Domains of ERRgamma that mediate homodimerization and interaction with factors stimulating DNA binding.
The estrogen receptor-related receptor gamma (ERRgamma/ERR3/NR3B3) is an orphan member of the nuclear receptor superfamily closely related to the estrogen receptors. To explore the DNA binding characteristics, the protein-DNA interaction was studied in electrophoretic mobility shift assays (EMSAs). In vitro translated ERRgamma binds as a homodimer to direct repeats (DR) without spacing of the nuclear receptor half-site 5'-AGGTCA-3' (DR-0), to extended half-sites, and to the inverted estrogen response element. Using ERRgamma deletion constructs, binding was found to be dependent on the presence of sequences in the ligand binding domain (LBD). A far-Western analysis revealed that ERRgamma forms dimers even in the absence of DNA. Two elements, located in the hinge region and in the LBD, respectively, are necessary for DNA-independent dimerization. DNA binding of bacterial expressed ERRgamma requires additional factors present in the serum and in cellular extracts. Fusion proteins of the germ cell nuclear factor (GCNF/NR6A1) with ERRgamma showed that the characteristic feature to be stimulated by additional factors can be transferred to a heterologous protein. The stimulating activity was further characterized and its target sequence narrowed down to a small element in the hinge region.


Preservative-free nasal drug-delivery systems.
Unpreserved nasal sprays are the latest trend in nasal drug delivery. Different technologies are discussed here in the context of mechanically protected systems, which may provide additional benefits. New test protocols are suggested to evaluate the improved microbiological protection that can be achieved.


Arbuscular mycorrhiza fungi facilitate rapid adaptation of Elsholtzia splendens to copper.
Closely associated microbes have been shown to drive local adaptation of plants. However, few studies provide direct evidence, disclosing the role of arbuscular mycorrhiza fungi (AMF) in their rapid adaptation of plants toward heavy metal tolerance. Elsholtzia splendens is a Cu-tolerant plant that was used as a model plant to study seed morphological traits as well as traits related to seed germination and seedling growth. This was achieved after acclimation for two generations with 1000mg/kg CuSO4 in either absence or presence of AMF. In the absence of AMF, acclimation to Cu for two generations significantly decreased surface area, perimeter length, and perimeter width of E. splendens seeds, as well as seedling survival rate and fresh weight of the radicle of seedlings. However, in the presence of AMF, both the germination rate and the germination index of E. splendens seeds as well as the fresh weights of hypocotyl and radicle significantly increased. These results revealed that after Cu acclimation treatment, seeds and seedlings that had been inoculated with AMF outperformed those without AMF inoculation under Cu addition, indicating that AMF can facilitate rapid adaptation of E. splendens to Cu stress. In addition, two generations of Cu acclimation under AMF absence significantly increased radicle length, while amplitude increased under AMF presence, indicating that the direct adaptive plasticity response of radicle length to Cu stress helps with the Cu stress adaptation of E. splendens.


Molecular analysis of minimally differentiated acute myeloid leukemia with chromosome 16 inversion.
We report a 3-year-old girl with minimally differentiated acute myeloid leukemia and chromosome 16 inversion (inv 16). Inv 16 is generally associated with acute myelomonocytic leukemia with dysplastic eosinophils in the bone marrow (AML-M4Eo). Recently, molecular analysis showed that a fusion gene is generated by this inversion between the CBFB gene on the q arm and the MYH11 gene on the p arm. Using reverse transcriptase-polymerase chain reaction analysis, we tried to detect CBFB/MYH11 chimeric mRNA in blasts from our patients, however, were unable to detect any chimeric mRNA in the blasts: The absence of CBFB/MYH11 transcripts in this case suggests that rare chimeric products might be formed as a result of inv 16 that could not be detected by the primer sets used in this study. Another possibility is that different genes are rearranged on the chromosome 16 with the inv 16. More detailed molecular analysis of this case might be necessary in order to elucidate these possibility. Analyzing leukemias with inv 16 which do not have a typical CBFB/MYH11 chimeric mRNA might lead to understanding an alternative pathogenesis for acute leukemia with inv 16.


Direct observation of depth-dependent atomic displacements associated with dislocations in gallium nitride.
We demonstrate that the aberration-corrected scanning transmission electron microscope has a sufficiently small depth of field to observe depth-dependent atomic displacements in a crystal. The depth-dependent displacements associated with the Eshelby twist of dislocations in GaN normal to the foil with a screw component of the Burgers vector are directly imaged. We show that these displacements are observed as a rotation of the lattice between images taken in a focal series. From the sense of the rotation, the sign of the screw component can be determined.


Meta-Analysis of the Ease of Care From a Patients' Perspective Comparing Fentanyl Iontophoretic Transdermal System Versus Morphine Intravenous Patient-Controlled Analgesia in Postoperative Pain Management.
The purpose of this meta-analysis was to evaluate patients' assessment of fentanyl iontophoretic transdermal system (ITS) and morphine intravenous patient-controlled analgesia (IV PCA) ease of care (EOC) using a validated patient EOC questionnaire. Fentanyl ITS is a preprogrammed, needle-free PCA system used for the management of acute pain in postoperative patients. This meta-analysis assessed the patient EOC of fentanyl ITS and morphine IV PCA using data from three randomized, active-comparator trials in adult postoperative patients with moderate-to-severe pain. All three studies utilized a validated patient EOC questionnaire which consists of 23 items grouped into seven subscales (confidence with device, comfort with device, movement, dosing confidence, pain control, knowledge/understanding, and satisfaction). Each item is scored on a six-point Likert scale. The weighted mean difference between treatments was calculated for the overall EOC and for each of the seven subscales. The EOC analyses were based on responses to questionnaires from 1,943 patients treated with either fentanyl ITS (n = 961) or morphine IV PCA (n = 982). There was a statistically significant advantage in favor of fentanyl ITS over morphine IV PCA in terms of overall EOC (weighted mean difference = 0.28; 95% confidence interval (0.22 to 0.34); P < 0.0001). Five of the seven subscales (confidence with device, comfort with device, movement, dosing confidence, and knowledge/understanding) on the patient EOC questionnaire showed a statistically significant advantage for fentanyl ITS versus morphine IV PCA. The two subscales that did not show any difference were pain control (P = 0.7303) and satisfaction (0.0561). In this meta-analysis, fentanyl ITS is associated with some advantages in terms of an EOC profile from a patients' perspective when compared with morphine IV PCA.


Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.
The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases. Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after. The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers. Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.


Topical issues in old age psychiatry.
With advancements in medical science over past decades, our aging population has increased substantially. Census studies in 2001 showed that 429,100 of the population of the Republic of Ireland were aged 65yrs and older, making up 11.2% of the overall population. While the overall population of the Republic is expected to remain stable over the next ten years, the demographic projections for the elderly population is for significant growth: numbers of over 65yrs are expected to increase by nearly 108,000 people between 1996 - 2011, comprising over 14.1% of the overall population. In particular, our communities will contain a much higher proportion of octogenarians and nonagenarians: at present 21% of our over 65's are 80 yrs or older; by 2011, it is projected that this number will increase to 25%. In tandem, the prevalence of dementia will increase. In 2000, it was estimated that 31,000 people suffered with dementia in the Republic of Ireland, and this figure is expected to increase by 5000 cases per year between 2001-2011. The ultimate outcome of this demographic shift, will be higher demands on medical services for older people, especially geriatric medicine and old age psychiatry. This paper will focus on two particular aspects of management which will increasingly impact on the work of old age psychiatrists - medicolegal issues and management issues in dementia.


Acute effects of the synthetic analogue of methionine enkephalin FK 33-824 in schizophrenic patients. A double blind trial.
16 patients with paranoid and hallucinatory symptoms, who were concurrently receiving no other medication, participated in a double blind trial. Either 3 mg FK 33-824 or 20 mg diazepam was injected i.m. over a 2-day period, with a subsequent cross-over for the second medication. Both FK 33-824 and diazepam caused a slight decrease in psychopathological symptoms as measured by the BPRS, but no differences could be observed in their effect on schizophrenic symptoms such as hallucinations and delusions.


[Uveal effusion syndrome and scleral thickening].
The uveal effusion syndrome associates bullous no rhegmatognous retinal detachment with shifting subretinal fluid, choroidal detachment and elevated spinal fluid protein. This syndrome could result of nonophthalmos, scleral thickening and/or vortex vein attenuation. The author describes a case of uveal effusion syndrome with isolated scleral thickening. Theoretical explanations of this syndrome are emphasized on the basis of literature and clinical and surgical guidelines are given.


Reduced susceptibility to IL-1 and endotoxin in transgenic mice expressing IL-1 in their lens.
To learn about the effects of chronic exposure to IL-1 we generated a transgenic (Tg) mouse line that expresses human IL-1 beta under the control of the lens alpha-A crystallin promoter. Expression of human IL-1 beta was restricted to the eye; neither the protein nor its mRNA were detected in various other organs of the Tg mice. The Tg mice develop severe ocular inflammation shortly after birth, which affects the lens and other eye tissues and apparently allows the release of IL-1 into the circulation. Here we report that the Tg mice exhibit decreased responsiveness to IL-1 and lipopolysaccharide (LPS), as compared to their wild-type littermate controls: (1) when injected with IL-1 the Tg mice produced lower levels of serum amyloid A than their controls; (2) thymocytes of the Tg mice responded less vigorously in culture to stimulation with IL-1; and (3) Tg mice showed lower morbidity and mortality than their controls when injected with toxic amounts of LPS. These data suggest that chronic exposure to IL-1 in the Tg mice induces partial resistance to this cytokine, analogous to the reduced responsiveness to IL-1 in animals pretreated with this proinflammatory cytokine.


[Discussion of laparoscopic transabdominal preperitoneal repair for recurrent inguinal hernia].
To explore the surgical techniques and the clinical efficacy of laparoscopic transabdominal preperitoneal repair (TAPP) for recurrent inguinal hernia. Clinical data of 367 patients with recurrent inguinal hernia who underwent TAPP repair from Mar. 2009 to Mar. 2015 in Beijing Chao-Yang Hospital of Capital Medical University were analyzed retrospectively. Laparoscopic operations were completed successfully in 365 cases, however, 2 cases were converted to open surgery.The operation time was (55.7±19.3) min (30-100 min) and the hospital stay was (4.9±2.7) d (2-12 d). The incidences of postoperative pain, hydrocele, and urinary retention were 4.1%(15/367), 13.1%(48/367), and 1.3%(5/367) respectively.Other complications such as foreign body sensation, wound infection, and intestinal obstruction.All cases were followed up from 3 to 72 months ((36.5±14.7) months), 2 recurrent cases was observed and no mesh infection and long-term chronic pain were observed. Laparoscopic TAPP repair has advantages of minimal invasion and few complications, which is safe and effective for recurrent inguinal hernia.


