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Κυριακή 30 Σεπτεμβρίου 2018

Primary amenorrhoea and clitoromegaly in a nulliparous woman: successful medical and surgical management

Clitoromegaly is an important sign of virilisation and poses difficulty in sex determination, when present since birth. The diagnosis and treatment in an adult is a major challenge to the treating gynaecologist. The primary reason for its development is androgen excess due to congenital adrenal hyperplasia, polycystic ovarian syndrome, ovarian virilising tumours, neurofibromas, adrenal neoplasm and prolonged intake of anabolic steroids. A case of young nulliparous married woman who presented with primary amenorrhoea and clitoromegaly and was managed successfully has been reported.



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Giant left breast hamartoma in a 45-year-old woman

This is a case of a woman in her fifth decade of life who presented with a lump in her left breast. The patient underwent extensive breast investigations which did not confirm one particular diagnosis. The lesion was excised, and histological findings confirmed the diagnosis of a giant breast hamartoma. This case is interesting due to the largeness. As well as this, giant breast hamartomas are uncommon, and this case highlights the difficulty in their diagnosis and frequent misdiagnoses, potentially contributing to their reported low incidence rates. Diagnosis is difficult due to the complex appearance of the mass on imaging, raising the possibility of malignancy. Core biopsy is unremarkable, with the final diagnosis only possible on histological examination of the resected mass.



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Hypoxic hepatitis and furosemide

Hypoxic hepatitis is a rather common complication of heart, circulatory or respiratory failure. We present the case of a patient with hypoxic hepatitis in the setting of heart failure and dehydration from furosemide as a reminder of an important clinical lesson. The pathogenesis of hypoxia (especially in the case of heart failure) is explained by a two-hit mechanism in which the liver at risk of hypoxic injury by passive hepatic congestion (right heart failure) is subsequently exposed to systemic hypoperfusion, which leads to a marked and transient elevation of aminotransferases. In the case presented, the use of furosemide (at least partially) promoted the second hit because it helped to generate hypotension and splanchnic hypovolaemia and favoured hepatic hypoxia.



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Red colour venous flow in the suprasternal view: a red flag sign

Description 

A 3-day-old full-term neonate, born by normal vaginal delivery, was presented with respiratory distress and mild cyanosis. His room air saturation in all four limbs was 84%. The clinical examination was unremarkable. Chest X-ray showed cardiomegaly and increased pulmonary vascular markings. Transthoracic echocardiography revealed 8 mm ostium secundum atrial septal defect (ASD) with bidirectional shunt and dilated right atrium and right ventricle with absence of individual pulmonary veins (PV) draining into left atrium (LA). Suprasternal view showed vertical vein (VV) which was recognised as a vessel lateral to LA with red-coloured continuous flow on Doppler (figure 1). The PVs were draining into the venous confluence behind the LA which was draining into the VV. VV connects into the left innominate vein which finally forms the right superior vena cava (figure 1, video 1).

Figure 1

Suprasternal view demonstrating vertical vein....



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Use of long saphenous vein graft in acute on chronic mesenteric ischaemia

Acute mesenteric ischaemia is a relatively rare surgical emergency, but despite advances in diagnostic tests, the mortality of this condition remains stubbornly high (50%–80%). This is principally because of the non-specific nature of the presenting symptoms and subsequent delay in diagnosis. We report an unusual case of acute mesenteric ischaemia treated by emergency laparotomy, small bowel resection and revascularisation using reversed long saphenous vein graft.



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Primary undifferentiated pleomorphic cardiac sarcoma with MDM2 amplification presenting as acute left-sided heart failure

Primary cardiac tumours are a rare clinical entity that can present with myriad of non-specific cardiopulmonary symptoms. We describe a case of a 61-year-old previously healthy woman who presented with progressive dyspnoea and lower extremity swelling, suggestive of acute left-sided heart failure. Transthoracic echocardiogram revealed a large, 3.7x3.2 cm intracardiac mass resulting in severe mitral valvular dysfunction. The patient underwent surgical resection of the mass, however, negative margins were not obtained, and the tumour quickly returned. Histological and molecular analysis was consistent with the diagnosis of undifferentiated pleomorphic sarcoma with murine double minute 2 (MDM2) amplification. Given the overall grim prognosis, the patient chose to pursue comfort-based care. She died at home 9 months after the initial diagnosis. Here, we provide an updated review of the literature for the classification of undifferentiated pleomorphic cardiac sarcoma and potential treatment modalities.



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A delayed diagnosis: recurrent fever and beta thalassaemia

Familial Mediterranean fever and beta-thalassaemia are two genetic disorders, with a largely common geographical distribution. However, they have not much else in common, as the first is an autoinflammatory disorder, while the other is a haemoglobinopathy. We describe a patient with known beta-thalassaemia intermedia who presented with recurrent fevers and he was diagnosed with familial Mediterranean fever 2 years later. We discuss whether there is an association between the two disorders and the cognitive biases that lead to the delay in the diagnosis of familial Mediterranean fever.



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Imaging features of toxic megacolon

Description 

A 27-year-old woman presents with vomiting and abdominal pain for 2 days. She had been diagnosed with ulcerative colitis (UC) 2 weeks prior and was started on oral sulfasalazine and prednisolone. Currently, she is afebrile and not tachycardic. On examination, the abdomen was distended and tender centrally. Serial abdominal radiographs showed persistently dilated transverse colon with loss of haustra (figure 1). CT abdomen revealed diffuse bowel thickening involving the ascending colon, caecum and terminal ileum with multiple pseudopolyps at the ascending colon (figure 2). The transverse colon is dilated up to 6.8 cm (figure 3). There are also multiple enlarged right-sided mesenteric nodes. A diagnosis of toxic megacolon (TM) was made. She deteriorated during admission due to acute pulmonary embolism. Blood investigations showed marked leucocytosis (32x109/L) and raised C-reactive proteins (98.7 mg/L). Subtotal colectomy involving the caecum until splenic flexure was performed followed by ileostomy and mucous...



