Surgical decompression improves recovery from neurological deficit and may provide a survival benefit in patients with diffuse large B-cell lymphoma-associated spinal cord compression: a case-series study.
Malignancy-associated spinal cord compression is generally treated by surgical decompression, radiotherapy or a combination of both. Since diffuse large B-cell lymphoma (DLBCL) is highly sensitive to both chemotherapy and radiotherapy, the role of surgical decompression in the treatment of DLBCL-associated spinal cord compression remains unclear. We therefore conducted a retrospective review to investigate the impact of surgical decompression on recovery from neurological deficit caused by DLBCL-associated spinal cord compression and patients' overall survival. Between March 2001 and September 2011, 497 newly diagnosed DLBCL patients were reviewed, and 11 cases had DLBCL-associated spinal cord compression. Six cases were treated surgically and five cases nonsurgically. The rates of complete recovery from neurological deficit were 100% (6/6) and 20% (1/5) for patients in the surgical and nonsurgical groups, respectively (P = 0.015), while the median survival for patients in the surgical and nonsurgical groups was 48.6 months and 17.8 months, respectively (P = 0.177). We conclude that surgical decompression can improve recovery from neurological deficit in patients with DLBCL-associated spinal cord compression, possibly providing these patients a survival benefit.


Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells.
A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a-5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.


Critical analysis and efficacy of BMPs in long bones non-union.
Non-union of long bone fractures is considered as multifactorial. The management of this entity continues to be difficult often requiring multiple procedures with unpredictable results. Bone morphogenetic proteins (BMPs) are power agents being used in the clinical setting for a variety of pathological conditions where tissue regeneration is required. This article analyses the currently existing evidence of the efficacy of BMPs for the management of non-union of long bone fractures.


Quantitative analysis of orb web patterns in four species of spiders.
The orb webs of the four species Araneus pima (species nova), Araneus diadematus (Clerck), Argiope aurantia (Lucas), and Neoscona domiciliorum (Hentz) built under controlled laboratory conditions were compared and evaluated quantitatively at two different points in the life cycle in regard to size, regularity, shape, and fine structure. Orb webs of two species from one genus can be distinguished, but are more alike than webs from different genera. Mature spiders built highly specific webs, a fact which may play a role in species isolation during courtship. In adults, web measures correlated in size with the spiders' taxon; young spiders' web size measurements corresponded rather to their body weight or leg length. A web's regularity seemed to be closely related to age. Adult and young spiders built oval-shaped webs with eccentric hubs. Mesh width was correlated with leg length at both age levels. Web data support the likelihood of a monophyletic evolution of the four species.


A morphologic study of chronic type B aortic dissections and aneurysms after thoracic endovascular stent grafting.
The long-term results of treating chronic aortic dissections and aneurysms in association with dissections with thoracic endovascular aortic repair (TEVAR) are unknown, and the timing for intervention is uncertain. We evaluated the morphology of stent graft and aorta remodeling and the volumetric changes in these patients after successful TEVAR. Serial computed tomography scans of 32 patients who underwent TEVAR for uncomplicated chronic dissections (group A, n = 17) and chronic dissections with aneurysms (group B, n = 15) were analyzed at 1, 6, 12, and 36 months. Stent graft diameter changes and positional migration were assessed three-dimensionally using Mimics 14.0 (Materialize, Leuven, Belgium). Volumetric data for true lumen, false lumen, thrombus load, and aortic size were measured by Aquarius iNtuition 4.4 software (TeraRecon, San Mateo, Calif). Results were compared between the two groups and with stent graft diameter, length, and oversizing. Aortic stent grafts remodeled progressively, with inlet area increasing 4.4%, 10.1%, and 14.2% and outlet area increasing 42.6%, 67.2%, and 72.3%, respectively, at 6, 12, and 36 months. True lumen volume increased progressively in group A (114 to 174 mL) and group B (124 to 190 mL) from baseline to 36 months. False lumen volume decreased in group A (150 to 88 mL) and group B (351 to 250 mL), whereas thrombus load in the false lumen increased from 73% to 80% in group A and 84% to 87% in group B in 3 years. Eight patients (4 in each group) showed an increase in total aortic volume of >10%, 12 showed a static volume, and 12 showed shrinkage. Aortic volume change had no relationship to pathology, stent graft sizing, and thrombus load but was positively associated with the placement of a longer graft. A small but progressive distal migration of stent grafts was noted in all patients (3.1, 4.5, and 5.1 mm at 6, 12, and 36 months) but was more prominent in shorter stent grafts (≤ 162 mm). No deaths, rupture, or secondary interventions occurred during follow-up. Aortic remodeling after TEVAR in chronic dissection is a continuous process. There were no significant differences between chronic dissections and aneurysms in all volumetric parameters. Treating chronic dissections early, before aneurysm formation, did not appear to have a morphologic advantage.


Use of medical resources and quality of life of patients with chronic heart failure: a prospective survey in a large Italian community hospital.
To assess the prevalence, clinical characteristics, use of medical resources and quality of life in consecutive patients with chronic heart failure (CHF) hospitalized in a large community hospital during 3 months. The study group included 354 patients with CHF, admitted in the Departments of Internal Medicine (97%) and Cardiology. Median age was 78 years [72;85], 45% were males. CHF was the main diagnosis in 72%; 28% were in NYHA class III and 49% in class IV; 42% had atrial fibrillation. The median hospital stay was 8 days [5;14], in-hospital mortality 9% in those admitted for CHF and 19% in those admitted primarily for other diseases. Patients with CHF occupied 15% of the beds; 1330 ECGs, 389 chest X-rays, 112 echocardiograms and 10 coronary angiograms were performed. A quality of life questionnaire revealed that 82% had problems with mobility, 54% with self-care and 88% with everyday activity. Thirty-nine percent of patients had at least one hospitalization during the previous year. Ninety-seven percent of hospitalized patients with CHF are admitted in the Internal Medicine wards and occupy 15% of beds. The majority of the patients are 72 years or older, with severe heart failure. The frequency of rehospitalization(s) and mortality rate in this population remains high. Echocardiography is performed only in 27% of patients.


Radiation therapy in the treatment of oral neoplasia.
Oral neoplasia occasionally may be treated adequately with a single modality. Multimodality therapy, however, more often is indicated. This article reviews the recommendations of treatment of oral neoplasia focusing on the role of radiation therapy both singly and as a part of multimodality therapy.


A comparative study between the use of analgesia/anaesthesia and of episiotomy in women delivered under consultant supervision or general practitioner care.
A retrospective cohort study based on obstetric records was performed, to compare the use of analgesia/anaesthesia during labour by consultants and general practitioners. The episiotomy rates for the two groups were also compared. 111 general practitioner patients were identified and these were matched with 111 consultant patients. No difference was found between the two groups for duration of stages I or II. The rates for episiotomy, 1 degree or 2 degrees tear or intact perineum were the same in each group. Women delivered under consultant supervision used more entonox than women delivered under general practitioner care, but this was counterbalanced by an increased use of pethidine in the latter group. No difference was found between the two groups with regard to the use of epidurals. There was an increased use of local anaesthetic by general practitioners. This was due to general practitioners preferring to use local anaesthetic for suturing after an epidural had worn off, whereas hospital doctors preferred to top-up the epidural to provide anaesthesia for suturing. This study supports the view that women delivered under the care of their own general practitioner in a hospital obstetric unit fare no worse than similar women delivered under consultant supervision. The former group have the advantage of continuity of care from their general practitioner.


Uptake of 131I-19-cholesterol by normal and spontaneously hyperfunctioning canine adrenals.
In six normal dogs the adrenals could be visualized as separate areas of radioactivity at 7--10 days after injection of 20--40 muCi 131I-iodocholesterol per kg of body weight. Image analysis revealed uptake values of 0.15--0.3% of the injected dose. In five dogs with pituitary-dependent hyperadrenocorticism the adrenals became visible at 3--5 days after injection of the radiopharmaceutical, with uptake values of 0.38--2.2%. In six dogs with hyperadrenocorticism due to adrenocortical tumor the scintigraphy contributed to the diagnosis and the presurgical localization. The uptake values were within the normal range; the tumor could be observed at 3--10 days after injection. Additional findings on adrenal asymmetry and a case of fluctuating pituitary-dependent hyperadrenocorticism are discussed.


CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal stromal tumors by activating Wnt/PCP-Rho signaling.
Gastrointestinal stromal tumors (GISTs) are the major gastrointestinal mesenchymal tumors with a variable malignancy ranging from a curable disorder to highly malignant sarcomas. Metastasis and recurrence are the main causes of death in GIST patients. To further explore the mechanism of metastasis and to more accurately estimate the recurrence risk of GISTs after surgery, the clinical significance and functional role of collagen triple helix repeat containing-1 (CTHRC1) in GIST were investigated. We found that CTHRC1 expression was gradually elevated as the risk grade of NIH classification increased, and was closely correlated with disease-free survival and overall survival in 412 GIST patients. In vitro experiments showed that recombinant CTHRC1 protein promoted the migration and invasion capacities of primary GIST cells. A luciferase reporter assay and pull down assay demonstrated that recombinant CTHRC1 protein activated noncanonical Wnt/PCP-Rho signaling but inhibited canonical Wnt signaling. The pro-motility effect of CTHRC1 on GIST cells was reversed by using a Wnt5a neutralizing antibody and inhibitors of Rac1 or ROCK. Taken together, these data indicate that CTHRC1 may serve as a new predictor of recurrence risk and prognosis in post-operative GIST patients and may play an important role in facilitating GIST progression. Furthermore, CTHRC1 promotes GIST cell migration and invasion by activating Wnt/PCP-Rho signaling, suggesting that the CTHRC1-Wnt/PCP-Rho axis may be a new therapeutic target for interventions against GIST invasion and metastasis.


Molecular basis of oligoubiquitin-dependent internalization of membrane proteins in Mammalian cells.
Ubiquitination induced down-regulation of cell surface proteins by internalization and lysosomal targeting plays a fundamental role in cell physiology and pathogenesis of diseases. The molecular basis of a single ubiquitin (Ub) as an autonomous endocytic signal, the widely accepted mechanism, however, remains elusive in higher eukaryotes. Using Ub containing reporter proteins without signalling abilities, we present evidence that only multiple Ub moieties, linked either covalently or assembled as oligomers with an intact interface for recognition by Ub-interacting motifs (UIMs), are recognized by the endocytic machinery in vivo and associate with a subset of Ub-binding clathrin adaptors in vitro. Genetic and pharmacological approaches show that internalization of plasma membrane proteins harbouring multiple Ub moieties is clathrin-dependent, but caveolin-independent. Functional assays demonstrate the cargo-dependent involvement of eps15/15R and epsin, UIM containing clathrin adaptors, in the endocytosis of model proteins, CD4 and the activated beta(2)-adrenergic receptor complex, containing polymeric or oligomeric Ub. These results provide a paradigm for the clathrin-mediated uptake of ubiquitinated membrane proteins in mammalian cells, requiring the assembly of multiple UIM-Ub interactions to overcome the low affinity binding of mono-Ub to UIM.


