Isoniazid effects on choreiform movement and on GABA, HVA, and 5-HIAA in CSF.
Isoniazid was administered in 4-week open trial in patients with choreiform movement. Gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were measured before and after treatment. Isoniazid did not improve choreiform movement. CSF GABA levels were significantly increased after treatment, but HVA and 5-HIAA levels were not significantly altered. The findings suggest that isoniazid influenced brain GABA metabolism but did not influence dopamine and serotonin metabolism in patients with chorieform movement.


The poverty of embodied cognition.
In recent years, there has been rapidly growing interest in embodied cognition, a multifaceted theoretical proposition that (1) cognitive processes are influenced by the body, (2) cognition exists in the service of action, (3) cognition is situated in the environment, and (4) cognition may occur without internal representations. Many proponents view embodied cognition as the next great paradigm shift for cognitive science. In this article, we critically examine the core ideas from embodied cognition, taking a "thought exercise" approach. We first note that the basic principles from embodiment theory are either unacceptably vague (e.g., the premise that perception is influenced by the body) or they offer nothing new (e.g., cognition evolved to optimize survival, emotions affect cognition, perception-action couplings are important). We next suggest that, for the vast majority of classic findings in cognitive science, embodied cognition offers no scientifically valuable insight. In most cases, the theory has no logical connections to the phenomena, other than some trivially true ideas. Beyond classic laboratory findings, embodiment theory is also unable to adequately address the basic experiences of cognitive life.


Intravesical chemotherapy in the United States. An overview.
Intravesical chemotherapy has been widely employed in this country as part of the treatment strategy for clinically localized bladder cancer. Although surgery remains the principal therapeutic modality, intravesical agents are increasingly being considered as adjuncts and as salvage or prophylactic therapy for polychronotopic superficial disease. Instillation treatment is first-line therapy for diffuse in situ carcinoma. Several compounds have been subjected to intravesical trials in this country, but thio-TEPA has been most extensively studied. More recently mitomycin C and Adriamycin have been utilized following encouraging preliminary reports from abroad. BCG, a biologic agent, has also stimulated interest and current trials. Phase I-II studies with intravesical interferon have been initiated. While the potential role for intravesical therapy is becoming clear, additional trails to test new agents, compare current agents, and refine dose, concentration, volume, and contact time are indicated.


Comparison of CT findings and histopathological characteristics of pulmonary cryptococcosis in immunocompetent and immunocompromised patients.
Pulmonary cryptococcosis (PC) is a common fungal infectious disease, and infection can occur in patients with any immune function. To better understand PC, we compared the CT findings and histopathological results in immunocompetent and immunocompromised patients. The clinical data of 68 patients with PC were collected retrospectively and divided into the immunocompetent group and immunocompromised group. The clinical characteristics, CT manifestations and histopathological characteristics of the two groups of patients were compared. Forty-two patients (61.8%) were immunocompetent, and 26 patients (38.2%) were immunocompromised. Compared with immunocompromised patients, 57.14% (24/42) of immunocompetent patients were asymptomatic (p = 0.002). Compared with immunocompetent patients, cough (14/26, 53.9%) and fever (13/26, 50.0%) were the main symptoms in immunocompromised patients (p = 0.044, p = 0.007). Nodular lesions (97.6%, 41/42) were the most common CT type in immunocompetent patients, and the CT characteristic was a single lesion (25/42, 59.5%); the main histopathological type was nodular fibrogranuloma (30/42, 71.4%), and the main histopathological characteristic was inflammatory granuloma (31/42, 73.81%) formed by macrophage phagocytosis of Cryptococcus. Consolidation (15/26, 57.7%) was more common in the CT type of immunocompromised patients. Multiple lesions (24/26, 92.31%), air bronchial signs (19/26, 73.081%) and cavities (9/26, 34.62%) were the main CT characteristics. The mucinous colloid type (19/26, 73.1%) was its main histopathological type, which was mainly characterized by a small amount of surrounding inflammatory cell infiltration (17/26, 65.4%). There were significant differences in the classification and characteristics of CT and pathology between the two groups (p < 0.05). Through the CT manifestations and histopathological characteristics of PC under different immune function states, it was found that immune function has a significant impact on the CT manifestations and histopathological characteristics of patients with PC.


Impact of coexisting diabetes on survival and risk of developing second primary cancer in diabetes patients receiving drug therapy: A multicenter retrospective cohort study of patients with cancer in Japan.
We investigated the association between coexisting diabetes at the time of cancer diagnosis, and the overall survival and incidence of second primary cancer in patients with cancer and receiving drug therapy for diabetes. We used cancer registry and administrative data of patients diagnosed with cancer at designated cancer care hospitals in Osaka Prefecture between 2010 and 2015. The presence of diabetes was identified from the prescription records of antidiabetic drugs in Diagnosis Procedure Combination System data. After adjusting for patient characteristics, we compared overall survival between patients with cancer with coexisting diabetes and those without coexisting diabetes using the Cox proportional hazards model. In addition, the impact of coexisting diabetes on the risk of developing second primary cancer was evaluated using a competing risk analysis. Of the 131,701 patients with cancer included in the analysis, 6,135 (4.7%) had coexisting diabetes. The 5-year survival rates for patients with and without coexisting diabetes were 56.2% (95% confidence interval 54.8-57.6) and 72.7% (95% confidence interval 72.4-73.0), respectively. Coexisting diabetes was associated with a higher risk of developing second primary cancer (subdistribution hazard ratio 1.23; 95% confidence interval 1.08-1.41). In site-specific analysis, coexisting diabetes was associated with an increased risk for the development of second primary cancer of multiple myeloma, and cancer of the uterus, pancreas and liver. Coexisting diabetes was associated with a higher mortality and risk of developing second primary cancer in Japanese patients with cancer and on drug therapy for diabetes.


Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV).
The natural course of chronic hepatitis non-A, non-B (HNANB) was documented for 3-20 yr (mean 8 yr) in 86 patients, who attended our special ambulance between 1981 and 1988. Sixty five of the 86 patients (75%) were positive for circulating antibodies against hepatitis C virus (HCV) (anti-HCV). Twenty four patients had chronic posttransfusion (PT)-HNANB (18 anti-HCV-positive; 75%), and 62 patients had sporadic (S)-HNANB (47 anti-HCV-positive; 75%). Twenty nine per cent of patients with chronic PT-HNANB had sustained normalization of aminotransferases after a period up to 5 yr, 55% demonstrated chronic persistent hepatitis (CPH) and 16% progressed to chronic active hepatitis (CAH) with transition to cirrhosis. In the group with chronic S-HNANB, 2% of patients showed remission, 43% had stable CPH and 55% progressed to CAH or cirrhosis. However, development of cirrhotic complications required many years. Transition from CAH to CPH or remission was not observed. The results indicate that 75% of both patients groups with chronic PT- and S-HNANB are infected with the same agent, of which antibodies are detected by the new anti-HCV assay. There was no statistical association between the severity of the disease and the presence of anti-HCV. The different proportions of progressive courses in chronic PT- and S-HNANB might be explained by the patient recruitment.


The Role of 3D-pCASL MRI in the Differential Diagnosis of Glioblastoma and Brain Metastases.
The first aim of this study was to compare the intratumoral and peritumoral blood flow parameters in glioblastomas and brain metastases measured by pseudocontinuous arterial spin labeling MRI (3D pCASL). The second aim of this study was to determine whether pCASL could aid in identifying the source of brain metastases. This study included 173 patients aged 12 to 83 years (median age-61 years), who were observed at the National Medical Research Center for Neurosurgery. All patients underwent preoperative MRI with pCASL perfusion. Thereafter patients were operated on and received histological diagnosis. No patients received preoperative chemo or radiotherapy. The values of maximum and normalized intratumoral blood flow were significantly higher in the group with gliblastoma than in the group with brain metastases: 168.98 + -91.96 versus 152.1 + -173.32 and 7.6 + -8.4 versus 9.3 + -5.33 respectively (p <0.01). However, ROC analysis showed low AUC specificity and sensitivity (0.64, 70%, 60% for mTBF and 0.66, 77%, 62% for nTBF). Peritumoral blood flow parameters were also higher in the glioblastoma group (29.61 + -22.89 versus 16.58 + -6.46 for mTBF and 1.63 + -1.14 versus 0.88 + -0.38 for nTBF, respectively; p <0.01). ROC analysis showed the following measurements of AUC, specificity, and sensitivity (0.75, 68%, 73% for mTBF and 0.77, 58%, 91% for nTBF). Regarding pCASL and various histological subsets of brain metastases, the study found statistically significant differences between the lung and melanoma metastases and the lung and kidney metastases. ROC analysis gave the following values for lung and melanoma metastases: AUC-0.76, specificity-75%, and sensitivity-73% for mTBF; 0.83, 67%, and 93% respectively, for nTBF. For lung and kidney metastases: AUC-0.74, specificity-70%, and sensitivity-93% for mTBF; 0.75, 70%, and 93% respectively, for nTBF. pCASL could aid in differential diagnosis between glioblastoma and brain metastases. Measurement of peritumoral blood flow demonstrates higher specificity and sensitivity than with intratumoral blood flow. Moreover, pCASL provides the ability to distinguish lung metastases from kidney and melanoma metastases.


The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial.
To determine whether the functional mu-opioid receptor (OPRM1) Asn40Asp variant predicts the comparative efficacy of different forms of NRT, we conducted a clinical trial of transdermal nicotine (TN) vs nicotine nasal spray (NS) in 320 smokers of European ancestry. Smokers carrying the OPRM1 Asp40 variant (n=82) were significantly more likely than those homozygous for the Asn40 variant (n=238) to be abstinent at the end of treatment, and reported less mood disturbance and weight gain. The genotype effect on treatment outcome was most pronounced among smokers receiving TN, particularly during the 21 mg dose phase. Smokers who carry the OPRM1 Asp40 variant are likely to have a favorable response to TN and may benefit from extended therapy with the 21 mg dose.


Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat.
Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses. We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group. Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.


National and provincial dioxin emissions from municipal solid waste incineration in China.
China presently lacks an up-to-date regional inventory of dioxin emissions from municipal solid waste incineration (MSWI), although MSWI has grown rapidly in recent decades. Based on dioxin concentrations from the official website for governments and enterprises, we created an inventory of dioxin emissions from 29 areas in mainland China. MSWI released a total of 22.56 g I-TEQ of dioxins in 2020. According to Monte Carlo simulation, the dioxin emissions with 95 %, 75 %, and 50 % certainty are 17.03-31.62, 19.24-27.71, and 20.43-25.96 g I-TEQ, respectively. Notably, Guangdong, Zhejiang, and Jiangsu provinces accounted for 38.8 %. The primary regions with considerable dioxin emission per capita and density are Zhejiang and Shanghai. Furthermore, Jilin and Heilongjiang provinces are the top two regions in terms of dioxin emissions per unit of billion gross domestic product. These indicators were affected significantly by the quantity of MSW generated and incinerated (MSWGI), capacity and operating years of incinerators, and degrees of air pollution control devices (APCDs). Dioxin emission factors (EFs) were about 100 times lower in 2020 than in 2004. Note, however, that there is a gap in dioxin EFs between China and European nations. We have proposed that MSW source classification, stable operation conditions of incinerators and APCDs, categories of incinerators selection, and technological upgrading should be China's major measures to curb dioxin emissions. Moreover, with the future increment in the quantity of MSWGI, it is essential to completely reinvent the dioxin monitoring program.


"Y" incision and rectangular patch enlargement of aortic annulus and valve reconstruction with autologous pericardium in congenital aortic stenosis.
Surgical aortic valve replacement in children who have undergone prior balloon or surgical valvuloplasty or both is a formidable challenge. The aortic annulus is small, there is no ideal prosthesis and lifelong anticoagulation is highly undesirable. A "Y" incision and rectangular patch enlargement of the aortic annulus introduced by Dr. Bo Yang in 2020 combined with aortic valve reconstruction introduced by Dr. Shigeyuki Ozaki in 2011, is feasible, as described in this case.


Comparing the strengths and weaknesses of observational and experimental studies using a postmarketing surveillance study as a protypic example.
A recent prospective, observational study in rheumatoid arthritis patients indicated that the addition of hydroxychloroquine to either aspirin or methotrexate therapy decreased the incidence of hepatic enzyme abnormalities. This interesting finding is of potential clinical importance, but its validity needs to be examined in terms of the potential confounders inherent in observational studies. Although one of the study's strengths is its derivation from "real-life" data, some potential confounders that might weaken the data include a need to examine whether any scientific rationale can be discerned for the observation; examination of control-case matching (issues of randomization and baseline disease characteristics); the potential for attribution bias; data-collection methods (prospective versus retrospective, uniform versus chart review); and equivalency of treatment protocols, dosing regimens, and concomitant medications. Potential scientific rationale exists for the observed interaction, and data collection is both uniform and prospective. These strengths are confounded by the inevitable lack of randomization in observational studies, the potential for differences in baseline disease characteristics, attribution bias, a lack of controlled dosing regimens and treatment protocols, and an assumption that all nonsteroid antiinflammatory drugs are alike (which is not true). On balance, the hypothesis generated by these data is compelling enough to deserve further testing in both observational and experimental settings.


Polymer electret guidance channels enhance peripheral nerve regeneration in mice.
Polytetrafluoroethylene (PTFE) tubes were prepared as electrets displaying a quasi-permanent surface charge due to the presence of trapped monopolar charge carriers. PTFE tubes containing either positive or negative charges and electrically neutral PTFE tubes were used as nerve guidance channels for the repair of a 4 mm nerve gap in the sciatic nerve of mice. After 4 weeks of implantation, positively and negatively charged PTFE electrets contained regenerated nerves with significantly more myelinated axons than nerves regenerated in uncharged PTFE tubes. This observation suggests that peripheral nerve regeneration can be enhanced by electrically charged nerve guidance channels.


Late life depression.
Depression has an overall prevalence of 5-8%. The prevalence of late life depression is estimated among people 65 years of age to be 15%. There is a great under-diagnosis and under-treatment of late life depression with the most serious consequence being premature death. Depression is also an important and independent risk factor for mortality following myocardial infarction, while patients with stroke associated with depression also have a higher death rate. The suicide rate is increased in elderly especially elderly men with depression. The aetiology of depression is more heterogeneous than depression in younger adults. Obviously age-related changes in the brain increase the risk for depression. Patients with neurodegenerative disorders also run a higher risk for being depressed. In Alzheimer's disease the frequency is around 50%. Deficiency of essential nutrients like folic acid and vitamin B12 is an obvious risk factor for both disorders with cognitive impairment and depression. Treatment of depression in the elderly follows the same lines as treatment of depression in younger patients. Many different drugs may be prescribed; however, the risk of adverse events is greater in the elderly. The drugs of choice are the selective serotonin re-uptake inhibitors (SSRIs), which have a response rate of around 65%. Of interest is that emotional disturbances like irritability, aggressiveness and anxiety also respond to treatment with SSRIs. A comprehensive treatment of late life depression, which includes social and psychological support, has a response rate of 80-90%.


Comparison of echocardiographic acoustic quantification with off-line manual tracing for determining left ventricular volume and ejection fraction in pediatric patients.
Echocardiographic measurement of left ventricular systolic and diastolic volume and ejection fraction in pediatric patients by acoustic quantification using automated border methods compares well with measurements done by manual trace. The time necessary for completion of measurements was similar for the two methods.


[A family with x-linked hydrocephaly followed for 20 years: echographic prenatal diagnosis; elective abortion].
In a Bickers-Adams family followed up for almost 20 years, authors report pregnancies of two propositus' sisters: echographic diagnosis of (normal) girls, of normal or affected boys and selective abortion in a case of dizygotic twin pregnancy with a normal girl and an affected boy.


Unexpected kinetic complexity in the formation of a nonheme oxoiron(IV) complex.
The stoichiometric formation of [FeIV(O)(TPA)(NCMe)]2+ (TPA = tris(2-pyridylmethyl)amine) from the reaction of [FeII(TPA)(NCMe)2]2+ with 1 equiv. peracetic acid exhibits more kinetic complexity than might be expected from the simple stoichiometry. A multiple-pathway mechanism with an FeIV-peracetic acid species, [(TPA)FeIV(O)((H)O3CR)]2+/+, as the primary oxidant is proposed.


Multinodular pilomatrixoma.
A hard deep nodule, 6 x 3 mm in size, was excised from the cheek of a 12-year-old girl. The histological sections showed a multinodular cyst-like proliferation, each nodule showing the typical structure and cytology of pilomatrixoma. A comparison is made between this case and the budding phenomenon that has been described in isthmus-catagen (tricholemmal) cyst.


Insulin and cyclic adenosine monophosphate increase prolactin gene expression through different response pathways.
Insulin and cAMP stimulate prolactin gene transcription and prolactin-CAT expression in rat pituitary tumor GH cells. Expression of prolactin-CAT construct, pPrl(-173/+75)CAT, is stimulated 10- to 30-fold by either insulin or cAMP. Addition of both insulin and cAMP resulted in an additive 20- to 60-fold stimulation. Although the regulatory sequences have not been defined precisely, both insulin and cAMP appear to stimulate transcription of prolactin-CAT expression through possibly identical sequences in the -106/-87 region of the promoter. Insulin mediated increases in prolactin-CAT expression are not ras-dependent in GH4 cells. Thus, a number of experiments were performed to determine that the effects of insulin and cAMP are independent. First, insulin does not stimulate cAMP levels in GH4 cells. Second, cAMP action was inhibited by expression of a mutant regulatory subunit of cAMP-dependent protein kinase A that does not bind cAMP and by expression of an inhibitor of cAMP-dependent protein kinase A, while insulin action was not affected by expression of these proteins. Thus, although the regulatory sequences for insulin and cAMP may be identical, the effects of insulin and cAMP on the prolactin gene are clearly mediated through distinct response pathway.


Comparison of improving energy use and mitigating pollutant emissions from industrial and non-industrial activities: Evidence from a variable-specific productivity analysis framework.
This paper seeks to account for differences in productivity of the industrial and non-industrial activities in the productivity analysis framework. The Luenberger productivity indicator is widely applied to analyze the productivity change, and can be decomposed as it follows the additive structure. But there have been few studies on sector operation performance and industrial structure involving both the industrial and non-industrial inputs, output and air pollutant emissions. Resorting on the China's province-level data on energy, output and air pollutants from 2006 to 2019, we find that the industrial SO2 emissions, energy consumption and NOX emissions are the major factors leading to sector operation inefficiency. By decomposing the operation performance indicator (OPI), we observe that contribution to productivity change by energy consumption, air pollutant emissions and output is higher than contribution by the non-industrial variables. Furthermore, technical progress offsets negative efficiency growth. In order to implement energy conservation, emissions reduction and industrial restructuring at the provincial level, China's government should take efforts to improve the efficiency of non-industrial energy consumption and support the development of cleaner industries.


Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Sublingual allergen-specific immunotherapy (SLIT) intervention improves the control of grass pollen allergy by maintaining allergen tolerance after cessation. Despite its widespread use, little is known about systemic effects and kinetics associated to SLIT, as well as the influence of the patient sensitization phenotype (Mono- or Poly-sensitized). In this quest, omics sciences could help to gain new insights to understand SLIT effects. 47 grass-pollen-allergic patients were enrolled in a double-blind, placebo-controlled, multicenter trial using GRAZAX® during 2 years. Immunological assays (sIgE, sIgG4, and ISAC) were carried out to 31 patients who finished the trial. Additionally, serum and PBMCs samples were analyzed by metabolomics and transcriptomics, respectively. Based on their sensitization level, 22 patients were allocated in Mono- or Poly-sensitized groups, excluding patients allergic to epithelia. Individuals were compared based on their treatment (Active/Placebo) and sensitization level (Mono/Poly). Kinetics of serological changes agreed with those previously described. At two years of SLIT, there are scarce systemic changes that could be associated to improvement in systemic inflammation. Poly-sensitized patients presented a higher inflammation at inclusion, while Mono-sensitized patients presented a reduced activity of mast cells and phagocytes as an effect of the treatment. The most relevant systemic change detected after two years of SLIT was the desensitization of effector cells, which was only detected in Mono-sensitized patients. This change may be related to the clinical improvement, as previously reported, and, together with the other results, may explain why clinical effect is lost if SLIT is discontinued at this point.


Coenzyme Q10 protects the aging heart against stress: studies in rats, human tissues, and patients.
With aging of the population, increasing numbers of elderly patients are presenting for cardiac surgery. However, the results in the elderly are inferior to those in the young. A likely contributing factor is an age-related reduction in cellular energy production in the myocardium during surgery, which is known to induce aerobic and ischemic stress. The lipophilic antioxidant and mitochondrial respiratory chain redox coupler, coenzyme Q10 (CoQ10), has the potential to improve energy production in mitochondria by bypassing defective components in the respiratory chain as well as by reducing the effects of oxidative stress. We hypothesized that CoQ10 pretreatment prior to stress could improve the recovery of the myocardium after stress.


In vitro experiments on neuronal and glial cell lineages among the ventricular cells of the mouse neural plate.
The proliferative ventricular cells of the early neural plate of the mouse are generally assumed to be pluripotent and equivalent to one another in their developmental capability. Ventricular cells from the rostral parts of the neural plates of mice (Theiler stages 11 and 12, embryonic days 71/2 and 8) were studied in tissue culture with respect to their potential to give rise to neurons or glial cells, or both. Autoradiographic and immunohistochemical analyses showed that ventricular cells developing into neuronal phenotypes stopped proliferating immediately upon transfer to cell culture. Using polyclonal anti-GFAP antibodies, a small proportion of immunoreactive cells could be detected after 4 days of culture. These cells retained their proliferative activity, displayed morphological characteristics of radial glial cells, and may have either developed from specific glial progenitor cells or have been induced to proceed along the glial differentiation pathway at the beginning of culture. Therefore, two distinct types of progenitor cells, committed either to neuronal or glial lineages, appear to co-exist among the cultured neural plate ventricular cells.


Octreotide scanning in the detection of a mesenchymal tumour in the pubic symphysis causing hypophosphataemic osteomalacia.
Oncogenic hypophosphataemic osteomalacia is a rare condition. The causative tumour is often difficult to locate. Primary tumours have been reported in the head and neck, skeleton, and soft tissue. Octreotide scanning was used in this case and detected a mesenchymal tumour in the pubic symphysis.


Prevalence of bovine subclinical mastitis and antibiotic susceptibility patterns of major mastitis pathogens isolated in Unguja island of Zanzibar, Tanzania.
A cross-sectional study was conducted between January and July 2014 in Unguja island of Zanzibar to establish prevalence of subclinical mastitis (SCM) in smallholder dairy cows and patterns of antibacterial susceptibility of major mastitis pathogens isolated. A total of 416 dairy cows from 201 farmers were randomly selected from three districts of Unguja Island to participate in the study. Questionnaire interview, field observation, individual cow examination, California Mastitis Test (CMT) and bacteriological examination were carried out. Kirby-Bauer disc diffusion technique was used to test drug sensitivity for common bacteria isolated. Based on CMT results, the overall prevalence of SCM was 28.6, 48.8 and 64.7% at quarter, cow and farm level, respectively. Prevalence of bacterial infection was recorded at 42.9, 70.9 and 78.6% at quarter, cow and farm examined, respectively. The common bacteria isolated included Staphylococcus aureus (36.8%), Pseudomonas aeruginosa (17.8%), Staphylococcus epidermidis (16.1%), Klebsiella spp. (9.5%), Micrococcus spp. (6.3%) and Escherichia coli (4.9%). In conclusion, findings of this study demonstrated high level of subclinical mastitis at farms, cows and quarters levels with both contagious and environmental bacterial pathogen involved. Therefore, efforts should be directed to the decreased subclinical mastitis by improving sanitary measures and proper milking practice.


Imperative persistent interaction analysis of anticancer noscapine-ionic liquid with calf thymus DNA.
In this study, we have shown the interaction between opium poppy alkaloid noscapine-based ionic liquid [Pip-Nos]OTf and ct-DNA using UV-visible absorption spectroscopy, fluorescence spectroscopy, CD, and computational studies. The absorption spectra showed a hypochromic shift with no shift in the absorption maxima suggesting groove or electrostatic binding. Fluorescence spectra showed an enhancement in fluorescence emission suggesting that the probable mode of binding should be groove binding. Ethidium bromide (EB) competitive and Ionic strength study showed the absence of intercalative and electrostatic modes of interaction. Further, CD analysis of ct-DNA suggested a groove binding mode of interaction of [Pip-Nos]OTf with ct-DNA. [Pip-Nos]OTf displayed a strong binding with the target ct-DNA with a molecular docking score of -41.47 kJ/mol with all 3D coordinates and full conformation. Also, molecular binding contact analyses depicted the stable binding of drug and ct-DNA with potential hydrogen bonds and hydrophobic interactions. The structural superimposition dynamics analysis showed the stable binding of [Pip-Nos]OTf with the ct-DNA model through RMSD statistics. Moreover, the ligand interaction calculations revealed the involvement of large binding energy along with a high static number of molecular forces including the hydrogen bonds and hydrophobic interactions in their complexation. These significant results report the potency of [Pip-Nos]OTf and its important futuristic role in cancer therapeutics.


Tumor-simulating giant serpentine aneurysm of the posterior cerebral artery.
A case of a giant aneurysm of the proximal segment of the posterior cerebral artery is reported. Complete neuroradiologic (computed tomography scan, angiography, magnetic resonance imaging) and pathological studies were performed. This type of aneurysm is extremely rare and may be difficult to differentiate from a cerebral tumor, both clinically and on computed tomography scan. Vertebral angiography is usually necessary to make, or confirm, the diagnosis.


A motion artefact in real-time ultrasound scanners.
Motion observed in real-time ultrasound images may be very misleading. The speckle pattern in images of soft tissue is an artefact and it may move in a way which bears no simple relationship to the motion of the tissues. The physical origin of this anomaly is described.


End-to-end automatic differentiation of the coronavirus disease 2019 (COVID-19) from viral pneumonia based on chest CT.
In the absence of a virus nucleic acid real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test and experienced radiologists, clinical diagnosis is challenging for viral pneumonia with clinical symptoms and CT signs similar to that of coronavirus disease 2019 (COVID-19). We developed an end-to-end automatic differentiation method based on CT images to identify COVID-19 pneumonia patients in real time. From January 18 to February 23, 2020, we conducted a retrospective study and enrolled 201 patients from two hospitals in China who underwent chest CT and RT-PCR tests, of which 98 patients tested positive for COVID-19 (118 males and 83 females, with an average age of 42 years). Patient CT images from one hospital were divided among training, validation and test datasets with an 80%:10%:10% ratio. An end-to-end representation learning method using a large-scale bi-directional generative adversarial network (BigBiGAN) architecture was designed to extract semantic features from the CT images. The semantic feature matrix was input for linear classifier construction. Patients from the other hospital were used for external validation. Differentiation accuracy was evaluated using a receiver operating characteristic curve. Based on the 120-dimensional semantic features extracted by BigBiGAN from each image, the linear classifier results indicated that the area under the curve (AUC) in the training, validation and test datasets were 0.979, 0.968 and 0.972, respectively, with an average sensitivity of 92% and specificity of 91%. The AUC for external validation was 0.850, with a sensitivity of 80% and specificity of 75%. Publicly available architecture and computing resources were used throughout the study to ensure reproducibility. This study provides an efficient recognition method for coronavirus disease 2019 pneumonia, using an end-to-end design to implement targeted and effective isolation for the containment of this communicable disease.


Comparison of streptokinase with heparin: late results in the treatment of deep venous thrombosis.
Nineteen cases were reinvestigated 8-14 years after treatment with SK or heparin. Judging from personal interviews, foot volumometry and phlebography, treatment with SK appears to be more preferable since it was less often followed by late severe postthrombotic changes.


An anatomic review of thalamolimbic fiber tractography: ultra-high resolution direct visualization of thalamolimbic fibers anterior thalamic radiation, superolateral and inferomedial medial forebrain bundles, and newly identified septum pellucidum tract.
Images obtained through ultra-high-field 7.0-tesla magnetic resonance imaging with track-density imaging provide clear, high-resolution tractograms that have been hitherto unavailable, especially in deep brain areas such as the limbic and thalamic regions. This study is a largely pictorial description of the deep fiber tracts in the brain using track-density images obtained with 7.0-T diffusion-weighted imaging. To identify the fiber tracts, we selected 3 sets of tractograms and performed interaxis correlation between them. These tractograms offered an opportunity to extract new information in areas that have previously been difficult to examine using either in vivo or in vitro human brain tractography. With this new technique, we identified 4 fiber tracts that have not previously been directly visualized in vivo: septum pellucidum tract, anterior thalamic radiation, superolateral medial forebrain bundle, and inferomedial forebrain bundle. We present the high-resolution images as a tool for researchers and clinicians working with neurodegenerative and psychiatric diseases, such as Parkinson disease, Alzheimer disease, and depression, in which the accurate positioning of deep brain stimulation is essential for precise targeting of nuclei and fiber tracts.