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Modified laparoscopic Janeway gastrostomy: a novel adjunct for the management of choledocholithiasis in Roux-en-Y patients

A 76-year-old woman with surgical history of Roux-en-Y gastric bypass presented with recurrent choledocholithiasis. Double balloon enteroscopy was unsuccessful in cannulating the biliary tree, thus, requiring surgically assisted endoscopic retrograde cholangiopancreaticogram (ERCP) access. Due to her stable clinical status, the non-urgent indication and multiple anticipated ERCPs for definitive biliary clearance, a more durable port of access to the ampulla was desired. A modified laparoscopic Janeway gastrostomy of the gastric remnant was performed and served as access for multiple subsequent endoscopic procedures with successful clearance of the biliary tree.



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DRESS syndrome due to vemurafenib treatment: switching BRAF inhibitor to solve a big problem

We present a case report of an early-onset drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) induced by vemurafenib (BRAF inhibitor) in a middle-age man affected by a metastatic, BRAF mutant melanoma who was started on first-line metastatic treatment with vemurafenib and cobimetinib.

After initiating the treatment, the patient presented an extensive cutaneous rash with eosinophilia and renal impairment. Due the constellation of signs and symptoms, a diagnosis of DRESS syndrome was made which strongly contraindicated the reintroduction of vemurafenib due to its hypersensibility reaction. Thus, vemurafenib was stopped immediately, and we started corticoid treatment with clinical improvement.

Due to the contraindication to start vemurafenib again, after multidisciplinary view of the case and having balanced the risks and benefits, we successfully performed a switch to another BRAF inhibitor in a progressively ascending pattern, without any skin toxicity and with a good response of the metastatic melanoma.



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Focus on saving money lets patients and surgeons down [Letters]



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Influence of socioeconomic events on cause-specific mortality in urban Shanghai, China, from 1974 to 2015: a population-based longitudinal study [Research]

Background:

Understanding how socioeconomic events influence cause-specific mortality is essential for optimizing disease-control strategies. We characterized long-term trends in cause-specific mortality in a stable population from a very large urban centre.

Methods:

We derived population data from 1974 to 2015 on vital status, demographics and causes of death from the death registration system in Yangpu District, Shanghai, China. We examined temporal trends in mortality and assessed the effects of age, period and birth cohort.

Results:

Over 41 879 864 person-years of follow-up, we analyzed 290 332 deaths: 3.80% from communicable conditions (group 1), 86.50% from noncommunicable diseases (group 2), and 5.56% from injuries (group 3). Age-standardized mortality decreased after 1988 for group 1 (average annual percentage change [AAPC] –6.7, 95% confidence interval [CI] –9.3 to –4.1), after 1995 for group 2 (AAPC –2.9, 95% CI –3.5 to –2.3), and after 1994 for group 3 (AAPC –5.4, 95% CI –6.3 to –4.5), after improvements in public health and clinical service infrastructure and the removal of polluting industries during the 1980s. We observed increased mortality from group 2 and group 3 causes in those born between 1955 and 1965, a period that included the Great Chinese Famine. Cause-specific mortality risks increased in those born after 1949 for cancer and diabetes only.

Interpretation:

Birth cohorts exposed to extreme starvation in early life had increased premature cause-specific mortality in later life. Decreased cause-specific mortality followed improvements in public health, medical infrastructure and pollution control, but not for cancer or diabetes, likely because of exposure to new risk factors.



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A perioperative approach to the opioid crisis [Commentary]



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Improving the quality of health care in Canada [Analysis]



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Medical students protest steadily rising tuition fees [News]



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Progressive renal failure complicated by transient and recurrent ureteral obstruction [Practice]



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To what end, evolutionary medicine? [Letters]



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Chronic pulmonary aspergillosis after pulmonary tuberculosis [Practice]



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How many doctors do we actually need? [News]



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An open letter to all of the medical journals who send me daily offers to publish my "high-impact research in next months issue" [Humanities]



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Closing male-female gaps in clinical care requires addressing entrenched ideas on gender risks [News]



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PET imaging of [ 11 C]PBR28 in Parkinson’s disease patients does not indicate increased binding to TSPO despite reduced dopamine transporter binding

Abstract

Purpose

To examine the hypothesis that cerebral binding to the 18 kDa translocator protein (TSPO), a marker of microglia activation, is elevated in Parkinson's disease (PD), and to assess the relationship between brain TSPO binding and dopaminergic pathology in PD.

Methods

The radioligand [11C]PBR28 was used for quantitative assessment of brain TSPO in 16 control subjects and 16 PD patients. To analyse the relationship between dopaminergic pathology and brain TSPO binding, PET studies of the dopamine transporter (DAT) were undertaken in PD patients using the DAT radioligand [18F]FE-PE2I. The total distribution volume of [11C]PBR28 was quantified in nigrostriatal regions, limbic cortices and thalamus, and the binding potential of [18F]FE-PE2I was quantified in nigrostriatal regions.

Results

Based on genotype analysis of the TSPO rs6971 polymorphism, 16 subjects (8 control subjects and 8 PD patients) were identified as high-affinity binders, and the remaining subjects were identified as mixed-affinity binders. A two-way ANOVA showed a strong main effect of TSPO genotype on the cerebral binding of [11C]PBR28, whereas no statistically significant main effect of diagnostic group, or a group by genotype interaction was found for any of the regions analysed. [18F]FE-PE2I PET studies in patients indicated a marked reduction in nigrostriatal binding to DAT. However, no correlations between the binding parameters were found for [11C]PBR28 and [18F]FE-PE2I.

Conclusion

The findings do not support the hypothesis of elevated cerebral TSPO binding or a relationship between TSPO binding and dopaminergic pathology in PD.