A comparison of participants and non-participants in the Chennai Glaucoma Study-rural population.
To study whether the difference in the demographic characteristics of participants and non participants could result in biased prevalence estimates and associations. To compare the non-participant and participant characteristics, and to ascertain if non-response bias is present in the rural population of the Chennai Glaucoma Study (CGS). Rural participants and non-participants were compared with regard to socio-demographic variables (age, gender, religion, mother tongue, literacy and employment). 4800 subjects aged 40 years or over were enumerated, 82% (3934: 45% male and 55% female) responded. Gender did not influence participation (adjusted OR-1.11, CI: .91-1.36). Subjects in the 70-79 year age group were more likely to respond (OR-1.76; CI-1.31-2.38). Hindus had a higher participation rate than Christians or Muslims (adjusted OR-2.63, CI: 1.80-3.84). The other predictors of participation were illiteracy (adjusted OR-1.44, CI: 1.22-1.70), unemployment (OR-1.28, CI: 1.04-1.58), place of residence (main villages) (OR-6.66, 95% CI: 4.6-9.64). Based on our study findings, it does not seem likely that participation bias will affect the study results.


Long-term success of mitomycin-augmented trabeculectomy for glaucoma after vitreoretinal surgery with silicone oil insertion: a prospective case series.
To evaluate the long-term success of trabeculectomy with mitomycin C for glaucoma after vitreoretinal surgery with silicone oil insertion. Prospective evaluation of patients who underwent trabeculectomy with mitomycin C (superior or inferior site) for glaucoma after vitreoretinal surgery. Parameters examined included intraocular pressure (IOP), visual acuity, and glaucomatous neuropathy status, preoperatively and at multiple follow-up visits postoperatively till 12 months. Success, both absolute (IOP <21 mmHg) and qualified (IOP <21 mmHg with the use of medications and/or needling), was determined at each follow-up visit. Nineteen patients with mean age of 29 ± 16 years had a mean untreated baseline IOP of 42.5 ± 10.66 mmHg, which reduced to 23.82 ± 7.58 at 1 year (P = 0.008). Preoperative decimal visual acuity was 0.12 ± 0.21, which worsened to 0.07 ± 0.08 at the final follow-up (P = 0.81). Total success rate was 36.9% at the end of 1 year, whereas absolute success rate was only 15.8%. Duration between vitreoretinal surgery and silicone oil removal, preoperative IOP, or site of surgery did not determine success rate. Twelve-month success rate for trabeculectomy with mitomycin C in glaucoma after vitreoretinal surgery with silicone oil insertion is lower than reported for most refractory glaucomas.


Compound Effect of Kidney Donor Profile Index and Cold Ischemic Time on 1-Year Kidney Transplant Recipient Outcomes.
Kidney Donor Profile Index (KDPI) and cold ischemic time (CIT) independently influence recipient outcomes after kidney transplantation; however, the compound effect of these variables on posttransplant outcomes is unknown. The Scientific Registry of Transplant Recipients database of deceased-donor kidney transplant recipients between January 2012 and December 2016 was reviewed. Recipients were stratified based on their KDPI (0%-20%, 21%-85%, 86%-100%) and then based on CIT (0-12, 13-24, 25-30, 31-36, ≥ 37 hours). The primary outcome is 1-year allograft loss. Secondary outcomes include primary nonfunction, delayed graft function, biopsy-proven rejection, and 1-year recipient mortality. Allograft loss was not affected by CIT for KDPI 0% to 20% (P = .898) or KDPI 86% to 100% (P = .731), but was significantly different for KDPI 21% to 85% (P < .001). The KDPI 21% to 85% group was the only group with a significant difference in primary nonfunction, demonstrating a linear rise with increasing CIT (P < .001). CIT did not affect recipient mortality for any KDPI group (KDPI 0%-20%, P = .306; KDPI 21%-85%, P = .098; KDPI 86%-100%, P = .774). Incidence of delayed graft function was greater for each KDPI group (P < .001) with increased CIT. Biopsy-proven rejection was not affected by CIT for KDPI 21% to 85% (P = .244) or KDPI 86% to 100% (P = .946). For KDPI 0% to 20%, there was a significant difference (P = .024); however, the incidence was not linear with increasing CIT. For the KDPI 86% to 100% group, incidence of mortality, allograft loss, primary nonfunction, and biopsy-proven rejection did not differ between CIT groups. Extended CIT alone should not hinder utilization of higher KDPI organs.


A new benzopyrans derivatives from a mangrove-derived fungus Penicillium citrinum from the South China Sea.
One new benzopyran derivative (2R(*),4R(*))-3,4-dihydro-5-methoxy-2-methyl-2H-1-benzopyran-4-ol (1), together with five known compounds (2-6), were obtained from the EtOAc extract of the endophytic fungus Penicillium citrinum HL-5126 isolated from the mangrove Brguiera sexangula var. rhynchopetala collected in the South China Sea. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. All compounds were evaluated for their antibacterial activities. Compound 6 exhibited potent inhibitory activity against Bacillus subtilis, Bacillus cereus and Micrococcus tetragenus with the same MIC values of 6.94 μM.


A battery-powered slide impinger for ultra-low volume droplet sampling.
A variation of the battery-powered slide impinger is described. The impinger uses a commercially available cordless screwdriver to rotate teflon-coated glass microscope slides for collection of aerosol droplets. The device is inexpensive and easy to construct.


A second case of contractures, webbed neck, micrognathia, hypoplastic nipples, and distinctive facial features: confirmation of the Dinno syndrome.
We report on a child with micrognathia, a short, webbed neck, joint contractures, hypoplastic nipples, and a number of other anomalies. There are striking similarities to a patient reported by [Dinno and Weisskopf (1976); Synd Ident, 4:10-12], and we postulate that this child represents the second patient with this condition.


Motion analysis.
The ability to make an objective evaluation of a surgeon's operative ability remains an elusive goal. In this study, we used motion analysis as a measure of dexterity in the performance of a simulated operation. Fifteen surgeons performed a total of 45 laboratory-based laparoscopic cholecystectomies on a cadaveric porcine liver model. Subjects were assigned to one of three groups according to their level of experience in human laparoscopic cholecystectomy. Electromagnetic tracking devices were used to analyze the surgeon's hand movements as they performed the procedure. Movement data (time, distance, number of movements, and speed of movement) were then compared. Analysis of variance (ANOVA) movement scores across the three groups showed significantly better performance among the experienced laparoscopic surgeons than the novices. Learning curves across repetitions of procedures were plotted. Novices made more improvement than experts. Motion analysis provides useful data for the assessment of laparoscopic dexterity, and the porcine liver model is a valid simulation of the real procedure.


A dataset on 24-h electrocardiograph, sleep and metabolic function of male type 2 diabetes mellitus.
This dataset provides a collection of 24 h electrocardiograph (ECG) signals, ECG analysis results based on circadian rhythm and R-peak detection, results of sleep quality assessment and clinical indicators of metabolic function acquired from 60 male type 2 diabetes mellitus (T2DM) inpatients. Upon admission, a fasting blood draw and urinary sample were obtained the next morning for routine glucose, lipid and renal panels. Subjects were also involved in investigation for diabetic complications. On the second day of hospitalization, subjects were monitored in hospital for 24-h ECG starting at 10 pm. Subjective sleep quality was assessed by Pittsburgh Sleep Quality Index and a brief sleep log was used to record sleep duration for the studied night. Objective sleep quality and sleep staging were assessed by cardiopulmonary coupling analysis. This dataset could be utilized to conduct conjoint research on the relationships among sleep, metabolic function, and function of cardiovascular system and autonomic nervous system derived from ECG analysis in T2DM, and further investigate the information in ECG signals based on circadian rhythm and physiological status, providing new insights into long term physiological signal processing.


Prevention of arthritic inflammation using an oriental herbal combination BDX-1 isolated from Achyranthes bidentata and Atractylodes japonica.
An oriental herbal combination (BDX-1) was isolated from Achyranthes bidentata and Atractylodes japonica. We previously tested the clinical effectiveness of BDX-1 in rheumatoid arthritis (RA) patients and found that it has a beneficial therapeutic effect. Here, we provide experimental evidence for the effectiveness of BDX-1 on RA in murine models. The oral administration of BDX-1 was found to markedly inhibit collagen-induced arthritis, adjuvant-induced arthritis, and zymosan-induced inflammation. It also inhibited carrageenan-induced acute edema and acetic acid-induced writhing response. In addition, the biological activity of BDX-1 was found to be strongly increased by fermentation. Our results suggest that BDX-1 could be useful for the treatment of rheumatoid arthritis.


HTLV-1 tropism and envelope receptor.
The identification of CD4 as the primary receptor for HIV followed shortly after the discovery of the virus, but the HTLV receptor remained long elusive, until its recent identification as the GLUT1 glucose transporter. In the present review, we describe the status of the literature that surrounded this discovery as well as the in vitro and in vivo observations that led to the identification of GLUT1. Also, we will explore a few tracks to conciliate the in vitro and in vivo data on HTLV-1 tropism within the context of the HTLV literature that has accumulated over the past 25 years. A close examination of these data leads us to conclude that the preferential detection of HTLV-1 in CD4+ T lymphocyte subsets in vivo, even in the absence of leukemia, is not likely to be directly related to envelope receptor interactions, but rather to an array of postentry selection bottlenecks in vivo. Furthermore, we propose that infection of other hematopoietic and nonhematopoietic cells is likely to take place during the lifetime of an individual, with a burst early during the infection.


