In vivo quantitative proton MRSI study of brain development from childhood to adolescence.
To quantify regional variations in metabolite levels in the developing brain using quantitative proton MR spectroscopic imaging (MRSI). Fifteen healthy subjects three to 19 years old were examined by in vivo multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), and peak area ratios were determined in selected frontal and parietal gray and white matter regions, basal ganglia, and thalamus. In cortical gray matter regions, the ratio of NAA/Cho increased to a maximum at 10 years and decreased thereafter (P = 0.010). In contrast, in white matter, average ratios NAA/Cho increased linearly with age (P = 0.045). In individual brain regions, age-related changes in NAA/Cho were found in the putamen (P = 0.044). No significant age-related changes in NAA, Cho, Cr, or other metabolite ratios could be determined. Consistent with recent studies using other structural and functional neuroimaging techniques, our data suggest that small but significant changes occur in regional cerebral metabolism during childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal and parietal areas, resembling previously reported age related changes in rates of glucose utilization and cortical volumes, may be associated with dendritic and synaptic development and regression. Linear age-related changes of NAA/Cho in white matter are also in agreement with age-related increases in white matter volumes, and may reflect progressive increases in axonal diameter and myelination.


Potentiation of the neurtalization of feline leukaemia virus in hypotonic medium.
The neutralization of feline leukaemia virus could be enhanced by performing the reaction in hypotonic medium. Absorption of antibody by virus specific antigens was also made more sensitive under these conditions.


Determination of Ki67 growth fraction and oestrogen receptors in screen-detected breast cancer using cytological preparations.
Oestrogen receptor (ER) status of 77 cases of screen-detected breast cancer has been determined using cytological preparations. In 48% ER status was positive, which was the same proportion as that formed in a control group of age-matched patients with symptomatic breast carcinoma. Since the screen-detected group contained more low grade tumours, the percentage of ER-positive cases would be expected to be higher. The reasons for the discrepancy are discussed. Ki67 score has been determined for 41 cases of screen-detected cancer. Ki67 score showed a positive correlation with histological tumour grade and a negative correlation with ER status. However, there was no correlation with tumour size or lymph node status. The Ki67 scores in the screen-detected cancers were essentially similar to those found in an age-matched symptomatic group, but the very low scores were only found in the screened group.


The significance of medicolegal autopsy in determining mode and cause of death.
A comparative examination has been made to evaluate decisions as to causes and modes of death among 436 consecutive medicolegal deaths before and after coming to autopsy. All available information was used. including police reports, in evaluating mode and cause of death prior to the autopsy. Among the women, the mode of death evaluation differed in 23.4% of the cases and the cause of death evaluation differed in 77.5% of the cases. Among the men, the mode of death evaluation differed in 23.4% of the cases and the cause of death evaluation differed in 46.9% of the cases. These figures were achieved, however, on the basis of the fact that in most cases the mode of death and cause of death were reported as unknown. After autopsy, the cause of death remained unknown in 3.3% of the females over the age of 2 years and in 4.2% of the male over the age of 2 years. No characteristic relationship was established between the differences found and the age groups. The investigation shows the importance of the medicolegal autopsy for correctly recording cases where the death is obscure.


Cell-matrix adhesion: the Wech connection.
Integrins link the extracellular matrix to the cytoskeleton via a complex of proteins: the integrin-cytoskeleton link. A recent study in Drosophila has uncovered a new component of the link, Wech, and shown that it is essential for integrin-mediated adhesion.


Spontaneous bacterial peritonitis due to Campylobacter coli.
A patient with alcoholic liver disease and ascites who developed fatal spontaneous bacterial peritonitis due to Campylobacter coli is reported herein. This is the first case report of spontaneous bacterial peritonitis due to this organism. Campylobacter infections and their relationship to spontaneous bacterial peritonitis are reviewed.


The BaSICS (Baby Skin Integrity Comparison Survey) study: A prospective experimental study using maternal observations to report the effect of baby wipes on the incidence of irritant diaper dermatitis in infants, from birth to eight weeks of age.
Baby wipes have been shown to be safe and effective in maintaining skin integrity when compared to the use of water alone. However, no previous study has compared different formulations of wipe. The aim of the BaSICS study was to identify any differences in incidence of irritant diaper dermatitis (IDD) in infants assigned to three different brands of wipe, all marketed as suitable for neonates, but which contained varying numbers of ingredients. Women were recruited during the prenatal period. Participants were randomly assigned to receive one of three brands of wipe for use during the first eight weeks following childbirth. All participants received the same nappies. Participants reported their infant's skin integrity on a scale of 1-5 daily using a bespoke smartphone application. Analysis of effect of brand on clinically significant IDD (score 3 or more) incidence was conducted using a negative binomial generalised linear model, controlling for possible confounders at baseline. Analysts were blind to brand of wipe. Of 737 women enrolled, 15 were excluded (admitted to neonatal intensive care, premature or other infant health issues). Of the 722 eligible babies, 698 (97%) remained in the study for the full 8-week duration, 24.6% of whom had IDD at some point during the study. Mothers using the brand with the fewest ingredients reported fewer days of clinically significant nappy rash (score≥3) than participants using the two other brands (p = 0.002 and p < 0.001). Severe IDD (grades 4 and 5) was rare (2.4%). Rarity of severe IDD suggested that sensitive formula baby wipes are safe when used in cleansing babies from birth to eight weeks during nappy changes. The brand with fewest ingredients had significantly fewer days of clinically significant IDD. Daily observations recorded on a smartphone application proved to be a highly acceptable method of obtaining real-time data on IDD. This study was not designed or registered as a clinical trial as no intervention in normal patterns of infant care took place. Mothers who had already decided to use disposable nappies and a baby wipe product agreed to observe and report on their infants' skin condition; in return they received a 9-week supply of free nappies and wipes.


Dose equivalence of midazolam and triazolam. A psychometric study based on flicker sensitivity, reaction time and digit symbol substitution test.
The pharmacodynamic potency of oral midazolam, a new ultrashort-acting hypnotic benzodiazepine, has been evaluated relative to a standard dose of triazolam, a well established oral benzodiazepine with a similar pharmacological profile. In a balanced design, double-blind cross-over study 6 healthy volunteers received 3.75, 7.5, and 15 mg midazolam and 0.25 mg triazolam orally, at 8 a.m., at weekly intervals. Drug effects were repeatedly measured over 8 h by a new psychometric method, the threshold amplitude for perception of flickering light (TPF) assessed at 5 and 30 Hz. Auditory reaction time, digit-symbol substitution test (DSST), and self-rating by subjects served as reference standards. Median midazolam doses equivalent to 0.25 mg triazolam, interpolated on dose-response curves for peak effects, were 5.2 mg (TPF 30 Hz), 6.4 mg (TPF 5 Hz), 6.5 mg (DSST), and 7.4 mg (reaction time), respectively. Alternative methods of data analysis gave similar results. Introduction of TPF as a highly reproducible and sensitive measure of the effect of benzodiazepines on the CNS offers new opportunities to compare the relative potencies of different benzodiazepines in man. Since clinical experience has shown 0.25 mg triazolam to be safe and effective, it is concluded that the corresponding single oral dose of midazolam is between 5 and 8 mg.


Protocol and statistical analysis plan for the Pragmatic Investigation of optimaL Oxygen Targets (PILOT) clinical trial.
Mechanical ventilation of intensive care unit (ICU) patients universally involves titration of the fraction of inspired oxygen to maintain arterial oxygen saturation (SpO2). However, the optimal SpO2 target remains unknown. The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is a prospective, unblinded, pragmatic, cluster-crossover trial being conducted in the emergency department (ED) and medical ICU at Vanderbilt University Medical Center in Nashville, Tennessee, USA. PILOT compares use of a lower SpO2 target (target 90% and goal range: 88%-92%), an intermediate SpO2 target (target 94% and goal range: 92%-96%) and a higher SpO2 target (target 98% and goal range: 96%-100%). The study units are assigned to a single SpO2 target (cluster-level allocation) for each 2-month study block, and the assigned SpO2 target switches every 2 months in a randomly generated sequence (cluster-level crossover). The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of invasive mechanical ventilation through 28 days after enrolment. The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).


In the balance: With the drama of Supreme Court arguments over, providers are left to worry what will happen if the individual mandate is struck down.
After last week's U.S. Supreme Court arguments on the landmark healthcare reform case, providers are left to wait and wonder what will happen. "If I were a betting person ... I would come away and think they would throw out the mandate," says William Petasnick, of Froedtert Health. "But I think there is some case law and precedent that might move them in a different way because of the consequences."


Identification of Brucella species isolated from proven brucellosis patients in Izmir, Turkey.
In many parts of the world, brucellosis has significantly decreased, but it is still a problem in some regions of Turkey. Totally, 11 Brucella strains isolated from the blood cultures of patients with presumptive diagnosis of brucellosis were identified to species and biovar level. For species identification, (i) CO2 requirements of isolates; (ii) detection of urease activation; (iii) detection of H2S production; (iv) dye sensitivities (thionine and basic fuchsin); (v) susceptibility to Brucella phage and (vi) agglutination with monospecific antisera (A and M) were performed. Ten out of 11 isolates were identified as B. melitensis biovar 3 and one out of 11 were identified as B. melitensis biovar 1. The sensitivity of isolates to antibiotics was determined by the E-test. All isolates were found to be sensitive to doxycycline, rifampin, ciprofloxacin and cephtriaxone. Only one out of 11 isolates was found to be semi-sensitive to trimethoprim/sulfamethoxazole (cotrimoxazole).


Safety and Cost-Effectiveness of Outpatient Unicompartmental Knee Arthroplasty in the Ambulatory Surgery Center: A Matched Cohort Study.
Using an age- and comorbidity-matched cohort, we compared patients who underwent unicompartmental knee arthroplasty in an ambulatory surgery center with those who underwent the procedure in a traditional hospital inpatient setting. Postoperatively, the ambulatory surgery center cohort had fewer major complications than the inpatient cohort. No ambulatory surgery center patients required acute hospital admission and none had major complications. Four major complications occurred in the inpatient cohort. There was no difference in complication rates. Our results suggest that outpatient unicompartmental knee arthroplasty in a freestanding ambulatory surgery center is a safe and reasonable alternative to the traditional inpatient hospital setting.


