Severe ocular injury and its management following self induced plant extracts: A case report.
Homemade and folk remedies' use is widely practiced in under developed countries, of the used materials are plant extracts, lemon juice and some dried insect bodies. We report a case of severe ocular injury and its management after self administered plants seeds in both the eyes of a 47-year-old man who had bilateral severe ocular damage after he put the seeds of a plant Lepidium Sativum (Rashad) in his eyes. He reported severe ocular pain and redness, conjunctival epithelial defect and symblepharon. A conjunctival biopsy was taken which turned out to be negative for the immunological staining studies for Ocular Cicatricial Pemphegoid (OCP). The patient's visual acuity improved from 20/40 before treatment to 20/25 after treatment with no further sequelae after 3 months follow-up. Self induced plant extracts can cause ocular complications. Public awareness is necessary to help in discouraging the use of these harmful plant extracts in human eyes.


Initial hospital length of stay and long-term survival of patients successfully resuscitated using extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest.
The long-term outcomes of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory ventricular tachycardia/ventricular fibrillation (VT/VF) out-of-hospital cardiac arrest (OHCA) remain poorly defined. The purpose of this study was to describe the hospital length of stay and long-term survival of patients who were successfully rescued with ECPR after refractory VT/VF OHCA. In this retrospective cohort study, the length of index admission and long-term survival of patients treated with ECPR after OHCA at a single centre were evaluated. In a sensitivity analysis, survival of patients managed with left ventricular assist device (LVAD) implantation or heart transplantation during the same period was also evaluated. Between 1 January 2016 and 12 January 2020, 193 patients were transferred for ECPR considerations and 160 underwent peripheral veno-arterial extracorporeal membrane oxygenation cannulation. Of these, 54 (33.7%) survived the index admission. These survivors required a median 16 days of intensive care and 24 days total hospital stay. The median follow-up time of the survivors was 1216 (683, 1461) days. Of all, 79.6 and 72.2% were alive at 1 and 4 years, respectively. Most deaths within the first year occurred among the patients requiring discharge to a long-term acute care facility. Overall survival rates at 4 years were similar in the ECPR and LVAD cohorts (P = 0.30) but were significantly higher for transplant recipients (P < 0.001). This data suggest that the lengthy index hospitalization required to manage OHCA patients with ECPR is rewarded by excellent long-term clinical outcomes in an expert ECPR programme.


Isoproterenol enhancement of I(Ks) current in amiodarone-induced long QT syndrome.
The response over time of the QT interval and the Transmural Dispersion of Repolarization (TDR) to Isoproterenol infusion (ISO) in an 85 year-old-man with severe and syntomatic bradycardia, in the setting of an Amiodarone-induced Long QT Syndrome (LQTS) is the subject of this communication. ISO shortened the QT and decreased the TDR. We propose that ISO increased the generation of signals from the beta-Adrenergic Receptor (beta-AR) restoring the components of the hKCNQ1 macromolecular complex, thereby enhancing the I(Ks) function; shortening of the QT interval, reduction of the TDR and normalization of the T wave morphology was then possible. In Amiodarone-induced LQTS, the increase in I(Ks) activity promoted by beta-AR stimulation is prominent; at the same time, during I(Kr) block, I(Ks) activation limits excessive QT prolongation. Clinically, severe and syntomatic bradycardia was the main concern: ISO activation of the beta-AR proved useful both to increase heart rate and to reduce QT prolongation. A slow heart rate, associated to a prolonged QT interval and to a big TDR, are not sufficient to develop Torsades de Pointes in Amiodarone-induced LQTS.


[Activity of the heart and blood volume in patients with rectal cancer operated on after gamma therapy].
It is found that in irradiated patients subjected to abdomino-perineal extirpation of the rectum, a decrease of arterial pressure, blood volume, minute heart volume is more pronounced than in control patients.


Insight Into Resistance Phenotypes of Emergent Non 13-valent Pneumococcal Conjugate Vaccine Type Pneumococci Isolated From Invasive Disease After 13-valent Pneumococcal Conjugate Vaccine Implementation in France.
Background. In 2010, the pneumococcal 13-valent conjugate vaccine (PCV13), containing 6 additional serotypes including the multidrug-resistant 19A, replaced the PCV7 in France. This study aimed at analyzing trends in antibiotic resistance in invasive pneumococcal disease (IPD) isolates in France after PCV13 introduction. Methods. A total of 5243 pneumococci isolated from IPD in 2008-2009 (late PCV7 era) and 2011-2012 (PCV13 era) were studied according to their serotype and antibiotic resistance profile. Multilocus sequence typing analysis was performed on strains of the predominant serotypes (12F and 24F) isolated from young children. Results. Overall, the prevalence of antibiotic resistance decreased in France (-21.5% for penicillin from 2008-2009 to 2011-2012), mainly driven by the decline of the 19A serotype. Among non-PCV13 serotypes that concomitantly emerged, serotypes 12F, 24F, 15A, and 35B were consistently associated with resistance to 1 or more antibiotics. In children under 2 years, serotypes 15A, 35B, and 24F accounted together for 37.8% and 31.9% of penicillin-nonsusceptible and erythromycin-resistant isolates, respectively. Chloramphenicol and cotrimoxazole resistance were mainly associated with serotypes 12F and 24F, respectively. Genetic analysis showed that although emergence of serotype 12F pneumococci resulted from the expansion of various pre-existing lineages, increase in serotype 24F was related to the clonal expansion of the ST162 penicillin-susceptible cotrimoxazole-resistant lineage. Conclusions. We showed that decline of PCV13-related IPD was associated with a decline in antibiotic resistance in France, but that it likely favored the spread of several resistant nonvaccine serotypes. However, antibiotic resistance does not seem to be the only element that may drive this phenomenon.


Interaction of transition metal ions with ribonuclease A. II. The selective effects of Mn2+, Zn2+, Cd2+ and Hg2+ on the histidine magnetic resonance.
Zn2+, Cd2+ and Hg2+ inhibit ribonuclease but Mn2+ does not except at very high concentrations. By high resolution NMR one can detect in the pH range 5-8 the C-2 protons of histidines 105, 12, and 119. The inhibiting ions produce large shifts of the resonance of His-12 but not of His-105. On the other hand Mn2+ broadens the C-2 proton of His-105 much more than it does those of His-12 and 119. The selective shifts suggest that the mechanism of inhibition is binding at or near the active site of which His-12 and 119 are a part. The selective broadening is a consequence of binding of the Mn2+ to a site very far from the active site but closer to His-105.


Central roles of NLRs and inflammasomes in viral infection.
The immune response to viral infections is determined by a complex interplay between the pathogen and the host. Innate immune cells express a set of cytosolic sensors to detect viral infection. Recognition by these sensors induces the production of type I interferons and the assembly of inflammasome complexes that activate caspase-1, leading to production of interleukin-1β (IL-1β) and IL-18. Here, I discuss recent progress in our understanding of the central roles of NOD-like receptors (NLRs) and inflammasomes in the immune response during viral infections. This information will improve our understanding of host defence mechanisms against viruses and provide new avenues for interfering in the pathogenesis of infectious diseases.


Solar tracking response to drought in a desert annual.
The responses to drought of the solar tracking winter annualLupinus arizonicus (Wats.) were examined under field and laboratory growth regimes. Under drought conditions tracking movements were maintained until the plant reached the wilting point. The leaves and leaflets were observed to cup in response to decreases in the xylem water potential. This resulted in a negative, but linear relationship between the cosine of the angle of incidence of the direct solar beam upon the leaf and water potential. Leaf conductance was also significantly related to xylem water potential in natural populations. Leaf and leaflet cupping seem to be responding directly to changing plant water status, resulting in reduced solar radiation load to drought stressed plants. It is hypothesized that this property may have adaptive consequences in relation to the water relations, energy budget, and carbon balance of the plant.


Bernoulli and binomial proliferation on evolutionary graphs.
In this paper we introduce random proliferation models on graphs. We consider two types of particles: type-1/mutant/invader/red particles proliferates on a population of type-2/wild-type/resident/blue particles. Unlike the well-known Moran model on graphs -as introduced in Lieberman et al. (2005)-, type-1 particles can occupy in a single iteration several neighbouring sites previously occupied by type-2 particles. Two variants are considered, depending on the random distribution involving the proliferation mechanism: Bernoulli and binomial proliferation. By comparison with fixation probability of type-1 particles in the Moran process, critical parameters are introduced. Properties of proliferation are studied and some particular cases are analytically solved. Finally, by updating the parameters that drive the processes through a density-dependent mechanism, it is possible to capture additional relevant features as fluctuating waves of type-1 particles over long periods of time. In fact, the models can be adapted to tackle more general, complex and realistic situations.


Study of the novel non-xanthine heterocyclic compound GU285 as a potent non-selective adenosine receptor antagonist in the rat.
The novel pyrazolo[3,4-d]pyrimidine compound GU285 (4-amino-6-alpha-carbamoylethylthio-1- phenylpyrazolo[3,4-d]pyrimidine, CAS 134896-40-5) was examined for its ability (1) to inhibit binding of adenosine (ADO) receptor ligands in rat brain membranes, (2) to antagonise functional responses to ADO agonists in rat right and left atria and coronary resistance vessels, and (3) to reduce the fall in heart rate and arterial blood pressure produced by the ADO A1 agonist N6-cyclopentyladenosine (CPA) in the intact, anaesthetized rat. GU285 competitively inhibited binding of the ADO A1 agonist [3H]-R-N6-phenylisopropyladenosine (R-PIA) yielding a Ki value of 11 (7-18) nmol.l-1 (geometric mean +/- 95% Cl). When assayed against the ADO A2A selective agonist [3H]-2-[p-(2-carboxyethyl)- phenethylamino]-5'-N-ethylcarboxamidoadenosine, (CGS21680), a Ki of 15 (10-24) nmol.l-1 was obtained. In spontaneously beating right atria, GU285 competitively antagonized negative chronotropic effects of R-PIA with a pA2 of 8.7 +/- 0.3 and in electrically paced left atria, GU285 competitively antagonized negative inotropic effects of R-PIA with a pA2 of 9.0 +/- 0.1. In the potassium-arrested, perfused rat heart GU285 (1 mumol.l-1) antagonized only the high sensitivity, ADO A2B mediated component of the biphasic relaxation of the coronary vasculature produced by NECA. The low sensitivity component was unchanged. GU285 (1 mumol.kg-1) antagonized the negative chronotropic and hypotensive effects of the adenosine A1 agonist CPA in anaesthetized rats, producing a 10-fold rightward shift in the dose-response relationship. These data demonstrate that in the rat, GU285 is a potent, non-selective adenosine receptor antagonist that maintains its activity in vivo.


Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets?
Abnormal neuronal signaling caused by metabolic changes characterizes several neurological disorders, and in some instances metabolic interventions provide therapeutic benefits. Indeed, altering metabolism either by fasting or by maintaining a low-carbohydrate (ketogenic) diet might reduce epileptic seizures and offer neuroprotection in part because the diet increases mitochondrial biogenesis and brain energy levels. Here we focus on a novel hypothesis that a ketogenic diet-induced change in energy metabolism increases levels of ATP and adenosine, purines that are critically involved in neuron-glia interactions, neuromodulation and synaptic plasticity. Enhancing brain bioenergetics (ATP) and increasing levels of adenosine, an endogenous anticonvulsant and neuroprotective molecule, might help with understanding and treating a variety of neurological disorders.


Comparisons of polybrominated diphenyl ethers levels in paired South Korean cord blood, maternal blood, and breast milk samples.
Polybrominated diphenyl ethers (PBDEs), commonly used flame retardants, have been reported as potential endocrine disruptor and neurodevelopmental toxicants, thus giving rise to the public health concern. The goal of this study was to investigate the relationship between umbilical cord blood, maternal blood, and breast milk concentrations of PBDEs in South Korean. We assessed PBDE levels in paired samples of umbilical cord blood, maternal blood, and breast milk. The levels of seven PBDE congeners were measured in 21 paired samples collected from the Cheil Woman's Hospital (Seoul, Korea) in 2008. We also measured thyroid hormones levels in maternal and cord blood to assess the association between PBDEs exposure and thyroid hormone levels. However, there was no correlation between serum thyroxin (T4) and total PBDEs concentrations. The total PBDEs concentrations in the umbilical cord blood, maternal blood, and breast milk were 10.7±5.1 ng g(-1) lipid, 7.7±4.2 ng g(-1) lipid, and 3.0±1.8 ng g(-1) lipid, respectively. The ranges of total PBDE concentrations observed were 2.28-30.94 ng g(-1) lipid in umbilical cord blood, 1.8-17.66 ng g(-1) lipid in maternal blood, and 1.08-8.66 ng g(-1) lipid in breast milk. BDE-47 (45-73% of total PBDEs) was observed to be present dominantly in all samples, followed by BDE-153. A strong correlation was found for major BDE-congeners between breast milk and cord blood or maternal blood and cord blood samples. The measurement of PBDEs concentrations in maternal blood or breast milk may help to determine the concentration of PBDEs in infant.


Adrenocorticotropin-independent macronodular adrenal hyperplasia treated by simultaneous bilateral laparoscopic adrenalectomy.
A 61-year-old woman was admitted to our hospital with hypertension and diabetes mellitus, and was found to have Cushing's syndrome. Radiological and endocrinological findings suggested adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Simultaneous bilateral laparoscopic adrenalectomy was performed, minimizing the number of trocar sites and operation time. Success was attributed to the careful selection of trocar sites to permit safe dissection.


Establishing standards for acceptable waveforms in nerve conduction studies.
The purpose of this position statement is to clarify what constitutes an acceptable nerve conduction study (NCS) waveform in the practice of electrodiagnostic (EDx) medicine. The American Association of Neuromuscular & Electrodiagnostic Medicine convened an expert panel to analyze the typical deficiencies of NCS waveforms seen when performed by unqualified providers and/or providers using substandard equipment and also to describe basic standards that all proper NCS waveforms should meet. An acceptable NCS waveform should include clearly identifiable polarity, configuration, onset, peak(s), and return to baseline. Only NCSs performed using appropriate EDx equipment and interpreted by trained physicians can accurately measure the speed of nerve conduction and amplitude of the nerve response. If these parameters cannot be clearly identified, then the waveform should be considered substandard and should not be submitted for reimbursement according to the Current Procedural Terminology guidelines of the American Medical Association.


How Are We Handling Fluoroscopy-Guided Lumbar Puncture Requests? A Nationwide Survey of Practice Trends.
Referrals to perform fluoroscopy-guided lumbar punctures by neuroradiologists have increased. The purpose of our study was to determine the management of fluoroscopy-guided lumbar puncture referrals in different practice settings. We sent an online questionnaire to neuroradiologists and radiology trainees between May and June 2020 to survey their handling of fluoroscopy-guided lumbar puncture requests, preprocedural work-up, and the use of physician extenders/trainees to perform fluoroscopy-guided lumbar punctures, among other questions. Categories were compared using ORs. Of the 123 US respondents, 81.3% were in combined academic and 18.7% in combined private practice groups. Regarding fluoroscopy-guided lumbar puncture referrals, 27.6% of respondents did not require a bedside lumbar puncture attempt before a fluoroscopy-guided lumbar puncture. Of private practice, 95.7%, and of academic respondents, 85.0%, were often asked to perform fluoroscopy-guided lumbar punctures by clinicians because of the clinician's lack of procedural competence. Of those, 74.8% stated that they always or sometimes agreed to the request. 41.5% of respondents stated that they would always comply with patients' requests for a fluoroscopy-guided lumbar puncture without a bedside lumbar puncture attempt, a 5.26 times higher likelihood (95% CI, 2.04-14.29) for private practice respondents. To perform fluoroscopy-guided lumbar punctures, 32.0% of academic respondents and 47.8% of private practice respondents use physician extenders. 75.0% of academic respondents reported that trainees perform >50% of their fluoroscopy-guided lumbar punctures. This survey demonstrates that many academic and private practice neuroradiologists engage in practices that may promote an increase in fluoroscopy-guided lumbar puncture referrals including not requiring a non-image-guided lumbar puncture attempt, complying with clinicians' requests for a fluoroscopy-guided lumbar puncture due to lack of competence in performing lumbar punctures, and fulfilling patient requests for fluoroscopy-guided lumbar punctures.


Bovine cervical bursitis co-infection caused by Brucella abortus and Onchocerca sp.
The presence of Onchocerca guturosa in cattle is responsible for lesions similar to those observed in cases suspected of brucellosis, however, Onchocerca sp. is not a trade barrier, although it is also responsible for economic losses due to the removal of the affected parts of the carcasses. Brucella sp. is a zoonotic agent transmitted to humans through the consumption of contaminated animal products, the contact with infected animals and the handling of carcasses. This agent is also responsible for non-tariff trade barriers. Cervical bursitis is Brucella sp. suggestive lesions in bovine carcasses that requires laboratory tests to confirm the diagnosis. The objective of this study was to record the co-infection of Brucella abortus and Onchocerca sp. as a first report of co-infection of these two agents in the same lesion. The sample constituted of a nuchal bursitis in the cervical ligament, a suggestive lesion common to these two agents, submitted to histopathology and Brucella spp. isolation in the Brucellosis reference laboratory of the Brazilian Ministry of Agriculture, Livestock and Food Supply. Brucellosis serological diagnosis were also performed in the animal's serum sample. B. abortus was isolated from the lesion and filarid nematode structures were identified in histopathology. All serological tests were positive for brucellosis. Further studies are needed, however, to understand the co-infection by Onchocerca sp. and B. abortus.


A direct hypothalamic projection to the superior salivatory nucleus neurons in the rat. A study using anterograde autoradiographic and retrograde HRP methods.
The location of the superior salivatory nucleus and terminal labelings of the hypothalamic descending fibers were demonstrated in the nucleus reticularis parvocellularis using HRP and the autoradiographic techniques, respectively. When both techniques were used in the same animals, some HRP-labeled neurons were seen among the accumulations of silver grains, suggesting pericellular terminations. The present study demonstrates that the hypothalamic efferents project directly to the superior salivatory nucleus innervating salivary and lacrimal glands.


Post-traumatic stress symptoms in children and adolescents with chronic pain: A topical review of the literature and a proposed framework for future research.
The co-occurrence of chronic pain and post-traumatic stress symptoms (PTSS) and post-traumatic stress disorder (PTSD) has gained increasing research attention. Studies on associations among pain and PTSS or PTSD in youth have largely been conducted in the context of acute injury or trauma. Less is known about the risk for co-occurrence with paediatric chronic pain. In this review, we (1) propose a conceptual framework to outline factors salient during childhood that may be associated with symptom severity, co-occurrence and mutual maintenance, (2) present relevant literature on PTSS in youth with acute and chronic pain and identify research gaps and (3) provide recommendations to guide paediatric research examining shared symptomatology. Electronic databases (PubMed and Google Scholar) were used to identify relevant articles using the search terms 'child, adolescent, paediatric, chronic pain, acute pain, post-traumatic stress symptoms and post-traumatic stress disorder'. Studies were retrieved and reviewed based on relevance to the topic. Our findings revealed that existing biobehavioural and ecological models of paediatric chronic pain lack attention to traumatic events or the potential development of PTSS. Paediatric studies are also limited by lack of a conceptual framework for understanding the prevalence, risk and trajectories of PTSS in youth with chronic pain. Our new developmentally informed framework highlights individual symptoms and shared contextual factors that are important when examining potential associations among paediatric chronic pain and PTSS. Future studies should consider bidirectional and mutually maintaining associations, which will be aided by prospective, longitudinal designs. WHAT DOES THIS REVIEW ADD?: This review presents relevant literature on pain and PTSS in youth and proposes a conceptual framework to examine factors salient during childhood that may be associated with symptom severity, comorbidity and mutual maintenance of chronic pain and PTSS in paediatric populations. We highlight dynamic factors that may change across children's development and provide recommendations to guide paediatric research examining potential associations among PTSS and chronic pain.


