Fatty Liver Through the Ages: Nonalcoholic Steatohepatitis.
The global epidemic of obesity and type 2 diabetes mellitus is the main driver of the growing global prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to review the current literature on NAFLD and nonalcoholic steatohepatitis (NASH) as it impacts children and adults. We performed a literature search on fatty liver specifically NAFLD and NASH among children and adults. The prevalence of NAFLD in children ranges from 8% to 12%, while the prevalence in adults ranges 25% to 48%. The prevalence of NASH among children with NAFLD is 23%, while it ranges from 13% to 65% in adults. There are similar risk factors for NAFLD among children and adults. However, in children, the diagnostic tests in the studies of NAFLD are limited to the elevation of the alanine aminotransferase level or a liver biopsy. In adults, additional diagnostic modalities, including noninvasive tests, have been used. From the spectrum of NAFLD, patients with NASH are predominantly at risk of progressive liver disease to cirrhosis and liver-related mortality. NAFLD is associated with impairment of health-related quality of life and substantial economic burden. The comprehensive burden (clinical, health-related quality of life, and economic) of NAFLD is high and increasing.


Targeting autophagy to overcome drug resistance: further developments.
Inhibiting cell survival and inducing cell death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins and damaged or aged cellular organelles to recycle their constituent metabolites that enable the maintenance of cell survival and genetic stability and even promotes the drug resistance, which severely limits the efficacy of chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect to suppress and promote tumor survival, which makes the effect of targeting autophagy on drug resistance more confusing and fuzzier. In the review, we summarize the regulation of autophagy by emerging ways, the action of targeting autophagy on drug resistance and some of the new therapeutic approaches to treat tumor drug resistance by interfering with autophagy-related pathways. The full-scale understanding of the tumor-associated signaling pathways and physiological functions of autophagy will hopefully open new possibilities for the treatment of tumor drug resistance and the improvement in clinical outcomes.


Greedy method for inferring tandem duplication history.
Genome analysis suggests that tandem duplication is an important mode of evolutionary novelty by permitting one copy of each gene to drift and potentially to acquire a new function. With more and more genomic sequences available, reconstructing duplication history has received extensive attention recently. An efficient method is presented for inferring the duplication history of tandemly repeated sequences based on the model proposed by Fitch (1977). We validate the method by using simulation results and real data sets of mucin genes, ZNF genes, and olfactory receptors genes. The agreement with conclusions drawn by other biological researchers strongly indicates that our method is efficient and robust. The program is available by request.


Telescopic endolaryngeal surgery.
Magnification for endolaryngeal visualization, biopsy, and removal of benign lesions and carcinoma in situ is achieved using a telescope inserted in stripping type forceps. The combined telescope and forceps are passed easily through any standard laryngoscope with a holder. Excellent visualization is achieved through the telescope, which can be provided with 0 degree, 30 degree, or 70 degree optics. In most circumstances, these instruments obviate the use of the operating microscope, being simpler and just as exact. The field of vision, however, is smaller. The instruments are also ideal for cervical tracheoscopy and mediastinoscopy.


Skylab experiment results: hematology studies.
These studies were designed and coordinated to evaluate specific aspects of man's immunologic and hematologic systems which might be altered by or respond to the space flight environment. The biochemical functions investigated included cytogenetic damage to blood cells, immune resistance to disease, regulation of plasma and red cell volumes, metabolic processes of the red blood cell, and physical chemical aspects of red blood cell functions. Only minor changes were observed in the functional capacity of erythrocytes as determined by measuring the concentrations of selected intracellular enzymes and metabolites. Tests of red cell osmotic regulation indicated some elevation in the activity of the metabolic dependent Na-K pump, with no significant alterations in the cellular Na and K concentrations or osmotic fragility. A transient shift in red cell specific-gravity profile was observed on recovery, possibly related to changes in cellular water content. Measurements of hemoconcentration (hematocrit, hemoglobin concentration, red cell count) indicated significant fluctuations postflight, reflecting observed changes in red cell mass and plasma volume. There was no apparent reticulocytosis during the 18 days following the first manned Skylab mission in spite of a significant loss in red cell mass. However, the reticulocyte count and index did increase significantly 5 to 7 days after completion of the second, longer duration, flight. There were no significant changes in either the while blood cell count or differential. However, the capacity of lymphocytes to respond to an in vitro mitogenic challenge was repressed postflight, and appeared to be related to mission duration. The cause of this repression is unknown at this time. Only minor differences were observed in plasma protein patterns. In the second mission there were changes in the proteins involved in the coagulation process which suggested a hypercoagulative condition.


Clinical outcome in children hospitalized with complicated measles.
To determine the association of clinical outcome of measles in children with demographic profile and complications. A cross-sectional analytical study. Isolation ward, The Children's Hospital, Pakistan Institute of Medical Sciences (PIMS), from January 2003 to August 2004. Detailed history and physical examination of all the hospitalized patients with complications of measles was filled in case report form. Immunization cards were assessed for measles vaccination status. Data was analyzed by using SPSS version 10 software. The clinical outcome of measles was compared with demographic profile and complications by using Chi-square test and p-values were obtained. Two hundred and five hospitalized patients with complications of measles were studied. There were 61.5% males. Mean age was 46.1 months and 57% patients were vaccinated against measles. Malnourished patients were 71.2% and had a longer hospital stay (p=0.010). Pneumonia (40.0%) and diarrhoea (38.5%) were the commonest complications. Seven children died. Mortality was significantly associated with younger age (p=0.04), unvaccinated status (p=0.04) and presence of encephalitis (p=0.00001). The most common complications of measles are pneumonia and diarrhoea with dehydration requiring hospitalization. Malnourished children experience more complications and have longer hospital stay. Mortality is significantly associated with infancy, unvaccinated status and encephalitis. A second dose of measles should be introduced at 15 months of age.


Gating machinery of InsP3R channels revealed by electron cryomicroscopy.
Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca(2+) signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP3Rs, a mechanistic understanding of their structure-function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 Å) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state. At this resolution, we are able to trace unambiguously ∼85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca(2+)-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed α-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.


America on the move.
The population is gaining weight, despite our best current obesity education and awareness efforts. America on the Move, a nonprofit public health initiative, was founded to promote small achievable behavioral changes to help stop weight gain, starting with (1) eating 100 kcal less per day and (2) increasing lifestyle activity by 2000 steps per day. These two small changes could stop weight gain and prevent overweight and obesity in many, if not most patients. America on the Move materials and tools to implement, support and sustain these behaviors are available free of charge for individuals, schools, groups, communities, and worksites via a Web based portal. A physician tool kit is also available for health care providers to facilitate these changes in clinical practices.


Pseudomonas aeruginosa clonal dissemination in Brazilian intensive care units.
Investigate clonal dissemination of nosocomial multidrug-resistant Pseudomonas aeruginosa isolates within and between Brazilian intensive care units, which participated in the MYSTIC Program Brazil 2002. Thirty-six P. aeruginosa isolates resistant to meropenem or imipenem plus at least two of the following drugs: ciprofloxacin, cefepime, ceftazidime or piperacillin/tazobactam were isolated during 2002 at 4 centres in São Paulo and 1 centre in Brasília. Chromosomal restriction fragments obtained with SpeI were separated by pulsed-field gel electrophoresis (PFGE). Electrophoretic patterns were analyzed with GelCompar II v. 2.5. Five major clones were identified (A, B, C, D, G). Clone A was constituted by 8 isolates with indistinguishable PFGE pattern present in 2 centres. Clone B was constituted by 4 indistinguishable isolates predominant in centre 6. Clone C had 3 indistinguishable isolates, with closely related clones (C1-3). Also, Clone D had 3 indistinguishable isolates, with closely related (D1) and possibly related (D2/D3) clones. Clones C and D were present in centre 1. Clone G was constituted by 2 indistinguishable isolates and was present in centre 7. Finally, 8 isolates were unique. Isolates from Centre 4 were unique. Clonal dissemination was detected within (clones A, B, C, D, and G) and between centres (clone A). These findings are important when analyzing surveillance data, since susceptibility rates may be significantly affected by the dissemination of a resistant clone.


Conformational analysis of the GTP-binding protein MxA using limited proteolysis.
Guanosine triphosphate (GTP)-binding proteins are known to function as molecular switches that cycle between GTP-bound and guanosine diphosphate (GDP)-bound states. Switching is achieved by the fact that G-proteins in the GTP-bound conformation can interact with a certain set of effector molecules while they interact with a different set of partners in their GDP-bound conformation. The antiviral properties of the interferon-induced MxA protein are critically dependent on the ability of MxA to bind GTP. Using limited proteolysis we analyzed the conformations of the MxA protein under nucleotide-free, GDP-bound, and GTP-bound conditions. We find that whereas the conformations of nucleotide-free MxA and GDP-bound MxA are essentially similar, GTP-binding causes a dramatic change in the conformation of MxA.


Mirror agnosia and the mirrored-self misidentification delusion: a hypnotic analogue.
Mirrored-self misidentification is the delusional belief that one's reflection in the mirror is a stranger. Current theories suggest that one pathway to the delusion is mirror agnosia (a deficit in which patients are unable to use mirror knowledge when interacting with mirrors). This study examined whether a hypnotic suggestion for mirror agnosia can recreate features of the delusion. Ten high hypnotisable participants were given either a suggestion to not understand mirrors or to see the mirror as a window. Participants were asked to look into a mirror and describe what they saw. Participants were tested on their understanding of mirrors and received a series of challenges. Participants then received a detailed postexperimental inquiry. Three of five participants given the suggestion to not understand mirrors reported seeing a stranger and maintained this belief when challenged. These participants also showed signs of mirror agnosia. No participants given the suggestion to see a window reported seeing a stranger. Results indicate that a hypnotic suggestion for mirror agnosia can be used to recreate the mirrored-self misidentification delusion. Factors influencing the effectiveness of hypnotic analogues of psychopathology, such as participants' expectations and interpretations, are discussed.


