Long-term follow-up of women hospitalized for acute pyelonephritis.
Long-term outcome of acute pyelonephritis (AP) in adults is unknown. We evaluated the frequency of renal damage 10-20 years after hospitalization for AP in adult women and the utility of technetium Tc 99m-labeled dimercaptosuccinic acid (Tc 99m-DMSA) scanning for detection of renal scars; 63 of 203 women hospitalized with AP during 1982-1992 were included in the study. Tc 99m-DMSA scanning detected renal scarring in 29 women (46%). Multivariate analysis showed that pregnancy and hypoalbuminemia (albumin level, <3.2 g/dL) at hospitalization were independent risk factors for subsequent development of renal scars. At follow-up, hypertension was observed in approximately one-fifth of patients, regardless of renal scarring status. Four women with scars had a glomerular filtration rate of < or =75 mL/min; none of them developed severe renal impairment. In conclusion, the risk of developing renal scarring after AP in adult women is high. However, clinically relevant renal damage is rare 10-20 years after AP. Tc 99m-DMSA scanning is useful for detecting renal scars in adults but is not routinely needed in practice.


Neurofibromatosis 2 in the pediatric age group.
Bilateral acoustic neurofibromatosis or neurofibromatosis 2 (NF2) is an autosomal dominant disease predisposing to the formation of multiple tumors in the central and peripheral nervous system. Vestibular schwannomas (VSs) are considered to be the hallmark of the disease, but other tumors and ocular findings occur as well. In patients that do not carry the NF2 mutation, VSs usually occur in the fifth or sixth decade of life. VSs in patients with NF2 are often bilateral and become symptomatic in the third or fourth decade of life. In order to define the early manifestations of NF2, we examined nine children who either had one parent with NF2 or had multiple skin or spinal tumors suggestive of NF2. In addition to neurological, dermatological, and ocular examinations, all patients were studied by gadolinium-enhanced magnetic resonance imaging of the brain and spine. None of the children exhibited symptoms or signs due to VSs. However, VSs were detected during the neuroradiological work-up in six children. Seven children developed symptoms or signs due to skin or spinal tumors. Slit lamp examination detected cataracts in four patients as young as 10 years of age. The diagnosis of NF2 in the pediatric age group requires a high degree of suspicion and should be considered in children with multiple central nervous system or skin tumors without cafe-au-lait spots or Lisch nodules. Because VSs are unlikely to produce the signs seen at the time of admission, careful examination of the skin and eyes is necessary and should be followed by gadolinium-enhanced magnetic resonance imaging of the brain and spine. First-degree relatives need to be examined as well.


[Renal transplantation in the elderly: characteristics of donor and recipient].
Aging is a natural process that occurs in all tissues and organs resulting in a decreasing functional capacity. Aging of the population results in an increased number of elderly patients who require replacement of renal function. Renal transplantation is the method of choice for this group of patients if they have no contraindications for immunosuppressive therapy. The lack of donors is the main obstacle for renal transplantation. However, the use of organs from elderly donors for transplantation in elderly recipients is an appropriate method of renal replacement therapy in this group of patients.


Copper-catalyzed arylation of biguanide derivatives via C-N cross-coupling reactions.
An efficient copper-catalyzed cross-coupling reaction of biguanide hydrochloride derivatives with both aryl iodides and bromides under mild conditions has been developed. The reaction occurred in good yields and tolerated aryl halides containing functionalities such as nitriles, sulfonamides, ethers, and halogens. Alkyl and cyclic substituted biguanidines were also well tolerated.


Proteomic characterization of fresh spermatozoa and supernatant after cryopreservation in relation to freezability of carp (Cyprinus carpio L) semen.
Our recent studies suggested that the freezability of carp semen is related to seminal plasma protein profiles. Here, we aimed to compare the spermatozoa proteomes of good (GF) and poor (PF) freezability semen of carp. To achieve this, we used two-dimensional difference in gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry. The semen was classified as GF or PF based on sperm motility after freeze/thawing. We identified proteins enriched in spermatozoa of GF (22 proteins) and PF (18 proteins) semen. We also identified 12 proteins enriched in the supernatant after cryopreservation of PF semen. Good freezability is related to high concentrations of proteins involved in the maintenance of flagella structure, membrane fluidity, efficient control of Ca2+ and sperm motility, energy production, and antioxidative protection, which likely reflects the full maturation status of spermatozoa of GF semen. On the other hand poor freezability seems to be related to the presence of proteins identified as released in high quantities from cryopreserved sperm of PF. Thus, the identified proteins might be useful bioindicators of freezing resilience and could be used to screen carp males before cryopreservation, thus improve long-term sperm preservation in carp. Data are available via ProteomeXchange with identifier PXD008187.


A ligament in the lumbar foramina: inverted Y ligament: an anatomic report.
The objective of this study was to investigate the ligaments in the exit zone of lumbar foramen and describe their anatomic relationships with adjacent structures. Few studies have been reported on the ligaments of foramen and the anatomic relationships on the lumbar level. The ligament described in this study is novel since it has not been reported previously. Ten male and five female cadavers were used to investigate intraforaminal area and ligaments of the lumbar level. The cadavers were filled with colored latex, and the lumbar foramen were examined under operative microscope. A lumbar foramen branched off into two or three main passages, composed of inverted Y ligament form. The medial lower arm of Y ligament was attached to the upper and anterior surface of the superior articular process of the lower corpus vertebra. Its lateral lower arm was attached to the upper surface of the area where the lower corpus vertebra and its pedicle met, and the upper arm was attached to the lower surface of the pedicle of upper vertebra where it met with transverse process. The anatomic properties of vascular and nervous structures in foramen and the relations among them are described. The ligament detected in the study was different from the other reported descriptions of foraminal ligaments. It divided the lumbar foramen into three passages. Because of its relations with adjacent structures, such as nerves and vessels, the inverted Y ligament may be an important structure for lumbar foramen. Thus, it may be an important anatomic landmark.


[Results of a multidisciplinary and intensified treatment program for type 1 Diabetes Mellitus in a Chilean Public Hospital].
During the last decade, the importance of glycemic control in the prevention of the microvascular complications of type 1 Diabetes Mellitus (DM1) was clearly demonstrated. To evaluate the metabolic and anthropometric results of a multidisciplinary intensified treatment program of DMI in children and adolescents. Report of 54 patients treated during 2001. The intensified treatment consisted of: multiple daily doses of insulin, frequent glycemic control, nutritional, psychological and educational support, and permanent availability of a diabetes nurse for telephonic support. Thirty one patients were female, their mean age was 10.4 +/- 0.5 years old and 52% were experiencing puberty. Fifty three percent of the patients used 3 insulin doses per day, 95% changed rapid insulin dose based on glucose levels and 18% considered carbohydrates in their rapid insulin dosing. Mean glycosilated hemoglobin was 8.18 +/- 0.23% without differences by sex or pubertal status. Sex, pubertal stage and the number of insulin doses did not contribute to glycosilated hemoglobin changes. There were no differences in weight or BMI, but there was a decrease in height Z score from the admission to the program until the last control (0.1 +/- 0.1 vs--0.3 +/- 0.1 DS; p < 0.01). A modified intensified modality of DM1 therapy for pediatric patients in a public hospital in Chile is feasible, achieving similar metabolic control, compared to international large centers.


Knockdown of chimeric glucocerebrosidase by green fluorescent protein-directed small interfering RNA.
Gaucher disease, the most common type of lysosomal storage disorder, is characterized by an inherited deficiency of the membrane-associated hydrolase, glucocerebrosidase. Glucocerebrosidase catalyzes the hydrolysis of glucocerebroside to ceramide and glucose, a crucial step in the recycling of membrane sphingolipids. The exorbitant cost of the current treatment standard for Gaucher disease, enzyme replacement therapy, prevents many from receiving treatment. This limitation has led to a wide-spread search for more efficient and cost-effective methods of protein production and alternate therapies, resulting in a closer examination of glucocerebrosidase biosynthesis and current treatment techniques. The use of specific small interfering RNAs (siRNAs) to knock down target genes is an attractive option for studying such processes, though a glucocerebrosidase-specific siRNA has yet to be reported. We note, however, that green fluorescent protein (GFP)-directed siRNAs can not only provide a positive control to test siRNA delivery and system integrity, but also serve as a means to knock down a fusion partner without having to design siRNAs specific to the partner. After effectively co-transfecting COS-1 cells with enhanced GFP (EGFP)-tagged glucocerebrosidase constructs and GFP-directed siRNAs, we report successful knockdown of all EGFP-containing constructs at both the RNA and protein levels. This provides a method of examining enzyme biosynthesis and treatment options. Furthermore, this technique is applicable to other systems, since we have demonstrated the usefulness of GFP as a siRNA target in mammalian cells when fused to another gene of interest.


Bias-Adaptable CO2-to-CO Conversion via Tuning the Binding of Competing Intermediates.
CO2 electroreduction powered by renewable electricity represents a promising method to enclose anthropogenic carbon cycle. Current catalysts display high selectivity toward the desired product only over a narrow potential window due primarily to unoptimized intermediate binding. Here, we report a functional ligand modification strategy in which palladium nanoparticles are encapsulated inside metal-organic frameworks with 2,2'-bipyridine organic linkers to tune intermediate binding and thus to sustain a highly selective CO2-to-CO conversion over widened potential window. The catalyst exhibits CO faradaic efficiency in excess of 80% over a potential window from -0.3 to -1.2 V and reaches the maxima of 98.2% at -0.8 V. Mechanistic studies show that the 2,2'-bipyridine on Pd surface reduces the binding strength of both *H and *CO, a too strong binding of which leads to competing formate production and CO poison, respectively, and thus enhances the selectivity and stability of CO product.


High altitude adaptation: genetic perspectives.
The goal of this review is to highlight the underlying genetics that may explain complex traits associated with high altitude adaptation. The review covers the traditional candidate gene approach for identifying molecular variants having a functional role and associating with high altitude adaptation and disorders. We review some of the salient features of these candidate genes, debating their potential role in high altitude fitness. The advancement in high-throughput techniques in molecular genetics and the availability of large-scale catalogs of genetic variation in the public domain have provided a better platform for genome-wide scans for identifying genetic components for many traits. Current techniques such as whole-genome scans, admixture mapping using powerful tag SNPs, and the vast data available from human genome sequencing and the HapMap project may aid in a comprehensive understanding of genomic patterns of high altitude adaptation as well as disease-related research.