Hypotension does not alter the antinociceptive effect of nifedipine.
We explored the relationship between antinociceptive and hypotensive effects of nifedipine (NIF) injected intraperitoneally ( ip, 15 mg/kg) and epidurally (epi, 20 microM), as compared to verapamil (VER, 10 mg/kg ip) and nitroglycerin (NTG, 0.1 and 0.15 mg/kg ip). The systolic blood pressure (BP) and tail-flick (TF) latencies were measured simultaneously every 10 min for 2 hours and individual values of both measurements were correlated. The highest antinociceptive as well as hypotensive effects were both measured in the group receiving NIF epi., with the correlation coefficient r2=0.2878. Injected ip., NIF revealed similar antinociceptive effect, whereas the other studied drugs were not effective. As to the degree of hypotensive activity, NIF epi was followed by VER, NTG 0.1, NIF ip. and NTG 0.15. No significant correlation was found between BP and TF latencies in any group receiving the drugs. We concluded that the antinociceptive response, measured by the tail-flick technique, is independent of the hypotensive activity of the studied drugs, including NIF.


Descriptions of two new and one newly recorded enchytraeid species (Clitellata, Enchytraeidae) from the Ozegahara Mire, a heavy snowfall highmoor in Central Japan.
Three species of semi-aquatic freshwater Enchytraeidae of the genera Mesenchytraeus Eisen, 1878, Chamaedrilus Friend, 1913 and Globulidrilus Christensen & Dózsa-Farkas, 2012 are described from stream, wet soil or snow habitats in the Ozegahara Mire, an extensive high moor in heavy snowfall area in central Japan. Among Mesenchytraeus speies, Mesenchytraeus nivalis sp. nov. is distinguished by not having enlarged chaetae and spermathecal diverticula, vas deferens with atrial glands 3 or 4 in number and club-shaped, spermathecal ental duct short, with sperm bundles in the sperm sack. Chamaedrilus ozensis sp. nov. closely resembles C. floridae, but the length of the sperm funnel and character of the coelomocytes are different. Globulidrilus helgei Christensen & Dózsa-Farkas, 2012 is recorded for the first time from Japan.


Sculpting the Transcriptome During the Oocyte-to-Embryo Transition in Mouse.
In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres. This transition is driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency. Full-grown oocytes are transcriptionally quiescent and mRNAs are remarkably stable in oocytes due to the RNA-binding protein MSY2, which stabilizes mRNAs, and low activity of the 5' and 3' RNA degradation machinery. Oocyte maturation initiates a transition from mRNA stability to instability due to phosphorylation of MSY2, which makes mRNAs more susceptible to the RNA degradation machinery, and recruitment of dormant maternal mRNAs that encode for critical components of the 5' and 3' RNA degradation machinery. Small RNAs (miRNA, siRNA, and piRNA) play little, if any, role in mRNA degradation that occurs during maturation. Many mRNAs are totally degraded but a substantial fraction is only partially degraded, their degradation completed by the end of the two-cell stage. Genome activation initiates during the one-cell stage, is promiscuous, low level, and genome wide (and includes both inter- and intragenic regions) and produces transcripts that are inefficiently spliced and polyadenylated. The major wave of genome activation in two-cell embryos involves expression of thousands of new genes. This unique pattern of gene expression is the product of maternal mRNAs recruited during maturation that encode for transcription factors and chromatin remodelers, as well as dramatic changes in chromatin structure due to incorporation of histone variants and modified histones.


Neuronal regulation of B-cell immunity: Anticipatory immune posturing?
The brain may sense, evaluate, modulate, and intervene in the operation of immune system, which would otherwise function autonomously in defense against pathogens. Antibody-mediated immunity is one arm of adaptive immunity that may achieve sterilizing protection against infection. Lymphoid organs are densely innervated. Immune cells supporting the antigen-specific antibody response express receptors for neurotransmitters and glucocorticoid hormones, and they are subjected to collective regulation by the neuroendocrine and the autonomic nervous system. Emerging evidence reveals a brain-spleen axis that regulates antigen-specific B cell responses and antibody-mediated immunity. In this article, we provide a synthesis of those studies as pertinent to neuronal regulation of B cell responses in secondary lymphoid organs. We propose the concept of defensive immune posturing as a brain-initiated top-down reaction in anticipation of potential tissue injury that requires immune protection.


What is a representative voiding pattern in children with lower urinary tract symptoms? Lack of consistent findings in ambulatory and conventional urodynamic tests.
Conventional urodynamics (CU) is a highly standardized evaluation of lower urinary tract function. However, in pediatric patients there is concern that the reliability of measurements could be influenced by development effects and measurement variability, as well as by the unfamiliar clinical environment. Ambulatory urodynamics (AU) provides an alternative to this - it uses natural filling, is measured over a prolonged period, and is conducted in a child-friendly environment. The aim of this study was to conduct a comparative analysis of AU and CU to evaluate the consistency in voiding patterns obtained with these two methods of urodynamic testing. Urodynamic parameters obtained by AU and CU methods in 50 pediatric patients aged >5 years were retrospectively analyzed. Voiding patterns were categorized into six types: coordinated contraction, detrusor after-contraction, fluctuated contraction, pre-void contraction, relief voiding, and weak or absent contraction. Voiding patterns were used to determine the repeatability within urodynamic tests and to identify consistency between AU and CU tests. Five urodynamic parameters were quantified and compared between AU and CU: voided volume, flow rate, maximum detrusor pressure, and detrusor pressure at peak flow rate. For inter-observer variation analysis, 100 voiding curves were randomly selected and categorized by two independent observers; inter-observer agreement was evaluated using the kappa statistic. A single pattern of voiding was identified in five patients using AU and 37 using CU. Consistency of a single pattern between AU and CU was identified in three patients, and consistency between a predominant pattern with AU, defined by one type of voiding occurring >50% of one's voids, and a single pattern with CU was identified in 10 patients (summary table). Flow rates were similar between methods; however, higher maximum detrusor pressure and detrusor pressure at peak flow and lower voided volume were recorded with AU. AU resulted in more diverse voiding patterns. Along with the differences in measured urodynamic parameters challenges the application of findings from one method to form a clinical diagnosis. Furthermore, CU may not be as sensitive as AU to the variability in lower urinary tract pathophysiology. More diverse voiding patterns were identified in AU compared with CU, with a lack of consistency in identified voiding pattern in both methods. Therefore, the urodynamic findings in children may have to be analyzed in more detail, taking the variations into account.


Cardiovascular risk of stimulant treatment in pediatric attention-deficit/hyperactivity disorder: update and clinical recommendations.
This review provides an update on the cardiovascular impact of therapeutic stimulant-class medication for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Relevant clinical literature was ascertained using PubMed searches limited to human studies and the English language as of May 2011. Current practice guidelines and consensus statements also were reviewed. Stimulant-class medications for healthy children and adolescents with ADHD are associated with mean elevations in blood pressure (≤5 mmHg) and heart rate (≤10 beats/min) without changes in electrocardiographic parameters. A subset (5-15%) of children and adolescents treated may have a greater increase in heart rate or blood pressure at a given assessment or may report a cardiovascular-type complaint during stimulant treatment. It is extremely rare for a child or adolescent receiving stimulant medication to have a serious cardiovascular event during treatment, with the risk appearing similar to groups of children not receiving stimulant medication. Clinicians should adhere to current recommendations regarding the prescription of stimulant medications for youth with ADHD. Scientific inquiry is indicated to identify patients at heightened risk and to continue surveillance for the longer-term cardiovascular impact of these agents.


Duplex scan in patients with clinical suspicion of deep venous thrombosis.
The incidence of deep venous thrombosis is 0.6/1000 habitants and when symptomatic its diagnosis by duplex scan has 100% sensitivity and 98% specificity. The aim of this study was to evaluate the findings of the duplex scan in patients with clinical suspicion of deep venous thrombosis. 239 consecutive outpatients (59.2 +/- 18.6 years, 164 female) were evaluated by duplex scan. According to symptoms 101 (42.3%) were related to the right lower limb; 113 (47.3%) to the left lower limb; and 25 were related to both lower limbs. Forty-eight patients presented a normal duplex scan. Venous thrombosis was found in 117 patients (0.49; CI 0.43-0.55): 75 with deep venous thrombosis (DVT), 22 with superficial venous thrombosis (SVT) and 20 with both DVT and SVT. Other pathologies were found in 74 patients. Among patients with DVT the most involved veins were below the knee. Among patients with SVT, 20 (47.6%) showed progression to the deep venous system: 9 (45%) by perforans veins; in 6 by saphenous-femoral junction (30%); and in 5 (25%) by saphenous-popliteal junction. Deep venous and superficial venous thromboses were diagnosed in 49% of cases. In 30.9% of cases, the duplex scan indicated other pathologies.


Ehrlichia's molecular tricks to manipulate their host cells.
Ehrlichia is a large genus of obligate intracellular Gram-negative bacteria transmitted by ticks that cause several emerging infectious diseases in humans and are pathogenic on rodents, ruminants, and dogs. Ehrlichia spp. invade and replicate either in endothelial cells, white blood cells, or within midgut cells and salivary glands of their vector ticks. In this review, we discuss the insights that functional studies are providing on how this group of bacteria exploits their host by subverting host innate immunity and hijacking cellular processes.


Consulting to children in crisis.
Although community consultation is common for psychiatrists, such activity is usually carried out on an elective rather than emergency basis. In a world troubled by community disaster situations--children are often at risk. Psychiatrists, through the use of skillful crisis consultation, can be of great help to these young people. This report describes the effort of a mental health consultation team to meet the needs of a large population of children under acute stress.


[Genescan analysis of non-small cell lung cancer in the long arm of chromosome 6].
To investigate if there are microsatellite loci in the long arm of chromosome 6 that have close relationship with non-small cell lung cancer. Multiple PCR approach was used to analyze the 18 loci in the long arm of chromosome 6. The PCR products were analyzed in PAGE, and then the electrophoresis maps were analyzed with Gene Scan(TM) and Genotyper(TM). There were different frequencies of loss of heterozygosity (LOH) in different loci (varying from 3.85% to 38.45%). The total frequency of LOH in 41 gastric cancers was 58.5%(24/41). Eight loci with the LOH frequency higher than 20% were mainly located in 2 regions: 6q24 and 6q27. The accurate location is 6q24-6q25.3 [D6S1699(35%), D6S409(23.33%), D6S441(33.33%)] and 6q26-27 [D6S1550(38.45%), D6S264(20%), D6S1585(25%), D6S446(33.33%), D6S281(30.77%)]. There may be tumor suppressor genes located in the region of 6q24 and 6q27, which have close relationship with non-small cell lung cancer.


