β-Sitosterol Bioconversion in Small-Scale Devices: From Microtiter Plates to Microfluidic Reactors.
Small-scale devices are routinely used as low-cost miniaturized bioreactors due to the large number of experiments that can be conducted simultaneously under similar conditions and replicate all functions of bench-scale reactors at dramatically smaller volumes. Microtiter plates, due to the standard footprint, can be integrated with liquid handling systems and associated equipment, expanding considerably their application and use. However, care has to be taken to operate the microtiter plates in optimized mixing and oxygen transfer conditions, preventing medium evaporation in prolonged experiment runs. Recently, to increase data quality, microbioreactors have emerged as an alternative to shaken systems. These systems offer higher degree of control over key process variables and when combined with sensing technology increase dramatically the reliability of translational process data. In this chapter, we describe the production of 4-androstene-3,17-dione (androstenedione (AD)), a key pharmaceutical steroid intermediate, by Mycobacterium sp. NRRL B-3805 via the selective cleavage of the side-chain of β-sitosterol using 24-well microtiter plates and microfluidic microbioreactors.


Incident falls impair ability to function in hip-fracture survivors: a prospective study of 95 elderly women.
The present study focused on home-dwelling women successfully discharged back to the community after a fall-related fracture of the hip. We investigated the role of incident falls in affecting ability to function in activities of daily living. Ninety-five of 103 consecutive women without cognitive impairment were recruited during in-patient rehabilitation following their first hip fracture. Functional independence in activities of daily living was assessed by using the Barthel Index (BI) score at discharge from in-patient rehabilitation and at a 6-month follow-up. Nineteen of the 95 women sustained one or more falls during a median observation time of 187 days. At a Mann-Whitney test, both BI scores assessed at the 6-month follow-up and gains in BI scores during the follow-up were significantly lower in the 19 fallers than in the 76 non-fallers (p=0.021 and p=0.030, respectively), whereas no significant differences were found in baseline BI scores between the two groups. At linear multiple regression, we found a negative association between incident falls and both functional scores (p=0.01) and their gains (p=0.006) after adjustment for several confounders. We conclude that incident falls were significantly associated with a worse functional score in our sample of hip-fracture women.


Interventions with battered women in health care settings.
Over the past decade advocates for battered women in the health care system, citing the large number of battered women who come to health care settings, have proposed interventions and trainings for health care personnel on behalf of battered women. However, little is currently known about the effectiveness of intervention efforts. This paper presents observation data on characteristics of battered women in four hospital Emergency Departments (EDs) and on staff responses to battered women in these EDs. The data show definite patterns in the women's characteristics and in staff responses to battered women. These data raise issues which should be considered in the researching and designing of interventions for battered women in the health care system.


Social class in the mental health center.
To test whether the preference for middle and upper class clients, found in psychotherapeutic clinics during the 1950s and early 1960s, exists in mental health centers, the relationships between social class and various aspects of psychiatric treatment are investigated in forty mental health centers which vary in several organizational dimensions. In general, clients are given treatment with little or no regard to social class. The variables that account for the different patterns of treatment in the two types of psychiatric treatment organizations are (1) the composition of the staffs; (2) the types and amount of individual psychotherapy given; and (3) the primary organizational goal.


The Mechanism Underlying the Regulation of LncRNA-ASLNC18810 Involved in the Abnormal Function of Vascular Endothelial Cell in Atherosclerosis: Its Function as a microRNA (miRNA) Sponge for miR-559.
Abnormal function of endothelial cells (ECs) is an important reason for vascular endothelial remodeling and atherosclerotic plaque formation in patients with atherosclerosis (AS). Here, we report for the first time that the vascular ECs with apoptosis resistance phenotype (ARECs) exist in peripheral blood of AS patients. Our research data showed that the switch of regulation modes between HIF-1α and Bax operated by lncRNA-ASLNC18810 is the direct cause for the formation of ARECs. When ASLNC18810 is low or missing, HIF-1α indirectly negatively regulates the Bax in post-transcription through HIF-1α/miR-559/Bax pathway which makes ECs acquire apoptosis resistance and form ARECs. The functional experiments results showed that ASLNC18810 could effectively eliminate the anti-apoptotic properties of ARECs by blocking the HIF-1α/miR559/Bax pathway and maintaining HIF-1α/Bax pathway. In a word, our study shows that ASLNC18810 has full potential to become a biological target for the prevention and treatment of atherosclerotic plaques by regulating ARECs. ASLNC18810 was significantly upregulated in ECs compared to ARECs. With high level of ASLNC18810 in ECs, ASLNC18810 binds to miR-559 as a miRNA sponge and suppresses the inhibition effect of miR-559 on Bax protein, this direct positive transcriptional regulation between HIF-1α and Bax endows the apoptotic property in ECs induced by Ox-LDL. However, with low expression of ASLNC18810 in ARECs, the post-transcriptional regulation of Bax by miR-559 dominates and the indirect negative regulation between HIF-1α and Bax endows the anti-apoptotic property of ARECs. To sum up, low ASLNC18810 expression-mediated switching of HIF-1α/Bax pathway to HIF-1α/miR-559/Bax pathway is the internal reason for ECs to obtain apoptosis resistance and the formation of ARECs under the ox-LDL induction.


Purification of human plasma lecithin:cholesterol acyltransferase and its specificity towards the acyl acceptor.
A simple and convenient method for the purification of human plasma lecithin-cholesterol acyltransferase was developed. The method involves the adsorption of the enzyme from diluted human plasma on DEAE-Sephadex, treatment with 1-butanol in the presence of (NH4)2SO4, DEAE-Sephadex chromatography, treatment with dextran sulfate in the presence of Ca2+, and hydroxyapatite chromatography. The enzyme purified showed a single main band by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. In addition, the enzyme obtained was stable for more than four weeks, when it was kept at 4 degrees C under N2 in a buffer of low ionic strength. The purified enzyme was used to study its specificity toward the acyl acceptor. This specificity was found to be broad in that not only sterols but also long chain primary alcohols exhibited considerable acceptor activity. Furthermore, in agreement with our previous observations with crude enzyme (Piran, U. and Nishida, T. (1976) J. Biochem. (Tokyo) 80, 887-889), the purified enzyme was found to be capable of hydrolyzing the ester linkage at the carbon-2 position of phosphatidylcholine. The transesterification, as well as the hydrolytic reaction, required the presence of the cofactor polypeptide, apolipoprotein A-I.


[Exploratory thoracotomies for unresectable lung cancer].
We analysed 55 exploratory thoracotomies undertaken in the Thoracic Surgery Service of the Geneva University Hospital between 1977 and 1987, to determine the preoperative examinations to prevent exploratory thoracotomy, a gesture that brings no benefits at all for the patients. We concluded that the most helpful preoperative examination is the CT-scan.


A review of the top 100 most influential articles on basilar artery aneurysms.
Basilar artery aneurysms account for approximately 5% of all intracranial aneurysms. This bibliometric analysis summarizes the most-cited articles on basilar artery aneurysms and highlights the contributing articles to today's evidence-based practice. In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until August 2022. The keyword "basilar artery aneurysm" or "basilar aneurysm" was used. Our results were arranged in descending order based on the article's citation count. The 100 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact Per Paper (SNIP), and Hirsch index. The keyword-based search showed that 699 articles were published between 1888 and 2022. The top 100 articles were published between 1961 and 2019. The top 100 most cited articles collected a total of 8869 citations with an average of 89 citations per paper. The rate of self-citations accounted for an average of 4.85% of the total number of citations. The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in basilar artery aneurysms by finding the top 100 most cited papers.


Preparation and antifouling performance of low-pressure carbon nanotube membranes based on polydopamine biomimetic modification.
In order to investigate the antifouling performance of low-pressure carbon nanotube membranes based on polydopamine (PDA) biomimetic modification, layered multi-walled carbon nanotubes PDA membrane (layered MWCNTs-PDA) and PDA blended MWCNTs membrane (blended PDA/MWCNTs) were prepared. The MWCNTs membranes' antifouling performance and recoverability was significantly improved in filtrating BSA, HA and SA after PDA biomimetic modification, and the total fouling and irreversible fouling were all decreased. Compared with the blended PDA/MWCNTs membrane, the layered MWCNTs-PDA membrane had higher antifouling property as it further improved the electronegativity and hydrophilicity of membrane surface. In addition, denser surface pore size of the layered MWCNTs-PDA membrane can effectively reduce the fouling by trapping foulants on its surface. The combination of PDA biomimetic modification with MWCNTs membrane had a superior antifouling performance and rejection performance in processing NOM and artificial wastewater, and the majority of humic-like foulants could be excluded by the layered MWCNTs-PDA membrane. PDA biomimetic modification alleviated the adhesion of FITC-BSA on the MWCNTs membrane. The layered MWCNTs-PDA membrane especially alleviated the attachment of bacteria and processed excellent antimicrobial ability for bacteria.


Extrathoracic Against Intrathoracic Vascular Accesses for Transcatheter Aortic Valve Replacement: A Systematic Review With Meta-Analysis.
Alternative vascular accesses to transfemoral access for transcatheter aortic valve replacement (TAVR) can be divided into intrathoracic (IT)-transapical and transaortic- and extrathoracic (ET)-transcarotid, transsubclavian, and transaxillary. This study aimed to compare the outcomes and safety of IT and ET accesses for TAVR as alternatives to transfemoral access. A systematic review with meta-analysis was performed by searching PubMed/MEDLINE and EMBASE databases for all studies comparing IT-TAVR with ET-TAVR published until April 2023. Outcomes included in-hospital or 30-day all-cause mortality (ACM), 1-year ACM, postoperative and 30-day complications. A total of 18 studies with 6,800 IT-TAVR patients and 5,032 ET-TAVR patients were included. IT accesses were associated with a significantly higher risk of in-hospital or 30-day ACM (relative risk 1.99, 95% confidence interval 1.67 to 2.36, p <0.001), and 1-year ACM (relative risk 1.31, 95% confidence interval 1.21 to 1.42, p <0.001). IT-TAVR patients presented more often with postoperative life-threatening bleeding, 30-day new-onset atrial fibrillation or flutter, and 30-day acute kidney injury needing renal replacement therapy. The risks of postoperative permanent pacemaker implantation and significant paravalvular leak were lower with IT-TAVR. ET-TAVR patients were more likely to be directly discharged home. There was no statistically significant difference regarding the 30-day risk of stroke. Compared with ET-TAVR, IT-TAVR was associated with higher risks of in-hospital or 30-day ACM, 1-year ACM and higher risks for some critical postprocedural and 30-day complications. Our results suggest that ET-TAVR could be considered as the first-choice alternative approach when transfemoral access is contraindicated.