Concise total synthesis of spirocurcasone.
A concise total synthesis of spirocurcasone was accomplished. Key features of the synthesis involved a vinylogous Mukaiyama aldol reaction, a Carroll rearrangement of β-keto allyl ester derivative, an intramolecular aldol condensation, and a spiro ring formation by ring-closing metathesis of the pentaene compound. This synthetic work was complete in nine steps from (S)- or (R)-perillaldehyde without the use of protecting groups. Interestingly, the optical rotation of the synthetic spirocurcasone was different from the reported value of the natural product.


Cemented femoral revision: technique and outcome.
Long-term pain relief and improved function in patients with failed or infected hip replacement, or, occasionally for patients with impending surgical failure, are the goals of total hip revision arthroplasty. Cement techniques for femoral and reconstructions in patients needing total hip revision are discussed in this article. Advantages of cemented technique include the ability to incorporate antibiotics into the cement during reimplantation following periprosthetic infection. Cemented technique is also preferable over cementless techniques when there is extensive diaphyseal bone loss, which precludes predictable biologic fixation. Cement-within-cement technique is indicated for well-fixed cemented femoral components that require revision for instability, improved acetabular exposure, equalization of leg lengths, or damage to a monoblock femoral head.


2-Hydroxyisoflavanone dehydratase is a critical determinant of isoflavone productivity in hairy root cultures of Lotus japonicus.
Hairy root cultures of a model legume, Lotus japonicus, were established to characterize two heterologous cDNAs encoding enzymes involved in isoflavone biosynthesis, i.e. licorice 2-hydroxyisoflavanone synthase (IFS) and soybean 2-hydroxyisoflavanone dehydratase (HID) catalyzing sequential reactions to yield isoflavones. While the control and the IFS overexpressor did not accumulate detectable isoflavones, the HID overexpressors did accumulate daidzein and genistein, showing that HID is a critical determinant of isoflavone productivity. Production of coumestrol in all the genotypes and isoliquiritigenin/liquiritigenin in IFS + HID-overexpressing lines was also noted. These results provide insight into the regulatory mechanism that controls isoflavonoid biosynthesis.


The use of herbal therapies in pediatric oncology patients: treating symptoms of cancer and side effects of standard therapies.
Complementary and alternative medicine is increasing in use in the pediatric oncology population. Although there is a multitude of herbal therapies used, the focus of this article is a review of the literature addressing some herbal therapies used to treat the symptoms of cancer and side effects of traditional methods of treatment. Ginger is used in the treatment of nausea and vomiting. St. John's wort is successful in treating depression and anxiety. Echinacea is used as an immunostimulant. Herbal therapies in the pediatric oncology population are usually initiated and managed by parents. Many herbal therapies are beneficial, but some potential herb-drug interactions should be considered. This poses a challenge to the oncology nurse because herbal treatments are managed by the parents and pharmaceuticals are managed by the practitioner. Educating the patient, family, and practitioner is important in ensuring a thorough health history assessment and, subsequently, safe and effective herbal and pharmacological therapies.


The effectiveness of a bundled intervention to improve resident progress notes in an electronic health record.
Providers nationally have observed a decline in the quality of documentation after implementing electronic health records (EHRs). In this pilot study, we examined the effectiveness of an intervention bundle designed to improve resident progress notes written in an EHR and to establish the reliability of an audit tool used to evaluate notes. The bundle consisted of establishing note-writing guidelines, developing an aligned note template, and educating interns about the guidelines and using the template. Twenty-five progress notes written by pediatric interns before and after this intervention were examined using an audit tool. Reliability of the tool was evaluated using the intraclass correlation coefficient (ICC). The total score of the audit tool was summarized in terms of means and standard deviation. Individual item responses were summarized using percentages and compared between the pre- and postintervention assessment using the Fisher exact test. The ICC for the audit tool was 0.96 (95% confidence interval: 0.91-0.98). A significant improvement in the total note score and in questions related to note clutter was seen. No significant improvement was seen for questions related to copy-paste. The study suggests that an intervention bundle can lead to some improvements in note writing.


Cyclic nucleotide phosphodiesterase isozymes in neuroblastoma cells.
Adenosine 3',5'-cyclic monophosphate (cAMP) content of neurons is determined not only by the rate of synthesis but also by the rate of hydrolysis by cyclic nucleotide phosphodiesterases. Multiple forms of cyclic nucleotide phosphodiesterase exist in brain and other tissues, and these may be regulated by various hormones and neuromodulators. The present study examines this regulation in a cloned line of neuroblastoma cells (N18TG2). A biphasic Lineweaver-Burk plot of cAMP hydrolysis revealed two Kms approximating 5 and 25 microM. Lineweaver-Burk plots of cGMP hydrolysis were linear over a range of 1 microM to 1 mM and exhibited a Km of 37 microM. Neither cAMP nor cGMP competed for hydrolysis of the alternative cyclic nucleotide. No evidence for an allosteric activation of cAMP phosphodiesterase by cGMP was found. Calcium regulation of phosphodiesterase was not found in spite of preparation of the cell extract with several protease inhibitors, and addition of exogenous calmodulin. No effect of calmodulin antagonists (calmidazolium, W7, or trifluoperazine) was observed in vitro or in situ. Growth of the cells in the presence of 200 nM 3,5,3'-triiodothyronine (T3) resulted in an increased hydrolysis of cAMP but of cGMP. This increase was attributed to an increase in Vmax with no change in either high or low Km. This response was blocked by cycloheximide, suggesting that the thyroid hormone effect requires protein synthesis. The thyroid hormone response in neuroblastoma cells is compared with the results of other studies of thyroid hormone effects on phosphodiesterase in other tissues in vivo.


Indoor mould testing in a historic building: Blickling Hall.
Indoor mould growth is a growing concern for all stakeholders of built environment, including residents, builders, insurance and building remediation industry as well as custodians of heritage buildings. The National Trust has reported this problem in a number of buildings under their ownership, and developed solutions and fine-tuned their maintenance programme so as to minimise indoor and surface mould growth risk. This paper reports findings from an extensive mould-testing scheme in Blickling Hall, a National Trust property in Norfolk, England, for an appraisal of airborne and surface mould levels within a total of eight rooms, including the famous Long Gallery. The testing protocol used combines active (aggressive) air sampling and surface sampling, analysis of the β-N-acetylhexosaminidase (NAHA) activity to quantify mould levels and particle counting. The results show that the airborne mould levels are quite low in all spaces, due to satisfactory maintenance of indoor hygrothermal conditions by conservation heating. On the other hand, while the National Trust's developed solutions and maintenance programme have proved effective to avoid surface mould growth in those locations that historically suffered from microbial activity (such as behind book presses, picture frames and tapestries), the results show that the surface cleaning around windows should be improved to tackle surface water due to condensation, which is considered to be the main driver behind high surface NAHA activity obtained in these areas.


A case of thymic cyst with elevated sialylated Lewis X-i, carbohydrate antigen 19-9 and tissue polypeptide antigen in the cystic fluid with no elevation of serum tumor markers.
A 56-year-old man, tentatively diagnosed as having cardiomegaly, was found to have a large cyst in the left anterior mediastinum. At thoracotomy a multilocular cystic mass containing a colorless serous fluid was found and resected. Histologically, the cyst was lined with flattened epithelial cells, and thymic tissue was present in the cyst's wall; a diagnosis of thymic cyst was made. There were no malignant components or inflammatory changes. Sialylated Lewis X-i (SLX), carbohydrate antigen 19-9 (CA19-9) and tissue polypeptide antigen (TPA) in the cystic fluid were markedly elevated, while the serum concentrations of these tumor markers were within the normal ranges. Immunohistochemical studies showed the epithelial cells lining the cyst to contain CA19-9 and SLX. The findings suggest the tumor markers to have originated in the thymic epithelium lining the cyst.


Improvements in physical activity and some dietary behaviors in a community health worker-led diabetes self-management intervention for adults with low incomes: results from a randomized controlled trial.
People with low incomes have a disproportionate prevalence of diabetes and its complications and experience many barriers to self-management, which community health workers (CHWs) may help address. We sought to examine the effects of an in-home CHW-led intervention for adults with diabetes and incomes <250% of the federal poverty line on self-management behaviors and test mediators and moderators. From 2010 to 2013, we randomized participants from three Washington State health systems with type 2 diabetes and hemoglobin A1c (HbA1c) ≥ 8% to the CHW intervention (N = 145) or usual care control (N = 142) arms. We examined effects on 12-month self-management: physical activity, dietary behaviors, medication taking, blood glucose monitoring, foot care, and tobacco use. For behaviors with significant intervention-control group differences, we tested mediation by self-efficacy and social support. We also investigated whether intervention-associated changes in behaviors varied by race/ethnicity, gender, and baseline values of HbA1c, diabetes distress, depression, and food insecurity (moderators). Compared to controls, intervention participants engaged in more physical activity and reported better dietary behaviors for some measures (general diet, frequency of skipping meals, and frequency of eating out) at 12-months, but there was no evidence of mediation by self-efficacy or social support. Evidence of moderation was limited: improvements in the frequency of skipping meals were restricted to participants with baseline HbA1c < 10%. Study findings suggest CHWs could be integrated into diabetes care to effectively support lifestyle changes around physical activity and some eating behaviors among adults with low incomes. More research is needed to understand mechanisms of change.


