Patient-reported outcome and cognitive measures to be used in vascular and brain tumor surgery: proposal for a minimum set.
The standardization of outcome measures is needed for comparing studies and using common measures in clinical practice. We aimed to identify cognitive and patient-reported outcomes and timing of assessment for glioma, meningioma, and vascular surgery. A consensus study was conducted. Participants selected cognitive and patient-reported measures among a list of instruments identified through a literature search. Seventeen cognitive tests for the glioma and meningioma's evaluation, 8 for the vascular diseases, and one questionnaire on quality of life and one on emotional distress were identified. The timing of outcome assessment selected was before surgery, at discharge, and after 3 and 12 months for glioma; before surgery and after 3 months for meningioma; before surgery, at discharge, and after 6 months for vascular diseases. The identification of common outcome measures is the first step toward a shared data collection improving the quality and comparability of future studies.


Measurement of intracellular Na in the rat salivary gland: a 23Na-NMR study using double quantum filtering.
23Na in the prefused rat mandibular salivary gland was measured by spin-echo double quantum filter 23Na-NMR spectroscopy at 8.45 T. Resonances due to the intracellular 23Na and the interstitial 23Na were observed in the perfused gland at 25 degrees C. The resonance due to intracellular 23Na consisted of two Lorentzian signals stemming from the [1/2 mean value of -1/2[ coherence (sharp resonance) and the [-1/2 mean value of -3/2[ and [3/2 mean value of 1/2[ coherences (broad resonance). The transverse relaxation rate constant corresponding to the [1/2 mean value of -1/2[ coherence was 95 +/- 4 s-1 and that corresponding to the [-1/2 mean value of -3/2[ and [3/2 mean value of 1/2[ coherences was 1360 +/- 75 s-1 (mean +/- S.E., n = 5). The resonance due to the interstitial 32Na had longer relaxation rate constants, and disappeared upon administration of dysprosium triethylenetetramine-N,N',N",N",N"'-hexaacetic acid.


Imidazole antifungals, but not triazole antifungals, increase membrane Zn2+ permeability in rat thymocytes Possible contribution to their cytotoxicity.
The use of zinc as a nutritional supplement has become common in many countries. Since zinc has diverse actions, it may be difficult to predict its synergistic and/or antagonistic action in simultaneous presence of drug(s). The combination of imidazole antifungals, but not triazole antifungals, with 3-30 microM ZnCl2 significantly increased the lethality of rat thymocytes. Since intracellular Zn2+ exerts various actions on the process of cell death, there is a possibility that imidazole antifungals, but not triazole antifungals, increases concentration of intracellular Zn2+ ([Zn2+]i). To test the possibility, we examined the effects of imidazole and triazole antifungals on [Zn2+]i of rat thymocytes in absence and presence of extracellular Zn2+ by the use of FluoZin-3, a fluorescent Zn2+ indicator. Imidazole antifungals (clotrimazole, econazole, and oxiconazole) increased the [Zn2+]i in the presence of extracellular Zn2+ while it was not the case for triazole antifungals (itraconazole and fluoconazole). Thus, it is suggested that imidazole antifungals increase the membrane permeability of Zn2+. The potency order in the augmentation of FluoZin-3 fluorescence by imidazole antifungals in the presence of extracellular Zn2+ was the same as that in their cytotoxic action. Therefore, the cytotoxic action of imidazole antifungals may be related to their action on membrane Zn2+ permeability.


Uncoupling of local blood flow and metabolism in the hippocampal CA3 in kainic acid-induced limbic seizure status.
Limbic seizure status was induced by microinjection of kainic acid into a unilateral amygdala in rats. Two hours after kainic acid injection, distant neuronal cell damage was produced, especially in the hippocampal CA3 on the kainic acid-injected side. In order to elucidate the mechanism of this neuronal cell damage, local cerebral glucose utilization and local cerebral blood flow were studied by means of an autoradiographic method using [14C]2-deoxyglucose and [14C]iodoantipyrine during kainic acid-induced limbic seizure status. These studies were performed 2 h after kainic acid microinjection into a unilateral amygdala. Both local cerebral glucose utilization and local cerebral blood flow were remarkably increased in the limbic system, ventrobasal complex of the thalamus, septal nucleus, nucleus accumbens, caudate nucleus, substantia nigra and hypothalamus on the kainic acid-injected side. In the hippocampus, local cerebral glucose utilization increased 2.6 times control in CA1 and 4.1 times in CA3, whereas the rates of increase in local cerebral blood flow were similarly low in CA1 and CA3: 1.2 and 1.4 times control, respectively. The results demonstrated that the degree of uncoupling of local cerebral glucose utilization and local cerebral blood flow were higher in CA3 than in CA1, and also suggested that relative hypoxia occurred in CA3 in this high degree of uncoupling, resulting in pyramidal cell damage in CA3 in kainic acid-induced limbic seizure status.


Effectiveness of aspiration in knee joint effusion management: a prospective randomized controlled study.
Knee effusion is a common symptom in various knee disorders of both traumatic and non-traumatic aetiology. Although intra-articular aspiration is a widespread treatment approach, its beneficial effect has not been confirmed by a randomized controlled study. The purpose was to evaluate the effectiveness and safety of joint aspiration in acute knee effusion, in relation to traumatic or non-traumatic aetiology. One hundred and sixty-seven consecutive patients with acute knee joint effusion were allocated in a randomized controlled fashion into two groups. In the first group, joint aspiration was performed, while in the second group, no aspiration was performed. Range of motion, pain relief, use of analgesics and oedema were evaluated post management. The Knee Society Score and the International Knee Documentation Committee Subjective Evaluation Form were also obtained. In addition, a subgroup analysis of our results in relation to the presence of trauma or not was performed. Aspiration exhibited a temporary improvement in all clinical parameters evaluated, especially in the post-traumatic effusion. However, this improvement lasted only for the first week, due to the early re-accumulation of the effusion. There was no difference between the different groups regarding the clinical outcome in neither trauma or non-trauma patients at the end of the follow-up period. Aspiration aided in earlier establishment of the diagnosis in the non-trauma cases of effusion. Aspiration resulted in only temporary improvement of the outcome in the treatment of traumatic or not traumatic knee effusion. Aspiration is suggested in effusions of unknown origin in order to establish the diagnosis and for immediate clinical relief. However, aspiration should be performed with consideration in the presence of trauma.


Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence.
There is limited evidence relating to the impact of disease modifying anti-rheumatic drugs (DMARDs) upon male fertility and peri-conception paternal exposure in men with rheumatic disease. Therefore, we conducted a systematic review of available evidence to update information on this subject and guide paternal counselling. A systematic search of PubMed and Embase was carried out up to September 2017, to find relevant peer-reviewed papers, using keywords for fertility/spermatogenesis/conception, men, and disease modifying or biologic drugs commonly prescribed in patients with rheumatic disease. The search yielded 724 papers, and the titles/abstracts were screened independently by 2 authors, duplicates removed and 233 potentially relevant papers selected for full text review. A total of 84 papers were included in the final analysis which covered the impact on fertility of over 611 male exposures to relevant drugs, and over 5986 pregnancies conceived during paternal exposure to (or within 3 months of stopping) these drugs. Aside from the known adverse impact of cyclophosphamide and sulfasalazine on spermatogenesis, overall there was no firm evidence of harm to fertility or pregnancy outcomes with paternal exposure to anti-TNF therapies, abatacept, rituximab, azathioprine, cyclosporine A, hydroxychloroquine, leflunomide, methotrexate or mycophenolate mofetil. There was no evidence found pertaining to the effects of male exposure to IVIG, tacrolimus, golimumab, anakinra or belimumab on fertility or pregnancy outcomes. These results provide further reassurance as to the safety of many DMARDs for men trying to conceive and will be useful when counselling men about risks of anti-rheumatic drugs to fertility and pregnancies, and following accidental conception.


T suppressor factor activity is due to two separate molecules. The Lyt-1(-)2+I-J+ cells of mice primed with antigen make an antigen binding molecule which is only active when complemented by cofactor made by Lyt-1+2(-)I-J+ cells.
Mice primed with picrylsulfonic acid (PSA) and then painted on the skin with picryl chloride produce antigen-specific T suppressor factor (TsF). In contrast unpainted primed mice fail to produce active TsF. This is not due to the absence of the antigen binding part of TsF but to the absence of a cofactor. This cofactor is (a) antigen nonspecific and occurs in potassium chloride extract of normal spleen cells. It also occurs in the 24 hr supernatant of normal cells modified by haptenisation with picryl or the unrelated NP antigen (4-hydroxy-3-nitrophenylacetyl), and in preparations of conventional TsF (PSA/PCl) from painted PSA-primed mice; (b) bears I-J determinants; and (c) is produced by Lyt-1+2(-)I-J+ cells. The antigen binding molecule occurs alone in the supernatant of PSA-primed mice. It lacks I-J determinants and has a molecular weight around 35,000 and 75,000. It is produced by Lyt-1(-)2+I-J+ cells and is only active when complemented by cofactor. However, the complementation is genetically restricted and the restriction maps to the I-J subregion of the MHC.


Application of robust NiTi-ZrO2-PEG SPME fiber in the determination of haloanisoles in cork stopper samples.
In this study, a novel solid-phase microextraction (SPME) fiber obtained using sol-gel technology was applied in the determination of off-flavor compounds (2,4,6-trichloroanisole (TCA), 2,4,6-tribromoanisole (TBA) and pentachloroanisole (PCA)) present in cork stopper samples. A NiTi alloy previously electrodeposited with zirconium oxide was used as the substrate for a poly(ethylene glycol) (PEG) coating. Scanning electronic microscopy showed good uniformity of the coating and allowed the coating thickness to be estimated as around 17 micarom. The optimization of the main parameters influencing the extraction efficiency, such as cork sample mass, sodium chloride mass, extraction temperature and extraction time were optimized using a full factorial design, followed by a Doehlert design. The optimum conditions were: 20 min of extraction at 70 degrees C using 60 mg of the cork sample and 10 mL of water saturated with sodium chloride in a 20 mL amber vial with constant magnetic stirring. Satisfactory detection limits between 2.5 and 5.1 ng g(-1) were obtained, as well as good precision (R.S.D. in the range of 5.8-12.0%). Recovery tests were performed on three different cork samples, and values between 83 and 119% were obtained. The proposed SPME fiber was compared with commercially available fibers and good results were achieved, demonstrating its applicability.