Acute toxicity and tolerability of anthracycline-based chemotherapy regimens in older versus younger patients with breast cancer: real-world data.
To compare the non-cardiac acute toxicity and tolerability profile of anthracycline-based regimens between older versus younger women diagnosed with breast cancer in a real-world setting. Retrospective cohort of female patients diagnosed with breast cancer and treated with neoadjuvant or adjuvant anthracycline-based regimens between 2017 and 2019. Patients were grouped in young versus older, using an age of 65 as cut-off. Differences in non-cardiac acute toxicity and change in treatment plan were examined. Among the 559 patients, 19.5% were aged ≥ 65 years. Regimens used were fluorouracil, epirubicin, and cyclophosphamide in 56.2% of patients, doxorubicin and cyclophosphamide in 33.3%, and epirubicin and cyclophosphamide in 10.5%; there were no differences in incidence of grade 3 or 4 toxicities between regimens (p = 0.184). Acute grade 3 or 4 toxicities occurred more frequently in the older group (33.9% versus 10.7%, p < 0.0001, OR 4.304, 95%-CI [2.619-7.073]). Delay of at least one chemotherapy cycle due to toxicity occurred more frequently in the older group (24.8% versus 9.3%, p < 0.0001, OR 3.199, 95%-CI [1.867-5.481]). Early termination of treatment also occurred more frequently in the older group (11.9% versus 1.6%, p < 0.0001, OR 8.571, 95%-CI [3.331-22.048]). Although acute grade 3 or 4 toxicities were more frequent in older patients, which resulted in increased cycle delay and/or premature termination of treatment, overall treatment was still reasonably well-tolerated, with 88.1% of older patients completing the planed anthracycline regimen.


A metal-organic framework loaded paper-based chemiluminescence sensor for trace acetone detection in exhaled breath.
Trace acetone determination in breath can be regarded as a noninvasive method for diagnosis of diabetes. Here, a paper-based CL gas sensor combined with UiO-66 as the preconcentrator was established for sensitive detection of trace acetone in exhaled breath. UiO-66 with excellent adsorption performance and unique water stability was used for the adsorption and enrichment of acetone gas under high humidity conditions in exhaled breath. As acetone can remarkably increase the chemiluminescence (CL) of the 2,4-dinitrophenylhydrazine (DNPH)-potassium permanganate (KMnO4) system, a sensitive CL device based on a paper substrate for trace acetone detection was established and the detection limit was 0.03 ppm. The fabricated method was used to assess the content of trace acetone in exhaled breath with satisfactory recoveries of 90-110%. It is expected to realize the noninvasive determination of acetone for diabetic patients in exhaled breath.


Deep fake detection and classification using error-level analysis and deep learning.
Due to the wide availability of easy-to-access content on social media, along with the advanced tools and inexpensive computing infrastructure, has made it very easy for people to produce deep fakes that can cause to spread disinformation and hoaxes. This rapid advancement can cause panic and chaos as anyone can easily create propaganda using these technologies. Hence, a robust system to differentiate between real and fake content has become crucial in this age of social media. This paper proposes an automated method to classify deep fake images by employing Deep Learning and Machine Learning based methodologies. Traditional Machine Learning (ML) based systems employing handcrafted feature extraction fail to capture more complex patterns that are poorly understood or easily represented using simple features. These systems cannot generalize well to unseen data. Moreover, these systems are sensitive to noise or variations in the data, which can reduce their performance. Hence, these problems can limit their usefulness in real-world applications where the data constantly evolves. The proposed framework initially performs an Error Level Analysis of the image to determine if the image has been modified. This image is then supplied to Convolutional Neural Networks for deep feature extraction. The resultant feature vectors are then classified via Support Vector Machines and K-Nearest Neighbors by performing hyper-parameter optimization. The proposed method achieved the highest accuracy of 89.5% via Residual Network and K-Nearest Neighbor. The results prove the efficiency and robustness of the proposed technique; hence, it can be used to detect deep fake images and reduce the potential threat of slander and propaganda.


The ABL oncogene in human leukemias.
The ABL proto-oncogene on the Philadelphia chromosome is 'activated' by its translocation in a manner similar to its activation by the murine Abelson leukemia virus--with the formation of a fusion protein with a new N-terminus and enhanced tyrosine kinase activity. Study of this BCR-ABL fusion gene has led to the development of molecular probes which are beginning to play an important role in the diagnosis and clinical management of chronic myelogenous leukemia, and may ultimately lead to better understanding of the biology of the disease. The role of ABL on the Philadelphia chromosome in acute lymphoblastic leukemia is only now beginning to be understood, but is likely to be similar, and a new ABL species has already been identified by several groups. It is likely that this protein is the product of a fusion gene, as it is in chronic myelogenous leukemia, but definitive proof awaits molecular cloning of the translocation breakpoint. Aside from its activation by the Ph1 chromosome, ABL has not been found to have a role in any other human cancer.


Comparison of the Efficacy of the Global Leadership Initiative on Malnutrition Criteria, Subjective Global Assessment, and Nutrition Risk Screening 2002 in Diagnosing Malnutrition and Predicting 5-Year Mortality in Patients Hospitalized for Acute Illnesses.
The Global Leadership Initiative on Malnutrition (GLIM) has developed new criteria for diagnosing patients with malnutrition. The aims of this study were to investigate the prevalence of malnutrition according to the GLIM criteria, Subjective Global Assessment (SGA), and Nutrition Risk Screening 2002 (NRS-2002) and their association with long-term mortality in patients hospitalized for acute illnesses. A retrospective analysis was performed in a sample of 231 patients with different comorbidities hospitalized for acute illnesses in medical or surgical wards. Nutrition status was retrospectively assessed with GLIM criteria using patients' records at admission in addition to SGA and NRS-2002. The agreement between the tools was calculated using κ statistics, and the association of malnutrition according to each tool and mortality were analyzed using Cox regression analysis. The mean age of the patients was 62.2 ± 18.2 years, and 56.7% were women. The prevalence of malnutrition was 35.9% with GLIM criteria, 37.2% with SGA, and 38% with NRS-2002. The agreement between tools was good (GLIM-SGA, κ = 0.804; GLIM-NRS-2002, κ = 0.784). During a median follow-up period of 63.2 months, 79 deaths occurred. The sensitivity in predicting 5-year mortality was 59.49%, 58.23%, and 58.23%, and specificity was 76.32%, 73.68%, and 72.37% for GLIM criteria, SGA, and NRS-2002, respectively. After adjusting for confounders, GLIM criteria best predicted 5-year mortality (hazard ratio, 3.09; 95% CI, 1.96-4.86; P < .001). Our findings support the effectiveness of GLIM in diagnosing malnutrition and predicting all-cause mortality among patients hospitalized for acute illnesses.


Contrast-enhanced endosonography for the diagnosis of anal and anovaginal fistulas.
We assessed whether contrast-enhanced anal endosonography (AES) with hydrogen peroxide improves the identification of anal fistulas and their internal openings compared with non-contrast AES. The study group comprised 12 patients who had various types of anal fistulas with visible external openings. AES was performed before and about 15 seconds after injection of 1 ml of 3% hydrogen peroxide into the fistula tract through the external opening. Both contrast and non-contrast AES revealed 7 transsphincteric, 2 intersphincteric, 1 suprasphincteric, and 2 anovaginal fistulas. Simple tracts were found in 8 cases and complex tracts in 4 cases on non-contrast AES. Contrast-enhanced AES revealed 9 simple and 3 complex fistulas. One fistula that appeared complex on the non-contrast study appeared simple after contrast agent administration. Contrast-enhanced AES demonstrated more internal openings than non-contrast AES did. Surgery confirmed 11 of the fistulas; an internal opening could not be located surgically for the other tract. Contrast-enhanced AES appears to be superior to non-contrast AES in the preoperative assessment of anal and anovaginal fistulas and in demonstrating and locating their internal openings.


Osteopenia of prematurity - the role of exercise in prevention and treatment.
Premature infants have an increased risk of osteopenia due to limited bone mass accretion in utero and a greater need for bone nutrients. Currently, the diagnosis of osteopenia is based on clinical and radiological signs and measurements of biochemical markers. Recent studies suggest that measurements of circulating bone turnover markers, and bone strength assessment using quantitative ultrasound measurements of bone speed of sound (SOS) may help in the evaluation of bone metabolism in preterm infants. So far, most of the preventive efforts of osteopenia of prematurity focused on nutritional changes. Recent studies indicate that the passive range of motion exercise of the extremities results in a significantly greater increase of body weight, increased bone mineralization, increased bone formation markers and leptin levels, and attenuation of the natural post-natal decline in bone SOS. These results suggest that exercise may play an important role in the prevention and treatment of osteopenia of prematurity.


Renal excretion capacity in hydrated desert rodents (Jaculus orientalis and Jaculus deserti).
The capacity to excrete a water load was studied in rats and in two desert rodents (Jaculus orientalis and Jaculus deserti) adapted to either 5 or 30 degrees C ambient temperature. The rat is able to eliminate the entire water load regardless of thermal adaptation. Cold-adapted J. orientalis and J. deserti excreted 60% of the water load in comparison to 20-30% in warm-adapted jerboas. At both adaptation temperatures, antidiuretic hormone (ADH) concentration was estimated at maximum diuresis in the two desert species. Though hydration induced a significant decrease in ADH concentration in both species, its level in the plasma remained relatively high. The decrease was more pronounced in J. orientalis than J. deserti.


Selective Access to 4-Substituted 2-Aminothiazoles and 4-Substituted 5-Thiocyano-2-aminothiazoles from Vinyl Azides and Potassium Thiocyanate Switched by Palladium and Iron Catalysts.
A highly selective construction of 4-substituted 2-aminothiazoles and 4-substituted 5-thiocyano-2-aminothiazoles, respectively, catalyzed by palladium(II) acetate and promoted by iron(III) bromide from vinyl azides and potassium thiocyanate has been developed. Use of readily available starting materials, high selectivity, as well as mild reaction conditions make this practical method particularly attractive.


Emergency medicine in the Third World: two years as director of the Kingston, Jamaica, Public Hospital Casualty Department.
A US emergency physician worked for two years as director of a busy emergency department in a large public hospital in Kingston, Jamaica (West Indies). As expected, medical practice in the Third World required caring for patients with far less than he was accustomed to in the way of diagnostic and therapeutic resources. However, more than one lesson in clinical medicine was provided by local approaches to local problems. Despite resource limitations, innovations and improvements were effected, particularly in wound care. Although working in the Third World can be a rewarding experience, well-meaning health workers from advantaged countries should ensure that their efforts contribute to, rather than detract from, the ability of their hosts to independently provide medical care.