Test of competing explanations of the bizarre response bias in recognition memory.
Recent research has demonstrated that a more liberal response criterion is used when people make judgments about bizarre items than about common items in old-new tests of recognition. The present study was designed to test 2 possible explanations of the bizarre response bias. The bizarre-relations explanation suggests that the bizarre response bias is triggered by the bizarre relations depicted in test items. The target-constituent explanation suggests that the bizarre response bias is the result of a sense of familiarity with constituents of bizarre test items. These explanations were tested by examining the influence of lure manipulations on memory discrimination and response bias for common and bizarre hand-drawn pictures. The results indicated support for the target-constituent explanation by reversing the response bias (obtaining a common response bias) in a recognition test that used common lures containing constituents from bizarre target items and bizarre lures containing constituents from common target items. The results also indicated that increased verbal elaboration enhanced memory discrimination and reduced response bias for both common and bizarre stimuli. The implications of these results are discussed with regard to the false memory controversy.


Immune responses during the peripartum period in dairy cows with postpartum endometritis.
Determining the immune responses to the development of endometritis during the peripartum period may assist in the development of more efficient reproductive management regimens for dairy herds. In this study, we compared the peripartum immune responses of dairy cows that develop endometritis by 4 weeks postpartum (n = 11) to cows that did not develop this disease (n = 19). Blood samples were collected 1 week before calving, just after or during calving, and then at weeks 1, 2, 3, and 4 postpartum. Cows that developed endometriris had significantly higher total leukocyte, neutrophil, lymphocyte, and monocyte counts than the control cows (P < 0.05) at all time points. The leukocytes from cows that developed endometritis were significantly less phagocytic than those from control cows at all sampling time points (P < 0.01). The serum TNFalpha concentrations of the control cows decreased linearly from the prepartum time point (P = 0.0029), but the endometritis cows showed a different profile (P > 0.05). As a result, the serum TNFalpha concentrations were greater in the endometritis group (P < 0.01) than in the control group during the third and fourth weeks postpartum. The greater total leukocyte numbers and neutrophil, lymphocyte and monocyte counts, and the maintenance of elevated serum TNFalpha levels in the cows with endometritis may be due to infection in the postpartum period. Furthermore, the decreased phagocytic capacity of leukocytes during the peripartum period, including at the prepartum time point, makes cows more susceptible to postpartum endometritis.


A new species of Tanytarsus van der Wulp, 1874 (Diptera: Chironomidae) and the first Japanese record of Tanytarsus ovatus Johannsen, 1932 with DNA barcodes.
A new species of the genus Tanytarsus van der Wulp, 1874 was described and illustrated based on an adult male. Tanytarsus trichovalis sp. nov. belongs to the eminulus species group, and is closely related to T. tamaundecimus Sasa, 1980, T. okuboi Sasa, 1986, and T. tonebeceus Sasa Tanaka, 2000. However, the species is distinguished from these species by the morphology of the hypopygium. We also present the first record of T. ovatus Johannsen, 1932 in Japan. In addition, DNA barcoding of 5 species including T. trichovalis sp. nov., T. ovatus, and other morphologically related species was undertaken. A new key of the eleven Japanese eminulus species group was compiled.


Cancers with wrong HATs: the impact of acetylation.
Lysine N-ε-acetylation is a post-translational modification that regulates the function of histone and non-histone proteins. In several malignancies, histone acetyltransferase (HAT) activities are disturbed as a consequence of various genetic or epigenetic alterations. In particular, HATs can function as tumor suppressors, helping cells control cellular proliferation and cell cycle, and also as oncogenes, because abnormal acetylation can activate malignant proteins and contribute to cancer. An impaired acetylation profile can be indicative of a pathological process, and thus evaluation of histone acetylation could be used as a predictive index of patient survival or therapy outcome. Therefore, epigenetic therapy might be a very effective strategy to defeat cancer. With the use of histone deacetylase inhibitors and acetylation modulators (e.g. HAT inhibitors, bromodomain inhibitors), we are paving the way for a future epigenetic drug control of human diseases.


Feasibility of a Cellular Telephone Follow-Up Program After Injury in Sub-Saharan Africa.
Injury disproportionately affects persons in low- and middle-income countries (LMIC). Most LMIC lack capacity for routine follow-up care, likely resulting in complications and disability. Cellular telephones may provide a new tool to improve health outcomes. The objective of this study was to establish the feasibility of a mobile health follow-up program after injury in Cameroon. Between February and October 2017, all injured patients admitted to a regional hospital in Cameroon were asked for mobile phone numbers as part of an existing trauma registry. Patients were contacted 2 weeks after leaving the hospital discharge to participate in a short triage survey. Data on program feasibility and patient condition were collected. Of 1180 injured patients who presented for emergency care, 83% provided telephone numbers, 62% were reached, and 48% (565) of all injured patients ultimately participated in telephone follow-up. Successfully contacted patients were reached after an average of 1.76 call attempts (SD 1.91) and median call time was 4.43 min (IQR 3.67-5.36). Five patients (1%) had died from their injuries at the time of follow-up. Among surveyed patients, 27% required ongoing assistance to complete activities of daily living. Nearly, half (47%) of patients reported inability to take medicines or care for their injury as instructed at discharge. Adequate pain control was achieved in only 38% of discharged patients. Pilot data suggest considerable under treatment of injury in Cameroon. Mobile telephone follow-up demonstrates potential as a feasible tool for screening discharged patients who could benefit from further care.


Free radical scavenging potential of Picrorhiza kurrooa Royle ex Benth.
For assessing free radical scavenging potential of P. kurrooa, the antioxidant activity of P. kurrooa extract was studied by lipid peroxidation assay using rat liver homogenate. The extract (1 mg/ml) showed marked protection (up to 66.68%) against peroxidation of liver phospholipids. Besides, reduced glutathione showed very encouraging activity. The extract also exhibited significant scavenging activity. Thus augmenting the wide use of plant in the indigenous system of medicine, which may partly be due to antioxidant and free radical scavening activity of the extract.


One-Carbon Metabolism in Prostate Cancer: The Role of Androgen Signaling.
Cancer cell metabolism differs significantly from the metabolism of non-transformed cells. This altered metabolic reprogramming mediates changes in the uptake and use of nutrients that permit high rates of proliferation, growth, and survival. The androgen receptor (AR) plays an essential role in the establishment and progression of prostate cancer (PCa), and in the metabolic adaptation that takes place during this progression. In its role as a transcription factor, the AR directly affects the expression of several effectors and regulators of essential catabolic and biosynthetic pathways. Indirectly, as a modulator of the one-carbon metabolism, the AR can affect epigenetic processes, DNA metabolism, and redox balance, all of which are important factors in tumorigenesis. In this review, we focus on the role of AR-signaling on one-carbon metabolism in tumorigenesis. Clinical implications of one-carbon metabolism and AR-targeted therapies for PCa are discussed in this context.


Efficacy and safety of berberine for premature ventricular contractions: a meta-analysis and systematic review of randomized controlled trials.
Berberine is a potential drug that can effectively treat cardiovascular diseases, including premature ventricular contractions (PVCs). This study was conducted to assess the efficacy and safety of berberine for PVCs. The literature was searched using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang, and Chinese Biomedical Literature Database (CBM) for randomized controlled trials (RCTs) from inception to October 1, 2022. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to assess the quality of evidence. Ten RCTs with 896 participants were included in the meta-analysis. The results showed that compared to antiarrhythmic drugs (AD), berberine (BE) combined with AD had a higher effective rate (RR = 1.26; 95% CI:1.12, 1.42; p = 0.0001) with no significant incidence of adverse reactions (RR = 0.93; 95% CI:0.33, 2.57; p = 0.88), and BE alone had no significant difference in effective rate (RR = 0.91; 95% CI:0.77, 1.07; p = 0.23), and a lower incidence of adverse reactions (RR = 0.38; 95% CI:0.15, 0.97; p = 0.04) and recurrence rate (RR = 0.40; 95% CI:0.18, 0.88; p = 0.02). The results suggest that BE is an effective and safe adjunctive method for PVCs. In addition, BE is recommended for patients with PVCs who had severe adverse reactions after administrating AD as an alternative therapy.


Multiple purine pathway enzyme activities are encoded at a single genetic locus in Drosophila.
The Drosophila melanogaster Gart locus, known from previous work to encode the enzyme activity phosphoribosylglycinamide formyltransferase (GART), specifies two alternatively processed mRNAs and two proteins. We introduced the entire Gart locus into a Drosophila tissue culture cell line in which the locus is active. The resulting cell clones contained numerous copies of the locus and overproduced both mRNAs and both expected proteins, thus markedly facilitating analysis of these molecules. We assayed extracts of the clones for the activities of 10 enzymes important for de novo purine synthesis and found that, in addition to GART, two other purine pathway activities, phosphoribosylamine-glycine ligase (phosphoribosylglycinamide synthetase, GARS) and phosphoribosylformylglycinamidine cyclo-ligase (phosphoribosylaminoimidazole synthetase, AIRS), are similarly overproduced. All three activities are present together on the larger overproduced protein. A smaller protein appears to possess only GARS activity. Therefore, alternative mRNA processing can allow cells to produce enzyme activities in forms that are either linked or unlinked to other activities.


Contributions of Forward-Focused Voice to Audio-Vocal Feedback Measured Using Nasal Accelerometry and Power Spectral Analysis of Vocal Fundamental Frequency.
The spectral powers of the modulations of vocal fundamental frequency (f o) less than 3 Hz (low-frequency power, LFP) and between 3 and 8 Hz (middle-frequency power, MFP) had been established to indicate the audio-vocal feedback status and vocal efficiency of a speaker, and a resonant voice may enhance the auditory-vocal feedback. This study aims to determine whether the auditory feedback can be augmented by a forward and resonant voice and therefore contribute to the modulations of f o variability. Vocal signals and accelerometric signals of lateral nasal cartilage were obtained from 27 healthy adults who, respectively, sustained vowels /a/ and /i/ with their habitual speaking voice and with a forward-focused voice under three auditory conditions: natural hearing (N0), high-level noise exposure (N90), and low-level noise exposure (N60). Nasal skin vibrations were measured using a nasal accelerometry to reflect voice resonance status. Vocal intensity and f o variability were also analyzed to show the auditory-vocal interactions under varied conditions of auditory feedback and voice resonance. In both N0 and N90 conditions, forward-focused voice showed a significantly lower LFP than the speakers' habitual voice. In addition, LFP of f o would significantly increase during natural voice production as the voice feedback was greatly masked by high-intensity noise; however, with a forward-focused voice, the noise-induced variation in LFP was significantly decreased. Under N90, MFP significantly decreased during forward-focused voice production compared with that measured during natural voice production. The stability of f o modulations was not adversely affected by N60. The results support the idea that vocalizing with a forward-focused voice enhance the auditory feedback of the speaker's own voice and, thus, reduce the variability of f o during sustained phonation, especially when vocalizing in the high noise condition.