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Effect of Nelumbo nucifera fruit on scopolamine induced memory deficits and motor coordination

Abstract

From prehistoric time till today herbal medications are supposed to have neuroprotective effects both by inhibiting acetyl cholinesterase enzyme or antioxidant ability and are also affordable. Thus extensive studies are necessary to investigate the pharmacological effects of herbal plants. The goal of the present study was to ascertain the outcome of Nelumbo nucifera fruit (NNF) on scopolamine induced amnestic rats along with motor coordination in mice in order to explore its pharmacological use in disorders like Alzheimer's disease (AD). The effect of NNF on learning and memory was assessed by Morris water maze test using 35 Wister rats weighing 200–230 g evenly divided in to five groups. While motor coordination was assessed using Rot rod test, 35 male locally bred albino mice weighing 20–25 g were equally divided in to five groups. Group I was kept as control (10 ml/kg gum tragacanth). Group II, III and IV were labeled as treated groups (NNF 50, 100 and 200 mg/kg). Group V served as reference group (piracetam 200 mg/kg). All drugs were given by oral route as a single dose for 15 days in both experiments to rats and mice, however scopolamine (1 mg/kg IP) was used in Morris water maze test 40 min after the administration of drugs to rats for the induction of amnesia. In Morris water maze test, N. nucifera fruit caused highly significant and significant decrease in escape latency in the amnestic rats at 200 and 100 mg/kg as compared to control. In Rota rod test, N. nucifera fruit did not exhibit any notable changes in the riding time at any dose as compared to control. N. nucifera fruit have demonstrated ameliorating effects on memory without affecting muscle coordination. Hence NNF seems to have great potential for therapeutic application in memory disorders, such as AD which may be due to its ability to enhance cholinergic neurotransmission and exerting antioxidant effect and thus encourage more preclinical and clinical trials in this field.



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FDA-Approved Drug Epidiolex (cannabidiol) Placed in Schedule V of Controlled Substance Act

September 27, 2018 -- WASHINGTON - The Department of Justice and Drug Enforcement Administration today announced that Epidiolex, the newly approved medication by the Food & Drug Administration, is being placed in schedule V of the Controlled...

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EM Nerd-An Addendum to the Case of the Non-inferior Inferiority

An-Addendum-to-the-Case-of-the-Non-infer

Until recently the management of acute appendicitis has lay squarely in the hands of the surgeon. But there is a growing body of evidence examining the use of antibiotics alone in uncomplicated appendicitis. Most of the data exploring this question has found that the majority of patients treated with antibiotics alone will avoid surgery in […]

EMCrit Project by Rory Spiegel.



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The Quantified Athlete: Associations of Wearables for High School Athletes

The adoption of wearable technology in competitive sports can be an advantage to performance and training. Athletes who use personalised data to quantify their performances with the possibilities of sharing with others may use wearables to reinforce the athletic identity. Despite these changes, few studies have actually examined the associations between wearables and developing athletes in their quest for professional sports. Student athletes (n = 437, age = 17y) still in high schools completed a web-based survey about their professional aspirations, athletic identity, and the association with wearables. Wearables were measured by ownership and usage of apps, fitness trackers, or sports watches. Odds ratio (OR) and 95% confidence intervals (CI) were reported. Most high school athletes had apps (64.3%) or fitness trackers (65.2%) and over half of the athletes (58%) had aspirations for professional sport. Athletic identity was positively associated with ownership and usage of apps and fitness trackers. The OR was greater for professional sport aspiration with fitness trackers owners (OR = 2.60, CI = 1.44-4.73) and users (OR = 4.04, CI = 2.09-7.81) than athletes without fitness trackers. Wearables were common among high school athletes and it was part of their athletic identity. For professional aspiring athletes, wearables have the potential to help provide data to support suitable training and competition schedules at a time when students may be overloaded with academic pressures.

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Predictive Role of Urinary Metabolic Profile for Abnormal MRI Score in Preterm Neonates

Background and Objective. Early identification of neonates at risk for brain injury is important to start appropriate intervention. Urinary metabolomics is a source of potential, noninvasive biomarkers of brain disease. We studied the urinary metabolic profile at 2 and 10 days in preterm neonates with normal/mild and moderate/severe MRI abnormalities at term equivalent age. Methods. Urine samples were collected at two and 10 days after birth in 30 extremely preterm infants and analyzed using proton magnetic resonance spectroscopy. A 3 T MRI was performed at term equivalent age, and images were scored for white matter (WM), cortical grey matter (cGM), deep GM, and cerebellar abnormalities. Infants were divided in two groups: normal/mild and moderately/severely abnormal MRI scores. Results. No significant clustering was seen between normal/mild and moderate/severe MRI scores for all regions at both time points. The ROC curves distinguished neonates at 2 and 10 days who later developed a markedly less mature cGM score from the others (2 d: area under the curve (AUC) = 0.72, specificity (SP) = 65%, sensitivity (SE) = 75% and 10 d: AUC = 0.80, SP = 78%, SE = 80%) and a moderately to severely abnormal WM score (2 d: AUC = 0.71, specificity (SP) = 80%, sensitivity (SE) = 72% and 10 d: AUC = 0.69, SP = 64%, SE = 89%). Conclusions. Early urinary spectra of preterm infants were able to discriminate metabolic profiles in patients with moderately/severely abnormal cGM and WM scores at term equivalent age. Urine spectra are promising for early identification of neonates at risk of brain damage and allow understanding of the pathogenesis of altered brain development.

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Monthly News Roundup - September 2018

Ajovy for Migraine Prevention Cleared With Two Dosing Options Ajovy (fremanezumab-vfrm), an injectable migraine preventive for adults was FDA-approved this month. From Teva, it is the second approved migraine preventive that targets the...

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Updates on the Status of Vitamin D as a Risk Factor for Respiratory Distress Syndrome

To update the guidelines regarding vitamin D status in respiratory distress syndrome, we reviewed recent human and animal studies on the benefits of vitamin D in respiratory distress. We searched PubMed and ProQuest for studies on the use of vitamin D from 2009 to 2017. The common parameters in these studies included the use of lung tissue, phospholipids, blood, and plasma to assess the effects of vitamin D on respiratory syndrome. The metabolized form of vitamin D used in these studies was 1,25(OH)2D3 in animal studies and 25(OH)D in human studies. Vitamin D supplementation decreases the risk of respiratory distress syndrome, improves the quality of life, and is relatively effective and safe for preterm neonates as well as during lung maturation. However, although vitamin D supplementation may offer benefits for respiratory distress syndrome, the optimal dosing strategies for specific types of risk factors in the lungs must be clarified to confirm the therapeutic efficacy.

