Remote pharmaceutical care for patients with rheumatoid arthritis and psoriasis.
BackgroundAccess to drugs with hospital-restricted dispensation, such as those for patients with rheumatoid arthritis or psoriasis, is regulated by healthcare policy. These drugs have the greatest cost-effective impact on the healthcare system. This is why a model for Pharmaceutical Care based on follow-up teleconsultations was defined in our hospital to improve patient well-being. Objective To evaluate clinical changes on patients when our remote Pharmaceutical Care model is applied and describe the work carried out by pharmacists when applying it. Setting Pharmacy Department of a Hospital in Barcelona, Spain. Method Cross-sectional observational study of the remote Pharmaceutical Care model developed by Clinical Pharmacists. All patients diagnosed with psoriasis or rheumatoid arthritis who were receiving active treatment with Hospital/Specialist only drugs, during the period from May to December 2018, were included. Main outcome measures The corresponding healthcare activity was recorded and to determine the utility of the model, the clinical response to treatment of patients included in the study was recorded. Results The implementation of teleconsultation is statistically related to the biological treatment response of patients with psoriasis (p = 0.006) and rheumatoid arthritis (p = 0.019). In those patients the healthcare activity of calculating and/or recording clinical variables of effectiveness/safety is statistically associated to biological treatment response (65.62% vs 35%, p = 0.015 and 73.14% vs 53.26%, p = 0.003). Conclusions The implementation of the model described lends added value to traditional pharmacotherapeutic management of biological treatments in patients with rheumatoid arthritis and psoriasis since response is improved but patient well-being is not diminished.


Evaluation of the bound state energies of some diatomic molecules from the approximate solutions of the Schrodinger equation with Eckart plus inversely quadratic Yukawa potential.
We have obtained analytically the bound state solutions for the non-relativistic Schrodinger equation for the Eckart plus inversely quadratic Yukawa potential (EIQYP) using the parametric Nikiforov-Uvarov (NU) method. In order to validate our approximation, the bound state energies were computed and predicted for some selected diatomic molecules at different adjustable screening parameters from the available spectroscopic model parameters. The fact-finding obtained are in agreement with previously reported results available in literature. Furthermore, the graphs of the effective potential against inter-nuclear distance for low and high values of the screening parameters were reported. From our graphs, we observed that the approximation is best fit for very low values of the screening parameter α ≪ 1.


How is paediatric dentistry taught? A survey to evaluate undergraduate dental teaching in dental schools in the United Kingdom.
The quality assurance of undergraduate dental education in the UK is regulated by the General Dental Council who describe the competencies expected of the newly qualified dentist or "safe beginner." Whilst the literature has explored the level of undergraduate training in a number of dental specialties within the UK, there is a paucity of information on the UK curriculum for undergraduate paediatric dental teaching. This study aimed to assess the undergraduate teaching of paediatric dentistry within dental schools in the UK. An anonymous questionnaire was distributed to all 16 UK dental schools via email. Twelve questionnaires were completed, giving a response rate of 75%. First exposure to both academic teaching and clinical teaching in paediatric dentistry ranged from years 1-4. Whilst there were broad similarities between units with regard to core components of the curricula, there were notable differences including the teaching of regenerative endodontics (75%) and the use of the titanium trauma splint (58%). Silver diamine fluoride was only used clinically in one unit (8%), and non-vital pulpotomy was taught by two units (16%). There was also considerable heterogeneity in assessment methods between universities. The undergraduate paediatric dental curriculum is broadly similar between UK dental schools. However, there are discrepancies in assessment methods and the teaching of new advances.


UK: court orders publication ban in case of HIV-positive health-care worker.
In November 2001, an HIV-positive health-care worker brought legal proceedings to prevent the National Health Service from notifying his previous patients that he is infected. The health authorities had intended to carry out a "look back" exercise to notify patients that they may have been exposed.


Methyl jasmonate and selenium synergistically mitigative cadmium toxicity in hot pepper (Capsicum annuum L.) plants by improving antioxidase activities and reducing Cd accumulation.
Methyl jasmonate (MeJA) or selenium (Se)-mediated response to cadmium (Cd) stress in plant has been widely reported, but the combined effects both on plant growth in response to Cd stress and the underlying mechanisms remain obscure. Here, we showed the combined effects of MeJA (2.5 μM) and Se (7 μM) on hot pepper growth under Cd stress (CdCl2, 5 μM). The results showed Cd suppressed the accumulation of total chlorophyll and carotenoid and reduced the photosynthesis, while it increased the content of endogenous signaling molecules, e.g. nitric oxide (NO) and hydrogen peroxide (H2O2), as well as Cd content in leaves. The combined application of MeJA and Se significantly decreased the malondialdehyde (MDA) accumulation and improved the activities of antioxidant enzymes (AOEs, e.g. SOD and CAT) and defense-related enzymes (DREs, POD and PAL). Additionally, the synergistic application of MeJA and Se also obviously improved photosynthesis in hot pepper plants under Cd stress compared with those treated with MeJA or Se respectively or not. Moreover, the treatment of MeJA associated with Se also effectively reduced the Cd accumulation in hot pepper leaves under Cd stress compared with the plants treated with MeJA or Se separately, which implied a potentially synergistic role of MeJA and Se in alleviating Cd toxicity in hot pepper plants. This study provides a theoretical reference for the further analysis of the molecular mechanism of MeJA and Se in jointly mediating the response to heavy metals in plants.


Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.
Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.


Transplantation for cystic fibrosis: outcome following early liver transplantation.
Life expectancy in patients with cystic fibrosis (CF) has recently improved due to numerous factors, including a multidisciplinary approach to their management. Prolonged survival may have led to an increasing impact of liver disease on the prognosis of CF patients. The aim of this study was to assess the role of liver transplantation in patients with CF. The factors influencing outcome in 24 patients (15 adults and nine children) with CF who have received single liver transplantation, triple heart-lung-liver transplantation (tx) or died while being assessed for triple grafting, were analyzed. Median age at tx in single liver recipients (13 years) was lower than in triple graft recipients (21 years) and those who died (23 years). All patients who received single liver tx made an excellent recovery, including significant improvement of their respiratory function (mean forced vital capacity (FVC) increased from 61% before transplantation to 82% of expected, 6-9 months after tx). Four out of five patients who received triple tx died (0-2 months) after operation. On the basis of our retrospective review, we propose modifications to an existing scoring system for liver tx assessment in CF by scoring additional points for elevated white blood count, bilirubin, and impaired pulmonary function. These changes will need to be evaluated prospectively to confirm their predictive value. Liver transplantation is effective therapy in young patients with cystic fibrosis, portal hypertension and hepatic dysfunction, and is indicated before a critical stage of deteriorating lung function is reached. In patients with both end-stage liver and lung disease, triple tx has a poor prognosis. Pre-emptive liver tx in younger patients with CF not only has a better outcome but improves lung function.


Design of titanium uncemented femoral stems for hip prosthesis suitable for the Colombian young adult population.
The increase of revision surgeries in hip replacement procedure in Colombian young adult population can be addressed by a new design of femoral stem that reduces stress shielding. A new femoral stem was designed using topology optimization as a design aid to reduce the mass in the femoral stem and its overall stiffness, combined with the theoretical, computational, and experimental assessment of the new design that complies with a static and fatigue safety factor greater than one. The new femoral stem design can be used as a design tool to reduce the number of revision surgeries caused by stress shielding.


Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome.
The aim of this study was to investigate whether prolonged and dispersed myocardial contraction duration assessed by tissue Doppler imaging (TDI) may serve as risk markers for cardiac events (documented arrhythmia, syncope, and cardiac arrest) in patients with long QT syndrome (LQTS). Seventy-three patients with genetically confirmed LQTS (nine double- and 33 single-mutation carriers with previous cardiac events and 31 single-mutation carriers without events) were studied. Myocardial contraction duration was prolonged in each group of LQTS patients compared with 20 healthy controls (P < 0.001). Contraction duration was longer in single-mutation carriers with previous cardiac events compared with those without (0.46 +/- 0.06 vs. 0.40 +/- 0.06 s, P = 0.001). Prolonged contraction duration could better identify cardiac events compared with corrected QT (QTc) interval in single-mutation carriers [area under curve by receiver-operating characteristic analysis 0.77 [95% confidence interval (95% CI) 0.65-0.89] vs. 0.66 (95% CI 0.52-0.79)]. Dispersion of contraction was more pronounced in single-mutation carriers with cardiac events compared with those without (0.048 +/- 0.018 vs. 0.031 +/- 0.019 s, P = 0.001). Dispersion of myocardial contraction assessed by TDI was increased in LQTS patients. Prolonged contraction duration was superior to QTc for risk assessment. These new methods can easily be implemented in clinical routine and may improve clinical management of LQTS patients.


Patterns of local and distant disease relapse in patients with breast cancer treated with primary chemotherapy: do patients with a complete pathological response differ from those with residual tumour in the breast?
This study aimed to evaluate patterns of local and distant disease recurrence in patients having primary chemotherapy and compared patterns of relapse in patients with a complete pathological response with those who had residual breast disease. This is an observational study using a sequential series of patients treated with primary chemotherapy. They were followed up for a minimum of 5 years. All data was collected prospectively. Three hundred forty-one consecutive patients with breast cancer were treated with up to eight cycles of doxorubicin-based chemotherapy. Clinical and pathological response rates were evaluated and patients were followed up for disease recurrence (local and distant) and overall survival. Fifty-two patients (16.5%) had a complete pathological response to chemotherapy. Distant disease recurrence occurred in nine patients (17.3%) but no local recurrence was observed. In patients not having a complete pathological response, 86 patients (32.6%) subsequently developed metastases. Local recurrence of disease occurred in 12 (4.5%). There was a statistically significant difference in overall survival between patients whose tumours had a complete pathological response compared with patients who had residual disease in the breast following chemotherapy (88% versus 70% at 5 years, p = 0.036). Following primary chemotherapy, about 84% of patients had residual disease in the breast. Surgery is necessary to ensure complete removal of residual tumour and excellent rates of local control are achievable. A complete pathological response is associated with fewer local and distant recurrences as well as improved survival although there are no differences in time to development of metastatic relapse.