A fractional differential equation model for the COVID-19 transmission by using the Caputo-Fabrizio derivative.
We present a fractional-order model for the COVID-19 transmission with Caputo-Fabrizio derivative. Using the homotopy analysis transform method (HATM), which combines the method of homotopy analysis and Laplace transform, we solve the problem and give approximate solution in convergent series. We prove the existence of a unique solution and the stability of the iteration approach by using fixed point theory. We also present numerical results to simulate virus transmission and compare the results with those of the Caputo derivative.


Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis) - study protocol and patient characteristics at baseline.
Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group. Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis) is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year. 313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0%) followed by sulfonylureas (14.8%). DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients during multiple adjustments of therapy.


Simple, rapid and micro high-pressure liquid chromatographic method for the simultaneous determination of tolbutamide and carboxy tolbutamide in plasma.
A rapid high-pressure liquid chromatographic (HPLC) assay is described for the quantitative analysis of tolbutamide and its major metabolite, carboxy tolbutamide in plasma. An aliquot (25--100 microliter) of plasma was prepared for chromatography by deproteinization as follows. One volume of plasma and 2.5 volumes of acetonitrile were vortex mixed for a few seconds and then centrifuged for approx. 1 min. A 50-microliter sample of the clear supernatant was injected into the chromatograph. A mu Bondapak C18 reversed-phase column was used with a mobile phase acetonitrile--0.05% phosphoric acid (45:55) at a flow-rate of 1.5 ml/min. The column effluent was monitored by a variable-wavelength UV detector set at 200 nm. Tolbutamide and its metabolite had retention times of 5.75 and 3.25 min, respectively. The procedure yuelds reproducible results with sensitivity adequate for routine clinical monitoring of plasma levels or for single-dose pharmacokinetic studies. A number of commonly used drugs do not interfere with the method. A single plasma sample can be analyzed in approx. 9 or 10 min.


Effect of electrical potential on the electro-demulsification of oily sludge.
Oily sludge, produced mostly in petroleum refineries and petrochemical industries, is one of the major industrial wastes that require treatment. Typically, these sludge wastes are water-in-oil emulsions that are stabilized by fine solids. These fine particles adsorb at the droplet surface and by lowering the demulsification rate constant, act as a barrier to prevent droplet coalescence. In this investigation, the effects of different electrical potential gradients and amphoteric surfactant on effectiveness of phase separation were investigated. It was concluded that lower electrical potential (0.5 V/cm) produced a higher demulsification rate. The solid phase remaining after the experiment was of a more compact and stable consistency. It was concluded that application of the amphoteric surfactant does not improve the total efficiency of the process. The role of oil constituents in stabilizing water-in-oil emulsions, and their effect on the dynamics of the process, were considered in every step of the experiment. Analysis of pH changes, resistance evolution, and hydrocarbon polarity analysis confirmed that the application of lower electrical gradient results in better phase separation.


What factors drive seasonal variation of phytoplankton, protozoans and metazoans on leaves of Posidonia oceanica and in the water column along the coast of the Kerkennah Islands, Tunisia?
A hierarchical sampling design was used during two seasons (spring (May) and summer (August) 2006). Using this design, three regions of the Kerkennah Islands (Tunisia) were analyzed for the distribution of microalgal, protozoan and metazoan assemblages in two different habitats: (1) the water column; and (2) on Posidonia oceanica (L.) Delile (P. oceanica) leaves in shallow meadows. A total of 85 species were obtained. In particular, the diatom family Naviculacea consistently dominated (both numerically and in their diversity) the micro-algae in all regions for the two seasons of the study and in both habitats. In the Chergui region, which is the closest area to a source of impact, fast growing centric diatoms (such as Thalassionema, Rhizosolenia, Striatella, and Skeletonema) were identified as indicators of high organic matter and nutrient enrichment in water bodies. Protozoan and metazoan species abundance in the different regions indicate a non-random spatial and temporal distribution of the epiphytic organisms on leaves of P. oceanica that correlated with phytoplankton. The results also indicate that (1) the abundance of micro- and macroorganisms in the three regions were higher on P. oceanica leaves than in the water column for the two seasons; (2) environmental factors such as currents and tide influenced assemblages; and (3) the highest abundance was due to direct exposure to the polluted coast of Sfax and the effect of tidal asymmetries generating nutrient-rich inputs from the city.


Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: Implications for principles underlying odor mapping.
Functional imaging signals arise from distinct metabolic and hemodynamic events at the neuropil, but how these processes are influenced by pre- and post-synaptic activities need to be understood for quantitative interpretation of stimulus-evoked mapping data. The olfactory bulb (OB) glomeruli, spherical neuropil regions with well-defined neuronal circuitry, can provide insights into this issue. Optical calcium-sensitive fluorescent dye imaging (OICa(2+)) reflects dynamics of pre-synaptic input to glomeruli, whereas high-resolution functional magnetic resonance imaging (fMRI) using deoxyhemoglobin contrast reveals neuropil function within the glomerular layer where both pre- and post-synaptic activities contribute. We imaged odor-specific activity patterns of the dorsal OB in the same anesthetized rats with fMRI and OICa(2+) and then co-registered the respective maps to compare patterns in the same space. Maps by each modality were very reproducible as trial-to-trial patterns for a given odor, overlapping by ~80%. Maps evoked by ethyl butyrate and methyl valerate for a given modality overlapped by ~80%, suggesting activation of similar dorsal glomerular networks by these odors. Comparison of maps generated by both methods for a given odor showed ~70% overlap, indicating similar odor-specific maps by each method. These results suggest that odor-specific glomerular patterns by high-resolution fMRI primarily tracks pre-synaptic input to the OB. Thus combining OICa(2+) and fMRI lays the framework for studies of OB processing over a range of spatiotemporal scales, where OICa(2+) can feature the fast dynamics of dorsal glomerular clusters and fMRI can map the entire glomerular sheet in the OB.


[Problems, complications, and emergencies during pacemaker implantation. Importance of access].
Pacemaker implantation represents a standard procedure with a perceived 100% success rate, without mortality and with extremely rare complications. However, some pacemaker implantations may develop into a very difficult procedure or even be associated with significant complications. Good venous access is crucial and may distinguish between comfortable, successful implantation and futile implantation with severe complications (e.g., pneumo- or hematothorax, venous dissection or perforation, accidental arterial implantation, or air embolism). This review summarizes acute problems and complications during lead implantation and provides tips and hints for prevention and acute reaction during implantation. If these simple precautions are considered, the majority of acute complications during implantation of pacemaker leads can be prevented.


Typical absence status in adults: diagnostic and syndromic considerations.
To study the electroclinical features of typical absence status (TAS) in adults with syndromes of idiopathic generalized epilepsies (IGEs). Twenty-one patients with one or more spells of TAS were identified among 136 consecutive adult patients with IGEs. All patients with TAS had comprehensive electroclinical investigations and EEG or video-EEG recorded absences. TAS occurred in 24.4% of 86 patients who had IGEs with typical absences alone or in combination with other seizures presisting in adult life. The prevalence of TAS appeared to be syndrome related, ranging from as high as 57.1% in perioral myoclonia with absences and 46.2% in "phantom" absences with GTCS to as low as 6.7% in juvenile myoclonic epilepsy. A varying degree of impairment of cognition was the cardinal clinical symptom shared in all TAS, but corresponding syndromes of IGE were often betrayed by other symptoms such as eyelid or perioral myoclonia. In phantom absences with GTCS, TAS was more numerous (p < or = 0.05) and more frequently the first overt seizure type (p = 0.006) than in any other IGE. Only in the syndrome of eyelid myoclonia with absences, TAS was always situation related, mainly as a result of antiepileptic drug discontinuation. The clinical EEG semiology and prevalence of TAS appear to be syndrome related with the highest prevalence in the syndromes of perioral myoclonia with absences and phantom absences with GTCS (p = 0.0024).


Effect of the chlorpropamide and fructose-1,6-bisphosphate of soluble TNF receptor II levels.
Inflammatory cytokines are central to the pathogenesis of septic shock, and future therapies will depend on interfering with the effects of these cytokines. The aim of this study was to investigate the effect of the two drugs, Fructose-1,6-bisphosphate (FBP), a high-energy glycolytic pathway intermediate, and chlorpropamide (sulfonylurea) on proliferation of T-lymphocytes and on the levels of soluble receptors of tumor necrosis factor (sTNFRII). Peripheral blood mononuclear cells (PMBCs) were isolated from the blood of healthy humans by gradient centrifugation. T-lymphocytes were stimulated for 96h with phytohemagglutinin (PHA) and varying concentrations of chlorpropamide and FBP. They were stimulated for 24h with lipopolysaccharide (LPS) and varying concentrations of chlorpropamide and FBP were used. Chlorpropamide at concentrations between 2.5 and 10mM and FBP at concentrations between 1.25 and 10mM decreased proliferation of T-lymphocytes. The chlorpropamide reduced the viability only at a concentration of 10mM and FBP at concentrations of 5.0 and 10mM. The levels of sTNFRII were reduced at chlorpropamide concentrations between 2.5 and 5mM and FBP between 1.25 and 2.5mM. In conclusion, our results suggest that FBP acts, as does chlorpropamide, to inhibit the cellular proliferation and thereby reducing the sTNFRII levels through blockage of the potassium channels. In this way it acts as a powerful immunomodulatory agent.


Evolutionary explanations for financial and prosocial biases: Beyond mating motivation.
Mating motivation likely plays a role in bias to attractive individuals, but there are other complementary theories drawn from the evolutionary literature related to competition, friendship, and leadership selection that also make relevant predictions concerning biases towards attractive individuals. The relative balance of these factors will be context dependent and so help explain why the pattern of bias is sometimes variable.


