and AFG2 at neutral pH of the gastrointestinal tract, and thus are associated with protection against the toxic effects of aflatoxins.


Pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease and therapeutic effects of glucocorticoids and N-acetylcysteine in rats.
T lymphocytes and matrix metalloproteinase (MMP) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the details of the mechanisms involved are unclear. The aims of this study were to investigate the changes in interferon-gamma (IFN-gamma), interleukin-4 (IL-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of glucocorticoids and N-acetylcysteine. Male Wistar rats were exposed to cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the last month. Lung function was measured at the end of the study. IL-4 and IFN-gamma levels were then determined in bronchoalveolar lavage fluid and lung tissue samples by enzyme-linked immunosorbent assay. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissue was determined by RT-PCR. In comparison with the control group, rats exposed to smoke had a significant increase in IL-4 and MMP-12 levels and a significant decrease in IFN-gamma levels. In addition, the IL-4/IFN-gamma ratio and MMP-12/TIMP-1 ratio were both higher. At the same time, the ratio of forced expiratory volume in 0.3 second to forced vital capacity (FEV(0.3)/FVC) and dynamic compliance (C(dyn)) decreased and expiratory resistance (Re) increased. By measuring pulmonary mean linear intercept and mean alveolar numbers, obvious emphysematous changes were observed in the smoke exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN-gamma increased. The IL-4/IFN-gamma ratio returned to normal, though the MMP-12/TIMP-1 ratio remained unchanged. FEV(0.3)/FVC was significantly higher and Re was significantly lower than that in untreated smoke exposed rats. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. After treatment with N-acetylcysteine, IFN-gamma increased and the IL-4/IFN-gamma ratio decreased. The MMP-12/TIMP-1 ratio remained unchanged. Re and C(dyn) both improved obviously. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. Correlation analysis indicated that IL-4 levels in lung tissue correlated negatively with FEV(0.3)/FVC (r = -0.53, P = 0.001), IFN-gamma levels in lung tissue correlated negatively with Re (r = -0.63, P = 0.000) and positively with C(dyn) (r = 0.44, P = 0.009), and that the IL-4/IFN-gamma ratio correlated negatively with FEV(0.3)/FVC (r = -0.44, P = 0.010) and C(dyn) (r = -0.42, P = 0.015) and positively with Re (r = 0.58, P = 0.000). Finally, MMP-12 correlated negatively with FEV(0.3)/FVC (r = -0.36, P = 0.026). Cigarette smoke exposure increases IL-4 levels and decreases IFN-gamma levels. This may be the result of smoke-induced changes in lung function. Budesonide can mitigate the changes in IL-4 and IFN-gamma levels induced by smoke exposure. N-acetylcysteine has no effect on IL-4, but increases IFN-gamma levels and brings the IL-4/IFN-gamma ratio back to normal. Cigarette smoke can also promote MMP-12 gene expression and elevate the MMP-12/TIMP-1 ratio. This effect may play a role in smoke-induced emphysema. Budesonide and N-acetylcysteine do not alter the MMP-12/TIMP-1 ratio in this study when given in the late phase of smoke exposure.


Effects of a probiotic Lactobacillus acidophilus strain on feed tolerance in dogs with non-specific dietary sensitivity.
This study investigated the effects of the probiotic Lactobacillus acidophilus strain DSM 13241 in dogs with non-specific dietary sensitivity (NSS). Six adult German Shorthair Pointers with NSS consecutively received a control dry diet and the same diet supplemented with the probiotic (6 x 10(6) cfu/g) for 12 weeks each, followed by another control period of four weeks. Frequency of defecations, faecal quality and nutrient digestibility were determined. Faeces were cultured for Clostridium perfringens, Escherichia spp., lactobacilli and bifidobacteria and quantitative fluorescence in situ hybridisation (FISH) was performed. Feeding the probiotic improved faecal consistency, faecal dry matter and defecation frequency (p < 0.05). Faecal concentrations of culturable lactobacilli and bifidobacteria increased numerically, but not significantly, also the decrease of the numbers of C. perfringens and Escherichia spp. did not reach the level of significance. Results from FISH showed more constant bacterial populations. It can be concluded that L. acidophilus DSM 13241 can stabilise the digestive processes in dogs with NSS.


Incorporation of Photo- and Thermoresponsive N-Salicylidene Aniline Derivatives into Cobalt and Zinc Layered Hydroxides.
In search of new multifunctional hybrid materials and in order to investigate the influence of chemical modification on the possible synergy between properties, the carboxylate and sulfonate derivatives of photo- and thermochromic N-salicylidene aniline were successfully inserted into Co(II)- and Zn(II)-based layered simple hydroxides, resulting in four novel hybrids: Co-N-Sali-COO, Co-N-Sali-SO3, Zn-N-Sali-COO, and Zn-N-Sali-SO3. All synthesized hybrids adopt a double organic layered configuration, which prevents the cis-trans photoisomerization ability of N-Sali-R molecules in the hybrids. However, the Zn hybrids exhibit fluorescence upon exposure to UV light due to the excited-state intramolecular proton transfer (ESIPT) mechanism. The thermally stimulated keto-enol tautomerization of N-salicylidene aniline in the hybrids was related with the changes in interlamellar spacings observed by temperature-dependent PXRD. This tautomerization process was prominently evident in the Co-N-Sali-SO3 hybrid (about 11% increase in d-spacing upon decreasing the temperature to -180 °C). Finally, the Co-N-Sali-R hybrids exhibit the typical magnetic behavior associated with Co(II)-based LSHs (ferrimagnetic ordering at TN = 6.8 and 7.7 K for Co-N-Sali-COO and Co-N-Sali-SO3, respectively). This work offers insights into isomerization in LSHs and the ESIPT mechanism's potential in new luminescent materials and prospects for designing new multifunctional materials.


An Inverse Problem: Trappers Drove Hares to Eat Lynx.
The Canadian lynx and snowshoe hare pelt data by the Hudson Bay Company did not fit the classical predator-prey theory. Rather than following the peak density of the hare, that of the lynx leads it, creating the hares-eat-lynx (HEL) paradox. Although trappers were suspected to play a role, no mathematical model has ever demonstrated the HEL effect. Here we show that the long-held assumption that the pelt number is a proxy of the wild populations is false and that when the data are modeled by the harvest rates by the trappers, the problem is finally resolved: both the HEL paradox and the classical theory are unified in our mechanistic hare-lynx-competitor-trapper (HLCT) model where competitor stands for all predators of the hares other than the lynx. The result is obtained by systematically fitting the data to various models using Newton's inverse problem method. Main findings of this study include: the prey-eats-predator paradox in kills by an intraguild top-predator can occur if the top-predator prefers the predator to the prey; the benchmark HLCT model is more sensitive to all lynx-trapper interactions than to the respective hare-trapper interactions; the Hudson Bay Company's hare pelt number maybe under-reported; and, the most intriguing of all, the trappers did not interfere in each other's trapping activities.


The Dose-Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial.
Observational data indicate that behaviors that shift energetic homeostasis, such as exercise, may decrease the risk of developing breast cancer by reducing the amount of energy-dense, metabolically active adipose tissue. Between December 2008 and April 2013, we conducted a single-blind, 5-month, clinical trial that randomized premenopausal women at high risk of developing breast cancer to one of three groups: 150 min/wk of aerobic exercise (low dose), 300 min/wk of aerobic exercise (high dose), or control. Body composition was assessed using dual-energy x-ray absorptiometry. Background parenchymal enhancement (BPE) was quantified using computerized algorithms on breast dynamic contrast-enhanced MRI. Over 5 months, compared with the control group: the low-dose and high-dose groups lost -1.5 ± 0.5 and -1.3 ± 0.5 kg of body mass (linear Ptrend = 0.032); -1.5 ± 0.4 and -1.4 ± 0.3 kg of fat mass (linear Ptrend = 0.003); -1.3 ± 0.3 and -1.4 ± 0.3% of body fat (linear Ptrend < 0.001); -15.9 ± 5.4 and -26.6 ± 5.0 cm(2) of subcutaneous adipose tissue (linear Ptrend < 0.001); and -6.6 ± 1.9 and -5.0 ± 1.9 cm(2) visceral adipose tissue (nonlinear Ptrend = 0.037). For each -1 cm(2) reduction in visceral adipose tissue, BPE decreased by -3.43 ± 1.34 cm(2) (P = 0.010) and explained 9.7% of the variability in BPE. Changes in other aforementioned body composition outcomes did not significantly correlate with changes in BPE. These mechanistic data support observational evidence that shifting energetic homeostasis through exercise may alter the risk of developing breast cancer. Additional adequately powered studies are needed to confirm and expand upon our findings that changes in body composition are associated with changes in BPE. Cancer Prev Res; 9(7); 581-8. ©2016 AACR.


