The distribution of substance P in turtle nervous system: a radioimmunoassay and immunohistochemical study.
The distribution of a substance P-like material in turtle brain, spinal cord, dorsal root ganglion, and retina was determined using radioimmunoassay (RIA) and immunohistochemistry. High levels of a substance P-like material were found in turtle neural tissue, particularly in basal telencephalon, hypothalamus, and tegmentum. In many regions, the concentration of a substance P-like material in turtle nervous tissue was found to be similar, in a region-to-region comparison, to that previously reported for birds and mammals, particularly for the more "phylogenetically conservative" parts of the nervous system (such as the basal ganglia, tegmentum, and hypothalamus). The slopes of substance P RIA dose-response curves for tissue extracts from nearly all regions of the turtle nervous system examined were parallel to a standard dose-response curve for synthetic substance P (SP). The immunohistochemical results, with anti-substance P antisera from guinea pig or rabbit, or with a monoclonal antibody, were consistent with the RIA data. Regions showing high concentration of an SP-like material by RIA were observed to contain numerous neurons and/or fibers containing an SP-like material. The immunohistochemical results provide evidence for the presence in turtle of numerous SP-containing pathways, several of which (e.g., an SP-containing strionigral pathway, an SP-containing striopallidal pathway and an SP-containing dorsal root ganglia-spinal dorsal horn pathway), have been described in birds and mammals. The present results thus suggest that the neuropeptide SP has had a largely stable evolutionary history as a transmitter or modulatory agent during amniote brain evolution.


Intravaginal controlled administration of flurogestone acetate I: Development of a stability-indicating liquid chromatographic method and stability kinetics of flurogestone acetate.
Flurogestone acetate is a synthetic progestin useful for estrus synchronization in sheep. The estrus synchronization is achieved by inserting the drug-impregnated vaginal sponge in the sheep for up to 15 d, during which time flurogestone acetate is administered continuously by intravaginal absorption to suppress estrus and ovulation. The sponge is then withdrawn to regain estrus within 2-4 d. A review of the literature suggests that the analytical methods currently available are not specific, sensitive, and rapid enough. A stability-indicating high-performance liquid chromatographic method was developed, which is capable of characterizing the stability kinetics of flurogestone acetate under various environmental conditions and quantifying the release and absorption profiles of the drug from the vaginal sponges.


A Radiotracer Strategy to Quantify PARP-1 Expression In Vivo Provides a Biomarker That Can Enable Patient Selection for PARP Inhibitor Therapy.
Despite the availability of PARP inhibitors for cancer therapy, a biomarker to clearly stratify patients for selection of this treatment remains lacking. Here we describe a radiotracer-based method that addresses this issue, using the novel compound [(125)I] KX1: as a PARP-1-selective radiotracer that can accurately measure PARP-1 expression in vitro and in vivo The pharmacologic properties of the PARP radiotracer [(125)I] KX1: was characterized in multiple cell lines where single-agent sensitivity was correlated with [(125)I] KX1: binding to PARP-1. In vivo evaluation of [(125)I] KX1: verified in vitro results, validating PARP radiotracers to define PARP-1 enzyme expression as an in vivo biomarker. Notably, PARP-1 expression as quantified by [(125)I] KX1: correlated positively with the cytotoxic sensitivity of cell lines evaluated with PARP inhibitors. Overall, our results defined a novel technology with the potential to serve as a companion diagnostic to identify patients most likely to respond therapeutically to a PARP inhibitor. Cancer Res; 76(15); 4516-24. ©2016 AACR.


A semi-analytic approach to determine dose rate constant of brachytherapy sources in compliance with AAPM TG 60 formalism.
Values of dose rate constant (DRC) in compliance with AAPM TG 60 formalism recommended for intravascular brachytherapy (IVBT) were calculated for different point isotropic mono-energetic photon sources in the energy range E = 20-1000 keV using a semi-analytic model. Based on these DRC values, DRC of some existing models of 192Ir and 125I brachytherapy sources were then calculated using (1) bare energy spectra and (2) a single energy parameter which represents mean energy (photon number weighted or air-kerma weighted) for bare and actual sources or the most probable energy of the spectra (energy line with the highest probability of emission) of the investigated sources (192Ir and 125I). Applicability of the semi-analytic approach was examined by also computing the values of DRC of the investigated sources using MCNP Monte Carlo simulation code (Version 3.1) that involved modeling of the sources accurately. A comparison of values of DRC resulting from MCNP calculations with those resulting from the semi-analytic approach showed that for 192Ir sources the agreement was within 0.40% and for 125I sources it was within 2.3%.


Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor.
Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase inhibitor (HDACi), to attenuate growth of primary ocular UM cell lines and, in particular, a liver MUM cell line in vitro and in vivo, and elucidate the underlying molecular mechanisms. A significant (p = 0.0001) dose-dependent reduction in surviving clones of the primary ocular UM cells, Mel270, was observed upon treatment with increasing doses of ACY-1215. Treatment of OMM2.5 MUM cells with ACY-1215 resulted in a significant (p = 0.0001), dose-dependent reduction in cell survival and proliferation in vitro, and in vivo attenuation of primary OMM2.5 xenografts in zebrafish larvae. Furthermore, flow cytometry revealed that ACY-1215 significantly arrested the OMM2.5 cell cycle in S phase (p = 0.0001) following 24 h of treatment, and significant apoptosis was triggered in a time- and dose-dependent manner (p < 0.0001). Additionally, ACY-1215 treatment resulted in a significant reduction in OMM2.5 p-ERK expression levels. Through proteome profiling, the attenuation of the microphthalmia-associated transcription factor (MITF) signaling pathway was linked to the observed anti-cancer effects of ACY-1215. In agreement, pharmacological inhibition of MITF signaling with ML329 significantly reduced OMM2.5 cell survival and viability in vitro (p = 0.0001) and reduced OMM2.5 cells in vivo (p = 0.0006). Our findings provide evidence that ACY-1215 and ML329 are efficacious against growth and survival of OMM2.5 MUM cells.


Immobilization of glucoamylase by adsorption on carbon supports and its application for heterogeneous hydrolysis of dextrin.
Glucoamylase (GA) was immobilized by adsorption on carbon support: on Sibunit, on bulk catalytic filamentous carbon (bulk CFC) and on activated carbon (AC). This was used to prepare heterogeneous biocatalysts for the hydrolysis of starch dextrin. The effect of the texture characteristics and chemical properties of the support surface on the enhancement of the thermal stability of the immobilized enzyme was studied, and the rates of the biocatalyst's thermal inactivation at 65-80 degrees C were determined. The thermal stability of glucoamylase immobilized on different carbon supports was found to increase by 2-3 orders of magnitude in comparison with the soluble enzyme, and decrease in the following order: GA on Sibunit>GA on bulk CFC>GA on AC. The presence of the substrate (dextrin) was found to have a significant stabilizing effect. The thermal stability of the immobilized enzyme was found to increase linearly when the concentration of dextrin was increased from 10 wt/vol % to 50 wt/vol %. The total stabilization effect for glucoamylase immobilized on Sibunit in concentrated dextrin solutions was about 10(5) in comparison with the enzyme in a buffer solution. The developed biocatalyst, 'Glucoamylase on Sibunit' was found to have high operational stability during the continuous hydrolysis of 30-35 wt/vol % dextrin at 60 degrees C, its inactivation half-time (t1/2) exceeding 350 h. To improve the starch saccharification productivity, an immersed vortex reactor (IVR) was designed and tested in the heterogeneous process with the biocatalyst 'Glucoamylase on Sibunit'. The dextrin hydrolysis rate, as well as the process productivity in the vortex reactor, was found to increase by a factor of 1.2-1.5 in comparison with the packed-bed reactor.


Treatment results of the thioether lipid ilmofosine in patients with malignant tumours.
In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.


Putative role of asymmetric dimethylarginine in microvascular disease of kidney and heart in hypertensive patients.
Despite the frequent simultaneous presentation of cardiac and renal dysfunction, the relationship between these pathophysiological processes remains unclear. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase, which has been linked to endothelial dysfunction and atherosclerosis. This study elucidates the relationship between ADMA and intrarenal and coronary microvascular diseases. In this study, we included 66 consecutive hypertensive patients with normal renal function or mild renal insufficiency (creatinine <or= 1.2 mg/dl). On the basis of their estimated glomerular filtration rate (eGFR), the patients were divided into two groups (normal group, eGFR >or=90 ml/min; renal insufficiency group, eGFR <90 ml/min). Coronary flow velocity reserve (CFVR) was measured using adenosine-triphosphate stress transthoracic Doppler echocardiography. In addition, a plasma ADMA assay, echocardiography, carotid ultrasound, and brachial-ankle pulse wave velocity measurement were performed. The plasma ADMA level was the highest in patients with both renal insufficiency and reduced CFVR. ADMA was significantly associated with eGFR (r = -0.342, P = 0.006) and CFVR (r = -0.459, P < 0.001), and eGFR and CFVR were significantly associated with each other (r = 0.337, P = 0.006). Multiple regression analysis revealed that ADMA was an independent clinical parameter associated with both eGFR and CFVR. Plasma ADMA is suggested to be an incipient biochemical marker of microvascular disease in both kidney and heart in hypertensive patients. ADMA might play an important role in the pathogenesis of organ damage in the kidney and heart in essential hypertension.


