Zero mortality after 152 consecutive pancreaticoduodenectomies with pancreaticogastrostomy.
Since 1968, there have been three published reports in the United States literature of 41, 118, and 145 consecutive patients undergoing pancreaticoduodenectomy without mortality. In all of these series, the pancreatic remnant was anastomosed to the jejunum. This study was designed to review 152 consecutive patients who underwent pancreaticoduodenectomy in whom the pancreatic remnant was anastomosed to the stomach (pancreaticogastrostomy). A total of 152 patients underwent pancreaticoduodenectomy with pancreaticogastrostomy between July 1992 and May 2002. There were 85 men and 67 women with a mean age of 65.7 years (range 31 to 90 years). Of the patients, 87 were less than 69 years of age and 65 were more than 69 years. A total of 114 patients had a malignant neoplasm and the remaining 38 had either cystic neoplasms or benign disease. When the two groups were compared, the patients who were more than 69 years of age had a significantly high incidence of hypertension, previous cancer, atrial fibrillation, and coronary artery disease. In addition, patients more than 69 years of age had a significantly high incidence of jaundice and placement of preoperative stents. Patients more than 69 years of age had significantly less operative time but there was no between-group difference in estimated blood loss, transfusion, number of units transfused, and postoperative length of stay. There was no postoperative mortality [corrected] in this series. Pancreatic leak and fistulae were the most common complications, followed by intraabdominal abscess, wound infection, and delayed gastric emptying. In this study, 152 consecutive patients underwent pancreaticoduodenectomy with pancreaticogastrostomy without postoperative mortality. Morbidity was mostly because of pancreatic leaks and fistulae, which were successfully treated nonoperatively. With proper selection, careful preoperative preparation, and proper intraoperative conduct of operation, the Whipple procedure can be performed without postoperative mortality.


Acute pulmonary edema due to ischemic heart disease without accompanying myocardial infarction. Natural history and clinical profile.
The natural history of acute cardiogenic pulmonary edema was studied in a group of patients who did not have acute myocardial infarction, cardiomyopathy, or valvular heart disease. Most of these patients had coronary artery disease. Cardiac catheterization in selected patients showed depressed contractility in some with segmental abnormalities. In the group older than 70 years, this carried a 70 percent two-year mortality rate. It is important to approach patients with this syndrome vigorously, both diagnostically and therapeutically. Acute, reversible segmental ischemia may be responsible for this syndrome and may respond to measures designed to prevent recurrent ischemia.


Microsomal cytochrome P450-mediated liver and brain anandamide metabolism.
Anandamide (AN) is an arachidonic acid congener, found in the brain, that binds to the cannabinoid receptor and elicits cannabinoid-like pharmacological activity. Cytochromes P450 (P450s) are known to oxidize arachidonic acid to a wide variety of metabolites, yielding many physiologically potent compounds. To determine if AN could be similarly oxidized by P450s, its metabolism by mouse liver and brain microsomes was examined. Mouse hepatic microsomal incubation of AN with NADPH resulted in the generation of at least 20 metabolites, determined after HPLC separation by increased UV-absorbance at 205 nm. Pretreatment of mice with various P450 inducers resulted in increased hepatic microsomal formation of several AN metabolites, with dexamethasone being the most effective inducer. Phenobarbital pretreatment resulted in a metabolic profile similar to that observed after dexamethasone pretreatment, whereas 3-methylcholanthrene pretreatment selectively increased the formation of several other metabolites. Clofibrate pretreatment had no effect on hepatic AN metabolism. Polyclonal antibodies prepared against mouse hepatic P450 3A inhibited the formation of several AN metabolites by hepatic microsomes from untreated mice as well as the formation of those metabolites found to be increased after dexamethasone pretreatment. AN metabolism by brain microsomes resulted in the formation of two NADPH- and protein-dependent metabolites. Hepatic P450 3A antibody partially inhibited the formation of only one of these metabolites. Thus, P450 3A is a major contributor to AN metabolism in the liver but not in the brain. The physiological consequences of P450-mediated AN metabolism remain to be determined.


Blood oxygen level-dependent MR imaging of the kidneys.
Oxygenation status plays a major role in renal physiology and pathophysiology, and thus has attracted considerable attention in recent years. While much of the early work and a significant amount of present work is based on invasive methods or ex vivo analysis, and is therefore restricted to animal models, blood oxygen level-dependent (BOLD) MR imaging has been shown to extend these findings to human beings. BOLD MR imaging is most useful in monitoring effects of physiologic or pharmacologic maneuvers. Several teams around the world have demonstrated reproducible data and have illustrated several useful applications. Studies supporting the use of renal BOLD MR imaging in characterizing disease with prognostic value have also been reported. This article provides an overview of current state-of-the art of renal BOLD MR imaging.


Abdominal, vaginal and total laparoscopic hysterectomy: perioperative morbidity.
The aim of our retrospective study was to assess and to compare the surgical complications of hysterectomy regarding the choice of procedure [abdominal (AH), vaginal (VH), and total laparoscopic hysterectomy (TLH)]. A total of 6,480 patient charts undergone hysterectomy were retrospectively analyzed. Data including transfusion, bladder, ureteral and bowel injury, cuff dehiscence, pulmoner embolus, febrile morbidity, hematoma, reoperation, pelvic wall problems were gathered. The Chi-square test and Student's t test were used in the statistical analysis. The most common perioperative complication was blood transfusion which occurred in 114 patients (2.6%). VH patients required significantly less blood transfusion than AH (2.1, 2.6%, respectively). AH had significantly more bladder injury than VH (0.7, 0.4%, respectively). AH had significantly more ureteral injury than VH (0.2, 0.1%, respectively). AH had the same bowel injury as VH (0.1%). AH and VH necessitated significantly more reoperation than TLH (0.4, 0.2, 0.0%, respectively). To our study, VH ensures less complication rates than AH. In experienced centers, VH can be a reliable alternative to AH. Controlled prospective studies with large patient volumes are required to compare TLH and VH according to complication rates.


Preparation and Crystal Structure of a Platinum(II) Complex of [CH(2)N(CH(2)COOH)CH(2)CONH(2)](2), the Hydrolysis Product of an Anti-Tumour Bis(3,5-Dioxopiperazin-1-YL)Alkane.
The synthesis and crystal and molecular structures of the platinum(II) complex Pt(HL)Cl where H(2)L is the diacid diamide -[CH(2)N(CH(2)COOH)CH(2)CONH(2)](2), a hydrolytic metabolite of an antitumour active bis(3,5-dioxopiperazin-1-yl)alkane are reported. The complex is square planar and contains HL(-) as a tridentate 2N (amino), O (carboxylate) donor. The metal to ligand bond distances are Pt-Cl 2.287(1) A, Pt-O 2.002 (1) A, Pt-N(trans Cl) 2.014(1) A and Pt-N(trans O) 2.073 A. There is extensive hydrogen bonding, each molecule of Pt(HL)Cl being intermolecularly hydrogen bonded to ten others giving a 3-dimensional network. There is also one intramolecular H-bond.


Bone resorption induced by transplanted bladder tumor (MBT-2) in mice.
The high incidence of metastatic bone resorption in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate basic interaction between cancer cells and bone in order to improve the treatment. A new model of bone resorption has been defined, namely the subcutaneous injection of tumor cell suspensions of invasive transitional cell carcinoma of the bladder (MBT-2) into mice after the periosteum of the calvaria has been disrupted. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. Moreover, we were able to show hypercalcemia accompanied with local bone resorption in this model.


Hyperactive transposase mutants of the Sleeping Beauty transposon.
Transposable elements have enormous potential to overcome one of the major hurdles in nonviral gene delivery, namely the lack of long-term gene expression. The Sleeping Beauty (SB) transposon is a promising vector system for nonviral gene therapy as it has the highest transposition activity of all known DNA transposons within mammalian cells. In an effort to generate a more efficient delivery vehicle, we conducted a systematic evaluation of several novel and previously identified SB transposase mutants. The results indicate that certain combinations of mutants do not enhance transposition, whereas others give a synergistic response. The most active mutant, designated HSB17, shows nearly 17-fold higher transposition activity compared to the original transposase SB10 when tested within the same expression cassette. In addition, synergistic activity is observed when this hyperactive mutant is combined with an improved transposon. Animal studies utilizing the hyperactive transposase show enhanced long-term reporter gene expression. These modifications further expand the utility of this transposon-based gene transfer system.


Peptide Mimetic of BDNF Loop 4 Blocks Behavioral Signs of Morphine Withdrawal Syndrome and Prevents the Increase in ΔFosB Level in the Striatum of Rats.
Activity of compound GSB-106, a low-molecular mimetic of loop 4 of the brain neurotrophic factor (BDNF), was studied in experimental morphine withdrawal syndrome simulated in outbred rats. Single and subchronic (5 intraperitoneal injections) administration of GSB-106 in a dose of 0.1 mg/kg significantly reduced the total index of morphine withdrawal syndrome by 55.2 and 45.6%, respectively. GSB-106 reduced the severity of some behavioral signs (piloerection, gnashing of teeth, wet-dog shaking, and runaway attempts), but had no effect on mechanical allodynia formed in the rats with dependence. Subchronic treatment with GSB-106 prevented the increase in the content of ΔFosB (product of early response gene) in the striatum induced by morphine withdrawal. The results confirmed the concept on the involvement of neurotrophins, specifically BDNF and its analogs, in the mechanisms associated with the formation of opiate dependence.


Singular value decomposition learning on double Stiefel manifold.
The aim of this paper is to present a unifying view of four SVD-neural-computation techniques found in the scientific literature and to present some theoretical results on their behavior. The considered SVD neural algorithms are shown to arise as Riemannian-gradient flows on double Stiefel manifold and their geometric and dynamical properties are investigated with the help of differential geometry.