DAF-shielded baculovirus-vectored vaccine enhances protection against malaria sporozoite challenge in mice.
Previous studies have shown that the baculovirus-vectored vaccine based on the "baculovirus dual expression system (BDES)" is an effective vaccine delivery platform for malaria. However, a point of weakness remaining for use of this vaccine platform in vivo concerns viral inactivation by serum complement. In an effort to achieve complement resistance, the gene encoding the human decay-accelerating factor (hDAF) was incorporated into the BDES malaria vaccine expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). The newly-developed BDES vaccine, designated BDES-sPfCSP2-Spider, effectively displayed hDAF and PfCSP on the surface of the viral envelope, resulting in complement resistance both in vitro and in vivo. Importantly, upon intramuscular inoculation into mice, the BDES-sPfCSP2-Spider vaccine had a higher protective efficacy (60%) than that of the control vaccine BDES-sPfCSP2-Spier (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. DAF-shielded BDES-vaccines offer great potential for development as a new malaria vaccine platform against the sporozoite challenge.


Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres.
Summary The purpose of this study was to evaluate telomere length in peripheral blood granulocytes and mononuclear cells collected from 22 women with polycythaemia vera (PV) and essential thrombocythaemia (ET). PV and ET are chronic myeloproliferative diseases whose heterogeneity of stem cell origin and clonal development has been established through analysis of X-chromosome inactivation patterns. The results from clonality assay and determination of telomere length show that only clonal granulocytes have shortened telomeres.


Aspects of statistical design for the Community Intervention Trial for Smoking Cessation (COMMIT).
We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation (COMMIT). One outcome measurement, the quit rate in randomly selected cohorts of smokers, is compared with another outcome measurement, the decrease in smoking prevalence, in terms of statistical efficiency and interpretability. The COMMIT study uses both types of outcome measurements. The merits of pair-matching the communities are considered, and sample size calculations take into account heterogeneity among pair-matched communities. In addition to significance tests based on the permutational (randomization) distribution, we also describe approaches for covariate adjustment. The COMMIT design includes 11 pair-matched communities, which should provide good power to detect a 10% or greater difference in quit rates between the intervention and control communities in cohorts of heavy smokers and in cohorts of light or moderate smokers. The power is only moderate to detect intervention effects on the decreases in overall smoking prevalence or in the prevalence of heavy smoking.


Branching Dilated Vessels: A Possible Trichoscopic Clue for Diagnosis of Erosive Pustular Dermatosis of the Scalp in Children.
Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory scalp condition that usually affects the elderly, while only few cases have been reported in childhood. In children, it may mimic fungal or bacterial infections, especially kerion. We describe the usefulness of trichoscopy as a supportive diagnostic tool in 2 cases of pediatric EPDS. Clinical distinction between EPDS and different types of alopecia in children is difficult, with a significant likelihood of diagnostic errors and delay in therapy. Trichoscopy may provide a noninvasive option that can help avoid invasive diagnostic procedures in children.


Biodiversity and abundance patterns of rock encrusting fauna in a temperate fjord.
Fjords are semi-enclosed systems often with usually strong physical and chemical gradients. These gradients provide the opportunity to test the influence of various physical and chemical factors on biodiversity. However study area of this investigation, Trondheimsfjord, is a large water body where especially salinity gradient along the fjord is not well pronounced. The goal of this study was to establish within a temperate fjord a baseline identifying encrusting fauna on rocks and determine the factors driving changes along the length of the fjord and changing depths. There was no trend in species composition change and increase or decrease in number of species, diversity and number of individuals along the fjord. This was likely due to the relative homogeneity of both substrate (rocks) and environmental parameters. Nevertheless, the influence of fresh water inflow in the vicinity of the river mouth was apparent by the presence of characteristic brackish-water species at these locations. Multidimensional scaling analysis revealed three separate assemblages: intertidal, shallow and deep subtidal (below 50 m). Intertidal assemblages were species poor (one to 11 species) but relatively abundant (six to 2374 indiv./m(2) of rocks). Number of individuals and biomass was highest in the shallow subtidal (2059-13,587 indiv./m(2) of rocks). Overall the highest species number (45) was recorded at 50 m depth which is probably result of low competition pressure yet still relatively high nutrient concentration in comparison to shallower locations. Environmental parameters (i.e., tidal currents, wave action, salinity) change more drastically with depth than along the fjord and these changes are the major driving forces in shaping encrusting assemblages in Trondheimsfjord.


Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism.
Bisphenol-A (BPA), a chemical -xenoestrogen- used in the production of the plastic lining of food and beverage containers, is present in the urine of almost the entire population. Recent studies have shown that BPA exposure is associated with podocytopathy, increased urinary albumin excretion (UAE), and hypertension. Since these changes are characteristic of early diabetic nephropathy (DN), we explored the renal effects of BPA and diabetes including the potential role of sexual dimorphism. Male and female mice were included in the following animals' groups: control mice (C), mice treated with 21.2 mg/kg of BPA in the drinking water (BPA), diabetic mice induced by streptozotocin (D), and D mice treated with BPA (D + BPA). Male mice form the D + BPA group died by the tenth week of the study due probably to hydro-electrolytic disturbances. Although BPA treated mice did not show an increase in serum creatinine, as observed in D and D + BPA groups, they displayed similar alteration to those of the D group, including increased in kidney damage biomarkers NGAL and KIM-1, UAE, hypertension, podocytopenia, apoptosis, collapsed glomeruli, as well as TGF-β, CHOP and PCNA upregulation. UAE, collapsed glomeruli, PCNA staining, TGF-β, NGAL and animal survival, significantly impaired in D + BPA animals. Moreover, UAE, collapsed glomeruli and animal survival also displayed a sexual dimorphism pattern. In conclusion, oral administration of BPA is capable of promoting in the kidney alterations that resemble early DN. Further translational studies are needed to clarify the potential role of BPA in renal diseases, particularly in diabetic patients.


TNFα-induced M-MDSCs promote transplant immune tolerance via nitric oxide.
Efficient induction of functional competent myeloid-derived suppressor cells (MDSCs) will be critical for the clinical application of MDSCs to treat autoimmune diseases and to induce transplantation immune tolerance. In the present study, we tried to establish the MDSC induction system with M-CSF and tumor necrosis factor α (TNFα) and investigated the immunosuppressive function of M-CSF + TNFα-induced MDSCs in transplant mouse models. Monocytic MDSCs (M-MDSCs) were induced by culture of the non-adherent mouse bone marrow cells with M-CSF or M-CSF + TNFα, respectively, for 7 days. Phenotype analysis revealed that the majority of M-CSF- and M-CSF + TNFα-induced MDSCs express F4/80. The addition of TNFα in the induction period increased Gr-1, Ly6C, CD80, and CD274 expressions on these cells. M-CSF + TNFα-induced M-MDSCs showed poor TNFα, IL-12, and IL-6 expressions after lipopolysaccharide (LPS) stimulation and decreased arginase 1 (Arg-1) and Fizz expressions after IL-4 stimulation compared with M-CSF-induced M-MDSCs. M-CSF + TNFα-induced M-MDSCs showed enhanced ability to suppress T cell proliferation and cytokine production than M-CSF-induced M-MDSCs. M-CSF + TNFα-induced M-MDSCs express high levels of inducing nitric oxide synthase (iNOS) and blocking iNOS activity by a chemical inhibitor or gene deficiency significantly reversed the inhibitory effects of M-CSF + TNFα-induced M-MDSCs on T cells. Adoptive transfer of M-CSF + TNFα-induced M-MDSCs promoted immune tolerance in a male-to-female skin-grafted mice, but M-CSF + TNFα-induced iNOS-deficient M-MDSCs failed to do so. Thus, M-CSF + TNFα-induced M-MDSCs have powerful immunosuppressive activity, which is mediated by an iNOS-dependent pathway. M-CSF + TNFα-induced M-MDSCs can promote immune tolerance to donor antigens in a transplant mouse model. The combination of M-CSF and TNFα efficiently induces functional M-MDSCs in vitro. M-CSF + TNFα-induced M-MDSCs promote immune tolerance in a transplant mouse model. The immunosuppressive ability of M-CSF + TNFα-induced M-MDSCs is dependent on iNOS.


Voiding dysfunction in patients with human T-lymphotropic virus type-1-associated myelopathy (HAM).
Voiding dysfunction was evaluated in 16 of 17 patients with human T-lymphotropic virus type-1 associated myelopathy (HAM). Among 16 patients 11 had both frequency and difficulty in voiding and 12 had urge incontinence of urine. Sensation of vesical filling and voiding remained either intact or only slightly suppressed in all patients. Residual urine ranging from 50 to 320 ml was observed in 14 patients. Urodynamic studies showed in every patient an overactive bladder with involuntary detrusor contraction. Only 2 patients had detrusor sphincter synergia, 6 patients had complete detrusor sphincter dyssynergia and 8 patients had incomplete detrusor sphincter dyssynergia. An overactive bladder associated with detrusor sphincter dyssynergia and less affected vesical sensation seems to be a characteristic urodynamic finding in HAM. These results combined with other neurological findings suggest that in patients with HAM lateral columns of the spinal cord between sacral and ponsmesencephalic micturition centre are mainly affected and that the posterior columns of the spinal cord are relatively less affected.


Uloma (Uloma) metogana Ren, 2004: redescription of the adult and descriptions of the larva and pupa (Coleoptera: Tenebrionidae, Ulomini).
The adult of Uloma (Uloma) metogana Ren, 2004, an endemic species to the southeastern Qinghai-Xizang Plateau of China, is redescribed and illustrated. The male of this species is newly discovered, its larva and pupa are described and illustrated for the first time. Meanwhile, sequences of three gene fragments (COI, Cytb and 16S rDNA) are obtained for the larva, pupa and adult to further confirm their identity.


Histological Review of Thyroid Lesions: A 13-year Retrospective Study (1989-2001).
We present a 13-years retrospective histological study of 444 thyroidectomies received between 1989 and 2001 at the Morbid Anatomy department of the Lagos University Teaching Hospital, Nigeria. The aim of the study is to update the available literature on the frequencies of the common thyroid lesions as well as compare with previous studies. The materials for this study consist of slides and paraffin embedded blocks of all thyroidectomies received from within and outside the teaching hospital. The clinical data such as the age, sex, and clinical summary were extracted from the request forms. The male: female ratio is 1: 7. The most common entity was goiter (74%); most of which occurred in the age group 30-39 yrs. Thyroid adenomas (majority; follicular), constituted 10%. There were 29 cases of thyroid carcinoma accounting for 7% of all lesions and occurring more in females than males (17:12). Histologically, follicular carcinoma predominated (48.3%), followed by papillary carcinoma (34.5%) and medullary carcinoma (13.8%). Thyroiditis was uncommon (only 2%). Goiter, adenoma and carcinoma remain the commonest pathologic entities of the thyroid gland in Lagos. The age and sex incidences as well as the histological characteristics concur with reports from other parts of Africa and Nigeria. However, unlike many of the Nigerian series except the latest from Ibadan, 4 cases of medullary carcinoma were encountered in this study. The frequencies of toxic hyperplasia and thyroiditis are also lower than those recorded in previous studies. thyroidectomy, histopathology, thyroid lesions.


