Supplementation with Cashew Nut and Cottonseed Meal to Modify Fatty Acid Content in Lamb Meat.
This study evaluates the effect of cashew nut meal (CNM), whole cottonseed (WCS), and calcium salts of long-chain fatty acids (Ca-LCFA) on the fatty acid profiles of meat from hair lambs. Thirty-five 60-d-old, male, noncastrated Santa Ines lambs with an initial average body weight of 13.00 ± 1.80 kg were used in a randomized complete-block design with 7 blocks and 5 treatments. The experimental treatments consisted of a control diet (CON) without supplemental lipids and 4 test diets with different lipid supplements that were selected according to the degree of protection from ruminal hydrogenation and their polyunsaturated fatty acid richness. The tests diets included the following modifications: supplementation with WCS, supplementation with CNM, supplementation with both cottonseed and CNM (CSCNM), and supplementation with Ca-LCFA. The C18:1n9c content was highest in the meat of the animals fed the CNM diet (42.00%). The meat from lambs fed the WCS and Ca-LCFA diets had higher C18:0 contents (25.23 and 22.80%, respectively). The C16:1 content was higher in the meat from the animals fed the CNM and CON diets (1.54 and 1.49%, respectively). C18:2c9t11 concentration was higher in the meat from the animals fed the Ca-LCFA and CNM diets. The estimated enzyme activity of Δ9-desaturase C18 was highest in the muscles of the lambs fed the CON, CNM, and CSCNM diets. The use of cashew nuts in the diet resulted in an increase in the C18:2c9t11 content of the lamb meat, which improved the nutritional characteristics of the fat.


[Expression of neuropilin 2 in human colorectal carcinoma and its correlation with lymphangiogenesis and lymphatic metastasis of tumor].
To explore the relationship between neuropilin 2 (NRP-2) and lymphangiogenesis and lymphatic metastasis of human colorectal carcinoma (CRC), as well as the expression of NRP-2 in CRC tissues. A total of 55 cases of CRC, adjacent and normal tissues of surgical resection were randomly selected at our hospital from March 2010 to January 2012. All pathological findings were confirmed by histopathology. The expression of NRP-2 was detected with reverse transcription (RT)-PCR and immunohistochemistry in parenchymatous and surrounding malignant tissues. Then lymphangiogenesis was marked with D2-40 monoclonal antibody and microlymphatic density (MLD) counted. Significant differences of MLD existed between those of tumor region (39 ± 19) and tumor margin (53 ± 26, P < 0.01). Both the number and shape of lymphangiogenesis were different between the parenchymatous and surrounding tissues. The expression of NRP-2 had a positive correlation with MLD both at the protein level (r = 0.325, P < 0.05) and at the gene level (r = 0.545, P = 0.000). And it was also correlated with the differentiation degree, infiltrative degree, lymphovascular invasion, lymph node metastasis and Dukes tumor staging (all P < 0.05). The expression of NRP-2 may regulate lymphangiogenesis and it may play an important role in the incidence and development of CRC.


Putrescine controls the formation of Escherichia coli persister cells tolerant to aminoglycoside netilmicin.
Persisters are suggested to be the products of a phenotypic variability that are quasi-dormant forms of regular bacterial cells highly tolerant to antibiotics. Our previous investigations revealed that a decrease in antibiotic tolerance of Escherichia coli cells could be reached through the inhibition of key enzymes of polyamine synthesis (putrescine, spermidine). We therefore assumed that polyamines could be involved in persister cell formation. Data obtained in our experiments with the polyamine-deficient E. coli strain demonstrate that the formation of persisters tolerant to netilmicin is highly upregulated by putrescine in a concentration-dependent manner when cells enter the stationary phase. This period is also accompanied by dissociation of initially homogenous subpopulation of persister cells to some fractions differing in their levels of tolerance to netilmicin. With three independent experimental approaches, we demonstrate that putrescine-dependent upregulation of persister cell formation is mediated by stimulation of rpoS expression. Complementary activity of putrescine and RpoS results in ~ 1000-fold positive effect on persister cell formation.


Failure of trypanosomal membrane antigens to induce protection against tsetse-transmitted Trypanosoma vivax or T. brucei in goats and rabbits.
A purified protein, relative molecular weight 83 kilodalton (kD), and plasma membranes from Trypanosoma brucei were tested as potential vaccines against tsetse-transmitted T. vivax and T. brucei in goats and rabbits. The 83 kD protein was found in lysates of all clones of T. brucei examined, as well as in lysates of T. vivax, T. congolense and T. rhodesiense. Rabbits and goats were immunized with various amounts of antigen in Freund's complete adjuvant and boosted twice with antigen in Freund's incomplete adjuvant. Two weeks after the last inoculation, the goats were challenged with T. vivax-infected and the rabbits with T. brucei-infected Glossina morsitans morsitans. Although high antibody levels were detected in all the animals immunized with either antigen as measured by radioimmunoassay and immunodiffusion, they became infected and the course of disease was the same as that in unimmunized controls.


Seroprevalence of Chikungunya Virus after Its Emergence in Brazil.
Chikungunya has had a substantial impact on public health because of the magnitude of its epidemics and its highly debilitating symptoms. We estimated the seroprevalence, proportion of symptomatic cases, and proportion of chronic form of disease after introduction of chikungunya virus (CHIKV) in 2 cities in Brazil. We conducted the population-based study through household interviews and serologic surveys during October-December 2015. In Feira de Santana, we conducted a serologic survey of 385 persons; 57.1% were CHIKV-positive. Among them, 32.7% reported symptoms, and 68.1% contracted chronic chikungunya disease. A similar survey in Riachão do Jacuípe included 446 persons; 45.7% were CHIKV-positive, 41.2% reported symptoms, and 75.0% contracted the chronic form. Our data confirm intense CHIKV transmission during the continuing epidemic. Chronic pain developed in a high proportion of patients. We recommend training health professionals in management of chronic pain, which will improve the quality of life of chikungunya-affected persons.


MiR-199a-3p inhibits the proliferation, migration, and invasion of endothelial cells and retinal pericytes of diabetic retinopathy rats through regulating FGF7 via EGFR/PI3K/AKT pathway.
MiR-199a-3p is low expressed in diabetic retinopathy (DR). In the current study, we investigated the effects of miR-199a-3p on DR and the potential mechanisms. A DR rat model was established, and endothelial cells (ECs) and retinal pericytes (RPs) were extracted from the DR model rats to detect miR-199a-3p expression. Bioinformatics analysis predicted that fibroblast growth factor 7 (FGF7) was a target gene for miR-199a-3p, which was confirmed by dual-luciferase assay. Cell proliferation, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation assay, wound-healing, and Transwell assay. Quantitative real-time polymerase chain reaction (q-PCR) and Western blot were performed to detect the expressions of mRNAs and proteins. MiR-199a-3p was low expressed and FGF7 was high-expressed in ECs and RPs. Overexpressed miR-199a-3p suppressed the proliferation, migration, and invasion, and FGF7 expression of ECs and RPs. However, overexpression of FGF7 effectively eliminated the suppressive effects of miR-199a-3p overexpression malignant behaviors of the cells. Meanwhile, up-regulation of FGF7 noticeably reversed the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the expression of epidermal growth factor receptor (EGFR) reduced by miR-199a-3p. Our findings revealed that in the DR rat model, miR-199a-3p inhibited cell proliferation, migration, and invasion of EC and RP through targeting FGF7 and inhibiting the activation of the EGFR/PI3K/AKT pathway. This study may provide a new direction for the search for the treatment of DR.


Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure.
Polycyclic aromatic hydrocarbons (PAHs) refer to a ubiquitous group of anthropogenic air pollutants that are generated through incomplete carbon combustion. Although the immunotoxic nature of PAHs has been previously reported, the underlying molecular mechanisms of this effect are not fully understood. In the present study, we investigated the mitochondrial-mediated epigenetic regulation of 2 PAHs, carcinogenic (benzo[a]pyrene; BaP) and noncarcinogenic (anthracene [ANT]), in peripheral lymphocytes. While ANT exposure triggered mitochondrial oxidative damage, no appreciable epigenetic modifications were observed. On the other hand, exposure to BaP perturbed the mitochondrial redox machinery and initiated cascade of epigenetic modifications. Cells exposed to BaP showed prominent changes in the expression of mitochondrial microRNAs (miR-24, miR-34a, miR-150, and miR-155) and their respective gene targets (NF-κβ, MYC, and p53). The exposure of BaP also caused significant alterations in the expression of epigenetic modifiers (DNMT1, HDAC1, HDAC7, KDM3a, EZH2, and P300) and hypomethylation within nuclear and mitochondrial DNA. This further induced methylation of histone tails, which play a crucial role in the regulation of chromatin structure. Overall, our study provides novel mechanistic insights into the mitochondrial regulation of epigenetic modifications in association with PAH-induced immunotoxicity.


Endovascular coiling versus neurosurgical clipping for patients with aneurysmal subarachnoid haemorrhage.
Patients who have had an aneurysmal subarachnoid haemorrhage (SAH) are at very high risk of rebleeding if the aneurysm is not treated. The standard treatment for several decades has been surgical clipping of the neck of the aneurysm. In recent years, an alternative, the introduction of detachable coils to occlude the aneurysm, has become more common. To compare the effects of endovascular coiling versus neurosurgical clipping in patients with aneurysmal subarachnoid haemorrhage. We searched the Cochrane Stroke Group Trials Register (last searched in February 2005). In addition we searched MEDLINE (1966 to January 2004) and EMBASE (1980 to January 2004), and contacted trialists. We included randomised trials in which endovascular coiling of aneurysms was compared with neurosurgical clipping in patients with SAH who have proven aneurysm. Two authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. We identified three randomised trials: two published and one unpublished. The trials included a total of 2272 patients (range per trial: 20 to 2143 patients). Most of the patients were in good clinical condition and had an aneurysm on the anterior circulation. After one year of follow up, the relative risk (RR) of poor outcome for coiling versus clipping was 0.76 (95% confidence interval (CI) 0.67 to 0.88). The absolute risk reduction was 7% (95% CI 4% to 11%). In the worst-case scenario analysis for poor outcome overall, the relative risk for coiling versus clipping was 0.81 (95% CI 0.70 to 0.92) and the absolute risk reduction was 6% (95% CI 2% to 10%). For patients with anterior circulation aneurysm the relative risk of poor outcome was 0.78 (95% CI 0.68 to 0.90) and the absolute risk decrease was 7% (95% CI 3% to 10%). For those with a posterior circulation aneurysm the relative risk was 0.41 (95% CI 0.19 to 0.92) and the absolute decrease in risk 27% (95% CI 6% to 48%). The evidence comes mainly from one large trial. For patients in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation we have firm evidence that, if the aneurysm is considered suitable for both surgical clipping and endovascular treatment, coiling is associated with a better outcome.