Human corneal endothelial cells from older donors can be cultured and passaged on cell-derived extracellular matrix.
To investigate the effect of culturing human corneal endothelial cells (HCEnCs) from older donors on extracellular matrix (ECM) derived from human corneal endothelial cell line (HCEC-12). HCEC-12 cells were cultured on lab-tek chamber slides for 9 days. Upon confluence, the cells were ruptured using ammonium hydroxide leaving the released ECM on the slide surface which was visualized using scanning electron microscope (SEM). HCEnCs from old aged donor tissues (n = 40) were isolated and cultured on either fibronectin-collagen (FNC) or HCEC-12 ECM at passage (P) 0. At subsequent passages (P1 and P2), cells were sub-cultured on FNC and ECM separately. Live/dead analysis and tight junction using ZO-1 staining were used to record percentage viability and morphological changes. The protein composition of HCEC-12 ECM was then analysed using liquid chromatography-mass spectrometry. SEM images showed long fibrillar-like structures and a fully laid ECM upon confluence. HCEnCs cultured from older donor tissues on this ECM showed significantly better proliferation and morphometric characteristics at subsequent passages. Out of 1307 proteins found from the HCEC-12 derived ECM, 93 proteins were evaluated to be matrix oriented out of which 20 proteins were exclusively found to be corneal endothelial specific. ECM derived from HCEC-12 retains protein and growth factors that stimulate the growth of HCEnCs. As the current clinical trials are from younger donors that are not available routinely for cell culture, HCEnCs from older donors can be cultured on whole ECM and passaged successfully.


Diffusion of fluoroquinolones into equine fetal fluids did not induce fetal lesions after enrofloxacin treatment in early gestation.
While recent work demonstrated that enrofloxacin and ciprofloxacin reach the fetoplacental unit without causing obvious lesions in the 9-month-old equine fetus or resulting foal, many practitioners still hesitate to prescribe a fluoroquinolone during pregnancy. Since early gestation is a critical time for fetal skeletal development, if fluoroquinolones are chondrotoxic to the fetus at any point during gestation, this period would be important. The aim of this study was to assess the effects of 2 weeks' exposure to enrofloxacin on the equine fetus between 46 and 60 days gestation. Twelve pregnancies from nine healthy mares were allocated into two groups: untreated (n=7), or treatment (7.5mg/kg enrofloxacin, PO×14days, n=6). Abortion was induced with prostaglandin 24h after the last enrofloxacin dose, or on the equivalent day of gestation for untreated mares. Four of nine mares were rebred for a second cycle and were assigned to the opposite treatment to serve as their own controls. Fetal fluids from treated mares were analysed for enrofloxacin and ciprofloxacin concentrations. Fetal organs (heart, lungs, spleen, kidney, and liver) and limbs were examined histopathologically. Enrofloxacin and ciprofloxacin diffused to the fetal fluids during early gestation and did not result in detectable abnormalities in the fetus after 14 days of treatment. While current research does not determine long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.


Seafood label quality and mislabelling rates hamper consumer choices for sustainability in Australia.
Seafood mislabelling and species substitution, compounded by a convoluted seafood supply chain with significant traceability challenges, hinder efforts towards more sustainable, responsible, and ethical fishing and business practices. We conducted the largest evaluation of the quality and accuracy of labels for 672 seafood products sold in Australia, assessing six seafood groups (i.e., hoki, prawns, sharks and rays, snapper, squid and cuttlefish, and tuna) from fishmongers, restaurants, and supermarkets, including domestically caught and imported products. DNA barcoding revealed 11.8% of seafood tested did not match their label with sharks and rays, and snappers, having the highest mislabelling rate. Moreover, only 25.5% of products were labelled at a species-level, while most labels used vague common names or umbrella terms such as 'flake' and 'snapper'. These poor-quality labels had higher rates of mislabelling than species-specific labels and concealed the sale of threatened or overfished taxa, as well as products with lower nutritional quality, reduced economic value, or potential health risks. Our results highlight Australia's weak seafood labelling regulations and ambiguous non-mandatory naming conventions, which impede consumer choice for accurately represented, sustainable, and responsibly sourced seafood. We recommend strengthening labelling regulations to mitigate seafood mislabelling and substitution, ultimately improving consumer confidence when purchasing seafood.


Expression of connexin 43 and E-cadherin protein and mRNA in non-small cell lung cancers in Chinese patients.
Connexin 43 (Cx43) and E-cadherin are important biomarkers related with cancer. Their expression at protein and mRNA levels was here investigated in 50 primary lung carcinoma tissues and 20 samples of adjacent normal tissue of Chinese patients with non-small cell lung cancer (NSCLC). Protein and mRNA expression were evaluated by ABC immunohistochemistry and RT-PCR. (1) The positive expression rates of Cx43 and E-cadherin protein were higher in the adjacent normal tissues than those in the primary lung carcinoma tissues; (2) the positive expression rates of Cx43 and E-cadherin protein decreased with NSCLC progression; (3) the expression of E-cadherin protein was not related with the pathological type of NSCLC; and (4) the relative quantity of the Cx43 or E-cadherin mRNA expression was correlated with the the histological type, clinical stage, cancer cell differentiation and the lymph node metastasis. The data suggested that the Cx43 and E-cadherin are reduced with NSCLC progression, and might be important biomarkers for judging the metastasis and prognosis.


Rest tremor suppression may separate essential from parkinsonian rest tremor.
Rest tremor at 4-6 Hz is typical for classical rest tremor (PT) of Parkinson's disease (PD). But rest tremor also appears in other tremor syndromes and may therefore cause a misdiagnosis. In this study we evaluated if suppression of tremor during movement onset is a characteristic feature of Parkinsonian Tremor distinguishing PT from Essential tremor (ET) and if this sign can be reliably diagnosed. Clinically diagnosed patients with PT (n = 44) and ET (n = 22) with rest tremor were included. Video sequences were recorded according to a standardized protocol focusing on the change of tremor amplitude during transition from rest to posture (test 1) or to a target-directed movement (test 2). These videos were assessed for rest tremor suppression by 4 reviewers (2 specialists and 2 residents) blinded to the clinical diagnosis and were compared to the personal assessment of an unblinded movement disorder specialist. Rest tremor suppression was found in 39/44 PD patients and in 2/22 patients with ET during the personal assessment. Rest tremor suppression showed a high sensitivity (0.92-1.00) and an acceptable specificity (0.69-0.95) for PD tremor in both tests. The interrater-reliability of the video-sequences was good to very good (κ 0.73-0.91). Less than 3% of the video sequences were misclassified. We conclude that the assessment of the suppression of rest tremor during movement initiation is a simple and reliable tool to separate PT from rest tremor in ET also suggesting that the mechanisms of rest tremor in these two diseases are different.


[Evaluation of the bone marrow granulocyte reserve in patients with Hodgkin's disease during antiblastic polychemo- and radiation therapy].
The ethiocholanolone test was used to evaluate the granulocyte reserve in 22 patients with Hodgkin's disease before and during polychemical antiblastic and radiation therapy. Under basal conditions, the reserve was normal and its behavior was fairly constantly related to histological type. Stress is laid on the inadequacy of the simple leukocyte count as a guide to the planning of treatment by comparison with the more accurate picture offered by the granulocyte reserve.


Anti-Tumoral Effects of Anti-Progestins in a Patient-Derived Breast Cancer Xenograft Model.
Breast cancer is a hormone-dependent disease in which estrogen signaling targeting drugs fail in about 10 % due to resistance. Strong evidences highlighted the mitogen role of progesterone, its ligands, and the corresponding progesterone receptor (PR) isoforms in mammary carcinoma. Several PR antagonists have been synthesized; however, some of them are non-selective and led to side or toxic effects. Herein, we evaluated the anti-tumor activity of a commercially available PR modulator, ulipristal acetate (UPA), and a new selective and passive PR antagonist "APR19" in a novel preclinical approach based on patient-derived breast tumor (HBCx-34) xenografted in nude mice. As opposed to P4 that slightly reduces tumor volume, UPA and APR19 treatment for 42 days led to a significant 30 % reduction in tumor weight, accompanied by a significant 40 % retardation in tumor growth upon UPA exposure while a 1.5-fold increase in necrotic areas was observed in APR19-treated tumors. Interestingly, PR expression was upregulated by a 2.5-fold factor in UPA-treated tumors while APR19 significantly reduced expression of both PR and estrogen receptor α, indicating a potential distinct molecular mechanism among PR antagonists. Cell proliferation was clearly reduced in UPA group compared to vehicle conditions, as revealed by the significant reduction in Ki-67, Cyclin D1, and proliferating cell nuclear antigen (PCNA) expression. Likewise, an increase in activated, cleaved poly(ADP-ribose) polymerase (PARP) expression was also demonstrated upon UPA exposure. Collectively, our findings provide direct in vivo evidence for anti-progestin-mediated control of human breast cancer growth, given their anti-proliferative and pro-apoptotic activities, supporting a potential role in breast cancer therapy.


Pharmacoproteomic analysis reveals that metapristone (RU486 metabolite) intervenes E-cadherin and vimentin to realize cancer metastasis chemoprevention.
Metapristone is the most predominant biological active metabolite of mifepristone, and being developed as a novel cancer metastasis chemopreventive agent by us. Despite its prominent metastasis chemopreventive effect, the underlying mechanism remains elusive. Our study, for the first time, demonstrated that metapristone had the ability to prevent breast cancer cells from migration, invasion, and interfere with their adhesion to endothelial cells. To explore the underlying mechanism of metapristone, we employed the iTRAQ technique to assess the effect of metapristone on MDA-MB-231 cells. In total, 5,145 proteins were identified, of which, 311 proteins showed significant differences in metapristone-treated cells compared to the control group (P-value < 0.05). Bioinformatic analysis showed many differentially expressed proteins (DEPs) functionally associated with post-translational modification, chaperones, translation, transcription, replication, signal transduction, etc. Importantly, many of the DEPs, such as E-cadherin, vimentin, TGF-β receptor I/II, smad2/3, β-catenin, caveolin, and dystroglycan were associated with TGF-β and Wnt signaling pathways, which were also linked to epithelial-to-mesenchymal transition (EMT) process. Further validation of the epithelial marker "E-caderin" and mesenchymal marker "vimetin" were carried out using immunoblot and immunofluorescence. These results have revealed a novel mechanism that metapristone-mediated metastasis chemoprevention is through intervening the EMT-related signaling pathways.