Development and validation of a survival prediction model and risk stratification for pancreatic neuroendocrine neoplasms.
We explored risk variables associated with cancer-specific survival (CSS) in patients with pancreatic neuroendocrine neoplasms (PNENs) and created a network dynamic nomogram model to predict patient survival time. A total of 7750 patients with PNENs were included in this analysis, including 134 with functional PNENs and 7616 with nonfunctional PNENs. Clinical feature and prognosis differences between functional and nonfunctional PNENs were compared. Independent prognostic factors affecting CSS were analyzed by univariate and multifactorial Cox regression. Nomogram and web-based prognosis prediction of PNENs were developed and validated by C indices, decision curve analysis, and calibration plots. Patients with functional PNENs were younger at diagnosis than those with nonfunctional PNENs. Functional PNENs had better prognoses than nonfunctional PNENs (5-year survival rates: 78.55% and 71.10%, respectively). Univariate and multifactorial Cox regression analyses showed that tumor infiltration (T), nodal metastasis (N), metastasis (M), tumor site, differentiation grade, age, marital status, and surgical treatment were independent prognostic risk factors for CSS, which were included in the prognostic nomogram and web-based prognosis calculator. The calibration plots and decision curve analysis showed that the nomogram had excellent prediction and clinical practical ability. The C indices for CSS in the training and validation cohorts were 0.848 (95% CI 0.838-0.8578) and 0.823 (95% CI 0.807-0.839), respectively. We scored all patients according to the nomogram and divided patients into three different risk groups. The prognosis of the low-risk population was significantly better than those of the middle- and high-risk populations based on Kaplan-Meier survival curve. We analyzed the clinical features of PNENs and developed a convenient and web dynamic nomogram to predict CSS.


Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting.
Serological studies can detect infection with a novel influenza virus in the absence of symptoms or positive virology, providing useful information on infection that goes beyond the estimates from epidemiological, clinical and virological data. During the 2009 A(H1N1) pandemic, an impressive number of detailed serological studies were performed, yet the majority of serological data were available only after the first wave of infection. This limited the ability to estimate the transmissibility and severity of this novel infection, and the variability in methodology and reporting limited the ability to compare and combine the serological data. To identify best practices for conduct and standardisation of serological studies on outbreak and pandemic influenza to inform public policy. An international meeting was held in February 2011 in Ottawa, Canada, to foster the consensus for greater standardisation of influenza serological studies. Best practices for serological investigations of influenza epidemiology include the following: classification of studies as pre-pandemic, outbreak, pandemic or inter-pandemic with a clearly identified objective; use of international serum standards for laboratory assays; cohort and cross-sectional study designs with common standards for data collection; use of serum banks to improve sampling capacity; and potential for linkage of serological, clinical and epidemiological data. Advance planning for outbreak studies would enable a rapid and coordinated response; inclusion of serological studies in pandemic plans should be considered. Optimising the quality, comparability and combinability of influenza serological studies will provide important data upon emergence of a novel or variant influenza virus to inform public health action.


Rapamycin protects against middle cerebral artery occlusion induced focal cerebral ischemia in rats.
Stroke is a major cause of mortality and disability. The management with thrombolytic therapy has to be initiated within 3-4 h and is associated with limitations like increased risk of intracranial hemorrhage and progression of cerebral injury. Immunophilin inhibitors such as cyclosporine A and tacrolimus have been shown to afford neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. In the present study, the effect of rapamycin in middle cerebral artery occlusion (MCAo) model of ischemic stroke was evaluated. Ischemic stroke was induced in rats by occluding the MCA using the intraluminal thread. After 1 h of MCAo, animals were administered rapamycin (50, 150, 250 μg/kg, i.p.). After 2 h of occlusion, reperfusion was done. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of protective effect of rapamycin. Twenty-four hours after MCAo, motor performance was assessed, the animals were euthanized and the brains were removed for estimation of malondialdehyde, glutathione, nitric oxide and myeloperoxidase. Significant improvement was observed with rapamycin 150 and 250 μg/kg in percent infarct area, apparent diffusion coefficient and signal intensity as compared to vehicle treated group. Rapamycin treatment ameliorated motor impairment associated with MCAo and significantly reversed the changes in levels of malondialdehyde, glutathione, nitric oxide and myeloperoxidase. The results of the present study indicate neuroprotective effect of rapamycin in MCAo model of stroke. Therefore, rapamycin might be considered as a therapeutic strategy for stroke management.


Effect of extracellular calcium on vascular contraction induced by phorbol ester.
In rat thoracic aorta, 12-0-tetradecanoyl-phorbol-13-acetate (TPA) caused a slowly onset, sustained vascular contraction. The contraction was markedly reduced in the absence of extracellular Ca2+, although small tension development was still observed. The tension developed by TPA in the presence of Ca2+ was decreased by serial addition of a Ca2+-channel blocker, verapamil in a concentration-dependent manner. TPA could cause vascular contraction to almost maximum level at lower concentration of extracellular Ca2+, compared with KCl- or norepinephrine-induced contraction. These results suggest that extracellular Ca2+ which influxes through Ca2+-channels into cytoplasm is necessary for full tension development by TPA, and that TPA increases sensitivity of contractile mechanisms coupling with Ca2+.


Fluorescence-guided extended pelvic lymphadenectomy during robotic radical prostatectomy.
We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectıvely. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements ın stagıng and oncologıc outcomes may also be seen ın intermediate- and high-risk patients.


How Long can we Store Blood Samples: A Systematic Review and Meta-Analysis.
To assess the effect of storage time and temperature on complete blood count (CBC) and comprehensive metabolic panel (CMP) testing. PubMed, EMBASE, the Cochrane Library of Systematic Reviews, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), WanFang databases and SinoMed databases were searched up to May 2017. Clinical trials with adult whole blood samples were identified. Paired reviewers independently screened, extracted data and evaluated the quality of evidence (MINORS tool). Analyses were conducted using Revman 5.3 and Stata 14.0. A total of 89 studies were confirmed. For CBC, except MPV, most parameters were stable at least for 24h. Some indices, such as WBC, PLt, HCT, HGB and MCH were stable up to 3 d. However, stable CMP test results could only be acquired within 12h. at 4°C, including GLU, AST, ALT, Na, ALB, Cl, DBIL, TC, TG and ALP. Values were less stable when stored at RT. Specimens stored >12h. for CMP may generate unreliable results. For CBC, samples could reliably be stored for 24h. For longer storage, refrigeration (at 4°C) would be a better choice.


Preventive skin analgesia with lidocaine patch for management of post-thoracotomy pain: Results of a randomized, double blind, placebo controlled study.
To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. This was a double-blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end-point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser-evoked potential (secondary end-points). A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser-evoked potential. The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post-thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies.


Scanning superlens microscopy for non-invasive large field-of-view visible light nanoscale imaging.
Nanoscale correlation of structural information acquisition with specific-molecule identification provides new insight for studying rare subcellular events. To achieve this correlation, scanning electron microscopy has been combined with super-resolution fluorescent microscopy, despite its destructivity when acquiring biological structure information. Here we propose time-efficient non-invasive microsphere-based scanning superlens microscopy that enables the large-area observation of live-cell morphology or sub-membrane structures with sub-diffraction-limited resolution and is demonstrated by observing biological and non-biological objects. This microscopy operates in both non-invasive and contact modes with ∼200 times the acquisition efficiency of atomic force microscopy, which is achieved by replacing the point of an atomic force microscope tip with an imaging area of microspheres and stitching the areas recorded during scanning, enabling sub-diffraction-limited resolution. Our method marks a possible path to non-invasive cell imaging and simultaneous tracking of specific molecules with nanoscale resolution, facilitating the study of subcellular events over a total cell period.


Percutaneous screw fixation for the acetabular fracture with quadrilateral plate involved by three-dimensional fluoroscopy navigation: surgical technique.
The percutaneous three-dimensional (3D)-fluoroscopic-navigated screw directing to the quadrilateral plate was attempted. Five patients with acetabular fractures were treated by 3D navigated percutaneous screw. The quadrilateral plate was involved in all the patients. The Arcadis 3D (ARCADIS Orbic 3D(®); Siemens AG Healthcare Sector, Erlangen, Germany) and computer navigation system (stryker navigation system) were employed, screwing trajectory was attempted to anchor the quadrilateral plate perpendicularly to the fracture line and close to the joint cartilage as much as possible. Parameters including fracture gap closure (P1), distance to the joint cartilage (P2), angulations between the screw and the fracture line (P3), were measured with the software installed on the machine of Arcadis 3D. Seven screws were inserted with the use of 3D fluoroscopic navigation. The quadrilateral plate was hold by percutaneous screws. The closure of fracture gap was achieved in 3 patients by 2-3mm. The nearest distance from the screw to the joint cartilage was ranged from <1mm to 6mm. The angulations between the screw and the fracture line was 80-90° in three patients, it was 60° and 65° respectively on the rest two patients. All patients felt pain free 1week after the operation. No complication was noted postoperatively. The surgical technique of percutaneous screwing for the acetabular fracture with three-dimensional fluoroscopy-based navigation was demonstrated.


Polyamines antagonize N-methyl-D-aspartate-evoked depolarizations, but reduce Mg2+ block.
This study utilized a grease-gap preparation to investigate the effects of polyamines on responses of CA1 hippocampal pyramidal cells to N-methyl-D-aspartate (NMDA) and on the block of the NMDA channel by Mg2+. In the absence of added Mg2+, 1,10-diaminodecane (0.1-1 mM) non-competitively antagonized NMDA-evoked depolarizations. Its antagonism slowly progressed to a stable value, was not use-dependent and did not reverse completely upon washout. Similar results were obtained with 100 microM spermine and 1 mM diethylenetriamine. Addition of 1 mM Mg2+ to the superfusion medium greatly reduced these effects. Conversely, the polyamines attenuated the blocking action of Mg2+. Postnatal treatment with alpha-difluoromethylornithine reduced the total polyamine content of area CA1 in 10- to 15-day-old rats almost to the adult level (although spermine content was unaffected). Mg2+ less potently antagonized NMDA-evoked depolarizations in slices from 10- to 15-day-old rats than in slices from adult rats, and this difference was unaffected by the alpha-difluoromethylornithine treatment. These results suggest (1) that there are rapid and slow components to the antagonism of NMDA-evoked depolarizations by polyamines, both of which may involve permeation of the polyamine into or through the NMDA channel: (2) that polyamine release in brain could modulate the Mg2+ sensitivity of responses to NMDA; and (3) that changes in the total content of endogenous polyamine do not explain developmental differences in the sensitivity of NMDA-evoked depolarizations to Mg2+.


