Alterations of choline phospholipid metabolism in ovarian tumor progression.
Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholine-producing enzymes, and uptake of [methyl-14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcholine metabolites contributing to the 1H NMR total choline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 +/- 0.9 and 5.2 +/- 2.4 nmol/10(6) cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 +/- 0.93 in EONT cells; average [phosphocholine] was 3- to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phosphatidylcholine metabolite, whereas average glycerophosphocholine/phosphocholine values decreased significantly to < or =0.2. Two-dimensional (phosphocholine/total choline, [total choline]) and (glycerophosphocholine/total choline, [total choline]) maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline kinase activity in EOC cells were 12- to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 +/- 0.1 nmol/10(6) cells/h), accounting for a consistently elevated (5- to 15-fold) [methyl-14C]choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher ( approximately 5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phosphatidylcholine cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvasive clinical tools for EOC diagnosis and treatment follow-up.


Prevalence of myopia among primary school children in eastern Sydney.
Worldwide there is concern that the prevalence of myopia is increasing but the prevalence of myopia in Australian school children has not been analysed in detail. This study examines the prevalence of refractive errors in a large unselected population of primary school children in the eastern suburbs of Sydney. Children visiting the Vision Education Centre at the School of Optometry and Vision Science, University of New South Wales, on a school excursion during the first half of the 1990s were refracted by non-cycloplegic retinoscopy. Spherical equivalents were computed and analysis of variance carried out. There were 1,459 boys and 1,076 girls in the study, a total of 2,535 children of whom approximately 40 per cent were born overseas or were first generation Australians. Overall, there was no significant difference in refractive error between girls and boys, although there were age/gender interactions with older girls exhibiting more hyperopia than boys. The refractive error ranged from -0.25 to +1.25 D spherical equivalent in 87.3 per cent of children. Mean spherical equivalent for the group was +0.50 +/- 0.82 D. There was a significant shift (p < 0.001) towards increasing myopia with age. The prevalence of myopia greater than -0.50 D rose from 1.0 per cent of four-year-olds to 8.3 per cent of 12-year-olds. The prevalence of myopia found in a large multi-ethnic group of non-clinical primary school children in eastern Sydney is lower than expected from other studies in the USA and Asia. Compared with Australian data from the 1970s and 1980s, only a weak increase in the prevalence of myopia is revealed.


New xenografts of human megakaryoblastic cell line (MEG-01) for evaluating anti-tumor agents.
A human megakaryoblastic cell line (MEG-01) was successfully transplanted into athymic nude mice. MEG-01 cells (5 x 10(7)) were inoculated subcutaneously in KSN-nu/nu mice, none of which were pretreated with irradiation or chemotherapeutic agents. All mice developed solid tumors at the site of injection after incubation for 10-14 days reaching a size of 200-400 mm2 (product of cross-sectional diameters) after 30 days. These tumors, designated as MEG-01/nu, were transplanted into other nude mice. The transplanted tumors infiltrated the liver and spleen, and leukemic megakaryoblastic cells appeared in the blood of some transplanted mice. Cells resuspended from MEG-01/nu tumors exhibited almost the same megakaryocytic characteristics as the original MEG-01 cells, and underwent in vitro differentiation to a mature form of megakaryocyte upon addition of phorbol diesters. MEG-01/nu was evaluated for sensitivity to cytosine arabinoside, vincristine, and daunorubicin in vitro and in vivo. Daunorubicin exhibited significant anti-tumor activity against MEG-01/nu in vivo, while cytosine arabinoside did so in vitro. Vincristine showed no activity against these cells. This cell line may provide a useful model for testing the in vivo efficacy of anti-tumor agents and immunotoxins, and for studying the pathophysiological mechanisms of human megakaryoblastic leukemia.


Organocatalyzed enantioselective fluorocyclizations.
Enantioenriched fluorinated heterocycles can be prepared through fluorocyclizations of prochiral indoles (see scheme; Ts=tosyl, Bn=benzyl, Boc=tert-butoxycarbonyl). More than twenty examples for this cascade fluorination-cyclization, which is catalyzed by cinchona alkaloids and employs N-fluorobenzenesulfonimide as the electrophilic fluorine source have been explored, and an unprecedented catalytic asymmetric difluorocyclization has also been identified.