[Experimental immune arteriosclerosis in the rabbit. Immunogenic and pathogenic properties of glycoproteins and elastins in arterial tissue].
Rabbits immunized with kappa elastin produced arteriosclerosis and antibodies that bound to target-structures (elastic fiber sheaths, endothelial and smooth muscle cells). These antibodies were cytotoxic for cultured rabbit or rat arterial smooth muscle cells. Absorption of the antielastin antiserum with pig aorta or human serum glycoproteins inhibited its binding to target-structures and suppressed its in vitro cytotoxicity. These data are discussed.


Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19.
The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermore, the limited supply of vaccines and promising antiviral drugs have created havoc in the present scenario. Plant-based phytochemicals (bioactive molecules) are promising because of their low side effects and high therapeutic value. In this study, we aimed to screen for suitable phytochemicals with higher therapeutic value using the two most crucial proteins of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). We used computational tools such as molecular docking and steered molecular dynamics simulations to gain insights into the different types of interactions and estimated the relative binding forces between the phytochemicals and their respective targets. To the best of our knowledge, this is the first report that not only involves a search for a therapeutic bioactive molecule but also sheds light on the mechanisms underlying target inhibition in terms of calculations of force and work needed to extractthe ligand from the pocket of its target. The complexes showing higher binding forces were subjected to 200 ns molecular dynamic simulations to check the stability of the ligand inside the binding pocket. Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro. Collectively, our findings could potentially aid in the development of novel therapeutics against COVID-19.


Patient pathway in a tertiary referral pelvic floor unit: Telephone triage assessment clinic.
To meet the increasing demands for colorectal pelvic floor services, a dedicated telephone triage assessment clinic (TTAC) was set up to establish a more efficient pathway, and reduce waiting times and patient's visits to the hospital. The primary aim of this study was to review TTAC in patients suffering from pelvic floor dysfunction and assess its feasibility. Secondary aims include measurement of waiting times for TTAC, main presenting complaints, and main treatment outcomes, including the need for review by a consultant surgeon. Review of data collected retrospectively in a single tertiary referral center collected from an institutional database. Between January 2016 and October 2017, 1192 patients referred to our pelvic floor unit were suitable for TTAC. Of these, 694 patients had complete records. There were 66 without follow-up after the initial TTAC, leaving 628 patients for analysis. In all, 86% were females and 14% were males, with a mean age of 52 years (range: 18-89). The median waiting time for TTAC was 31 days (range: 0-184). The main presenting complaint during the TTAC was obstructive defecation in 69.4%, fecal incontinence in 28.5%, and rectal prolapse in 2.1%. In our study, 611 patients had conservative management (97.3%), with a median of three sessions per patient (range: 1-16), while 82 patients (13.1%) needed a surgical intervention. Only 223 patients (35.5%) were reviewed by a consultant at some stage during the study period. To optimize resources, an adequate triage system allowed us to streamline the pathway for each individual patient with pelvic floor dysfunction according to their symptoms and/or test results with the aim of reducing waiting times and expediting treatment.


Comparison of pharmacological and antimicrobial properties of cefadroxil and cephalexin.
Pharmacological and antimicrobial properties of cefadroxil, a new cephalosporin antibiotic, were compared with cephalexin. Absorption and excretion were studied in 20 healthy men. Peak concentrations of the drugs in serum were similar after ingestion of single 500-mg tablets. The concentration of cefadroxil in serum was more sustained than that of cephalexin. Levels of cefadroxil in serum after a dose of 1,000 mg were approximately twice those after a 500-mg dose through 6 h. Each drug administered in a dose of 500 mg every 6 h for 24 h resulted in concentrations in serum that were similar to a single dose without accumulation. Ninety-three percent of the cefadroxil and 85% of the cephalexin were excreted in urine after ingestions of single 500-mg tablets. The urine concentration of cefadroxil was more sustained than cephalexin. Minimal inhibitory and minimal bactericidal concentrations for clinical isolates were comparable with each drug. Cefadroxil compares favorably with cephalexin in this study. Sustained levels of cefadroxil in serum and urine suggest that this drug may be given at less frequent intervals than cephalexin.


Pharmacokinetics of lithium: elimination half-time, renal clearance and apparent volume of distribution in schizophrenia.
The elimination half-time and renal clearance of lithium was measured in 12 schizophrenic patients. Minimum plasma lithium concentrations during alternate dosage intervals in 5 patients increased rapidly during the first 2 to 3 days of treatment and reached a steady state level after 5 to 6 days. After the establishment of the remaining 7 patients on lithium the decline in plasma lithium concentration when treatment was stopped was monoexponential. Elimination half-times ranged from 19.3 to 41.3 hours (mean +/- SD = 28.9 +/- 7.9h) and were significantly correlated with renal creatinine clearance (p less than 0.01). Renal lithium clearances ranged from 13.5 to 36.8 ml/min (mean +/- SD = 24.4 +/- 8.0 ml/min) and the apparent volumes of distribution ranged from 0.39 to 1.39 L/kg (mean +/- SD = 0.79 +/- 0.34 L/kg). There was no evidence that the elimination parameters of lithium in schizophrenic patients were significantly different from those in healthy individuals or manic-depressive patients.


Development of an electrophysiology (EP)-enabled intracardiac ultrasound catheter integrated with NavX 3-dimensional electrofield mapping for guiding cardiac EP interventions: experimental studies.
We have developed an integrated high-resolution intracardiac echocardiography (ICE) catheter for electrophysiology (EP) testing, which can be coregistered in 3-dimensional space with EP testing and ablation catheters using electrofield sensing. Twelve open-chest pigs (34-55 kg) and 3 closed-chest pigs were studied. After introduction from the jugular or femoral venous locations, the 9F side-looking, highly steerable (0 degrees -180 degrees), 64-element array catheters could be manipulated easily throughout the right side of the heart. Multisite cardiac pacing was performed for assessing left ventricular (LV) synchrony using tissue Doppler methods. Also, in the open-chest pigs, right atrial (RA) and right ventricular (RV) ablations were performed with a separate radio frequency catheter under fluoroscopic guidance and visualized with ICE to characterize the changes. In the 3 closed-chest pigs, electrofield NavX 3-dimensional coregistration (St Jude Medical Corp, Minneapolis, MN) allowed us to test whether this additional feature could shorten the time necessary to perform 4 targeted ablations in each animal while imaging the ablation catheter and the adjacent region by ICE. Intracardiac anatomy, tricuspid, aortic, pulmonary, and mitral valve function, and pulmonary vein flow were all imaged reproducibly from scanning locations in the RA or RV in all animals, along with assessment of cardiac motion and the effects of multisite pacing. Three-dimensional electrofield displays detailed the spatial relationship between the ICE catheter and ablation catheters such that the time to visualize and ablate 4 sites in each of the 3 closed-chest animals was reduced. This new technology is a first step in the integration of ICE with EP procedures.


The Mental Health Education Gap among Primary Care Providers in Rural Nepal.
In low- and middle-income countries, the majority of individuals with mental illness go untreated largely because of a severe shortage of mental health professionals. Global initiatives to close the mental health treatment gap focus on primary care providers delivering this care. For this to be effective, primary care providers require the skills to assess, diagnose, and treat patients with mental illness. To assess primary care providers' training and experience in caring for mental health patients, the authors conducted five focus groups at three isolated district hospitals in rural Nepal where there was no access to mental health professionals. Primary care providers reported limited training, lack of knowledge and skills, and discomfort in delivering mental health care. To address the mental health education gap, primary care providers in Nepal, and perhaps other low- and middle-income countries, require more training during both undergraduate and graduate medical education.


Retailer's Dual Role in Digital Marketplaces: Reference Architectures for Retail Information Systems.
Digital marketplaces have entered the retail sector and have proven to be a successful business model compared to traditional retailing. Established retailers are increasingly launching digital marketplaces as well as participating in marketplaces of pure online companies. Retailers transforming to digital marketplaces orchestrate formerly independent markets and enable retail transactions between participants while simultaneously selling articles from their own assortment to customers in the digital marketplace (dual role). A retailer's dual role must be supported by retail information systems. However, this support is not explicitly represented in existing reference architectures for retail information systems. Thus, we propose to develop a reference architecture for retail information systems that facilitates the orchestration of supply- and demand-side participants, selling their own articles, and providing innovation platform services. We apply a design science research approach and present nine architectural requirements that a reference architecture for a multi-sided market business model in retail needs to fulfill (dual role, additional participants, affiliation, matchmaking, variety of services, innovation services, smart services, aggregated assortment, and boundary resources) from the rigor cycle. From the first design iteration, we propose four exemplary, conceptual architectural patterns as a solution for the requirements (matchmaking for participants, innovation platform services, boundary resources, and aggregated assortment). These patterns can form a conceptual reference architecture that guides the design and implementation of information systems.


Screening of multi-faceted phosphate-solubilising bacterium from seagrass meadow and their plant growth promotion under saline stress condition.
Soil salinity is one of the major limiting factors of the crop production, it has been constantly increasing in agricultural land due to the impact of climate change and urbanisation. High salinity in the agrolands can lead ionic, oxidative, osmotic and water stress to crops. A potential phosphate solubilising bacterium, Curtobacterium luteum was isolated from marine environment (seagrass meadow) and was evaluated for the enhancement of plant growth promotion of three different agro plants (rice, tomato and chilli) using agro saline soil. The strain C. luteum exhibited efficient phosphate solubilisation in both qualitative (SI-2.88) and quantitative (208.41 µg/ml) analysis at optimised conditions. In addition to phosphate solubilisation, it showed numerous valuable traits to promote plant growth such as - production of organic acids (Tartaric and malic acids), phosphatase, phytase (SI-2.9), IAA (4.1 µg/ml), urease and nitrogen fixation. The bacterium potentially enhances the plant growth under saline stress conditions and exhibited prominent plant growth promotion in all the three plants (rice, tomato and chilli) compared to the control. Also, it enhances the concentration of phosphorous in the soil and balances the soil pH. The present results indicate that the C. luteum can serve as a multifaceted biofertilizer under saline stress condition and be an effective alternative to the toxic chemical phosphate fertilizers that cater to the single purpose of providing phosphorous to plants.