Combined chemo and photo therapy of programmable prodrug carriers to overcome delivery barriers against nasopharyngeal carcinoma.
Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.


Identification of metabolites of benzo[j]fluoranthene formed in vitro in rat liver homogenate.
The metabolites of benzo[j]fluoranthene (BjF) as formed in vitro using the 9000 X g supernatant from Aroclor-pretreated rats have been identified. Two dihydrodiols, trans-4,5-dihydro-4,5-dihydroxyBjF and trans-9,10-dihydro-9,10-dihydroxyBjF have been identified as major metabolites by comparison of their spectral and chromatographic properties with those of pure synthetic standards. There was no evidence that any of the isomeric 2,3-dihydrodiol was formed as a metabolite of BjF under these incubation conditions. Neither of the metabolic dihydrodiols of BjF were formed with a high degree of stereoselectivity. The enantiomeric purity of the 4,5-dihydrodiol was 20% while that of the 9,10-dihydrodiol was 46%. At least four phenols were detected among the metabolites of BjF. These were identified as 3-, 4-, 6- and 10-hydroxyBjF based upon comparison of their UV spectra and HPLC retention times with those of synthetic reference standards. BjF-4,5-dione was also identified as a metabolite under these incubation conditions.


Comparison of performances of conventional and deep learning-based methods in segmentation of lung vessels and registration of chest radiographs.
Conventional machine learning-based methods have been effective in assisting physicians in making accurate decisions and utilized in computer-aided diagnosis for more than 30 years. Recently, deep learning-based methods, and convolutional neural networks in particular, have rapidly become preferred options in medical image analysis because of their state-of-the-art performance. However, the performances of conventional and deep learning-based methods cannot be compared reliably because of their evaluations on different datasets. Hence, we developed both conventional and deep learning-based methods for lung vessel segmentation and chest radiograph registration, and subsequently compared their performances on the same datasets. The results strongly indicated the superiority of deep learning-based methods over their conventional counterparts.


Dissolved inorganic carbon determines the abundance of microbial primary producers and primary production in Tibetan Plateau lakes.
Climate change globally accelerates the shrinkage of inland lakes, resulting in increases in both water salinity and dissolved inorganic carbon (DIC). The increases of salinity and DIC generate contrasting effects on microbial primary producers and primary production, however, their combined effects remain unclear in aquatic ecosystems. We hypothesized that increased DIC mitigates the constraints of enhanced salinity on microbial primary producers and primary production. To test this, we employed isotope labeling and molecular methods to explore primary production and four dominant types of microbial primary producers (form IA, IB, IC and ID) in lakes on the Tibetan Plateau. Results showed that DIC was positively correlated with the abundance of the form IAB and ID microbial primary producers and primary production (all P < 0.001) and offset salinity constraints. Structural equation models elucidated that DIC substantially enhanced primary production by stimulating the abundance of form ID microbial primary producers. The abundance of form ID primary producers explained more variations (14.6%) of primary production than form IAB (6%) and physicochemical factors (6.8%). Diatoms (form ID) played a determinant role in primary production in the lakes by adapting to high DIC and high salinity. Our findings suggest that inland lakes may support higher primary productivity in future climate change scenarios.


Preclinical assessment of abuse liability of drugs.
Studies that are used in preclinical assessment of the liability of a drug to become an abuse problem are reviewed. These studies examine the capacity of a drug to produce physiological dependence or to function as a reinforcer. Studies that examine physiological dependence by assessing whether a drug reverses signs of withdrawal from a standard drug are rapid, reliable and inexpensive methods for determining if a drug produces dependence of a type similar to the standard. However, these techniques will not determine if the drug produces a unique type of dependence. Studies that examine whether a drug functions as a reinforcer have been predictive of whether a drug will be abused in human populations. Attempts to rank order drugs with respect to their efficacy as reinforcers, however, are not predictive of measures of extent of abuse in human populations. Since abuse of drugs in human populations is a function of societal variables in addition to pharmacological factors, it is unlikely that preclinical assessments will ever yield more than qualitative information on abuse liability of drugs.


Automatic identification of activity-rest periods based on actigraphy.
We describe a novel algorithm for identification of activity/rest periods based on actigraphy signals designed to be used for a proper estimation of ambulatory blood pressure monitoring parameters. Automatic and accurate determination of activity/rest periods is critical in cardiovascular risk assessment applications including the evaluation of dipper versus non-dipper status. The algorithm is based on adaptive rank-order filters, rank-order decision logic, and morphological processing. The algorithm was validated on a database of 104 subjects including actigraphy signals for both the dominant and non-dominant hands (i.e., 208 actigraphy recordings). The algorithm achieved a mean performance above 94.0%, with an average number of 0.02 invalid transitions per 48 h.


Association Between Obesity and Circulating Tumor Cells in Early Breast Cancer Patients.
Obesity and the presence of circulating tumor cells (CTCs) before and/or after chemotherapy are associated with poor outcome in breast cancer (BC) patients. The activation of oncogenic pathways in fatty tissue leads to cell proliferation, suggesting a possible link between obesity and CTCs. In the phase III SUCCESS A trial, 3754 patients with early BC were randomized to 3 cycles of fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel with or without gemcitabine. Data of 1088 patients with CTC assessments (CellSearch-System; Menarini Silicon Biosystems, Italy) and body mass index (BMI) measurements both before and after chemotherapy were available. Patients were classified according to the WHO's international definitions as underweight, normal weight, overweight, or obese, and according to their weight-change during chemotherapy into a weight-loss group (> 5% decrease), stable-weight group (≤ 5% weight-change) or weight-gain group (>5% increase). Associations between CTC positivity and, BMI or weight-change group were analyzed using frequency-table methods. At study entry, 47.4% patients were underweight or normal weight, 33.6% were overweight and 18.9% were obese. Before and after chemotherapy, CTCs were detected in 20.1% and 22.6% of patients, respectively. There was no association between CTC positivity and BMI before (P = 0.104) or after (P = 0.051) chemotherapy. Furthermore, there was no association between weight-change group and CTC status before/after chemotherapy (P = 0.332). According to our analysis, the risk factors obesity and prevalence of CTCs are not associated and may represent independent prognostic factors.


Defining foci of cellular alteration in short-term and medium-term rat liver tumor models.
Evaluation of foci of cellular alteration is utilized in short-term and mid-term rat liver models to assess chemicals for potential carcinogenic effects. Such foci are morphologically defined and readily identified by a variety of histological stains. No single morphological marker appears capable of identifying all foci because of their phenotypic heterogeneity. Since most rodent hepatocarcinogens induce an increase in the size and/or the number of foci prior to tumor appearance, foci are believed to be precursors to hepatic tumors. The size, number, phenotype and conversion rate of foci to tumors is chemical dependent. Despite certain limitations, the quantitation of rat liver foci provides a useful means to study the mechanism of action of selected chemicals and assess their carcinogenic potential.


A two-year clinical outcomes study of 400 patients, comparing open surgery and arthroscopy for rotator cuff repair.
The aim of this study was to determine whether there is any significant difference in temporal measurements of pain, function and rates of re-tear for arthroscopic rotator cuff repair (RCR) patients compared with those patients undergoing open RCR. This study compared questionnaire- and clinical examination-based outcomes over two years or longer for two series of patients who met the inclusion criteria: 200 open RCR and 200 arthroscopic RCR patients. All surgery was performed by a single surgeon. Most pain measurements were similar for both groups. However, the arthroscopic RCR group reported less night pain severity at six months, less extreme pain and greater satisfaction with their overall shoulder condition than the open RCR group. The arthroscopic RCR patients also had earlier recovery of strength and range of motion, achieving near maximal recovery by six months post-operatively whereas the open RCR patients took longer to reach the same recovery level. The median operative times were 40 minutes (20 to 90) for arthroscopic RCR and 60 minutes (35 to 120) for open RCR. Arthroscopic RCR had a 29% re-tear rate compared with 52% for the open RCR group (p < 0.001). Arthroscopic RCR involved less extreme pain than open RCR, earlier functional recovery, a shorter operative time and better repair integrity.


ATP dependence of Na+-driven Cl-HCO3 exchange in squid axons.
Squid giant axons recover from acid loads by activating a Na(+)-driven Cl-HCO(3) exchanger. We internally dialyzed axons to an intracellular pH (pH( i )) of 6.7, halted dialysis and monitored the pH(i) recovery (increase) in the presence of ATP or other nucleotides, using cyanide to block oxidative phosphorylation. We computed the equivalent acid-extrusion rate (J(H)) from the rate of pH(i) increase and intracellular buffering power. In experimental series 1, we used dialysis to vary [ATP](i), finding that Michaelis-Menten kinetics describes J (H) vs. [ATP](i), with an apparent V(max) of 15.6 pmole cm(-2 )s(-1) and K (m) of 124 microM. In series 2, we examined ATP gamma S, AMP-PNP, AMP-PCP, AMP-CPP, GMP-PNP, ADP, ADP beta S and GDP beta S to determine if any, by themselves, could support transport. Only ATP gamma S (8 mM) supported acid extrusion; ATP gamma S also supported the HCO (3)(-) -dependent (36)Cl efflux expected of a Na(+)-driven Cl-HCO(3) exchanger. Finally, in series 3, we asked whether any nucleotide could alter J (H) in the presence of a background [ATP](i) of approximately 230 microM (control J (H) = 11.7 pmol cm(-2 )s(-1)). We found J (H) was decreased modestly by 8 mM AMP-PNP (J (H) = 8.0 pmol cm(-2 )s(-1)) but increased modestly by 1 mM ADP beta S (J (H) = 16.0 pmol cm(-2 )s(-1)). We suggest that ATP gamma S leads to stable phosphorylation of the transporter or an essential activator.