Failure to return to receive HIV-test results: the Cameroon experience.
To be acquainted of one's HIV serological status is an important strategy for the fight against HIV/AIDS, but many patients still miss the appointment to receive their HIV-test result. The aim of this study was to determine the epidemiological and serological profiles of patients not coming back to collect their HIV-test result in a tertiary health care facility in Yaoundé, Cameroon. We undertook a retrospective analysis of data of patients who visited the HIV-day care unit of the Yaoundé Central Hospital (Yaoundé, Cameroon) from January to December 2009 in order to be screened for HIV, and who did not come back to retrieve their result. Of the 3990 patients who visited the unit during the study period, 396 (9.92%) did not come back to collect their HIV-test result, of whom 21% were aged 26-30 years representing the most encountered age group. Females (57.8%) were significantly more present than males (p = 0.023). More than half of these patients (54.9%) visited the unit for a voluntary HIV testing. Two hundred and three patients (51.3%) had a positive HIV-test result, of whom 63.5% were females. The most HIV-infected group was the one coming for a voluntary screening (36.5%). Women not returning to receive their results were more likely to be tested HIV-positive (odds ratio = 1.62, 95% confidence interval: 1.08-2.42; p < 0.05). Almost 10% of patients screened for HIV infection did not come back to collect their result. More strategies should be implemented to reduce this rate, especially targeting young adults (20-35 years) and women. The delay in delivering patients' results should be shortened. Concurrently, there is need to increase voluntary HIV-testing in our settings.


Evolution and diversity of cadherins and catenins.
Cadherin genes encode a superfamily of conserved transmembrane proteins that share an adhesive ectodomain composed of tandem cadherin repeats. More than 100 human cadherin superfamily members have been identified, which can be classified into three families: major cadherins, protocadherins and cadherin-related proteins. These superfamily members are involved in diverse fundamental cellular processes including cell-cell adhesion, morphogenesis, cell recognition and signaling. Epithelial cadherin (E-cadherin) is the founding cadherin family member. Its cytoplasmic tail interacts with the armadillo catenins, p120 and β-catenin. Further, α-catenin links the cadherin/armadillo catenin complex to the actin filament network. Even genomes of ancestral metazoan species such as cnidarians and placozoans encode a limited number of distinct cadherins and catenins, emphasizing the conservation and functional importance of these gene families. Moreover, a large expansion of the cadherin and catenin families coincides with the emergence of vertebrates and reflects a major functional diversification in higher metazoans. Here, we revisit and review the functions, phylogenetic classifications and co-evolution of the cadherin and catenin protein families.


AzBio Speech Understanding Performance in Quiet and Noise in High Performing Cochlear Implant Users.
To evaluate high-performing cochlear implant patients' performance on AzBio sentence testing. Retrospective review of prospectively collected database at a tertiary care hospital. Unilateral cochlear implant patients with AzBio testing were included. The primary outcome of interest was AzBio performance scores in quiet and at +10 and +5 decibels signal to noise (dB S/N). One hundred eighty five subjects met inclusion criteria with scores for AzBio in quiet, 114 at +10 dB S/N, and 66 at +5 dB S/N. Linear mixed effects models showed performance significantly correlated with time since activation in all conditions (8.4%/yr; p < 0.0001). Strong correlations between mean performance in quiet and at +10 dB S/N (r = 0.77, p < 0.0001), and between +10 and +5 dB S/N (r = 0.73, p < 0.0001) were found. The correlation between quiet and +5 dB S/N (r = 0.45, p = 0.01) was less robust. Shapiro-Wilks test of normality found only +10 dB S/N to correspond to a normal distribution. Skew analysis demonstrated values of -0.64, -0.11, and 0.8 for quiet, +10 dB S/N, and +5 dB S/N, respectively. AzBio scores at +10 dB S/N show a strong correlation with, but avoid the ceiling effects that limit the usefulness of testing in quiet for high performing cochlear implant users, making it the preferred test in this population. Significant complexities exist in the study of outcomes in cochlear implant recipients, and there is no single test that is ideal for the entirety of this population.


Exploring young people's perspectives on mental health support: A qualitative study across three geographical areas in England, UK.
Improving young people's (YP) mental health and well-being is a global public health priority. Despite continued commitment within the UK policy agenda to improve the mental health and well-being of YP, the incidence of mental health issues continues to rise. This has been further compounded by the outbreak of COVID-19 which has disproportionately affected YP in the most socioeconomically disadvantaged areas. Understanding YP's perspectives on what supports their mental health is important to develop policies that meet their needs. We conducted focus groups (n = 18 with 42 YP aged 13-21) in three geographical areas with high levels of deprivation in England, UK. Recruited through six local youth organisations, each group of YP took part in three interlinked focus groups designed to explore their perceptions of what impacts their health in their local area, and their understandings of health inequalities through participatory methods. Throughout their discussions, YP foregrounded the significance of mental health and mental health support structures. YP perceived challenges to accessing mental health provision and an unmet need for support within their local communities. Alongside this, YP consistently highlighted the importance of youth groups for promoting good mental health and mitigating challenges to poor mental health. However, ongoing cuts to the voluntary sector and universal services continue to impact areas and individuals in the greatest need. In the face of deficits in formal mental health support, our findings highlight the pressing need for increased investment in services focused on prevention (such as youth groups) in areas of high deprivation.


Characterization and sequence analysis of a developmentally regulated putative cell wall protein gene isolated from soybean.
A cDNA clone, pTU04, which hybridizes to two different sizes of mRNA on Northern blots was isolated from soybean suspension culture cell poly(A) RNA. Northern analysis reveals that meristematic tissue produces a 1050-nucleotide mRNA while quiescent mature cells produce primarily a 1220-nucleotide mRNA homologous to pTU04. The cDNA and its corresponding genomic clone have been partially characterized. The nucleotide sequence of the gene predicts a proline-rich protein, designated SbPRP1, which contains a signal peptide sequence and 43 repeats of a sequence consisting primarily of Pro-Pro-Val-Tyr-Lys (CCA-CCA-GTT-TAC-AAG). From nuclease S1 and hybrid-select translation analyses, the cDNA clone pTU04 appears to represent the mRNA for the mature tissue 1220-nucleotide RNA observed on Northern blots. Although there is no direct proof that the encoded protein is a cell wall protein, it has the properties similar to previously isolated cell wall proteins: 1) it is very basic with a high content of Pro, Tyr, and Lys; 2) it has similar hydropathic properties; and 3) its repeating unit shares sequence homology with that of more highly characterized cell wall proteins, generally termed extensin (Chen, J., and Varner, J. E. (1985) EMBO J. 4, 2145-2151; Smith, J. J., Muldoon, E. P., Willard, J. J., and Lamport, D. T. A. (1986) Phytochemistry 25, 1021-1030.


Synthesis, crystal structures, and properties of 6,12-diaryl-substituted indeno[1,2-b]fluorenes.
Fused polycyclic indeno[1,2-b]fluorene derivatives with aryl substituents at the 6,12-positions have been prepared as a potential antiaromatic 20π electronic system. They showed strong absorptions in the visible region and amphoteric redox properties. The quinoid-type molecular structures were revealed by X-ray crystal-structure analysis, which indicated that the bond lengths of the quinoid unit depend on the aryl substituents. Whereas nucleus-independent chemical shift NICS(1) calculations indicate the antiaromatic nature of the s-indacene core, they have higher stability than substituted acene derivatives. The derivatives with difluorophenyl or anthryl groups were stable in solution. Vapor-deposited thin films showed ambipolar carrier transportation in the field-effect transistor devices.


Novel minimally invasive transoral surgery bleeding model implemented in a nationwide otolaryngology emergencies bootcamp.
Post-operative hemorrhage is the most concerning complication after minimally invasive transoral surgery, as can result in airway compromise. Simulation-based medical education provides trainees with structured learning in an intensive and immersive environment allowing deliberate practice of skills and behaviors in the management of real-life situations. We implemented a novel post-oropharyngeal surgery bleeding model in a nationwide otolaryngology emergencies bootcamp, to teach and evaluate technical and non-technical skills required to competently manage this clinical scenario. 28 Otolaryngology residents from 11 programs in Canada participated in the annual Otolaryngology Emergencies Bootcamp of Western University in London, Ontario. After teaching technical aspects of emergency surgical airways in models, the course culminated with a complex scenario of a post-minimally invasive transoral surgery bleeding model using a fresh cadaver. The Non-Technical Skills for Surgeons (NOTSS) rating scale was applied to video analysis and a scenario-specific Medical Expert Checklist was implemented. The model design in a cadaveric torso is described for use in a simulation of a high-volume oropharyngeal bleed after a minimally invasive approach. Participants agreed that the model evoked an elevated degree of realism and conveyed the emotion of a life-threatening event. NOTSS analysis identified a marginal score in the domains of decision-making and communication and teamwork. Critical action checklist analysis highlighted the early mobilization of available resources and time to decision for surgical airway. We present the first report of a post-minimally invasive transoral surgery bleeding model. It was successful in recreating with high fidelity such a high-stake event and to teach technical and non-technical skills.


The role of enterocyte cholesterol metabolism in intestinal cell growth and differentiation.
Cholesterol is an essential constituent of all mammalian cell membranes, and its availability is therefore a prerequisite for cellular growth and other functions. To define further the role of cholesterol metabolism in the intestine both in vitro and in vivo, studies were performed. Several lines of evidence based on these studies suggest that the main purpose of local cholesterol synthesis in the gut is the support of rapid enterocyte proliferation: 1) growth was inhibited during pharmacologic suppression of cholesterol synthesis in intestinal organ or cell culture; 2) the endocrine regulation of intestinal growth was in most but not all instances accompanied by appropriate changes in cholesterol synthesis; 3) most of cholesterol synthesis and lipoprotein uptake was localized predominantly in the crypt and lower villus region; and 4) very little of the sterol synthesized by the intestinal mucosa was exported into lymph but seems rather to be incorporated into cell membranes.