Sclerodermic hand: a retrospective study on the role of ultrasonography in the detection of subclinical joint involvement.
The inflammatory involvement of joints and tendons is common in Systemic Sclerosis (SSc). Ultrasonography (US) is a non-invasive tool commonly applied for the assessment of the main inflammatory arthropathies and could be also used in identifying pathological features in SSc patients, even without clinical evidence of joint complaint. So, the aim of this study was to assess the prevalence of US pathological features in a cohort of SSc patients and assessed the role of US in the detection of subclinical joint involvement. In this retrospective study, we collected data about the prevalence of US pathological features at the level of hands and wrists in a cohort of patients with a definite diagnosis of SSc, submitted to an ultrasound examination of hands and wrists according to the clinician's opinion, with or without joint involvement symptoms, in order to assess the US ability in detecting subclinical inflammatory signs in SSc patients. In total, 47.5% of patients reported at least one US pathological feature. The most common was synovial hypertrophy (62.1%). Other assessed lesions were effusion (48%), tenosynovitis (37.9%), power Doppler (PD) signal (31.0%), and erosions (0.7%). Effusion and PD signal appeared significantly higher in symptomatic patients, with a p<0.01 and p=0.045, respectively. In this cohort of SSc subjects, almost the half of the US-positive patients were clinically asymptomatic. Therefore, the application of US could be useful to detect the musculoskeletal involvement of SSc patients, a potential markers of disease severity. Further studies are required to assess the role of US in monitoring SSc patients. Key Points • The inflammatory involvement of joints and/or tendons is common in systemic sclerosis (SSc) but could be partially covered by other disease features. • Among the diagnostic methods able to increase the sensitivity of the musculoskeletal evaluation, Ultrasonography (US) is one of the most promising to reveal subclinical inflammation and predict the joint damage progression. • We retrospectively investigated the prevalence of US pathological features in a cohort of SSc patients, with or without symptoms of joint involvement, assessing the role of US in the detection of subclinical joint involvement. • We found that joint and tendon involvement, a potential marker of disease severity, is common in SSc.


Ultrasonic degradation of Rhodamine B in aqueous solution: influence of operational parameters.
The aim of the study was to investigate decolorization of Rhodamine B (RB) in aqueous solution using ultrasonic degradation. The results showed that decolorization follows pseudo-first-order reaction kinetics. The apparent reaction rate constant (kap) was found to increase with decreasing pH and decreases with increasing initial RB concentration. Power density was very important parameter and increasing it causes a considerable increase of removal efficiency. UV-vis spectral changes of RB indicate that in the sonolysis of RB, the cleavage of aromatic chromophore ring structure and the N-deethylation take place, but decomposition of aromatic structure is predominant.


Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: A potential pitfall for the diagnosis.
Infantile onset cardiomyopathies are highly heterogeneous with several phenocopies compared with adult cardiomyopathies. Multidisciplinary management is essential in determining the underlying etiology in children's cardiomyopathy. Elevated urinary excretion of 3-methylglutaconic acid (3-MGA) is a useful tool in identifying the etiology in some metabolic cardiomyopathy. Here, we report the delayed appearance of 3-MGA-uria, between 6 and 18 months in three patients (out of 100 childhood onset cardiomyopathy) with neonatal onset cardiomyopathy, secondary to TMEM70 mutations and TAZ mutations (Barth syndrome), in whom extensive metabolic investigations, performed in the first weeks of life, did not display 3-MGA-uria. Serial retrospective evaluations showed full characteristic features of TMEM70 and TAZ mutations (Barth syndrome) in these three patients, including a clearly abnormal monolysocardiolipin/cardiolipin ratio in the two Barth syndrome patients. Serially repeated metabolic investigations finally discovered the 3-MGA-uria biomarker in all three patients between the age of 6 and 18 months. Our observation provides novel insights into the temporal appearance of 3-MGA-uria in TMEM70 and TAZ mutations (Barth syndrome) and focus the importance of multidisciplinary management and careful evaluation of family history and red flag signs for phenocopies in infantile onset cardiomyopathies.


Hemoglobin A1c in pregestational diabetic gravidas and the risk of congenital heart disease in the fetus.
This study aimed to determine whether poor glycemic control in early pregnancy is associated with an increased risk of congenital heart disease (CHD) for infants of women with preexisting diabetes. A retrospective review examined two tertiary care centers of diabetic pregnancies that recorded early hemoglobin A1c (HbA1c) values (<20 weeks). The incidence of prenatally diagnosed CHD was calculated and stratified by HbA1c level. Poor glycemic control was defined as an HbA1c level of 8.5 % or higher. Fetal echocardiography was used to identify fetuses that resulted in infants with suspected CHD. Neonatal echocardiograms and pathology reports were reviewed for confirmation of the diagnosis. Of 535 patients, 30 (5.6 %) delivered an infant with confirmed CHD. Among the patients with poor glycemic control, 8.3 % (n = 17) delivered an infant with CHD, whereas 3.9 % (n = 13) of those with an HbA1c level lower than 8.5 % delivered an infant with CHD (p = 0.03). Poor glycemic control in early pregnancy is associated with an increased risk of CHD in offspring. The incidence of CHD in patients with adequate glycemic control still is sufficiently high to justify routine fetal echocardiography for all gravidas with preexisting diabetes regardless of HbA1c level.


Multiple-step polyclonal versus one-step monoclonal enzyme immunoassay in the detection of Helicobacter pylori antigen in the stools of children.
Evaluation of a polyclonal and a monoclonal Helicobacter pylori stool antigen test (HpSAT) for the detection of Helicobacter pylori (HP) infection in children. 43 children underwent a 13C-urea breath test (13C UBT) and a HpSAT for the detection of HP. A child was considered HP positive if the 13C UBT was positive. Two HpSATs were tested: the "Premier Platinum HpSA" test (PP HpSAT) (polyclonal enzyme immunoassay) and the "ImmunoCard STAT! HpSA" test (ICS HpSAT) (one-step immunochromatographic assay). The mean age of the children was 8.9 y (range 3.5-17.5 y). Of the 43 children, 18 (41.9%) were HP positive and 25 (58.1%) were HP negative. The PP HpSAT showed a sensitivity of 94.4% and a specificity of 100.0%. With the ICS HpSAT, equivocal results occurred in 5/42 (11.9%) of the tests due to a problem with the visual interpretation of the change in colour of the test-line. The ICS HpSAT had a sensitivity of 100.0% and a specificity of 76.0% when the test was considered positive in case of any change of colour of the test-line, which is the correct practice according to the manufacturer. The ICS HpSAT had a sensitivity of 100.0% and a specificity of 96.0% when the test was considered positive only in case of a "significant change of colour" of the test-line. Compared to the 13C UBT, the PP HpSAT shows a comparably good sensitivity and specificity, the ICS HpSAT has a comparably good sensitivity but lower specificity due to a high percentage of equivocal results when the test is used according to the manufacturer's instructions, and the ICS HpSAT has a comparably good sensitivity and specificity when a weakly positive test is considered negative for the diagnosis of HP infection in children. The ICS HpSAT is easy to perform with results available within 10 min, and is therefore of particular interest in ambulatory medicine.


Mechanism and inhibition kinetics of peptide P13 as thrombin inhibitor.
Excessive coagulation can easily lead to arterial and venous thrombosis, which is the main reason for the evolution of myocardial infarction and cerebrovascular accidents. As a key coagulation factor for the coagulation pathway, thrombin has become a remarkable target for the control of thrombosis. The synthesized peptide P13 with amino acid sequence of N-RGDAGFAGDDAPR was expected to be an inhibitor with higher antithrombotic activity. The results showed that the IC50 (50% inhibition of thrombin activity) of the peptide P13 was determined by colorimetric method to be 115 µM. And enzyme kinetic experiments showed that P13 was a competitive inhibitor of thrombin with Ki = 106 µM. Fluorescence spectra and three-dimensional fluorescence showed that P13 could alter the secondary structure of thrombin and the microenvironment of certain chromogenic amino acids. P13 can spontaneously bind with thrombin exosite 1 in the form of 1:1 mainly through hydrogen bonding and van der Waals force. And the optimal docking mode of P13 and thrombin was revealed by molecular docking with "-CDOCKER_Energy" of 178.679 kcal mol-1. This study revealed P13 may become a potential anticoagulant drug widely used after further studies in preclinical and clinical trials.


MDR/XDR-TB Colour Test for drug susceptibility testing of Mycobacterium tuberculosis, Northwest Ethiopia.
Appropriate technology tests are needed for Mycobacterium tuberculosis drug-susceptibility testing (DST) in resource-constrained settings. This study was performed to evaluate the MDR/XDR-TB Colour Test (a colour platethin-layer agar test; TB-CX) for M. tuberculosis DST by directly testing sputum at University of Gondar Hospital. Sputum samples were each divided into two aliquots. One aliquot was mixed with disinfectant and applied directly to the TB-CX quadrant petri-plate containing culture medium with and without isoniazid, rifampicin, or ciprofloxacin. Concurrently, the other aliquot was decontaminated with sodium hydroxide, centrifuged, and cultured on Lӧwenstein-Jensen medium; the stored M. tuberculosis isolates were then sub-cultured in BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 for reference DST. The TB-CX test yielded DST results for 94% (123/131) of positive samples. For paired DST results, the median number of days from sputum processing to DST was 12 for TB-CX versus 35 for LJ-MGIT (p<0.001). Compared with LJ-MGIT for isoniazid, rifampicin, and multidrug-resistant tuberculosis, TB-CX had 59%, 96%, and 95% sensitivity; 96%, 94%, and 98% specificity; and 85%, 94%, and 98% agreement, respectively. All ciprofloxacin DST results were susceptible by both methods. The TB-CX test was simple and rapid for M. tuberculosis DST. Discordant DST results may have resulted from sub-optimal storage and different isoniazid concentrations used in TB-CX versus the reference standard test.