The incidence of dural tears after complete resection of lumbar synovial cysts and the relation to the outcome.
Synovial cysts in the lumbar spine are uncommon causes of radicular pain. In cases where conservative treatment fails, surgical resection is recommended. Dural adhesions are common intraoperative findings; therefore, the removal of the cyst may sometimes result in dural tears. The frequency of dural tears is greater with synovial cysts than in other lumbar surgeries. Clinical parameters and characteristics seen on magnetic resonance imaging were assessed to investigate the correlation between the outcome after surgery of lumbar synovial cysts and dural tears. This study was designed as a retrospective practice audit. Patient data were drawn from an electronic medical record system. Included were consecutive patients after microsurgical resection of symptomatic lumbar synovial cysts between May 2013 and November 2015. The surgical report was evaluated retrospectively regarding the extent of decompression and cyst resection as well as surgery-related complications. Pre-operative magnet resonance imaging was assessed concerning the reason for compression of the neural structures, the dimension of the cyst, and the signal of the cyst content in T2 images. In a follow-up examination about four weeks after surgery, the patient satisfaction index was evaluated. Forty-four consecutive patients after resection of a lumbar synovial cyst met the inclusion criteria. The mean patient satisfaction index was 2.0±1.0. Twenty-nine patients of the 38 patients with follow-up (76.3%) with a satisfaction index of 1 or 2 were rated as favorable. One revision surgery was necessary because of a cerebrospinal fluid fistula. Furthermore, in 4 patients an incidental durotomy occurred without any symptoms after surgery. Accordingly, the rate of dural tears was 11.4%. Dural tears were significantly more common in patients with a satisfaction index of 3 or 4 (P=0.04). Sixty percent of the patients with dural tears were operated on in level L5/S1 compared to 3 patients without a dural tear (P=0.008). There was no statistically significant difference between the different patient subgroups in any other analyzed parameter. Dural tears were found significantly more often in patients without a good outcome; they appear to portend a poorer prognosis. The level L5/S1 was significantly more often affected. During surgery, it should be considered whether to remove the cyst completely and risk a dural tear, or to leave residuals of the cyst wall if otherwise a good decompression is achieved.


Characterization of the toxicity and cytopathic specificity of a cloned Bacillus thuringiensis crystal protein using insect cell culture.
An insecticidal protein gene from Bacillus thuringiensis var. aizawai was cloned in Escherichia coli. The cloned gene expressed at a high level and the synthesized protein appeared as an insoluble, phase-bright inclusion in the cytoplasm. These inclusions were isolated by density gradient centrifugation, the isolated protein was activated in vitro by different proteolytic regimes and the toxicity of the resulting preparations was studied using insect cells grown in tissue culture. The inclusions consisted of a 130 kDa polypeptide which was processed to a protease-resistant 55 kDa protein by tryptic digestion. This preparation lysed lepidopteran (Choristoneura fumiferana) CF1 cells but not dipteran (Aedes albopictus) cells. When the crystal protein was activated by sequential treatment, first with trypsin and then with Aedes aegypti gut proteases, the resulting 53 kDa polypeptide was now toxic only to the dipteran cells and not to the lepidopteran cells. Thus the dual specificity of this var. aizawai toxin results from differential proteolytic processing of a single protoxin. The trypsin-activated preparation was weakly active against Spodoptera frugiperda cells. Membrane binding studies of the trypsin-activated toxin revealed a 68 kDa protein in the lepidopteran cell membranes, which may be the receptor for this toxin.


Dermatophytosis survey in Lagos State of Nigeria.
A dermaphytosis survey covering 3,860 schoolchildren was conducted in Lagos, Nigeria, between January 1973 and January 1974. Seven species of dermatophytes, namely, Trichophyton mentagrophytes (four isolates), T. rubrum (three isolates), T. soundanense (11 isolates), Microsporum canis (five isolates), M. gypseum (two isolates), M audouinii (four isolates), and Epidermophyton floccosum (three isolates) were recovered from specimens collected from the hair, skin and scalp scrapings of 81 schoolchildren. The incidence of dermatophytosis (2.10%) is low in schoolchildren covered in this survey. This is the first time M. canis and M. Gypseum have been isolated from superficial skin lesions in human beings in Nigeria.


Separation of the yellow chromophores in individual brunescent cataracts.
Quantitative changes in the 330 nm absorbing chromophores and 350/450 nm fluorophores of water-soluble (WS) and water-insoluble (WI) proteins of individual human cataract lenses were characterized and compared with aged normal human lens. Twenty-five brunescent cataract lenses from India were selected from five different stages (types I-V) based upon the color of the lens. The WS and WI proteins from each lens were collected and subjected to an extensive enzymatic digestion procedure under argon. The lens protein digests were separated by Bio-Gel P-2 size-exclusion chromatography and individual peaks were analyzed further by reversed-phase HPLC. The total WI proteins increased and the total WS protein decreased with the development of cataract, especially in the late stages of cataract (III-V). The total 330 nm absorbance and 350/450 nm fluorescence of the WI fraction also increased, however, the A(330) and fluorescence per mg lens protein were constant except for type V (black) lenses. Bio-Gel P-2 chromatography separated the chromophores and fluorophores into four fractions. The main fraction (designated as peak 2+3) from the cataract WI proteins was several times higher than that present in aged normal human lens WI proteins. A significant increase of this fraction was observed in WI proteins, but not in WS proteins with cataract development. Similarly, fractions 1 and 4 in the WI proteins also increased gradually but fraction 5 did not. Reversed-phase HPLC resolved fraction (2+3) of the water-insoluble sonicate supernatant proteins into four 330 nm absorbing peaks and eight fluorescent peaks. Among these peaks, a late-eluting peak (peak 8) increased 10 to 15-fold with the progress of cataract, and accounted for 80% of the total chromophores in type V lenses. This peak may represent limit digests of advanced glycation end-products (AGEs) derived protein cross-links. HPLC profiles of fraction 5 from both WS and WI proteins showed numerous new peaks which were not observed in either WS protein from cataract or WI proteins from aged normal human. The severe coloration and the higher levels of numerous novel chromophores and fluorophores in brunescent cataractous lenses reveal the possibility that a different chemistry occurs during cataract development.


Impact of the drilling fluid system on the effectiveness of a high pressure jetting assisted rotary drilling system.
An enhanced drill bit combining high pressure fluid jetting with a conventional rotary drilling system incorporating a tailored drilling fluid was designed to improve drilling performance in hard crystalline rock. Full scale drilling experiments (8 ½ inch bit size) were performed utilizing a specially designed sepiolite fluid and comparing its performance with water and xanthan gum as a standard geothermal drilling fluid. The novel drilling system improved the rate of penetration by over 70% compared to the conventional drill bit without jetting assistance. In addition, the sepiolite drilling fluid retained its fluid properties even after high pressure jetting.


Direct comparison of binding equilibrium, thermodynamic, and rate constants determined by surface- and solution-based biophysical methods.
The binding interactions of small molecules with carbonic anhydrase II were used as model systems to compare the reaction constants determined from surface- and solution-based biophysical methods. Interaction data were collected for two arylsulfonamide compounds, 4-carboxybenzenesulfonamide (CBS) and 5-dimethyl-amino-1-naphthalene-sulfonamide (DNSA), binding to the enzyme using surface plasmon resonance, isothermal titration calorimetry, and stopped-flow fluorescence. We demonstrate that when the surface plasmon resonance biosensor experiments are performed with care, the equilibrium, thermodynamic, and kinetic constants determined from this surface-based technique match those acquired in solution. These results validate the use of biosensor technology to collect reliable data on small molecules binding to immobilized macromolecular targets. Binding kinetics were shown to provide more detailed information about complex formation than equilibrium constants alone. For example, although carbonic anhydrase II bound DNSA with twofold higher affinity than CBS, kinetic analysis revealed that CBS had a fourfold slower dissociation rate. Analysis of the binding and transition state thermodynamics also revealed significant differences in the enthalpy and entropy of complex formation. The lack of labeling requirements, high information content, and high throughput of surface plasmon resonance biosensors will make this technology an important tool for characterizing the interactions of small molecules with enzymes and receptors.


Orbital solitary fibrous tumor: A painless mass after a dacryochystorhinostomy.
The solitary fibrous tumor (STF) is a rare spindle cell tumor that most often occurs in the pleura, mediastinum and other serosal sites, but it can be found anywhere. The authors present a case report of a 35-year-old male who was submitted to an eventless left external dacryocystorhinostomy (DCR) due to epiphora. During the surgery no tumors or anomalous tissues were visualized. Five months later the patient presented a painless mass at the lower medial quadrant of the left orbit, near the lacrimal fossa. A computed tomography, a magnetic resonance imaging and an orbital ultrasound were performed. A round, very vascularized and highly contrast enhanced mass was found. An anterior orbitotomy was done. Histological aspects and immunohistochemical markers were consistent with STF. The tumor was not visualized during the DCR. The authors think that the growth of the tumor and the weakening of the tissues in the medial canthus after the DCR allowed the tumor to move anteriorly within the orbit.


Identification and characterization of a super-stable Cu-Zn SOD from leaves of turmeric (Curcuma longa L.).
We report a novel super stable superoxide dismutase (SOD) extracted from the leaves of Curcuma longa L.-a post-harvest waste. The scavenging activity of this SOD remains intact both in crude and purified forms before and after heating at boiling temperatures (80-100 degrees C) up to 20 min, autoclaving (6-20 bars up to 10 min) and microwaving (frequency of 2,450 megahertz (MHz) or million cycles per second for 1-3 min). This SOD has significant shelf life at room temperature (25-35 degrees C) and is stable for at least 18 months at 4 degrees C and with the retained activity of 82% at -10 degrees C and 88% at -20 degrees C without any infection or contamination. The heat stable enzyme is present both in cytoplasm and chloroplasts. The enzyme is also stable under wide range of pH, alcohol and SDS concentrations. The heat stability of this SOD protein is not due to any associated phenolic compound as no phenolic compound was bound to the novel thermo-stable SOD. The activity staining through native PAGE and purification of the enzyme protein have shown that this form of enzyme has a native molecular weight of 30.8 kDa and has two subunits of 15 kDa as shown by SDS PAGE. The characterized novel isoform is a Cu-Zn SOD as is indicated by its sensitivity to both H2O2 and KCN. Indian, US and PCT patents have been filed and products are being developed using this hyperthermophilic enzyme.