Troponin T after endoscopic retrograde cholangiopancreatography: no evidence of harm.
It is well recognized that myocardial ischemia can occur during endoscopic retrograde cholangiopancreatography (ERCP). Acute arrhythmias and ST segment changes have been reported by a number of authors, but the longer-term sequelae with regard to permanent myocardial damage are not known. The aim of this study was to determine the presence or absence of significant injury to the heart muscle. Sixty-two patients undergoing therapeutic ERCP were assessed clinically and with electrocardiography (ECG) for the presence of ischemic heart disease before the procedure. Extensive intraprocedural monitoring was carried out, postprocedural ECGs were recorded, and serum troponin T levels were measured. The ECGs were evaluated blindly by a single cardiologist. In 61 of the 62 patients, no changes were observed between the ECGs before and after the procedure. One patient had postprocedural T wave inversion but a normal troponin T level, excluding myocardial damage. One patient with mild renal insufficiency and treated heart failure had borderline troponin T elevation (0.05 microg/l) but no ECG changes. No complications of ERCP occurred. Whilst ECG and rhythm changes indicating transient myocardial ischemia do occur during ERCP, there is no evidence that myocardial damage takes place as a consequence of this.


The role of intimal hyperplasia in arterial spasm.
It has been postulated that even moderate spasm in an artery with intimal hyperplasia can produce organ hypoxia because there is an excessive reduction in the diameter of the lumen. To test this hypothesis we created intimal hyperplasia in one femoral artery in five pigs and then induced arterial spasm by administering ergonovine maleate. Arterial spasm did not produce a greater reduction in the luminal diameter of the femoral artery with intimal hyperplasia than it did in the normal femoral artery. Until further evidence appears this hypothesis must be viewed with caution.


Acceleration of 3D DOSY NMR by Spatial Encoding of the Chemical Shift.
Diffusion-ordered NMR spectroscopy (DOSY) is a powerful method for the analysis of solution mixtures. With 3D DOSY, the 2D NMR spectra of a mixture's components can be separated according to the translational diffusion coefficient of each component. The acquisition of 3D DOSY data is, however, very time-consuming because of the need to consecutively acquire scans for both the diffusion and the indirect spectral dimensions. We show that spatial encoding of the indirect spectral dimension, of the kind used in ultrafast 2D NMR, can accelerate 3D DOSY experiments by an order of magnitude or more. This is illustrated with homonuclear single-quantum (COSY) and double-quantum (DQS) correlation spectra. Implementations with concatenated and incorporated (iDOSY) diffusion blocks are compared and in both cases, 2D spectra are separated with less than 6 min of experiment time.


Identification of a Rare Germline Heterozygous Deletion Involving the Polycistronic miR-17-92 Cluster in Two First-Degree Relatives from a BRCA 1/2 Negative Chilean Family with Familial Breast Cancer: Possible Functional Implications.
Micro-RNAs (miRNAs) have emerged as novel gene expression regulators. Recent evidence strongly suggests a role for miRNAs in a large variety of cancer-related pathways. Different studies have shown that 18.7 to 37% of all human miRNA genes are clustered. miR-17-92 polycistronic cluster overexpression is associated with human hematolymphoid and solid malignancies including breast cancer (BC). Here, we report the identification of rs770419845, a rare 6 bp deletion located within the polycistronic miR-17-92 cluster, in two first-degree relatives from a Chilean family with familial BC and negative for point mutations in BRCA 1/2 genes. The deletion was identified by Sanger sequencing when 99 BRCA1/2 mutation-negative BC cases with a strong family history were initially screened. In silico analysis predicts that rs770419845 affects the secondary structure and stability of the pre-miR-17-pre-miR-18 region and the entire 17-92 cluster. The deletion was screened in 458 high-risk BRCA1/2-negative Chilean families and 480 controls. rs770419845 was not detected in any control but identified in a single family with two cases of BC and other cancers. Both BC cases, the mother and her daughter, carried the deletion. Based on bioinformatic analyses, the location of the deletion and its low frequency, we presume rs770419845 may be a pathogenic variant. Functional studies are needed to support this hypothesis.


Requirement of the lipopolysaccharide O-chain biosynthesis gene wxocB for type III secretion and virulence of Xanthomonas oryzae pv. Oryzicola.
Xanthomonas oryzae pv. oryzicola causes bacterial leaf streak of rice. A mutant disrupted in wxocB, predicted to encode an enzyme for lipopolysaccharide (LPS) synthesis, was previously shown to suffer reduced virulence. Here, we confirm a role for wxocB in virulence and demonstrate its requirement for LPS O-chain assembly. Structure analysis indicated that wild-type LPS contains a polyrhamnose O chain with irregular, variant residues and a core oligosaccharide identical to that of other Xanthomonas spp. and that the wxocB mutant lacks the O chain. The mutant also showed moderate impairment in exopolysaccharide (EPS) production, but comparison with an EPS-deficient mutant demonstrated that this impairment could not account entirely for the reduced virulence. The wxocB mutant was not detectably different from the wild type in its induction of pathogenesis-related rice genes, type II secretion competence, flagellar motility, or resistance to two phytoalexins or resveratrol, and it was more, not less, resistant to oxidative stress and a third phytoalexin, indicating that none of these properties is involved. The mutant was more sensitive to SDS and to novobiocin, so increased sensitivity to some host-derived antimicrobials cannot be ruled out. However, the mutant showed a marked decrease in type III secretion into plant cells. This was not associated with any change in expression of genes for type III secretion or the ability to attach to plant cells in suspension. Thus, virulence of the wxocB mutant is likely reduced due primarily to a direct, possibly structural, effect of the loss of the O chain on type III delivery of effector proteins.


BRAF testing modalities in histiocytic disorders: Comparative analysis and proposed testing algorithm.
Understanding of histiocytic disorders has been revolutionized by demonstration of mitogen-activated protein kinase (MAPK) pathway mutations, most commonly BRAFV600E. The optimal testing strategy to assess BRAFV600E is unknown. We aimed to compare performance of testing modalities, to propose a framework for evaluation of BRAFV600E mutation status in histiocytic disorders. We retrospectively reviewed patients with histiocytic disorders and BRAF mutation testing on a lesional tissue specimen. In 120 patients, BRAF assessment included immunohistochemistry (IHC) in 97 (80.2%), polymerase chain reaction (PCR) in 35 (28.9%), and next-generation sequencing (NGS) in 62 (51.2%). Forty-five underwent both NGS and IHC. With NGS as the gold standard, the sensitivity and specificity of IHC were 82.4% and 96.4%. Three false negatives were observed in biopsy specimens with low BRAFV600E variant allele frequency or decalcified tissue. One false-positive IHC was observed in a lung biopsy specimen, likely due to antibody cross-reactivity with respiratory cilia. Among 14 with successful NGS and PCR, a single discordance was observed. Two PCR-to-IHC discrepancies were observed, including one other false-positive IHC. Immunohistochemistry was highly specific for detection of BRAFV600E. Main caveats were false negatives and lack of detection of non-BRAFV600E mutations. We propose the use of IHC as initial screening in general practice with reflex molecular testing if negative.


Transfer RNA methyltransferases with a SpoU-TrmD (SPOUT) fold and their modified nucleosides in tRNA.
The existence of SpoU-TrmD (SPOUT) RNA methyltransferase superfamily was first predicted by bioinformatics. SpoU is the previous name of TrmH, which catalyzes the 2'-Omethylation of ribose of G18 in tRNA; TrmD catalyzes the formation of N1-methylguanosine at position 37 in tRNA. Although SpoU (TrmH) and TrmD were originally considered to be unrelated, the bioinformatics study suggested that they might share a common evolution origin and form a single superfamily. The common feature of SPOUT RNA methyltransferases is the formation of a deep trefoil knot in the catalytic domain. In the past decade, the SPOUT RNA methyltransferase superfamily has grown; furthermore, knowledge concerning the functions of their modified nucleosides in tRNA has also increased. Some enzymes are potential targets in the design of antibacterial drugs. In humans, defects in some genes may be related to carcinogenesis. In this review, recent findings on the tRNA methyltransferases with a SPOUT fold and their methylated nucleosides in tRNA, including classification of tRNA methyltransferases with a SPOUT fold; knot structures, domain arrangements, subunit structures and reaction mechanisms; tRNA recognition mechanisms, and functions of modified nucleosides synthesized by this superfamily, are summarized. Lastly, the future perspective for studies on tRNA modification enzymes are considered.


Synthesis Characterization and Biological Activities of Coordination Compounds of 4-Hydroxy-3-nitro-2H-chromen-2-one and Its Aminoethanoic Acid and Pyrrolidine-2-carboxylic Acid Mixed Ligand Complexes.
Coordination compounds of 4-hydroxy-3-nitro-2H-chromen-2-one and their mixed ligand complexes with aminoethanoic acid and pyrrolidine-2-carboxylic acid were synthesized by the reaction of Cu(II) and Zn(II) salts in molar ratio 1 : 2 for the coumarin complexes and 1 : 1 : 1 for the mixed ligand complexes, in basic media. The compounds formed were characterized using infrared, Uv-vis spectrophotometric analyses, mass spectrometry, magnetic susceptibility measurements, and EDX analyses. It was concluded that 4-hydroxy-3-nitro-2H-chromen-2-one coordinated as a monobasic ligand for all the complexes; it also coordinated via the carbonyl moiety in the case of the Cu(II) mixed ligand complexes. Similarly it was proposed that the amino acids also coordinated in a bidentate fashion via their amino nitrogen and carboxylate oxygen atoms. The synthesized compounds were screened for their antimicrobial and cytotoxic activities. The complexes exhibited marginal antimicrobial activity but good cytotoxic activity.


