Preimplantation Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease Applied in China

Murphy et al1 state that patients with autosomal dominant polycystic kidney disease (ADPKD) of childbearing potential could benefit from preimplantation genetic diagnosis (PGD) counseling. This benefit may extend to patients with ADPKD outside North America; however, current circumstances in other countries such as China make it challenging or impossible to obtain. Although ADPKD affects about 1.5 million people in China,2 financial barriers prohibit access to PGD and counseling despite patients' desire for it.

https://ift.tt/2KQyky1

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study

Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population.

https://ift.tt/2N7eScQ

Associations Between Kidney Disease Measures and Regional Pulse Wave Velocity in a Large Community-Based Cohort: The Atherosclerosis Risk in Communities (ARIC) Study

Arterial stiffness is suggested as a mediator of cardiorenal interaction. However, previous studies reported inconsistent associations between chronic kidney disease (CKD) and arterial stiffness and were limited by using either estimated glomerular filtration rate (eGFR) or albumin-creatinine ratio (ACR) and examining arterial stiffness at limited segments.

https://ift.tt/2KQyfdH

Open versus Laparoscopic Surgery for Advanced Low Rectal Cancer: A Large, Multicenter, Propensity Score Matched Cohort Study in Japan

Background: Laparoscopic surgery for rectal cancer is widely performed all over the world and several randomized controlled trials have been reported. However, the usefulness of laparoscopic surgery compared with open surgery has not been demonstrated sufficiently, especially for the low rectal area. Objective: The aim of this study was to investigate the hypothesis that laparoscopic primary tumor resection is safe and effective when compared with the open approach for locally advanced low rectal cancer. Patients and Methods: Data from patients with clinical stage II to III low rectal cancer below the peritoneal reflection were collected and analyzed. The operations were performed from 2010 to 2011. Short-term outcomes and long-term prognosis were analyzed with propensity score matching. Results: Of 1608 cases collated from 69 institutes, 1500 cases were eligible for analysis. The cases were matched into 482 laparoscopic and 482 open cases. The mean height of the tumor from the anal verge was 4.6 cm. Preoperative treatment was performed in 35% of the patients. The conversion rate from laparoscopic to open surgery was 5.2%. Estimated blood loss during laparoscopic surgery was significantly less than that during open surgery (90 vs 625 mL, P

https://ift.tt/2uny3at

The Whiteboard Technique: Personalized Communication to Improve Operating Room Teamwork

No abstract available

https://ift.tt/2uuVkrp

Directed Change in TNFα Specificity to Create DR5 Antagonists

Death receptor 5 (DR5) is a promising target for antitumor therapy due to its high expression on different tumor cells. Resistance of various tumor cells against TRAIL, a natural ligand for the death receptors, reduces its therapeutic potential and prompts the search for novel agonists at these receptors. Previous screening across the combinatorial peptide library yielded a peptide sequence KVVLTHR that specifically binds DR5. Incorporation of this sequence into TNFα resulted in binding DR5 with mutant protein TNFα-mut and appearance of cytotoxicity against lymphoma cells.

https://ift.tt/2KRMrDd

Generation of Highly Specific Proteolytic Biocatalysts by Screening Technologies

We propose a yeast display-based system for screening of proteolytic enzyme libraries that utilizes substrate protein adsorbed on the yeast cell surface and containing a desired cleavage sequence. Specific cleavage of the substrate protein releases its biotin-binding center. The cells carrying the target proteinase can be selected by cytofluorometry due to interaction with biotinylated fluorescent protein. Using human enterokinase light chain as the model proteinase we showed that the proposed screening system highly effectively selects the proteolytic enzymes with preset specificity.

https://ift.tt/2N7Woc8

Expression of New Recombinant IgG-Binding Polypeptides and Analysis of Their Capacity to Bind Human IgG

Protein G is present in group G streptococcus strain (G4223); the IgG-binding part of this protein contains three IgG-binding domains and binds human IgG with very high activity. We obtained two recombinant polypeptides G4223 and G₁4223 with high IgG-binding activity. Polypeptide G₁4223 consisting of three IgG-binding domains and W region has higher molecular weight and is characterized by higher affinity for IgG than polypeptide G4223 consisting of only three IgG-binding domains. It was shown that polypeptide affinity depends on its structure and size.

https://ift.tt/2KR7FB1

Proliferative and Apoptotic Activity of Bone Marrow Monocyte Lineage Cells in the Offspring of Female Rats with Chronic Toxic Liver Injury

We analyzed proliferative and apoptotic activity of bone marrow monocyte lineage cells in the offspring of mothers with experimental toxic injury to the liver. Rat pups were examined at different times of ontogeny. Inhibition of proliferative activity and increase in apoptotic activity in bone marrow monocyte cells of experimental rat pups in comparison with intact ones were found.

https://ift.tt/2N7eET2

Effect of Erythrocyte Density on Blood Clot Properties in Healthy Individuals and in Patients with Hemophilia A

We measured specific volume and hematocrit of blood clots prepared from the whole blood of patients with hemophilia A and healthy male volunteers. It was shown that in the hematocrit range of 43.5-52.5%, specific volume of the blood clot in hemophilia patients with low level of factor VIII (1-4%) was higher than in volunteers. After injection of factor VIII, specific volume of blood clots in hemophilia patients decreased. Hematocrit of the blood clots derived from the whole blood linearly depended on the mean erythrocyte density in both volunteers (r=-0.74, p=0.01) and patients with factor VIII level of 1-4% (r=-0.95, p<0.0001). The increase in the mean erythrocyte density led to a decrease in blood clot hematocrit. The curve describing blood clot hematocrit as a function of the mean erythrocyte density in hemophilia patients was lower than in healthy volunteers. The increase in factor VIII level was associated with an increase in blood clot hematocrit. The results showed that blood clot hematocrit depends on the mean erythrocyte density, and therefore, hematocrit of the blood clot can be changed by modulating the properties of erythrocyte population.

https://ift.tt/2KSnuHK

Subpopulation Structure of IFNγ-Producing T Lymphocytes in Patients with Pulmonary Tuberculosis

The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3⁺ IFNγ⁺ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4⁺ IFNγ⁺IL-17A⁺) and, conversely, decreased number of blood γδT cells was detected.

https://ift.tt/2N8DWA5

Method for Studies of Orientation and Exploratory Behavior in Humans. Effects of Emotional Stress

We developed a new experimental model for studies of orientation and exploratory behavior in humans. This method allows analysis of variants of orientation and exploratory behavior in humans, including risky behavior, and cognitive and individual typological parameters. The model allows distinguishing examinees with high and low orientation and exploratory activity, which helps to determine their psychoemotional status. Surprisingly, individuals in emotional strain demonstrated longer orientation and exploratory behavior. This allows them to achieve the results more rapidly during purposeful behavior under similar conditions. This model provides the tool for evaluation of the electrophysiological, autonomic, and biochemical mechanisms of orientation and exploratory behavior of humans.

https://ift.tt/2KT4OYx

Association of 3111T/C Polymorphism of the Clock Gene with Circadian Rhythm of Melatonin in Menopausal Women with Insomnia

We carried out a comparative analysis of circadian rhythms of melatonin secretion in Caucasian menopausal women with and without insomnia depending on the 3111T/C polymorphism of the Clock gene. Melatonin levels was measured in the saliva 4 times a day (06.00-07.00, 12.00-13.00, 18.00-19.00, and 23.00-00.00 h). Carriers of the TT genotype with insomnia demonstrated significantly higher level of melatonin in the early morning hours compared to the carriers of the minor allele C (12.60±7.58 and 8.98±8.62 pg/ml, respectively, p=0.023). In the control group, no statistically significant differences were revealed. The carriers of the TT genotype with sleep disorders have higher morning melatonin level compared to control group women (12.60±7.58 and 5.48±4.74 pg/ml, respectively, p=0.005) and low nocturnal melatonin level (6.42±4.97 and 12.52±10.40 pg/ml, respectively, p=0.039).

https://ift.tt/2N7evPu

Moricizine (Ethmozine) Can Break Electrical Coupling between Rat Right Atrial Working Cardiomyocytes In Vitro

A previously popular antiarrhythmic drug moricizine (ethmozine) is known for its blocking action on the fast sodium channels in cardiomyocytes. Its effects were examined only in isolated cardiomyocytes or in vivo. Here, the effect of moricizine (10 μM) was examined in vitro on perfused right atrial preparation, where it completely reproduced all the previously observed phenomena and disturbed electrical coupling between the working cardiomyocytes in 35.3±3.4 min, which arrested generation of action potentials. During washing, the cardiomyocytes restored rhythmic firing in 34.1±3.7 min. Inhibition of firing in the working atrial cardiomyocytes was not accompanied by suppression of rhythmic activity in the pacemaker cells of sinoatrial node as attested by rhythmic miniature spikes in the records of resting (diastolic) potential of these cardiomyocytes. Thus, moricizine disturbed conduction between the working atrial cardiomyocytes without affecting the pacemaker activity.

https://ift.tt/2KRMqPF

Dihydroquercetin and Fucoidin Inhibit the Increase of Angiotensin-Converting Enzyme Activity in the Rat Aorta after Irradiation

The time course of angiotensin-converting enzyme activity in the rat aorta after fractionated exposure to ionizing radiation and the effects of dihydroquercetin and fucoidin on this parameter were studied. Male Wistar rats were exposed to single or repeated (fractionated) X-ray radiation in a dose of 2.5 Gy at 200 kV. Activity of angiotensin-converting enzyme in aorta segments was evaluated 2 h after the last exposure by hydrolysis of hippuryl-histidineleucin substrate. Enzyme activity in the rat aorta was higher than normally after all the studied doses of fractionated exposure (2.5 Gy per fraction) with the maximum effect after the total dose of 7.5 Gy (3 fractions). Fucoidin, a blocker of endothelium receptors realizing the leukocyte adhesion to the endothelium, and flavonoid dihydroquercetin inhibiting expression of adhesion molecules in the endothelium abolished the increase in activity of angiotensinconverting enzyme in the rat aorta after single exposure; moreover, dihydroquercetin reduced significantly the effect of fractionated exposure. These data indicate that leukocyte adhesion to the endothelium is an important factor contributing to the increase of angiotensin-converting enzyme activity in the aorta.

https://ift.tt/2N57ij1

Peculiarities of Osteogenesis by Periosteal Cells after Experimental Ectopic Transplantation

We carried out a comparative study of the features of osteogenesis from the progenitor osteogenic periosteal cells in rabbit and human. At the initial stages, high osteogenic potential of both human and rabbit periosteal cells was observed. However, at the later stages, the cell response favors resorption of the new bone tissue formed from periosteal cells in rabbits, but does not affect the bone tissue formed from human progenitor osteogenic periosteal cells. These functional characteristics of rabbit periosteal cells should be considered when planning the experiment.

https://ift.tt/2KRzmd1

Effects of Glycolipid Rhodococcus Biosurfactant on Innate and Adaptive Immunity Parameters In Vivo

The glycolipid biosurfactant complex from actinobacterium Rhodococcus ruber IEGM 231 inhibits the innate and adaptive immunity parameters after intraperitoneal and intramuscular injection. Marked suppression of antibody production, bactericidal potential, and production of proinflammatory cytokines by peritoneal macrophages, detected in vivo, do not agree with the previously detected immunostimulatory activity of biosurfactants towards the immunocompetent cell cultures; this fact indicates an important role of the cell environment in the formation of immune response under the effect of bacterial glycolipids.

https://ift.tt/2N57ezN

Greater Breastfeeding in Early Infancy Is Associated with Slower Weight Gain among High Birth Weight Infants

To examine whether feeding patterns from birth to age 6 months modify the association between birth weight and weight at 7-12 months of age.

https://ift.tt/2KSntUc

Subsyndromal Manifestations of Depression in Children Predict the Development of Major Depression

To evaluate the utility of assessing subsyndromal symptoms of major depressive disorder in childhood, indexed through the Child Behavior Checklist (CBCL) anxiety/depression scale, in predicting risk of developing major depressive disorder in adolescent and young adult years.

https://ift.tt/2N7egUA

Second opinions in orthopedic oncology imaging: can fellowship training reduce clinically significant discrepancies?