Hypoxia Promotes Osteogenesis of Human Placental-Derived Mesenchymal Stem Cells.
Placental-derived mesenchymal stem cells (pMSCs) are promising candidates for regenerative medicine because they possess high proliferative capacity and multi-differentiation potential. Human pMSCs are residing in an environment with low oxygen tension in the body. Heme oxygenase-1 (HO-1) is known to participate in the regulation of MSC differentiation. The present study aimed to investigate the impact of hypoxia on the osteogenic differentiation of human pMSCs, and to elucidate the role of HO-1 in the osteogenic differentiation of hypoxic pMSCs. Human pMSCs were cultured under normoxia (21% O2) or hypoxia (5% O2) for 3 days. We found that hypoxia maintained the morphology and immunophenotype of human pMSCs. The expression of stemness markers Oct4, Nanog, and Sox2 was increased under hypoxia. After a 5-day hypoxic culture, the proliferation ability of pMSCs was increased, which might be correlated with the increased expression of stem cell factor. During osteogenic induction, hypoxia increased the expression of osteogenic genes including osteopontin, osteocalcin, and alkaline phosphatase (ALP). Moreover, hypoxia increased the mineralization and ALP levels of human pMSCs as evidenced by Alizarin Red staining and ALP staining. Upregulation of HO-1 by cobalt-protoporphyrin treatment increased the osteogenic differentiation of pMSCs under hypoxia, while inhibition of HO-1 by Zn-protoporphyrin reduced the osteogenic differentiation of hypoxic pMSCs. Taken together, our data suggest that hypoxia can promote the osteogenic differentiation of human pMSCs. Upregulation of HO-1 can further increase the osteogenesis of human pMSCs under hypoxia. Our findings will highlight the therapeutic potential of MSCs in the tissue engineering of bones.


Deorphanisation of G protein-coupled receptors: A tool to provide new insights in nervous system pathophysiology and new targets for psycho-active drugs.
G protein-coupled receptors represent the largest family of membrane receptors translating extracellular into intracellular signals. Endogenous ligands for these receptors range from physical stimuli (e.g., light and odorants) to ions and chemical transmitters, such as "classical" biogenic amines, nucleotides and peptides. Some of these receptors are pathologically altered in neurodegenerative and psychiatric diseases and indeed represent the target for a variety of already marketed psycho-active drugs. With the publication of the human genome, it has become evident that there still are many "orphan" G protein-coupled receptors, i.e., receptors responding to yet-unidentified endogenous ligands. A large amount of these receptors are expressed in nervous tissues, but, apart from their molecular structure, we have no information concerning their physiological roles and alterations in disease states. In this review, we summarise the advancements and pitfalls of the strategies that have been exploited in recent years to "deorphanise" some of these receptors. We also show how, in some cases, this deorphanisation process has resulted in the identification of new potential targets for drug development as well as in the discovery of previously unknown neurotransmitters, including bioactive peptides and substances that had been merely known as metabolic intermediates. We envisage that the deorphanisation of the remaining orphan G protein-coupled receptors will further advance our knowledge of nervous system pathophysiology and unveil additional targets for new therapeutic approaches to human diseases, including psychosis, depression, anxiety, pain and aging-associated neurodegenerative disorders.


Socio-economic status and oral health-related behaviours in Korean adolescents.
The principle objective of this study was to assess the association between socio-economic status (SES) and oral health-related behaviours in Korean adolescents aged 13-18, using the Family Affluence Scale (FAS). The secondary objective was to assess the influences of other factors (pocket money, school type, family structure and psychological factors) on this association. Cross-sectional data were from the national 2007 Korean Youth Risk Behavior Web-based Survey. Oral health-related behaviours included health-enhancing behaviours (frequency of toothbrushing and dental visits) and health-compromising behaviours (smoking and frequency of intake of soft drinks and confections). Logistic regression models were used to analyse the data. To assess the influence of other factors, additional models adjusting for sex, school grade and each of the other factors were compared to the initial model, which adjusted for sex and school grade only. We found that family affluence had a linear association with health-enhancing behaviours and a roughly U-shaped association with health-compromising behaviours. After adjusting for a number of variables, the linear association with health-enhancing behaviours persisted. The U-shaped association with health-compromising behaviours remained but was partly attenuated and flattened. In addition, we found a marked influence of school type and family structure and pocket money on the association between FAS and oral health-compromising behaviours. The findings indicate that the health-enhancing behaviours of adolescents were strongly associated with family affluence, but the health-compromising behaviours were more strongly linked to factors other than family affluence. However, it is difficult to determine which factors contribute most in relation to family affluence because of other confounding factors, such as the education system, peer group, youth culture, part-time work and advertising. Therefore, further studies are needed to assess factors that interact with family SES to better understand the association between the SES and the oral health-compromising behaviours of adolescents.


Effectiveness of tramadol as an analgesic in oral surgery.
In a randomised, double-blind, cross-over trial, 15 healthy, young patients undergoing surgical removal of bilateral, impacted, third-molar teeth received the analgesic tramadol 50 mg, as a single dose, either 2 hours prior or immediately before the surgical procedure. There were no differences in the post-operative pain levels or degree of trismus between the two methods of administration of tramadol (P > 0.05), suggesting absence of any pre-emptive analgesic effect for the drug in the dose studied. The prevalence of unwanted side effects such as nausea (37 percent) was high within the first 24 hours.


Prostate Artery Embolization for Benign Prostate Hyperplasia Review: Patient Selection, Outcomes, and Technique.
Prostate artery embolization (PAE) is a minimally invasive technique in managing men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BPH is one of the commonest causes of LUTS in men, associated with high morbidity and economic burden. Patients suffering from LUTS secondary to BPH, severe enough to warrant intervention traditionally underwent transurethral resection of the prostate or open prostatectomy. PAE is an emerging alterative technique with promising data. In this paper we review important elements to running a safe PAE practice including careful patient selection, exclusion criteria, complications, and efficacy of PAE compared to other techniques. This paper also reviews the basic anatomy and techniques relevant to PAE, including common anatomical variants.


Identification of fruity/fermented odorants in high-temperature-cured roasted peanuts.
Gas chromatography/olfactometry on a concentrate of volatiles obtained by solvent-assisted flavor evaporation (SAFE) from roasted peanuts containing a fruity/fermented off-note was used to identify the odorants responsible for the flavor defect. Freshly dug peanuts were divided into two classes, mature and immature, using pod mesocarp color, and subjected to normal (27 degrees C) and high (40 degrees C) temperature curing. Sensory evaluation of the roasted peanuts found that immature peanuts cured at high temperature contained the fruity/fermented off-note. Mature peanuts cured at high temperature and both immature and mature peanuts cured at low temperature were free of the off-note. Peanuts with the off-flavor were found to contain fruit-like esters (ethyl 2-methylpropanoate, ethyl 2-methylbutanoate, and ethyl 3-methylbutanoate) along with increased levels of short chain organic acids (butanoic, 3-methylbutanoic, and hexanoic). These findings were confirmed by sensory evaluation of models, where the addition of these compounds produced the fruity/fermented flavor defect in a control peanut paste. This is the first time that the odorants responsible for this off-note in roasted peanuts have been identified.


Dissociable Roles of Cerebral μ-Opioid and Type 2 Dopamine Receptors in Vicarious Pain: A Combined PET-fMRI Study.
Neuroimaging studies have shown that seeing others in pain activates brain regions that are involved in first-hand pain, suggesting that shared neuromolecular pathways support processing of first-hand and vicarious pain. We tested whether the dopamine and opioid neurotransmitter systems involved in nociceptive processing also contribute to vicarious pain experience. We used in vivo positron emission tomography to quantify type 2 dopamine and μ-opioid receptor (D2R and MOR, respectively) availabilities in brains of 35 subjects. During functional magnetic resonance imaging, the subjects watched short movie clips depicting persons in painful and painless situations. Painful scenes activated pain-responsive brain regions including anterior insulae, thalamus and secondary somatosensory cortices, as well as posterior superior temporal sulci. MOR availability correlated negatively with the haemodynamic responses during painful scenes in anterior and posterior insulae, thalamus, secondary and primary somatosensory cortices, primary motor cortex, and superior temporal sulci. MOR availability correlated positively with orbitofrontal haemodynamic responses during painful scenes. D2R availability was not correlated with the haemodynamic responses in any brain region. These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain.