[Liver resection: prt II. Operative procedure].
Hepatic surgery has grown considerably in importance during the last two decades. Major roles in this development have been played by improvements in imaging diagnostics and intensive care and particularly advancements in general hepatic surgical techniques. We present the terminology of functional and segmental anatomy of the liver on which current hepatic surgery is based, along with operative strategies for standard, nonconventional, and repeat resections. Intraoperative complications are also discussed.


Clinical Predictive Score for Cholecystectomy Wound Infection: WEBAC Score.
Most common surgical complications in cholecystectomy are surgical site infections (SSIs). SSIs have many factors, including patient, surgical, and disease factors. This study aims to find the factors which relate to SSIs 30 days after cholecystectomy and contribute to the scoring system to predict SSIs. The data of patients who underwent cholecystectomy from January 2015 to December 2019 were retrospectively collected from a prospectively collected infectious control registry. The SSI was defined following the CDC criteria and assessed before discharge and at a 1-month follow-up. Variables that were independently predictive of the increased SSIs were included in the risk score. The patients who underwent cholecystectomy were 949, which were divided into 28 patients who had SSIs and 921 who had no SSIs. The rate of SSIs was 3%. The factors related to SSI in cholecystectomy were age ≥ 60 years (p = 0.045), history of smoking (p = 0.004), retrieval bag use (p = 0.005), preoperative ERCP (p = 0.02), and wound class III and IV (p = 0.007). Risk assessment was using five variables (WEBAC): (1) wound classifications, (2) preoperative ERCP, (3) retrieval plastic bag use, (4) aged ≥ 60 years, and (5) history of smoking (cigarette). If patients were aged ≥ 60 years and had a history of smoking, no plastic bag use, preoperative ERCP, or wound class III or IV, these parameters would all be scored 1 each. The WEBAC score revealed the probability of SSIs in cholecystectomy wounds. The WEBAC score represents a convenient and simple tool to predict the probability of SSI in the patients who underwent cholecystectomy and might increase the surgeons' awareness of postoperative SSI.


The effect of hypertension and anti-hypertensive drugs on endometrial thickness and pathology.
We sought to clarify if hypertension has a direct effect on endometrial pathology. Furthermore, we wanted to evaluate the effect of possible differences among the various antihypertensive drugs on the clinico-pathological findings. The records of 228 patients who underwent D&C at our tertiary cancer hospital were examined. All other aetiopathogenic factors (DM, tamoxifen, obesity, etc.) for endometrial pathology were excluded, as well as endometrial carcinoma cases. We compared the differences in the clinical symptoms and signs between hypertensive and normotensive women, as well as differences in their histological findings. Furthermore, we carried out a subgroup analysis of the above with respect to the antihypertensive agent(s) the patients used. One hundred and twenty-three patients (54%) were hypertensive and 105 (46%) were normotensive. Vaginal spotting was present in approximately 75% of patients in both groups, but sonographic endometrial thickening was significantly more prevalent among hypertensive women (52.8% versus 34.3%, p=0.004). Hyperplasia was the commonest positive histological finding among hypertensive women (44.7%), compared with polyps for the normotensives. Furthermore, atypia was censored in 4.1% of hypertensive patients only. The subgroup analysis with respect to the various antihypertensives was similar to the above histological distribution, with the exception of the combination b-blocker plus calcium antagonist, which had a significantly more favourable histological profile with over 60% normal endometria. Hypertensive patients tend to require D&C more frequently. Sonographic endometrial thickening is significantly more frequent among them. Hyperplasia with or without atypia occurs in approximately 50% of hypertensive women. No differences in the above were justified depending on the different antihypertensive agents used, with the exception of the b-blocker plus calcium antagonist (+/-ACE inhibitor) combination, which requires further evaluation.


Ultrasound findings in intersection syndrome.
The purpose of our study is to demonstrate the role of ultrasound as a first-line technique in the evaluation of intersection syndrome, reporting and illustrating its typical and atypical findings. In a 2-year period, we reviewed nine patients who received an ultrasound examination for non-specific inflammatory signs in the distal forearm: four men (28-53 years old) and five women (34-57 years old), with a mean age of 44.1 years. The ultrasound examination revealed, in all patients, the presence of peritendinous oedema and a small amount of synovial fluid within the tendon sheaths at the crossing intersection point between the first and the second dorsal extensor tendon compartments, with loss of the hyperechoic cleavage plane between the two tendon groups. In two patients, we observed an irregularly thickened tendon sheath, with small hyperechoic nodules within the fluid, related to proliferation of the synovial membrane. In one case, we detected a relevant thickening of the extensor carpi radialis longus and brevis tendon. Only one patient showed moderate muscle oedema within the first extensor compartment muscles, while another one had significant subcutaneous oedema. Ultrasound is effective in the first-level diagnosis of intersection syndrome.


Quinolones: a new class of antimicrobial agents with wide potential uses.
Quinolone antibiotics provide potentially important therapy for many infections that heretofore required extensive hospitalization. Improper use of these agents rapidly can lead to resistance and thereby remove them from the physician's arsenal of antimicrobial compounds. It also is possible that with more extensive use, these drugs will demonstrate adverse reactions that to date are unknown. Attention to how the agents are used can simultaneously avoid the problems of resistance and toxicity.


Criminal injury case using vegetable juice intermixed with triazolam.
This article explores an injury case in which a middle-aged male offered two female colleagues vegetable juice containing triazolam. The concentration of triazolam in one subject's vegetable juice was of a higher concentration than the other. This subject suffered from such symptoms as numbness, sleepiness, visual disturbance and anterograde amnesia. Conversely, despite having consumed a considerable quantity of vegetable juice, the other subject, with a relatively lower concentration of triazolam in her drink carton, exhibited no symptoms. The differences in the amount of triazolam ingested by each subject, particularly with respect to the expression of symptoms in just one subject, sparked considerable medico-legal discussion. The advice of a medico-legal expert was thus required to explain the reason for these differences.


Application study of DTI combined with ASL in the crossed cerebellar diaschisis after subacute cerebral hemorrhage.
To study the value of 3.0T magnetic resonance imaging with diffusion tensor imaging (DTI) and 3D-arterial spin labeling (ASL) perfusion imaging in the diagnosis of the crossed cerebellar diaschisis (CCD) after the unilateral supratentorial subacute cerebral hemorrhage. Fifty-eight patients with the unilateral supratentorial subacute cerebral hemorrhage who underwent diffusion tensor imaging (DTI), 3D-arterial spin labeling (ASL), and conventional magnetic resonance imaging (MRI) scanning were enrolled. Cerebral blood flow (CBF) values of the perihematomal edema (PHE) and bilateral cerebellar hemisphere were measured on ASL mapping, and the fractional anisotropy (FA) and mean diffusivity (MD) values of the bilateral cortical, pontine, and middle cerebellar peduncle (MCP) were measured on DTI mapping. In the CCD(+) group, FA values of the cerebral cortex and pontine ipsilateral to the lesion were statistically reduced compared to the contralateral side (P < 0.05), and the FA and MD values of the middle cerebellar peduncle (MCP) contralateral to the lesion were statistically reduced compared to the ipsilateral side (P < 0.05). Positive correlation was detected between the CBF values of the perihematomal edema (PHE) and the CBF values of cerebellar hemispheres (r = 0.642, P < 0.05), whereas the CBF values of PHE had a significantly high positive correlation with the FA in the contralateral MCP (r = 0.854, P < 0.05). CBF values in the contralateral cerebellar hemisphere correlated with FA (r = 0.466, P < 0.05) and MD values (r = 0.718, P < 0.05) in the contralateral MCP. Hemodynamic alterations of PHE and cortical-ponts-cerebellum (CPC) fibrous pathway damage are associated with the development of CCD; DTI technique can assess the degree of CPC fiber pathway injury at an early stage.


Detection of the MYD88L265P and CXCR4S338X mutations by cell-free DNA in Waldenström macroglobulinemia.
We aimed to detect the MYD88L265P and CXCR4S338X mutations in cell-free DNA (cfDNA) in patients with Waldenström macroglobulinemia (WM). We collected peripheral blood and paired bone marrow aspirates from 27 WM patients (including 16 patients with newly diagnosed WM, 3 patients with WM in relapse and 8 patients with WM during treatment). cfDNA was extracted from peripheral blood using a QIAamp Circulating Nucleic Acid Kit. The MYD88L265P and CXCR4S338X mutations were detected by real-time allele-specific PCR (AS-PCR) in cfDNA and genomic DNA (gDNA) extracted from bone marrow aspirates. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was determined using a serial dilution of 10%, 2%, 0.4% and 0.08% MYD88L265P cfDNA in wild-type cfDNA. Among the 27 patients, MYD88L265P was detected in 88.9% of them in gDNA and in 85.2% of them in cfDNA, with a concordance rate of 96.3%. The concordance rates were 93.8%, 100% and 100% in patients with newly diagnosed WM, patients with WM in relapse and patients with WM during treatment, respectively. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was 0.4%. CXCR4S338X was detected in 6.3% of the 16 newly diagnosed WM patients in both gDNA and cfDNA, with a concordance rate of 100.0%. It is feasible to apply cfDNA to detect MYD88L265P and CXCR4S338X in WM patients with a high concordance rate.