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Manipulating the stereoselectivity of a thermostable alcohol dehydrogenase by directed evolution for efficient asymmetric synthesis of arylpropanols

Journal Name: Biological Chemistry
Issue: Ahead of print


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Characterization of the cholesterol efflux of apolipoprotein E-containing high-density lipoprotein in THP-1 cells

Journal Name: Biological Chemistry
Issue: Ahead of print


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Saccharomyces cerevisiae Exponential Growth Kinetics in Batch Culture to Analyze Respiratory and Fermentative Metabolism

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Here we present a protocol to estimate the respiratory and fermentative metabolism by fitting the exponential growth of Saccharomyces cerevisiae to the exponential growth equation. Calculation of the kinetic parameters allows for the screening of influences of substances/compounds on fermentation or mitochondrial respiration.

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Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells

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We describe a method for the isolation of endocrine cells from embryonic, neonatal and postnatal pancreases followed by single-cell RNA sequencing. This method allows analyses of pancreatic endocrine lineage development, cell heterogeneity and transcriptomic dynamics.

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Common Variable Immunodeficiency with Genetic Defects Identified by Whole Exome Sequencing

Common variable immunodeficiency (CVID) belongs to the primary immunodeficiency disorders (PIDs), presenting a profound heterogeneity in phenotype and genotype, with monogenic or complex causes. Recurrent respiratory infections are the most common clinical manifestations. CVID patients can also develop various autoimmune and lymphoproliferative complications. Genetic testing such as whole exome sequencing (WES) can be utilized to investigate likely genetic defects, helping for better clinical management. We described the clinical phenotypes of three sporadic cases of CVID, who developed recurrent respiratory infections with different autoimmune and lymphoproliferative complications. WES was applied to screen disease-causing or disease-associated mutations. Two patients were identified to have monogenic disorders, with compound heterozygous mutations in LRBA for one patient and a frameshift insertion in NFKB1 for another. The third patient was identified to be a complex form of CVID. Two novel mutations were identified, respectively, in LRBA and NFKB1. A combination of clinical and genetic diagnosis can be more extensively utilized in the clinical practice due to the complexity and heterogeneity of CVID.

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Understanding the Motives of Undertaking Physical Activity with Different Levels of Intensity among Adolescents: Results of the INDARES Study

Background. The aim of this study was to evaluate the relationship between the motives for undertaking physical activity (PA) and the intensity of PA in Polish adolescents. Methods. The study included 1,231 students, 515 boys (age 16.2 ± 0.7 years) and 716 girls (age 16.3 ± 0.6 years). The participants were recruited from secondary schools in 20 conurbations throughout Poland. The International Physical Activity Questionnaire-Long Form and the Motives for Physical Activity Measure-Revised were used. Results. In boys, all motives predicted a 10.4% variance in vigorous intensity of PA (F(5, 509) = 11.822, p

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Multiple Low Frequency Ultrasound Enhances Bactericidal Activity of Vancomycin against Methicillin-Resistant Staphylococcus aureus Biofilms

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections are difficult to treat due to the high antimicrobial resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. This study was to investigate whether low frequency ultrasound (LFU) can enhance the activity of antimicrobial agents against MRSA biofilm infection. Broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of vancomycin (VAN), linezolid (LIN), and levofloxacin (LEV) against three clinical isolated strains, including one methicillin-susceptible Staphylococcus aureus (MSSA) strain and two MRSA strains. Effects of various influencing factors, such as antimicrobial agents, drug concentrations, ultrasonic intensity, and single (S-LFU, 5 or 15 min) or multiple ultrasound (M-LFU, 5 min every 8 h), on the inhibition of biofilms were investigated. The bactericidal effects of S-LFU or M-LFU on MRSA or MSSA biofilms were determined by colony counts. Right after ultrasound, synergistic effects were observed in groups of S-LFU combined with three antimicrobial agents against MSSA biofilm, but for MRSA biofilm, only S-LFU plus VAN had synergistic effect. At the time point of 24 h, M-LFU plus VAN treatment had synergistic bactericidal effect against MRSA and MSSA biofilms, and the synergy showed that VAN is concentration-dependent, but no synergistic effects were observed in all S-LFU combination groups. In conclusion, combination of M-LFU and antimicrobial agents had a better synergistic effect than S-LFU against MRSA or MSSA biofilm. LFU may be useful in treating biofilm infection in the future.

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Potential of Maintaining a Healthy Vaginal Environment by Two Lactobacillus Strains Isolated from Cocoa Fermentation

Bacteria in the genera Mycoplasma and Ureaplasma do not have cell walls and therefore interact with host cells through lipid-associated membrane proteins (LAMP). These lipoproteins are important for both surface adhesion and modulation of host immune responses. Mycoplasma and Ureaplasma have been implicated in cases of bacterial vaginosis (BV), which can cause infertility, abortion, and premature delivery. In contrast, bacteria of the genus Lactobacillus, which are present in the vaginal microbiota of healthy women, are thought to inhibit local colonization by pathogenic microorganisms. The aim of the present study was to evaluate the in vitro interactions between lipoproteins of Mycoplasma and Ureaplasma species and vaginal lineage (HMVII) cells and to study the effect of Lactobacillus isolates from cocoa fermentation on these interactions. The tested Lactobacillus strains showed some important probiotic characteristics, with autoaggregation percentages of 28.55% and 31.82% for L. fermentum FA4 and L. plantarum PA3 strains, respectively, and percent adhesion values of 31.66 and 41.65%, respectively. The two strains were hydrophobic, with moderate to high hydrophobicity values, 65.33% and 71.12% for L. fermentum FA4 and L. plantarum PA3 in toluene. Both strains secreted acids into the culture medium with pH=4.32 and pH=4.33, respectively, and showed antibiotics susceptibility profiles similar to those of other lactobacilli. The strains were also able to inhibit the death of vaginal epithelial cells after incubation with U. parvum LAMP from 41.03% to 2.43% (L. fermentum FA4) and 0.43% (L. plantarum PA3) and also managed to significantly decrease the rate of cell death caused by the interaction with LAMP of M. hominis from 34.29% to 14.06% (L. fermentum FA4) and 14.61% (L. plantarum PA3), thus demonstrating their potential for maintaining a healthy vaginal environment.