Posterior polar cataract: A review.
Posterior polar cataract is a rare form of congenital cataract. It is usually inherited as an autosomal dominant disease, yet it can be sporadic. Five genes have been attributed to the formation of this disease. It is highly associated with complications during surgery, such as posterior capsule rupture and nucleus drop. The reason for this high complication rate is the strong adherence of the opacity to the weak posterior capsule. Different surgical strategies were described for the handling of this challenging entity, most of which emphasized the need for gentle maneuvering in dealing with these cases. It has a unique clinical appearance that should not be missed in order to anticipate, avoid, and minimize the impact of the complications associated with it.


Circulating cytokines after hip and knee arthroplasty: a preliminary study.
Several studies show cytokine concentrations in the peripheral blood are associated with inflammatory activity and surgical trauma. Cytokine concentrations have more rapid increase and quicker return to normal values than either C-reactive protein or erythrocyte sedimentation rate - a matter of hours rather than weeks; some studies suggest they are better predictors of postoperative infection than C-reactive protein and erythrocyte sedimentation rate. Threshold levels of interleukin-6 after joint arthroplasty have been determined, but levels of other potentially useful cytokines (tumor necrosis factor-alpha, interleukin-8, interleukin-10, etc) are not known. We measured the serum levels of 25 different cytokines before and after hip and knee arthroplasties and identified those associated with surgical trauma. Peripheral venous blood samples (one preoperative and three postoperative) from 49 patients undergoing hip or knee arthroplasty were analyzed by laser chromatography. Three of the 25 cytokines had a relationship with postsurgical trauma, which included one deep infection. Serum levels of these three cytokines might be useful to identify periprosthetic infections during the early postoperative period when C-reactive protein and erythrocyte sedimentation rate remain elevated. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Author Correction: Environmental stimuli drive a transition from cooperation to competition in synthetic phototrophic communities.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Laparoscopic versus open appendectomy for acute appendicitis: a metaanalysis.
Currently, laparoscopic appendectomy (LA) provides a safe and effective alternative to open appendectomy (OA), but its use remains controversial. This study aimed to evaluate the efficiency and safety of LA through a metaanalysis. Randomized controlled trials (RCTs) comparing LA and OA published between January 1992 and February 2010 were included in this study. Strict literature appraisal and data extraction were carried out independently by two reviewers. A metaanalysis then was performed to evaluate operative time, hospital cost, postoperative complications, length of analgesia, bowel function recovery, day liquid diet began, hospital stay, and return to work and normal activity. The metaanalysis comprised 25 RCTs involving 4,694 patients (2,220 LA and 2,474 OA cases). No significant differences were found between the LA and OA groups in terms of age, gender, body mass index (BMI), or type of appendiceal inflammation. Compared with OA, LA showed advantages of fewer postoperative complications (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55-0.98; p = 0.04), less pain (length of analgesia: weighted mean difference [WMD], -0.53; 95% CI, -0.91 to -0.15; p = 0.007), earlier start of liquid diet (WMD, -0.51; 95% CI, -0.75 to -0.28; p < 0.0001), shorter hospital stay (WMD, -0.68; 95% CI, -1.02 to -0.35; p < 0.0001), and earlier return to work (WMD, -3.09; 95% CI, -5.22 to -0.97; p = 0.004) and normal activity (WMD, -4.73; 95% CI, -6.54 to -2.92; p < 0.00001), but a comparable hospital cost (WMD of LA/OA ratio, 0.11; 95% CI, -0.18 to 0.40; p = 0.47) and a longer operative time (WMD, 10.71; 95% CI, 6.76-14.66; p < 0.00001). Despite the longer operative time, LA results in less postoperative pain, faster postoperative rehabilitation, a shorter hospital stay, and fewer postoperative complications than OA. Therefore, LA is worth recommending as an effective and safe procedure for acute appendicitis.


A mouse zinc finger gene which is transiently expressed during spermatogenesis.
Zinc finger proteins are polypeptides with sequence-specific, nucleic acid-binding properties. Substantial evidence has established them as a class of trans-acting molecules with regulatory roles in cellular growth and differentiation. We have screened an 11.5 day post coitum urogenital ridge cDNA library with an oligonucleotide encoding a sequence conserved between a variety of zinc finger proteins. By cDNA cloning and sequencing we show that a novel mouse gene, Zfp-35, encodes a protein with a block of 18 zinc finger domains and an N-terminal region rich in acidic residues. The 2.4 kb mRNA encoding this polypeptide is selectively expressed in adult testis, by comparison with other organs. We have analysed Zfp-35 expression in whole testes of sex-reversed mice, whole testes of prepuberal XY animals, germ cell fractions from XY adult testes and by in situ hybridization to sections from adult XY testes. Our studies show that a considerable increase in expression is restricted to spermatocytes at the pachytene stage of meiotic prophase. These experiments suggest that Zfp-35 may act to control gene activity during this particular stage of spermatogenesis.


Cutaneous polyarteritis nodosa in children.
The purpose of this study was to present the clinical courses and histologic findings of 4 children with cutaneous vasculitis characterized by tender cutaneous nodules and fever in the absence of major organ involvement. We conducted a retrospective chart review of 4 patients with cutaneous vasculitis followed up for a mean of 68 months (range, 12-114 months). The patients included 3 boys and 1 girl (ages at onset, 2-10 years). Clinical and laboratory manifestations included tender erythematous cutaneous nodules (n = 4/4), fever 39 degrees C or higher (4/4), nondeforming arthritis (3/4), leukocytosis and elevated erythrocyte sedimentation rate (4/4), positive antinuclear antibodies (1/4), and elevated streptococcal enzymes (3/4). Skin biopsy results showed inflammation of medium-sized cutaneous arteries with a mixed inflammatory cell infiltrate consistent with cutaneous polyarteritis nodosa (4/4). Patients were treated with prednisone with good initial response, but exacerbation occurred once prednisone was tapered. Additional medications given were methotrexate (2/4), dapsone (2/4), colchicine (1/4), and cyclophosphamide (1/4). One patient is in clinical remission after 48 months of disease; the others have continuing disease that requires treatment. Patients with evidence of streptococcal infection received oral penicillin prophylaxis; two of the three patients had recurrent attacks of vasculitis despite penicillin. No patients have developed major organ system involvement after 12 to 114 months of follow-up. Cutaneous polyarteritis nodosa in children is a recognizable entity characterized by painful nodules, fever, absence of major organ involvement, and chronic or recurrent course. Patients should be screened for streptococcal infection and treated with antibiotics when needed.


Liquid-crystalline membrane permeation ability for selected nitro hair dyes.
A comparison of permeation ability of selected semi-permanent hair dyes and an attempt to estimate the influence of fundamental physicochemical parameters on dyes' epidermal penetration rate. Dyes' permeation ability through liposome membrane (as a model of stratum corneum) with side-by-side cells was assessed. It has been shown that the chosen dyes are capable of permeating the membrane. High penetration coefficients (Kp) were obtained for a simple nitrophenylenediamines and nitroaminophenols. Their N-, O-hydroxyalkyl substitution significantly limits penetration. H-bonding capability has a major impact on the investigated dyes' permeation ability. Substituents with H-bonding properties can significantly limit dyes' penetration, even in the case of lipophilic structures. Special attention should be placed into compounds with strong intramolecular H-bonding properties, which improve transmembrane transport. Substitution patterns have an influence on selected nitro dyes' permeation through a model stratum corneum. Permeation is limited by dyes diffusive properties (mostly by its H-bonding properties). Hydroxyalkylation results in hindered dyes permeation: purple, violet and blue nitrophenylenediamine or nitroaminophenol derivatives are less permeable than its not substituted analogues.


Stenotrophomonas maltophilia--the most worrisome threat among unusual non-fermentative gram-negative bacilli from hospitalized patients: a prospective multicenter study.
Isolation rates of unusual non-fermentative Gram-negative bacilli (i.e. other than Pseudomonas aeruginosa and Acinetobacter baumannii) are increasing but studies are limited to few observations. We aimed at determining risk factors for infection and influence of antibiotic treatment on the outcome. A six-month (December 1, 2008-May 31, 2009) prospective multicenter cohort study was conducted in nine French teaching hospitals. Characteristics of patients colonized or infected by unusual NF-GNB, adequacy of antimicrobial therapies, and outcome were analyzed. Analysis of 158 patients (median age, 62.7 years) was conducted. Stenotrophomonas maltophilia was the predominant bacterial species isolated (39%) followed by Achromobacter group (15%) and non-baumannii Acinetobacter species (13%). Compared to colonized patients, infected ones were more frequently immunocompromised [relative risk (RR) = 1.63, (95% confidence interval (CI) = 1.02-2.60, P = 0.05)], hospitalized within the last three months [RR 1.67 (95% CI 1.09-2.58, P = 0.02)], admitted in an intensive care unit with central venous catheter [RR 1.74 (95% CI 1.15-2.63, P = 0.01)]. The overall hospital mortality concerned 28 patients (18%) but no association with inadequate antimicrobial treatment was found except in the group of S. maltophilia infected cases [RR 2.81 (95% CI 1.01-7.83, P = 0.02)]. Naturally carbapenems-resistant S. maltophilia is the main unusual NF-GNB pathogen in hospitalized patients, leading to inappropriate empirical antibiotic treatment at the time of emerging extended-spectrum β-lactamase-producing bacteria.


