Long term rehabilitation management and outcome of anti-NMDA receptor encephalitis: case reports.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an auto immune-disorder. It is a life threatening condition that typically presents with viral illness, headaches, severe psychiatric symptoms, seizures, behavioural changes, decreasing levels of unconsciousness and progressive unresponsiveness, cognitive impairment, abnormal movements (e.g., dyskinesia), ataxia and hypoventilation. This paper describes the long term outcome and rehabilitation management of patients with NMDAR encephalitis and highlights the diverse outcome of this condition and the unique and individual long term management needs associated with this disorder. This is a case report study of three different patients with NMDAR encephalitis. All three cases are young women, two of whom presented with ovarian teratoma. Patient KH is the most impaired and was resident in a slow stream rehabilitation care home and presented with challenging behaviour. Patients RM and OA both lived in the community and presented with similar anxieties but diverse levels of cognition and motivation. A review of the literature is provided summarizing the disorder, interventions, management and challenges of this varied and complex condition. Standard neuropsychological tests and questionnaires to assess community integration (BICRO-39), quality of life (QOLIBRI-OS) and mood (HADS) were administered. Positive outcomes were achieved for all three patients using a variety of interventions which included behavioural management, family psycho-education and an integrated holistic multi-disciplinary team community approach. Memory and executive deficits were persistent in the long term and severity of impairments showed wide variability between patients. Emotional distress and behavioural difficulties were prominent and persistent and had a pronounced impact on rehabilitation. Continence issues were also a major factor impacting on the rehabilitation. Long term integrated and multi-disciplinary input by a variety of therapies and health disciplines is required in order to improve the long term outcome and quality of life for NMDAR patients and their families, and ultimately leads to improved positive outcomes. Each of these cases had markedly differing cognitive profiles suggesting that in the context of long term rehabilitation outcome, cognition may have less valence than emotional and behavioural factors. Guidelines and standardised procedures for ethical issues and counselling for iatrogenic infertility should be developed and integrated into long term programmes of rehabilitation care.


Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.
Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons.


A systematic approach to document cyclotide distribution in plant species from genomic, transcriptomic, and peptidomic analysis.
Cyclotides are a large family of plant peptides characterized by their cyclic cystine knot composed of a circular backbone and three disulfide bonds that impart exceptional stability. They, and several acyclic variants, have been isolated from plants within the Rubiaceae, Violaceae, Cucurbitaceae, Fabaceae, Solanaceae, and Poaceae families. A variety of chemical and genetic approaches have been applied for the discovery and characterization of cyclotides. As investigations of cyclotide expression, distribution, and phylogeny rapidly increase, the authors have proposed the inclusion of information pertaining to plant species that have been analyzed but do not appear to express cyclotides into the CyBase database. CyBase is dedicated to providing web tools and information about cyclic peptides and proteins to the scientific community. Including detailed information about sampling and analysis parameters of plant species that have been investigated but not published elsewhere should assist in the process of selecting species for establishing new cyclotide discovery projects, as well as for detailed reanalysis using alternative technical approaches. In summary, the collection and deposition of all plant species that have been examined (whether cyclotides have been found or not) would help to impart a deeper understanding of cyclotide discovery, evolution, and physiological function.


[Studies on functions of neutrophils in MPO-ANCA related glomerulonephiritis and plasma effect on MPO release from neutrophils].
In order to examine the role of myeloperoxidase (MPO) and neutrophil activation in the pathogenesis of MPO-ANCA related necrotizing crescentic glomerulonephritis (GN), we investigated MPO release and superoxide anion (O-2) production from the neutrophils in MPO ANCA related GN. Plasma effect on MPO release from neutrophils was also studied in MPO-ANCA related GN. Neutrophils and plasma were obtained from 10 patients with MPO-ANCA-related GN (A), 10 patients with MPO-ANCA non related GN (B) and 10 healthy controls (C). MPO release and O-2 production were assayed by using chemotactic factor, N-formyl-methionyl-leucyl-phenyalanine (FMLP) and cytochalasin B (CB). In MPO-ANCA related GN, MPO release and O-2 production were significantly higher than in the other groups. [MPO release (%) A: 43.02 +/- 18.33, B: 33.26 +/- 11.58, C: 19.73 +/- 8.38, sensitivity to FMLP (%) A: 894.56 +/- 381.96, B: 512.86 +/- 314.91, C: 301.12 +/- 139.8, O-2 production (nmoles/min/10(6) cells) A: 13.06 +/- 5.28, B: 3.57 +/- 2.02, C: 2.83 +/- 1.16] Furthermore, MPO release, sensitivity to FMLP and O-2 production were shown to increase in parallel with clinical disease activity. Plasma from MPO-ANCA related GN increased sensitivity to FMLP in neutrophils obtained from healthy controls [plasma concentration 1%, A: 311.5 +/- 110.3, B: 227.2 +/- 101.4, C: 215.5 +/- 93.7], and plasma from MPO-ANCA related GN suppressed %MPO release from neutrophils with MPO-ANCA related GN [plasma concentration 0.1%, A: 11.56 +/- 6.17, C: 15.51 +/- 8.01]. It was concluded that in patients with MPO-ANCA related GN, large amounts of MPO can be easily released from activated neutrophils and this might be influenced by some stimulating and suppressing factors contained in the plasma.


New directions in hospital governance.
This article suggests new directions for hospital governance to meet the demands of a rapidly changing health care environment. Board members must increasingly play roles as risk takers, strategic directors, experts, mentors, and evaluators. Lessons from other industries regarding risk taking, use of expertise, and streamlining decision making must be adapted to meet hospital needs. Recent data suggest that these needs may still differ by hospital ownership despite a convergence in investor-owned and not-for-profit corporate structures. The effectiveness of hospital boards in the future will depend on their ability to: (1) manage a diverse group of stakeholders; (2) involve physicians in the management and governance process; (3) meet the governance needs of multi-institutional systems and hospital restructuring; (4) meet the challenges of diversification and vertical integration; and (5) understand strategy formulation and implementation as interdependent and interrelated processes.


Increasing values of serum acid phosphatase in a child with Mycoplasma pneumoniae-associated hemophagocytic histiocytic syndrome.
We describe a 3 1/2-year-old boy with disseminated histiocytic disease probably induced by Mycoplasma pneumoniae. In this patient, acid phosphatase was elevated in serum and was also detected histochemically in the infiltrating histiocytes. The serum acid phosphatase levels increased as his histiocytosis progressed, apparently mirroring the activity of the disease. This observation suggests that serum acid phosphatase levels should be evaluated further to determine whether they will be a useful indicator of disease in children with different histiocytosis syndromes.


[Experimental study of cartilage reconstruction using directed inducing MSCs-alginate complex].
To evaluate the practicability of cartilage reconstruction using directed inducing bone marrow stem cells(MSCs)- alginate complex. The MSCs were seperated by gradient centrifugation on Percoll, then were induced into chon-drogenic differentiation. After 14 days,immunohistochemical techique was applied to detect the expression of collagen type II. Then, the MSCs and calcium alginate were mixed to form a complex and were planted under the skin of nude mice. Histochemical or immuno-histochemical tests were made at 4 weeks and 8 weeks later. The MSCs showed the positive result of collagen type II. There were chondrcytes and cartilage lacuna at 4 weeks later, and chondrocytes and the collagen secreted by them became more at 8 weeks later. But, the MSCs without directed inducing did not show the character of the chondrocyte. The way of using directed inducing MSCs-alginate complex can form cartilage; it is possible to repair the defect of cartilage in clinical practice.


Effect of bone density on the survival of 407 sandblasted and acid-etched dental implants: A retrospective multicenter study.
This study evaluated the success and survival rate of sandblasted and acid-etched dental implants according to the patient's bone quality. A multicenter retrospective study was conducted in five clinical centers between 2016 and March 2019. A total of 407 implants (KONTACTTM S, Biotech Dental, France) placed in 229 patients (61.5±12.9 years old) were included. Bone quality, classified as types D1 to D4 (Misch classification), maximal insertion torque, and bone loss were measured. The implant survival rate was evaluated after one year for the overall cohort and for each bone quality. The overall survival rate after four years was also estimated with a Kaplan-Meier analysis. After one year (12.8±9.6 months), eight implants were lost out of 407, representing an overall survival rate of 98%. It ranged from 100% for D1 to 89.7% for D4 (n=39), with significantly higher survival rates for D2 (n=93) and D3 (n=165) (98.9% and 98.2%, respectively) compared to D4. According to the Kaplan-Meier analysis, an overall survival rate of 96.5% was estimated after four years. An average maximal insertion torque of 45±12.6 N.cm and bone loss of 0.2±1.2 mm were measured. The high overall survival rate (98%), the average maximal insertion torque (45 N.cm), and the low marginal bone loss indicated good clinical results with acid-etched implants. Despite the relatively high survival rate for each bone quality, the significantly lower results in the D4 group highlight the expected benefits of bone quality-based implants and surgical protocols.


A Shift in Thinking: Cellular Thermal Shift Assay-Enabled Drug Discovery.
A decade has passed since the cellular thermal shift assay (CETSA) was introduced to the drug discovery community. Over the years, the method has guided numerous projects by providing insights about, for example, target engagement, lead generation, target identification, lead optimization, and preclinical profiling. With this Microperspective, we intend to highlight recently published applications of CETSA and how the data generated can enable efficient decision-making and prioritization throughout the drug discovery and development value chain.


Significance of liquid biopsy in glioblastoma - A review.
Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor with a 16-24 -months overall survival time (OS). Effective management is hindered by intratumoral heterogeneity, a characteristic trait of GBM which results in subpopulations of cells with altered therapeutic responsiveness, different invasiveness and growth potential. Correct initial molecular profiling of the tumor, as well as following its molecular biological changes are further impeded by the intracranial location of the tumors, hence the risks of surgical interventions. Radiological examination, the sole non-invasive method of obtaining information about the tumors, also has limitations. This review article aims to summarize the currently available information about the promising applicability of liquid biopsy, extracellular vesicles (EVs), and circulating cell-free nucleic acids (cf-NAs) in GBM patients. Liquid biopsy is a quick and inexpensive way of obtaining exceptionally relevant information about tumors, and can be performed multiple times during the clinical course of the disease. Furthermore, integrating analyses of EVs and related cf-NAs in clinical practice might also help to establish diagnosis in a non-invasive manner, and complex oncotherapy could be indicated in the future without high-risk neurosurgical interventions.