Effects of cognitive behavioural therapy for depression in heart failure patients: a systematic review and meta-analysis.
This systematic review and meta-analysis aimed to evaluate the effects of cognitive behavioural therapy (CBT) on depression, quality of life, hospitalisations and mortality in heart failure patients. The search strategy was developed for Ovid MEDLINE and modified accordingly to search the following bibliographic databases: PubMed, EMBASE, PsycINFO, CENTRAL and CINAHL. Databases were searched from inception to 6 March 2016 for randomised controlled trials (RCTs) or observational studies that used CBT in heart failure patients with depression or depressive symptoms. Six studies were identified: 5 RCTs and 1 observational study, comprising 320 participants with predominantly NYHA classes II-III, who were mostly male, with mean age ranging from 55 to 66 years. Compared to usual care, CBT was associated with a greater improvement in depression scores both initially after CBT sessions (standardised mean difference -0.34, 95% CI -0.60 to -0.08, p = 0.01) and at 3 months follow-up (standardised mean difference -0.32, 95% CI -0.59 to -0.04, p = 0.03). Greater improvement in quality of life scores was evident for the CBT group initially after CBT sessions, but with no difference at 3 months. Hospital admissions and mortality were similar, regardless of treatment group. CBT may be more effective than usual care at improving depression scores and quality of life for heart failure patients initially following CBT and for depression at 3 months. Larger and more robust RCTs are needed to evaluate the long-term clinical effects of CBT in heart failure patients.


Rehabilitation program for prosthetic tracheojejunal voice production and swallowing function following circumferential pharyngolaryngectomy and neopharyngeal reconstruction with a jejunal free flap.
The case of a 68-year-old woman with postoperative speech and swallowing problems following a circumferential pharyngolaryngectomy and neopharyngeal reconstruction with a jejunal free flap is presented. The primary tumor was an extended papillary thyroid carcinoma (pT4N0M0). For vocal restoration, an indwelling Provox(®) 1 voice prosthesis was inserted secondarily. The patient received speech and swallowing therapy, including digital maneuvers at the level of the proximal (cervical) part of the jejunal graft to improve speech and swallowing function. Pre- and/ or post-treatment data on speech and swallowing function were gathered using the following assessment methods: esophageal insufflation test, Voice Handicap Index (VHI), videofluoroscopy of phonation (VFSph), digital high-speed endoscopy of jejunal vibration during voice production, fiber-optic endoscopic evaluation of swallowing (FEES), and videofluoroscopy of swallowing (VFSs). This case clearly demonstrates that even after extensive laryngopharyngectomy with jejunal free flap reconstruction, a tailored rehabilitation program can improve both voice and swallowing function, and that these results clearly can be objectified/visualized, underlining the validity of this approach.


Studies on the role of the plasma protease inhibitors on in vitro C3 activation and in acute pancreatitis.
Plasma samples from 32 patients with severe acute pancreatitis contained cleavage products of C3, and the C3 levels were significantly lower than those of control subjects. Peritoneal exudate from all patients showed complete degradation of C3 on crossed immunoelectrophoresis. Alpha 1-Antitrypsin and alpha 2-macroglobulin showed no signs of complex formation in plasma. However, in the peritoneal exudate, 5%-25% of the alpha 1-antitrypsin and 45%-100% of the alpha 2-macroglobulin were in complex. Trypsin-alpha 1-antitrypsin complexes were demonstrated in all peritoneal exudates. All patients showed significantly decreased levels of alpha 2-macroglobulin in their plasma. Alpha 1-Antitrypsin levels varied greatly, but the mean value was not significantly increased compared with those of normal controls. Orosomucoid, another acute-phase reactant, was present in increased concentration in the plasma of all patients. The addition of increasing amounts of human trypsin to serum in vitro resulted in the appearance of cleavage products of C3 upon saturation of alpha 2-macroglobulin, when the alpha 1-antitrypsin was found to be only about 40% saturated. Taken together, these data are evidence of complement catabolism in acute pancreatitis and suggest that this process takes place mainly in the abdominal cavity as a result of a protease-antiprotease imbalance. Alpha 2-Macroglobulin, but not alpha 1-antitrypsin, can protect against C3 degradation caused by trypsin in vitro.


Intracranial space, brain, and cerebrospinal fluid volume measurements obtained with the aid of three-dimensional computerized tomography in patients with and without Crouzon syndrome.
The authors attempt to provide a standard for volumes of the intracranial space, brain, and cerebrospinal fluid (CSF) in healthy control individuals by using in vivo three-dimensional (3D) computerized tomography (CT) data and to compare these data with those obtained from a group with Crouzon syndrome. Fifty-seven individuals underwent 3D head CT scanning for nonintracranial-related disease to produce a set of normal volumes for the intracranial space, brain, and CSF. Prediction limits of 95% were obtained to provide a range of acceptable volumes throughout the growing period and early adulthood. Eleven patients (seven boys and four girls, age range 2.2 months-13.4 years) with Crouzon syndrome underwent identical measurements, which were compared with those of the control patients. The control group comprised 35 boys and 22 girls who ranged in age from 0.26 months to 24.4 years. Intracranial space and brain volume showed a progressive increase with age, with three different slopes from birth to adulthood. Male patients were found to have larger volumes than female patients in the same age group. Volume patterns for CSF were not significantly different within a given age or sex. Six patients with Crouzon syndrome had intracranial and brain volumes within the 95% prediction limit, three patients measured above the limit, and two measured below. A standard for volumes of intracranial space and structures provides a guideline for the evaluation of patients with intracranial disease. Volumes in patients with Crouzon syndrome can be matched to their normal age- and sex-matched counterparts.


Leukocyte migration inhibition detects cross-reacting antigens between cells transformed by Epstein-Barr virus (EBV) and EBV-like simian viruses.
The leukocyte migration inhibition (LMI) technique was used to measure the T cell-mediated immune response of Epstein-Barr-virus (EBV)-seropositive human donors to antigens associated with B cell lines of simian origin, transformed by simian EBV-like viruses, Herpesvirus papio (HVP), H. pan, H. gorilla and H. pongo. Extracts of cell lines carrying three of the four simian viruses (from gorilla, chimpanzee and orangutan) induced a positive LMI response, whereas lines carrying baboon-derived HVP were ineffective. None of the simian virus-transformed lines elicited an LMI reaction in human EBV-seronegative individuals. Leukocytes from patients with acute infectious mononucleosis (IM) failed to respond to any of the lines transformed by EBV or the simian EBV-like viruses. Such lines express the virally encoded nuclear antigen, but have only a low level of viral cycle-associated antigens. Extracts of the EBV-carrying human cell line P3HR-1 induced with 12-O-tetradecanoylphorbol-13-acetate to express high levels of early and virus capsid antigens (EA, VCA, respectively) however, elicited a strong response with leukocytes from patients with acute IM. During convalescence, IM patients became responsive to EBV, H. gorilla-, H. pan- and H. pongo-transformed lines, indicating that the LMI reaction induced by these simian virus-transformed lines was directed against the antigens expressed in immortalized cells rather than against antigens of the lytic cycle. It is highly probable that this reaction reflects a cross-recognition of the nuclear antigens associated with these four transforming viruses (excluding H. papio) at the level of human T cells.


The effect of n-3 polyunsaturated fatty acids on plasma lipids and lipoproteins in patients with chronic renal failure--a meta-analysis of randomized controlled trials.
To systemically review and analyze the effect of n-3 polyunsaturated fatty acid (PUFA) consumption on plasma lipids and lipoproteins in patients with end-stage renal disease. Systemic review, with meta-analysis of randomized controlled clinical trials. We performed a systemic review and meta-analysis of the lipid-modulating effects of n-3 PUFAs by combining evidences from 10 randomized controlled trials including 557 patients with end-stage renal disease. Pooled analysis revealed that n-3 PUFA intake significantly reduced serum triglyceride levels by -0.78 mmol/L (95% confidence interval: -1.12 to -0.44 mmol/L, P < .0001). Consumption of n-3 PUFAs also reduced the plasma low-density lipoprotein cholesterol levels by -0.09 mmol/L and elevated plasma high-density lipoprotein cholesterol levels by -0.25 mmol/L, but these changes were not statistically significant. Plasma levels of total cholesterols were elevated in both n-3 PUFA and control groups, with a lesser increase in the n-3 PUFA group, without statistical significance. Metaregression showed no correlation between the amounts or duration of n-3 PUFA intake and their lipid-modulating effects. In our meta-analysis, n-3 PUFA consumption significantly lowered the serum triglyceride levels. No significant changes were found on the degrees of low-density lipoprotein cholesterol reduction and total cholesterol or high-density lipoprotein cholesterol elevation effects.


Eicosapentaenoic and Docosahexaenoic Acids Attenuate Progression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease.
Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation attenuates progression of albuminuria in subjects with coronary artery disease. Two-hundred sixty-two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin-to-creatinine ratio (ACR) was compared. Mean (SD) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% (P<0.001) in diabetic subjects not receiving Lovaza, whereas those receiving Lovaza had no change. In diabetic subjects on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker, those receiving Lovaza had no change in urine ACR, whereas those not receiving Lovaza had a 64.2% increase (P<0.001). Change in ACR was directly correlated with change in systolic blood pressure (r=0.394, P=0.01). EPA and DHA supplementation attenuated progression of albuminuria in subjects with type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624727.


An evaluation of nasogastric (NG) tube removal practices and nutritional intake parameters in an acute neurosurgical population: The development of an NG Transition Feeding Protocol.
As a result of the complex nature of neurosurgical patients, nasogastric (NG) tube feeding is often implemented for patients who are unable to consume adequate oral intake. During recovery, patients on enteral nutrition (EN) are progressed to oral nutrition, which can result in NGT removal and discontinuation of supportive feeding plans. This is often before patients become established on sufficient oral intake to meet their nutritional requirements. We conducted an exploration of current NG removal practices in patients (n = 23) across five neurosurgical wards over a 3-month period to assess practitioner review response times, NG feeding duration, decision making on NG removal, and the influence of dietary recommendations and differing EN protocols on patients' ability to meet their nutritional requirements. Our aim was to use this data to design and implement a protocol to improve consistency of these practices. After oral intake was commenced, only those receiving supplementary EN achieved nutritional targets immediately. Conversely, no patient who had their NGT removed at this stage achieved these targets. Following NG removal, the likelihood of a patient meeting nutritional targets was influenced by the decision maker, supporting the practice of registered dietitian led cessation of NG feeding. These findings led us to develop an "NG Transition Feeding Protocol" to serve as a simple, clear pathway which treating teams can utilise to guide NG feeding decisions. NG feeding supports neurosurgical patients to meet nutritional requirements in the early stages following commencement of oral intake. The development of an "NG Transition Feeding Protocol" may help to improve consistency of transition feeding on neurosurgical wards, allowing time for nutrition assessment to support informed decisions around NG removal. The aim of this protocol is to improve the efficiency of transition feeding, improve dietetic workload efficiency, nursing staff confidence and avoid compromising nutritional status of patients as a result of the early cessation of EN.