Chetomin induces degradation of XIAP and enhances TRAIL sensitivity in urogenital cancer cells.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising anti-cancer agents, but some tumor types develop resistance to TRAIL. Here, we report that chetomin, an inhibitor of hypoxia-inducible factors, is a potent enhancer of TRAIL-induced apoptosis. TRAIL or chetomin alone weakly induced apoptosis, but the combination of chetomin and TRAIL synergistically induced apoptosis in prostate cancer PC-3 cells. The combination of chetomin and TRAIL induces the activation of caspase-3, -8, -9 and -10. Among the apoptotic factors related to the TRAIL pathway, chetomin markedly decreased the X-linked inhibitor of apoptosis (XIAP) protein levels in a dose-dependent manner, but other IAP family members, TRAIL receptors and Bcl-2 family members were not altered by chetomin. Using XIAP siRNA instead of chetomin, down-regulation of XIAP sensitized PC-3 cells to TRAIL-induced apoptosis. Conversely, transient transfection of XIAP reduced the apoptotic response to combined treatment with chetomin and TRAIL. Treatment with chetomin induced a rapid decrease in XIAP protein levels but had no effect on XIAP mRNA levels. Since chetomin-mediated XIAP down-regulation was completely prevented by proteasome inhibitors, it was suggested that chetomin induces the degradation of the XIAP protein in a proteasome-dependent manner. Additionally, chetomin also sensitized renal cancer Caki-1 cells and bladder cancer UM-UC-3 cells to TRAIL-induced apoptosis via down-regulation of XIAP. Co-treatment of chetomin and TRAIL did not enhance apoptosis in normal peripheral blood mononuclear cells (PBMC). Taken together, these findings suggest that TRAIL and chetomin synergistically induce apoptosis in human urogenital cancer cells through a mechanism that involves XIAP down-regulation by chetomin.


Palladium(II)-Catalyzed Directed anti-Hydrochlorination of Unactivated Alkynes with HCl.
A regioselective anti-hydrochlorination of unactivated alkynes is reported. The reaction utilizes in situ generated HCl as the source of both the Cl- and H+ and is catalyzed by palladium(II) acetate, with loadings as low as 25 ppm. Removable picolinamide and 8-aminoquinoline bidentate directing groups are used to control the regioselectivity of the chloropalladation step and stabilize the resulting alkenylpalladium(II) intermediate for subsequent protodepalladation. This method provides access to a broad array of substituted alkenyl chlorides in excellent yields and with high regioselectivity. The products from this transformation were successfully derivatized via Stille coupling to a variety of trisubstituted alkene products. Reaction progress kinetic analysis was performed, shedding light on a possible mechanism for this catalytic process.


Update on the treatment of lupus nephritis.
Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities. Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront. Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.


Aging-related changes in knee flexor muscle strength and cross-sectional area.
Weakening muscle strength around the knee tends to render it vulnerable to aging-related damage. This study aimed to examine the association between knee flexor muscle strength and its cross-sectional area (CSA). We also evaluated aging-related changes in flexor muscle strength and CSA. We retrospectively analyzed 252 patients with acute-onset knee pain (<1 month) between September 2006 and August 2009 in accordance with the Strengthening the Reporting of Observational studies in Epidemiology statement. The CSA of each knee flexor muscle (biceps femoris, sartorius, gracilis, semitendinosus (ST), and semimembranosus (SM)) was measured on magnetic resonance imaging axial images at the suprapatellar level. We evaluated flexor muscle strength (peak torque in N.m) using a Cybex dynamometer at 60°/second and 180°/second and its correlation with CSA. In total, 252 patients (mean age, 34.5 years; range, 11 to 66 years; 184 men and 68 women) were included in this study. No significant intergroup differences in demographic data such as sex or body mass index were found. Mean CSA was 605.4 mm2 for the SM, 444.7 mm2 for the biceps femoris, 282 mm2 for the sartorius, 55.4 mm2 for the ST, and 34.1 mm2 for the gracilis. Mean peak torques were 67.4 N.m and 52.7 N.m at 60°/second and 180°/second, respectively. CSA was positively correlated with flexion strengths of 60°/second (R = 0.363, P < .001) and 180°/second (R = 0.354, P < .001). Muscle strength was associated with CSA in all muscles but the gracilis (R = 0.056, P = .375). Flexion strength decreased significantly with aging from the thirties. Total CSA decreased with aging (r = -0.247, P < .001). The CSA of the biceps femoris, sartorius, SM, and ST decreased significantly, whereas that of the gracilis tended to decrease non-significantly with aging. Flexor muscle strength was associated with total muscle CSA on magnetic resonance imaging and the CSA of every muscle except the gracilis. Flexion strength decreased significantly with aging after the twenties, while total CSA decreased significantly with aging. The CSA of all flexor muscles decreased significantly with aging, whereas that of the gracilis decreased only slightly.


