Hypercapnic ventilatory response of anesthetized female rats subjected to neonatal maternal separation: insight into the origins of panic attacks?
Neonatal maternal separation (NMS) is a form of stress that interferes with the regulation of the stress response, an effect that predisposes to the emergence of panic and anxiety related disorders. We previously showed that at adulthood, awake female (but not male) rats subjected to NMS show a hypercapnic ventilatory response (HCVR; 5% CO2) that is 63% greater than controls (Genest et al., 2007). To understand the mechanisms underlying the sex-specific effects of NMS on the ventilatory response to CO2, we used two different anesthetized female rat preparations to assess central CO2 chemosensitivity and contribution of sensory afferents (stretch receptors and peripheral chemoreceptors) that influence the HCVR. Data show that anesthesia eliminated the respiratory phenotype observed previously in awake females and CO2 chemosensitivity did not differ between groups. Finally, the assessment of the ovarian hormone levels across the oestrus cycle failed to reveal significant differences between groups. Since anesthesia did not affect the manifestation of NMS-related respiratory dysfunction in males (including the hypercapnic ventilatory response) (Kinkead et al., 2005; Dumont and Kinkead, 2010), we propose that the panic or anxiety induced by CO2 during wakefulness is responsible for enhancement of the HCVR in NMS females.


Laser-mediated cell ablation during post-implantation mouse development.
Laser-mediated cell ablation is a powerful tool that has been used to understand cell fate in a variety of externally developing organisms but has not been used during mammalian post-implantation development. We describe a method pairing laser ablation with murine embryo culture and establish parameters that can be used to precisely ablate cells in the selected field with minimal disruption to adjacent cells or the underlying cell matrix. Ablation of a large domain of endoderm, followed by ~1 day of culture results in a phenotypically normal embryo and gut tube, indicating that laser ablation is compatible with normal development. We next focused on one of the three precursor populations that have been shown to produce the liver bud. Ablations of a single progenitor domain result in a unilateral delay in the liver bud while the contralateral side is unaffected. We demonstrate that laser ablation is a specific and useful technique for studying cell fate in the mouse embryo. This method represents a powerful advance in developmental studies in the mouse and can be used to provide information on the specification of organs, differentiation, cell migration, and vital tissue interactions during development.


Acerentulus tortii sp. nov. from Greece (Protura: Acerentomidae).
A new species of Protura, Acerentulus tortii sp. nov., from the island of Euboea, central Greece, is described and illustrated. The new species belongs to the A. cunhai species group, based on a short foretarsal sensillum a not reaching seta γ3, and sensilla b and c subequal in length. The most similar species are A. christensoni (Ewing, 1940) and A. rafalskii Szeptycki, 1979), from which A. tortii sp. nov. differs by the porotaxy of sternite III and the lengths of various foretarsal sensilla.


[Postmortem MSCT Analysis and Identification of Fall from Height: One Case Report].
To explore the application value of postmortem multi-slice spiral computed tomography (MSCT) in cases of fall from height through observing and analyzing the injury features of the fall and reconstructing the process of the fall based on the the above procedure. One real fatal case due to fall from height was fully examined using MSCT and three-dimensional reconstruction technique. Analyzing the manner and cause of death through combination of MSCT and systemic autopsy was also implemented. The differences between autopsy and MSCT in getting information of injuries were compared. Fractures involving multiple body regions and liver rupture were found through MSCT and three-dimensional reconstruction. The autopsy got the same results with imageological examination. The case of death was deduced to be fall leading to systemic polytrauma. Application of MSCT can be used as the complimentary for traditional autopsy in the analysis of injury manner of fall from height.


GP73 promotes epithelial-mesenchymal transition and invasion partly by activating TGF-β1/Smad2 signaling in hepatocellular carcinoma.
The transforming growth factor-β1 (TGF-β1) signaling pathways contribute to cell metastasis and epithelial-mesenchymal transition (EMT). Golgi protein 73 (GP73), a type II transmembrane protein in the Golgi apparatus, was initially regarded as a potential biomarker for the diagnosis of hepatocellular carcinoma (HCC). Recently, it was reported that GP73 acts as a key oncogene by promoting HCC growth and metastasis. However, the role of GP73 in metastasis, especially when involving signaling pathways, is uncertain. Here, we report that GP73, which is upregulated in HCC tissues and cell lines, is associated with tumor size, tumor node metastasis stage, distant metastasis and vascular invasion. The ectopic overexpression of GP73 increased HCC cell invasion, EMT and metastasis both in vitro and in vivo. Conversely, GP73 knockdown inhibited invasion and EMT. Moreover, GP73 enhanced p-Smad2 and p-Smad3 levels by mediating TGF-β1, thus leading to the promotion of EMT and invasion in HCC cells. In contrast, we used SB431542 (SB) to repress p-Smad2 and p-Smad3 expression, which resulted in a reversion of EMT. Furthermore, when the TGF-β1/Smad pathway was blocked, upregulation of GP73 still caused an enhanced EMT and invasion, and downregulation of GP73 resulted in a decreased in EMT and invasion. In clinical HCC samples, GP73 positively correlated with TGF-β1/Smad2, which was upregulated in HCC. Taken together, our findings highlight the important role of GP73 in regulating EMT and metastasis in HCC partly by targeting TGF-β1/Smad2 signaling, suggesting that GP73 may represent a novel potential therapeutic target and prognostic marker for the treatment and diagnosis of HCC.


The curse of experiencing and committing violence as a criminal recidivism predictor: A comparison between female forensic psychiatric patients with severe mental disorders and substance use disorder.
Violence occurs frequently in the life of forensic psychiatric patients, both as active aggression and in the form of victimization. Undoubtedly, these incidents shape personality, behavior, and affect the ability to interact adequately socially. Thus, such experiences may influence criminal recidivism and serve as forensic psychiatric/psychological predictors upon hospital discharge. Hence, this study aimed at characterizing two distinct female forensic psychiatric patient populations (nonsubstance use mental disorders [n = 110] versus substance use disorder [n = 415]) regarding their active and passive violent experiences as well as contextualizing these with their individual crime recidivism rates. The analysis followed a record-based, retrospective approach. While both groups experienced aggression throughout childhood and youth equally often, substance use disorder patients were significantly more often exposed to violence during adulthood. On the other hand, severely mentally ill patients tended to react more often with violence during their hospital confinement. However, regarding their violent recidivism rate, no intergroup effects were observed. Finally, within the addicted group, a violent index crime as well as physical aggression during hospital confinement increased the odds for violent reoffending by approximately 2.4-fold (95% confidence interval 1.3-4.5) and 2.5-fold (95% confidence interval 1.1-5.9), respectively. In summary, these findings underline the importance of active aggression rather than victimization as an influencing factor on resocialization especially in a substance use disorder patient population.


First observation of a potential non-invasive breath gas biomarker for kidney function.
We report on the search for low molecular weight molecules-possibly accumulated in the bloodstream and body-in the exhaled breath of uremic patients with kidney malfunction. We performed non-invasive analysis of the breath gas of 96 patients shortly before and several times after kidney transplantation using proton-transfer-reaction mass spectrometry (PTR-MS), a very sensitive technique for detecting trace amounts of volatile organic compounds. A total of 642 individual breath analyses which included at least 41 different chemical components were carried out. Correlation analysis revealed one particular breath component with a molecular mass of 114 u (unified atomic mass units) that clearly correlated with blood serum creatinine, which is the currently accepted marker for assessing the function of the kidney. In particular, daily urine production showed good correlation with the identified breath marker. An independent set of seven samples taken from three patients at the onset of dialysis and three controls with normal kidney function confirmed a significant difference in concentration between patients and controls for a compound with a molecular mass of 114.1035 u using high mass resolving proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS). A chemical composition of C7H14O was derived for the respective component. Fragmentation experiments on the same samples using proton-transfer-reaction triple-quadrupole tandem mass spectrometry (PTR-QqQ-MS) suggested that this breath marker is a C7-ketone or a branched C7-aldehyde. Non-invasive real-time monitoring of the kidney function via this breath marker could be a possible future procedure in the clinical setting.


MS2Tox Machine Learning Tool for Predicting the Ecotoxicity of Unidentified Chemicals in Water by Nontarget LC-HRMS.
To achieve water quality objectives of the zero pollution action plan in Europe, rapid methods are needed to identify the presence of toxic substances in complex water samples. However, only a small fraction of chemicals detected with nontarget high-resolution mass spectrometry can be identified, and fewer have ecotoxicological data available. We hypothesized that ecotoxicological data could be predicted for unknown molecular features in data-rich high-resolution mass spectrometry (HRMS) spectra, thereby circumventing time-consuming steps of molecular identification and rapidly flagging molecules of potentially high toxicity in complex samples. Here, we present MS2Tox, a machine learning method, to predict the toxicity of unidentified chemicals based on high-resolution accurate mass tandem mass spectra (MS2). The MS2Tox model for fish toxicity was trained and tested on 647 lethal concentration (LC50) values from the CompTox database and validated for 219 chemicals and 420 MS2 spectra from MassBank. The root mean square error (RMSE) of MS2Tox predictions was below 0.89 log-mM, while the experimental repeatability of LC50 values in CompTox was 0.44 log-mM. MS2Tox allowed accurate prediction of fish LC50 values for 22 chemicals detected in water samples, and empirical evidence suggested the right directionality for another 68 chemicals. Moreover, by incorporating structural information, e.g., the presence of carbonyl-benzene, amide moieties, or hydroxyl groups, MS2Tox outperforms baseline models that use only the exact mass or log KOW.