The embryonic development of the lateral nasal wall from 8 to 24 weeks.
This histological study of 20 fetal heads aged between 8 and 24 weeks of gestation demonstrates and describes the embryonic development of the lateral wall of the nose. The three turbinates (inferior, middle, and superior) arise as soft-tissue swellings (preturbinates) by 8 weeks' gestation. A cartilage capsule surrounds the nose at 8 weeks and by 9 weeks, medially directed flanges of cartilage have invaded all three preturbinates. The uncinate process arises from the medial surface of the lateral cartilaginous capsule and is first identifiable by 10 weeks. An "air space" progressively develops from 11 to 12 weeks lateral to the cartilaginous uncinate process and from this space, the embryonic channel to the maxillary sinus develops. The embryonic woven bone of the maxilla can be identified from 9 to 10 weeks and enlarges both absolutely and relatively to the nasal cavity, so that by 13 to 14 weeks, this expanding bone forms the lateral wall of the inferior meatus as the cartilaginous nasal capsule regresses.


Dietary high vanadium causes oxidative damage-induced renal and hepatic toxicity in broilers.
The purpose of this study was to investigate the renal and hepatic oxidative damage and toxicity caused by dietary high vanadium in broilers. A total of 420 one-day-old avian broilers were divided into six groups and fed on a corn-soybean basal diet as control diet (vanadium 0.073 mg/kg), and five high vanadium diets (vanadium 5 mg/kg, high vanadium group I; 15 mg/kg, high vanadium group II; 30 mg/kg, high vanadium group III; 45 mg/kg, high vanadium group IV; and 60 mg/kg, high vanadium group V) throughout the experimental period of 42 days. The results showed that the renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, ability to inhibit hydroxy radical, and malondialdehyde (MDA), glutathione, and vanadium contents were not significantly changed in high vanadium group I and II when compared with those of the control groups. However, the SOD and GSH-Px activities, ability to inhibit hydroxy radical, and GSH content were significantly decreased, and the MDA and vanadium contents were markedly increased in high vanadium groups III, IV, and V. At the same time, the lesions were also observed in the kidney and liver of high vanadium groups III, IV, and V. The renal tubular epithelial cells showed granular degeneration and vacuolar degeneration, and hepatocytes showed granular degeneration, vacuolar degeneration, and fatty degeneration. It was concluded that dietary vanadium in the range of 30-60 mg/kg could cause oxidative damage and vanadium accumulation, which induced renal and hepatic toxicity and lesions. The renal and hepatic function was finally impaired in boilers.


Who participates in child sexual abuse research?
This paper stems from a prospective case control study of the effects of child sexual abuse and explores issues of sampling bias resulting from non-participation in research. Despite similarities in family demographics and in the level of abuse experienced, differences between the study participants and non-participants emerged. The more dysfunctional families were less likely to participate, the research was not a passive experience for the families and finally, non-participants were offered less therapy following clinical assessment. The implications of these differences for the main prospective study will be explored.


Benign giant-cell tumor of bone with pulmonary metastases: clinical findings and radiologic appearance of metastases in 13 cases.
Tumors that metastasize are considered "malignant" by definition. However, benign giant-cell tumor of bone is an exception because of the potential for histologically benign pulmonary metastases, a fact seldom emphasized in the radiologic literature. We therefore report our experience with 13 cases of pulmonary metastasis among 475 patients (prevalence, 3%) in whom benign giant-cell tumor of bone was diagnosed before 1990 at our institution. Five (38%) of the 13 primary bone tumors were located in the distal radius. Local recurrence at the site of the primary bone tumor tumor occurred in seven patients (54%) before pulmonary metastases developed. The mean interval from the diagnosis of the primary bone tumor to the onset of pulmonary metastasis was 3.8 years, with a maximum of 10.7 years. Fifty-four percent of the patients (7/13) had pulmonary metastases 3 years after diagnosis of the primary bone lesion, and 92% (12/13) had pulmonary metastases 7.5 years after diagnosis. Overall mortality rate directly due to giant-cell tumor and its metastases was 23%. On chest radiographs and CT scans, pulmonary metastases appeared as rounded, nodular opacities of homogeneous density, ranging from 0.5 cm to 8.0 cm in diameter. Peripheral regions of the lungs were involved in 85% of the cases and basilar regions in 62%. Our study shows that benign giant-cell tumor of bone can produce pulmonary metastases, that metastases most often occurred with recurrent local disease and distal radial lesions, that the prognosis was relatively favorable, and that such metastases had no distinguishing radiologic features.


A comparative study in the post-operative spine surgeries: Epidural ropivacaine with dexmedetomidine and ropivacaine with clonidine for post-operative analgesia.
Anaesthesia for spine surgeries is not only concerned with relieving pain during surgeries but also during the post-operative period. A prospective randomised study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to ropivacaine, in epidural analgesia with special emphasis on their quality of analgesia and the ability to provide the smooth post-operative course. A total of 60 subjects, 33 were men and 27 were women between the age of 18 and 65 years of American Society of Anaesthesiologists (ASA) I/II class who underwent spine surgeries were randomly allocated into two groups, ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC), comprising 30 patients each. Group RD received 20 ml of 0.2% ropivacaine and 1 μg/kg of dexmedetomidine while group RC received 20 ml of 0.2% ropivacaine and 2 μg/kg of clonidine through the epidural catheter. Onset of analgesia, time of peak effect, duration of analgesia, cardiorespiratory parameters, side-effects and need of rescue intravenous (IV) analgesics were observed. The demographic profile and ASA class were comparable between the groups. None of the patients needed rescue analgesics in either group. Group RD had early onset, early peak effect, prolonged duration and stable cardiorespiratory parameters when compared with group RC. The side-effects profile was also comparable with a little higher incidence of nausea and dry mouth in both groups. Epidural route provided acceptable analgesia in spine surgeries and avoided the need of IV analgesics in either group. Dexmedetomidine is a better neuraxial adjuvant compared with clonidine for providing early onset and prolonged post-operative analgesia and stable cardiorespiratory parameters.


NAC domain function and transcriptional control of a secondary cell wall master switch.
NAC domain transcription factors act as master switches for secondary cell wall thickening, but how they exert their function and how their expression is regulated remains unclear. Here we identify a loss-of-function point mutation in the NST1 gene of Medicago truncatula. The nst1-3 mutant shows no lignification in interfascicular fibers, as previously seen in tnt1 transposon insertion alleles. However, the C→A transversion, which causes a T94K mutation in the NST1 protein, leads to increased NST1 expression. Introduction of the same mutation into the Arabidopsis homolog SND1 causes both protein mislocalization and loss of target DNA binding, with a resultant inability to trans-activate downstream secondary wall synthesis genes. Furthermore, trans-activation assays show that the expression of SND1 operates under positive feedback control from itself, and SND1 was shown to bind directly to a conserved motif in its own promoter, located within a recently described 19-bp secondary wall NAC binding element. Three MYB transcription factors downstream of SND1, one of which is directly regulated by SND1, exert negative regulation on SND1 promoter activity. Our results identify a conserved amino acid critical for NST1/SND1 function, and show that the expression of the NAC master switch itself is under both positive (autoregulatory) and negative control.


Pseudomonas keratitis complicated with spontaneous expulsive suprachoroidal hemorrhage: A case report.
Spontaneous expulsive suprachoroidal hemorrhage (SESCH) is a rare condition. The correlation between SESCH and chronic glaucoma has been reported previously. However, few reports have indicated a correlation between infective keratitis and SESCHs. Here, we report the case of an 82-year-old woman with a corneal ulcer who presented with left eye pain for 6 days. We found that she has Pseudomonas keratitis and history of chronic glaucoma. During admission, her left eye showed elevated intraocular pressure (IOP). Three days later, the eyeball began to bleed and became painful. She had high blood pressure on that day. Hours after complaints of eye pain, intraocular tissue exposure related to eyeball rupture, and SESCH. The patient underwent evisceration and insertion of a silicone ball for the socket reconstruction. Histopathological evaluation revealed acute inflammation of the cornea and the choroidal vessels. In elderly patients with infective keratitis and a history of glaucoma and hypertension, it is important to control intraocular pressure and blood pressure and pay attention to the risk of spontaneous expulsive suprachoroidal hemorrhage.


Amino Acid Oxidation: A Combined Study of Cysteine Oxo Forms by IRMPD Spectroscopy and Simulations.
The redox activity of cysteine sulfur allows numerous post-translational protein modifications involved in the oxidative regulation of metabolism, in metal binding, and in signal transduction. A combined approach based on infrared multiple photon dissociation spectroscopy at the Centre Laser Infrarouge d'Orsay (CLIO) free electron laser facility, calculations of IR frequencies, and finite temperature ab initio molecular dynamics simulations has been employed to characterize the gas-phase structures of deprotonated cysteine sulfenic, sulfinic, and sulfonic acids, [cysSOx ]- (x=1, 2, 3, representing the number of S-bound oxygen atoms), which are key intermediates in the redox-switching chemistry of proteins. The ions show different structural motifs owing to preferential binding of the proton to either the carboxylate or sulfur-containing group. Due to the decreasing basicity of the sulfenic, sulfinic, and sulfonic terminals, the proton bound to SO- in [cysSO]- migrates to the carboxylate in [cysSO3 ]- , whereas it turns out to be shared in [cysSO2 ]- . Evidence is gathered that a mixture of close-lying low-energy conformers is sampled for each cysteine oxo form in a Paul ion trap at room temperature.