Polypeptide linkages and resulting structural features as powerful chromogenic factors in the Lowry phenol reaction. Studies on a glycoprotein containing no Lowry phenol-reactive amino acids and on its desialylated and deglycosylated products.
With bovine serum albumin as the reference standard, the armadillo salivary-gland glycoprotein, although containing no chromogenic amino acids and only small amounts of colour-yielding peptides [Chou & Goldstein (1960) Biochem. J. 75, 100-115], is highly reactive in the Lowry phenol protein assay [Wu & Pigman (1977) Biochem. J. 161, 37-47]. After desialylation and Smith degradation of the glycoprotein, the Lowry phenol value increased by 13 and 30% respectively, which suggests that both sialic acid and N-acetylhexosamine exert shielding effects in this reaction. Acid hydrolysis for 30 min decreased the Lowry phenol value by more than 45%, which indicates that the peptide linkages and steric features affect the Lowry phenol reactivity. After hydrolysis for up to 6h, the remaining Lowry phenol value of the partially hydrolysed core protein paralleled the amount of unhydrolysed peptides, inferring that both acid-sensitive and acid-resistant chromophoric peptides are fairly evenly distributed along the whole polypeptide chain. As with bovine serum albumin, more than 80% of the colour yield obtained in the Lowry phenol assay with this glycoprotein is Cu2+-dependent.


Recent increase in fluconazole-nonsusceptible Candida parapsilosis in a global surveillance with the expansion of the Erg11 Y132F genotype and a rapid detection method for this alteration.
We evaluated the rates of fluconazole nonsusceptibility among 1103 Candida parapsilosis isolates collected globally from 2018 to 2021. These rates were <10.3% until 2020 but increased to 15.4% in 2021. Fluconazole-nonsusceptible C. parapsilosis rates were highest in Europe (96/466 isolates; 20.6%) followed by the US (23/386; 6.0%). As the Erg11 Y132F alteration has been a common fluconazole nonsusceptibility mechanism in C. parapsilosis, we developed a PCR assay to detect this mutation. This assay displayed 100% sensitivity and specificity when tested against 56 isolates previously submitted to whole genome sequencing. The Erg11 Y132F alteration was detected in 83.2% of the isolates (104/125) collected during 2018 to 2021 using the PCR assay. The highest rates of the Erg11 Y132F genotype were observed among fluconazole-nonsusceptible isolates from Europe (93.8%), followed by the US (60.9%). An increase in fluconazole-nonsusceptible C. parapsilosis was documented in 2021. Most isolates from Europe and the US carried the Y132F Erg11 alteration that has been reported in various countries.


Lyme disease in children.
This article reviews pediatric Lyme disease in the United States. The agent of Lyme disease includes three pathogenic species (Borrelia burgdorferi, B afzelii, and B garinii), but only B. burgdorferi strains are found in the United States. The article's discussion is limited to the single species B burgdorferi.


[Cutaneous healing after topical application of nebacetin and gingilone to infected wounds. Clinical and histological study in rats].
It was performed a study to examine the cutaneous cicatrization of infected wound of skin after daily topic application of Nebacetin and Gingilone. Following clinical observations the animals were sacrificed after 4, 10 and 17 post-operative days. The pieces were treated, analyzed, in an optical microscope. The topic application of Nebacetin showed to be more efficient in the epithelial reparation comparatively to the Gingilone and control group.


Flight patterns of butterfly species in woodlands.
The flight patterns of twenty species of butterflies present in two coniferous woods and one coppiced wood in eastern England were recorded from April to September 1979. The most mobile species were those characteristic of disturbed habitats, with spatially segregated larval and adult habitats, and those butterflies with early successional larval host plants. The least mobile species were those of permanent habitats and those with ubiquitous larval host plants. Flights of poorly vagile species, but not vagile species, were restricted in both coniferous and coppiced woodland, but were shorter in the latter due to the presence of vegetational barriers to flight. Vagile species remained in coppiced areas longer than in areas of coniferous woodland, flights being influenced by the location of larval and adult food resources.


Clinical outcomes of conservative treatment with a non-weight-bearing abduction brace for Legg-Calvé-Perthes disease.
Treatment with a brace is the first choice as conservative treatment via the containment method for Legg-Calvé-Perthes disease (LCPD). The purpose of this study is to evaluate clinical outcomes and influential factors of conservative treatment with the non-weight-bearing abduction brace for LCPD. One hundred thirty hips in 130 patients were examined in this study. The mean age at onset was 7.0 years (3.3-12.4 years) and the mean follow-up period was 8.4 years (4.1-17.6 years). The extent of necrosis and lateral collapse of the femoral head were evaluated using the Catterall classification and the lateral pillar classification, respectively. Radiological outcome was assessed as good (classes I and II), fair (III), and poor (IV), according to the modified Stulberg classification. Radiographic outcome at final follow-up was good in 82 hips (63%), fair in 40 hips (31%), and poor in 8 hips (6%). Multinomial logistic regression analysis showed that major influential factors for good outcomes were as follows: age at onset, lateral pillar classification, and Catterall classification. From the receiver operating characteristic curve, the cut-off value for age at onset was 8.4 years old to obtain good outcomes. Hips with Catterall group I and II and lateral pillar group A and B had significantly better results. Patients younger than 8.4 years old at onset with lateral pillar group A or B or Catterall group I or II showed good outcomes with a non-weight-bearing abduction brace for LCPD. These results show that alternative treatment, such as surgery, may be another option for patients who are not included in the above groups.


Composition of the Cutaneous Bacterial Community in Japanese Amphibians: Effects of Captivity, Host Species, and Body Region.
The cutaneous microbiota plays a significant role in the biology of their vertebrate hosts, and its composition is known to be influenced both by host and environment, with captive conditions often altering alpha diversity. Here, we compare the cutaneous bacterial communities of 61 amphibians (both wild and captive) from Hiroshima, Japan, using high-throughput amplicon sequencing of a segment of the 16S rRNA gene. The majority of these samples came from a captive breeding facility at Hiroshima University where specimens from six species are maintained under highly standardized conditions for several generations. This allowed to identify host effects on the bacterial communities under near identical environmental conditions in captivity. We found the structure of the cutaneous bacterial community significantly differing between wild and captive individuals of newts, Cynops pyrrhogaster, with a higher alpha diversity found in the wild individuals. Community structure also showed distinct patterns when comparing different species of amphibians kept under highly similar conditions, revealing an intrinsic host effect. Bacterial communities of dorsal vs. ventral skin surfaces did not significantly differ in most species, but a trend of higher alpha diversity on the ventral surface was found in Oriental fire-bellied toads, Bombina orientalis. This study confirms the cutaneous microbiota of amphibians as a highly dynamic system influenced by a complex interplay of numerous factors.


Characteristics of the Japanese histological classification for breast cancer: correlations with imaging and cytology.
The Japanese histological classification of breast cancer is a unique classification that was published as the 2nd edition of the General Rules for Clinical and Pathological Recording of Breast Cancer in 1971. According to this classification, breast cancers are divided into three subgroups: noninvasive, invasive, and Paget's disease. Invasive carcinomas are further divided into two groups: invasive ductal carcinomas (IDCs) and special types. IDCs are the most common types, representing 70-80 % of all breast cancers, and most of them correspond to invasive carcinoma-not special type-according to the latest WHO classification (4th edition). In particular, IDCs are subdivided into three subgroups as follows: (1) papillotubular carcinoma, which is characterized by the projection of papillae into spaces, and includes cribriform and comedo patterns; (2) solid-tubular carcinoma, which is a solid cluster of cancer cells with expansive growths that form relatively sharp borders; and (3) scirrhous carcinoma, which grows in a scirrhous manner characterized by cancer nests or cells accompanied by marked fibrosis. The concept of subclassification originated in Japan. The Japanese histological classification has taken on important roles since its publication, in particular for comparisons between histology and imaging or cytology.


Enhancing self-belief with EMDR: developing a sense of mastery in the early phase of treatment.
Deep inside each of us is a seed that holds our vision of truth, peace, and happiness. Our early childhood attachments, societal influences, and innate capacity determine how well that seed is nurtured and the deepest inner vision is set free. This article is about the ways that vision becomes clouded by attachment deficits, trauma, and subsequent symptoms. The deep inner wish to heal allows for transformation, and approaches like Eye Movement Desensitization and Reprocessing, and hypnotherapy can assist in creating a more rapid acceleration of trauma resolution and transformation of self.


Risk of major congenital anomalies after assisted hatching: analysis of three-year data from the national assisted reproduction registry in Japan.
To assess perinatal risk of major congenital anomalies in children born after embryo transfer with assisted hatching (AH). Retrospective cohort study. Not applicable. Cycles registered from 2010 to 2012 and conceived via single-embryo transfer were included for the analysis. Live births, still births after 22 weeks of gestation, and selectively terminated cases because of congenital anomalies were included. None. Major congenital anomaly. AH was performed in 35,488 cycles among 72,125 included cycles (49.2%). A total of 1,046 major congenital anomalies (1.4%) were identified (1.36% in AH group vs. 1.50% in non-AH group). Overall risks for major congenital anomalies were not significantly different between AH and non-AH groups adjusting for maternal age, calendar year, fetal sex, embryo stage at transfer, and status of cryopreservation. There were 1,009 cases of twins (1.5%) and 10 cases of triplets (0.015%) among all included cycles. No specific organ system demonstrated significant association between AH and non-AH groups. Subgroup analysis demonstrated no significant association between AH and non-AH groups in intracytoplasmic sperm injection cycles or in vitro fertilization in fresh cycles. Similar nonsignificant association was observed between early-cleavage or blastocyst stage at transfer in frozen-thawed cycles. Our results suggest that AH alone does not increase the risk of major congenital anomaly.


Case Report: A rare case of familial lung cancer requiring pneumonectomy in three male siblings.
Lung cancer is a disease with a unique genetic pattern and is occasionally related to hereditary syndromes such as Lynch, Louis-Bar, and Li-Fraumeni. In some patients, germinal mutations may be discovered in combination with somatic alterations. For instance, Li-Fraumeni syndrome often reveals a mixture of TP53 and EGFR mutations. The development of new target therapies necessitates an extensive search for new pathogenic mutations. In this article, we present a rare case report of lung cancer, requiring a pneumonectomy, in three sibling brothers.