[Radiofrequency ablation for Barrett's esophagus. Preliminary experience].
Endoscopic radiofrequency ablation makes use of warm energy to ablate the esophagus's surface where the epithelial anomaly is located. 50 adults patients with the diagnosis of EB according to Vienna Classification were included. To evaluate the security and efficacy of ARF in patients with EB. 50 ARF treated patients were included with a medium follow up of 18 months. The median age was 58 years. 1.4 sessions of ARF perpatient were made to obtain EB erradication. The procedure morbidity was 6%, the more frequent complication was the esophageal stenosis (two cases). During the follow up, intestinal metaplasia recurrence was not observed. In the experience of our team, ARF is a secure procedure with low morbidity. These observations added to the published results help to evaluate the currentfollow up protocols.


Removal of exhausted oils by adsorption on mixed Ca and Mg oxides.
Adsorption tests were performed on two different exhausted oils to reduce their polluting and health hazard potential: a "water-insoluble oil", utilised for automotive engine lubrication, and an "emulsified" oil, used as coolant for metal-cutting tools. Dolomite, a low-cost recovery material, was used to prepare two effective adsorbents: (a) a mixed Ca and Mg oxide obtained by thermal decomposition of dolomite at 1800 degrees C, and (b) an activated material obtained by submitting this product to chemical treatment with HCl. Preliminary tests carried out with an excess of the former material showed that the insoluble oil was adsorbed with lower yield (Y = 0.40) than the soluble (emulsified) oil (Y = 0.60). The material activation with HCl remarkably improved the adsorption of soluble oil organic fraction (Y > 0.90), while only a little increase in the removal yield was observed for the insoluble oil (Y = 0.44). The results presented and discussed in this work pointed out that the products of dolomite calcination can successfully replace the conventional adsorbing materials in the removal of organic pollutants, with particular concern to exhausted soluble oils, which cannot usually be recycled, thus reducing the operational costs of their treatment.


HBC-porphyrin--close contact chromophores.
A photo/redoxactive hexa-peri-hexabenzocoronene-porphyrin conjugate with a direct connection between the two chromophores was synthesised using a formylated hexaphenylbenzene precursor.


Influence of cefoperazone and azithromycin on the pharmacokinetics of pazufloxacin in rats.
The effects of cefoperazone and azithromycin administered separately on the pharmacokinetics of pazufloxacin (PZFX) mesilate were investigated in rats. Animals were injected with cefoperazone at a high dose (180 mg/kg) or azithromycin at a dose of 45 mg/kg through the tail vein 10 min before intravenous (i.v.) administration of PZFX (45 mg/kg). Blood concentrations of PZFX were determined by HPLC. Parameters relating to the pharmacokinetic interaction between PZFX and cefoperazone or azithromycin were estimated by a two-compartmental model. The experimental results showed that the presence of azithromycin significantly delayed the t(1/2 beta) and mean residence time (MRT) of PZFX in the plasma. However, no significant changes between the control group and the cefoperazone-treated animals in the pharmacokinetic parameters of PZFX, such as t(1/2 beta), volume of distribution (Vd), area under the curve (AUC) and the clearance (Cl) were observed.


Membrane protein and glycoprotein composition of beef brain synaptic vesicles.
Synaptic vesicles were isolated from adult bovine cortical gray matter by differential centrifugation and membrane filtration of a hypoosmotically lysed crude mitochondrial fraction. Vesicle preparations were analyzed for purity by electron microscopy and enzyme assays. Polyacrylamide gel electrophoresis of SDS-solubilized and 2-mercaptoethanol-reduced vesicle membrane proteins revealed 4 major proteins with molecular weights ranging from 17,000 to 60,000, and about 10 minor proteins with molecular weights up to 170,000. The protein profile of the Triton X-100-extracted vesicle membranes was less complex, with 1 major protein and 5 minor bands. The major protein of the Triton extract was identified as a glycoprotein with a molecular weight of 45,000. Two additional minor PAS-positive bands were seen, with molecular weights of 78,000 and 95,000.


The Limping Child - What a Pediatrician Should Know?
Diagnosis of a limping child can be challenging for the clinician given the vast array of conditions that present in this manner. This review article discusses the history, examination and subsequent differential diagnoses that should be considered along with the most appropriate investigations for each diagnosis. The latest evidence regarding choice of investigation to make the clinician's task less onerous is also discussed.


The effects of topical parasympatholytic drugs on pupil diameter and intraocular pressure in healthy dogs treated with 0.005% latanoprost.
Prostaglandin analogs induce miosis and lower intraocular pressure (IOP). As pupils of latanoprost-treated eyes may have to be dilated for ophthalmoscopy or intraocular surgery, we studied whether 0.5% tropicamide or 1% atropine alter the effects of 0.005% latanoprost on pupil diameter (PD) and IOP in healthy dogs. IOP and PD were measured hourly, 8 AM-4 PM, with the right and left eyes serving as control (CE) and treated (TE) eyes, respectively. Measurements were conducted in ten Labrador retrievers with one-week washout: (i) baseline values, (ii) latanoprost at 8 AM, (iii) tropicamide at 8 AM, (iv) latanoprost at 8 AM and tropicamide at 11 AM, and (v) latanoprost at 8 AM and atropine at 11 AM (n = 4). At 4 PM, TE PD was 5.88 ± 0.59, 3.62 ± 0.66, 6.33 ± 1.00, 5.42 ± 0.57, and 8.12 ± 1.24 mm in sessions 1-5, respectively. TE PD was significantly different between treatment sessions 2, 4, and 5 (P = 0.018, Friedman), being most mydriatic in session 5. At 4 PM, TE IOP was 11.27 ± 2.07, 7.10 ± 1.07, 11.1 ± 2.21, 7.70 ± 1.85, and 8.87 ± 1.42 mm Hg in sessions 1-5, respectively, with no differences between treatment sessions 2, 4, and 5 (P = 0.105, Friedman). Tropicamide and atropine counteracted latanoprost's miotic effect, with atropine causing significantly larger mydriasis, sufficient for indirect ophthalmoscopy. Neither drug counteracted the hypotensive effect of latanoprost during this study period. Further studies are necessary to evaluate the potential risks in glaucomatous dogs.


Indications for genetic study in gastro-entero-pancreatic and thoracic neuroendocrine tumors.
Gastro-entero-pancreatic (GEP-NET) and thoracic neuroendocrine tumours (NETs) are one of the most heritable groups of neoplasms in the body, being multiple endocrine neoplasia syndrome type 1 (MEN1), the genetic syndrome most frequently associated with this type of tumours. Moreover, Von Hippel Lindau syndrome, tuberous sclerosis, type 4 multiple neoplasia syndrome, and type 1 neurofibromatosis are associated with an increased risk of developing GEP-NETs. Another important aspect in GEP-NETs and thoracic NETs is the knowledge of the molecular background since the molecular profile of these tumours may have implications in the prognosis and in the response to specific treatments. This review summarizes the main indications for performing a genetic study in patients with GEP-NETs and thoracic NETs, and the methods used to carry it out. Moreover, it offers a description of the main hereditary syndromes associated with these NETs and their molecular background, as well as the clinical implications of the molecular profile.


Causes and predictors of immediate and short-term readmissions following percutaneous left atrial appendage closure procedure.
Percutaneous left atrial appendage device closure has been offered as an alternative to anticoagulation for high-risk patients with nonvalvular atrial fibrillation. Given the relative novelty of the procedure, we aimed to analyze the rates and causes of immediate (30 days) and short-term (90 days) readmission after the procedure. We performed a retrospective observational study using the Nationwide Readmissions Database for 2018. We studied 29 449 hospitalizations for percutaneous left atrial appendage (LAA) device closure. In both the 30- and 90-day cohorts, the most common causes of readmissions were gastrointestinal bleeding (16.1% and 14.8%), heart failure exacerbation (11.1% and 11.6%), and atrial fibrillation (6.2% and 7.2%). Female sex, liver disease, chronic kidney disease, chronic pulmonary disease, presence of heart failure, human immunodeficiency virus/acquired immunodeficiency syndrome status, and diabetes mellitus were independently associated with higher odds of readmission in both cohorts. Our study highlights the need for further deliberation on the choice and duration of anticoagulation periprocedurally after percutaneous LAA closure, especially among those with high bleeding risk. It also highlights the need for optimization of heart failure status periprocedurally to avoid readmissions for exacerbations.


The cost of treating small cell lung cancer.
To determine the cost of treating small cell lung cancer (SCLC) and to assess quality-adjusted survival in these patients. Retrospective analysis. Westmead Hospital, a tertiary referral institution. Consecutive sample of 31 patients with histologically proved SCLC, treated between January 1987 and December 1987. The cost of investigation, hospitalisation, chemotherapy, radiotherapy and follow-up of patients overall and for those with limited and extensive disease respectively. Quality-adjusted survival was based on a Q-TWiST analysis. The median overall cost per patient was $14,413 (range, $1188-$39,598) for all patients and for limited disease and extensive disease was $18,234 (range, $1914-$39,598) and $13,177 (range, $1188-$32,798) respectively. The two major costs were hospitalisation (42%) and chemotherapy (18%). Radiotherapy accounted for 11% of all costs. The Q-TWiST analysis suggests that for patients with limited disease, quality-adjusted survival is similar to absolute survival. The treatment of SCLC at our institution was expensive but the cost may be reduced by reduction in the duration of hospitalisation, the use of less expensive combination drug regimens, or the use of "true" outpatient chemotherapy. Despite intensive therapy, patients with limited disease maintained a reasonable quality of life.