Abstract

Objective

To determine factors that lead to significant discrepancies in second-opinion consultation of orthopedic oncology patients, and particularly if musculoskeletal fellowship training can decrease clinically significant discrepancies.

Methods

A PACS database was queried for secondary reads on outside cross-sectional imaging studies, as requested by orthopedic oncology from 2014 to 2017. Comparison of original and secondary reports was performed using a published seven-point scale that defines clinically significant discrepancies. An online search was performed for each original radiologist to record if a fellowship in musculoskeletal imaging was completed. Additionally, years of post-residency experience, number of Medicare part B patients billed per year (marker of practice volume), and average hierarchical condition category for each radiologist (marker of practice complexity) was recorded.

Results

A total of 571 patients met the inclusion criteria, with 184 cases initially interpreted by an outside fellowship trained musculoskeletal (MSK) radiologist and 387 cases initially interpreted by a non-MSK trained radiologist. The rate of clinically significant discrepancy was 9.2% when initially interpreted by MSK radiologists compared with 27.9% when initially performed by non-MSK radiologists (p < 0.05). After adjustment by both patient characteristics and radiologist characteristics, the likelihood of clinically significant discrepancies was greater for initial interpretations by non-MSK radiologists compared with MSK radiologists (OR = 1.36; 95% CI = 1.23–2.49).

Conclusion

In orthopedic oncology patients, the rate of clinically significant discrepancies was significantly higher when initially interpreted by non-MSK radiologists compared with MSK radiologists. The lower rate of clinically significant discrepancies demonstrates that subspecialty training may direct more appropriate diagnosis and treatment.

https://ift.tt/2Jgptjz

Superficial siderosis misdiagnosed as idiopathic bilateral neurosensorial deafness

Superficial siderosis (SS) is a rare condition resulting from different sources of bleeding into the subpial space. The most common symptoms are: hypoacusia, ataxia, incontinence, dementia and parkinsonism. Since several neurodegenerative disorders may present with same clinical features, SS is often misdiagnosed. Here we present a case of SS misdiagnosed as idiopathic bilateral neurosensorial deafness.

https://ift.tt/2KR239V

Multiple intestinal perforations due to blister pill pack ingestion

A 72-year-old woman with morbid obesity and history of psychosis attended the emergency room due to abdominal pain. CT scan revealed a mesenteric infiltration surrounding a thickened wall bowel agglomeration; inside, a dense 2 cm foreign body with no pneumoperitoneum or peritoneal effusion. Surgery revealed four contained bowel perforations due to a blister pill pack inside the ileum; consequently, a 30 cm bowel resection was performed. Ingestion was restarted on day 2, a superficial wound infection was evacuated on day 4 and the patient was discharged 6 days after surgery. Foreign body ingestion is relatively common in paediatric patients. Adult cases are usually related to vision problems, intellectual disability and psychiatric or cognitive disorders. Mostly, no consequences are reported, but some cases (<1%) can lead to complications such as perforations or gastrointestinal (GI) bleeding. Endoscopic extraction may be considered when placed in the upper GI tract, but surgery remains imperative if perforation is established.

https://ift.tt/2N93ZY5

A challenging case of primary amenorrhoea

The differential diagnosis of a girl presenting with primary amenorrhoea includes numerous conditions. Often, patients of 46XY disorder of sex development (DSD) are reared as girl and present with primary amenorrhoea. Their further evaluation to reach the final diagnosis is often a great challenge. In this article, we report a challenging case of 46XY DSD presented with primary amenorrhoea. Patient had spontaneous breast development which initially confused the diagnosis to complete androgen insensitivity syndrome. However, low testosterone suggested against this possibility and further evaluation revealed hormonal findings consistent with 17α hydroxylase/17,20 lyase (CYP17A1) deficiency. Patient had 46XY karyotype and in consistence with hormonal findings patient was found to have a likely pathogenic homozygous c.1345C>T (p.Arg449Cys) variation in exon 8 of CYP17A1.

https://ift.tt/2KP07Po

Squamous cell carcinoma arising in hypertrophic lichen planus

Hypertrophic lichen planus (HLP) is a chronic T-cell-mediated inflammatory disease characterised by pruritic hypertrophic or verrucous plaques on the lower limbs. We report a case of an 87-year-old woman with a 12-year history of HLP on both lower legs presenting with malignant transformation of one lesion into a squamous cell carcinoma (SCC). Malignancy developing in cutaneous lichen planus is rare, with less than 50 cases reported in the literature. This case highlights the need to be aware of suspicious changes in long-standing HLP to allow early detection of a developing SCC.

https://ift.tt/2L9230W

Vesicovaginal fistula and vesicocutaneous fistula in a patient having pelvic ectopic kidney with pyonephrosis: a unique therapeutic challenge

Patients with ectopic kidney require special considerations in their management due to the anatomic characteristics predisposing the kidney to obstruction and related complications. Pelvic ectopic kidneys have the added disadvantage of being confined in the bony pelvis giving less manoeuvrability during surgery of that unit. Vesicovaginal fistulas are usually managed surgically and careful surgical dissection has to be carried out because the highest success rates are usually seen at the first operation. It is rare to find a combination of such challenging diseases in a single patient. We present the case of a young woman who developed iatrogenic vesicovaginal and vesicocutaneous fistulae during an attempt to surgically manage a pyonephrotic ectopic pelvic kidney.

https://ift.tt/2L24xl8

Uterine artery pseudoaneurysm with an anastomotic feeding vessel requiring repeat embolisation

Uterine artery pseudoaneurysm (UAP) is a rare cause of delayed postpartum haemorrhage. Early diagnosis and endovascular management are effective in treating this condition. We present the case of a 36-year-old gravida 3, para 2 woman with delayed postpartum haemorrhage and endometritis following a spontaneous vaginal delivery. Ultrasound and catheter angiogram demonstrated a UAP arising from the distal aspect of the left uterine artery. Significant bleed persisted despite selective bilateral uterine artery embolisation. A repeat angiogram confirmed complete occlusion of bilateral uterine arteries, but abdominal aortogram demonstrated that the left ovarian artery was now feeding the pseudoaneurysm. A repeat embolisation procedure was performed to occlude the left ovarian artery. The patient was discharged the following day. Selective arterial embolisation is effective in the management of UAP. Persistent bleeding despite embolisation should raise the suspicion of anastomotic vascular supply and may require repeat embolisation.

https://ift.tt/2Jg9qlM

Visible-free cholesterol crystal emboli adjacent to microinfarcts in myocardial capillaries and arterioles on H&E-stained frozen sections of an autopsied patient

The number of released free cholesterol crystal emboli (fCCE) and their role during percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) have not been documented yet. Furthermore, fCCE manifesting in the coronary lumen following plaque rupture has been historically overlooked owing to the standard tissue preparation for light microscopy which uses ethanol as a dehydrating agent that can dissolve fCCE, leaving behind empty tissue. In this case report, we evaluated fCCE released during PCI for ACS and their relationship with myocardial injury and coronary artery obstruction on the H&E-stained sections by using polarised light microscopy. To our knowledge, there has been no mention of the visibility of fCCE on H&E-stained frozen polarised sections before.

https://ift.tt/2KZZa5U

Metastatic Merkel-cell carcinoma: the dawn of a new era

Merkel-cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy arising most often in sun-exposed Caucasians who are immunosuppressed or the elderly. Patients with metastatic disease treated with chemotherapy have a median progression-free survival of just 3 months. This report describes a 58-year-old man with a background history of psoriasis treated with immunosuppressive therapy and subsequently diagnosed with metastatic MCC. Chemotherapy produced a partial response. Then, a novel immunotherapy agent, pembrolizumab, induced a complete response maintained for at least 19 months. Quality of life was unaffected, and toxicity from immunotherapy was minimal. At the time of writing, there was no clinical or radiological evidence of recurrence and treatment is ongoing.

https://ift.tt/2JfnJqy

Secondary spindle cell sarcoma following external beam radiotherapy for prostate cancer: a rare but devastating complication

We report a case of rapidly growing sarcoma that resulted in mortality only 6 years after radiotherapy for low-grade prostate cancer.

At the age of 69 years and a prostate-specific antigen (PSA) that had risen to 9.0 µg/L, transrectal ultrasound-guided biopsy of the prostate found a single core of Gleason 3+3 disease involving 4 mm of a 10 mm core. The patient declined active surveillance and completed 78 Gy of external beam radiotherapy over 39 fractions to a prostate volume of 46 mL.

His PSA nadir was 0.62 µg/L 1-year postradiation; however, in April 2017, his PSA began to rise satisfying the definition of biochemical recurrence. He underwent cystoscopy, biopsy favoured an undifferentiated pleomorphic sarcoma. Restaging scans (CT/bone scan) were completed showing no metastasis, and repeat MRI showed rapid growth of the lesion in 3 months.