Vascular endothelial growth factor single-nucleotide polymorphism in gallbladder cancer.
Angiogenesis plays a key role in growth, progression, and metastasis of various cancers. Vascular endothelial growth factor (VEGF) polymorphism has been associated with several cancers. Role of VEGF has not been reported in gallbladder cancer (GBC). Present study was designed to investigate the role of VEGF polymorphism in GBC and in other (benign) gallbladder diseases, that is chronic cholecystitis (CC) and xanthogranulomatous cholecystitis (XGC). Blood samples were collected from 195 GBC, 140 CC, and 47 XGC patients and 300 normal healthy controls. VEGF polymorphisms were investigated using amplification refractory mutation system polymerase chain reaction for g.43737830A>G and g.3437A>C, polymerase chain reaction-restriction fragment length polymorphism for c.*237C>T, and g.43736418delTinsG amplified by polymerase chain reaction. At g.43737830A>G, GA genotype showed susceptibility (odds ratio [OR] = 1.65 and OR = 1.68) and GG genotype showed protective association (OR = 0.58 and OR = 0.50) with GBC and CC. Allele A of VEGF g.43737830A>G was risk associated with GBC and CC (OR = 1.48 and OR = 1.70), while G allele was risk protective for GBC and CC (OR = 0.67 and OR = 0.58). At g.3437A>C, genotype CA was risk protective for GBC (OR = 0.61). TT genotype of c.*237C>T was susceptible for GBC and CC (OR = 2.59 and OR = 3.48), while CC genotype was risk protective for GBC and CC (OR = 0.61 and OR = 0.34). T allele of c.*237C>T polymorphism was risk associated with GBC and CC (OR = 1.63 and OR = 2.90), while C allele was risk protective for GBC and CC (OR = 0.38 and OR = 0.28). Haplotype I-C-A-C was risk protective for GBC (OR = 0.27). The present study suggests that c.*237C>T and g.43737830A>G polymorphisms are useful markers of susceptibility to GBC.


[The SARS-CoV-2, a new pandemic zoonosis that threatens the world].
On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (> 85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.


The role of leptin on the organization and expression of cytoskeleton elements in nucleus pulposus cells.
Obesity is an important risk factor for intervertebral disc degeneration and leptin is a biomarker of obesity. However, the expression of leptin receptors has not been determined in disc tissue. It is not known whether leptin has a direct effect on the nucleus pulposus (NP) cells. To determine whether the NP tissues and cells express leptin receptors (OBRa and OBRb) and whether leptin affects the organization and the expression of major cytoskeletal elements in NP cells. Messenger RNA (mRNA) and protein levels of OBRa and OBRb were measured by real-time PCR and Western blot, respectively, in NP tissues and cells. Immunofluorescence and real-time PCR and Western blot were performed to investigate the effect of leptin on cytoskeleton reorganization and expression. Results show that mRNA and proteins of OBRa and OBRb were expressed in all NP tissues and cells, and that OBRb expression was correlated with patients' body weight. Increased expression of β-actin and reorganization of F-actin were evident in leptin-stimulated NP cells. Leptin also induced vimentin expression but had no effect on β-tubulin in NP cells. These findings provide novel evidence supporting the possible involvement of leptin in the pathogenesis of intervertebral disc degeneration.


The Most Useful Pharmaceutical Formulations (Individualized Medications) in Pediatric Dermatology: A Review.
The administration of appropriate doses of active ingredients and excipients is crucial for achieving desired treatment outcomes in pediatric dermatology. A number of factors need to be considered, including the characteristics of the lesion, the patient, and the drug. An additional challenge in pediatric settings is the limited number of commercially available formulations suitable for use in children. Drug compounding, which is the preparation of medications tailored to the needs of individual patients, is a good alternative for pediatric populations for a number of reasons. Using a customized compound, the clinician can prescribe formulations that contain the optimal dose of the active ingredients within acceptable limits and the most suitable vehicle and formulation components. Compounding can also be used to combine several active ingredients in a single medication and even adapt the vehicle to the characteristics of the lesion and the needs of the patient. The pharmaceutical formulations described in this review are based on extensive clinical experience and can be customized to meet individual needs.


Common regularities in changes of the neutrophil functional activity during in vivo growth of tumors of different immunogenic activity.
Studies on BALB/c mice with tumors of different immunogenic activity (nonimmunogenic J774, WEHI 164 and immunogenic NS0) have showed that the development of a tumor is associated with changes in the neutrophil morphology and functions: the counts and size of the cells migrating to the focus increase and their capacity to produce active oxygen species is changed.


Fate of Cryptosporidium and Giardia through conventional and compact drinking water treatment plants.
Over the past three decades, a notable rise in the occurrence of enteric protozoan pathogens, especially Giardia and Cryptosporidium spp., in drinking water sources has been observed. This rise could be attributed not only to an actual increase in water contamination but also to improvements in detection methods. These waterborne pathogens have played a pivotal role in disease outbreaks and the overall escalation of disease rates in both developed and developing nations worldwide. Consequently, the control of waterborne diseases has become a vital component of public health policies and a primary objective of drinking water treatment plants (DWTPs). Limited studies applied real-time PCR (qPCR) and/or immunofluorescence assay (IFA) for monitoring Giardia and Cryptosporidium spp., particularly in developing countries like Egypt. Water samples from two conventional drinking water treatment plants and two compact units (CUs) were analyzed using both IFA and qPCR methods to detect Giardia and Cryptosporidium. Using qPCR and IFA, the conventional DWTPs showed complete removal of Giardia and Cryptosporidium, whereas Mansheyat Alqanater and Niklah CUs achieved only partial removal. Specifically, Cryptosporidium gene copies removal rates were 33.33% and 60% for Mansheyat Alqanater and Niklah CUs, respectively. Niklah CU also removed 50% of Giardia gene copies, but no Giardia gene copies were removed by Mansheyat Alqanater CU. Using IFA, both Mansheyat Alqanater and Niklah CUs showed a similar removal rate of 50% for Giardia cysts. Additionally, Niklah CU achieved a 50% removal of Cryptosporidium oocysts, whereas Mansheyat Alqanater CU did not show any removal of Cryptosporidium oocysts. Conventional DWTPs were more effective than CUs in removing enteric protozoa. The contamination of drinking water by enteric pathogenic protozoa remains a significant issue globally, leading to increased disease rates. Infectious disease surveillance in drinking water is an important epidemiological tool to monitor the health of a population.


2.5 A structure of aspartate carbamoyltransferase complexed with the bisubstrate analog N-(phosphonacetyl)-L-aspartate.
In an X-ray diffraction study using the method of multiple isomorphous replacement, the structure of aspartate carbamoyltransferase (EC 184.108.40.206) complexed with the bisubstrate analog N-(phosphonacetyl)-L-aspartate (PALA) has been solved to 2.5 A. Ten rounds of model building and 123 cycles of restrained reciprocal space refinement have resulted in a model containing 94.4% of the theoretical atoms of the protein-inhibitor complex with an R-factor of 0.231. The fit of the model to the density is excellent, except for occasional side-chains and two sections of the regulatory chains that may be disordered. The electron density for the PALA molecule is readily identifiable for both catalytic (c) chains of the asymmetric unit and bonding interactions with several important residues including Ser52, Arg54, Thr55, Ser80, Lys84, Arg105, His134, Arg165, Arg229 and Gln231 are apparent. The carboxylate groups of the PALA molecule are in a nearly cis conformation. Gross quaternary changes between the T and R forms are noted and in agreement with earlier work from this laboratory. Namely, in the new structure the catalytic trimers move apart by 12 A along the 3-fold axis of the enzyme and relocate by 10 degrees relative to each other, adopting a more eclipsed position. The regulatory (r) chains in the new structure reorient about their 2-fold axis by 15 degrees. Large tertiary changes that include domain migration and rearrangement are also present between these two forms. In the R form both domains of the catalytic chain relocate closer to each other in order to bind to the inhibitor. The polar domain seems to bind primarily to the carbamoyl phosphate moiety of PALA, and the equatorial domain binds primarily to the L-aspartate moiety. Other changes in tertiary structure bring the 80s loop (from an adjacent catalytic chain) and the 240s loop into a position to interact with the PALA molecule. Changes have been searched for in all interface regions of the enzyme. While the C1-C4 and C1-R4 regions have been completely altered, most of the other interchain interfaces are similar in the T and R forms. The intrachain interfaces, between domains of the same catalytic chains, have undergone some reorganization as these domains move closer to each other when the inhibitor is bound. This new structure allows a reinterpretation of genetic and chemical modification studies done to date.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified.
Few studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database. A total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups. There were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival. MBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.


Joint hypermobility syndrome.
Although perceived as a rare condition, joint hypermobility syndrome is common. Its prevalence in rheumatology clinics is extremely high. Early estimates suggest that it may be the most common of all rheumatologic conditions. The problem lies in the general lack of awareness of the syndrome, its means of recognition, and the resultant failure to diagnose it correctly when present. It is a worldwide problem. This article provides an overview of hypermobility and hypermobility syndrome, stressing its multisystemic nature and the negative impact that it may have on quality of life, with particular reference to gastrointestinal involvement.


[Possibilities and prospects of noninvasive bypass diagnosis. Comparison of different nuclear magnetic resonance tomography methods with conventional coronary angiography].
The aim of the study was to evaluate the patency of coronary artery bypass grafts (CABGs) with different MR imaging techniques. 25 patients with 63 bypass grafts and a total of 78 distal anastomoses were studied at a 1.5-Tesla scanner. A 2-D T2-weighted breath-hold turbo spin echo sequence (Haste), a 3-D breath-hold contrast-enhanced MR angiography sequence (Fisp-3-D), and 3-D angiography sequence in navigator techniques were used. With the Haste and Fisp-3-D sequences, 44 of the 47 patent and 14 of the 16 occluded grafts were recognized, the sensitivity and specificity were 94% and 88%, respectively. With the Haste sequence, 80% (43/54) of the distal anastomoses were seen in good image quality, and with the Fish-3-D sequence 70% (38/54). The navigator sequence showed less sensitivity and specificity (74% and 63%, respectively). The patency of CABGs can be evaluated noninvasively with the Haste and the Fisp-3-D angiography sequences. Better results can be expected with the development of a blood-pool contrast medium and an improvement of the spatial resolution.