Effect And Predictive Value Of Routine Preoperative Laboratory Testing For Endoscopic Retrograde Cholangiopancreatography.
Several studies and guidelines are questioning routine preoperative laboratory tests in surgical and endoscopic procedures. Their effect in endoscopic retrograde cholangiopancreatography is not currently known. This study was carried out to evaluate the risk of adverse effects in endoscopic retrograde cholangiopancreatography and their association with preoperative lab tests. A single-center, prospective observational study on all 956 patients undergoing 1196 endoscopic retrograde cholangiopancreatographies in the Endoscopy Unit of Helsinki University Central Hospital from 1 March 2012 to 28 February 2013. Routine preoperative laboratory test results (basic blood count, creatinine, potassium, sodium, international normalized ratio/thromboplastin time, and amylase), health status, medication, and demographic information of all patients were analyzed in relation to adverse effects related to endoscopic retrograde cholangiopancreatography and procedural sedation. Multivariate analysis showed post-endoscopic retrograde cholangiopancreatography pancreatitis (43 cases, 3.6%) to have no association with abnormal routine preoperative laboratory tests. Respiratory depression caused by sedation (128 cases, 11%) was not associated with abnormal routine preoperative laboratory tests, and anemia was found to be a slightly protecting factor. Cardiovascular depression caused by sedation was associated with thrombocytopenia (odds ratio = 1.87, p = 0.025) and, in male patients, hyponatremia (odds ratio = 3.66, p < 0.001). Incidence of other adverse effects was too low for statistical analysis. Routine universal preoperative lab testing was not found to be successful in predicting adverse effects in endoscopic retrograde cholangiopancreatography procedures. Laboratory testing should be done focusing on each patient's individual needs.


Ligand-DNA interaction in a nanocage of reverse micelle.
We have studied intercalation of ethidium bromide (EB) to genomic DNA encapsulated in a nanospace of an anionic AOT reverse micelle (RM). Circular dichroism (CD) study on the DNA in the RM reveals its condensed form. Here, we have used temporal decay-associated spectra (DAS) and time-resolved area normalized emission spectral (TRANES) techniques to investigate EB-binding to condensed DNA because the interference of emission from unbound EB in the RM makes conventional steady state and picosecond resolved fluorescence spectroscopic techniques challenging. The binding affinity of the ligand EB with the DNA in the RM is found to increase with the size of the RM, reflecting the effect of lessening of DNA condensation on the binding affinity. CD spectra of the DNA in the RM with various sizes indicate the structural change of the condensed DNA with reverse micellar size. DAS and TRANES techniques along with dynamic light scattering studies of the EB-DNA complex in the RM further reveal two kinds of binding modes of the ligand with the condensed DNA even in essentially monodispersed RMs. To investigate the role of RM on the ligand binding and secondary structure of the DNA, we have also studied complexation of EB with two synthetic self-complimentary oligonucleotides of sequences (CGCAAATTTGCG)2 and (CGCGCGCGCGCG)2 in the RM.


Microplastics impact the accumulation of metals in earthworms by changing the gut bacterial communities.
Microplastics (MPs) are defined as plastic debris with particle size smaller than 5 mm, which have been frequently detected in environments. In this study, earthworms (Eisenia foetida) were exposed to three different sized polystyrene (PS; 0.1, 10 and 100 μm) at 10 and 100 mg per kg soil for 21 days. We examined the contents of metals (Cu, Zn, Ni and Pb) and gut microbial communities in earthworms exposed to MPs. Results showed that MPs reduced the accumulation of Ni and Pb in earthworms on the 21st day. The composition of gut bacterial communities was altered in earthworms exposed to MPs, especially 10 μm MPs, featuring a higher relative abundance of Proteobacteria (44.5%) and Bacteroidetes (27.1%) than the control group. Additionally, gut microorganisms including genus Paenibacillus and Achromobacter in earthworms were expected to be potential biomarkers for Cu and Zn. The microbial community networks showed that MPs affected bacterial community connections by size effect, and MPs with smaller size increased the complexity of earthworm microbial community networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolism was the main difference in the bacterial communities in different treatments, especially carbohydrate metabolism and amino acid metabolism, which was relevant to the survival and growth of bacteria. This study provides insight into the environmental risks of MPs on terrestrial organisms.


Photoelectron Spectroscopic and Computational Study of Pyridine-Ligated Gold Cluster Anions.
Pyridine-ligated gold cluster anions were studied through a combination of negative ion photoelectron spectroscopy and density functional theory calculations. Small gold cluster anions ligated by pyridine, Aun(py)- were generated with a ligation cell coupled to a laser vaporization source (LVS). We showed that pyridine is weakly bound (physisorbed) to the Au2- moiety of Au2(py)- by interactions between its gold atoms and either the hydrogen atoms or the π-ring of pyridine. We also found that pyridine's lone electron pair strongly binds (chemisorbs) to both Au3(py)- and Au4(py)- through single gold atoms on each of these clusters. Bonding analysis of two isomers of Au4(py)- supported the presence of two different ligand binding motifs, these differing in terms of the gold atom to which pyridine binds.


Molecular dynamics study of structure and stability of a model coiled coil.
This paper employs methods used earlier to study helix propensity in a model alpha-helix. The methods are extended to simulations of a motif structure of the alpha-helical coiled coil, i.e., a structure with a simple amino acid sequence, containing only alanine, leucine, and valine, with leucine and valine forming hydrophobic contacts in the helix interface (positions "d" and "a"). Dynamic simulations of the model coiled-coil structure reproduce characteristic features of the coiled-coil motif seen in experimental studies. Free energy simulations were used to assess the change in stability of the model when a leucine pair or a valine pair in the helix interface was replaced with an alanine pair. A leucine pair at position d was found to contribute 3.4 kcal/mol to the stability of the coiled coil relative to an alanine pair, and a valine pair at position a was found to contribute 0.8 kcal/mol relative to an alanine pair. The value for the leucine pair agrees with reports in two experimental studies with molecules having different amino sequence. The value for the valine pair is reasonable given the smaller size of the valine side chain and the intrinsic low helix propensity of valine. No experimental value was available for comparison.


Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection.
Granulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR(-/-) mice following intratracheal injection with Pseudomonas aeruginosa-laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis. G-CSFR(-/-) mice are markedly susceptible to bronchopulmonary P aeruginosa infection, exhibiting decreased survival and bacterial clearance as well as extensive damage to lung tissue. The systemic neutrophil response was mediated primarily by enhanced neutrophil release from the bone marrow rather than increased neutrophil production and was attenuated in G-CSFR(-/-) mice. Despite normal to increased local production of inflammatory chemokines, neutrophil accumulation into the infected lung of G-CSFR(-/-) mice was markedly reduced. Moreover, the percentage of apoptotic neutrophils in the lung was elevated, suggesting that G-CSF signals may play an important role in regulating neutrophil survival at the inflammatory site. Collectively, these data provide new evidence that G-CSF signals play important but specific roles in the regulation of the systemic and local neutrophil response following infection.


[Nitrogen utilization and xanthan production by Xanthomonas campestris].
In media with mixed nitrogen sources (nitrate plus yeast extract) a three auxic growth is observed. The first growth phase is characterized by preferential utilization of the amino acids of the yeast autolysate and the utilization of only small amounts of nitrate. During the second growth phase nitrate is preferentially utilized. In the third phase there is only growth without dividing of cells and the accumulation of xanthan takes place. The change from growth by dividing to growth without dividing means a change from balanced to unbalanced growth. It is proposed that xanthan production is connected with unbalanced growth.


Lung Ultrasound in Patients With Dyspnea From Infective Lung Disease.
Infective lung disease is a spectrum of pulmonary disorders with high prevalence in clinical practice. In the last decade, many studies focused on the clinical usefulness of lung ultrasound (LUS) in the management of patients presenting with dyspnea from infective lung disease. We report data on the methodological and standardized use of bedside LUS in the differential diagnosis of patients with acute dyspnea from infective lung diseases. We performed a cross-sectional study in 439 patients (160 women and 279 men, mean age 64.2 ± 11.5 years, age range 23-91 years) with infective lung diseases. A bedside LUS with a convex probe and chest X-ray were performed in all subjects. Chest CT was performed in a subgroup of patients, as clinically needed. We observed a statistically significant difference in the percentage of pleural effusion and pulmonary consolidation assessed by LUS, compared to X-ray (52.7 vs. 20%, respectively, p < 0.05; 93.6 vs. 48.2%, p < 0.001). The majority of the consolidations detected by LUS were mixed, hypo- and hyperechoic, lesions, with air bronchogram in 40% of cases. All findings assessed by LUS were confirmed by chest CT, when performed. We describe the actual role of LUS in the assessment of patients with infective lung disease. It has higher sensitivity compared to chest X-ray in the detection of pleural effusion. Consolidations from infective lung disease have mostly mixed echogenicity by LUS.


[The effect of several factors on the osmotic resistance of erythrocytes].
Measurements of red cell osmotic resistance in urea test have shown the stabilizing effect of hydrocortisone and ascorbic acid on red cell membrane permeability. This permitted a conclusion on the fitness of the test for assessment of the drug effects on red cell membrane permeability and on the possibility of the use of this test in choosing an individual dose of UV irradiation.