Cordycepin/Hydroxyurea synergy allows low dosage efficacy of cordycepin in MOLT-4 leukemia cells.
Cordycepin requires the relatively toxic co-drug, deoxycoformycin, for full efficacy as an anticancer agent. We sought to improve cordycepin efficacy using other, less toxic co-drugs. We evaluated the ability of hydroxyurea (HU) to enhance the effects of cordycepin against MOLT-4 leukemia cells with the MTT cell viability assay. We determined the relationship of the combination drug treatment with CalcuSyn statistical analysis program according to the Chou-Talalay method. HU (50 microg/ml) was found to reduce the IC50 of cordycepin from 100 microM to 0.3 microM, a reduction similar to that observed for deoxycoformycin. CalcuSyn analysis of the cordycepin/HU combination revealed the dose effect as synergistic. Further statistical analysis demonstrated a clear synergy between the two drugs at a range of dosages. HU was identified as a promising potential alternative for anti-cancer therapy with cordycepin, thus eliminating the need for the toxic deoxycoformycin.


[Regional and gender variations in appendicectomy : Nationwide small-area development of operation rates in the time series].
Previous analyses of small-area appendicectomy rates showed significantly higher regional differences in the frequency of operations in women than in men OBJECTIVE: This work proposes valid measures to represent regional variations and analyzes gender-specific changes of appendicectomy rates at the county level in the time series. Appendicectomy frequencies for 2014, 2016 and 2018 by gender and at the county level were taken from the DRG statistics. Regional variations were calculated and assessed using the systematic component of variation (SCV). In comparison to the extreme ratio and coefficient of variation, the SCV is more robust with respect to strongly fluctuating denominator populations. The SCV values greater than 5 indicate high variation and greater than 10 indicate very high variation. In the male population only minor regional variations in operation rates could be observed, remaining at similar levels over time (SCV2014 = 2.1, SCV2016 = 1.8, and SCV2018 = 2.0). For women the SCV was above 5 in 2014 as well as in 2016 (SCV2014 = 6.1, SCV2016 = 5.3) and dropped to 4.5 in 2018. Plots as a funnel plot account for higher scatter in surgery rates in counties with low populations. Regarding women, a decreasing trend in regional variation of appendicectomy could be observed. It remains unclear whether this trend reflects a change in the indications or a modified clinical management when appendicitis is suspected. Using robust variation measures and the graphic preparation as funnel plots it is possible to distinguish systematically caused regional differences in care from random effects.


Incidence of postoperative stroke using the Heartstring device in 1,380 coronary artery bypass graft patients with mild to severe atherosclerosis of the ascending aorta.
Atherosclerotic disease of the ascending aorta during coronary artery bypass graft surgery (CABG) increases the risk for postoperative stroke. The objective of this study was to examine the incidence of postoperative stroke in CABG utilizing the Heartstring (Maquet Cardiovascular, San Jose, CA) proximal anastomotic device. Intraoperative epiaortic ultrasonography was used to grade atherosclerosis in CABG patients at Emory University from April 2003 to December 2012. The Heartstring device was utilized in 1,380 patients: 407 (29.5%) grade I (minimal atherosclerosis), 367 (26.6%) grade II, 437 (31.7%) grade III, 110 (8.0%) grade IV, and 59 (4.3%) grade V (severe atherosclerosis). Logistic regression analysis was used to estimate the effect of aortic grade on outcomes adjusted for Society of Thoracic Surgeons predicted risk of mortality and predicted risk of stroke scores. The mean age of all patients was 66.7 ± 10.5 years, and 31.9% were female. An increasing risk profile was apparent with rising aortic grade. Most CABG was done off pump (n = 1,277, 92.5%). There was no significant association between aortic grade and frequency of postoperative stroke (p = 0.83). In all patients, use of the Heartstring device reduced the predicted risk of stroke by 44% (O:E risk 0.56). The benefit for postoperative stroke was least apparent in the grade I aorta patients (O:E 0.8) compared with patients having grade II and greater. There were no strokes among patients with severe atherosclerosis using the Heartstring device. Compared with the Society of Thoracic Surgeons predicted risk for stroke, the Heartstring proximal anastomotic device can be safely used with all aortic grades. The most prominent benefit appears to be for patients with grade II disease and greater.


Identification of putative molecular imaging probes for BACE-1 by accounting for protein flexibility in virtual screening.
β-secretase (BACE-1), an enzyme critical in the process of amyloid-β (Aβ) peptides deposition in human brain, is closely associated with the onset and progression of Alzheimer's disease (AD). A strong need exists, therefore, to identify molecular imaging probes homing at BACE-1 for use with positron emission tomography (PET) that is recognized as an effective tool for detecting AD. Through this imaging, an early diagnosis of AD could be made. Herein, to identify suitable molecular probes for use with PET, we searched the Molecular Imaging and Contrast Agent Database (MICAD), an online database warehousing scientific information regarding molecular imaging and contrast agents, and applied a virtual screening approach against the different confirmations of BACE-1 obtained from the World Wide Protein Database. The lack of considering receptor flexibility is a key drawback in virtual screening for drug discovery. Therefore, we incorporated protein flexibility into the virtual screening by using an ensemble of 143 experimental BACE-1 structures derived from the Protein Data Bank. Finally, the best performing affinity was recorded and used in the ranking of each ligand. To the best of our knowledge, this is the first virtual screening approach used to identify four new molecular probes that could target BACE-1 with favorable affinity, a discovery that can lead to the development of new PET probes for the early detection and therapy of AD. However, the actual utility of these probes can only be ascertained after in vitro and in vivo investigations.


The Power of Perception: Lived Experiences with Diagnostic Labeling in Mental Health Recovery without Ongoing Medication Use.
The recovery movement in mental health emphasizes holistic and individualized treatment through many pathways to recovery, though the majority of mental health treatment and existing literature emphasize pharmacotherapy and medication adherence for major mental health conditions. The reimbursement system and research literature are oriented around formal diagnostic categories based in a biomedical perspective of mental health problems, but diagnostic labels also carry stigma and influence how clients perceive themselves and their mental health problems. To investigate the influence of labeling and perception in alternate pathways to recovery, this qualitative study explores the lived experience of diagnostic labeling and self-perception among persons in sustained recovery without ongoing medication use. The study used a grounded theory approach to analyze data from in-depth interviews with 19 participants. Participants had previously received diagnoses of schizophrenia, bipolar disorder, and/or major depression, met criteria for functional recovery, and were no longer taking psychotropic medications for 12 months. The participants identified positive perceptions-externalization of the problem and hope for an external "cure"-and negative perceptions-stigma and powerlessness-following a diagnostic label. Notably, the theme of powerlessness related to the initially positive themes as the diagnosis placed the problem outside their control and some participants experienced treatments as unhelpful. Participants succeeded in overcoming powerlessness by finding internalized solutions and redefining their mental health experience as transformative. Rather than pressing clients to accept their diagnosis or "illness," mental health providers can support multiple pathways to recovery by emphasizing empowerment and personal meaning-making in the recovery process.


Mislocalization of Kir channels in malignant glia.
Inwardly rectifying potassium (K(ir)) channels are a prominent feature of mature, postmitotic astrocytes. These channels are believed to set the resting membrane potential near the potassium equilibrium potential (E(K)) and are implicated in potassium buffering. A number of previous studies suggest that K(ir) channel expression is indicative of cell differentiation. We therefore set out to examine K(ir) channel expression in malignant glia, which are incapable of differentiation. We used two established and widely used glioma cell lines, D54MG (a WHO grade 4 glioma) and STTG-1 (a WHO grade 3 glioma), and compared them to immature and differentiated astrocytes. Both glioma cell lines were characterized by large outward K(+) currents, depolarized resting membrane potentials (V(m)) (-38.5 +/- 4.2 mV, D54 and -28.1 +/- 3.5 mV, STTG1), and relatively high input resistances (R(m)) (260.6 +/- 64.7 MOmega, D54 and 687.2 +/- 160.3 MOmega, STTG1). These features were reminiscent of immature astrocytes, which also displayed large outward K(+) currents, had a mean V(m) of -51.1 +/- 3.7 and a mean R(m) value of 627.5 +/- 164 MOmega. In contrast, mature astrocytes had a significantly more negative resting membrane potential (-75.2 +/- 0.56 mV), and a mean R(m) of 25.4 +/- 7.4 MOmega. Barium (Ba(2+)) sensitive K(ir) currents were >20-fold larger in mature astrocytes (4.06 +/- 1.1 nS/pF) than in glioma cells (0.169 +/- 0.033 nS/pF D54, 0.244 +/- 0.04 nS/pF STTG1), which had current densities closer to those of dividing, immature astrocytes (0.474 +/- 0.12 nS/pF). Surprisingly, Western blot analysis shows expression of several K(ir) channel subunits in glioma cells (K(ir)2.3, 3.1, and 4.1). However, while in astrocytes these channels localize diffusely throughout the cell, in glioma cells they are found almost exclusively in either the cell nucleus (K(ir)2.3 and 4.1) or ER/Golgi (3.1). These data suggest that mislocalization of K(ir) channel proteins to intracellular compartments is responsible for a lack of appreciable K(ir) currents in glioma cells.


Structures and development of the venous system in congenital malformations of the brain.
Cerebral venograms of 21 clinical cases of midline anomalies of the brain and of 80 human fetuses between 3 and 8 months old were examined. The diagnostic value of the venogram was fully proven, particularly for the midline cerebral anomalies, where deep cerebral structures and configuration of the tentorium cerebelli were not well visualized by other neuroradiologic maneuvers. Abnormal structures of the deep cerebral veins as well as the dural sinuses in these malformations were proved to retain the venous structures in the early fetal period. The time of formation of these malformations was also inferred from the viewpoint of the venous development. Study of the fetal venous system was found quite useful for embryologic analysis and classification of congenital malformations of the brain.


Hyaluronuria in a case of progeria. (Hutchinson-Gilford syndrome).
A classic case of progeria (Hutchinson-Gilford syndrome) in a 9-year-old Japanese boy is presented. The characteristic clinical features in this patient were similar to those reported in the literature. The total amount of acid glycosaminoglycans excreted in the urine was within the normal range, but there was an increase in hyaluronic acid excretion. The hyaluronuria was a novel finding in progeria, providing a common linkage with the hyaluronuria found in Werner's syndrome.


The comprehension of humorous materials by adolescents with high-functioning autism and Asperger's syndrome.
This study investigated the ability of adolescents with Asperger's syndrome or high-functioning autism and an age-matched group of typical adolescents to comprehend humorous materials. The analysis of humor focused on picking funny endings for cartoons and jokes. As expected, the adolescents with autism had significantly poorer comprehension of cartoons and jokes. Both groups had more difficulty with the joke than the cartoon task, but when compared with the typical group, the adolescents with autism performed significantly poorer. Examination of the error patterns revealed that subjects with autism had difficulty handling surprise and coherence within humorous narratives.