Combination therapy with telmisartan and oxacalcitriol suppresses the progression of murine adriamycin nephropathy.
Blockade of the renin-angiotensin system plays a key role in suppressing the progression of renal diseases. It has not been well established whether this therapy provides additional effects when combined with vitamin D or its analog in a model of adriamycin (ADR)-induced nephropathy. We evaluated the effect of an angiotensin II subtype 1 receptor blocker (telmisartan) combined with a vitamin D analog (oxacalcitriol) on mice ADR-induced nephropathy (9.5 mg/kg single intravenous injection). We also tested immortalized murine podocytes to examine the effects on podocyte apoptosis. Mice with ADR-induced nephropathy developed progressive albuminuria and glomerulosclerosis within 30 days accompanied by decreased expression of slit diaphragm (SD)-associated proteins (nephrin and podocin), reduced numbers of podocytes, and increased systolic blood pressure. Treatment with telmisartan or oxacalcitriol alone moderately ameliorated kidney injury. The combined treatment most effectively reduced the albuminuria and glomerulosclerosis. These effects were accompanied by the restoration of SD-associated proteins, reduction of podocyte apoptosis, and prevention of podocyte depletion in the glomeruli. Treatment with telmisartan, oxacalcitriol, and the combination therapy resulted in similar reductions in systolic blood pressure. In cultured murine podocytes, ADR stimulated the expression of Bax/Bcl-2 and apoptosis as determined by Hoechst 33342 staining. These changes were effectively inhibited by telmisartan or oxacalcitriol, but the combination treatment most effectively reduced these effects. These data demonstrated that application of a renin-angiotensin system blocker plus a vitamin D analog effectively prevented renal injury in ADR-induced nephropathy. The observed amelioration of renal injury may be partly attributable to antiapoptotic effects in podocytes.


Chemsex, Identity and Sexual Health among Gay and Bisexual Men.
This article focuses on some of the social, cultural and psychological aspects of drug use in sexualized settings in gay and bisexual men (referred to as "chemsex"). Using a narrative review approach, the article examines previous empirical research in this area and presents a novel theoretical approach for understanding and predicting chemsex behavior. Tenets of identity process theory from social psychology are drawn upon to offer an integrative theoretical framework within which the social, cultural and psychological underpinnings of chemsex can be collectively examined. Existing empirical research suggests that gay and bisexual men may experience sexuality-related stressors that can undermine feelings of self-esteem, self-efficacy, continuity and positive distinctiveness. Identity process theory examines how individuals react to threats to identity brought about by these stressors. In response to identity threat, gay and bisexual men may engage in chemsex as a coping response that encompasses and facilitates various, largely maladaptive, coping strategies and tactics. The more chemsex is perceived as enhancing identity processes and as averting identity threat, the more central it is likely to be to the identities of participants. The centrality of chemsex to one's identity may preclude self-withdrawal from the practice. Several directions for future research are presented based on existing work on chemsex viewed through the lens of identity process theory. These should form the basis of future empirical research in the sphere of sexual health among gay and bisexual men and the outcomes of this research should inform policy and practice in this area.


Rubinstein-Taybi syndrome with normal FISH result and CREBBP gene analysis: a case report.
We report on a six-year-old boy with typical Rubinstein-Taybi syndrome (RSTS) phenotype. Clinical findings included mental and motor retardation, patent ductus arteriosus (PDA), undescended testes, hirsutism, broad thumbs with radial angulation and broad toes, and inguinal hernia. His karyotype was normal (46, XY) and fluorescence in situ hybridization (FISH) showed no deletion of the CREBBP [cAMP response element-binding (CREB) binding protein] gene on chromosome 16p13.3. CREBBP gene sequencing also revealed normal results. We wish to present this case because this patient had typical RSTS phenotype, but normal FISH and CREBBP gene sequencing results. It could be possible that genetic heterogeneity is related with novel mutations in other genes. With the publication of such cases, their significance will be brought to the attention of researchers in this field.


Altered phospholipid metabolism in pressure-overload hypertrophied hearts.
The content and fatty acyl composition of phospholipids were examined in pressure-overload hypertrophied hearts. Cardiac hypertrophy was induced in rats by abdominal aortic constriction. Twenty-one days postconstriction the content of myocardial phosphatidylcholine (PC), sphingomyelin, and phosphatidylinositol (PI) was significantly elevated by 10, 10, and 20%, respectively. The essential fatty acid, linoleic acid, was markedly reduced in PC, phosphatidylethanolamine (PE), PI, and cardiolipin (CL) of hypertrophied hearts. The associated changes in fatty acyl composition were specific for the individual phospholipid class as evidenced by a significant elevation of palmitic acid in PC, docosahexaenoic acid in PE and oleic acid in CL. Alterations in fatty acyl composition of phospholipids were associated with no change in the composition of cardiac triglycerides, cardiac free fatty acids or serum lipids. The fatty acyl composition of phospholipids was also altered in pressure-overload hypertrophied hearts of cats, as evidenced by a reduction of linoleic acid and an elevation of arachidonic acid in total phospholipids. These findings demonstrate that changes in phospholipid metabolism occur in the pressure-overloaded mammalian heart. Such alterations may contribute to altered membrane function in the hypertrophied myocardium.


Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer.
Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancer-induced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited. Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. The activity of immune checkpoint inhibitors is currently been assessed in treatment-naïve patients with PD-L1-positive advanced NSCLC. Combinatorial approaches with other immune checkpoint inhibitors, chemotherapy, or targeted agents are being explored in ongoing clinical trials, and may improve outcome in NSCLC.


Clinical and epidemiological features of adenovirus keratoconjunctivitis.
The pattern of adenovirus infection of the eye in the Bristol area has been considered over a period of 9 years. During this time three outbreaks of keratoconjunctivitis, caused in turn by serotypes 8, 10/19, and 4, were observed. When adenoviruses are subdivided into three groups, based on their haemagglutination properties, it is evident that those serotypes responsible for epidemic keratoconjunctivitis belong to Group II. Ocular infection by serotypes in Groups I and III usually results in a follicular conjunctivitis, with or without upper respiratory tract infection, and with markedly less corneal involvement.


Production of enteritis in calves by the oral inoculation of pure cultures of Campylobacter fetus subspecies intestinalis.
Pure cultures of an isolate of Campylobacter fetus subspecies intestinalis obtained from the congested small intestinal mucosa of a two-week-old calf were used to infect three milk-fed calves and three ruminating calves in two separate controlled experiments. Inoculated animals all developed clinical signs which included fever (to 40 degrees C) and diarrhoea with excess clear mucus containing occasional spots of blood. C fetus subspecies intestinalis was isolated from the faeces of all infected animals in the two experiments but not from those of the five control animals. Changes in the enteric tract were most marked in the ileum which was thickened and mildly inflamed with accumulations of lymphoid cells and crypts filled with inflammatory cells in all six infected animals. The mesenteric lymph nodes were pale and enlarged. C fetus subspecies intestinalis was recovered from the jejunum, ileum, caecum and colon of the infected animals and less frequently from the abomasum, mesenteric lymph nodes, liver and gall bladder. It was never isolated from the control animals. Antibody to the inocular strain of C fetus subspecies intestinalis was demonstrated, at titres of at least 1 in 320, in the serum of all inoculated animals and was absent from all the control sera. The findings were considered to indicate that C fetus subspecies intestinalis caused the syndrome described above and that the syndrome produced differed only in minor details from that produced in calves by infection with C jejuni.


Orphan SelD proteins and selenium-dependent molybdenum hydroxylases.
Bacterial and Archaeal cells use selenium structurally in selenouridine-modified tRNAs, in proteins translated with selenocysteine, and in the selenium-dependent molybdenum hydroxylases (SDMH). The first two uses both require the selenophosphate synthetase gene, selD. Examining over 500 complete prokaryotic genomes finds selD in exactly two species lacking both the selenocysteine and selenouridine systems, Enterococcus faecalis and Haloarcula marismortui. Surrounding these orphan selD genes, forming bidirectional best hits between species, and detectable by Partial Phylogenetic Profiling vs. selD, are several candidate molybdenum hydroxylase subunits and accessory proteins. We propose that certain accessory proteins, and orphan selD itself, are markers through which new selenium-dependent molybdenum hydroxylases can be found.