The impact of cognitive impairment on survival and medication adherence among older women with breast cancer.
The purpose of this study was to examine the impact of preexisting cognitive impairments on survival and medication adherence, and whether chronic medication adherence mediates or moderates the association between cognitive impairments and mortality in patients with breast cancer. This retrospective cohort study of older female patients diagnosed with breast cancer was conducted using the Surveillance, Epidemiology, and End Results Medicare Linked Database. We examined the risk of mortality from cancer and non-cancer causes in patients with and without a history of cognitive impairment. In addition, we examined if chronic medication adherence rates differ between these groups of patients and if medication adherence mediates or moderates the association between cognitive impairments and non-cancer mortality. Mortality from cancer-specific (HR 1.13, 95% CI 1.04-1.23) and non-cancer causes (HR 1.16, 95% CI 1.11-1.21) as well as all-cause mortality (HR 1.30, 95% CI 1.23-1.38) was significantly higher in patients with cognitive impairments compared to those without cognitive impairment. Both groups showed low adherence levels to chronic medication before and after the breast cancer diagnosis. Further analysis did not show that medication adherence mediates or moderates the relationship between cognitive impairment and non-cancer mortality (p value > 0.05). The results of this study indicate that older female patients with cognitive impairments and a breast cancer diagnosis have a heightened risk of cancer-specific and non-cancer mortality. Our findings do not indicate that chronic medication adherence plays a role in the association between a history of cognitive impairment and mortality, it is still necessary to further investigate this issue.


Medial leg skin flap: vascular anatomy and clinical applications.
A new medial leg skin flap was reported with 100% success in 17 clinical cases. The surgical anatomy and the details of the technique are described.


Papillary tumor of the pineal region in a child: case report and review of the literature.
A 13-year-old boy presented with a history of intracranial hypertension. Radiologic studies revealed triventricular hydrocephalus secondary to a space-occupying lesion in the pineal region. Endoscopic third ventriculostomy was performed to treat hydrocephalus, and the lesion was biopsied. Complete resection of the tumor was subsequently performed. After a period of uncertainty, the diagnosis of papillary tumor of the pineal region was established. Tumor bed radiotherapy at a dose of 50 Gy was associated. With a follow-up of 15 months, the postoperative course was satisfactory with return to school and no residual tumor on magnetic resonance imaging. Papillary tumors of the pineal region constitute a rare entity, with a difficult diagnosis, an uncertain prognosis, and a high risk of local recurrence; they must be treated by a combination of surgery and radiotherapy. The only identified prognostic factor is the complete or incomplete nature of surgical resection.


Useful clinical criteria for the diagnosis of ventricular tachycardia.
Misdiagnosis occurs upon initial presentation to medical attention in a considerable number of patients referred for evaluation of wide QRS tachycardia. In order to improve diagnostic accuracy (ventricular versus supraventricular tachycardia), the answers to two key bedside questions were prospectively evaluated: (1) Had the patient experienced a prior myocardial infarction? (2) Did symptoms of tachyarrhythmia start only after the infarction? A patient presenting with a wide QRS tachycardia was considered to have ventricular tachycardia if he or she answered in the affirmative to both of these questions. Of 31 consecutive patients referred with electrocardiographically documented sustained wide QRS tachycardia that was reproduced in the electrophysiology laboratory, the diagnoses made when the patients first presented to medical attention were ventricular tachycardias in 17 patients and supraventricular tachycardias in 14 patients. Following electrophysiologic evaluation, 29 were diagnosed as having ventricular tachycardia and two as supraventricular tachycardia. If the diagnoses were made solely on the basis of responses to the bedside questions mentioned earlier, 28 of the 29 patients having a final diagnosis of ventricular tachycardia would have been correctly identified. It is concluded that the use of these two questions can be very helpful in improving the clinical diagnosis of ventricular tachycardia.


In vivo therapeutic potentiality of red seaweed, Asparagopsis (Bonnemaisoniales, Rhodophyta) in the treatment of Vibriosis in Penaeus monodon Fabricius.
The crude extract of the red seaweed, Asparagopsis sp. was evaluated for in vivo antibacterial activity against the shrimp vibrio pathogens. The algal extract was rationalized with commercial shrimp feed and orally administered for different duration of time followed by the artificial bacterial challenge experiment. In dose titration experiments, the oral administration of Asparagopsis sp. at a dosage of 850 mg kg(-1) of biomass was highly efficacious in the treatment of natural infestations of Vibriosis in Penaeus monodon. The results of the confirmatory dose experiment revealed that the prophylactic treatment with moderate dose of 850 mg kg(-1) of biomass day(-1) for four weeks followed by 14 days of post infection therapy was highly effective in controlling Vibrio infection in shrimps. Moreover, results of the percent survival index and microbiological analysis clearly show that Asparagopsis extract incorporated medicated feed had broad therapeutic potential for managing shrimp Vibriosis. In addition, in vivo trials and results obtained in this work are based on the crude organic extract sourced from an unidentified Asparagopsis cryptic lineage, therefore further molecular analysis to identify the species will be required.


Metabolite ratios in the posterior cingulate cortex do not track cognitive decline in Parkinson's disease in a clinical setting.
Parkinson's Disease (PD) is classified as a motor disorder, but most patients develop cognitive impairment, and eventual dementia (PDD). Predictive neurobiomarkers may be useful in the identification of those patients at imminent risk of PDD. Given the compromised cerebral integrity in PDD, we investigated whether brain metabolites track disease progression over time. Proton Magnetic Resonance Spectroscopy (MRS) was used to identify brain metabolic changes associated with cognitive impairment and dementia in PD. Forty-nine healthy participants and 130 PD patients underwent serial single voxel proton MRS and neuropsychological testing. At baseline patients were classified as either having normal cognitive status (PDN, n = 77), mild cognitive impairment (PDMCI, n = 33), or dementia (PDD, n = 20). Posterior cingulate cortex (PCC) was examined to quantify N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI). A hierarchical Bayesian model was used to assess whether cognitive ability and other covariates were related to baseline MRS values and changes in MRS over time. At baseline, relative to controls, PDD had significantly decreased NAA/Cr and increased Cho/Cr. However, these differences did not remain significant after accounting for age, sex, and MDS-UPDRS III. At follow-up, no significant changes in MRS metabolite ratios were detected, with no relationship found between MRS measures and change in cognitive status. Unlike Alzheimer's disease, single voxel MR spectroscopy of the PCC failed to show any significant association with cognitive status at baseline or over time. This suggests that MRS of PCC is not a clinically useful biomarker for tracking or predicting cognitive impairment in Parkinson's disease.


Inflammatory disease of the colon: ulcerative colitis and Crohn's colitis.
Ulcerative colitis differs from Crohn's colitis in several ways. In ulcerative colitis the disease is limited to the mucosa and, occasionally, the submucosa; Crohn's colitis may involve all layers of the large intestine. Ulcerative colitis almost always begins in the rectum, is diffuse, and spreads proximally. Crohn's colitis may spare the rectum and has a patchy distribution. Perianal fistulas and ulcers are rare in ulcerative colitis but are common in Crohn's colitis. Granulomas and giant cells are not found in ulcerative colitis but are seen in the majority of patients with Crohn's colitis. Colonic and extraintestinal symptoms in the two illnesses may be indistinguishable but growth failure is far more severe in Crohn's colitis and may precede intestinal symptoms by months to years. Cancer of the colon is a risk in patients with either ulcerative or Crohn's colitis but is far more common in the former. It is important to distinguish between ulcerative colitis and Crohn's colitis because response to treatment and prognosis are different. Although neither condition can be cured by medical management, patients with ulcerative colitis may respond more frequently. Unfortunately, in the pediatric age range most cases of ulcerative and Crohn's colitis may be classified as moderate to severe. Fortunately for patients with ulcerative colitis, total colectomy with ileostomy will result in cure of illness. Patients with Crohn's colitis who require surgery may obtain remission of symptoms, but the disease is likely to recur in the small intestine.


Long-term depot maintenance of chronic schizophrenic out-patients: the seven year follow-up of the Medical Research Council fluphenazine/placebo trial I. Course of illness, stability of diagnosis, and the role of a special maintenance clinic.
A follow-up study of all patients entering the MRC double-blind trial of fluphenazine decanoate in chronic schizophrenic out-patients achieved a trace rate of 94%. In general, these patients were severely disabled, continued under the care of the maintenance clinic, and their diagnoses remained remarkably consistent; more than one-fifth were found to be in acute schizophrenic relapse and in over a half of these cases, the relapse was not known to the treatment agency. The maintenance clinic attenders were little different from those who no longer used such a facility.


Analysis of 30 Biallelic INDEL Markers Using the Investigator DIPplex(®) Kit.
Insertion/deletion polymorphisms (INDELs) are a relatively new class of a DNA marker to be used in forensic casework; used most commonly as a supplementary method to STR-based typing. INDELs, like SNPs, are particularly useful for the analysis of highly degraded DNA as the amplicon sizes are typically below 160 bp; they can also be valuable as an additional tool to help resolve kinship cases, with the advantage over STRs that they do not have high mutation rates. INDELs have an advantage over SNPs in that they are length polymorphisms and so can be analyzed by simply measuring the length of the allele(s). The Qiagen Investigator(®) DIPplex Kit is currently only one of two commercially available kits for the amplification of INDEL polymorphisms; it amplifies 30 biallelic INDEL loci and the amelogenin locus. The primers used are fluorescence labeled with 6-FAM, BTG, BTY, and BTR. This technique is robust, relatively simple, and the results are analyzed using the same capillary electrophoresis equipment and software as used for STR typing.


Lactic acid and protein interactions: implications for the NMR visibility of lactate in biological systems.
The addition of bovine serum albumin (BSA) to a solution of lactate and alanine resulted in the disappearance of the 1H-NMR resonances from lactate but not alanine. As temperature is increased lactate becomes increasingly NMR visible and after heating above 65 degreesC and cooling to 25 degreesC lactate binding is reduced. With a concentration of 0.2 mM BSA, there was a linear relationship between NMR visible lactate versus total lactate over a range of lactate concentrations of 0.2-35 mM (slope 0.384+/-0.003) indicating that approx. 60% of the added lactate is not visible in the 1H-NMR spectrum. With a 0.1 mM BSA solution, however, the slope was markedly higher indicating that under these conditions only 25-30% of the lactate was NMR invisible. The results from this study indicate that decreased NMR visibility of lactate in proteinaceous solutions is due to non-specific binding which is dependent on the tertiary structure of the protein. This has important implications not only for the interpretation of in vivo 1H-NMR experiments but also for 13C, and 14C studies of metabolism.