High-pressure liquid chromatography of free nucleotide patterns in normal and abnormal keratinocytes.
A method for analyzing free nucleotides in the epidermis of the guinea pig is presented. Free nucleotides were extracted by using a methylalethanol mixture, and the analysis was carried out by high-pressure liquid chromatography on a column of Lichrosorb-NH2 with a single buffer of potassium phosphate. The concentration of total free nucleotides in the epidermis is about 4 times greater than that in the liver, kidney, spleen, or intestinal epithelium.l The free nucleotide level is markedly elevated in the hyperkeratotic epidermis induced by n-hexadecane. The alternation of free nucleotides in hyperkeratotic epidermis is discussed in relation to nucleic acid content, DNase, disc-electrophoretic properties of DNase, and salvage pathway enzymatic activity. Significant increases in the enzyme activity of the salvage pathway and in neutral DNase were observed in the hyperkeratotic stage. However, the DNA content and acid DNase activity were decreased. It is suggested that the pool size of free nucleotides in the epidermis is affected by the salvage enzyme system.


miR‑146b‑5p promotes the neural conversion of pluripotent stem cells by targeting Smad4.
Pluripotent stem cells (PSCs) are regarded as potential sources that provide specific neural cells for cell therapy in some nervous system diseases. However, the mechanisms underlying the neural differentiation of PSCs remain largely unknown. MicroRNAs (miRNAs or miRs) are a class of small non‑pro-tein-coding RNAs that act as critical regulatory molecules in many cellular processes. In this study, we found that miR‑146b‑5p expression was markedly increased following the neural induction of mouse embryonic stem cells (ESCs) or induced PSCs (iPSCs). In this study, to further identify the role of miR‑146b‑5p, we generated stable miR‑146b‑5p-overexpressing ESC and iPSC cell lines, and induced the differentiation of these cells by the adherent monolayer culture method. In the miR‑146b‑5p-overexpressing ESC- or iPSC-derived cultures, RT-qPCR analysis revealed that the mRNA expression levels of neuroectoderm markers, such as Sox1, Nestin and Pax6, were markedly increased, and flow cytometric analysis verified that the number of Nestin‑positive cells was higher in the miR‑146b‑5p-overexpressing compared with the control cells. Mechanistically, the miR‑146b‑5p-overexpressing ESCs or iPSCs exhibited a significant reduction in Oct4 expression, which may be an explanation for these cells having a tendency to differentiate towards the neural lineage. Moreover, we confirmed that miR‑146b‑5p directly targeted Smad4 and negatively regulated the transforming growth factor (TGF)-β signaling pathway, which contributed to the neural commitment of PSCs. Collectively, our findings uncover the essential role of miR‑146b‑5p in the neural conversion of PSCs.


["Tèt asanm pou la sante": ethnographic notes on international cooperation for health in Haiti].
This article discusses the functioning of a health-oriented development project pursued in an emergency situation and its impacts beyond its stated goals. The tripartite project between Brazil, Haiti, and Cuba was designed to strengthen Haiti's health and epidemiologic surveillance system, introduced in 2010 as part of the aid effort after the earthquake. An essentially ethnographic perspective is taken, with a focus on describing the practices and perspectives of the agents involved in the program. The networks of agents were mapped out, paying particular attention to translators, drivers, and journalists, who were understood as being "cooperation brokers". Finally, the article discusses the project's position in the broader context of international health initiatives in Haiti.


Inhibition of H3K9 methyltransferase G9a ameliorates methylglyoxal-induced peritoneal fibrosis.
Activity of H3K9 histone methyltransferase G9a is reportedly induced by transforming growth factor-β1 (TGF-β1) and plays an important role in the progression of cancer and fibrosis. In this study, we investigated whether inhibition of G9a-mediated H3K9 methylation attenuates peritoneal fibrosis in mice and human peritoneal mesothelial cells (HPMCs). Nonadherent cells of peritoneal dialysis (PD) patients were isolated from PD effluent to examine expression of G9a. Peritoneal fibrosis was induced by peritoneal injection of methylglyoxal (MGO) in male C57/B6 mice for 3 weeks. BIX01294, a G9a inhibitor, was administered by subcutaneous injection. Effects of BIX01294 on MGO-induced pathological and functional changes in mice were evaluated by immunohistochemistry and a peritoneal equilibration test. HPMCs were isolated from human omentum, and the inhibitory effect of BIX01294 on TGF-β1-induced fibrotic changes was investigated in the HPMCs by western blotting. G9a was upregulated in nonadherent cells of human PD effluent, the peritoneum of MGO-injected mice, and TGF-β1-stimulated HPMCs. BIX01294 significantly reduced the submesothelial zone thickness and cell density in MGO-injected mice. Immunohistochemical staining revealed that BIX01294 treatment decreased not only mono-methylation of H3K9 (H3K9me1), but also the number of mesenchymal cells, accumulation of collagen, and infiltration of monocytes. In addition to the pathological changes, BIX01294 reduced the level of TGF-β1 in peritoneal fluid and improved peritoneal functions. Furthermore, BIX01294 inhibited TGF-β1-induced fibrotic changes along with suppression of H3K9me1 in HPMCs. Therefore, inhibition of H3K9 methyltransferase G9a suppresses peritoneal fibrosis through a reduction of H3K9me1.


Stopped-flow Fourier transform infrared spectroscopy of nitromethane oxidation by the diiron(IV) intermediate of methane monooxygenase.
The hydroxylase component (MMOH) of soluble methane monooxygenase from Methylococcus capsulatus (Bath) was reduced to the diiron(II) form and then allowed to react with dioxygen to generate the diiron(IV) intermediate Q in the first phase of a double-mixing stopped-flow experiment. CD3NO2 was then introduced in the second phase of the experiment, which was carried out in D2O at 25 degrees C. The kinetics of the reaction of the substrate with Q were monitored by stopped-flow Fourier transform infrared spectroscopy, observing the disappearance of the asymmetric NO2 bending vibration at 1548 cm-1. The data were fit to a single-exponential function, which yielded a kobs of 0.45 +/- 0.07 s-1. This result is in quantitative agreement with a kobs of 0.39 +/- 0.01 s-1 obtained by observing the disappearance of Q by double-mixing stopped-flow optical spectroscopy at its absorption maximum of 420 nm. These results provide for the first time direct monitoring of the hydroxylation of a methane-derived substrate in the MMOH reaction pathway and demonstrate that Q decay occurs concomitantly with substrate consumption.


Emerging links between endoplasmic reticulum stress responses and acute kidney injury.
All cell types must maintain homeostasis under periods of stress. To prevent the catastrophic effects of stress, all cell types also respond to stress by inducing protective pathways. Within the cell, the endoplasmic reticulum (ER) is exquisitely stress-sensitive, primarily because this organelle folds, posttranslationally processes, and sorts one-third of the proteome. In the 1990s, a specialized ER stress response pathway was discovered, the unfolded protein response (UPR), which specifically protects the ER from damaged proteins and toxic chemicals. Not surprisingly, UPR-dependent responses are essential to maintain the function and viability of cells continuously exposed to stress, such as those in the kidney, which have high metabolic demands, produce myriad protein assemblies, continuously filter toxins, and synthesize ammonia. In this mini-review, we highlight recent articles that link ER stress and the UPR with acute kidney injury (AKI), a disease that arises in ∼10% of all hospitalized individuals and nearly half of all people admitted to intensive care units. We conclude with a discussion of prospects for treating AKI with emerging drugs that improve ER function.


Carbonyl reductase inactivation may contribute to mouse lung tumor promotion by electrophilic metabolites of butylated hydroxytoluene: protein alkylation in vivo and in vitro.
Promotion of lung tumors in mice by the food additive butylated hydroxytoluene (BHT) is mediated by electrophilic metabolites produced in the target organ. Identifying the proteins alkylated by these quinone methides (QMs) is a necessary step in understanding the underlying mechanisms. Covalent adducts of the antioxidant enzymes peroxiredoxin 6 and Cu,Zn superoxide dismutase were detected previously in lung cytosols from BALB/c mice injected with BHT, and complimentary in vitro studies demonstrated that QM alkylation causes inactivation and enhances oxidative stress. In the present work, adducts of another protective enzyme, carbonyl reductase (CBR), were detected by Western blotting and mass spectrometry in mitochondria from lungs of mice one day after a single injection of BHT and throughout a 28-day period of weekly injections required to achieve tumor promotion. BHT treatment was accompanied by the accumulation of protein carbonyls in lung cytosol from sustained oxidative stress. Studies in vitro demonstrated that CBR activity in lung homogenates was susceptible to concentration- and time-dependent inhibition by QMs. Recombinant CBR underwent irreversible inhibition during QM exposure, and mass spectrometry was utilized to identify alkylation sites at Cys 51, Lys 17, Lys 189, Lys 201, His 28, and His 204. Except for Lys 17, all of these adducts were eliminated as a cause of enzyme inhibition either by chemical modification (cysteine) or site-directed mutagenesis (lysines and histidines). The data demonstrated that Lys 17 is the critical alkylation target, consistent with the role of this basic residue in NADPH binding. These data support the possibility that CBR inhibition occurs in BHT-treated mice, thereby compromising one pathway for inactivating lipid peroxidation products, particularly 4-oxo-2-nonenal. These data, in concert with previous evidence for the inactivation of antioxidant enzymes, provide a molecular basis to explain lung inflammation leading to tumor promotion in this two-stage model for pulmonary carcinogenesis.


Comparative aspects of Na+/K+ pump-mediated uncoupled Na+ efflux in red blood cells and kidney proteoliposomes.
Ouabain-sensitive uncoupled Na+ efflux has been studied in human, pig, and rat red cells and in vesicles containing reconstituted kidney Na+/K+ pumps obtained from these same species. The red cells from the different species gave qualitatively similar results; the uncoupled Na+ efflux was 15-30% of the Na+/K+ exchange rate, and this flux was inhibited at 5 mM extracellular Na+ (Na+o). At higher levels of Na+o there was a monotonic increase in the Na+ efflux. As has previously been observed in human red cells, the uncoupled efflux from pig red cells consists of Na+ and anion cotransport, suggesting that anion cotransport may be a general characteristic of uncoupled Na+ efflux in red cells. The uncoupled Na+ efflux carried out by pig and rat kidney Na+/K+ pumps differs from the red cell activity in that it represents no more than 2-4% of the Na+/K+ exchange rate and that 5 mM Na+o does not inhibit this efflux. Furthermore, the efflux does not appear to be dependent on anion cotransport. Vesicles containing human kidney Na+/K+ pumps differ from vesicles derived from pig or rat kidneys in that the Na+ efflux is not inhibited or stimulated by Na+ present on the opposite side; it thus appears that the Na+,K(+)-ATPase in these vesicles may be incapable of Na+/Na+ exchange. These results indicate that the ligand and kinetic properties of the uncoupled Na+ efflux mode of red cells are markedly different from kidney-derived Na+/K+ pumps reconstituted into proteoliposomes. The basis for these differences may be inherent in the Na+/K+ pumps themselves or represent differences between the two types of preparations studied.