Personality traits and social loafing among employees working in teams at small and medium enterprises: A cultural perspective data from emerging economies.
The main objective of this research is to examine the association between personality traits such as conscientiousness and neuroticism and social loafing behavior of employees with moderating impact of individualistic behaviors. A multi correlational survey was used to investigate and analyze this study. The survey sample consisted of 241 supervisors and subordinates who attended a survey at manufacturing firms operating in three South Asian countries e.g., Pakistan, Bangladesh, and India. In the data analysis, a reliability and validity test were conducted and then correlation and regression analyses were used to investigate the results. Statistically substantial differences on some study variables were perceived vis-à-vis cultural traits. Correlation and regression verdicts exhibited that there was a substantial negative association between conscientiousness and social loafing, and a positive association between neuroticism and social loafing. Furthermore, this relationship between variables was strengthened when an individual behavior was included as moderator.


Locus of Control or Self-Esteem; Which One is the Best Predictor of Academic Achievement in Iranian College Students.
Self-esteem and behavioral consequences, which are due to external or internal locus of control, are effective on academic achievement of students. The aim of this study was to determine the prediction of locus of control and self-esteem in academic achievement among the students. This cross-sectional study was conducted on 300 college students in Kermanshah University of Medical Sciences in 2014. Data collection tools were in three sections: demographic, Rotter internal-external locus of control scale and Coopersmith self-esteem inventory. Data were analyzed using the SPSS software version 21. Results showed that 29.8% and 76.2% of the participants had internal locus of control, and high self-esteem, respectively. There was a significant correlation between self-esteem, locus of control and academic achievement of the students. Self-esteem accounted for 39.5% of the variation in academic achievement. It seems that interventions to increase self-esteem among student can help improve academic achievement among them.


Blood pressure measurement in children and adolescents: key element in the evaluation of arterial hypertension.
Arterial hypertension is the main modifiable risk factor for cardiovascular disease, occupying the first place among the causes of loss of life years adjusted for disability. In recent years, arterial hypertension in children and adolescents has gained ground in cardiovascular medicine thanks to progress made in several areas, fundamentally in pathophysiological and clinical research. Despite the advances that have been made in recent years, the prevention, diagnosis and treatment of high blood pressure in children and adolescents still have room for improvement. In this sense, the correct measurement of blood pressure is especially important, since it includes a series of essential elements such as the measurement devices, the regulated procedure and the interpretation of the results based on percentiles according to age, gender and height. The availability of a free access calculator facilitates the diagnosis and monitoring of arterial hypertension https://hyperchildnet.eu/.


Accessing to electronic medical history using a mobility intra hospital system.
The aim of this paper is to describe the solution that has been developed in Valencia Region (Spain) to provide health professionals (physicians and nurses) access to all the functionalities of a Hospital Information System (HIS) already available at fixed clients workstations. These functionalities are adapted to the care process carried out at patient bedside. In this way, professionals will have access to treatment and administration, recording of vital signs, nursing assessment, scales, care plan, extractions, medical records, progress notes so that they have all necessary information at the bedside, and record swiftly changes that occur in-situ. In addition, clinical safety is reinforced, including RFID patient identification mechanisms and barcode readers for blood samples or unidosis medication.


Cytokines secreted by IL-2-activated lymphocytes induce endogenous nitric oxide synthesis and apoptosis in macrophages.
IL-2-activated killer (LAK) cells secrete inflammatory cytokines such as IFN-gamma and TNF-alpha, which can induce NO synthesis (NOS). In this study, we investigated IL-2-activated lymphocyte-mediated macrophage apoptosis via NOS. LAK cells and their culture supernatants induced NOS in murine macrophages. NOS was markedly inhibited by blocking antibodies to IFN-gamma and TNF-alpha, suggesting the key role of these lymphocyte cytokines in mediating NOS. Endogenous NO production inhibited macrophage proliferation and induced apoptosis in concordance with p53 accumulation and caspase-3 activation, processes that were inhibited by N(G)-monomethyl-l-arginine (a NOS inhibitor) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (a NO scavenger). Our study demonstrated a novel, noncontact-dependent mechanism of macrophage suppression by IL-2-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages as a result of endogenous NOS induced by cytokines secreted from IL-2-activated lymphocytes.


High-resolution genomic assays provide insight into the division of labor between TLS and HDR in mammalian replication of damaged DNA.
The multitude of DNA lesions that continuously form in DNA cannot all be detected and removed prior to replication. Thus, encounters of the replication fork with DNA damage become inevitable. Such encounters inhibit fork progression, leading to replication fork arrest or to replication re-priming downstream of the damage site. Either of these events will result in the formation of gap-lesion structures, in which a damaged base is located in a single stranded stretch of DNA, that is vulnerable to subsequent nicking. The double strand break that would ensue if ssDNA becomes nicked constitutes escalation of the damage from nucleotide(s)-specific to chromosomal scale. Cells employ two universal DNA damage tolerance (DDT) strategies to resolve these situations, by converting the gap-lesion structures into dsDNA without repairing the damage. The first is translesion DNA synthesis (TLS), in which a specialized low-fidelity DNA polymerase inserts a nucleotide opposite the damaged one. TLS is inherently mutagenic, due to the miscoding nature of most damaged nucleotides. The second strategy is homology-dependent repair (HDR), which relies on the presence of an identical intact sister chromatid. The molecular mechanisms that regulate the division of labor between these pathways are poorly understood. This review focuses on the balance between TLS and HDR in mammalian cells, discussing recent findings that were made possible thanks to newly developed high resolution genomic assays, and highlighting the role of the DNA lesion's properties in DDT pathway choice.


Preparatory processes in a case of hemi-parkinsonism.
Reaction times and movement times were recorded in a subject with parkinsonian symptoms confined largely to the left side of the body. Advance information concerning the movement was varied, being with complete, partial or no preparation. The results suggest that processing of preparation for the movement is not qualitatively different for the more affected side, but is substantially slowed.


The look-ahead effect of phenotypic mutations.
The evolution of complex molecular traits such as disulphide bridges often requires multiple mutations. The intermediate steps in such evolutionary trajectories are likely to be selectively neutral or deleterious. Therefore, large populations and long times may be required to evolve such traits. We propose that errors in transcription and translation may allow selection for the intermediate mutations, if the final trait provides a large enough selective advantage. We test this hypothesis using a population based model of protein evolution. If an individual acquires one of two mutations needed for a novel trait, the second mutation can be introduced into the phenotype due to transcription and translation errors. If the novel trait is advantageous enough, the allele with only one mutation will spread through the population, even though the gene sequence does not yet code for the complettrait. Thus, errors allow protein sequences to "look-ahead" for a more direct path to a complex trait.


The effects of wall thickness, axial strain and end proximity on the pressure-area relation of collapsible tubes.
Segments of silicone rubber tube were suspended between rigid pipes and subjected to slowly varying transmural pressure covering a range from slight distension to collapse with osculation. The local inside cross-sectional area at a chosen axial site was simultaneously measured via catheter by an electrical impedance method. Pressure-area relations were recorded thus at various axial sites, under varying conditions of axial tube wall tension, in tubes of two different wall thickness (0.3 and 0.4 of mean radius). Unsupported tube segment length was also varied by means of an insert device. The relations were used to calculate the variation of wave velocity with area according to Young's equation. First opposite wall contact during collapse was shown to occur at a smaller fraction of undistended circular cross-sectional area than in the thin-walled tubes investigated previously by others.


Is There a Return on a Children's Hospital's Investment in a Pediatric Residency's Community Health Track? A Cost Analysis.
Academic Medical Centers incur significant expenses associated with training residents and caring for underserved populations. No previous studies have analyzed hospital-level graduate medical education economics for pediatric residency training. Using data from the 2010-2011 academic year, we quantified total direct costs per year for training 12 community health track (CHT) residents. Utilizing sensitivity analyses, we estimated revenues generated by residents in inpatient and outpatient settings. The total yearly direct cost of training 12 CHT residents was $922,640 including salaries, benefits, and administrative costs. The estimated additional yearly inpatient net revenue from attending-resident clinical teams compared to attendingonly service was $109,452. For primary care clinics, the estimated yearly revenue differential of resident-preceptor teams was $455,940, compared to attending-only clinics. The replacement cost of 12 CHT residents with advanced practitioners was $457,596 per year.This study suggests there is positive return on a children's hospital's investment in a CHT.


Correction to: Determinants of prenatal care use and HIV testing during pregnancy: a population-based, cross-sectional study of 7080 women of reproductive age in Mozambique.
Following publication of the original article [1], we have been notified that the name of the author two was spelled incorrectly as Oladimeji Olarewaju, when the correct spelling is Oladimeji, Olanrewaju.