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Harmful Roles of TLR3 and TLR9 in Cardiac Dysfunction Developing during Polymicrobial Sepsis

We determined the roles of TLR3 and TLR9 in adverse events of polymicrobial sepsis, with a focus on development of septic cardiomyopathy, progression of which we have recently shown to be complement- and histones-dependent. So Wt, TLR3-knocked out (K.O.), and TLR9-K.O. mice were subjected to polymicrobial sepsis following cecal ligation and puncture (CLP). In the absence of either TLR3 or TLR9, the intensity of echocardiogram (Echo)-Doppler dysfunction during development of cardiomyopathy was substantially reduced in the K.O. mice. Based on our prior studies emphasizing the adverse effects of plasma C5a and histones in the cardiomyopathy of sepsis, in TLR3- and TLR9-K.O. mice, there were striking reductions in plasma levels of C5a and histones as well as reduced levels of cytokines in plasma and heart tissue after CLP. Since we know that histones cause cardiac dysfunction, rat cardiomyocytes (CMs) were exposed in vitro to the histones (purified from calf thymus), which caused bleb formation on the surfaces of CMs, suggesting histones may perturb the cell membrane of CMs. In vitro, exposure of CMs to the histones for 3 hours caused lactate dehydrogenase release from CMs. These data indicate that sepsis-induced cardiac dysfunction requires presence of TLR3 and TLR9 and may be linked to histone-induced damage of CMs.

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Green Tea Polyphenols and Padma Hepaten Inhibit Candida albicans Biofilm Formation

Candida albicans (C. albicans) is the most prevalent opportunistic human pathogenic fungus and can cause mucosal membrane infections and invade the blood. In the oral cavity, it can ferment dietary sugars, produce organic acids and therefore has a role in caries development. In this study, we examined whether the polyphenol rich extractions Polyphenon from green tea (PPFGT) and Padma Hepaten (PH) can inhibit the caries-inducing properties of C. albicans. Biofilms of C. albicans were grown in the presence of PPFGT and PH. Formation of biofilms was tested spectrophotometrically after crystal violet staining. Exopolysaccharides (EPS) secretion was quantified using confocal scanning laser microscopy (CSLM). Treated C. albicans morphology was demonstrated using scanning electron microscopy (SEM). Expression of virulence-related genes was tested using qRT-PCR. Development of biofilm was also tested on an orthodontic surface (Essix) to assess biofilm inhibition ability on such appliances. Both PPFGT and PH dose-dependently inhibited biofilm formation, with no inhibition on planktonic growth. The strongest inhibition was obtained using the combination of the substances. Crystal violet staining showed a significant reduction of 45% in biofilm formation using a concentration of 2.5mg/ml PPFGT and 0.16mg/ml PH. A concentration of 1.25 mg/ml PPFGT and 0.16 mg/ml PH inhibited candidal growth by 88% and EPS secretion by 74% according to CSLM. A reduction in biofilm formation and in the transition from yeast to hyphal morphotype was observed using SEM. A strong reduction was found in the expression of hwp1, eap1, and als3 virulence associated genes. These results demonstrate the inhibitory effect of natural PPFGT polyphenolic extraction on C. albicans biofilm formation and EPS secretion, alone and together with PH. In an era of increased drug resistance, the use of phytomedicine to constrain biofilm development, without killing host cells, may pave the way to a novel therapeutic concept, especially in children as orthodontic patients.

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Utilization Pattern of Traditional Chinese Medicine among Fracture Patients: A Taiwan Hospital-Based Cross-Sectional Study

Traditional Chinese medicine (TCM) divides fracture treatment into three stages. Many TCM herbs and formulas have been used to treat fractures for thousands of years. However, research regarding the Chinese herbal products (CHPs) that should be used at different periods of treatment is still lacking. This study aims to identify the CHPs that should be used at different periods of treatment as well as confirm the TCM theory of fracture periods medicine. We used prescriptions of TCM outpatients with fracture diagnoses analyzed using the Chang Gung Research Database (CGRD) from 2000 to 2015. According to the number of days between the date of the fracture and the clinic visit date, all patients were assigned to one of three groups. Patients with a date gap of 0-13 days were assigned to the early period group; those with a date gap of 14-82 days were assigned to the middle period group; and those with a date gap of 83-182 days were assigned to the late period group. We observed the average number of herbal formulas prescribed by the TCM doctor at each visit was 2.78, and the average number of single herbs prescribed was 6.47. The top three prescriptions in the early fracture period were Zheng-gu-zi-jin-dang, Shu-jing-huo-xue-tang, and Wu-ling-san. In the middle fracture period, the top three formulas were Zheng-gu-zi-jin-dang, Shu-jing-huo-xue-tang, and Zhi-bai-di-huang-wan. In the late fracture period, the top three formulas were Shu-jing-huo-xue-tang, Gui-lu-er-xian-jiao, and Du-huo-ji-sheng-tang. The main single herbs used in the early fracture period were Yan-hu-suo, Gu-sui-bu, and Dan-shen. From the middle to the late period, the most prescribed single herbs were Xu-duan, Gu-sui-bu, and Yan-hu-suo. We concluded that the results showed that the CGRD utilization pattern roughly meets the TCM theory at different fracture periods.

https://ift.tt/2Oq12GE

Anti-Inflammatory and Antioxidant Properties of the Extract, Tiliroside, and Patuletin 3-O-β-D-Glucopyranoside from Pfaffia townsendii (Amaranthaceae)