Statistical Approaches Used to Assess the Equity of Access to Food Outlets: A Systematic Review.
Inequalities in eating behaviours are often linked to the types of food retailers accessible in neighbourhood environments. Numerous studies have aimed to identify if access to healthy and unhealthy food retailers is socioeconomically patterned across neighbourhoods, and thus a potential risk factor for dietary inequalities. Existing reviews have examined differences between methodologies, particularly focussing on neighbourhood and food outlet access measure definitions. However, no review has informatively discussed the suitability of the statistical methodologies employed; a key issue determining the validity of study findings. Our aim was to examine the suitability of statistical approaches adopted in these analyses. Searches were conducted for articles published from 2000-2014. Eligible studies included objective measures of the neighbourhood food environment and neighbourhood-level socio-economic status, with a statistical analysis of the association between food outlet access and socio-economic status. Fifty-four papers were included. Outlet accessibility was typically defined as the distance to the nearest outlet from the neighbourhood centroid, or as the number of food outlets within a neighbourhood (or buffer). To assess if these measures were linked to neighbourhood disadvantage, common statistical methods included ANOVA, correlation, and Poisson or negative binomial regression. Although all studies involved spatial data, few considered spatial analysis techniques or spatial autocorrelation. With advances in GIS software, sophisticated measures of neighbourhood outlet accessibility can be considered. However, approaches to statistical analysis often appear less sophisticated. Care should be taken to consider assumptions underlying the analysis and the possibility of spatially correlated residuals which could affect the results.


An efficient and highly stereoselective synthesis of new P-chiral 1,5-diphosphanylferrocene ligands and their use in enantioselective hydrogenation.
An efficient and highly stereoselective synthesis of P-chiral 1,5-diphosphanylferrocene ligands has been developed, and the introduction of P-chirality in ferrocene-based phosphine ligands enhances the enantioselective discrimination produced by the corresponding catalyst when matching of the planar chirality, the chirality at carbon and the chirality at phosphorus occurs.


Attenuation of endoplasmic reticulum stress-related myocardial apoptosis by SERCA2a gene delivery in ischemic heart disease.
Previous studies suggested that endoplasmic reticulum (ER) stress-associated apoptosis plays an important role in the pathogenesis of ischemic heart disease. Gene transfer of sarco/endoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) attenuates myocardial apoptosis in a variety of heart failure models. This study is to investigate the effects of SERCA2a gene delivery on the myocardial apoptosis and ER stress pathway in a porcine ischemic heart disease model. Eighteen pigs were either subjected to ameroid implantation in the coronary artery or sham operation. Eight wks after gene delivery, the protein level and activity of SERCA2a were measured. Myocardial apoptosis was determined using terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling assay. Regional myocardial perfusion and function were evaluated by (99m)Tc-sestamibi ((99m)Tc-MIBI) single photon emission computed tomography and echocardiography. The ER stress signaling was assessed by Western blot. SERCA2a protein level and activity were significantly decreased in the ischemic myocardium and restored to normal after SERCA2a gene transfer. Restoration of SERCA2a expression significantly improved the cardiac function, although no improvement of regional myocardial perfusion was detected. Restoration of SERCA2a significantly attenuated myocardial apoptosis and reversed the activation of unfolded protein response (UPR) pathway and the ER stress-associated apoptosis pathways. These findings demonstrate a robust role of SERCA2a in attenuation of ischemic myocardial apoptosis, correlating with reverse activation of the ER stress-associated apoptosis pathways, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of ER stress-associated myocardial apoptosis.


Development of low-cost inverted microscope to detect early growth of Mycobacterium tuberculosis in MODS culture.
The microscopic observation drug susceptibility (MODS) assay for rapid, low-cost detection of tuberculosis and multidrug resistant tuberculosis depends upon visualization of the characteristic cording colonies of Mycobacterium tuberculosis in liquid media. This has conventionally required an inverted light microscope in order to inspect the MODS culture plates from below. Few tuberculosis laboratories have this item and the capital cost of $5,000 for a high-end microscope could be a significant obstacle to MODS roll-out. We hypothesized that the precise definition provided by costly high-specification inverted light microscopes might not be necessary for pattern recognition. In this work we describe the development of a low-cost artesenal inverted microscope that can operate in both a standard or digital mode to effectively replace the expensive commercial inverted light microscope, and an integrated system that could permit a local and remote diagnosis of tuberculosis.


Neuroanatomical basis of cochlear coding mechanisms.
The afferent cochlear neurons to outer and inner hair cells differ not only in their relative numbers (95% to inner hair cells and only 5% to outer hair cells) and distribution pattern (great convergence for outer hair cells and divergence for inner hair cells) but also in their degeneration behaviour and metabolism. Some special afferent fibres seem to exist. The afferent neurons present three types of ganglion cells in the spiral ganglion with no morphological evidence for an extensive direct interaction between afferent neurons of the outer and the inner hair cell system at any level in the cochlea and even their efferent nerve supply is essentially separated.


Characterization of the peptide fraction from digested Parmigiano Reggiano cheese and its effect on growth of lactobacilli and bifidobacteria.
Parmigiano Reggiano (PR) is a raw-milk, hard cooked, long-ripened cheese of high quality and nutritional value. Long ripening times allow for extensive proteolysis of milk proteins to yield a number of peptides, some of which have potential healthy bioactive properties. This study aimed to: i) determine the peptide profile of PR cheese subjected to simulated gastrointestinal transit; ii) evaluate in vitro whether the peptides could support growth of beneficial microbial groups of the gut microbiota. PR samples were subjected to in vitro digestion, simulating oral, gastric, and duodenal transit. Liquid chromatography coupled with tandem mass spectrometry revealed that digestion caused the disappearance of the serum proteins and most of the original peptides, while 71 new peptides were found, all ranging from 2 to 24 residues. The digests were given as sole nitrogen source to pure cultures of Bifidobacterium (27 strains) and Lactobacillus (30 strains), and to bioreactor batch cultures of human gut microbiota. Most of bifidobacteria and lactobacilli grew more abundantly on PR digests than on the control peptone, and exhibited strain- or species-specific peptide preferences, as evidenced by principal component analysis. Bifidobacteria generally consumed a greater amount of peptides than lactobacilli, in terms of both the mean peptide consumption and the number of peptides consumed. For bifidobacteria, peptide preferences were very diverse, but a core of 10 peptides with 4 or 5 residues were consumed by all the strains. Lactobacilli behaved more homogenously and consumed nearly only the same 6 peptides, mostly dipeptides. The peptide preferences of the different groups of bifidobacteria and lactobacilli could not be ascribed to features such as the length of the peptide or the abundance of residues with peculiar properties (hydrophobicity, polarity, charge) and likely depend on specific proteases and/or peptide transporters preferentially recognizing specific sequence motifs. The cultures of human colonic microbiota confirmed that PR digest promoted the growth of commensal bifidobacteria. This study demonstrated that peptides derived from simulated gastrointestinal digestion of PR supported the growth of most lactobacilli and bifidobacteria.


Host selection behavior and the fecundity of Plutella xylostella (Lepidoptera: Plutellidae) on multiple host plants.
Insect herbivores often have higher densities on host plants grown in monocultures than those in diverse environments. The underlying mechanisms are thought to be that polyphagous insects have difficulty in selecting food or oviposition sites when multiple host plants exist. However, this hypothesis needs to be extensively investigated. Our field experiments revealed that the population of the diamondback moths, Plutella xylostella (L.) (Lepidoptera: Plutellidae), significantly decreased in a mixed cropping field compared with a monoculture. To determine the reasons for the reduction in population in the mixed cropping field, the takeoff behavior and fecundity of females in no-choice and free-choice laboratory environments were compared by video recordings of host selection by P. xylostella. Adults displayed a significantly higher takeoff frequency in free-choice environments than those in no-choice treatments and preferred landing on Brassica campestris (L.) or Brassica juncea (Coss) plants in contrast with Brassica oleracea (L.). Female adults in the free-choice environment also laid fewer eggs compared with the monoculture. Olfaction experiments demonstrated orientation by P. xylostella to host volatiles when presented with a choice between plant odors and clean air, but females showed no preference when odors from three Brassicaceae species were presented simultaneously. We conclude that mixed cropping alters the host-finding behavior of P. xylostella resulting in reduced oviposition.


Longitudinal change in plasma total homocysteine during pregnancy and postpartum in Brazilian women and its relation with folate status and other factors.
Fasting plasma total homocysteine (tHcy) concentration was determined in a cohort of pregnant Brazilian women (n = 46) supplemented with folic acid from the second trimester of pregnancy. Blood samples were obtained in the first and third trimesters from all women, and 30-40 days postpartum from seventeen women. Plasma tHcy decreased during pregnancy from 10.3 to 8.7 micromol/L, and was 11.6 micromol/L in the postpartum. Plasma and erythrocyte folate increased, consistent with use of the folate supplement, but decreased slightly in the postpartum, whereas the opposite occurred for plasma vitamin B12. tHcy was inversely correlated with plasma and erythrocyte folate in the third trimester (r = -0.585 and -0.460, respectively). This relationship occurred despite the fact that all women had attained what could be considered adequate levels of folate indices. Furthermore, the change (third trimester minus first trimester levels) of tHcy was inversely correlated (p < 0.01) with the changes in plasma (r = -0.573) and erythrocyte folate (r = -0.525). tHcy had no correlation in any of the periods tested with plasma vitamin B12, plasma albumin, hematocrit, hemoglobin, iron indices, dietary intakes of folate, vitamins B12 and B6, and levels of folate supplement.