Randomized controlled trial assessing the impact of a combined treatment of insulin glargine and propylene glycol on the resolution of hyperketonemia and milk production in postpartum dairy cows.
Multiple treatments for hyperketonemia have been studied, and although propylene glycol has been the most constantly reported as successful in mitigating the effects of this condition, a recent study showed that a subpopulation of cows affected by hyperketonemia and hypoglycemia could benefit from a combined treatment of propylene glycol and insulin glargine. The objective of the present study was to assess the effect of this combination on the time-to-hyperketonemia resolution, and on milk production following the initial treatment. A randomized controlled trial was conducted on 2 commercial farms on which postpartum exams were conducted twice a week. Cows naturally affected by both hyperketonemia [β-hydroxybutyrate (BHB) ≥ 1.4 mmol/L] and hypoglycemia (glucose <2.2 mmol/L) were enrolled and randomly assigned to receive 2 mL of placebo (physiological saline) subcutaneously (PBO), or to receive 2 mL of insulin glargine (200 IU) subcutaneously (INS). Cows in both groups also received 300 g of propylene glycol orally for 3 d. Time-to-hyperketonemia resolution (return to BHB <1.4 mmol/L) and daily milk production following the initial treatment were compared between groups using Cox proportional hazard and mixed linear regression models, respectively. A total of 248 cows between 1 and 30 d in milk (median = 16) were enrolled in the trial from January 2018 to February 2022. Cows were of first (32.3%; n = 80/248), second (32.3%; n = 80/248), or third or greater (35.4%; n = 88/248) parity. The overall time-to-hyperketonemia resolution was not different between treatments, but there was a 2-way interaction between treatment group and parity. Primiparous cows had a shorter time-to-resolution in the INS group than in the PBO group; no difference was observed between treatment groups for older cows. The overall milk production of cows in the INS group was 3.4 kg higher than cows in the PBO group during the 14 d after enrollment. There was a 2-way interaction between treatment group and parity. Primiparous cows in the INS group produced 5.3 kg more milk daily than primiparous cows in the PBO group; no effect of treatment was found for older cows. These results suggest that cows affected simultaneously by hyperketonemia and hypoglycemia benefited from a combined treatment of propylene glycol and insulin glargine to improve subsequent milk production and that the effect primarily came from the positive effect in primiparous cows. Time-to-hyperketonemia resolution was also improved in primiparous cows but not in older cows.


Decoding chromatin goes high tech.
Identifying proteins that recognize histone methylation is critical for understanding chromatin function. Vermeulen et al. (2010) now describe a cutting-edge strategy to identify and characterize several nuclear proteins and complexes that recognize five major histone trimethyl marks.


Patient Perspectives of Quality of the Same-Day Antiretroviral Therapy Initiation Process in Gauteng Province, South Africa: Qualitative Dominant Mixed-Methods Analysis of the SLATE II Trial.
HIV patients in South Africa continue to report operational barriers to starting antiretroviral therapy (ART). In the Simplified Algorithm for Treatment Eligibility (SLATE) II trial, same-day initiation (SDI) of ART increased the number of patients commencing ART and achieving HIV viral suppression by using a screening tool to distinguish between patients eligible for SDI and those requiring additional care before starting treatment. We conducted a mixed-methods evaluation to explore trial patients' perceptions and experiences of SDI. SLATE II was implemented at three urban, public primary health care clinics in Gauteng Province, South Africa. We conducted a short quantitative survey and in-depth interviews among a purposive sample of 89 of the 593 trial participants in the intervention and standard arms, using a mixed inductive-deductive framework approach. Nearly all respondents (95%) were satisfied with their care, despite reporting clinic wait times of ≥ 3 h (72%). Intervention patients found the initiation process to be easy; standard patients found it complicated and were frustrated with being shuffled around the clinic. No intervention arm patients felt that SDI was "too fast" or indicated a preference for a more gradual process. Both groups highlighted the need for good counselling and non-judgmental, respectful staff. Standard patients suggested improving patient-provider relations, strengthening counselling, reducing wait times, and minimising referrals. While it is difficult to untangle the role of providers from that of the SLATE algorithm in influencing patient experiences, adoption of SLATE II implementation procedures could improve patient experience of treatment initiation. Clinicaltrials.gov NCT03315013, registered October 19, 2017.


Chinese adolescents' mindfulness and internalizing symptoms: The mediating role of rumination and acceptance.
Internalizing problems during adolescence are common psychiatric symptoms. Previous research has demonstrated that mindfulness was significantly and negatively associated with and mindfulness-based interventions would be efficacious for aiming at adolescents' internalizing problems. However, research about how mindfulness could improve internalizing symptoms among Chinese adolescents is sparse and its potential mechanism is still unclear. The present study adopted rumination and acceptance to examine their mediation effects between Chinese adolescents' mindfulness and internalizing symptoms. A final sample of 1,554 adolescents (aged from 10 to 18 years old, M = 15.58, SD =1.25) were recruited from schools in South China. Participants were asked to complete a package of questionnaires measuring mindfulness, internalizing problems (indicated by generalized anxiety and depression), rumination, and acceptance. Structural equation model confirmed our hypothesis and showed that rumination, as well as acceptance, significantly mediated the relationship between Chinese adolescents' mindfulness level and internalizing symptoms (generalized anxiety and depression). a) only cross-sectional design was employed in the study; b) most of participants were normal adolescent students, without a diagnosis of any psychiatric disorder; c) all the measures were self-reported by adolescents. Mindfulness not only directly impacted on adolescents' internalizing problems, but also indirectly improved their anxious and depression emotions via the reduction of rumination and the increase of acceptance. Hence, mindfulness training as well as the application of emotion regulation skills may be useful for adolescents exposed to the likelihood of suffering from internalizing problems.


Cytochemical properties of euchromatin and heterochromatin.
Two classic cytochemical tests, the Feulgen-Schiff reaction and Toluidine Blue basophilia, have been employed for investigating the differential characteristics of heterochromatin and euchromatin. Differences have been detected in the Feulgen hydrolysis kinetics, the Feulgen absorption spectrum, the image analysis of Feulgen-stained material, and the binding of Toluidine Blue under ordinary and Mg2+ competitive staining conditions. The differences are assumed to be a function of the composition and stereo-arrangement of the DNA and DNA-protein complexes present in these chromatin types and are possibly associated with physiological activities whose whole meaning is far from being clear. Differences in optical retardations in Toluidine Blue-stained material were also found. These are interpreted as being due to chromatin packing state and selective removal of histones promoted by the acetic acid-ethanol fixative.


Characterisation of recent trends in cardiovascular risk factors in young and middle-aged patients with ischaemic stroke and/or transient ischaemic attack.
Strokes in the young and middle-aged are associated with a disproportionately large economic and social impact in addition to their clinical effects. Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes mellitus and smoking) are key drivers of cardiovascular disease including strokes, however recent temporal trends in the younger stroke population have not been well characterised. We aimed to evaluate recent trends of SMuRFs in a cohort of younger patients with ischaemic stroke. Consecutive patients aged <65 years with clinical and/or radiological diagnosis of ischaemic stroke or transient ischaemic attack in a tertiary referral centre (2013-2017) were retrospectively appraised. The demographic and clinical comorbidities of these patients were assessed including their SMuRF profile. The prevalence over time and clinical associations of patients with no SMuRFs were studied and compared to patients with SMuRFs. Of 487 patients (53.49 ± 9.13 yrs., 60% men) analysed, 23% did not have SMuRFs. The proportion of "non-SMuRF" patients increased over time (p < 0.01) and this trend was not influenced by age (p = 0.48) or gender (p = 0.68). The presence of SMuRFs was not associated with in-hospital outcomes, however patients without SMuRFs were significantly less likely to be discharged on blood pressure (p < 0.01) and lipid-lowering therapies (p = 0.03). The proportion of younger stroke patients without SMuRFs is substantial and has increased over time. Our findings highlight the need for further research to better understand the mechanisms underlying stroke development in this population and whether less risk factor treatment in this population could impact longer term outcomes.


Distinct redox state regulation in the seedling performance of Norway maple and sycamore.
Norway maple and sycamore, two Acer genus species, have an important ecological value and different sensitivity to stressing factors being currently aggravated by climate change. Seedling growth is postulated to be the main barrier for successful plant establishment under the climate change scenarios. Therefore, the differences in redox regulation during the seedling performance of Norway maple and sycamore were investigated. Seeds of the two Acer species exhibited an identical high germination capacity, whereas seedling emergence was higher in sycamores. PCA analyses revealed that there is more diversification in the leaf characteristics than roots. Norway maple displayed a higher chlorophyll content index (CCI) with a similar leaf mass whereas sycamore seedlings exhibited a higher normalized difference vegetation index (NDVI), higher water content, higher root biomass and higher shoot height. Based on NDVI, sycamore seedlings appeared as very healthy plants, whereas Norway maple seedlings displayed a moderate healthy phenotype. Therefore, redox basis of seedling performance was investigated. The total pool of glutathione was four times higher in sycamore leaves than in Norway maple leaves and was reflected in highly reduced half-cell reduction potential of glutathione. Sycamore leaves contained more ascorbate because the content of its reduced form (AsA) was twice as high as in Norway maple. Therefore, the AsA/DHA ratio was balanced in sycamore leaves, reaching 1, and was halved in Norway maple leaves. Nicotinamide adenine dinucleotide phosphate content was twice as high in sycamore leaves than in Norway maples; however, its reduced form (NADPH) was predominant in Norway maple seedlings. Norway maple leaves exhibited the highest anabolic and catabolic redox charge. The higher reduction capacity and the activity of NADPH-dependent reductases in Norway maple leaves possibly resulted in higher CCI, whereas the larger root system contributed to higher NDVI in sycamore. The different methods of controlling redox parameters in Acer seedlings grown at controlled conditions provided here can be useful in understanding how tree species can cope with a changing environment in the future.


Implementation and physician behavior change : an industry perspective.
Clinical practice guidelines are omnipresent and increasing in number; however, their utility and applicability are questioned. A great deal of effort is expended in their creation, but how they reach their ultimate customers is very variable. The pharmaceutical industry has considerable resources that may assist in this process; however, they need to be more involved in the development of clinical practice guidelines. This can happen only if both guideline developers and industry set aside their fears, concerns, and prejudices and collectively try to improve health care through more appropriate management of patients.