Mechanism of differential staining in carious dentin.
The caries detector, 1.0% acid red solution in propylene glycol, failed to stain EDTA-demineralized bovine dentin matrix, but stained the same matrix when treated by lactic acid in a concentration above 0.01 M. Thus, acid of bacterial origin could possibly be responsible for the stainability change of carious dentin in vivo.


Treatment and Prevention of Spinal-Induced Hypotension in the Cesarean Section Patient: What Does the Evidence Say?
Most anesthesia providers prefer to do a subarachnoid block (SAB) for cesarean section because of its rapid onset and reliability to provide adequate anesthesia. However an effect of the SAB is that it causes a spinal-induced hypotension (SIH) in up to 85% of the population. There have been multiple studies that assessed fluid administration, vasopressor administration, maternal positioning, or serotonin blockers given prophylactically to attenuate the SIH response. Despite these multiple studies, the method to prevent and treat SIH remains varied from one anesthesia practice to another. The purpose of this chapter is to review the evidence on the various methods used to prevent and treat SIH.


A comparative study of Liandan Xiaoyan Formula metabolic profiles in control and colitis rats by UPLC-Q-TOF-MS combined with chemometrics.
Liandan Xiaoyan Formula (LDXYF) is a traditional Chinese medicine prescription (TCMP) consisting of Herba Andrographis (dried herb of Andrographis paniculata) and Picrasmae ramulus et folium (dried twiggeries and leaves of Picrasma quassioides). It is used to treat diarrhea, acute gastroenteritis, colitis, and dysentery, among other inflammatory gastrointestinal diseases. However, because of less research on the in vitro chemical composition and holistic metabolism of LDXYF, in vivo mechanisms of action and quality control of LDXYF have not yet been fully assessed due to the lack of studies into its bioactive components. In this study, ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established for comprehensive analysis of chemical compounds of LDXYF and their metabolites in serum and urine samples of control and colitis rats. As a result, totally 94 compounds in LDXYF were unambiguously identified or tentatively characterized. And a total of 91 LDXYF-related xenobiotics were characterized, including 61 (16 prototypes and 45 metabolites) in serum, and 72 (26 prototypes and 46 metabolites) in urine. Besides, we compared the exposure of metabolites in normal and colitis rats by chemometrics and summarize similarities and differences of metabolic pathways of mainly compounds in normal and colitis conditions, and found that in control and colitis conditions, alkaloids predominantly went through phase I reaction combined phase II reaction (hydroxylation and sulfation, hydroxylation and glucuronidation, demethylation and glucuronidation), while the major metabolic reaction of diterpene lactones were phase Ⅱ reactions (glucuronidation, sulfation). And there were no significant differences in metabolic pathways between control and colitis groups, just the exposure of prototype and their metabolites absorbed into serum or excreted through the urine were different, and 17 alkaloids and 6 diterpene lactone prototypes and their metabolites in serum could be considered as potential pharmacodynamic substances. A comprehensive analysis of the compounds and metabolic characteristics of LDXYF was conducted in our study, and the results laid the chemical foundation for further research into effective substances and the action mechanism of LDXYF.


Reduced DNA ligase activity in etoposide resistant human lymphatic leukaemia CEM cells.
Drug resistance is an obstacle preventing success of cancer chemotherapy. Resistance of vaccinia virus towards the topoisomerase II (topo II) targeting anti-cancer drug etoposide has been mapped to the viral DNA ligase gene. The present study was performed to elucidate if the DNA ligase activity, besides topo II levels, was altered in human lymphatic leukaemia cell strains with different levels of etoposide resistance. At measurements of DNA ligase activity with specific substrates, to distinguish between different DNA ligases, a reduced DNA ligase activity was observed in the resistant substrains. In contrast, the initial step of the ligation process, formation of DNA ligase--AMP complex, did not decrease in the resistant cell strains, suggesting an alteration in a later reaction leading to a deteriorated DNA ligation. The results suggest that decreased DNA ligase activity, besides topo II alterations, may contribute to etoposide resistance of the investigated CEM cells. The relevance of this finding will be further investigated.


Fetal cortical transplants reduce the thalamic atrophy induced by frontal cortical lesions in newborn rats.
Fetal neocortical tissue was grafted into frontal cortex lesion cavities made in newborn rats. After survival periods extending up to 14 months, volumetric measurements of the total thalamus and of the lateral, medial and anterior thalamic compartments showed an amelioration of the thalamic atrophy that normally is found after cortical lesions. These results correspond to previous findings demonstrating interconnections between fetal cortical transplants and the host thalamus.


Selective serotonin reuptake inhibitors and manic switch: A pharmacovigilance and pharmacodynamical study.
There is still no approved mechanism of manic switch in bipolar disorder, yet many selective serotonin reuptake inhibitors were accused for this important adverse event. Therefore, we aimed to investigate to estimate SSRI's risk for reporting mania and elevated mood using FEARS database and investigate receptor mechanisms involved. Mania and relevant side effects approved by FDA were screened in this dataset from the first quarter of 2004 to the third quarter of 2020. Disproportionality analysis were performed to estimate reporting odds ratio (ROR) and linear regressions were conducted to investigate relationship between ROR and Ki values. Receptor occupancy ratios were calculated from in vitro receptor binding profiles. The pharmacodynamical profile was extracted from the International Union of Basic and Clinical Pharmacology and the British Pharmacology Society dataset. Child and adolescent population was also investigated separately. The analysis showed that the odds of a spontaneous report of mania in the FAERS database involving an SSRI were higher than the odds that such a report involved other types of drugs (ROR: 5.324 [CI: 3.773; 7.514]). The largest effect size in this estimation was found in fluvoxamine (ROR: 13.957 [CI: 10.391; 18.747]). Significant effects were found in regression analysis for Ki values of H1 and M1 receptors on ROR. Receptor occupation was not found to have an effect on ROR. Lower degress of Ki values on M1 and H1 may be plausible pharmacological mechanism. Further pharmacological data and clinical assessments may be important to validate this safety signal.


Breast Reduction and Mastopexy for Repair of Asymmetry After Breast Conservation Therapy: Lessons Learned.
Breast conservation therapy (BCT) can cause breast distortion and asymmetry. Repair of this asymmetry by means of breast reduction or mastopexy procedures can be challenging and harbor considerably high rates of complications. In this retrospective study, we describe our experience in repairing post-BCT breast asymmetry by performing breast reduction or mastopexy. The surgical protocol we followed consisted of stringent patient selection, thorough surgical planning, basic surgical refinements, and patient education for enhancing the likelihood of achieving a good outcome with minimal surgical complications. Our search of the departmental database identified 25 patients with breast asymmetry who had undergone breast reduction or mastopexy between 2009 and 2017. Corrective surgery was performed 4 years on average after the completion of radiotherapy, and those patients included eleven who had undergone breast reduction and fourteen who had undergone mastopexy on the radiated side. Two patients (8%) had major complications that required further surgery (major fat necrosis, wound infection, and breast deformation), and five patients (20%) had minor complications (infection, minor fat necrosis, wound dehiscence, and nipple congestion). All complications developed on the radiated breast. There was no correlation between the occurrence of complications and patients' demographics, tumor type, tumor location, and breast tissue resection (p > 0.05). Only two of our 25 patients had major complications following breast reduction and mastopexy for the repair of asymmetry post-BCT. Following our four-step protocol was instrumental in leading to the successful performance of these procedures. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The effects of ammonium sulfate and acid on horse and human serum butyrylcholinesterase (EC 126.96.36.199).
1. Results of laboratory experiments which compared horse and human serum butyrylcholinesterase (EC 184.108.40.206) with respect to their acid inactivation and ammonium sulfate protection show: 2. Horse serum butyrylcholinesterase is more resistant to inactivation at pH 3.0 than human serum butyrylcholinesterase. 3. The loss of activity at pH 3.0 for both horse and human butyrylcholinesterase does not follow first order kinetics. 4. Both human and horse serum butyrylcholinesterase are protected from pH 3.0 inactivation by ammonium sulfate concentrations up to 33% saturation (1.37 M).


Measurement precision for repeat examinees on a standardized patient examination.
Examinees who initially fail and later repeat an SP-based clinical skills exam typically exhibit large score gains on their second attempt, suggesting the possibility that examinees were not well measured on one of those attempts. This study evaluates score precision for examinees who repeated an SP-based clinical skills test administered as part of the US Medical Licensing Examination sequence. Generalizability theory was used as the basis for computing conditional standard errors of measurement (SEM) for individual examinees. Conditional SEMs were computed for approximately 60,000 single-take examinees and 5,000 repeat examinees who completed the Step 2 Clinical Skills Examination(®) between 2007 and 2009. The study focused exclusively on ratings of communication and interpersonal skills. Conditional SEMs for single-take and repeat examinees were nearly indistinguishable across most of the score scale. US graduates and IMGs were measured with equal levels of precision at all score levels, as were examinees with differing levels of skill speaking English. There was no evidence that examinees with the largest score changes were measured poorly on either their first or second attempt. The large score increases for repeat examinees on this SP-based exam probably cannot be attributed to unexpectedly large errors of measurement.