Nicotinic acid induces antinociceptive and anti-inflammatory effects in different experimental models.
Although in vitro studies have shown that nicotinic acid inhibits some aspects of the inflammatory response, a reduced number of in vivo studies have investigated this activity. To the best of our knowledge, the effects induced by nicotinic acid in models of nociceptive and inflammatory pain are not known. Per os (p.o.) administration of nicotinic acid (250, 500 or 1000 mg/kg, -1 h) inhibited the first and the second phases of the nociceptive response induced by formalin in mice. Nicotinic acid (250 or 500 mg/kg, -1 and 3 h) also inhibited the mechanical allodynia induced by carrageenan in rats, a model of inflammatory pain. However, in a model of nociceptive pain, exposure of mice to a hot-plate, nicotinic acid was devoid of activity. In addition to inhibiting the nociceptive response in models of inflammatory pain, nicotinic acid (250 or 500 mg/kg, p.o., -1 and 3 h) inhibited paw edema induced by carrageenan in mice and rats. Picolinic acid (62.5 or 125 mg/kg, p.o., -1 h), a nicotinic acid isomer, inhibited both phases of the nociceptive response induced by formalin, but not paw edema induced by carrageenan in mice. The other nicotinic acid isomer, isonicotinic acid, was devoid of activity in these two models. In conclusion, our results represent the first demonstration of the activity of nicotinic acid in experimental models of nociceptive and inflammatory pain and also provide further support to its anti-inflammatory activity. It is unlikely that conversion to nicotinamide represents an important mechanism to explain the antinociceptive and anti-inflammatory activities of nicotinic acid. The demonstration of new activities of nicotinic acid, a drug that has already been approved for clinical use and presents a positive safety record, may contribute to raise the interest in conducting clinical trials to investigate its usefulness in the treatment of painful and inflammatory diseases.


[The fragmentation of occupational health and safety in the meat industry through contracts to produce a work (Werkverträge) - and the need for an integrated occupational health and safety strategy].
The devastating working conditions in the meat industry have not only been known since the Corona pandemic, but this spring slaughterhouses in particular proved to be hotspots of the Sars-CoV-2 spread. In the summer of this year, the Federal Government presented a draft for an occupational health and safety control law. Among other things, the bill provides for a ban on the use of contracts to produce a work (Werkverträge) and temporary agency work in the core area of the meat industry from 1 January and 1 April 2021 respectively.This article traces the omissions of recent years and shows why, in third-party employment constellations, the important inter-company cooperation in occupational health and safety cannot represent a model for success in the meat industry, since in the meat industry the contracting companies are neither able nor willing to assert themselves with regard to occupational health and safety. The article highlights why the proprietor's organisational obligations are crucial for compliance with national and EU occupational health and safety law as well as food hygiene regulations, and must ultimately be monitored by the occupational health and safety inspectorates. The contribution supports the objectives of the bill, but at the time of the editorial deadline (16.11.2020) it is still uncertain whether the Bundestag will pass the law without substantial deterioration.


Multiple system atrophy: a clinical and neuropathological perspective.
Multiple system atrophy (MSA) is a neurodegenerative disease involving motor abnormalities that include akinesia, rigidity and postural instability. While improved diagnostic criteria have aided the accurate diagnosis of MSA, our understanding of the neuropathological aspects underlying MSA was bolstered by the identification of α-synuclein (α-syn) as the primary constituent of the abnormal protein aggregates observed in the brains of MSA patients. The generation of transgenic animal models of MSA coupled with an increasing understanding of the biochemical structure and function of α-syn has highlighted a number of key pathological pathways thought to underlie the neurodegeneration observed in MSA. This review summarizes key findings in the field, discusses current areas of debate, and describes current experimental approaches towards disease-modifying therapies.


Isoform-specific regulation of transforming growth factor-β mRNA expression in macrophages in response to adrenoceptor stimulation.
Transforming growth factor-beta (TGF-β) is a multifunctional cytokine responsible for both immune regulation and tissue repair. Although TGF-β consists of TGF-β1, -β2, and -β3 in mammals, isoform-selective transcriptional regulation is less well documented in myeloid linage cells such as macrophages. In the present study, the effect of the stress-related catecholamine adrenaline on the expression of TGF-β isoforms in RAW264.7 macrophages and murine bone marrow-derived macrophages was examined. Treatment with adrenaline markedly increased the mRNA expression of TGF-β3 but not of TGF-β1 and -β2. Agonist and antagonist studies indicated that adrenaline-induced TGF-β3 mRNA expression is mediated via β2 -adrenoceptor. Protein kinase A (PKA) inhibitor H89 was found to block an increase in adrenoceptor-mediated TGF-β3 mRNA expression. The membrane-permeable cAMP analog 8-Br-cAMP increased the mRNA expression of TGF-β3 but not of TGF-β1 and -β2. Thus, the β2 -adrenoceptor-mediated cAMP-PKA pathway appears to enhance TGF-β3 mRNA expression in macrophages. Adrenoceptor-mediated TGF-β3 expression by macrophages may influence immune regulation and tissue repair in conditions of stress, during which the sympathetic-nervous system releases catecholamines.


Prevention of the ultraviolet B-mediated skin photoaging by a nuclear factor kappaB inhibitor, parthenolide.
The skin photoaging is characterized by keratinocyte hyperproliferation and degradation of collagen fibers, causing skin wrinkling and laxity and melanocyte proliferation that leads to pigmentation. UV is considered to be a major cause of such skin changes. It is well established that nuclear factor kappaB (NF-kappaB) is activated upon UV irradiation and induces various genes including interleukin-1 (IL-1), tumor necrosis factor alpha (TNFalpha), and matrix metalloprotease-1 (MMP-1). It is also known that basic fibroblast growth factor (bFGF) production is induced by UV and promotes the proliferation of skin keratinocytes and melanocytes. We found that UVB, IL-1, and TNFalpha induced NF-kappaB activation and then produced MMP-1 and bFGF in HaCaT keratinocytes and skin fibroblasts. In this experiment, we examined if parthenolide, an NF-kappaB inhibitor, could block the UVB-mediated skin changes. We found that parthenolide could effectively inhibit the gene expression mediated by NF-kappaB and the production of bFGF and MMP-1 from cells overexpressing p65, a major subunit of NF-kappaB. We also found that parthenolide could inhibit the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin. These findings suggest that NF-kappaB inhibitors should be useful for the prevention of skin photoaging.


True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence.
We assessed the influence of medication adherence on blood pressure (BP) control and target organ damage in a pre-specified analysis of a published trial comparing sequential nephron blockade (SNB) or sequential renin-angiotensin system blockade (SRASB) in patients with resistant hypertension. Patients were randomized to SNB (n = 82) or SRASB (n = 82) and studied at baseline and after 12 weeks. BP was measured by ambulatory blood pressure monitoring. Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry and left ventricular mass (LVM) by echocardiography. Low medication adherence was assessed through plasma irbesartan concentration below 20 ng/ml; urinary N-acetyl-seryl-aspartyl-lysyl-proline/creatinine ratio below 4 nmol/mmol; last medication intake before visit greater than 24 h and pill counting below 80% of theoretical intake. Medication adherence score (sum of items, max = 4) is defined as low (medication adherence score <2) or acceptable (medication adherence score ≥2). Among 164 patients, 134 (81.7%) had acceptable medication adherence and 30 (18.3%) low medication adherence, with similar proportions in the SNB and SRASB arms. After 12 weeks, in patients with acceptable medication adherence, BP was more frequently controlled in those treated with SNB (64%), than SRASB (18%; P < 0.001). The difference in daytime SBP was -11.5 mmHg [95% confidence interval (CI) -15.4 to -7.5, P < 0.0001] in patients with acceptable medication adherence. In contrast, in patients with low medication adherence, the difference between groups was smaller and not significant (-9.4 mmHg, 95% CI -20.4 to 1.7, P = 0.09). Independently of BP changes, PWV and LVM decreased more in the SNB than in the SRASB arm when medication adherence was acceptable (-0.52 m/s, 95% CI -1.3 to -0.007, P = 0.047; and -24 g/m, 95% CI -36 to -12, P = 0.0003), whereas no significant changes were observed in low medication adherence patients. Medication adherence contributes to BP-lowering and regression of target organ damage. The differential effects of SNB and SRASB is observed in patients with acceptable medication adherence, and not in patients with low medication adherence.


The antitumor complex ethylenediamine platinum (II) malonate: x-ray structure analysis, and studies of its stability in solution.
The anti-tumour compound ethylenediamine platinum (II) malonate has been examined by x-ray crystallography. The molecular structure has a square-planar arrangement around the platinum atom, with the malonate group in a boat conformation and cis to the ethylenediamine group. Solution studies have shown that the malonate ion may be readily displaced from the complex, especially by chloride ion, and at low pH. The implications of this finding for in vivo drug administration are discussed.


Development and validity of the Korea psychiatric triage algorithm.
Psychiatric emergencies require timely intervention because of the risk of harm to individuals and society, including others. The aim of the present study was to test the content validity of a psychiatric triage algorithm developed for use in South Korea. The initial algorithm was developed through systematic literature review. Its validity was then verified by 10 experts. Based on results of expert validity, the algorithm was modified and the final algorithm was developed. Its clinical validity was then verified by 37 emergency room nurses who had used triage. Four questions of expert validity results with a CVI of 0.8 or less were revised to reflect expert opinion. The usefulness, adequacy, and convenience of the final modified algorithm was 2.98 ~ 3.53. After sufficiently validated by follow-up studies, it is expected that the use of psychiatric classification algorithms in emergency room nurses will not only improve the quality of care, but also can improve patient outcomes and experience.


Self-management strategies to support performance of daily activities in hand osteoarthritis.
The main aim of this study was to explore self-management strategies in persons with hand osteoarthritis (HOA). Self-management strategies were explored in semi-structured interviews, in which 125 participants described strategies, use of devices or equipment, and advice they would give to people with HOA concerning how to manage their daily life. The participants made a total of 483 statements, which were classified into 27 discrete strategies, and thereafter grouped into 13 broader strategies within three categories: general behavioural strategies, HOA-specific behavioural strategies, and cognitive strategies. The broad strategy "activity accommodations" specifically addressed performance of daily activities in people with HOA, comprising "use assistive devices", "adapt tools, materials or working techniques", "practise activity pacing" and "stop or avoid certain activities", of which the two first were the most frequently stated by participants. People with HOA use a wide variety of self-management strategies to support performance of daily activities, in which use of assistive devices and activity adaptation are the most frequently reported strategies. Patient-recommended self-management strategies should be included in written information material and patient education programmes, which should be developed in cooperation with patient representatives and made available for patients soon after they are diagnosed.