Suicidal ideation and attempts in unipolar versus bipolar depression: analysis of 131,740 adolescent inpatients nationwide.
Objective To evaluate the risk of suicidal ideation and suicidal attempt in adolescents with unipolar depression (UD) versus bipolar depression (BD). Method We included 131,740 adolescents (12-17y), with primary diagnoses of UD (92.6%) and BD (7.4%) from the nationwide inpatient sample. We calculated odds ratio (OR) for suicidal behaviors using logistic regression adjusted for demographic confounders and comorbidities. Results Suicidal ideation and suicidal attempt were seen in 14.5% and 38.6% respectively of total inpatients and both were seen in higher proportion of UD. Females have higher odds for suicidal attempt (OR 1.13, 95%CI 1.09-1.16) compared to males. After adjusting for confounders, UD had a marginally higher odds (OR 1.06, 95%CI 1.02-1.11) of suicidal attempt and 1.2 times higher odds (95%CI 1.11-1.26) of suicidal ideation compared to BD. Among adolescents with suicidal attempt, 93.2% had bipolar depression and 6.8% had unipolar depression.The majority of suicidal attempt in the inpatient setting was seen in females, with bipolar depression (74.6% vs. 67.3% in unipolar). Conclusion Our finding is clinically relevant and accentuates the need for early identification of BD, accurate differentiation of UD versus BD for targeted and adequate treatment to minimize suicidal behaviors, treat and manage them per treatment guidelines, and evolving research.


Subacute renal injury in hypothyroidism: a case report of an unusual phenomenon.
Severe hypothyroidism is known to cause elevation of creatinine and this phenomenon has been reported in clinical settings in the past. Screening for hypothyroidism is not regularly performed in the differential workup for acute kidney injury due to its rare presentation. Therefore, to most physicians hypothyroidism is not known as a cause of acute kidney injury. In this clinical case report, we describe a case of subacute kidney injury in a patient with severe hypothyroidism prior to iodine-131 ablation therapy. Hypothyroidism was not recognized as the cause of elevated creatinine, which in this case led to unnecessary hospital admission and diagnostics. This case report serves as a reminder for clinicians to consider hypothyroidism in the differential diagnosis of (sub)acute kidney injury.


Effect of heat-treatment atmosphere on the bond strength of apatite layer on Ti substrate.
The purpose of this study was to investigate the bond strength of apatite layer on titanium (Ti) substrate coated by biomimetic method and to improve the bonding of apatite layer to Ti substrate by optimizing the alkali heat-treatment process. Ti plates pre-treated with an alkali solution of 10 M sodium hydroxide (NaOH) were heat-treated at 600 degrees C for 1h at different atmospheres: in air and in vacuum. A dense apatite layer formed on top of the sodium titanate layer after soaking the alkali and heat-treated Ti samples in simulated body fluid (SBF) for up to 3 weeks. The bond strengths of the sodium titanate layer on Ti substrate, and apatite layer on the sodium titanate layer, were measured, respectively, by applying a tensile load. The fracture sites were observed with a scanning electron microscope (SEM). The apatite layer on the substrate after alkali heat-treatment in air achieved higher bond strength than that on the substrate after alkali heat-treatment in vacuum. It was found that the interfacial structure between the sodium titanate and Ti substrate has a significant influence on the bond strength of the apatite layer. It is advised that titanium implants can achieve better osseointegration under load-bearing conditions by depositing an apatite layer in vivo on a Ti surface subjected to alkali and heat-treated in air.


Genome Sequence of Hafnia alvei bta3_1, a Bacterium with Antimicrobial Properties Isolated from Honey Bee Gut.
Hafnia alvei bta3_1, a strain with antibacterial properties, was isolated from honey bee gut and cultured under aerobic and anaerobic conditions. To explore the potential genetic bases of its antibacterial and possible pathogenic properties, the complete genome of this organism was sequenced and analyzed.


Evaluating the efficacy of Atriplex spp. in the phytoextraction of road salt (NaCl) from contaminated soil.
Soil and freshwater salinization are growing issues worldwide. Road salt, primarily sodium chloride (NaCl), is a significant contributor to this issue in North America. In this study, the ability of three native Canadian halophytes (Atriplex patula, Atriplex hortensis, and Atriplex canescans) to remove Na+ and Cl- from contaminated soil was investigated. Field and greenhouse studies determined plant survivability in roadside areas, as well as Na+ and Cl- extraction levels. The Atriplex spp. accumulated 18-55 mg Na+ g-1 dry weight (DW) and 41-64 mg Cl- g-1 DW when grown for a two-month period in soil spiked with NaCl to simulate a very highly contaminated roadside. Using A. patula, it would theoretically take 6 growing seasons to remove all salt from an area contaminated with 1540 μg Cl- g-1, while A. hortensis and A. canescens would take 19 and 9 years, respectively. Salt content in shoot components (seeds, stem, leaves) was determined to provide further insight on phytoextraction processes. In all three Atriplex species, the leaves had the highest Cl- concentration, followed by the seeds (bracteoles included), with the lowest concentrations found in the stem. These novel findings provide important information for road salt remediation and indicate that using Atriplex spp. may be a viable way in which to reduce the environmental impact of road salting.


[Health education: team work at school].
In this field, team work is invaluable, as the relevant frame for both content and method to be permanently readjusted to various levels imposed by the specific objectives. The better the members of this team are integrated into the educational system, as straff members of a service, the deeper the impact of the programme.


Women in dentistry: A perspective on major universities in Saudi Arabia. Part 2: Analysis and statistical data.
THE PURPOSES OF THIS STUDY WERE TO: (1) report the number of female graduates from the two oldest dental schools in Saudi Arabia; (2) compare the number of male and female graduates per year from these two major schools; and (3) compare these numbers of female dental graduates to those in the United States for the most recent year available, 2007. This study was conducted using a descriptive non-experimental design. The study sample was the number of dental school graduates from the two major dental schools in Saudi Arabia. There were 1621 graduates of the College of Dentistry of King Saud University (KSU) since its inception up to 2007 of which 853 graduates were males and 768 were females, respectively. The total number of graduates from the Faculty of Dentistry of King Abdulaziz University (KAU) since its inception up till 2007 was 628 of which 264 were males and 364 were females. There was no statistically significant difference between the total number of male and female dental school graduates, although there was a significant difference between KSU and KAU dental schools. The proportion of female graduates from the two major Saudi dental schools was just over 50 % in 2007, which is slightly higher than the 45% female graduates from dental schools in the United States and Puerto Rico. Females currently comprise approximately half of the enrolled dental students at the KSU and KAU, a percentage slightly greater than that in the United States. The substantial enrollments suggested that women in Saudi Arabia consider dentistry to be an excellent career choice.


Correction: Neuroradiological and Neurophysiological Characteristics of Patients With Dyskinetic Cerebral Palsy.
[This corrects the article on p. 189 in vol. 38, PMID: 24855613.].


Fluorescent monitoring of proteins during sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting.
Fluorescent labeling of proteins was found to be a very sensitive and reliable alternative to conventional methods for monitoring proteins on Western blots. Proteins were labeled with 2-methoxy-2,4-diphenyl-3(2H)-furanone (MDPF) before SDS-PAGE. After electrophoresis and subsequent electro-blotting the fluorescent-labeled proteins were visible upon ultraviolet illumination of the nitrocellulose membranes, and could be photographed to yield an accurate record of the blots before subsequent serological analysis. The sensitivity for detecting MDPF-labeled proteins on nitrocellulose was 100-200 ng, 50 to 100 fold less sensitive than on gels. Fluorescent-labeled TMV and MStpV capsid proteins that were blotted onto nitrocellulose still reacted in serological tests and were detected when present in quantities as low as 100 pg. Fluorescent labeling allows accurate photographic records of the SDS-gel, blot and probed blot using only one sample, and no subsequent staining steps are required.


Male infertility rate: a retrospective study.
Worldwide, male responsible infertility is on the rise. In this retrospective study, we evaluated the infertility rate of this area. Cases reported from 1989 to 1993 to the Institute for Post Graduate Teaching and Research in Ayurved University were studied. Semen reports were also scrutinized. A total number of 1,17,979 cases were examined. Male infertility rate was 45%. Patients' semen report showed that they were with oligozoospermia (22%), asthenozoospermia (11%) and azoospermia (12%). The reported value (45%) for male infertility is high, which is compared and discussed with that of authors from worldwide.


Impulsivity, Gambling-Related Cognitions, Cognitive Reappraisal and Gambling Behaviour in a Malaysian Sample.
The relationships between cognitive reappraisal and problem gambling have been widely studied in different contexts. However, previous research findings remain inconsistent. This discrepancy might be attributed to the effects of interactions between cognitive reappraisal and other risk factors for problem gambling. Using moderation models, this study examined the association between impulsivity, gambling-related cognitive distortions, cognitive reappraisal and problem gambling in a sample of Malaysian gamblers. A total of 149 community gamblers (103 males, 46 females; mean age = 32.18) completed an online questionnaire. Problem gambling was measured with the South Oaks Gambling Screen (SOGS); cognitive reappraisal was measured using the Emotion Regulation Questionnaire-Cognitive Reappraisal Subscale (ERQ-CR); impulsivity was measured with the Short-UPPS-P Impulsive Behaviour Scale (SUPPS-P); and gambling-related cognitive distortions were measured using the Gambling Related Cognitions Scale (GRCS). The results revealed impulsivity and gambling-related cognitive distortions as significant predictors of problem gambling. At high levels, impulsivity and cognitive distortions are significant moderator variables that strengthen the association between cognitive reappraisal and problem gambling. These findings demonstrate that reappraisal skills could exacerbate problem gambling severity amongst impulsive or self-deceptive gamblers. Future research with larger and more representative samples is needed to validate and generalise these findings.


[Action of high and superhigh doses of fission neutrons and gamma quanta on the central noradrenergic formation of the brain--on the locus coeruleus (the blue spot)].
Most of the blue spot neurons of Wistar rats exhibited a pronounced central chromatolysis 24 h following irradiation with fission neutrons (above 100 Gy) and gamma-quanta (above 200 Gy). The changes in the mesencephalic nucleus of the trigeminal nerve were distinct on day 2 after 200 Gy gamma-irradiation. The number of the modified nervous cells in these regions was higher than that in other brain parts.