Hydrogen-bond effect and ion-pair association in the separation of neutral calix[4]pyrroles by nonaqueous capillary electrophoresis.
A study on the migration behavior of four neutral macrocyclic compounds calix[4]pyrroles (C4Ps) by nonaqueous capillary electrophoresis (NACE) with tetrabutylammonium halide salts as background electrolyte (BGE) is described. Systematic studies were carried out with different BGE in acetonitrile (ACN) to elucidate the involved phenomena. The effect of BGE concentration on analytes effective mobilities mu eff,i was studied. Rough values of analytes absolute mobilities mu infinity,i were obtained by extrapolation of effective mobilities to zero ionic strength of BGE. Stokes radius of C4Ps in the form of C4PF(-) and C4PCl(-) was calculated. The complex constants of C4Ps with F(-) anion and Cl(-) anion and ion-pair association constants of each C4PF(-) and C4PCl(-) with tetrabutylammonium cations was evaluated and confronted. Hydrogen bonding effect is prerequisite in the separation; meanwhile ion-pair association which is intensified by steric hindrance effect plays an important role.


Broiler chickens fusariotoxicosis - A histopathological study of lymphoid organs and testes.
The addition of fiveFusarium species, cultured on wheat grain, to the standart chicken diet DKA starter, caused atrophic changes in the thymus and testes, as observed in the microscopic picture of these organs. The degree of lesions were depended on theFusarium species and its amount added to the standart diet.


Neonatal IgE values in the black population.
Ninety-three cord blood samples from black neonates were evaluted for the total IgE level using the PRIST method. The results reveal values comparable to the IgE levels in other racial groups, suggesting that the influence of racial differences was not obvious at this stage.


Structure-based function analysis of putative conserved proteins with isomerase activity from Haemophilus influenzae.
Haemophilus influenzae, a Gram-negative bacterium and a member of the family Pasteurellaceae, causes chronic bronchitis, bacteremia, meningitis, etc. The H. influenzae is the first organism whose genome was completely sequenced and annotated. Here, we have extensively analyzed the genome of H. influenzae using available proteins structure and function analysis tools. The objective of this analysis is to assign a precise function to hypothetical proteins (HPs) whose functions are not determined so far. Function prediction of these proteins is helpful in precise understanding of mechanisms of pathogenesis and biochemical pathways important for selecting novel therapeutic target. After an extensive analysis of H. Influenzae genome we have found 13 HPs showing high level of sequence and structural similarity to the enzyme isomerase. Consequently, the structures of HPs have been modeled and analyzed to determine their precise functions. We found these HPs are alanine racemase, lysine 2, 3-aminomutase, topoisomerase DNA-binding C4 zinc finger, pseudouridine synthase B, C and E (Rlu B, C and E), hydroxypyruvate isomerase, nucleoside-diphosphate-sugar epimerase, amidophosphoribosyltransferase, aldose-1-epimerase, tautomerase/MIF, Xylose isomerase-like, have TIM barrel domain and sedoheptulose-7-phosphate isomerase like activity, signifying their corresponding functions in the H. influenzae. This work provides a better understanding of the role HPs with isomerase activities in the survival and pathogenesis of H. influenzae.


Application of a time-delay SIR model with vaccination in COVID-19 prediction and its optimal control strategy.
In the classical infectious disease compartment model, the parameters are fixed. In reality, the probability of virus transmission in the process of disease transmission depends on the concentration of virus in the environment, and the concentration depends on the proportion of patients in the environment. Therefore, the probability of virus transmission changes with time. Then how to fit the parameters and get the trend of the parameters changing with time is the key to predict the disease course with the model. In this paper, based on the US COVID-19 epidemic statistics during calibration period, the parameters such as infection rate and recovery rate are fitted by using the linear regression algorithm of machine science, and the laws of these parameters changing with time are obtained. Then a SIR model with time delay and vaccination is proposed, and the optimal control strategy of epidemic situation is analyzed by using the optimal control theory and Pontryagin maximum principle, which proves the effectiveness of the control strategy in restraining the transmission of COVID-19. The numerical simulation results show that the time-varying law of the number of active cases obtained by our model basically conforms to the real changing law of the US COVID-19 epidemic statistics during calibration period. In addition, we have predicted the changes in the number of active cases in the COVID-19 epidemic in the USA over time in the future beyond the calibration cycle, and the predicted results are more in line with the actual epidemic data.


Construction of a novel S-scheme heterojunction piezoelectric photocatalyst V-BiOIO3/FTCN and immobilization with floatability for tetracycline degradation.
A high-performance piezoelectric photocatalyst (V-BiOIO3/FTCN) was constructed to improve removal efficiency of tetracycline hydrochloride (TCH). The role of V-BiOIO3 in the composite was to introduce piezoelectric effect and construct S-scheme heterojunction photocatalyst with fish scale tubular carbon nitride (FTCN). The morphology, structure, chemical composition and optoelectronic characteristics of the as-prepared photocatalysts were studied by SEM, TEM, XRD, XPS and UV-Vis DRS. Combined with UV-Vis DRS, XPS valence band, Mott-schottky curve and theoretical calculations, the mechanism of TCH degradation was deeply analyzed. A series of degradation experiments showed that the V-BiOIO3/FTCN could effectively degrade TCH, and the removal efficiency was further improved under the action of ultrasound. Importantly, the further immobilized V-BiOIO3/FTCN/MS could float on the water surface to degrade TCH without additional stirring, which facilitated the recovery of photocatalysts and showed excellent practical application value. This work provided a reference for the design and immobilization of carbon nitride-based piezoelectric photocatalysts.


Exosomal long noncoding RNAs MAGI2-AS3 and CCDC144NL-AS1 in oral squamous cell carcinoma development via the PI3K-AKT-mTOR signaling pathway.
Long noncoding RNAs (lncRNAs) are essential and critical components of signal and transduction, regulating the intracellular microenvironment. Serum exosomes (SEs) are involved in rearranging the intercellular functional lncRNAs, which may also play a role in oral squamous cell carcinoma (OSCC). The function of lncRNAs at the transcription level in SEs of patients with OSCC is partially understood. The lncRNA expression profiles were examined derived from SEs from patients with OSCC with lymph node metastasis (OSCC-LNM), OSCC with no LNM (OSCC-NLNM), postoperative metastasis and recurrence OSCC (rOSCC) and healthy controls (HCs). Bioinformatics analysis was used to analyse differentially expressed lncRNAs (DE lncRNAs) and a total of 150 subjects were enrolled for RT-PCR verifications. The correlations of four lncRNAs and clinicopathologic factors, biochemical indexes were evaluated. MAGI2-AS3 and CCDC144NL-AS1 were overexpressed or silenced in oral cancer (OC) cells. The proliferation, invasion, and migration were evaluated to investigate the effect of MAGI2-AS3 and CCDC144NL-AS1 on the development of OSCC. The related proteins of PI3K-AKT-mTOR signal pathway were also detected. The expressions of the lncRNAs, namely MAGI2-AS3 and CCDC144NL-AS1, were significantly upregulated in rOSCC and OSCC-LNM. MAGI2-AS3 was overexpressed in cancer tissue compared to other control groups. AC109587.1 and AC010978.1 were significantly associated with the clinical stage, and CCDC144NL-AS1 was significantly associated with aging. MAGI2-AS3 and CCDC144NL-AS1 might promote cell proliferation, invasion, and migration in OSCC cells by regulating the PI3K-AKT-mTOR pathway. our results suggest that MAGI2-AS3 an d CCDC144NL-AS1 may have clinical applications in the treatment of OSCC.


Probe of CYP3A by a single-point blood measurement after oral administration of midazolam in healthy elderly volunteers.
Midazolam (MDZ) is used as an assessment of human cytochrome P450 3A (CYP3A) activity. A single blood measurement is used as a marker of its activity based on an observed correlation between MDZ clearance and the 1'-hydroxymidazolam (1'-OH-MDZ): MDZ plasma ratio is assessed at 0.5 h followig the intake of a single 7.5 mg oral dose of MDZ in healthy young volunteers. In addition, a 4-h plasma MDZ measurement has been found to be an excellent predictor of AUC and CYP3A activity. The main aim of this study was to define a single-point blood sampling in healthy elderly volunteers. The secondary objective was to investigate the pharmacological effects of a low oral dose of MDZ (5 mg) and its potential psychometric changes. Eight healthy elderly Caucasian volunteers participated in a single-dose, open-label, non-comparative study. Each subject received a single 5 mg oral dose of MDZ. Plasma concentrations of MDZ and its major metabolite, 1'-OH-MDZ, were assayed over 12 h. Secondary assessments of critical flicker fusion (CFF), body sway and mini-mental state examination were also carried out during the 12-h post-administration period. A moderate correlation was observed between MDZ clearance and the 1'-OH-MDZ: MDZ plasma concentration ratio at 9 h post-dosing (Rho=0.81; p=0.04), but an even better correlation (Rho=0.99; p<0.009) was found between MDZ AUC and MDZ plasma concentration at 6 h post-dosing, with the latter value corresponding approximately to the average mean residence time (MRT) determined in our trial. This study was well-tolerated despite a significant transitory decrease (relative to baseline) in cortical arousal at 1 h post-dosing, as assessed by CFF, and a non-significant decrease (relative to baseline) in balance and vigilance also measured at 1 h and assessed on body sway, compared to baseline values. Despite the small sample size, based on the results of healthy, elderly volunteers, a single MDZ plasma measurement taken at 6 h post-oral administration may represent an accurate marker of CYP3A phenotype. This single-time-point method could be used safely for predicting drug-drug or diet interactions and identifying individuals with genetic polymorphism that affect CYP3A activity.


Blood-pressure responses during social interaction in high- and low-cynically hostile males.
The Cook and Medley Hostility (Ho) Scale has been found to predict the development of coronary heart disease, coronary death, and death from other causes. Enhanced physiological responsiveness among high-Ho subjects may represent a link between hostility and health. The present study examined the systolic and diastolic blood-pressure (SBP, DBP) and heart-rate (HR) responses of high- and low-Ho undergraduate males while they presented their position and listened to their partner's opposing position in a current events discussion task. Compared to low-Ho subjects, the high-Ho group displayed larger SBP and DBP responses. These results and others suggest that cynical hostility is associated with greater physiological responses to interpersonal stressors.