Intraparenchymal supratentorial papillary meningioma: a case report.
Although intraparenchymal meningiomas have rarely been reported in the literature, the papillary type has been reported only as infratentorial. Here we report the case of a 21-year-old female patient with intraparenchymal lesion. To our knowledge, this case describes the first report of a patient with a supratentorial intraparenchymal papillary meningioma.


Unlocking the Potential: Predicting Redox Behavior of Organic Molecules, from Linear Fits to Neural Networks.
Redox-active organic molecules, i.e., molecules that can relatively easily accept and/or donate electrons, are ubiquitous in biology, chemical synthesis, and electronic and spintronic devices, such as solar cells and rechargeable batteries, etc. Choosing the best candidates from an essentially infinite chemical space for experimental testing in a target application requires efficient screening approaches. In this Review, we discuss modern in silico techniques for predicting reduction and oxidation potentials of organic molecules that go beyond conventional first-principles computations and thermodynamic cycles. Approaches ranging from simple linear fits based on molecular orbital energy approximation and energy difference approximation to advanced regression and neural network machine learning algorithms employing complex descriptors of molecular compositions, geometries, and electronic structures are examined in conjunction with relevant literature examples. We discuss the interplay between ab initio data and machine learning (ML), i.e., whether it is better to base predictions on low-level quantum-chemical results corrected with ML or to bypass first-principles computations entirely and instead rely on elaborate deep learning architectures. Finally, we list currently available data sets of redox-active organic molecules and their experimental and/or computed properties to facilitate the development of screening platforms and rational design of redox-active organic molecules.


[Diagnosis and treatment of gastrointestinal carcinoid. Report of a clinical case with duodenal site].
Carcinoid tumors are among the most frequently neuroendocrine neoplasms of the gastrointestinal tract. They occur more commonly as benign diseases but malignant ones can also be found. The peak age incidence varies with the location of the tumor, with appendiceal tumors being diagnosed at an overage of 36 years, whereas non appendiceal tumors are found typically in the fifth sixth decades of life. There is no sex predilection of the tumors. Most carcinoid tumors are found within the appendix (40-50%) or small intestine (25%). Less common sites include the rectum (15%), main bronchus (10%), duodenum (3-8%) and stomach (2%). Most carcinoid tumors are found incidentally at operation and cause no symptoms. If symptoms do occur, they can be either non specific include intermittent crampy abdominal pain, vomiting and distension caused by intestinal obstruction. The prognosis depends on the site of the tumor and its size. Most carcinoid tumors (75%) are less than 1 cm in size and only 5% are greater than 2 cm. The incidence of metastatic disease is related directly to the size of the tumor at all locations. Carcinoid tumor with size less than 1 cm give linfonodal metastasis only in 3-5%; the other with size over 2 cm give metastasis in the 70-75% of the cases. The 5-years survival for all carcinoid tumors are approximately 85%. Five years rate is higher (> 80%) in carcinoid tumors of appendix and rectum than in gastroduodenal, ileal and colonic neoplasm (< 60%). In this paper the authors report a case of malignant carcinoid of the duodenum.


Cognitive status in the oldest old and centenarians: a condition crucial for quality of life methodologically difficult to assess.
Human life expectancy and the number of the oldest old are rapidly increasing worldwide. Advanced age is the main risk factor for dementia, representing one of the major causes of disability/dependency among older people with a strong impact on their families/caregivers. Centenarians have reached the extreme limits of human life escaping or delaying the major age-related diseases. Thus, these extraordinary individuals embody the best model to answer the crucial question if cognitive decline and dementia are progressive and unavoidable occurrences of increasing age. Despite a growing amount of data underlines the importance of cognitive function for quality of life and survival in old age, studies on centenarians have paid more attention to their physical condition rather than the assessment of their actual cognitive abilities. Accordingly, this work aims to summarize available data on the prevalence of dementia in centenarians and to critically address topics which can have a relevant impact on the cognitive assessment/status of the oldest old: (i) lack of standardized tools for cognitive assessment; (ii) criteria and threshold to establish the presence of dementia; (iii) influence of birth cohort and education; (iv) role of depression or positive attitude towards life; (v) gender differences.


Endoscopic hemostasis by local injection of epinephrine and polidocanol in bleeding ulcer. A prospective randomized trial.
The present prospective randomized trial has been carried out to assess the efficacy of the endoscopic injection of epinephrine plus polidocanol, in the prompt treatment of upper gastrointestinal bleeding due to peptic lesions. Over a period of one year, 72 patients were admitted to the study. Thirty-six of these underwent endoscopic treatment (group A), while the others received medical treatment (group B). Definitive hemostasis was achieved in 29 patients in group A, and in 21 in group B (p less than 0.05). Seven patients in group A and 12 in group B underwent emergency surgery for persistent or recurrent bleeding (p = NS). Three patients from group B received endoscopic treatment owing to relative surgical contraindications. It was successful in all of them. Patients from group A needed a significantly lower number of units of packed red cells (p less than 0.05). Our results show that it is justified to employ endoscopic injection as the first therapeutic step in upper GI bleeding due to peptic gastroduodenal lesions.


Total hip arthroplasty combined with subtrochanteric shortening osteotomy for Crowe type IV hip dysplasia in dwarfism: a case report.
Dwarfism is a condition of extreme short stature. Total hip arthroplasty (THA) in patients with dwarfism is a very demanding procedure due to their specific joint deformity and small bone size, which increases the technical difficulty of the THA procedure in such patients with hip dysplasia. This current case report describes a 29-year-old female patient that was admitted due to shortening of the right lower limb, as compared with the contralateral side, which had been present for 18 years. She also complained of pain in the right hip that had been present for 2 months. The hip pain was aggravated by physical exertion, but relieved by rest. She had pituitary dwarfism without mental retardation or delayed sexual development and Crowe type IV dysplasia of the right hip. A THA combined with femoral shortening osteotomy was undertaken, which resolved the pain symptoms and improved her ability to undertake activities of daily living such as walking without pain. Dwarfism with hip dysplasia is a rare but extremely challenging problem that can be successfully treated with THA combined with femoral shortening osteotomy using an S-ROM stem.


Willingness and acceptability of cervical cancer screening among HIV positive Nigerian women.
The proven benefit of integrating cervical cancer screening programme into HIV care has led to its adoption as a standard of care. However this is not operational in most HIV clinics in Nigeria. Of the various reasons given for non-implementation, none is backed by scientific evidence. This study was conducted to assess the willingness and acceptability of cervical cancer screening among HIV positive Nigerian women. A cross sectional study of HIV positive women attending a large HIV treatment centre in Lagos, Nigeria. Respondents were identified using stratified sampling method. A pretested questionnaire was used to obtain information by trained research assistants. Obtained information were coded and managed using SPSS for windows version 19. Multivariate logistic regression model was used to determine independent predictor for acceptance of cervical cancer screening. Of the 1517 respondents that returned completed questionnaires, 853 (56.2%) were aware of cervical cancer. Though previous cervical cancer screening was low at 9.4%, 79.8% (1210) accepted to take the test. Cost of the test (35.2%) and religious denial (14.0%) were the most common reasons given for refusal to take the test. After controlling for confounding variables in a multivariate logistic regression model, having a tertiary education (OR = 1.4; 95% CI: 1.03-1.84), no living child (OR: 1.5; 95% CI: 1.1-2.0), recent HIV diagnosis (OR: 1.5; 95% CI: 1.1-2.0) and being aware of cervical cancer (OR: 1.5; 95% CI: 1.2-2.0) retained independent association with acceptance to screen for cervical cancer. The study shows that HIV positive women in our environment are willing to screen for cervical cancer and that the integration of reproductive health service into existing HIV programmes will strengthen rather than disrupt the services.


Physiologic aspects of drug therapy and large artery elastic properties.
Vasoactive drugs alter smooth muscle tone not only in arterial resistance vessels, but also in large conduit arteries. The resultant changes in smooth muscle tone alter both conduit vessel size and stiffness and hence influence pulsatile components of left ventricular afterload. The effects of smooth muscle relaxation and contraction on arterial elastic properties are complex and have not been fully characterized. Several recent studies have utilized a new intravascular ultrasound technique to study the effects of changes in smooth muscle tone on brachial artery elastic mechanics in normal human subjects in vivo. Smooth muscle relaxation with nitroglycerin improves isobaric brachial artery compliance without significantly altering arterial wall stiffness as measured by incremental elastic modulus (Einc). The improvement in compliance with smooth muscle relaxation is the net result of factors that: (1) increase wall stiffness (increased tension in parallel elastin and collagen fibers); (2) decrease wall stiffness (decreased tension in the smooth muscle and its associated series elastic component); and (3) increase vessel lumen size. Using a modified Maxwell model for the arterial wall, smooth muscle relaxation is also shown to shift the predominant elements contributing to wall stress and Einc from smooth muscle and the collagen fibers in series with the smooth muscle to collagen fibers in parallel with the smooth muscle. A better understanding of the mechanisms contributing to changes in arterial elastic mechanics following alterations in smooth muscle tone will help in developing pharmacologic therapies aimed at reducing pulsatile components of left ventricular afterload.