Phase I study of neoadjuvant S-1 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02).
Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study. Patients diagnosed with resectable stage II-IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg/m2), 80 mg/m2 of S-1, and 50.4 Gy of external beam radiation. The recommended dose was defined as a dose one-step lower than the maximum-tolerated dose, which was defined when dose-limiting toxicity was observed in three or more of the six patients. Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose-limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum-tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery. We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality.


Triple negative mixed metaplastic breast carcinoma with squamous and spindle cells in an 84-year-old woman: a rare entity with unclear management strategy and poor prognosis.
Metaplastic carcinoma of the breast, a rare neoplasm, usually presents at an advanced stage, metastasises to distant sites more frequently, has higher Ki-67 expression and is more often triple negative compared with other invasive breast cancers. Here, the authors discuss a case of an 84-year-old woman with triple negative mixed metaplastic breast carcinoma treated with radical modified mastectomy, axillary lymph node dissection and radiation therapy. Because of the rarity of the disease, the pathogenesis and the management remain controversial, thus contributing to overall poor prognosis.


MicroRNA-137 acts as a tumor suppressor in osteosarcoma by targeting enhancer of zeste homolog 2.
MicroRNA (miR) are short non-coding RNA that bind to the 3'-untranslational region of their target genes, inhibiting translation and causing mRNA degradation. miR deregulation has been implicated in human cancer; however, the detailed regulatory mechanism of miR-137 in osteosarcoma (OS) remains largely unknown. In the present study, miR-137 and enhancer of zeste homologue 2 (EZH2) mRNA and protein expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. MTT and transwell assays were performed to evaluate cell viability and invasion capacities and a luciferase reporter gene assay was used to determine the targeting relationship. The results of the current study indicated that miR-137 expression was significantly downregulated in OS tissues and cell lines (P<0.01). Moreover, it was observed that low miR-137 expression levels were significantly associated with lung metastasis and advanced TMN stage (P<0.05), but not associated with age, gender, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. Increasing levels of miR-137 significantly inhibited U2OS cell viability and invasion (P<0.01). By contrast, knockdown of miR-137 markedly increased U2OS cell viability and invasion. EZH2 was identified as a direct target gene of miR-137 in U2OS cells by luciferase reporter assay and EZH2 expression was found to be significantly increased in OS tissues and cell lines (P<0.01). EZH2 was significantly downregulated following miR-137 overexpression (P<0.01), and was upregulated following miR-137 knockdown in U2OS cells. Furthermore, EZH2 overexpression significantly attenuated the suppressive effects of miR-137 on U2OS cell viability and invasion (P<0.01), suggesting that miR-137 inhibits the viability and invasion of OS cells by targeting EZH2. Therefore, the results of the current study suggest that the miR-137/EZH2 axis may be a potential target for novel potential therapeutic strategies to treat OS.


Membrane stretch as the mechanism of activation of PIEZO1 ion channels in chondrocytes.
Osteoarthritis is a chronic disease that can be initiated by altered joint loading or injury of the cartilage. The mechanically sensitive PIEZO ion channels have been shown to transduce injurious levels of biomechanical strain in articular chondrocytes and mediate cell death. However, the mechanisms of channel gating in response to high cellular deformation and the strain thresholds for activating PIEZO channels remain unclear. We coupled studies of single-cell compression using atomic force microscopy (AFM) with finite element modeling (FEM) to identify the biophysical mechanisms of PIEZO-mediated calcium (Ca2+) signaling in chondrocytes. We showed that PIEZO1 and PIEZO2 are needed for initiating Ca2+ signaling at moderately high levels of cellular deformation, but at the highest strains, PIEZO1 functions independently of PIEZO2. Biophysical factors that increase apparent chondrocyte membrane tension, including hypoosmotic prestrain, high compression magnitudes, and low deformation rates, also increased PIEZO1-driven Ca2+ signaling. Combined AFM/FEM studies showed that 50% of chondrocytes exhibit Ca2+ signaling at 80 to 85% nominal cell compression, corresponding to a threshold of apparent membrane finite principal strain of E = 1.31, which represents a membrane stretch ratio (λ) of 1.9. Both intracellular and extracellular Ca2+ are necessary for the PIEZO1-mediated Ca2+ signaling response to compression. Our results suggest that PIEZO1-induced signaling drives chondrocyte mechanical injury due to high membrane tension, and this threshold can be altered by factors that influence membrane prestress, such as cartilage hypoosmolarity, secondary to proteoglycan loss. These findings suggest that modulating PIEZO1 activation or downstream signaling may offer avenues for the prevention or treatment of osteoarthritis.


[Protective effects of puerarin on 60Co-gamma-induced acute injury of sertoli cells of testis in mice].
To study the protective effects of puerarin on 60Co-y-induced acute injury of sertoli cells of testis in mice and the mechanisms for its radiation protection. Forty male Wistar mice were randomly divided into four groups, i. e., the normal group, the model group, the low dose puerarin group, and the high dose puerarin group, respectively, 10 in each. The lower abdomen and scrotal area of mice were irradiated with a single dose of 8 Gy 60Co-gamma ray for 517 s in the model and two puerarin groups. Twenty-four h after modeling, different concentrations of puerarin (at the daily dose of 230 and 450 mg/kg respectively) were given to mice in the low and high dose groups by gastrogavage, once daily for two successive weeks. Equal volume of physiological saline was given to mice in the normal group and the model group, once daily for two successive weeks. The morphology of the testicular tissues was observed. The levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin beta were determined by ELISA. The relative expressions of Inhibin beta mRNA in the testicular tissues were determined by Real-time quantitative PCR. Sertoli cells and spermatogenic cells were injured at different degrees in the model group. They were improved in the low and high dose puerarin groups, more obviously in the high dose puerarin group. Compared with the normal group, the level of serum FSH in the model group was significantly improved, while the serum level of Inhibin beta and the expression of Inhibin beta mRNA obviously decreased, showing statistical difference (P<0.05). Compared with the model group, the levels of serum FSH, Inhibin beta, and the expression of Inhibin beta mRNA were significantly improved in the low and high dose puerarin groups (P<0.05), more obviously in the high dose puerarin group (P<0.01, P<0.05). Chinese medicine monomer of puerarin had certain protective effects on 60Co-gamma-induced acute injury of Sertoli cells in mice.


Fractional diffusion in a periodic potential: Overdamped and inertia corrected solutions for the spectrum of the velocity correlation function.
Anomalous diffusion of a particle in a cosine periodic potential is treated using fractional diffusion equations in both phase and configuration space. Exact solutions of two distinct forms of the fractional Klein-Kramers (Fokker-Planck) equation for the distribution function in phase space are obtained via matrix continued fractions yielding the average velocity, the velocity autocorrelation function, its spectrum, etc. In the overdamped limit, the results yielded by both equations agree with those from a fractional probability density diffusion equation in configuration space. A simple analytic solution for the spectrum of the velocity correlation function is also given using the effective eigenvalue approximation. The results represent generalizations of the conventional solutions for the normal diffusion of a Brownian particle in a cosine potential to fractional dynamics (giving rise to anomalous diffusion).


Best Practices for Effective Management of Point of Care Testing.
With the recent COVID-19 pandemic, point-of-care testing has gained tremendous attention, particularly in acute care settings. The point-of-care testing landscape is rapidly expanding and being contemplated for any crucial test with a central laboratory turnaround time >25% of the clinical decision time. A typical point-of-care testing program within a large hospital system encompasses a multitude of operators utilizing a wide range of devices across multiple testing sites. Thus, managing a large point-of-care testing network remains a daunting task with challenges related to staffing, standardization, quality management, training and competency assessment, and data management. This review will focus on understanding the general organization as well as the roles and responsibilities of various point-of-care testing stakeholders in addressing these challenges. More importantly, it will discuss the strategies and best practices for effective point-of-care testing management based on consensus recommendations from professional societies as well as our experience at Texas Childrens Hospital.


Transforming growth factor beta and progression of renal disease.
End-stage renal disease (ESRD) is more frequent in African Americans compared to whites. Many factors may be responsible, including genetic differences, increased prevalence of risk factors, and socioeconomic factors; however, to date, these proposed genetic or environmental factors have not provided a satisfactory explanation for the increased risk of ESRD in African Americans. Because renal fibrosis is a correlate of progressive renal failure and a dominant feature of ESRD, and because transforming growth factor beta 1 (TGF-beta1) can induce fibrosis and renal insufficiency, we explored the hypothesis that TGF-beta1 hyperexpression is more frequent in African Americans compared to whites. We tested our hypotheses by measuring TGF-beta1 levels in African Americans and white patients with ESRD, hypertension, and in normal patients. In hypertensive and normal patients, we also evaluated TGF-beta1 mRNA levels, and TGF-beta1 DNA polymorphisms. We demonstrated that circulating levels of TGF-beta1 are higher in African American ESRD patients, hypertensive patients, and normal control patients compared to their white counterparts. We also reported that TGF-beta1 mRNA levels are higher in hypertensives compared to normotensives. Our preliminary genetic analyses suggest that TGF-beta1 DNA polymorphisms may distinguish hypertensives from normotensives, and our laboratory is currently investigating racial differences in TGF-beta1 DNA polymorphisms. Our observations of hyperexpression of TGF-beta1 in African Americans suggest a mechanism for the increased prevalence of renal failure and hypertensive target organ damage in this population.


Comparing outcomes in new pulmonary sputum positive and sputum negative cases under RNTCP in rural India.
The study was carried out at the Bagula TU, Nadia, West Bengal, India. To find out the treatment outcomes of new smear negative cases, in low HIV prevalence population, and to compare the results with new smear positive cases in the same population. It was a retrospective record based study. All patients registered between January 1999 and June 2005 were divided into new smear positive and new smear negative groups and the difference in the outcomes analysed. Favourable outcome was less in new smear negative cases, compared to new smear positive (84% vs. 86%, p = 0.002).Death and default were more in new smear negative cases, compared to new smear positive (death: 6.8% vs. 3.7%; DEFAULT: 6.02% vs. 4.18%), (p < 0.05). Failure and transferred out were non- significantly higher in new smear positive group. Smear negative patients had a worse treatment outcome compared to smear positive patients including lower favourable outcomes and higher deaths and defaults. The possible reasons need to be explored and corrective actions need to be taken accordingly.