Laparoscopic Suturing as a Barrier to Broader Adoption of Laparoscopic Surgery.
Laparoscopic surgery is increasingly replacing the open procedure because of its many patient-related benefits that are well aligned with policies and programs that seek to optimize health system performance. However, widespread adoption of laparoscopic surgery has been slow, in part, because of the complexity of laparoscopic suturing. The objective of this study was to review the clinical and economic impacts of laparoscopic suturing in key procedures and to assess its role as a barrier to the broader adoption of laparoscopic surgery. A medical literature search of MEDLINE, EMBASE, and BIOSIS from January 2010 through June 2016 identified 47 relevant articles. Laparoscopic suturing and intracorporeal knot tying may result in extended surgical time, complications, and surgeon errors, while improving patient quality of life through improved cosmesis, diet toleration, and better bowel movements. Despite advancement in surgical techniques and the availability of newer surgical tools, the complexity of laparoscopic suturing continues to be a barrier to greater adoption of MIS. The results of the study underscore the need for development of proficiency in laparoscopic suturing, which may help improve patient outcomes and reduce healthcare costs.


Comparison of proanthocyanidins in commercial antioxidants: grape seed and pine bark extracts.
The major constituents in grape seed and pine bark extracts are proanthocyanidins. To evaluate material available to consumers, select lots were analyzed using high-performance liquid chromatography, gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), gel permeation chromatography (GPC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Atmospheric pressure chemical ionization (APCI) LC/MS was used to identify monomers, dimers, and trimers present. GC/MS analyses led to the identification of ethyl esters of hexadecanoic acid, linoleic acid, and oleic acid, as well as smaller phenolic and terpene components. The GPC molecular weight (MW) distribution indicated components ranging from approximately 162 to approximately 5500 MW (pine bark less than 1180 MW and grape seed approximately 1180 to approximately 5000 MW). MALDI-TOF MS analyses showed that pine bark did not contain oligomers with odd numbers of gallate units and grape seed contained oligomers with both odd and even numbers of gallate. Reflectron MALDI-TOF MS identified oligomers up to a pentamer and heptamer, and linear MALDI-TOF MS showed a mass range nearly double that of reflectron analyses.


Regret of treatment decision and its association with disease-specific quality of life following prostate cancer treatment.
We examined decisional regret among prostate cancer patients and its association with disease-specific quality of life. Patients (N = 793) completed questionnaires at diagnosis, at 6 months, and 12 months thereafter. Although levels of decisional regret were low, regret increased significantly between 6 and 12 months after diagnosis. The increase was substantial for patients treated with prostatectomy compared to patients treated with external beam radiation or brachytherapy. Cross-sectional, significant, and positive associations among regret, activity limitation attributed to urinary dysfunction, and bother with sexual and urinary dysfunction emerged. Longitudinally, the change in the level of regret was significantly associated with treatment modality and with the change in bother with sexual dysfunction over the first 6 months after diagnosis. Extensive discussions about disease-specific quality of life should be included when physicians counsel patients about treatment options.


Inhibition of PI3K/AKT molecular pathway mediated by membrane estrogen receptor GPER accounts for cryptotanshinone induced antiproliferative effect on breast cancer SKBR-3 cells.
Breast cancer is the most frequently diagnosed malignancy among women and the second leading cause of cancer death worldwide. Among which nuclear estrogen receptor (nER) negative breast cancer is always with much poor prognosis. Recently, membrane G protein coupled estrogen receptor (GPER), a newly recognized estrogen receptor has been documented to take essential part in the development and treatment of breast cancer. The present study was designed to investigate the anti nER negative breast cancer effect of cryptotanshinone (CPT), an important active compound of traditional Chinese medicine Danshen and its possible molecular pathway. The following in vitro tests were performed in nER negative but GPER positive breast cancer SKBR-3 cells. The effect of CPT on cell proliferation rate and cell cycle distribution was evaluated by MTT cell viability test and flow cytometry assay respectively. The role of PI3K/AKT pathway and the mediated function of GPER were tested by western blot and immunofluorescence. Technique of gene silence and the specific GPER agonist G-1 and antagonist G-15 were employed in the experiments to further verify the function of GPER in mediating the anticancer role of CPT. The results showed that proliferation of SKBR-3 cells could be blocked by CPT in a time and dose dependent manner. CPT could also exert antiproliferative activities by arresting cell cycle progression in G1 phase and down regulating the expression level of cyclin A, cyclin B, cyclin D and cyclin-dependent kinase 2 (CDK2). The antiproliferative effect of CPT was further enhanced by G-1 and attenuated by G-15. Results of western blot and immunofluorescence showed that expression of PI3K and p-AKT could be downregulated by CPT and such effects were mediated by GPER which were further demonstrated by gene silence test. The current study showed that the antiproliferative action of CPT on SKBR-3 cells was realized by inhibition of GPER mediated PI3K/AKT pathway. These findings provide further validation of GPER serving as useful therapeutic target.


A PRELIMINARY INVESTIGATION OF PATHOGEN EXPOSURE OF ADULT FEMALE WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) AND SURVIVAL OF ASSOCIATED FAWNS IN THE WESTERN DAKOTAS, USA.
Exposure of a dam to pathogens may potentially affect her fawns positively or negatively. Mammalian females transfer immunologic protection to their offspring via colostrum obtained while nursing. Conversely, chronic diseases in dams may potentially result in small and weak neonates, reduced milk production or quality, or infection. Little is known about how pathogen exposure in adult female white-tailed deer (Odocoileus virginianus) affects offspring survival. Our objective was to assess pathogen exposure for female white-tailed deer and subsequent survival rates of fawns in Dunn and Grant counties, North Dakota, and Perkins County, South Dakota, USA. We collected blood serum from 150 adult female deer during 2014. We compared survival of 49 fawns to maternal exposure to 10 pathogens from 37 of 150 adult females. There was no difference in fawn mass between dams based on antibody status and no difference in fawn survival for nine pathogens. The 12-wk survival for fawns born to mothers with antibodies against bovine herpesvirus 1 (BoHV-1, causing infectious bovine rhinotracheitis) was lower than for fawns born from mothers without antibodies against BoHV-1; however, the indirect or direct impacts of BoHV-1 exposure in mothers on fawn survival are unclear. Although our findings suggest that the cost of exposure to previous diseases may have minimal impact on short-term fawn survival for most pathogens, additional research with increased sample sizes is needed to confirm our findings.


A Review of the Mechanism of Vascular Endothelial Injury in Immunoglobulin A Vasculitis.
Immunoglobulin A (IgA) vasculitis (IgAV), also known as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. It is characterized by cutaneous hemorrhage, resulting from red blood cell leakage into the skin or mucosae, possibly caused by damage to small blood vessels. These acute symptoms usually disappear without treatment. Endothelial cells are distributed on the inner surfaces of blood vessels and lymphatic vessels, and have important functions in metabolism and endocrine function, as well as being the primary targets of external stimuli and endogenous immune activity. Injury to endothelial cells is a feature of IgA vasculitis. Endothelial cell damage may be related to the deposition of immune complexes, the activation of complement, inflammatory factors, and chemokines, oxidative stress, hemodynamics, and coagulation factors. Both epigenetic mechanisms and genetic diversity provide a genetic background for endothelial cell injury. Here, research on the role of endothelial cells in allergic IgA vasculitis is reviewed.


Transthoracic repair of Morgagni's hernia: a 20-year experience from open to video-assisted approach.
Foramen of Morgagni's hernia is an uncommon congenital diaphragmatic hernia. Repair is mostly performed through laparotomy. We prefer the transthoracic approach, which allows better and safer control during thoracic dissection, although it is considered more painful and related to greater morbidity. In recent years we introduced the transxiphoid hand-assisted videothoracoscopic approach, which combines the advantages of the thoracic route with a mini-invasive procedure facilitated by one hand inside the chest. A retrospective review was performed over a 20-year period (1985-2005). Twenty-two patients who had a foramen of Morgagni's hernia repaired were identified and relevant data were collected. Average age was 57 +/- 10 years and one half of the patients were asymptomatic. Chest roentgenograms, chest computerized tomography, and barium enema were used as diagnostic utilities. Posterolateral thoracotomy was performed in 17 (15 right-sided) patients, whereas in 5 (all right-sided) the defect was repaired by transxiphoid hand-assisted videothoracoscopy. Operative time, pain scored by visual analog scale, hospital stay, and cosmetic results by acceptance score were reviewed for every patient. Hernial sac was present in all cases and contained only omentum (n = 13), omentum plus transverse colon (n = 7), omentum plus transverse colon and small bowel (n = 2). In 6 patients (2 videothoracoscopy) we repaired the large defects with polypropylene mesh. Videothoracoscopy achieved significant good results compared to thoracotomy in operative time (85 +/- 7.9 versus 110 +/- 11.3 min, p < 0.01), 24-h visual analog scale (3.5 +/- 1.1 versus 6.7 +/- 3.9, p < 0.01), hospital stay (2.6 +/- 0.5 versus 6.4 +/- 1.2 days, p < 0.01), and acceptance score (4.3 +/- 0.5 versus 3.1 +/- 0.8, p < 0.05). Postoperative course was always uneventful. Patients were followed for an average period of 58.6 +/- 14.7 and 109.7 +/- 43.5 months, respectively: no recurrences were found in any group. We believe that the transthoracic approach is a safe and effective method for repairing Morgagni's hernia. The videothoracoscopic approach is a promising alternative and it may be facilitated by introducing a hand inside the chest.