Incidence, prevalence, mortality, and causes of death in Waldenström macroglobulinemia: a nationwide, population-based cohort study.
The epidemiological features of Waldenström macroglobulinemia (WM) have seldom been investigated at a national level, particularly in East Asia. The goal of our study is to present the incidence, prevalence, mortality, survival with competing risks, and causes of death of patients with WM. We used a national population-based database, operated by the Health Insurance Review and Assessment Service of the Korean government. This data includes information on all WM patients diagnosed according to uniform criteria, between 2003 and 2016. The total number of patients newly diagnosed with WM during the study period was 427, with a male-to-female ratio of 3.2:1. The incidence increased from 0.03 to 0.10 per 105 between 2003 and 2016, and the prevalence was 0.42 per 105 in 2016. A total of 217 patients with WM died during the study period (standardized mortality ratio = 7.57), and the overall survival (OS) of WM patients was 47.5%. On multivariate analysis, older age was associated with worse OS (P < 0.0001). WM was the most common cause of death (n = 102, 48.6%), followed by other malignant neoplasms (n = 82, 39.0%). The national incidence of WM in Korea, a racially homogeneous country in Asia, was lower than that in previous reports from other countries, reflecting ethnic disparities. However, the incidence increased, and mortality was the highest ever reported. The main cause of death was WM in itself. This study reflects the need for greater awareness of WM, particularly in Asian countries.


Scleritis Caused by In Vitro Linezolid-Resistant Nocardia asteroides.
Purpose. To describe a case of postoperative scleritis caused by a novel strain of Nocardia resistant to linezolid and trimethoprim-sulfamethoxazole (TMP-SMX). Methods. Case report of a patient with microbiologically proven scleritis due to Nocardia asteroides. Results. The patient presented with pain, redness, and nodules on the sclera three months following pterygium excision with mitomycin C and amniotic membrane placement. As no response was noted with empiric treatment for bacterial scleritis, debridement was performed. The cytopathology report showed gram positive filamentous bacteria. A presumptive diagnosis of Nocardia scleritis was made and therapy was initiated based on a literature review on treatments for Nocardia infections. Cultures returned growing Nocardia asteroides. Antibiotic sensitivity testing revealed resistance to linezolid and TMP-SMX which are the traditional drugs of choice for Nocardia. The patient was treated with amikacin and imipenem as well as extensive debridement with pedicle grafts. The patient's scleritis resolved with a good visual outcome. Conclusions. Cultures should be obtained in all cases of necrotizing scleritis in patients with a recent history of conjunctival surgery to rule out unusual organisms such as Nocardia. Although literature states that resistance to linezolid and TMP-SMX is rare in Nocardia, sensitivity testing can be useful in unresponsive cases.


Comparison of four different serological methods for detection of antibodies to Borrelia burgdorferi in erythema migrans.
Three different enzyme-linked immunosorbent assays (ELISA) and Western blot were compared in regard to the detection of antibodies to Borrelia burgdorferi in sera from 100 patients with erythema migrans and from 100 controls. For IgG detection, a commercial indirect ELISA kit with flagellum antigen (flagellum ELISA) was significantly more sensitive than the routinely-used indirect ELISA with sonicated whole-cell antigen (sonicate ELISA) (p = 0.008). The difference in positivity in the IgM test was of borderline significance (p = 0.058). An IgM antibody-capture ELISA with sonicated whole-cell antigen (capture ELISA) was significantly more sensitive than either the IgM sonicate ELISA (p less than 0.001) or IgM flagellum ELISA (p less than 0.001). With the Western blot pattern chosen as the criterion for positivity, IgM Western blot was at least equal to IgM capture ELISA in terms of the number of positive erythema migrans sera, but a frequent discrepancy between these two tests was noted as to positivity in individual sera. IgG Western blot was considered to be of less value for the diagnosis of current disease due to a high occurrence of positivity among controls.


Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis.
Autoreactive CD4+ T lymphocytes play a vital role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Since the discovery of T helper 17 cells, there is an ongoing debate whether T helper 1, T helper 17 or both subtypes of T lymphocytes are important for the initiation of autoimmune neuroinflammation. We examined peripheral blood CD4+ cells from patients with active and stable relapsing-remitting multiple sclerosis, and used mice with conditional deletion or over-expression of the transforming growth factor-beta inhibitor Smad7, to delineate the role of Smad7 in T cell differentiation and autoimmune neuroinflammation. We found that Smad7 is up-regulated in peripheral CD4+ cells from patients with multiple sclerosis during relapse but not remission, and that expression of Smad7 strongly correlates with T-bet, a transcription factor defining T helper 1 responses. Concordantly, mice with transgenic over-expression of Smad7 in T cells developed an enhanced disease course during experimental autoimmune encephalomyelitis, accompanied by elevated infiltration of inflammatory cells and T helper 1 responses in the central nervous system. On the contrary, mice with a T cell-specific deletion of Smad7 had reduced disease and central nervous system inflammation. Lack of Smad7 in T cells blunted T cell proliferation and T helper 1 responses in the periphery but left T helper 17 responses unaltered. Furthermore, frequencies of regulatory T cells were increased in the central nervous system of mice with a T cell-specific deletion and reduced in mice with a T cell-specific over-expression of Smad7. Downstream effects of transforming growth factor-beta on in vitro differentiation of naïve T cells to T helper 1, T helper 17 and regulatory T cell phenotypes were enhanced in T cells lacking Smad7. Finally, Smad7 was induced during T helper 1 differentiation and inhibited during T helper 17 differentiation. Taken together, the level of Smad7 in T cells determines T helper 1 polarization and regulates inflammatory cellular responses. Since a Smad7 deletion in T cells leads to immunosuppression, Smad7 may be a potential new therapeutic target in multiple sclerosis.


Transcatheter atrioventricular valve-in-valve implantation for Fontan circulation and dextrocardia.
Transcatheter heart valve-in-valve implantation in failed surgical bioprosthetic valves has shown promising outcomes, prompting the stepwise expansion of their applications in different clinical scenarios. Recently, there is increased interest in valve-in-valve techniques for the treatment of patients with complex congenital heart disease. Herein, we report a case of successful transapical transcatheter atrioventricular valve-in-valve implantation in a patient with Fontan circulation and dextrocardia. The patient was previously treated with total cavopulmonary connection and atrioventricular valve replacement with recurrent prosthesis dysfunction.


Proteomics: A new perspective for the understanding of pterygia.
Pterygia is a common ocular surface disease bothering both the patient because of its unsightly appearance and the surgeon because of its tendency to recur. The pathogenesis of pterygia is complex and the exact mechanism(s), especially at the molecular level, remains unknown. The use of modern proteomic techniques such as iTRAQ may yield new knowledge on the underlying pathogenesis of pterygia. In this issue of Proteomics Clinical Applications, Linghu et al. (article number 1600094) identified a total of 156 proteins that expressed differently between the pterygia and healthy conjunctiva using the isobaric tags for relative and absolute quantification based quantitative proteomic analysis. Most significantly, western blotting confirmed that two candidate proteins matrix metalloproteinase 10 (MMP-10) and CD34 were significantly upregulated in pterygia, suggesting that they have potential roles in the pathogenesis of pterygia. The findings in Linhu's study may provide a new perspective for the understanding of pterygia and develop a new therapeutic target.


Hormonal regulation of platelet-activating factor-acetyltransferase activity in rat tissues.
Platelet-activating factor (PAF) plays a very important role in a number of physiological or pathological conditions. Recently, we and others have suggested that the PAF concentration in various tissues may be regulated by the enzyme that inactivates PAF, PAF acetylhydrolase (PAF-AH). Furthermore, it has been shown that the plasma isozyme of PAF-AH is regulated by various steroid hormone. Lyso-PAF:acetyl-CoA acetyltransferase (PAF-AT) is a key enzyme in PAF biosynthesis by the remodeling pathway. In the present study, the hormonal effects on the tissue levels of PAF-AT activity were investigated in various organs of the rat. The microsomal fraction was prepared from the spleen, lung, uterus, and liver of female rats which had been pretreated with dexamethasone, 17 alpha-ethynylestradiol, medroxyprogesterone-acetate, or vehicle and the PAF-AT activity was assayed. The rats treated with dexamethasone demonstrated significantly lower PAF-AT specific activity in the liver (P < 0.001) and spleen (P < 0.01), compared to the control group. A dose-dependent decrease of PAF-AT specific activity was demonstrated following dexamethasone treatment. Medroxyprogesterone injection also caused a significant decrease of PAF-AT activity in the liver (P < 0.01). No change of PAF-AT activity in any tissue was observed in the 17 alpha-ethynylestradiol-injected animals. Plasma PAF-AH activity was increased significantly by the administration of dexamethasone (P < 0.001) or medroxyprogesterone (P < 0.001), and decreased by 17 alpha-ethynylestradiol (P < 0.001), as previously described. The observation that dexamethasone or medroxyprogesterone treatment decreases the activity of PAF-AT and increases the plasma PAF-AH activity provides a mechanism for the tight control of PAF in tissues.


Role of probiotics and functional foods in health: gut immune stimulation by two probiotic strains and a potential probiotic yoghurt.
There are numerous reports that show the benefits on the health attributed to the probiotic consumptions. Most of the studies were performed using animal models and only some of them were validated in controlled human trials. The present review is divided in two sections. In the first section we describe how the probiotic microorganisms can interact with the intestinal epithelial cells that are the first line of cell in the mucosal site, focusing in the studies of two probiotic strains: Lactobacillus casei DN-114001 (actually Lactobacillus paracasei CNCMI-1518) and Lactobacillus casei CRL 431. Then we describe same beneficial effects attributed to probiotic administration and the administration of fermented milks containing these microorganisms or potential probiotic yoghurt, principally on the immune system and on the intestinal barrier in different experimental mouse models like enteropathogenic infection, malnutrition, cancer and intestinal inflammation.