Pharmacokinetic and pharmacodynamic interactions in an outpatient maintenance therapy of intravenous heroin users with levomethadone.
The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intravenous heroin users were measured before and, respectively, 1, 2 or 4 hours after oral routine administration and related to the individual additional drug usage (detected by urine drug screening), liver function, side-effects and withdrawal symptoms. In general, accelerated levomethadone metabolism induced by additional misuse of benzodiazepines, barbiturates and opiates resulted in significantly lower plasma levels of the substitute. In particular, high gamma-glutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased beta-globulins resulted in an insufficient body clearance and drug accumulation. Major side effects, such as sweating, were not related to plasma levels whereas withdrawal symptoms like diarrhoea or "feeling cold" correlate with lower plasma concentrations. It is concluded that polydrug misuse in the methadone maintenance therapy creates a vicious circle of enzyme induction, thus increasing "instrumental drug utilization". However, underestimated maintenance dosage may lead to additional drug consumption resulting, finally, in therapeutic failure.


The Inlet and Outlet Ratio: Retrospective and Prospective Study on an Improved Diagnostic Ultrasound Tool for Carpal Tunnel Syndrome.
This study hypothesized that ratios of sonographic cross-sectional areas (CSAs) throughout the median nerve provide a more reliable tool for diagnosing carpal tunnel syndrome (CTS) than a single CSA value. We first tested this hypothesis in a retrospective cohort and subsequently confirmed it in a prospective blinded case-control series. Seventy patients were included in the retrospective study, and 50 patients and matched controls were included for the prospective study. We evaluated 4 CSAs, at the forearm, inlet, tunnel, outlet, and their ratios (Rforearm, Rinlet, Routlet, Routlet forearm) to evaluate compression of the median nerve. All patients underwent nerve conduction studies. For the prospective cohort, Disabilities of the Arm, Shoulder, and Hand scores and Boston Carpal Tunnel Questionnaire scores were evaluated, and ultrasound was performed by 2 examiners for each participant. The Boston and Disabilities of the Arm, Shoulder, and Hand scores showed worse subjective function in patients with CTS than in controls. Three ultrasonography parameters (CSAs at the inlet, Rinlet, and Routlet) correlated significantly with subjective function. Age and Rinlet were significantly correlated with severity of CTS in the nerve conduction studies. In both the retrospective and prospective patient groups, the numbers of CSAs at the inlet and outlet were significantly higher than that of CSAs at the tunnel, whereas in the control group, no such compression was found. Of the single measurements, CSAs at the inlet had the best diagnostic performance with an optimized cutoff of 11.75 mm2. The Rinlet and Routlet ratios performed even better and showed the highest adjusted odds ratios for predicting CTS of all parameters (cutoff Rinlet, 1.25; Routlet, 1.45). Inter-observer correlation was generally high, with better values for single CSAs than for ratios. The 3 CSA measurements of the median nerve and the associated ratios improved diagnostic power for ultrasonography in CTS in our study. Diagnostic I.


A randomized clinical trial of triamcinolone acetonide injection for suppression of inflammation after blepharoptosis surgery.
This study aimed to determine the effectiveness of triamcinolone acetonide in suppressing inflammation after blepharoptosis surgery. The study was designed as prospective, randomized, two medical centers' clinical trial. Thirty-two patients with involutional blepharoptosis of the same degree in both eyelids underwent bilateral transcutaneous levator advancement. At the end of the surgery, 4 mg/0.1 ml of triamcinolone acetonide was injected into a randomly selected upper eyelid. The fellow eyelid was not injected and was used as control. Facial photographs were taken on day 1, week 1, month 1, and month 3, and the degree of inflammation, the margin reflex distance 1 (MRD-1), and levator function (LF) between the two eyelids of each patient were compared. The primary outcome was the selection of the less inflamed eyelid decided by the majority of three individuals unrelated to the study. MRD-1 and LF were analyzed for secondary outcomes. As a result, the injected eyelid was judged to be the less inflamed eyelid in all cases. The MRD-1 in the postoperative period less than 1 month was significantly larger in the injected eyelids than the control eyelids (P<0.03). The postsurgical MRD-1 at month 3, the postsurgical LF at all postsurgical examination times were not statistically different. Adverse complications by the injection, including ptosis, levator dysfunction, increase of the intraocular pressure, and visual disturbance were not observed. In conclusion, a triamcinolone acetonide injection after ptosis surgery is both safe and effective in reducing the early postsurgical inflammation and helpful in an earlier return to a daily routine for the patients.


The mode of production of endotoxin-induced interferon in rabbit tissue cells. I. Development of priming by pretreatment with interferon.
In vitro production of endotoxin-induced interferon in rabbit tissue cell cultures could be enhanced by pretreatment with interferon. The enhancible state developed from the first hr of incubation at 37 C and a maximal priming effect was attained at 6 hr of incubation. Yields of interferon from unprimed cultures were usually 20-200 units/ml. In contrast, the primed cultures constantly yielded 1,000-2,500 units/ml of interferon. The pretreatment with interferon seemed to cause an earlier appearance of detectable interferon and the primed cells became more sensitive to endotoxin. It turned out that 10--30 units/ml of rabbit interferon were enough to develop the maximal priming. Even when cells were pretreated with higher doses of rabbit interferon such as 1.0 x 10(4) - 1.0 x 10(5) units/ml, the same level of priming effect was always observed without diminution. Various types of homologous (rabbit) and heterologous (human and mouse) interferon preparations showed similar dose-dependent enhancement of interferon production in proportion to the antiviral titers of these preparations as tested with RK-13 cells of rabbit origin.


Comparisons of efficacy and tolerance of moricizine with other antiarrhythmic agents in the treatment of chronic ventricular arrhythmias.
Comparative trials of a new drug with standard antiarrhythmic agents are important for establishing relative efficacy and tolerance. For moricizine, such trials have included comparisons with propranolol, disopyramide and quinidine. Furthermore, the Cardiac Arrhythmia Pilot Study compared moricizine in postinfarction patients with encainide and flecainide. These trials show moricizine to be superior in efficacy to a beta blocker (propranolol) and disopyramide and equivalent to quinidine. Although the class IC drugs (encainide and flecainide) showed somewhat greater efficacy in the Cardiac Arrhythmic Pilot Study, they are now known to increase the risk of mortality in postinfarction patients. Moricizine was also shown to be well tolerated in these trials and associated with fewer discontinuations than propranolol, disopyramide and quinidine. Thus, moricizine is a promising new agent when profiled against other drugs frequently used for therapy of chronic ventricular arrhythmias.


Dysregulation of lipid metabolism and appearance of slow myofiber-specific isoforms accompany the development of Wooden Breast myopathy in modern broiler chickens.
Previous transcriptomic studies have hypothesized the occurrence of slow myofiber-phenotype, and dysregulation of lipid metabolism as being associated with the development of Wooden Breast (WB), a meat quality defect in commercial broiler chickens. To gain a deep understanding of the manifestation and implication of these two biological processes in health and disease states in chickens, cellular and global expression of specific genes related to the respective processes were examined in pectoralis major muscles of modern fast-growing and unselected slow-growing chickens. Using RNA in situ hybridization, lipoprotein lipase (LPL) was found to be expressed in endothelial cells of capillaries and small-caliber veins in chickens. RNA-seq analysis revealed upregulation of lipid-related genes in WB-affected chickens at week 3 and downregulation at week 7 of age. On the other hand, cellular localization of slow myofiber-type genes revealed their increased expression in mature myofibers of WB-affected chickens. Similarly, global expression of slow myofiber-type genes showed upregulation in affected chickens at both timepoints. To our knowledge, this is the first study to show the expression of LPL from the vascular endothelium in chickens. This study also confirms the existence of slow myofiber-phenotype and provides mechanistic insights into increased lipid uptake and metabolism in WB disease process.


Leptin treatment in activity-based anorexia.
Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN). In ABA, scheduled feeding together with voluntary access to a running wheel results in increased running wheel activity (RWA), hypophagia, and body weight loss. Previously it was shown that leptin treatment reduced semi-starvation-induced hyperactivity in rats. The present study was performed to confirm and extend this finding, to evaluate leptin's effect on energy balance in ABA. The effects of chronic leptin treatment (intracerebroventricular, 4 microg/day) in ABA rats, ad libitum-fed running rats, and sedentary rats exposed to ad libitum feeding or scheduled feeding were investigated. Leptin treatment decreased RWA in ABA rats. Additionally, leptin treatment reduced food intake and increased energy expenditure by thermogenesis in ABA rats. Ad libitum-fed running/sedentary rats or food-restricted sedentary rats did not reduce activity after leptin treatment, whereas all leptin-treated rats showed hypophagia. Body temperature was slightly increased in leptin-treated food-restricted sedentary rats. Although leptin treatment reduced RWA in ABA rats, it also prevented hypothermia and decreased food intake. Altogether, this resulted in a stronger negative energy balance and body weight loss in leptin-treated ABA rats.


Microvolt T-wave alternans: a review of techniques, interpretation, utility, clinical studies, and future perspectives.
Microvolt T-wave alternans (TWA) testing involves measuring variation in the morphology of the T-wave on an every other beat basis. The magnitude of the variation observed is typically on the order of a few microvolts. Thus in order to detect microvolt TWA, specialized recording and signal processing methods must be employed for reliable measurement. Additionally, microvolt TWA is not generally present at rest even in patients at risk of ventricular tachyarrhythmias and therefore exercise stress, pharmacologic stress, or atrial pacing must be utilized in order to elevate the heart rate. A positive MTWA test is one in which sustained TWA is present with an onset heart rate < or = 110 bpm. With current instrumentation, microvolt TWA represents an inexpensive, convenient non-invasive testing modality. Microvolt TWA has been evaluated prospectively in a variety of patient populations as a means of predicting occurrence of ventricular tachyarrhythmic events and its association with the genesis of ventricular arrhythmias has been demonstrated. Future role of microvolt TWA testing in noninvasive risk stratification is awaiting results of ongoing clinical trials. In this article, we tried to review the techniques, interpretation, indications, clinical studies, and future perspectives of microvolt TWA.