Monoclonal SBF produced by a hybridoma: in-vitro and in-vivo suppression of B tumour-cell proliferation.
A suppressive B-cell factor (SBF)-producing hybridoma termed TS-4.44 was established by fusion of B cells which possessed receptors for the Fc portion of IgG (FcR gamma + B cells) and thymidine kinase defective fibroblasts, 3T3-4E cells. The biological properties of hybridoma-produced SBF (Hyb-SBF) are almost the same as those of conventionally prepared SBF (Conv-SBF). Hyb-SBF suppresses (i) plaque-forming cell (PFC) responses in an antigen non-specific manner, (ii) DNA synthesis of lipopolysaccharide (LPS)-activated B cells, but neither concanavalin A (Con A) nor phytohaemagglutinin (PHA)-induced activation of T cells, and (iii) the proliferation of B, but not non-B tumour cells. Once absorbed with L-1210 cells, Hyb-SBF failed to inhibit both PFC and LPS responses. It is important is that Hyb-SBF suppresses the proliferation of L-1210 cells not only in vitro, but also in vivo. The physicochemical properties of Hyb-SBF such as sensitivity to trypsin, pronase and neuraminidase and its molecular weight (43,000), as judged by gel filtration and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) are in accord with those of Conv-SBF. Moreover, it is eluted from a DEAE cellulose column with 0.1-0.3 M phosphate buffer. Thus, monoclonal SBF is thought to be identical with Conv-SBF and could provide us with sufficient material for the analysis of FcR-dependent immunoregulation including surveillance mechanisms controlling the proliferation of B tumour cells.


[Electroconvulsive therapy and schizophrenia. Update from the data of the literature].
The place of electroconvulsive therapy (ECT) in the treatment of affective disorders is presently important and even inequaled in some depressive illness forms. But ECT is still controversial and its indications in the treatment of schizophrenia remain debated. In order to evaluate the place of this "vielle thérapeutique du futur" (39) in the treatment of schizophrenia, we reviewed the literature of the two last decades and tried to answer these questions. 1) Is ECT effectiveness in treatment of schizophrenic symptoms proved? 2) What is the effectiveness of ECT compared with other efficacious treatment? 3) Does the ECT + neuroleptic combination provide some advantage? and in which cases? The literature provides many studies in the topic. However, a considerable proportion of these studies make no use of modern methodological criteria. We only consider papers which: --give a clear diagnostic definition in patients groups and control groups, --use a standardized method of treatment, --use quantitative tools to evaluate results, --randomize treatment and use, when possible, double blind design. 1) Curative effects of ECT in schizophrenic symptoms: Brandon et al. (14) compare two groups of schizophrenic patients diagnosed according to PSE for schizophrenia and receiving equivalent doses of neuroleptics. The first group receives ECT when the other one receives simulate ECT. The former improved significantly better than the later. The difference persists but is no longer significant from the forth week of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Red cell mass measurement in patients with clinically suspected diagnosis of polycythemia vera or essential thrombocythemia.
The cut off for hemoglobin or hematocrit that indicates the need for an isotopic red cell mass study was investigated in 179 patients with a presumptive diagnosis of polycythemia vera or essential thrombocythemia. Hematocrit showed better diagnostic accuracy than hemoglobin. Hemoglobin over 18.5 g/dL in males or over 16.5 g/dL in females showed a high specificity indicating that red cell mass study could be avoided in such cases, but it showed low sensitivity leading to 46% false negatives. The best value of hematocrit to indicate a red cell mass study was 0.50 L/L in males (specificity 75%, sensitivity 87.5%) and 0.48 L/L in females (specificity 73%, sensitivity 94%). Lowering the hematocrit threshold to 0.48 L/L in males increased sensitivity up to 95%. A red cell mass study should be performed in patients with suspected diagnosis of essential thrombocythemia or polycythemia vera and with hematocrit between 0.48 L/L and 0.52 L/L.


Operando XANES from first-principles and its application to iridium oxide.
Efficient electro-catalytic water-splitting technologies require suitable catalysts for the oxygen evolution reaction (OER). The development of novel catalysts could benefit from the achievement of a complete understanding of the reaction mechanism on iridium oxide (IrO2), an active catalyst material that is, however, too scarce for large-scale applications. Considerable insight has already been provided by operando X-ray absorption near-edge structure (XANES) experiments, which paved the way towards an atomistic description of the catalyst's evolution in a working environment. We combine here first-principles simulations augmented with a continuum description of the solvent and electrolyte to investigate the electrochemical stability of various IrO2 interfaces and to predict the XANES cross-section for selected terminations under realistic conditions of applied potential. The comparison of computed O K-edge XANES spectra to corresponding experiments supports the formation of electron-deficient surface oxygen species in the OER-relevant voltage regime. Furthermore, surface hydroxyl groups that are found to be stable up to ∼1 V are suggested to be progressively oxidized at larger potentials, giving rise to a shift in the Ir L3-edge cross-section that qualitatively agrees with measurements.


Coronary angioplasty and the internet: what can patients searching online expect to find?
This study set out to assess the quality of online information available on coronary angioplasty. Patients searching for healthcare information frequently use the Internet. However the lay reader may not be able to discern the robustness of evidence presented. At present, the overall quality and accuracy of online content regarding coronary angioplasty is unknown. The search term "coronary angioplasty" was entered into three popular search engines (Google, Yahoo, and Bing), and the first 50 webpages provided by each search engine pooled. Exclusion criteria consisted of duplicated sites, sites requiring a registration or login, and direct links to documents or videos. The remaining sites were analyzed using the LIDA instrument; a validated method for assessing websites based on accessibility, usability, and readability. Readability was also separately assessed using the Flesch Reading Ease Score (FRES). Of 150 weblinks reviewed, 86 were excluded on the basis of the criteria listed above. The remaining 64 sites achieved mean scores of 50/60 (83%) on accessibility, 40/54 (74%) on usability, 32/51 (62%) on reliability, and 47.5 on FRES. Significant variability was noted among the LIDA scores, with no correlation between LIDA score and search engine ranking. Although most websites are easy to access, content is frequently out-of-date and fails to be presented in an easily comprehensible format. A minority of websites display factually incorrect information. Clinicians should be wary of patients being misled by erroneous or commercially biased online content, and be able to redirect their patients to more robust, up-to-date sources.


2022 cancer statistics: Focus on lung cancer.
This is a plain language summary of a medical journal article called 'Cancer statistics, 2022'. The data in this summary provides detailed information about lung cancer and less detailed information about other cancers. The researchers from the original study used data gathered from previous years to produce a cancer forecast, predicting the number of new cancer diagnoses and deaths in the United States in 2022. The review of the data up to 2019 found that compared to previous years: Advanced lung cancer diagnoses had decreased Local stage lung cancer diagnoses had increased Deaths had slowed for lung cancer Deaths continued to reduce for breast cancer, but the rate of this reduction had slowed down Female breast cancer diagnoses were slowly increasing each year Prostate cancer diagnoses stayed similar Local stage prostate cancer diagnoses stayed similar Advanced prostate cancer diagnoses had increased each year The researchers estimated that over 1.9 million new cancer cases would be diagnosed and over half a million cancer deaths would occur in the United States in 2022. This figure includes approximately 350 deaths per day from lung cancer, which was found to be the leading cause of cancer death in the United States. The study found that progress in reducing the number of people being diagnosed with breast and prostate cancer has stalled. Although there were fewer lung cancers diagnosed, this reduction was likely caused by changes in screening and advancements in lung cancer treatments. The American Cancer Society recommended that investing more funds in detecting cancers early as well as developing targeted treatments would help to reduce cancer death rates. This would also help to address the differences in access to cancer care that exist based on racial, social and economic inequalities.


Abdominal aortic aneurysm associated with systemic fungal infection in a German shepherd dog.
A 2 yr old spayed female German shepherd presented with a chief complaint of acute onset paraparesis and weight loss. At presentation, the dog was pyrexic, nonambulatory, and had generalized muscle wasting. Neurolocalization was consistent with a thoracolumbar spinal cord lesion. An abdominal ultrasound was performed and revealed a focal dilation (4 cm) of the terminal aorta with evidence of blood stasis consistent with an aortic aneurysm. The dog was euthanized shortly after admission to the hospital and a post mortem examination was performed. Fungal organisms were identified in the aortic aneurysm as well as from the thoracic vertebrae, mesenteric lymph nodes, axillary lymph nodes, spleen, kidneys, liver, lungs, and heart. Although the morphology was consistent with Candida spp., immunohistochemistry and PCR could not definitively identify the causative organism. Mycotic aortic aneurysms are a rare finding in humans and have not been previously reported in the dog. To the authors' knowledge, this is the first known report of an aortic aneurysm associated with systemic fungal infection in a dog.


Mechanics of respiratory muscles.
Lung ventilation is a mechanical process in which the respiratory muscles are acting in concert to remove air in and out of the lungs. Any alteration in the performance of the respiratory muscle may reduce the effectiveness of ventilation. Thus, early diagnosis of their weakness is vital for treatment and rehabilitation. Different techniques, which are based on different measurement protocols, can be utilized for evaluation of respiratory muscle strength. Respiratory muscle strength can be assessed using pressure measurement either from the mouth or from the nostril during quasi-static breathing. However, it estimates only global performance of respiratory muscles. Techniques that are based on electromyography measurements during muscle contraction (EMG) enable the differentiation between the different respiratory muscles. Along with the above clinical and physiological techniques for assessment of respiratory muscle strength and endurance, mechanical and mathematical models of the chest wall were developed in the last few decades for analysis of chest wall movements and the contribution of its components to respiration. In this review, the different methods and the models utilized for evaluation of respiratory muscles function will be discussed.


[2 cases of AIDS in patients with hemophilia A].
The authors report the first two cases of lethal AIDS in haemophilia A in France. One French case of AIDS in haemophilia B has already been reported. The diagnosis was based on the observation of opportunist infections associated with severe depression of cell-mediated immunity in both cases. The possibility of active transmission of the LAV retrovirus by factor VII concentrate is discussed. This raises the problem of the signification of anti-LAV antibodies in haemophiliac patients and the control of products used for the treatment of haemophilia.