Nutritional status of maintenance hemodialysis patients.
Fat and fat-free tissues were determined in hemodialysis patients using either anthropometric measurements or indirectly from total body water (TBW) determined from urea kinetics. A very close correlation between the two methods in determining either fat or fat-free tissue (r greater than 0.8, n = 43) was shown. Twenty-two patients were followed for 2 yr. We found that fat increased while fat-free tissue decreased over that period of time. The latter appears to reflect methodological problems since both fat-free determinations depend upon TBW rather than somatic proteins. This was further confirmed by finding a proportional decrease in TBW with time, while creatinine appearance rate remained unaffected. Adherence to prescribed diet was monitored through diet records and periodic determination of urea N appearance rate during interdialysis periods. Our present studies determined body composition of hemodialysis patients and examined the relative validity of the commonly used methods. We demonstrate that no malnutrition occurs with time in patients adhering to their prescribed diet.


Angiosarcoma of the Right Atrium with Extension to SVC and IVC Presenting with Complete Heart Block and Significant Pericardial Effusion.
Primary cardiac neoplasms are particularly unusual. Angiosarcoma is the most frequently seen histological subtype and is described by its infiltrating and damaging nature. Inappropriately, primary cardiac angiosarcoma is often missed as a preliminary diagnosis because of its scarcity. We present a 29-year-old previously healthy man with complete heart block and pericardial effusion who was finally diagnosed with angiosarcoma of the right atrium with extension to SVC and IVC.


Combination of factor Xa inhibition and antiplatelet therapy after stenting in patients with iliofemoral post-thrombotic venous obstruction.
Studies addressing optimal postprocedural pharmacological management after endovascular stenting of iliofemoral post-thrombotic venous obstruction are lacking. We report our early clinical experience with a combination of rivaroxaban and clopidogrel in patients after iliofemoral post-thrombotic venous obstruction stenting. Demographic, procedural, and follow-up data of nine patients (seven women; mean age of 32 ± 11 years) undergoing 10 procedures for iliofemoral post-thrombotic venous obstruction performed between August 2012 and January 2014 were retrospectively reviewed. After endovascular intervention, all patients were administered 20 mg rivaroxaban once daily (s.i.d.) and 75 mg clopidogrel s.i.d. or every second day depending on the individual drug responsiveness for at least six months. The adenosine diphosphate-induced platelet aggregation (platelet aggregation, in aggregation units × min) was assessed on a Multiplate analyzer. Patency was verified venographically at procedure end and was evaluated with duplex ultrasound in regular follow-ups. Iliofemoral venous flow was successfully re-established by percutaneous endovascular angioplasty and stent implantation in nine left-sided and one bilateral iliofemoral post-thrombotic venous obstruction. Under dual treatment strategy of rivaroxaban and clopidogrel with platelet aggregation control (median (range): 285 aggregation units × min (192; 402)), none of the patients experienced restenosis or stent thrombosis, respectively. After a median follow-up of 14 months (range: 6-26 months), the primary patency rate was 100% and no in-stent restenosis, stent occlusion or relevant minor or major bleeding occurred. Combined factor Xa inhibition and tailored antiplatelet therapy after stenting of iliofemoral post-thrombotic venous obstruction were safe and performed favorably in terms of vessel patency.


Diet and dementia.
The ageing brain adapts to the accumulation of damage caused by oxidative stress and inflammation. Adaptive processes include neuroprotective and neurorestorative mechanisms. Individual differences in susceptibility to dementia arise when these mechanisms are impaired or are overwhelmed by the molecular pathology of Alzheimer's disease. Neuroprotection relies upon extrinsic and intrinsic defences. An adequate intake of antioxidant micronutrients (eg, vitamin C and vitamin E) and anti-inflammatory macronutrients (eg, omega-3 polyunsaturated fatty acids) forms an essential component of extrinsic defences against brain ageing. There are many epidemiological data to support an association between an inadequate intake of antioxidants and/or fish oils (an important source of omega-3 polyunsaturated fatty acids) and a greater than expected incidence of late onset dementia. These associations are confounded by established links between poverty, poor diet and failing health, especially in old age. Such links may be sufficient to explain some of the effects of an inadequate diet on the retention of cognitive function and increased risk of dementia in old age. More compelling is the association between increased plasma homocysteine concentration and later increased risk of dementia. This association is possibly caused by an inadequate intake of vitamin B(12)/folate.


67Ga citrate versus 99mTc-labeled LL2-Fab' (anti-CD22) fragments in the staging of B-cell non-Hodgkin's lymphoma.
The value of 67Ga citrate scanning as a transferrin receptor agent was compared in this study with a 99mTc-labeled anti-CD22 (B-cell) Fab' fragment (LL2) in patients with low- and high-grade B-cell non-Hodgkin's lymphoma (NHL). Thirteen patients with histologically confirmed NHL were examined prospectively with both radiopharmaceuticals within 8 days. The results of immunoscintigraphy were compared with those of 67Ga scanning and the clinical and radiological workup (computed tomography, ultrasound, and magnetic resonance imaging) of the patients. The overall sensitivity of 67Ga citrate and 99mTc-labeled LL2 fragment was each 80% in a total of 43 lesions. Low-grade lymphoma patients had a higher sensitivity in LL2 imaging (82% versus 71%), and high-grade lymphoma patients in 67Ga citrate scanning (100% versus 75%). The target:background ratio in low-grade NHL for LL2 was 1.43 +/- 0.3:1 versus 1.8 +/- 0.5:1 in 67Ga scans; in high-grade NHL, 1.49 +/- 0.35:1 versus 2.2 +/- 0.8:1, respectively. Single-photon emission computed tomography imaging was necessary in 21.7% of the patients 4 h after injection to localize the lesions. In conclusion, the overall sensitivity of 99mTc-labeled LL2 is comparable to 67Ga citrate scanning in patients with B-cell NHL. 99mTc-labeled LL2 antibodies are rapid to use, are safe, and need a shorter imaging time (24 h versus 72 h). Because of these advantages, 99mTc-labeled LL2 may be superior to 67Ga scanning for the staging of lymphoma patients.


Surgical site infection following spinal instrumentation for scoliosis: a multicenter analysis of rates, risk factors, and pathogens.
Surgical site infection following correction of pediatric scoliosis is well described. However, we are aware of no recent multicenter study describing the rates of surgical site infection, and associated pathogens, among patients with different etiologies for scoliosis. A multicenter, retrospective review of surgical site infections among pediatric patients undergoing spinal instrumentation to correct scoliosis was performed at three children's hospitals in the United States. Study subjects included all patients undergoing posterior spinal instrumentation from January 2006 to December 2008. Surgical site infections were defined according to the Centers for Disease Control and Prevention's National Healthcare Safety Network case definition, with infections occurring within one year after surgery. Following the analysis of 1347 procedures performed in 946 patients, surgical site infection rates varied among procedures performed in patients with different scoliosis etiologies. Procedures performed in patients with neuromuscular scoliosis had the highest surgical site infection rates (9.2%), followed by those performed in patients with syndromic scoliosis (8.8%), those performed in patients with other scoliosis (8.4%), those performed in patients with congenital scoliosis (3.9%), and those performed in patients with idiopathic scoliosis (2.6%). Surgical site infection rates varied among procedures in patients undergoing primary spinal arthrodesis based on etiology, ranging from 1.2% (95% confidence interval, 0.1% to 1.3%) in patients with idiopathic scoliosis to 13.1% (95% confidence interval, 8.4% to 17.8%) in patients with neuromuscular scoliosis. Surgical site infection rates following primary and revision procedures were similar among patients with different etiologies. In distraction-based growing constructs, rates were significantly lower for lengthening procedures than for revision procedures (p = 0.012). Multivariate analysis demonstrated that non-idiopathic scoliosis and extension of instrumentation to the pelvis were risk factors for surgical site infections. The three most common pathogens were Staphylococcus aureus (25.0% [95% confidence interval, 17.8% to 32.2%]), coagulase-negative staphylococci (17.1% [95% confidence interval, 10.9% to 23.3%]), and Pseudomonas aeruginosa (10.7% [95% confidence interval, 5.6% to 15.8%]). Overall, 46.5% (95% confidence interval, 35.5% to 57.5%) of surgical site infections contained at least one gram-negative organism; 97.0% (95% confidence interval, 90.8% to 100.0%) of these infections were in patients with non-idiopathic scoliosis. Surgical site infection rates were significantly higher following procedures in patients with non-idiopathic scoliosis (p < 0.001). Lengthening procedures had the lowest rate of surgical site infection among patients with early onset scoliosis who had undergone instrumentation with growing constructs. Gram-negative pathogens were common and were most common following procedures in patients with non-idiopathic scoliosis. These findings suggest a role for targeted perioperative antibiotic prophylaxis to prevent surgical site infection following pediatric scoliosis instrumentation procedures.


Plasma homocysteine and parental myocardial infarction in young adults in Jerusalem.
A causal role for mildly elevated plasma homocysteine (tHcy) in cardiovascular disease remains undetermined. To address the unresolved issue of the antecedent-consequent directionality of the relationship, we assessed the familial association of tHcy with parental myocardial infarction (MI) in young Israeli men and women. We also compared tHcy concentrations in Jerusalem, where rates of coronary heart disease (CHD) are high, with the United States Third National Health and Examination Survey (NHANES III). A total of 8646 17-year-olds and 6952 parents were examined from 1976 to 1979 in Jerusalem. At ages 28 to 32 years, offspring of parents who experienced a documented MI during a 10-year follow-up (n=133 men, 62 women; 72% response) and offspring of CHD-free parents (n=389 men, 208 women; 71% response) were reexamined. tHcy levels were determined by the same laboratory for the NHANES non-Hispanic white population aged 25 to 34 years (n=379) and the Jerusalem population sample (n=858). Men from Jerusalem, but not women, had clearly higher tHcy levels than the sample from the United States (90th percentile, 23 versus 14 micromol/L). This difference was largely attributable to lower plasma vitamin B12 levels in the Israeli population. Male case offspring had higher adjusted tHcy than did controls (1.9 micromol/L, P=0.002). Logistic modeling revealed a graded increase in risk of parental MI across quintiles of offspring tHcy, with an adjusted odds ratio of 2.7 in the 5th quintile (P=0.0026 for trend). The higher tHcy in young male offspring of parents with CHD suggests that elevated tHcy precedes manifestation of CHD. The elevated population tHcy in men may contribute to the high incidence of CHD in Israel.