Quasilistrophorus microticolus gen. n. et sp. n. (Acari: Listrophoridae) from North American microtine rodents.
The authors describe a new genus and a new species Quasilistrophorus microticolus (Acari: Listrophoridae) from Arborimus from Oregon and Synaptomys from Indiana.


Stereoinversion of Stereocongested Carbocyclic Alcohols via Triflylation and Subsequent Treatment with Aqueous N,N-Dimethylformamide.
A convenient method for the stereoinversion of secondary alcohols, applicable to stereocongested carbocyclic substrates, is reported. A simple three-step procedure, including triflylation of the hydroxy group, nucleophilic oxygenative displacement by the treatment with aqueous N,N-dimethylformamide (DMF), and methanolysis, allowed for efficient stereoinversion of various substrates, including sugar derivatives, in one pot.


Odontogenic keratocysts presenting as periapical disease.
This article presents four examples of odontogenic keratocysts which appeared radiographically as periapical cysts. This unusual presentation of odontogenic keratocysts is discussed, and its significance for the clinician is reviewed. This article emphasizes the need for microscopic examination of all material surgically removed from the periapical region.


Disruption of myofibrillar proteins in cardiac muscle of Calomys callosus chronically infected with Trypanosoma cruzi and treated with immunosuppressive agent.
Calomys callosus (Rodentia: Cricetidae) chronically infected with CL strain of Trypanosoma cruzi undergo recrudescence of the acute phase when treated with the immunosuppressor cyclophosphamide. The distribution of cytoskeletal proteins in cardiac tissue of immunosuppressed animals was mapped by immunofluorescence and electron microscopy to evaluate myofibrillar distribution during the intracellular life cycle of T. cruzi. Cardiac muscle sections showed enhancement of myocarditis and parasite proliferation after immunosuppression. Immunofluorescence using monoclonal antibodies against myosin, actin, desmin, titin, tropomyosin, and troponin T demonstrated disruption and loss of contractile proteins, such as myosin and actin. Desmin and titin were irregularly distributed in close proximity to parasite nests. Ultrastructural observations confirmed alterations of cardiac cells with Z-line fragmentation, indistinguishable I-bands and A-bands, and loss of myofibrillar elements. The disruption of the muscle cell architecture was greater as infection progressed, probably as a result of increased myocarditis and physical displacement due to the activity of flagellated parasites.


A case of mixed connective tissue disease with pseudo-pseudo Meigs' syndrome (PPMS)-like features.
Pseudo-pseudo Meigs' syndrome (PPMS) has been reported to be a rare presentation of patients with systemic lupus erythematosus (SLE). However, such a presentation is not common in other forms of connective tissue disease. We presented a case of gross ascites, pleural effusion, and marked elevation of CA-125 level (PPMS-like features) that led to a diagnosis of MCTD. The patient responded to systemic steroid therapy.


Falls and Fractures in Patients with Parkinson's Disease-Related Psychosis Treated with Pimavanserin vs Atypical Antipsychotics: A Cohort Study.
Parkinson's disease-related psychosis increases patients' risk of falls. Pimavanserin is an atypical antipsychotic approved in the USA in 2016 for the treatment of hallucinations and delusions associated with Parkinson's disease-related psychosis. We aimed to compare the risk of falls/fractures among patients with Parkinson's disease-related psychosis treated with pimavanserin vs other atypical antipsychotics. We identified a cohort of patients with Parkinson's disease-related psychosis aged ≥ 40 years initiating either pimavanserin or a comparator antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) in US commercial insurance and supplementary Medicare claims (2015-2019). Comparators were propensity score matched 2:1 with pimavanserin initiators; incidence rates of falls/fractures were compared using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). We identified 112 eligible pimavanserin initiators and 982 comparators. Pimavanserin initiators were younger and had fewer severe comorbidities, indicators of impairment, and healthcare encounters, though they had higher Parkinson's disease medication use. The crude incidence rates [cases/100 person-years] (95% CI) for composite falls/fractures were 17.8 (7.7-35.0) for pimavanserin and 40.8 (35.0-47.4) for comparators. Matching retained 108 pimavanserin initiators and 216 comparators-all characteristics were well balanced after matching-with a matched IRR (pimavanserin vs comparator) of 0.71 (95% CI 0.27-1.67). Sensitivity analysis IRR estimates were consistently below 1.00, with a sensitivity analysis not requiring a diagnosis of psychosis resulting in an IRR estimate of 0.55 (95% CI 0.34-0.86). The results of this study do not suggest an increase in the risk of falls or fractures associated with pimavanserin compared with other antipsychotics in patients with Parkinson's disease-related psychosis. Sensitivity analyses suggest a decreased risk.


Injection and sublingual immunotherapy in the management of allergies affecting the unified airway.
The spectrum of allergic disease involves both the upper and lower airways. Immunotherapy has been shown to produce immunologic changes that can result in the improvement of allergic diseases. Numerous clinical trials have demonstrated the effectiveness of injection and sublingual immunotherapy in the treatment of rhinitis and asthma. Recent data suggest that immunotherapy may have a role in preventing the development of new sensitizations or in decreasing the progression of allergic disease from rhinitis to asthma. Models of immunotherapy may therefore transition from symptom-relieving treatments to preventive methodologies for the management of allergic disease.


Failure of lichen planopilaris to respond to ustekinumab.
Lichen planopilaris failed to respond to ustekinumab after 10 months of treatment.


Social play alters regional brain opioid receptor binding in juvenile rats.
An in vivo autoradiographic procedure was employed to visualize local changes in brain opioid receptor occupancy in juvenile rats. This procedure is based on the assumption that released endogenous ligand will exclude exogenously applied tracer, in this case [3H]diprenorphine, from opioid receptors. Increases in availability of opioid peptides will then result in decreased opioid receptor binding. From behavioral studies there is ample evidence that opioid systems are involved in the regulation of social play behavior in juvenile rats. In the present study, changes in regional brain opioid activity as a result of social isolation-induced social play behavior were monitored. Twenty-one-day-old rats were socially isolated for 0, 3.5 or 24 h prior to testing, and tested alone or in a dyadic encounter. After behavioral testing, [3H]diprenorphine was administered and the brain was prepared for autoradiography. Social isolation caused increases in social behavior (dyadic encounters) but not in non-social behavior (singly tested animals). Modest differences in brain opioid receptor binding due to social isolation, social play behavior, or an interaction of the two, were found in claustrum, nucleus accumbens, globus pallidus, paraventricular and arcuate nuclei of the hypothalamus, and the dorsolateral and paratenial thalamic nuclei. These results support the notion that opioid systems are involved in the regulation of social play behavior. In addition, the observation of changes in opioid binding in areas involved in reward processes, adds evidence to the hypothesis that opioid systems are involved in the regulation of the rewarding aspects of social play in juvenile rats.


Cumulative pregnancy rates for donor insemination according to ovulatory function and tubal status.
From our study of 234 cases of AID with fresh semen, we conclude the following: (1) women who do not have other infertility problems, such as ovulatory dysfunction or evidence of tubal disease, have approximately a 90% chance of pregnancy if they stay in the program for up to 12 cycles; (2) with even greater persistence (i.e., greater than 12 cycles), it is predicted that virtually 100% of these women would conceive, but this conclusion is based on extrapolated data and therefore must be interpreted with caution; (3) women with ovulatory dysfunction who are treated with CC during their AID cycles ultimately achieve the same likelihood of pregnancy as women with normal ovulatory function, but at a slower rate; and (4) women with one patent tube (possibly a marker for generalized tubal damage) have a poorer outcome from AID than those with bilaterally patent tubes, from the standpoint of both the ultimate likelihood of pregnancy and the pregnancy rate per cycle.


First case of Arcobacter species isolated in pericardial fluid in an HIV and COVID-19 patient with worsening cardiac tamponade.
Arcobacter spp. is an emerging pathogen that is increasingly recognized as a cause of human infections. Gastrointestinal manifestations are most described in the case report literature. We present a case of the first documented case of Arcobacter spp. isolated in pericardial fluid in an immunocompromised patient with worsening cardiac tamponade that was successfully managed with an urgent pericardiocentesis and ensuing steroids, antibiotics, and a pericardial drain. The patient had a past medical history of HIV, latent syphilis, PCP pneumonia, ESRD, and hypertension, and presented with worsening dyspnea, subjective fever, myalgias, cough, pleuritic chest pain, and pericardial rub. Diagnostic workup revealed a positive COVID-19 PCR test, elevated high-sensitive cardiac troponins, elevated CRP, elevated D-dimer, and elevated creatinine. An ECG revealed diffuse ST-segment elevation, and imaging showed cardiomegaly with pulmonary vascular congestion and diffuse interstitial edema. Urgent TTE showed a large circumferential pericardial effusion with tamponade physiology present. Culture on aerobic blood agar grew Arcobacter spp. of unknown specific species, and blood cultures were also positive for Arcobacter spp. Treatment involved intravenous meropenem for five days, followed by oral ciprofloxacin, low-dose colchicine, and a tapered dose of ibuprofen. Repeat laboratory data and TTE showed complete resolution of the pericardial effusion and improved left ventricular function. This case highlights the potential for Arcobacter spp. to cause severe infections and the importance of considering it as a possible pathogen in patients with atypical presentations.


Using a tobit regression model to analyse risk factors for foot-pad dermatitis in commercially grown broilers.
A model was developed to explain the influence of different local and regional factors on the prevalence of foot-pad dermatitis in broilers at the time of slaughter. Data from a recent two-year study of broiler foot-health in Sweden were used to construct the model. The model was based on regression analysis, using a Tobit model for censored data. This type of Tobit regression model has been used for several decades in econometrics and can also be found in the medical-scientific literature. It has, however, reportedly not been used in veterinary medicine although there appears to be several situations where it should be considered useful. Week of slaughter was significantly (p < 0.001) associated with total foot-pad score, which decreased over time. The birds' age at slaughter was also significantly (p < 0.01) associated with total foot-pad score. Five out of the 11 slaughterhouses included in the study were included as significant (p < 0.01) variables in the final model. Three feed suppliers (p < 0.05) and four regions (p < 0.01) were also included as significant variables in the model. There were also significant (p < 0.001) interactions between several of these factors (mainly, between the time variable and specific slaughterhouses, feed suppliers or regions, respectively). The information gathered in this study regarding the influence of a number of risk factors for the development of foot-pad dermatitis and their reciprocal interactions will enable us to modify the Swedish broiler foot-health programme.