Sodium azide is less suitable as a positive control of drug-induced lethality for in vitro clonogenic assays.
Sodium azide (6 mg/ml) was used as a positive control for drug-induced lethality in an in vitro clonogenic assay. Petri dishes containing control and sodium azide treated cultures of WiDr cells were placed together in a large Petri dish and incubated at 37 degrees C in an atmosphere of 10% CO2 in air. No growth was observed. Control cells formed colonies only when the dishes were separated from the sodium azide dishes. Using a microtiter plate the toxic effect was inversely related to the distance of the test cultures from the sodium azide treated cultures. These results suggested the formation of a toxic gas or vapour from sodium azide under cell culture conditions, probably an azide. Chemical analysis was based on characteristic reactions, such as the production of a precipitate with silver ions or formation of a red-coloured complex with ferric salts. On a microtiter plate, a gradient of the expected precipitate or red colour was observed, the highest amounts adjacent to the wells containing sodium azide. These results show that sodium azide acts as a positive control of drug-induced lethality for in vitro clonogenic assays. However, the formation of a highly toxic vapour, most likely hydrazaic acid, makes it a less suitable standard.


Traumatic axillary artery dissection with radial artery embolism.
This report describes a case of pathologically proven traumatic arterial dissection, presenting as complete occlusion of the axillary artery with radial artery embolism. Occlusion of the axillary artery by traumatic dissection mimicked transection and radial artery embolism mimicked congenital absence of the radial artery on the initial angiogram, but these were correctly diagnosed with the following sonogram.


Surgical Management of Nasal Airway Obstruction.
The management and diagnosis of nasal airway obstruction requires an understanding of the form and function of the nose. Nasal airway obstruction can be structural, physiologic, or a combination of both. Anatomic causes of airway obstruction include septal deviation, internal nasal valve narrowing, external nasal valve collapse, and inferior turbinate hypertrophy. Thus, the management of nasal air obstruction must be selective and carefully considered. The goal of surgery is to address the deformity and not just enlarge the nasal cavity.


Potential usefulness of Mediterranean diet polyphenols against COVID-19-induced inflammation: a review of the current knowledge.
The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence of COVID-19 and its severity, and the Mediterranean diet is one of them. This review gathers data from studies supporting the potential usefulness of the main phenolic compounds present in the Mediterranean diet, based on their antioxidant and anti-inflammatory effects, as preventive/therapeutic agents against COVID-19. The current evidence supports the potential benefits that hydroxytyrosol, resveratrol, flavonols such as quercetin, flavanols like catechins, and flavanones on the order of naringenin could have on COVID-19. This is due to the increase in the synthesis and translocations of Nrf-2, which increases the activity of antioxidant enzymes and thus reduces ROS production, the scavenging of free radicals, and the suppression of the activity of MMP-9, which is involved in the cytokine storm, and the inhibition of NF-κB.


Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia.
Wild waterfowl, including ducks, are natural hosts of influenza A viruses. These viruses rarely caused disease in ducks until 2002, when some H5N1 strains became highly pathogenic. Here we show that these H5N1 viruses are reverting to nonpathogenicity in ducks. Ducks experimentally infected with viruses isolated between 2003 and 2004 shed virus for an extended time (up to 17 days), during which variant viruses with low pathogenicity were selected. These results suggest that the duck has become the "Trojan horse" of Asian H5N1 influenza viruses. The ducks that are unaffected by infection with these viruses continue to circulate these viruses, presenting a pandemic threat.


[Local haemostasis with an adhesive cyanoacrylate-coated membrane following tooth extraction in patients under anticoagulant or anti-platelet therapy].
Assessment of a local hemostasis with a compressive, extemporaneous gutter glued to the alveolar crest after tooth avulsion in patients under anticoagulant and/or platelet aggregation inhibitors, and economical impact of this technique. Ninety-seven tooth extractions were performed in patients under AVK and/or anti-platelet drugs. The interventions were consecutive and concerned 251 teeth (138 different alveolar sites). The extraction alveolus was protected by an absorbable oxycellulose membrane coated with sterilized cyanoacrylate adhesive for medical use. This procedure was used with all patients, whatever the hemorrhagic risk (the only inclusion criterion was INR less than 4 for patients under AVK). All procedures were performed under local anesthesia. There was one hemorrhagic complication (0.72%) due to mechanical gutter destruction by an antagonist tooth. The adhesive did not run, there was no tissue necrosis, and no wound infection requiring gutter removal. This local hemostasis procedure is reliable. It may be an alternative to substitution of heparin, without or with hospitalization. This procedure, requiring modification of treatment, greatly decreases healthcare costs. Contra-indications include the presence of an antagonist tooth harmful for the gutter, and patients with impaired consciousness or tongue dyspraxia.


Peripheral nerve injuries in the pediatric population: a review of the literature. Part II: entrapment neuropathies.
Entrapment neuropathies are infrequent in children, and therefore remain unrecognized. The incidence of radial, median, and cubital mononeuropathies are all similar. Despite the rarity of such cases, extensive, albeit scattered, literature has accumulated concerning entrapment neuropathies in children. To the literature concerning entrapment neuropathies in children. A systematic review of the existing literature has been made. The management of chronic pediatric pain is very important in such patients to prevent youths from experiencing prolonged absences from school, sports, or other productive activities, and limit the psychological burden of chronic disease. Nonsurgical treatment of both cubital and carpal tunnel syndromes has been disappointing in pediatric patients, with only limited success; and, to date, there is no clear explanation for the outcome differences generated by nonsurgical management between adults and youths. Simple decompression of the ulnar nerve at the elbow also has much higher rates of failure in children than in adults. The presence of an entrapment neuropathy (specially carpal tunnel syndrome) in a pediatric-age patient should alert medical care providers to the potential of some underlying genetic condition or syndrome.


Triple-D network for efficient undersampled magnetic resonance images reconstruction.
Compressed sensing (CS) theory can help accelerate magnetic resonance imaging (MRI) by sampling partial k-space measurements. However, conventional optimization-based CS-MRI methods are often time-consuming and are based on fixed transform or shallow image dictionaries, which limits modeling capabilities. Recently, deep learning models have been used to solve the CS-MRI problem. However, recent researches have focused on modeling in image domain, and the potential of k-space modeling capability has not been utilized seriously. In this paper, we propose a deep model called Dual Domain Dense network (Triple-D network), which consisted of some k-space and image domain sub-network. These sub-networks are connected with dense connections, which can utilize feature maps at different levels to enhance performance. To further promote model capabilities, we use two strategies: multi-supervision strategies, which can avoid loss of supervision information; channel-wise attention layer (CA layer), which can adaptively adjust the weight of the feature map. Experimental results show that the proposed Triple-D network provides promising performance in CS-MRI, and it can effectively work on different sampling trajectories and noisy settings.


Hereditary hemorrhagic telangiectasia is caused by the Q490X mutation of the ACVRL1 gene in a large Arab family: support of homozygous lethality.
In a large Saudi Arabian family with hereditary hemorrhagic telangiectasia (HHT), we identified ACVRL1 (ALK1) nonsense mutation Q490X in 40 HHT patients and three healthy children, but neither in 11 individuals with epistaxis, 41 other healthy family members, nor in 50 healthy unrelated Saudi Arabian controls. Sequence analysis of the entire coding region of the ACVRL1 and ENG genes in five of the 11 epistaxic individuals did not reveal any other disease-causing mutation. Epistaxis seems to be a relatively common phenocopy of HHT in the family under study. One couple, both affected by HHT and carriers of Q490X, had 12 pregnancies. Three of them ended in spontaneous abortion, four in early neonatal death, and only five yielded living offspring, all of which had HHT and were Q490X heterozygous. This observation corroborates previous claims that homozygosity for HHT-causing mutations is lethal.


Direct structure elucidation by powder X-ray diffraction of a metal-organic framework material prepared by solvent-free grinding.
Powder X-ray diffraction (XRD) has been exploited to establish the structural properties of a porous interpenetrated mixed-ligand metal-organic framework material prepared by solid-state grinding, recognizing that product phases from mechanochemical synthesis are typically microcrystalline powders. The importance of subjecting the powder XRD data to rigorous scrutiny in such applications is emphasized.


Assessment of cancer control capacity and readiness: the role of the International Atomic Energy Agency.
During the past six decades, the International Atomic Energy Agency (IAEA) has helped to address the growing cancer burden, by delivering substantial cancer-related assistance to low-income and middle-income member states. IAEA assistance has primarily been facilitated through sustainable radiotherapy and nuclear medicine programmes to establish safe and effective diagnostic imaging, nuclear medicine, and radiotherapy capacity to safely treat patients with cancer. Planning of a National Cancer Control Programme starts with a needs assessment of all aspects of cancer control in the country to ensure evidence-based strategies are adapted to the country's specific needs. The IAEA offers its member states a tool, known as an integrated mission of Programme of Action for Cancer Therapy Review, to assess the status of national capacities for implementation and delivery of cancer control plans and activities and the readiness to develop and implement a long-term radiation medicine infrastructure and plan to improve capacity.


An Update on Key Nutritional Factors in Ferret Nutrition.
It is understood that ferrets are obligate carnivores. Constraints of manufacturing and cost make it difficult to align a single commercial diet to meet all physiological needs of ferrets. Thus, a combination of dietary formats should be offered. Ferret diets should be high in protein and fat and low in carbohydrates. Emphasis should be placed on fat concentrations and protein-to-fat ratios, which can be targeted at 2:1. Plant-based ingredients do not have a place in ferret diets and could unbalance diets, particularly in amino acids. Items such as fruits, while highly palatable to ferrets, should be avoided.


Compostable cutlery and waste management: an LCA approach.
The use of disposable cutlery in fast food restaurants and canteens in the current management scenario generates mixed heterogeneous waste (containing food waste and non-compostable plastic cutlery). The waste is not recyclable and is disposed of in landfills or incinerated with or without energy recovery. Using biodegradable and compostable (B&C) plastic cutlery, an alternative management scenario is possible. The resulting mixed homogeneous waste (containing food waste and compostable plastic cutlery) can be recycled through organic recovery, i.e., composting. This LCA study, whose functional unit is "serving 1000 meals", shows that remarkable improvements can be obtained by shifting from the current scenario to the alternative scenario (based on B&C cutlery and final organic recovery of the total waste). The non-renewable energy consumption changes from 1490 to 128MJ (an overall 10-fold energy savings) and the CO(2) equivalents emission changes from 64 to 22 CO(2) eq. (an overall 3-fold GHG savings).