The Binding Mode to Orthosteric Sites and/or Exosites Underlies the Therapeutic Potential of Drugs Targeting Cannabinoid CB2 Receptors.
The classical terms agonists and antagonists for G protein coupled receptors (GPCRs) have often become misleading. Even the biased agonism concept does not describe all the possibilities already demonstrated for GPCRs. The cannabinoid CB2 receptor (CB2R) emerged as a promising target for a variety of diseases. Reasons for such huge potential are centered around the way drugs sit in the orthosteric and/or exosites of the receptor. On the one hand, a given drug in a specific CB2R conformation leads to a signaling cascade that differs qualitatively and/or quantitatively from that triggered by another drug. On the other hand, a given drug may lead to different signaling outputs in two different tissues (or cell contexts) in which the conformation of the receptor is affected by allosteric effects derived from interactions with other proteins or with membrane lipids. This highlights the pharmacological complexity of this receptor and the need to further unravel the binding mode of CB2R ligands in order to fine-tune signaling effects and therapeutic propositions.


Streptococcus group A pneumonia in an intravenous drug misuser (IVDM).
Streptococcus pyogenes appears to have become an uncommon cause of pneumonia. In view of the recent increase in S. pyogenes infections this situation is likely to change. An intravenous drug user presented with acute onset of fever and chills. At presentation pleuritic chest pain was a prominent symptom, and later he developed pulmonary abscesses and an empyema. The patient had a good response to benzyl penicillin, and his pulmonary lesions resolved completely. Although his clinical picture was characteristic of S. pyogenes pneumonia, it could easily be mistaken for Staphylococcus aureus septicaemia.


Exocrine pancreatic insufficiency is common in people living with HIV on effective antiretroviral therapy.
The primary aim of this prospective study was to determine the prevalence of exocrine pancreatic insufficiency (EPI) in people living with HIV (PLHIV) on suppressive antiretroviral therapy (ART). PLHIV ≥18 years of age and on ART for >6 months and with HIV RNA <50 copies/mL plasma were included. Faecal elastase-1 measurement was performed on a single stool sample, serum markers of malnutrition were collected, and participants answered a short questionnaire about gastrointestinal symptoms. Participants with EPI and symptoms were offered pancreatic enzyme replacement therapy (PERT), and the result of this therapy was also evaluated. Of 100 participants, 32% had EPI (faecal elastase-1 < 200 μg/g) and 20% severe EPI (faecal elastase-1 < 100 μg/g). We did not find any correlation between self-reported symptoms and degree of EPI. Twelve out of the 32 participants with EPI accepted to start PERT. Nine out of 12 (75%) reported improvement or became asymptomatic within 14 days. EPI is common in PLHIV on effective ART. We could, however, not find a correlation between gastrointestinal symptoms and the presence of EPI. Assessment of pancreatic exocrine function could be considered in PLHIV particularly in those with gastrointestinal discomfort, since there is a possible gain in treating them with relief of symptoms and improved quality of life. The effects of PERT in PLHIV on effective ART need further study.


Impact of the Femtosecond Laser in Line with the Femtosecond Laser-Assisted Cataract Surgery (FLACS) on the Anterior Chamber Characteristics in Comparison to the Manual Phacoemulsification.
To assess the alterations of the anterior chamber conditions including laser flare photometry after femtosecond laser-assisted cataract surgery (FLACS) compared to the manual phacoemulsification. Data of n=70 FLACS (mean age 67.2 ± 8.9 years) and n=40 manual phacoemulsification (mean age 69.5 ± 9.6 years) were analyzed. The procedures were performed by LenSx Alcon, USA, and Alcon Infiniti Vision System, USA. The following parameters were recorded: laser flare photometry (Kowa FM 700, Japan), anterior chamber (AC) depth, AC volume, AC angle (Pentacam, Oculus Inc., Germany), lens density, pupil diameter, endothelial cell count and pachymetry. The analysis was performed preoperatively, immediately after femtosecond laser procedure and one day postoperatively. Between FLACS and the phaco control group, there was a significant difference in the AC depth (p=0.023, 3.77 mm vs. 4.05 mm) one day postoperatively. The AC angle (p=0.016) showed a significant difference immediately after the femto laser treatment. The central and thinnest pachymetry and endothelial cell count did not show a significant difference between the two study cohorts (p=0.165, p=0.291, p=0.979). The phaco cohort (n=40) demonstrated a non-statistically significant difference in the flare photometry of 15.80 photons/ms one postoperative day compared to the FLACS group 26.62 photons/ms (p=0.322). In this study population, no evidence for an additive damage caused by the use of the femtosecond laser was demonstrated. Furthermore, no increase in the central and thinnest corneal thickness and no increased endothelial cell loss was demonstrated by the laser energy.


T-cell stimulation through the T-cell receptor/CD3 complex regulates CD2 lateral mobility by a calcium/calmodulin-dependent mechanism.
T lymphocyte activation through the T cell receptor (TCR)/CD3 complex alters the avidity of the cell surface adhesion receptor CD2 for its ligand CD58. Based on the observations that activation-associated increases in intracellular [Ca2+] ([Ca2+]i) strengthen interactions between T cells and antigen-presenting cells, and that the lateral mobility of cell surface adhesion receptors is an important regulator of cellular adhesion strength, we postulated that [Ca2+]i controls CD2 lateral mobility at the T cell surface. Human Jurkat T leukemia cells were stimulated by antibody-mediated cross-linking of the TCR/CD3 complex. CD2 was labeled with a fluorescently conjugated monoclonal antibody. Quantitative fluorescence microscopy techniques were used to measure [Ca2+]i and CD2 lateral mobility. Cross-linking of the TCR/CD3 complex caused an immediate increase in [Ca2+]i and, 10-20 min later, a decrease in the fractional mobility of CD2 from the control value of 68 +/- 1% to 45 +/- 2% (mean +/- SEM). One to two hours after cell stimulation the fractional mobility spontaneously returned to the control level. Under these and other treatment conditions, the fraction of cells with significantly elevated [Ca2+]i was highly correlated with the fraction of cells manifesting significantly reduced CD2 mobility. Pretreatment of cells with a calmodulin inhibitor or a calmodulin-dependent kinase inhibitor prevented Ca2+-mediated CD2 immobilization, and pretreatment of cells with a calcineurin phosphatase inhibitor prevented the spontaneous reversal of CD2 immobilization. These data suggest that T cell activation through the TCR/CD3 complex controls CD2 lateral mobility by a Ca2+/calmodulin-dependent mechanism, and that this mechanism may involve regulated phosphorylation and dephosphorylation of CD2 or a closely associated protein.


A locked derivative of 8-aza-7-deazaadenosine.
The title compound [systematic name: (1S,3S,4R,7S)-3-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-hydroxymethyl-2,5-dioxabicyclo[2.2.1]heptan-7-ol], C(11)H(13)N(5)O(4), belongs to a family of nucleosides with modifications in both the sugar and nucleobase moieties: these modifications are known to increase the thermodynamic stability of DNA and RNA duplexes. There are two symmetry-independent molecules in the asymmetric unit that differ significantly in conformation, and both exhibit a high-anti conformation about the N-glycosidic bond, with chi torsion angles of -85.4 (3) and -87.4 (3) degrees . The sugar C atom attached to the nucleobase N atom is -0.201 (4) and 0.209 (4) A from the 8-aza-7-deazaadenine skeleton plane in the two molecules. The molecules are assembled into layers via hydrogen bonds and pi-pi stacking interactions between the modified nucleobases.


Identification of β integrin-like- and fibronectin-like proteins in the bivalve mollusk Mytilus trossulus.
Integrins play a key role in the intermediation and coordination between cells and extracellular matrix components. In this study, we first determined the presence of the β integrin-like protein and its presumptive ligand, fibronectin-like protein, during development and in some adult tissues of the bivalve mollusc Mytilus trossulus. We found that β integrin-like protein expression correlated with the development and differentiation of the digestive system in larvae. Besides the presence of β integrin-like protein in the digestive epithelial larval cells, this protein was detected in the hemocytes and some adult tissues of M. trossulus. The fibronectin-like protein was detected firstly at the blastula stage and later, the FN-LP-immunoreactive cells were scattered in the trochophore larvae. The fibronectin-like protein was not expressed in the β integrin-positive cells of either the veliger stage larvae or the adult mussel tissues and the primary hemocyte cell culture. Despite the β integrin- and fibronectin-like proteins being expressed in different cell types of mussel larvae, we do not exclude the possibility of direct interaction between these two proteins during M. trossulus development or in adult tissues.


[Various diagnostic problems in CAT in cerebral vascular lesions].
Findings TAC are shown in some cases of vascular cerebral lesions. It is emphasized the patognomonic value in the cerebral hemorrhagy. In the cerebral hischemy TAC findings mass correlate for any case to neurologic, angiographic, Doppler findings. It is emphasized the evolution of the sintomatology. Then, it is shown the transitory fenomen of "fogging" who cause the TAC false negative findings.


Paucity of dorsal inspiratory neuron collateral projections to ventral inspiratory neurons.
The inspiratory region of the ventral respiratory group was mapped in six Nembutal anaesthetized cats. Records multi-unit activity were taken in five or six locations at 0.5 mm spacings. These locations were then used as stimulating sites to test for the antidromic activation of 40 bulbospinal, inspiratory neurons recorded in the ipsilateral, dorsal respiratory group. Only four (10%) were antidromically activated. In a single anatomical experiment, rhodamine labelled microspheres were injected into the ventral group, and Flurogold was injected into the contralateral spinal cord. No neurons in the dorsal group were found to be double-stained. It was concluded that, ipsilateral collaterals from inspiratory dorsal group neurons to the inspiratory region of the ventral group are rare.