Hyperbaric oxygen reduces matrix metalloproteinases in ischemic wounds through a redox-dependent mechanism.
Little is known about the impact of hyperbaric oxygen treatment (HBOT) on matrix metalloproteinase (MMP) production in pre-existing high-oxidant wounds. This study aimed to investigate whether HBOT modulates reactive oxygen species (ROS) and MMP regulation in ischemic wound tissue. Using a validated ischemic wound model, Sprague-Dawley rats were divided into four groups for daily treatment: HBOT, N-acetylcysteine (NAC), HBO and NAC, and control (normoxia at sea level). High levels of inducible nitric oxide synthase (iNOS), gp91-phox, and 3-nitrotyrosine were detected in ischemic wounds, indicating high-oxidant stress. HBOT not only increased antioxidant enzyme expression, such as Cu/Zn-superoxide dismutase, catalase, and glutathione peroxidase, but also significantly decreased pro-oxidant enzyme levels, such as iNOS and gp91-phox, thereby decreasing net oxygen radical production by means of negative feedback. This effect was blocked by NAC treatment in ischemic wounds. HBO-treated ischemic wounds also manifested reduced phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinase, and c-Jun, indicating downregulation of mitogen-activated protein kinases (MAPKs). Furthermore, HBOT decreased the expression of several MMPs while simultaneously increasing tissue inhibitor of MMP (tissue inhibitor of metalloproteinase 2). These results indicate that HBOT acts via the ROS/MAPK/MMP signaling axis to reduce tissue degeneration and improve ischemic wound healing.


Oxygen uptake and heart rate kinetics after different types of resistance exercise.
Oxygen uptake (VO2) and heart rate (HR) kinetics after exercise are important indicators of fitness and cardiovascular health. However, these variables have been little investigated in resistance exercise (RE). The current study compared post-exercise kinetics of VO2 and the HR among different types of REs. The study included 14 males (age: 26.5±5.4 years, body mass: 80.1±11.4 kg, body height: 1.77±0.07 m, fat content: 11.3±4.6%) with RE experience. Dynamic muscle strength was measured using one repetition maximum (1RM) with regard to the half-squat, bench press, pull-down, and triceps pushdown exercises. The participants performed a maximum number of repetitions at 80% of 1RM for each exercise, separated by a recovery period of 60 minutes. VO2 was measured using ergospirometry. VO2 and HR kinetics were assessed using the time constant of the recovery curves, and excess oxygen consumption (EPOC) was calculated afterward. Significant differences were not observed across the exercises with regard to VO2 kinetics. However, the half-squat exercise elicited a greater EPOC than the bench press and triceps pushdown exercises (p<.05). HR kinetics was slower for the half-squat exercise than for the other exercises (p<.05). These findings confirm that the type of RE influences both the cardiac autonomic response post-exercise and EPOC, but not VO2 kinetics.


EVOLUTION OF SOCIAL BEHAVIOR IN A RESOURCE-RICH, STRUCTURED ENVIRONMENT: SELECTION EXPERIMENTS WITH MEDAKA (ORYZIAS LATIPES).
Schooling and aggression in fish are known to be partially inherited traits. Their genetic relationship to growth rate and to each other is, however, not fully understood. In this study we present evidence that schooling, social tolerance, and agonistic behavior in medaka (Oryzias latipes) are altered as an indirect result of selection on growth in two environments that differed in the intensity of social interactions required to obtain access to food. In the high interaction environment food was provided to excess inside a floating cork ring, which limited access to the food and allowed fish to attempt to monopolize it. In the low interaction environment the same amount of food was spread over the container's surface. After two generations of selection on growth the correlation of agonistic behavior and mean growth of broods was negative in the line selected for fast growth, when selection took place in a high interaction environment, but not when it took place in a low interaction environment. School cohesion was higher in the lines selected for fast growth than in those selected for slow growth when selection and rearing environments were both the same, either high or low interaction, but not when they were different. The correlation of social tolerance with growth was significantly more positive in the line selected for fast growth than in that selected for slow growth, but only when selection took place under high social interaction. It appears from these experiments that when resources are aggregated, but unlimited in quantity, competition favors individuals that avoid wasting time and energy on unnecessary and ultimately futile attempts to monopolize food and that also exhibit higher tolerance of nearby conspecifics. The results are interpreted in terms of a hypothesized stimulus-response threshold level for agonistic responses to conspecifics. We suggest that this threshold, which is altered by selection on growth, could provide a common causal (genetic) link between growth and the observed aspects of social behavior. By combining the probabilities from the separate behavioral experiments to obtain an overall significance of our hypothesis we conclude that the probability of no change in threshold is in fact low (P < 0.01).


Prevalence of hepatitis B and hepatitis C in an orthopaedics and traumatology ward.
The prevalence of hepatitis C (HCV) was studied in the operative practice of one surgeon for a period of 18 months (1/1/98-31/6/99). Patients were also tested for measurement of liver enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatitis B virus surface antigen (HbsAg). Out of a total of 911 consecutive patients, 37 (4.06%) were found to have anti-HCV antibodies, using a second-generation screening assay, and 10 (1.09%) to have anti-HBV antibodies. None of the patients (0%) had both anti-HBV antibodies and anti-HCV antibodies. Ten and 21 patients positive for HCV (27% and 56%) were found to have high AST and ALT levels, respectively; 1 and 1 patients positive for HBV (10% and 10%) were found to have high AST and ALT levels, respectively. The authors demonstrated the prevalence of HCV and HBV infection or previous exposure to be higher in the trauma patients (6.6%) who required orthopaedic surgery than in the elective orthopaedic patients (3.3%), and the need for full screening without risk factors. All values for p were calculated using Yates's corrected X2 or Student's t test.


Development of methylthiosemicarbazones as new reversible monoamine oxidase-B inhibitors for the treatment of Parkinson's disease.
Selective monoamine oxidase-B (MAO-B) inhibition is an attractive subject for the treatment of Parkinson's disease (PD). In the current study, we synthesized some selected derivatives of methylthiosemicarbazones and investigated their MAOs and acetylcholinesterase (AChE) inhibitory activities. Among the series synthesized, compounds SM5, SM4, and SM9 most inhibited MAO-B with IC50 values of 5.48, 7.06, and 8.03 µM, respectively. All compounds tested weakly inhibited MAO-A at 10 µM with the residual activities of >50%. Compound SM5 had the highest selectivity index (SI) value for MAO-B (>7.30), followed by SM4 (>5.67). Kinetic experiments revealed that SM5 competitively inhibited MAO-B, with a mean Ki value of 2.39 ± 0.15 µM. Reversibility experiments showed that SM5 reversibly inhibited MAO-B, and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays revealed that SM5 was not toxic to Vero cells (IC50 = 198.96 µg/mL). The SM5/MAO-B interaction was ascertained by molecular docking and dynamics studies. The study shows that SM5 competitively inhibits MAO-B in a reversible, moderate selective manner, and that it is non-toxic to Vero cells.Communicated by Ramaswamy H. Sarma.


Ceramide-Induced Lamellar Gel Phases in Fluid Cell Lipid Extracts.
The effects of increasing amounts of palmitoylceramide (pCer) on human red blood cell lipid membranes have been studied using atomic force microscopy of supported lipid bilayers, in both imaging (bilayer thickness) and force-spectroscopy (nanomechanical resistance) modes. Membranes appeared homogeneous with pCer concentrations up to 10 mol % because of the high concentration of cholesterol (Chol) present in the membrane (∼45 mol %). However, the presence of pCer at 30 mol % gave rise to a clearly distinguishable segregated phase with a nanomechanical resistance 7-fold higher than the continuous phase. These experiments were validated using differential scanning calorimetry. Furthermore, Chol depletion of the bilayers caused lipid domain generation in the originally homogeneous samples, and Chol-depleted domain stiffness significantly increased with higher amounts of pCer. These results point to the possibility of different kinds of transient and noncompositionally constant, complex gel-like phases present in RBC lipid membranes rich in both pCer and Chol, in contrast to the widespread opinion about the displacements between pCer-enriched "gel-like" domains and liquid-ordered "raft-like" Chol-enriched phases. Changes in the biophysical properties of these complex gel-like phases governed by local modulation of pCer:Chol ratios could be a cell mechanism for fine-tuning the properties of membranes as required.


Leptin Resistance in the Ovary of Obese Mice is Associated with Profound Changes in the Transcriptome of Cumulus Cells.
Obesity is associated with infertility, decreased ovarian performance and lipotoxicity. However, little is known about the aetiology of these reproductive impairments. Here, we hypothesise that the majority of changes in ovarian physiology in diet-induced obesity (DIO) are a consequence of transcriptional changes downstream of altered leptin signalling. Therefore, we investigated the extent to which leptin signalling is altered in the ovary upon obesity with particular emphasis on effects on cumulus cells (CCs), the intimate functional companions of the oocyte. Furthermore, we used the pharmacological hyperleptinemic (LEPT) mouse model to compare transcriptional profiles to DIO. Mice were subjected to DIO for 4 and 16 weeks (wk) and leptin treatment for 16 days, to study effects in the ovary in components of leptin signalling at the transcript and protein levels, using Western blot, Real-time PCR and immunostaining. Furthermore, we used low-cell RNA sequencing to characterise changes in the transcriptome of CCs in these models. In the DIO model, obesity led to establishment of ovarian leptin resistance after 16 wk high fat diet (HFD), as evidenced by increases in the feedback regulator suppressor of cytokine signalling 3 (SOCS3) and decreases in the positive effectors phosphorylation of tyrosine 985 of leptin receptor (ObRb-pTyr985) and Janus kinase 2 (pJAK2). Transcriptome analysis of the CCs revealed a complex response to DIO, with large numbers and distinct sets of genes deregulated at early and late stages of obesity; in addition, there was a striking correlation between body weight and global transcriptome profile of CCs. Further analysis indicated that the transcriptome profile in 4 wk HFD CCs resembled that of LEPT CCs, in the upregulation of cellular trafficking and impairment in cytoskeleton organisation. Conversely, after 16 wk HFD CCs showed expression changes indicative of augmented inflammatory responses, cell morphogenesis, and decreased metabolism and transport, mainly as a consequence of the physiological changes of obesity. Obesity leads to ovarian leptin resistance and major time-dependent changes in gene expression in CCs, which in early obesity may be caused by increased leptin signalling in the ovary, whereas in late obesity are likely to be a consequence of metabolic changes taking place in the obese mother.