Outbreaks of dermatopathy caused by Tephrosia noctiflora intoxication in Brazilian cattle.
This study aims to update the knowledge concerning the intoxication by Tephrosia noctiflora in Brazilian cattle herds by reporting new cases of intoxication in lactating cows, their calves and bulls and highlight the epidemiology, clinical signs, pathogenesis, gross, and microscopic lesions. The morbidity and mortality of this intoxication in the farms studied was low. Gross lesions in all affected cattle consisted of dermatitis with hyperpigmentation, crusts, ulceration, erythema, and lichenification in the skin of limbs, ventral abdomen, perianal and perineal areas of lactating calves and adult cattle. Microscopically, the main lesion observed consisted of severe dermatitis with parakeratotic hyperkeratosis, papillated proliferation, and diffuse, accentuated lymphoplasmacytic inflammatory infiltrate in the epidermis and dermis. The presence of skin lesions mainly in the limbs and ventral abdomen of cattle implies the pathogenesis of intoxication is related to a primary contact dermatitis, and the occurrence of similar lesions on the skin of nursing calves reinforces this hypothesis. The putative toxins of T. noctiflora have been thought to be rotenoids. Additional work is needed to define better if these compounds are the main toxin responsible for the dermatopathy observed in these herds.


Calcium-dependent [3H]acetylcholine release and muscarinic autoreceptors in rat cortical synaptosomes during development.
A number of presynaptic cholinergic parameters (high affinity [3H]choline uptake, [3H]acetylcholine synthesis, [3H]acetylcholine release, and autoinhibition of [3H]acetylcholine release mediated by muscarinic autoreceptors) were comparatively analyzed in rat brain cortex synaptosomes during postnatal development. These various functions showed a differential time course during development. At 10 days of age the release of [3H]acetylcholine evoked by 15 mM KCl from superfused synaptosomes was Ca2+-dependent but insensitive to the inhibitory action of extrasynaptosomal acetylcholine. The muscarinic autoreceptors regulating acetylcholine release were clearly detectable only at 14 days, indicating that their appearance may represent a criterion of synaptic maturation more valuable than the onset of a Ca2+-dependent release.


Vibrational Circular Dichroism Unravels Supramolecular Chirality and Hydration Polymorphism of Nucleoside Crystals.
Invited for the cover of this issue are Valery Andrushchenko, Monika Krupová, and co-workers at the Institute of Organic Chemistry and Biochemistry (IOCB Prague) of the Czech Academy of Sciences. The image depicts a "crystal city" illuminated by "chiral suns" shining left- and right-circularly polarized light (L-CPL and R-CPL), which reveals differences in the structure of the chiral crystalline "skyscrapers". Designed by Tomáš Belloň @ IOCB Prague. Read the full text of the article at 10.1002/chem.202201922.


Minimally invasive surgery for thyroid and parathyroid diseases.
During the past 4 years, some minimally invasive procedures for thyroid and parathyroid surgery have been described. All these techniques have been demonstrated as feasible and safe. Nevertheless, the surgeon should be well trained to obtain the best results with these approaches. Moreover, not all patients are eligible for minimally invasive procedures. At the moment, they can be proposed for most patients with sporadic primary hyperparathyroidism, but only for a minority of patients with thyroid nodules. The results from minimally invasive procedures are almost comparable with those of conventional surgery, but they have additional advantages in terms of cosmetic result and postoperative pain. Therefore, these procedures should be considered a valid option by surgeons dealing with neck endocrine surgery.


Selective renal embolisation for renovascular hypertension?
An 11 year old girl developed hypertensive encephalopathy and renal failure from reflux nephropathy. Resection of her shrunken left kidney did not control her hypertension. Two selective arterial embolisations of the scarred right lower pole produced only transient benefit, but a heminephrectomy gave good control. Embolisation may delay definitive treatment.


Effects of salbutamol on the absorption and disposition of sulphamethoxazole in adult volunteers.
On the basis of the reports that beta-adrenergic stimulation affects gastrointestinal motility in man as well as induces N-acetyltransferase in rat pineal gland, we decided to assess the effects of salbutamol pretreatment on the absorption as well as disposition of sulphamethoxazole (SMZ). After a control pharmacokinetic study of SMZ, each of six healthy volunteers took salbutamol at a dose of 4 mg four times daily for two weeks, and the kinetic study of SMZ was repeated after the morning dose on the fifteenth day. None of SMZ half-life, volume of distribution, renal and hepatic clearance rates was significantly altered. However, salbutamol pretreatment resulted in significant reduction in the absorption rate constant of SMZ from 1.168 +/- 0.509 h-1 (mean +/- S.D.) to 0.688 +/- 0.348 h-1 (P less than 0.025), and this was associated with prolongation of tmax from 3.00 +/- 1.69 h to 4.33 +/- 1.51 h (P less than 0.025). Cmax, however, was not correspondingly reduced probably as a result of significant increase in the extent of SMZ absorption from 611 +/- 108 mg to 749 +/- 78 mg (P less than 0.025). Our findings suggest that beta-adrenergic stimulation does not significantly induce human hepatic N-acetyltransferase enzyme. However, it does reduce the absorption rate as well as increase the extent of absorption of SMZ.


Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study.
This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole-brain radiotherapy (WBRT) given first in chemotherapy-naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care. After stratification by Eastern Cooperative Oncology Group performance status (ECOG PS) (0-1 vs 2), the number of intracranial metastases (<3 vs 3< or =), and the presence of extrathoracic extracranial metastasis, eligible patients were randomized to the primary chemotherapy arm or the WBRT-first arm. World Health Organization (WHO) response criteria, National Cancer Institute Common Toxicity Criteria (NCI-CTC; version 2.0), and the European Organization for Research and Treatment of Cancer (EORTC) C-30/LC-13 questionnaire were used. A total of 48 patients were enrolled between August 2002 and November 2005. The response rate of chemotherapy and survival outcomes in the primary chemotherapy arm were not statistically different from those in the WBRT-first arm (overall response rate, 28.0% vs 39.1%; progression-free survival, 3.6 months vs 4.4 months; overall survival, 9.1 months vs 9.9 months). There was close correlation noted between intracranial and extracranial tumor responses (k = 0.82). However, in the WBRT-first arm, grade 3 of 4 neutropenia was more frequent (79% vs 40%) during chemotherapy and 4 patients (17.4%) did not receive further chemotherapy because of early death or poor performance after WBRT. Cognitive function appeared to deteriorate during primary chemotherapy, but was also found to deteriorate after WBRT. Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting.


Bisphosphonate treatment and renal function in 201 myeloma patients undergoing stem cell transplantation.
Administration of bisphosphonates (BPs) is an essential supportive treatment for reducing bone-related complications in cancer. Deterioration of renal function is one possible side effect of BPs as well as a clinical feature in multiple myeloma. It has been suggested that the nephrotoxicity of different BPs may differ. We performed a retrospective evaluation of renal function in 201 myeloma patients undergoing myeloablative chemotherapy and treatment with ibandronate (I), pamidronate (P), or zoledronate (Z) for up to 36 months. There was no significant deterioration in mean creatinine clearance (CreaCl) in the entire cohort. The percentage of patients experiencing a decrease in CreaCl ≥ 25 % from baseline was 33.0 % in the I group, 44.4 % in the P group and 21.4 % in the Z group, respectively. CreaCl at baseline (P < 0.0001), relapse/progression (P = 0.0019), proteinuria at baseline (P = 0.039), age (P = 0.0031) were identified as significant independent predictors of decrease in renal function. In both descriptive multivariant analyses, we found no evidence of an advantage of any particular BP with respect to effects on renal function. In line with these data, in a subgroup of 90 patients with a baseline CreaCl <90 ml/min, no significant difference was evident between the cohorts of patients treated with different BPs. Regular treatment with the BPs I, P and Z in myeloma patients undergoing intensive chemotherapy appear to be equally safe for up to 3 years in terms of nephrotoxicity.


Diagnostic Performance of Machine Learning Based CT-FFR in Detecting Ischemia in Myocardial Bridging and Concomitant Proximal Atherosclerotic Disease.
The diagnostic performance of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) in detecting ischemia in myocardial bridging (MB) has not been investigated to date. This retrospective multicentre study included 104 patients with left anterior descending MBs. MB was classified as either superficial or deep, short, or long, whereas all MB vessels were further divided into <50%, 50% to 69%, and ≥70% groups, according to proximal lumen stenosis on invasive coronary angiography. Diagnostic performance and receiver operating characteristics (ROC) of CT-FFR to detect lesion-specific ischemia was assessed on a per-vessel level, using invasive FFR as reference standard. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for agreement measurement. Forty-eight MB vessels (46.2%) showed ischemia by invasive FFR (≤0.80). Sensitivity, specificity, and accuracy of CT-FFR to detect functional ischemia were 0.96 (0.85 to 0.99), 0.84 (0.71 to 0.92), and 0.89 (0.81 to 0.94), respectively, in all MB vessels. There were no differences in diagnostic performance between superficial and deep MB or between short and long MB (all P > 0.05). The accuracy of CT-FFR was 0.96 (0.85 to 0.99) in ≥70% stenosis, 0.82 (0.67 to 0.91) in 50% to 69% stenosis, and 0.89 (0.51 to 0.99) in <50% stenosis (P = 0.081). Bland-Altman analysis showed a slight mean difference between CT-FFR and invasive FFR of 0.014 (95% limit of agreement, -0.117 to 0.145). The ICC was 0.775 (95% confidence interval, 0.685-0.842, P < 0.001). CT-FFR demonstrated high diagnostic performance for identifying functional ischemia in vessels with MB and concomitant proximal atherosclerotic disease when compared with invasive FFR. However, the clinical use of CT-FFR in patients with MB needs further study for stronger and more robust results.