Spectrum of trabecular pigmentation in open-angle glaucoma: a clinicopathologic study.
In eight patients with chronic open-angle glaucoma and associated trabecular pigmentation, trabeculectomy and peripheral iridectomy specimens were studied by light and electron microscopy. Clinically, three patients displayed signs of classic pigmentary glaucoma (Group 1). In the other cases chronic open-angle glaucoma was associated with varying degrees of expression of the full pigmentary glaucoma syndrome (Group 2). Histopathologic examination of peripheral iridectomy and trabeculectomy specimens from Group 1 showed: (1) marked focal atrophy and hypopigmentation of iris pigmented epithelium with an apparent delay in melanogenesis. The dilator muscle was thickened except for occasional thinned areas. (2) The trabeculectomy specimens revealed excessive amounts of pigmented epithelial melanosomes and moderate accumulation of electron-dense basement membrane-like material in the juxtacanalicular meshwork. Similar specimens from Group 2 showed: (1) minimal hypopigmentation of the iris pigmented epithelium with normal melanogenesis. The iris stroma and dilator muscle were normal. (2) Trabeculectomy specimens displayed excessive electron-dense basement membrane-like material in the juxtacanalicular meshwork and minimal to moderate accumulation of melanosomes.


Effective-Loading of Platinum-Chloroquine into PEGylated Neutral and Cationic Liposomes as a Drug Delivery System for Resistant Malaria Parasites.
The trans platinum-chloroquine diphosphate dichloride (PtCQ) is a new type of antimalarial drug used to fight parasites resistant to traditional drugs. PtCQ is synthesized by mixing platinum and chloroquine diphosphate (CQ). This study examines two efficient methods for forming a nanodrug, PtCQ-loaded liposomes, for use as a potential antimalarial drug-delivery system: the thin drug-lipid film method to incorporate the drug into a liposomal membrane, and a remote-loading method to load the drug into the interior of a cationic liposome. The membranes accordingly comprised PEGylated neutral or cationic liposomes. PtCQ was efficiently loaded into PEGylated neutral and cationic liposomes using the thin drug-lipid film method (encapsulation efficiency, EE: 76.1±6.7% for neutral liposomes, 1 : 14 drug-to-lipid weight ratio; 70.4±9.8% for cationic liposomes, 1 : 14 drug-to-lipid weight ratio). More PtCQ was loaded into PEGylated neutral liposomes using the remote-loading method than by the thin drug-lipid film method and the EE was maximum (96.1±4.5% for neutral liposomes, 1 : 7 (w/w)). PtCQ was encapsulated in PEGylated cationic liposomes comprising various amounts of cationic lipids (0-20 mol%; EE: 96.9-92.3%) using the remote-loading method. PEGylated neutral liposomes and cationic liposomes exhibited minimum leakage of PtCQ after two months' storage at 4°C, and further exhibited little release under in vitro culture conditions at 37°C for 72 h. These results provide a useful framework for the design of future liposome-based in vivo drug delivery systems targeting the malaria parasite.


Nutritional hepatic steatosis and mortality after burn injury in rats.
To investigate the effects of diet composition and starvation on hepatic steatosis and mortality after severe burn injury in rats. Experiment 1: rats received either normal chow (55 cent of energy carbohydrates, 14 cent fat, 31 cent protein), a high-fat (40 cent carbohydrates, 40 cent fat, 20 cent protein), or a high-carbohydrate diet (81 cent carbohydrates, 4 cent fat, 15 cent protein) ad libitum for 6 days. Another three groups received these diets ad libitum for 6 days after 48|h starvation. Experiment 2: mortality after 60 cent total body surface area scald burn was determined in a control group of rats and a group with nutritionally induced hepatic steatosis. Hepatic steatosis was induced by feeding the rats a high-fat diet (40 cent carbohydrates, 4 cent fat, 15 cent protein) ad libitum for 6 days. Without starvation, liver triglyceride content (mg/g liver) increased in response to the high-fat diet (25.6'6.9) compared to normal chow (9.4'3.8; P < 0. 05); the high-carbohydrate diet had no influence on liver triglyceride content (12.4'3.7). Refeeding after starvation resulted in elevated (P < 0.05) liver triglyceride content in the high-fat (18.8'8.3) and the high-carbohydrate group (28.7'14.4 vs control 6. 7'3.7). Liver triglyceride content correlated (R2=0.72; P < 0.05) to non-protein energy intake but not to total energy intake. Burn caused 33 cent mortality in the hepatic steatosis group and no deaths in the control group (P < 0.05). Diet composition and preceding starvation independently manipulate hepatic fat content in rats. Hepatic steatosis increases mortality after burn injury. Thus, nutritional interventions to reduce hepatic fat accumulation may be beneficial.


Cloning of Two Acetylcholinesterase Genes and Analysis of Point Mutations Putatively Associated with Triazophos Resistance in Chilo auricilius (Lepidoptera: Pyralidae).
Acetylcholinesterase (AChE) is the target of organophosphate (OP) and carbamate insecticides. Mutations in the AChE gene (ace) leading to decreased insecticide susceptibility is the main resistance mechanism in insects. In this study, two Chilo auricilius acetylcholinesterase genes, designated as Caace1 and Caace2, were cloned using RT-PCR and RACE. Caace1 cDNA is 2534 bp, with ORF of 2082 bp, and it encodes an acetylcholinesterase 1 (CaAChE1) protein comprising a calculated 693 amino acid (aa) residues. Caace2 cDNA contains 2280 bp, with a full-length ORF of 1917 bp, encoding acetylcholinesterase 2 (CaAChE2) comprising a calculated 638 aa residues. At the aa level, CaAChE1 displays the highest similarity (97%) with the Chilo suppressalis AChE1, and CaAChE2 shows the highest similarity with the C. suppressalis AChE2 (99%). From the restriction fragment length polymorphism (RFLP) PCR (RFLP-PCR) analysis, one mutation in Caace1, similar to the ace1 mutation associated with triazophos resistance in C. suppressalis, was detected. Detailed examination of field populations of C. auricilius indicated this resistance mutation in C. auricilius is still quite infrequent. Based on the assay of AChE activity and RFLP-PCR testing, an individual that contains resistance mutation has lower AChE activities, while the individual that does not contain the resistance mutation has higher AChE activities. This study provides a basis for future investigations into the mechanism of OP resistance in C. auricilius, as well as a guidance for C. auricilius control with reasonable choice of pesticides.


Use of a continuous twin screw granulation and drying system during formulation development and process optimization.
Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and tablet quality attributes were obtained during the start-up phase of the 1h run. For the single cell runs, granule and tablet properties were comparable with results obtained during the second part of the 1h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for tablet quality obtained during continuous production using the ConsiGma™-25 system.


Optical characteristics of CdSe quantum dots depending on growth conditions and surface passivation.
We investigated the effects of different growth conditions and surface passivation on the growth of CdSe quantum dots (QDs). The synthesis of CdSe QDs by pyrolysis of organometallic reagents was performed by using the hot-matrix method. In order to modify the size and quality of CdSe QDs, we controlled the growth temperature from 250 degrees C to 350 degrees C and the relative amount of trioctylphosphin (as the ligand of the Cd and Se precursors) to be injected into the coordinating solvent trioctylphosphineoxide. Moreover, an effective surface passivation of mono-disperse CdSe QDs was achieved by overcoating them with a larger band gap material, such as ZnS.


Laminin-bound integrin α6β4 promotes non-small cell lung cancer progression via the activation of YAP/TAZ signaling pathway.
Laminin is an extracellular matrix multidomain trimeric glycoprotein, that has a potential role in tumor progression. Here, we studied the effects of non-small cell lung cancer (NSCLC) cells interaction on laminin and explored the underlying mechanism of laminin associated NSCLC progression. Culture of A549 and NCI-1299 cells on 2D collagen gels (containing laminin) significantly promoted the proliferative and tumorigenic characteristics, as well as cell invasion of tumor cells in vitro. Consistently, comparing the clinical NSCLC tumor tissues, a poor overall survival was observed in patients with high laminin expression. Mechanistically, the expression of integrin α6β4 was required for the pro-tumor effects of laminin. Meanwhile, we showed that the downstream signaling of integrin α6β4, involved the focal adhesion kinase (FAK)/Yes-Associated Protein (YAP)/TAZ signaling pathway. The activation of FAK/YAP/TAZ signaling pathway induced by laminin was validated in tumor tissues from NSCLC patients. Suppression of integrin α6β4/FAK/YAP/TAZ signaling pathway efficiently suppressed the laminin-induced tumor growth, and strengthened the anticancer effects of chemotherapy, describing a novel target for NSCLC treatment.


Mass flux through asymmetric nanopores: Microscopic versus hydrodynamic motion.
The crossover from hydrodynamic to microscopic motion in nanoscopic channels with broken spatial symmetry is investigated by means of many-body molecular dynamics simulations at various pore diameters. It is found that both hydrodynamic and microscopic regimes favor motion along the convergent over the divergent directions, although with a different scaling of the mass flow with the pore diameter. In either cases, departure from linear response and the ensuing detection of spatial asymmetry seems to respond more to the intensity of the external drive than to the granularity of the flowing system. Our simulations suggest that this property lies at the heart of microscopic ratchet motion and its capability of echoing the symmetry-breaking detection realized by macroscopic fluids at nonzero Reynolds numbers.


Dietary fibres and IBS: translating functional characteristics to clinical value in the era of personalised medicine.
Clinical guidelines in the use of fibre supplementation for patients with IBS provide one-size-fits-all advice, which has limited value. This narrative review addresses data and concepts around the functional characteristics of fibre and subsequent physiological responses induced in patients with IBS with a view to exploring the application of such knowledge to the precision use of fibre supplements. The key findings are that first, individual fibres elicit highly distinct physiological responses that are associated with their functional characteristics rather than solubility. Second, the current evidence has focused on the use of fibres as a monotherapy for IBS symptoms overall without attempting to exploit these functional characteristics to elicit specific, symptom-targeted effects, or to use fibre types as adjunctive therapies. Personalisation of fibre therapies can therefore target several therapeutic goals. Proposed goals include achieving normalisation of bowel habit, modulation of gut microbiota function towards health and correction of microbial effects of other dietary therapies. To put into perspective, bulking fibres that are minimally fermented can offer utility in modulating indices of bowel habit; slowly fermented fibres may enhance the activities of the gut microbiota; and the combination of both fibres may potentially offer both benefits while optimising the activities of the microbiota throughout the different regions of the colon. In conclusion, understanding the GI responses to specific fibres, particularly in relation to the physiology of the individual, will be the future for personalising fibre therapy for enhancing the personalised management of patients with IBS.