Reversible denaturation of thermophilic malate dehydrogenase by guanidine hydrochloride and acid.
Thermophilic malate dehydrogenase [L-malate:NAD+ oxidoreductase, EC 126.96.36.199] was denatured at pH 2.0 with complete loss of enzyme activity but without dissociation to monomers, suggesting the presence of strong intersubunit contact. On the other hand, the enzyme was completely denatured and dissociated to monomers in the presence of 5 M GdnHCl. Inactivation and denaturation of the enzyme by acid and GdnHCl were reversible. Upon dilution of the denaturants, the inactivated enzyme regained enzyme activity and the native structure with high yield (80-90%). Kinetic analyses of reactivation of the enzyme denatured by GdnHCl and by acid revealed that the reaction obeyed first-order kinetics. The rate constant and Arrhenius activation energy of the reactivation of the acid-inactivated enzyme were almost the same as those of the enzyme inactivated by GdnHCl. These results suggest that the rate-limiting steps in the reactivation processes of the enzyme denatured by GdnHCl and by acid are the same and that a conformational change of the inactive dimer to active dimer is the rate-limiting step in the reactivation reaction.


Post Myocardial Infarction Ventricular Septal Rupture Revealed By Acute Liver Failure Symptoms: A Case Report.
The mechanical complications of acute myocardial infarction (AMI) still kill despite the evolution of medicine. Early diagnosis and adequate management are necessary to improve the prognosis, and this requires first, a good clinical examination that should raise the suspicion of a mechanical complication, then the echocardiography is performed to confirm the diagnosis. We present a case of a 64-year-old patient admitted to the emergency room for jaundice with delayed ST-segment elevation myocardial infarction (STEMI). Physical examination revealed signs of right heart failure, which led us to associate jaundice with signs of acute liver failure secondary to right heart failure. Echocardiography confirmed the diagnosis of a ventricular septal rupture (VSR) with left-right shunt, and a significant dilation of the right ventricle. The patient underwent surgical closure of the VSR with fatal evolution. VSR is a rare life-threatening mechanical complication of AMI. The clinical signs depend on the left-right shunt and the onset of heart failure, which are 2 major determinants of the therapeutic strategy and the timing of the surgery. Despite surgical closure of the VSR, the mortality remains high, but the prognosis is better in patients treated with surgery than in patients who are treated medically only. The clinical presentation of VSR may differ from a patient to another. Good clinical sense and echocardiography are essential to set early diagnosis, and thus decide on the adequate management at the right time.


Downregulation of miR-125b-5p and Its Prospective Molecular Mechanism in Lung Squamous Cell Carcinoma.
Background: To explore the clinical significance of miR-125b-5p and its potential mechanisms in lung squamous cell carcinoma (LUSC). Materials and Methods: An integrated analysis of data from in-house quantitative real-time polymerase chain reaction (qRT-PCR), microRNA-sequencing, and microarray assays to appraise the expression level of miR-125b-5p in LUSC tissues compared to adjacent noncancerous controls. The authors identified the candidate targets of miR-125b-5p and conducted functional analysis using computational biology strategies from gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, disease ontology (DO), and protein-protein interaction (PPI) network analyses to investigate the prospective mechanisms. Results: According to qRT-PCR results, the expression level of miR-125b-5p was markedly decreased in LUSC tissues compared to noncancerous control tissues. Receiver operating characteristic and summary receiver operating characteristic analyses showed that miR-125b-5p had good specificity and sensitivity for distinguishing LUSC tissue from noncancerous lung tissue. The standard mean difference revealed that men and women with lower expression levels of miR-125b-5p may have a higher risk for LUSC. KEGG analysis and DO analysis intimated that target genes were evidently enriched in pyrimidine metabolism and pancreatic carcinoma. The PPI network of the top assembled KEGG pathway indicated that RRM2, UMPS, UCK2, and CTPS1 were regarded as crucial target genes for miR-125b-5p, and RRM2 was eventually deemed a key target. Conclusions: The authors' findings implicate a low expression level of miR-125b-5p in LUSC. A tumor-suppressive role of miR-125b-5p is proposed, based on its effects on LUSC tumor growth, clinical stage progression, and lymph node metastasis.


Speaking rate consistency in native and non-native speakers of English.
Non-native speech differs from native speech in multiple ways. Previous research has described segmental and suprasegmental differences between native and non-native speech in terms of group averages. For example, average speaking rate for non-natives is slower than for natives. However, it is unknown whether non-native speech is also more variable than native speech. This study introduces a method of comparing rate change across utterances, demonstrating that non-native speaking rate is more variable than native speech. These results suggest that future work examining non-native speech perception and production should investigate both mean differences and variability in the signal.


Hydrogen Attenuates Thyroid Hormone-Induced Cardiac Hypertrophy in Rats by regulating angiotensin II type 1 receptor and NADPH oxidase 2 mediated oxidative stress.
Cardiac hypertrophy occurs as a result of high levels of thyroid hormone, which may contribute to heart failure and is closely related to oxidative stress. Hydrogen is a good antioxidant. In this study, we found that intragastric levothyroxine administration for two weeks caused obvious cardiac hypertrophy without reduced systolic function. Additionally, hydrogen inhalation ameliorated the levothyroxine-induced metabolic increase and cardiac hypertrophy in rats. Serum brain natriuretic peptide expression was also attenuated by hydrogen treatment. However, hydrogen had no significant effect on levothyroxine -induced serum troponin I and serum thyroid hormone changes. Hydrogen treatment also reduced the levothyroxine-induced increase in cardiac malondialdehyde, 8-hydroxy-2-deoxyguanosine and serum hydrogen peroxide levels and upregulated superoxide dismutase and glutathione peroxidase activity. Additionally, western blotting results showed that hydrogen inhalation inhibited the expression of cardiac nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), angiotensin II type 1 receptor, sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospho-phospholamban and α-myosin heavy chain proteins. In conclusion, the present study revealed a protective effect of hydrogen on levothyroxine -induced cardiac hypertrophy by regulating angiotensin II type 1 receptors and NOX2-mediated oxidative stress in rats.


HLA-B locus sequence-based typing.
We describe an approach for HLA-B high-resolution typing. A single locus-specific amplification generates a 1-kb fragment useful for direct sequencing. Four internal primers are necessary for exon 2 and 3 cycle-sequencing in both directions. Fluorescent dye-labelled nucleotides are incorporated during cycle-sequencing and reaction products are analyzed in an automated DNA sequencer. At present, software programs allow automatic assignment of exon 2 only; analysis of exon 3 is not automatic. In the future, the development of more sophisticated software will improve allele assignment. The approach described in this work offers a precise and efficient identification of known allele sequences and at the same time can differentiate new alleles. Furthermore, it may be applied as a model for the development of similar molecular typing approaches for other polymorphic HLA loci.


Development of a student nurses' clinic for homeless men.
A nursing clinic for homeless men was developed by a faculty member and her senior community health nursing students in a city mission over a 2.5-year period. The development of this clinic and a conceptualization of their nursing roles are described. Nursing care focused on promoting access to primary care through screening and referral and through nursing interventions of education, counseling, advocacy, and collaboration. Because the Student Nurses' Clinic was instrumental in clarifying and conceptualizing what nurses can do to promote primary care, mission administrators and staff gained insights about nursing and are better prepared to plan programs for the health care needs of the homeless men-the "guests" at the mission.


Chloroplast biogenesis: the use of mutants to study the etioplast-chloroplast transition.
In angiosperm plants, the etioplast-chloroplast transition is light-dependent. A key factor in this process is the protochlorophyllide oxidoreductase A (PORA), which catalyzes the light-induced reduction of protochlorophyllide to chlorophyllide. The import pathway of the precursor protein prePORA into chloroplasts was analyzed in vivo and in vitro by using homozygous loss-of-function mutants in genes coding for chlorophyllide a oxygenase (CAO) or for members of the outer-envelope solute-channel protein family of 16 kDa (OEP16), both of which have been implied to be key factors for the import of prePORA. Our in vivo analyses show that cao or oep16 mutants contain a normally structured prolamellar body that contains the protochlorophyllide holochrome. Furthermore, etioplasts from cao and oep16 mutants contain PORA protein as found by mass spectrometry. Our data demonstrate that both CAO and OEP16 are dispensable for chloroplast biogenesis and play no central role in the import of prePORA in vivo and in vitro as further indicated by protein import studies.


Plasma beta-endorphin, beta-lipotropin and corticotropin in polycystic ovarian disease.
In 9 women with polycystic ovarian disease (PCOD) and in 11 control subjects at the follicular phase of the normal cycle, blood samples were collected at 15-min intervals during a 2 h period of bed rest for the assay of beta-endorphin, beta-lipotropin, corticotropin, cortisol and prolactin. During the study period, the plasma levels of these hormones decreased more significantly in the PCOD than in the control group, suggesting that the PCOD patients had a more significant stress response to the puncture of the vein than the control subjects. The second hour of the study period was considered to represent resting levels of hormones. The mean resting levels (+/- S.E.) of the hormones between the PCOD and control groups, respectively, were as follows: beta-E, 2.0 +/- 0.4 vs. 1.1 +/- 0.1 pmol/l, p less than 0.05; beta-LPH, 3.4 +/- 0.6 vs. 2.1 +/- 0.5 pmol/l, N.S.; corticotropin, 2.0 +/- 0.3 vs. 1.1 +/- 0.5 pmol/l, p less than 0.05; cortisol, 176 +/- 24 vs. 128 +/- 16, N.S.; and prolactin; 3.9 +/- 0.6 vs. 5.6 +/- 1.2 ng/ml, N.S. These results confirm the previous findings on increased circulating levels of beta-E in PCOD. A concomitant increase of the plasma level of corticotropin suggests that the basal secretion of both beta-E and corticotropin from the anterior pituitary gland is increased in women with PCOD.


Barriers and facilitators to linkage to ART in primary care: a qualitative study of patients and providers in Blantyre, Malawi.
Linkage from HIV testing and counselling (HTC) to initiation of antiretroviral therapy (ART) is suboptimal in many national programmes in sub-Saharan Africa, leading to delayed initiation of ART and increased risk of death. Reasons for failure of linkage are poorly understood. Semi-structured qualitative interviews were undertaken with health providers and HIV-positive primary care patients as part of a prospective cohort study at primary health centres in Blantyre, Malawi. Patients successful and unsuccessful in linking to ART were included. Progression through the HIV care pathway was strongly influenced by socio-cultural norms, particularly around the perceived need to regain respect lost during a period of visibly declining health. Capacity to call upon the support of networks of families, friends and employers was a key determinant of successful progression. Over-busy clinics, non-functioning laboratories and unsuitable tools used for ART eligibility assessment (WHO clinical staging system and centralized CD4 count measurement) were important health systems determinants of drop-out. Key interventions that could rapidly improve linkage include guarantee of same-day, same-clinic ART eligibility assessments; utilization of the support offered by peer-groups and community health workers; and integration of HTC and ART programmes.