Immigrant Enclaves and Inadequate Prenatal Care among Mexican-origin Mothers.
This study is an investigation of the relationships between residing in different types of ethnic enclave neighborhoods and inadequate use of prenatal care among Mexican-origin mothers. A unique dataset was created using National Center for Health Statistics 2008 restricted-use detailed natality files, the 2005-2009 American Community Survey, and the Department of Health and Human Services Area Resource file. Hierarchical modeling was used. Mexican-origin mothers' residential contexts are associated with the inadequacy of their prenatal care utilization beyond their individual characteristics. Specifically, residing in Mexican immigrant enclaves is associated with increased odds of having inadequate use of prenatal care. In contrast, residing in other types of ethnic enclaves (Mexican/Hispanic ethnic enclaves) and non-Hispanic white neighborhoods is associated with decreased odds of having inadequate utilization of prenatal care even after the inclusion of contextual-level controls for individual characteristics, neighborhood socioeconomic status, and the availability of healthcare infrastructure resources. Residing in immigrant enclaves is important for understanding the inadequacy of prenatal care utilization for Mexican-origin mothers. These findings have policy implications for designing place-based programs to target certain residential contexts where women are at greater risk of having inadequate use of prenatal care.


Indigenous Cultural Safety in Recognizing and Responding to Family Violence: A Systematic Scoping Review.
This systematic scoping review synthesizes the recommended approaches for providing culturally safe family violence interventions to Indigenous peoples in health care and social service settings. A total of 3783 sources were identified through our electronic database searches, hand-searching of Indigenous-focused journals, and backward and forward citation chaining. After screening those sources in duplicate, 28 papers were included for synthesis in June 2020. Forward citation chaining of these 28 included articles in June 2022 identified an additional 304 possible articles for inclusion; following the screening of those 304 articles, an additional 6 were retained in the review. Thus, a total of 34 articles were included for data extraction and narrative synthesis. Initial results were presented to members of the Six Nations of the Grand River Youth Mental Wellness Committee, and their feedback was incorporated into our inductive organization of findings. Our findings represent three thematic areas that reflect key recommendations for health care and social service provision to Indigenous families for whom family violence is a concern: (1) creating the conditions for cultural safety; (2) healing at the individual and community level; and (3) system-level change. These findings demonstrate the need to center Indigenous peoples and perspectives in the development and implementation of cultural safety approaches, to acknowledge and address historically contingent causes of past and present family violence including colonization and related state policies, and to transform knowledge and power relationships at the provider, organization, and government level.


Measurement of Head Kinematics Using Instrumented Mouthguards During Introductory Boxing Courses in U.S. Military Academy Cadets.
Use of wearable impact sensor devices to quantitatively measure head impact exposure remains largely unstudied in military-style martial arts training and combat sports, particularly at the beginner levels. The baseline frequency and severity of head impact exposure during introductory military-style martial arts trainings, such as combatives training, is valuable information for developing future programs of instruction and exposure monitoring programs. The purpose of this study was to describe head impact exposures experienced during introductory combatives training (a boxing course) at U.S. Military Academy. This study used instrumented mouthguards to measure head impact exposure in U.S. Military Academy cadets during a compulsory boxing course. Summary exposures from a preliminary dataset are presented. Twenty-two male subjects (19.9 ± 1.1 years, 86.6 ± 11.7 kg) participated in 205 analyzed player-bouts (full contact sparring sessions) with 809 video verified impacts (average 3.9 impacts per player-bout). The mean peak linear acceleration was 16.5 ±7.1 G, with a maximum of 70.8 G. There was a right-skewed distribution, with 640/809 (79.1%) events falling between 10 and 20 G. The mean peak angular acceleration was 1.52 ± 0.96 krad/s2, with a maximum of 8.85 krad/s2. Compared to other high-risk sports at Service Academies, head impacts from beginner boxing were of similar magnitude to those reported for Service Academy football and slightly lower than those reported for Service Academy rugby. Based on these preliminary data, the risk profile for introductory military-style martial arts training, such as boxing or combatives, may be similar to other contact sports like football and rugby, but further research is required to confirm these findings and understand the effects of the exposures in a shorter duration.


CD79a is heterogeneously expressed in neoplastic and normal myeloid precursors and megakaryocytes in an antibody clone-dependent manner.
CD79a, a component of the B-cell antigen receptor complex, can also be expressed in certain non-B-cell malignancies. The reported frequency of CD79a expression in acute myeloid leukemias (AML) ranges from 0% to 90%. We evaluated 39 bone marrow biopsy specimens (29 AML and 10 normal cases) using 5 different commercially available anti-CD79a monoclonal antibody (MoAb) clones. Of 7 acute promyelocytic leukemia (APL) cases, 6 (86%) stained for CD79a with clones HM47/A9 (Novocastra, Newcastle Upon Tyne, England) and HM57 (DAKO, Carpinteria, CA) but were negative with clones 11E3 (Novocastra), and JCB117 (DAKO). Half of 6 acute megakaryoblastic leukemia (AMKL) cases and normal megakaryocytes in 14 (67%) of 21 cases were immunoreactive using clone 11D10 (Novocastra). Approximately one third of non-APL/non-AMKL AML and myeloid precursors in normal marrow specimens stained with clones HM57 and 11D10. This heterogeneity of CD79a expression in AML, megakaryocytes, and myeloid precursors is MoAb clone-dependent, likely owing to different epitope detection, and may be of diagnostic usefulness.


Double repression of soluble starch synthase genes SSIIa and SSIIIa in rice (Oryza sativa L.) uncovers interactive effects on the physicochemical properties of starch.
Soluble starch synthases (SSs) are major enzymes involved in starch biosynthesis in developing rice (Oryza sativa L.) endosperm. Despite extensive studies of SSs in various plant species including rice, the functional modes of action among multiple SS genes are still not clear. Here, we generated transgenic RNA interference (RNAi) repressed lines for seven of the eight members of the rice SS gene family and studied their effects on starch synthesis and grain formation. Consistent with their expression domains, RNAi repression of genes that encode isozymes SSI, SSIIa, and SSIIIa had strong effects on grain development, whereas no obvious phenotypic changes were observed in transgenic plants with the other SS genes being RNAi repressed, indicating functional redundancies among the genes. To study the potential functional interactions of SS genes, we generated SSIIa/SSIIIa double repression lines whose kernels displayed a chalky kernel appearance and had increased amylose levels, increased pasting temperatures, and decreased viscosities. The double mutation also reduced short (degree of polymerization (DP) 5-6) and long (DP 12-23) amylopectin chain contents in the grain and increased the medium long types (DP 7-11). The nonadditive nature of the double mutation line suggests that SSIIa and SSIIIa interact with each other during starch synthesis. Such interaction may be physical via starch phophorylase as indicated by our pair-wise yeast two-hybrid assays on major starch synthesis enzymes. Collectively, the data showed that SSIIa and SSIIIa play distinctive, but partially overlapping, roles during rice grain starch synthesis. The possibility of extensive redundancy or complementarity among SS isozymes is discussed.


Re-definition of claudin-low as a breast cancer phenotype.
The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors are distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflect characteristics of their intrinsic subtype. Finally, we explore an alternative method for identifying claudin-low tumors and thereby uncover potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.


Interleukin-9 in human myeloid leukemia cells.
Here we review our recent data addressing the role of recombinant human (rh) interleukin 9 (IL-9) in acute myeloblastic leukemia (AML). We first evaluated the proliferative response of 3 leukemic cell lines and 32 primary samples from AML patients to IL-9 alone and combined with rh-IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF, c-kit ligand). The colony forming ability of leukemic cells was assessed by a clonogenic assay in methylcellulose, whereas the cell cycle characteristics of the same samples were determined by the acridine-orange (AO) flow cytometric technique and the bromodeoxyuridine (BRDU) incorporation assay. In addition, the terminal deoxynucleotidyl transferase Assay (TDTA) and standard analysis of DNA cleavage by gel electrophoresis were used to evaluate induction or prevention of apoptosis by IL-9. IL-9, used as a single cytokine, at various concentrations stimulated the colony formation of the 3 myeloid cell lines under serum-containing and serum-free conditions and this effect was completely abrogated by anti-IL-9 monoclonal antibodies (MoAbs). When tested on fresh AML samples, optimal concentrations of IL-9 resulted in the increase of the blast colony formation in all the cases studied and was the most effective CSF for promoting leukemic cell growth among those tested in this study including SCF, IL-3, and GM-CSF. The addition of SCF to IL-9 demonstrated an additive or synergistic effect of the 2 cytokines in 5 out of 8 AML cases tested for their CFU-L growth (187 +/- 79 colonies in comparison with 107 +/- 32 CFU-L; p = 0.05). Positive interaction was also observed when IL-9 was combined with IL-3 and GM-CSF. Studies of cell cycle distribution of AML samples demonstrated that IL-9 alone significantly augmented the number of leukemic cells in S-phase in the majority of the cases evaluated. IL-9 and SCF in combination resulted in a remarkable decrease of the G0 cell fraction (38.2 +/- 24% compared to 58.6 +/- 22% of control cultures; p < 0.05) and induced an increase of G1 and S-phase cells. Conversely, neither IL-9 alone nor the combination of IL-9 and SCF had any effect on induction or prevention of apoptosis of leukemic cells. Furthermore, in this study, reverse transcriptase-polymerase chain reaction amplification (RT-PCR) did not show the constitutive expression of IL-9 mRNA in the cell lines and the AML samples studied at diagnosis. In summary, IL-9 may play a role in the development of acute myeloid leukemia by stimulating the proliferation of leukemic cells perhaps through a paracrine growth loop.