Lived-in experiences of health care professionals affected with COVID-19.
Healthcare providers (HCPs) were vital during the COVID-19 pandemic. The healthcare providers affected by COVID-19 underwent various life changing events while continuing their profession during the pandemic. This study is aimed to explore the lived-in experiences of HCPs affected by COVID-19 at a tertiary care Mental Health Institute in India. The sampling method was purposive. Twenty two HCPs (eight nursing educators, seven nursing officers, five contractual cleaning workers, and two laboratory technicians) participated in the interviews conducted by the researchers to obtain the lived-in experiences of HCPs who have recovered from COVID-19. Researchers used a sociodemographic form and an interview guide to collect the data. Interviews were audio recorded and analyzed by using Atlas-ti-9 software. All the participants were female, and they revealed various physical, psychological, and social issues faced by HCPs while balancing home and workplace. Thematic data analysis resulted in the emergence of two themes and 11 subthemes related to life changing events. The findings concluded that although the healthcare providers had working experience in the field of mental health, they too experienced mild psychological issues like anxiety, depression, and fear of death because of this pandemic situation.


Patient-derived zebrafish xenografts of uveal melanoma reveal ferroptosis as a drug target.
Uveal melanoma (UM) has a high risk to progress to metastatic disease with a median survival of 3.9 months after metastases detection, as metastatic UM responds poorly to conventional and targeted chemotherapy and is largely refractory to immunotherapy. Here, we present a patient-derived zebrafish UM xenograft model mimicking metastatic UM. Cells isolated from Xmm66 spheroids derived from metastatic UM patient material were injected into 2 days-old zebrafish larvae resulting in micro-metastases in the liver and caudal hematopoietic tissue. Metastasis formation could be reduced by navitoclax and more efficiently by the combinations navitoclax/everolimus and flavopiridol/quisinostat. We obtained spheroid cultures from 14 metastatic and 10 primary UM tissues, which were used for xenografts with a success rate of 100%. Importantly, the ferroptosis-related genes GPX4 and SLC7A11 are negatively correlated with the survival of UM patients (TCGA: n = 80; Leiden University Medical Centre cohort: n = 64), ferroptosis susceptibility is correlated with loss of BAP1, one of the key prognosticators for metastatic UM, and ferroptosis induction greatly reduced metastasis formation in the UM xenograft model. Collectively, we have established a patient-derived animal model for metastatic UM and identified ferroptosis induction as a possible therapeutic strategy for the treatment of UM patients.


Aggressive Lennert's lymphoma: report of three cases in comparison to non-aggressive Lennert's lymphoma.
The present article describes three cases of Lennert's lymphoma exhibiting aggressive clinical courses. These cases were accompanied by disseminated intravascular coagulation (DIC) or hemophagocytic syndrome (HPS). These cases were compared to non-aggressive type of Lennert's lymphoma. Of the three cases, two demonstrated involvement of the liver and the other possessed bone marrow involvement. In one patient, while a lymph node biopsy revealed Lennert's lymphoma histologically, a liver biopsy obtained 2 months later revealed a high-grade large cell cytotoxic T-cell lymphoma. Two of these cases showed HPS and the other exhibited DIC. All patients died within 1 year of diagnosis, with the shortest survival period being 1.5 months. Immunohistochemically, lymphoma cells were CD8+, CD4-, granzyme B+, and T-cell intracellular antigen-1 (TIA-1)+, showing a cytotoxic T-cell phenotype. Two cases demonstrated positive reactivity for Epstein-Barr virus in lymphoma cells by in situ hybridization. These cases were compared with eight cases of non-aggressive Lennert's lymphoma. In comparison to non-aggressive disease, these three cases displayed a higher percentage of Ki-67-positive cells. In conclusion it was found that a subset of Lennert's lymphoma cases share common features with high-grade cytotoxic T-cell lymphoma, indicating that Lennert's lymphoma may be part of the spectrum of cytotoxic T-cell lymphoma.


Postpartum contraceptive acceptance in León, Mexico: a multivariate analysis.
The aim of the present study was to identify the reasons for the acceptance or rejection of contraceptive methods among postpartum women at the Hospital of Obstetrics and Gynecology in León, Mexico. A prospective cross-sectional study of 1025 postpartum women was undertaken. Reasons for acceptance or refusal of contraceptives were registered in a written survey. Twelve sociodemographic variables were included as predictors in a logistic regression analysis; the acceptance or refusal was the dependent variable, and statistical significance was set at 0.05. There were 513 patients who accepted contraceptives (50.0%) and 512 (50.0%) who refused them. The main reasons for accepting contraceptives were definitive desire for no more children (17.0%) and satisfaction with previous contraceptive methods (21.5%). The main contraceptive methods chosen were intrauterine device (67.7%) and tubal sterilization (28.5%). Reasons for contraceptive refusal were husband's rejection (33.2%) and delaying contraceptive use until after finishing the postpartum period (31.8%). In the logistic regression model, the variables previous deliveries (p < 0.001), number of Cesarean sections (p < 0.001) and women's level of education (p < 0.02) were included as predictors of acceptance. Previous deliveries, previous Cesarean sections and women's level of education were significant in contraception acceptance. The rejection of contraceptives was mainly attributed to husbands.


First generation leishmaniasis vaccines: a review of field efficacy trials.
First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.


Gastrointestinal symptoms and the severity of COVID-19: Disorders of gut-brain interaction are an outcome.
Many of the studies on COVID-19 severity and its associated symptoms focus on hospitalized patients. The aim of this study was to investigate the relationship between acute GI symptoms and COVID-19 severity in a clustering-based approach and to determine the risks and epidemiological features of post-COVID-19 Disorders of Gut-Brain Interaction (DGBI) by including both hospitalized and ambulatory patients. The study utilized a two-phase Internet-based survey on: (1) COVID-19 patients' demographics, comorbidities, symptoms, complications, and hospitalizations and (2) post-COVID-19 DGBI diagnosed according to Rome IV criteria in association with anxiety (GAD-7) and depression (PHQ-9). Statistical analyses included univariate and multivariate tests. Five distinct clusters of symptomatic subjects were identified based on the presence of GI symptoms, loss of smell, and chest pain, among 1114 participants who tested positive for SARS-CoV-2. GI symptoms were found to be independent risk factors for severe COVID-19; however, they did not always coincide with other severity-related factors such as age >65 years, diabetes mellitus, and Vitamin D deficiency. Of the 164 subjects with a positive test who participated in Phase-2, 108 (66%) fulfilled the criteria for at least one DGBI. The majority (n = 81; 75%) were new-onset DGBI post-COVID-19. Overall, 86% of subjects with one or more post-COVID-19 DGBI had at least one GI symptom during the acute phase of COVID-19, while 14% did not. Depression (65%), but not anxiety (48%), was significantly more common in those with post-COVID-19 DGBI. GI symptoms are associated with a severe COVID-19 among survivors. Long-haulers may develop post-COVID-19 DGBI. Psychiatric disorders are common in post-COVID-19 DGBI.


Implications and impact of the new US Centers for Disease Control and prevention HIV testing guidelines.
Of the 1.2 million Americans estimated to be living with HIV in the United States, approximately 250,000 are unaware of their diagnosis and therefore unable to access clinical care and life-sustaining treatment. The revised 2006 US Centers for Disease Control and Prevention's guidelines for HIV testing recommend universal, routine, and voluntary HIV screening in public and private health care settings for all adults and adolescents between 13 and 64 years old. These major revisions present new challenges for health care providers, hospitals, government agencies, and community advocacy groups. In this review, we discuss the important issues in diverse care venues such as opt-out testing, consent and confidentiality, barriers to treatment, and financial impact. The implications of the revised recommendations for HIV testing are addressed in the context of a fragmented, overstressed, underfunded US health care system.


Characteristic 1H NMR spectra of β-d-ribofuranosides and ribonucleosides: factors driving furanose ring conformations.
A series of β-d-ribofuranosides and ribonucleosides fused with 2,3-O-isopropylidene ring was synthesized and studied in terms of their conformational preferences. Based on the 1H NMR spectra, DFT calculations, and X-ray analysis the E 0-like and E 4-like conformations adopted by these furanosides are identified. The 3 E-like and 2 E-like conformations are assigned to ribonucleosides without the 2,3-O-isopropylidene group. The studies are supported by analysis of the structural data of β-d-ribofuranosides and ribonucleosides deposited in the Cambridge Crystallographic Data Center (CCDC) database. Finally, the factors influencing the conformational preferences of the furanose ring with the β-d-ribo configuration are indicated. These are the unfavorable ecliptic orientation of the 2-OH and 3-OH groups, the 1,3-pseudodiaxial interaction of the aglycone and terminal hydroxymethyl group and the endo-anomeric effect. It is also proved that the exo-anomeric effect acts in β-d-ribofuranosides.


Behaviour profile of Hungarian adolescent outpatients with a dual diagnosis.
The behaviour dimensions of 244 Hungarian adolescent psychiatric outpatients with a dual diagnosis (intellectual disability and psychiatric diagnosis) were examined by means of the adapted version of the Behaviour Problem Inventory (BPI, Rojahn, Matson, Lott, Esbensen, & Smalls, 2001). Four IQ subgroups were created: borderline, mild, moderate and profound ID subsamples. Significantly higher means were found in the self-injury/stereotyped behaviour/summarized scale categories both in the frequency and severity of symptoms in the more disabled groups against the samples having milder IQ impairment. Adolescents with a dual diagnosis showed much higher BPI scale means than an adult residential ID sample. ADHD and emotional disorders were the most frequent psychiatric diagnostic comorbidities of ID (20.67% and 11.73%). Academic achievement disorder, depression and psychosis had low occurrences (3.35, 2.23 and 1.17%, respectively) but showed convergency with other authors' data. The comorbid emotional disorders may create challenges for the care of the mildly intellectually disabled group.