[Factors associated with slow walking speed in older adults of a district in Lima, Peru].
To determine the factors associated with slow walking speed in older adults living in a district of Lima, Peru. Analysis of secondary data. Adults older than 60 years were included in the study, while adults with physical conditions who did not allow the evaluation of the walking speed were excluded. The dependent variable was slow walking speed (less than 1 m/s), and the independent variables were sociodemographic, clinical, and geriatric data. Raw and adjusted prevalence ratios (PR) were calculated with 95% confidence intervals (95% CI). The study sample included 416 older adults aged 60 to 99 years, and 41% of the participants met the slow walking speed criterion. The factors associated with slow walking speed in this sample were female gender (PR, 1.45; 95% CI, 1.13-1.88), age > 70 years (PR, 1.73; 95% CI, 1.30- 2.30), lower level of education (PR, 2.07, 95% CI, 1.20-3.55), social-familial problems (PR, 1.66; 95% CI, 1.08-2.54), diabetes mellitus (PR, 1.35; 95% CI, 1.01-1.80), and depression (PR, 1.41; 95% CI, 1.02-1.95). The modifiable factors associated with slow walking speed in older adults included clinical and social-familial problems, and these factors are susceptible to interventions from the early stages of life.


A study of transgender adults and their non-transgender siblings on demographic characteristics, social support, and experiences of violence.
A national sample of 295 transgender adults and their nontransgender siblings were surveyed about demographics, perceptions of social support, and violence, harassment, and discrimination. Transwomen were older than the other 4 groups. Transwomen, transmen, and genderqueers were more highly educated than nontransgender sisters and nontransgender brothers, but did not have a corresponding higher income. Other demographic differences between groups were found in religion, geographic mobility, relationship status, and sexual orientation. Transgender people were more likely to experience harassment and discrimination than nontransgender sisters and nontransgender brothers. All transgender people perceived less social support from family than nontransgender sisters. This is the first study to compare trans people to nontrans siblings as a comparison group.


Safety of Silicone Oil Removal in Cases of Gunshot Perforating Eye Injuries.
To evaluate the feasibility and safety of silicone oil (SO) removal in cases of gunshot perforating eye injuries (PEI). A retrospective, consecutive, interventional study from medical records regarding cases of gunshot PEI during the periods of Egyptian political instability (January 2011 until December 2013). The main outcomes were to evaluate the feasibility of SO removal in cases of gunshot PEI and management of retinal detachment (RD) after SO removal in such cases. One hundred ninety-six eyes of 193 patients were reviewed. SO was removed in 72 eyes of 70 patients (36.7%). After SO removal, five eyes (6.9%) developed RD. One case refused any other intervention. RD in the remaining four cases was treated with revision surgery and SO reinjection. The retina remained stable throughout follow-up. None of the eyes developed phthisis bulbi after SO removal. Mean follow-up after SO removal was 10.86 months (range: 3 months to 30 months). Mean follow-up after management of RD after SO removal was 17.7 months (range: 13 months to 21 months). Patients aged younger than 20 years were associated with extensive fibrous proliferation, which might affect the safety profile of SO removal in cases of gunshot PEI. Rate of RD after SO removal in cases of apparent retinal stability and localized fibrous proliferation was 6.9%. Retinal detachment after SO removal in such cases can be treated with revision surgery and SO reinjection. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:242-250.].


Experimental radiation-induced heart disease: past, present, and future.
Radiation-induced heart disease (RIHD) is a serious side effect of radiotherapy for intrathoracic and chest wall tumors. The threshold dose for development of clinically significant RIHD is believed to be lower than previously assumed. Therefore, research into mechanisms of RIHD has gained substantial momentum. RIHD becomes clinically apparent ten to fifteen years after radiation exposure. Chronic manifestations of RIHD include accelerated atherosclerosis, cardiomyopathy, and valve abnormalities. Reducing exposure of the heart during radiotherapy is the only known method of preventing RIHD, and there are no approaches to reverse RIHD once it occurs. We use a combination of pharmacological and genetic animal models to determine biological mechanisms of RIHD. Major technological advances in small animal research have made this type of study more valuable. The long-term goal of this work is to identify targets for intervention in RIHD, thereby enhancing the efficacy and safety of thoracic radiotherapy.


Digesting the Impact of Diet on Irritable Bowel Syndrome (IBS): Exploring Solutions for Controlling IBS.
Irritable bowel syndrome (IBS) plagues nearly a fifth of the general population. It is a chronic illness that can significantly lower quality of life (QoL) and work productivity. The relationship between diet and the functional gastrointestinal (GI) symptoms present in IBS is gaining more and more attention. In addition to being a factor in the pathophysiology of IBS, diet also has a significant impact on symptoms and overall well-being. Recent research has also shown that short-chain fermentable carbohydrates increase colonic gas production and small intestine water volume, which in turn causes functional GI symptoms in those with visceral hypersensitivity. This review article has consolidated various studies highlighting the association between certain foods and the pathophysiology of IBS. It has also talked about how restricting certain food items from the diet of affected individuals can relieve symptoms and in some cases can be more effective than pharmacotherapy. Although the low reduced fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) is a well-known method of treating IBS symptoms, over a third of individuals do not benefit from it. This article has also discussed the effectiveness and applicability of the LFD compared to other dietary therapies for the long-term management of IBS.


New 3D printed polymers in orthodontics: a scoping review.
The aim of this scoping review is to assess the application of new 3D printed polymeric materials in orthodontics, including polyamide-12 (PA-12) and Shape Memory Polymers (SMPs). A search for articles published until January 2023 was carried out using PubMed, Scopus, Web of Knowledge, Lilacs, Opengrey, Embase and Cochrane Library databases and by applying the search terms (orthodontic* OR paediatric* OR paedodontic*) AND ("3D printed" OR "three-dimensional printed") AND (polymer* OR material* OR resin* OR technopolymer*). Additional records were also screened through hand or electronic search. No restriction in terms of language or publication period was applied. Due to their mechanical, aesthetic and biocompatibility characteristics, PA12 and SMPs can be used in orthodontic practice. However, additional studies should be performed to evaluate the clinical efficiency of these recent materials.


Acute and chronic changes in the control of breathing in a rat model of bronchopulmonary dysplasia.
Infants born very prematurely (<28 wk gestation) have immature lungs and often require supplemental oxygen. However, long-term hyperoxia exposure can arrest lung development, leading to bronchopulmonary dysplasia (BPD), which increases acute and long-term respiratory morbidity and mortality. The neural mechanisms controlling breathing are highly plastic during development. Whether the ventilatory control system adapts to pulmonary disease associated with hyperoxia exposure in infancy remains unclear. Here, we assessed potential age-dependent adaptations in the control of breathing in an established rat model of BPD associated with hyperoxia. Hyperoxia exposure ( FIO2 ; 0.9 from 0 to 10 days of life) led to a BPD-like lung phenotype, including sustained reductions in alveolar surface area and counts, and modest increases in airway resistance. Hyperoxia exposure also led to chronic increases in room air and acute hypoxic minute ventilation (V̇e) and age-dependent changes in breath-to-breath variability. Hyperoxia-exposed rats had normal oxygen saturation ( SpO2 ) in room air but greater reductions in SpO2 during acute hypoxia (12% O2) that were likely due to lung injury. Moreover, acute ventilatory sensitivity was reduced at P12 to P14. Perinatal hyperoxia led to greater glial fibrillary acidic protein expression and an increase in neuron counts within six of eight or one of eight key brainstem regions, respectively, controlling breathing, suggesting astrocytic expansion. In conclusion, perinatal hyperoxia in rats induced a BPD-like phenotype and age-dependent adaptations in V̇e that may be mediated through changes to the neural architecture of the ventilatory control system. Our results suggest chronically altered ventilatory control in BPD.


[Ultrasound in oncology, current perspectives].
In tumor diagnostics, especially in the staging diagnostic of tumor patients, ultrasound is predominantly an additive method in the age of modern imaging (CT/MRT/PET-CT), because of the limitation by interobserver variability and poor sound conditions. The aim of this thesis is to elaborate specific oncological questions on the sonography and to describe the requirements for sonography and the importance of the method in the diagnosis of tumor diseases in the age of CT, MRT and PET-CT. In general, the requirements on the sonography must be differentiated between primary diagnosis, staging diagnostic, treatment response, and tumor aftercare. This paper will present these in the context of the current guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and the Working Community of the Scientific Medical Societies as well as the requirements in clinical practice.


Thermally induced ribonucleic acid degradation and leakage of substances from the metabolic pool in Staphylococcus aureus.
The effects of temperatures of 50 and 60 C on log-phase and stationary-phase cell suspensions of Staphylococcus aureus are described. There is a leakage of free amino acids, protein, and 260 mmu-absorbing material from both types of cell suspension, and membrane damage, as measured by the intracellular penetration of 8-anilino-1-naphthalene-sulfonic acid, may be partially related to this leakage. Ribonucleic acid (RNA) degradation at any one temperature is virtually the same for both types of cell suspension, proceeding initially at a more rapid rate at 60 C than at 50 C. However, at the lower temperature, there is a secondary breakdown of RNA, which may be the result of enzyme action on a particularly labile RNA fraction. With stationary-phase cell suspensions heated in 1 m sucrose, there is a more rapid degradation of RNA at 60 C than with cells in water. The results are discussed in relation to the biochemical effects of moist heat on the organism.