Diffraction correction methods for insertion ultrasound attenuation estimation.
We describe diffraction effects in acoustic ultrasound attenuation coefficient estimation using an insertion technique. We characterize the estimation error produced by diffraction as a function of distance and nominal attenuation values. Two new methods for correcting for the diffraction effect are presented. They are termed the Theoretical Diffraction Correction (TDC) and Experimental Diffraction Correction (EDC) techniques, respectively. Experimental validation of the two techniques is also presented, using two different sets of ultrasound measurements obtained with 1 MHz and 500 kHz transducer pairs, respectively. Significant improvement in the accuracy of the acoustic attenuation coefficient is demonstrated using both techniques.


Fibrous lesions of the gingiva: a histopathologic analysis of 204 cases.
Two hundred four cases of fibrous lesions of the gingiva were studied histologically for the presence of calcified tissue, the nature of the connective tissue, the type of keratinization, and the degree of epithelial thickness. Initially these lesions were subcategorized into four specific entities, namely fibrous epulis, fibroepithelial polyp, calcifying fibroblastic granuloma, and ossifying fibrous epulis. It was found that 46.5% of the lesions contained calcifications. The connective tissue was represented predominantly by either the collagenous type (50.5%) or the mixed (cellular and collagenous) type (44.6%). It was also found that 36% of the lesions were ulcerated, and, of these, 79.5% were associated with the cellular type of connective tissue and calcifications. In an attempt to subcategorize the fibrous lesions into specific entities, it was found that 32 cases (15.7%) had mixed features. This fact supports the suggestion that these lesions are stages in the spectrum of a single disease process and should collectively be termed fibroblastic gingival lesions. However, it is also suggested that the two terms, namely peripheral fibroma and fibrous epulis with and without ossification, should be retained whereas the usage of other terminologies should be avoided.


Modulation of cell proliferation and hypertrophy by gangliosides in cultured human glomerular mesangial cells.
Glomerular mesangial cells (GMCs) in diverse renal diseases undergo cell proliferation and/or hypertrophy, and gangliosides have been reported to play an important role in modulating cell structure and function. This study compared the effects of transforming growth factor-beta1 (TGF-beta1) and the effects of the application of exogenous gangliosides on GMCs and investigated whether the application of exogenous gangliosides regulated cellular proliferation and hypertrophy. Human GMCs were cultured with exogenous gangliosides and TGF-beta1 in a media containing 10% fetal bovine serum and in a media without the fetal bovine serum. Exogenous gangliosides biphasically changed the proliferation of human GMCs (0.1-1.0 mg/mL). A low concentration (0.1 mg/mL) of gangliosides mainly increased the number of human GMCs, whereas cellular proliferation was significantly reduced by raising the concentration of exogenous gangliosides. TGF-beta1 greatly reduced the number of human GMCs in a concentration-dependent manner (1-10 ng/mL). Serum deprivation accelerated the gangliosides- and TGF-beta1-induced inhibition of mesangial cell proliferation to a greater extent. Gangliosides (1.0 mg/ mL) and TGF-beta1 (10 ng/mL) both caused a significant increase in the incorporation of [3H]leucine per cell in the serum-deprived condition, whereas it was completely reversed in serum-supplemented condition. Similar results to the [3H]leucine incorporation were also observed in the changes in cell size measured by flow cytometric analysis. These results show that exogenous gangliosides modulate cell proliferation and hypertrophy in cultured human GMCs, and these cellular responses were regulated differently based on whether the media contained serum or not. Results from the present study raise new possibilities about the potential involvement of gangliosides in the development of mesangial cell proliferation and hypertrophy.


Impaired saccadic eye movements on stationary targets in patients with schizophrenia spectrum disorder.
This study examined tracking eye movements on predetermined stationary targets in patients with schizophrenia spectrum disorder. The targets were 8 black points or 8 arabic-numbered points placed on the circumference of a circle. Self-paced eye movements during clockwise tracking of these points by 23 patients and 23 normal controls were recorded using an infrared eye-mark recorder. Eye movements were analyzed at two settings: firstly, when "fixation point" was defined as a point at which a gaze was held for at least 200-ms; and secondly, when held for at least 100-ms. The results indicated that at the 200-ms setting schizophrenic patients track with significantly fewer correct scores and more deviant scores than controls under black-point conditions. At the 100-ms setting, however, the correct scores of patients were not significantly different from those of controls, although patients displayed more aberrant paths than controls. The superfluous fixations in the patients improved significantly under numbered-point conditions, but patients still achieved lower correct scores than controls. Four of the 23 patients exhibited centering (aberrant path directed toward the center point), suggesting immature control of eye movements under black-point conditions, but not numbered-point conditions. These results suggest that some schizophrenic patients viewed the targets too quickly, and that they have impaired directed attention, which can be improved by cues, and may have impaired preprogramming of eye movements, which is not improved by external cues.


Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-alpha, soluble TNFR2 and altered TNF-alpha signaling.
Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-alpha plays a role in immune-mediated processes we evaluated the levels of TNF-alpha/TNF-alpha receptors and the downstream signaling molecule nitric oxide (NO) during disease in both retinal degeneration susceptible BALB/c and degeneration resistant CD-1 mice. Following coronavirus injection, TNF-alpha mRNA was detected at higher levels within the retinas, and concentrations of TNF-alpha (p<0.005) and sTNFR1 (p<0.0005) proteins were increased within the sera of BALB/c but not CD-1 mice. While concentrations of sTNFR2 proteins were elevated in both BALB/c (p<0.00005) and CD-1 (p<0.005) mice compared to controls, concentrations were higher in BALB/c mice (p<0.0005). Gene expression of iNOS while initially high in BALB/c mice decreased during the acute phase of infection, while it increased in CD-1 mice. These trends are attributable to differences in monocyte TNFR2 release (p<0.0005) between the strains since sTNFR2 decreased (p<0.01) levels of NO production. These studies demonstrate that retinal degeneration following viral infection is associated with increased release of TNF-alpha/TNF receptors combined with a down-regulation of NO. Furthermore they suggest that these molecules are involved in alterations in immune response leading to autoimmune reactivity.


Identification and validation of PGLS as a metabolic target for early screening and prognostic monitoring of gastric cancer.
Gastric cancer is the third leading cause of cancer-related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6-phosphogluconolactonase (PGLS) in gastric cancer. The protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8-plex) reagents, and followed by LC-ESI-MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan-Meier plotter database. The present study found that PGLS was significantly up-regulated in gastric cancer by using iTRAQ-based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post-progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e-05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her-2 (-). These findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post-progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow-up monitoring for gastric cancer.


Synthesis of some new 2-(substituted-phenyl)imidazo[4,5-c] and [4,5-b]pyridine derivatives and their antimicrobial activities.
The synthesis of 5H-imidazo[4,5-c]pyridines analogues (1a - 1h) and 4H-imidazo[4,5-b]pyridines (3a - 3c) was achieved by reacting 3,4-diaminopyridine or 2,3-diaminopyridine with Na2S2O5 adduct of corresponding benzaldehydes (a1 - a8). Alkylation of compounds (1a - 1h) and (3a - 3c) using 4-chlorobenzyl and /or butyl bromide under basic conditions (K2CO3, DMF) predominantly resulted in the formation of N5 regioisomers (2a - 2l) and N4,3 regioisomers (4a - 4c1,2), respectively. The N5,4,3-regioisomeric structures were confirmed using 2D-NOESY (Nuclear Overhauser Effect Spectroscopy) and HMBC (Heteronuclear Multiple Bond Correlation) spectra. The antibacterial and antifungal activities of the synthesized compounds (2a - 2g, 4a - 5d) were evaluated in vitro against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin resistant S. aureus, Enterococcus faecalis and Candida albicans, Candida parapsilosis. Among the synthesized compounds, promising activities were observed with compounds 2g, 2h, 4a and 4b with lowest MIC values (4-8 µg/mL). The compounds 2i, 2j, 2k, 2l showed moderate activity. Additionally, a computational approach (ADMETlab 2.0) was used to evaluate the drug likeness properties of the compounds.


[Surgical treatment with prosthesis implantation in 100 patients with erectile sexual dysfunction].
We present our case study of 100 penile prostheses in patients suffering from erectile sexual dysfunction of different etiologies. We carry out a review of the different diagnostic stages and the different surgical approaches for prosthetic implant and their complications.


Pharmacokinetics of 5,6-dihydro-5-azacytidine (NSC-264880) in the foxhound.
An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The decline in DHAC plasma concentrations was greater than three log decades after dosing. The plasma concentration-time data was computer-fitted by NONLIN to a three compartment open model with first-order elimination using the equations for a short intravenous infusion. The half-lives corresponding to the three exponential phases were: t1/2 alpha = 5.78 min, t1/2 beta = 1.57 h and t1/2 gamma = 22.0 h in dog 1 and t1/2 alpha = 7.41 min, t1/2 beta = 2.25 h and t1/2 gamma = 21.6 h in dog 2. The terminal phase of the plasma concentration time profiles represented a minor contribution (2.2-3.2%) to the total area under the curve. The plasma concentration time data for the first 12 h after dosing was computer fitted to a two compartment open model. The initial and terminal half-lives determined from the two compartment fits were similar to the t1/2 alpha and t1/2 beta values of the fits to the three compartment open model. Similar total body clearance values were calculated from the areas under the plasma concentration time curves from time zero to infinity for the computer fits to the three and two compartment models, respectively. Thus, for practical purposes, it appears feasible to define adequately the total body clearance of DHAC by analysis of the plasma concentration time data during the time interval in which the plasma concentration is described as a bi-exponential equation. Renal excretion of the parent drug is the principal route of excretion of DHAC from the dog.