Preliminary results on Ochratoxin A concentrations in blood of patients with various kidney diseases in Germany.
Ochratoxin A (OTA) is supposed to induce renal diseases in man and animals and a correlation between renal diseases and OTA concentration in blood is suspected. Therefore, we measured OTA concentrations in blood of subjects suffering from various renal diseases as e.g. interstitial nephritis or mesangial proliferating glomerular nephritis (GN) and compared them with the blood concentration of healthy individuals. We found OTA in 87% of all samples. There was no significant difference between OTA concentrations of healthy individuals and patients but some renal diseases (e.g. chronic glomerular nephritis) showed increased numbers of samples containing more than 1.5 nmol/l OTA in sera. In contrast, in samples from patients suffering from membranous or focal-sclerotic glomerular nephritis no concentrations above 1.5 nmol/l were found. Our preliminary results show that OTA is abundant in nearly all serum samples but some renal diseases show increased numbers of samples with high (>1.5 nmol/l) OTA concentrations.


Expression QTL mapping in grapevine--revisiting the genetic determinism of grape skin colour.
Expression quantitative locus (eQTL) mapping was proposed as a valuable approach to dissect the genetic basis of transcript variation, one of the prime causes of natural phenotypic variation. Few eQTL studies have been performed on woody species due to the difficulty in sample homogenisation. Based on previous knowledge on berry colour formation, we performed eQTL mapping in field experimentation of grapevine with appropriate sampling criteria. The transcript level of VvUFGT, a key enzyme for anthocyanin synthesis was measured by real-time qRT-PCR in grape berry on a 191-individual pseudo-F1 progeny, derived from a cross between Syrah and Grenache cultivars. Two eQTLs were identified: one, explaining 20%, of genotypic variance and co-locating with VvUFGT itself (cis-eQTL), was principally due to the contrast between Grenache alleles; the other, explaining 35% of genotypic variance, was a trans-eQTL due to Syrah allelic contrast and co-located with VvMYBAs, transcription factors known to activate the expression of VvUFGT. This study assessed and validated the feasibility of eQTL mapping approach in grapevine and offered insights and new hypotheses on grape skin colour formation.


Generation of random sequences with jointly specified probability density and autocorrelation functions.
A new method is presented for the generation of stochastic (random) sequences with an arbitrarily specified first-order probability distribution function (PDF) and an arbitrarily specified first-order auto-correlation function (ACF). A set of numbers with the desired PDF are first generated. These are then given a white (independent) ACF by double stochastic interchange. The desired ACF is then obtained by stochastically shuffling the series to minimize a sum of squares criterion between desired and actual ACFs. The technique is particularly useful for generating experimental stimuli for system identification, sequences for numerical stimulation, and test series for evaluating signal processing algorithms when colored (non-white) non-Gaussian data are required.


Antimicrobial activity of bacteria isolated from Red Sea marine invertebrates.
Marine invertebrates-associated microorganisms were considered to be important sources of marine bioactive products. This study aims to isolate marine invertebrates associated bacteria with antimicrobial activity from the Red Sea and test their biosynthetic potential through the detection of PKS and NRPS gene clusters involved with the production of bioactive secondary metabolites. In this respect, fifty bacterial strains were isolated from eight different Red Sea marine invertebrates and screened for their antimicrobial activity against standard pathogenic bacteria (Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633) and yeast (Candida albicans ATCC 10231) using the standard well diffusion assay. Five isolates showed antifungal activity against Candida albicans with no activity recorded against other pathogenic bacterial strains. On the other hand when these isolates were screened for the presence of biosynthetic gene clusters (PKS and NRPS) by PCR using five sets of degenerative primers, 60% of the isolates were shown to contain at least one type of PKS and NRPS gene clusters, which indicates the biosynthetic potential of these isolates even if the isolates didn't express any biological activity in vitro. Moreover the 16S rRNA molecular identification of the isolates reveal the biodiversity of the red sea marine invertebrates associated bacteria as they were found to belong to several bacterial groups present in Alphaproteobacteria, Gammaproteobacteria, Actinobacteria and Firmicutes.


Faced with one's fear: Attentional bias in anorexia nervosa and healthy individuals upon confrontation with an obese body stimulus in an eye-tracking paradigm.
Cognitive biases, particularly attentional biases, have been shown to be central to anorexia nervosa (AN). This study looked at attention deployment when consecutively viewing an obese and own body stimulus that both might represent feared stimuli in AN. Individuals with AN (n = 26) and mentally healthy controls (MHCs; n = 16) viewed a picture of themselves and a standardized computer-generated obese body in random order for 4,000 ms each and then rated the attractiveness of the body parts of both stimuli. We compared dwell times on subjectively unattractive versus attractive body parts, and body parts that show weight status and gain most strongly (stomach, hips, thighs) versus least strongly. For both stimuli, participants focused longer on the subjectively unattractive body parts (p < .01 and .001), with an even stronger attentional bias in individuals with AN regarding the obese stimulus (p < .05). Both groups also gazed longer at body parts indicative of weight status or gain (both stimuli p < .001), with no group differences. The attentional bias to one's own subjectively unattractive body parts might represent a mechanism maintaining body image disturbance in women in general. This attentional bias is even stronger when women with AN are confronted with an obese stimulus, highlighting a potential mental preoccupation with being fat or weight gain and a behavior distinct for the disorder.


[Daptomycin in complicated skin and soft tissue infections].
In recent years, Staphylococcus aureus, the most commonly identified infectious agent causing skin and soft tissue infections (SSTIs), has shown an increase in methicillin resistance and decreased susceptibility to vancomycin. Because of its spectrum, microbiological activity, pharmacokinetics, and safety, as well as clinical experience in its use, daptomycin seems to be a highly appropriate antibiotic in the treatment of SSTIs, especially those produced by methicillin-resistant S. aureus.


The African variant of BKV in a Turkish renal transplant patient.
In renal transplant recipients, BK polyomavirus (BKV) is linked to nephropathy. BK virus genotypes have a strong geographic component. This paper presents the African variant of BKV in a Turkish renal transplant patient, which is a rare cause of infection in the Northern Hemisphere and, to our knowledge, the first case from Turkey.


The pathology of noncirrhotic portal fibrosis: a review of 32 autopsy cases.
A wide spectrum of clinical and morphologic changes in 32 autopsy cases of noncirrhotic portal fibrosis have been described. The disease frequently occurs in younger patients with a long history of splenomegaly, usually with a history of hematemesis. Females are affected almost equally as often as males in contrast to cirrhosis. The patients tolerate the bleeding episodes well. Death is usually due to massive hemorrhage. The diagnosis is achieved through a process of exclusion. A critical analysis of hemodynamic data, a splenoportogram, liver function tests (particularly Bromsulphalein retention) and angiographic data is mandatory. Needle biopsy of the liver appears to have limited value in making the diagnosis. The gross anatomic findings vary from a nearly normal liver to gross nodularity, seen particularly on the posteroinferior surface. In some cases these nodules are seen to physically impede the portal blood flow and contribute to portal hypertension. Phlebosclerosis of the smaller radicles of the portal vein and irregular scarring are the outstanding morphologic features of the disease. These changes are usually associated with irregular dilatation of some of the larger intrahepatic branches of the portal vein as well as fibroelastosis with or without occluding or organizing thrombi in both intra- and extrahepatic branches of the portal vein. The changes in hepatic venous radicles are characterized by irregular sclerosis, which seems to contribute significantly toward postsinusoidal block in advanced cases. The probable mode of evolution is discussed.


Effects of two sec genes on protein assembly into the plasma membrane of Escherichia coli.
We have examined the effects of thermosensitive mutations in secA and secY (prlA) genes on the export of proteins to the three layers of the Escherichia coli cell surface. After several hours at the nonpermissive temperature, the export of two major outer membrane proteins, lipoprotein and OmpA, is delayed, then essentially blocked, in either a secA or secY strain. These mutations also have a strong effect on the export of several proteins, such as maltose binding protein, to the periplasm, though the export of many periplasmic proteins is not affected. secA and secY block the assembly of leader peptidase, which is made without a leader sequence, into the inner membrane. However, the membrane assembly of M13 coat protein (an inner membrane protein made with an amino-terminal leader sequence) is not affected. Thus, the requirement for sec function for export does not correlate with the presence or absence of leader peptide or with a particular subcellular compartment, but rather is specific to each particular protein.


Use of 129I and 137Cs in soils for the estimation of 131I deposition in Belarus as a result of the Chernobyl accident.
Using radioactivity measurements for 131I and 137Cs and nuclear activation analysis (NAA) or accelerator mass spectrometry (AMS) for 129I, ratios of 131I/137Cs and 129I/137Cs have been determined in soils from Belarus. We find that the pre-Chernobyl ratio of 129I/137Cs in Belarus is significantly larger than expected from nuclear weapons fallout. For the Chernobyl accident, our results support the hypothesis that there was relatively little fractionation of iodine and caesium during migration and deposition of the radioactive cloud. For sites having 137Cs > 300 Bq/kg, 129I can potentially give more reliable retroactive estimates of Chernobyl 131I deposition. However, our results suggest that 137Cs can also give reasonably good (+/-50%) estimates for 131I in Belarus.


Cervical metastasis of germ cell tumors: evaluation, management, complications, and outcomes.
Head and neck surgeons can be involved in the management of germ cell tumor (GCT) metastatic to the neck from initial diagnosis through postchemotherapy management of residual neck masses. This article reports on 34 consecutive patients with GCT metastatic to the neck. Retrospective chart review. A single-institution retrospective chart review of 34 consecutive patients with GCT metastatic to the neck who underwent postchemotherapy neck surgery between 1991 and 2009 was performed. Seventy-four percent of patients had a neck mass at initial diagnosis, with 50% of patients having a neck mass as the presenting symptom leading to a diagnosis of GCT. Of the 37 neck procedures, positive nodes were found in 22. No significant relationship between preoperative tumor markers and neck pathology (P = .35) was identified. No patients had neck recurrence. No patients had permanent nerve injury or chyle leak. As a secondary end point, survival analysis related to cervical pathology showed that viable tumor in the neck predicted disease-specific survival (P = .01). Five- and 10-year disease-specific survival was 82.3% (median, 52-month follow-up). Operative management for patients with metastatic GCT to the neck can achieve long-term durable cervical control with limited complications.