Design of an IoT-based indoor tracking and condition monitoring system for the safe and transparent management of drums storing low- and intermediate-level radioactive waste.
Regulatory agencies and civil society organizations concerned with radioactive waste management are demanding maximized safety management of radioactive-waste-containing drums using advanced technology for more efficient and safe management. In the present paper, we propose a sensor system that can track and monitor drums containing low- and intermediate-level radioactive waste using advanced technology based on the Internet of Things (IoT). The proposed system consists of drum nodes, pallet nodes, and gateways. A drum node and magnetic sensor installed on a drum can be used to remotely check whether the drum lid is open or closed, and the location of the drum can be tracked using a near-field communication reader and an infrared module installed on the pallet node. Considering that radioactive waste is stored for a long time period, the proposed sensors are designed for low power consumption. Moreover, a pilot test involving 48 drums and 12 pallets was conducted to verify the system prototype. Accordingly, from the results of the pilot test, drawbacks were noted and solutions were proposed to improve the system in future work. Implications: We designed a test bed by fabricating a sensor-system prototype and used it in a simulation experiment. The results of this study will be used as basic data for establishing safety measures for radioactive waste management in the future through computer simulation of radioactive waste anomalies in a digital-twin system.


DNA excision repair and double-strand break repair gene polymorphisms and the level of chromosome aberration in children with long-term exposure to radon.
To study polymorphic variants of repair genes in people affected by long-term exposure to radon. The chromosome aberration frequency in peripheral blood lymphocytes was used as the biological marker of genotoxicity. Genotyping of 12 single nucleotide polymorphisms in DNA repair genes (APE, XRCC1, OGG1, ADPRT, XpC, XpD, XpG, Lig4 and NBS1) was performed in children with long-term resident exposure to radon. Quantification of the aberrations was performed using light microscopy. The total frequency of aberrations was increased in carriers of the G/G genotype for the XpD gene (rs13181) polymorphism in recessive model confirmed by the results of ROC-analysis ('satisfactory predictor', AUC = 0.609). Single chromosome fragments frequency was increased in carriers of the G/G genotype in comparison with the T/T genotype. In respect to the total frequency of aberrations, the G/G genotype for the XpG gene (rs17655) polymorphism was also identified as a 'satisfactory predictor' (AUC = 0.605). Carriers of the T/C genotype for the ADPRT gene (rs1136410) polymorphism were characterized by an increased level of single fragments relative to the T/T genotype. The relationships with several types of cytogenetic damage suggest these three SNP (rs13181, rs17655 and rs1136410) may be considered radiosensitivity markers.


Progress in understanding type 1 diabetes through its genetic overlap with other autoimmune diseases.
Type 1 diabetes mellitus (T1DM) is the most common autoimmune disease in pediatrics with a prevalence of roughly 1 in 500 children in the USA. Genome-wide association studies have identified more than 50 variants associated with increased risk for type 1 diabetes. Comparison of these variants with those identified in other autoimmune diseases reveals three important findings: (1) there is a high degree of overlap in implicated variants in diseases with similar pathophysiology, (2) in diseases with differing pathophysiology the same variants are often implicated in opposite roles, (3) in diseases with differing pathophysiology that have many non-overlapping or oppositely implicated variants there are still several variants which are overlapping or shared. Thus, the genetic overlap between T1DM and other autoimmune diseases forms the basis for our understanding of druggable targets in type 1 diabetes.


A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal.
The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic cells. It comprises one 20S catalytic complex (composed of four stacked rings of seven members) and two axially positioned 19S regulatory complexes (each containing about 18 subunits) that control substrate access to the catalytic chamber. In most cases, targeting to the 26S proteasome depends on tagging of the substrate with a specific type of polyubiquitin chain. Recognition of this signal is followed by substrate unfolding and translocation, which are presumably catalysed by one or more of six distinct AAA ATPases located in the base-a ring-like 19S subdomain that abuts the axial pore of the 20S complex and exhibits chaperone activity in vitro. Despite the importance of polyubiquitin chain recognition in proteasome function, the site of this signal's interaction with the 19S complex has not been identified previously. Here we use crosslinking to a reactive polyubiquitin chain to show that a specific ATPase subunit, S6' (also known as Rpt5), contacts the bound chain. The interaction of this signal with 26S proteasomes is modulated by ATP hydrolysis. Our results suggest that productive recognition of the proteolytic signal, as well as proteasome assembly and substrate unfolding, are ATP-dependent events.


Catalytic activity and thermostability of enzymes immobilized on silanized surface: influence of the crosslinking agent.
In this work, we investigate the influence of crosslinkers on the operational and heat stability of immobilized enzymes on a silanized silicon surface. To this end, glucose-6-phosphate dehydrogenase (G6PDH), a model multimeric enzyme, was attached through bifunctional crosslinkers able to bind covalently the -NH2 in the silane layer and of amine residues in the enzyme. Five bifunctional crosslinkers in the form of "X-spacer-X" were used, differing by the reactive functional groups (X=aldehyde: -CHO, isothiocyanate: -NCS, isocyanate: -NCO), by the nature of the spacer chain (aromatic or aliphatic) or by the geometry (bifunctional groups positioned in meta- or para- on an aromatic ring). A thermostability enhancement has been obtained for enzymes immobilized using 1,4-phenylene diisothiocyanate (PDC) and 1,4-phenylene diisocyanate (DIC). Moreover, using the latter crosslinker, activity was the mostly preserved upon successive uses, thus giving the best operational stability achieved. Changing the geometry of the cross-linker, i.e., 1,4- as compared to 1,3-phenylene diisothiocyanate (PDC and MDC, respectively), has a crucial effect on operational and thermal stabilities. Indeed, among all used crosslinkers, the most important loss was observed for MDC (residual activity after 6 times use is ~16%). Using dialdehyde crosslinkers: glutaraldehyde (GA) and terephtalaldehyde (TE), activity was significantly less well preserved than with DIC and PDC (for GA and TE, a loss of about 50% at 30°C against no loss for PDC and DIC). These effects can be explained by a multipoint attachment model, in which a higher number of anchoring points stabilizes the three-dimensional structure and especially the binding of the two subunits in the active dimer, at the expense of a greater rigidity which is detrimental to the absolute activity. The differences observed with the crosslinkers are mainly due to steric hindrance at the interface which seems to be greatly influenced by the structure and the reactivity of the linkers.


Mammary tumorigenesis in C3H/HeN-MTV + mice treated with diethylstilboestrol for varying periods.
C3H/HeN-MTV+ female mice were fed diets containing 320 or 640 ppb diethylstilboestrol (DES). DES feeding was started at 3 wk of age and was either continued throughout life or discontinued after 4, 8 or 26 wk of administration. A control group consisted of mice fed the same diet without DES, for the duration of the experiment. Mice were killed when palpable body masses (presumed to be mammary adenocarcinomas) reached a diameter of 1 cm. Adenocarcinomas developed in 79% of control mice and 96% of the mice exposed to DES for 26 wk, irrespective of the dose. The frequency and rate of removal of tumour-bearing mice were not increased further with lifetime exposure at a given dose. The time at which the first tumour occurred was largely dependent on the duration of exposure, not dose. The rate of occurrence of subsequent tumours was dependent on dose and duration of exposure; the rate of removal of mice with mammary adenocarcinomas was significantly greater at 640 ppb than at 320 ppb DES. Tumour frequency was 83% in mice exposed to 320 ppb DES for 8 wk and in those exposed for 4 wk; however, tumours developed at a faster rate in mice exposed for 8 wk. Tumour frequency was 94-96% in mice exposed to 640 ppb DES for 4 wk and 8 wk, and tumours developed more rapidly in mice exposed for 8 wk than in those exposed for 4 wk. When data were plotted as log-dose v. log-t50 (time to a probability that half the mice would be removed with mammary tumours) linear extrapolation to the control log-t50 gave an estimate of the no-effect level of exposure to DES. This estimate was remarkably consistent for all data sets (40-93 ppb) and was independent of the duration of exposure.


In vitro toxicological assessment of free 3-MCPD and select 3-MCPD esters on human proximal tubule HK-2 cells.
Chloropropanols are chemical contaminants that can be formed during industrial processing of foods, such as lipids used in commercially available infant and toddler formula in the USA. Many researchers have studied the most common chloropropanol contaminant, 3-monochloropropane-1,2-diol (3-MCPD), as well as its lipid ester derivatives. A plethora of toxicological outcomes have been described in vivo, including effects on the heart, nervous system, reproductive organs, and kidneys. To better understand the concordance of some of these effects to in vitro outcomes, we focused our research on using an in vitro cellular model to investigate whether the proximal tubule cells of the kidney would be vulnerable to the effects of free 3-MCPD and nine of its common esters in commercial formula. Using the established human kidney proximal tubule cell line, HK-2, we performed 24-h treatments using 3-MCPD and nine mono- or di-esters derived from palmitate, oleate, and linoleate. By directly exposing HK-2 cells at treatment doses ranging from 0 to 100 μM, we could evaluate their effects on cell viability, mitochondrial health, reactive oxygen species (ROS) production, and other endpoints of toxicity. Since chloropropanols reportedly inhibit cellular metabolism through interference with glycolysis, we also tested the extent of this mechanism. Overall, we found mild but statistically significant evidence of cytotoxicity at the highest tested treatment concentrations, which were also associated with mitochondrial dysfunction and transient perturbations in cellular metabolism. Based on these findings, further studies will be required to better understand the effects of these compounds under conditions that are more physiologically relevant to human infant and toddler proximal tubules in order to mimic their exposure to chloropropanol-containing foods.