Using baseline respiratory function data to optimize cycle exercise test duration.
It is often difficult to select an appropriate workload increment for progressive cycle exercise tests in order to achieve optimal test duration (8-12 min). We hypothesize that baseline respiratory function can be systematically used to select appropriate workload increment to optimize test duration in patients referred to the clinical laboratory. One hundred and eighty consecutive exercise tests (with increments of 15 W/min) were retrospectively assessed. Using regression analysis, an equation was generated that predicts the work rate increment that would provide exercise duration of 8-12 min. The validity of this equation was tested prospectively in 231 consecutive tests performed with the calculated workload increment rounded to the nearest 5 watts (W). The best regression equation was: workload increment (W/min)=1.94 x FEV1 (L) + 0.63 x TLCO (mmol/min per kPa) - 0.07 x age + 1.94 x gender (male=1, female=0) + 4.12 (r=0.85, P < 0.0001). Using this equation allowed selection of the most appropriate workload increment in 79% of tests and reduced the number of tests of non-optimal duration from 72% (for a fixed increment of 15 W/min) to 38%. Utilization of this regression equation allows standardization in the selection of workload increment, and reduces the number of cycle exercise tests of inadequate duration.


Disrupted rich-club network organization and individualized identification of patients with major depressive disorder.
Altered structural and functional brain networks have been extensively studied in major depressive disorder (MDD) patients. However, whether the differential connectivity patterns in the rich-club organization, assessed from structural brain network analyses, and the associated connections of these regions are particularly susceptible to depression remain unclear. We acquired resting-state functional magnetic resonance imaging (R-fMRI) and diffusion tensor imaging (DTI) from 31 unmedicated MDD patients and 32 cognitively normal (CN) subjects and completed a series of neuropsychological tests. Rich-club organization, network properties, and coupling between structural and functional connectivity (SC-FC) were explored. Furthermore, whether these indices could potentially deliver effective clinical predictive value for MDD patients were examined. The MDD patients showed disrupted structural rich-club organization and modularity, as well as a distinct correlation pattern between global efficiency and rich-club organization. Importantly, reduced SC-FC coupling, reflecting a decreased agreement in the integrity of the networks, was significantly associated with the strength of structural rich-club connections in the MDD patients. Furthermore, the disrupted structural rich-club organization, which was primarily located in the default mode network (DMN) and executive control network (ECN), emerged as a valuable indicator to distinguish between MDD and CN. Findings of this study identified that the disrupted rich-club structural organization significantly influenced brain structural network modularity and integrity and could serve as a promising biological marker for the identification of MDD patients.


Quality of life among caregivers of sickle cell disease patients: a cross sectional study.
To assess the quality of life (QoL) of caregivers of children with sickle cell disease (SCD) and to determine the risk factors associated with poor QoL. A cross sectional study was conducted between 01 and 30 June 2015, in a tertiary care center in western Saudi Arabia to assess various dimensions of QoL by using TNO-AZL Questionnaire for Adult's Health-related Quality of Life (TAAQOL). A total 164 adult caregivers (aged 16 years or more) of children with SCD, who were regularly visiting the department were enrolled (refusal rate = 61.6%). The questionnaire scores were transformed into 0-100 scale; with higher scores indicating less difficulty and better QoL Demographic, socioeconomic data and a satisfaction questionnaire regarding participants' lifestyle were collected and analyzed as risk factors for impaired QoL, by comparing different QoL dimensions' scores using independent t-test, Oneway ANOVA, or linear regression, as appropriate. Sixty-three caregivers were included; 79.4% were mothers, age range 21-71 years, 64.5% were from low social class receiving insufficient support and financial needs were unmet for considerable number of families. Analysis of QoL using TAAQOL showed that emotions (median [75th centile] = 44.44 [66.67] for negative and 61.11 [72.22] for positive emotions), sleep quality (66.67 [91.67]) and sexual life (50.00 [83.33]) were the most affected dimensions. Professional achievement (91.67 [100]), cognitive skills (83.33 [100]), and social contact (100 [100]) were relatively preserved. Negative emotions were more marked in mothers and mostly predicted by satisfaction with social relations notably with partner (B = 3.14, p = 0.016), friends (B = 2.51, p = 0.015) and relatives (B = 2.69, p = 0.016). Positive emotions were predicted by the levels of satisfaction of the caregiver with his/her health (B = 2.56, p = 0.001), job achievement (B = 4.54, p = 0.001), living conditions (B = 2.60, p = 0.034) and the condition of the diseased child (B = 2.55, p = 0.011). A strong correlation was found between sleep quality and cognitive skills. There are notable financial and emotional burdens on the caregivers of children with SCD affecting various aspects of their QoL, which are likely to be impacted by the individual levels of social and professional achievement. Physicians and health authorities should give particular attention to the QoL of caregivers and families of children with SCD, to help them cope up with the disease and overcome its related psychological and financial impacts.


The lncRNA BORG Drives Breast Cancer Metastasis and Disease Recurrence.
Long noncoding RNAs (lncRNAs) have emerged as potent regulators of breast cancer development and progression, including the metastatic spread of disease. Through in silico and biological analyses, we identified a novel lncRNA, BMP/OP-Responsive Gene (BORG), whose expression directly correlates with aggressive breast cancer phenotypes, as well as with metastatic competence and disease recurrence in multiple clinical cohorts. Mechanistically, BORG elicits the metastatic outgrowth of latent breast cancer cells by promoting the localization and transcriptional repressive activity of TRIM28, which binds BORG and induces substantial alterations in carcinoma proliferation and survival. Moreover, inhibiting BORG expression in metastatic breast cancer cells impedes their metastatic colonization of the lungs of mice, implying that BORG acts as a novel driver of the genetic and epigenetic alterations that underlie the acquisition of metastatic and recurrent phenotypes by breast cancer cells.


[Leisure time and sports. Sports for all ages].
Studies about life-time sport of different groups of population in Switzerland showed that 82% of 1990 apprentices in the town of Zürich and 59% of young peasants were active in sports in their leisure time. On Saturdays, 45% of the inhabitants of Zürich spent any hours with leisure time sport, on Sundays even 70% (including mountaineering). From seniors (80 years old), 63% were active in sports formerly in their life, from men dead before 65 years from the same factory only 44%.


[Eosinophilic gastroenteritis].
Two case stories of eosinophilic gastroenteritis are described. Both patients presented with chronic diarrhoea and weight loss. The first patient had eosinophilic infiltration predominantly in the mucosal layer of the intestine, and had in addition loss of protein in the stool. The other patient had predominantly subserosal eosinophilic infiltration and presented with eosinophilic ascites. Both patients were treated with prednisolone and responded immediately to therapy.


New efficient meta-fermentation process for lactic acid production from municipal solid waste.
The global market for lactic acid is witnessing growth on the back of increasing applications of lactic acid for manufacturing polylactic acid. Indeed, the lactic acid market is expected to reach 9.8 billion US dollars by 2025. The new concept of meta-fermentation has been proposed in recent years as an alternative to fermentation with pure cultures, due to multiple advantages such as lower susceptibility to contamination, no need for sterilization of culture media or lower raw material costs. However, there are still challenges to overcome to increase the conversion efficiency, decrease formation of by-products and facilitate fermentation control. In this context, the purpose of the study was to develop a robust meta-fermentation process to efficiently produce lactic acid from the OFMSW, stable at pre-industrial scale (1500 L). To maximize lactic acid production, operating conditions (pH, HRT) were modified, and a novel bioaugmentation strategy was tested. A LAB-rich inoculum was generated with LAB isolated from the digestate and grown in the laboratory with MRS medium. After feeding this inoculum to the digester (bioaugmentation), lactic acid accumulation up to 41.5 gO2/L was achieved under optimal operating conditions. This corresponds to more than 70% of the filtered COD measured in the digestate. The amount of lactic acid produced was higher than the volatile fatty acids under all feeding strategies applied. The operating conditions that enhanced the production of lactic acid from mixed cultures were 55ºC, 2 days HRT and pH 4.8-5.7, with pH-control once a day. The bioaugmentation strategy improved the results obtained in the prototype without applying reinoculation. Lactic acid was the main product along with other carboxylic acids. Further improvements are needed to increase purity as well as lactic acid concentration to reach economic feasibility of the whole process (digestion of OFMSW and downstream).


Denoising of MR spectroscopic imaging data using statistical selection of principal components.
To evaluate a new denoising method for MR spectroscopic imaging (MRSI) data based on selection of signal-related principal components (SSPCs) from principal components analysis (PCA). A PCA-based method was implemented for selection of signal-related PCs and denoising achieved by reconstructing the original data set utilizing only these PCs. Performance was evaluated using simulated MRSI data and two volumetric in vivo MRSIs of human brain, from a normal subject and a patient with a brain tumor, using variable signal-to-noise ratios (SNRs), metabolite peak areas, Cramer-Rao bounds (CRBs) of fitted metabolite peak areas and metabolite linewidth. In simulated data, SSPC determined the correct number of signal-related PCs. For in vivo studies, the SSPC denoising resulted in improved SNRs and reduced metabolite quantification uncertainty compared to the original data and two other methods for denoising. The method also performed very well in preserving the spectral linewidth and peak areas. However, this method performs better for regions that have larger numbers of similar spectra. The proposed SSPC denoising improved the SNR and metabolite quantification uncertainty in MRSI, with minimal compromise of the spectral information, and can result in increased accuracy.


Novel functional Renilla luciferase mutant provides long-term serum stability and high luminescence activity.
Fluorescent and luminescent chemical probes are essential in recent medical diagnostics. However, the use of these probes in vivo has raised concerns due to their low sensitivity, background signal interference, and non-biocompatibility. Therefore, biological chromophores have received much attention as new alternatives. In particular, luciferase, a class of oxidative enzyme with bioluminescence, has emerged as a promising fluorophore due to its improved biocompatibility. However, the enzyme usually possesses weaker luminescence and stability relative to its chemically-based competitors. Here, we report a novel functional mutant luciferase with both enhanced luminescence and long-term serum stability. For the preparation of the modified Renilla luciferase, a new bacterial subcloning design was established. The luciferase coding DNA sequence was redesigned so that mutant luciferase could be easily expressed in an Escherichia coli system. The mutant Renilla luciferase, which we called "m-Rluc," demonstrated characteristic enzymatic functions and showed a 5.6-fold increase in luminescence activity. In addition, the enzyme's physiological stability remained >80% for more than 5days, in contrast to conventional luciferase, termed "hrluc," which disappeared within a few hours. We suggest that this novel biological luciferase probe may be a great tool for both in vitro and in vivo medical diagnostics.