Inhibiting Ferroptosis through Disrupting the NCOA4-FTH1 Interaction: A New Mechanism of Action.
Ferroptosis is an iron-dependent form of oxidative cell death, and the inhibition of ferroptosis is a promising strategy with which to prevent and treat neurological diseases. Herein we report a new ferroptosis inhibitor 9a with a novel mechanism of action. It is demonstrated that nuclear receptor coactivator 4 (NCOA4), a cargo receptor for ferritinophagy, is the target of 9a. Compound 9a blocks ferroptosis by reducing the amount of bioavailable intracellular ferrous iron through disrupting the NCOA4-FTH1 protein-protein interaction. Further studies indicate that 9a directly binds to recombinant protein NCOA4383-522 and effectively blocks the NCOA4383-522-FTH1 interaction. In a rat model of ischemic stroke, 9a significantly ameliorates the ischemic-refusion injury. With the first ligand 9a, this work reveals that NCOA4 is a promising drug target. Additionally, 9a is the first NCOA4-FTH1 interaction inhibitor. This work paves a new road to the development of ferroptosis inhibitors against neurological diseases.


Vaginal candidosis: relation between yeast counts and symptoms and clinical signs in non-pregnant women.
Of 277 non-pregnant women, 67 (24%) harboured Candida albicans in the genital tract. Of 56 women yielding C albicans who had no other infection diagnosed, 14 were symptomless and 10 had no clinical signs of vulval redness, vaginitis, or discharge. Symptoms and signs tended to be more severe in women with higher yeast counts. Of 22 women with moderate or severe symptoms (pruritus with or without discharge) and signs, 15 had yeast counts of more than 10(3) colony forming units (cfu)/ml, whereas six of nine women with no symptoms or signs had counts of fewer than 10(3) cfu/ml.


Sexual behaviour after antiretroviral therapy initiation in female sex workers and HIV-positive patients from the general population, Cotonou, Benin.
From September 2008 to December 2011, we enrolled and followed-up 247 HIV-negative, 88 untreated and 32 treated HIV-positive female sex workers (FSWs), as well as 238 untreated and 115 treated HIV-positive patients from the general population (GP) of Cotonou, Benin. We wanted to assess the effect of antiretroviral therapy (ART) on sexual risk-taking in FSWs and patients from the GP. We used multivariate log binomial regression models for repeated measures to compare risky behaviours reported during pre-ART and post-ART visits and we performed linear time-trend analyses to assess changes in condom use in all five groups. At 58.8% of pre-ART and 45.3% of post-ART visits (adjusted p-value=0.293), treated FSWs have reported ≥16 clients during the last week of work. Inconsistent condom use with clients over the same period decreased by more than 50% (from 20.7 to 10.0%, adjusted p-value=0.082). In treated patients from the GP, inconsistent condom use with regular partners during the last four months was reported at 52.8% of pre-ART and 53.5% of post-ART visits (p=0.778). Reported casual sex was stable (36.8% versus 38.7%, adjusted p-value=0.924). In linear time-trend analyses, there was a significant downward trend in inconsistent condom use at the early stage of the study and stability thereafter in all HIV-negative and HIV-positive FSWs. There was no negative alteration in sexual behaviour following ART initiation either inpatients from the GP or in FSWs. The results underscore the key role of concomitant sexual risk-reduction strategies.


Solution-processable polytriazoles from spirocyclic monomers for membrane-based hydrocarbon separations.
The thermal distillation of crude oil mixtures is an energy-intensive process, accounting for nearly 1% of global energy consumption. Membrane-based separations are an appealing alternative or tandem process to distillation due to intrinsic energy efficiency advantages. We developed a family of spirocyclic polytriazoles from structurally diverse monomers for membrane applications. The resulting polymers were prepared by a convenient step-growth method using copper-catalysed azide-alkyne cycloaddition, providing very fast reaction rates, high molecular weights and solubilities in common organic solvents and non-interconnected microporosity. Fractionation of whole Arabian light crude oil and atmospheric tower bottom feeds using these materials enriched the low-boiling-point components and removed trace heteroatom and metal impurities (comparable performance with the lighter feed as the commercial polyimide, Matrimid), demonstrating opportunities to reduce the energy cost of crude oil distillation with tandem membrane processes. Membrane-based molecular separation under these demanding conditions is made possible by high thermal stability and a moderate level of dynamic chain mobility, leading to transient interconnections between micropores, as revealed by the calculations of static and swollen pore structures.


Interaction of Polyamines, Abscisic Acid, Nitric Oxide, and Hydrogen Peroxide under Chilling Stress in Tomato (Lycopersicon esculentum Mill.) Seedlings.
Polyamines (PAs) play a vital role in the responses of higher plants to abiotic stresses. However, only a limited number of studies have examined the interplay between PAs and signal molecules. The aim of this study was to elucidate the cross-talk among PAs, abscisic acid (ABA), nitric oxide (NO), and hydrogen peroxide (H2O2) under chilling stress conditions using tomato seedlings [(Lycopersicon esculentum Mill.) cv. Moneymaker]. The study showed that during chilling stress (4°C; 0, 12, and 24 h), the application of spermidine (Spd) and spermine (Spm) elevated NO and H2O2 levels, enhanced nitrite reductase (NR), nitric oxide synthase (NOS)-like, and polyamine oxidase activities, and upregulated LeNR relative expression, but did not influence LeNOS1 expression. In contrast, putrescine (Put) treatment had no obvious impact. During the recovery period (25/15°C, 10 h), the above-mentioned parameters induced by the application of PAs were restored to their control levels. Seedlings pretreated with sodium nitroprusside (SNP, an NO donor) showed elevated Put and Spd levels throughout the treatment period, consistent with increased expression in leaves of genes encoding arginine decarboxylase (LeADC. LeADC1), ornithine decarboxylase (LeODC), and Spd synthase (LeSPDS) expressions in tomato leaves throughout the treatment period. Under chilling stress, the Put content increased first, followed by a rise in the Spd content. Exogenously applied SNP did not increase the expression of genes encoding S-adenosylmethionine decarboxylase (LeSAMDC) and Spm synthase (LeSPMS), consistent with the observation that Spm levels remained constant under chilling stress and during the recovery period. In contrast, exogenous Put significantly increased the ABA content and the 9-cis-epoxycarotenoid dioxygenase (LeNCED1) transcript level. Treatment with ABA could alleviate the electrolyte leakage (EL) induced by D-Arg (an inhibitor of Put). Taken together, it is concluded that, under chilling stress, Spd and Spm enhanced the production of NO in tomato seedlings through an H2O2-dependent mechanism, via the NR and NOS-like pathways. ABA is involved in Put-induced tolerance to chilling stress, and NO could increase the content of Put and Spd under chilling stress.


Solid-phase radioimmunoassay for detection of alcoholic hyalin antigen (AHAg) and antibody (anti-AH).
Alcoholic hyalin (AH) was isolated and purified from post-mortem livers of patients with alcoholic hepatitis. Antibodies against AH (anti-AH) were raised in guinea-pigs. Their specificity was demonstrated by immunofluorescence and by immunoabsorption. The antisera were positive in immunofluorescence and complement fixation up to serum dilutions of 1:320 and 1:32 respectively. In order to achieve a higher sensitivity a solid-phase radioimmunoassay (SP-RIA) was established for detection of alcoholic hyalin antigen (AHAg) and anti-AH. Anti-AH could thus be measured up to a 10(5) serum dilution. Using a blocking test, solubilized AH at protein concentrations as low as 80 to 160 ng/ml could be detected. With this SP-RIA, neither AHAg nor anti-AH was found in the sera of 32 patients with histologically proven alcoholic hepatitis. The sera were likewise negative by indirect immunofluorescence, complement fixation and immune adherence haemagglutination test.


Automated drusen detection in retinal images using analytical modelling algorithms.
Drusen are common features in the ageing macula associated with exudative Age-Related Macular Degeneration (ARMD). They are visible in retinal images and their quantitative analysis is important in the follow up of the ARMD. However, their evaluation is fastidious and difficult to reproduce when performed manually. This article proposes a methodology for Automatic Drusen Deposits Detection and quantification in Retinal Images (AD3RI) by using digital image processing techniques. It includes an image pre-processing method to correct the uneven illumination and to normalize the intensity contrast with smoothing splines. The drusen detection uses a gradient based segmentation algorithm that isolates drusen and provides basic drusen characterization to the modelling stage. The detected drusen are then fitted by Modified Gaussian functions, producing a model of the image that is used to evaluate the affected area.Twenty two images were graded by eight experts, with the aid of a custom made software and compared with AD3RI. This comparison was based both on the total area and on the pixel-to-pixel analysis. The coefficient of variation, the intraclass correlation coefficient, the sensitivity, the specificity and the kappa coefficient were calculated. The ground truth used in this study was the experts' average grading. In order to evaluate the proposed methodology three indicators were defined: AD3RI compared to the ground truth (A2G); each expert compared to the other experts (E2E) and a standard Global Threshold method compared to the ground truth (T2G).The results obtained for the three indicators, A2G, E2E and T2G, were: coefficient of variation 28.8 %, 22.5 % and 41.1 %, intraclass correlation coefficient 0.92, 0.88 and 0.67, sensitivity 0.68, 0.67 and 0.74, specificity 0.96, 0.97 and 0.94, and kappa coefficient 0.58, 0.60 and 0.49, respectively. The gradings produced by AD3RI obtained an agreement with the ground truth similar to the experts (with a higher reproducibility) and significantly better than the Threshold Method. Despite the higher sensitivity of the Threshold method, explained by its over segmentation bias, it has lower specificity and lower kappa coefficient. Therefore, it can be concluded that AD3RI accurately quantifies drusen, using a reproducible method with benefits for ARMD evaluation and follow-up.


Potential drug therapies for the treatment of fibromyalgia.
Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.