Relationships of uterine and ovarian tumors to pre-existing chronic conditions.
Several chronic diseases have been hypothesized to affect the risk of subsequent gynecologic malignancies, possibly through shared hormonal mechanisms. Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for gallbladder disease, diabetes, hypertension, thyroid diseases and obesity and the subsequent development of uterine and ovarian cancers in Denmark between 1978 and 1998. Based on a subsample of more than 99,000 women, including 1398 uterine and 2491 ovarian cancers, we derived relative risks (RRs) and 95% confidence intervals (CIs) associated with overall and histology-specific cancer risks after adjustment for age, calendar time and reproductive characteristics. Uterine cancers were related to previous diagnoses of thyroid diseases (RR=1.52, 95% CI 1.17-1.98) and obesity (2.05, 1.40-3.00). Associations with diabetes were confounded by obesity, but there were some elevations in risk for subjects diagnosed with obesity prior to age 45 (RRs 1.66-1.79). Although the "usual types" of endometrial cancer largely accounted for the observed associations, there was some evidence that uterine sarcomas (n=137) were related to prior diagnoses of thyroid diseases (2.78, 1.41-5.50). In contrast, ovarian cancers were not strongly related to most documented chronic diseases. Serous carcinomas were associated with gallbladder diseases of short durations, but detection bias or misdiagnosis probably accounts for this association. An association of obesity and endometrioid ovarian cancer was not identified. Uterine cancers, including sarcomas, appear to be influenced by selected chronic diseases. Further attention should focus on possible biologic mechanisms underlying observed associations with thyroid diseases and obesity.


Transplantation of pancreatic islets.
The currently limited supply of human pancreatic glands, and the fact that multiple glands may be required to isolate sufficient numbers of islets to treat a single patient, indicate that techniques must be further developed and refined for xenografting of isolated islets from animal sources to diabetic patients. An increasing body of evidence using immunoisolation techniques strongly suggests that this will be achieved during the next few years. Several different types of systems employing selectively permeable membranes and matrix supports for cells have been successfully tested in animals, including devices anastomosed to the vascular system as arteriovenous (AV) shunts, tubular membrane chambers, and spherical micro- and macrocapsules. Results in diabetic animals indicate that these systems can function for periods of several months to > year without the use of any immunosuppression. Our data suggest that this approach has the potential not only to allow the transplantation of islets across wide species barriers, but that it can be achieved using injectable microreactors fabricated from biodegradable polymers. The use of these various immunoisolation systems to transplant islets and other cells and tissues offers the opportunity to revolutionize current therapy for many human disease.


Field evaluation of primaquine in the control of Plasmodium vivax.
Two regimens of primaquine in combination with amodiaquine have been compared with amodiaquine alone in known cases of Plasmodium vivax in an endemic area of El Salvador, C.A. A 5-day regimen of primaquine, with dosages based on an adult dose of 15 mg per day, produced a substantial reduction in the numbers of patients experiencing renewed parasite activity and in the number of parasitemias experienced by the group during 9 mo of posttreatment observation, when compared with patients treated only with amodiaquine. A single dose regimen, based on an adult dose of 45 mg, similarly reduced the number of patients with renewed parasite activity and the number of parasitemias in the group. Those patients who experienced malaria attacks subsequent to treatment with either primaquine regimen experienced fewer such attacks than did those receiving amodiaquine alone. It is concluded that such primaquine regimens, which are more practicable for field use than the full 14-days curative regimen, are of value to both the patient and the community through the reduction of parasite episodes and the reduction of the source of mosquito infection for continuation of transmission.


Characterization of cognitive functioning in a subgroup of children with congenital HIV infection.
The cognitive status of 12 clinically stable children with congenital HIV infection, nine of whom were neurologically impaired, age three to nine years, was assessed using the Kaufman ABC test. Seven of the children had ARC; five were diagnosed as having AIDS. The same children were evaluated by standard neurologic examinations with Characterization of tone and fine motor functioning. Two were diagnosed as being mildly retarded; six were borderline; and four tested as being of average intelligence. Visual-spatial perceptual based functioning was found to be more impaired than were abstract reasoning and verbally mediated skills in six (50%) of the patients. This pattern of impaired information processing was found irrespective of overall cognitive status. On neurological and physiatric examination abnormal developmental histories were obtained, or poor fine motor coordination, abnormal tone and gait, and impaired rapidly alternating movements were found in 9 of the 12 subjects. These findings suggest selective impairment in distinct areas of neurologic and neuropsychological functioning during stable phases of HIV infection in a select group of children. These patterns appear to persist over time. They differ from the clustering of impaired skills seen in children of comparable socio-cultural backgrounds without HIV infection. Similarities in functioning are noted between this subgroup of children with AIDS and ARC and comparable groups with cerebral palsy.


Urologic problems in spina bifida patients transitioning to adult care.
To identify the urologic needs of adult patients with spina bifida (SB) at the time of their transition from pediatric to adult care. We hypothesized that delays in transition to adult care would be associated with higher rates of active problems. We retrospectively reviewed patients seen at adult dedicated SB clinics at the Universities of Utah and Minnesota from April 2011 to April 2012. We reviewed bladder management, urologic problems, time from last urologic care, and necessary interventions. We identified 65 patients from these clinics with SB. The mean age was 30.6 years (standard deviation, 11.3). The median time since last urologic evaluation at Utah and Minnesota was 17 months and 12 months, respectively (range 1 month-10 years). Fifty-five patients (85%) reported a urologic problem at the time of their visit. Urinary incontinence was most common in 34 (52%), followed by recurrent urinary tract infection in 22 (34%), catheterization troubles in 8 (12%), and calculi in 6 (9%). Sixty-three patients (97%) required some sort of intervention. These were diagnostic (cystoscopy, ultrasonography, computed tomography scan, urodynamics) in 50 patients (77%), surgical (urinary diversion, onabotulinum toxin A injection, stone surgery, and so forth) in 22 (34%), and medical (antimicrobial prophylaxis, bladder irrigations, anticholinergics, self-catheterization) in 16 (25%). There was no association between longer transition times and higher rates of active problems. On presentation to adult SB clinics, patients had many active urologic problems and operative management was often needed; however, there was no association between longer transition times and higher rates of active problems.


Incidence of patient safety events and process-related human failures during intra-hospital transportation of patients: retrospective exploration from the institutional incident reporting system.
Intra-hospital transportation (IHT) might compromise patient safety because of different care settings and higher demand on the human operation. Reports regarding the incidence of IHT-related patient safety events and human failures remain limited. To perform a retrospective analysis of IHT-related events, human failures and unsafe acts. A hospital-wide process for the IHT and database from the incident reporting system in a medical centre in Taiwan. All eligible IHT-related patient safety events between January 2010 to December 2015 were included. Incidence rate of IHT-related patient safety events, human failure modes, and types of unsafe acts. There were 206 patient safety events in 2 009 013 IHT sessions (102.5 per 1 000 000 sessions). Most events (n=148, 71.8%) did not involve patient harm, and process events (n=146, 70.9%) were most common. Events at the location of arrival (n=101, 49.0%) were most frequent; this location accounted for 61.0% and 44.2% of events with patient harm and those without harm, respectively (p<0.001). Of the events with human failures (n=186), the most common related process step was the preparation of the transportation team (n=91, 48.9%). Contributing unsafe acts included perceptual errors (n=14, 7.5%), decision errors (n=56, 30.1%), skill-based errors (n=48, 25.8%), and non-compliance (n=68, 36.6%). Multivariate analysis showed that human failure found in the arrival and hand-off sub-process (OR 4.84, p<0.001) was associated with increased patient harm, whereas the presence of omission (OR 0.12, p<0.001) was associated with less patient harm. This study shows a need to reduce human failures to prevent patient harm during intra-hospital transportation. We suggest that the transportation team pay specific attention to the sub-process at the location of arrival and prevent errors other than omissions. Long-term monitoring of IHT-related events is also warranted.