Percutaneous surgery for thoraco-lumbar fractures in ankylosing spondylitis: Study of 31 patients.
The risk of vertebral fracture is increased 4-fold in patients with ankylosing spondylitis (AS). Diagnostic challenges and the vulnerability associated with AS combine to generate high morbidity and mortality rates. The objective of this study was to assess the outcome of percutaneous thoraco-lumbar fracture surgery in patients with AS, in terms of quality of life, fracture healing, and complications. Percutaneous surgery used to treat thoraco-lumbar fractures in patients with AS reliably provides fracture healing, preserves self-sufficiency, and minimises post-operative complications. Two centres included 31 patients with AS who were managed by percutaneous surgery for thoraco-lumbar fractures in 2013-2015. The data were reviewed retrospectively, although admission data were collected prospectively. Clinical outcomes were assessed by comparing the values at baseline and last follow-up of three variables: the Parker score, the visual analogue scale (VAS) pain score, and the EuroQol five dimensions (EQ-5D) quality-of-life score. Computed tomography was performed 1 year after surgery to evaluate bone healing, screw position, and implant loosening. Intra- and post-operative complications were recorded. The 31 patients had a mean age at surgery of 75.1 years, a mean follow-up of 35.6 months, and a minimum follow-up of 12 months. Three patients died during follow-up. Mean hospital stay duration was 6 days. Cemented screw fixation was used in 18 patients. At last follow-up, all patients had recovered their self-sufficiency; the mean Parker score was 7.14, compared to 6.73 at baseline, the mean VAS pain score was 1.8, and the mean EQ-5D score decrease versus baseline was 0.07 (P=0.02). Bone healing was consistently achieved. Loosening of an uncemented pedicle screw was noted in 1 patient. Of the 228 screws implanted, 6 (2.6%) were improperly positioned, including 1 within the spinal canal in a patient free of neurological manifestations. Asymptomatic cement leakage was noted in 2 patients. Percutaneous fixation of thoraco-lumbar fractures in patients with AS is a reliable method that produces a high healing rate and allows prompt patient mobilisation with preservation of self-sufficiency. The post-operative complication rate is low. IV, retrospective observational study.


Controlling Selectivity in Shuttle Hetero-difunctionalization Reactions: Electrochemical Transfer Halo-thiolation of Alkynes.
Shuttle hetero-difunctionalization reaction, in which two chemically distinct functional groups are transferred between two molecules, has long been an unmet goal due to the daunting challenges in controlling the chemo-, regio-, and stereoselectivity. Herein, we disclose an electrochemistry enabled shuttle reaction (e-shuttle) to selectively transfer one RS- and one X- group between β-halosulfides and unsaturated hydrocarbons via a consecutive paired electrolysis mechanism. The preferential anodic oxidation of one anion over the other, which is controlled by their distinct redox potentials, plays a pivotal role in controlling the high chemoselectivity of the process. This easily scalable methodology enables the construction of a myriad of densely functionalized β-halo alkenyl sulfides in unprecedented chemo-, regio-, and stereoselectivity using benign surrogates, e.g., 2-bromoethyl sulfide, avoiding the handling of corrosive and oxidative RS-Br reagents. In a broader context, these results open up new strategies for selective shuttle difunctionalization reactions.


Localization of the dominant flocculation genes FLO5 and FLO8 of Saccharomyces cerevisiae.
In the yeast Saccharomyces cerevisiae three dominant flocculation genes, FLO1, FLO5 and FLO8 have been described. Until now only the FLO1 gene, which is located at chromosome I, has been cloned and sequenced. FLO5 and FLO8 were previously localized at chromosomes I and VIII respectively (Vezinhet, F., Blondin, B. and Barre, P. (1991). Mapping of the FLO5 gene of Saccharomyces cerevisiae by transfer of a chromosome during cytoduction. Biotechnol. Lett. 13, 47-52; Yamashita, I. and Fukui, S. (1983). Mating signals control expression of both starch fermentation genes and a novel flocculation gene FLO8 in the yeast Saccharomyces. Agric. Biol. Chem. 47, 2889-2896). This was not in agreement with our results. Here, we report the location of FLO5 and FLO8 on chromosomes VIII and I respectively. By induced chromosome loss and genetic mapping, the FLO5 gene was localized at the right end of chromosome VIII approximately 34 cM centromere distal of PET3. This is part of the region that is present both at chromosome I and chromosome VIII. The location of FLO5 in this area of chromosome VIII made it necessary to re-evaluate the localization of FLO8, which was previously thought to occur in this region. Both genetic and physical mapping showed that FLO8 is allelic to FLO1. Hence, there are only two known dominant flocculation genes, FLO1 and FLO5. Analysis of the nucleotide sequence of chromosome VIII of a non-flocculent strain revealed an open reading frame encoding a putative protein that is approximately 96% identical to the Flo1 protein. This suggests that both dominant flocculation genes encode similar, cell wall-associated, proteins with the same function in the flocculation mechanism.


Myelofibrosis with complex chromosome abnormality in a patient with erythrocytosis due to hemoglobin Rainier and treated with 32P.
A patient with familial erythrocytosis associated with Hemoglobin Rainier, and previously treated with 32P, developed myelofibrosis with a hyperdiploid chromosome clone in the myeloid cells (51,XX,+1,2q-(q33),+6,+9,+11,-19,+20q+,+mar 1.) This transformation from a benign disorder of differentiated erythrocytes to a malignant disorder may have been secondary to radiophosphorus therapy.


One-dimensional silver(I) chain of lacunary alpha-Keggin anions.
A novel chain-like silver polyoxotungstophosphate is formed when Ag(I) metal centres, exhibiting an unusual eight-coordination fashion, bridge a monolacunary [PW11O39]7- anion to four bridging mu2-oxygen atoms of a neighbouring lacunary alpha-Keggin anion.


Efficient removal of As(III) via simultaneous oxidation and adsorption by magnetic sulfur-doped Fe-Cu-Y trimetal oxide nanoparticles.
A novel magnetic sulfur-doped Fe-Cu-Y trimetal oxide (MST) nanomaterial was successfully synthesized by a chemical coprecipitation method to remove As(III) via simultaneous oxidation and adsorption and then characterized by BET, VSM, FESEM, XPS, and FTIR techniques. The effect of solution initial pH on the adsorption of As(III), and the adsorption kinetics and isotherm were investigated in detail. The results indicated that the MST nanoparticles exhibited an excellent performance for As(III) removal in a pH range of 7-10 and were easily separated from aqueous solution with a magnet. The maximum removal capability for As(III) reached 202.0 mg/g at pH 7.0. The adsorption of As(III) was well fitted by the pseudo-second-order kinetic model and Langmuir isotherm model, respectively. The investigation of mechanism revealed that As(III) could be oxidized to As(V) by O2- and OH free radicals, generated via the dissolved O2 obtaining an electron from Cu(I) on the surface of the adsorbent and Fenton/Fenton-like reaction, respectively. Meanwhile, the produced As(V) was adsorbed onto the surface of the nanoparticles through the electrostatic attraction or diffusion. The adsorbed As(V) further interacted with -OH groups via ion exchange or with Y(III) on the surface of the adsorbent to form a precipitate. Therefore, the MST nanoparticles are promising for the removal of arsenic from water.


Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having Type I diabetes.
Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are the cause of maturity-onset diabetes of the young type 3 (MODY3), which is characterised by a severe impairment of insulin secretion and an early onset of the disease. Also at onset of diabetes some MODY patients show similar clinical symptoms and signs as patients with Type I (insulin-dependent) diabetes mellitus. The objective of this study was to estimate the prevalence of MODY3 patients misclassified as Type I diabetic patients. From a large population-based sample of unrelated Danish Caucasian Type I diabetic patients with an affected first degree relative, 39 patients (6.7%) who did not carry any high-risk HLA-haplotypes, i.e. DR3 or DR4 or both were examined by single-strand conformational polymorphism scanning and direct sequencing of the coding region and the minimal promoter of the HNF-1alpha gene. Four of the 39 Type I diabetic patients (10%) were identified as carrying mutations in the HNF-1alpha gene. One patient carried a missense mutation (Glu48Lys) in exon 1, two patients carried a missense mutation (Cys241Gly) in exon 4 and one patient carried a frameshift mutation (Pro291fsdelA) in exon 4. The mutations were all identified in heterozygous form, segregated with diabetes, and were not identified in 84 unrelated, healthy subjects. Furthermore, family history in three of the four families showed diabetes in four consecutive generations, suggestive of an autosomal dominant inheritance. In conclusion, about 10% of Danish diabetic patients without a high-risk HLA-haplotype, originally classified as having Type I diabetes could have diabetes caused by mutations in the HNF-1alpha gene. Clinical awareness of family history of diabetes and mode of inheritance might help to identify and reclassify these diabetic subjects as MODY3 patients.


Two major subgroups of human T-cell leukemia virus-1 in Japan.
T lymphocytes of patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were cultured. After cultivating for several months, HAM-derived cell lines were tested for the presence of HTLV-1 proviral genome. We have found two major subgroups, the SacI type and the PstI type, of HTLV-1 by the restriction map analysis. They were almost equally distributed among HAM patients. We have also found two types of the provirus in DNA derived from fresh peripheral blood lymphocytes (PBL) or lymph node cells of adult T-cell leukemia/lymphoma (ATL) patients. The PstI type proviruses were predominant in ATL patients. It was concluded that two major subgroups of HTLV-1 exist in Japan and both types have an ability to cause either of two diseases, ATL or HAM.


Studies on methanol - oxidizing yeast. III. Enzyme.
Oxidation of methanol, formaldehyde and formic acid was studied in cells and cell-free extract of the yeast Candida boidinii No. 11Bh. Methanol oxidase, an enzyme oxidizing methanol to formaldehyde, was formed inducibly after the addition of methanol to yeast cells. The oxidation of methanol by cell-free extract was dependent on the presence of oxygen and independent of any addition of nicotine-amide nucleotides. Temperature optimum for the oxidation of methanol to formaldehyde was 35 degrees C, pH optimum was 8.5. The Km for methanol was 0.8mM. The cell-free extract exhibited a broad substrate specificity towards primary alcohols (C1--C6). The activity of methanol oxidase was not inhibited by 1mM KCN, EDTA or monoiodoacetic acid. The strongest inhibitory action was exerted by p-chloromercuribenzoate. Both the cells and the cell-free extract contained catalase which participated in the oxidation of methanol to formaldehyde; the enzyme was constitutively formed by the yeast. The pH optimum for the degradation of H2O2 was in the same range as the optimum for methanol oxidation, viz. at 8.5. Catalase was more resistant to high pH than methanol oxidase. The cell-free extract contained also GSH-dependent NAD-formaldehyde dehydrogenase with Km = 0.29mM and NAD-formate dehydrogenase with Km = 55mM.