Brazilian ginseng, including Pfaffia townsendii, is used in popular medicine as a natural anti-inflammatory, tonic, analgesic, and antidiabetic agent. In this study, we investigated the chemical composition and evaluated the antioxidant and anti-inflammatory activities of the P. townsendii ethanolic extract as well as the major isolated glycoside flavonoids tiliroside and patuletin 3-O-β-D-glucopyranoside. Chromatographic techniques and spectroscopic analysis were used for the isolation and identification of the major compounds. The antioxidant potential was determined through DPPH and ORAC-FL assays. The total phenolic content was measured using Folin-Ciocalteu reagent. The anti-inflammatory activity was determined based on a model of paw edema and carrageenan- (Cg-) induced pleurisy. We identified three phenolic acids, one carboxylic acid and two flavonoids, patuletin 3-O-β-D-glucopyranoside, and tiliroside. The ethanol crude extracts, partitions and isolated flavonoids (4581 μmol of Trolox equivalents/g of extract in ORAC and a SC50 of approximately 31.9 μg/mL in the DPPH assay) demonstrated antioxidant activity, and the ethanolic extract as well as isolated flavonoids inhibited paw edema induced by Cg and leukocyte migration in the Cg-induced pleurisy model. The extract, tiliroside, and patuletin 3-O-β-D-glucopyranoside obtained from P. townsendii have therapeutic potential against oxidative stress-related and inflammatory disorders.

https://ift.tt/2y0NUh6

The Effect of Xialiqi Capsule on Testosterone-Induced Benign Prostatic Hyperplasia in Rats

Benign prostatic hyperplasia (BPH) is common among elderly men, of which inflammation, oxidative stress, proliferative, and apoptotic changes play important roles. Xialiqi (XLQ) capsule, a traditional Chinese herbal formula, is used as a potential drug in treating BPH. This study aims to evaluate the therapeutic effect of XLQ capsule on testosterone propionate- (TP-) induced BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: sham control, BPH model, high and low dose of XLQ, and finasteride as a positive control group. All groups were treated with appropriate drugs/normal saline for 28 consecutive days. Prostate weights were recorded; histopathological changes and content of IL-8, TNF-α, DHT, SOD, MDA, caspase-3, and PCNA of the prostate were determined. Animals with BPH demonstrated significantly increased prostate weights and prostate index, higher levels of IL-8, TNF-α, DHT, MDA, and PCNA, but lower activity of SOD and reduced expression of caspase-3. After treatment with XLQ, significant reductions of prostate weights, prostate index, IL-8, TNF-α, DHT, MDA, and PCNA, increased activity of SOD, and higher level of caspase-3 were shown. The present study indicates that XLQ can effectively prevent the development of TP-induced BPH model through mechanisms of anti-inflammation, antioxidation, antiproliferation, and proapoptosis.

https://ift.tt/2Oq1ftq

Immunological and Clinical Characteristics of Systemic Lupus Erythematosus: A Series from Morocco

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with a high female predominance. To date, studies about SLE in Morocco are few. This retrospective study describes the clinical and immunological features in a series of 50 SLE Moroccan patients in University Hospital Center of Rabat, Morocco, between December 2011 and December 2013. All patients were screened for antinuclear antibodies (ANA) and anti-DNA antibodies by indirect immunofluorescence, followed by identification of anti-extractable nuclear antigen antibodies by ELISA. The female to male ratio was 6.1:1. Mean age was 31.72 years. The main clinical manifestations were arthritis (82%), mucocutaneous manifestations (80%), renal manifestations (50%), and hematological features (46%). Of the mucocutaneous features, the highest frequencies were observed in the malar rash (68%) and photosensitivity (60%). Of the hematological features, lymphopenia was most frequently observed in 30% of patients, followed by hemolytic anemia in 16% and leucopenia and thrombocytopenia in 8%. Central nervous system was involved in 10%. ANA were found in 88%, anti-DNA antibodies in 56%, and anti-Sm antibodies in 50%. Anti-SSA, anti-SSB, anti-Sm/RNP, and anti-Scl70 antibodies were detected in 38%, 10%, 48%, and 8%, respectively. Our data show that, in our patients, the main clinical and immunological features of SLE remain comparable to patients from other Arab countries.

https://ift.tt/2xOJ2fX

Characterisation of Patients with Systemic Lupus Erythematosus in Malta: A Population Based Cohort Cross-Sectional Study

Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disorder. The aim of this study was to characterise the SLE patients living in Malta in order to estimate the prevalence and incidence of SLE and characterise the clinical presentation as well as identify any unmet needs. 107 SLE patients who fulfilled SLICC classification criteria were identified. These were invited to participate in the study by means of an interview, blood and urine tests, and filling of the following questionnaires: Fatigue Severity Scale (FSS), visual analogue scale (VAS) for fatigue, Hospital Anxiety and Depression Scale (HADS), VAS for pain, Pittsburgh Sleep Quality Index (PSQI), and modified Health Assessment Questionnaire (mHAQ). The estimated prevalence of SLE in Malta is 29.3 patients per 100,000 and the estimated incidence is 1.48 per 100,000 per year. 93.5% of SLE patients were female, and the mean age at diagnosis was 33.1 years. 60.8% were overweight or obese and body mass index (BMI) had a significant positive correlation with daily dose of prednisolone (R=0.177, p=0.046). 20.7% and 3.3% had a moderate and high disease activity, respectively, as measured by SLEDAI-2K. Disease activity had a significant positive correlation with functional disability measured by mHAQ (R=0.417, p3.7) and 57.6% had a high level of anxiety (HADS ≥8). This study has identified a number of unmet needs of SLE patients, including obesity, uncontrolled disease activity, fatigue, and anxiety.

https://ift.tt/2P476lC

Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

https://ift.tt/2NPdNuY

Diabetes and Metabolism Disorders Medicinal Plants: A Glance at the Past and a Look to the Future 2018



https://ift.tt/2QkFg4F

Investigating the Antiproliferative and Antioxidant Properties of Pancratium maritimum L. (Amaryllidaceae) Stems, Flowers, Bulbs, and Fruits Extracts