Iron-sulfur cluster biogenesis, trafficking, and signaling: Roles for CGFS glutaredoxins and BolA proteins.
The synthesis and trafficking of iron-sulfur (Fe-S) clusters in both prokaryotes and eukaryotes requires coordination within an expanding network of proteins that function in the cytosol, nucleus, mitochondria, and chloroplasts in order to assemble and deliver these ancient and essential cofactors to a wide variety of Fe-S-dependent enzymes and proteins. This review focuses on the evolving roles of two ubiquitous classes of proteins that operate in this network: CGFS glutaredoxins and BolA proteins. Monothiol or CGFS glutaredoxins possess a Cys-Gly-Phe-Ser active site that coordinates an Fe-S cluster in a homodimeric complex. CGFS glutaredoxins also form [2Fe-2S]-bridged heterocomplexes with BolA proteins, which possess an invariant His and an additional His or Cys residue that serve as cluster ligands. Here we focus on recent discoveries in bacteria, fungi, humans, and plants that highlight the shared and distinct roles of CGFS glutaredoxins and BolA proteins in Fe-S cluster biogenesis, Fe-S cluster storage and trafficking, and Fe-S cluster signaling to transcriptional factors that control iron metabolism--.


[Pesticide residues in food plants: the role of plant metabolism].
The plant metabolism of pesticides typically leads to various classes of persistent "soluble" and "insoluble" conjugates whose structures and modes of formation and storage have been characterized only in recent years. Pesticide risk assessment should include studies on animal bioavailability and toxicological properties of the conjugates.


Age determination of the adult blow fly Lucilia sericata (Diptera: Calliphoridae) through quantitative pteridine fluorescence analysis.
Determination of a minimal postmortem interval via age estimation of necrophagous diptera has been restricted to the juvenile stages and the time until emergence of the adult fly, i.e. up until 2-6 weeks depending on species and temperature. Age estimation of adult flies could extend this period by adding the age of the fly to the time needed for complete development. In this context pteridines are promising metabolites, as they accumulate in the eyes of flies with increasing age. We studied adults of the blow fly Lucilia sericata at constant temperatures of 16 °C and 25 °C up to an age of 25 days and estimated their pteridine levels by fluorescence spectroscopy. Age was given in accumulated degree days (ADD) across temperatures. Additionally, a mock case was set up to test the applicability of the method. Pteridine increases logarithmically with increasing ADD, but after 70-80 ADD the increase slows down and the curve approaches a maximum. Sex had a significant impact (p < 4.09 × 10-6) on pteridine fluorescence level, while body-size and head-width did not. The mock case demonstrated that a slight overestimation of the real age (in ADD) only occurred in two out of 30 samples. Age determination of L. sericata on the basis of pteridine levels seems to be limited to an age of about 70 ADD, but depending on the ambient temperature this could cover an extra amount of time of about 5-7 days after completion of the metamorphosis.


Mapping proteins to disease terminologies: from UniProt to MeSH.
Although the UniProt KnowledgeBase is not a medical-oriented database, it contains information on more than 2,000 human proteins involved in pathologies. However, these annotations are not standardized, which impairs the interoperability between biological and clinical resources. In order to make these data easily accessible to clinical researchers, we have developed a procedure to link diseases described in the UniProtKB/Swiss-Prot entries to the MeSH disease terminology. We mapped disease names extracted either from the UniProtKB/Swiss-Prot entry comment lines or from the corresponding OMIM entry to the MeSH. Different methods were assessed on a benchmark set of 200 disease names manually mapped to MeSH terms. The performance of the retained procedure in term of precision and recall was 86% and 64% respectively. Using the same procedure, more than 3,000 disease names in Swiss-Prot were mapped to MeSH with comparable efficiency. This study is a first attempt to link proteins in UniProtKB to the medical resources. The indexing we provided will help clinicians and researchers navigate from diseases to genes and from genes to diseases in an efficient way. The mapping is available at: http://research.isb-sib.ch/unimed.


[Closed spinal fractures in children].
The experience with the treatment of 267 children with closed fractures of the vertebrae is described. The conservative functional treatment was conducted. Good favourable issues were noted in remote periods following the correct timely treatment.


Functioning and psychological status among individuals with COPD.
We examined the link between functioning and psychological status among persons with chronic obstructive pulmonary disease (COPD), using measures of both general functional status and performance of life activities. 334 persons with COPD were interviewed by telephone. Functioning was assessed with two measures of difficulty with specific types of activities (self-care, recreational activities/hobbies) and a general measure of functional status (SF-12 Physical Component Score (PCS)). About 16.2% of the sample had SF-12 Mental Component Score (MCS) scores indicative of psychological distress (MCS < 35). In separate regression models, difficulty with self-care and recreational activities was associated with an increased likelihood of distress (self-care: OR=2.9, 95%CI 1.3, 6.6; recreation: OR=7.5 [2.4, 23.7]), while PCS scores were not. In a model including all three predictors, difficulty with recreation was strongly associated with distress (OR=7.7 [2.1, 29.2]), difficulty with self-care was less strongly associated with distress (OR=2.1 [0.8, 5.5]), and PCS did not contribute significantly to the predictive ability of the model. However, low functioning as measured by the PCS was a significant risk factor for difficulty performing activities. Measures of activity difficulty were independent predictors of psychological distress, while general physical function was not. Poor general physical function was a risk factor for activity difficulties, suggesting an indirect relationship between low PCS and psychological distress, with activity difficulties as the intermediate variable.


Modulation of proper name recall by transcranial direct current stimulation of the anterior temporal lobes.
We often fail to recall another person's name. Proper names might be more difficult to memorize and retrieve than other pieces of knowledge, such as one's profession because they are processed differently in the brain. Neuroimaging and neuropsychological studies associate the bilateral anterior temporal lobes (ATL) in the retrieval of proper names and other person-related knowledge. Specifically, recalling a person's name is thought to be supported by the left ATL, whereas recalling specific information such as a person's occupation is suggested to be subserved by the right ATL. To clarify and further explore the causal relationship between both ATLs and proper name retrieval, we stimulated these regions with anodal, cathodal and sham transcranial direct current stimulation (tDCS) while the participants memorized surnames (e.g., Mr. Baker) and professions (e.g., baker) presented with a person's face. The participants were then later asked to recall the surname and the profession. Left ATL anodal stimulation resulted in higher intrusion errors for surnames than sham, whereas right ATL anodal stimulation resulted in higher overall intrusion errors, both, surnames and professions, compared to cathodal stimulation. Cathodal stimulation of the left and right ATL had no significant effect on surname and profession recall. The results indicate that the left ATL plays a role in recalling proper names. On the other hand, the specific role of the right ATL remaines to be explored.


Forced migration-induced diminished social networks and support, and its impact on the emotional wellbeing of older refugees in Western countries: A scoping review.
As the number of refugees continues to increase globally, so does the number of older adults forced to migrate from their home region to Western countries. Many of these older refugees lose their social networks and support to the events leading to forced migration and may be unable to recreate them once resettled. We used Arksey and O'Malley's (2005) framework to explore how forced migration has diminished the social networks and support of older refugees in Western countries and its impact on their emotional well-being. Eight databases were searched for the review; abstracts were reviewed using Rayyan QCRi(c) before the full-text review. A total of 25 studies were included in the final analysis, and findings revealed that forced migration reduced the quantity of social networks and the quality of social support older refugees received. The reduced social network and support led to social isolation, increased migration-related grief, and mental health challenges. Advances in digital technology are not yet capable of filling the support gap. With this, we hope to inform future research on the social support needs of older refugees and raise awareness of the need for humanitarian support intervention to cushion the impact of the migration-induced loss of social networks and support.


Are you ready for audits.
Audits can cost your practice thousands--if not millions--of dollars. Protect yourself with internal audits to ensure compliance.


Odor-active constituents of Cedrus atlantica wood essential oil.
The main odorant constituents of Cedrus atlantica essential oil were characterized by GC-Olfactometry (GC-O), using the Aroma Extract Dilution Analysis (AEDA) methodology with 12 panelists. The two most potent odor-active constituents were vestitenone and 4-acetyl-1-methylcyclohexene. The identification of the odorants was realized by a detailed fractionation of the essential oil by liquid-liquid basic extraction, distillation and column chromatography, followed by the GC-MS and GC-O analyses of some fractions, and the synthesis of some non-commercial reference constituents.


A two-stage culture system for the induction of antibody-forming cell clones in cultures of normal human blood lymphocytes.
A two-stage culture method is described for the induction of a specific antibody response to sheep red cells (SRC) in microcultures at limiting dilutions of human peripheral blood lymphocytes (PBL). PBL from normal donors were cultured for 4 days with antigen and EBV using well defined conditions. The cells were then distributed in 10 microliter microcultures at different cell densities in order to estimate the frequency of responding units. The culture wells were tested for the presence of anti-SRC antibody by the spot test. The results show that the expression of antibody-forming cell clones in the second stage microcultures is strictly dependent on the presence of both antigen and EBV during the first stage cultures. The efficiency of the system was improved by the addition of 4% polyethylene glycol (PEG, MW 6000) in the first stage and its removal in the second stage and by the use of human serum (instead of fetal calf) in both stages. This approach permits the separation of different cellular events, occurring when human B cells are stimulated by antigen and represents a useful approach for studying the mechanisms of the specific immune response in man.


Intracranial Hemorrhage Following Intrathecal Methotrexate Therapy for Acute Lymphoblastic Leukaemia.
Acute toxic leukoencephalopathy following intrathecal methotrexate administration is well documented but intracranial haemorrhage is extremely rare. A 2-year-6 months old girl with acute lymphoblastic leukemia developed sudden onset neurological deterioration following intrathecal methotrexate. Computed tomography scan of brain demonstrated intraventricular and subarachnoid hemorrhage. Child improved gradually on conservative management. Follow-up neuroimaging showed resolution of hemorrhage. Intracranial haemorrhage is a rare but serious complication of intrathecal methotrexate.