He underwent palliative pelvic exenteration, however, 1 month later presented with large volume tumour recurrence and was subsequently palliated and died.

https://ift.tt/2KZZ6mG

Combination therapy for systemic sclerosis-associated pneumatosis intestinalis

We present a case of a patient with pneumatosis intestinalis and pneumoperitoneum secondary to gastrointestinal systemic sclerosis, who presented following recurrent accident and emergency attendances with abdominal pain. Pneumatosis intestinalis is a rare complication of systemic sclerosis; management approaches focus largely on exclusion of life-threatening surgical pathologies and subsequent symptom control. To date, there are still no established gold-standard treatment strategy and no large-scale trial data to support a specific management strategy. We describe a case of successful medical management with a combination of antimicrobial, elemental diet and high-flow inhalation oxygen therapy, with supporting evidence of CT image confirming resolution. This case therefore contributes to the literature, being the first to report both symptomatic and radiological improvement following combination therapy without the need for surgical intervention.

https://ift.tt/2JfnCv8

Neutropaenia and splenomegaly without arthritis: think rheumatoid arthritis

Felty syndrome(FS) is an uncommon, but severe, extra-articular manifestation of rheumatoid arthritis (RA). It occurs in patients with longstanding RA. It is extremely rare for RA to present as FS or develop after initially presenting as neutropaenia and splenomegaly. We describe a case of 47-year-old woman who was diagnosed simultaneously with FS and possible RA after testing positive for anticyclic citrullinated peptide antibody, but a negative rheumatoid factor. She had an excellent response to methotrexate. We review the existing literature of such cases and emphasise the importance of serological testing for RA in patients presenting with neutropaenia and splenomegaly, even in the absence of joint symptoms or prior diagnosis of RA.

https://ift.tt/2KZZ3Hw

Azathioprine-induced pancytopenia with normal TPMT activity presenting with HSV oral ulcers

A 65-year-old man with treatment-resistant psoriatic arthritis, hypertension, dyslipidaemia and benign prostatic hyperplasia (BPH) presented with herpes simplex virus (HSV) oral ulcers and a recent 15 lb weight loss due to reduced consumption. Five weeks previously, his methotrexate was tapered and he had begun taking azathioprine. The patient's thiopurine S-methyltransferase (TPMT) activity level was normal prior to starting azathioprine. He was found to have pancytopenia with normal folate levels and azathioprine was discontinued. His pancytopenia worsened, with a nadir 8 days after stopping azathioprine, before returning to normal levels. His oral ulcers improved and he was able to tolerate solid food. This case illustrates that decreased TPMT activity is not the only risk factor for pancytopenia as an adverse reaction to azathioprine. Furthermore, HSV stomatitis may be the presenting symptom of pancytopenia. The timeline of improvement in cell counts illustrated in this patient has implications for the management of suspected azathioprine-induced pancytopenia.

https://ift.tt/2Lb7sF1

Giant pituitary incidentaloma

Description 

A 78-year-old woman, independent, with medical history of hypertension, dyslipidaemia and bilateral cataract surgery. The patient underwent a head CT after a traumatic brain injury where a giant pituitary incidentaloma of 60 mm in the largest diameter was found. The patient mentioned decreased left eye acuity for the past 20 years, with no complaints of headaches or diplopia. The physical examination was unremarkable with no stigmata of endocrine disease. Anterior pituitary hormonal profile was normal. Additional MRI showed an extensive infiltrative lesion, 60x40 mm, with cavernous and sphenoidal sinus invasion, suprasellar extension and left optic nerve encapsulation (figures 1 and 2). Visual field campimetry revealed left amaurosis and right inferior temporal quadrantanopia. A nasal endoscopic biopsy was performed and the histopathology was compatible with pituitary adenoma with rare cells staining positive for adrenocorticotropic hormone and alpha subunit. Cytological atypia was absent and the Ki67 index...

https://ift.tt/2KZcKqj

Small bowel perforation by toothpick

Toothpick ingestion is a rare but potentially fatal condition which may cause bowel perforation and rare complications if it migrates out of the gastrointestinal tract. This case report describes a delayed presentation of toothpick-induced small bowel injury leading to abdominal wall abscess and spondylodiscitis. A 51-year-old man was admitted twice with fever and loin pain, but repeated non-contrast CT was reported to be unremarkable. However, 5 months later, he presented with a left lower quadrant abdominal wall abscess and back pain. An updated CT showed a linear hyperdensity which was already present in previous scans, causing small bowel perforation, abdominal wall abscess and spondylodiscitis. Emergency laparotomy identified a toothpick causing small bowel perforation. The abdominal wall abscess was incised and drained, and small bowel was repaired.

https://ift.tt/2Lc3jke

Acute upper gastrointestinal bleeding in a patient with malignant melanoma

Description 

The patient is a 73-year-old woman who was diagnosed with nodular melanoma of the calf almost 2 years prior to presentation. The melanoma was treated with wide-margin surgical resection (pT4b, 21 mitoses/high power field, 8 mm depth), followed by sentinel lymph node biopsy, which was negative. However, surveillance CT scan done less than a year after the original excision showed metastases to the liver, bone, lungs and adrenal glands. After oncological assessment, the patient had decided not to proceed with chemotherapy. The gastroenterology service was consulted when the patient presented with melena and significant anaemia (haemoglobin 54 g/L, haematocrit 0.17 L/L). Her haemoglobin level was normal 1 year prior (128 g/L). She also had mild renal impairment (creatinine 135 μmol/L, urea 11.4 mmol/L, glomerular filtration rate 32 mL/min/1.73 m²). She was resuscitated, including blood transfusions, and underwent urgent gastroscopy.

The gastroscopy showed multiple lesions in the fundus and body of the stomach (figure 1). The lesions were nodular with central...

https://ift.tt/2KZYMV0

Knowledge and Assertion in Korean

Cognitive Science, EarlyView.


https://ift.tt/2N93vBf

Why Choo‐Choo Is Better Than Train: The Role of Register‐Specific Words in Early Vocabulary Growth

Cognitive Science, EarlyView.


https://ift.tt/2KSVWCd

The Relation Between Factual and Counterfactual Conditionals

Cognitive Science, EarlyView.


https://ift.tt/2N9UCHs

Effect of Calcium on Slow Force Responses in Isolated Right Ventricle Preparations of Healthy and Hypertrophied Myocardium in Male and Female Rats

Effect of different Ca²⁺ concentrations in the bathing solution [Ca²⁺]_o on the parameters of single isometric contraction and slow force response to stretching was studied in isolated preparations of healthy and hypertrophied myocardium of male and female Wistar rats. In all groups of experimental animals, the increase in calcium concentration was followed by a decrease in the myocardium slow response intensity. We revealed a complementary relationship between the current and medium-term systems of myocardial contractility regulation by the length of the myocardium aimed at the maintenance of the constant level during adaptation to the load. Slow responses of the hypertrophied rat heart myocardium were suppressed in comparison with those in the healthy myocardium and their intensity did not depend on animal sex.

https://ift.tt/2m8UP2h

Effect of Metabolic Stress on Lysosomal Proteolysis in the Liver and Brain of Rats Receiving Q10-Enriched Ration

Activation of lysosomal proteolysis and increased coenzyme Q10 level were revealed in the liver and brain of rats with individual typological features under conditions of food deprivation. Changes in cathepsin B activity in these tissues were different in behaviorally active and passive animals. We observed indirect modulating effect of coenzyme Q10 in the regulation of activity of lysosomal endopeptidases in the brain of animals with different behavior during adaptation to metabolic stress.

https://ift.tt/2zvL1ZT

Correlations between Extracellular Matrix Components in Mouse Lungs during Chronic BCG-Induced Granulomatosis

Correlations between extracellular matrix components in mouse lungs were examined during various terms of BCG-induced granulomatosis (on postinfection days 3, 30, 60, 90, and 180). During the development of pathological process, the revealed dynamic interrelations between structural units of proteoglycans and hydroxyproline weakened. Most correlations were observed on postinfection day 180. They reflect the relationships not only between the structural units of proteoglycans but also between collagens, presumably determining the maximum degree of fibrosis at this period. The established correlations characterize the systemic nature of reactions in extracellular matrix and its versatile implications determined by the processes going on in the organs and tissues during the onset and development of generalized pathology.

https://ift.tt/2m868aW

Influence of Low-Intensive Red Light on the Myocardium in Experimental Asphyxia

We studied the effects of low-intensity broadband red light on electrical activity of the heart and oxidative modification of proteins in the myocardium of rats after asphyxia. It was shown that low-intensity red light reduced the content of oxidatively modified proteins in rat heart after oxidative stress caused by asphyxia. Exposure to low-intensity red light normalized ECG parameters in rats after asphyxia.

https://ift.tt/2uqzaGG

Influence of Caffeine Consumption by Pregnant Rats on Behavior and Learning in Their Offspring

We studied the effect of long-term prenatal administration of caffeine on the behavior and learning of rats in postnatal ontogeny. Experiments were carried out on male rats born by females receiving caffeine solution as the only source of fluid throughout gestation. The control group consisted of pups obtained from females receiving drinking water throughout pregnancy. It was found that long-term caffeine intake by female rats during pregnancy determined increased locomotor activity of the offspring. Rat pups born from mothers treated with caffeine during pregnancy faster reached the underwater platform in the Morris maze, i.e. demonstrated better spatial memory formation than control animals.

https://ift.tt/2m8662O

Hypolipidemic and Hepatoprotective Effects of a Polyprenol-Containing Drug in Patients with Acute Coronary Syndrome

In a double-blind placebo-controlled trial POLYNCOR (registration No. NCT03122340 at clinicaltrials.gov), lipid-lowering and hepatoprotective effects of polyprenol-containing drug Ropren were evaluated in patients with acute coronary syndrome. After 2-months therapy, total cholesterol and ALT in the patients receiving Ropren were significantly (p<0.05) lower than in the control group. The number of patients who needed to discontinue or reduce the dose of atorvastatin due to an increase in the level of transaminases in the main group was significantly (p<0.05) lower than in the control group: 0 (0%) vs. 5 (33.3%). The more pronounced decrease in cholesterol level and hepatoprotective effect of Ropren allowed recommending this preparation to patients with acute coronary syndrome in addition to standard therapy.

https://ift.tt/2zvktaS

Individual differences in early body mass affect thermogenic performance and sibling interactions in litter huddles of the house mouse

Developmental Psychobiology, EarlyView.


https://ift.tt/2m85VEG

Syncope: An Atypical Presentation of Pulmonary Embolism Secondary to Occult Uterine Malignancy

All syncopal patients who present to the emergency department should be considered for pulmonary embolism (PE) as part of their differential diagnosis. PE presenting as a syncopal episode and associated with occult uterine malignancy is uncommon. Review of the literature indicates that up to 10% of patients with unprovoked venous thromboembolism (VTE) are diagnosed with cancer in the year following that first episode of VTE. In patients suspected of having a PE who do not manifest any source of an embolism require eventual workup to screen for an occult malignancy. Here, we report a 74-year-old female who presented to the emergency department following an unexplained sudden loss of consciousness and eventually was found to have a massive saddle embolus caused by a uterine malignancy-induced VTE.