Perioperative nonhormonal pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy: a systematic review and network meta-analysis.
To synthesize evidence on the most effective pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy. Systematic review and network meta-analysis of randomized controlled trials (RCTs). Not applicable. Trials assessing efficacy of pharmacological interventions during different types of myomectomy. Misoprostol, oxytocin, vasopressin, tranexamic acid (TXA), epinephrine, or ascorbic acid. Intraoperative blood loss and need for blood transfusion. The present review included 26 randomized control trials (RCTs) (N = 1627). For minimally invasive procedures (9 RCTs; 474 patients), network meta-analysis showed that oxytocin (mean difference [MD] -175.5 mL, 95% confidence interval [CI] -30.1.07, -49.93), ornipressin (MD -149.6 mL, 95% CI - 178.22, -120.98), misoprostol, bupivacaine plus epinephrine, and vasopressin were effective in reducing myomectomy blood loss, but the evidence is of low quality. Ranking score of treatments included in subgroup analysis of minimally invasive myomectomy showed that oxytocin ranked first in reducing blood loss, followed by ornipressin. For open myomectomy (17 RCTs; 1,153 patients), network meta-analysis showed that vasopressin plus misoprostol (MD -652.97 mL, 95% CI - 1113.69, -174.26), oxytocin, TXA, and misoprostol were effective; however, the evidence is of low quality. Vasopressin plus misoprostol ranked first in reducing blood loss during open myomectomy (P = .97). There is low-quality evidence to support uterotonics, especially oxytocin, and peripheral vasoconstrictors as effective options in reducing blood loss and need for blood transfusion during minimally invasive myomectomy. Oxytocin is the most effective intervention in minimally invasive myomectomy. For open myomectomy, a combination of uterotonics and peripheral vasoconstrictors is needed to effectively reduce blood loss.


The interaction of MMP-2/B7-H3 in human osteoporosis.
The immune costimulatory molecule B7-H3 has been shown to be involved in the regulation of murine bone formation. However, the role of B7-H3 in bone metabolic diseases remains unknown. In our study, matrix metalloproteinase 2 (MMP-2) and soluble B7-H3 (sB7-H3) were found to be correlatively up-regulated in the sera of osteoporosis patients. Furthermore, our results showed that MG63 cells treated with MMP-2 inhibitors produced lower amounts of sB7-H3 while cells with recombinant MMP-2 had an increased membrane B7-H3 (mB7-H3) shedding. Therefore, elevated MMP-2 levels resulted in an elevation of serum sB7-H3 and reduction of osteoblastic mB7-H3. B7-H3 knockdown in MG63 cells significantly decreased osteoblastic markers and substantially decreased the number of mineralized nodules after 21days. Thus, B7-H3-deficient MG63 cells exhibited impaired bone formation. These results suggest that mB7-H3 is required for the later phases of osteoblast differentiation and that MMP-2/B7-H3 plays a negative regulatory role in osteoporosis.


Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer.
The objective of this study was to assess the feasibility and effectiveness of an induction chemoradiotherapy regimen followed by surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). A total of 22 patients with LA-NSCLC were treated with induction chemoradiotherapy consisting of cisplatin (40 mg m(-2)) and docetaxel (40 mg m(-2)) given on days 1, 8, 29 and 36 plus concurrent thoracic irradiation at a dose of 40-60 Gy (2 Gy fraction(-1) day(-1)). Surgical resection was performed within 6 weeks after completion of induction therapy. Objective response to the induction therapy was obtained in 16 patients (73%). In all, 20 patients (91%) underwent surgery and complete resection was achieved in 19 patients (86%). Pathological downstaging and pathological complete response were obtained in 14 (64%) and five (23%) patients, respectively. With a median follow-up period of 32 months, the calculated 3-year overall and progression-free survival rates were 66 and 61%, respectively. It is noteworthy that the 3-year overall survival rate in 14 patients achieving pathological downstaging was extremely high (93%). Toxicity was manageable with standard approaches. No treatment-related deaths occurred. This combined modality treatment is feasible and highly effective in patients with LA-NSCLC. The results warrant further large-scale study to confirm the effectiveness of this regimen.


Outcomes after knee arthroplasty in extra-articular deformity.
To assess functional outcomes in patients undergoing total knee arthroplasty (TKA) without previous corrective osteotomy for treatment of knee osteoarthritis associated with extra-articular deformity. From January to December 2016, patients with knee osteoarthritis with extra-articular deformities who presented for preoperative assessment before TKA were evaluated prospectively. Physical and radiological characteristics were documented pre- and postoperatively. TKA was performed in 33 knees; 25 were considered for analysis. The mean age was 65.2 years (range, 48-79 years). Sixteen deformities were secondary to fractures and nine to failed osteotomies. The mean Knee Society Score (KSS) improved from 27.1 pre-operatively to 68.7 post-operatively (p = 0.000). Pre-operative mechanical axis ranged from 32° varus (negative) to 26° valgus. After correction, 20 knees were within 3° (varus or valgus) of mechanical alignment. In patients with extra-articular deformities, TKA with asymmetric intra-articular resection and ligament balancing can relieve pain and realign the mechanical axis of the lower limb.


Quantitative analysis of global phosphorylation changes with high-resolution tandem mass spectrometry and stable isotopic labeling.
Quantitative measurement of specific protein phosphorylation sites is a primary interest of biologists, as site-specific phosphorylation information provides insights into cell signaling networks and cellular dynamics at a system level. Over the last decade, selective phosphopeptide enrichment methods including IMAC and metal oxides (TiO₂ and ZrO₂) have been developed and greatly facilitate large scale phosphoproteome analysis of various cells, tissues and living organisms, in combination with modern mass spectrometers featuring high mass accuracy and high mass resolution. Various quantification strategies have been applied to detecting relative changes in expression of proteins, peptides, and specific modifications between samples. The combination of mass spectrometry-based phosphoproteome analysis with quantification strategies provides a straightforward and unbiased method to identify and quantify site-specific phosphorylation. We describe common strategies for mass spectrometric analysis of stable isotope labeled samples, as well as two widely applied phosphopeptide enrichment methods based on IMAC(NTA-Fe³⁺) and metal oxide (ZrO₂). Instrumental configurations for on-line LC-tandem mass spectrometric analysis and parameters of conventional bioinformatic analysis of large data sets are also considered for confident identification, localization, and reliable quantification of site-specific phosphorylation.


Reduction of GC --> TA transversion mutation by overexpression of MutS in Escherichia coli K-12.
Overexpression of the MutS repair protein significantly decreased the rate of lacZ GC --> TA transversion mutation in stationary-phase and exponentially growing bacteria and in mutY and mutM mutants, which accumulate mismatches between 8-oxoguanine (8-oxoG) and adenine residues in DNA. Conversely, GC --> TA transversion increased in mutL or mutS mutants in stationary phase. In contrast, overexpression of MutS did not appreciably reduce lacZ AT --> CG transversion mutation in a mutT mutant. These results suggest that MutS-dependent repair can correct 8-oxoG:A mismatches in Escherichia coli cells but may not be able to compete with mutation fixation by MutY in mutT mutants.


Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond syndrome.
Shwachman-Diamond syndrome (SDS) is a rare genetic disorder characterized by pancreatic insufficiency, short stature, skeletal abnormalities and bone marrow dysfunction. Patients with SDS have varying degrees of marrow aplasia, which can be severe or progress to leukemic transformation. While allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for the hematologic disturbances of SDS, a recent review of the literature reveals few survivors. Poor outcome with HSCT is often related to excessive cardiac and other organ toxicity from transplant preparative therapy. We describe two young children with SDS who developed aplastic anemia and subsequently underwent successful allografting using a non-cardiotoxic conditioning regimen. Case 1 received marrow from an HLA-identical sibling while case 2 received partially matched umbilical cord blood from an unrelated donor. Both patients are presently alive and well with sustained donor engraftment and excellent hematopoietic function at 36 and 22 months post-HSCT.


[Usefulness of a geriatric intervention program in the improvement of drug treatment for institutionalised patients].
To determine the prevalence of polypharmacy, and inadequate or suboptimal prescriptions. To analyse the impact of a geriatric intervention program on the optimisation and rationalisation of the use of drugs in institutionalised patients. A prospective study on a cohort of 21 sheltered subjects. Drug prescription, inadequate prescription according to "Screening Tool for Older Person's Prescriptions" (STOPP) criteria and suboptimal prescriptions according to "Screening Tool to Alert doctors to Right Treatment" (START) criteria. The intervention was based on analysing treatments and medication issues, correlate treatments to functional and mental situation, together with life expectancy, determine efficient and safe drugs, prescribe generic drugs, detect and avoid polymedication, inadequate and suboptimal prescriptions. Twenty one subjects were include in the study,(mean age 80.43±8.84 years old, with 57.1% women, 76.86±27.76 Barthel and 14.52±7.73 MMSE). On admittance, the number of drugs was 6.29±3.48 (generics on a 20.23% ratio), 14.4% consumed 9 or more, 71.4% complied with any STOPP criteria and 52.4% complied with any START criteria. After the intervention, the number of drugs was 4.9±3.03 (generics on a 61.78 % ratio), 14.3% complied with any STOPP criteria and 4.8% complied with any START criteria. Polymedication, inadequate prescription and suboptimal prescription are frequent issues in residential and nursing environment. For our study population in an intervention program based upon geriatric assessment and the rationalisation on drug use, the drug consumption as well as inadequate and suboptimal prescription has reduced, along with increasing the use of generic drugs.


MC3R links nutritional state to childhood growth and the timing of puberty.
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.