Evidence for a bi-partition of the Younger Dryas Stadial in East Asia associated with inversed climate characteristics compared to Europe.
The Younger Dryas Stadial (YDS) was an episode of northern hemispheric cooling which occurred within the Last Glacial Interglacial Transition (LGIT). A major driver for the YDS climate was a weakening of the Atlantic Meridional Overturning Circulation (AMOC). It has been inferred that the AMOC began to strengthen mid-YDS, producing a bipartite structure of the YDS in records from continental Europe. These records imply that the polar front and westerlies shifted northward, producing a warmer second phase of the YDS in Europe. Here we present multi-proxy data from the sediments of Lake Suigetsu (Japan), as evidence that a related bi-partition of the YDS also occurred in East Asia. Besides showing for the first time that the bi-partition was not limited to the North Atlantic/European region, the data also imply a climatic dipole between Europe and East Asia since the cold-warm characteristics are reversed at Lake Suigetsu. We suggest that changes in eastward moisture transport from the North Atlantic are the primary mechanism by which the teleconnection can be explained.


Revised "hPSC-Sac Method" for Simple and Efficient Differentiation of Human Pluripotent Stem Cells to Hematopoietic Progenitor Cells.
The human hematopoietic differentiation in vitro of human pluripotent stem cells (hPSCs) has provided new tools to elucidate the mechanisms of related genetic abnormalities, such as congenital diseases and acquired hematopoietic malignancies, and to discover new treatments. The differentiation can also be applied to developing a stable source of blood products for transfusion with minimal risk of several blood-borne infections. We previously proposed a method for hematopoietic progenitor cell (HPC) differentiation, the "hPSC-sac method", in which hPSCs are cocultured with C3H10T1/2 mouse stromal cells and mixed with a single cytokine, VEGF. The hPSC-sac method can differentiate hPSCs to multiple blood lineages. Here we describe improvements in the method by adding bFGF, TGFβ inhibitor and heparin to the culture, which increases the yield of CD34+CD43+ HPCs 50-fold compared with the original protocol. This revised hPSC-sac method is expected to contribute to the development of disease models and regenerative medicine using hematopoietic lineage cells.


Soil recovery across a chronosequence of restored wetlands in the Florida Everglades.
The restoration project in the Hole-in-the-Donut of Everglades National Park in Florida, USA is to reestablish native wetlands by complete removal of the invasive plants and the associated soil. However, there is little information available about changes in properties of the newly formed Marl soils in restored wetlands. In this study, we measured soil physicochemical properties, soil enzymatic activities, and stable isotopes of carbon (δ(13)C) in plants and soil organic carbon (SOC) in an undisturbed natural wetland (UNW) and three wetlands restored respectively in 1989, 1996 and 1999 (WR89, WR96 and WR99). The older restored wetlands (WR89 and WR96) are characterized by greater SOC and mineral nitrogen. The values of soil dehydrogenase and phosphatase activities in the four wetlands follow the order: UNW > WR89 > WR96 > WR99, and are consistent with changes in vegetation coverage. The principal component analysis shows that dehydrogenase and phosphatase activities are the vital variables contributing to the soil of UNW. The similar δ(13)C values of SOC and plants in the restored wetlands suggest the formation of SOC during restoration is mainly derived from the associated plants. These results indicate that the newly restored soils develop toward the soil in the UNW with time since restoration.


Investigations and management of gastrointestinal and hepatic manifestations of systemic lupus erythematosus.
Gastrointestinal (GI) manifestations of systemic lupus erythematosus (SLE) are protean. Any part of the GI tract and the hepatobiliary system can be involved. Up to two-third of SLE patients develop GI symptoms at some stage of their illnesses. Clinical presentations of GI lupus are non-specific and can be difficult to differentiate from infective, thrombotic, therapy-related and non-SLE etiologies. Clinical acumen and appropriate endoscopic, biopsy and imaging procedures are essential for establishing the correct diagnosis. Acute abdominal pain in SLE patients can herald an intra-abdominal catastrophe and should be evaluated promptly. Surgical intervention should be instituted without delay if conservative management fails or when there is clinical or radiological suspicion of visceral perforation or intra-abdominal collections.


Non-thermal plasma treated solution with potential as a novel therapeutic agent for nasal mucosa regeneration.
Adequate and rapid mucosal regeneration is one of the most important factors in the healing process of nasal mucosa after surgery or trauma. In particular, delayed mucosal regeneration after surgery is an important cause of surgical failure. However, no effective treatment is available yet. Non-thermal plasma (NTP) has several medical effects, but the existing probe type is limited to local direct treatment. Therefore, we investigated the various effects using liquid type plasma to overcome this limitation. In addition, the therapeutic effects of non-thermal plasma treated solution (NTS) on nasal mucosa have yet to be determined. Experiments were carried out using BEAS-2B, a human bronchial epithelial cell line similar to nasal mucosa epithelium. NTS had no cytotoxicity to the BEAS-2B cells and enhanced cell proliferation. NTS also promoted migration of BEAS-2B cells. NTS increased cell proliferation and migration via epidermal growth factor receptor (EGFR) activities and epithelial-to-mesenchymal transition (EMT) signaling. Furthermore, NTS enhanced wound healing of nasal mucosa in an animal model. Accordingly, NTS promotes nasal mucosa wound healing by increasing cell proliferation and migration. These findings suggest the therapeutic potential of NTS in nasal mucosa wound healing.


Chronic oxycodone induces integrated stress response in rat brain.
Oxycodone is an opioid that is prescribed to treat multiple types of pain, especially when other opioids are ineffective. Unfortunately, similar to other opioids, repetitive oxycodone administration has the potential to lead to development of analgesic tolerance, withdrawal, and addiction. Studies demonstrate that chronic opioid exposure, including oxycodone, alters gene expression profiles and that these changes contribute to opioid-induced analgesic effect, tolerance and dependence. However, very little is known about opioids altering the translational machinery of the central nervous system. Considering that opioids induce clinically significant levels of hypoxia, increase intracellular Ca(2+) levels, and induce the production of nitric oxide and extracellular glutamate transmission, we hypothesize that opioids also trigger a defensive mechanism called the integrated stress response (ISR). The key event in the ISR activation, regardless of the trigger, is phosphorylation of translation initiation factor 2 alpha (eIF2α), which modulates expression and translational activation of specific mRNAs important for adaptation to stress. To test this hypothesis, we used an animal model in which female rats were orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days. We demonstrated increased levels of hsp70 and BiP expression as well as phosphorylation of eIF2α in various rat brain areas after oxycodone administration. Polysomal analysis indicated oxycodone-induced translational stimulation of ATF4 and PDGFRα mRNAs, which have previously been shown to depend on the eIF2α kinase activation. Moreover, using breast adenocarcinoma MCF7 cells, which are known to express the μ-opioid receptor, we observed induction of the ISR pathway after one 24-h treatment with oxycodone. The combined in vivo and in vitro data suggest that prolonged opioid treatment induces the integrated stress response in the central nervous system; it modulates translational machinery in favor of specific mRNA and this may contribute to the drug-induced changes in neuronal plasticity.


An iterative algorithm for the separation of action potential sequences.
Various iterative algorithms for separation of superimposed event sequences were designed, and their efficiency examined through simulation studies. It has been found that a double parallel-serial algorithm improved markedly the efficiency of the filtration process. For the same probability of detection of the event series to be extracted, the probability of 'impurity' events dropped by roughly 0.10, as compared to the non-iterative fixed window width algorithm. Conclusions are drawn regarding separation of motor unit action potential sequences from the total electromyogram.


Aberrant expression of oxytocin receptor in endometrium and decidua in women who have experienced recurrent implantation failure.
To detect the oxytocin receptor (OTR) expression levels in the endometrium and decidua from women who have experienced recurrent implantation failure (RIF) and fertile women. Laboratory study using human endometrial and decidual samples. University-affiliated hospital. Six patients with RIF and six fertile women were recruited for endometrial sampling on day 20-24 of the menstrual cycle. Decidual tissues were collected from women who had a history of RIF and experienced a spontaneous abortion at 6-8 weeks of gestation (n = 8) and women with healthy pregnancies that terminated for nonmedical reasons (n = 8). None. OTR expression in the endometrial and decidual tissues was detected with the use of real-time quantitative polymerase chain reaction and Western blotting. OTR protein and mRNA were significantly increased in the endometria of RIF patients. In the decidua, OTR protein was significantly up-regulated in the RIF group, whereas mRNA was significantly decreased in this group. Women who experienced RIF presented with an aberrant expression pattern of OTR in the endometria and decidua.


[Intramuscular lengthening and range of motion after local tendon transfer for repair of retracted supraspinatus tendon defects. A biomechanical study].
The current cadaver study was performed to evaluate and compare infraspinatus (ISP) vs. subscapularis (SSC) tendon transfer used for the repair of a large supraspinatus (SSP) rotator cuff defect. The main outcome measures were the range of motion and intramuscular length changes during motion. Thirteen fresh-frozen cadaver shoulders were used in the study. A supraspinatus defect extending to the apex of the humeral head (Patte size II) was created. Transosseous repair was then attempted with the ISP and with the SSC in all cases; intramuscular length changes were measured by Hall effect transducers during motion of the arm in steps of 30 degrees. Repair was successful in all cases when the ISP was used, while use of the SSC resulted in a successful repair in only 8 of the 13 (61.5%). Passive range of motion did not differ between ISP and SSC. ISP was shortened during flexion and abduction in contrast to the SSC that was lengthened during flexion (p<0.05) and shortened to a lesser degree (p<0.05). Length changes during rotation were not significantly different. In this cadaver model the ISP proved more favorable than the SSC for covering a Patte size II SSP defect if the assumption is true that lengthening of a muscle is less favorable than shortening because of the vascularization of the tendon.


An ultrasensitive photoelectrochemical nucleic acid biosensor.
A simple and ultrasensitive procedure for non-labeling detection of nucleic acids is described in this study. It is based on the photoelectrochemical detection of target nucleic acids by forming a nucleic acid/photoreporter adduct layer on an ITO electrode. The target nucleic acids were hybridized with immobilized oligonucleotide capture probes on the ITO electrode. A subsequent binding of a photoreporter--a photoactive threading bis-intercalator consisting of two N,N'-bis(3-propyl-imidazole)-1,4,5,8-naphthalene diimides (PIND) linked by a Ru (bpy)2(2) (bpy = 2,2'-bipyridine) complex (PIND-Ru-PIND)-allowed for photoelectrochemical detection of the target nucleic acids. The extremely low dissociation rate of the adduct and the highly reversible photoelectrochemical response under visible light illumination (490 nm) make it possible to conduct nucleic acid detection, with a sensitivity enhancement of four orders of magnitude over voltammetry. These results demonstrate for the first time the potential of photoelectrochemical biosensors for PCR-free ultrasensitive detection of nucleic acids.