Mortality of Finnish acute psychiatric hospital patients.
The mortality of psychiatric patients is higher than that of the general population. Earlier studies have typically focused on specific diagnostic categories or causes of death. The aim of this study was to assess the overall mortality in acute psychiatric hospital patients covering all diagnostic groups, with special emphasis on substance abuse. The sample consisted of all 18-64-year old patients (n = 3,835) treated or evaluated in the acute wards of the Department of Psychiatry at Tampere University Hospital between the years 1999 and 2003, who were followed-up until the end of the year 2005. We assessed the various causes of death according to background variables in bivariate and multivariate analyses and calculated the standardized mortality ratios (SMRs). During the study period 379 subjects died (9.9% of the sample). Mortality among men was almost twice as high as among women. Of all deaths, 45.6% were considered to be alcohol or drug related. SMR covering all subjects was 6.55. The SMRs for unnatural causes were higher than those for natural causes. The highest SMRs for unnatural causes of death were found in patients with mood disorders and the highest SMRs for natural causes of death in patients with schizophrenia spectrum disorders. Use of coercive measures was associated with increased mortality. Mortality among Finnish psychiatric acute hospital patients is considerably higher than in general population. Excessive alcohol consumption plays a major role in causing excess deaths that could be potentially avoided.


[Increase of calcium-dependent activity of phospholipase C in the myocardium in adaptation of animals to short-term stress effects].
The effect of adaptation of rats to repeated short-term stress exposures was studied on the density and the affinity of alpha 1-adrenoceptors in the heart and on the phospholipase C activity and sensitivity to changes in Ca2+ concentration. It was found that adaptation to stress was accompanied by a desensitization of alpha 1-adrenoceptors and also by an increase in Ca(2+)-dependence of phospholipase C activity in the heart. The role of increased activity of phospholipase C and activated inositol triphosphate-diacylglycerol regulatory cascade is discussed as regard to the previously revealed accumulation of heat shock proteins in the myocardium and to the adaptive protection of the heart.


Development of a multiplex qPCR-based approach for the diagnosis of Dirofilaria immitis, D. repens and Acanthocheilonema reconditum.
Dirofilaria immitis, D. repens and Acanthocheilonema reconditum are the main causative agents of zoonotic canine filariosis. We developed a combined multiplex approach for filaria and Wolbachia detection using the 28S-based pan-filarial and 16S-based pan-Wolbachia qPCRs, respectively, involving a fast typing method of positive samples using triplex qPCR targeting A. reconditum, D. immitis and D. repens, and a duplex qPCR targeting Wolbachia of D. immitis and D. repens. The approach was complemented by a duplex qPCR for the differential diagnosis of heartworms (D. immitis and Angiostrongylus vasorum) and pan-filarial cox1 and pan-Wolbachia ftsZ PCRs to identify other filarial parasites and their Wolbachia, respectively. A total of 168 canine blood and sera samples were used to validate the approach. Spearman's correlation was used to assess the association between filarial species and the strain of Wolbachia. Positive samples for both the heartworm antigen-test after heating sera and at least one DNA-positive for D. immitis and its Wolbachia were considered true positive for heartworm infection. Indeed, the presence of D. repens DNA or that of its Wolbachia as well as A. reconditum DNA indicates true positive infections. The detection limit for Wolbachia and filariae qPCRs ranged from 5 × 10-1 to 1.5 × 10-4 mf/ml of blood. When tested on clinical samples, 29.2% (49/168) tested positive for filariae or Wolbachia DNA. Filarial species and Wolbachia genotypes were identified by the combined multiplex approach from all positive samples. Each species of Dirofilaria was significantly associated with a specific genotype of Wolbachia. Compared to the true positives, the approach showed excellent agreement (k = 0.98-1). Unlike D. immitis DNA, no A. vasorum DNA was detected by the duplex qPCR. The immunochromatographic test for heartworm antigen showed a substantial (k = 0.6) and a weak (k = 0.15) agreements before and after thermal pre-treatment of sera, respectively. The proposed approach is a reliable tool for the exploration and diagnosis of occult and non-occult canine filariosis. The current diagnosis of heartworm disease based on antigen detection should always be confirmed by qPCR essays. Sera heat pre-treatment is not effective and strongly discouraged.


Designed beta-sheet peptides that inhibit proliferation and induce apoptosis in endothelial cells.
Novel beta-sheet-forming peptide 33 mers, beta pep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences or proposed key residues from the beta-sheet domains of interleukin-8 (IL-8), platelet factor-4 (PF4) and bactericidal/permeability increasing protein (B/PI). Since PF4 and B/PI are anti-angiogenic and IL-8 is angiogenic, the library of 30 beta pep peptides was assayed for the ability to affect the growth of endothelial cells. Results indicate that five beta pep peptides (beta pep-2, 7, 8, 21 and 25) demonstrate greater than 50% anti-proliferative activity at 30 micrograms/ml, and one of those (beta pep-25) is similarly active at 10 micrograms/ml. Insight into the mechanism of action was probed in an apoptosis assay. Anti-proliferative activity was found to be correlated with the induction of apoptosis. For example, at 100 micrograms/ml beta pep-25 induces 85% of endothelial cells to undergo apoptosis within 2 days. These effects from beta pep peptides appear to be selective for endothelial cell (EC) because normal cells (fibroblasts and leukocytes) and various tumor cells are not significantly affected at peptide concentrations used in this study. Comparison of active and inactive beta pep sequences allows structure-function relationships to be deduced. Five hydrophobic residues and two lysines appear to be crucial to activity. This research contributes to the development of novel anti-angiogenic peptides.


Combined histochemical and biochemical investigation to the reliability of the demonstration of arylsulphatase activity in cryostat sections.
The reliability of the enzyme histochemical technique, for the demonstration of arylsulphatase activity, using 6-bromo-2-naphthylsulphate as a substrate, is biochemically tested by using partly purified lysosome and microsome preparations from fresh human placenta tissue. Microsomes from frozen placenta with an arylsulphatase deficiency and lysosomes from rat liver, are also investigated. For the biochemical test methods, 6-bromo-2-naphthylsulphate and p-nitrocatecholsulphate are used as substrates. Under similar reaction conditions, varying the pH of the incubation medium and adding inhibitors or activators, the histochemical and biochemical reactions are compared. The results of this study show that the enzyme histochemical technique--except for some limitations--is suitable for the demonstration of microsomal arylsulphatase in cryostat sections.


Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation.
Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique. 17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401. Oxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin (p ≤ 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups (p = 0.04). Oxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner.


Gorham's disease involving the left parietal bone: a case report.
Gorham's disease is a rare bone disease, is characterized by the proliferation of thin-walled vascular channels associated with regional osteolysis. There have been fewer than 150 cases reported in the literature. Shoulder and pelvic region is common site. Skull is the least common site of involvement. We describe a case of a 35-year-old female of Indian origin presented with this rare condition involving her left parietal bone. She was treated successfully with excision of diseased bone and cranioplasty. This is the first reported case in India. We provide a review of the clinical, radiological and pathological diagnosis of this rare condition and describe treatment options.


Comparative evaluation of four competitive/blocking ELISAs for the detection of influenza A antibodies in horses.
New Zealand is free from equine influenza and has never experienced an incursion in its horse population. As part of New Zealand's preparedness to an incursion of an exotic animal disease, it was considered necessary to select the most accurate test for equine influenza (EI) from the array of those available. Four readily available blocking/competitive enzyme-linked immunosorbent assays (ELISA), originally developed and marketed for the detection of antibodies against the avian influenza virus, were evaluated using serum samples from New Zealand non-infected, non-vaccinated horses (n=365), and Australian field infected (n=99) and experimentally infected horses (n=3). Diagnostic specificities (DSP) and diagnostic sensitivities (DSE) were determined as follows: ELISA-1=98.1%/99.0%; ELISA-2=90.1%/99.0%; ELISA-3=98.1%/96.0%; ELISA-4=95.3%/99.0%. For ELISA-1, DSP and DSE results were comparable to previously published data on a larger sample number from Australian horses (Sergeant et al., 2009). Receiver operating characteristics (ROC) and frequency histogram analysis were also performed. The area under the curve (AUC) ranged from 0.996 to 0.979, with ELISA-1 possessing the highest AUC, followed by ELISA-2, ELISA-4 and ELISA-3. Separation of the negative and the positive serum panel was best for ELISA-4, followed by ELISA-2, ELISA-1 and ELISA-3. In three experimentally infected horses, sero-positivity was detected between 7 and 9 days post-infection, with ELISA-4 being most sensitive, followed by ELISA-1, ELISA-2 and ELISA-3. Overall, the four ELISAs performed well in this evaluation but some differences were observed.


Correlation-driven machine learning for accelerated reliability assessment of solder joints in electronics.
The quantity and variety of parameters involved in the failure evolutions in solder joints under a thermo-mechanical process directs the reliability assessment of electronic devices to be frustratingly slow and expensive. To tackle this challenge, we develop a novel machine learning framework for reliability assessment of solder joints in electronic systems; we propose a correlation-driven neural network model that predicts the useful lifetime based on the materials properties, device configuration, and thermal cycling variations. The results indicate a high accuracy of the prediction model in the shortest possible time. A case study will evaluate the role of solder material and the joint thickness on the reliability of electronic devices; we will illustrate that the thermal cycling variations strongly determine the type of damage evolution, i.e., the creep or fatigue, during the operation. We will also demonstrate how an optimal selection of the solder thickness balances the damage types and considerably improves the useful lifetime. The established framework will set the stage for further exploration of electronic materials processing and offer a potential roadmap for new developments of such materials.