X chromosome inactivation in human parthenogenetic embryonic stem cells following prolonged passaging.
The present study aimed to investigate the X chromosome inactivation (XCI) status in long-term cultured human parthenogenetic embryonic stem cells. One human embryonic stem (hES) cell line and 2 human parthenogenetic embryonic stem (hPES) cell lines were subjected to long-term culture in vitro (>50 passages). Karyotyping, array-based comparative genomic hybridization (aCGH), X-inactive specific transcript (XIST) RNA, immunofluorescence staining and real-time PCR were used to assess the chromosome karyotypes of these cells and the XCI status. X chromosome microdeletion was observed in the hPES-2 cells following culture for 50 passages. As early as 20 passages, XIST RNA expression was detected in the hPES-2 cells and was followed by low X-linked gene expression. The XIST RNA expression level was higher in the differentiated hPES-2 cells. The hPES-2' cells that were subclones of hPES-2 retained the XCI status, and had low XIST and X-linked gene expression. XIST RNA expression remained at a low level in the differentiated hPES-2' cells. The human biparental embryonic stem (hBES)-1 and hPES-1 cells did not exhibit XCI, and the differentiated hPES-1 cells had high expression levels of XIST RNA. In conclusion, the chromosome karyotypes of some hPES cell lines revealed instabilities. Similar to the hES cells, the hPES cells exhibited 3 XCI statuses. The unstable XCI status of the hPES-2 line may have been related to chromosome instability. These unstable chromosomes renedered these cells susceptible to environmental conditions and freezing processes, which may be the result of environmental adaptations.


Postural and locomotor control in normal and vestibularly deficient mice.
We investigated how vestibular information is used to maintain posture and control movement by studying vestibularly deficient mice (IsK-/- mutant). In these mutants, microscopy showed degeneration of the cristae of the semicircular canals and of the maculae of the utriculi and sacculi, while behavioural and vestibulo-ocular reflex testing showed that vestibular function was completely absent. However, the histology of Scarpa's ganglia and the vestibular nerves was normal in mutant mice, indicating the presence of intact central pathways. Using X-ray and high-speed cineradiography, we compared resting postures and locomotion patterns between these vestibularly deficient mice and vestibularly normal mice (wild-type and IsK+/-). The absence of vestibular function did not affect resting posture but had profound effects on locomotion. At rest, the S-shaped, sagittal posture of the vertebral column was the same for wild-type and mutant mice. Both held the head with the atlanto-occipital joint fully flexed, the cervico-thoracic junction fully flexed, and the cervical column upright. Wild-type mice extended the head and vertebral column and could walk in a straight line. In marked contrast, locomotion in vestibularly deficient mice was characterized by circling episodes, during which the vertebral column maintained an S-shaped posture. Thus, vestibular information is not required to control resting posture but is mandatory for normal locomotion. We propose that vestibular inputs are required to signal the completion of a planned trajectory because mutant mice continued rotating after changing heading direction. Our findings support the hypothesis that vertebrates limit the number of degrees of freedom to be controlled by adopting just a few of the possible skeletal configurations.


Radioprotective activity of ethylcellulose microspheres containing WR 2721, after oral administration.
Ethylcellulose microspheres containing WR 2721 were prepared by the emulsion-solvent evaporation technique. No significant loss or degradation of this phosphorothioate was noted during preparation. Oral administration of these microspheres to mice gave an important lowering of WR 2721 toxicity and an enhancement of its radioprotective activity with a D.R.F. of about 1.7-1.8 over 2-3 h. This action is explained by the protection of WR 2721 from acid hydrolysis and degradation in the gastro-intestinal tract. The adsorption of a fraction of WR 2721 onto the surface of microspheres constitutes an inconvenience. This study confirms the interest of such carriers for providing important sustained radioprotection after oral administration.


A comparative analysis of quality of life data from a Southwest Oncology Group randomized trial of advanced colorectal cancer.
Longitudinal quality of life measurements from an advanced-stage cancer clinical trial are analysed using a variety of methods, and the results compared. The methods used require different assumptions about the mechanism that produces the missing data. They include analyses that require the data to be missing completely at random; fixed-effects models and weighted generalized estimating equations, which require missing at random data; and a fully parametric approach where the outcomes and the missingness mechanism are jointly modelled, allowing non-ignorable missing data. The data show evidence of non-random missingness, but a formal test of non-ignorable missing data is not significant.


[Cardio-respiratory anomalies in disseminated sclerosis].
A case of acute pulmonary edema without cardiac failure, infectious or toxic cause, revealing a Multiple Sclerosis (M.S.), one case of bradycardia during a bout in a known M.S. and one case of orthostatic hypotension without change of cardiac frequency, during a bout of a known M.S. are reported. The common point of these 3 cases is that during their autonomic failure, there were disorders pointing to the medulla oblongata: swallowing difficulties, rotatory nystagmus, vestibulo-cerebellar syndrome, sensory and motor defect of upper limbs. A plaque of M.S. in the medulla oblongata, particularly near the tractus solitarius could explain these cardio-pulmonary abnormalities unusual in M.S.


Clinical features of de novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations.
De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AML DNMT3A/FLT3/NPM1 ) has been suggested to represent a unique AML subset on the basis of integrative genomic analysis, but the clinical features of such patients have not been characterized systematically. We assessed the features of patients (n = 178) harboring mutations in DNMT3A, FLT3 and/or NPM1, including an index group of AML DNMT3A/FLT3/NPM1 patients. Patients with AML DNMT3A/FLT3/NPM1 (n = 35) were significantly younger (median, 56.0 vs. 62.0 years; p = 0.025), mostly women (65.7% vs. 46.9%; p = 0.045), and presented with a higher percentage of bone marrow blasts (p < 0.001) and normal cytogenetics (p = 0.024) in comparison to patients within other mutation groups in this study. Among patients <60 years old, those with AML DNMT3A/FLT3/NPM1 had a shorter event-free survival (EFS) (p = 0.047). DNMT3A mutations and not FLT3 or NPM1 mutations were independently associated with overall survival (OS) (p = 0.026). Within mutation subgroups, patients with AML DNMT3A/NPM1 had a significantly shorter OS compared to those with AML FLT3-ITD/NPM1 (p = 0.047) suggesting that the adverse impact of DNMT3A mutations is more pronounced than that of FLT3-ITD among patients with NPM1 mutation. DNMT3A has a significant dominant effect on the clinical features and outcomes of de novo AML patients with concurrent DNMT3A, FLT3 and NPM1 mutations.


The rapunzel syndrome: an unusual trichobezoar presentation.
The Rapunzel syndrome is an unusual form of trichobezoar found in patients with a history of psychiatric disorders, trichotillomania (habit of hair pulling) and trichophagia (morbid habit of chewing the hair), consequently developing gastric bezoars. The principal symptoms are vomiting and epigastric pain. In this case report, we describe this syndrome in a young girl.


Signal peptide specificity in posttranslational processing of the plant protein phaseolin in Saccharomyces cerevisiae.
We linked the cDNA coding region for the bean storage protein phaseolin to the promoter and regulatory region of the Saccharomyces cerevisiae repressible acid phosphatase gene (PHO5) in multicopy expression plasmids. Yeast transformants containing these plasmids expressed phaseolin at levels up to 3% of the total soluble cellular protein. Phaseolin polypeptides in S. cerevisiae were glycosylated, and their molecular weights suggested that the signal peptide had been processed. We also constructed a series of plasmids in which the phaseolin signal-peptide-coding region was either removed or replaced with increasing amounts of the amino-terminal coding region for acid phosphatase. Phaseolin polypeptides with no signal peptide were not posttranslationally modified in S. cerevisiae. Partial or complete substitution of the phaseolin signal peptide with that from acid phosphatase dramatically inhibited both signal peptide processing and glycosylation, suggesting that some specific feature of the phaseolin signal amino acid sequence was required for these modifications to occur. Larger hybrid proteins that included approximately one-half of the acid phosphatase sequence linked to the amino terminus of the mature phaseolin polypeptide did undergo proteolytic processing and glycosylation. However, these polypeptides were cleaved at several sites that are not normally used in the unaltered acid phosphatase protein.


Droplets, dust and guinea pigs: an historical review of tuberculosis transmission research, 1878-1940.
The transmission of tuberculosis (TB) occurs mainly via inhalation of airborne droplet nuclei; however, the precise details of this process remain uncertain. We reviewed the literature from 1870 to 1940, when Mycobacterium tuberculosis was discovered and the concept of transmission emerged as a hallmark of the infectious disease. By 1940, laboratory experiments, animal studies and clinical observation had demonstrated that cough was central to TB transmission, and that guinea pigs close to patients with cough could be infected, mainly by patients coughing small droplets likely containing only 1-2 bacilli. A minority of pulmonary TB patients, usually during the early stages of the disease, with thin watery sputum, more successfully coughed small infectious droplets than patients with heavily smear-positive tenacious sputum who were often too ill and too weak to cough vigorously. There was ongoing debate regarding the possible importance of desiccated sputum particles found in surface dust. Investigation of TB transmission has a history of more than 130 years.


Efficacy and safety of rt-PA intravenous thrombolysis in patients with wake-up stroke: A meta-analysis.
: Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies for patients with acute ischemic stroke. However, wake-up stroke (WUS) is typically excluded from intravenous thrombolytic therapy because of the unclear time of symptom onset. Therefore, we aimed to assess the efficacy and safety of rt-PA intravenous thrombolysis in patients with WUS by meta-analysis. : We completed a systematic literature search of PubMed, Embase, the Cochrane Library, and SinoMed and included relevant studies of WUS patients covering rt-PA thrombolysis and nonthrombolysis (published from January 1, 2000, to February 28, 2021, with no language restrictions). The primary outcomes included safety outcomes and functional outcomes. Safety outcomes were measured according to the incidence of symptomatic intracranial hemorrhage and mortality within 90 days. The efficacy outcomes were measured based on 90-day modified Rankin Scale scores. We assessed pooled data using either a random-effects model (when P < .10, I2 > 50%) or a fixed-effects model (when P > .10, I2 < 50%). : A total of 913 patients from 9 studies were included in the meta-analysis. All patients had ischemic stroke confirmed by computed tomography or magnetic resonance imaging. The incidence of modified Rankin Scale 0 to 2 was significantly higher in the rt-PA thrombolysis group compared with the nonthrombolysis group. And rt-PA thrombolytic WUS patients did not differ significantly from nonthrombolytic WUS patients in terms of 90-day mortality. However, the incidence of Symptomatic intracranial hemorrhage was also significantly higher in the rt-PA thrombolysis group than that in the nonthrombolysis group. : Patients with WUS who received rt-PA thrombolysis had a significant positive effect within 90 days. In addition, although there was no significant increase in mortality, we need to be aware of the risk of intracranial hemorrhage transformation associated with rt-PA thrombolysis despite no obvious increase in mortality. The safety of rt-PA intravenous thrombolysis should be closely monitored in patients with WUS.