Therapeutic plasma exchange in alloimmune platelet refractoriness.
Patients with alloimmune platelet refractoriness can present complex clinical conundrums. Herein we describe a case of platelet refractoriness in the setting of combined HLA and HPA alloimmunization in a patient with acute myeloid leukemia and life-threatening bleeding. We discuss causative antibodies and compare prevailing therapeutic modalities. We highlight plasma exchange as a potentially feasible, repeatable, and personalized treatment option for patients with extensive platelet alloimmunization who require transfusion.


[Block excision with tectonic corneoscleral graft for traumatic pediatric epithelial implantation cysts].
Invasion of corneal epithelium into the anterior chamber can arise after ocular surgery or penetrating injury. This is extremly rare with an incidence of 0-0.2%. Three different types can be distiguished: cystic, diffuse and mixed form. Only cystic epithelial invasion can be treated with a curative therapeutic option that is blockexzision with tectonic corneoscleral transplantation.


Computational Prediction of Novel miRNAs from Genome-Wide Data.
The computational prediction of novel microRNAs (miRNAs) within a full genome involves identifying sequences having the highest chance of being bona fide miRNA precursors (pre-miRNAs). These sequences are usually named candidates to miRNA. The well-known pre-miRNAs are usually only a few in comparison to the hundreds of thousands of potential candidates to miRNA that have to be analyzed. Although the selection of positive labeled examples is straightforward, it is very difficult to build a set of negative examples in order to obtain a good set of training samples for a supervised method. In this chapter we describe an approach to this problem, based on the unsupervised clustering of unlabeled sequences from genome-wide data, and the well-known miRNA precursors for the organism under study. Therefore, the protocol developed allows for quick identification of the best candidates to miRNA as those sequences clustered together with known precursors.


Urinary vanadium concentration in relation to premature rupture of membranes: A birth cohort study.
Heavy metal exposure has been indicated to be linked with reproductive and developmental toxicity. However, human studies on the association between heavy metal exposure and premature rupture of membranes (PROM) are limited. Thus, we aimed to evaluate the associations between urinary metal concentrations in pregnant women and the risk of PROM. The study was conducted among 7290 pregnant women from an ongoing cohort study in China. Levels of urinary metals were determined using an inductively coupled plasma-mass spectrometry and adjusted by creatinine concentration (μg/g creatinine). Adjusted odds ratios (OR) and 95% confidence intervals (CI) for PROM and preterm PROM were estimated using logistic regression models. Among 12 urinary metals detected, vanadium (V) have shown stable positive associations with PROM and preterm PROM. With one unit increase in natural logarithmically transformed urinary V concentration, adjusted OR of 1.57 (95% CI: 1.47, 1.66) for PROM was observed. Compared with the lowest tertile of urinary V, we also observed positive associations between V levels and PROM (for the medium tertile, adjusted OR = 1.66, 95% CI: 1.34, 2.05; for the highest tertile, adjusted OR = 3.75, 95% CI: 3.09, 4.54). In addition, higher adjusted ORs for preterm PROM were observed (for the highest tertile, adjusted OR = 8.14, 95% CI: 4.55, 14.55). Further stratified analysis suggested the associations were more pronounced among women delivering male infants than those with female infants. Our present epidemiological study indicated that pregnant women exposure to higher level of V might lead to an increased risk of PROM.


A single centre study of coil embolization of intracranial aneurysms comparing bare platinum and PGLA-coated coils.
There is no robust consensus on the efficacy of polyglycolic/polylactic acid (PGLA)-coated coils used in the endovascular embolization of intracranial aneurysms. We present a comparative study of bare platinum coils and PGLA-coated Gugliemi Detachable Coils (GDC) in the treatment of intracranial aneurysms at a single centre, using target aneurysm recurrence and angiographic recanalization as the primary endpoints. We included all patients treated between 1998 and 2009 who had undergone at least one angiographic post-procedural follow-up. Patient demographics, clinical presentation, operative notes, and all relevant imaging were collected. Of the 441 aneurysms with follow-up, 290 were treated with at least one PGLA coil and 151 aneurysms were treated exclusively with bare platinum coils. At follow-up, 26.5% of platinum controls demonstrated angiographic recanalization, compared to 31.4% of PGLA-treated aneurysms (p=0.002). PGLA-treated aneurysms were more likely to have an angiographic remnant at follow-up (odds ratio [OR]=1.96, 95% confidence interval [CI]=1.26-3.04, p=0.003). The post-operative Raymond score was the only predictor of retreatment (OR=1.6, 95% CI=1.08-2.24, p=0.020), and was the second strongest predictor of a complete angiographic result at follow-up (OR=1.67, 95% CI=1.22-2.27, p=0.001). We concluded that PGLA-coated coils demonstrated poorer post-operative and long-term angiographic occlusion in the treatment of intracranial aneurysms, compared to bare platinum coils.


[A comparison of manual methods and enterotube II (Roche) for the identification of gram-negative enteric bacteria isolated from feces].
The Enterotube II and classic manual methods were used in parallel to identify 100 members of the enteric bacteria isolated from feces culture. Among these isolated bacteria Shigella, Salmonella and E. coli were found 34%, 25%, 22% respectively. The Enterotube II and classic manual methods gave the same results for identification of Salmonella and Shigella. The Enterotube II correctly identified 98% of all gram negative enteric bacteria. Other advantages and disadvantages of these methods are discussed in our study.


The Digital Hospital: A Scoping Review of How Technology Is Transforming Cardiopulmonary Care.
Innovative models of health care that involve advanced technology in the form of a digital hospital are emerging globally. Models include technology such as machine learning and smart wearables, that can be used to integrate patient data and improve continuity of care. This model may have benefits in situations where patient deterioration must be detected quickly so that a rapid response can occur such as cardiopulmonary settings. The purpose of this scoping review was to examine the evidence for a digital hospital model of care, in the context of cardiac and pulmonary settings. Scoping review. Databases searched were using PsycInfo, Ovid MEDLINE, and CINAHL. Studies written in English and containing key terms related to digital hospital and cardiopulmonary care were included. The Joanna Briggs Institute methodology for systematic reviews was used to assess the risk of bias. Thirteen (13) studies fulfilled the inclusion criteria. For cardiac conditions, a deep-learning-based rapid response system warning system for predicting patient deterioration leading to cardiac arrest had up to 257% higher sensitivity than conventional methods. There was also a reduction in the number of patients who needed to be examined by a physician. Using continuous telemonitoring with a wireless real-time electrocardiogram compared with non-monitoring, there was improved initial resuscitation and 24-hour post-event survival for high-risk patients. However, there were no benefits for survival to discharge. For pulmonary conditions, a natural language processing algorithm reduced the time to asthma diagnosis, demonstrating high predictive values. Virtual inhaler education was found to be as effective as in-person education, and prescription error was reduced following the implementation of computer-based physician order entry electronic medical records and a clinical decision support tool. While we currently have only a brief glimpse at the impact of technology care delivery for cardiac and respiratory conditions, technology presents an opportunity to improve quality and safety in care, but only with the support of adequate infrastructure and processes. Open Science Framework (OSF: DOI 10.17605/OSF.IO/PS6ZU).


The ethnic density effect as a contextual influence in ecological disease models: Establishing its quantitative expression.
Research suggests higher neighbourhood ethnic minority density to be associated with lessened chances of ethnic group illness. We focus on the density effect on psychosis, arguing that (at higher ethnic concentrations) it acts as a contextual influence attenuating the compositional influence whereby minority ethnicity is associated with higher psychosis risk. In terms of ecological disease regression, the ethnic density effect will then be apparent in nonlinear impacts of minority concentration. Contextual effects may also be evident in spatially varying regression coefficient models for psychosis. Nonlinearity or heterogeneity may be associated with other contextual processes where geography modifies demography (e.g. deprivation amplification). We illustrate these issues with an analysis of psychosis prevalence in 4835 London neighbourhoods. The data are collected in primary care (during 2019/20) using clinical diagnosis (e.g. based on referrals to specialists or psychosis hospitalisation), and refer to patients currently under care: such care may extend retrospectively over several years. The data offer a complete population perspective in contrast to survey data, which typically offer limited geographic perspectives. We consider impacts on psychosis prevalence of non-white ethnicity, as well as those of deprivation, social fragmentation and urbanicity. We find evidence suggesting nonlinear impacts of non-white ethnicity on psychosis (essentially flat risk above a threshold concentration), but find no evidence for deprivation amplification.


Left ventricular adaptation to aortic regurgitation in adults with repaired coarctation of aorta.
Aortic regurgitation (AR) can develop in adults with repaired coarctation of aorta (COA), but there are limited data about left ventricular (LV) remodeling and clinical outcomes in this population. The purpose of the study was to compare LV remodeling (LV mass index [LVMI], LV ejection fraction [LVEF], and septal E/e') and onset of symptoms before aortic valve replacement, and LV reverse remodeling (%-change in LVMI, LVEF and E/e') after aortic valve replacement in patients with versus without repaired COA presenting with AR. Asymptomatic adults with repaired COA presenting with moderate/severe AR (AR-COA group) were matched 1:2 to asymptomatic adults without COA and similar severity of AR (control group). Although both groups (AR-COA n = 52, and control n = 104) had similar age, sex, body mass index, aortic valve gradient, and AR severity, the AR-COA group had higher LVMI (124 ± 28 versus 102 ± 25 g/m2, p < 0.001) and E/e' (12.3 ± 2.3 versus 9.5 ± 2.1, p = 0.02) but similar LVEF (63 ± 9% versus 67 ± 10%, p = 0.4). COA diagnosis (adjusted HR 1.95, 95%CI 1.49-2.37, p < 0.001), older age, E/e', and LV hypertrophy were associated with onset of symptoms. Of 89 patients (AR-COA n = 41, and control n = 48) with echocardiographic data at 1-year post- aortic valve replacement, the AR-COA group had less regression of LVMI (-8% [95%CI -5 to -11] versus -17% [95%CI -15 to -21], p < 0.001) and E/e' (-5% [95% CI -3 to -7] versus -16% [95% CI -13 to -19], p < 0.001). Patients with COA and AR had a more aggressive clinical course, and perhaps may require a different threshold for surgical intervention.