Pancratium maritimum stems, flowers, bulbs, and fruits extracts were investigated for their antiproliferative and antioxidant properties. Total phenols and total flavonoids were also determined. The in vitro antiproliferative activity was tested against seven cancer cell lines such as C32, HeLa, MDA-MB-231, PC3, A549, MCF-7, and LNCaP by using SRB assay. Interesting results were obtained with stems ethanol extract (ET1) against C32 cells (IC50 of 27.1 μg/mL) and fruits aqueous extract (AQ) against MCF-7 cell line (IC50 of 36.5 μg/mL). To define the antioxidant activity, four tests such as DPPH, ABTS FRAP, and β-carotene bleaching tests were used. The most promising ABTS scavenging capacity was observed with fruits ethanol extract (ET1) that showed an IC50 value of 6.9 μg/mL. According to the correlation results, the phenols and flavonoids content could provide a fundamental contribution to the antioxidant and antiproliferative activity of P. maritimum extracts.

https://ift.tt/2NO1XRQ

A retrospective cohort study of peri‐implant condition in Chinese patients with different periodontal condition and maintenance frequency

Clinical Oral Implants Research, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OYwqJB

Manipulation of the balance between Th2 and Th2/1 hybrid cells affects parasite nematode fitness in mice

European Journal of Immunology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OlIsj6

Intravenous immunoglobulin protects from experimental allergic bronchopulmonary aspergillosis via a sialylation‐dependent mechanism

European Journal of Immunology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Qf8Fgu

A New Model of Diarrhea with Spleen-Kidney Yang Deficiency Syndrome

Objective. The aim of this study was to examine a new method to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome. Methods. A senna leaf (Folium sennae) decoction was made in 3 concentrations of 1.0, 0.5, and 0.25 g/mL. Rats were randomly divided into 4 groups: the control (C)-, high (H)-, middle (M)-, and low (L)- dose groups. The groups received saline, 1.0, 0.5, or 0.25 g/mL senna leaf decoction, respectively, for 4 weeks. Body weight monitoring, food consumption, water intake, defecation frequency, stool Bristol score, weight-loaded forced swimming test, forelimb grip strength test, D-xylose absorption test, serum cortisone, adrenocorticotropic hormone (ACTH), 24 h urine 17-hydroxycorticosteroid (17-OHCS), and histopathological detection were conducted to assess the success of the senna leaf decoction-induced model. Results. This study showed that the senna leaf decoction could induce diarrhea and dose-dependently slow body weight growth, reduce food consumption, and increase water intake, stool Bristol score, and defecation frequency. Statistical differences were found between groups H and M in rectal temperature, weight-loaded forced swimming time, forelimb grip strength, and serum cortisone. The D-xylose absorption test also showed dysfunction of intestinal absorption in groups H and M. The serum cortisone and 24 h urine 17-OHCS were significantly reduced in group H. Conclusions. Gastric gavage of 10 mL/kg of body weight of a high concentration of a senna leaf decoction (1.0 g/mL) for 4 weeks was used to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome.

https://ift.tt/2QkwPX3

Gynura procumbens Improved Fertility of Diabetic Rats: Preliminary Study of Sperm Proteomic

Gynura procumbens (GP) is a medicinal herb that has long been known as anti-inflammatory and antihyperglycaemic. Recently, this herbal extract has been associated with a profertility effect, suggesting its applicability in treating both diabetes and male infertility. In this study, the effects of GP aqueous extract (GPAE) on diabetic rats were investigated through evaluating testes histology and androgen hormone levels as well as the implantation sites of female rats on copulation with the treated male rats. Three dosages of GPAE were used (150, 300, and 450 mg/kg), and there were three control groups [normal, diabetic, and metformin-treated diabetic]. Testes histology, androgen hormone levels, and number of implantation sites of the GPAE-treated groups matched those of the normal group in contrast to the diabetic and metformin-treated diabetic controls. Sperm proteomics analysis identified 666 proteins, but only 88 were consistently found in all the control and 450-mg/kg GPAE-treated groups. Four proteins, including cysteine-rich secretory protein 1, carboxylesterase 5A, zona pellucida binding protein, and phosphatidylethanolamine-binding protein 1, were significantly upregulated with GPAE treatment compared with the diabetic control, matching the protein levels of the normal group. These proteins were mainly involved in sperm maturation, sperm capacitation, and sperm-egg interaction, suggesting that GP treatment was able to restore the fertility of male diabetic rats at molecular protein level. In conclusion, GP treatment effectively treats infertility of male diabetic rats, possibly through the upregulation of proteins related to sperm maturation and sperm-egg interaction.

https://ift.tt/2RelU2a

Acupuncture and Related Therapies for Obesity: A Network Meta-Analysis

Obesity is a worldwide public health problem. Currently, increasing evidence suggests acupuncture and related therapies are effective for obesity. This network meta-analysis (NMA) was performed to compare the effectiveness of different acupuncture and related therapies. We searched potential randomized controlled trials (RCTs) in three international databases. Thirty-four trials involving 2283 participants were included. Pairwise meta-analysis showed that acupuncture and related therapies were superior to lifestyle modification and placebo in reducing weight and body mass index (BMI). Based on decreases in body weight, results from NMA showed that acupoint catgut embedding (standard mean difference [SMD]: 1.26; 95% credible interval [95% CI], 0.46–2.06), acupuncture (SMD: 2.72; 95% CrI, 0.06–5.29), and combination of acupuncture and related theories (SMD: 3.65; 95% CrI, 0.96–6.94) were more effective than placebo. Another NMA result indicated that acupoint catgut embedding (SMD: 0.63; 95% CI, 0.25–1.11), acupuncture (SMD: 1.28; 95% CrI, 0.43–2.06), combination of acupuncture and related therapies (SMD: 1.44; 95% CrI, 0.64–2.38), and electroacupuncture (SMD: 0.60; 95% CrI, 0.03–1.22) were superior to lifestyle modification in decreasing BMI. Combination of acupuncture and related therapies was ranked the optimal method for both reducing weight and BMI. Further studies will clarify which combination of acupuncture and related therapies is better.