Effects of nicorandil on monocrotaline-induced pulmonary arterial hypertension in rats.
We investigated whether nicorandil might prevent and reverse monocrotaline (MCT)-induced pulmonary arterial hypertension. Rats were injected with 50 mg/kg of MCT subcutaneously and randomized to either 7.5 mg/kg/d of nicorandil in drinking water or placebo for 3 weeks. Animals that were treated with MCT and survived for 3 weeks were assigned to either nicorandil or placebo. Nicorandil markedly attenuated pulmonary arterial hypertension with severe structural remodeling of the pulmonary vessels. The survival rate at 3 weeks after treatment was significantly increased in the nicorandil group compared with the placebo group (73% versus 39%, P<0.05). In the placebo group, endothelial nitric oxide synthase (eNOS) protein was significantly decreased, the numbers of the CD45-positive cells and those of the proliferating cell nuclear antigen-positive cells were increased in the lung tissue, and P-selectin was intensely expressed on the endothelium of the pulmonary arteries. These features were prevented by nicorandil. Late treatment with nicorandil did not palliate established pulmonary arterial hypertension nor improved survival. Thus, nicorandil inhibited development of MCT-induced pulmonary arterial hypertension but failed to reverse it. These effects were associated with marked up-regulation of diminished lung eNOS protein along with improvement of pulmonary vascular endothelial activation and anti-inflammatory and anti-proliferative effects in the lung tissue.


An explanatory model of the dental care utilization of low-income children.
Factors related to the utilization of dental care by 5- to 11-year-old children from low-income households were investigated using a comprehensive multivariate model that assessed the contribution of structure, history, cognition, and expectations. The influence of dentist-patient interactions, psychosocial and health beliefs, particularly fear of the dentist, on utilization were investigated. Children were chosen randomly from public schools, and 895 mothers were surveyed and their children were interviewed in the home. Utilization was studied during the 1991-1992 school year, including a 6-month follow-up period after the interview. The overall utilization rate was 63.2%, and the rate for nonemergent (preventive) visits was 59.9%. Utilization was unrelated to actual oral health status. Race and years the guardian lived in the United States were predictive of an episode of care. Preventive medical visits and perceived need were strong predictors of a visit to the dentist, as were beliefs in the efficacy of dental care. Mothers who were satisfied with their own care and oral health and whose children were covered by insurance were more likely to utilize children's dental care. In contrast, child dental fear and absences from school for family problems were associated with lower rates of utilization. Mutable factors that govern the use of care in this population were identified. These findings have implications for the design of dental care delivery systems for children and their families.


Adaptive redundant lifting wavelet transform based on fitting for fault feature extraction of roller bearings.
A least square method based on data fitting is proposed to construct a new lifting wavelet, together with the nonlinear idea and redundant algorithm, the adaptive redundant lifting transform based on fitting is firstly stated in this paper. By variable combination selections of basis function, sample number and dimension of basis function, a total of nine wavelets with different characteristics are constructed, which are respectively adopted to perform redundant lifting wavelet transforms on low-frequency approximate signals at each layer. Then the normalized l(P) norms of the new node-signal obtained through decomposition are calculated to adaptively determine the optimal wavelet for the decomposed approximate signal. Next, the original signal is taken for subsection power spectrum analysis to choose the node-signal for single branch reconstruction and demodulation. Experiment signals and engineering signals are respectively used to verify the above method and the results show that bearing faults can be diagnosed more effectively by the method presented here than by both spectrum analysis and demodulation analysis. Meanwhile, compared with the symmetrical wavelets constructed with Lagrange interpolation algorithm, the asymmetrical wavelets constructed based on data fitting are more suitable in feature extraction of fault signal of roller bearings.


Demography and life history of Thomas langurs (Presbytis thomasi).
Life history data from wild primate populations are necessary to explain variation in primate social systems and explain differences between primates and other mammals. Here we report life history data from a 12.5-year study on wild Thomas langurs. Mean age at first reproduction was 5.4 years and the sex ratio at birth was even. The mean interbirth interval (IBI) after a surviving infant was 26.8 mo, after nonsurviving infants 17.7 mo, and combined 22.0 mo. Mean annual birth rate of adult females was 0.44, while reaching a peak at 6 years of age and showing no decrease with age. Mortality was highest during the first year of life (48.0% for males and 43.0% for females) and consistently higher for males than females. The oldest female observed during the study was estimated to be 20 years of age, whereas the oldest male disappeared at age 13 years, indicating that males die at a much earlier age than females. A Leslie matrix based on these estimates yielded a growth rate of 1.01, which is comparable to the nonsignificant increase in density indicated by our long-term field data. A comparison with life history data for sympatric frugivorous primates suggests that folivory might be associated with faster life history.


Meckel Gruber syndrome: occurrence in non-consanguineous marriages.
Meckel Gruber syndrome is an uncommon, lethal, autosomal recessive disorder, associated consistently with polycystic kidneys, posterior encephalocoele and polydactly. We report three cases in non-consanguineous marriages, suggesting that the single gene defect occurs more commonly in non-consanguineous marriages than mutant genes associated with other autosomal recessive disorders that are usually related with consanguineous marriages. The usefulness of prenatal diagnosis is discussed.


Functional Connectivity Density, Local Brain Spontaneous Activity, and Their Coupling Strengths in Patients With Borderline Personality Disorder.
In this study, combining degree centrality (DC) and fractional amplitude of low frequency fluctuation (fALFF) analyses of resting state (rs)-functional magnetic resonance imaging (fMRI) data, we aimed to explore functional connectivity density, local brain spontaneous activity, and their coupling strengths in borderline personality disorder (BPD). Forty-three BPD patients and 39 demographically-matched controls underwent rs-fMRI after completing a series of psychological tests. Two-sample t-tests were performed to compare DC and fALFF between these two groups. Across-voxel correlation analysis was conducted to assess DC-fALFF coupling strengths in each group. Imaging parameters and psychological variables were correlated by Pearson correlation analysis in the BPD group. Altered DC and fALFF values in the BPD group, compared with the control group, were distributed mainly in default mode network (DMN), and DC-fALFF coupling strengths were decreased in the left middle temporal gyrus (MTG) and right precuneus in the BPD group. Additionally, insecure attachment scores correlated positively with left precuneus DC and negatively with fALFF of the right posterior cingulate cortex (PCC) in the BPD group. These altered DC and fALFF findings indicate that the BPD patients had disturbed functional connectivity density and local spontaneous activity in the DMN compared with control subjects. Their decreased connectivity-amplitude coupling suggests that the left MTG and right precuneus may be functional impairment hubs in BPD. Disturbed rs function in the left precuneus and right PCC might underlie insecure attachment in BPD.


Characterization of free and bound volatile compounds in six Ribes nigrum L. blackcurrant cultivars.
This study investigated the profiles of free and bound volatile compounds of six currant cultivars grown in China. Results showed that 166 free and 111 bound volatiles were found in these cultivars with esters and terpenoids as the major volatiles. Additionally, 10 hydroxy esters were detected in these cultivars for the first time. Floral, fruity, and sweet flavors appeared to be the feature aroma in these cultivars, which resulted from the contribution of 17 volatiles. Principal component analysis indicated the cultivar "Fertodi", "Risagar" and "Liangye" had the similar profiles of free and bound volatile compounds, whereas the cultivar "Brodtrop" and "Yadrionaya" exhibited the similarity on their free and bound volatiles. The cultivar "Sofya" showed a different volatile composition. Cluster analysis revealed the cultivar "Fertodi", "Risagar", and "Liangye" had the similar profiles of free and bound volatile compounds, whereas the similar free and bound volatile compositions were observed in the cultivar "Sofya" and "Yadrionaya". This study could provide useful information on quality control of commercial currant products.


Ten pearls every dermatologist should know about the appropriate use of relaxers.
Chemical relaxers are products marketed to straighten the hair and have been principally used by African Americans since the early twentieth century. They contain alkaline agents that break and reform hydrogen and disulfide bonds, leaving hair permanently straightened. Relaxers cause loss of tensile strength and increased fragility of the hair shaft that lead to increased risk of hair breakage and thinning. When used improperly, they can also cause local irritant contact dermatitis and chemical burns to the scalp and hairline that can potentially lead to a scarring alopecia. After interviewing several cosmetology educators in the field and reviewing the literature, we generated a list of ten pearls that all dermatologists should know about relaxers to provide professional guidance to their patients.


A unique insertion in STARD9's motor domain regulates its stability.
STARD9 is a largely uncharacterized mitotic kinesin and putative cancer target that is critical for regulating pericentriolar material cohesion during bipolar spindle assembly. To begin to understand the mechanisms regulating STARD9 function and their importance to cell division, we took a multidisciplinary approach to define the cis and trans factors that regulate the stability of the STARD9 motor domain. We show that, unlike the other ∼50 mammalian kinesins, STARD9 contains an insertion in loop 12 of its motor domain (MD). Working with the STARD9-MD, we show that it is phosphorylated in mitosis by mitotic kinases that include Plk1. These phosphorylation events are important for targeting a pool of STARD9-MD for ubiquitination by the SCFβ-TrCP ubiquitin ligase and proteasome-dependent degradation. Of interest, overexpression of nonphosphorylatable/nondegradable STARD9-MD mutants leads to spindle assembly defects. Our results with STARD9-MD imply that in vivo the protein levels of full-length STARD9 could be regulated by Plk1 and SCFβ-TrCP to promote proper mitotic spindle assembly.


The Epidemiology of Pediatric Basketball Injuries Presenting to US Emergency Departments: 2011-2020.
The purpose of this study is to describe the national epidemiology of basketball-related injuries in children and adolescents presenting to US emergency departments (EDs) from 2011 to 2020 and to quantify the effect of the COVID-19 pandemic. The National Electronic Injury Surveillance System database was queried for cases of injury in persons aged 0 to 19 years related to product code 1205 (basketball and related equipment) presenting from January 1, 2011 to December 31, 2020. National injury estimates were calculated using National Electronic Injury Surveillance System-recommended weights and strata. The US Census data were used to determine the incidence of injury by age group and by sex. To quantify the effect of COVID-19, an interrupted time series analysis was performed using March 1, 2020 as the interrupting time point. The pre-COVID-19 trend was used to estimate the difference in injuries attributable to the COVID-19 pandemic. From 2011 to 2020, an estimated 3,210,953 (95% confidence interval = 2,655,812-3,788,094) visits were made to US EDs for basketball-related injuries in those aged younger than 20 years, corresponding to a mean annual incidence of 391 injuries per 100,000 population. The mean age of injury was 14.4 years (95% confidence interval = 14.3-14.5). Boys were more often injured than girls (76% vs 24% of all injuries, respectively). The foot was the most injured body part, accounting for 24% of injuries. Strains or sprains were the most common injury type (38% of injuries). During the COVID-19 pandemic, there were 155,638 fewer injuries than were expected based on pre-COVID-19 trends. During COVID-19, there were no significant differences in the proportions of injury types, body parts involved, sex, or age. Basketball remains a frequent cause of injury, especially in adolescents. The COVID-19 pandemic profoundly reduced the frequency of basketball-related injuries, but did not affect the type and body location of injuries presenting to the ED.