Ambulatory ST-recording has no additional value to exercise test for identification of severe coronary lesions after an episode of unstable coronary artery disease in men.
One month after an episode of unstable coronary artery disease, 95 male patients performed coronary angiography, 48 hours ambulatory ST-recording and also an exercise test. ST-depression occurred in 29.5% during the ST-recording and in 44.2% during the exercise test (p < 0.05). In patients with ST-depression at ambulatory monitoring, 79% demonstrated the same finding at the exercise test. A high risk response at the exercise test--defined as either ST-depression in > or = 3 leads, ST-depression in 1-2 leads with a maximal work load below the 60th percentile or a maximal work load below the 30th percentile regardless of the ECG reaction--occurred in 56.8%. Severe coronary lesions--defined as three vessel disease, left main stenosis or proximal left anterior descending artery stenosis as part of two vessel disease--was observed in 46.3%. Patients with a high risk exercise test response and patients with ST-depression during ST-recording had severe coronary lesions in 67% and 64% respectively. However, a high risk exercise test response occurred in 82%, while ST-depression at ambulatory monitoring was observed only in 41% of the patients with severe coronary lesions (p < 0.001). Thus, ambulatory ST-recording one month after an episode of unstable coronary artery disease in men adds no further information to a symptom limited exercise test in order to identify patients with severe coronary lesions.


Teaching Preschool Children Correct Toothbrushing Habits Through Playful Learning Interventions: A Randomized Controlled Trial.
This study aimed to investigate the effect of playful learning interventions (with toys, visual and auditory sources) on appropriate toothbrushing behaviors and the amount of accumulated plaque in preschool children. The study was carried out as a parallel-group, randomized and controlled study during the period October-December 2018, with 100 preschool children. The preschool students were randomly assigned to an intervention and a control group. The children in the intervention group were given instructions on how to brush their teeth while the children in the control group were not given any instruction outside of what they had learned in preschool. The playful learning interventions that were carried out consisted of three rounds of meetings designed to educate the children about adopting appropriate toothbrushing behaviors. The study groups were well matched at baseline (p = .537) and the intervention group showed statistically significant improvements in toothbrushing (p = .001) and plaque control (p = .001) following the intervention in comparison to the controls. Additionally, while the amount of plaque decreased in the children in the intervention group (p = .001), plaque increased in the control group after the intervention (p = .001). This study showed that after the playful learning interventions carried out with the preschool children, appropriate toothbrushing behaviors were acquired and there was a decrease in the amount of plaque. Nurses who work with preschool children could use toys and songs as effective and entertaining nursing interventions for developing correct toothbrushing behaviors.


GABA neurons in the superficial layers of the rat dorsal cochlear nucleus: light and electron microscopic immunocytochemistry.
This article is an application of light and electron microscopic immunocytochemistry to the study of the neuronal circuit of the superficial layers in the rat dorsal cochlear nucleus (DCN). An antiserum against the intrinsic marker glutamate decarboxylase (GAD) is used to identify and map axon terminals and neurons that use gamma aminobutyric acid (GABA) as a neurotransmitter. It is demonstrated that layers 1 and 2 of the DCN contain a very high density of GABAergic boutons, matched only by the granule cell domains of the ventral cochlear nucleus, especially the superficial granule cell domain. These two layers also contain much higher concentrations of GABAergic cell bodies than all other magnocellular regions of the cochlear nuclear complex. Cartwheel and stellate neurons, and probably also Golgi cells, previously characterized in Golgi and electron microscopic investigations, appear immunostained and, therefore, are presumably inhibitory. The synaptic relations between parallel fibers, the axons of granule cells, and cartwheel and stellate neurons are confirmed. The present study also supports the conclusion that stellate cells are coupled to one another by gap junctions. Also scattered in layer 1 are large, GABAergic neurons that occur with irregular frequency and presumably represent displaced Purkinje cells, previously identified with a Purkinje-cell-specific marker. Granule neurons and pyramidal neurons remain unstained, even after topical injection of colchicine, which enhances immunostaining of the other glutamate-decarboxylase-positive cells, and therefore must use transmitters different from GABA. The possible analogies between the spiny cartwheel and the aspiny stellate cells of the DCN and the cerebellar Purkinje and stellate/basket cells are discussed in the light of data from Golgi, electron microscopy, and transmitter imunocytochemistry.


Visual dysfunction in workers exposed to a mixture of organic solvents.
The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmann's areas of visual cortex in the brain.


MDM2-PROTAC versus MDM2 Inhibitors: Beyond p53 Reactivation.
In this issue of Cancer Discovery, Adams and colleagues present the discovery of a potent PROTAC, MDM2 degrader, which activates wild-type p53 leading to cancer cell death. Importantly, in a number of in vitro and in vivo experiments, the authors show that the depletion of MDM2 by PROTAC kills p53-mutant or p53-null cancer cells. See related article by Adams et al., p. 1210 (5).


Enantioselective acylation of 1,2- and 1,3-diols catalyzed by aminophosphinite derivatives of (1S,2R)-1-amino-2-indanol.
A phosphinite derivative that can be easily prepared in two steps from commercially available aminoindanol was found to be an effective catalyst for enantioselective acylation of diols. For the asymmetric desymmetrization of meso-1,2-diols, the corresponding monoester was obtained in up to 95% ee from the reaction in the presence of 5 mol % catalyst.


Synthesis of hierarchal SAPO-34 nano catalyst with dry gel conversion method in the presence of carbon nanotubes as a hard template.
In this study, the silicoaluminophosphate (SAPO) particles were synthesized based on dry gel conversion method using diethyl amine (DEA) as an organic structure directing agent (SDA). Transport pores were introduced into the crystalline structure of the catalyst using carbon nanotubes (CNT) as a hard template. The significance of molar ratio of CNT in the starting gel and the other synthesis parameters such as crystallization time, gel drying temperature and water content added in the crystallization stage, on crystallinity of SAPO-34, crystal phase, particle size and morphology were studied. The products were characterized by XRD, SEM, TEM, BET and EDX. D-optimal experimental design with four numeric factors including gel drying temperature, crystallization time, water/dry gel mass ratio and mole of CNT in the precursor gel each at three levels was implemented to optimize the experimental parameters by analysis of variance (ANOVA). The Fischer test results showed that, all the parameters have significant effect on the crystallinity of the synthesized samples.


The HLA-A2-restricted PSMA peptide LLHETDSAV is poorly immunogenic in patients with metastatic prostate cancer.
Increasing evidence suggests that prostate cancer is visible to the immune system and is potentially responsive to immunotherapeutic interventions. Previous work has identified prostate-specific membrane antigen (PSMA) as a potential antigen for T-cell recognition, and specific PSMA epitopes presented by HLA-A2 have been described. One vaccination strategy that is being pursued in the clinic utilizes peptide-pulsed peripheral blood mononuclear cells (PBMC) + IL-12. HLA-A2(+) patients with castrate-resistant prostate cancer and normal organ function were considered. Vaccines were prepared using autologous PBMC loaded with a PSMA peptide previously reported to be immunogenic (LLHETDSAV) administered subcutaneously every 3 weeks. T-cell responses and tumor activity were assessed. Although the vaccine was well tolerated, no clinical responses were observed in 12 enrolled patients and no immune responses were detected based on an ex vivo IFN-gamma ELISPOT assay. To examine immunogenicity of this PSMA peptide in more detail, an in vitro priming assay was utilized with normal donor PBMC, and no detectable reactivity was observed. Our results suggest that the PSMA peptide LLHETDSAV is poorly immunogenic in humans and that alternative prostate cancer antigens should be pursued.


A review on coumarins as acetylcholinesterase inhibitors for Alzheimer's disease.
Acetylcholinesterase (AChE) enzyme inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the main stay drugs for its management. Coumarins are the phytochemicals with wide range of biological activities including AChE inhibition. The scientists have attempted to explore the coumarin template for synthesizing novel AChE inhibitors with additional pharmacological activities including decrease in beta-amyloid (Aβ) deposition and beta-secretase inhibition that are also important for AD management. Most of the designed schemes have involved incorporation of a catalytic site interacting moiety at 3- and 4-positions of the coumarin ring. The present review describes these differently synthesized coumarin derivatives as AChE inhibitors for management of AD.


Localization of cyclooxygenases-1 and -2, and prostaglandin F synthase in human kidney and renal cell carcinoma.
Prostaglandin (PG)F2alpha is one of the major prostanoids produced by the kidney, and its renal synthesis is regulated by sodium depletion, potassium depletion, and adrenal steroids. PGF synthase activity is detected in kidney of various mammals. Herein, we demonstrated immunochemically that PGF synthase was localized in proximal tubule of human kidney, together with cyclooxygenase (COX)-1, and that it was localized in human renal cell carcinoma, together with COX-2. These results suggest that PGF synthesized through COX-1 and PGF synthase plays an important physiological role in the kidney and that the expression of COX-2 in kidney is a useful maker for tumorigenesis of the renal call carcinoma in vivo.