https://ift.tt/2QlTnXu

Applications of Bioinformatics and Systems Biology in Precision Medicine and Immunooncology



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Innervation of the Anconeus Epitrochlearis Muscle: MRI and Cadaveric Studies

Clinical Anatomy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2y1QBz4

Adoptive Transfers of CD4+CD25+ Tregs Raise Foxp3 Expression and Alleviate Mouse Enteritis

CD4+CD25+Foxp3+ Tregs control the immune response and maintain immune homeostasis. This study examined whether Tregs can affect mouse enteritis and the Foxp3 (Forkhead transcription factor) transcriptional pathway. Mouse CD4+CD25+ Treg cells were labelled using CFSE (5,6-carboxyfluorescein diacetate succinimidyl ester) and transferred to enteritis model mice. The mice were randomly divided into an enteritis group, a Treg-infusion group, a Treg-inhibiting group, and a control group. Histopathology, ELISA, flow cytometry, western blot, immunohistochemistry, and immunofluorescence were performed. Our results demonstrated that CD4+CD25+ Tregs were successfully transferred. The disease activity index (DAI) scores in the Tregs-infusion group were lower than those of the enteritis and Tregs-inhibiting groups. The number of goblet cells and inflammatory cells was reduced, and the levels of IL-1β, TNF-α, NO, and PGE2 were significantly decreased in the Tregs-infusion group compared to those in the enteritis group (p

https://ift.tt/2xV4FeD

Emergency versus Elective Cervical Cerclage: An Audit of Our First Two Years of Service

One of the biggest obstetric challenges is the diagnosis and management of a short cervix as cervical length has an inverse relationship with risk of preterm birth. A cervical cerclage is a surgical procedure to reduce the risk of preterm birth and can be placed in an elective or emergency setting. This is a retrospective review of cervical cerclages inserted at an outer metropolitan hospital from February 2014 to May 2017. Since the introduction of the service, a total of 43 patients were identified as requiring a cervical cerclage. Four of these patients were transferred to tertiary hospitals. Of the 39 cerclages inserted, 26 were elective and 13 were emergency, placed at a mean gestation of 15.6 and 19.6 weeks. In total, there were 35 live births, 2 stillbirths, and 2 neonatal deaths. The maternal demographics (age, gravidity, parity, and preterm risk factors) were not statistically significant between the two groups. The mean pregnancy prolongation and birthweight was greater in the elective than the emergency group (21.4 versus 14.1 weeks; 3148.2 versus 2447.2 grams). There was no obvious pattern with which patients received antibiotics pre-, intra-, or postoperatively or received a vaginal swab. This audit identified the need for improvements to guidelines to standardise the use of antibiotics and progesterone in women with a cervical cerclage.

https://ift.tt/2DIihPD

Attitude towards Mental Illness among Primary Healthcare Providers: A Community-Based Study in Rural China

Objective. There are no studies that have explored attitudes towards mental illness that are held by rural primary healthcare (PHC) providers. The aim of this study was to conduct evidential and comparative research about attitudes towards mental illness among primary healthcare providers from different mental health service models in China rural communities. Methods. A self-administered questionnaire was conducted with a total of 361 rural primary healthcare providers engaged in mental health service delivery. Results. Total attitude score mark of rural primary healthcare providers shows that most PHC providers still held pessimistic and negative attitude towards mental illness patients. 71.3% of respondents agreed that "the mental patients often impulsively perform destruction of property"; 72.9% agreed that "mental patients are burdens to the families and society." There are also positive correlations between attitudes and abilities of primary healthcare providers to mental illness. Conclusion. This study provides baseline evidence that primary healthcare providers in rural China hold negative attitudes towards mental illness. It is critical to improve negative attitudes and understanding about the importance of the management of severe mental illness among rural primary healthcare workers in mental health services. We should take comprehensive methods to enrich primary healthcare providers' professional knowledge about mental illness and eliminate discrimination and inappropriate perception against the mental illness.

https://ift.tt/2DP89nY

Polyunsaturated fatty acids and atherosclerosis: insights from pre‐clinical studies

European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2DE5Ynn

Characterization of nitrophospholipid‐peptide covalent adducts by electrospray tandem mass spectrometry: a first screening analysis using different instrumental platforms

European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OldBmH

Minding the Gap: A Qualitative Study of Provider Experience to Optimize Care for Critically Ill Children in General Emergency Departments

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.


https://ift.tt/2zFO7bz

Whole exome sequencing resolves complex phenotype and identifies CC2D2A mutations underlying non‐syndromic rod‐cone dystrophy

Clinical Genetics, Volume 0, Issue ja, -Not available-.


https://ift.tt/2xLeueU

Genetic variant in the β2‐Adrenergic receptor (Arg16Gly) influences fat free mass, muscle strength, and motor unit behavior in young men

Experimental Physiology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2RczeV6

Finite Element Investigation of the Effects of the Low-Frequency Vibration Generated by Vehicle Driving on the Human Lumbar Mechanical Properties

Long-term exposure to low-frequency vibration generated by vehicle driving impairs human lumbar spine health. However, few studies have investigated how low-frequency vibration affects human lumbar mechanical properties. This study established a poroelastic finite element model of human lumbar spinal segments L2–L3 to perform time-dependent vibrational simulation analysis and investigated the effects of different vibrational frequencies generated by normal vehicle driving on the lumbar mechanical properties in one hour. Analysis results showed that vibrational load caused more injury to lumbar health than static load, and vibration at the resonant frequency generated the most serious injury. The axial effective stress and the radial displacement in the intervertebral disc, as well as the fluid loss in the nucleus pulposus, increased, whereas the pore pressure in the nucleus pulposus decreased with increased vibrational frequency under the same vibrational time, which may aggravate the injury degree of human lumbar spine. Therefore, long-term driving on a well-paved road also induces negative effects on human lumbar spine health. When driving on a nonpaved road or operating engineering machinery under poor navigating condition, the auto seat transmits relatively high vibrational frequency, which is highly detrimental to the lumbar spine health of a driver.

https://ift.tt/2RaKocT