Radicaloid-type oxidative decomposition of beer bittering agents revealed.
trans-Isohumulones, dihydroisohumulones, tetrahydroisohumulones, and humulinones, which are important hop-derived flavor components of beer, were found, by using electrolysis of organic solutions, to be stable against oxidation, like weak acids; however, they are readily oxidized in their anionic forms as present in beer. Oxygen- and carbon-centered radicals were formed by oxidation and identified by using spin trapping under aerobic and anaerobic conditions, followed by EPR (electron paramagnetic resonance) spectroscopy. Generated radicals were reactive, most likely degrading into products lacking the tricarbonyl chromophore; this is typical of five-membered-ring hop derivatives. Thus, flavor-active beer constituents may degrade oxidatively in the absence of oxygen, thereby leading to reaction products that escape UV detection.


Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.
Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation.


[Palliative care--objectives and accomplishments of the Association for the Development of Palliative Care].
Associations involved in Palliative Cares want to develop a better use of therapeutic resources and a better support of patients threatened in their Lives. They want to help developing of adjusted structures to a better global tacking charge of patient and his family in hospital and at home. The Association for development of Palliative Cares (ASP) founded 1984 has chosen from the beginning the concept of continuous care and has set since 1986 the first coordinated team of voluntary "Support", selected and trained, in a curative care unit cancer patients with fatal prognostic, after a possible remission. They participated, the ASP also, to the architectural conception and the financing of the first unit of palliative cares in France. The ASP conceived a help to home support for patients in the end of their life, by a team reinforced by a referent nurse, in collaboration with a home hospitalisation unit and a pain consulting. The ASP is now taking action in Paris and its area, with its 180 volunteers and 12 teams in 11 Hospitals and one at home.


Mechanisms of inhibition by fluoride of urease activities of cell suspensions and biofilms of Staphylococcus epidermidis, Streptococcus salivarius, Actinomyces naeslundii and of dental plaque.
Fluoride is known to be a potent inhibitor of bacterial ureases and can also act in the form of hydrofluoric acid as a transmembrane proton conductor to acidify the cytoplasm of intact cells with possible indirect, acid inhibition of urease. Our research objectives were to assess the inhibitory potencies of fluoride for three urease-positive bacteria commonly found in the mouth and to determine the relative importance of direct and indirect inhibition of ureases for overall inhibition of intact cells or biofilms. The experimental design involved intact bacteria in suspensions, mono-organism biofilms, cell extracts, and dental plaque. Standard enzymatic assays for ammonia production from urea were used. We found that ureolysis by cells in suspensions or mono-organism biofilms of Staphylococcus epidermidis, Streptococcus salivarius or Actinomyces naeslundii was inhibited by fluoride at plaque levels of 0.1-0.5 mm in a pH-dependent manner. The results of experiments with the organic weak acids indomethacin and capric acid, which do not directly inhibit urease enzyme, indicated that weak-acid effects leading to cytoplasmic acidification are also involved in fluoride inhibition. However, direct fluoride inhibition of urease appeared to be the major mechanism for reduction in ureolytic activity in acid environments. Results of experiments with freshly harvested supragingival dental plaque indicated responses to fluoride similar to those of S. salivarius with pH-dependent fluoride inhibition and both direct and indirect inhibition of urease. Fluoride can act to diminish alkali production from urea by oral bacteria through direct and indirect mechanisms.


A major outbreak of botulism in cattle being fed ensiled poultry litter.
Eighty of a group of 150 housed beef cattle showed classical signs of botulism after eating a batch of ensiled poultry litter. Sixty-eight of the animals died and Clostridium botulinum type C toxin was detected in 18 of 22 sera examined. C botulinum organisms were isolated from the ensiled litter and type C toxin was demonstrated in samples of decomposed poultry carcases present in the litter. This outbreak of bovine botulism was the most serious to have been recorded in Europe and was the first associated with feeding ensiled poultry litter.


Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.
Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Focal cerebral ischemia was induced in Vasp(-/-) mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p<0.05) and edema volumes (1.7 mm(3)±0.5 mm(3) versus 0.8 mm(3)±0.4 mm(3); p<0.0001) were significantly enhanced in Vasp(-/-) mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm(3)±17.3 mm(3) versus 39.3 mm(3)±10.7 mm(3), respectively; p<0.01) and a non significant trend (p>0.05) towards worse neurological outcomes. Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.


Does Alcohol or Delinquency Help Adolescents Feel Better Over Time? A Study on the Influence of Heavy Drinking and Violent/Property Offending on Negative Emotions.
Conceptualizing adolescent drinking and delinquency as adaptations to strain, we explore whether they (a) decrease or increase the probability of feeling depression and anxiety later and (b) ameliorate or aggravate the effect of strain on the negative emotions over time. These relationships are also examined for gender differences by analyzing data separately for males and females as well as both combined. We conducted ordinary least squares regression analysis of panel data from the first two waves of the National Longitudinal Study of Adolescent to Adult Health. Heavy drinking and serious delinquency were found to increase the probability of feeling depression and anxiety later, whereas they tend to ameliorate the emotionally deleterious effect of strain for males and, to a lesser extent, females.


Identification of TMEM230 mutations in familial Parkinson's disease.
Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter-p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies.


A novel method for the preparation of alpha,alpha'-difluoroesters and acids using BrF3.
Alkyl-, haloalkyl-, and ketoalkyl-2-ethoxycarbonyl-1,3-dithianes were easily made from the appropriate primary or secondary alkyl bromides, 1,3-dithiane, and ethyl chloroformate. They were reacted with BrF(3) to form the corresponding alpha,alpha-difluoro esters in 65-75% yield. Reaction conditions are very mild (1-2 min, 0 degrees C). The two sulfur atoms of the dithiane are essential for the reaction.


Malignant evolution of monoclonal gammopathy of undetermined significance: analysis of 633 consecutive cases with a long term follow-up.
In 633 consecutive patients with monoclonal gammopathy of undetermined significance (MGUS) the probability of malignant evolution was 9, 17 and 51 % at 5, 10 and 15 years, respectively, after diagnosis. The values of monoclonal component, Bence-Jones proteinuria and erythrocyte sedimentation rate were associated with malignant transformation.


Characterization of Staphylococcus aureus Isolates That Colonize Medical Students in a Hospital of the City of Cali, Colombia.
Introduction. Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) represents a risk for the spread of bacteria. This study characterized the S. aureus isolated from medical students, who were in their clinical rotation at a hospital in the city of Cali. Materials and Methods. 216 students participated in the study and 63 isolates of S. aureus were evaluated for susceptibility and PCR amplification of agr and mecA genes. The origin of MRSA isolates was established by analyzing agr polymorphisms. Results. A total of 29.2% of students were colonized by S. aureus and nasal carriage rate was 23.6% and 14.3% MRSA. Three agr groups (agr II, and agr III) were identified; the agr I group was the most common, with a 35% prevalence; this group is from community origin. Conclusion. The present study demonstrates that medical students carry S. aureus strains, with the threat of spreading them both to community and hospital environments.


Tomasello's tin man of moral obligation needs a heart.
In place of Tomasello's explanation for the source of moral obligation, we suggest that it develops from the concern for others already implicit in the human developmental system. Mutual affection and caring make the development of communication and thinking possible. Humans develop as persons within such relationships and this develops into respect and moral obligation.


[Inhibitors of enzymes with potential medical applications].
From the earliest times, medicine has focused on finding the most suitable and effective treatment for every patient. At present, a dynamic development of diagnostic methods and techniques for designing new drugs allows to create therapies for many diseases at the molecular level. Among the many drugs appearing on the medical market every year, special attention should be paid to those whose action is based on the inhibition of proteolytic enzyme activity. Protease inhibitors are a diverse group of biologically active molecules for which antiviral, antimicrobial, antifungal, antiparasitic or anticancer effects have been documented. Successes in the treatment of HIV infection, hepatitis C and influenza diseases certainly encourage researchers to look for new inhibitors that could be used in new therapies. This paper provides an overview of selected information on enzyme inhibitors, especially protease inhibitors, which are already registered medicines and substances that are promising candidates for medical use.


AKIN10, a representative Arabidopsis SNF1-related protein kinase 1 (SnRK1), phosphorylates and downregulates plant HMG-CoA reductase.
HMG-CoA reductase (HMGR) is a key enzyme in the mevalonate pathway for sterols and cytosolic isoprenoid production. Although HMGR kinases from spinach, barley, and cauliflower tissues have been strongly suggested as members of SNF1-related protein kinases 1 (SnRK1), the phosphorylation and inactivation of HMGR by plant SnRK1s has not been demonstrated. In this study, we elucidated that AKIN10, an Arabidopsis SnRK1, acts as an HMGR kinase. The recombinant AKIN10 phosphorylates and inactivates AtHMGR1S using recombinant GRIK1 as the AKIN10 activator. In contrast, AKIN10-GRIK1 fails to inactivate AtHMGR1S-S577A, suggesting that this is achieved through Ser577 phosphorylation. Moreover, phosphorylation is detected not only in AtHMGR1S but also in AtHMGR1S-S577A, suggesting the presence of a novel regulatory mechanism of plant HMGR.