https://ift.tt/2um9Xgg

Behind Schedule — Reconciling Federal and State Marijuana Policy

The long-standing chasm between federal and state marijuana policy recently widened when U.S. Attorney General Jeff Sessions rescinded Obama-era guidance indicating that the Justice Department would not make it a priority to prosecute federal marijuana crimes in states where the activities are…

https://ift.tt/2JgFeGT

Fractional-Dose Yellow Fever Vaccination — Advancing the Evidence Base

In 2016, a global shortage of yellow fever vaccine occurred as a result of major yellow fever outbreaks in Angola and the Democratic Republic of Congo (DRC). By October, 7136 cases and 493 deaths were reported in the two countries. Reactive vaccination campaigns were conducted in areas with…

https://ift.tt/2L94As4

Fractional-Dose Yellow Fever Vaccination — Advancing the Evidence Base

In 2016, a global shortage of yellow fever vaccine occurred as a result of major yellow fever outbreaks in Angola and the Democratic Republic of Congo (DRC). By October, 7136 cases and 493 deaths were reported in the two countries. Reactive vaccination campaigns were conducted in areas with…

https://ift.tt/2L94As4

Behind Schedule — Reconciling Federal and State Marijuana Policy

The long-standing chasm between federal and state marijuana policy recently widened when U.S. Attorney General Jeff Sessions rescinded Obama-era guidance indicating that the Justice Department would not make it a priority to prosecute federal marijuana crimes in states where the activities are…

https://ift.tt/2JgFeGT

Life Lessons from Paul in the Face of Death

My brother Paul, a rabbi, died recently, just shy of 3 years after the diagnosis of widely metastatic colon cancer. The story of his diagnosis and treatment is all too familiar. An apparently healthy 64-year-old man has a sudden onset of lower abdominal pain. Imaging reveals an obstructing lesion.…

https://ift.tt/2L2I0oo

Behind Schedule — Reconciling Federal and State Marijuana Policy

The long-standing chasm between federal and state marijuana policy recently widened when U.S. Attorney General Jeff Sessions rescinded Obama-era guidance indicating that the Justice Department would not make it a priority to prosecute federal marijuana crimes in states where the activities are…

https://ift.tt/2JgFeGT

A mathematical model relates intracellular TLR4 oscillations to sepsis progression

Oscillations of physiological parameters describe many biological processes and their modulation is determinant for various pathologies. In sepsis, toll-like receptor 4 (TLR4) is a key sensor for signaling the...

https://ift.tt/2NLCbtJ

Development of a laboratorial platform for diagnosis of schistosomiasis mansoni by PCR-ELISA

We developed a laboratorial platform to release a commercial platform used in the PCR-ELISA for the molecular diagnosis of schistosomiasis mansoni. On following, PCR-ELISA platform laboratorial was evaluated i...

https://ift.tt/2LauDPM

Effects of lyophilization and storage temperature on Wuchereria bancrofti antigen sensitivity and stability

Antigen-based rapid diagnostic tests for Lymphatic filariasis (LF) do not come with external quality control (QC) materials, and research and disease control programmes rely on stored positive samples. This st...

https://ift.tt/2NG58Y6

The Post Clinic Ambulatory Blood Pressure (PC-ABP) study correlates Post Clinic Blood Pressure (PCBP) with the gold standard Ambulatory Blood Pressure

Our previous study showed that post-clinic blood pressure (BP) taken 15 min after a physician–patient encounter was the lowest reading in a routine clinic. We aimed to validate this reading with 24 h Ambulator...

https://ift.tt/2LauDzg

Same old song and dance: an exploratory study of portrayal of physical activity in television programmes aimed at young adolescents

Exposure to health-related behaviours on television has been shown to influence smoking and drinking in young people, but little research has been conducted on the portrayal physical activity. The aim of the c...

https://ift.tt/2NJln6T

Normal breast-derived epithelial cells with luminal and intrinsic subtype-enriched gene expression document inter-individual differences in their differentiation cascade

Cell type origin is one of the factors that determine molecular features of tumors, but resources to validate this concept are scarce because of technical difficulties in propagating major cell types of adult organs. Previous attempts to generate such resources to study breast cancer have yielded predominantly basal-type cell lines. We have created a panel of immortalized cell lines from core breast biopsies of ancestry-mapped healthy women that form ductal structures similar to normal breast in 3D cultures and expressed markers of major cell types including the luminal-differentiated cell-enriched ERα-FOXA1-GATA3 transcription factor network. We have also created cell lines from PROCR (CD201)+/EpCAM- cells that are likely the "normal" counterpart of the claudin-low subtype of breast cancers. RNA-seq and PAM50 intrinsic subtype clustering identified these cell lines as the "normal" counterparts of luminal A, basal, and normal-like subtypes and validated via immunostaining with basal-enriched KRT14 and luminal-enriched KRT19. We further characterized these cell lines by flow cytometry for distribution patterns of stem/basal, luminal-progenitor, mature/differentiated, multi-potent PROCR+ cells, and organogenesis-enriched epithelial/mesenchymal hybrid cells using CD44/CD24, CD49f/EpCAM, CD271/EpCAM, CD201/EpCAM, and ALDEFLUOR assays and E-Cadherin/Vimentin double-staining. These cell lines showed inter-individual heterogeneity in stemness/differentiation capabilities and baseline activity of signaling molecules such as NF-κB, AKT2, pERK, and BRD4. These resources can be used to test the emerging concept that genetic variations in regulatory regions contribute to widespread differences in gene expression in 'normal' conditions among the general population and can delineate the impact of cell type origin on tumor progression.

https://ift.tt/2KOGxmm

ZNF677 suppresses Akt phosphorylation and tumorigenesis in thyroid cancer

The zinc finger protein 677 (ZNF677) belongs to the zinc finger protein family, which possesses transcription factor activity by binding sequence-specific DNA. Previous studies have reported its downregulated by promoter methylation in non-small cell lung cancer (NSCLC). However, its biological role and exact mechanism in human cancers including thyroid cancer remain unknown. In this study, we demonstrate that ZNF677 is frequently downregulated by promoter methylation in primary papillary thyroid cancers (PTC) and show that decreased expression of ZNF677 is significantly associated with poor patient survival. Ectopic expression of ZNF677 in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration, invasion, and tumorigenic potential in nude mice and induced cell cycle arrest and apoptosis. Conversely, knockdown of ZNF677 promoted thyroid cancer cell proliferation and colony formation. ZNF677 exerted its tumor suppressor functions in thyroid cancer cells through transcriptional repression of two targets CDKN3 and HSPB1 (or HSP27), thereby inhibiting phosphorylation and activation of Akt via distinct mechanisms. Taken together, our data show that ZNF677 functions as a tumor suppressor and is frequently silenced via promoter methylation in thyroid cancer.

https://ift.tt/2N8xcT7

Altered cell-cycle control, inflammation and adhesion in high-risk persistent bronchial dysplasia

Persistent bronchial dysplasia (BD) is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive BD would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes (ANOVA, FDR ≤ 0.05). 31 pathways showed significantly altered activity between the two groups, many of which were associated with cell cycle control and proliferation, inflammation, or epithelial differentiation/cell-cell adhesion. Cultured persistent BD cells exhibited increased expression of polo-like kinase 1 (PLK1), which was associated with multiple cell cycle pathways. Treatment with PLK1 inhibitor induced apoptosis and G2/M arrest and decreased proliferation compared to untreated cells; these effects were not seen in normal or regressive BD cultures. Inflammatory pathway activity was decreased in persistent BD, and the presence of an inflammatory infiltrate was more common in regressive BD. Regressive BD were also associated with trends toward overall increases in macrophages and T lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of BD. These results identify alterations in the persistent subset of BD that are associated with high risk for progression to invasive SCC. These alterations may serve as strong markers of risk and as effective targets for lung cancer prevention.

https://ift.tt/2KP13De

USPSTF: Evidence Lacking for ABI for PAD Screen in Asymptomatic

WEDNESDAY, July 11, 2018 -- The U.S. Preventive Services Task Force (USPSTF) concludes that there is currently insufficient evidence to assess the benefits and harms of screening for peripheral artery disease (PAD) with the ankle branchial index...

https://ift.tt/2ukwKKz

USPSTF: Evidence Lacking for Nontraditional CVD Risk Factors

WEDNESDAY, July 11, 2018 -- The U.S. Preventive Services Task Force concludes that there is currently insufficient evidence to assess the benefits and harms of adding nontraditional risk factors to traditional cardiovascular disease (CVD) risk...

https://ift.tt/2zwYHDJ

Taking Multivitamins/Minerals Doesn't Improve CVD Outcomes

WEDNESDAY, July 11, 2018 -- Multivitamin/mineral (MVM) supplementation seems not to be associated with cardiovascular disease (CVD) outcomes, according to a review published online July 10 in Circulation: Cardiovascular Quality and...

https://ift.tt/2ufx9xF

Metformin Tied to Acidosis Risk at eGFR <30mL/min/1.73 m²

WEDNESDAY, July 11, 2018 -- Metformin use is associated with an increased risk of acidosis at estimated glomerular filtration rate (eGFR) <30mL/min/1.73 m², according to a study published in the July issue of JAMA Internal Medicine. Benjamin...

https://ift.tt/2ukBSNM

FDA Requires Safety Label Changes for Fluoroquinolones

WEDNESDAY, July 11, 2018 -- The U.S. Food and Drug Administration has strengthened current warnings in the prescribing information about fluoroquinolone antibiotics causing significant decreases in blood glucose as well as mental health side...

https://ift.tt/2ukwJpZ

8q22.1 Microduplication Syndrome: Why the Brain Should Be Spared? A Literature Review and a Case Report

Microduplication of chromosome 8q22.1 is mainly associated to Leri's pleonosteosis syndrome phenotype, an extremely rare autosomal dominant disease encompassing the GDF6 and SDC2 genes. To date, most of the authors focus their attention only on skeletal symptoms of the disease, and they do not systematically research or describe the co-occurrence of psychiatric illnesses or mental disorders with these muscular-skeletal diseases. In this report, we provide a description of an 8-year-old girl, with a positive family history for both skeletal malformations and bipolar disorders (BD). We suggest a possible association between Leri's pleonosteosis features and psychiatric symptoms. Furthermore, our report could be added to the large amount of reports that describe the correlation between genetic regions and disease risk for both psychiatric and rheumatological disorders.

https://ift.tt/2NIbcPS

Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer’s Disease

Alzheimer's disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.

https://ift.tt/2Jkfaek

Effect of Different Head-Neck Postures on the Respiratory Function in Healthy Males

Normal respiration is a very intricate function that comprises mechanical as well as nonmechanical components. It is shown to be affected by various factors including age, lifestyle, disease, and change in posture. With the increased use of hand held devices, everyone is prone to poor sitting postures like forward head posture. The purpose of this study was to evaluate the effect of assumed forward head posture and torticollis on the diaphragm muscle strength. A sample of 15 healthy males, aged 18-35 years, was recruited for this study. All subjects performed spirometry to measure the forced expiratory volume in 1 second (FEV1), the forced vital capacity (FVC), and FEV1/FVC ratio. SNIP was measured during upright sitting, induced forward head posture, and torticollis. Subject's mean age (SD) was 23(6) years. The SNIP score of the subjects during sitting with FHP was lower as compared to that during upright sitting. It decreased significantly during induced right torticollis position. This is the first study exploring the impact of different head and neck positions on respiratory function. Alteration of head and neck positions had an immediate negative impact on respiratory function. Clinicians should be prompted to assess respiratory function when assessing individuals with mal-posture.

https://ift.tt/2NGYVeJ

Failure Predictor Factors of Conservative Treatment in Pediatric Forearm Fractures

The aim of this study is to evaluate the predictive efficacy of the radiographic parameters and the relationship between the radiographic results and the clinical data. We carried out a retrospective study analyzing the data of 225 pediatric patients with forearm fractures treated conservatively. Two orthopaedists examined 4 different radiographic parameters. They compared CI and radial translation parameters at T0, in terms of indication of type of treatment and predictive efficacy. Afterwards, the two orthopaedists analyzed X-rays performed at T1, evaluating radiographic results according to radial shortening and angle parameters. From the analysis of the CI measured by Observer 1, 135 patients out of 225 had retrospective indication to conservative treatment; the frequency of failure was 18/135 (13.3%). Observer 2 indicated conservative treatment in 144 patients out of 225 and the proportion of failure was 21/144 (14.6%). As regards the radial translation, Observer 1 reported a frequency of failure of 78/225 (34.7%) and Observer 2 reported 75/222 (33.8%). Furthermore the authors detected a deficit of pronosupination for the patients considered to have failure according to radiographic results. The authors defined the greater reliability of CI with respect to the radial translation parameter and the direct relationship between radiographic failure and clinical-functional data.

https://ift.tt/2Jkf5r2

CRP Monitoring in Fractured Neck of Femur. A Waste of Resource?