Factors Influencing Threshold Energy in Subthreshold Photocoagulation for Diabetic Macular Edema.
Subthreshold photocoagulation is one of the treatments for diabetic macular edema. However, the range of adequate laser energy that can be used for subthreshold photocoagulation is very restricted. Therefore, determination of the titration settings for the threshold energy is an essential part of the subthreshold-photocoagulation procedure. This study examined factors influencing the threshold energy used in subthreshold photocoagulation for diabetic macular edema. For 20 consecutive cases (29 eyes) who had received treatment using Endpoint Management (EpM) between April 2019 and June 2020 for persistent diabetic macular edema after completion of panretinal photocoagulation, multiple regression analysis was used to examine factors influencing threshold energy. Analysis evaluating all the surgical procedures (n=150) determined there was statistical significance for a history of vitrectomy and cataract surgery, central macular thickness, interval from completion of panretinal photocoagulation, superior 6 mm subfield, and nasal 6 mm subfield. Further analysis examined surgical procedures that had been done in patients with a history of vitrectomy and cataract surgery (n=116). This analysis showed that central macular thickness, axial length, interval from completion of panretinal photocoagulation, and HbA1c were all statistically significant factors. Threshold energy for diabetic macular edema was significantly influenced by a history of vitrectomy and cataract surgery, central macular thickness, and interval between the completion of panretinal photocoagulation and initial EpM. Transparency of ocular media and intraocular inflammation were speculated to be associated with these results.


Integration of proteomics and metabolomics reveals energy and metabolic alterations induced by glucokinase (GCK) partial inactivation in hepatocytes.
Glucokinase (GCK) acts as the glucose sensor in maintaining glucose homeostasis. The inactivating mutation of the GCK gene leads to glucokinase-maturity onset diabetes of the young (GCK-MODY). This study aims to gain further insights into the molecular alterations triggered by GCK partial inactivation in hepatocytes, potentially underlying the favorable prognosis of GCK-MODY. A GCK knockdown HepG2 cell model was established, and the integration of proteomics and metabolomics was used to gain a comprehensive understanding of the molecular pathway changes caused by GCK inactivation in the liver. Proteomic analysis identified 257 differential proteins. KEGG pathway enrichment analysis showed that protein expression changes in the GCK knockdown group were significantly enriched in central carbon metabolism, the TCA cycle, amino acid metabolism and the oxidative phosphorylation pathway. Among them, enzymes in the TCA cycle (PC, IDH2, SDH) were significantly downregulated in GCK-knockdown group. Targeted metabolomics revealed that in the GCK knockdown hepatocytes, TCA cycle intermediates were significantly decreased, including pyruvate, oxaloacetate, citrate and succinic acid, and three metabolites increased including glycine, betaine and homocysteine. These metabolic alterations in turn reduced the accumulation of reactive oxygen species in GCK knockdown hepatocytes. Correlation analysis indicated that TCA cycle metabolites were positively correlated with proteins involved in the TCA cycle, carbon metabolism, glycolysis, Ras signaling, fibrosis and inflammation. In conclusion, GCK knockdown reduced TCA cycle flux and oxidative stress in hepatocytes by influencing the levels of key transcription factors and enzymes, providing a comprehensive understanding of the effects of GCK partial inactivation on liver metabolism and molecular mechanisms.


fMRI activation maps based on the NN-ARx model.
The most significant progresses in the understanding of human brain functions have been possible due to the use of functional magnetic resonance imaging (fMRI), which when used in combination with other standard neuroimaging techniques (i.e., EEG) provides researchers with a potential tool to elucidate many biophysical principles, established previously by animal comparative studies. However, to date, most of the methods proposed in the literature seeking fMRI signs have been limited to the use of a top-down data analysis approach, thus ignoring a pool of physiological facts. In spite of the important contributions achieved by applying these methods to actual data, there is a disproportionate gap between theoretical models and data-analysis strategies while trying to focus on several new prospects, like for example fMRI/EEG data fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In this paper, we propose a new approach which will allow many of the abovementioned hot topics to be addressed in the near future with an underlying interpretability based on bottom-up modeling. In particular, the theta-MAP presented in the paper to test brain activation corresponds very well with the standardized t test of the SPM99 toolbox. Additionally, a new Impulse Response Function (IRF) has been formulated, directly related to the well-established concept of the hemodynamics response function (HRF). The model uses not only the information contained in the signal but also that in the structure of the background noise to simultaneously estimate the IRF and the autocorrelation function (ACF) by using an autoregressive (AR) model with a filtered Poisson process driving the dynamics. The short-range contributions of voxels within the near-neighborhood are also included, and the potential drift was characterized by a polynomial series. Since our model originated from an immediate extension of the hemodynamics approach [Friston, K.J., Mechelli, A., Turner, R., Price C.J. (2000a). Nonlinear responses in fMRI: the balloon model, volterra kernels, and other hemodynamics. NeuroImage 12, 466-477.], a natural interpretability of the results is feasible.


Meta-analysis of job-exposure matrix data from multiple sources.
The objectives of this study were to determine the heterogeneity of data sources used to construct a job-exposure matrix (JEM) for occupational noise, and to calculate pooled exposure estimates for different job titles using different sources. The JEM was populated with measurements from government databases, private industry, and the published literature. Data were organized by job title using the US standard occupational classification (SOC). Using data from the literature as prior information, adjusted mean exposure was calculated for both the government and industry data following a simple Bayesian approach. A meta-analysis was conducted to measure data heterogeneity across sources and to calculate a pooled exposure estimate for each SOC and SOC group. In total, 715,867 measurements across 259 SOCs were analyzed. Using the data from literature as a prior, 15 of 28 applicable SOCs in the government and industry data had adjusted mean exposures above the OSHA action level (85 dBA). The meta-analysis showed that 63% of SOCs, and 78% of SOC groups, had moderate to high heterogeneity. Fifty-one percent of SOCs and 43% of SOC groups had pooled estimated exposures >85 dBA. The pooled estimates suggested that workers in 131 of 259 SOCs (51%) were exposed beyond the threshold of 85 dBA.


Oxygen octahedral distortions in LaMO3/SrTiO3 superlattices.
In this work we study the interfaces between the Mott insulator LaMnO3 (LMO) and the band insulator SrTiO3 (STO) in epitaxially grown superlattices with different thickness ratios and different transport and magnetic behaviors. Using atomic resolution electron energy-loss spectral imaging, we analyze simultaneously the structural and chemical properties of these interfaces. We find changes in the oxygen octahedral tilts within the LaMnO3 layers when the thickness ratio between the manganite and the titanate layers is varied. Superlattices with thick LMO and ultrathin STO layers present unexpected octahedral tilts in the STO, along with a small amount of oxygen vacancies. On the other hand, thick STO layers exhibit undistorted octahedra while the LMO layers present reduced O octahedral distortions near the interfaces. These findings are discussed in view of the transport and magnetic differences found in previous studies.


Mammalian GGAs act together to sort mannose 6-phosphate receptors.
The GGAs (Golgi-localized, gamma ear-containing, ADP ribosylation factor-binding proteins) are multidomain proteins implicated in protein trafficking between the Golgi and endosomes. We examined whether the three mammalian GGAs act independently or together to mediate their functions. Using cryo-immunogold electron microscopy, the three GGAs were shown to colocalize within coated buds and vesicles at the trans-Golgi network (TGN) of HeLa cells. In vitro binding experiments revealed multidomain interactions between the GGAs, and chemical cross-linking experiments demonstrated that GGAs 1 and 2 form a complex on Golgi membranes. RNA interference of each GGA resulted in decreased levels of the other GGAs and their redistribution from the TGN to cytosol. This was associated with impaired incorporation of the cation-independent mannose 6-phosphate receptor into clathrin-coated vesicles at the TGN, partial redistribution of the receptor to endosomes, and missorting of cathepsin D. The morphology of the TGN was also altered. These findings indicate that the three mammalian GGAs cooperate to sort cargo and are required for maintenance of TGN structure.


Evaluation of common bile duct diameter using high resolution computed tomography.
The visibility rate and mean diameter of the common bile duct (CBD) were determined in 172 patients scanned with a routine abdominal technique on a GE CT/T 9800. Ninety-two (53%) had visible CBDs with the mean diameter measuring 5.3 mm. The visibility rate varied from 45 to 66% in healthy and ill patients, although the CBD diameters were similar (4.5 and 5.1 mm). The CBD was visualized more often in patients after cholecystectomy (87%), and the mean diameter was larger (8.2 mm). Using high resolution CT it seemed that the CBD could be demonstrated more frequently than the previously reported 30%.


[Features of the clinical picture and course of ambulatory schizophrenia with onset in young adulthood (clinico-catamnestic study)].
From a population of epidemiologically examined schizophrenics of three Moscow regions a group of 96 patients was selected. These patients have fallen ill in adolescence and youth and have never been hospitalized after their primary dispensary examination. A catamnestic examination of them carried out in 10 to 15 years has shown that the "ambulatory" schizophrenia of the juvenile age is characterized by prevalence of neurosis-like and effaced forms, and takes a course mainly in the form of lingering atypical pubertal "schube" (the so-called "state of juvenile asthenic inadequacy"). This state ends in regression of the symptoms and in the patients' social and working re-adaptation, as the juvenile age is past, however, shallow schizophrenic changes still remain. The question on the expedience of extramural treatment of such patients and expansion of indications for their social and working rehabilitation is discussed.