Assessment of the Anti-Cancer Efficiency of Silver Moringa oleifera Leaves Nano-extract against Colon Cancer Induced Chemically in Rats.
Colorectal cancer (CRC) categorized as the most common type of gastrointestinal cancers affected both genders equally. Chemotherapeutic drugs became limited due to their deleterious side effects. Therefore, efficiency of M. oleifera leaves extract increased by incorporating silver nanoparticles (Ag-NPs) then studied against colon cancer induced by azoxymethane (AOM) in rats. Different hematological and biochemical measurements in addition to specific tumor and inflammatory markers were quantified. Histopathological examination for Colonic tissues was performed. Native proteins and isoenzyme patterns were electrophoretically detected in addition to assaying expression of Tumor Protein P53 (TP53) and Adenomatous Polyposis Coli (APC) genes in colonic tissues. M. oleifera nano-extract restored levels of the hematological and biochemical measurements in addition to levels of tumor and inflammatory markers to normalcy in both of nano-extract simult- and post-treated groups. Also, it minimized severity of the histopathological alterations in the simult-treated group and prevented it completely in the post-treated group. The lowest similarity index (SI%) values were noticed with electrophoretic protein (SI=61.54%), lipid (SI=0.00%) and calcium (SI=75.00%) moieties of protein patterns, catalase (SI=85.71%), peroxidase (SI=85.71%), α-esterase (SI=50.00%) and β-esterase (SI=50.00%) isoenzymes in addition to altering the relative quantities of total protein and isoenzyme bands in colon of cancer induced group. Moreover, levels of TP53 and APC gene expression increased significantly (P≤0.05) in colon cancer induced group. The nano-extract prevented the qualitative and quantitative alterations in the different electrophoretic patterns in addition to restoring levels of the gene expressions to normalcy in both of simult- and post-treated groups. M. oleifera nano-extract exhibited ameliorative effect against the biochemical, physiological and molecular alterations induced by AOM in nano-extract simult- and post-treated groups.<br />.


Heavy metals in the volcanic and peri-urban terrain watershed of the River Yautepec, Mexico.
Thirty-four water samples were collected all along the course of River Yautepec, Morelos State, Central Mexico, in three different zones based on the physical and anthropogenic setting. In situ measurements of physical characteristics (temperature, pH, conductivity, and turbidity) were also performed at each sampling station. Likewise, total/dissolved metal concentrations (Fe, Mn, Cr, Cu, Ni, Pb, Zn, Cd, As, and Pb) were determined using an atomic absorption spectrophotometer. Located in a peri-urban and volcanic zone of Central Mexico, the river system presented impacts of both natural and anthropogenic activities. Results revealed differences in pH values (6.7-8.23) in all the three zones probably due to the influences of volcanic ash and local geological formations, whereas conductivity levels (635-1098 μs/cm) were high indicating the effect of agricultural and industrial activities. The relative order of the concentrations of metals in both the total and dissolved fractions was observed to be in the following order: zone I, Fe > Zn > Mn > Cu > Pb > Ni > Cr > As > Cd > Hg; zone II, Fe > Zn > Pb > Ni > Mn > Cu > Cr > Cd > As > Hg; zone III, Fe > Pb > Zn > Mn > Ni > Cu > As > Cd > Cr > Hg. Calculated heavy metal evaluation index (HEI) values indicated less contamination. However, concentrations of Fe and Pb were observed to be higher than the permissible limits set forth by the Mexican government for human consumption. Henceforth, the prerequisite for maintaining and improving the health of a river system depends on continuous long-term monitoring of the dynamic ecosystem for sustainable management.


Spinal Subdural Hematoma: Rare Complication of Spinal Decompression Surgery.
Spinal subdural hematoma (SSH) is a rare and infrequently reported complication of hemilaminectomy, laminectomy, and other spinal decompression surgeries. In this review, we aim to analyze the available literature for reported cases of SSH to better identify risk factors and presenting symptoms, as well as highlight the importance in prompt investigation and management of SSH to prevent long-term morbidity and chronic neurologic deficit. A review of the medical literature was undertaken using search terms hemilaminectomy OR laminectomy AND spinal subdural haematoma. All identified reports were screened for language, adult population, and human studies. Report abstracts were screened for relevance to question, with SSH occurring postoperatively following hemilaminectomy or laminectomy included. Four reports were included in the review. SSH is a rare, emergency condition with neurologic deficit that can present as recurrent back pain and acute cauda equina postoperatively following hemilaminectomy and laminectomy procedures. Vigilance, early investigation, and surgical evacuation is important in preventing short- and long-term morbidity. Further collation of data and analysis is required to better identify patients at high risk for developing SSH postoperatively.


Cardenolide glycosides from seeds of Corchorus olitorius.
Three new cardenolide glycosides were isolated from the seeds of Corchorus olitorius L. On the basis of chemical and spectroscopic evidence, their structures were established as cannogenol 3-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-boivinopyranoside, periplogenin 3-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-digitoxopyranoside and digitoxigenin 3-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl-(1-->4)-O-beta - D-digitoxopyranoside.


Effects of aminoglycoside antibiotics on renal antioxidants, malondialdehyde levels, and some serum biochemical parameters.
Effects of amikacin, gentamicin, kanamycin, and streptomycin on renal tissue superoxide dismutase, glutathione peroxidase, glutathione and malondialdehyde, serum creatinine, potassium, sodium, total protein, glucose, uric acid, and total bilirubin levels were investigated. All aminoglycoside antibiotics decreased renal tissue glutathione levels.


The influence of density and material on oral perception of ball size with and without palatal coverage.
The size of a bolus determines how it will be manipulated in the mouth and swallowed. Ten healthy individuals assessed the size of ball bearings of five sizes (4-11 mm diameter) and four materials with different densities in order to investigate the effect of weight on oral size perception. To study the role of the tongue and palate, the experiment was performed with and without a custom-made plastic palate. The results revealed that size itself determines size perception, and that material and weight are negligible factors. An illusional effect in the direction of under-estimation was found for the ball bearings, especially for the small sizes up to 8 mm diameter. While wearing a plastic palate a significant improvement (P<0.05) occurred; the participants performed better and there was less under-estimation. An explanation for this could be that only a minor part of the total area of the ball bearing touches the palate and is hence detected, while the tongue alone is more compliant and thereby able to sense the ball's whole size.


Effects of clamping procedures on central venous pressure during liver resection.
Various clamping procedures are used to decrease bleeding during liver resections but their effect on central venous pressure (CVP) remains unclear. The aim of this study was to assess the variations of the CVP during two different clamping procedures. We retrospectively reviewed 29 patients (19 males, 10 females) who had Pringle maneuver (PM) and clamping of the inferior vena cava below the liver (IVCC) during major liver resections. Mean decrease of the CVP after PM, IVCC, and PM+IVCC was 0.84 ± 1.37, 2.17 ± 2.13 and 3.17 ± 2.56 cmH20, respectively (P=0.02, P<0.0001 and P<0.0001, respectively). IVCC was more effective in inducing a decrease of the CVP than PM alone (P<0.05). The combination of both PM and IVCC induced the greatest decrease but not to a level of significance compared to IVCC alone (P=0.25). IVCC remains the more efficient procedure to lower the CVP. However, although PM is commonly used to control vascular inflow within the liver its significant influence on the CVP could participate to the reduction of bleeding during liver resections.


A simple, rapid fluorimetric assay of amoxycillin in plasma.
A method for estimation of amoxycillin in plasma is described, based on the formation of a fluorescent derivative which is measured in the presence of 2-methoxyethanol. Drugs commonly administered together with amoxycillin do not appear to interfere with the assay. Data on the sensitivity, accuracy and linearity of the assay are presented together with a comparison with the microbiological assay.


Variation in the assessment of adequacy in cervical smears.
To assess the interobserver reproducibility of the diagnosis of 'adequacy' of cervical smears according to the Bethesda System criteria in cervical smears. 358 cervical smears were obtained from three Italian cytopathological centres in 1998-99. All centres provided consecutively collected smears. The cervical smears were independently and blindly assessed by four cytologists. The screening was performed using a 10x objective and an additional evaluation of the percentage of cellularity was performed using a 4x objective. The proportion of smears assessed by the four cytologists as 'adequate' ranged from 60% to 70%, the proportion of 'satisfactory for evaluation but limited by' ranged from 27% to 38%, and the proportion of 'inadequate smears' ranged from 2% to 4%. Full agreement in the assessment of smear adequacy was observed in 311 slides and disagreement was observed only in 47. The category 'inadequate smear' was less reliable than the other two; however, the kappa value observed was acceptable. The present study shows that it is possible to achieve a high reproducibility in the assessment of smear adequacy, at least among expert cytologists who follow the Bethesda System criteria strictly.


Restorative thresholds for primary and permanent molars in children: French dentist decisions.
Worldwide, numerous surveys have investigated practices and knowledge about caries management in adults, but few are available for children. The present cross-sectional survey aimed to assess the restorative thresholds (RTs) in primary and permanent molars in children used by a population of dentists treating children and practicing in France. The study population consisted of French dentists treating children (Fr-DTCs) who were registered in the French Society of Pediatric Dentistry (n = 250). A specific questionnaire was developed. Descriptive and statistical analyses were performed. Response rate was 80.4% (n = 201). Considering that an appropriate RT is at the stage of a moderate lesion (occlusal: International Caries Detection and Assessment System 4; approximal: lesion involving the external third of dentine), more than 50% of respondents showed a tendency for iatrogenic treatment, except for occlusal carious lesions in primary molars. Inappropriate invasive strategies were more often reported for occlusal lesions in permanent than primary molars. Moreover, for both molar types, these inappropriate RTs were more often chosen for approximal than occlusal lesions. The present survey suggested that Fr-DTCs tend to overtreat in terms of caries management in both primary and permanent molars.