PEP-1-SIRT2 causes dedifferentiation and COX-2 expression via the MAPK pathways in rabbit articular chondrocytes.
SIRT2 is a member of the mammalian sirtuin protein family, primarily found in the cytoplasm. It regulates numerous cellular processes including aging, DNA repair, cell cycle, and survival under stress conditions. However, the biological function and mechanism of the SIRT2 protein was not well understood in normal cells such as primary chondrocytes. In this study, we examined the effects of SIRT2 on differentiation and inflammation in rabbit articular chondrocytes by using a cell-permeative PEP-1-SIRT2 protein. Our results indicate that PEP-1-SIRT2-induced a loss of type II collagen and decreased sulfate proteoglycan levels in a dose- and time-dependent manner, as examined by Western blotting, alcian blue staining, and immunohistochemistry. Furthermore, PEP-1-SIRT2 caused an inflammatory response by inducing the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). In addition, after treatment with PEP-1-SIRT2, phosphorylation of both p38 and ERK was observed. Inhibition of ERK with PD98059 (PD) suppressed PEP-1-SIRT2-induced dedifferentiation and COX-2 expression. Reduction in PEP-1-SIRT2-induced inflammatory response was observed upon inhibition of p38 by SB203580 (SB). The same pattern was demonstrated in PEP-1-SIRT2-induced dedifferentiation and inflammatory response during culture with serial passages. During expansion to four passages, levels of type II collagen decreased, whereas levels of COX-2 and SIRT2 increased and activated ERK and p38. Furthermore, PEP-1-SIRT2 enhances dedifferentiation through the ERK pathway and inflammatory response through the ERK and p38 pathways in rabbit chondrocytes in vitro. These findings suggest that PEP-1-SIRT2 induces dedifferentiation via the ERK pathway and inflammation through the p38 and ERK pathways in rabbit articular chondrocytes.


Efficient synthesis of β'-amino-α,β-unsaturated ketones.
A general and simple procedure to access chiral β'-amino-α,β-enones, in seven steps, from an α,β unsaturated ester has been described. The use of a Horner-Wadsworth-Emmons reaction as a key step for generating the β'-amino-α,β-enones, permits access to a range of substrates under mild conditions and in moderate to high yield.


A case of Endovascular Treatment of Blunt Aortic Bifurcation Transection using peripheral stentgraft.
We present a case of endovascular management of aortic transection at the aortic bifurcation in a polytrauma patient.


The effects of ketamine anesthesia on glucose clearance in African green monkeys.
Ketamine hydrochloride's effect on glucose clearance-insulin secretion during intravenous glucose tolerance testing was studied in five African green monkeys. Animals were tested with ketamine anesthesia and then had indwelling cannulas implanted and were retested both in the presence and absence of ketamine anesthesia. Serum glucose and insulin concentrations were determined. There were no significant differences in the glucose clearance rate (K value), basal glucose and insulin concentrations, maximum insulin concentration, and area under the insulin response curve, among the three different conditions.


Extensive drug resistant Acinetobacter baumannii: a comparative study between non-colistin based combinations.
Background The Gastrointestinal Surgery Center (GISC)-Mansoura University, faced a series of extensive drug resistant (XDR) A. baumannii cases, that were microbiologically resistant to penicillins, cephalosporins, fluoroquinolones, aminoglycosides, carbapenems and tigecycline. Colistin would have been a last resort therapy in such situation, however, intravenous polymyxins E (colistin) is relatively unavailable in Egypt. Many practitioners tried to form antibiotic combinations from the available antibiotics to overcome the resistance mechanisms of the pathogen. Objective Evaluate the clinical outcomes of these combinations retrospectively. Setting The study took place at the GISC, which is an academic specialized center affiliated with Mansoura University-Egypt. Method Clinical data were collected from the patients' files, where the subjects were classified into two major groups according to the therapeutic intervention. Group 1 included 24 patients divided into 4 subgroups. The first was treated by a Cephalosporin with a Fluoroquinolone (1A), The second was treated by a Carbapenem with a Fluoroquinolone (1B), The third was treated by a B-lactam with an Aminoglycoside (1C) and the fourth was treated by Carbapenem with a Glycylcycline (1D). Group 2 included 6 patients, treated with Tigecycline and Ampicillin-Sulbactam. Main outcome measure Primary outcomes are the A. baumannii microbiological culture negativity after 14 days of therapy and the 30 days' survival after the antibiotic course, while the secondary outcomes are the expected therapies' side effects. Results Group 2 is associated with significant higher primary outcomes without a significant difference regarding the secondary outcomes. Conclusion The combination of Tigecycline and Ampicillin-Sulbactam, appears to be a clinically effective therapy against XDR A. baumannii, despite each agent being resistant alone, without alerting adverse effects.


Splenic B-cell lymphoma with villous lymphocytes (SLVL). A lymphocytic lymphoma simulating hairy cell leukemia. A study of 8 cases.
Splenic B cell lymphoma with circulating villous lymphocytes (SLVL) is a lymphoproliferative disorder characterized by the presence in the peripheral blood of atypical B-lymphocytes with hairy appearance. Although the clinical features with massive splenomegaly, absence of peripheral lymphadenopathy and blood cytopenia may mimic hairy cell leukemia (HCL), precise analysis of the morphologic and immunologic features allow differential diagnosis between these two entities. Bone marrow and spleen histology resemble the pattern in chronic lymphocytic leukemia (CLL). We studied 8 patients with this entity illustrating the difficulty of diagnosis between SLVL and HCL.


Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study.
Insulin resistance and declining beta-cell function are the core defects in type 2 diabetes mellitus. It has been suggested that deteriorating glycemic control is related to baseline hemoglobin A(1c) (HbA(1c)) values and remaining beta-cell function. We report glycemic data from a 3.5-year, open-label, observational, primary care study comparing 30 mg/day pioglitazone with 3.5 mg/day glibenclamide add-on to stable metformin monotherapy in 500 patients with type 2 diabetes. Insulin commencement was considered for patients with HbA(1c) > or = 8.0% or when vascular complications occurred. The change in HbA(1c) compared with baseline and the difference in time to failure to maintain glycemic control were calculated. At endpoint, HbA(1c) had decreased by 1.0% in the pioglitazone group (p < 0.005) and by 0.6% in the glibenclamide group (p < 0.05). Annual progression rates to insulin treatment were 6.6% (pioglitazone) and 16.4% (glibenclamide; p < 0.001 between-group difference). Mean weight increases of 3.5 +/- 0.42 kg in the pioglitazone group and 3.3 +/- 0.38 kg in the glibenclamide group were noted. Overall, both treatments were well tolerated. Pioglitazone add-on to metformin revealed significant benefits in long-term glycemic control compared with glibenclamide. This difference may be explained by a large between-group difference in HOMA-S, which was shown to correlate significantly to the change in HbA(1c). This suggests that a strategy to reduce insulin resistance to lower the burden of the beta-cell is superior to treatment with glibenclamide.


Conjunctival cysts of the orbit after enucleation: the use of trichloroacetic acid.
Orbital cyst formation after enucleation is a rare but serious complication. Complete excision may be difficult, and the final cosmetic result may be poor. In contrast, in this study, intralesional trichloroacetic acid injection proved successful in resolving the problematic cyst without surgical intervention. A 20% trichloroacetic acid solution was injected to treat four cases of orbital conjuctival cyst in anophthalmic socket. All four patients were treated successfully. No recurrence or other complications developed. The average follow-up interval was 16 months (range, 8 to 33 months). Intralesional trichloroacetic acid injection proved successful in resolving the problematic cyst without surgical intervention in anophthalmic orbit. It is a safe procedure and is recommended for treatment of anteriorly located orbital conjuctival cysts.


Area-based comparison of risk factors and testing rates to improve sexual health care access: cross-sectional population-based study in a Dutch multicultural area.
Areas with high sexually transmitted infection (STI) testing rates may not require additional strategies to improve testing. However, it may be necessary to intervene in areas with elevated STI risk, but with low STI testing rates. We aimed to compare STI-related risk profiles and STI testing rates by geographical area to determine areas for improvement of sexual healthcare access. Cross-sectional population-based study. Greater Rotterdam area, the Netherlands (2015-2019). All residents aged 15-45 years. Individual population-based register data were matched with laboratory-based STI testing data of general practitioners (GPs) and the only sexual health centre (SHC). Postal code (PC) area-specific STI risk scores (based on age, migratory background, education level and urbanisation), STI testing rates and STI positivity. The study area consists of approximately 500 000 residents aged 15-45 years. Strong spatial variation in STI testing, STI positivity and STI risk was observed. PC area testing rate ranged from 5.2 to 114.9 tests per 1000 residents. Three PC clusters were identified based on STI risk and testing rate: (1) high-high; (2) high-low; (3) low, independently of testing rate. Clusters 1 and 2 had comparable STI-related risk and STI positivity, but the testing rate differed greatly (75.8 vs 33.2 per 1000 residents). Multivariable logistic regression analysis with generalised estimating equation was used to compare residents in cluster 1 and cluster 2. Compared with cluster 1, residents in cluster 2 more often did not have a migratory background, lived in less urbanised areas with higher median household income, and more distant from both GP and SHC. The determinants associated with individuals living in areas with high STI-related risk scores and low testing rates provide leads for improvement of sexual healthcare access. Opportunities for further exploration include GP education, community-based testing and service (re)allocation.