Protective role of alpha-phenyl-N-t-butylnitrone against ionizing radiation in U937 cells and mice.
Ionizing radiation (IR) induces the production of reactive oxygen species (ROS), which play an important causative role in radiation damage. alpha-Phenyl-N-t-butylnitrone (PBN) is one of the most widely used spin-trapping compounds for investigating the existence of free radicals in biological systems. We investigated the protective role of PBN against IR in U937 cells and mice. On exposure to IR, there was a distinct difference between the control cells and the cells pretreated with PBN in regard to viability, cellular redox status, and oxidative damage to cells. Lipid peroxidation, oxidative DNA damage, and protein oxidation were significantly lower in the cells treated with PBN when the cells were exposed to IR. Although the activities of antioxidant enzymes were comparable in PBN-treated and control cells, the [GSSG]:[GSH + GSSG] ratio and the generation of intracellular ROS were higher and the [NADPH]:[NADP(+) + NADPH] ratio was lower in control cells compared with PBN-treated cells. The IR-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of ROS, the reduction of ATP production, and the morphological change were significantly higher in control cells compared with PBN-treated cells. PBN administration for 14 days with a daily dosage of 30 mg/kg provided substantial protection against killing and oxidative damage to mice exposed to whole body irradiation. These data indicate that PBN may have great application potential as a new class of in vivo, nonsulfur-containing radiation protector.


A novel urease-negative Helicobacter species associated with colitis and typhlitis in IL-10-deficient mice.
A spiral-shaped bacterium with bipolar, single-sheathed flagella was isolated from the intestines of IL-10 (interleukin-10)-deficient (IL-10(-/-)) mice with inflammatory bowel disease. The organism was microaerobic, grew at 37 and 42 degrees C, and was oxidase and catalase positive but urease negative. On the basis of 16S rRNA gene sequence analysis and biochemical and phenotypic criteria, the organism is classified as a novel helicobacter. Cesarean section-rederived IL-10(-/-) mice without helicobacter infection did not have histological evidence of intestinal inflammation. However, helicobacter-free IL-10(-/-), SCID/NCr, and A/JNCr mice experimentally inoculated with the novel urease-negative Helicobacter sp. developed variable degrees of inflammation in the lower intestine, and in immunocompetent mice, the experimental infection was accompanied by a corresponding elevated immunoglobulin G antibody response to the novel Helicobacter sp. antigen. These data support other recent studies which demonstrate that multiple Helicobacter spp. in both naturally and experimentally infected mice can induce inflammatory bowel disease. The mouse model of helicobacter-associated intestinal inflammation should prove valuable in understanding how specific microbial antigens influence a complex disease process.


Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles.
Patterns of DNA methylation change with age and these changes are believed to be associated with the development of common complex diseases. The hypothesis that Long Interspersed Nucleotide Element 1 (LINE-1) DNA methylation (an index of global DNA methylation) is associated with biomarkers of metabolic health was investigated in this study. Global LINE-1 DNA methylation was quantified by pyrosequencing in blood-derived DNA samples from 228 individuals, aged 49-51 years, from the Newcastle Thousand Families Study (NTFS). Associations between log-transformed LINE-1 DNA methylation levels and anthropometric and blood biochemical measurements, including triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, fasting glucose and insulin secretion and resistance were examined. Linear regression, after adjustment for sex, demonstrated positive associations between log-transformed LINE-1 DNA methylation and fasting glucose {coefficient 2.80 [95% confidence interval (CI) 0.39-5.22]}, total cholesterol [4.76 (95% CI 1.43-8.10)], triglycerides [3.83 (95% CI 1.30-6.37)] and LDL-cholesterol [5.38 (95% CI 2.12-8.64)] concentrations. A negative association was observed between log-transformed LINE-1 methylation and both HDL cholesterol concentration [-1.43 (95% CI -2.38 to -0.48)] and HDL:LDL ratio [-1.06 (95% CI -1.76 to -0.36)]. These coefficients reflect the millimoles per litre change in biochemical measurements per unit increase in log-transformed LINE-1 methylation. These novel associations between global LINE-1 DNA methylation and blood glycaemic and lipid profiles highlight a potential role for epigenetic biomarkers as predictors of metabolic disease and may be relevant to future diagnosis, prevention and treatment of this group of disorders. Further work is required to establish the role of confounding and reverse causation in the observed associations.


A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility.
The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Treatment of urinary tract infections during pregnancy.
Urinary tract infections complicate 7-10% of pregnancies. Early detection and treatment of bacteriuria prevents most cases of pyelonephritis and its associated maternal and neonatal morbidity. The high risk for recurrence of bacteriuria and pyelonephritis mandate close monitoring of previously infected women and may require chronic suppressive therapy through the remainder of pregnancy. Acute cystitis is a distinct syndrome with a low recurrence rate and rarely associated with pyelonephritis.


Towards meaningful simulation-based learning with medical students and junior physicians.
This research provides an educational perspective on simulation-based medical education by implementing both the characteristics of meaningful learning and the concepts of facilitating, training, and learning processes. This study aims to evaluate, from the perspectives of both facilitators and students, the meaningfulness of five different simulation-based courses. The courses were implemented in the spring of 2010. The data were collected from facilitators (n = 9) and students (n = 25) using group interviews (one individual interview), observations, video recordings, and pre- and post-questionnaires. The research analyzes qualitative data using the qualitative content analysis method to answer the following research question: From facilitators' and students' perspectives, how does the facilitating and training in simulation-based learning environments (SBLEs) foster the meaningful learning of students? It seems that simulation-based learning is, at its foundation, meaningful since it inherently supports the many characteristics of meaningful learning. However, characteristics also exist that simulation-based learning does not inherently support. In this study, the goal-oriented, self-directed, and individual training characteristics were only somewhat supported during the facilitation and training in SBLEs. In running these courses in the future, facilitators should concentrate on those characteristics that were only somewhat supported.


Successful treatment of naturally occurring influenza A/USSR/77 H1N1.
Forty-five university students with proved influenza A/USSR/77 H1N1 infection were randomly treated with either amantadine hydrochloride (14 students), rimantadine hydrochloride (19 students), or placebo (12 students). By 48 hours after initiation of therapy, amantadine and rimantadine recipients had significantly less fever and greater improvement compared with subjects given the placebo. Minor reversible CNS side effects at the end of the five-day course of therapy were observed in one third of the amantadine-treated subjects. However, both amantadine and rimantadine recipients returned to classes earlier and shed smaller amounts of virus than placebo recipients. Thus, both drugs exerted a notable therapeutic effect. Hence, during an influenza outbreak, five days of empirical therapy with amantadine or rimantadine for persons with an influenza-like syndrome should ameliorate clinical symptoms and might decrease spread of virus.


Modeling microbial diversity in anaerobic digestion.
The aim of this study is to develop a modeling approach able to handle microbial diversity both in normal and abnormal situations. Normal situations are defined as changing input characteristics that do not imply process imbalance while abnormal situations are illustrated by the presence of toxicant into the reactor. In both cases, modeling is performed by adding a stochastic term on top of a well defined and well structured model such as the IWA Anaerobic Digestion Model No1. Experimental data from a 1 m3 pilot scale anaerobic digester treating wine distillery wastewater are provided to demonstrate the applicability of this approach. Discussion also highlights that monitoring of digesters might receive a renewed consideration in the near future in order to handle explicitly microbial diversity within the control objectives.


Endoscopic Treatment of Colo-Colonic Intussusception in a Patient with Peutz-Jeghers Syndrome.
A 19-year-old man with a history of Peutz-Jeghers syndrome (PJS) and two previous partial small bowel resections because of intussusception presented with lower abdominal pain. Computed tomography (CT) showed concentric multilayer and cord-like structures in the transverse colon. Colo-colonic intussusception was suspected and he was hospitalized. After two therapeutic enemas were unsuccessful, a colonoscopy was performed. The intussusception was reduced and a 40-mm transverse colon polyp with a thick stalk was resected. After the procedure, his abdominal pain was relieved and he was discharged on the sixth hospital day. This case and several previous reports suggest that PJS polyps with tumor diameter exceeding 30 mm and location in the transverse or sigmoid colon can cause intussusception. Endoscopic treatment should be considered for these lesions.