Anti-G antibody in alloimmunized pregnant women: Report of two cases.
Anti-G has been reported as a possible cause of hemolytic disease of the fetus and newborn (HDFN), either independently or in association with anti-D, anti-C or both. The antibody mimics the pattern of anti-C and anti-D reactivity in the identification panel and is often present along with either or both of these antibodies. The differentiation of anti-D, -C and-G in routine pretransfusion workup is particularly essential in antenatal cases. We report two antenatal cases where anti-G was identified on advanced immunohematological workup, in addition to other alloantibodies.


Novel laparo-endoscopic hybrid technique of management of a rare case of duodeno-duodenal intussusception.
We herein report a rare case of duodeno-duodenal intussusception (IS) presenting with obstruction caused by tubulovillous adenoma in an adult with malrotation that was managed by a novel laparoendoscopic hybrid technique. This was done by passing transjejunal nasogastric tube (NG) through one of the ports and manoeuvring it towards the IS. Two hundred and fifty millilitre of saline was flushed by aseptosyringe with pressure connected to the NG. This hydrostatic reduction technique resulted in distension of the jejunal and duodenal loop achieving reduction of IS. Intraoperative endoscopy was performed to exactly localise the mass lesion. The duodenum was kocherised and was delivered through a 4-cm transverse incision. Anterior duodenotomy was performed; the mass was excised; and duodenotomy was closed transversely. An extensive literature search did not show any case report of duodenoduodenal IS being managed by this technique. The combination of novel retrograde decompression and intraoperative endoscopy helped us to manage this rare case by this novel technique.


Ultrahigh and Broad Spectral Photodetectivity of an Organic-Inorganic Hybrid Phototransistor for Flexible Electronics.
The creation of new organic-inorganic phototransistors with high and broad spectral photosensitivity is reported. The extended charge transport and photoconductivity between the layers in the bilayer structure results in a notable detectivity of over 10(12) Jones and a linear dynamic range of over 100 dB at a broad spectral bandwidth across the UV-NIR range. Furthermore, the considerably reduced persistent photocurrent effect of In-Ga-Zn-O (IGZO)-based hybrid phototransistors is first demonstrated via an organic-inorganic bilayer approach.


Pancreatic exocrine function testing.
It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.


Phagosome maturation proceeds independently of stimulation of toll-like receptors 2 and 4.
Toll-like receptors modulate many aspects of the innate immune response. Recent reports suggest that the maturation of phagosomes following particle uptake is modulated through signaling of Toll-like receptors. In the current study, the kinetics of phagosome maturation was evaluated quantitatively by ratio fluorometry to determine the lumenal pH of the phagosomes and a FRET-based technique to determine the degree of phagosome/lysosome fusion. Profiles generated for phagosomes containing experimental particles with or without the TLR ligands Pam3Cys-Ser-(Lys)4 or LPS failed to reveal a difference in maturation despite activating TLR-signaling pathways. Moreover, while macrophages defective in individual TLRs generated phagosome maturation profiles identical to wild-type macrophages, MyD88-deficient macrophages exhibited a marked depression in phagosome/lysosome fusion that appears independent of short-term TLR-mediated effects. The results demonstrate that the rate of maturation of phagosomes proceeds independently of TLR signaling pathways.


FDG uptake in liposclerosing myxofibrous tumor causes upstaging of Hodgkin lymphoma.
A 22-year-old woman with Hodgkin lymphoma underwent a staging 18F-FDG PET/CT scan, which showed an intense uptake in the right proximal femur, in addition to FDG-avid mediastinal and cervical lymph nodes. The patient thus was diagnosed with stage IV lymphoma with bone marrow involvement. Postchemotherapy restaging scan showed complete resolution of nodal uptake but persistent activity in the right femur. Radiography and biopsy confirmed liposclerosing myxofibrous tumor.


Effect of heparin on the inhibition of the contact system enzymes.
1. One can accurately predict the contribution of each inhibitor to the total inactivation of an enzyme in plasma once its pseudo-first-order reaction rate constant and concentration are known. 2. Because the mechanism of augmentation of the inactivation rate of an enzyme by ATIII occurs via formation of an ATIII-heparin complex, the degree of potentiation can be predicted by knowing the binding capacity (sites per mole) of the heparin preparation and the concentration of heparin in the reaction (to calculate the concentration of the ATIII-heparin complex). 3. The augmentation by heparin of the inactivation rate of a particular enzyme by ATIII is dependent upon the presence of other enzymes with higher kassoc, since these would strongly compete for the ATIII-heparin complex. 4. In a plasma environment, using therapeutic levels of heparin, there is no augmentation of the inactivation rate of any of the contact enzymes.


Cost-Effectiveness and Net Monetary Benefit of Olaparib Maintenance Therapy Versus No Maintenance Therapy After First-line Platinum-based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-mutated Ovarian Cancer in the Italian National Health Service.
The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective. We developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based chemotherapy to compare cost-effectiveness and net monetary benefit of the 2 strategies. Data on clinical outcomes were obtained from related clinical trial literature and extrapolated using parametric survival analyses. Data on costs were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio (ICUR), and incremental net monetary benefit (INMB) were computed and compared against an incremental cost per quality-adjusted life-year (QALY) gained of €16,372 willingness-to-pay (WTP) threshold. We used deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) to assess how uncertainty affects results; we also performed scenario analyses to compare results under different pricing settings. In the base-case scenario, during a 50-year time horizon, the total costs for patients treated with olaparib therapy and active surveillance were €124,359 and €97,043, respectively, and QALYs gained were 7.29 and 4.88, respectively, with an ICER of €9,515 per life-year gained, an ICUR of €11,345 per QALY gained, and an INMB of €12,104. In scenario analyses, considering maximum selling prices for all other drugs, ICUR decreased to €11,311 per QALY and €7,498 per QALY when a 10% and 20% discount, respectively, was applied to the olaparib official price, and the INMB increased to €12,186 and €21,366, respectively. DSA found that the model results were most sensitive to the proportion of patients with relapsing disease in response to platinum-based chemotherapy, time receiving olaparib first-line maintenance treatment, and subsequent treatments price. According to PSAresults, olaparib was associated with a probability of being cost-effective at a €16,372 per QALY WTP threshold ranging from 70% to 100% in the scenarios examined. Our analysis indicates that olaparib maintenance therapy may deliver a significant health benefit with a contained upfront cost during a 50-year time horizon, from the Italian NHS perspective, providing value in a setting with curative intent.


The effect of angiotensin-converting enzyme inhibitors on human neutrophil chemotaxis in vitro.
1. Myocardial 'reperfusion injury' has been partly attributed to the production of free radicals which are cytotoxic towards cells. Neutrophils are recruited by ischaemic tissue and are one source of free radicals. Angiotensin-converting enzyme (ACE) inhibitors can reduce 'reperfusion injury' and we decided to determine if ACE inhibitors might contribute to this effect by inhibiting neutrophil chemotaxis. 2. The effects of captopril (a thiol containing ACE inhibitor) and enalaprilat (a nonthiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG) (a simple thiol) on neutrophil chemotaxis were tested in an in vitro Boyden chamber assay. 3. The chemotactic response of human neutrophils to fMLP was reduced by 27.6% with MPG (n = 8; P < 0.05), by 13.2% with enalaprilat (n = 8; P = 0.075) and by 5.2% with captopril (n = 8; P = 0.66) at 5 microM (therapeutic concentration.) 4. Neutrophil chemotaxis was significantly decreased with 50 microM and 500 microM MPG and enalaprilat and 500 microM captopril. 5. Supratherapeutic concentrations of ACE inhibitors can reduce neutrophil chemotaxis at high concentrations and this effect does not appear to be -SH dependent.


Rate of HIV transmission and associated factors among HIV-exposed infants in selected health facilities of East and West Gojjam Zones, Northwest Ethiopia; retrospective cohort study.
In 2014, there were 170,000 new HIV-infected children globally. The rate of HIV transmission from mother to child in Ethiopia was 18%. Though there are a number of HIV-related studies conducted in Ethiopia, there is a scarcity of evidence on the rate of mother to child transmission. So, the aim of this study was to determine the rate of HIV transmission and associated factors among HIV-exposed infants in selected health facilities in East and West Gojjam Zones, Northwest Ethiopia. Retrospective cohort study design was conducted. A total of 305 exposed infant- and mother pairs were included in this study. Data were collected from seven selected health facilities in East and West Gojjam Zone, Northwest Ethiopia. The study included a four-year duration PMTCT data, registered from July/2011 to July/2015. Data was collected using a prepared checklist. Data was entered using EpiData and analyzed using SPSS software. Descriptive, bivariate and multiple variable logistic regression analysis were conducted. A p-value less than 0.05 were used to declare statistical significant association. Three hundred five infants and their mothers were included in this study. The mean age of mothers was 27.4 with a standard deviation of 4.3 years. The majority, 96.4% of infants were on exclusive breastfeeding before six months. The rate of HIV transmission at the end of 24 months were 5.9% (95% CI: 3.9%-7.9%). The number of positive children was reduced from 14 (10.29%) to 4(2.37%) due to the program shift from option A to option B+. Factors which were associated with transmission of HIV from mother to child were; children who were born from older mothers (AOR = 5.4, 95% CI = 1.15, 25.70), and infants whose mother couldn't get PMTCT intervention (AOR = 15.95, 95% CI = 3.35, 75), and mothers who became pregnant after they knew they were HIV positive (AOR = 0.22, 95%CI = 0.049,096). There is significant progress on the reduction of the rate of HIV transmission from mother to child in Ethiopia. Age of the mother, status of the mother at an entry to PMTCT program and presence of PMTCT interventions were significant factors associated with HIV transmission. Hence, the above factors should be given due emphasis on controlling HIV transmission from mother to child.