Adenoidal and tonsillar lymphocyte subsets in AIDS children.
Tonsils and adenoids are secondary lymphoid organs exposed to the environment. The most important classifications of AIDS include the lymphocyte subsets of peripheral blood. We have studied the lymphocyte subsets in peripheral blood and secondary lymphoid organs in a control group of children suffering adenotonsillar pathology and in five children with AIDS and the same adenotonsillar pathology. The antigen surface markers were determined by flow cytometry in lymphocytes isolated from peripheral blood, and from tonsils and adenoids after tonsillectomy and adenoidectomy, in the control group and in children diagnosed with AIDS. The most important findings in tonsils and adenoids were a decrease of the total T lymphocytes, helper T lymphocytes and CD4/CD8 ratio; an increase of cytotoxic T lymphocytes and B lymphocytes, as well as a 200% increase in monocytes of AIDS-affected children. These observations show the value of analyzing the lymphocyte subsets of the tonsils and adenoids of AIDS-affected children, and establishing an earlier relation to clinical symptoms.


Evaluation of cervicothoracic junction injury.
Cervical spine injury is a significant cause of morbidity and mortality in the traumatized patient. Little of the trauma literature addresses injury to the cervicothoracic junction (C7-T1); we were able to find only two studies that evaluated the incidence of injury in this area. The spinal injury registry of St Joseph's Hospital and Medical Center and Barrow's Neurological Institute in Phoenix, Arizona, was reviewed for cervical spine-injured patients. Of the 397 patients with cervical spine injury admitted between January 1980 and June 1985, 37 (9%) had cervicothoracic junction injury. Documentation of signs and symptoms of neck injury was recorded for each patient. All available lateral cervical spine radiographs were evaluated for indirect evidence of injury through the level of C7 as currently recommended in the trauma literature. Films were reviewed after being masked at the middle of the body of C7 thereby visualizing the C6-C7 junction. The incidence of C7-T1 injury in our cervical spine-injured population was 9%. Nine of the patients (24%) had a depressed level of consciousness and had neurologic examination that was not diagnostic of spinal injury. All of the cervical injuries in these patients were diagnosed by radiographic evaluation alone. We recommend that adequate visualization of the cervical spine through the cervicothoracic junction must be the standard for trauma care.


Establishment and validation of a nomogram model for postoperative surgical site infection after transforaminal lumbar interbody fusion: A retrospective observational study.
Surgical site infection is one of the serious complications of transforaminal lumbar interbody fusion surgery, and many factors affect its occurrence. A total of 1,277 patients who underwent transforaminal lumbar interbody fusion between 2018 and 2021 were enrolled in this study. Subsequently, 1,277 patients were randomly assigned to a training cohort (N = 958) and a validation cohort (N = 319) in a 3:1 ratio. We developed a nomogram according to the results of binary logistic regression analysis in the training cohort. The nomogram's predictive accuracy and discriminative ability were evaluated by calibration curve and receiver operating characteristic analysis. Decision curve analysis was performed to estimate the clinical value of our nomogram. In univariate and multivariate analysis, smoking, diabetes, intraoperative blood loss, American Society of Anesthesiologists class ≥III, serum calcium, albumin, and serum glucose were identified as significant independent predictors. The nomogram was developed using these independent predictors, which showed good diagnostic accuracy for surgical site infection of the training and validation cohorts. The calibration curves for the 2 cohorts showed optimal agreement between nomogram prediction and actual observation. The decision curve analysis of the nomogram model showed the great clinical use of the nomogram. The nomogram based on smoking, diabetes, intraoperative blood loss, American Society of Anesthesiologists class, serum calcium, albumin, and serum glucose has the potential as a clinically useful predictive tool of surgical site infection after transforaminal lumbar interbody fusion surgery. It is helpful to visualize the risk factors of surgical site infection.


Neuropathological assessment of artemether-treated severe malaria.
In animals, high doses of intramuscular artemether and artemotil have been shown to cause an unusual pattern of selective damage to certain brainstem nuclei, especially those implicated in hearing and balance. We aimed to investigate whether a similar pattern arises in human adults. We examined the brainstems of adults who died after treatment with high dose artemether or quinine for severe falciparum malaria for evidence of a pattern of selective neuronal damage. Neuropathological findings were similar in recipients of quinine (n=15) and artemether (n=6; total artemether doses received 4-44 mg/kg). No evidence was recorded for artemether-induced neurotoxic effects.


Home blood pressure monitoring in an ethnically diverse inner-city cardiology practice.
To evaluate home blood pressure monitoring (HBPM) in an inner city cardiology practice. Retrospective study. Inner city cardiology practice. Consecutive patients were evaluated for hypertension and had > or = 8 home blood pressure recordings during 2-4 weeks while clinically stable on a medical regimen. Blood pressure differences, blood pressure load, defined as %HBPM systolic blood pressure readings > 140 and/or diastolic blood pressure readings > 90 mm Hg. 55 patients, (33 female, age 62 +/- 12.5 years). Office systolic, diastolic and mean BPs were higher than HBPM values (147 +/- 19 mmHg vs 139 +/- 17 mmHg, P = < .0001), (86 +/- 10 mm Hg vs 79 +/- 10 mm Hg, P < .0001), and (106 +/- 11 mm Hg vs 99 +/- 10 mmHg, P < .0001) respectively. Office and home pulse pressure (PPs) were similar (61 +/- 17 mm Hg vs 60 +/- 17 mm Hg, P = .42). Office and home PPs were more strongly correlated (r = .78, P < .0001) than were systolic (r = .51, P < .0001), diastolic (r = .51, P < .0001). Blood pressure load increased in a step-wise manner with increasing office blood pressure, 7.5% for patients with office blood pressure < 120/80 mm Hg to 73.5% in patients with office blood pressure > 160/100 mm Hg (P = .02). Office BPs showed 10/55 patients were normal or controlled (blood pressure < 140/ 90 mmHg) and 45 were high or uncontrolled (blood pressure > or = 140/90 mmHg). HBPM reclassified 2/10 patients as high/uncontrolled whereas 17/45 patients became normal/controlled. Office systolic and diastolic BPs are 7-8 mm Hg higher than home recordings in ethnically diverse patients. Office and home PPs are more strongly correlated than systolic, diastolic or mean arterial BPs. Blood pressure load is related to office BPs. HBPM reclassified approximately one third of the patients. HBPM appears useful in managing minority populations with hypertension.


Behavioral contingency analysis.
This paper presents a formal symbolic language, with its own specialized vocabulary and grammar, for codifying any behavioral contingency, including the complex multiparty contingencies encountered in law, economics, business, public affairs, sociology, education, and psychotherapy. This language specifies the "if, then" and temporal relationships between acts and their consequences for the parties involved. It provides for the notation of the probabilities, magnitudes, positive or negative valences, or time delays of the consequences for the parties, and for the parties that would perceive, misperceive, not perceive, predict, mispredict, or not predict events. The language's fractal-like hierarchical and recursive grammar provides for the flexible combination and permutation of the modifiers of the language's four nouns: acts, consequences, time intervals, and agents of acts; and its four verbs: consequate, prevent, perceive, and predict-thereby giving the language the ability to describe and codify various nuances of such complex contingencies as fraud, betting, blackmail, various types of games, theft, crime and punishment, contracts, family dynamics, racing, competition, mutual deterrence, feuding, bargaining, deception, borrowing, insurance, elections, global warming, tipping for service, vigilance, sexual overtures, decision making, and mistaken identity. Applications to the management of practical situations and techniques for doing so, as well as applications in current behavior analysis research and neuroscience, are discussed.


A fractal analysis of the spatial distribution of tumoral mast cells in lymph nodes and bone marrow.
The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells distribution through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. We have compared diffuse large B cells lymphoma (DLBCL) and systemic mastocytosis in two different anatomical localizations (lymph nodes for DLBCL and, respectively, bone marrow for mastocytosis). Results have indicated that, despite the high difference in size exhibited by the mast cells patterns in the two conditions, the spatial relationship between the mast cells forming the aggregates resulted similar, characterized by a significant tendency of the mast cells to self-organize in clusters.


Effect of Liposuction on Body Weight and Serum Concentrations of Leptin, Lipids, Glucose, and Insulin: A Meta-Analysis.
Abdominal obesity has been associated with an increased risk of insulin resistance, metabolic syndrome, and diabetes. Central fat removal procedures such as liposuction, lipectomy, and abdominoplasty are among the most common surgical procedures. The impact of the latter on the former is controversial and understudied. The authors aimed to explore the effect of subcutaneous fat elimination procedures on insulin resistance measures and adipokine levels. Relevant studies regarding the effects of surgical subcutaneous fat removal on glucose, insulin, adipokines, and lipid metabolism, as well as blood pressure, were identified by searching PubMed and Ovid-Cochrane without limits in date, type of publication, or language. After the selection process, 24 studies were obtained. The results of the articles were summarized using descriptive statistics. For the final analysis, a randomized effects model was used to evaluate heterogeneity; averages and meta-analytic differences were expressed with a confidence interval of 95%. All studies reported a reduction in weight (-2.64 kg; 95% CI, -4.32 to -0.96; P = 0.002; I 2 = 36%; P of I 2 < 0.001) and body mass index after liposuction. A significant improvement in triglycerides (-10.06 mg/dL; 95% CI, -14.03 to -6.09; P < 0.001; I 2 = 48%; P of I 2 = 0.05), serum glucose concentration (-4.25 mg/dL; 95% CI, -5.93 to -2.56; P < 0.001; I 2 = 68%; P of I 2 < 0.001), serum insulin concentration (-2.86 μIU/mL; 95% CI, -3.75 to -1.97; P < 0.001; I 2 = 59%; P of I 2 = 0.003), and serum leptin concentration (-7.70 ng/mL; 95% CI, -11.49 to -3.92; P = 0.0001; I 2 = 96%; P of I 2 < 0.001) was consistently observed. In addition to weight loss, there is a significant decrease in leptin, triglyceride, glucose, and insulin serum concentrations after liposuction, a fact that should be considered in future discussions.