The Effect of Ancestry and Genetic Variation on Lung Function Predictions: What Is "Normal" Lung Function in Diverse Human Populations?
Lung function measures are an invaluable screening test for respiratory health and have been associated with the morbidity and mortality related to different airway disease as well as all-cause mortality. Currently, reference values for spirometric measurements are obtained using equations derived from individual ethnic or racial groups. The rapid expansion of more racially and ethnically diverse populations will challenge current race-based lung function reference equations. Recent international general population studies and ancestry-based genetic studies have found that ancestry and genetic variation are determinants of lung function and have suggested a role for genetic ancestry or gene variants in future lung function reference equations. In this review, we discuss the potential limitations of current lung function reference equations in a global society which is becoming more ethnically, racially, and, thus, genetically diverse. We also focus on how an individual's ancestral background or genetic profile could provide the basis for more accurate, personalized predictions of an individual's baseline lung function.


Life-cycle exposure to cadmium induced compensatory responses towards oxidative stress in the liver of female zebrafish.
The current study examined effects of waterborne cadmium (Cd) at environmental relevant concentrations (0, 2.5 and 5 μg/L) on growth, survival, histology, ultrastructure, metal homeostasis, and antioxidant responses in female zebrafish from embryos to sexually maturity for 15 weeks. Growth and survival rate were not significantly affected by Cd exposure. There were no significant changes in ultrastructure of cellular organelles, reactive oxygen species (ROS) levels, lipid peroxidation (LPO) in liver. However, Cd exposure increased Cd and lipid accumulation, reduced contents of zinc, copper and reduced glutathione (GSH), and down-regulated activity of copper/zinc-superoxide dismutase (Cu/Zn-SOD) in liver of zebrafish. Contrarily, the mRNA and activity levels of catalase (CAT), the mRNA levels of Cu/Zn-SOD, and the mRNA and protein levels of metallothioneins (MTs) were up-regulated. The transcriptional regulation of Cu and Zn transporters might be a vital mechanism by which fish slow the Zn and Cu uptake. Taken together, our data demonstrated that long-term and low-dose Cd induced adaptive responses with interlinked compensatory mechanism, which may protect fish against oxidative stress.


Probing structures of large protein complexes using zero-length cross-linking.
Structural mass spectrometry (MS) is a field with growing applicability for addressing complex biophysical questions regarding proteins and protein complexes. One of the major structural MS approaches involves the use of chemical cross-linking coupled with MS analysis (CX-MS) to identify proximal sites within macromolecules. Identified cross-linked sites can be used to probe novel protein-protein interactions or the derived distance constraints can be used to verify and refine molecular models. This review focuses on recent advances of "zero-length" cross-linking. Zero-length cross-linking reagents do not add any atoms to the cross-linked species due to the lack of a spacer arm. This provides a major advantage in the form of providing more precise distance constraints as the cross-linkable groups must be within salt bridge distances in order to react. However, identification of cross-linked peptides using these reagents presents unique challenges. We discuss recent efforts by our group to minimize these challenges by using multiple cycles of LC-MS/MS analysis and software specifically developed and optimized for identification of zero-length cross-linked peptides. Representative data utilizing our current protocol are presented and discussed.


Mapping of early SV40-specific functions by microinjection of different early viral DNA fragments.
DNA sequences within the early simian virus 40 (SV40) genome region responsible for virus-specific tumor (T) and U antigenicity, stimulation of cell DNA synthesis, initiation of late SV40 gene expression and helper function for human adenovirus 2 were confined by experiments using microinjection of different early SV40 DNA fragments. All these early functions were detected in cells supplied with complete early viral information. Cells microinjected with DNA fragments containing about 80, 70 or 60% of thea early SV40 genome were still stained positively when challenged with antibody against T antigen, and the same cells were stimulated for cellular DNA synthesis when about 70% or more of the early viral information was available. DNA sequences at map position 0.67 are required for intracellular early viral transcription.


Angiotensin-converting enzyme in substantia nigra: reduction of activity in Huntington's disease and after intrastriatal kainic acid in rats.
The substantia nigra of Huntington's disease brains shows a 78% reduction in angiotensin-converting enzyme activity in the pars reticulata and a 48% reduction in the pars compacta. The nucleus accumbens shows a 28% reduction in converting enzyme activity. In the rat, after intrastriatal injections of kainic acid (2.5 microgram), an agent which selectively destroys neuronal cell bodies, there is a 55% reduction in angiotensin-converting enzyme activity in the ipsilateral substantia nigra. Both human and animal data suggest that a major part of the angiotensin-converting enzyme in the substantia nigra is localized in nerve terminals whose cell bodies originate in the striatum.


Assessing the accuracy of electronic portal imaging device (EPID)-based dosimetry: II. Evaluation of a dosimetric uncertainty budget and development of a new film-in-EPID absorbed dose calibration methodology.
The aim of this study is to reduce the uncertainty associated with determining dose-to-water using an amorphous silicon electronic portal imaging detector (EPID) under reference conditions by developing a direct calibration formalism based on radiochromic film measurements made within the EPID panel and detailed Monte Carlo simulations. To our knowledge, this is the first EPID-based dosimetry study reporting an uncertain budget METHODS: Pixel sensitivity and relative off-axis response were mapped by simultaneously irradiating film contained within the imager panel and acquiring an EPID image set. The detector panel was disassembled for the purpose of modeling the EPID in detail using the EGSnrc DOSXYZnrc usercode, which was in turn used to calculate dose-to-film in the EPID and dose-to-water in water conversion factors RESULTS: A direct comparison of the two correction methodologies investigated in this work, the previously established empirical method and the proposed simultaneous measurement approach involving in-EPID film dosimetry, produced an agreement with an RMS deviation of 1.4% overall. A combined standard relative uncertainty of 3.3% (k = 1) was estimated for the determination of absorbed dose to water at the position of the EPID using the proposed calibration methodology CONCLUSIONS: This work describes a direct method of calibrating EPID response in terms of absorbed dose to water requiring fewer measurements than other empirical approaches, and without 2D spatial interpolation of correction factors.


[Development of guideline-based quality indicators: a qualitative study on barriers and facilitating factors from the perspective of S3-guideline authors].
Evidence-based and formally consensus-based clinical practice guidelines (S3-CPGs) are a valuable source for the development of quality indicators (QIs) in Germany. While deriving QIs from guideline recommendations is a mandatory part of the development of S3-CPGs within the National Program for Disease Management Guidelines (DMGP) and the German Guideline Program in Oncology (GGPO), there is no such obligation in the guideline program of the Association of the Scientific Medical Societies in Germany (AWMF) (MS program). Despite that, several S3-CPGs in the MS program have been published with QIs in the last years while some DMGP and one GGPO S3 guidelines have failed to meet this requirement. From the perspective of the guideline authors of all three mentioned programs, the present qualitative study examined why S3-CPGs do or do not contain QIs and explored the factors perceived by authors as either facilitating or hampering in the QI development process. Semi-structured interviews were conducted with authors of 22 S3-CPGs, 11 of which represented guidelines containing QIs and 11 of which represented guidelines without QIs. Authors of guidelines containing QIs (n=11) were asked about the perceived decisive reasons for formulating QIs and about facilitators and barriers during the QI development process. Authors of guidelines without QIs (n=11) gave reasons for not formulating QIs. Interviews were analyzed using structuring qualitative content analysis. Within the MS program, not formulating QIs was mainly attributed to the lack of a mandatory requirement and to insufficient funding of guideline projects. Amongst DMGP authors, a low priority of QI development prevailed, which was, for example, due to already existing QIs or to their lacking implementation. In the GGPO guideline examined, not formulating QIs was due to the guideline topic (prevention) - for this topic, there was a lack of suitable evidence and data sources. If QIs were developed, the most important facilitating factor in the development process, across all programs, was the methodological support provided by the guideline program. Important hampering factors included the additional time required for QI development and concerns regarding the implementation of many potential QIs, especially due to a lack of data availability. For regular development of QIs within S3-CPG projects, the incorporation of such a requirement in the guideline program is a necessary, but not a sufficient, condition. Other pivotal factors include systematic methodological support, adequate financial and staff resources and the perceived meaningfulness and relevance of guideline-based QI development, measured in terms of the actual implementation of already existing QIs. The study reveals starting points for measures to strengthen the consideration of QI development in German S3-CPG projects, especially within the MS program. Without substantial structural changes, especially of the resources of guideline groups, and without an overall concept covering the entire process from QI development to QI implementation, guideline-based QI development will remain heavily dependent on the (self-)motivation of guideline groups.


Psychiatric resident and attending diagnostic and prescribing practices.
This study investigates whether two patient population groups, under resident or attending treatment, are equivalent or different in the distribution of patient characteristics, diagnoses, or pharmacotherapy. Demographic data, psychiatric diagnoses, and pharmacotherapy data were collected for 100 random patient charts of psychiatric residents, and were then compared with 100 random patient charts of attending psychiatrists. Student's t test and chi square analysis suggested no statistically significant differences in the average number of comorbid Axis I diagnoses, percentages of patients with Axis II diagnoses, or major differences in the specific percentages of the 10 most common Axis I diagnoses. Furthermore, there were no statistically significant differences in the average number of psychiatric medications prescribed for pharmacological management of mental illness, or ratios of specific drug classes utilized. There seems to be no major differences in patient characteristics or in the treatment techniques that were utilized.