The Granulocyte Progenitor Stage Is a Key Target of IRF8-Mediated Regulation of Myeloid-Derived Suppressor Cell Production.
Alterations in myelopoiesis are common across various tumor types, resulting in immature populations termed myeloid-derived suppressor cells (MDSCs). MDSC burden correlates with poorer clinical outcomes, credited to their ability to suppress antitumor immunity. MDSCs consist of two major subsets, monocytic and polymorphonuclear (PMN). Intriguingly, the latter subset predominates in many patients and tumor models, although the mechanisms favoring PMN-MDSC responses remain poorly understood. Ordinarily, lineage-restricted transcription factors regulate myelopoiesis that collectively dictate cell fate. One integral player is IFN regulatory factor (IRF)-8, which promotes monocyte/dendritic cell differentiation while limiting granulocyte development. We recently showed that IRF8 inversely controls MDSC burden in tumor models, particularly the PMN-MDSC subset. However, where IRF8 acts in the pathway of myeloid differentiation to influence PMN-MDSC production has remained unknown. In this study, we showed that: 1) tumor growth was associated with a selective expansion of newly defined IRF8lo granulocyte progenitors (GPs); 2) tumor-derived GPs had an increased ability to form PMN-MDSCs; 3) tumor-derived GPs shared gene expression patterns with IRF8-/- GPs, suggesting that IRF8 loss underlies GP expansion; and 4) enforced IRF8 overexpression in vivo selectively constrained tumor-induced GP expansion. These findings support the hypothesis that PMN-MDSCs result from selective expansion of IRF8lo GPs, and that strategies targeting IRF8 expression may limit their load to improve immunotherapy efficacy.


Long-term remission of folliculitis decalvans after treatment with the long-pulsed Nd:YAG laser.
Folliculitis decalvans (FD) is a rare inflammatory scalp disorder presenting with tufted folliculitis, follicular papules and pustules, progressing to cicatricial alopecia. Current treatments mainly consist of antibiotic and immunomodulatory therapies and are often disappointing. FD has previously shown to respond to treatment with neodymium:yttrium aluminium garnet (Nd:YAG) laser in one case. We present a case of recalcitrant FD, successfully treated with a long-pulsed Nd:YAG laser.


Evaluation of suicide risk in children: psychometric properties of the Spanish version of the Risk of Suicide Questionnaire (RSQ).
Risk of Suicide Questionnaire (RSQ) is a useful self-administered tool to assess suicide risk among children. The aim of this study was to translate RSQ into Spanish and determine its validity and reliability among Mexican children. After a culturally sensitive RSQ items translation, all fifth and sixth grade elementary school students of both genders, from a private educational Institution in Guadalajara (Mexico) whose parents gave informed consent to participate, completed the RSQ Spanish version and the Beck's Depression and Hopelessness Inventories. The parents of the children who had a suicide risk were contacted and invited to come with their child to a subsequent appointment for evaluation and free treatment in the Jalisciense Mental Health Institute. For correlation analysis, item number 9 related to suicide was eliminated. A total sample of 88 students participated. Their mean age was 11.23 +- 0.78 years old, and 55.7 % were male. Mean total scales were as follows: RSQ: 8.3 +- 9.05; depression: 7.4 +- 6.7, and hopelessness: 18 +- 3.3. Cronbach's alpha for RSQ was 0.68. Intra class coefficients correlations between RSQ and depression and hopelessness inventories were 0.74 and 0.52, respectively. Only one of the 56 minors considered to have a certain suicide risk (n=56) came to a professional evaluation with their parents. The Spanish version of the RSQ showed adequate validity and reliability in Mexican students.


Updated Methodology for Projecting U.S.- and State-Level Cancer Counts for the Current Calendar Year: Part II: Evaluation of Incidence and Mortality Projection Methods.
The American Cancer Society (ACS) and the NCI collaborate every 5 to 8 years to update the methods for estimating the numbers of new cancer cases and deaths in the current year for the U.S. and individual states. Herein, we compare our current projection methodology with the next generation of statistical models. A validation study was conducted comparing current projection methods (vector autoregression for incidence; Joinpoint regression for mortality) with the Bayes state-space method and novel Joinpoint algorithms. Incidence data from 1996-2010 were projected to 2014 using two inputs: modeled data and observed data with modeled where observed were missing. For mortality, observed data from 1995 to 2009, 1996 to 2010, 1997 to 2011, and 1998 to 2012, each projected 3 years forward to 2012 to 2015. Projection methods were evaluated using the average absolute relative deviation (AARD) between observed counts (2014 for incidence, 2012-2015 for mortality) and estimates for 47 cancer sites nationally and 21 sites by state. A novel Joinpoint model provided a good fit for both incidence and mortality, particularly for the most common cancers in the U.S. Notably, the AARD for cancers with cases in 2014 exceeding 49,000 for this model was 3.4%, nearly half that of the current method (6.3%). A data-driven Joinpoint algorithm had versatile performance at the national and state levels and will replace the ACS's current methods. This methodology provides estimates of cancer data that are not available for the current year, thus continuing to fill an important gap for advocacy, research, and public health planning.


[Glucagon-like peptide-1--a new hormone and a new drug].
Glucagon-like peptide-1 (GLP-1 is an insulinotropic hormone, which is secreted from endocrine cells of the intestinal mucosa in relation to meal ingestion. It plays an important role as an incretin hormone; thus, mice with a null-muation in the gene encoding the GLP-1 receptor are glucose intolerant. In addition, GLP-1 inhibits gastrointestinal secretion and motility and is thought to act as one of the hormones of the "ileal brake". The insulinotropic effect of GLP-1 is preserved in patients with non insulin-dependent diabetes mellitus (NIDDM) and, because GLP-1 also inhibits glucagon secretion, it effectively lowers blood glucose in such, and given as an intravenous infusion it may completely normalise blood glucose. Furthermore, because its actions on insulin and glucagon secretion are dependent on the blood glucose levels it will not cause hypoglycemia. Efforts are therefore currently being made to employ GLP-1 or analogues thereof in clinical diabetes treatment, not least because recent investigations have shown that GLP-1, perhaps due to its gastrointestinal actions, is capable of reducing food intake in humans.


Sleep-Disordered Breathing Impact on Efficacy of Prolonged Exposure Therapy for Posttraumatic Stress Disorder.
There is growing evidence that sleep disturbances may impede the utility of existing therapeutic interventions for people with posttraumatic stress disorder (PTSD). This retrospective medical record review examined the hypothesis that sleep disturbance affects the outcome of prolonged exposure (PE) therapy for PTSD. We identified 18 combat veterans with PTSD who had completed PE therapy. There were 6 subjects who had sleep-disordered breathing, 5 of whom were documented by sleep polysomnography. All subjects in the sleep-disordered group took part in a minimum of 10 sessions; the mean number of sessions was comparable between the sleep-disordered group and the group without a sleep disorder. Posttreatment PTSD Checklist scores were significantly reduced in those without a sleep disorder (-28.25; 58.0% reduction, F(1, 11) = 59.04, p < .001), but were not reduced in those with sleep-disordered breathing (-7.17; 13.5% reduction, dIGPP = 2.25 [independent groups pretest-posttest design]). These observations supported the hypothesis that the efficacy of PE therapy is affected by sleep quality. If these findings are replicated, treatment algorithms may need to incorporate the presence or absence of sleep disorders as a factor in treatment choice.


Representational difference analysis of cDNA of genes expressed in embryonic kidney.
Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based differential cloning method. It involves hybridization of two populations of cDNA with selective amplification of differentially expressed genes. To isolate the differentially expressed genes during renal development, mRNAs from embryonic kidneys at day 13 (E13) and postnatal kidneys from three-week-old (P3) mice were extracted, and double stranded cDNAs prepared. Double stranded cDNAs were digested with DpnII, adaptor-ligated, and amplified by PCR, using adaptor primer to generate "representative amplicons." These reflect the "representation" of most of the cDNA population. The term "amplicons" denotes amplified PCR product. Among the two populations of cDNA, E13 kidney cDNA was used as a "tester," containing target genes, and P3 kidney cDNA as a "driver," driving the process of subtraction, following which, they were subjected to cDNA-RDA under low stringency conditions. During the first round of cDNA-RDA embryonic globin genes were isolated. To competitively eliminate these genes, plasmid DNAs of globin genes were supplemented into driver, and subjected to the second round of cDNA-RDA. This resulted in the isolation of four cDNA clones: H19 gene, mesoderm-specific cDNA, COL2A1 gene, and a novel cDNA. By Northern blot analyses, the H19 gene and mesoderm-specific cDNA exhibited a high degree of developmental regulation, that is, they were abundantly expressed in E13 kidney, and their expression was barely detectable in P3 kidney. The differential developmental regulation of mesoderm-specific cDNA was confirmed by tissue in situ hybridization experiments. The COL2A1 and novel cDNA were rare transcripts in the embryonic Kidney. However, Southern blot analyses of representations indicated their up-regulated expressions in E13 kidneys. The novel gene was differentially expressed in 13-day embryonic lung, and Northern blot analysis revealed an approximately 10 Kb transcript. These results indicate that cDNA-RDA is a sensitive technique to identify rare transcripts with differential expression, and since there is a minimal chance to isolate false positive clones, cDNA-RDA may serve as a powerful tool for delineating up- or down-regulation of the genes involved in various pathological or physiological states of the kidney.