Development of an improved Amplex Red peroxidation activity assay for screening cytochrome P450 variants and identification of a novel mutant of the thermophilic CYP119.
Biocatalysts are increasingly utilized in the synthesis of drugs and agrochemicals as an alternative to chemical catalysis. They are preferred in the synthesis of enantiopure products due to their high regioselectivity and enantioselectivity. Cytochrome P450 (P450) oxygenases are valuable biocatalysts, since they catalyze the oxidation of carbon-hydrogen bonds with high efficiency and selectivity. However, practical use of P450s is limited due to their need for expensive cofactors and electron transport partners. P450s can employ hydrogen peroxide (H2O2) as an oxygen and electron donor, but the reaction with H2O2 is inefficient. The development of P450s that can use H2O2 will expand their applications. Here, an assay that utilizes Amplex Red peroxidation, to rapidly screen H2O2-dependent activity of P450 mutants in cell lysate was developed. This assay was employed to identify mutants of CYP119, a thermophilic P450 from Sulfolobus acidocaldarius, with increased peroxidation activity. A mutant library of CYP119 containing substitutions in the heme active site was constructed via combinatorial active-site saturation test and screened for improved activity. Screening of 158 colonies led to five mutants with higher activity. Among improved variants, T213R/T214I was characterized. T213R/T214I exhibited fivefold higher kcat for Amplex Red peroxidation and twofold higher kcat for styrene epoxidation. T213R/T214I showed higher stability towards heme degradation by H2O2. While the Km for H2O2 and styrene were not altered by the mutation, a fourfold decrease in the affinity for another substrate, lauric acid, was observed. In conclusion, Amplex Red peroxidation screening of CYP119 mutants yielded enzymes with increased peroxide-dependent activity.


Amyloid corneal deposition in corneal buttons of congenital hereditary endothelial dystrophy (CHED) - A clinical and histopathological case series.
To determine the frequency, pathology and clinical relevance of amyloid deposited in corneas of CHED. Clinical and histopathological case series. Amyloid subepithelial deposition was found in 5 (6.6%) corneal buttons of 75 patients with histopathologically confirmed CHED diagnosis. Clinical findings included history of parental consanguinity, poor vision (ranging from counting fingers from one foot to 3/200), corneal edema, and central whitish subepithelial corneal nodules in all the five cases and positive family history in 4 of 5 cases. The patients underwent PKP at a mean age of 15 years (range 3-22 years). Histological findings included attenuated endothelium (6/6) thickened Descemet's membrane (6/6), stromal edema (2/6), and subepithelial amyloid deposits (6/6). All patients improved from vision point of view. To date, no recurrence of the amyloid has been seen in the grafts. Considering the consanguinity, family history, early onset, and bilaterality, this study supports our hypothesis that the amyloid is primary in nature in our patients and indicates a new subtype of autosomal recessive CHED that require further chemical and genetic analysis. This subtype has the same prognosis for PKP as all CHED patients, if not better.


Cerebellar opiate receptors in lagomorphs. Demonstration, characterization and regional distribution.
The cerebellum of lagomorphs (pika, rabbit, hare) binds 100--200 femtomoles of [3H]etorphine per milligram of protein. This is very high in comparison with the 10--15 fmol/mg found in the cerebellum of rodents (mouse, hamster, rat). In the rabbit cerebellum, the etorphine sites have binding properties indistinguishable from those of genuine opiate receptor sites in brain. They exhibit a high affinity for [3H]etorphine (KD = 1 X 10(-10) M), [3H]naloxone (KD = 9 X 10(-10) M), morphine and levorphanol but not for dextrophan. Moreover, sodium ions enhance binding of naloxone (antagonist response) and diminish binding of etorphine, morphine and levorphanol (agonist response) to cerebellum homogenates. The regional distribution of [3H]etorphine binding sites in the rabbit cerebellum points toward concentrations higher in the neocerebellum (hemispheres) than in the archecerebellum (lingula and flocculonodular lobe). Finally, the specific concentration of opiate receptor sites in the isolated molecular layer is at least two times that in the isolated granular layer and ten times that in white matter.


Inflammatory breast carcinoma: outcomes with trimodality therapy for nonmetastatic disease.
The objectives of this study were to summarize a single-institution experience in treating patients with inflammatory breast carcinoma (IBC) using trimodality therapy and to identify prognostic factors for outcome. Sixty-one women underwent radiation therapy with curative intent for IBC between 1982 and 2001. All but five women received trimodality therapy. Neoadjuvant chemotherapy was given to the majority of women (n = 43 patients), although some received "up-front" surgery as first therapy (n = 18 patients). With a median potential observation time after diagnosis of 14 years, freedom from locoregional disease progression was 78%, freedom from distant metastasis was 45%, and the cause-specific survival rate was 47% at 5 years. Approximately 40% of the 56 patients who received trimodality therapy remained free of disease. Multivariate analysis demonstrated three factors that were found to be associated significantly with improved cause-specific survival: pathologic tumor size < 4 cm (P = 0.0001), up-front surgery (P = 0.0078), and local disease control (P = 0.0003). Factors that were found to be associated with better freedom from locoregional disease progression were pathologic tumor size (< 4 cm; P = 0.0157), age (> 55 years; P = 0.0596), and radiation dose (> or = 60 grays [Gy]; P = 0.0621). IBC is an aggressive disease that is treated effectively in select patients by multimodality therapy. Patient outcomes may be improved with therapies that result in better local and systemic control. Further studies are warranted to address the optimal sequence of trimodality therapy and the optimal administration of each agent.


Abundance and mortality of a specialist leafminer in response to experimental shading and fertilization of American holly.
Phytomyza ilicicola (Diptera: Agromyzidae), a univoltine specialist leafminer, typically reaches higher population densities on cultivated host planted in sunny, urban sites than it does on native trees in the forest understory. I tested the hypothesis that environmental factors, more specifically differences in light intensity and soil fertility, are responsible for this observed pattern, either by affecting leaf morphology or nutritional quality, or indirectly through early leaf abscission. Clonal trees were planted at a common site and experimentally shaded and fertilized for 14 months before being exposed to oviposition by adult flies. Differences in leaf thickness, nitrogen and water status, and in the abundance, developmental rate, survival, pupal weights and abscission-related mortality of leafminers were compared among trees. Leaves from experimentally shaded trees were larger and thinner, with only two palisade cell layers as compared to three to four layers in leaves from unshaded trees. Crystals, probably of calcium oxalate, are abundant in the abaxial cell layer, and it was hypothesized that these might set mechanical constraints on larvae feeding within shaded leaves. However, there was little or no difference in leafminer abundance, developmental rate, survival to pupation, area of finished mines, or pupal weight between shaded and unshaded trees. Leafminers compensated for feeding within thinner, shaded leaves by consuming portions of the abaxial and adaxial palisade layers and leaving a thinner roof on the mine. Furthermore, there was no difference in thickness between leaves with successful or aborted mines in either shade or sun. Leaves from fertilized trees contained 37% higher total nitrogen than those from unfertilized control trees. Fertilization did not significantly affect leafminer abundance, developmental rate, mine area or pupal weight, but survival to pupation was slightly lower on fertilized trees. Abscission-related mortality of P. ilicicola was much higher in full sun than for shaded trees, opposite of what would be predicted if early abscission per se were a primary determinant of relative abundance between habitats. These results indicate that structural constraints on leafminer larvae within shaded leaves, differences in leaf nitrogen related to soil fertility, and/or differential mortality resulting from early leaf abscission are probably not the proximate causes of density variation of this leafminer between woods and urban habitats.


Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen.
Mammary carcinomas have been induced by 3.5 Gy whole-body gamma radiation administered at age 40 to 50 days to virgin female Sprague-Dawley rats. In 142 irradiated controls carcinoma incidence averaged 7.8% in survivors observed less than 300 days and 38.3% of those surviving longer (P less than 0.001 by t test). Mammary cancer promotion was inhibited by two methods: estriol (E3) 638 micrograms/month (2.2 microns/mo) subcutaneously for natural life span begun 2 weeks after exposure reduced cancer incidence from 76% in controls to 48% after 331 to 449 mean days observation until neoplasia was palpable (P less than 0.02 by chi-square analysis). Uterine weights were similar in control and treated groups, and were 15% to 18% greater than uteri of nonirradiated controls from other simultaneous experiments. Six monthly 638-micrograms doses of 17 alpha ethinyl estriol (EE3) reduced tumors from 88% in controls to 64% (P less than 0.05 by chi-square analysis) and delayed cancer onset (P less than 0.01-0.04 by life table analysis). Ethinyl estradiol (EE2) after 6 months' treatment similarly delayed mammary tumor development reducing incidence to 75% (NS), with a six-fold increase in nonmammary epithelial malignant tumors. Estriol administration begun between 3 days before to 5 days after radiation did not alter mammary cancer incidence in six experiments. Monthly implantation of 2.5 mg tamoxifen (4.44 microns/mo) started 2 weeks after radiation reduced mammary cancer incidence from 83% to 14% after 307 to 314 days' observation (P less than 0.001 by chi-square analysis). Treated rats had atrophic ovaries and uteri consistent with blockade of endogenous estradiol activity. Short-term parenteral E3 or EE3 therapy using 10 to 30 micrograms/kg/day (35-100 microns/kg/day) rapidly differentiated virgin rat mammary glands without impairment of subsequent estrus cycles and offers an alternative to castration or life-long antiestrogen therapy for reduction of risk of radiogenic mammary carcinoma.


Metyrapone effects on systemic and cerebral energy metabolism.
Metyrapone is a cytochrome P(450) inhibitor that protects against ischemia- and excitotoxicity-induced brain damages in rodents. This study examines whether metyrapone would act on energy metabolism in a manner congruent with its neuroprotective effect. In a first investigation, the rats instrumented with telemetric devices measuring abdominal temperature, received i.p. injection of either metyrapone or saline. One hour after injection, their blood and hippocampus were sampled. Hippocampus metabolite concentrations were measured using (1)H high-resolution magic angle spinning-magnetic resonance spectroscopy ((1)H HRMAS-MRS). The hippocampus levels in phosphorylated mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) were measured by Western Blot analysis and those of c-fos and HSP70-2 mRNA were quantified by RT-PCR. In a second investigation, the rats received the same treatment and were sacrificed 1h after. The functioning of mitochondria was immediately studied on their whole brain. Metyrapone provoked a slight hypothermia which was correlated to the increase in blood glucose concentration. Metyrapone also increased blood lactate concentrations without modifying hippocampus lactate content. In the hippocampus, metyrapone decreased γ-aminobutyric acid (GABA) and glutamate levels but increased glutamine and N-acetyl-aspartate contents (NAA). Phosphorylated mTOR and AMPK and the c-fos and HSP70-2 mRNA levels were similar between treatment groups. Metyrapone did not modify blood corticosterone levels. Mitochondrial oxygen consumption was similar in both groups whatever the substrate used. These metabolic modifications, which take place without modifying blood glucocorticoid levels, are consistent with the neuroprotective properties of metyrapone as demonstrated in animal models.