Prevalence of Sexually Transmitted Infection in Teenage Pregnancy in Rajavithi Hospital, Thailand.
Behavioral and social changes in the modern era have triggered an increase in the incidence of early sexual contact and teenage pregnancy. Since there is no routine Gonococcal & Chlamydial (GC & CT) screening in teens in antenatal clinics in Thailand, the present study was performed to find the prevalence of STI, especially Chlamydial infection, in teenage pregnancy. To evaluate the prevalence of sexually transmitted infections (STIs), especially Chlamydial infection (CT), in teenage pregnancy and its related factors. One hundred and twenty-one teenage pregnancies were recruited at the ANC in Rajavithi Hospital from October 2006 to May 2007. After signing informed consent forms, they were asked to answer questionnaires about baseline data, sexual information and risk factors, after which urine specimens were collected for screening for GC and CT using the PCR technique (AMPLICOR by Roche). Later, pelvic examination was per formed by the gynecologist at the STD (sexually transmitted disease) clinic. All the data and LAB results were recorded and analyzed by the SPSS program. Numbers, percentages, means with SD, Chi-squared test, Fisher's exact test and odds ratio were used. Potential risk factors were analyzed using binary logistic regression. The prevalence of STI in pregnant teenagers was 28.1% (CT = 19.8%, GC = 1.7%, hepatitis B = 3.3%, trichomoniasis 1.7%, Herpes simplex = 0.8% and condyloma acuminata = 0.8%). No Syphilis, chancroid or HIV were found in the present study Other non-STI like candidiasis and bacterial vaginosis were found in 45.5% of participants (candidiasis and bacterial vaginosis at 19.0% and 24.8%, respectively). The risk of CT infection was significantly related (6.9 times higher) to having previous sexual contact before the current partner (95% CI, 1.8-27.0). STI, especially Chlamydial infection, was found in a significant number of teenage pregnancies. Measures should be taken to prevent this resulting in complicated outcomes in the future.


C-reactive protein decreases expression of thrombomodulin and endothelial protein C receptor in human endothelial cells.
C-reactive protein (CRP) is associated with atherosclerosis and thrombosis. However, it is unclear whether CRP has direct effects on the antithrombogenic properties of endothelial cells. The objective of the present study was to determine the effect of CRP on the expression of thrombomodulin (TM) and the endothelial protein C receptor (EPCR) in human endothelial cells. Human coronary artery endothelial cells (HCAECs) were treated with CRP in a dose- and time-dependent manner. The messenger RNA levels of TM and EPCR were determined by real-time polymerase chain reaction. Anti-CD32 antibody and curcumin were used to block the potential effects of CRP. In HCAECs, CRP (10 and 25 microg/mL) significantly reduced TM messenger RNA levels by 18 and 30%, respectively, compared with controls (P < .05). This effect was also confirmed in other types of human endothelial cells from umbilical veins and skin microvessels. The cells treated with CRP (10 and 25 microg/mL) showed significant reductions of EPCR mRNA levels by 34% and 33%, respectively (P < .05). Anti-CD32 antibody partially blocked CRP-induced downregulation of TM and EPCR in HCAECs. Furthermore, curcumin (5 and 10 microM) in combination with CRP (10 microg/mL) significantly increased TM mRNA levels by 45 and 100%, respectively, and increased EPCR mRNA levels by 24 and 45%, respectively, compared with those in CRP-treated cells (P < .05). CRP significantly decreases the expression of TM and EPCR in human endothelial cells, thereby promoting thrombogenic conditions. This effect is partially mediated by CD32. Curcumin completely blocks CRP-induced downregulation of TM and EPCR in HCAECs.


Dual targeting of IGF-1R and ErbB3 as a potential therapeutic regimen for ovarian cancer.
Therapeutically targeting receptor tyrosine kinases has proven to be paramount to overcoming chemotherapy resistance in several cancer indications, improving patient outcomes. Insulin-Like Growth Factor Receptor 1 (IGF-1R) and Epidermal Growth Factor Receptor 3 (ErbB3) have been implicated as two such drivers of resistance, however their simultaneous role in ovarian cancer chemotherapy resistance remains poorly elucidated. The aim of this work is to determine the effects of dual IGF-1R/ErbB3 inhibition on ovarian cancer cell signaling, growth, and in vivo efficacy. Assessment of in vitro chemotherapy response across a panel of ovarian cancer cell lines revealed that increased IGF-1R cell surface expression correlates with decreased sensitivity to chemotherapy, and that growth induced by IGF-1R and ErbB3 ligands is blocked by the tetravalent bispecific antibody targeting IGF-1R and ErbB3, istiratumab. In vitro chemotherapy treatment increased ovarian cancer cell line capacity to activate prosurvival PI3K signaling in response to ligand, which could be prevented with istiratumab treatment. Furthermore, in vivo efficacy of standard of care chemotherapies using a xenograft model of ovarian cancer was potentiated with istiratumab. Our results suggest a role for IGF-1R and ErbB3 in driving chemotherapy resistance of ovarian cancer.


Estimating Granger causality after stimulus onset: a cautionary note.
How the brain processes sensory input to produce goal-oriented behavior is not well-understood. Advanced data acquisition technology in conjunction with novel statistical methods holds the key to future progress in this area. Recent studies have applied Granger causality to multivariate population recordings such as local field potential (LFP) or electroencephalography (EEG) in event-related paradigms. The aim is to reveal the detailed time course of stimulus-elicited information transaction among various sensory and motor cortices. Presently, interdependency measures like coherence and Granger causality are calculated on ongoing brain activity obtained by removing the average event-related potential (AERP) from each trial. In this paper we point out the pitfalls of this approach in light of the inevitable occurrence of trial-to-trial variability of event-related potentials in both amplitudes and latencies. Numerical simulations and experimental examples are used to illustrate the ideas. Special emphasis is placed on the important role played by single trial analysis of event-related potentials in experimentally establishing the main conclusion.


Functional characterization and gene expression profile of perforin-2 in starry flounder (Platichthys stellatus).
The membrane attack complex/perforin (MACPF) superfamily consists of multifunctional proteins that form pores on the membrane surface of microorganisms to induce their death and have various immune-related functions. PFN2 is a perforin-like protein with an MACPF domain, and humans with deficient PFN2 levels have increased susceptibility to bacterial infection, which can lead to fatal consequences for some patients. Therefore, in this study, we confirmed the antimicrobial function of PFN2 in starry flounder (Platichthys stellatus). The molecular properties were confirmed based on the verified amino acid sequence of PsPFN2. In addition, the expression characteristics of tissue-specific and pathogen-specific PsPFN2 mRNA were also confirmed. The recombinant protein was produced using Escherichia coli, and the antimicrobial activity was then confirmed. The coding sequence of PFN2 (PsPFN2) in P. stellatus consists of 710 residues. The MACPF domain was conserved throughout evolution, as shown by multiple sequence alignment and phylogenetic analysis. PsPFN2 mRNA is abundantly distributed in immune-related organs such as the spleen and gills of healthy starry flounder, and significant expression changes were confirmed after artificial infection by bacteria or viruses. We cloned the MACPF domain region of PFN2 to produce a recombinant protein (rPFN2) and confirmed its antibacterial effect against a wide range of bacterial species and the parasite (Miamiensis avidus).


Wheat NAC transcription factor TaNAC29 is involved in response to salt stress.
Soil salinity is considered as one of the most severe abiotic stress factors, which limit plant growth and cause significant losses in crop yield. NAC transcription factors have been proven to play vital roles in abiotic stress signaling in plants. As a staple crop, wheat production is severely constrained by salt stress whereas only a few NAC genes have been characterized functionally. To promote the application of NAC genes in wheat improvement by genetic engineering, a NAC gene designated TaNAC29 was characterized in common wheat. Expression analysis showed that TaNAC29 gene was involved in response to salt, drought and ABA treatments. TaNAC29 protein displays transactivation activity. To determine its role, transgenic Arabidopsis overexpressing TaNAC29 controlled by the CaMV-35S promoter was generated and subjected to salt stress for morphological and physiological assays. Morphological analysis showed that transgenic plants had enhanced tolerance to salt stress, as indicated by improved physiological traits, including more green leaves, reduced H2O2 accumulation, strengthened cell membrane stability and higher SOD, POD, CAT and APX activities. Moreover, the transcript levels of stress-related genes were significantly higher in TaNAC29 overexpression line than those in WT under salt treatment. Taken together, our results demonstrate that TaNAC29 confers salt stress tolerance through reducing H2O2 accumulation and membrane damage by enhancing the antioxidant system, and participating in regulating the abiotic stress-responsive signaling pathway.


Retrospective Analysis of Survival in Patients with Brain Metastases from an Unknown Primary Tumor.
To evaluate the patients with brain metastases from unknown primary (BMUP) cancers, and to analyze the prognostic factors and survival rates. We conducted a retrospective study with 110 patients (mean age: 62.8 years [range 23?90], n=85- 77.3% male and n=25-22.7% female) with BMUP cancers at the time of diagnosis, who presented to our outpatient oncology clinic between January 2015 and December 2019. We employed the following variables as significant prognostic factors for a prominent index of patients? survival: age, gender, Karnofsky performance score (KPS), number of metastatic lesions, primary site, and type of treatment were analyzed for their prognostic effects on survival outcomes. Patients? survival was evaluated from plotted Kaplan? Meier curves, and the log-rank test was used for univariate analysis. The mean follow-up was 13 months (range 4?60 months). The means of survival after the diagnosis of brain metastasis was 18.7 months for the study group. Lung cancer was the most common primary tumor (74, 5%). The KPS and number of lesions were found to have a prognostic effect on survival. Survival analysis showed no statistical significance with age and gender, primary site, type of treatment. This study showed that KPS, and the number of lesions affect the survival outcomes but both the other variables. Therefore, BMUP cancer is indeed related to poor prognosis.


Auditory apparent motion under binaural and monaural listening conditions.
This investigation examined the ability of listeners to perceive apparent motion under binaural and monaural listening conditions. Fifty-millisecond broadband noise sources were presented through two speakers separated in space by either 10 degrees, 40 degrees, or 160 degrees, centered about the subject's midline. On each trial, the sources were temporally separated by 1 of 12 interstimulus onset intervals (ISOIs). Six listeners were asked to place their experience of these sounds into one of five categories (single sound, simultaneous sounds, continuous motion, broken motion, or successive sounds), and to indicate either the proper temporal sequence of presentation or the direction of motion, depending on whether or not motion was perceived. Each listener was tested at all spatial separations under binaural and monaural listening conditions. Motion was perceived in the binaural listening condition at all spatial separations tested for ISOIs between 20 and 130 msec. In the monaural listening condition, motion was reliably heard by all subjects at 10 degrees and 40 degrees for the same range of ISOIs. At 160 degrees, only 3 of the 6 subjects consistently reported motion. However, when motion was perceived in the monaural condition, the direction of motion could not be determined.