The C50 carotenoid bacterioruberin regulates membrane fluidity in pink-pigmented Arthrobacter species.
Carotenoids have several crucial biological functions and are part of the cold adaptation mechanism of some bacteria. Some pink-pigmented Arthrobacter species produce the rare C50 carotenoid bacterioruberin, whose function in these bacteria is unclear and is found mainly in halophilic archaea. Strains Arthrobacter agilis DSM 20550T and Arthrobacter bussei DSM 109896T show an increased bacterioruberin content if growth temperature is reduced from 30 down to 10 °C. In vivo anisotropy measurements with trimethylammonium-diphenylhexatriene showed increased membrane fluidity and a broadening phase transition with increased bacterioruberin content in the membrane at low-temperature growth. Suppression of bacterioruberin synthesis at 10 °C using sodium chloride confirmed the function of bacterioruberin in modulating membrane fluidity. Increased bacterioruberin content also correlated with increased cell resistance to freeze-thaw stress. These findings confirmed the adaptive function of bacterioruberin for growth at low temperatures for pink-pigmented Arthrobacter species.


Hybrid Additive Microfabrication Scaffold Incorporated with Highly Aligned Nanofibers for Musculoskeletal Tissues.
Latest tissue engineering strategies for musculoskeletal tissues regeneration focus on creating a biomimetic microenvironment closely resembling the natural topology of extracellular matrix. This paper presents a novel musculoskeletal tissue scaffold fabricated by hybrid additive manufacturing method. The skeleton of the scaffold was 3D printed by fused deposition modeling, and a layer of random or aligned polycaprolactone nanofibers were embedded between two frames. A parametric study was performed to investigate the effects of process parameters on nanofiber morphology. A compression test was performed to study the mechanical properties of the scaffold. Human fibroblast cells were cultured in the scaffold for 7 days to evaluate the effect of scaffold microstructure on cell growth. The tip-to-collector distance showed a positive correlation with the fiber alignment, and the electrospinning time showed a negative correlation with the fiber density. With reinforced nanofibers, the hybrid scaffold demonstrated superior compression strength compared to conventional 3D-printed scaffold. The hybrid scaffold with aligned nanofibers led to higher cell attachment and proliferation rates, and a directional cell organization. In addition, there was a nonlinear relationship between the fiber diameter/density and the cell actinfilament density. This hybrid biofabrication process can be established as a highly efficient and scalable platform to fabricate biomimetic scaffolds with patterned fibrous microstructure, and will facilitate future development of clinical solutions for musculoskeletal tissue regeneration.


Establishing brown trout primary hepatocyte spheroids as a new alternative experimental model-Testing the effects of 5α-dihydrotestosterone on lipid pathways.
Three-dimensional (3D) fish liver cultures mimic the in vivo cellular microenvironment, which is ideal for ecotoxicological research. Despite that, the application of these cultures to evaluate toxic effects in fish is scarce. A 3D model of brown trout (Salmo trutta f. fario) primary hepatocyte spheroids was optimized in this study by using DMEM/F-12 with 15 mM of HEPES, 10 mL/L of an antibiotic and antimycotic solution and FBS 10% (v/v), at 18 °C with ∼100 rpm. The selection of optimal conditions was based on a multiparametric characterization of the spheroids, including biometry, viability, microanatomy and immunohistochemistry. Biometric and morphologic stabilization of spheroids was reached within 12-16 days of culture. To our knowledge, this study is the first to culture and characterize viable spheroids from brown trout primary hepatocytes for over 30 days. Further, the 3D model was tested to explore the androgenic influences on lipidic target genes after 96 h exposures to control, solvent control, 10 and 100 µM of 5α-dihydrotestosterone (DHT), a non-aromatizable androgen. Spheroids exposed to 100 µM of DHT had decreased sphericity. DHT at 100 µM also significantly down-regulated Acox1-3I, PPARγ and fatty acid synthesis targets (i.e., ACC), and significantly up-regulated Fabp1. Acsl1 was significantly up-regulated after exposure to both 10 and 100 µM of DHT. The results support that DHT modulates distinct lipidic pathways in brown trout and show that this 3D model is a new valuable tool for physiological and toxicological mechanistic studies.


Mammary stroma in development and carcinogenesis.
Mammary glands of adult human females are secretory organs comprised of interdependent epithelial and mesenchymal cells. These cells constitute an assemblage of collecting ducts that end in terminal duct lobular units with hollow alveolar ductules that can differentiate to produce and expel milk. Systemic and maternal hormones, autocrine and paracrine growth factors, and cytokines regulate virtually all phases of mammary gland development. During organogenesis, epithelial and mesenchymal cells interact to form precursors of the parenchyma and stroma in the mature gland. Organogenesis precedes five stages of postnatal development: puberty, pregnancy, lactation, involution, and menopause. Each stage requires a specific set of morphogenetic changes in glandular structure and function. Cycles of cell proliferation, differentiation, and involution may recur until menopause. In addition, physiological responses such as inflammation and pathological events such as tumorigenesis are remarkable for their similarities to embryonic morphogenesis. Here we take a succinct look at the ever-improving understanding of stroma-epithelial interactions and mesenchyme function in mammary gland biology.


Combining partial liver resection and local ablation of liver tumours: a preliminary Dutch experience.
The combination of partial liver resection and radiofrequency ablation (RFA) is a novel concept in the treatment of unresectable liver malignancies. The aim of this study is to evaluate the results of this combined strategy in the Netherlands. Thirty-five patients treated with a combination of partial liver resection and RFA were identified from a prospectively registered pooled multicentre database. All patients were operated between June 1999 and November 2003 in 8 medical centres in The Netherlands. Main outcome parameters were morbidity, mortality, local success rate, and survival. Thirty-seven operations were performed in 35 patients. The group consisted of 20 male and 15 female patients with a median age of 59 years (range 41-76). Seventy-six lesions were resected and RFA was performed to ablate 82 unresectable liver tumours. Twelve patients developed a total of 24 complications, resulting in an overall perioperative morbidity rate of 32%. In two patients major complications resulted in postoperative death (postoperative mortality rate 5.4%). Local success rate after RFA was 88% and the estimated 1-, 2- and 3-year overall survival rates were 84%, 70% and 43%, respectively. This strategy should only be performed following strict patient selection and within the context of prospective clinical trials.


Controlling Gun Violence: Assessing the Impact of Australia's Gun Buyback Program Using a Synthetic Control Group Experiment.
Gun Buyback programs have been implemented in various forms in countries such as the UK, USA, Brazil, Australia, and Argentina. Whether or not these programs are an effective approach for reducing national violent crime and homicides, however, remains unclear. Much of the uncertainty is due to the different ways in which Gun Buyback programs have been implemented. The Australian Gun Buyback program is distinguished from Gun Buyback programs in other countries by its abrupt implementation, its narrow focus on a particular class of firearms, and its broad application across the entire population. We assess the impact of Australia's 1996 Gun Buyback program on national homicide rates using a synthetic control group quasi-experimental design, comparing the results to suicide and motor vehicle fatality trends to test for plausible alternative hypotheses. Results suggest that the Gun Buyback program significantly reduced Australia's homicide rate in the decade following the intervention (1997-2007).


On the evolutionary origins of life-course persistent offending: a theoretical scaffold for Moffitt's developmental taxonomy.
The study of human crime and violence represents a flashpoint for discussion across academia. Multiple theories exist pertaining to the topic, all aimed at organizing numerous findings surrounding correlates of antisocial behavior. Along these lines, Moffitt's developmental taxonomy has emerged as a theory well supported by empirical research. Noticeably absent, though, has been an effort to apply an evolutionary framework to Moffitt's dual taxonomy of offending. With this in mind, the current study is intended to examine Moffitt's different typologies in the context of Rushton's Differential K theory (an adaptation of r-K selection from life history theory). Our findings suggest that life-course persistent offending may represent a viable reproductive strategy characterized by higher levels of sexual involvement over the life-course.


[Auricular tuberculosis with regressive facial palsy after surgical intervention (author's transl)].
The authors have observed the complete regression of a facial palsy in a tuberculous otitis by precocious decompression of the nerve and anti-tuberculous medical treatment.


Annual oration. Diagnostic clues in the growing ends of bone.
Abnormalities of the growth plate account for many of the radiologic manifestations in non-neoplastic pediatric bone disease. A good understanding of the physiology of this area is helpful in radiologic diagnosis.


Neutral Red Uptake Assay to Assess Cytotoxicity In Vitro.
The neutral red uptake (NRU) assay is a cell viability assay that can be used for the assessment of compound-induced cytotoxicity. It is based on the ability of living cells to incorporate neutral red, a weak cationic dye, in lysosomes. The quantification of xenobiotic-induced cytotoxicity is expressed as a concentration-dependent reduction of the uptake of neutral red when compared to cells exposed to corresponding vehicle controls. The NRU assay is mainly used for hazard assessment in in vitro toxicology applications. Hence, this method has been incorporated in regulatory recommendations such as the OECD test guideline TG 432, in which an in vitro 3T3-NRU-phototoxicityassay is described to assess the cytotoxicity of compounds in the presence or absence of UV light.This book chapter describes a detailed protocol to carry out the NRU assay using the human hepatoma cell line HepG2, which is frequently employed as an alternative in vitro model for human hepatocytes. As an example, the cytotoxicity of acetaminophen and acetylsalicylic acid is assessed.


Symbiotic deficiencies associated with a coxWXYZ mutant of bradyrhizobium japonicum
The terminal oxidase complexes encoded by coxMNOP and coxWXYZ were studied by analysis of mutations in each of the two oxidases. Carbon monoxide difference spectra obtained from membranes of coxMNOP mutant bacteroids were like those obtained for the wild type, whereas bacteroid membranes of a coxWXYZ mutant were deficient in CO-reactive cytochrome b. Experiments involving cyanide inhibition of oxidase activity were consistent with the conclusion that the coxX mutant is deficient in a membrane-associated O2-binding component. The viable cell number (bacteria that could be recultured from crushed nodules) was 20 to 29% lower for the coxX mutant than for the wild-type or the CoxN- strain. In three separate greenhouse studies, nodules of a coxX mutant had significantly lower (28 to 34% less) acetylene reduction rates than the wild-type nodules did, and plants inoculated with a double mutant (coxMNOP coxWZYZ) had rates 30% lower than those of wild-type-inoculated plants.