Metabolomics and lipidomics to identify biomarkers of effect related to exposure to non-dioxin-like polychlorinated biphenyls in pigs.
Recent epidemiological studies show that current levels of exposure to polychlorinated biphenyls (PCBs) remain of great concern, as there is still a link between such exposures and the development of chronic environmental diseases. In this sense, most studies have focused on the health effects caused by exposure to dioxin-like PCBs (DL-PCBs), although chemical exposure to non-dioxin-like PCB (NDL-PCB) congeners is more significant. In addition, adverse effects of PCBs have been documented in humans after accidental and massive exposure, but little is known about the effect of chronic exposure to low-dose PCB mixtures. In this work, exposure to Aroclor 1260 (i.e. a commercially available mixture of PCBs consisting primarily of NDL-PCB congeners) in pigs is investigated as new evidence in the risk assessment of NDL-PCBs. This animal model has been selected due to the similarities with human metabolism and to support previous toxicological studies carried out with more frequently used animal models. Dietary exposure doses in the order of few ng/kg body weight (b.w.) per day were applied. As expected, exposure to Aroclor 1260 led to the bioaccumulation of NDL-PCBs in perirenal fat of pigs. Metabolomics and lipidomics have been applied to reveal biomarkers of effect related to Aroclor 1260 exposure, and by extension to NDL-PCB exposure, for 21 days. In the metabolomics analysis, 33 metabolites have been identified (level 1 and 2) as significantly altered by the Aroclor 1260 administration, while in the lipidomics analysis, 39 metabolites were putatively annotated (level 3) and associated with NDL-PCB exposure. These biomarkers are mainly related to the alteration of fatty acid metabolism, glycerophospholipid metabolism and tryptophan-kynurenine pathway.


Dopamine modified natural glucomannan as a highly efficient inhibitor for mild steel: Experimental and theoretical methods.
In this work, Glucomannan was modified with dopamine to synthesize a new polysaccharide Schiff base (GAD). After confirmation of GAD by NMR and FT-IR spectroscopic methods, it was introduced as a sustainable corrosion inhibitor with excellent anti-corrosion action for mild steel in 0.5 M hydrochloric acid (HCl) solution. Employing electrochemical test, morphology measurement, and theoretical analysis, the anticorrosion performance of GAD on mild steel in 0.5 M HCl solution is determined. Maximum efficiency of GAD for suppressing the corrosion rate of mild steel at 0.12 g L-1 reaches 99.0 %. After immersion in HCl solution for 24 h, the results from scanning electron microscopy indicate that GAD is firmly attached to the mild steel surface by making a protective layer. According to the X-ray photoelectron spectroscopy (XPS), FeN bonds existed on the steel surface indicate the presence of chemisorption between GAD and Fe to form stable complexes attracted to the active position on the mild steel. The effects of Schiff base groups on the corrosion inhibition efficiencies were also investigated. Moreover, the inhibition mechanism of GAD was further illustrated by the free Gibbs energy, quantum chemical calculation and molecular dynamics simulation.


3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces.
Owing to the unique combination of electrical conductivity and tissue-like mechanical properties, conducting polymer hydrogels have emerged as a promising candidate for bioelectronic interfacing with biological systems. However, despite the recent advances, the development of hydrogels with both excellent electrical and mechanical properties in physiological environments is still challenging. Here we report a bi-continuous conducting polymer hydrogel that simultaneously achieves high electrical conductivity (over 11 S cm-1), stretchability (over 400%) and fracture toughness (over 3,300 J m-2) in physiological environments and is readily applicable to advanced fabrication methods including 3D printing. Enabled by these properties, we further demonstrate multi-material 3D printing of monolithic all-hydrogel bioelectronic interfaces for long-term electrophysiological recording and stimulation of various organs in rat models.


Tolerance strategies for stem-cell-based therapies.
There is much interest in using embryonic stem cells to regenerate tissues and organs. For this approach to succeed, these stem cells or their derivatives must engraft in patients over the long term. Unless a cell transplant is derived from the patient's own cells, however, the cells will be targeted for rejection by the immune system. Although standard methods for suppressing the immune system achieve some success, rejection of the transplant is inevitable. Emerging approaches to address this issue include 're-educating' the immune system to induce tolerance to foreign cells and reducing the immune targeting of the transplant by administering 'self stem cells' instead of foreign cells, but each of these approaches has associated challenges.


Goldfish (Carassius auratus L.) possess natural antibodies with trypanocidal activity towards Trypanosoma carassii in vitro.
Natural infection of cyprinids, such as carp, with the extracellular protozoan parasite Trypanosoma carassii can attain up to 100% prevalence and cause significant host morbidity and mortality, particularly in aquaculture settings. Host recovery from T. carassii infection has been shown to be antibody (Immunoglobulin M; IgM)-mediated, conferring long-term immunity in recovered animals upon challenge. To assess the role of IgM in parasite clearance in the goldfish, IgM was purified by PEG-6000 precipitation from goldfish serum collected at 0 (naïve), 21 (peak parasitaemia) and 42 (recovery phase; immune) days post infection (dpi) and used for in vitro assays. Purified IgM from 0, 21, and 42 dpi serum showed dose- and time-dependent trypanocidal activity in vitro. Incubation of T. carassii with 0 dpi IgM showed the greatest reduction in trypanosome numbers after 24 h, followed by 42 dpi IgM, and finally by 21 dpi IgM. The trypanocidal activity of the PEG-purified IgM was abrogated by pre-absorption with parasites in vitro and was affected by temperature. Furthermore, studies using 0 dpi IgM purified using gel permeation chromatography showed increased trypanocidal activity, with complete elimination of parasites after 12 h when incubated with 200 μg of 0 dpi IgM, or by 24 h when incubated with 80 μg or 100 μg of 0 dpi IgM. Lastly, in vivo passive transfer experiments demonstrated that while immune serum or purified IgM from 42 dpi serum conferred protection against a challenge, neither 0 dpi serum or 0 dpi purified IgM conferred protection against challenge with T. carassii.


Observer variability in the quantitation of Doppler color flow jet areas for mitral and aortic regurgitation.
Early studies using Doppler color flow imaging have suggested that measurement of the regurgitant jet area provides information regarding the severity of valvular insufficiency. This study was performed to assess the observer variability of mitral and aortic regurgitant jet area measurements using the Doppler color technique. Color Doppler recordings from 45 patients were reviewed: 23 patients had aortic regurgitation and 22 had mitral regurgitation. To assess interobserver variability, the largest definable mitral regurgitant jets from three cardiac cycles were independently chosen and measured by planimetry by two observers who were unaware of other patient information. Measurements were repeated by both observers at a separate time to obtain intraobserver data. Videotapes from 23 patients with aortic regurgitation were similarly analyzed. Each observer measured the isovolumic aortic jet (before mitral valve opening) and the maximal aortic regurgitant jet (at any time during diastole) using computer-assisted planimetry. Both intraobserver and interobserver correlations were excellent for mitral regurgitant jet areas (r = 0.97 and r = 0.93, respectively). The intraobserver correlation for isovolumic aortic regurgitant jet was r = 0.73; the interobserver correlation for this measurement was only fair (r = 0.57). For the maximal aortic regurgitant jet area, intraobserver correlation was good (r = 0.86) and interobserver correlation was fair (r = 0.72). These findings suggest that intraobserver and interobserver reproducibility are acceptable for the measurement of mitral regurgitant jet area.(ABSTRACT TRUNCATED AT 250 WORDS)


Demographic and social context of deaths during the 1854 cholera outbreak in Soho, London: a reappraisal of Dr John Snow's investigation.
Deaths from cholera in Soho, London (late July to end of September 1854) exposed the epidemiology of the disease and demonstrated applied geospatial analysis by highlighting the shortest path principle followed by local residents when they obtained drinking water from a contaminated pump. The present investigation explores if households and individuals with different demographic and socio-economic characteristics were more or less likely to obtain their water from the pump and succumb to the disease. It combines information from the 1851 Population Census and topographic databases with the digital deaths and water pump data to reveal the risk of exposure and the mortality rate were greater for certain occupations, age groups and people living at high residential density irrespective of proximity to the contaminated water pump.


Gas chromatographic on-column methylation technique for the simulataneous determination of antiepileptic drugs in blood.
An on-column methylation technique (OCMT) is described for the simultaneous, gas chromatographic determination in blood of ethosuximide (ES), phenobarbital (PB), primidone (PD), phenytoin (DPH), and 5-ethyl-5-phenylhydantoin (EPH). Multiple internal standards are employed in the OCMT, in order to eliminate or to minimize greatly error sources common to the technology of gas chromatography and to compensate for the different chemical dispositions of the antiepileptic drugs in an OCMT. The internal standards used in the OCMT were as follows: alpha,alpha,beta-trimethylsuccinimide (TMS) was used for the determination of ES; 5-ethyl-5-para-tolylbarbituric acid (MPB), for PB; 5-ethyl-5-(para-tolyl) hexahydropyrimidine-4,6-dione (MPD), for PD; and 5-(para-tolyl)-5-phenylhydantoin (MPPH), for EPH and DPH. The use of ether, the buffering of the plasma sample at pH 7.6, and the use of dilute (0.30-0.35 M) trimethyl-phenylammonium hydroxide (TMPAH) contributed to the specificity of the extraction scheme of the OCMT. The precision and accuracy of the OCMT was attributed to the use of appropriate, multiple internal standards. A method is described for the preparation of standard solutions of drugs in blank plasma (biological matrix) and for the use of the standards in calibration and daily intra-laboratory control of the OCMT.


The changing epidemiology of Acinetobacter spp. producing OXA carbapenemases causing bloodstream infections in Brazil: a BrasNet report.
We evaluated the epidemiology of Acinetobacter spp. recovered from patients diagnosed with bloodstream infections in 9 tertiary hospitals located in all Brazilian geographic regions between April and August 2014. Although OXA-23-producing Acinetobacter baumannii clones were disseminated in most hospitals, it was observed for the first time the spread of OXA-72 among clonally related A. baumannii isolated from distinct hospitals. Interestingly, Acinetobacter pittii was the most frequent species found in a Northern region hospital. Contrasting with the multisusceptible profile displayed by A. pittii isolates, the tetracyclines and polymyxins were the only antimicrobials active against all A. baumannii isolates.


IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice.
Macrophages are central to inflammatory response and become polarized towards the M1 or M2 states upon activation by immunostimulants. In this study, we investigated the effects of lipopolysaccharides (LPS) and interleukin (IL)-17A on the activation of macrophages in in vivo mouse skin. We examined whether macrophages are activated in the skin of imiquimod (IMQ)-treated mice, a model for IL-17A-induced psoriasis-like skin inflammation, and flaky-tail (Flg ft ) mice, a model for IL-17A-induced chronic atopic dermatitis-like skin inflammation. LPS and IL-17A independently increased the expression levels of iNOS, CX3CR1, CD206, phospho-STAT1 and phospho-STAT3 proteins in the skin of B6 mice, and the effects of LPS was not altered by IL-17A. The expression levels of these proteins were increased in the skin of IMQ-treated and Flg ft mice. IL-17A neutralization increased the expressions of iNOS and phospho-STAT1 in the IMQ-treated skin, but it decreased the expressions of CD206 and phospho-STAT3 proteins in the skin of Flg ft mice, suggesting that macrophages to change from the M2 to the M1 state in the skin of these mice. These results suggest that IL-17A is involved in the activation of macrophages that are in the process of adopting the heterogeneous profiles of both the M1 and M2 states.


[Hand robotic devices in neurorehabilitation: A systematic review on the feasibility and effectiveness of stroke rehabilitation].
Robot-assisted therapy is a relatively new intervention, increasingly used in the rehabilitation treatment of stroke patients. It allows to increase the number of repetitions in the performance of specific tasks movements. For this review, a search was carried out between August and October 2021 in the PubMed, Web of Science, Scopus, Cochrane, PEDro and OTseeker databases, selecting a total of six randomized controlled trials where robot-assisted hand therapy was used in stroke rehabilitation. Studies agree that robot-assisted hand therapy has benefits in all phases of stroke rehabilitation that translate into motor and functional improvements of the upper limb and improvements in hemispatial neglect.


Recovery of bovine oocytes from small vesicular follicles for in vitro maturation and fertilization.
Five dairy and four beef breed, mature cows were used as oocyte donors to develop a system of multiple recovery of oocytes for in vitro maturation and fertilization. The animals were alternately treated with either 20 mg of follicle stimulating hormone (FSH) in four equal intramuscular injections or saline at 12 h intervals starting between days 9 and 13 of the oestrous cycle, and the procedure was repeated at three-week intervals for up to four collections. Eighteen collections resulted in the recovery of 124 oocytes from 181 follicles (69%). No serious side-effects were observed. Recovery was equally successful in both breeds and was not reduced in repeat attempts upon the same animal. Treatment with FSH only marginally increased the recovery rate (p less than 0.07) and did not affect the number of follicles aspirated (p greater than 0.05), which varied significantly (p less than 0.05) between cows. From 110 oocytes matured and fertilized in vitro, 70 embryos were recovered after culture in the rabbit oviduct or with trophoblastic vesicles in vitro, of which 30 had cleaved and 5 had progressed to an advanced stage of development. Hormone treatment did not affect zygote development (p greater than 0.05). Four non-surgical transfers of embryos obtained in these studies have resulted in two pregnancies determined ultrasonographically and the birth of a heifer calf. This suggests that the procedure for multiple oocyte recovery is safe and that it can be used successfully for obtaining oocytes for in vitro maturation and fertilization.


Feeding behaviour of the terrestrial isopod Porcellionides pruinosus Brandt, 1833 (Crustacea, Isopoda) in response to changes in food quality and contamination.
Soil decomposition is mainly dependent on the nature and characteristics of organic matter within the soil, the environmental conditions and the activity of microorganisms and soil fauna. Isopods play an important role in decomposition through litter fragmentation and stimulating and/or ingesting fungi and bacteria. The aim of this study was to jointly evaluate the effect of different food types and the effect of heavy metal contamination of those foods through isopod feeding performance assays. These studies used the terrestrial isopod Porcellionides pruinosus. After feeding with different leaf types for the study on feeding performance, alder leaves were chosen for the contamination experiments. Feeding parameters like consumption, assimilation, egestion and growth ratios were calculated and compared among treatments and food type. Lower quality food decreased isopods performance. Exotic food types were shown to be less preferred than alder or oak leaves. Contaminated food also resulted in a decrease in performance among the feeding parameters studies, although isopods can tolerate in certain cases high amounts of heavy metals. For this reason it is possible that in future this crustacean can be used as bioindicators of soil contamination or in the evaluation of contaminated sites or remediation processes.


[Nonsecreting or so-called malignant adrenocortical tumors. Contribution of immunohistochemistry].
The authors mention two cases of adreno cortical carcinoma treated by surgery. They insist upon complete hormonal exploration in order to assert the characteristic non functioning of these growths. An immuno histo clinical examination of the operated part could complement these biological explorations. The existence of a hormonal secretion brought to light by this method can simplify future biological supervision and establish a reason to apply systematically a complementary treatment of OP'DDD or Ketoconazole. A literary precis is prepared.


From Challenge to Opportunity: Addressing Oxidative Stress in Animal Husbandry.
Years of study have explored the issues caused by oxidative stress in livestock and poultry production [...].


Phase II trial of concomitant neoadjuvant chemotherapy with oxaliplatin and capecitabine and intensity-modulated radiotherapy (IMRT) in rectal cancer.
The purposes of this study are to evaluate the activity and safety of preoperative intensity-modulated radiotherapy and concurrent capecitabine and oxaliplatin (Xelox), the accuracy of preoperative magnetic resonance (MRI) for predicting pathologic results, and the correlation between carcinoembryonic antigen (CEA) and the existence of a pathologic complete response (pCR). Twenty-seven patients (pt) with T3/T4N0/N+ rectal cancer were included. Capecitabine was administered at 825 t.i.d. mg/m2 the days of the radiotherapy (RT), and oxaliplatin was administered weekly at 50 mg/m2. RT was planned to 50.4 Gy. Surgery was scheduled 6 to 8 weeks after completion of Xelox RT. Before the intervention, a pelvic MRI was performed and a CEA level was determined. After Xelox RT, 7 pt had pCR (26%), 2 pt progression disease, and 18 pt tumor downstaging. Presurgical MRI did not predict the pathological result in 21 pt. Main side effects were diarrhea grade (G) 3 in four pt, hand and foot G1 five Pt and G2 four pt. Paresthesias G1 ten pt, G2 seven pt, and leukopenia six pt G1. Median RT dose was 49.7 Gy (47.5-50.4 Gy). At a mean follow-up of 22.5 months, four pt presented metastatis. Mean pretreatment CEA was 6.8 ng/mL (2.1-17.0). A difference statistically significant when compared pretreatment CEA with presurgical CEA (p < 0.001) was detected. We found a nadir of <5 ng/mL as significantly associated with pCR (p = 0.036). Preoperative chemoradiotherapy with oxaliplatin and capecitabine is safe and well tolerated, and offers an interesting ratio of pCR and of tumor downstaging. Presurgical CEA level should be studied as predictors of pCR.


Temporal response of the fetal pulmonary circulation to pharmacologic vasodilators.
To determine the temporal response of the fetal pulmonary circulation to pharmacologic vasodilators and to assess vasoreactivity following vasodilation, we infused either acetylcholine, histamine, or bradykinin directly into the left pulmonary artery of 21 chronically prepared fetal sheep. Blood flow (Q) to the left lung was measured by electromagnetic flow transducer. Left pulmonary artery infusion of acetylcholine at 1.5 micrograms.min-1 for 2 hr produced an increase in Q from 59 +/- 8 ml.min-1 to a peak of 113 +/- 10 ml.min-1 at 20 min into the infusion (P less than 0.001). After the peak at 20 min, Q steadily declined toward baseline to 66 +/- 7 ml.min-1 at the end of the 2-hr infusion period (P less than 0.01). Q in the 1/2-hr period following infusion was significantly less than the baseline period (47 +/- 6; P less than 0.04) with no change in pulmonary artery pressure. Similar patterns were seen with 2-hr infusions of histamine (150 ng.min-1) and bradykinin (100 ng.min-1). After a 2-hr infusion of one of the agents, a repeat infusion with that agent or a different one resulted in a diminished response. We conclude that fetal pulmonary vasodilation in response to local infusion of acetylcholine, histamine, or bradykinin is not sustained over a 2-hr period, and that following 2-hr exposure to vasodilators, pulmonary vascular resistance is increased and pulmonary vasoreactivity to pharmacologic vasodilators is decreased.


A novel method for removal of human immunodeficiency virus: filtration with porous polymeric membranes.
We propose a new method to rid solutions of a virus by using a novel regenerated multilayered structured cellulose membrane (BMM). When the filtrate of human immunodeficiency virus (HIV) preparation was obtained through BMM it showed no infectivity. Electron microscopic observation revealed that HIV was completely caught by the multilayers of the BMM. Conveniently, BMM was seldomly found to adsorb protein molecules and also to have a high filtration rate. These characteristics may have a use in the removal of other variously sized pathogenic agents from plasma.


The cerebellum in dual-task performance in Parkinson's disease.
Parkinson's disease (PD) patients have difficulty in performing a dual-task. It has been suggested that the cerebellum is important in dual-tasking. We used functional MRI to investigate the role of the cerebellum in performing a dual motor and cognitive task in PD patients. We have examined whether there are any areas additionally activated for dual-task performance, and compared the neural activity and functional connectivity pattern in the cerebellum between PD patients and healthy controls. We found that the right cerebellar vermis and left lobule V of cerebellar anterior lobe were additionally activated for dual-task performance in healthy controls and for motor task in PD patients. We didn't find any cerebellar regions additionally activated while performing dual-task in PD patients. In addition, the right cerebellar vermis had enhanced connectivity with motor and cognitive associated networks in PD patients. PD patients have limited cerebellar resources that are already utilized for single tasks and, for dual tasks, cannot augment as necessary in order to integrate motor and cognitive networks.