Quality of care of modern health services as perceived by users and non-users in Burkina Faso.
Only one-fifth of the population in rural Burkina Faso uses modern health services. This article aims to identify barriers to increased use, which may help decision makers to develop policies to remove them. This article compares perceived quality of care of 853 pairs of users and non-users of modern health services. Non-users were matched to users on age, sex, occupation of the head of the household and distance to health post. Questions were structured according to four dimensions of quality of care. Nouna health care district, Burkina Faso. Both users and non-users were relatively favourable about health personnel practices and conduct (77% versus 70% of the maximum attainable score), and about health care delivery (77% versus 74%). They were less favourable about adequacy of resources and services (51% versus 46%), and financial and physical accessibility of care (57% versus 51%). Both groups were very negative regarding the availability of drugs (33% versus 27%). Users were more favourable than non-users overall (66% versus 61%), and especially regarding payment arrangements (51% versus 43%) and costs (50% versus 40%). Observed differences were generally significant. To remove barriers to increase utilization, policy makers may do good to target their attention to improve financial accessibility of modern health services and improve drugs availability. These factors seem most persistent in decisions of ill people to stay with home-based care and/or traditional medicine, or go to consult modern health services.


Structural Evolution of Cu/ZnO Catalysts during Water-Gas Shift Reaction: An In Situ Transmission Electron Microscopy Study.
Supported metal catalysts experience significant structural evolution during the activation process and reaction conditions, which is critical to achieve a desired active surface and interface enabling efficient catalytic processes. However, such dynamic structural information and related mechanistic understandings remain largely elusive owing to the limitation of real-time capturing dynamic information under reaction conditions. Here, using in situ environment transmission electron microscopy, we demonstrate the atomic-scale structural evolution of the model Cu/ZnO catalyst under relevant water-gas shift reaction (WGSR) conditions. Under a CO gas environment, Cu nanoparticles decompose into smaller Cu species and redistribute on ZnO supports with either the crystalline Cu2O or amorphous CuOx phase due to a strong CO-Cu interaction. In addition, we visualize various metal-support interactions between Cu and ZnO under reaction conditions, e.g., ZnO clusters precipitating on Cu nanoparticles, which are critical to understand active sites of Cu/ZnO as catalysts for WGSR. These in situ atomic-scale observations highlight the dynamic interplays between Cu and ZnO that can be extended to other supported metal catalysts.


Preparation of [B23-D-alanine]des-(B25-B30)-hexapeptide-insulin by a combination of enzymic and non-enzymic synthesis.
Des-(B25-B30)-hexapeptide-insulin with B23-glycine replaced by D-alanine was prepared by a combination of enzymic and non-enzymic syntheses. The purified product was homogeneous in polyacrylamide-gel electrophoresis and could be crystallized. The biological activity in vivo of crystalline [B23-D-Ala]des-(B25-B30)-hexapeptide-insulin was determined as 58% of that of standard pig insulin (27 i.u./mg).


Radical hysterectomy.
Radical hysterectomy for the treatment of cervical cancer was first performed just over 100 years ago. Refinements of surgical technique and improvements in supportive measures, such as transfusions and antibiotics, have brought about a marked decrease in morbidity and mortality from surgery and improvement in overall survival. The indications for operation, pre-operative investigations and preparation, surgical technique, post-operative complications and their management, and factors influencing prognosis are discussed.


Emotion regulation promotes persistence in a residential substance abuse treatment.
Emotion regulation at treatment entry was evaluated among 115 patients in an inner-city substance use residential facility who either persisted (N = 94) or discontinued treatment (N = 21). Emotion regulation capacity including emotional clarity and the ability to engage in goal-directed behavior despite emotional distress, as well as lower scores on a measure of trait-negative emotionality, were associated with treatment persistence, whereas motivational variables were not. Findings indicate the importance of regulating negative emotions for treatment engagement among substance abusers.