Sympathetic cochleolabyrinthitis in revision stapedectomy surgery.
The purpose of this study was to determine whether revision stapedectomy could precipitate sensorineural hearing loss in the contralateral ear. We conducted a retrospective review of 148 patients undergoing primary or revision stapedectomy at an academic, tertiary care facility. Stapedectomy resulted in significant improvements in mean air conduction thresholds in the ipsilateral ear. Overall, there were no significant changes in either the air or bone conduction values of the contralateral ear. Two patients demonstrated a >20-dB decline in speech reception threshold and/or >20% decrease word recognition in the contralateral ear. Both of these patients demonstrated the decline only after revision surgery. Revision stapedectomy is on rare occasions associated with hearing loss in the contralateral ear. Contralateral hearing loss after revision stapedectomy may be due to sympathetic cochleolabyrinthitis.


[Supporting families in the management of gastroesophageal reflux disease in children].
Gastroesophageal reflux disease (GERD) in children is a frequent reason for medical consultation. It is defined as the involuntary passage of gastric contents into the esophagus, with or without regurgitation and vomiting. It can become pathological if it leads to embarrassing symptoms and complications. Often confronted with this pathology, nursery nurses sometimes find themselves at a loss when it comes to treating the symptoms of pathological GERD in a toddler, as well as in supporting the parents. In order to give them some ideas, a review of the literature on the benefits of non-medicinal strategies on regurgitation in full-term infants with pathological GERD was conducted.


Cell-free prototyping enables implementation of optimized reverse β-oxidation pathways in heterotrophic and autotrophic bacteria.
Carbon-negative synthesis of biochemical products has the potential to mitigate global CO2 emissions. An attractive route to do this is the reverse β-oxidation (r-BOX) pathway coupled to the Wood-Ljungdahl pathway. Here, we optimize and implement r-BOX for the synthesis of C4-C6 acids and alcohols. With a high-throughput in vitro prototyping workflow, we screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selectivity. Implementation of these pathways into Escherichia coli generates designer strains for the selective production of butanoic acid (4.9 ± 0.1 gL-1), as well as hexanoic acid (3.06 ± 0.03 gL-1) and 1-hexanol (1.0 ± 0.1 gL-1) at the best performance reported to date in this bacterium. We also generate Clostridium autoethanogenum strains able to produce 1-hexanol from syngas, achieving a titer of 0.26 gL-1 in a 1.5 L continuous fermentation. Our strategy enables optimization of r-BOX derived products for biomanufacturing and industrial biotechnology.


Electrokinetic study of calcium carbonate and magnesium hydroxide particles in lime softening.
Significant effort has been made to measure and understand the surface charge of CaCO3 and Mg(OH)2 particles. Many laboratory experiments have been reported on zeta potential of natural and prepared CaCO3 and a few have also been published for Mg(OH)2, however, there are very few reported measurements of zeta potential of CaCO3 and Mg(OH)2 particles at conditions relevant to lime softening, despite lime softening being a common and established process for water treatment. The present study aims to understand the interactions and electrokinetic properties of these two particles in lime softening. Effects of various experimental parameters such as pH, temperature, aging, inorganic carbon (CO32-/HCO3-), and divalent cations (Ca2+/Mg2+) on the electrokinetic properties (i.e. zeta potential) of CaCO3 and Mg(OH)2 particles were individually studied. The interactions between humic acid (mimicking natural organic matter), silicate (representing silica), clay (mimicking suspended solids) and CaCO3/Mg(OH)2 particles were studied, as well as the interactions between CaCO3 and Mg(OH)2. Thermodynamic modeling was used to predict precipitates as a function of solution chemistry and assist with data interpretation. The results provide considerable insight into factors that are of importance to lime softening.


Substitution of the native srfA promoter by constitutive Pveg in two B. subtilis strains and evaluation of the effect on Surfactin production.
The genetic enhancement of Surfactin production increasingly gained attention in the last years, since relatively low product yields limit the industrial application of this biosurfactant. The natural quorum sensing regulation of the srfA operon (coding for the Surfactin synthetase) can reasonably be assumed to be the bottleneck of Surfactin synthesis. Therefore, the replacement of the naturally quorum sensing regulated, and herewith cell density dependent, promoter PsrfA against the Bacillus subtilis endogenous and constitutive promoter Pveg was hypothesized to generally enhance Surfactin yields. The markerless promoter replacement was conducted in the two B. subtilis Surfactin producer strains 3A38 and DSM 10(T). The promoter substitution led to an enhancement of Surfactin concentrations in the producer strain 3A38, initially producing only minor amounts of Surfactin (0.07g/L increased to 0.26g/L). In contrast, promoter exchange in B. subtilis DSM 10(T) (wild-type strain producing 0.62g/L Surfactin) did not achieve an enhancement of Surfactin concentrations (detrimental reduction to 0.04g/L). These findings implicate that Surfactin synthesis is differently regulated in minor and strong Surfactin producer strains. The hypothesized general enhancement of Surfactin yields after substitution of the native promoter was therefore not confirmed.


X chromosome inactivation in females with multiple sclerosis.
The aetiology of multiple sclerosis (MS) is unknown. Autoimmune mechanisms are most probably involved. Loss of immunological tolerance to self-antigens is a common feature of autoimmune disorders. Response to X-linked self-antigens could be influenced by X-chromosome inactivation, and contribute to the gender bias observed in autoimmune disorders. Previous studies have indicated an association between skewed X inactivation and autoimmune thyroid disease and scleroderma. To investigate a potential role of X inactivation in MS, we compared the X-inactivation pattern in 568 female MS patients with controls. We found no difference in degree of skewing between patients (median 64%) and controls (median 65%) (P = 0.474). The X-inactivation pattern did thus not explain the female predominance of MS patients in general. As the aetiology of different subgroups of MS may differ, patients were grouped according to disease course: relapsing-remitting (RR-MS), secondary progressive (SP-MS) and primary progressive (PP-MS). A comparison of the X-inactivation pattern between subgroups indicated a possible difference in degree of skewing between patients with a progressive versus a relapsing course (P = 0.05).


Changes in morphological and structural characteristics of high amylose maize starch in alkaline solution at different temperatures.
In this study, high amylose maize starch(HAMS)was treated by Hydrothermal-alkali. SEM, SAXS, XRD, FTIR, LC-Raman, 13C CP/MAS NMR, GPC and TGA were used to study the changes in the granules and structure of HAMS. The results show that the granule morphology, lamellar structure, and birefringence of HAMS remained intact at 30 °C and 45 °C. With increasing temperature, the starch granules are fragmented, and the crystallinity, DD, FWHM values, molecular weight, and thermal stability of HAMS decrease. The double helical structure dissociated, and the content of amorphous regions increased, indicating the from order to the disorder of the HAMS structure. A similar annealing behavior occurred in HAMS at 45 °C, with the rearrangement of amylose and amylopectin occurring. At 75 °C and 90 °C, the short-chain starch produced by chain breakage regroups to form an ordered double helix structure. In general, the granule structure level of HAMS was damaged to different degrees at varying temperatures. HAMS showed gelatinization behavior in alkaline solutions when the temperature is 60 °C. This study expects to provide a model for the gelatinization theory of HAMS systems.


Effects of the prebiotic inulin-type fructans on post-antibiotic reconstitution of the gut microbiome.
Interventions using prebiotic inulin-type fructans (ITFs) are widely prescribed to modulate the gut microbiota composition and activity to promote health. However, the impacts of ITFs on post-antibiotic reconstitution of the gut microbiome remain incompletely understood. The aim of the present study was to investigate the effects of ITFs supplementation on intestinal inflammation, the composition of the intestinal microbiota and the colonic transcriptome after antibiotic treatment. Male BALB/c mice were subjected to an antibiotic cocktail (ABx) treatment for 7 days, and their microbiomes were then reconstituted either spontaneously or with ITFs supplementation (5%) for 14 days. Our data showed that ITFs supplementation delayed the recovery of antibiotic-induced colitis compared with the spontaneous recovery. Neither ITFs supplementation nor spontaneous recovery could restore the microbial community composition at the genus level back to its initial composition. ITFs supplementation increased the relative abundance of some beneficial bacteria and butyrate levels, but resulted in selective blooms of some opportunistic pathogens and elevated the pathways associated with diseases linked to gut microbiota function. Both ITFs supplementation and spontaneous recovery could restore the colonic transcriptome nearly to the initial profile to a certain extent; however, ITFs supplementation delayed the restoration of the immunoglobulin genes compared to spontaneous recovery. These data showed that post-antibiotic ITFs consumption did not always lead to beneficial effects but might lead to potential adverse effects in the context of dysbiosis. These findings highlighted that caution is required when supplementing ITFs to restore intestinal homeostasis in the context of dysbiosis resulting from broad-spectrum antibiotics.


Immunoarchitectural patterns in splenic marginal zone lymphoma: correlations with chromosomal aberrations, IGHV mutations, and survival. A study of 76 cases.
To describe 76 cases of splenic marginal zone lymphoma (SMZL), including correlations with clinical and other characteristics. Patients were predominantly female, with a median age of 62 years. The main clinical presentation was splenomegaly, except for eight cases presenting with evolution of autoimmune disorders or spontaneous splenic rupture. White pulp infiltration was nodular, with a monophasic (42%) or biphasic (53%) pattern, and associated diffuse or nodular infiltration of the red pulp, except for four cases which had atrophic white pulp. Plasmacytic differentiation and the MYD88 L265P mutation were observed in 18% and 5% of the cases, respectively. Histological progression was considered in cases with a significant association of large cells with Ki67 > 30% and macronodular architecture (P = 0.001). Other significant correlations were found between del7q (44%) and del6q (17%) (P = 0.018), IGHV1-2*04 segment usage (35%) (P = 0.001) and unmutated IGHV (39%) (P = 0.019), and between CD5 expression (27%) and higher lymphocytosis (P = 0.002). Patients requiring intensive chemotherapy after splenectomy because of clinical and/or histological progression had significantly shorter overall survival (P = 0.012). We report the histological spectrum of SMZL, and discuss the differential diagnosis and requirement for molecular and cytogenetic analysis in atypical cases.