[Effects of 9,10-dihydroxysteatic acid on glucose metabolism in KKAy mice].
To study the effect of 9,10-dihydroxystearic acid (DHSA) on glucose tolerance and insulin sensitivity in KKAy diabetic mice. 48 male KKAy mice were randomly divided into four groups and were fed with high fat diet containing 4% DHSA, 2% DHSA, 4% Olive oil and 4% Corn oil, respectively. Glucose tolerance and insulin sensitivity were measured after 5 and 6 weeks respectively. Effects of DHSA on activating PPAR-alpha and PPAR-gamma in CV-1 cells were also carried out. In glucose tolerance test, the blood glucose at 0.5 h and 1 h and the area under glucose curve in the group fed with 4% DHSA diet were significantly lower than those of other groups. In insulin sensitivity test, the blood glucose level at 0.5 h and 1 h after injection of insulin was lower in the 4% DHSA diet group, indicating the insulin sensitivity of this group was obviously higher than other groups (P < 0.05). The body weight of the mice fed with 4% DHSA diet was much lower than those mice fed with 4% Corn diet (P < 0.05). 5 - 20 micromol/L DHSA did not activate PPAR-gamma in CV-1 cells but 50 - 100 micromol/L DHSA activated PPARgamma in a dose-dependent way although the activating effect of DHSA on PPARgamma was significantly lower than that of rosiglitazone. DHSA did not activate PPAR-alpha in CV-1 cells. DHSA may improve glucose tolerance and insulin sensitivity in KKAy mice and the effect might be related to the activation of PPAR-gamma by DHSA.


Pentose oxidation by acetic acid bacteria led to a finding of membrane-bound purine nucleosidase.
D-Ribose and 2-deoxy-D-ribose were oxidized to 4-keto-D-ribonate and 2-deoxy-4-keto-D-ribonate respectively by oxidative fermentation, and the chemical structures of the oxidation products were confirmed to be as expected. Both pentoses are important sugar components of nucleic acids. When examined, purine nucleosidase activity predominated in the membrane fraction of acetic acid bacteria. This is perhaps the first finding of membrane-bound purine nucleosidase.


Direct acting antivirals for the treatment of chronic hepatitis C: one pill a day for tomorrow.
Chronic hepatitis C is one of the leading causes of chronic liver disease with approximately 170 million people infected worldwide. Sustained virological response (SVR) is equivalent to viral eradication and associated with a reduction in the risk of cirrhosis. Nowadays the treatment for hepatitis C virus (HCV) genotype 1 chronic infection is the addition of direct acting antivirals (DAA) with a protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG-IFN) plus ribavirin (RBV) regimen. The future management of patients with these new molecules will require good clinical practice, knowledge of indications, management of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet and require studies in special populations (HIV-HCV coinfected patients, transplanted patients, etc.…) and also in HCV non-1 genotype patients and in non-responders. Second generation DAA are in development. Combinations of antivirals with additive potency that lack cross resistance and with a good safety profile may provide new regimens in the future to make HCV the first chronic viral infection eradicated worldwide with a finite duration of combination DAA therapy without IFN. The aim of this review is to summarize mechanisms of action and results obtained with DAAs.


HIV-1 Very Low Level Viremia Is Associated with Virological Failure in Highly Active Antiretroviral Treatment-Treated Patients.
The aim of this study was to evaluate the impact of HIV-1 very low-level viremia (<50 copies/ml) on the 2-year risk of virological failure. A retrospective analysis including HIV-positive patients presenting two consecutive HIV RNA below 50 copies/ml (outpatient clinic in Italy, first semester of 2010) was performed. HIV RNA was measured through real time polymerase chain reaction (PCR) assay CAP/CTM HIV-1 version 2.0 (detection limit: 20 copies/ml) and stratified as undetectable RNA ("Target Not Detected", TND), <20 copies/ml, 20-50 copies/ml. After 96 weeks virological failure was defined as two consecutive viral loads above 50 copies/ml. Log-rank tests and a multivariate Cox proportional hazard model were used for univariate and multivariate analysis. A total of 1,055 patients (71.4% male, 87.4% white, aged 46.7 years) were included: nadir and current CD4 cell counts were 203 cells/mm(3) (106-292) and 554 cells/mm(3) (413-713.5). HIV RNA was undetectable in 781 patients (74%), <20 copies/ml in 190 patients (18%) and 20-50 copies/ml in 84 patients (8%). Virological failure was observed in 81 patients (7.7%); at multivariate analysis detectable RNA at baseline (p=0.017), HCV infection (p=0.020), more than three pills in the regimen (p=0.003), and duration of HIV RNA <50 copies/ml below 2 years (p<0.001) were independently associated with virological failure. In 14 patients newly selected resistance-associated mutations were observed. Undetectable HIV RNA by real-time PCR is significantly associated with a lower 2-year risk of virological failure along with Ab HCV negativity, longer viral control, and lower pill burden. Studies investigating the management of residual viremia under antiretroviral treatment are warranted.


"Obesity paradox" has not an impact on minimally invasive anatomical lung resection.
The paradoxical benefit of obesity, the 'obesity paradox', has been analyzed in lung surgical populations with contradictory results. Our goal was assessing the relationship of body mass index (BMI) to acute outcomes after minimally invasive major pulmonary resections. Retrospective review of consecutive patients who underwent pulmonary anatomical resection through a minimally invasive approach for the period 2014-2019. Patients were grouped as underweight, normal, overweight and obese type I, II and III. Adjusted odds ratios regarding postoperative complications (overall, respiratory, cardiovascular and surgical morbidity) were produced with their exact 95% confidence intervals. All tests were considered statistically significant at p<0.05. Among 722 patients included in the study, 37.7% had a normal BMI and 61.8% were overweight or obese patients. When compared with that of normal BMI patients, adjusted pulmonary complications were significantly higher in obese type I patients (2.6% vs 10.6%, OR: 4.53 [95%CI: 1.86-12.11]) and obese type II-III (2.6% vs 10%, OR: 6.09 [95%CI: 1.38-26.89]). No significant differences were found regarding overall, cardiovascular or surgical complications among groups. Obesity has not favourable effects on early outcomes in patients undergoing minimally invasive anatomical lung resections, since the risk of respiratory complications in patients with BMI≥30kg/m2 and BMI≥35kg/m2 is 4.5 and 6 times higher than that of patients with normal BMI.


Clinical versus C.T. scan diagnosis in stroke--a comparative study of 50 cases.
Cerebrovascular disease is one of the three leading causes of death in the world along with cancer and heart disease. Differentiation between cerebral infarction and intracerebral haemorrhage is important because now a days proper management of the acute stroke syndrome is based on the correct diagnosis of the pathological type. This study compared clinical and C.T. scan diagnosis of stroke and determined the reliability of the clinical diagnosis in cases of stroke. This study was conducted on 50 patients of stroke at Postgraduate Medical Institution, Lady Reading Hospital, Peshawar from Jan 1995 to May 1996. Clinical diagnoses were made in conformity with criteria for clinical diagnosis of intracranial haemorrhage, cerebral infarction due to embolism or thrombosis. The clinical diagnosis was then compared with the CT diagnosis. We found that from careful history and clinical examination differentiation could be made between cerebral infarction and haemorrhage. In our study at Government Lady Reading Hospital, cerebral hemorrhage accounted for 42% of cases of stroke and cerebral infarction in 58%. In order to make a clinical diagnosis of stroke, a detailed history and thorough clinical examination is mandatory. As far as treatment planning is concerned clinical diagnosis of stroke is not safe enough as a guide for anticoagulant or thrombolytic therapy. In order to confirm the aetiological diagnosis of stroke one must rely on C.T. scan examination.


HIV Nef inhibits T cell migration.
Nef is a viral regulatory protein of the human immunodeficiency virus (HIV) that has been shown to contribute to disease progression. Among its putative effects on T cell functions are the down-regulation of CD4 and major histocompatibility class I surface molecules. These effects occur in part via Nef interactions with intracellular signaling molecules. We sought to better characterize the effects of HIV Nef on T cell function by examining chemotaxis in response to stromal cell-derived factor-1alpha (SDF-1alpha) as well as CXCR4 signaling molecules. Here, we report the novel observation that HIV Nef inhibited chemotaxis in response to SDF-1alpha in both Jurkat T cells and primary peripheral CD4+ T lymphocytes. Our data indicate that HIV Nef altered critical downstream molecules in the CXCR4 pathway, including focal adhesion kinases. These findings suggest that HIV Nef may blunt the T cell response to chemokines. Because T lymphocyte migration is an integral component of host defense, HIV Nef may thereby contribute to the pathogenesis of AIDS.


[Establishment and application of TLR2 receptor-based cell screening model].
TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.


Registration of planar bioluminescence to magnetic resonance and x-ray computed tomography images as a platform for the development of bioluminescence tomography reconstruction algorithms.
The procedures we propose make possible the mapping of two-dimensional (2-D) bioluminescence image (BLI) data onto a skin surface derived from a three-dimensional (3-D) anatomical modality [magnetic resonance (MR) or computed tomography (CT)] dataset. This mapping allows anatomical information to be incorporated into bioluminescence tomography (BLT) reconstruction procedures and, when applied using sources visible to both optical and anatomical modalities, can be used to evaluate the accuracy of those reconstructions. Our procedures, based on immobilization of the animal and a priori determined fixed projective transforms, should be more robust and accurate than previously described efforts, which rely on a poorly constrained retrospectively determined warping of the 3-D anatomical information. Experiments conducted to measure the accuracy of the proposed registration procedure found it to have a mean error of 0.36+/-0.23 mm. Additional experiments highlight some of the confounds that are often overlooked in the BLT reconstruction process, and for two of these confounds, simple corrections are proposed.


ADHD familial loading and abnormal EEG alpha asymmetry in children with ADHD.
Abnormal brain laterality (ABL) is indicated in ADHD. ADHD and brain laterality are heritable. Genetic factors contributing to lateralization of brain function may contribute to ADHD. If so, increased ADHD family loading should be associated with greater ABL. Previous studies have shown increased rightward alpha asymmetry in ADHD. We tested whether this was more pronounced in ADHD children with increased ADHD family loading. We compared EEG alpha asymmetry at rest and during the Conner's Continuous Performance Test (CPT) in ADHD children with and without ADHD affected parents, and replicated our findings in a second larger sample. The replication study additionally stratified the parent-affected sample by parental persistent versus non-persistent ADHD status, increased spatial resolution of EEG measures, and assessed low versus high-alpha. Study-1: the parent-affected group showed increased rightward asymmetry across frontal and central regions and reduced rightward parietal asymmetry during an eyes closed (EC) condition, as well as increasing rightward parietal asymmetry with advancing age during the CPT. Study-2 replicated these findings and further delineated influences of low versus high-alpha, recording site, and effects of parental persistent versus non-persistent ADHD status. Increased ADHD familial loading was associated with increased rightward frontal asymmetry. In contrast, increased rightward parietal asymmetry was associated with reduced ADHD family loading. Frontal results are consistent with an ADHD endophenotype. Parietal results suggest an ADHD adaptive trait prevalent with less ADHD family loading. Age effects indicate a unique developmental course among ADHD children whose parents have non-persistent ADHD.