Complementary system vs conventional trifocal intraocular lens: comparison of optical quality metrics and unwanted light distribution.
To evaluate the ARTIS Symbiose complementary intraocular lens (IOL) system, consisting of the MID and PLUS models, in comparison with a conventional trifocal IOL (AcrySof IQ PanOptix). The David J. Apple Center for Vision Research, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. Laboratory investigation. Modulation and phase transfer functions were obtained in polychromatic light using an optical bench setup. Simulated visual acuity (VA) values were derived from optical quality metrics weighted by neural contrast sensitivity. United States Air Force (USAF) chart images were acquired and processed. Furthermore, the light distribution beyond the center of a polychromatic point spread function was assessed. The peak simulated VA values of ARTIS Symbiose MID were at 0 diopters (D) of defocus (-0.02 logMAR) and at -1.5 D (0.00 logMAR); of ARTIS Symbiose PLUS, they were at 0 D of defocus (-0.01 logMAR) and at -2.5 D (0.01 logMAR). AcrySof IQ PanOptix demonstrated 3 peaks: at 0 D of defocus (-0.02 logMAR), at -1.75 D (0.03 logMAR), and at -2.5 D (0.02 logMAR). The summation of USAF chart images in the simulated binocular IOL system produced a slightly better image quality at -1.0 D and -1.5 D than AcrySof IQ PanOptix. The IOLs yielded comparable light spread across the studied range except for a localized intensity spike of the ARTIS Symbiose IOLs. The complementary IOL system may yield better monocular intermediate VA compared with the conventional trifocal IOL. However, the effect of binocular summation in terms of VA and the perception of photic phenomena still needs to be investigated.


[Treatment of cryptococcal meningitis by use of shunting and review in literature].
To evaluate the time and effect of shunt operation on cryptococcal meningitis. A total 7 patients received shunt operation for the therapy of cryptococcal meningitis patients and the data was retrospectively analyzed. Intracranial hypertension-caused symptoms were resolved immediately. There was no complication, no infection dissemination and no recrudescence of cryptococcal meningitis. Shunt operation is effective for intracranial hypertension caused by cryptococcal meningitis. It does not affect the antifungal treatment.


Localised giant pseudopolyposis secondary to ulcerative or granulomatous colitis.
Pseudopolyps which represent polypoid oedematous tags, regenerating mucosal islands between ulcerations or heaped-up granulation tissue covered by epithelium, are a common sequela of ulcerative colitis and may also occur secondary to granulomatous colitis. Occasionally, a large discrete mass of pseudopolyps occurs simulating a villous-like or polypoid neoplasm and the term 'localised giant pseudopolyposis' has been applied to this phenomenon. In this paper the radiological appearances of localised giant pseudopolyposis secondary to ulcerative or granulomatous colitis are described and illustrated. The differential diagnosis is discussed and four new cases are added to eight previously reported in the literature.


Scapholunate kinematics after flexible anchor repair.
The scapholunate joint is one of the keystones of the wrist kinematics, and its study is difficult due to the carpal bones size and the richness of surrounding ligaments. We propose a new method of quantitative assessment of scapholunate kinematics through bone motion tracking in order to investigate scapholunate ligament lesion as well as repair techniques. On 6 intact wrists, steel beads were inserted into the bones of interest to track their motions. Experimental set up allowed wrist flexion extension and radio-ulnar deviation motions. Low-dose bi-planar radiographs were performed each 10° of movement for different configurations: 1) intact wrist, 2) scapholunate ligament division, 3) repair by soft anchors at the posterior then 4) anterior part. Beads' 3D coordinates were computed at each position from biplanar X-Rays, allowing accurate registration of each wrist bone. The Monte Carlo sensitivity study showed accuracy between 0.2° and 1.6 ° for the scaphoid and the lunate in motions studied. The maximum flexion-extension range of motion of the scaphoid significantly decreased after anterior repair from 73° in injured wrist to 62.7°. The proposed protocol appears robust, and the tracking allowed to quantify the anchor's influence on the wrist kinematics.


Camphanic acid chloride: a powerful derivatization reagent for stereoisomeric separation and its DMPK applications.
Camphanic acid chloride has proven to be an efficient chiral derivatization reagent for determination of stereoisomers. The utility of chemical derivatization of various stereoisomers containing hydroxy functional groups with camphanic acid chloride in the presence or absence of a base is highlighted. This procedure is shown to be relatively simple, fast and a cost-effective method of separating racemic drugs and stereoisomeric metabolites in biological matrices. Camphanic derivatives contain two additional chirogenic centers, which are found to enhance stereoisomeric separation on both traditional and chiral stationary phases. Four methodologies described herein for separation of multiple stereoisomers in biological samples confirm camphanic acid chloride to be a powerful chiral reagent for stereoisomeric resolution for drug metabolism and PK applications.


Zn(++) binding disrupts the Asp(23)-Lys(28) salt bridge without altering the hairpin-shaped cross-β Structure of Aβ(42) amyloid aggregates.
Observations like high Zn(2+) concentrations in senile plaques found in the brains of Alzheimer's patients and evidences emphasizing the role of Zn(2+) in amyloid-β (Aβ)-induced toxicity have triggered wide interest in understanding the nature of Zn(2+)-Aβ interaction. In vivo and in vitro studies have shown that aggregation kinetics, toxicity, and morphology of Aβ aggregates are perturbed in the presence of Zn(2+). Structural studies have revealed that Zn(2+) has a binding site in the N-terminal region of monomeric Aβ, but not much is precisely known about the nature of binding of Zn(2+) with aggregated forms of Aβ or its effect on the molecular structure of these aggregates. Here, we explore this aspect of the Zn(2+)-Aβ interaction using one- and two-dimensional (13)C and (15)N solid-state NMR. We find that Zn(2+) causes major structural changes in the N-terminal and the loop region connecting the two β-sheets. It breaks the salt bridge between the side chains of Asp(23) and Lys(28) by driving these residues into nonsalt-bridge-forming conformations. However, the cross-β structure of Aβ(42) aggregates remains unperturbed though the fibrillar morphology changes distinctly. We conclude that the salt bridge is not important for defining the characteristic molecular architecture of Aβ(42) but is significant for determining its fibrillar morphology and toxicity.


Phosphorylation of the C terminus of Fos protein is required for transcriptional transrepression of the c-fos promoter.
Proto-oncogene fos encodes a nuclear phosphoprotein of 380 amino acids that can modulate the transcription of other genes either by transactivation or by transrepression. The v-Fos protein (381 amino acids) shares the first 332 amino acids with the c-Fos protein (with five single amino-acid changes), but differs at the C terminus. We have previously reported that the c-Fos protein undergoes more extensive post-translational modification than v-Fos (refs 9, 10). The major modification of the c-Fos protein involves serine phosphoesterification of sites in the extreme C terminus. We therefore argued that modification of the C-terminal region of the c-Fos protein may be involved in its ability to transrepress transcription without compromising its ability to transactivate other genes. Here we show that mutant c-Fos protein which is hypophosphorylated at its C terminus is unable to repress transcription of the c-fos promoter following induction with serum or tetraphorbol acetate. The C-terminal phosphorylation-deficient mutant is, however, fully competent to activate transcription of promoters containing a phorbol response element. The requirement for phosphorylation can be offset by the introduction of a net negative charge in the C terminus of the Fos protein.


Noninvasive mitochondrial imaging in live cell culture.
The observed distribution of mitochondria in a cell can vary with environmental influence, degree of differentiation and disease. Differences in the distribution of mitochondrial autofluorescence may be used to distinguish these different cellular states.


In vitro apoptotic cell death during erythroid differentiation.
Erythropoiesis occurs in bone marrow and it has been shown that during in vivo erythroid differentiation some immature erythroblasts undergo apoptosis. In this regard, it is known that immature erythroblasts are FasL- and TRAIL-sensitive and can be killed by cells expressing these ligand molecules. In the present study, we have investigated the cell death phenomenon that occurs during a common unilineage model of erythroid development. Purified CD34+ human haemopoietic progenitors were cultured in vitro in the presence of SCF, IL-3 and erythropoietin. Their differentiation stages and apoptosis were followed by multiple technical approaches. Flow cytometric evaluation of surface and intracellular molecules revealed that glycophorin A appeared at day 3-4 of incubation and about 75% of viable cells co-expressed high density glycophorin A (Gly(bright)) and adult haemoglobin at day 14 of culture, indicating that this system reasonably recapitulates in vivo normal erythropoiesis. Interestingly, when mature (Gly(bright)) erythroid cells reached their higher percentages (day 14) almost half of cultured cells were apoptotic. Morphological studies indicated that the majority of dead cells contained cytoplasmic granular material typical of basophilic stage, and DNA analysis by flow cytometry and TUNEL reaction revealed nuclear fragmentation. These observations indicate that in vitro unilineage erythroid differentiation, as in vivo, is associated with apoptotic cell death of cells with characteristics of basophilic erythroblasts. We suggest that the interactions between different death receptors on immature basophilic erythroblasts with their ligands on more mature erythroblasts may contribute to induce apoptosis in vitro.


Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas.
Pattern and extent of epithelial membrane antigen (EMA) immunoreactivity in ependymomas as compared to other glial tumors have only been investigated in small series. To determine sensitivity and specificity of EMA staining, 54 ependymomas were evaluated in comparison to 54 glioblastomas, 43 fibrillary astrocytomas and 21 oligodendrogliomas. Distinct punctate intracytoplasmic EMA immunoreactivity was observed in 48/54 ependymomas (89%), whereas ring-like EMA staining was observed in 17/54 ependymomas (31%). Apart from the absence in most myxopapillary ependymomas, neither staining pattern was related to tumor grade or localization. Dot-like EMA immunoreactivity was less frequently observed in glioblastomas [32/54 (59%), P<0.05 vs ependymomas], fibrillary astrocytomas [10/43 (23%), P<0.001 vs ependymomas] and oligodendrogliomas [2/21 (10%), P<0.001 vs ependymomas], whereas ring-like EMA staining was absent. Sensitivity and specificity of punctate EMA staining for the diagnosis of ependymoma as compared to other glial tumors were determined: A finding of 5 EMA dots/high-power field was associated with a sensitivity of 72% and a specificity of 81%. The presence of ring-like EMA positive structures was less sensitive (32%), but highly specific (100%). To conclude, distinct punctate and ring-like EMA staining might serve as sensitive and specific markers of ependymal differentiation in glial tumors and, thus, may aid the diagnosis of ependymoma.


Ultrastructural and enzyme histochemical study of ovarian hilar cells in women and their relationships with sympathetic nerves.
The ultrastructure of normal ovarian hilar cells, both during the reproductive era and after the menopause, shows evidence of steroid hormone synthesis. In this respect these cells are very similar to Leydig cells in that they contain mitochondria with a dense matrix, a highly developed smooth endoplasmic reticulum, Reinke crystals, and microcystalline inclusions. The latter are much more numerous than in the normal testis. Their enzymatic activities are quite similar to those of Leydig cells. Ovarian hilar cells seem to originate from progressive metamorphosis of fibroblastic cells under the induction of sympathetic nervous structures. Their relations with hilar nerves are of three types: simple direct membrane contact without a Schwann cell sheath, intimate intracytoplasmic relationships, and specialized contacts, which are comparable to a synapse.