Host-tree susceptibility to the coccid Icerya seychellarum Westw. (Margarodidae: Homoptera) on Aldabra Atoll: the rôle of leaf morphology, chemistry and phenology.
The relative susceptibility of thirty-tree species to feeding by the coccid, Icerya seychellarum, (from a previous atoll survey) were correlated with four morphological characters (leaf lamina and midrib thicknesses, density of hairs on leaf underside and presence of waxy upper leaf surface) and the concentrations of six mineral elements (N, P, K, Ca, Mg and Na) and three measures of chemical defense (total phenols, condensed tannins and alkaloids). For twenty-two species four phenological variables, from a separate two year study, were also correlated with susceptibility.Lamina thickness, presence of dense hairs and the concentrations of alkaloids or condensed tannins were significantly correlated with host susceptibility. The ideal host has thick, evergreen and hairless leaves. Some host species with high concentrations of secondary chemicals were also highly susceptible and a new hypothesis suggests that stylet manoeuvrability enables a coccid to avoid these substances in thick, but not thin, leaves.Experimental 'seeding' of crawlers on to eleven host species showed marked differences in susceptibility in different stages of the life-cycle: presence of dense hairs appeared to deter settlement whilst thick lamina enhanced coccid survival.


Obstetric cholestasis: A case report on rapid bile acid elevation.
Obstetric cholestasis is a pregnancy-specific liver disorder which most commonly develops in the second or third trimester. It typically presents with generalised pruritus, often worst on the hands and feet, and no rash. Diagnosis is made on the basis of clinical presentation and elevated bile acid levels. Whilst obstetric cholestasis usually has no significant maternal adverse outcomes, aside from decreased quality of life from pruritus, it can lead to significant foetal complications, including stillbirth. There are no treatments for obstetric cholestasis, which resolves only following delivery. Thus, depending on the severity of obstetric cholestasis, early induction of labour may be recommended. As symptoms may precede bile acid elevation, repeat testing after a week is usually recommended when initial levels are normal. This report describes a case where a 35-year-old pregnant woman presented with pruritus but a normal bile acid level of 3 μmol/L. On repeat testing the following day the level had risen to 62, diagnosing obstetric cholestasis, and resulting in an urgent induction of labour at 38 weeks and 2 days of gestation. The patient gave birth to a healthy girl. This highlights the importance of close monitoring and consideration of early repeated blood tests where clinical suspicion is high, and/or a diagnosis of obstetric cholestasis would have significant management implications, to prevent adverse foetal outcomes.


Corneal and conjunctival sensitivity in rosacea patients.
To assess corneal and conjunctival sensitivity in rosacea patients. A total of 55 patients with rosacea and 37 control subjects participated in the study. Corneal and conjunctival sensitivity was determined by Cochet-Bonnet esthesiometer. Subjective symptoms of ocular dryness were evaluated using Ocular Surface Disease Index (OSDI). Schirmer's I test (ST), tear breakup time (tBUT) and ocular surface staining with fluorescein were carried out to measure objective signs. The mean corneal and conjunctival sensitivity did not differ significantly between rosacea patients and controls (all p > 0.05). Schirmer's I test and tBUT were significantly reduced (p = 0.004 for OD and p < 0.001 for OS) and grade of ocular surface staining was significantly high (p = 0.018 for OD and p = 0.038 for OS) in rosacea patients. Corneal and conjunctival sensitivity did not show significant correlation with ST, tBUT, ocular surface staining (Oxford Schema), duration of rosacea and OSDI score. Corneal and conjunctival sensitivity did not change significantly in rosacea.


The patterns of [14C]2-deoxyglucose uptake in female rat brain produced by electrical stimulation of hypothalamic and limbic brain areas.
The aim of this study was to investigate the pattern of [14C]2-deoxyglucose uptake in anaesthetized rat brain produced by electrical stimulation of brain areas implicated, by previous electrical stimulation studies, in the neural control of pituitary hormone and especially gonadotrophin secretion. Stimulation of the median eminence led to a significant increase in the relative metabolic activities of the arcuate, ventromedial hypothalamic, supraoptic and paraventricular nuclei and the preoptic area. Stimulation of the suprachiasmatic or paraventricular nuclei or the medial preoptic area, anterior hypothalamic area, the dorsal or ventral hippocampus or amygdala led to an increase in the relative metabolic activity of many brain regions known to have direct connections with these areas, but in addition produced increases in the relative metabolic activity of areas which have secondary connections. Hippocampal stimulation confirmed previous neuroanatomical findings of major intrinsic functional connections between different fields of the ipsilateral and contralateral hippocampus. Stimulation of the amygdala, unexpectedly, did not change the relative metabolic activity of the arcuate nucleus and medial preoptic area which have neuroanatomical connections with the amygdala. Similarly, stimulation of the medial preoptic area did not change significantly the relative metabolic activity of the mamillary body and dorsomedial thalamic area. The effect of preoptic area stimulation on the relative metabolic activity of several brain regions was changed by ovariectomy and by injection of oestradiol benzoate. Stimulation of the preoptic area and suprachiasmatic nuclei, but not the anterior hypothalamic area or other brain regions, increased significantly the plasma concentrations of luteinizing hormone. These results show that (i) electrical stimulation of brain areas concerned with the control of gonadotrophin and other pituitary hormone secretion changes the metabolic activity of nuclei and neural pathways extrinsic as well as intrinsic to the hypothalamic-pituitary system, (ii) the [14C]2-deoxyglucose method can detect changes in antidromic as well as orthodromic activity and in multi-synaptic pathways, (iii) neuroanatomical pathways are not always activated metabolically by electrical stimulation, and (iv) the preoptic-suprachiasmatic nucleus gonadotrophin control system is discrete and is little affected by increased metabolic activity of the hypothalamus produced by stimulation of the anterior hypothalamic area or other brain areas.


Systemic lymphoma mimicking acute disseminated encephalomyelitis.
We describe a 10-year-old immunocompetent male whose initial presentation was consistent with the diagnosis of acute disseminated encephalomyelitis. He relapsed 3 months later, with new neurologic signs and lymphadenopathy. T-cell lymphoma was diagnosed by lymph node and stereotaxic brain biopsy. This patient represents a rare report of T-cell lymphoma in an immunocompetent child presenting with central nervous system symptoms.


Influence of crosshead speed on micro-tensile bond strength of two-step adhesive systems.
The purpose of this study was to determine the influence of crosshead speed on the micro-tensile bond strength of two separate adhesive systems to dentin. The systems used were the Clearfil SE Bond (Kuraray Medical) and the Single Bond (3M ESPE) combined with a resin composite Clearfil AP-X (Kuraray Medical). Dentin surfaces of bovine madibular incisors were primed with self-etching primer followed by air blowing for Clearfil SE Bond, or etched with phosphoric acid followed by rinsing with distilled water for Single Bond, and adhesive was applied. The resin composite was then built up in three layers and light activated. After 24 h storage in water, specimens were sectioned and trimmed to a cross-sectional area of 1 mm(2) and subjected to a micro-tensile bond-strength test. Ten samples per test group were tested at crosshead speeds of 0.5, 1.0, 5.0 and 10.0 mm/min. Micro-tensile bond-strength values (in MPa) were calculated from the peak load at failure divided by the specimen surface area. Two-way ANOVA was performed at the 0.05 probability level. The mean dentin bond strength at different crosshead speeds ranged from 34.6 to 37.1MPa for Clearfil SE Bond and from 44.3 to 50.4 MPa for Single Bond. There was no significant difference among the same adhesive systems with the different crosshead speeds tested. The influence of the crosshead speed might be negligible when measuring micro-tensile bond strengths.


Methods for assessing the physical demands of manual lifting: a review and case study from warehousing.
Assessment of the physical demands of potentially hazardous manual material handling (MMH) activities is fundamental to the prevention of disabilities from occupationally related low back pain, a problem costing the nation billions of dollars annually. Although there is a variety of ergonomic assessment methods available for assessing MMH activities, there is a lack of practical information to assist users in choosing the most appropriate assessment methods of a particular job. This article reviews currently available assessment methods and presents case study results of a physically demanding repetitive manual lifting job in two grocery warehouses. The case study will provide a framework for a comparison of the methods and a discussion of relevant application issues designed to assist users in selecting appropriate methods for assessing MMH jobs. Based on the results of the study, it is concluded that all of the ergonomic methods were in agreement that the job of grocery selector has a high level of risk for low back pain. Differences between the methods were noted, however, that should be considered when choosing a specific method for a specific application.


Effects of multiple injections of luteinizing hormone-releasing hormone on the induction of pregnancy in androgenized female rats.
A study of the effect of cyclic (every 4 days) administration of gonadotropin releasing hormone on reproductive performance of the androgenized female rat was carried out. The responses measured were indirect indices of increased gonadotropin output; ovulation rate, uterine decidualization, mating and implantation.


Effects of repetitive exercise and thermal stress on human cognitive processing.
Cognitive performances may improve after acute moderate exercise, but not after prolonged and/or heavy exercise. The present study aimed to investigate the effects of environmental temperature during exercise on human cognitive processing. Fifteen healthy males performed four bouts of a 15-min cycling exercise with a 10-min rest between each bout, and event-related potentials (ERPs) were recorded in five sessions during somatosensory Go/No-go paradigms (i.e., Pre, post-first exercise bout, post-second exercise bout, post-third exercise bout, and post-fourth exercise bout) in an environmental chamber with temperature controlled at 20°C (Temperate) and 35°C (Hot). Increases in external canal temperature and heart rate were greater under the 35°C condition than under the 20°C condition. Regardless of thermal conditions, reaction times (RT) and error rates were not affected by the repetition of moderate exercise, whereas the peak amplitude of the N140 component, which is mainly related to somatosensory processing, was significantly reduced with the repetition of the exercise. However the peak amplitude of P300, which is linked to cognitive processes of context updating, context closure, and event-categorization, was significantly smaller in post-third and post-fourth exercise bouts under the 35°C condition than under the 20°C condition, and this decrease was more prominent in No-go trials under the 35°C condition. These results suggest that executive function, which is based on RTs and error rates, is not affected by prolonged exercise and different thermal conditions, whereas the exercise in a hot environment impairs human cognitive processing, particularly response inhibition.