Fungal effector proteins.
It is accepted that most fungal avirulence genes encode virulence factors that are called effectors. Most fungal effectors are secreted, cysteine-rich proteins, and a role in virulence has been shown for a few of them, including Avr2 and Avr4 of Cladosporium fulvum, which inhibit plant cysteine proteases and protect chitin in fungal cell walls against plant chitinases, respectively. In resistant plants, effectors are directly or indirectly recognized by cognate resistance proteins that reside either inside the plant cell or on plasma membranes. Several secreted effectors function inside the host cell, but the uptake mechanism is not yet known. Variation observed among fungal effectors shows two types of selection that appear to relate to whether they interact directly or indirectly with their cognate resistance proteins. Direct interactions seem to favor point mutations in effector genes, leading to amino acid substitutions, whereas indirect interactions seem to favor jettison of effector genes.


Computational Neuroscience Approach to Psychiatry: A Review on Theory-driven Approaches.
Translating progress in neuroscience into clinical benefits for patients with psychiatric disorders is challenging because it involves the brain as the most complex organ and its interaction with a complex environment and condition. Dealing with such complexity requires powerful techniques. Computational neuroscience approach to psychiatry integrates multiple levels and types of simulation, analysis and computation according to the different types of computational models to enhance comprehending, prediction and treatment of psychiatric disorder. This approach comprises two approaches: theory-driven and data-driven. In this review, we focus on recent advances in theory-driven approaches that mathematically and mechanistically examine the relationships between disorder-related changes and behavior at different level of brain organization. We discuss recent progresses in computational neuroscience models that relate to psychiatry and show how principles of neural computational modeling can be employed to explain psychopathology.


Idiopathic reversible cerebral vasoconstriction syndrome (RCVS).
Reversible cerebral vasoconstriction syndrome is characterised by severe thunderclap headache with associated characteristic transient, multifocal, segmental vasoconstriction of cerebral arteries lasting several weeks to months. We describe a 50-years old woman who presented with a severe sudden onset occipital headache. Neuroimaging revealed segmental vasospasm affecting the intracerebral arteries. The pain improved gradually over the next 6 weeks. Repeat brain MR angiography at 12 weeks showed complete resolution of the segmental narrowing.


Gonadotropin-releasing hormone agonist reduces aromatase cytochrome P450 and cyclooxygenase-2 in ovarian endometrioma and eutopic endometrium of patients with endometriosis.
To investigate whether the GnRH agonist may reduce aromatase P450 and COX-2 in the eutopic endometrium of patients with endometriosis and ovarian endometrioma. Endometrial specimens and ovarian endometrioma were obtained from 15 women with endometriosis undergoing laparoscopic surgery. The stromal cells of the eutopic endometrium and ovarian endometroma were cultured in the presence of the GnRH agonist (leuprolide acetate 0, 1, 5 and 10 microM) for 24 h. To investigate the effects of the GnRH agonist on the eutopic endometrium in vivo, biopsy samples of the endometrium (n = 5) among the patients who underwent laparoscopy were obtained after GnRH agonist therapy. The protein production of aromatase cytochrome P450 and COX-2 was examined by Western blot. Proteins of aromatase P450 and COX-2 were reduced in the eutopic endometrium of patients with endometriosis treated with the GnRH agonist for 3 months. The stromal cells in the culture of endometrial explants and ovarian endometrioma which were treated with the GnRH agonist reduced the aromatase P450 and COX-2. The GnRH agonist reduced aromatase P450 and COX-2 by direct action on the eutopic endometrium of patients with endometriosis and ovarian endometrioma.


Evaluation of the clinical course and prognostic indices of acute pancreatitis in elderly patients : a prospective study.
Acute pancreatitis (AP) is a life- threatening condition across all age groups. In this study, it was aimed to investigate the severity of the disease and associated mortality in the geriatric population. This single-center, prospective study elderly (≥65 years of age) and younger (18-65 years of age) total 147 patients with AP are enrolled To diagnose and asses the severity of AP Atlanta classification was used. Baseline and 12-months follow-up data included Ranson, Imrie, BISAP, APACHE-II, SOFA, Modified Marshall, Balthazar, and Computed Tomography Severity Index (CTSI) as prognostic tools. 6 (15%) patiens in elderly and 5 (6,7%) patients in non elderly group had modarete-severe AP . Patients were followed up 1 year and during this time no systemic complications were seen , 8 (20%) patients in elderly group and 10 (13,6%) patients in younger group had local complications. 1 patients in elderly and 2 patients in non elderly group had acute necrotic collection whereas 1 patient developed walled of necrosis in non elderly group. The elderly patients with any of the following index characteristics would not be expected to have a mild disease course: Imrie score ≥ 3, BISAP score ≥ 3, APACHE-II ≥ 11, CRP ≥ 195 mg/dl. AP caused a prolonged hospitalization in the elderly compared to younger patients but its severity and clinical outcomes were not different in the two groups.


MR imaging features of obturator internus bursa of the hip.
The authors report two cases with distension of the obturator internus bursa identified on MR images, and describe the location and characteristic features of obturator internus bursitis; the "boomerang"-shaped fluid distension between the obturator internus tendon and the posterior grooved surface of the ischium.


Effects of a Phosphorus Flame Retardant System on the Mechanical and Fire Behavior of Microcellular ABS.
The present work deals with the study of phosphorus flame retardant microcellular acrylonitrile⁻butadiene⁻styrene (ABS) parts and the effects of weight reduction on the fire and mechanical performance. Phosphorus-based flame retardant additives (PFR), aluminum diethylphosphinate and ammonium polyphosphate, were used as a more environmentally friendly alternative to halogenated flame retardants. A 25 wt % of such PFR system was added to the polymer using a co-rotating twin-screw extruder. Subsequently, microcellular parts with 10, 15, and 20% of nominal weight reduction were prepared using a MuCell® injection-molding process. The results indicate that the presence of PFR particles increased the storage modulus and decreased the impact energy determined by means of dynamic-mechanical-thermal analysis and falling weight impact tests respectively. Nevertheless, the reduction of impact energy was found to be lower in ABS/PFR samples than in neat ABS with increasing weight reduction. This effect was attributed to the lower cell sizes and higher cell densities of the microcellular core of ABS/PFR parts. All ABS/PFR foams showed a self-extinguishing behavior under UL-94 burning vertical tests, independently of the weight reduction. Gradual decreases of the second peak of heat release rate and time of combustion with similar intumescent effect were observed with increasing weight reduction under cone calorimeter tests.


Cellular and molecular mechanisms of estrogen regulation of memory function and neuroprotection against Alzheimer's disease: recent insights and remaining challenges.
This review focuses on recent advances in our knowledge of estrogen action in the brain. The greatest amount of attention was devoted to those studies that impact our understanding of estrogen regulation of memory function and prevention of degenerative diseases associated with memory systems, such as Alzheimer's disease. A review of recent advances in our understanding of estrogen receptors, both nuclear and membrane, is also presented. Finally, these data are considered in regard to their relevancy to the use of estrogen replacement therapy for cognitive health throughout menopause and the development of an estrogen replacement therapy designed for the unique requirements of the brain.


LANA-Mediated Recruitment of Host Polycomb Repressive Complexes onto the KSHV Genome during De Novo Infection.
One of the hallmarks of the latent phase of Kaposi's sarcoma-associated herpesvirus (KSHV) infection is the global repression of lytic viral gene expression. Following de novo KSHV infection, the establishment of latency involves the chromatinization of the incoming viral genomes and recruitment of the host Polycomb repressive complexes (PRC1 and PRC2) to the promoters of lytic genes, which is accompanied by the inhibition of lytic genes. However, the mechanism of how PRCs are recruited to the KSHV episome is still unknown. Utilizing a genetic screen of latent genes in the context of KSHV genome, we identified the latency-associated nuclear antigen (LANA) to be responsible for the genome-wide recruitment of PRCs onto the lytic promoters following infection. We found that LANA initially bound to the KSHV genome right after infection and subsequently recruited PRCs onto the viral lytic promoters, thereby repressing lytic gene expression. Furthermore, both the DNA and chromatin binding activities of LANA were required for the binding of LANA to the KSHV promoters, which was necessary for the recruitment of PRC2 to the lytic promoters during de novo KSHV infection. Consequently, the LANA-knockout KSHV could not recruit PRCs to its viral genome upon de novo infection, resulting in aberrant lytic gene expression and dysregulation of expression of host genes involved in cell cycle and proliferation pathways. In this report, we demonstrate that KSHV LANA recruits host PRCs onto the lytic promoters to suppress lytic gene expression following de novo infection.


Nonsteroidal antiinflammatory drugs may affect the presentation and course of community-acquired pneumonia.
Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used as antipyretics and analgesics and may affect the host response to acute infection. We investigated the potential influence of NSAIDs on the presentation and short-term outcomes of nonimmunocompromised inpatients with community-acquired pneumonia (CAP) admitted to the ICU. All consecutive patients with CAP admitted to the ICU or step-down unit of a university hospital during a 4-year period were prospectively included, except when receiving long-term NSAIDs or steroids. Drug exposures, presentation, and hospital course were recorded. Of the 90 patients included, 32 (36%) had taken NSAIDs prior to hospital referral. Compared with nonexposed patients, they were younger and had fewer comorbidities but similar severity of disease at presentation, despite a longer duration of symptoms before referral. However, they more often developed pleuropulmonary complications, such as pleural empyema and lung cavitation (37.5% vs 7%; P = .0009), and had a trend to more-invasive disease, with a higher frequency of pleural empyema (25% vs 5%, P = .014) and bacteremia, especially in those not having received concomitant antibiotics (69% vs 27%, P = .009). Nevertheless, the patients in the NSAID group had no more severe systemic inflammation or remote organ dysfunction. In multivariable analyses, NSAID exposure was independently associated with the occurrence of pleuropulmonary complications (OR, 8.1; 95% CI, 2.3-28). Our findings suggest that NSAID exposure at the early stage of CAP is associated with a more complicated course but a blunted systemic response, which may be associated with a delayed diagnosis and a protracted course.