A diagnostic algorithm for urachal anomalies.
Urachal anomalies are rare. Variable presentations can be a diagnostic challenge. We combine our series with a review of literature to delineate the most common presentations, highest yield diagnostic studies and a diagnostic algorithm. We reviewed records of 22 boys and 15 girls with the diagnosis of a urachal anomaly from 2000 through 2005. This revealed 19 cysts, seven patent urachuses, five sinuses, four patients with unspecified "urachal anomalies," and two patients with no urachal anomaly by surgical exploration. Ultrasound was the most common diagnostic study, followed by computed tomography (CT), voiding cystourethrogram and sinogram. Thirty-five of 37 patients underwent surgery. Clinical presentation included periumbilical leakage in 54%, pain in 30%, periumbilical mass in 22% and irritative voiding symptoms in 14%. In many patients diagnosis was made on clinical examination alone. When an ultrasound was used it was diagnostic for 82% of cysts, 100% of sinuses and 100% of patent urachuses. A voiding cystourethrogram was diagnostic for 100% of patent urachuses, but less successful in the other anomalies. CT scans correctly diagnosed 71% of cysts. Overall complication rate was 9%, all wound infections. Reviewing the results of this and four other large series showed that the most common anomaly is the urachal cyst followed by urachal sinus and patent urachus. Periumbilical drainage is the most common presentation. Physical exam alone can be diagnostic. When this is not possible ultrasound is our recommended initial study, followed by a CT scan if unsuccessful.


Data from necropsy studies and in vitro tissue studies lead to a model for allometric scaling of basal metabolic rate.
The basal metabolic rate (BMR) of a mammal of mass M is commonly described by the power function alphaM(beta) where alpha and beta are constants determined by linear regression of the logarithm of BMR on the logarithm of M (i. e., beta is the slope and alpha is the intercept in regression analysis). Since Kleiber's demonstration that, for 13 measurements of BMR, the logarithm of BMR is closely approximated by a straight line with slope 0.75, it has often been assumed that the value of beta is exactly 3/4 (Kleiber's law). For two large collections of BMR data (n = 391 and n = 619 species), the logarithm of BMR is not a linear function of the logarithm of M but is a function with increasing slope as M increases. The increasing slope is explained by a multi-compartment model incorporating three factors: 1) scaling of brain tissue and the tissues that form the surface epithelium of the skin and gastrointestinal tract, 2) scaling of tissues such as muscle that scale approximately proportionally to body mass, and 3) allometric scaling of the metabolic rate per unit cell mass. The model predicts that the scaling exponent for small mammals (body weight < 0.2 kg) should be less than the exponent for large mammals (> 10 kg). For the simplest multi-compartment model, the two-compartment model, predictions are shown to be consistent with results of analysis using regression models that are first-order and second-order polynomials of log(M). The two-compartment model fits BMR data significantly better than Kleiber's law does. The F test for reduction of variance shows that the simplest multi-compartment allometric model, the two-compartment model, fits BMR data significantly better than Kleiber's law does and explains the upward curvature observed in the BMR.


Sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, Aedes aegypti.
The midgut of hematophagous insects is the initial site of infection by arthropod-borne viruses (arboviruses) and plays a crucial role in vector competence. To further understand processes that occur in the midgut in response to infection by an arbovirus, DNA microarrays were used to analyze gene expression changes following infection by the alphavirus, Sindbis (MRE16 Malaysian strain). Midgut transcription profiles from mosquitoes fed blood containing 10(8)pfu/ml of virus were compared with those from mosquitoes ingesting blood meals having no virus. Transcription profiles from both experimental groups were analyzed at 1, 4, and 8 days post-feeding. Among the many transcription changes observed by microarray analysis, the most dramatic involved three genes that had 25-40-fold increases in transcript levels in virus infected mosquitoes at 4 days post-infection. These genes were synaptic vesicle protein-2 (SV2), potassium-dependent sodium/calcium exchanger (NCKX), and a homologue of Caenorhabditis elegans Unc-93, a putative component of a two-pore potassium channel. We speculate that these changes represent changes in vesicle transport processes. In addition to these observations, transcript changes were observed in infected mosquitoes that suggested involvement of Toll and c-jun amino terminal kinase immune cascades as a response to viral infection.


Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study.
We determined the pharmacokinetics and safety of 750 mg long acting testosterone undecanoate given intramuscularly at 0, 4 and 14 weeks to men with hypogonadism. A 24-week, single arm, open label, multicenter trial in 130 hypogonadal men 18 years or older who were screened for serum total testosterone less than 300 ng/dl was performed at 31 research sites in the United States between March and November 2007. Testosterone undecanoate (750 mg) was administered at baseline, and at weeks 4 and 14. Serum testosterone samples were collected on days 4, 7, 11, 14, 21, 28, 42, 56 and 70 following injection 3. Safety was assessed, eg biochemical markers and adverse events, secondary to testosterone undecanoate treatment. Of the 130 patients 116 with a mean +/- SE age of 54.2 +/- 0.90 years completed the 24-week trial. Following the week 14 injection mean +/- SD average serum testosterone was 494.9 +/- 141.46 ng/dl during the 70-day dosing interval and mean +/- SD maximum serum testosterone was 890.6 +/- 345.11 ng/dl with a mean concentration within the young healthy adult male range (300 to 1,000 ng/dl) in 94% of patients and a mean maximum concentration of below 1,500 ng/dl in 92%. Mean +/- SE hematocrit and hemoglobin increased from baseline to week 24 (43.3% +/- 0.32% to 45.7% +/- 0.35% and 14.6 +/- 0.11 to 15.5 +/- 0.13 gm/dl, respectively). Mean +/- SE prostate specific antigen increased from baseline to 24 weeks (1.0 +/- 0.08 to 1.3 +/- 0.10 ng/ml). No prostate cancer or gynecomastia was observed during this 24-week study. This 24-week clinical study demonstrated that 750 mg testosterone undecanoate depot injection administered intramuscularly at 0, 4 and 14 weeks achieves serum testosterone levels in the normal range during a 10-week dosing interval.


An efficient fluctuating charge model for transition metal complexes.
A fluctuating charge model for transition metal complexes, based on the Hirshfeld partitioning scheme, spectroscopic energy data from the NIST Atomic Spectroscopy Database and the electronegativity equalization approach, has been developed and parameterized for organic ligands and their high- and low-spin Fe(II) and Fe(III), low-spin Co(III) and Cu(II) complexes, using atom types defined in the Momec force field. Based on large training sets comprising a variety of transition metal complexes, a general parameter set has been developed and independently validated which allows the efficient computation of geometry-dependent charge distributions in the field of transition metal coordination compounds.


Sex-specific associations among infant food and atopic sensitizations and infant neurodevelopment.
Food sensitization is a first and strong indicator of immune deviation in the progression to other allergic conditions. Sensitization to food or other allergens and related inflammation during critical windows of infant development may adversely affect neurodevelopmental milestones. However, additional research is needed to test this association further. Associations between atopic (any food or aeroallergen) or food sensitization (specific to egg, soybean, peanut, and milk) at age 1 year and neurodevelopment up to 2 years of age were evaluated in the national CHILD Cohort Study, with a secondary aim examining whether these associations were sex-specific. Food and atopic sensitization were assessed by skin prick tests (SPT) in 1-year-old infants, with neurodevelopment assessed using the cognitive, language, motor, and social-emotional subscales of the Bayley Scales of Infant Development (BSID-III) administered at 1 and 2 years of age. Atopic sensitization was present among 16.4% of infants, while 13.4% had food sensitizations. Only socioemotional scores reached statistical significance among the four BSID-III domains. Both atopic and food sensitization at 1 year of age was associated with lower social-emotional scores, independent of the infant's ethnicity. These findings were sex-specific and only observed among boys, among whom social-emotional scores were lowered by 5 points if atopic sensitization was present (-5.22 [95% CI: -9.96, -0.47], p = 0.03) or if food sensitization was present (-4.85 [95% CI: -9.82,0.11], p = 0.06). Similar results were observed using the standard SPT cut-off of ≥3 mm - for atopic sensitization (-5.17 [95% CI: -11.14, -0.80], p = 0.09) and for food sensitization (-4.61 [95% CI: -10.96, 1.74], p = 0.15). In our study of term infants, we found an inverse, cross-sectional association between atopic and food sensitization status and social-emotional development scores in male children but not female children.


Qualitative and quantitative changes in the ultrastructure of the dog heart after temporary ischaemia and coronary reperfusion.
A total ischaemia of one area of the myocardium was produced by ligature of a coronary artery in dogs. After 30 min, 1 hr, 2 hrs, and 4 hrs the ligature was loosened and the artery was for 1--2 hrs reperfused up to 4--7 days. At the end of the ischaemia and after reperfusion the ultrastructure of the myocardium was qualitatively and morphometrically investigated. The findings concerned: loss of glycogen (partly glycogen accumulation), mitochondrial swellings and fusions and development of megamitochondria, loss of cristae, rupture of the mitochondrial outer membranes, relaxation or supercontraction of the myofibrils, vesicular and vacuolar changes of the sarcoplasmic reticulum, oedema of the sarcoplasm, rupture of the sarcolemma. No significant differences of the quantitative parameters could be observed during the ischaemia from 30 min to 4 hrs: myofibrils 53.65--59.74%, mitochondria 26.51--33.59%, sarcoplasm 8.22--11.86%, sarcoplasmic reticulum 1.41--2.63%, lipofuscin 0.05--0.87%, lipids 0.01--0.10%. In comparing the data of the single animals we could determine significant differences between some parameters at the ends of the ischaemic phase and of the reperfusion phase, but as far as the findings are concerned both increases and decreases could be observed. The investigations show that the limit of the reversibility of damages in myocardial cells is about 45 min; in special cases a longer survival time may be taken into account. Reperfusion has different, though not always positive, effects.


Pep5, a new lantibiotic: structural gene isolation and prepeptide sequence.
A wobbled 14-mer oligonucleotide was derived from the amino acid sequence of the 34-residue propeptide of the lantibiotic Pep5 (Kellner et al. 1989). Using this hybridization probe, the structural gene of Pep5, pepA, was located on the 18.6 kbp plasmid pED503. The nucleotide sequence of pepA codes for a prepeptide with 60 residues and proves that Pep5 is ribosomally synthesized. The N-terminus of the prepeptide has a high alpha-helix probability and a characteristic proteolytic cleavage site precedes the C-terminal 34-residue propeptide. Our present theory is that maturation of Pep5 involves (a) enzymic conversion of Thr, Ser and Cys into dehydrated amino acids and sulfide bridges, (b) membrane translocation and cleavage of the modified prepeptide.