Prior approval: the growth of Bayesian methods in psychology.
Within the last few years, Bayesian methods of data analysis in psychology have proliferated. In this paper, we briefly review the history or the Bayesian approach to statistics, and consider the implications that Bayesian methods have for the theory and practice of data analysis in psychology.


Endogenous phosphorylation of rat brain synaptosomal plasma membranes in vitro: some methodological aspects.
The time course of endogenous phosphorylation in vitro of total or separated synaptic plasma membrane proteins (SPM) has been correlated with that of hydrolysis of the phosphate donor (ATP) in the incubation medium. The ATP/SPM ratio in the medium was varied. In a low-ratio medium (7.5 muM ATP; 2.2 microgram SPM/microliter) a complete hydrolysis of ATP occurred almost instantaneously as was measured by the release of free phosphate in and the disappearance of ATP from the medium. As a consequence, only a very short peak of phosphorylation, followed by dephosphorylation was observed. However, when higher ATP/SPM ratios were used (200 muM ATP; 0.4 microgram SPM/microliter and 500 muM ATP; 0.4 microgram SPM/microliter), the incorporation of phosphate into SPM proteins was linear for 20 sec, and the maximum level of phosphate incorporation was increased. Similar results were obtained after separation of 32P-labeled phosphoproteins by slab gel electrophoresis. However, analysis of the autoradiographs obtained from one SPM preparation under different ATP/SPM ratios revealed dependence of phosphorylation of individual protein bands on the conditions used.


Lack of a differential radiation response for proliferative and non-proliferative rat thyroid cells (FRTL-5) in vitro.
FRTL-5 rat thyroid epithelial cells maintain normal thyroid function and morphology in vitro, exhibit an absolute requirement for thyroid stimulating hormone (TSH) for proliferation and display radiation dose response characteristics indistinguishable from those of rat thyroid epithelial cells in vivo (Rad. Res. 105:138-146, 1986). In TSH-free medium cells remain in a non-proliferative, yet viable, state for prolonged periods of time and respond to TSH re-stimulation by a return to exponential growth. Flow cytometric analysis using two-step acridine orange (AO) staining revealed an accumulation of cells in the G1 phase of the cell cycle accompanied by a pronounced reduction in red fluorescence (indicative of RNA content) in FRTL-5 cells cultured in the absence of TSH. The response of proliferative and non-proliferative FRTL-5 cells to single dose, split dose and fractionated radiation was compared to determine whether proliferative status was an important response determinant. The response of FRTL-5 cells was not influenced by proliferative status at the time of irradiation. Additionally, dose response was not altered by variable (12 hr-8 days) non-proliferative intervals before or after irradiation. As revealed by split dose experiments, the rate and extent of sublethal damage repair was likewise similar for proliferative and non-proliferative cells. Multifraction experiments employing three fractions separated by 6 hr intervals indicate that non-proliferative FRTL-5 cells completely repair sublethal damage between fractions. These results indicate that the radiation response of FRTL-5 cells is not influenced by the proliferative status of the cells prior to or post-irradiation.


Successful treatment of hepatitis C, genotype 3, with sofosbuvir/ledipasvir in decompensated cirrhosis complicated by mixed cryoglobulinaemia.
Advances in the treatment of chronic hepatitis C (HCV) have given HCV providers access to treatment regimens able to achieve sustained virological response (SVR or 'cure') in the majority of patients. There are, however, groups of patients in whom HCV treatment outcomes with direct acting antivirals (DAAs) are suboptimal (genotype (GT) 3 patients, decompensated cirrhosis, renal failure) or have not been studied in large cohorts (patients with cryoglobulinaemia (CG)). This case outlines the successful eradication of GT-3 hepatitis C (HCV) in a patient with decompensated cirrhosis and renal failure secondary to mixed CG with DAA failure, using a 12-week course of sofosbuvir, ledipasvir and ribavirin. The achievement of SVR in this patient resulted in significant improvement in hepatic and renal function. Patients with decompensated cirrhosis and GT-3 disease remain a difficult to treat population, and the safety and efficacy of sofosbuvir, ledipasvir and ribavirin in this cohort require further study.


4-Hydroxy-1,2,3-triazole moiety as bioisostere of the carboxylic acid function: a novel scaffold to probe the orthosteric γ-aminobutyric acid receptor binding site.
The correct application of bio(iso)steric replacement, a potent tool for the design of optimized compounds, requires the continuous development of new isosters able to respond to specific target requirements. Among carboxylic acid isosters, as the hydroxylated pentatomic heterocyclic systems, the hydroxy-1,2,3-triazole represents one of the most versatile but less investigated. With the purpose to enlarge its bioisosteric application, we report the results of a study devoted to obtain potential biomimetics of the γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system (CNS). A series of N1- and N2- functionalized 4-hydroxy-1,2,3-triazole analogues of the previous reported GABAAR ligands, including muscimol, 4-PIOL, and 4-PHP has been synthesized and characterized pharmacologically. Furthermore, this study led to development of straightforward chemical strategies directed to decorate the hydroxytriazole core scaffold, opening for further elaborative studies based on this system. The unsubstituted N1- and N2-piperidin-4-yl-4-hydroxy-1,2,3-triazole analogues (3a, 4a) of 4-PIOL and 4-PHP showed weak affinity (high to medium micromolar range), whereas substituting the 5-position of the triazole core with a 2-naphthylmethyl or 3,3-diphenylpropyl led to binding affinities in the low micromolar range. Based on electrostatic analysis and docking studies using a α1β2γ2 GABAAR homology model we were able to rationalize the observed divergence in SAR for the series of N1- and N2- piperidin-4-yl-4-hydroxy-1,2,3-triazole analogues, offering more detailed insight into the orthosteric GABAAR binding site.


Nucleoporin domain topology is linked to the transport status of the nuclear pore complex.
Nuclear pore complexes (NPCs) facilitate macromolecular exchange between the nucleus and cytoplasm of eukaryotic cells. The vertebrate NPC is composed of approximately 30 different proteins (nucleoporins), of which around one third contain phenylalanine-glycine (FG)-repeat domains that are thought to mediate the main interaction between the NPC and soluble transport receptors. We have recently shown that the FG-repeat domain of Nup153 is flexible within the NPC, although this nucleoporin is anchored to the nuclear side of the NPC. By using domain-specific antibodies, we have now mapped the domain topology of Nup214 in Xenopus oocytes and in human somatic cells by immuno-EM. We have found that whereas Nup214 is anchored to the cytoplasmic side of the NPC via its N-terminal and central domain, its FG-repeat domain appears flexible, residing on both sides of the NPC. Moreover, the spatial distribution of the FG-repeat domains of both Nup153 and Nup214 shifts in a transport-dependent manner, suggesting that the location of FG-repeat domains within the NPC correlates with cargo/receptor interactions and that they concomitantly move with cargo through the central pore of the NPC.


Anti-inflammatory and pro-apoptotic activities of chlorinated flavonoids in human neutrophils.
Flavonoids have been suggested as potential therapeutic agents due to their ability avoid tissue damage resulting from inflammatory processes. Flavonoids are known to react with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated products. However, in spite of the possible production of these products at inflammatory sites, little is known about their potential biological activity. In this study, we investigated the effect of chlorinated flavonoids and their parent compounds in neutrophils' oxidative burst and in its lifespan. The obtained results demonstrate that chlorinated flavonoids were more efficient than their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils. Some of the tested flavonoids induce neutrophil apoptosis in a caspase 3-dependent fashion. The present data showed that some of the tested favonoids constitute an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms engaged at the onset and progression of inflammation.


Pattern of distribution of serotonergic fibers to the orbitomedial and insular cortex in the rat.
As is well recognized, serotonergic (5-HT) fibers distribute widely throughout the brain, including the cerebral cortex. Although some early reports described the 5-HT innervation of the prefrontal cortex (PFC) in rats, the focus was on sensorimotor regions and not on the 'limbic' PFC - or on the medial, orbital and insular cortices. In addition, no reports have described the distribution of 5-HT fibers to PFC in rats using antisera to the serotonin transporter (SERT). Using immunostaining for SERT, we examined the pattern of distribution of 5-HT fibers to the medial, orbital and insular cortices in the rat. We show that 5-HT fibers distribute massively throughout all divisions of the PFC, with distinct laminar variations. Specifically, 5-HT fibers were densely concentrated in superficial (layer 1) and deep (layers 5/6) of the PFC but less heavily so in intermediate layers (layers 2/3). This pattern was most pronounced in the orbital cortex, particularly in the ventral and ventrolateral orbital cortices. With the emergence of granular divisions of the insular cortex, the granular cell layer (layer 4) was readily identifiable by a dense band of labeling confined to it, separating layer 4 from less heavily labeled superficial and deep layers. The pattern of 5-HT innervation of medial, orbital and insular cortices significantly differed from that of sensorimotor regions of the PFC. Serotonergic labeling was much denser overall in limbic compared to non-limbic regions of the PFC, as was striking demonstrated by the generally weaker labeling in layers 1-3 of the primary sensory and motor cortices. The massive serotonergic innervation of the medial, orbital and insular divisions of the PFC likely contributes substantially to well established serotonergic effects on affective and cognitive functions, including a key role in many neurological and psychiatric diseases.


Recognition and diagnosis of sleep disorders in Parkinson's disease.
Sleep disturbances are among the most frequent and incapacitating non-motor symptoms of Parkinson's disease (PD), and are increasingly recognized as an important determinant of impaired quality of life. Here we review several recent developments regarding the recognition and diagnosis of sleep disorders in PD. In addition, we provide a practical and easily applicable approach to the diagnostic process as a basis for tailored therapeutic interventions. This includes a stepwise scheme that guides the clinical interview and subsequent ancillary investigations. In this scheme, the various possible sleep disorders are arranged not in order of prevalence, but in a 'differential diagnostic' order. We also provide recommendations for the use of sleep registrations such as polysomnography. Furthermore, we point out when a sleep specialist could be consulted to provide additional diagnostic and therapeutic input. This structured approach facilitates early detection of sleep disturbances in PD, so treatment can be initiated promptly.