Ruptured spleen in the adult: an account of 205 cases with particular reference to non-operative management. Papua New Guinea Splenic Injury Study Group.
A series of 205 ruptured adult spleens, half of them due to personal assault, has been collected from several hospitals. In some of these cases a trial of non-operative management has become standard practice unless other abdominal injuries are suspected. One hundred and thirty-seven cases were managed this way initially, successfully so in 80%. Splenectomy was performed in 70 patients with eight deaths; three of them in the 27 instances where non-operative management was said to have failed. None of these eight deaths was due to operative delay.


Diagnostic Accuracy of Diastolic Fractional Flow Reserve for Functional Evaluation of Coronary Stenosis: DIASTOLE Study.
In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure-derived physiological index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated. The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory-based environment. In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease. Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval [CI]: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113). Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906).


Topographic maps of brain electrical activity--pitfalls and precautions.
Topographic mapping of brain electrical activity is a popular, powerful, and potentially misleading technique. The map lies at the end of a long chain of physiological, technical, electronic, and mathematical processes and is vulnerable to artifact, error, and distortion at many points. Close attention must be paid to data collection parameters, subject cooperation, minimization of artifact, limitations of resolutions, selection, and transformation of parameters for display, and map generation strategy to yield an accurate, physiologically interpretable map. Review of the data at each step of analysis, from the paper electroencephalogram (EEG) to sets of maps on video display, may be necessary for optimum understanding. Development of more sophisticated qualitative and quantitative concepts of "normal" physiology is needed. These improvements in electrophysiological data analysis demand, rather than obviate, sophistication on the part of the user.


Cardiometabolic risk reduction through lifestyle intervention programs in the Brazilian public health system.
Public health strategies to reduce cardiovascular morbidity and mortality should focus on global cardiometabolic risk reduction. The efficacy of lifestyle changes to prevent type 2 diabetes have been demonstrated, but low-cost interventions to reduce cardiometabolic risk in Latin-America have been rarely reported. Our group developed 2 programs to promote health of high-risk individuals attending a primary care center in Brazil. This study compared the effects of two 9-month lifestyle interventions, one based on medical consultations (traditional) and another with 13 multi-professional group sessions in addition to the medical consultations (intensive) on cardiometabolic parameters. Adults were eligible if they had pre-diabetes (according to the American Diabetes Association) and/or metabolic syndrome (International Diabetes Federation criteria for Latin-America). Data were expressed as means and standard deviations or percentages and compared between groups or testing visits. A p-value < 0.05 was considered significant. 180 individuals agreed to participate (35.0% men, mean age 54.7 ± 12.3 years, 86.1% overweight or obese). 83 were allocated to the traditional and 97 to the intensive program. Both interventions reduced body mass index, waist circumference and tumor necrosis factor-α. Only intensive program reduced 2-hour plasma glucose and blood pressure and increased adiponectin values, but HDL-cholesterol increased only in the traditional. Also, responses to programs were better in intensive compared to traditional program in terms of blood pressure and adiponectin improvements. No new case of diabetes in intensive but 3 cases and one myocardial infarction in traditional program were detected. Both programs induced metabolic improvement in the short-term, but if better results in the intensive are due to higher awareness about risk and self-motivation deserves further investigation. In conclusion, these low-cost interventions are able to minimize cardiometabolic risk factors involved in the progression to type 2 diabetes and/or cardiovascular disease.


RTEL1 maintains genomic stability by suppressing homologous recombination.
Homologous recombination (HR) is an important conserved process for DNA repair and ensures maintenance of genome integrity. Inappropriate HR causes gross chromosomal rearrangements and tumorigenesis in mammals. In yeast, the Srs2 helicase eliminates inappropriate recombination events, but the functional equivalent of Srs2 in higher eukaryotes has been elusive. Here, we identify C. elegans RTEL-1 as a functional analog of Srs2 and describe its vertebrate counterpart, RTEL1, which is required for genome stability and tumor avoidance. We find that rtel-1 mutant worms and RTEL1-depleted human cells share characteristic phenotypes with yeast srs2 mutants: lethality upon deletion of the sgs1/BLM homolog, hyperrecombination, and DNA damage sensitivity. In vitro, purified human RTEL1 antagonizes HR by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis. We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer.


Clinical outcomes of multiple aneurysms microsurgical clipping: Evaluation of 90 patients.
The incidence of multiple intracranial aneurysms (MIAs) among patients who are diagnosed with aneurysm is 15-45% in the literature. Treatment options depend on the patient's status, age, aneurysm location and neurosurgeon's experience. In this study outcomes of micro-surgically clipped 90 patients have been evaluated. Medical records of 90 (49 women and 41 men) patients of MIAs who underwent surgery by the authors, during a 3-year period from 2011 to 2013 were retrospectively reviewed of prospectively collected patients' data. Surgically treated patients underwent a lateral supraorbital craniotomy followed by microsurgical clipping of all reachable aneurysms. The mean age of the sample is 50.8±11.9 (25-82) years. There were 67 patients presented with SAH. The most common complaint was severe headache of sudden onset (94%) in SAH group and migraine type headache (60.8%) in incidentally diagnosed group. According to location of the arteries; ACoA (50), MCA (R:49,L:45), ICA (R:34,L:15), PCoA (R:9,L:4), ACA (R:6,L:4), basilar artery (3) and SCA (2). Mortality rate was 13.3% (n=12), morbidity rate (new deficit was developed) was 18.8% (n=17) [7 out of them were partially/completely dependent on others for daily living activities before surgery (i.e. GOS<3)] and 67.8% (n=61) of the patients returned to their normal jobs and daily activities. Multiple cerebral aneurysms are not associated with a less favorable outcome than are single aneurysm cases. Authors prefer microsurgical clipping of all the aneurysms, be it on the reverse side, if the aneurysm location is reachable and that includes bilaterally presenting MIAs.


Bone Regenerative Efficacy of Limited-Dose Escherichia Coli-Derived rhBMP-2 With Biphasic Calcium Phosphate Carrier in Rabbit Calvarial Defect Model.
The aim of this study was to characterize the healing in rabbit calvarial bone defects after delivery of limited-dose (1.5 μg) Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2), and evaluate biphasic calcium phosphate (BCP) as a carrier. Four 8-mm diameter circular calvarial bone defects were made in 16 rabbits and filled with one of the following: (1) nothing, (2) BCP alone, (3) ErhBMP-2-loaded absorbable collagen sponge (ACS), or (4) ErhBMP-2-loaded BCP. The animals were allowed to heal for either 2 or 8 weeks and were evaluated in clinical, microcomputed tomographic, histological, and histomorphometric analyses. Microcomputed tomography revealed extensive new bone formation in both of the limited-dose ErhBMP-2-loaded groups. However, bony collapse of the upper defect borders was found in the ErhBMP-2-loaded ACS group. Histomorphometric examination revealed significantly greater new bone formation at 8 weeks than at 2 weeks in all 4 groups (P < 0.05). Both new bone formation and the size of the augmented area differed significantly between the ErhBMP-2-loaded BCP group (6.88 ± 0.74 and 19.62 ± 0.77) and the ErhBMP-2-loaded ACS group (3.04 ± 0.27 and 5.41 ± 0.43) at 8 weeks of healing. ErhBMP-2 promotes bone regeneration in rabbit calvarial defects, even at a limited dose (1.5 μg). The results of this study suggest that BCP is the more efficient carrier for this protein than ACS.


Raft coalescence and FcγRIIA activation upon sphingomyelin clustering induced by lysenin.
Activation of immunoreceptor FcγRIIA by cross-linking with antibodies is accompanied by coalescence of sphingolipid/cholesterol-rich membrane rafts leading to the formation of signaling platforms of the receptor. In this report we examined whether clustering of the raft lipid sphingomyelin can reciprocally induce partition of FcγRIIA to rafts. To induce sphingomyelin clustering, cells were exposed to non-lytic concentrations of GST-lysenin which specifically recognizes sphingomyelin. The lysenin/sphingomyelin complexes formed microscale assemblies composed of GST-lysenin oligomers engaging sphingomyelin of rafts. Upon sphingomyelin clustering, non-cross-linked FcγRIIA associated with raft-derived detergent-resistant membrane fractions as revealed by density gradient centrifugation. Pretreatment of cells with GST-lysenin also increased the size of detergent-insoluble molecular complexes of activated FcγRIIA. Sphingomyelin clustering triggered tyrosine phosphorylation of the receptor and its accompanying proteins, Cbl and NTAL, in the absence of receptor ligands and enhanced phosphorylation of these proteins in the ligand presence. These data indicate that clustering of plasma membrane sphingomyelin induces coalescence of rafts and triggers signaling events analogous to those caused by FcγRIIA activation.


Postnatal hippocampal granule cell agenesis in the rat: effects on two types of rhythmical slow activity (RSA) in two hippocampal generators.
Hippocampal slow wave activity was studied in rats which were normal or had been subjected to denate gyrus granule cell agenesis by focal X-irradiation starting at birth (0-day group) or two days (2-day group) of age. X-irradiation reduced adult brain weight, abolished most (2-day) or all (0-day) granule cells in the lower (endal) blade of the dentate gyrus, and reduced granule cell density by up to 70% in the upper (ectal) blade of the dentate gyrus. X-irradiation did not affect pyramidal cells of the hippocampus proper. Tracking with microelectrodes in urethane anesthetized rats given eserine, sensory, or brain stimulation showed two foci of hippocampal rhythmical slow activity (theta or RSA), one in stratum oriens of CA1 and one in stratum moleculare of the dentate gyrus. These were opposite in phase by approximately 180 degrees and separated by a null zone and phase reversal point occurring at stratum radiatum. There were no significant differences in the amplitude, frequency, null, or phase reveral points in the normal or X-irradiated groups. However, the width of the RSA amplitude peak in the ectal blade was reduced, correlated with the reduction in the length of the ectal blade, and the RSA amplitude peak in the lower blade was absent, correlated with the absence of the lower blade. The fast activity recorded in the hilus of normal rats was absent in the X-irradiated groups. RSA recorded during spontaneous movement (walking) had identical amplitude, frequency, anatomical foci, and phase in both the hippocampus proper and dentate gyrus in normal and X-irradiated rats. Antimuscarinic, but not antinicotinic, agents abolished anesthesia-related RSA, but not movement-related RSA, in all groups of rats. The results are discussed in terms of their relevance to the two-generator hypothesis of RSA.