Professional Use of Social Media Among Surgeons: Results of a Multi-Institutional Study.
Among surgeons, professional use of social media (SM) is varied, and attitudes are ambiguous. We sought to characterize surgeons' professional use and perceptions of SM. Surgical faculty and trainees received institutional review board-approved e-mail surveys assessing SM usage and attitudes. Regression analyses identified predictors of SM attitudes and preference for professional contact. Surveys were administered to surgical faculty, fellows, and residents at 4 academic medical centers between January and April 2016. Of 1037 surgeons, clinical fellows, and residents e-mailed, 208 (20%) responded, including 132 faculty and 76 trainees. Among 208 respondents, 46 (22%) indicated they preferred some form of SM as their preferred networking and communication modality. A total of 145 (70%) indicated they believe SM benefits professional development. The position of clinical resident predicted preference to maintain professional contact via SM (p = 0.03). Age <55 predicted positive attitude (p = 0.02) and rank of associate professor predicted negative attitude toward SM (p = 0.03). Lack of time as well as personal and patient privacy concerns were cited most commonly as reasons for not using SM. Most of surgeons responding to our survey used some form of SM for professional purposes. Perceived barriers include lack of value, time constraints, and personal and patient privacy concerns. Generational differences in surgeon attitudes suggest usage of SM among surgeons will expand over time.


Administration of progestogens to hasten pituitary desensitization after the use of gonadotropin-releasing hormone agonist in in vitro fertilization--a prospective randomized study.
To assess the effect of administration of adjuvant IM progestogen to patients undergoing IVF who were not pituitary desensitized after 14 days of GnRH agonist (GnRH-a) administration. Prospective randomized study. A tertiary referral center for assisted conception. Forty-nine patients undergoing 51 IVF treatment cycles. Patients in whom the endometrial thickness was > 5 mm or who had an ovarian cyst > 15 mm after 14 days of GnRH-a administration were recruited if the serum E2 concentration was > 27.24 pg/mL (> 100 pmol/L). Patients in group 1 (n = 22) received a single IM injection of 100 mg P whereas patients in group 2 (n = 29) did not. Patients in both groups continued to receive SC GnRH-a 500 micrograms/d and had serum E2 levels measured every 3 days until the concentrations were < or = 100 pmol/L. The number of days of GnRH-a administration from recruitment until serum E2 concentration measured < or = 100 pmol/L, number of cycles with withdrawal bleeding, number of days from recruitment to withdrawal bleeding, total dose of hMG used, number of follicles > 14 mm, number of oocytes, number of embryos, and pregnancy rates per cycle commenced and per ET. There were no significant differences in all the above parameters except in the mean number of days from recruitment to onset of withdrawal bleeding, which were 5.33 +/- 0.7 (mean +/- SEM) and 8.62 +/- 1.26 days in groups 1 and 2, respectively. The pregnancy rate per ET was higher in group 1 (38.88%) when compared with group 2 (19.04%). However, this difference was not statistically significant. Adjuvant administration of a single IM injection of progestogen hastens the onset of withdrawal bleeding in patients who are not pituitary desensitized after 2 weeks of administration of SC GnRH-a. It does not appear to affect the length of time the serum E2 concentrations take to reach basal levels or to alter the ovarian responsiveness to exogenous gonadotropins.


Ultrasonic evaluation of gastric clearing in young infants.
Gastric emptying was determined using ultrasound in young infants. Gastric volume was calculated from anteroposterior, craniocaudal and laterolateral antral diameters. There was a linear decline of the logarithm of a gastric filling index over time in normal subjects. The mean clearing angle in normal subjects was 52 degrees (range 45-59). Examples of significantly different clearing rates could be demonstrated in a variety of clinical conditions. In several subjects gastric emptying rate was not exponential. Ultrasound seems very promising for the study of gastric emptying, especially in young children.


A novel mutation in RASA1 causes capillary malformation and limb enlargement.
Capillary malformations are common vascular malformations. Several syndromes have been described in which CMs are present in association with limb enlargement, among these are Klippel-Trenaunay syndrome (KTS) and Parkes Weber syndrome (PWS). Mutations in the RASA1 gene have been shown to underlie the capillary malformation-arterio-venous malformation (CM-AVM) syndrome, sometimes presenting with PWS. We identified a family comprising a patient with CMs and limb enlargement and a number of family members with CM/CM-AVM. A novel mutation in RASA1 was found to underlie the disease in this case. The present results illustrate the extensive degree of phenotypic heterogeneity associated with deleterious mutations in RASA1.


Abatement of circumneutral mine drainage by Co-treatment with secondary municipal wastewater.
Acid mine drainage is a persistent and problematic source of water pollution. Co-treatment with municipal wastewater at existing wastewater treatment plants has several advantages; however, potential impacts on plant physicochemical and biological processes have not been well explored. The primary purpose of this bench-scale study was to examine the impact of co-treatment by combining a mild acid mine drainage at various ratios with municipal wastewater, followed by sludge settling and supernatant comparative analysis using a variety of effluent water quality parameters. These measurements were combined with carbonate system and adsorption isotherm modeling to elucidate the mechanisms underlying the experimental results. Acid mine drainage addition decreased municipal wastewater effluent PO43- concentrations below 0.2 mg/L with greater than 97% removal, demonstrating co-treatment as an alternative solution for municipal wastewater nutrient removal. Biochemical oxygen demand remained similar to controls with <10% variation after co-treatment. Coagulation from metals in acid mine drainage was incomplete due to PO43- adsorption, confirmed by comparing experimental results with Langmuir isotherm behavior. Sweep flocculation was the dominating particle aggregation mechanism, and co-treatment led to improved particle clarification outcomes. Improved clarification led to up to 50% Fe removal. Final pH had little variation with all conditions having pH > 6.0. Carbonate system modeling adequately explains pH effects, and can also be applied to varying acid mine drainage matrices. The impact of acid mine drainage addition on the municipal wastewater microbial community was also investigated which provided evidence of microbial adaptation. This study demonstrates post-aeration co-treatment enables mitigation of mild acid mine drainage without adversely affecting wastewater treatment plant processes. Reported results also frame required future studies to address extant questions prior to full-scale adaptation.


Diagnostic ascertainment of suspicious pancreatic mass: a threshold analysis.
It is frequently difficult to differentiate between a benign and malignant pancreatic mass. The aim of this study was to assess the parameters that affect the decision to perform surgery on a suspicious pancreatic head lesion. A cost-benefit analysis, using decision tree and threshold analysis, accumulates costs and quality-adjusted life years in patients undergoing pancreaticoduodenectomy or expectant management. The threshold value is defined as the diagnostic probability for pancreatic cancer when the cost-benefit relationships of pancreaticoduodenectomy or expectant management are equal. For a localized pancreatic head lesion, the threshold probability of cancer is 43%. Any higher probability of pancreatic cancer makes pancreaticoduodenectomy the preferred treatment option. Within a range of $20,000 to $80,000 spent on surgery, the threshold in favor of Whipple procedure remains relatively low at 40% to 65%. A reduced quality of life after surgery weighs against surgery and raises its threshold. Varying quality of life between 100% and 80% changes the threshold between 31% and 67%. The threshold also is increased in younger patients because of the potentially more dire consequences of unnecessary surgery in instances of long life expectancy. Even if diagnostic certainty cannot be achieved, it frequently is beneficial to perform surgery despite the risk of subjecting the occasional patient with benign pancreatic head lesion to an unnecessary pancreaticoduodenectomy.


Anomia for people names in DAT--evidence for semantic and post-semantic impairments.
Proper name anomia is a frequent finding among patients in the early stages of Alzheimer's disease. The present study investigates naming of famous persons in a group of DAT patients, a group of persons with mild cognitive impairment (MCI) and healthy controls. The study is aimed at distinguishing the relative contributions of semantic and post-semantic factors to difficulties in proper name retrieval. As shown by a significantly lower score in answering semantic questions, DAT patients retrieve less biographical knowledge related to famous persons than healthy elderly subjects and persons with mild cognitive impairment. This finding is in line with the frequent observation of semantic deficits in early and moderate DAT. The high number of Tip-of-the-Tongue (TOT) answers in DAT found in relation to few spontaneously named items shows that post-semantic deficits are as important as semantic deficits in determining anomia for people names in DAT. Moreover, DAT patients were less sensitive to phonological cueing than healthy persons or persons with mild cognitive impairment. These findings suggest that proper name anomia in DAT is not only due to semantic deficits, but also to problems in accessing the phonological representation, as well as to a degradation of phonological representations. Thus, naming deficits in DAT differ not only quantitatively, but also qualitatively from the difficulties of healthy elderly persons. No significant differences were found between persons with mild cognitive impairment and healthy controls in proper name retrieval.


Aldose reductase inhibitory compounds from Xanthium strumarium.
As part of our ongoing search for natural sources of therapeutic and preventive agents for diabetic complications, we evaluated the inhibitory effects of components of the fruit of Xanthium strumarium (X. strumarium) on aldose reductase (AR) and galactitol formation in rat lenses with high levels of glucose. To identify the bioactive components of X. strumarium, 7 caffeoylquinic acids and 3 phenolic compounds were isolated and their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with published data. The abilities of 10 X. strumarium-derived components to counteract diabetic complications were investigated by means of inhibitory assays with rat lens AR (rAR) and recombinant human AR (rhAR). From the 10 isolated compounds, methyl-3,5-di-O-caffeoylquinate showed the most potent inhibition, with IC₅₀ values of 0.30 and 0.67 μM for rAR and rhAR, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate, methyl-3,5-di-O-caffeoylquinate showed competitive inhibition of rhAR. Furthermore, methyl-3,5-di-O-caffeoylquinate inhibited galactitol formation in the rat lens and in erythrocytes incubated with a high concentration of glucose, indicating that this compound may be effective in preventing diabetic complications.


Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro.
For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities.