[IL-2 responsiveness in antigen-specific lymphocyte proliferation test with sulfhydryl drug-sensitized murine lymphocytes--using rapid fluorochromasia assay].
Response of murine lymphnode cells (LNC) sensitized with sulfhydryl drugs to recombinant interleukin 2 (rIL-2) was studied in antigen-specific lymphocyte proliferation test (LPT). Mice were primed with tiopronin (TP) and gold sodium thiomalate (GTM) and the secondary response to LNC was measured in a proliferative assay in vitro. Rapid fluorochromasia assay with propidium iodide (RFP) was used for the quantitative measurement of LPT instead of 3H-thymidine uptake. There was no difference in proliferative response to specific antigen between TP or GTM-primed LNC and control ones. In contrast, a significant proliferation was observed when LNC from sensitized mice were cultured with sensitizing antigen and rIL-2. The strength of response was dependent on the concentration of rIL-2. It was considered that adding rIL-2 to LPT of TP or GTM-sensitized mice enhanced antigen-specific lymphocyte proliferative response and the measurement of IL-2 responsiveness using RFP method might be useful to detect sulfhydryl drug allergy in man.


Salvator Karabaić (1884-1956): the profile of an eyceptional Psychiatrist/Neuropsychiatrist with outstanding managing capabilities.
Salvator Karabaić was born in Krk in 1884. In 1904, he finished a grammar school in Susak, and in 1910 graduated from the Vienna Medical School. From 1910 to 1919, he worked in Pula/Pola and Kovin. From 1919 to 1929 he worked at the Institute for Mental illnesses Stenjevec (today the Psychiatric Hospital Vrapce) where in 1921 he became the head physician (orig. primarius) at the age of 37 years only. Between 1929 and 1945, he worked in Sarajevo as a Head of the State Hospital's Neuropsychiatry Department. In 1948 he was appointed the director of the Hospital for Mental Illnesses in Sarajevo. The hospital was in fact a remodelled rope factory with a favourable position near a homestead. He managed this institution until 1956. He died on 24 September 1956 at a hospital surgery ward in Sarajevo. Judging by Dr Karabaić's ability to take care of 200 psychiatric patients alone, he was an outstanding figure with enormous experience. A lot of it he earned during the Vrapce hospital period between 1919 and 1929. He had the opportunity to work with the outstanding figures of Croatian psychiatry such as Dr Ivo Zirovcić, Dr Laza Stanojević, Dr Ivan Barbot, and Dr Aleksej KuljZenko The author suggests that a more systematic research is needed to understand the work and the life of Dr Salvator Karabaić, who was a talented and hardworking psychiatrist/ neuropsychiatrist with outstanding managing capabilities, and a person who above all cared for his patients.


The internet: from basics to telesurgery.
The exponential growth in information technology is resulting in a rapid increase in the ability to develop useful applications on the Internet. The purpose of the present article is to provide a brief review of the Internet with a consideration of its relevance to surgeons. This review is intended to indicate a range of relevant issues, rather than to discuss any specific topic in depth. It is becoming difficult for surgeons to reach their full potential unless they exploit Internet-based activities. This is because the ability to rapidly capture information of quality is an essential ingredient in a reflective approach to surgical problems. More futuristic is the prospect of using computer-based technology to operate upon patients from a distance (telesurgery).


Diversity for endoribonuclease nsp15-mediated regulation of alpha-coronavirus propagation and virulence.
Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) nsp15 proteins antagonize SeV-induced interferon-β (IFN-β) production in human embryonic kidney 293 cells. Interestingly, compared with wild-type infection, infection with EnUmt-TGEV or EnUmt-FIPV did not change the IFN-β response or reduce viral propagation in immunocompetent cells. The results of animal experiments showed that EnUmt viruses did not reduce the clinical presentation and mortality caused by TGEV and FIPV. Our findings enrich the understanding of nsp15-mediated regulation of alpha-CoV propagation and virulence and reveal that the conserved functions of nonstructural proteins have diverse effects on the pathogenicity of CoVs.


Comparative study of the analgesic effect of transcutaneous nerve stimulation (TNS); electroacupuncture (EA) and meperidine in the treatment of postoperative pain.
Seventy two patients, from 15 to 60 years old, in good physical status and submitted to surgery in the upper or lower abdominal, rectal or lumbar areas were studied. In the immediate postoperative period, they were randomly divided in three groups and each group was submitted to one of the following treatments: intravenous meperidine, transcutaneous nerve stimulation (TNS) or electroacupuncture (EA). Each treatment was divided in two phases with one hour interval between them. Each phase was constituted of 30 minutes of stimulation in case of TNS and EA and fractionated administration of meperidine in all groups. The pain level was evaluated through a visual analogue scale before and after each phase of treatment. The results were compared among groups and, on each group, between the phases of treatment. In all surgery types, the postoperative pain relief presented by TNS and EA groups of patients was greater than that of meperidine treated group. But, the analgesia presented by the EA treated group of patients lasted longer and increased with the repetition of treatment. The differences of behaviour of TNS and EA analgesia suggest that their neurochemical mechanisms may not be the same.


Evaluation of vaccination of horses as a strategy to control equine monocytic ehrlichiosis.
To determine whether preferentially vaccinated horses were at risk for exposure to Ehrlichia risticii, whether horses with equine monocytic ehrlichiosis (EME) were likely to have been nonvaccinated, and whether clinical severity and financial costs associated with care and treatment of EME were less for vaccinated horses with EME than for nonvaccinated horses with EME. Cross-sectional and case-control studies. Information on usage of E risticii bacterins to control EME was collected for 2,587 horses located on 511 farms throughout New York. Each horse was tested for serum antibodies directed against E risticii. Data on efficacy of vaccination to reduce the prevalence and clinical severity of EME and monetary losses associated with EME were collected from 68 horses with EME and 132 clinically normal horses. A correlation was not detected between the county seropositive proportion and the proportion of horses vaccinated against EME. Among horses diagnosed for EME, median date of diagnosis was not delayed for vaccinated horses, compared with that for nonvaccinated horses. Mean cost per case was not significantly different for nonvaccinated horses, compared with that for vaccinated horses ($ 1,082 and $ 1,001, respectively). Vaccination was not associated with a reduction in prevalence or in severity of EME-related clinical signs. Administering killed E risticii bacterin once a year to control EME in New York appears to have limited success. Among horses in which EME was diagnosed, severity of illness and financial costs attributable to EME were indistinguishable for vaccinated and nonvaccinated horses.


The future of the welfare state: crisis myths and crisis realities.
Accounts of the future of the welfare state are often presented in crisis terms. Some commentators identify globalization as a force that has already led to a major retreat by the state and is likely to lead to further downsizing of the public sector. Others see the future burden of an aging population as creating huge public expenditure pressures that can be countered only by increased parsimony in most areas of spending. Although both crisis scenarios contain elements of truth, analysis of recent public expenditure trends shows that both are substantially exaggerated as general representations of likely developments over the next two or three decades. However, unnoticed by most commentators, a real, longer-term crisis is beginning to make itself felt. This crisis arises, in part, from the demographic impact of a cultural transformation in the labor market, in progress for several decades. Extreme scenarios of possible consequences over the next 50 to 100 years include population implosion, mass migration, increasingly dangerous eruptions of right-wing populism, and, possibly, territorial conflict between developed and underdeveloped nations. This is not a crisis of the welfare state but rather a crisis for which the welfare state may be an essential part of the answer. The only way Western societies can lessen the future impact of the ongoing cultural transformation of the labor market is through the redesign of welfare state institutions to confront these new challenges.


[Coccidioidomycosis. Two case reports with discussion of current diagnostic and therapeutic issues].
Coccidioidomycosis is a systemic mycosis that is acquired by inhalation. It is endemic in desert-like areas of the southwest USA and neighboring regions, but is becoming increasingly prevalent in other regions of the world as a result of widespread travel. The clinical spectrum is broad, ranging from inapparent infections or symptoms of acute respiratory infection with spontaneous recovery to various manifestations of disseminated coccidioidomycosis. Since the majority of patients with disseminated coccidioidomycosis present with cutaneous manifestations, early diagnosis of this potentially life-threatening disease by dermatologists is important. Atypical skin changes, pulmonary infiltrates and a history of travel to areas where the disease is endemic are indicative of coccidioidomycosis. For conclusive diagnosis, identification of the fungus by histopathologic examination or culture is desirable. Serological tests can be helpful for establishing the diagnosis and monitoring the course of the disease. The treatment of choice for cutaneous coccidioidomycosis is currently oral azole antifungal agents, such as itraconazole 400 mg daily, continued for 6 months after clinical response. Since relapses are frequent after discontinuation of the treatment, close clinical, serological and radiological follow-up is required for years.


New Jersey's waste management data: retrospect and prospect.
Reliable data about collection, volume, tonnage, stream composition, and disposal price have long been described as key components of successful solid waste management planning. Yet, concerns about data quality and quantity have continued to limit even the most sincere, progressive waste management schemes. This paper examines solid waste management data that has been collected in the US state of New Jersey starting in the 1960s. We present the origins of waste management data collection in New Jersey and trace some of the applications that have been made with the data over time. We compare the New Jersey dataset to waste management data that has been collected in other US states. We then describe our work collecting, cleaning, and preparing for public dissemination and use in a geospatial visualization exercise a digital version of the data spanning approximately 1993 to 2016, before presenting some illustrations of the type of modeling and analysis that researchers or the concerned public would be able to undertake now that the dataset is available. (We are publishing the 1993-2016 dataset alongside this paper). We argue that the New Jersey waste management dataset is much better than most other waste datasets in the US, but despite this fairly high quality, there remain significant gaps which inhibit the ability of planners to design and implement comprehensive waste management plans. That there are limits inherent to the New Jersey dataset suggests, we argue, a ceiling to the usefulness of waste management data as a category of environmental knowledge with possible implications for 'big' environmental data more broadly.