Publication date: Available online 11 July 2018

Source: Injury

Author(s): Mobeen Qureshi, Ignatius Liew, Oliver Bailey

Abstract

Aim

We aim to assess post-operative CRP serum values in a cohort of patients who underwent surgical treatment for neck of femur fracture (NOF#), and whether CRP is a valid tool for the assessment of these patients post-operatively.

Study Design and Methods

Retrospective analysis was carried out on all NOF#'s admitted for surgical fixation between August 2015 and July 2016 in a district general hospital. Primary analysis included serum CRP levels until day 7 post-operatively, with secondary analysis of any documented evidence of post-operative complications (medical and surgical) within 30 days post-operatively.

Results

A total of 365 patients were surgically treated for NOF#'s over the study period. CRP serum levels peaked over the first two days post-operatively to median (IQ range) of 226 mg/L (158 – 299 mg/L), decreasing to 67 mg/L (45.5 – 104 mg/L) by day 7 post-operatively. 116 patients had documented post-operative complications within 30 daysof operation. CRP levels in patients with and without complications showed no statistical significance in day-1, day-2 and day-3 post-operatively. However, a significant difference was demonstrated on day-4 (p = 0.017), day-5 (p = 0.003), day-6 (p = 0.02) and day-7 (p = 0.031)

Conclusions

During the first three days of the postoperative period we cannot recommend routine CRP serum blood test monitoring in NOF# patients, as it is not diagnostic in the acute inflammatory phase for medical or surgical complications.

https://ift.tt/2L64hl5

Comparison of the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo)

Abstract

Purpose

To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo).

Methods

MoCo PET/DCE-MRI of the upper abdomen was acquired in 44 consecutive oncologic patients and compared with non-MoCo PET/MRI. SUVmax and MTV of FDG-avid upper abdominal malignant lesions were assessed on MoCo and non-MoCo PET images. Image quality was compared between MoCo DCE-MRI and non-MoCo CE-MRI, and between fused MoCo PET/MRI and fused non-MoCo PET/MRI images.

Results

MoCo PET resulted in higher SUVmax (10.8 ± 5.45) than non-MoCo PET (9.62 ± 5.42) and lower MTV (35.55 ± 141.95 cm³) than non-MoCo PET (38.11 ± 198.14 cm³; p < 0.005 for both). The quality of MoCo DCE-MRI images (4.73 ± 0.5) was higher than that of non-MoCo CE-MRI images (4.53±0.71; p = 0.037). The quality of fused MoCo-PET/MRI images (4.96 ± 0.16) was higher than that of fused non-MoCo PET/MRI images (4.39 ± 0.66; p < 0.005).

Conclusion

MoCo PET/MRI provided qualitatively better images than non-MoCo PET/MRI, and upper abdominal malignant lesions demonstrated higher SUVmax and lower MTV on MoCo PET/MRI.

https://ift.tt/2L3KWAY

Antibacterial efficacy of leaf extracts of Combretum album Pers. against some pathogenic bacteria

Plant derived medicines show significant contributions to mankind in treating infections of pathogenic bacteria. Recently plants are used in pharmaceutical industries for novel drug preparations because to ens...

https://ift.tt/2LaTliX

Fractional-Dose Yellow Fever Vaccination — Advancing the Evidence Base

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2L8TDu5

Effect of the use of a national information brochure about foetal movements on patient delay

Publication date: Available online 11 July 2018

Source: Women and Birth

Author(s): Karin J.W.M. Wackers, Martine M.L.H. Wassen, Bert Zeegers, Luc Budé, Marianne J. Nieuwenhuijze

Abstract

Background

Perinatal audits in the Netherlands showed that stillbirth was nearly always preceded by a period of reduced foetal movements. Patient or caregiver delay was identified as a substandard care factor.

Aim

To determine whether the use of a new information brochure for pregnant women on foetal movements results in less patient delay in contacting their maternity caregiver.

Methods

A pre- and post-survey cohort study in the Netherlands, including 140 women in maternity care with a singleton pregnancy, expecting their first child. All participating women filled out a baseline questionnaire, Cambridge Worry Scale and pre-test questionnaire at the gestational age of 22–24 weeks. Subsequently, the intervention group received a newly developed information brochure on foetal movements. At a gestational age of 28 weeks, all women received the post-test questionnaire. Multiple regression analyses were used.

Findings

Per-protocol analysis showed less patient delay in the intervention group compared to the control group (Odds Ratio 0.43; 95% Confidence Interval 0.17–0.86, p = 0.02). A significant linear relation was observed between reading the information brochure and an increase of knowledge about foetal movements (B = 1.2, 95% Confidence Interval 1.0–1.4, p < 0.001). Maternal concerns did not affect patient delay to report reduced foetal movements.

Conclusion

Use of an information brochure regarding foetal movements has the potential to reduce patient delay and increase knowledge about reduced foetal movements. A national survey to determine the effect of an information brochure about reduced foetal movements on patient delay and stillbirth rates is needed.

https://ift.tt/2KOCpCI

Primary invasive laryngeal mycosis in an immunocompetent patient: a case report and clinico-epidemiological update

Laryngeal aspergillosis is uncommon and is usually secondary to pulmonary involvement in immunocompromised patients. Primary laryngeal aspergillosis in immunocompetent individuals is extremely rare, with a few...

https://ift.tt/2N6VVqF

Trend of HIV/AIDS for the last 26 years and predicting achievement of the 90–90-90 HIV prevention targets by 2020 in Ethiopia: a time series analysis

HIV infection continues to be epidemic of public health importance with a prevalence of 1.1% and incidence of 0.33/1000 population having low-intensity mixed epidemic. Ethiopia has adopted the 90–90-90 by 2020...

https://ift.tt/2KPF3Ix

Population-wide administration of single dose rifampicin for leprosy prevention in isolated communities: a three year follow-up feasibility study in Indonesia

Indonesia ranking third in the world, regarding leprosy burden. Chemoprophylaxis is effective in reducing risk of developing leprosy among contacts. 'Blanket approach' is an operational strategy for leprosy po...

https://ift.tt/2NbfGO6

Evidence of rickettsiae in Danish patients tested for Lyme neuroborreliosis: a retrospective study of archival samples

With a prevalence of 4.7–13% in Danish Ixodes ricinus ticks, Rickettsia helvetica is one of the most frequently detected tick-borne organisms in Denmark. Most reports of human exposure have described asymptomatic...

https://ift.tt/2KQdz5p

Relationship between Helicobacter pylori and Rosacea: review and discussion

Rosacea is an inflammatory disease affecting the central part of face characterized by persistent or recurrent episodes of erythema, papules, pustules and telangiectasias of unknown etiology. Helicobacter pylori ...

https://ift.tt/2N6aGKo

Fractional-Dose Yellow Fever Vaccination — Advancing the Evidence Base

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2L8TDu5

Primary small bowel adenomas and adenocarcinomas—recent advances

Abstract

The small intestine represents 75% of the length and 90% of the absorptive surface area of the gastrointestinal tract (GIT), yet only 2% of digestive system cancers occur at this site. Adenocarcinoma accounts for half of small bowel malignancies. There have been a number of important recent advances in our understanding, classification and treatment of small bowel tumours. Over recent years, ampullary tumours have become recognised as a form of small bowel carcinoma, distinct from head of pancreas and lower biliary tract tumours. This is reflected in separate TNM systems and increasing interest in separating intestinal from pancreatobiliary subtypes. The recognition of the importance of microsatellite (MSI) status and the advent of molecular pathology has also changed our approach to these neoplasms.

https://ift.tt/2m7W2aa

https://ift.tt/2ut52dQ

Universal Screening Best Strategy for Hepatitis C in France

WEDNESDAY, July 11, 2018 -- Universal screening is the most effective strategy for hepatitis C virus (HCV) in France, according to a study published online July 1 in the Journal of Hepatology. Sylvie Deuffic-Burban, from the Université Paris...

https://ift.tt/2Jj57G6

Attending Surgeon Influences Genetic Testing in Breast Cancer

WEDNESDAY, July 11, 2018 -- The attending surgeon is associated with variation in the receipt of genetic testing after breast cancer diagnosis, according to a study published online July 3 in JAMA Surgery. Steven J. Katz, M.D., M.P.H., from the...

https://ift.tt/2NGjSGF

Unhealthy Food Behaviors May Signal Eating Disorder in Teen

WEDNESDAY, July 11, 2018 -- Almost 3 percent of teenagers aged 13 to 18 years have food, weight, and body image issues severe enough to constitute an eating disorder, according to a behavioral health resource posted by The Family Institute at...

https://ift.tt/2ND7gjv

CDC: Nearly One-Third of Injury Deaths Occur at Home

WEDNESDAY, July 11, 2018 -- Just under one-third of deaths from all causes of injury occur in the person's home, according to a QuickStats report published in the July 6 issue of the U.S. Centers for Disease Control and Prevention's Morbidity and...

https://ift.tt/2Jfv6yh

Early Introduction of Solids Linked to Better Infant Sleep

WEDNESDAY, July 11, 2018 -- Early introduction of solids is associated with significantly longer sleep and less-frequent waking for infants, according to a study published online July 9 in JAMA Pediatrics. Michael R. Perkin, Ph.D., from the...

https://ift.tt/2NGjEPP

Apixaban Is Safest Direct Oral Anticoagulant Versus Warfarin

WEDNESDAY, July 11, 2018 -- Apixaban seems to be the safest direct oral anticoagulant (DOAC) compared with warfarin, according to a study published July 4 in The BMJ. Yana Vinogradova, Ph.D., from the University of Nottingham in the United Kingdom,...

https://ift.tt/2L9GjlR

EHR Tools Improve Medication Reconciliation in Hypertension

WEDNESDAY, July 11, 2018 -- Use of electronic health record (EHR) tools in isolation improves medication reconciliation but does not improve systolic blood pressure among patients with hypertension, according to a study published online July 9 in...

https://ift.tt/2NGjAj3

Restricting Benefits for Single Moms May Harm Mental Health

WEDNESDAY, July 11, 2018 -- An adverse impact on mental health is seen with reducing the age at which Lone Parent Obligations (LPO) -- which require lone parents in the United Kingdom to seek work as a condition for receiving welfare benefits --...