Risk factors for acquiring sporadic Campylobacter infection in France: results from a national case-control study.
To better document the risk factors for sporadic Campylobacter infection in France, we conducted a national case-control study from September 2002 to June 2004. Cases with confirmed Campylobacter infection were sampled through the national surveillance laboratory network. Cases and controls who were matched for age, as well as attending physicians, were interviewed about foods consumed, food preparation practices, travel history, contact with cases and animals during the 8 days before the onset of infection, and any antibiotic use occurring during the 30 days before onset. Matched odds ratios [ORs] were calculated using conditional logistic regression and multiple imputation methods. A total of 285 pairs of cases and matched controls were enrolled. "Ate undercooked beef" (OR, 2.86; 95% confidence interval [CI], 1.65-4.95), "ate at restaurant" (OR, 2.20; 95% CI, 1.23-3.93), and "poor utensils hygiene in the kitchen" (OR, 2.12; 95% CI, 1.33-3.37) were the main independent risk factors for infection. Cases infected with a ciprofloxacin-resistant Campylobacter jejuni strain were more likely than controls to have used antibiotics in the month before onset. Good hygiene practices in the kitchen remain a strong recommendation to avoid cross-contamination. However, studies are needed to explore the mechanism of contamination throughout the food chain. The use of antibiotics in humans may favor the development of a resistant infection.


No Increased Risk of Overall Infection in Adults with Moderate-to-Severe Atopic Dermatitis Treated for up to 4 Years with Dupilumab.
Patients with atopic dermatitis (AD) have an increased risk for infections. This open-label extension study, LIBERTY AD OLE, reports the incidence of infections in adults with moderate-to-severe AD treated with dupilumab for up to 4 years. We evaluated infections in adults with moderate-to-severe AD treated with dupilumab 300 mg weekly (qw) or every 2 weeks (q2w; approved regimen) for up to 4 years. Topical corticosteroids (TCS) and calcineurin inhibitors (TCI) were permitted. Exposure-adjusted incidence rates (number of patients with at least one event per 100 patient-years [nP/100 PY]) are reported. Overall, 2677 patients were enrolled and treated with dupilumab: 352 (13.1%) completed up to week 204; 226 patients (8.4%) switched from qw to q2w during the trial. Rates of overall infections (71.27 nP/100 PY), serious and/or severe infections (1.39 nP/100 PY), and infections leading to discontinuation (0.34 nP/100 PY) were consistent with a previous 3-year analysis of this study and low compared with 1-year results in adults with AD treated with placebo + TCS. The cumulative number of patients with treatment-emergent serious or severe infections, non-herpetic or herpetic infections, and total skin infections decreased year-over-year. Limitations included open-label study design with no placebo arm; decreasing sample size at later time points due to sponsor decision to close sites following regulatory approval; qw dosing differs from approved q2w dosing; and patients could use TCS/TCI throughout the study, which may have impacted infection rates. Continuous long-term dupilumab treatment in adults with moderate-to-severe AD is not associated with an increased risk of overall systemic or cutaneous infections. ClinicalTrials.gov Identifier: NCT01949311. Video Abstract INFOGRAPHIC.


Assessment of lesion evolution in experimental autoimmune neuritis by gadofluorine M-enhanced MR neurography.
Experimental autoimmune neuritis (EAN) represents an animal model of acute inflammatory nerve injury mirroring pathophysiological aspects of the human Guillain-Barré syndrome. In the present study, we for the first time visualized the spatiotemporal evolution of autoimmune nerve injury and recovery by magnetic resonance imaging (MRI) by use of the novel micellar magnetic resonance (MR) contrast agent gadofluorine M (Gf). EAN was induced in Lewis rats by T-cell transfer (AT-EAN) leading to severe axonal damage, and Gf was applied intravenously at various disease stages mostly 24 h before MRI. In naive rats, Gf enhancement was present solely in the vascular compartment. In AT-EAN, clinically asymptomatic rats already showed consistent Gf uptake in spinal nerves on day 3, while sciatic nerves were spared. The cauda equina correspondingly exhibited massive T-cell infiltration. Gf enhancement further extended to the plexus lumbosacralis on day 4. On days 5 and 6, the entire peripheral neuraxis from the cauda equina, along the sciatic down to the tibial and peroneal nerves, showed strong Gf enhancement. Spinal and peripheral nerves now exhibited massive inflammation and axonal injury on parallel histological analysis. Gf enhancement persisted in the afflicted nerves until complete recovery and disappeared with a proximodistal gradient. In conclusion, Gf-enhanced MR neurography opens a new avenue for monitoring nerve damage in-vivo during an immune attack.


Prenatally Diagnosed Congenital Ventricular Outpouchings: An Institutional Experience and Review of the Literature.
Congenital ventricular outpouchings (CVOs) are rare congenital heart defects with limited data regarding prognosis and outcomes. We aimed to describe the characteristics, outcomes and factors associated with morbidity and mortality of prenatally diagnosed CVOs using our institutional experience and a review of published cases. A total of 86 cases of prenatally diagnosed CVOs were identified, including 3 from our institution and 83 cases identified from a review of the literature. Fetal and postnatal outcomes were analyzed for each case. Pericardial effusions (44%) and ventricular dysfunction (17%) were the most common associated findings. Excluding cases that resulted in pregnancy termination, mortality was 17%, with the majority (11/13) occurring in the prenatal period. Factors associated with mortality included an outpouching located on the left ventricle, a diagnosis of hydrops fetalis, the presence of a pericardial effusion, and an earlier gestational age at diagnosis. Of those that survived to delivery, 57% remained asymptomatic without the need for intervention, and the outpouching regressed or resolved in an additional 15%. Prenatally diagnosed congenital ventricular outpouchings are a dynamic form of congenital heart disease with a high fetal mortality rate. The outcomes associated with the outpouchings appear to be the most variable in the prenatal period and the first year after birth. Serial prenatal and postnatal evaluations should be performed to evaluate for a change in the characteristics of the outpouching.


[Fahr syndrome discovered following a bacterial meningitis].
Fahr's disease refers to a rare syndrome characterized by symmetrical and bilateral intracranial calcifications. The basal ganglia and dentate nucleus are the most common site of involvement and most cases present extrapyramidal symptoms. This disease is mostly associated with a phosphocalcic metabolism disorder, especially to hypoparathyroidism. The authors report a case of Fahr syndrome (FS) discovered when a young patient with hypocalcemia and bacterial meningitis had a cerebral CT scan disclosing intracerebral calcifications. She fully recovered after both meningitis and hypocalcemia were treated.


Modified bilateral neurovascular cheek flaps: a new technique for reconstruction of difficult and extensive lower lip defect.
The reconstruction of the extensive lip defects after surgical resection of tumors is challenging. Various methods have been used for reconstruction of these defects, however, the ideal functional reconstruction of these lip defects are difficult to achieve. The author describes a modified bilateral neurovascular flaps technique which provide a satisfactory cosmetic appearance and good functional results.


Studies on the relationship between the equilibrium curve of oxyhemoglobin and 2,3-diphosphoglycerate in open-heart surgery.
The relationship between decreased oxygen affinity of hemoglobin and intraerythrocyte 2,3-diphosphoglycerate (2,3 DPG) concentration was confirmed and its existence during the period of open-heart surgery was demonstrated. It is suggested that the trauma sustained by the erythrocytes during their extracorporeal circulation is responsible, in large measure, for the decrease in 2,3 DPG concentration.


Gendered Pattern and Predictors of Tobacco use in India: Evidence from the Second Round of Global adult Tobacco Survey.
India has completed the second round of the Global Adult Tobacco Survey (GATS) to monitor adult tobacco use and progress in tobacco control efforts. This study assesses the gendered pattern of tobacco use and its predictors in the second rounds of GATS. Publicly available GATS-2 (2016-2017) data was analyzed which contains self-reported tobacco use information of ≥15 years Indians (n = 74,037). The independent predictors of "smoking only," "smokeless only," and "dual use" among current male and female tobacco users were assessed using the multinomial regression model. The burden of "smoking only," "smokeless only," and "dual-use" of tobacco were 8.9% (8.74-9.15), 16.69% (16.42-16.96), and 3.89% (3.75-4.03), respectively, in the second round with wide regional variation as well as male dominance in use. Region, age, education, caste, and religion were significantly and consistently associated with different types of tobacco use in both genders. Other contextual predictors of tobacco use were residence, marital status, occupation, awareness, and wealth index (WI). Tobacco use predictors and their gendered patterns are contextual. Monitoring the predictors for tobacco use, which may change over time, should be given priority in the national tobacco control program.


Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low. Effect of pravastatin sodium in combination with cholestyramine.
We investigated the possibility that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed or even regressed when their serum cholesterol levels were kept extremely low. Ten-month-old WHHL rabbits were divided into 3 groups, i.e. control rabbits, sacrificed at age 10 months, and placebo and treated rabbits, sacrificed at age 18 months. The treated rabbits were given pravastatin sodium (50 mg/kg/day), an HMG-CoA reductase inhibitor, in combination with cholestyramine (2% in diet), a bile acid sequestrant, for 36 weeks. The serum cholesterol levels and atherogenic lipoproteins in the treated group were markedly reduced, by about 60% (P less than 0.005 and P less than 0.001). Consequently, the degrees of both coronary and aortic atherosclerosis in the treated group were significantly reduced compared with the placebo group, and were almost the same as in the control group. The histopathological findings supported the above results. In addition, the incidence and degree of xanthomas in digital joints in the treated group were significantly reduced. These results suggest that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed by keeping their serum cholesterol levels extremely low by the combination drug treatment.


From disorganized capitalism to transnational fine tuning? Recent trends in wage development, industrial relations, and 'work' as a sociological category.
The disorganization thesis concentrates upon globalization and market dynamics, which are believed to trigger the breakdown of any kind of institutional structures. The diversity of capitalism approach, by contrast, places much emphasis on the persistence of distinct paths of national economies. Referring to comparative data from the OECD and other sources it is shown that some variables indicate a robustness of national styles of capitalism. Others hint at resemblance: e.g. there is a striking synchronization of the overall and sectoral wage development, there is a significant decrease in industrial disputes, and the class composition tends to become more similar. A move beyond the disorganization thesis and diversity of capitalism approach is suggested. Special attention should be paid to the profound impacts of transnational institutions and knowledge carriers in the form of experts and guidelines.