Single-scan measurement of conductance of a quartz crystal microbalance array coupled with resonant markers for biosensing in liquid phase.
This work presents a method for sensing the viscoelastic property of liquid/solid interface using a quartz crystal microbalance (QCM) array. Each sensor in a QCM array has a unique resonant frequency and can be identified by a single-scan measurement of admittance (or impedance). The resonant frequency encoding at each sensor in an array was realized by connecting a capacitor with a known capacitance, called a resonant marker, to the sensor in series. Changes in the resonant frequency of all sensors in an array can be determined using an impedance analyzer and a program that determines the frequencies at which the conductance is at a local maximum. The sensing method allows every sensor output (resonant frequency) to be obtained without the use of time-consuming multiplexed hardware and software. Adsorptions of biomolecules by multiple sensor are monitored in the liquid phase to demonstrate the feasibility of frequency encoding using resonant markers and the single-scan measurement of conductance of a QCM array.


Magnetic resonance imaging in pediatric pulmonary hypertension.
The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children. This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ≥25 mmHg by catheter angiography. The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both P=0.001) but statistically similar ratios of main pulmonary artery diameter-to-ascending aortic diameter. If the main pulmonary artery diameter was ≥25 mm, pediatric pulmonary hypertension was diagnosed with 72% sensitivity and 84% specificity. In the event that the ratio of main pulmonary artery diameter-to-ascending aorta diameter was ≥1, pediatric pulmonary hypertension was diagnosed with 60% sensitivity and 53% specificity. When compared with children who had New York Heart Association functional class II pulmonary hypertension, the children with functional class III pulmonary hypertension had significantly larger main (P=0.046), right (P=0.036), and left (P=0.003) pulmonary arteries. Cardiovascular magnetic resonance imaging is useful in the diagnosis of children with pulmonary hypertension. Pediatric pulmonary hypertension can be diagnosed with high sensitivity and specificity when the main pulmonary artery diameter measures ≥25 mm.


Diurnal Growth of Tall Fescue Leaf Blades : II. Dry Matter Partitioning and Carbohydrate Metabolism in the Elongation Zone and Adjacent Expanded Tissue.
The spatial distributions of net deposition rates of water soluble carbohydrate-free dry matter (WSC-free DM) and WSC were evaluated within and above the elongation zone of tall fescue (Festuca arundinacea Schreb.) leaf blades during light and darkness. Imported DM used for WSC-free DM synthesis during darkness (67% of the total in experiment I and 59% in experiment II) was greater than during light (47% in both experiments), suggesting that the 65% higher leaf elongation rate during darkness was accompanied by higher rates of synthesis of cellular structural components. Deposition rates of WSC in the basal and central part of the elongation zone (0-20 mm from the ligule) were similar during light and darkness, but above 20 millimeters WSC deposition occurred during light and WSC loss occurred during darkness. WSC deposition and loss throughout the elongation zone and the recently expanded tissue were mostly due to net synthesis and degradation of fructan. Fructan was predominantly low molecular weight and contributed about 50% of the total osmotic partial pressure of WSC. In the most actively growing region, where fructan synthesis was most rapid, no diurnal change occurred in molecular weight distribution of fructan. WSC solute concentrations were diluted in the most actively growing tissue during darkness because net monosaccharide and fructan deposition were unaltered and sucrose deposition was decreased, but growth-associated water deposition was increased by 77%. Net rates of fructan synthesis and degradation were not related to tissue sucrose concentration, but appeared to respond to the balance between assimilate import and assimilate use in synthesis of cellular structural components (i.e. WSC-free DM) and deposition of monosaccharides. Fructan synthesized in tissue during most active elongation was degraded when the respective tissue reached the distal limit of the elongation zone where assimilate import in darkness was insufficient to maintain synthetic processes associated with further differentiation of cells.


Loss of Barx1 promotes hepatocellular carcinoma metastasis through up-regulating MGAT5 and MMP9 expression and indicates poor prognosis.
Metastasis is the major dominant reason for poor prognosis of hepatocellular carcinoma (HCC) after surgical treatment. However, the molecular mechanism of metastasis has not been well characterzied. Here, we report a novel function of Barx homeobox1 (Barx1) in inhibiting HCC invasion and metastasis. Barx1 expression is significantly decreased in human HCC tissues than in adjacent non-tumorous tissues and normal liver tissues. Low Barx1 expression is correlated with higher tumor-nodule-metastasis stage and indicates poor prognosis. Down-regulation of Barx1 promotes HCC migration, invasion and metastasis, whereas up-regulation of Barx1 inhibits HCC migration, invasion and metastasis. Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase 5 (MGAT5) and matrix metallopeptidase 9 (MMP9) are direct target genes of Barx1. Knockdown of Barx1 up-regulates MGAT5 and MMP9 expression in HCC cells with low metastatic capability, whereas over-expression of Barx1 suppresses their expression in HCC cells with high metastatic capability. Knockdown of both MGAT5 and MMP9 significantly decreases the invasion and metastasis abilities induced by Barx1 knockdown. Barx1 expression is negatively correlated with MGAT5 and MMP9 expression in human HCC tissues. Patients with low expression of Barx1 and high expression of MGAT5 or MMP9 are associated with poorer prognosis. Thus, loss of Barx1 represents a prognostic biomarker in human HCC patients.


Signal transducer and activator of transcription 3 signaling upregulates fascin via nuclear factor-κB in gastric cancer: Implications in cell invasion and migration.
Fascin protein plays important roles in tumor metastasis and is prognostically relevant to human gastric cancer (GC). However, its role in the development and progression of GC has not been comprehensively investigated. In the present study, results revealed that upregulation of fascin by interleukin-6 promotes GC cell migration and invasion in a signal transducer and activator of transcription 3 (STAT3)-dependent manner in MKN45 cells. Furthermore, STAT3 directly regulated fascin expression and nuclear factor-κB (NF-κB) bound to the fascin promoter in a STAT3-dependent and Notch-independent manner. Therefore, results demonstrate that STAT3 and NF-κB are required for upregulation of fascin and for cell migration and invasion in MKN45 cells. Effects of the treatments on cell signaling were detected by qPCR, western blot analysis and chromatin immunoprecipitation (ChIP) assay. Cell migration and invasion were analyzed using in vitro scratch wound healing assay, transwell and Matrigel assays, and xenograft model. In addition, the STAT3-NF-κB-fascin signaling axis is identified as a therapeutic target for blocking GC cell invasion and migration.


Socioeconomic inequalities in non- coverage of full vaccination among children in Bangladesh: a comparative study of Demographic and Health Surveys, 2007 and 2017-18.
Vaccination is considered as a powerful and cost-effective weapon against many communicable diseases. An increase in full vaccination among the most vulnerable populations in Bangladesh was observed in the last decade. This study aimed to capture the socioeconomic inequalities in non-coverage of full vaccination among children aged 12-23 months using the nationally representative data from the Bangladesh Demographic and Health Surveys (BDHS). Data for this study have been drawn from the 2007 and 2017-18 BDHS, which covered 10,996 and 20,127 ever-married women aged 15-49 years in 2007 and 2017-18, respectively. Binary logistic regression analysis was performed to find the factors associated with children who did not receive full vaccination. Further, the concentration index was used to observe the socioeconomic inequality for the outcome variable. The proportion of children who did not get fully vaccinated decreased by more than 6 points (18.2 percent to 11.8 percent) between the years 2007 and 2017-18. In 2017-18, the odds of children who were not fully vaccinated were 58 percent and 53 percent less among mothers who had primary education in 2007 [adjusted odds ratio (AOR): 0.42; confidence interval (CI): 0.24-0.73] and 2017-18 [AOR: 0.47; CI: 0.23-0.94] respectively, compared to mothers with no education. The inequality for children who were not fully vaccinated had declined between two survey periods [concentration index (CCI) value of - 0.13 in 2007 and -0.08 in 2017-18]. The concentration of inequality in children with higher parity who did not receive full vaccination had increased from 5 percent in 2007 to 16.9 percent in 2017-18. There was a drastic increase in the socioeconomic inequality contributed by place of delivery from 2.9 percent (2007) to 60.5 percent (2017-18) among children who did not receive full vaccination. The present study provide eminent evidence that non-coverage of full vaccination is more prevalent among children from poor households in Bangladesh, which is mainly associated with factors like mother's education, father's education and working status and household wealth index across the two rounds. These factors suggest multifaceted pro-poor interventions that will protect them from hardship and reduce their socioeconomic inequalities in coverage of full vaccination.


Lignans and indole alkaloids from the seeds of Centaurea vlachorum Hartvig (Asteraceae), growing wild in Albania and their biological activity.
The present phytochemical investigation of the seeds of Centaurea vlachorum led to the isolation and characterisation of four compounds including two indole alkaloids N-(p-coumaroyl) serotonin (1) and moschamine (2) and two dibenzylbutyrolactone lignans matairesinol (3) and arctiin (4). This is the first report on the isolation of non-volatile secondary metabolites from C. vlachorum. The chemataxonomic significance of these compounds was summarised. Moreover, the isolated compounds were tested for their free radical scavenging activity using the following in vitro assays: (i) interaction with the free stable radical of DPPH (1,1-diphenyl-2-picrylhydrazyl), (ii) inhibition of linoleic acid peroxidation with the dihydrochloric acid of 2,2-Azobis-2-amidinopropane (AAPH). Finally, their inhibitory activity towards soybean lipoxygenase was evaluated, using linoleic acid as substrate.


Abdominal neuroblastoma in a child with inferior vena cava anomaly.
Congenital anomalies of the inferior vena cava are rare. Such anomalies pose great challenges to the surgeon in neuroblastoma surgery, especially when unrecognised preoperatively. We report the first case of an abdominal neuroblastoma detected in a child with a developmental anomaly of the left-sided inferior vena cava. The patient underwent surgical resection after good response to preoperative chemotherapy.