Use of 157-nm photodissociation to probe structures of y- and b-type ions produced in collision-induced dissociation of peptide ions.
y- and b-type fragment ions produced in the collisional dissociation of arginine-terminated peptide ions are photodissociated with 157-nm light in a linear trap. y-type ions are shown to have the same structure as that of intact peptides of the same sequence with the ionizing proton located at the most basic residue(s). For generic b-type ions, the ionizing proton is shown to be sequestered at the N-terminal arginine, which is consistent with the proposed oxazolone structure.


2. Mechanism of steroid action. Immunoreactivity of the core of estrogen receptors found in different subcellular compartments of target cells from a variety of mammalian species.
A goat antiserum was raised by immunization with the endoglycosidase fission product of porcine estrogen receptor. Its IgG fraction was employed for ascertaining the interrelationship of receptor forms extracted from three subcellular compartments of target cells and for comparing receptors from various species. Unspecific alignments of (non-immune) IgGs giving rise to soluble complexes were avoided by removal of the receptor entity responsible with carrier-attached trypsin. Coincubation of the estradiol-tagged tryptic receptor cores and immune IgG resulted in the formation of labelled precipitates and in the release of estradiol from its binding site, in every instance tested. A minimum of three common antigenic determinants must therefore exist not only on all porcine receptor forms, but also on human, ovine, bovine, rabbit, guinea-pig and rat estrogen receptors, pointing to a high degree of phylogenetic conservation.


S-100 protein in carcinoid tumours of appendix.
A series of 12 carcinoid tumours of the appendix were examined with regard to S-100 protein immunoreactivity. All tumours were both argentaffin and argyrophil, and displayed immunoreactivity after application of a monoclonal antibody against serotonin. The S-100 protein immunoreactivity appeared in 11 of the 12 tumours, preferably in cells presumably of Schwann cell origin with long slender processes localized at the periphery of the carcinoid tumour buds. Immunoreactive cells with cytoplasmic processes were also seen extending between individual tumour cell in the tumour aggregates. In a few tumours S-100 immunoreactivity occurred in the cytoplasm of tumour cells with or without cytoplasmic extensions. The presence of S-100 protein immunoreactive cells, apparently as an integral component, and its shape and distribution indicate that the peripheral nervous system (PNS) is histogenetically involved in the development of carcinoid tumours of the appendix.


Depression and its association with adverse childhood experiences in people with substance use disorders and comorbid medical illness recruited during medical hospitalization.
People who have experienced adverse childhood experiences (ACEs) are more susceptible to substance use disorder (SUD) and depression. The present study examined depression prevalence in hospitalized patients with SUD and examined the association of individual ACEs with major depression. Depression rates 3 months after discharge were also examined. Medical inpatients with SUD were recruited from Temple University Hospital. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) at baseline and 3 months post-discharge. Participants were also assessed using an ACE scale at baseline. Of 79 baseline participants, 48% (38) had moderate to severe major depressive disorder (MDD) with PHQ-9 scores ≥15. Among those with baseline MDD, 38% (9/24) continued to have MDD 3 months post discharge, and 42.9% (12/28) of those without MDD at baseline met criteria at 3 months. Sixty-three percent (50/79) of the participants reported 4+ ACEs at baseline. Two ACEs, Household Incarceration and Household Mental Illness, were significantly associated with having MDD at baseline and 3 months (adjusted mean PHQ-9 total score increase (SE) and p-value: 2.97 (1.35), p < .05; 5.32 (1.37), p < .005, respectively). In this exploratory study, nearly half of medical inpatients with substance use disorder had moderate to severe major depression, with a similar percentage of participants having MDD as outpatients at 3 months. Approximately two thirds of participants reported four or more adverse childhood experiences at baseline. Inpatient medical hospitalization should be utilized as an opportunity to engage people with SUD in multidisciplinary treatment including psychiatric, trauma informed care, and substance abuse treatment.


Preliminary experience with a novel model assessing in vivo mechanical strength of bone grafts and substitute materials.
A novel canine tibia model was used to evaluate four bone graft materials: autologous cortical bone, allograft cortical bone, hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic granules, and a HA/TCP and collagen composite. Mechanical material properties were assessed using custom-designed stainless steel plugs for control of graft volume and interface surface area. These plugs held the bone graft materials in the cortex of the tibia shaft and allowed in vivo mechanical testing. After 6 months of ad lib weight bearing, the grafts were harvested and tested in torsion. The samples in each animal were compared with the test plugs into which new bone had grown without the addition of graft. Control bone peak shear strength averaged 47 (+/- 8.3) MPa (6.78 +/- 1.2 kpsi). Compared on the basis of peak torque, stiffness, and energy to peak torque, no significant differences were found among any of the graft materials or control bone. Histologic examination revealed the materials to be osteoconductive with the extensive formation of dense, compact cancellous bone. The new bone in the autograft and allograft samples completely filled the available space, whereas gaps persisted in the synthetic ceramics.


Biochemical correlates of alpha 1-adrenoceptor activation.
An impressive body of evidence based on radioligand binding, biochemical, functional and structural data supports the existence of two sub-types of the alpha 1-adrenoceptor (alpha 1a and alpha 1b) in the CNS and in peripheral tissues. Both elevate intracellular Ca2+ concentrations, although by different mechanisms, resulting in a cascade of intracellular events dependent upon the cell type involved.


Dyslipidemia, Diet and Physical Exercise in Children on Treatment With Antiretroviral Medication in El Salvador: A Cross-sectional Study.
Dyslipidemias are common in HIV-infected children, especially if treated with protease inhibitors, but there are few data on how to treat dyslipidemias in this population. We estimated the dyslipidemia prevalence and its association with treatment, diet and physical exercise in children on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). Information was gathered regarding socio-demographic characteristics, treatment, diet and physical activity of 173 children aged 5-18 years and receiving antiretroviral therapy. Triglycerides, total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), viral load and CD4 T-lymphocytes were measured. Abnormal concentrations were defined as triglycerides ≥130 mg/dL in 10- to 18-year olds and ≥100 mg/dL in <10-year olds; total cholesterol ≥200 mg/dL; LDL-C ≥130 mg/dL and HDL-C ≤35 mg/dL. We adjusted 4 different multivariate models to assess the independent association of each type of dyslipidemia with protease inhibitors, diet and physical exercise. Of the 173 children, 83 (48%) had hypertriglyceridemia and 25 (14.5%) hypercholesterolemia. High LDL-C concentrations were observed in 17 children (9.8%) and low HDL-C in 38 (22%). Treatment with protease inhibitors was significantly associated with hypertriglyceridemia [prevalence ratio (PR) 2.8; 95% confidence interval (CI): 2.0-3.8] and hypercholesterolemia (PR 9.0; 95% CI: 3.6-22.2). Higher adherence to a "high fat/sugar diet" was associated with hypercholesterolemia (PR 1.6; 95% CI: 1.1-2.3) and high LDL-C (PR 1.7; 95% CI: 1.0-2.9). Compared with those exercising <3 times/week, children exercising ≥7 times were less likely to have low HDL-C (PR = 0.4; 95% CI: 0.2-0.7). These results suggest that a healthy diet and exercise habits can contribute to controlling some aspects of the lipid profile in this population.


Statistical Evolutionary Laws in Music Styles.
If a cultural feature is transmitted over generations and exposed to stochastic selection when spreading in a population, its evolution may be governed by statistical laws and be partly predictable, as in the case of genetic evolution. Music exhibits steady changes of styles over time, with new characteristics developing from traditions. Recent studies have found trends in the evolution of music styles, but little is known about their relations to the evolution theory. Here we analyze Western classical music data and find statistical evolutionary laws. For example, distributions of the frequencies of some rare musical events (e.g. dissonant intervals) exhibit steady increase in the mean and standard deviation as well as constancy of their ratio. We then study an evolutionary model where creators learn their data-generation models from past data and generate new data that will be socially selected by evaluators according to the content dissimilarity (novelty) and style conformity (typicality) with respect to the past data. The model reproduces the observed statistical laws and can make non-trivial predictions for the evolution of independent musical features. In addition, the same model with different parameterization can predict the evolution of Japanese enka music, which is developed in a different society and has a qualitatively different tendency of evolution. Our results suggest that the evolution of musical styles can partly be explained and predicted by the evolutionary model incorporating statistical learning, which can be important for other cultures and future music technologies.


Pomegranate juice and punicalagin-mediated chemoprevention of hepatocellular carcinogenesis via regulating miR-21 and NF-κB-p65 in a rat model.
Hepatocellular carcinoma (HCC) is the most common neoplasm among primary liver malignancies, accounting for 70%-85% of total liver cancer cases worldwide. It is also the second-leading cause of cancer-related death worldwide. Recent research has investigated naturally occurring products high in polyphenolic compounds in the regression and prevention of HCC. This study investigated the chemoprevention effects of pomegranate juice (PJ) and punicalagin (PCG) against diethylnitrosamine (DENA)-induced hepatocarcinogenesis in male albino rats. Animals were randomized into six groups and treated for 11 weeks as follows: group 1 was a negative control group, group 2 was treated orally with 10 mL PJ per kilogram body weight (kg bw), group 3 was treated orally with 18.5 mg PCG/kg bw, and groups 4-6 were injected with an intraperitoneal dose of DENA (50 mg/kg bw) weekly beginning in the third week. Group 4 was a HCC control (DENA-treated group), group 5 was HCC + PJ, and group 6 was HCC + PCG. PJ antagonized DENA-induced elevations of ALAT, TNF-α, NF-κB-p65, GST, MDA, and NO and restored total protein, IL-10, SOD, and CAT levels. Moreover, PJ resulted in downregulation of miR-21, Bcl-2, and Bcl-XL and an upregulation of caspase-3 and Bax mRNA expressions. These chemoprevention effects of PJ also alleviated the hepatic preneoplastic lesions induced by DENA. Although PCG treatment induced some modulation in DENA-treated rats, it did not show potent chemoprevention activity and induced some side effects. Both of PJ and PCG downregulated miR-21 expression and triggered apoptosis. However, PJ was more effective than pure PCG in alleviating the hepatic antioxidant defense state and the inflammatory status. So, PJ was superior in prevention of DENA-induced hepatocellular carcinogenesis in rats than pure PCG.