[Study on status of nutrition in children under three years old in rural area in China].
To understand the nutrition status of children under three years in rural area of western China and to explore the influencing factors so as to provide reasonable suggestions for policy making. Use PPS sampling method to investigate the 13,532 children under three years old. Height and weight were used as nutritional indexes. The prevalence of stunting (height for age Z-score < -2), underweight (weight for age Z-score < -2) and wasting (weight for height Z-score < -2) were 12.4%,11.8% and 5.7% respectively. Boys, minority and the children from western China had higher prevalence rate. The prevalence rates of the Han nationality children's underweight and stunting were 9.5% and 9.8%, but these rates of the minority children were 15.6% and 16.5% respectively, which were obviously higher than the Han ethnicity children with significant differences between them (P <0.01).The prevalence of malnutrition was rising with age and the peak age of stunting, underweight and wasting appeared at 21 months, 12 months and 15 months, respectively. Compared with growth reference of NCHS/WHO, the HAZ, WAZ and WHZ left moved 0.59,0.60 and 0.26 units which indicated the whole nutritional status of children from program area impaired to some extent. Underweight inclined to have higher two-week prevalence rates of diarrhea and flu than in the normal children,achieving 15.9% and 13.5%, but with significant differences between them (P<0.01). We administered non-conditional logistic regression analysis to identify the influencing factors of malnutrition. Under-6-month children who were not taken care by their mothers showed higher risk of stunting. Over-6-month children stunting had significant relationship with age, gender, sibling order, nationality,maternal educational level,special cooking for children and residential region. Underweight of over-6-month children significantly related to age, nationality, and maternal educational level, yolk supply during 6-8 month old and living region. Malnutrition was really prevalent among children in China,suggesting that intervention should be done according to the influencing factors.


Mutations in the herpes simplex virus DNA polymerase gene conferring hypersensitivity to aphidicolin.
Fourteen mutants known or likely to contain mutations in the herpes simplex virus DNA polymerase gene were examined for their sensitivity to aphidicolin in plaque reduction assays. Eleven of these exhibited some degree of hypersensitivity to the drug; altered aphidicolin-sensitivity correlated with altered sensitivity to the pyrophosphate analog, phosphonoacetic acid. The DNA polymerase specified by one of these mutants, PAAr5, required roughly seven-fold less aphidicolin to inhibit its activity by 50% than did polymerase specified by its parental strain. Mutations responsible for the aphidicolin-hypersensitivity phenotype of PAAr5 were mapped to an 0.8 kbp region in the herpes simplex virus DNA polymerase locus. These data taken together indicate that 1) mutations in the herpes simplex virus DNA polymerase gene can confer altered sensitivity to aphidicolin, 2) that the HSV polymerase is sensitive to aphidicolin in vivo, and 3) that amino acid alterations which affect aphidicolin binding may affect the pyrophosphate exchange-release site as well, suggesting that aphidicolin binds in close proximity to this site.


Context and Meaning in EHR Displays.
Many Electronic Health Record (EHRs) data displays are insensitive to their settings, contexts, and to clinicians' needs. Yet, the contexts in which the data are displayed critically affect EHR usability and patient safety. Medication prescribing is a complex task; especially sensitive to contextual variation in EHR displays as vast variations in formats and logic are often unnecessarily confusing, leading to unwanted cognitive burdens and medical errors. With examples of EHR screenshots, we illustrate contextual variations in medication and allergy displays across different EHR systems and implementations-noting often seemingly haphazard differences that can lead to misunderstandings and misinterpretations.


Recruitment to mail and telephone interventions for obesity in a managed care environment: the Weigh-To-Be project.
To evaluate the success of mail- and telephone-based weight loss programs in recruiting a representative sample of overweight members of a managed care organization (MCO). Cross-sectional. A total of 1801 members of an MCO were recruited by direct mail, clinic flier, and physician referral for a research study evaluating mail- and telephone-based weight loss programs; 412 additional overweight members of the same MCO were identified in a general member survey for comparison purposes. Body mass index, demographics, diet, and exercise habits were measured. Study volunteers were heavier, more likely to be women, more likely to be minorities, more educated, and younger than the general sample of overweight members. They also had a more extensive history of dieting, ate a diet higher in fat and lower in fruit and vegetables, and were more likely to report binge eating than the general sample. However, study volunteers reported a higher level of physical activity. Invitations to participate in weight loss programs can attract large numbers of people in a managed care setting. However, the participation bias in recruitment to such programs is similar to that seen in traditional face-to-face interventions. Women of higher socioeconomic status who are severely obese and who have an extensive history of weight control efforts are more likely to participate. Additional research is needed to find ways to reach more men and older adults.


[Determination and utilisation of the plasmatic concentration of homocysteine in clinical practice].
Homocysteine is a methionine-derived amino acid and its metabolism depends on B12, B6 and B2 vitamins and folic acid. The total homocysteine plasmatic concentration can be measured in most laboratories by means of enzymeimmunoassays. Hyperhomocysteinemia may be caused by genetic defects of the enzymes involved in its metabolism, nutritional deficiencies or absorption deficiencies of the vitamin cofactors of these enzymes, chronic diseases or administration of some drugs. An increase in the total plasmatic concentration of homocysteine represents a sensitive marker of folate and cobalamin deficiencies as well as an independent risk factor of cardiovascular disease. Furthermore, total plasmatic concentrations of homocysteine are related to the development of congenital malformations, pregnancy complications, psychiatric diseases and to cognitive impairment in the elderly. Therefore, the measurement of the concentration of homocysteine has a notable clinical interest, which may increase in future if it is confirmed that the association with these disorders is causal and that they can be prevented by treating hyperhomocysteinemia.


Dynamics of plant mitochondrial genome: model of a three-level selection process.
The plant mitochondrial genome is composed of a set of molecules of various sizes that generate each other through recombination between repeated sequences. Molecular observations indicate that these different molecules are present in an equilibrium state. Different compositions of molecules have been observed within species. Recombination could produce deleted molecules with a high replication rate but bearing little useful information for the cell (such as "petite" mutants in yeast). In this paper we use a multilevel model to examine selection among rapidly replicating incomplete molecules and relatively slowly replicating complete molecules. Our model simulates the evolution of mitochondrial information through a three-level selection process including intermolecular, intermitochondrial, and intercellular selection. The model demonstrates that maintenance of the mitochondrial genome can result from multilevel selection, but maintenance is difficult to explain without the existence of selection at the intermitochondrial level. This study shows that compartmentation into mitochondria is useful for maintenance of the mitochondrial information. Our examination of evolutionary equilibria shows that different equilibria (with different combinations of molecules) can be obtained when recombination rates are lower than a threshold value. This may be interpreted as a drift-mutation balance.


Effects of divorce on Dutch boys' and girls' externalizing behavior in Gene × Environment perspective: diathesis stress or differential susceptibility in the Dutch Tracking Adolescents' Individual Lives Survey study?
The effects of divorce on children's behavioral development have proven to be quite varied across studies, and most developmental and family scholars today appreciate the great heterogeneity in divorce effects. Thus, this inquiry sought to determine whether select dopaminergic genes previously associated with externalizing behavior and/or found to moderate diverse environmental effects (dopamine receptors D2 and D4, catechol-O-methyltransferase) might moderate divorce effects on adolescent self-reported externalizing problems; and, if so, whether evidence of gene-environment (G × E) interaction would prove consistent with diathesis-stress or differential-susceptibility models of environmental action. Data from the first and third wave of the Dutch Tracking Adolescents' Individual Lives Survey (n = 1,134) revealed some evidence of G × E interaction reflecting diathesis-stress but not differential susceptibility. It is intriguing that some evidence pointed to "vantage sensitivity," which are benefits accruing to those with a specific genotype when their parents remained together, the exact opposite of diathesis-stress. The limits of this work are considered, especially with regard to the conditions for testing differential susceptibility, and future directions are outlined.


Multivariate analysis of prognostic factors in chronic lymphocytic leukemia.
Prognostic factors in a group of 90 patients with chronic lymphocytic leukemia were studied by methods of survival analysis. The relationship between survival and a set of demographic, clinical and laboratory variables, and identification of subsets of variables that are associated with survival, was tested by multivariate analysis, which is based upon Cox proportional hazards regression models in a stepwise procedure. Six variables showed significant correlation with survival: lymph node enlargement, splenomegaly, hepatomegaly, increased percentage (greater than 80%) of lymphocytes, hyperuricemia, and anemia. Stepwise analysis showed that the number of coexistent risk factors was a better predictor of survival than any single risk marker (P less than 0.001). Median survival of patients with 0 or 1 risk marker was 120 months; with 2 or 3, 96 months; with 4, 36 months; and with 5 or 6, only 24 months. Comparison of staging by number of risk markers with staging of the same patients by the Rai system showed a significant trend of decreasing survival with increasing number of risk markers within the same Rai stage. Staging by the number of coexistent risk markers is a simple and readily available method, which may complement existing methods to provide a more accurate assessment of prognosis in patients with chronic lymphocytic leukemia.