Spontaneous tumescence after implantation of three-piece hydraulic penile prostheses: a short-term experience.
We evaluated spontaneous tumescence after penile prostheses implantation in a retrospective study. A total of 32 patients with three-piece hydraulic implants (17 Mentor Alpha I, 15 AMS Ultrex Plus) were enrolled. Consultation, personal interviews and questionnaires for both the patients and their partners provided the necessary information. The average follow-up period was 29 months. In total, 50 % of the patients reported spontaneous tumescence without activation of the implant and one further patient (3%) claimed full rigid spontaneous erections. General satisfaction with the prosthetic result was high at 91%. The following complications arose: one case of prosthesis infection, one case of mechanical failure, one case of cylinder dislocation and two cases of paraphimosis. A possible explanation for spontaneous tumescence after penile prosthesis implantation is the elevated preload of the compressed rather than destructed cavernous tissue. The artificial erection evoked by the prosthesis then takes the form of a normal physiological reaction and/or a good objective ridigity, and could account for the high patient satisfaction rate with three-piece hydraulic implants.


Patients with primary hypothyroidism presenting as prolactinomas.
Hyperprolactinemia can occur in patients with primary hypothyroidism. Two women with hypothyroidism who had elevated serum prolactin levels, galactorrhea, amenorrhea, and pituitary computed tomographic scans that demonstrated the presence of "pituitary tumors" were recently evaluated. It was believed that they had prolactinomas, and they were referred for possible surgery. An elevated serum thyroid-stimulating hormone level, however, suggested that they had primary hypothyroidism and probably pituitary enlargement secondary to pituitary hyperplasia. Detailed evaluation of thyroid-stimulating hormone and prolactin secretion was performed. These studies revealed several abnormalities in dopamine-prolactin interactions; however, the primary event responsible for the hyperprolactinemia is unclear. These women were given thyroxine therapy, and subsequent radiologic and endocrine studies documented resolution of their "pseudotumors" and normalization of the serum thyroxine and prolactin levels. Hence, thyroid-stimulating hormone levels should be measured in all patients presenting with a suspected prolactinoma so that any hypothyroidism that is noted is not presumed to be due to secondary hypothyroidism from tumor involvement of the pituitary.


Identifying health information technology related safety event reports from patient safety event report databases.
The objective of this paper was to identify health information technology (HIT) related events from patient safety event (PSE) report free-text descriptions. A difference-based scoring approach was used to prioritize and select model features. A feature-constraint model was developed and evaluated to support the analysis of PSE reports. 5287 PSE reports manually coded as likely or unlikely related to HIT were used to train unigram, bigram, and combined unigram-bigram logistic regression and support vector machine models using five-fold cross validation. A difference-based scoring approach was used to prioritize and select unigram and bigram features by their relative importance to likely and unlikely HIT reports. A held-out set of 2000 manually coded reports were used for testing. Unigram models tended to perform better than bigram and combined models. A 300-unigram logistic regression had comparable classification performance to a 4030-unigram SVM model but with a faster relative run-time. The 300-unigram logistic regression model evaluated with the testing data had an AUC of 0.931 and a F1-score of 0.765. A difference-based scoring, prioritization, and feature selection approach can be used to generate simplified models with high performance. A feature-constraint model may be more easily shared across healthcare organizations seeking to analyze their respective datasets and customized for local variations in PSE reporting practices. The feature-constraint model provides a method to identify HIT-related patient safety hazards using a method that is applicable across healthcare systems with variability in their PSE report structures.


Cyclosporin-associated nephropathy in patients with autoimmune diseases.
Renal biopsy specimens were evaluated from patients with different autoimmune diseases treated with cyclosporin (CyA). Ten biopsies were done before CyA, 10 biopsies after low-dose (less than 7.5 mg/kg/day, initial dose or mean daily dose within the first month, respectively), and 9 after high-dose (greater than 7.5 mg/kg/day) treatment. Definite chronic CyA nephrotoxicity (cyclosporin-associated arteriolopathy and/or interstitial fibrosis striped form with tubular atrophy) was only present in the initial high-dose group. In this group a significant serum creatinine increase was noted and 8 of the 9 patients were hypertensive. No significant correlation was found between the severity of morphologic lesions and the mean daily dose during total treatment, cumulative dose, and duration of therapy. The morphologic changes in the low-dose group did not differ from the control biopsy specimens before CyA treatment. Based on these results, it can be concluded that major nephrotoxicity can be avoided by initial low CyA doses.


HIV and Mother-Child Conflict: Associations with Mother's Mental and Physical Health.
Maternal illness is a stressor that can disrupt family processes and contribute to negative child outcomes, and researchers have considered family variables that mediate or moderate the maternal illness-child outcome relationship. Through reliance on a diverse sample (ethnically and racially, as well as geographically), the current study expands prior literature with a focus on parent-child conflict. Specifically, associations between aspects of HIV positive mothers' illness and mother-child conflict were explored. One goal of the study was to determine if there were direct or indirect associations with aspects of mothers' HIV and mother-child conflict. HIV-positive mothers (N = 136) provided CD4 count and completed measures assessing their perceived level of physical functioning, depressive symptoms, HIV health-related anxiety, and mother-child conflict with their healthy school-age children. Path analysis considered the pattern of relationships across variables. Results showed maternal vitality and depressive symptoms were directly associated with mother-child conflict. CD4 cell count and health-related anxiety operated indirectly through maternal depressive symptoms. Mediation analyses further assessed the influence of maternal CD4 cell count on mother-child conflict behavior; results indicated an indirect effect was mediated by vitality. HIV health-related anxiety and vitality separately showed indirect effects on mother-child conflict, mediated by maternal depressive symptoms. These findings are the first to focus on mother-child conflict among children affected by maternal HIV and highlight the need for screening and intervention to address depressive symptoms among HIV-positive mothers.


Minimally invasive vein harvesting in femoropopliteal bypass surgery: does using an old technique give new perspectives? Short report of five patients.
Femoropopliteal bypass surgery is the most commonly performed type of peripheral bypass in vascular surgery. The great saphenous vein (GSV) is the preferred bypass conduit. Commonly used methods of GVS harvesting are related to morbidity, such as wound infection, skin necrosis, hematoma, and edema. In this feasibility study we present an "old-new" way of harvesting of the GSV by inversion stripping, which is significantly less invasive than conventional GSV harvesting, resulting in less morbidity. All patients recovered uneventfully and all lower limb wounds healed with conventional wound management. No excessive bruising was seen in the VSM trail nor were there any surgical wound infections. The inversion stripping of the GSV is an easy, safe, and minimally invasive harvesting technique for bypass surgery.


Cytogenetic Features and Clinical Outcomes of Patients With Non-secretory Multiple Myeloma in the Era of Novel Agent Induction Therapy.
Non-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study. This study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. These patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease. Future multi-institution studies confirming these above findings on this rare entity are warranted.


Impact of Body Mass Index on Serum Concentrations of Antidepressants and Antipsychotics.
Rates of overweight and obesity are higher in patients suffering from psychiatric disorders than in the general population. Body composition and enzyme functions are affected by overweight, and consequently, the pharmacokinetics of drugs may vary in overweight patients. Thus, overweight and obesity are important factors in psychiatric disorders and their treatment. This analysis aimed to investigate the impact of body mass index (BMI) on serum concentrations of the antidepressant drugs amitriptyline, doxepin, escitalopram, mirtazapine, and venlafaxine, and the antipsychotic drugs clozapine, quetiapine, and risperidone, taking into account the following confounding parameters: age, sex, and smoking habit. Inpatients and outpatients (N = 1657) who took at least one of the target drugs were included in this retrospective analysis. Serum concentrations of the target drugs and their metabolites were determined at the Department of Psychiatry, Psychosomatics, and Psychotherapy of the University Hospital of Würzburg during routine therapeutic drug monitoring (January 2009-December 2010), which was performed in the morning (trough level) at steady state. Dose-corrected serum concentrations (CD) of the active moiety of doxepin and venlafaxine and of O-desmethylvenlafaxine were negatively associated with BMI (partial Pearson correlation, R = -0.267, P = 0.002; R = -0.206, P ≤ 0.001; R = -0.258, P ≤ 0.001), and the CDs were different in normal weight, overweight, and obese patients (analysis of covariance, P = 0.004, P < 0.001, P ≤ 0.001). No association was found between BMI and serum concentrations of amitriptyline, escitalopram, mirtazapine, clozapine, quetiapine, and risperidone. In obese patients, higher doses of doxepin and venlafaxine are necessary to achieve similar serum concentrations as in normal weight patients and to avoid treatment-resistant depression.


Rhythm versus rate control for atrial fibrillation in heart failure with preserved ejection fraction.
There are few prospective studies assessing the benefits of rhythm control of atrial fibrillation (AF) in patients with heart failure and preserved ejection fraction (HFpEF), which accounts for 50% of all heart failure patients. Conduct a meta-analysis to assess the effects of rhythm control (ablation and/or antiarrhythmic medications) vs rate control on all-cause mortality in AF patients with HFpEF. Databases were searched for studies reporting the effect of rhythm control vs rate control on mortality in patients with HFpEF (Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL). The search was not restricted to time or publication status. The primary endpoint was all-cause mortality. The minimum duration of follow-up required for inclusion was 1 year. The literature search identified 1210 candidate studies; 5 studies and 16,825 patients were included. The study population had 57% men with a mean age of 71± 2.5 years. Rhythm control for AF was associated with lower all-cause mortality (odds ratio 0.735, 95% confidence interval 0.665-0.813; P < .001) as compared to rate control. Rhythm control for AF in patients with HFpEF was associated with decreased all-cause mortality.