Long-term effects of maternal citrulline supplementation on renal transcriptome prevention of nitric oxide depletion-related programmed hypertension: the impact of gene-nutrient interactions.
Maternal malnutrition can elicit gene expression leading to fetal programming. L-citrulline (CIT) can be converted to L-arginine to generate nitric oxide (NO). We examined whether maternal CIT supplementation can prevent N(G)-nitro-L-arginine-methyl ester (L-NAME, NO synthase inhibitor)-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received L-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% L-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, L-NAME, and L-NAME + CIT. L-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in L-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP) and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification.


Considerations for point-of-care diagnostics: evaluation of acridine orange staining and postprocessing methods for a three-part leukocyte differential test.
There exists a broad range of techniques that can be used to classify and count white blood cells in a point-of-care (POC) three-part leukocyte differential test. Improvements in lenses, light sources, and cameras for image-based POC systems have renewed interest in acridine orange (AO) as a contrast agent, whereby subpopulations of leukocytes can be differentiated by colorimetric analysis of AO fluorescence emission. We evaluated the effect on test accuracy using different AO staining and postprocessing methods in the context of an image-based POC colorimetric cell classification scheme. Thirty blood specimens were measured for percent cell counts using our POC system and a conventional hematology analyzer for comparison. Controlling the AO concentration used during whole-blood staining, the incubation time with AO, and the colorimetric ratios among the three population of leukocytes yielded a percent deviation of 0.706%, ? 1.534 % , and ? 0.645 % for the lymphocytes, monocytes, and granulocytes, respectively. Overall, we demonstrated that a redshift in AO fluorescence was observed at elevated AO concentrations, which lead to reproducible inaccuracy of cell counts. This study demonstrates there is a need for a strict control of the AO staining and postprocessing methods to improve test accuracy in these POC systems.


On limits of contact tracing in epidemic control.
Contact tracing and quarantine are well established non-pharmaceutical epidemic control tools. The paper aims to clarify the impact of these measures in evolution of epidemic. The proposed deterministic model defines a simple rule on the reproduction number [Formula: see text] in terms of ratio of diagnosed cases and, quarantine and transmission parameters. The model is applied to the early stage of Covid19 crisis in Poland. We investigate 3 scenarios corresponding to different ratios of diagnosed cases. Our results show that, depending on the scenario, contact tracing prevented from 50% to over 90% of cases. The effects of quarantine are limited by fraction of undiagnosed cases. The key conclusion is that under realistic assumptions the epidemic can not be controlled without any social distancing measures.


Carcinogenic risk of dark vs. light liquor.
A previous report suggested that the cancer risk associated with hard liquor is greater among users of dark liquors, which may contain more potentially carcinogenic compounds than light liquors. To test this hypothesis, we examined alcohol consumption data obtained by interview with 921 cases and 900 controls who participated in 1984-1985 in a population-based case-control study of oral and pharyngeal cancer conducted in 4 areas of the United States. Among heavy liquor drinkers (30+ drinks/week), odds ratios were 13.2 (95% CI = 5.2-33.5) for those who usually drank light liquors vs. 4.6 (95% CI = 2.7-7.9) for those who usually drank dark liquors, with higher risks for light vs. dark liquors at each anatomical subsite. This analysis provides no support for the notion that dark liquors are more carcinogenic than light liquors or that non-ethanolic ingredients of alcoholic beverages are major contributors to the excess risk of oral and pharyngeal cancer.


Feature Selection Based on a Sparse Neural-Network Layer With Normalizing Constraints.
Feature selection (FS) is an important step in machine learning since it has been shown to improve prediction accuracy while suppressing the curse of dimensionality of high-dimensional data. Neural networks have experienced tremendous success in solving many nonlinear learning problems. Here, we propose a new neural-network-based FS approach that introduces two constraints, the satisfaction of which leads to a sparse FS layer. We performed extensive experiments on synthetic and real-world data to evaluate the performance of our proposed FS method. In the experiments, we focus on high-dimensional, low-sample-size data since they represent the main challenge for FS. The results confirm that the proposed FS method based on a sparse neural-network layer with normalizing constraints (SNeL-FS) is able to select the important features and yields superior performance compared to other conventional FS methods.


Peripartum dissociation, sense of control, postpartum posttraumatic stress disorder and emotional adjustment to motherhood in adult survivors of childhood maltreatment.
Survivors of childhood maltreatment (CM) may experience difficulties in the peripartum period and in adjustment to motherhood. In this study we examined a model wherein CM is associated with maternal self-efficacy and maternal bonding three months postpartum, through mediation of peripartum dissociation and reduced sense of control during childbirth and postpartum-posttraumatic-stress disorder (P-PTSD). Women were recruited in a maternity ward within 48 h of childbirth (T1, N = 440), and contacted three-months postpartum (T2, N = 295). Participants completed self-report questionnaires: peripartum dissociation, sense of control (T1), and CM, P-PTSD, postpartum-depression, maternal self-efficacy and bonding (T2). Obstetrical data were collected from medical files. Structural equation modeling was conducted to test the hypothesized model, controlling for mode of delivery and postpartum-depression. Reported CM included child emotional neglect (CEN; 23.5%), child emotional abuse (CEA; 16.3%), child sexual abuse (CSA; 12.9%) and child physical abuse (CPA; 7.1%). CM was positively associated with peripartum dissociation and P-PTSD (p < .001). Peripartum dissociation was positively associated with P-PTSD (p < .001). P-PTSD was negatively associated with maternal self-efficacy (p < .001) and maternal bonding (p < .001). Association between CM and maternal self-efficacy and bonding was serially mediated by peripartum dissociation and P-PTSD, but not by sense of control. Findings remained significant after controlling for mode of delivery and postpartum-depression. CM is a risk factor for adjustment to motherhood, owing to its effects on peripartum dissociation and P-PTSD. Implementation of a trauma-informed approach in obstetric care and recognition of peripartum dissociative reactions are warranted.


Primary PCI: should we stent every single culprit artery?
In four selected patients presenting with ST-segment elevation myocardial infarction (STEMI), aspiration thrombectomy allowed for full filling defect angiographic 'cleaning' of the culprit arteries without need for stent implantation. Obtaining good angiographic results and uneventful early and long-term clinical outcome after thrombus aspiration alone raises the question as to whether stenting the infracted thrombotic artery is mandatory and routinely indicated in every single STEMI patient treated with primary percutaneous coronary intervention.


Cyclofructan 6 based stationary phases for hydrophilic interaction liquid chromatography.
New stationary phases for hydrophilic interaction liquid chromatography (HILIC) were synthesized by covalently attaching native cyclofructan 6 (CF6) to silica gel. The chromatographic characteristics of the new stationary phases were evaluated and compared to three different types of commercial HILIC columns. The CF6 columns produced considerably different retention and selectivity patterns for various classes of polar analytes, including nucleic acid compounds, xanthines, β-blockers, salicylic acid and its derivatives, and maltooligosaccharides. Univariate optimization approaches were examined including organic modifier (acetonitrile) contents and buffer pH and salt concentration. The thermodynamic characteristic of the CF6 stationary phase was investigated by considering the column temperature effect on retention and utilizing van't Hoff plots. CF6 based stationary phases appear to have exceptionally broad applicability for HILIC mode separations.


Emerging technologies in transdermal therapeutics.
Until very recently, the only drugs that could permeate transdermally were those possessing a very narrow and specific combination of physicochemical properties. However, rapid advances in bioengineering have led to the emergence of various new "active" enhancement technologies designed to transiently circumvent the barrier function of the stratum corneum. These novel systems, using iontophoresis, sonophoresis, electroporation, or microneedle arrays, will greatly expand the range of drugs that can be delivered transdermally. Crucially, the delivery of macromolecules will become possible and the transdermal flux of other molecules could be enhanced by several orders of magnitude. This article sequentially reviews the basis of each of the new enhancement techniques and discusses how these emerging technologies will influence transdermal therapy in the coming years.


Washing-Free Electrochemical Detection of Amplified Double-Stranded DNAs Using a Zinc Finger Protein.
Recombinase polymerase amplification (RPA) has been combined with electrochemical detection for simple and rapid point-of-care testing. However, there are two major hindrances to this simple and rapid testing: (i) washing or purification steps are required to remove unbound labeled probes and interfering species in the sample; (ii) it is difficult to quantify double-stranded DNA (dsDNA) electrochemically by using biospecific affinity binding without dsDNA denaturation. In the present study, we describe a wash-free and rapid electrochemical method to detect RPA-amplified dsDNAs using a zinc finger protein, Zif268. Electrochemical detection is achieved using proximity-dependent electron mediation of ferrocenemethanol between a glucose-oxidase (GOx) label and an electrode, which differentiates the specifically electrode-bound and -unbound labels without a washing or purification step. RPA-amplified dsDNA containing a biotin-terminated forward primer is specifically bound to a neutravidin-modified electrode, and GOx-conjugated Zif268 is specifically bound to the dsDNA. The whole detection is performed within 17 min (15 min for the RPA reaction and <2 min for the electrochemical measurement). Electrochemical detection is carried out without an additional incubation period, because the specific binding between Zif268 and the dsDNA occurs during the RPA reaction. The detection method could discriminate between target template DNA of Piscirickettsia salmonis and nontarget DNAs (random sequence and calf thymus DNA). The detection limit for the target DNA is approximately 300 copies in 13.2 μL, indicating that the detection method is ultrasensitive. We believe that the method could offer a promising solution for simple and rapid point-of-care testing.


Paraformaldehyde effect on ruthenium red and lysine preservation and staining of the staphylococcal glycocalyx.
The utility of lysine in glutaraldehyde-ruthenium red fixatives for the preservation and/or staining of the fibrous staphylococci glycocalyx was improved by inclusion of paraformaldehyde. Short, 20 min prefixation times for paraformaldehyde-glutaraldehyde fixatives containing lysine, with or without ruthenium red, were compared to an extended overnight fixation. Samples were often lost in fixatives that did not contain paraformaldehyde at extended fixation times hampering the effective use of these fixatives for clinical or environmental applications. Inclusion of paraformaldehyde in the fixation with lysine permitted longer fixation times as well as stabilized the staphylococcal glycocalyx. Thus, the technical usefulness of fixatives employing lysine was significantly improved.