Differential expression of genes involved in the degeneration and regeneration pathways in mouse models for muscular dystrophies.
The genetically determined muscular dystrophies are caused by mutations in genes coding for muscle proteins. Differences in the phenotypes are mainly the age of onset and velocity of progression. Muscle weakness is the consequence of myofiber degeneration due to an imbalance between successive cycles of degeneration/regeneration. While muscle fibers are lost, a replacement of the degraded muscle fibers by adipose and connective tissues occurs. Major investigation points are to elicit the involved pathophysiological mechanisms to elucidate how each mutation can lead to a specific degenerative process and how the regeneration is stimulated in each case. To answer these questions, we used four mouse models with different mutations causing muscular dystrophies, Dmd (mdx), SJL/J, Large (myd) and Lama2 (dy2J) /J, and compared the histological changes of regeneration and fibrosis to the expression of genes involved in those processes. For regeneration, the MyoD, Myf5 and myogenin genes related to the proliferation and differentiation of satellite cells were studied, while for degeneration, the TGF-β1 and Pro-collagen 1α2 genes, involved in the fibrotic cascade, were analyzed. The result suggests that TGF-β1 gene is activated in the dystrophic process in all the stages of degeneration, while the activation of the expression of the pro-collagen gene possibly occurs in mildest stages of this process. We also observed that each pathophysiological mechanism acted differently in the activation of regeneration, with distinctions in the induction of proliferation of satellite cells, but with no alterations in stimulation to differentiation. Dysfunction of satellite cells can, therefore, be an important additional mechanism of pathogenesis in the dystrophic muscle.


The effect of self-care counseling on health practices of adolescent pregnant women: a randomized controlled trial.
Pregnancy and childbirth at an early age are associated with potential risks and complications for adolescent mothers. Health practices are behaviors that can positively affect maternal and fetal health. This study aimed to investigate the effects of self-care counseling on health practices (main outcome), attitudes towards motherhood and pregnancy, and pregnancy symptoms (secondary outcomes) in adolescent pregnant women. In this randomized controlled trial, 54 adolescent pregnant women admitted to the health centers of Bukan, Iran in 2020 were enrolled. Using randomized block design, the participants were randomly assigned to the counseling (n=27) and control (n=27) groups. Those in the intervention group attended 6 self-care group counseling sessions. The Health Practices Questionnaire-II (HPQ-II), Attitudes towards Motherhood and Pregnancy Questionnaire (PRE-MAMA), and Pregnancy Symptoms Inventory (PSI) were completed before and 4 weeks after the intervention. Based on the results of ANCOVA with controlled baseline values, after the intervention the mean health practices score of the participants in the intervention group was significantly higher than those in the control group (adjusted mean difference (AMD): 36.34; 95% CI: 34.69 to 37.98; P<0.001). The mean attitude towards motherhood score of the participants in the intervention group was significantly higher than those in the control group (AMD: 1.01; 95% CI: 0.06 to 1.96; P= 0.038). However, the mean pregnancy symptoms score of the participants in the intervention group was partially lower than those in the control group (AMD: -1.37; 95% CI: -4.32 to 1.58; P= 0.354). Self-care counseling sessions can improve the health practices of adolescent pregnant women and enhance their attitudes towards maternal role and pregnancy. Therefore, planners are recommended to organize self-care counseling programs for all pregnant women, especially for adolescent pregnant women. Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N54 . Date of registration: 2/3/2020. URL: https://en.irct.ir/user/trial/42571/view ; Date of first registration: February 3, 2020.


[One-stage reconstruction of oral and maxillofacial soft tissue defect by using forearm free flap].
To study technique of one-stage reconstruction of oral and maxillofacial soft tissue defect by using forearm free flap. The microsurgery procedure was used in the treatment of 4 oral cancer patients with oral and maxillofacial soft tissue defect after surgery. The forearm free flap was survived, for 4-18 months the oral function was well, and the appearance was satisfactory. This is a good approach to the reconstruction of oral and maxillofacial soft tissue defect by using forearm free flap technique.


High density lipoprotein alterations induced by bezafibrate in healthy male volunteers.
The alterations of HDL structure and metabolism induced by bezafibrate administration were studied in healthy male volunteers. As usually observed in hyperlipaemic patients, bezafibrate induced a decrease of the plasma concentrations of apo B and LDL-cholesterol and an increase of that of HDL-cholesterol. Analysis of HDL by gradient polyacrylamide gel electrophoresis revealed that bezafibrate administration resulted in a change of the particle size distribution likely suggesting a drop of the HDL2/HDL3 ratio. This was accompanied by a 30% enhancement of the plasma concentration of apoprotein A-II, while that of apoprotein A-I remained unchanged. These data suggest an increase of the HDL concentration, preferentially in the HDL3 subfraction. In spite of these HDL alterations, there was no evidence of change in the three stages of the reverse pathway of cholesterol, since bezafibrate did not induce any significant alteration in the in vitro properties of plasma with respect to (a) cholesterol transport from cultured cells, (b) cholesterol esterification, and (c) transfer of cholesteryl esters from HDL to VLDL-LDL.


Effect of active arm swing to local dynamic stability during walking.
Arm swing is an essential component in regulating dynamic stability of the whole body during walking, while the contribution of active arm swing to local dynamic stability of different motion segments remains unclear. This study investigated the effects of arm swing under natural arm swing condition and active arm swing condition on local dynamic stability and gait variability of the trunk segments (C7 and T10 joint) and lower extremity joints (hip, knee and ankle joint). The local divergence exponents (λs) and mean standard deviation over strides (MeanSD) of 24 young healthy adults were calculated while they were walking on treadmill with two arm swing conditions at their preferred walking speed (PWS). We found that in medial-lateral direction, both λs and MeanSD values of the trunk segments (C7 and T10 joint) in active arm swing condition were significantly lower than those in natural arm swing condition (p<0.05), while no significant difference of λs or MeanSD in lower extremity joints (hip, knee and ankle joint) was found between two arm swing conditions (p>0.05, respectively). In anterior-posterior and vertical direction, neither λs nor MeanSD values of all body segments showed significant difference between two arm swing conditions (p>0.05, respectively). These findings indicate that active arm swing may help to improve the local dynamic stability of the trunk segments in medial-lateral direction.


Evaluation of CCNU and misonidazole in the treatment of advanced colorectal cancer.
Eighteen adult colorectal cancer patients, previously untreated with systemic chemotherapy, were given CCNU and MISO. One patient had an excellent partial response of pulmonary metastases, but the overall response rate was only 6%. Gastrointestinal toxicity was modest, hematologic toxicity was similar to what would have been predicted for CCNU alone, and there was no neurotoxicity detected. This Phase II study demonstrates that these two agents can be administered safely, but have no advantage over CCNU alone.


Serotonergic changes in specific areas of rat brain associated with activity--stress gastric lesions.
To study serotonergic involvement in the development of gastric lesions following activity wheel stress, three groups of rats (gastric lesions, no gastric lesions, and home--cage controls) were killed following exposure to the experimental procedures. The brains were dissected into eight specific areas and subjected to analyses for serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) using high performance liquid chromatography with EC detection. Lower levels of 5-HT were found in the midbrain, cortex, and hippocampus of rats with gastric lesions compared to either the no lesion group, subjected to shorter periods of activity--stress, or the home--cage control group. Levels of 5-HT and 5-HIAA were elevated in the pons/medulla oblongata of both the lesion and the no lesion groups compared to the home--cage controls. Corticosterone levels in blood were also significantly elevated in the lesion group. These data on serotonin changes in the CNS suggest a possible role for this neurotransmitter in stress-induced gastric pathology.


Molecular cytogenetics: applications in clinical genetics.
To illustrate the advantage of fluorescence in situ hybridization (FISH) in clinical genetics, we have chosen six clinical cases from our routine laboratory where we have used molecular cytogenic techniques to optimise the cytogenetic analysis. Using centromere-specific DNA probes and whole chromosome DNA libraries either obtained from somatic cell hybrids or generated from flow-sorted chromosomes, we have been able to identify small marker chromosomes, chromosomal duplications and inversions, to determine the ploidy in interphase nuclei, and to characterize subtle chromosomal translocations. We conclude that molecular cytogenetics is a valuable technique that should be used as a supplement to conventional cytogenetics to reduce the number of unresolved karyotypes in clinical genetics.


Mutagenicity and cytotoxicity of 2-methoxyethanol and its metabolites in Chinese hamster cells (the CHO/HPRT and AS52/GPT assays).
2-Methoxyethanol (ethylene glycol monomethyl ether) (EGME), is one of the most commonly used solvents for industrial and consumer products. Although the solvent has been shown to be a reproductive toxin the genotoxic activities of EGME especially its metabolites, have not been adequately investigated. The mutagenicity and cytotoxicity of EGME and its major metabolites, methoxyacetaldehyde (MALD) and methoxyacetic acid (MAA) in Chinese hamster ovary (CHO) cells were therefore examined by us. We have determined the mutagenicity of these compounds at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in CHO-K1-BH4 cells (CHO/HPRT assay) and the xanthine-guanine phosphoribosyl transferase (gpt) locus in CHO AS52 cells (AS52/GPT assay). The results show that these chemicals are not mutagenic to the hprt locus in CHO-K1-BH4 cells either with or without rat liver S9 mix as the metabolic activating system. With AS52 cells, only MALD is mutagenic in the absence of S9. It induced a dose-dependent mutagenic response. A dose-dependent cytotoxicity was induced by all compounds in both cell lines. MALD is the most and EGME is the least cytotoxic compounds. Our study shows that a metabolite of EGME, MALD, is highly cytotoxic and likely induces deletion-type mutations in AS52 cells. The genotoxic effect of EGME is, therefore, dependent upon its metabolism and its detection is dependent upon the assays used.


Direct diagnosis of scrub typhus by full-length 16S ribosomal RNA gene analysis using Oxford Nanopore sequencing.
Scrub typhus (caused by Orientia tsutsugamushi) is a neglected and underdiagnosed disease due to its non-specific clinical presentation and challenging diagnostics. We document the first study of direct diagnosis of scrub typhus from the blood sample of a patient by full-length 16S ribosomal RNA gene amplicon analysis using Oxford Nanopore sequencing.