Huge solitary gallstone complicated with liver cirrhosis in a middle-aged woman: case report.
Gallstones are increasingly becoming a common diagnosis in hospitals across the continents, with predominance in women. Patients suspected of a gallstone disease require thorough evaluation including endoscopic ultrasound, magnetic resonance imaging, or magnetic resonance cholangiography. A delayed or missed diagnosis is associated with serious complications and poor prognosis. A 44-year-old female patient presented with fever, vomiting, hypochondria, and epigastric pain for 10 days. Clinical examination showed jaundice and tenderness at the right hypochondriac region. Blood analysis revealed elevated bilirubin, alkaline phosphatase, and white blood cells. The patient was sent for a computed tomography (CT) scan which showed a grossly enlarged liver about 17.2 cm in length and a hypo-attenuating mass in the gallbladder fossa that enhanced moderately and heterogeneously following intravenous contrast administration. Dilated intrahepatic biliary ducts were also appreciated. Explorative laparotomy was performed and revealed an enlarged, cirrhotic-appearing liver, a thickened gallbladder, and a whitish-yellow gallstone about 3 cm in the largest diameter situated at its neck. No isolated tumour was found. Although gallstone disease is very common, misdiagnosis still occurs especially in low and lower-middle-income countries. Inadequate evaluation and increased utilization of CT in emergency and surgical departments are the contributing factors for a missed diagnosis. A missed gallstone disease occurs due to various factors including inappropriate standard operating procedures, which set a CT scan as the first imaging test for all internal conditions. This case report presents the appropriate approach to achieving the diagnosis of a gallstone disease before surgical intervention.


[Effects of the COVID-19 pandemic and associated non-pharmaceutical interventions on diagnosis of myocardial infarction and selected infections in Iceland 2020].
Nonpharmaceutical interventions to contain the spread of COVID-19 infections in Iceland in 2020 were successful, but the effects of these measures on incidence and diagnosis of other diseases is unknown. The aim of this study was to evaluate the impact of the COVID-19 pandemic on the diagnosis of myocardial infarction (MI) and selected infections with different transmission routes. Health records of individuals 18 years or older who were admitted to Landspitali University Hospital (LUH) in 2016-2020 with pneumonia or MI were extracted from the hospital registry. We acquired data from the clinical laboratories regarding diagnostic testing for Chlamydia trachomatis, influenza, HIV and blood cultures positive for Enterobacterales species. Standardized incidence ratio (SIR) for 2020 was calculated with 95% confidence intervals (95%CI) and compared to 2016-2019. Discharge diagnoses due to pneumonia decreased by 31% in 2020, excluding COVID-19 pneumonia (SIR 0.69 (95%CI 0.64-0.75)). Discharge diagnoses of MI decreased by 18% (SIR 0.82 (95%CI 0.75-0.90)), and emergency cardiac catheterizations due to acute coronary syndrome by 23% (SIR 0.77 (95%CI 0.71-0.83)), while there was a 15% increase in blood stream infections for Enterobacterales species (SIR 1.15 (95%CI 1.04-1.28)). Testing for Chlamydia trachomatis decreased by 14.8% and positive tests decreased by 16.3%. Tests for HIV were reduced by 10.9%, while samples positive for influenza decreased by 23.6% despite doubling of tests being performed. The number of pneumonia cases of other causes than COVID-19 requiring admission dropped by a quarter in 2020. MI, chlamydia and influensa diagnoses decreased notably. These results likely reflect a true decrease, probably due to altered behaviour during the pandemic.


Locative prepositional phrases in severe aphasia.
Six severely aphasic patients were trained on C-VIC, a computerized alternative communication system. Patients with both global and Broca's aphasia were able to produce and comprehend locative prepositions using C-VIC. The Broca's aphasic patients were able to produce and interpret symbol order correctly in C-VIC locative prepositional phrases, despite their difficulties in performing the same tasks using English. One patient's verbal production of locative prepositional phrases improved markedly after C-VIC training. These results suggest that the "mapping" impairment suffered by some Broca's aphasics may be ameliorated by use of alternative communication system, such as C-VIC.


Determinants of Mortality among Cervical Cancer Patients Attending in Tikur Anbessa Specialized Hospital, Ethiopia: Institutional-Based Retrospective Study.
Globally, about 570,000 cases and 311,000 deaths of cervical cancer occurred in 2018. It was the leading cause of cancer-related deaths among women in Africa. The global mean age at death of cervical cancer was about 59 years. This study aimed to assess the determinants of cervical cancer mortality among cervical cancer patients attending in Tikur Anbessa Specialized Hospital (TASH). Institutional-based retrospective cohort study was conducted in the oncology center of TASH, Ethiopia, from March to April 2019. Data were extracted from patients' chart using structured checklist and analyzed using Stata 14.2. Cox regression was used to identify variables that affect the outcome variable. From the total of 2045 reviewed medical records of cervical cancer patients, 1057 medical records were found to be complete and included in this study. The incidence of mortality among cervical cancer patients was 15.6/100/years. Mortality was significantly increased with advanced age (adjusted hazard ratio (AHR) = 1.02, 95% CI (1.01-1.03)), comorbidity (AHR = 1.8, 95% CI (1.39-1.89)), being anemic (AHR = 1.42, 95% CI (1.07-1.89)), advanced stage (AHR = 1.63, 95% CI (1.24-2.13)), and being substance user (AHR = 2.71, 95% CI (2.08-3.53)). The study revealed that the incidence of mortality within the cohort was 15.6/100/years. Mortality was significantly increased with advanced age, anemia, advanced stage, comorbidity, and using substances. It is better to give special attention to patients with anemia, advanced age, advanced stage, comorbidity, and substance usage. In addition, expanding cervical cancer early screening will decrease the mortality of patients.


[Superselective feeder embolization for hemorrhage from cutaneous angiosarcoma in scalp].
A 76-year-old male developed a hemorrhagic nodule and a surrounding purple-red, irregularly shaped macule on his scalp after head trauma. The diagnosis of angiosarcoma was confirmed histologically. A transarterial feeder embolization was performed followed by a surgical excision. It was effective for bleeding from a tumor, and superselective catheterization was important for this specific tumor. The early diagnosis by neurosurgeon may lead to improved survival.


[Effects study of standardized tertiary rehabilitation on promoting of the neurological functions in stroke patients with hemiplegia].
To investigate the effects of standardized tertiary rehabilitation (STR) on promotion of the neurological functions in stroke patients with hemiplegia. A large-sample, multi-center, randomized, controlled prospective study was conducted nationwide. 1209 stroke patients with hemiplegia, aged 40 - 80, within 11 d +/- 5 d after the onset, stabilized in vital life signs in the past one week, of 20 hospitals affiliated to medical colleges or of hospitals at the provincial level in mainland China were randomly allocated to one of the 2 baseline data-matched groups: control group (n = 599, 446 with cerebral infarction and 153 with cerebral hemorrhage) receiving routine intervention of internal medicine, and STR group (n = 610, 455 with cerebral infarction and 155 with cerebral hemorrhage), receiving routine intervention and STR including physical therapy and occupational therapy (OT) in addition. Evaluation was conducted by the time of enrollment, and by the ends of the first, third, and sixth months by the national clinical neurological function defects (CNFD) scoring. There were no significant differences in the baseline indexes between these 2 groups. The scores of CNFD at enrollment of the patients with cerebral infarction in the STR group was 21.55, not significantly different from that of the patients with cerebral infarction in the control group (22.16), however, the scores of these patients with cerebral infarction in the STR group by the ends of the first, third, and sixth months were 16.32, and 11.48, and 8.63 respectively, all significantly lower than those of the corresponding patients in the control group (18.95, 15.57, and 13.78 respectively, all P < 0.01). The CNFD score at enrollment of the patients with cerebral hemorrhage in the STR group was 23.27, not significantly different from that of the corresponding patients in the control group (24.36), however, the scores of the patients with cerebral hemorrhage in the STR group by the ends of the first, third, and sixth months were 17.61, 11.20, and 7.95 respectively, all significantly lower than those of the corresponding patients in the control group (20.36, 15.01, and 13.57 respectively, all P < 0.01). By the end of the sixth month, the CNFD score of the cerebral infarction and hemorrhage patients in the STR group were improved by 12.79 and 15.23, both higher than the corresponding patients in the control group (8.30 and 10.65 respectively). The trend of decrease of CNFD score moved faster in the STR group than in the control group, especially at the early stage. STR significantly helps improved the neurological function in the patients with cerebral stroke accompanied with hemiplegia.


Predation by Podisus maculiventris (Say) (Hemiptera: Pentatomidae) on viburnum leaf beetle, Pyrrhalta viburni (Paykull) (Coleoptera: Chrysomelidae), under laboratory and field conditions.
To evaluate the potential of Podisus maculiventris (Say) (Heteroptera: Pentatomidae) as a biological control agent against viburnum leaf beetle, Pyrrhalta viburni (Paykull) (Coleoptera: Chrysomelidae), laboratory trials were conducted to measure prey consumption of P. maculiventris over nymphal development. Field trials tested the impact of augmentative releases of P. maculiventris nymphs on populations of P. viburni, using both open shrubs and caged branches of Viburnum trilobum. In the laboratory, P. maculiventris nymphs successfully developed while preying on P. viburni larvae and adults. Each nymph consumed an average of 100.6 larvae or 16.9 adults. Immature development duration was comparable between nymphs feeding on P. viburni adults and those given Galleria mellonella (L.) (Lepidoptera: Pyralidae) larvae as prey. In field trials, inundative releases of 30 P. maculiventris nymphs on naturally infested V. trilobum shrubs significantly reduced pest defoliation on shrubs infested with < 3,000 larvae but had no effect on shrubs with heavier infestations. On caged branches, individual nymphs successfully developed when feeding only on P. viburni larvae. These results show that P. viburni larvae and adults are suitable prey for P. maculiventris and this predator could potentially be developed as a biological control agent against P. viburni.