Evaluation of area under the concentration-time curve-guided vancomycin dosing with or without piperacillin-tazobactam on the incidence of acute kidney injury.
Recent studies suggest that the combination of piperacillin-tazobactam (P-T) and vancomycin increases the risk for acute kidney injury (AKI). The purpose of this study was to determine if area under the concentration-time curve (AUC)-guided vancomycin dosing reduced the incidence of AKI in a sample of patients who also received P-T. This single-centre, retrospective, pre-post quasi-experimental study compared the incidence of AKI before and after a health-system-wide change from trough- to AUC-guided vancomycin dosing using two post-distribution levels. The primary outcome was AKI, defined as an increase in serum creatinine ≥0.5 mg/dL or 50% from baseline for two consecutive measurements, in patients who received vancomycin with or without concomitant P-T. In total, 636 patients were included in this study (308 trough-guided, 328 AUC-guided); of these, 118 patients in each group received concomitant P-T. The primary outcome occurred in 35 (11.4%) patients in the trough-guided group and 24 (7.3%) patients in the AUC-guided group (P=0.105). There was no difference in the incidence of AKI in the population receiving concomitant P-T between dosing strategies. The incidence of AKI was significantly higher in patients who received concomitant P-T compared with patients who did not receive concomitant P-T in both the trough-guided group [21/118 (17.8%) versus 14/190 (7.4%), respectively; P=0.003] and the AUC-guided group [16/118 (13.6%) versus 8/210 (3.8%), respectively; P=0.0011]. The incidence of AKI did not differ significantly between trough- and AUC-guided vancomycin dosing. Caution should be taken when combining vancomycin and P-T regardless of dosing strategy. Larger studies are needed to confirm these findings.


The gender-paradox among patients with implantable cardioverter-defibrillators: a propensity-matched study.
Several meta-analyses of the implantable cardioverter-defibrillator (ICD) clinical trials have demonstrated that while men derived a mortality reduction with prophylactic ICD implantation, women did not. These trials also observed that women receive less appropriate ICD shock therapy compared to men. We aimed to investigate this "gender-paradox" among a heterogeneous community cohort of patients receiving ICDs. We identified 1,445 consecutive patients undergoing ICD implantation from 1997 to 2007. The study population consisted of 582 patients, of whom 291 were women who could be propensity matched to 291 men, based on age, ejection fraction, implantation indication (primary or secondary), etiology of cardiomyopathy (ischemic or nonischemic), and the presence of a cardiac resynchronization therapy-defibrillator (CRT-D) device. The impact of gender difference on the probability of death and appropriate ICD shocks for ventricular arrhythmias was calculated using multivariable Cox proportional hazards analyses. During a mean follow-up of 909 ± 901 days, compared to men, women demonstrated a similar risk of death (25% vs 25%, adjusted hazard ratio [AHR] 1.05 [95% confidence interval (CI) 0.81-1.35], P = 0.74). In contrast, women demonstrated a decreased probability of appropriate ICD-shock therapy (14% vs 19%, AHR 0.80 [95% CI 0.59-0.88], P = 0.03) compared to men, and among cohorts with a nonischemic cardiomyopathy (10% vs 20%, P < 0.001) and CRT-D devices (7% vs 19%, P = 0.01). Among a community cohort with ICDs, women have a similar mortality compared to men while experiencing less appropriate ICD therapy. These results support the findings of a lower arrhythmic mortality among women.


Morphological and functional evaluation of normal and abnormal fetal growth by ultrasonography.
Correction or estimation of gestational age is essential for the evaluation of fetal growth. When necessary, an appropriate fetal biometric parameter should be selected depending on fetal size. In the first trimester, crown-rump length (CRL) is appropriate, especially when the CRL is 20-40 mm. In the second trimester, biparietal diameter (BPD), head circumference (HC), and femur length (FL) are of equal predictability. Fetal weight estimation is still the basis of evaluation of fetal growth. The most predictable formula currently available includes the parameters BPD (or HC), abdominal circumference (AC), and FL. Serial measurements of AC are useful for diagnosis of intrauterine growth restriction (IUGR) and macrosomia. Quantitative evaluation of soft tissue deposition may be informative for macrosomia. Functional evaluation using Doppler velocimetry is essential in IUGR cases associated with uteroplacental insufficiency. Analysis of blood velocity waveforms of the umbilical and intracranial arteries, predominantly the middle cerebral artery, is widely performed. An increase in the pulsatility index (PI) or resistance index (RI) of the umbilical artery and/or a decrease in the PI or RI of the middle cerebral artery are highly predictable for fetal hypoxia and/or acidosis.


Leptin regulates sugar and amino acids transport in the human intestinal cell line Caco-2.
Studies in rodents have shown that leptin controls sugars and glutamine entry in the enterocytes by regulating membrane transporters. Here, we have examined the effect of leptin on sugar and amino acids absorption in the human model of intestinal cells Caco-2 and investigated the transporters involved. Substrate uptake experiments were performed in Caco-2 cells, grown on plates, in the presence and the absence of leptin, and the expression of the different transporters in brush border membrane vesicles was analysed by Western blot. Leptin inhibited 0.1 mm α-methyl-D-glucoside uptake after 5 or 30 min treatment and decreased SGLT1 protein abundance in the apical membrane. Uptake of 20 μm glutamine and 0.1 mm phenylalanine was also inhibited by leptin, indicating sensitivity to the hormone of the Na(+) -dependent neutral amino acid transporters ASCT2 and B(0) AT1. This inhibition was accompanied by a reduction in the transporters expression at the brush border membrane. Leptin also inhibited 1 mm proline and β-alanine uptake in Na(+) medium at pH 6, conditions for optimal activity of the H(+) -dependent neutral amino acid transporter PAT1. In this case, abundance of PAT1 in the brush border membrane after leptin treatment was not modified. Interestingly, leptin inhibitory effect on β-alanine uptake was reversed by the PKA inhibitor H-89 suggesting involvement of PKA pathway in leptin's regulation of PAT1 activity. These data show in human intestinal cells that leptin can rapidly control the activity of physiologically relevant transporters for rich-energy molecules, that is, D-glucose (SGLT1) and amino acids (ASCT2, B(0) AT1 and PAT1).


Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab.
The optimal treatment sequence for patients with advanced BRAF V600 mutant melanoma is unknown. BRAF/MEK inhibition (BRAF/MEKi), single agent anti-PD-1 (aPD-1) antibodies and combination immune checkpoint inhibition with nivolumab and ipilimumab (niv/ipi) are all approved; however, they have not been prospectively compared. Therefore, we sought to compare overall survival of patients with advanced BRAF mutant melanoma treated with either front-line BRAF/MEKi, aPD-1, or niv/ipi. Patients with advanced BRAF mutant melanoma who had received BRAF/MEKi, niv/ipi, or aPD-1 in the front-line setting were identified from a nationwide database comprising de-identified patient-level structured and unstructured data derived from electronic health records. Survival was compared using Kaplan-Meier curves and log-rank analysis. Univariate and multivariate Cox regression models were used to measure the effect of front-line treatment, age (>64 or not), LDH (elevated or not), and Eastern Cooperative Oncology Group (ECOG) performance status (>1 or not) on survival. Five hundred and sixty seven patients with advanced disease and treated with front-line aPD-1 (n = 162), BRAF/MEKi (n = 297) or niv/ipi (n = 108) were identified. With a median follow-up of 22.4 months, median overall survival (OS) for patients treated with front-line niv/ipi was not reached (NR) while median OS for patients treated with aPD-1 or BRAF/MEKi was 39.5 months and 13.2 months, respectively. Front-line treatment with PD-1 and niv/ipi were associated with statistically longer survival than BRAF/MEKi in multivariate analyses. In our real-world retrospective analysis, patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi.


Subgaleal hematoma in child abuse.
The mother brought her 31/2-year-old son to a paediatric clinic as his forehead was swollen and bluish in appearance. She was unable to give any explanation for this lesion. Clinically it was noted that a very visible and also palpable, doughy swelling was present both in the forehead as well as the hard skull areas. Some hours later, a massive bilateral periocular haematoma appeared. Whilst X-rays were unable to provide any diagnostic help, the sonographic examination of the skull carried out on the same day revealed an extensive subgaleal haematoma. This phenomenon is described in radiological literature as "scalping" and is caused by the use of considerable, blunt violence against the head (shear stresses, e.g. by pulling at the hair). The mother's boyfriend later confessed forceful pulling of the hair.


Weaving a cocoon on the way to aging transcendence: Grounded theory study on aging perception during menopause transition.
During menopause, women experience major changes, including the onset of aging as a natural and inevitable event. The present study aimed to explore and explain the process of aging perception during menopausal transition. This study was a qualitative grounded theory research, which was going to be implemented in 2019-2020 on 18 Baluch women settled in the Sistan & Baluchestan province in South-East Iran and among midlife or older menopause experienced women. Sampling was started first by Purposive sampling, and then it was performed with theoretic sampling. Data analysis was performed according to Corbin and Straus's approach (2015) in four phases: (1) identifying and developing concepts; (2) analyzing data for the context; (3) entering the process stage into analysis; and (4) integrating categories to build a theory. In this study, seven main categories were obtained: "Sunset of youth", "aging as the other side of the coin of menopause", "Weaving a cocoon", "aging as a mental trap", "social acceptance", "aging domino", and "feeling of transcendence". It seems that menopause plays an important role in Baluch women's view toward aging. The practical results of this study can be applied to better understand the middle-aged and older Baluch women's attitudes toward aging. Also study shows a new evolutionary and situational perspective on the lives of middle-aged menopausal Baluch women. Baluch women in menopause accept the sunset of youth and look forward to experiencing the Feeling of transcendence. Identify and respond to their needs by developing and establishing health policies to change their negative attitudes.


A head-to-head comparison of infusion and bolus doses of adenosine for stress myocardial contrast echocardiography.
This study was a head-to-head, intraindividual comparison of the diagnostic accuracy and side effect profile of bolus and infusion administration of adenosine for stress myocardial contrast echocardiography (MCE). Adenosine MCE was performed in 64 subjects, referred for stress thallium-201 single-photon emission computed tomography (SPECT) for known or suspected CAD. Each patient received adenosine by multiple boluses (6-12 mg/bolus) and infusion (140 mug/kg per min for 6 min) forms in random order, given at least 20 minutes apart. No prolonged or serious adverse events occurred during either adenosine bolus or infusion. Compared to SPECT imaging, the sensitivity, specificity, and concordance for the diagnosis of CAD were 77%, 87%, and 82% for adenosine infusion MCE and 81%, 90%, and 86% for adenosine bolus MCE, respectively. Both adenosine infusion and adenosine bolus protocols are safe for MCE in humans and can be used for the diagnosis of CAD.