Triiodothyronine antibodies in patients with goiter.
To investigate the prevalence of triiodothyronine (T(3)) antibodies in patients with goiter, the influence of these antibodies on the results of thyroid hormone measurements, and the potential relationship between T(3) antibodies and thyroid autoantibodies. We undertook a study of 100 healthy control subjects (80 female and 20 male subjects) who had no clinical or biochemical evidence of thyroid disease and 100 patients (81 female and 19 male patients) with goiter. Serum concentrations of total T(3), total thyroxine, free T(3), and free thyroxine were measured by radioimmunoassay kits with a coated tube method. An immunoprecipitation method was used to detect anti-triiodothyronine auto-antibodies. Patients with a T(3) antibody binding ratio +3 standard deviations (SD) above the mean for the normal control group were considered to have T(3) antibodies. Normal control group binding was 2.4 +/- 1.3%. On the basis of +3 SD, seven patients had T(3) antibodies. The mean serum total T(3) level was 1.61 +/- 0.1 nmol/L in patients with binding ratios above +3 SD, whereas the mean serum total T(3) level was 2.23 +/- 0.3 nmol/L in patients without T(3) antibodies. Thus, patients with a binding ratio above +3 SD had a significant decrement in total T(3) levels. No correlation was found between the presence of T(3) antibody and antimicrosomal and antithyroglobulin antibodies. When serum thyroid hormone concentrations are measured with a coated tube-radioimmunoassay method, antibodies can result in low T(3) concentrations. T(3) antibodies should be suspected whenever a discordance is noted between the measured thyroid hormone concentrations and the clinical status.


Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): Early report from the United States.
Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), is an ongoing pandemic that has already affected millions of patients worldwide, and is associated with significant morbidity and mortality burden. Although the clinical and laboratory characteristics of this illness have been reported in patients from China and Europe, data are scant in the United States. Methods We extracted data regarding all patients hospitalized at our hospital with COVID-19 infection between March 1 and April 4, 2020. Presenting signs and symptoms, laboratory and imaging findings, treatment, and complications were recorded from electronic medical records (EMRs). The primary composite endpoint was admission to intensive care unit (ICU), shock, or death. Results We had a total of 43 patients tested for COVID-19 at the emergency room (ER) or during hospitalization, 16 (37%) of whom were admitted with COVID-19 infection. The mean age was 65.5 years and 75% were males. The most common presenting symptoms were fever (94%), cough (88%), and dyspnea (81%). A loss of smell and taste sensations were reported by three (19%) patients. Low oxygen saturation was present in 38% of patients, whilst 31% were hypotensive on admission. Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively. The primary composite endpoint occurred in 50% of patients. A total of three patients died; all were aged 70 years or older. Conclusions Laboratory abnormalities and acute renal failure were common in hospitalized patients with SARS-CoV2 infection in our center. Admission to ICU and mechanical ventilation were common.


Human endolymphatic duct. An ultrastructural study.
The fine structure of the human endolymphatic duct was observed by transmission electron microscopy. Well-preserved specimens were obtained after fixation of inner ear tissue by perilymphatic perfusion. The morphologic findings seemed to be in accordance with earlier propositions that the human endolymphatic duct may be involved in endolymph resorption. The duct was found to contain otoconialike bodies, suggesting that the endolymphatic duct and sac in man may also play a role in the turnover of macular otoconia.


Prevalence, trend and associated factors of obesity-related cancers among U.S. adults with metabolic syndrome: Evidence from the National Health and Nutrition Examination Survey 2001-2018.
This study evaluated the prevalence, associated factors and trends in the prevalence of obesity-related cancer (ORC) among U.S. adults with metabolic syndrome (MetS) and age ≥20 years. This study used cross-sectional data from the 2001-2018 National Health and Nutrition Examination Survey. The total period analyses included prevalence estimation, chi-square tests for comparing ORC vs non-ORC within subgroups, and a multivariable-logistic regression model to evaluate associated factors of ORC. For trend analysis, the total period was divided into three time periods: 2001-2006, 2007-2012 and 2013-2018. Age-standardized prevalence of ORC in each time period was calculated. The ORC prevalence was 35.8% representing 4463614 adults with MetS. A higher odds of ORC was observed among females (OR = 7.1, 95% CI = 4.9-10.3) vs males, Hispanic (OR = 2.9, 95% CI = 1.7-4.8) and non-Hispanic Black (OR = 2.7, 95% CI = 1.8-4) vs non-Hispanic White, age ≥60 (OR = 5.4, 95% CI = 1.9-15.4) vs age 20-39 years. Individual ORCs were thyroid (10.95%), breast (10%), uterine (9.18%), colorectal (7.86%), ovarian (5.74%), and stomach (0.80%). The age-standardized prevalence of ORC was observed stable in three time periods (30.6%, 30.3% and 30.7%). However, an increasing trend was seen for thyroid, uterine, colorectal and ovarian cancers while decreasing trend for breast cancer. Hispanic people showed a significant increasing trend of ORC (p = 0.004). ORC was found significantly higher among female, Hispanic, non-Hispanic black and older people with MetS. The stable temporal trend of overall ORC, with an increasing trend in certain ORCs, makes the disease spectrum a public health priority. The findings imply the importance of intensifying efforts to reduce the burden of MetS comorbidities among U.S. adults.