Anesthesia efficacy of bupivacaine in pregnant participants with breech presentation receiving external cephalic version: A protocol of systematic review of randomized controlled trials.
The objective of this study is to appraise the efficacy and safety of bupivacaine in pregnant participants with breech presentation (BP) receiving external cephalic version (ECV). The following electronic databases will be searched from the origin to the January 31, 2020: PUBMED, EMBASE, Cochrane Library, CINAHL, ACMD, PsycINFO, Scopus, OpenGrey, and China National Knowledge Infrastructure. No language and publication time limitations will be applied to all of them. Randomized controlled trials comparing bupivacaine to other interventions for pain relief in pregnant participants with BP undergoing ECV will be included in this study. Two authors will employ the selection of searched records, extraction of essential data from included RCTs, and risk of bias assessment for each eligible trail independently and respectively. Any doubts between 2 authors will be figured out by a third author through discussion. The risk of bias assessment will be judged using Cochrane risk of bias tool. The data pooling and analysis will be performed using RevMan 5.3 software. This study will summarize the up-to-date high-quality evidence and will synthesis the outcome data from that evidence to explore the efficacy and safety of bupivacaine for pain relief in pregnant participants with BP undergoing ECV. The findings of this study may present important guidance for patients, clinical practice, as well as health-policy makers regarding the utilization of bupivacaine for pain relief in pregnant participants with BP receiving ECV. PROSPERO CRD42020164409.


Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis.
Mutations in the ABCC6 gene, encoding the multidrug resistance-associated protein 6 (MRP6), cause pseudoxanthoma elasticum (PXE). This heritable disorder leads to pathological alterations in connective tissues. The implication of MRP6 deficiency in PXE is still unknown. Moreover, nothing is known about a possible compensatory expression of other ATP binding-cassette (ABC) transporter proteins in MRP6-deficient cells. We investigated the gene expression profile of 47 ABC transporters in human dermal fibroblasts of healthy controls (n=2) and PXE patients (n=4) by TaqMan low-density array. The analysis revealed the expression of 37 ABC transporter genes in dermal fibroblasts. ABCC6 gene expression was not quantifiable in fibroblasts derived from PXE patients. Seven genes (ABCA6, ABCA9, ABCA10, ABCB5, ABCC2, ABCC9 and ABCD2) were induced, whereas the gene expression of one gene (ABCA3) was decreased, comparing controls and PXE patients (with at least twofold changes). We reanalyzed the gene expression of selected ABC transporters in a larger set of dermal fibroblasts from controls and PXE patients (n=6, each). Reanalysis showed high interindividual variability between samples, but confirmed the results obtained in the array analysis. The gene expression of ABC transporter genes, as well as lineage markers of PXE, was further examined after inhibition of ABCC6 gene expression by using specific small-interfering RNA. These experiments corroborated the observed gene expression alterations, most notably in the ABCA subclass (up to fourfold, P<0.05). We therefore conclude that MRP6-deficient dermal fibroblasts exhibit a distinct gene expression profile of ABCA transporters, potentially to compensate for MRP6 deficiency. Moreover, our results point to a function for ABCC6/MRP6 in sterol transport, as sterols are preferential regulators of ABCA transporter activity and expression. Further studies are now required to uncover the role of ABCA transporters in PXE.


Pregnancy-Related Venous Thromboembolism Risk in Asymptomatic Women With Antithrombin Deficiency: A Systematic Review.
To evaluate the risk of pregnancy-associated venous thromboembolism in women with asymptomatic antithrombin deficiency. The search was performed on MEDLINE (Ovid and PubMed databases) for the period 1966 to June 2012 and ClinicalTrials.gov as of December 15, 2015. A systematic review including randomized controlled trials, cohort studies, and case-control studies was conducted. Selection criteria included objectively diagnosed venous thromboembolism or venous thromboembolism treated with 3 months of anticoagulation before the availability of objective testing. The study population consisted of pregnant women with asymptomatic antithrombin deficiency. Seven publications were included in the review. No randomized controlled trials were identified. The best available data consist of three retrospective cohort studies and four case-control studies. Pooled results from case-control studies yielded an estimated odds ratio for venous thromboembolism of 6.09 (95% confidence interval 1.58-23.43). No pooled estimates could be obtained for cohort studies. Data on use of thromboprophylaxis were scarce. Despite the small number of patients included, and the variation in study designs, pooled results from case-control studies show a significant association between asymptomatic antithrombin deficiency and pregnancy-associated venous thromboembolism. Thromboprophylaxis during pregnancy and postpartum should be considered in these women.


[Additional pathway of the metabolic activation of N-nitrosodiethylamine in the rat liver].
A cytosolic enzyme, aldehyde oxidase (AO), was shown to be involved in metabolic activation of carcinogenic diethylamine (DENA). DENA was reduced to corresponding hydrazines by AO in the presence of benzaldehyde. Products of DENA reduction by AO possessed mutagenic activity for Salmonella typhimurium TA 1950. Pretreatment of rats by antioxidant butylhydroxytoluene had no effect on this process of DNA bioactivation.


Psychedelic medicines for end-of-life care: Pipeline clinical trial review 2022.
People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the therapeutic use of psychedelics at end of life. Much uncertainty remains, however, mainly due to methodological difficulties that beset existing trials. We conducted a scoping review of pipeline clinical trials of psychedelic treatment for depression, anxiety, and existential distress at end of life. Proposed, registered, and ongoing trials were identified from 2 electronic databases (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform). Recent reviews and both commercial and non-profit organization websites were used to identify additional unregistered trials. In total, 25 studies were eligible, including 13 randomized controlled trials and 12 open-label trials. Three trials made attempts beyond randomization to assess expectancy and blinding effectiveness. Investigational drugs included ketamine (n = 11), psilocybin (n = 10), 3,4-methylenedioxymethamphetamine (n = 2), and lysergic acid diethylamide (n = 2). Three trials involved microdosing, and fifteen trials incorporated psychotherapy. A variety of onging or upcoming clinical trials are expected to usefully extend evidence regarding psychedelic-assisted group therapy and microdosing in the end-of-life setting. Still needed are head-to-head comparisons of different psychedelics to identify those best suited to specific indications and clinical populations. More extensive and rigorous studies are also necessary to better control expectancy, confirm therapeutic findings and establish safety data to guide the clinical application of these novel therapies.


The role of nucleus accumbens dopamine in responding on a continuous reinforcement operant schedule: a neurochemical and behavioral study.
Two experiments were undertaken to investigate the role of nucleus accumbens dopamine (DA) in instrumental lever pressing on a continuous reinforcement (CRF) schedule. Rats trained to press a lever for food reinforcement on a CRF schedule, and food-deprived control rats, were implanted with dialysis probes in the nucleus accumbens. The day after implantation, rats were tested and dialysis samples were assayed for DA and the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). Performance of the lever-pressing task resulted in significant increases in extracellular levels of DA and DOPAC relative to control rats. The increases in extracellular DA were significantly correlated (r = 0.92) with the number of lever press responses committed. In the second experiment, the neurotoxic agent 6-hydroxydopamine was infused directly into the nucleus accumbens to investigate the effects of DA depletion on lever-pressing performance. DA depletion had only a modest effect on the total number of lever presses, and there was a significant effect on total lever presses only on the first test day (third day postsurgery). Analyses also were performed on responding across the 45-min session by breaking down the session into three 15-min periods. There was a significant group x time interaction, with DA-depleted rats showing a significant reduction in the numbers of responses in the first 15-min period, but no significant effects over the second or third 15 min in the session. This initial slowing of response rate was present across all 5 test days. These results indicate that DA release and metabolism increases in rats performing on a CRF schedule, and that DA depletion produces a slowing of initial response rate.


Mikania micrantha extract enhances cutaneous wound healing activity through the activation of FAK/Akt/mTOR cell signaling pathway.
Mikania micrantha (MM) has been traditionally used for various health benefits, including mental health, anti-inflammatory, wound dressing, and healing of sores. However, the molecular mechanisms and dose required for the wound healing activity of MM have yet to be reported. Therefore, a study was conducted to evaluate the wound healing potential of a cold methanolic extract of MM through in vitro and in vivo studies. Human dermal fibroblast adult (HDFa) cells were treated with 0 (control), 75 ng/ml, 125 ng/ml, 250 ng/ml, and 500 ng/ml of MMmethanolic extract (MME) for 24 h. MME at 75 ng/ml has significantly (p˂0.05) promoted HDFa cell proliferation and migration. Further, MME has also been shown to enhance the invasiveness of human umbilical vascular endothelial cells (HUVECs), indicating the neovasculature for wound healing. The tube formation assay demonstrated a significant (p<0.05) increase in the angiogenic effect of the MME starting at a concentration of 75 ng/ml as compared to the control. Treatment of excision wounds in Wistar rats with 5% and 10% MME ointment significantly enhanced wound contraction compared to control animals. Incision wounds in rats treated with 5% and 10% MME showed a significant (p<0.01) increase in tensile strength compared to control. HDFa cells, and granulation tissue collected on day 14 post-wounding, revealed the modulation of the FAK/Akt/mTOR cell signaling pathway during the enhancement of wound healing. The results of gel zymography showed increased activity of MMP-2 and MMP-9 in the HDFa cells after treatment with the extract. It is concluded that MMEcan potentially accelerate cutaneous wound healing.


Distribution and properties of the mannose-resistant hemagglutinin produced by Salmonella species.
Presence or absence of mannose-resistant hemagglutination (MRHA) or sheep erythrocytes by Salmonella species was found to be consistent within most serotypes tested and did not correlate with O-antigen. Broad-host-range serotypes including S. typhimurium and S. enteritidis produced MRHA while host-specific serotypes including S. typhi, S. dublin, and S. gallinarum were MRHA-negative. MRHA produced by S. typhimurium was soluble, heat-stable, and not inhibited by any of eleven carbohydrates tested. Further investigation of MRHA may provide insight into mechanisms of Salmonella pathogenesis.