https://ift.tt/2NMFjG2

Circadian System, Misalignment Have Distinct Impact on Insulin

WEDNESDAY, July 11, 2018 -- The endogenous circadian system, behavioral cycle, and circadian misalignment have distinct effects on insulin sensitivity and β-cell function, according to a study published online June 4 in Diabetes, Obesity and...

https://ift.tt/2L86wkA

Reorganization of Destabilized Nodes of Ranvier in {beta}IV Spectrin Mutants Uncovers Critical Timelines for Nodal Restoration and Prevention of Motor Paresis

Disorganization of nodes of Ranvier is associated with motor and sensory dysfunctions. Mechanisms that allow nodal recovery during pathological processes remain poorly understood. A highly enriched nodal cytoskeletal protein βIV spectrin anchors and stabilizes the nodal complex to actin cytoskeleton. Loss of murine βIV spectrin allows the initial nodal organization, but causes gradual nodal destabilization. Mutations in human βIV spectrin cause auditory neuropathy and impairment in motor coordination. Similar phenotypes are caused by nodal disruption due to demyelination. Here we report on the precise timelines of nodal disorganization and reorganization by following disassembly and reassembly of key nodal proteins in βIV spectrin mice of both sexes before and after βIV spectrin re-expression at specifically chosen developmental time points. We show that the timeline of nodal restoration has different outcomes in the PNS and CNS with respect to nodal reassembly and functional restoration. In the PNS, restoration of nodes occurs within 1 month regardless of the time of βIV spectrin re-expression. In contrast, the CNS nodal reorganization and functional restoration occurs within a critical time window; after that, nodal reorganization diminishes, leading to less efficient motor recovery. We demonstrate that timely restoration of nodes can improve both the functional properties and the ultrastructure of myelinated fibers affected by long-term nodal disorganization. Our studies, which indicate a critical timeline for nodal restoration together with overall motor performance and prolonged life span, further support the idea that nodal restoration is more beneficial if initiated before any axonal damage, which is critically relevant to demyelinating disorders.

SIGNIFICANCE STATEMENT Nodes of Ranvier are integral to efficient and rapid signal transmission along myelinated fibers. Various demyelinating disorders are characterized by destabilization of the nodal molecular complex, accompanied by severe reduction in nerve conduction and the onset of motor and sensory dysfunctions. This study is the first to report in vivo reassembly of destabilized nodes with sequential improvement in overall motor performance. Our study reveals that nodal restoration is achievable before any axonal damage, and that long-term nodal destabilization causes irreversible axonal structural changes that prevent functional restoration. Our studies provide significant insights into timely restoration of nodal domains as a potential therapeutic approach in treatment of demyelinating disorders.

https://ift.tt/2LbvRud

Homeostatic Feedback Modulates the Development of Two-State Patterned Activity in a Model Serotonin Motor Circuit in Caenorhabditis elegans

Neuron activity accompanies synapse formation and maintenance, but how early circuit activity contributes to behavior development is not well understood. Here, we use the Caenorhabditis elegans egg-laying motor circuit as a model to understand how coordinated cell and circuit activity develops and drives a robust two-state behavior in adults. Using calcium imaging in behaving animals, we find the serotonergic hermaphrodite-specific neurons (HSNs) and vulval muscles show rhythmic calcium transients in L4 larvae before eggs are produced. HSN activity in L4 is tonic and lacks the alternating burst-firing/quiescent pattern seen in egg-laying adults. Vulval muscle activity in L4 is initially uncoordinated but becomes synchronous as the anterior and posterior muscle arms meet at HSN synaptic release sites. However, coordinated muscle activity does not require presynaptic HSN input. Using reversible silencing experiments, we show that neuronal and vulval muscle activity in L4 is not required for the onset of adult behavior. Instead, the accumulation of eggs in the adult uterus renders the muscles sensitive to HSN input. Sterilization or acute electrical silencing of the vulval muscles inhibits presynaptic HSN activity and reversal of muscle silencing triggers a homeostatic increase in HSN activity and egg release that maintains ~12–15 eggs in the uterus. Feedback of egg accumulation depends upon the vulval muscle postsynaptic terminus, suggesting that a retrograde signal sustains HSN synaptic activity and egg release. Our results show that egg-laying behavior in C. elegans is driven by a homeostat that scales serotonin motor neuron activity in response to postsynaptic muscle feedback.

SIGNIFICANCE STATEMENT The functional importance of early, spontaneous neuron activity in synapse and circuit development is not well understood. Here, we show in the nematode Caenorhabditis elegans that the serotonergic hermaphrodite-specific neurons (HSNs) and postsynaptic vulval muscles show activity during circuit development, well before the onset of adult behavior. Surprisingly, early activity is not required for circuit development or the onset of adult behavior and the circuit remains unable to drive egg laying until fertilized embryos are deposited into the uterus. Egg accumulation potentiates vulval muscle excitability, but ultimately acts to promote burst firing in the presynaptic HSNs which results in egg laying. Our results suggest that mechanosensory feedback acts at three distinct steps to initiate, sustain, and terminate C. elegans egg-laying circuit activity and behavior.

https://ift.tt/2NFxqBY

{alpha}2{delta}-1 Is Essential for Sympathetic Output and NMDA Receptor Activity Potentiated by Angiotensin II in the Hypothalamus

Both the sympathetic nervous system and the renin-angiotensin system are critically involved in hypertension development. Although angiotensin II (Ang II) stimulates hypothalamic paraventricular nucleus (PVN) neurons to increase sympathetic vasomotor tone, the molecular mechanism mediating this action remains unclear. The glutamate NMDAR in the PVN controls sympathetic outflow in hypertension. In this study, we determined the interaction between α2-1 (encoded by Cacna2d1), commonly known as a Ca²⁺ channel subunit, and NMDARs in the hypothalamus and its role in Ang II-induced synaptic NMDAR activity in PVN presympathetic neurons. Coimmunoprecipitation assays showed that α2-1 interacted with the NMDAR in the hypothalamus of male rats and humans (both sexes). Ang II increased the prevalence of synaptic α2-1–NMDAR complexes in the hypothalamus. Also, Ang II increased presynaptic and postsynaptic NMDAR activity via AT1 receptors, and such effects were abolished either by treatment with pregabalin, an inhibitory α2-1 ligand, or by interrupting the α2-1–NMDAR interaction with an α2-1 C terminus-interfering peptide. In Cacna2d1 knock-out mice (both sexes), Ang II failed to affect the presynaptic and postsynaptic NMDAR activity of PVN neurons. In addition, the α2-1 C terminus-interfering peptide blocked the sympathoexcitatory response to microinjection of Ang II into the PVN. Our findings indicate that Ang II augments sympathetic vasomotor tone and excitatory glutamatergic input to PVN presympathetic neurons by stimulating α2-1-bound NMDARs at synapses. This information extends our understanding of the molecular basis for the interaction between the sympathetic nervous and renin-angiotensin systems and suggests new strategies for treating neurogenic hypertension.

SIGNIFICANCE STATEMENT Although both the sympathetic nervous system and renin-angiotensin system are closely involved in hypertension development, the molecular mechanisms mediating this involvement remain unclear. We showed that α2-1, previously known as a calcium channel subunit, interacts with NMDARs in the hypothalamus of rodents and humans. Angiotensin II (Ang II) increases the synaptic expression level of α2-1–NMDAR complexes. Furthermore, inhibiting α2-1, interrupting the α2-1–NMDAR interaction, or deleting α2-1 abolishes the potentiating effects of Ang II on presynaptic and postsynaptic NMDAR activity in the hypothalamus. In addition, the sympathoexcitatory response to Ang II depends on α2-1-bound NMDARs. Thus, α2-1–NMDAR complexes in the hypothalamus serve as an important molecular substrate for the interaction between the sympathetic nervous system and the renin-angiotensin system. This evidence suggests that α2-1 may be a useful target for the treatment neurogenic hypertension.

https://ift.tt/2NMlYEW

EMCrit RACC 228 – Physiology-Guided Cardiac Arrest Management in 2018 with Dr. Robert Sutton

Physiology-Guided Cardiac Arrest Management in 2018 with Dr. Robert Sutton

EMCrit Project by Scott Weingart.

https://ift.tt/2ub2txl

Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons

The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDC+), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO. We further characterized GABAergic neurons electrophysiologically in the VLPO (GABA^VLPO neurons) that make direct synaptic contact with these hypothalamic arousal-related neurons. These neurons (GABA^VLPO->HDC or GABA^VLPO->orexin neurons) were both potently inhibited by noradrenaline and serotonin, showing typical electrophysiological characteristics of sleep-promoting neurons in the VLPO. This work provides direct evidence of monosynaptic connectivity between GABA^VLPO neurons and hypothalamic arousal neurons and identifies the effects of monoamines on these neuronal pathways.

SIGNIFICANCE STATEMENT Rabies-virus-mediated tracing of input neurons of two hypothalamic arousal-related neuron populations, histaminergic and orexinergic neurons, showed that they receive similar distributions of input neurons in a variety of brain areas, with rich innervation by GABAergic neurons in the preoptic area, including the ventrolateral preoptic area (VLPO), a region known to play an important role in the initiation and maintenance of sleep. Electrophysiological experiments found that GABAergic neurons in the VLPO (GABA^VLPO neurons) that make direct input to orexin or histaminergic neurons are potently inhibited by noradrenaline and serotonin, suggesting that these monoamines disinhibit histamine and orexin neurons. This work demonstrated functional and structural interactions between GABA^VLPO neurons and hypothalamic arousal-related neurons.

https://ift.tt/2Jf31qG

Brain Circuits Mediating Opposing Effects on Emotion and Pain

The amygdala is important for processing emotion, including negative emotion such as anxiety and depression induced by chronic pain. Although remarkable progress has been achieved in recent years on amygdala regulation of both negative (fear) and positive (reward) behavioral responses, our current understanding is still limited regarding how the amygdala processes and integrates these negative and positive emotion responses within the amygdala circuits. In this study with optogenetic stimulation of specific brain circuits, we investigated how amygdala circuits regulate negative and positive emotion behaviors, using pain as an emotional assay in male rats. We report here that activation of the excitatory pathway from the parabrachial nucleus (PBN) that relays peripheral pain signals to the central nucleus of amygdala (CeA) is sufficient to cause behaviors of negative emotion including anxiety, depression, and aversion in normal rats. In strong contrast, activation of the excitatory pathway from basolateral amygdala (BLA) that conveys processed corticolimbic signals to CeA dramatically opposes these behaviors of negative emotion, reducing anxiety and depression, and induces behavior of reward. Surprisingly, activating the PBN–CeA pathway to simulate pain signals does not change pain sensitivity itself, but activating the BLA–CeA pathway inhibits basal and sensitized pain. These findings demonstrate that the pain signal conveyed through the PBN–CeA pathway is sufficient to drive negative emotion and that the corticolimbic signal via the BLA–CeA pathway counteracts the negative emotion, suggesting a top-down brain mechanism for cognitive control of negative emotion under stressful environmental conditions such as pain.