The refolding of urea-denatured ribonuclease A is catalyzed by peptidyl-prolyl cis-trans isomerase.
The refolding of urea-denatured ribonuclease A was measured at 0.31-3.1 mol . l-1 urea in the presence of various concentrations of peptidyl-prolyl cis-trans isomerase isolated from pig kidney. The rate of the slow CT-phase in the refolding reaction was found to be sensitive to this enzyme. A rate enhancement proportional to the isomerase activity has been observed. The activity of the enzyme was assayed with Glt-Ala-Ala-Pro-Phe-4-nitroanilide. The catalytic activity of the isomerase against unfolded ribonuclease is suppressed after preincubation of the enzyme with 0.001 mol . l-1 Cu2+, 0.01 mol . l-1 H+ and by heat inactivation. The results indicate the involvement of the cis/trans interconversion of proline peptide bonds during the refolding of ribonuclease A.


Amelanotic malignant melanoma arising in an ovarian dermoid cyst.
Malignant transformation occurs in about 2% only of ovarian dermoid cysts. The clinical and histopathological findings in a rare case of primary ovarian malignant melanoma of amelanotic type are presented.


Preparation and evaluation of poly(polyethylene glycol methyl ether acrylate-co-polyethylene glycol diacrylate) monolith for protein analysis.
A poly(polyethylene glycol methyl ether acrylate-co-polyethylene glycol diacrylate) monolith was prepared by UV-initiated polymerization. Methanol and ethyl ether were selected as porogens from a variety of organic solvents to achieve the desirable characteristics of the monolith. The preparation of the monolith could be achieved within 10 min. The monolith was macroscopically homogeneous, had low flow resistance, and did not swell or shrink significantly in tetrahydrofuran. Inverse size-exclusion data indicate that the monolith had a total porosity of 75.4% and an internal porosity of 9.1%. The monolith could be used for size-exclusion separation of peptides, although it could not separate proteins with molecular masses between 10 and 100 K due to its unique pore size distribution. It was found to resist adsorption of proteins in capillary liquid chromatography when using 100 mM phosphate buffer (pH 7.0) containing 0.5 M NaCl. Complete recovery of both acidic and basic proteins was achieved. The monolith can be used for applications in which inert materials are required for protein analysis.


Angry wives, abusive husbands: relationship between domestic violence and psychosocial variables.
A small number of studies conducted in Pakistan have shown high rates of domestic violence. None of the studies, however, discussed associated psychosocial factors. We interviewed a group of women to look at violence and associated psychosocial factors. We wanted to see if self-esteem, quality of relationships, social support, stressful life events, psychiatric symptoms, and different measures of anger were associated with domestic violence. In a cross-sectional survey of women presenting to primary care physicians, we used Women's Experience with Battering and Domestic Abuse Checklist to measure domestic violence. The Relationship Assessment Scale, Oslo Social Support Scale, State Trait Anger Inventory, and Evaluative Belief Scale were used to look at the correlates of violence. We used the information in a regression model to identify independent predictors of violence in this sample. More than half of the women reported experiencing battering and/or violence. Women in abusive relationships reported unhappiness with their intimate relationships and had high scores on 1 subscale of anger. Living in extended families was protective against violence. We were able to replicate findings that women in abusive relationships are not satisfied with the relationships with their partners. Living in extended families was protective against violence. Community studies may provide a better design to look at the association between abuse and poverty, literacy, self-esteem, and social support.


Effects of Vortioxetine and Escitalopram on Electroencephalographic Recordings - A Randomized, Crossover Trial in Healthy Males.
The antidepressant drug vortioxetine has a multimodal action modulating neurotransmission through inhibition of the serotonin transporter and modulation of serotonin receptors. Vortioxetine has also been shown to alleviate cognitive symptoms in preclinical studies and in patients with depression. However, it is largely unclear how vortioxetine affects the brain processing in humans. The present study was conducted in 32 healthy males in a randomized, double-blinded, placebo-controlled, active comparator, four-way crossover design. Treatments were 10 and 20 mg/day vortioxetine, 15 mg/day escitalopram, and placebo, administered orally once daily for three days. Results were compared to placebo. Treatment effect was assessed by recording spontaneous electroencephalography (EEG) and 40 Hz auditory steady state responses. For the spontaneous EEG, both vortioxetine and escitalopram decreased the frequency content in the theta band (4-8 Hz) and increased power in the beta (12-32 Hz) and gamma (32-45 Hz) bands. Vortioxetine and escitalopram decreased connectivity during rest in the theta band and increased connectivity in the gamma bands. Finally, both treatments caused decreased power in the evoked gamma band in response to 40 Hz auditory stimulation. Although the global EEG changes were comparable between vortioxetine and escitalopram, subtle differences between treatment effects on the EEG in terms of effect size and regional distribution of the EEG changes were apparent. To our knowledge, the current results are the first data on how vortioxetine affects EEG in humans. The present study calls for further investigations addressing the possible electrophysiological and cognitive effects of vortioxetine.


Self-management interventions for people with intellectual disabilities: A systematic review.
People with intellectual disabilities (ID) often experience difficulties managing their affairs. This study reviewed self-management interventions for people with mild to moderate ID, studying interventions' effectiveness and applied behavioural change techniques (BCTs). A systematic literature search was conducted in PubMed, PsychINFO, Web of Science, Embase, Emcare, Cochrane, and ProQuest. Data were extracted on study, intervention, and participant characteristics, and results. Of the 681 studies retrieved, 36 met the inclusion criteria. Most studies used case study designs and small samples. There were eight randomised controlled trials and one non-randomised study. Studies were mostly of moderate quality (Mixed Methods Appraisal Tool). Twenty-two interventions targeted a singular practical skill for a specific context. In allinterventions, the provider applied several BCTs; in 13 studies participants were also trained to apply BCTs themselves. In all studies, improvements in self-management were reported, which mostly maintained over time (n = 20). If measured, generalisation to other settings was also found. Future studies should aim for a higher methodological quality and couldconsider targeting more generic self-management and a wider application of BCTs by people with ID themselves. The findings suggest that training can promote self-management in people with ID.


Progressive muscular dystrophies.
Infancy- or childhood-onset muscular dystrophies may be associated with profound loss of muscle function, affecting ambulation, posture, cardiac and respiratory functions, while those of late onset may be mild and associated with slight weakness or fatigability induced by effort. In addition to the distribution of muscle weakness, symptoms, and course of the disease, the diagnosis of muscular dystrophy is usually ascertained by histological findings. There is connective tissue proliferation in the perimysium and endomysium, variation in muscle fiber size, cytoarchitectural alterations of myofibers such as internal nuclei, myofibrillar whorls, and fiber splitting and lobulation, but, most of all, degeneration and regeneration of myofibers. Causes of muscular dystrophies characterized by muscle weakness and wasting are heterogeneous and include dysfunction of diverse genetic pathways and genes encoding proteins of the plasma membrane, extracellular matrix, sarcomere, and nuclear membrane components. Duchenne and Becker muscular dystrophies are prototypes illustrating advances in the field of myology. Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous, some with autosomal dominant (LGMD1) and others with autosomal recessive (LGMD2) inheritance. Neither clinical and genetic grounds nor biopsy patterns are specific enough to distinguish them, but two common denominators are: (1) weakness and wasting predominating in pelvic and shoulder girdle muscles, with occasional involvement of the myocardium; and (2) necrosis and regeneration of myofibers. While identification of genetic causes and molecular diagnosis are increasingly improved, especially with the advent of new generation sequencing technologies, optimized care, information for the family, and prevention, including genetic counseling and prenatal diagnosis, require multidisciplinary follow-up with genetic, pediatric, and psychological involvement.


Use of cultivated plants and non-plant remedies for human and animal home-medication in Liubań district, Belarus.
To use any domestic remedy, specific knowledge and skills are required. Simple logic dictates that the use of wild plants in the context of limited interaction with nature requires prior identification, while in the case of non-plant remedies and cultivated plants this step can be omitted. This paper aims to document the current and past uses of non-plant remedies and cultivated plants in the study region for human/animal medication; to analyze the human medicinal and veterinary use areas in the context of the remedy groups; to qualitatively compare the results with relevant historical publications; and to compare the intensity and purpose of use between the remedy groups. During field studies 134 semi-structured interviews were conducted with locals from 11 villages in the Liubań district of Belarus. Currently used home-remedies as well as those used in the past were documented by employing the folk history method. The subject was approached through health-related uses, not by way of remedies. Interview records were digitalized and structured in Detailed Use Records in order to ascertain local perceptions. An Informant Consensus Factor (FIC) was calculated for remedy groups as well as for different use categories. In the human medication area the use of nearby remedies was neither very diverse nor numerous: 266 DUR for 45 taxa belonging to 27 families were recorded for cultivated plants along with 188 DUR for 58 different non-plant remedies. The FIC values for both remedy groups were lower than for wild plants. In the ethnoveterinary medicine use area there were 48 DUR referring to the use of 14 cultivated plant taxa from 12 families and 72 DUR referring to the use of 31 non-plant remedies. The FIC value for the whole veterinary use area of cultivated plants was relatively low, yet similar to the FIC of wild plants. Differences between remedy groups were pronounced, indicating that in domestic human medicine cultivated plants and non-plant remedies are either remarkably less important than wild ones or not considered worth talking about. In ethnoveterinary medicine non-plant remedies are almost equally important as wild plants, while cultivated plants are the least used. People in study area seem to still more often rely on, or are more willing to talk to strangers about, wild plants, as promoted by both official medicine and popular literature.