Intelligence … moving beyond the lowest common denominator.
Despite a century of use in assessing children for predicting academic success, IQ theory and assessments largely overlook the intellectual repertoires of adolescents and adults that are not common, including declarative, procedural, and tacit knowledge. Such knowledge and skill repertoires are essential elements of adult intellectual life and livelihood. A proposal for considering a wider range of knowledge and skills in the definition and assessment of intelligence is offered, along with ideas for moving forward in both research and applications. When intelligence is considered beyond the lowest common denominator, it is clear that there are many important questions have yet to be answered about adolescent and adult intellectual development, maintenance, and decline, occupational performance, relations between intelligence and nonability traits, and the role of engagement in day-to-day intellectual functioning. The proposed focus is to reconsider what it means to be an intelligent adult beyond the IQ measures and to recognize that adults, on average, are far more "intelligent" than they have been considered to be by traditional IQ assessments developed over the last century. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


MiR-492 impairs the angiogenic potential of endothelial cells.
Endothelial cells growing in high glucose-containing medium show reduced cell proliferation and in vitro angiogenesis. Evidence suggests that the molecular pathways leading to these cellular responses are controlled by microRNAs, endogenous post-transcriptional regulators of gene expression. To identify the microRNAs and their targeted genes involved in the glucose responses, we performed the miRNA signature of Human Umbelical Vein Endothelial Cells (HUVECs) exposed and unexposed to high glucose. Among differentially expressed microRNAs, we analysed miR-492 and showed that its overexpression was able to reduce proliferation, migration and tube formation of HUVEC. These effects were accompanied by the down-regulation of eNOS, a key regulator of the endothelial cell function. We showed that eNOS was indirectly down-regulated by miR-492 and we discovered that miR-492 was able to bind mRNAs involved in proliferation, migration, tube formation and regulation of eNOS activity and expression. Moreover, we found that miR-492 decreased VEGF expression in HUVEC and impaired in vivo angiogenesis in a tumour xenograft model, suggesting a role also in modulating the secretion of pro-angiogenic factors. Taken together, the data indicate that miR-492 exerts a potent anti-angiogenic activity in endothelial cells and therefore miR-492 seems a promising tool for anti-angiogenic therapy.


The Type III Effector AvrBs2 in Xanthomonas oryzae pv. oryzicola Suppresses Rice Immunity and Promotes Disease Development.
Xanthomonas oryzae pv. oryzicola, the causal agent of bacterial leaf streak, is one of the most important bacterial pathogens in rice. However, little is known about the functions of individual type III effectors in virulence and pathogenicity of X. oryzae pv. oryzicola. Here, we examined the effect of the mutations of 23 putative nontranscription activator-like effector genes on X. oryzae pv. oryzicola virulence. The avrBs2 knock-out mutant was significantly attenuated in virulence to rice. In contrast, the xopAA deletion caused enhanced virulence to a certain rice cultivar. It was also demonstrated that six putative effectors, including XopN, XopX, XopA, XopY, XopF1, and AvrBs2, caused the hypersensitive response on nonhost Nicotiana benthamiana leaves. Virulence function of AvrBs2 was further confirmed by transgenic technology. Pathogen-associated molecular pattern-triggered immune responses including the generation of reactive oxygen species and expression of pathogenesis-related genes were strongly suppressed in the AvrBs2-expressing transgenic rice lines. Although not inhibiting flg22-induced activation of mitogen-activated protein kinases, heterologous expression of AvrBs2 greatly promotes disease progression in rice caused by two important bacterial pathogens X. oryzae pvs. oryzae and oryzicola. Collectively, these results indicate that AvrBs2 is an essential virulence factor that contributes to X. oryzae pv. oryzicola virulence through inhibiting defense responses and promoting bacterial multiplication in monocot rice.


Spontaneous hypochlorhydria in man: possible causes and consequences.
There have been many reports of the development of achlorhydria in individuals and in groups of subjects with previously normal levels of gastric acid secretion. The evidence that this phenomenon is due to an infective agent has been considered. Retrospective identification of CLO in gastric mucosal biopsies from some of these patients is an interesting observation, but does not conclusively prove a causal relationship. The exact significance of CLO remains speculative at present; there is more evidence to suggest that it plays a role in gastritis than in peptic ulceration. Ongoing research in this area may have major consequences for the medical treatment of gastritis, 'non-ulcer dyspepsia' and perhaps also for peptic ulcer disease.


Short-Term versus Long-Term Mentalization-Based Therapy for Borderline Personality Disorder: A Randomized Clinical Trial (MBT-RCT).
Borderline personality disorder (BPD) is a severe and prevalent psychiatric disorder. Mentalization-based therapy (MBT) is an evidence-based intervention for BPD, and several countries offer treatment programs for BPD lasting for years, which is resource demanding. No previous trial has compared short-term with long-term MBT. The aim of the study was to assess the efficacy and safety of short-term versus long-term MBT for outpatients with BPD. Adult outpatients (≥18 years) with subthreshold or diagnosed BPD were randomly assigned (1:1) to short-term MBT (5 months) or long-term MBT (14 months). The primary outcome was BPD symptoms assessed with the Zanarini Rating Scale for Borderline Personality Disorder. Secondary outcomes were functional impairment, quality of life, global functioning, and severe self-harm. All outcomes were primarily assessed at 16 months after randomization. This trial was prospectively registered at <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, NCT03677037. Between October 4, 2018, and December 3, 2020, we randomly assigned 166 participants to short-term MBT (n = 84) or long-term MBT (n = 82). Regression analyses showed no evidence of a difference when assessing BPD symptoms (MD 0.99; 95% CI: -1.06 to 3.03; p = 0.341), level of functioning (MD 1.44; 95% CI: -1.43 to 4.32; p = 0.321), quality of life (MD -0.91; 95% CI: -4.62 to 2.79; p = 0.626), global functioning (MD -2.25; 95% CI: -6.70 to 2.20; p = 0.318), or severe self-harm (RR 1.37; 95% CI: 0.70-2.84; p = 0.335). More participants in the long-term MBT group had a serious adverse event compared with short-term MBT (RR 1.63; 95% CI: 0.94-3.07; p = 0.088), primarily driven by a difference in psychiatric hospitalizations (RR 2.03; 95% CI: 0.99-5.09; p = 0.056). Long-term MBT did not lead to lower levels of BPD symptoms, nor did it influence any of the secondary outcomes compared with short-term MBT.


Video-based administration of the La Trobe Communication Questionnaire for adults with traumatic brain injury and their communication partners.
To explore the use of direct video-based review for administration of the LaTrobe Communication Questionnaire (LCQ), and explore use of the LCQ as a tool for identifying and prioritizing targets for partner-based intervention. Between-groups design comparing self- vs partner ratings of social communication behaviours in conversation and qualitative analysis of response patterns and participant feedback. Eight adults with moderate-to-severe TBI and their partners engaged in 20-minute videotaped conversations, elicited using a topic-starter task. Each participant with TBI and his or her partner then completed the LCQ while viewing the dyad's videotaped conversation. Self- and partner ratings of the person with TBI were compared to each other and to published LCQ data. Based on direct review of their videotaped conversations, six of eight individuals with TBI rated themselves as having more frequent problem behaviours than did their partners. Overall agreement between individuals with TBI and their partners was 0.70. The present study suggests that direct review of videotaped conversations might avoid some of the limitations associated with recall of previous events, which can be biased toward negative events and confounded by memory impairments in individuals with TBI. Participants stated that the video segment reflected their typical interactions and, thus, behaviours observed in this context could serve as a starting point for intervention planning.


Multi-charged bis(p-calixarene)/pillararene functionalized gold nanoparticles for ultra-sensitive sensing of butyrylcholinesterase.
A series of supramolecular assemblies based on multi-charged calixarene (SC4A), bis(p-calixarene) (BSC4A) and pillararene (CP5A) modified gold nanoparticles (AuNP) was constructed to realize colorimetric sensing of both succinylcholine (SuCh) and butyrylcholinesterase (BChE). With the high binding affinity of BSC4A and CP5A towards SuCh, BSC4A-AuNPs and CP5A-AuNPs could assemble with micromolar level SuCh as SuCh-BSC4A/CP5A-AuNPs. More interestingly, the enzymatic hydrolysis of SuCh by BChE could lead to the disassembly of SuCh-BSC4A/CP5A-AuNPs and provide a sensitive time-dependent color change from blue to red which could be observed by the naked eye and used to monitor BChE activity. As BChE activity is an important biomarker for diseases and poor health conditions, this novel supramolecular tandem colorimetric sensing strategy may have potential use for early diagnosis of diseases.