The influence of biochar position in a leach bed system anaerobically digesting chicken litter.
As a consequence of the rapidly growing poultry industry, chicken litter is becoming an abundant and problematic waste. Anaerobic digestion of chicken litter can mitigate environmental issues while producing valuable by-products. Recent studies have shown that leach bed reactor (LBR) systems are suitable for processing chicken litter and that anaerobic digestion can be enhanced using biochar. This study investigates the influence of biochar position within an LBR system on anaerobic digestion of chicken litter. Compared to a system without biochar, application of biochar in both the LBR (mixed in with the feedstock or as a layer below the feedstock) and coupled leachate tank (LT) increased methane yield by 6 to 8% at 51 days and accelerated VFA degradation and methane production. More significant differences in methane yield were observed at shorter solid retention times. Biochar mixed in feedstock in addition to a filter in the LT performed best in terms of both methane and hydrogen sulfide production, with a 77% reduction in hydrogen sulfide yield and hydrogen sulfide contents maintained below 500 ppm. The enhanced rates of VFA degradation and methane production when applying biochar in both reactors corresponds with observed differences in the methanogen population. Biochar application in both reactors increased the abundance of Methanobacteriales in digestate and Methanosarcinaceae in leachate compared to the control. Microbial attachment and activity on biochar also increased when mixed in feedstock. Increased diversity of the methanogen population throughout the system, as well as increased activity on biochar, may have facilitated the syntrophic relationship between acetogenic bacteria and methanogens, thus accelerating VFA degradation and methane production. These results suggest mixing biochar in feedstock, in addition to a biochar filter in the LT, to enhance anaerobic digestion of chicken litter in this system.


Structural, Optical, and Electrical Properties of Hafnium-Aluminum-Zinc-Oxide Films Grown by Atomic Layer Deposition for TCO Applications.
ZnO is a widely studied material that exhibits versatile doping possibilities. Most research presents singly doped ZnO, leaving the potential of codoping unexplored. Within this study, hafnium-aluminum codoped zinc oxide (HAZO) thin films were grown on a glass substrate using the atomic layer deposition technique at 200 °C. A comprehensive analysis of the surface morphology and electrical and optical properties of the samples was conducted for varying the Al/Hf doping ratio. X-ray diffraction studies showed that the obtained films are polycrystalline, exhibiting a preferential growth direction along the (1 0 0) plane without any detectable precipitates. Moreover, the electrical measurements of HAZO films revealed that they exhibit lower resistivity (∼9.5 × 10-4 Ωcm) than the commonly used aluminum zinc oxide films (AZO). This improvement can be primarily attributed to the promotion of the n-type carrier concentration to 4.45 × 1020 cm-3 while maintaining a mobility value equal to 14.7 cm2/Vs. The doping also influences the optical properties of the material by widening the band gap and changing the refractive index, as observed by spectroscopy and ellipsometry studies. These findings highlight the potential of proposed HAZO thin films for future applications in electronic devices utilizing transparent conducting oxides.


A bubble-mediated intelligent microscale electrochemical device for single-step quantitative bioassays.
An intelligent microscale electrochemical device (iMED) for one-step, quantitative and multiplexed electrochemical detection of biomarkers for infectious diseases and tumors is developed. A "plug-in-cartridge" technology is introduced and adapted for use in screen-printed electrodes (SPEs) in electrochemical devices. Using this iMED, biomarkers for two types of tumors and one infectious disease are detected at sub-ng/mL levels in less than 30 min.


Nasal septal perforation from bevacizumab: a discussion of outcomes, management, and pharmacovigilance.
To date, the published literature describes 18 reports of nasal septal perforation in cancer patients with the administration of bevacizumab. This complication was detected during post-marketing surveillance of bevacizumab. How should patients who develop this complication be managed? This discussion summarizes suggestions for management of bevacizumab-associated nasal septal perforation and, as relevant to healthcare providers, discusses some of the practical aspects of post-marketing pharmacovigilance.


Acyl coenzyme A: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum and Aspergillus nidulans.
A study of the final stages of the biosynthesis of the penicillins in Penicillium chrysogenum has revealed two types of enzyme. One hydrolyses phenoxymethyl penicillin to 6-aminopenicillanic acid (6-APA). The other, also obtained from Aspergillus nidulans, transfers a phenylacetyl group from phenylacetyl CoA to 6-APA. The acyltransferase, purified to apparent homogeneity, had a molecular mass of 40 kDa. It also catalyses the conversion of isopenicillin N (IPN) to benzylpenicillin (Pen G) and hydrolyses IPN to 6-APA. In the presence of SDS it dissociates, with loss of activity, into fragments of ca 30 and 10.5 kDa, but activity is regained when these fragments recombine in the absence of SDS.


An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis.
The epithelial-mesenchymal transition (EMT) and primary ciliogenesis induce stem cell properties in basal mammary stem cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis upon entry into intermediate EMT states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote ubiquitination and inactivation of a transcriptional repressor, GLIS2, which localizes to the ciliary base. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the mammary tumor–initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC stemness, mammary gland development, and claudin-low breast cancer formation.


Myelography for severe thoracolumbar injuries.
Myelography was carried out on 30 patients with severe thoracolumbar injuries. In ten cases the myelography gave specific information which could not have been obtained by any other method. Myelography made within 1 month of trauma gave specific information in only one of 16 cases. Late myelography, in nine of 14 cases, provided valuable specific information about the type of cord atrophy, dorsal scar formation and transsection of the cord.


Editorial Commentary: Leveraging the Literature: What Can a Half-Century's Worth of Studies Tell Us About Recurrent Instability Following Primary Shoulder Dislocation?
A benefit of systematic review (SR) research methods is that well-performed reviews allow authors and readers to identify weaknesses and variability in the orthopaedic literature. An SR on the topic of recurrence rates after conservative treatment of first-time shoulder dislocation provides an excellent example. The example reviews studies covering more than one-half century of time and employing varying methodological designs; the results include estimates of recurrence of shoulder dislocation ranging widely (from 4% to 94.5%). These methods and results raise concerns over the comparability of the studies included in the review. Fortunately, the authors are careful in their use of these data. Although there is little doubt that the review includes a heterogeneous group of articles (and patients), there is value in knowing that much of the variability in the reported rate of recurrence could be related to variations in patient age. Future research, building on more than 50 years of study, would be wise to consider the rate of recurrence among specific age groups. This seems a worthy finding and demonstrates the value of SR methods and the importance of critical analysis of research data.


Immunomodulatory role of PPAR-gamma in alveolar macrophages.
The lung is constantly exposed to inhaled pathogens and toxins yet totally dependent on the integrity of a delicate alveolar-capillary interface for its function. Much of the balance between protection and collateral damage rests on the alveolar macrophage, which not only phagocytoses inhaled particles but also modulates the activity of both innate and acquired immune systems to limit unnecessary or exuberant inflammation. In its resting state, the alveolar macrophage secretes anti-inflammatory mediators while limiting antigen presentation to the adaptive immune system. The alveolar macrophage's state of activation is regulated by a variety of factors, including the activity of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). Peroxisome proliferator-activated receptor gamma agonists reduce the ability of inflammatory stimuli to activate the alveolar macrophage while simultaneously stimulating phagocytosis of both opsonized and unopsonized particles, via the Fcgamma and CD36 receptors, respectively. All known endogenous PPAR-gamma ligands are fatty acid derivatives, and macrophage-specific knockout of the enzyme that converts esterified fatty acids to free fatty acids results in severe lung inflammation. Peroxisome proliferator-activated receptor gamma expression is reduced in alveolar macrophages from patients with pulmonary sarcoidosis and alveolar proteinosis, suggesting that the deficiency may play a role in pathogenesis of these diseases. In summary, these observations point to PPAR-gamma in the context of the alveolar macrophage as a crucial factor in limiting excessive and possibly injurious inflammation in the lung.


The Incidence and Risk Factors for Lumbar or Sciatic Scoliosis in Lumbar Disc Herniation and the Outcomes after Percutaneous Endoscopic Discectomy.
Some patients with lumbar herniated intervertebral disc disease (HIVD) suffer from both pain and lateral shift or trunk list. In addition to pain, patients have concerns regarding whether trunk list is reversible. Surgical treatment is performed when pain is intractable to conservative management, but a reversal of trunk list is an incidental outcome. Percutaneous lumbar endoscopic discectomy (PELD) is one of the surgical treatment options for lumbar HIVD, but no results concerning its effect on trunk list have been reported. The objectives of the present study were to determine the incidence of, and risk factors for, trunk list scoliosis or lateral shift and to report the outcomes of trunk list after PELD. Retrospective case study. IRB No. H 1111-025-384 SETTING; University medical Center, Seoul, Korea. We selected 164 patients who were less than 60 years old, complained of unilateral leg pain, and underwent PELD. We measured the maximum trunk shift from the central sacral vertical line (CSVL-max) on preoperative whole spine radiographs and classified trunk list as CSVL-max ≥ 10 mm. CSVL-max was measured on serial radiographs taken at one, 3, 6, and 12 months postoperatively in patients with trunk list. Twenty-nine patients (17.9%) had trunk list (M:F=10:19; mean age, 37.1 ± 11.24 years). Female gender (OR 4.28; 95% CI, 1.49-12.3) and HIVD at L4-5 (OR 5.6; 95% CI, 1.8-16.7) were risk factors for trunk list. Trunk list was normalized (CSVL-max < 10 mm) in 15 (52%) patients after PELD, and the median time for normalization was 3-6 months. Prognostic factors for the recovery of trunk list were not identified. Selection bias should be considered in interpreting these results. Trunk list, scoliosis or lateral shift, was observed in 18% of the patients at the time of surgery. Female gender and L4-5 disc herniation were risk factors for trunk list. Trunk list was reversible in more than 50% of patients within 6 months of PELD.