SIGNIFICANCE STATEMENT It remains unclear how the amygdala circuits integrate both negative and positive emotional responses and the brain circuits that link peripheral pain to negative emotion are largely unknown. Using optogenetic stimulation, this study shows that the excitatory projection from the parabrachial nucleus to the central nucleus of amygdala (CeA) is sufficient to drive behaviors of negative emotion including anxiety, depression, and aversion in rats. Conversely, activation of the excitatory projection from basolateral amygdala to CeA counteracts each of these behaviors of negative emotion. Thus, this study identifies a brain pathway that mediates pain-driven negative emotion and a brain pathway that counteracts these emotion behaviors in a top-down mechanism for brain control of negative emotion.

https://ift.tt/2Jex2qI

Dominant Neuropeptide Cotransmission in Kisspeptin-GABA Regulation of GnRH Neuron Firing Driving Ovulation

A population of kisspeptin-GABA coexpressing neurons located in the rostral periventricular area of the third ventricle (RP3V) is believed to activate gonadotropin-releasing hormone (GnRH) neurons to generate the luteinizing hormone (LH) surge triggering ovulation. Selective optogenetic activation of RP3V kisspeptin (RP3V^KISS) neurons in female mice for >30 s and ≥10 Hz in either a continuous or bursting mode was found to reliably generate a delayed and long-lasting activation of GnRH neuron firing in brain slices. Optogenetic activation of RP3V^KISS neurons in vivo at 10 Hz generated substantial increments in LH secretion of similar amplitude to the endogenous LH surge. Studies using GABA_A receptor antagonists and optogenetic activation of RP3V GABA (RP3V^GABA) neurons in vitro revealed that low-frequency (2 Hz) stimulation generated immediate and transient GABA_A receptor-mediated increases in GnRH neuron firing, whereas higher frequencies (10 Hz) recruited the long-lasting activation observed following RP3V^KISS neuron stimulation. In vivo, 2 Hz activation of RP3V^GABA neurons did not alter LH secretion, whereas 10 Hz stimulation evoked a sustained large increase in LH identical to RP3V^KISS neuron activation. Optogenetic activation of RP3V^KISS neurons in which kisspeptin had been deleted did not alter LH secretion. These studies demonstrate the presence of parallel transmission streams from RP3V neurons to GnRH neurons that are frequency dependent and temporally distinct. This comprises a rapid and transient GABA_A receptor-mediated activation and a slower onset kisspeptin-mediated stimulation of long duration. At the time of the LH surge, GABA release appears to be functionally redundant with the neuropeptide kisspeptin being the dominant cotransmitter influencing GnRH neuron output.

SIGNIFICANCE STATEMENT Miscommunication between the brain and ovaries is thought to represent a major cause of infertility in humans. Studies in rodents suggest that a population of neurons located in the rostral periventricular area of the third ventricle (RP3V) are critical for activating the gonadotropin-releasing hormone (GnRH) neurons that trigger ovulation. The present study provides evidence that an RP3V neuron population coexpressing kisspeptin and GABA provides a functionally important excitatory input to GnRH neurons at the time of ovulation. This neural input releases GABA and/or kisspeptin in the classical frequency dependent and temporally distinct nature of amino acid-neuropeptide cotransmission. Unusually, however, the neuropeptide stream is found to be functionally dominant in activating GnRH neurons at the time of ovulation.

https://ift.tt/2La78q1

Comparison of Decision-Related Signals in Sensory and Motor Preparatory Responses of Neurons in Area LIP

Neurons in the lateral intraparietal (LIP) area of Macaques exhibit both sensory and oculomotor preparatory responses. During perceptual decision making, the preparatory responses have been shown to track the state of the evolving evidence leading to the decision. The sensory responses are known to reflect categorical properties of visual stimuli, but it is not known whether these responses also track evolving evidence. We recorded neural responses from lateral intraparietal area of 2 female rhesus monkeys during a direction discrimination task. We compared sensory and oculomotor-preparatory responses in the same neurons when either the discriminandum (random dot motion) or an eye movement choice-target was in the neuron's response field. The neural responses in both configurations reflected the strength and direction of motion and were correlated with the animal's choice, albeit more prominently when the choice-target was in the response field. However, the variance and autocorrelation pattern of only the motor preparatory responses reflected the process of evidence accumulation. Simulations suggest that the task related activity of sensory responses could be inherited through lateral interactions with neurons that are carrying evidence accumulation signals in their motor-preparatory responses. The results are consistent with the proposal that evolving decision processes are supported by persistent neural activity in the service of actions or intentions, as opposed to high-order representations of stimulus properties.

SIGNIFICANCE STATEMENT Perceptual decision making is the process of choosing an appropriate motor action based on perceived sensory information. Association areas of the cortex play an important role in this sensory-motor transformation. The neurons in these areas show both sensory- and motor-related activity. We show here that, in the macaque parietal association area LIP, signatures of the process of evidence accumulation that underlies the decisions are predominantly reflected in the motor-related activity. This finding supports the proposal that perceptual decision making is implemented in the brain as a process of choosing between available motor actions rather than as a process of representing the properties of the sensory stimulus.

https://ift.tt/2NJiXVV

Anterior Thalamic Excitation and Feedforward Inhibition of Presubicular Neurons Projecting to Medial Entorhinal Cortex

The presubiculum contains head direction cells that are crucial for spatial orientation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei. Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin-expressing interneurons are directly and monosynaptically activated, with depressing dynamics, whereas somatostatin-expressing interneurons are indirectly excited, during repetitive anterior thalamic nuclei activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feedforward inhibition is largely mediated by parvalbumin interneurons, which have a high probability of connection to presubicular pyramidal cells, and it may enforce temporally precise head direction tuning during head turns. Our data point to the potential contribution of presubicular microcircuits for fine-tuning thalamic head direction signals transmitted to medial entorhinal cortex.

SIGNIFICANCE STATEMENT How microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei excite layer 3 pyramidal cells and parvalbumin interneurons, which mediate disynaptic feedforward inhibition. Somatostatin interneurons are excited indirectly. Presubicular circuits may switch between two regimens depending on the angular velocity of head movements. During immobility, somatostatin-pyramidal cell interactions could support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, parvalbumin-mediated feedforward inhibition may act to tune the head direction signal transmitted to medial entorhinal cortex.

https://ift.tt/2NJLIBK

Prophylactic angiographic embolisation in high-risk peptic ulcer bleeding after achieved endoscopic control: maximising outcomes

We read with great interest the article by Lau et al recently published in Gut and evaluating the role of prophylactic angiographic arterial embolisation performed after achieved endoscopic haemostasis in the management of patients with high-risk ulcer bleeding.1 We have several comments. First of all, we would like to congratulate the authors for their study which represents the largest multicentre randomised controlled trial to date reporting results of additional embolisation in selected high-risk patients with peptic ulcer bleeding. The authors' hypothesis was that added angiographic embolisation performed within 12 hours from successful endoscopic therapy may reduce the rate of rebleeding in patients with bleeding from high-risk peptic ulcers. Unfortunately, the authors failed to demonstrate any statistically significant impact of added embolisation on outcomes of these patients, as a consequence of lack of power. Indeed, of 118 patients randomised to receive added angiographic embolisation, 22 (18.6%) did not undergo allocated...

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Microenvironmental derived factors modulating dendritic cell function and vaccine efficacy: the effect of prostanoid receptor and nuclear receptor ligands

Abstract

Dendritic cells (DCs) are widely used in DC-based immunotherapies because of their capacity to steer immune responses. So far treatment success is limited and more functional knowledge on how DCs initiate and stably drive specific responses is needed. Many intrinsic and extrinsic factors contribute to how DCs skew the immune response towards immunity or tolerance. The origin and type of DC, its maturation status, but also factors they encounter in the in vitro or in vivo microenvironment they reside in during differentiation and maturation affect this balance. Treatment success of DC vaccines will, therefore, also depend on the presence of these factors during the process of vaccination. Identification and further knowledge of natural and pharmacological compounds that modulate DC differentiation and function towards a specific response may help to improve current DC-based immunotherapies. This review focuses on factors that could improve the efficacy of DC vaccines in (pre-)clinical studies to enhance DC-based immunotherapy, with a particular emphasis on compounds acting on prostanoid or nuclear receptor families.

https://ift.tt/2NJ67XK

Effectiveness and Safety of Compound Chinese Medicine plus Routine Western Medicine in In-Stent Restenosis: A Meta-Analysis and Systematic Review

Objective. To examine the effects and safety of oral compound Chinese medicine (CCM) plus routine western medicine (RWM) in in-stent restenosis (ISR). Methods. Various electronic databases (CBM, CNKI, VIP, Wanfang, PubMed, EMBASE, and Cochrane Library) were searched until April 2017. The quality of the included studies was evaluated, and meta-analyses were performed using RevMan5.3 and STATA 12.0 software. Moreover, funnel plot and Egger's publication bias plots were analysed to identify publication bias and adverse reactions were reported. A sensitive analysis was carried out according to the quality score. Results. In all, 40 RCTs involving 4536 patients were selected for this review. The pooled estimates of three studies showed that the benefit to the number of ISRs (NoR) was more substantial for CCM plus RWM than for RWM alone (RR 0.24, 95% CI 0.10 to 0.57, , ). The rate of ISR was significantly lower for CCM plus RWM than for the same RWM alone (RR 0.44, 95% CI 0.37 to 0.53, ; , ). CCM plus RWM benefitted the rate of ISR when a CM placebo plus RWM was used as the control intervention (RR 0.34, 95% CI 0.20 to 0.57, ; , ). The difference of adverse reactions was not significant. For secondary outcomes, the CCM plus RWM group did not reduce the rates of revascularization and cardiac death, but it did reduce the rate of recurrent angina over the results observed in the RWM alone group. In addition, funnel plot and Egger's publication bias plot indicated that there was publication bias. The association between the use of CCM plus RWM and RWM alone remained significant after the sensitivity analysis excluding studies with low quality score (quality score ⩽ 4) with a pooled RR of 0.41 (95% CI, 0.34–0.50). Conclusion. Oral CCM plus RWM clearly benefitted patients with percutaneous coronary intervention (PCI) because it prevented and treated ISR better than was observed for either RWM alone or a CM placebo plus RWM.

https://ift.tt/2JcdEe4

Comparative Studies of Different Extracts from Eucommia ulmoides Oliv. against Rheumatoid Arthritis in CIA Rats

To compare efficacy of different extracts from Eucommia ulmoides Oliv. with both immune inflammation and joint destruction in collagen induced arthritis (CIA) rat model. Rats were divided into normal group (Nor), control group (CIA), TG group (treated with tripterygium glycoside), E70 group (treated with 70% ethanol extract from Eucommia ulmoides Oliv.), EA group (treated with ethyl acetate fraction from E70), and EN group (treated with n-butyl alcohol fraction from E70). All extracts from Eucommia ulmoides Oliv. could significantly inhibit ankle swelling, pathological manifestations, and cytokine levels in serum and spleen, by using foot volume measurement, H&E staining, ELISA, and RT-QPCR methods, respectively. All extracts could significantly inhibit rough joint surface and marginal osteophytes, improve RANKL/OPG ratio, and decrease MMP-9 expression, by using micro-CT and immunohistochemical staining. The activation of IKK/NF-κB signaling pathway was also inhibited by all extracts. In addition, ethyl acetate fraction from E70 presented better effect on RANKL/OPG system. This study identified effective extracts from Eucommia ulmoides Oliv. relieving immune inflammation and maintaining structural integrity of joints in CIA rats.