The management of hypercholesterolaemia in patients with coronary artery disease referred for coronary angiography.
There are clear benefits in treating hypercholesterolaemia in patients with ischaemic heart disease, especially those with previous myocardial infarction. Following publication of trial evidence and treatment guidelines for hypercholesterolaemia, we investigated the current practice of the management of hypercholesterolaemia in patients with coronary artery disease referred for coronary angiography by general physicians. We prospectively reviewed 156 consecutive patients (117 men; mean age 61.5+/-9.6 [S.D.] years) with a history of angina pectoris who attended the day case unit for coronary angiography in a 10 week period. Nearly a tenth of these patients had not been screened for hypercholesterolaemia in this study. Of those patients with a cholesterol level > or =5.5 mmol/l, almost a quarter were not on a statin or any other cholesterol-lowering therapy. Continued effort should be given to the screening and effective management of hypercholesterolaemia in patients with coronary artery disease.


Cytochrome P-450 and monooxygenase activity in hepatic microsomes from N-phenylimidazole-treated rats.
Repeated administration of N-phenylimidazole (PI) to rats (3 daily doses of 200 mumol/kg/day) enhanced hepatic microsomal cytochrome P-450 levels (approx. 130%) and aminopyrine N-demethylase (APDM) and aniline p-hydroxylase (APH) activities (approx. 140%); aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (ECOD) activities were not enhanced over control values under similar conditions. Spectral studies with PI-induced microsomes indicated that although type II PI-binding characteristics were similar to those observed in controls, the 427 nm/455 nm absorbance ratio of the type III dihydrosafrole metabolite-cytochrome P-450 complex was lower than that in control microsomes. The results suggest that the inducing characteristics of PI bear some resemblance to those of phenobarbital (PB).


Gene-Hormone Therapy Interaction and Fracture Risk in Postmenopausal Women.
Evidence supports a protective effect of menopausal hormone therapy (HT) on bone. However, whether genetic susceptibility modifies the association of HT and fracture risk is not sufficiently explored. The objective was to test an interaction between genetic susceptibility and HT on fracture risk. We constructed two weighted genetic risk scores (GRSs) based on 16 fracture-associated variants (Fx-GRSs) and 50 bone mineral density variants (BMD-GRSs). We used Cox regression to estimate the main effects of GRSs and their interactions with HT on fracture risk. We estimated the relative excess risk due to interaction (RERI) as a measure of additive interaction. We also used the case-only approach to test for a multiplicative interaction. Forty US clinical centers. A total of 9922 genotyped white postmenopausal women (age, 50 to 79) from the Women's Health Initiative HT randomized trials. Adjudicated fracture incidence. Both GRSs were associated with fracture risk per 1-unit increment in GRS (hazard ratio, 1.04 [95% confidence interval, 1.02 to 1.06] for Fx-GRS and hazard ratio, 1.03 [95% confidence interval,1.02-1.04] for BMD-GRS). We found no evidence for multiplicative interaction for either of the GRS. However, we observed a substantial additive interaction, where the highest quartile of both GRSs and randomization to placebo have excess fracture risk: Fx-GRS P for RERI = 0.047, BMD-GRS P for RERI = 0.046. These results suggest that HT reduces fracture risk in postmenopausal women, especially in those at highest genetic risk of fracture and low BMD.


The use of temperature biofeedback in the treatment of chronic pain due to causalgia.
A patient with chronic pain due to a reflex sympathetic dystrophy in his hand and arm was successfully treated with temperature biofeedback after several months of conservative standard medical care brought little relief. Over the 18 treatment sessions the patient learned to emit a reliable handwarming response of 1 to 1.5 degrees C. Coincident with his learning, the pain in his hand and arm decreased markedly and remained absent at 1-year follow-up.


Deficient natural killer cell activity in patients with idiopathic dilated cardiomyopathy.
Dilated (congestive) cardiomyopathy is a disease of uncertain aetiology in which viral and immune factors are postulated to be of importance. Natural killer cells mediate natural resistance to viral infections and certain tumours. To evaluate natural killer (NK) activity in patients with cardiomyopathy, circulating peripheral blood mononuclear cells were obtained from 16 patients, from 54 normal blood donors, and from 14 patients with heart failure due to other causes (primarily coronary disease). NK activity was assessed as a lymphocyte to target cell ratio causing 50% killing (L/T50). L/T50 in normals was 17.2 +/- 11.4. A normal L/T50 distribution was also noted in heart failure controls (L/T50 = 19.6 +/- 9.9) and 8/16 cardiomyopathy patients (L/T50 = 17.5 +/- 9.5). NK activity was deficient (L/T50 greater than or equal to 50) in 8/16 patients with cardiomyopathy but in only 2/54 normals (p less than 0.001) and 0/14 heart failure controls (p less than 0.01). Of the several clinical and laboratory variables examined, only the frequency of the HLA-A3 tissue type was associated with NK deficiency. NK deficiency is an independent disease marker in about 50% of patients with cardiomyopathy and should be evaluated for a possible role in its pathogenesis.


A novel platform for electromagnetic navigated ultrasound bronchoscopy (EBUS).
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes is essential for lung cancer staging and distinction between curative and palliative treatment. Precise sampling is crucial. Navigation and multimodal imaging may improve the efficiency of EBUS-TBNA. We demonstrate a novel EBUS-TBNA navigation system in a dedicated airway phantom. Using a convex probe EBUS bronchoscope (CP-EBUS) with an integrated sensor for electromagnetic (EM) position tracking, we performed navigated CP-EBUS in a phantom. Preoperative computed tomography (CT) and real-time ultrasound (US) images were integrated into a navigation platform for EM navigated bronchoscopy. The coordinates of targets in CT and US volumes were registered in the navigation system, and the position deviation was calculated. The system visualized all tumor models and displayed their fused CT and US images in correct positions in the navigation system. Navigating the EBUS bronchoscope was fast and easy. Mean error observed between US and CT positions for 11 target lesions (37 measurements) was [Formula: see text] mm, maximum error was 5.9 mm. The feasibility of our novel navigated CP-EBUS system was successfully demonstrated. An EBUS navigation system is needed to meet future requirements of precise mediastinal lymph node mapping, and provides new opportunities for procedure documentation in EBUS-TBNA.


siRNA silencing of angiotensin-converting enzyme 2 reduced severe acute respiratory syndrome-associated coronavirus replications in Vero E6 cells.
The outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 has had a significant impact worldwide. No effective prophylaxis or treatment for SARS is available up to now. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-associated coronavirus (SARS-CoV). By expressing a U6 promoter-driven small interfering RNA containing sequences homologous to part of ACE2 mRNA, we successfully silenced ACE2 expression in Vero E6 cells. By detecting negative strand SARS-CoV RNA and measuring RNA copy numbers of SARS-CoV by real-time reverse transcription polymerase chain reaction (RT-PCR), we demonstrated that SARS-CoV infection was reduced in the ACE2-silenced cell lines. These findings support the involvement of ACE2 in SARS-CoV infections and provide a basis for further studies on potential use of siRNA targeting ACE2 as a preventive or therapeutic strategy for SARS.


Dynamics of Endo- and Epicardial Focal Fibrillation Waves at the Right Atrium in a Patient With Advanced Atrial Remodelling.
Focal waves appear frequently at the epicardium during persistent atrial fibrillation (AF), however, the origin of these waves is under debate. We performed simultaneous endo-epicardial mapping of the right atrial wall during longstanding persistent AF in a patient undergoing cardiac surgery. During 10 seconds 53 and 59 focal waves appeared at random at respectively the endocardium and epicardium. Repetitive focal activity did not last longer than 3 cycles. Transmural asynchrony and conduction might be the origin of focal waves. Asynchronous propagation of fibrillation waves in 3 dimensions would stabilize the arrhythmia and could explain the limited success of persistent AF ablation.


Sorption of copper(II) ions in the biomass of alga Spirogyra sp.
Sorption of copper ions by the alga Spirogyra sp. was investigated to determine the influence of experimental conditions and the methods of sample preparation on the process. The experiments were carried out both under the static and the dynamic conditions. Kinetics and equilibrium parameters of the sorption were evaluated. In addition, the influence was studied of the algae preparation methods on the conductivity of demineralized water in which the algae samples were immersed. The static experiments showed that the sorption of Cu(2+) ions reached equilibrium in about 30 min, with approximately 90% of the ions adsorbed in the initial 15 min. The sorption capacity determined from the Langmuir isotherms appeared highly uncertain (SD=±0.027 mg/g dry mass or ±11%, for the live algae). Under static conditions, the slopes of the Langmuir isotherms depended on the ratio of the alga mass to the volume of solution. The conductometric measurements were proven to be a simple and fast way to evaluate the quality of algae used for the experiments.


The influence of fluoro-phenyl-alanine on the synthesis of simian virus 40 DNA and T antigens.
Treatment of Simian Virus 40 (SV40) infected monkey cells with fluorophenylalanine (FPA) resulted in increased uptake of thymidine by the cells, and progressive inhibition of both viral and cellular DNA synthesis. Viral DNA synthesis was more sensitive to inhibition by FPA than cell DNA synthesis. Synthesis of SV40 T antigens was however unaffected by FPA, as judged from immunofluorescence assays. The M.W. of the major polypetides immunoprecipitated from cell extracts by antibodies from tumor bearing hamster sera was similarly unaffected. It is suggested that T antigen synthesized in the presence of FPA is non functional.