Molecular forms of cathepsin B in rat thyroid cells (FRTL5): comparison with molecular forms in liver (Hep G2) and insulin-secreting cells (HIT T15).
A radiolabelled peptide chloromethyl ketone (125I-tyrosyl-L-alanyl-L-lysyl-L-arginine chloromethyl ketone) was used to affinity-label proteinases in rat thyroid cells (FRTL5). Two major proteins of 34 kDa and 32 kDa were affinity-labelled. Inhibitor competition studies demonstrated that both proteins were cysteine proteinases. Over the range pH 5-8, they exhibited maximum activity against the affinity probe at pH 5. They were soluble rather than membrane-bound and were both glycosylated. The 32 kDa proteinase but not the 34 kDa proteinase was immunoprecipitated using an anti-rat liver cathepsin B antibody. The data suggested that these proteinases were molecular forms of cathepsin B. The affinity-labelled proteins in the thyroid were compared with those in an insulin-secreting cell line (HIT T15) and a liver cell line (Hep G2). Two molecular forms of cathepsin B of Mr 39,000 and 33,000 were identified in the insulin-secreting cell line and a single form of Mr 34,000 in the liver cell line. These molecular forms of cathepsin B may reflect the different functions and compartmentation of cathepsin B in these cells.


Role of matrix metalloproteinases in dental caries, pulp and periapical inflammation: An overview.
Matrix metalloproteinases (MMPs) are a group of more than 25 secreted and membrane bound enzymes that represent class of enzymes responsible for degradation of pericellular substrates. They have been isolated from dentine, odontoblasts, pulp and periapical tissue. They play an important role in dentine matrix formation, modulating caries progression and secondary dentine formation. Earlier microbial proteolytic enzymes were believed to be responsible for degradation of dentine organic matrix, but lately the accumulated body of evidence suggests that MMPs have an important role in the process. During normal tissue modelling, differentiation during development, in modulating the cell behaviour, maintaining homeostasis and in numerous extracellular pathologic conditions, MMPs tends to be an equally important participant. Odontoblasts secrete some of the essential MMPs for both physiologic and pathologic conditions. MMPs also appear to be a participant in the process of reversible and irreversible pulpitis. Although they tend to have low expression and activity in adult tissues but at the onset of any destructive pathologic process, their production shoots up. They appear to have a significant presence during times of inflammation in the periapical region as well. We take a look at the various factors and evidence pointing towards the role of MMPs in the progression of caries, pulpal and periapical inflammation.


There is no difference in perioperative results between posterior instrumentation with and without interbody cage and debridement in primary spondylodiscitis in adults: a multicenter surveillance study from the German Spine Registry (DWG Register).
Primary spondylodiscitis is a medically challenging disease that can lead to recurrent back pain, progressive kyphotic deformity, and neurologic deficits. The incidence rate of primary non-tuberculosis spondylodiscitis has been estimated from 2.2 to 2.4 cases per 100,000 person-years, and it has been reported to be increasing because of the aging population. The objectives were to determine the safety and efficacy of posterior instrumentation (PI) with and without interbody cage, bony attachment and debridement in the treatment of primary spondylodiscitis by comparing perioperative data, functional outcomes, and overall infection-free survival. Analysis of data from the DWG Registry on patients who have undergone posterior instrumentation with and without interbody cage, bony attachment and debridement in primary spondylodiscitis from the thoracolumbar junction to S1 (Th10-S1) at 10 institutions from January 2012 to December 2016. In total, 420 posterior instrumentations with and without interbody cage, bony attachment and debridement in primary spondylodiscitis in the thoracolumbar junction to S1 were identified in the registry; N.=138 were exclusively percutaneous posterior instrumented (PPI), while N.=102 underwent open posterior instrumentation (OPI) without interbody cage, bony attachment and debridement and N.=180 OPI with interbody cage, bony attachment and debridement. Clinical evaluation after surgery did not show a significant difference between groups including improvement of the mobilization and infection-free survival. However, with PPI the duration of operation and blood loss was significantly less than OPI with and without interbody cage, bony attachment and debridement. The results suggest interbody cage, bony attachment and debridement as not indispensable for treatment in primary spondylodiscitis. Therefore, we encourage the use of posterior stabilization alone in the treatment of spondylodiscitis as less invasive procedure reducing costs in instrumentation.


Acute Charcot neuro-osteoarthropathy.
Charcot neuro-osteoarthropathy (CN) is one of the most challenging foot complications in diabetes. Common predisposing and precipitating factors include neuropathy and increased mechanical forces, fracture and bone resorption, trauma and inflammation. In the last 15 years, considerable progress has been made in the early recognition of the acute Charcot foot when the X ray is still negative (stage 0 or incipient Charcot foot). Recent advances in imaging modalities have enabled the detection of initial signs of inflammation and underlying bone damage before overt bone and joint destruction has occurred. Casting therapy remains the mainstay of medical therapy of acute CN. If timely instituted, offloading can arrest disease activity and prevent foot deformity. In cases with severe deformity, modern surgical techniques can correct the unstable deformity for improved functional outcome and limb survival. Emerging new studies into the cellular mechanisms of severe bone destruction have furthered our understanding of the mechanisms of pathological bone and joint destruction in CN. It is hoped that these studies may provide a scientific basis for new interventions with biological agents.


Acute Coronary Syndromes in Sub-Saharan Africa: A 10-Year Systematic Review.
Background Data in the literature on acute coronary syndrome in sub-Saharan Africa are scarce. Methods and Results We conducted a systematic review of the MEDLINE (PubMed) database of observational studies of acute coronary syndrome in sub-Saharan Africa from January 1, 2010 to June 30, 2020. Acute coronary syndrome was defined according to current definitions. Abstracts and then the full texts of the selected articles were independently screened by 2 blinded investigators. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. We identified 784 articles with our research strategy, and 27 were taken into account for the final analysis. Ten studies report a prevalence of acute coronary syndrome among patients admitted for cardiovascular disease ranging from 0.21% to 22.3%. Patients were younger, with a minimum age of 52 years in South Africa and Djibouti. There was a significant male predominance. Hypertension was the main risk factor (50%-55% of cases). Time to admission tended to be long, with the longest times in Tanzania (6.6 days) and Burkina Faso (4.3 days). Very few patients were admitted by medicalized transport, particularly in Côte d'Ivoire (only 34% including 8% by emergency medical service). The clinical presentation is dominated by ST-elevation sudden cardiac arrest. Percutaneous coronary intervention is not widely available but was performed in South Africa, Kenya, Côte d'Ivoire, Sudan, and Mauritania. Fibrinolysis was the most accessible means of revascularization, with streptokinase as the molecule of choice. Hospital mortality was highly variable between 1.2% and 24.5% depending on the study populations and the revascularization procedures performed. Mortality at follow-up varied from 7.8% to 43.3%. Some studies identified factors predictive of mortality. Conclusions The significant disparities in our results underscore the need for a multicenter registry for acute coronary syndrome in sub-Saharan Africa in order to develop consensus-based strategies, propose and evaluate tailored interventions, and identify prognostic factors.


Undisclosed Financial Conflicts of Interest of Authors of Clinical Drug Trials Published in Influential Medical Journals: A Cohort Study.
The International Committee of Medical Journal Editors requires authors to disclose all financial conflicts of interest (COI) that can be perceived as influencing the related trials. Undisclosed financial COI may influence the perception of the authors' scientific impartiality and erode the public trust in the reported results. Data regarding completeness of COI disclosure in high-impact-factor general medicine journals are limited. We compared payments disclosed by US-based physicians who were first or last authors of clinical drug trials published between August 2016 and August 2018 in the New England Journal of Medicine, JAMA, and Lancet, to payments reported by industry to the Centers for Medicare & Medicaid Services Open Payments Database. Of 247 included authors, 198 (80%) have not disclosed some or all received payments. The median undisclosed sum was $8409 (US Dollars) (interquartile range [IQR] $123 to $44,890). Most authors (n=170, 69%) have received more than $10,000 per year (median $120,403, IQR $58,905 to $242,014). The median undisclosed sum for these authors was $26,530 (IQR $7462 to $71,562). Median undisclosed sums for authors of papers from studies performed with and without industry funding were $20,899 (IQR $4191 to $59,883) and $149 (IQR $0 to $3276), respectively. In 10 (8%) of 125 industry-funded trials, the first or last author had not disclosed personal payments from the study sponsor (median $9741, IQR $4508 to $101,484). These findings could raise concerns about the authors' equipoise toward the trial results and influence the public perception of the credibility of reported data. Health care professionals, reviewers, and journal editors should demand more transparent reporting of financial COI.


Neuronal Nitric Oxide Synthase Critically Regulates the Endocannabinoid Pathway in the Murine Cerebellum During Development.
The cerebellum is a major site of endocannabinoid (eCB) production and signaling. The predominant eCB within the cerebellum, 2-arachidonoylglycerol (2-AG), is produced by a metabotropic glutamate receptor type 1 (mGluR1)-initiated signaling cascade within Purkinje neurons (PNs). 2-AG retrogradely stimulates cannabinoid 1 receptors (CB1Rs) located on presynaptic terminals. The activated CB1R decreases neurotransmitter release and leads to the production of nitric oxide (NO), a gaseous molecule. Recently, our group discovered that during development in mice lacking neuronal nitric oxide synthase (nNOS-/-), PNs display an excitotoxic phenotype associated with overactivated mGluR1. Considering the importance of mGluR1 in 2-AG synthesis, the present study explored the role of nNOS-derived NO in regulating the eCB pathway within the cerebella of wildtype (WT) and nNOS-/- mice at postnatal day 7 (PD7), 2 weeks (2 W), and 7 weeks (7 W). Our analysis showed that diacylglycerol lipase α, the enzyme that catalyzes 2-AG production, was elevated at early postnatal ages, and followed by elevated levels of 2-AG in nNOS-/- cerebella compared to WT. CB1R expression in nNOS-/- cerebella was upregulated at PD7 but decreased at 2 W and 7 W when compared to age-matched WT mice cerebella. Importantly, treating organotypic nNOS-/- cerebellar slice cultures with an NO-donor-attenuated CB1R levels after 7 days in vitro. In addition, expression of the eCB hydrolases fatty acid amide hydrolase and monoacylglycerol lipase were significantly downregulated in nNOS-/- cerebella compared to WT cerebella at 7 W. Together, these results reveal a novel role for nNOS/NO in regulating eCB signaling in the cerebellum.