The nature of sleep in 10 bedridden elderly patients with disorders of consciousness in a Japanese hospital.
No previous study has satisfactorily clarified the nature of sleep in elderly bedridden people with disorders of consciousness (DOC). The objective of the present study was to clarify the sleep states of 10 elderly bedridden patients with DOC in a Japanese hospital to facilitate provision of evidence-based nursing care and appropriate adjustment of patients' environments. Nocturnal polysomnography recordings were analyzed according to the standard scoring criteria, and the patients' sleep stages and quality were investigated. Of the 10 patients, 9 showed slow wave sleep (SWS), 4 showed very high values for sleep efficiency (96-100%), and in 3 of these patients, the percentage of SWS was ≥ 20%. Furthermore, three of these four patients had 200 or more changes in sleep stage. Although the mechanism is unknown, the amount of SWS combined with the value of sleep efficiency suggests that the quality of sleep is poor in elderly bedridden patients with DOC. Further study is needed to determine better indicators of good sleep in this population.


Gastrointestinal endocrine cell hyperplasia in celiac disease: a selective proliferative process of serotonergic cells.
Untreated celiac disease is characterized by gastrointestinal endocrine cell hyperplasia (ECH). This study investigated the constitutive nature of the ECH. Ten duodenal biopsies showing villous atrophy from adult celiacs were evaluated against ten sex- and age-matched controls. The mean number of endocrine cells per unit length of mucosa in the celiacs was compared with the control group using the Student t test. These values, respectively, were as follows: Churukian-Schenk method, 52.4 versus 29.6 (P = 0.001); Fontana-Masson, 32.5 versus 18.4 (P = 0.016); chromogranin, 33.4 versus 23.6 (P = 0.017); serotonin, 44.7 versus 26.7 (P = 0.006); somatostatin, 5.0 versus 5.4 (P = 0.631); and gastrin, 0.37 versus 0.37 (P = 1.000). There was thus ECH as shown by the first four stains with, in some areas, the endocrine cells continuously abutting against each other to form linear profiles. With respect to specific hormonal products, only serotonin showed ECH. These results suggest that the ECH in celiac disease is not a haphazard process but, instead, a selective proliferation of certain endocrine cell types.


Effect of oral aminophylline on pulmonary function improvement and tolerability in different age groups of COPD patients.
Aminophylline therapy in elderly patients with COPD is rarely studied. This study attempted to explore the symptoms, pulmonary function improvement, and adverse events related to aminophylline therapy in COPD patients of different age groups. We designed a 10-week prospective study. Two groups of COPD patients were classified based on age (30 patients in group 1, 55 to 74 years old; 30 patients in group 2, 75 to 90 years old), with matched disease severity. After stopping all methylxanthines for 2 weeks in the washout period, therapy began with long-acting 225-mg aminophylline compounds bid po for 8 weeks. Pulmonary functions, respiratory symptoms, and laboratory examinations were checked at the initial visit and at every 4-week visit. After aminophylline therapy, the drug serum level showed no significant difference in either group (9.73 +/- 6.35 mg/dL [+/- SD] in group 1 and 7.82 +/- 6.68 mg/dL in group 2, p = 0.359). Improvements of FEV1 and FVC were noted in both groups; however, there was no significant difference. Peak expiratory flow rate (PEFR) was significantly improved in group 1 but not in group 2 (group 1, from 3.51 to 3.97 L/s, p < 0.05; group 2, from 2.78 to 3.08 L/s, p > 0.05). The degree of improvement in symptom scores was not different between the groups, except there was significantly less chest tightness in group 2 (from 0.79 +/- 0.74 to 0.40 +/- 0.50, p < 0.05). Electrolyte imbalance and arrhythmia did not appear in either group. Our study demonstrated that the safety and drug concentration of aminophylline at a standard dose are not different in the sixth to ninth decades of COPD patients. Younger patients have more improvement in PEFR than older patients; however, older COPD patients have more symptoms relief in chest tightness after aminophylline therapy.


Qualitative Content Analysis of Coworkers' Safety Reports of Unprofessional Behavior by Physicians and Advanced Practice Professionals.
The aims of the study were to develop a valid and reliable taxonomy of coworker reports of alleged unprofessional behavior by physicians and advanced practice professionals and determine the prevalence of reports describing particular types of unprofessional conduct. We conducted qualitative content analysis of coworker reports of alleged unprofessional behavior by physicians and advanced practice professionals to create a standardized taxonomy. We conducted a focus group of experts in medical professionalism to assess the taxonomy's face validity. We randomly selected 120 reports (20%) of the 590 total reports submitted through the medical center's safety event reporting system between June 2015 and September 2016 to measure interrater reliability of taxonomy codes and estimate the prevalence of reports describing particular types of conduct. The initial taxonomy contained 22 codes organized into the following four domains: competent medical care, clear and respectful communication, integrity, and responsibility. All 10 experts agreed that the four domains reflected essential elements of medical professionalism. Interrater reliabilities for all codes and domains had a κ value greater than the 0.60 threshold for good reliability. Most reports (60%, 95% confidence interval = 51%-69%) described disrespectful or offensive communication. Nine codes had a prevalence of less than 1% and were folded into their respective domains resulting in a final taxonomy composed of 13 codes. The final taxonomy represents a useful tool with demonstrated validity and reliability, opening the door for reliable analysis and systems to promote accountability and behavior change. Given the safety implications of unprofessional behavior, understanding the typology of coworker observations of unprofessional behavior may inform organization strategies to address this threat to patient safety.


A multicenter, parallel comparative study of the antihypertensive efficacy of once-daily lisinopril vs enalapril with 24-h ambulatory blood pressure monitoring in essential hypertension.
The aim of the study was to compare the antihypertensive efficacy of once-daily lisinopril vs enalapril both during normal daily activity and sleep, in mild-to-moderate essential hypertension. After a 4-week wash-out period, 34 patients (17 M, 17 F) aged 22 to 67 years were randomized in a multicenter, open, parallel fashion: 17 received lisinopril (10-20 mg) and 17 enalapril (10-20 mg) for a 12-week period. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed using an oscillometric non-invasive automated device at both the end of the 4-week drug-free baseline period and during the last week of treatment. With no differences in initial blood pressure (BP) between groups, both drugs significantly reduced office and ABPM values. Lisinopril tended to reduce BP in a greater extension than enalapril, but only the reduction of office systolic BP (SBP) (p = 0.0062), 24-h SBP load (P = 0.0182) and night time SBP load (P = 0.0316) reached statistical significance. We conclude that, in spite of a more prominent reduction of SBP by lisinopril, both drugs have a similar efficacy in reducing BP, assessed by both office and ABPM measurements.


Acute pancreatitis possibly due to arginine use: a case report.
Arginine has been used by millions of athletes over the past 20 years to enhance production of human growth hormone. The effects of arginine supplementation include increased fat burning and muscle building, enhanced immunity, and improvement in erectile function in men. Excessive doses of basic amino acids such as ethionine, methionine and lysine are known to damage the rat pancreas. Recent studies have demonstrated that excessive doses of arginine induce necrotizing pancreatitis in rats. In this article, we report a 16-year-old male patient hospitalized in our clinic because of severe pain in upper abdomen, nausea and vomiting who was suspected to have arginine-induced acute pancreatitis.


No evidence of compensatory changes in energy balance, despite reductions in body weight and liver fat, during dapagliflozin treatment in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, cross-over trial (ENERGIZE).
This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)-determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). Patients were given dapagliflozin 10 mg once daily in a randomized, double-blind, placebo-controlled trial with short-term (1 week) and long-term (12 weeks) cross-over periods. The primary outcome was the difference in test meal food intake between long-term dapagliflozin and placebo treatment. Secondary outcomes included short-term differences in test meal food intake, short- and long-term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1 H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2 , glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91-16.27, p = .004], and body weight (-2.84 vs. -0.87 kg) versus placebo. There was no short- or long-term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI -127.9 to 139.3, p = .933); 15.8 g (95% CI -147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction -4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.


Bacillus sp. BS061 Suppresses Powdery Mildew and Gray Mold.
The use of a microorganism, or its secretions, to prevent plant disease offers an attractive alternative or supplement to synthetic fungicides for the management of plant disease without the negative effects of chemical control mechanisms. During a screening for microorganisms with the potential to be used as microbial fungicides, Bacillus sp. BS061 was isolated from a plant leaf. The strain BS061 potently inhibited the mycelial growth of Botrytis cinerea, and significantly reduced disease incidence of powdery mildew in cucumber and strawberry. We also found that the culture filtrate of BS061 inhibited the mycelial growth of various plant pathogens.


Effect of Helicobacter sp. infection on the number of antral gastric endocrine cells in swine.
The aim of the present study was to evaluate the effect of Candidatus Helicobacter suis (CHS) and other Helicobacter sp. different from Candidatus Helicobacter suis (non-Candidatus Helicobacter suis, non-CHS) infection on the number of endocrine G and D cells and G/D cells ratio in antral gastric mucosa in swine. Twenty nine stomachs were obtained from clinical healthy pigs about 6 months old and weighing approximately 100-120 kg after slaughter at abattoir located in central Poland. From each stomach samples of the antral gastric mucosa were taken for histopathology, and PCR examination for presence of Helicobacter genus and Candidatus Helicobacter suis. Samples for histopathology and immunohistochemistry were fixed in 10% buffered formalin. To reveal the expression of gastrin- and somatostatin-producing cells specific antibodies were used. Selected endocrine cells were counted in the midzone of pyloric glands, the results were expressed as a mean of the number of immunoreactive cells in one microscopic field, and as the ratio of gastrin to somatostatin cells (G/D). It can be concluded that some species of swine Helicobacter can alter the number of endocrine cells in gastric antral mucosa. Some of these alterations, for example increase the number of G cells, decrease of the D cells and especially increase of ratio G to D cells can be responsible for development of gastroesophageal ulcers in swine.