Adverse birth outcomes associated with household air pollution from unclean cooking fuels in low- and middle-income countries: A systematic review.
Approximately 3.8 billion people in low- and middle-income countries use unclean fuels as a source of primary cooking fuel as well as for heating. For pregnant women, the toxic chemicals produced by combustion of unclean fuels not only affect women's health directly, but particulate matter and carbon monoxide are absorbed in maternal blood and cross the placental barrier impairing fetal tissue growth. PRISMA 2009 guidelines were used for this systematic review. The inclusion criteria were quantitative, peer reviewed journal articles published within a date range of May 1, 2013-June 12, 2021 examining birth outcomes related to household air pollution from type of cooking fuel in low- and middle-income countries. The quality of available evidence was evaluated using the Office of Health Assessment and Translation (OHAT) risk of bias rating tool. Of the 553 studies screened, 23 satisfied the inclusion criteria. Of the studies that met the inclusion criteria, 14 were cross-sectional, 5 cohort, 1 case-control and 3 randomized control trials conducted across 15 different countries. A range of birth outcomes are reported across studies including birthweight (19), small for gestational age (6), spontaneous abortion (3), preterm birth (6), stillbirth (7) and neonatal mortality (6). The reviewed studies presented evidence for an increased risk of low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), stillbirth, neonatal mortality and reduction in birthweight with solid fuel and kerosene use compared to cleaner fuels like gas and LPG. Systematically reviewing the evidence and risk of bias ratings illuminated several gaps in the current literature related to exposure assessment, outcome measurement and adequacy of adjustment for confounding.


Online program for treating chemical dependency breaks down barriers.
Providers caring for patients with substance abuse difficulties know how hard it is to get those patients the kind of help they need. Beyond insurance difficulties and a significant shortage of treatment programs, many patients lack the time needed to enter into traditional programs or they have privacy concerns that keep them from accessing this type of care. A new online approach to treatment seeks to address all these barriers while providing a traditional 12-step approach to care.


Preoperative Pressure Ulcers, Mortality, and Complications in Older Hip Fracture Surgery Patients.
The effect of a preoperative pressure ulcer (PPU) in hip fracture patients on postoperative outcomes has not been well studied. We hypothesized that the presence of a PPU would be associated with increased mortality and serious complications in hip fracture surgery patients. We conducted a cohort study of 19,520 hip fracture patients from 2016 to 2019 with data from the National Surgical Quality Improvement Program. The study exposure was the presence of a PPU. This study's primary outcome was 30-day mortality. Secondary outcomes included deep vein thrombosis (DVT), pulmonary embolism, surgical site infection, pneumonia, and unplanned hospital readmission. Propensity score analysis and inverse probability of treatment weighting were used to control for confounding and reduce bias. The presence of a PPU was independently associated with a 21% increase in odds of 30-day mortality (odds ratio (OR) = 1.2, P = 0.004). The presence of a PPU was also independently associated with increased odds of DVT (OR = 1.59, P < 0.001), pneumonia (OR = 1.39, P < 0.001), and unplanned hospital readmission (OR = 1.43, P < 0.001) and a significant increase in the mean length of hospital stay of 0.4 days (P = 0.007). We found that PPUs were independently associated with increased 30-day mortality, DVT, pneumonia, hospital length of stay, and unplanned hospital readmission.


Spermine enhances IgM productivity of human-human hybridoma HB4C5 cells and human peripheral blood lymphocytes.
The polyamine spermine was assessed for enhancement of IgM production by human-human hybridoma, HB4C5 cells, under serum-free conditions. IgM production of HB4C5 cells was stimulated approximately 6-fold by the addition of 7.3 mM of spermine. The facilitating effect was observed soon after inoculation. In spite of suppression of cell growth, the IgM production rate was accelerated for at least 5 days without medium change. Moreover, laser confocal microscopic analysis revealed that the IgM content inside HB4C5 cells was increased by spermine treatment. These findings suggest that spermine enhances specific IgM productivity of the hybridoma line. Spermine also facilitated IgM production by human peripheral blood lymphocytes under serum-free conditions. This result implies that spermine enhances immunoglobulin production of not only specific hybridoma lines, but also non-specific immunoglobulin producers. Immunoglobulin production stimulating activity of spermine was accelerated 2-fold by the addition of DNA whith a chain length of about 400-7000 base pairs (bp). However, degraded short-chain DNA fragments (less than 200 bp) did not facilitate the immunoglobulin production stimulating activity of spermine.


Evaluating the causal effect of tobacco smoking on white matter brain aging: a two-sample Mendelian randomization analysis in UK Biobank.
Tobacco smoking is a risk factor for impaired brain function, but its causal effect on white matter brain aging remains unclear. This study aimed to measure the causal effect of tobacco smoking on white matter brain aging. Mendelian randomization (MR) analysis using two non-overlapping data sets (with and without neuroimaging data) from UK Biobank (UKB). The group exposed to smoking and control group consisted of current smokers and never smokers, respectively. Our main method was generalized weighted linear regression with other methods also included as sensitivity analysis. United Kingdom. The study cohort included 23 624 subjects [10 665 males and 12 959 females with a mean age of 54.18 years, 95% confidence interval (CI) = 54.08, 54.28]. Genetic variants were selected as instrumental variables under the MR analysis assumptions: (1) associated with the exposure; (2) influenced outcome only via exposure; and (3) not associated with confounders. The exposure smoking status (current versus never smokers) was measured by questionnaires at the initial visit (2006-10). The other exposure, cigarettes per day (CPD), measured the average number of cigarettes smoked per day for current tobacco users over the life-time. The outcome was the 'brain age gap' (BAG), the difference between predicted brain age and chronological age, computed by training machine learning model on a non-overlapping set of never smokers. The estimated BAG had a mean of 0.10 (95% CI = 0.06, 0.14) years. The MR analysis showed evidence of positive causal effect of smoking behaviors on BAG: the effect of smoking is 0.21 (in years, 95% CI = 6.5 × 10-3 , 0.41; P-value = 0.04), and the effect of CPD is 0.16 year/cigarette (UKB: 95% CI = 0.06, 0.26; P-value = 1.3 × 10-3 ; GSCAN: 95% CI = 0.02, 0.31; P-value = 0.03). The sensitivity analyses showed consistent results. There appears to be a significant causal effect of smoking on the brain age gap, which suggests that smoking prevention can be an effective intervention for accelerated brain aging and the age-related decline in cognitive function.


Contribution of fortified margarines and other plant-based fats to micronutrient intake in the Netherlands.
In the Netherlands, margarines and other plant-based fats (fortified fats) are encouraged to be fortified with vitamin A and D, by a covenant between the Ministry of Health and food manufacturers. Frequently, these types of fats are also voluntarily fortified with other micronutrients. The current study investigated the contribution of both encouraged as well as voluntary fortification of fortified fats on the micronutrient intakes in the Netherlands. Data of the Dutch National Food Consumption Survey (2012-2016; N = 4, 314; 1-79 year.) and the Dutch Food Composition Database (NEVO version 2016) were used to estimate micronutrient intakes. Statistical Program to Assess Dietary Exposure (SPADE) was used to calculate habitual intakes and compared to dietary reference values, separate for users and non-users of fortified fats. Of the Dutch population, 84% could be considered as user of fortified fats. Users consumed mostly 1 fortified fat a day, and these fats contributed especially to the total micronutrient intake of the encouraged fortified micronutrients (vitamins D and A; 44% and 29%, respectively). The voluntary fortification also contributed to total micronutrient intakes: between 7 and 32%. Vitamin D and A intakes were up to almost double among users compared to non-users. Intakes were higher among users for almost all micronutrients voluntarily added to fats. Higher habitual intakes resulted into higher risks of excessive vitamin A-intakes among boys and adult women users. Consumption of fortified fats in the Netherlands resulted into higher vitamin A and D-intakes among users, compared to non-users of these products.


Induction of proapoptotic Daxx following ischemic acute kidney injury.
Transcriptome profiling has shown that the pro-apoptotic death-domain-associated protein Daxx is rapidly induced in the kidney of animals following ischemic injury. Here we found that Daxx protein was increased 5-fold in tubule cells in both animal and human models of ischemic acute kidney injury. Further there was upregulation of its primary interacting partner, Fas and phosphorylation of its primary downstream activator (JNK) in parallel to Daxx induction. In cultured tubule cells, partial ATP depletion resulted in a rapid induction of Daxx, Fas, JNK phosphorylation and apoptosis. Antisense oligonucleotides to Daxx and specific JNK inhibitors blunted the apoptotic response to ATP depletion. These studies indicate that Daxx may play an unrecognized role in the early apoptotic response to ischemic renal injury.


IgG subclass-restricted immune responses to allergens.
The IgG responses to a variety of allergens are predominated by IgG1 and IgG4 antibodies. With several allergens, the IgG1 response appears to precede the IgG4 response and this switch may be driven by repeated allergen exposure. It remains to be determined whether there is any causal relationship between subclass restriction and the regulation of specific IgE. The question of whether IgG4 antibodies are protective or pathological is still unresolved. Human models are needed to further analyze the interrelationships between T cells, cytokines and B cell isotype expression. The antibody response to allergens appears to be an ideal experimental system for studying antigen-specific isotype regulation in humans. The subclass patterns are remarkably reproducible between individuals, and allergic and normal human subjects, who have been immunized naturally or therapeutically, are readily available as a source of cells. Isolation of allergen-specific T cells that putatively regulate subclass expression would seem to be a worthwhile endeavor. Understanding the molecular and cellular events that initiate and control isotype expression will play an important role in the rational design of immunogens and therapeutics, aimed at optimizing protective immunity and diminishing the pathological effects of autoimmune and allergic responses.


Patients' perspectives on what works in psychoeducational groups for schizophrenia: a qualitative study.
Psychoeducational groups are a common component of interventions in schizophrenia. To explore patients' views about wanted and unwanted effects of group psychoeducation. Subjective feedback of 103 participants of a psychoeducational intervention as well as data from two specific focus groups-one with "enthusiastic" and one with "critical" participants-were analyzed by means of qualitative content analysis. Participants emphasized the importance of information received and of exchanging information with others suffering from the same disorder. Positive effects on coping, activation and social interaction were reported. Perceived overemphasis on illness related information produced defensive reactions, whereas the integration of quality of life topics was appreciated. A pleasant group atmosphere and clinical stability were suggested as important determinants of success. Qualitative analyzses of participants' views help to understand the potentials of a psychoeducational intervention in schizophrenia.