https://ift.tt/2NHrZTi

Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons

Abstract

α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory. It also increased extracellular amyloid-β oligomers (AβOs), αSyn oligomers, exacerbated tau conformational and phosphorylation variants associated with AD, and enhanced neuronal cell cycle re-entry (CCR), a frequent prelude to neuron death in AD. Conversely, ablation of the SNCA gene encoding for αSyn in APP mice improved memory retention in spite of increased plaque burden. Reminiscent of the effect of MAPT ablation in APP mice, SNCA deletion prevented premature mortality. Moreover, the absence of αSyn decreased extracellular AβOs, ameliorated CCR, and rescued postsynaptic marker deficits. In summary, this complementary, bidirectional genetic approach implicates αSyn as an essential mediator of key phenotypes in AD and offers new functional insight into αSyn pathophysiology.

https://ift.tt/2L5EeHs

Microenvironmental derived factors modulating dendritic cell function and vaccine efficacy: the effect of prostanoid receptor and nuclear receptor ligands

Abstract

Dendritic cells (DCs) are widely used in DC-based immunotherapies because of their capacity to steer immune responses. So far treatment success is limited and more functional knowledge on how DCs initiate and stably drive specific responses is needed. Many intrinsic and extrinsic factors contribute to how DCs skew the immune response towards immunity or tolerance. The origin and type of DC, its maturation status, but also factors they encounter in the in vitro or in vivo microenvironment they reside in during differentiation and maturation affect this balance. Treatment success of DC vaccines will, therefore, also depend on the presence of these factors during the process of vaccination. Identification and further knowledge of natural and pharmacological compounds that modulate DC differentiation and function towards a specific response may help to improve current DC-based immunotherapies. This review focuses on factors that could improve the efficacy of DC vaccines in (pre-)clinical studies to enhance DC-based immunotherapy, with a particular emphasis on compounds acting on prostanoid or nuclear receptor families.

https://ift.tt/2NJ67XK

223 Ra-Dichloride in castration-resistant metastatic prostate cancer: improving outcomes and identifying predictors of survival in clinical practice

Abstract

Purpose

We first assessed whether the pattern of referrals to a nuclear medicine clinic improved as experience with ²²³Ra-dichloride increased, and whether referral patterns affected patient outcomes, and second assessed the value of bone scintigraphy, total alkaline phosphatase (tALP) and lymphadenopathy as prognostic factors in patients receiving ²²³Ra-dichloride.

Methods

A total of 57 patients eligible to receive ²²³Ra-dichloride over a 2-year period (March 2014 to March 2016) were retrospectively assessed and prospectively followed (median follow up 298 days). ²²³Ra-Dichloride was administered at 4-week intervals for a maximum of six injections. The numbers of patients in years 1 and 2 referred in relation to extent of bone disease (EOBD) category and overall survival (OS) were determined. The prognostic factors EOBD category, baseline tALP (tALP_BL), tALP response, greatest percentage reduction in tALP from baseline in any treatment cycle (ALP_max; among patients with elevated ALP_BL), and the presence of lymphadenopathy were assessed as predictors of OS.

Results

The proportion of patients with EOBD1 was higher in year 2 than in year 1 (29% and 4%, respectively), and in year 2 there was a lower rate of symptomatic skeleton-related events, a higher proportion of patients completing six cycles, and longer (albeit nonsignificant) OS (p = 0.55). There were significant differences in OS between EOBD4 patients and those in all other groups and between EOBD1 and EOBD3 patients (p < 0.05). OS was longer in patients with normal tALP_BL than in those with elevated tALP_BL (p = 0.01), in ALP responders than in nonresponders (p < 0.05), and in patients without lymphadenopathy than in those with lymphadenopathy (p = 0.29). OS was correlated with ALP_max (r² = 0.24).

Conclusion

A collaborative multidisciplinary referrals pathway, together with increased experience with ²²³Ra-dichloride, led to improved outcomes. In patients with elevated tALP_BL, tALP dynamics may be useful for monitoring response and predicting OS. Imaging and prognostic markers may therefore be of value for individualizing ²²³Ra-dichloride treatment and planning retreatment; however, further studies are required.

https://ift.tt/2uaHFGq

Understanding adjuvant endocrine therapy persistence in breast Cancer survivors

Abstract

Background

Adjuvant endocrine therapy (AET) significantly decreases the risk of breast cancer recurrence and mortality. Notwithstanding the demonstrated efficacy of AET, 31–73% of breast cancer survivors do not persist with AET. The purpose of this study was to explore breast cancer survivors' experiences and perspectives of persisting with AET and to identify the psychosocial and healthcare system factors that influence AET persistence.

Methods

Informed by interpretive descriptive methodology and relational autonomy theory, individual interviews were conducted with 22 women diagnosed with early-stage breast cancer who had been prescribed AET. These participants also completed a demographic form and a survey that assessed their perceived risk of recurrence. Interviews were analysed using inductive thematic and constant comparative analysis to iteratively compare data and develop conceptualizations of the relationships among data. Descriptive statistics were used to summarize the quantitative data.

Results

The personal, social, and structural factors found to influence AET persistence included AET side effects, perception of breast cancer recurrence risk, medication and necessity beliefs, social support, the patient-provider relationship, and the continuity and frequency of follow-up care. For most women, over time, the decision-making process around AET persistence became a balancing act between quality of life and quantity of life. The interplay between the personal, social, and structural factors was complex and the weight women placed on some factors over others influenced their AET persistence or non-persistence.

Conclusion

Expanding our understanding of the factors affecting breast cancer survivors' AET persistence from their perspective is the first step in developing efficacious, patient-centered interventions aimed at improving AET persistence. In order to improve AET persistence, enhanced symptom management is required, as well as the development of supportive care strategies that acknowledge the values and beliefs held by breast cancer survivors while reinforcing the benefits of AET, and addressing women's reasons for non-persistence. Improved continuity of health care and patient-healthcare provider communication across oncology and primary care settings is also required. The development and evaluation of supportive care strategies that address the challenges associated with AET experienced by breast cancer survivors hold the potential to increase both women's quality and quantity of life.

https://ift.tt/2ub1GNb

Six natural ways to whiten teeth

Teeth inevitably begin to yellow with age, but a range of strategies can slow the process and even reverse it. In this article, learn how to whiten teeth naturally at home using baking soda, oil pulling, hydrogen peroxide, and other techniques. We also look at which strategies to avoid to prevent damage to the teeth.

https://ift.tt/2N31lmH

Quality indicators of clinical cancer care for prostate cancer: a population-based study in southern Switzerland

Abstract

Background

Quality of cancer care (QoCC) has become an important item for providers, regulators and purchasers of care worldwide. Aim of this study is to present the results of some evidence-based quality indicators (QI) for prostate cancer (PC) at the population-based level and to compare the outcomes with data available in the literature.

Methods

The study included all PC diagnosed on a three years period analysis (01.01.2011–31.12.2013) in the population of Canton Ticino (Southern Switzerland) extracted from the Ticino Cancer Registry database. 13 QI, approved through the validated Delphi methodology, were calculated using the "available case" approach: 2 for diagnosis, 4 for pathology, 6 for treatment and 1 for outcome. The selection of the computed QI was based on the availability of medical documentation. QI are presented as proportion (%) with the corresponding 95% confidence interval.

Results

700 PC were detected during the three-year period 2011–2013: 78.3% of them were diagnosed through a prostatic biopsy and for 72.5% 8 or more biopsy cores were taken. 46.5% of the low risk PC patients underwent active surveillance, while 69.2% of high risk PC underwent a radical treatment (radical prostatectomy, radiotherapy or brachytherapy) and 73.5% of patients with metastatic PC were treated with hormonal therapy. The overall 30-day postoperative mortality was 0.5%.

Conclusions

Results emerging from this study on the QoCC for PC in Canton Ticino are encouraging: the choice of treatment modalities seems to respect the international guidelines and our results are comparable to the scarce number of available international studies. Additional national and international standardisation of the QI and further QI population-based studies are needed in order to get a real picture of the PC diagnostic-therapeutic process progress through the definition of thresholds of minimal standard of care.

https://ift.tt/2udr9FD

BET Bromodomain inhibition promotes De-repression of TXNIP and activation of ASK1-MAPK pathway in acute myeloid leukemia

Abstract

Background

Targeted therapy has always been the focus in developing therapeutic approaches in cancer, especially in the treatment of acute myeloid leukemia (AML). A new small molecular inhibitor, JQ1, targeting BRD4, which recognizes the acetylated lysine residues, has been shown to induce cell cycle arrest in different cancers by inhibiting MYC oncogene. However, the downstream signaling of MYC inhibition induced by BET inhibitor is not well understood.

Methods

In this study, we explored the more mechanisms of JQ1-induced cell death in acute myeloid lukemia and downstream signaling of JQ1.

Results

We found that JQ1 is able to reactivate the tumor suppressor gene, TXNIP, and induces apoptosis through the ASK1-MAPK pathway. Further studies confirmed that MYC could repress the expression of TXNIP through the miR-17-92 cluster.

Conclusions

These findings provide novel insight on how BET inhibitor can induce apoptosis in AML, and further support the development of BET inhibitors as a promising therapeutic strategy against AML.

https://ift.tt/2zsRowK

Feasibility of stereotactic radiotherapy for lung lesions and conventional radiotherapy for nodal areas in primary lung malignancies

Abstract

Background

Combined stereotactic body radiotherapy (SBRT) for lung lesions and conventional radiotherapy (CRT) for nodal areas may be more effective than CRT alone in patients with locally advanced lung cancer.

Methods

This study included 21 patients with small primary lung tumors distant from the regional nodal areas. The SBRT dose was 40–60 Gy in 4 fractions. CRT doses were 66 Gy in 30 fractions for non-small cell lung cancer and 52.5 Gy in 25 fractions for small cell lung cancer.

Results

The median follow-up duration was 12 months, and the median survival was 13 months. The 1 year overall survival, local recurrence-free survival, and distant metastasis-free survival rates were 60.5, 84.8, and 62.1%, respectively. Two patients experienced in-field local recurrence combined with out-field regional recurrence and/or distant failure. The major recurrence pattern was distant failure (crude incidence, 43%). Three patients aged ≥79 years experienced grade ≥ 3 acute radiation pneumonitis, and one also had idiopathic interstitial pneumonia.

Conclusion

The combination of SBRT for the lung lesion and CRT for the nodal region seems to be effective and safe for lung malignancies. However, patients older in age and/or with underlying pulmonary disease require stricter lung dose constraints.

https://ift.tt/2udCXaO