A review and analysis of the effectiveness of early intervention programs.
A review was made of 27 studies describing early intervention for biologically impaired infants and young children. Although every study provided some type of documentation of outcome, most studies failed to meet common criteria for scientific research, such as specification of inclusion criteria, documentation of reliability, random assignment, and/or the use of control/contrast groups. Studies were grouped into four classifications on the basis of experimental design as follows: retrospective, prospective-no control group, prospective-control/contrast group, and prospective-random group assignment. A comparative analysis was made of the effectiveness of findings on the basis of statistical evidence and clinical support. Statistical procedures were used in 59% of the studies and statistical support for the effectiveness of early intervention was reported in 48% of the studies. Effectiveness on the basis of subjective, clinical conclusions was reported in 93% of the studies. Implications of the discrepancy between effectiveness based on statistical evidence and clinical conclusions are discussed.


Mechanisms of cytoskeleton-mediated mechanical signal transmission in cells.
Recent experiments have demonstrated very rapid long-distance transmission of mechanical forces within cells. Because the speed of this transmission greatly exceeds that of reaction-diffusion signaling, it has been conjectured that it occurs via the propagation of elastic waves through the actin stress fiber network. To explore the plausibility of this conjecture, we recently developed a model of small amplitude stress fiber deformations in prestressed viscoelastic stress fibers subjected to external forces. The model results demonstrated that rapid mechanical signal transmission is only possible when the external force is applied orthogonal to the stress fiber axis and that the dynamics of this transmission are governed by a balance between the prestress in the stress fiber and the stress fiber's material viscosity. The present study, which is a follow-up on our previous model, uses dimensional analysis to: (1) further evaluate the plausibility of the elastic wave conjecture and (2) obtain insight into mechanical signal transmission dynamics in simple stress fiber networks. We show that the elastic wave scenario is likely not the mechanism of rapid mechanical signal transmission in actin stress fibers due to the highly viscoelastic character of these fibers. Our analysis also demonstrates that the time constant characterizing mechanical stimulus transmission is strongly dependent on the topology of the stress fiber network, implying that network organization plays an important role in determining the dynamics of cellular responsiveness to mechanical stimulation.


[Current status and future development of the comprehensive rehabilitation of transverse paralyzed patients].
The principles developed some 40 years ago by Sir Ludwig Guttmann and Ernest Bors for the treatment of spinal cord injured persons have in the Federal Republic of Germany been taken up, in the fifties, by a few doctors as well as the Central Association of Industrial Injuries Insurance Institutes. Their efforts have brought about a radically different situation concerning life expectancy and life-styles of SCI patients, not only the accident-injured but increasingly also for persons with disease-related spinal lesions. The emphases of development have been: improved mechanisms for referral to specialized facilities, rescue system progress, new findings in diagnosis and therapy, improvement of social and vocational re-integration, growing mutual understanding of paraplegics and their environments, as well as increased self-assertiveness of the paraplegic population. These aspects are examined more closely. Further improvements may be achieved through: admission to specialized treatment facilities immediately following onset, appraisal of relevant issues pertaining to indications for, and techniques of spinal surgery, improved preventive efforts relative to thromboses and embolism, control of the paralytic bladder, a smoother provision of adapted living conditions outside the clinic-based special facilities, and through extension as well as lifelong availability of adequate aftercare services. In the event of certain illnesses, up-to-date treatment of paraplegics must be ensured by the hospital departments concerned with the basis illness. Recreational facilities, and inclusion of psychological and psychotherapeutic services in residential rehabilitation programmes for SCI patients require further attention.


Cefotaxime in Enteric Fever: Therapeutic Reappraisal.
Enteric fever is one of the most common infectious diseases in the economically developing world and this bacterial infection is the common most cause of fever in travelers to these endemic areas. Even after the availability and deployment of preventive measures like vaccination against Salmonella typhi (S. typhi) and sanitation practices; effective treatment is paramount to reduce the associated morbidity and mortality. Cephalosporins are antimicrobials belonging to the β-lactam class with established efficacy, pharmacokinetic, and safety profile by virtue of which, they belong to the group of antibiotics most commonly utilized in clinical practice. They have a broadspectrum of activity against various gram-positive and gram-negative bacteria. Like penicillin, they belong to the β-lactam class of drugs. Amid such a scenario of rising antimicrobial resistance, a broad-spectrum antibiotic like cefotaxime is a real bliss. Distinctive properties of cefotaxime like broad-spectrum of activity, bactericidal action, stability against the common resistance-causing mechanisms, and good safety profile make it a reliable choice in the therapy landscape of enteric fever. It delivers desired efficacy in such difficult-to-treat scenarios at a manageable tolerability profile. Cefotaxime and ceftriaxone have a comparable spectrum of antimicrobial activity, but both differ in terms of pharmacokinetics. Considering the published literature, cefotaxime seems to be a dependable option for the management of typhoid owing to its effectiveness against S. typhi bundled with an acceptable tolerability profile.


Genome-wide evidence for positive selection and recombination in Actinobacillus pleuropneumoniae.
Actinobacillus pleuropneumoniae is an economically important animal pathogen that causes contagious pleuropneumonia in pigs. Currently, the molecular evolutionary trajectories for this pathogenic bacterium remain to require a better elucidation under the help of comparative genomics data. For this reason, we employed a comparative phylogenomic approach to obtain a comprehensive understanding of roles of natural selective pressure and homologous recombination during adaptation of this pathogen to its swine host. In this study, 12 A. pleuropneumoniae genomes were used to carry out a phylogenomic analyses. We identified 1,587 orthologous core genes as an initial data set for the estimation of genetic recombination and positive selection. Based on the analyses of four recombination tests, 23% of the core genome of A. pleuropneumoniae showed strong signals for intragenic homologous recombination. Furthermore, the selection analyses indicated that 57 genes were undergoing significant positive selection. Extensive function properties underlying these positively selected genes demonstrated that genes coding for products relevant to bacterial surface structures and pathogenesis are prone to natural selective pressure, presumably due to their potential roles in the avoidance of the porcine immune system. Overall, substantial genetic evidence was shown to indicate that recombination and positive selection indeed play a crucial role in the adaptive evolution of A. pleuropneumoniae. The genome-wide profile of positively selected genes and/or amino acid residues will provide valuable targets for further research into the mechanisms of immune evasion and host-pathogen interactions for this serious swine pathogen.


Computed tomography as a first-line investigation for elderly patients admitted to a surgical assessment unit.
Background Increases in life expectancy has meant that a higher proportion of patients presenting to surgical assessment units are now elderly. Abdominal computed tomography (CT) can provide early and accurate diagnosis in the elderly, even in the presence of incomplete clinical and biological findings. The aim of this study was to investigate the use of early CT imaging in elderly patients presenting directly to the surgical assessment unit. Materials and methods All consecutive patients aged 65 years and over admitted directly to the surgical assessment unit between January 2017 and April 2017 were identified. Data were collected on demographics, laboratory investigations, radiological investigations and hospital admission. The primary outcome measure was overall length of stay. Results A total of 200 consecutive patients were identified and included over a six-month period. This comprised 110 women and 90 men with a median age of 78 years (range 64-98 years). A total of 83 patients underwent CT on admission to the surgical assessment unit. White cell count (WCC) and C-reactive protein (CRP) results were significantly higher in patients undergoing CT (P = 0.001). Median length of stay for patients undergoing CT was 5 days (range 1-19 days). This was significantly lower than those patients not receiving CT imaging, at 6 days (range 1-105 days; P = 0.034). Discussion CT should be considered as a first-line investigation when elderly patients with an acute abdomen are admitted to surgical assessment units. Early CT can accelerate hospital discharge and decrease overall length of hospital stay.


The future for the Australian Nutrition Foundation: A survey assessing members' nutrition information needs.
The Australian Nutrition Foundation (ANF) conducted a survey of members which investigated their nutrition information needs together with their preferred communication formats, considering the technological advances in informatics. The survey was completed by 103 respondents with a large proportion of health professionals represented. It was found that members were quite satisfied with the performance of the ANF in critical areas like nutrition updates, but less satisfied with the ANF's response to topical nutrition issues in the media. Health professionals used the ANF as a source of nutrition information significantly less often than other occupation categories like teachers and the general public. Strategies were presented which could help the ANF management provide an improved service to the health professionals, a sector which is considered to be very important by the ANF. Print and electronic communication formats were those most preferred by the respondents for their nutrition information needs. Implications for the future directions of the ANF are discussed.


Simulated MRI Artifacts: Testing Machine Learning Failure Modes.
Objective. Seven types of MRI artifacts, including acquisition and preprocessing errors, were simulated to test a machine learning brain tumor segmentation model for potential failure modes. Introduction. Real-world medical deployments of machine learning algorithms are less common than the number of medical research papers using machine learning. Part of the gap between the performance of models in research and deployment comes from a lack of hard test cases in the data used to train a model. Methods. These failure modes were simulated for a pretrained brain tumor segmentation model that utilizes standard MRI and used to evaluate the performance of the model under duress. These simulated MRI artifacts consisted of motion, susceptibility induced signal loss, aliasing, field inhomogeneity, sequence mislabeling, sequence misalignment, and skull stripping failures. Results. The artifact with the largest effect was the simplest, sequence mislabeling, though motion, field inhomogeneity, and sequence misalignment also caused significant performance decreases. The model was most susceptible to artifacts affecting the FLAIR (fluid attenuation inversion recovery) sequence. Conclusion. Overall, these simulated artifacts could be used to test other brain MRI models, but this approach could be used across medical imaging applications.