Is Web-only self-care education sufficient for heart failure patients?
Heart failure patients require complex, long-term care. Research shows that self-care education improves health outcomes of these patients. This study reports the results of a randomized trial which compared the effects of two remote educational interventions on heart failure patients' knowledge of self-care practices. The first group reviewed self-care content on a Web site and had email access to a cardiac nurse. The second group had access to the Web site, and participated in four telephone-based sessions with the cardiac nurse. The test scores of both groups significantly improved following the intervention. However, the post-intervention test scores of the group that included telephone sessions were significantly higher than the scores for the group that had access to the Web site only. These results show a benefit to learning of a teleconferencing intervention that is over and above the benefit of an intervention based on Web information and email access alone.


Effect of extracorporeal blood irradiation on lymphocytes and the lymphatic tissue in a goat.
In a long-term study discontinuous extracorporeal blood irradiation (ECIB) was applied to a goat using a 500 Ci-137 Caesium source. Lymphocytes of the peripheral blood were examined by light and electron microscopy. After application of a transit dose of 466,500 rad the lymphocytes in the peripheral blood were found to be decreased from 6,900/microliter to 500/microliter, revealing a complete dissolution of the nuclei in electron microscopic preparations. Histological examinations showed a severe atrophy of the whole lymphatic tissue.


Intubation success rates by air ambulance personnel during 12-versus 24-hour shifts: does fatigue make a difference?
To determine whether the skill performance and psychomotor agility, as measured by the endotracheal intubation success rate, of air ambulance medical personnel would be affected by the potential fatigue incurred when increasing the length of their shifts from 12 to 24 hours. This was a retrospective review of all flight and intubation records from a large air medical transport system from 1997, when 24-hour shifts were in place, and six months (March-August) of 1996, during which 12-hour shifts were scheduled. Records of all intubation efforts during both periods, including multiple attempts per patient, and outcomes of all attempts, were recorded. Results of successes and failures were tabulated for both ultimate intubation outcome per patient and all attempts per patient for each calendar day and for the 12 hours between 19:00 and 07:00 when fatigue might play a role. Results from the two study periods were compared using Fisher's exact test. During the six months of 1996, 190 of 199 (95.5%) patients were ultimately successfully intubated. These patients required 237 attempts (80.1% successful). During 1997, 362 of 376 (96.3%) patients were successfully intubated, and required 438 attempts (82.6% successful). There was no statistically significant difference in the number of ultimately successful intubations (p = 0.66) or total intubation attempts (p = 0.37) between 1996 and 1997. Analysis of intubations between 19:00 and 07:00 revealed 81 of 84 (96.4%) patients successfully intubated in 1996, with 81 of 103 (78.6%) attempts successful. During 1997, 173 of 180 (96.1%) patients were ultimately successfully intubated, with 173 of 212 (81.6%) attempts successful. Again, there was no significant difference in the number of successful intubations (p = 0.99) or intubation attempts (p = 0.55) between 1996 and 1997. Psychomotor agility of air ambulance medical personnel, as measured by the success rate of endotracheal intubation, was not affected by the potential additional fatigue incurred as a result of increasing shift length from 12 to 24 hours.


Nocturnal enuresis in children: The role of arginine-vasopressin.
Nocturnal enuresis is the involuntary pass of urine during sleep beyond the age of 5 years. It is a common condition in childhood and has an impact on the child's well-being. Research into the pathophysiology of the condition in the last decades has led to a paradigm shift, and enuresis is no longer considered a psychiatric disorder but rather a maturation defect with a somatic background. An excess urine production during sleep is a common finding in children with enuresis and disturbances in the circadian rhythm of arginine-vasopressin (AVP) is found in the majority of children with nocturnal polyuria. Children with enuresis and nocturnal polyuria lack the physiologic increase in AVP levels during sleep and treatment with the AVP analogue desmopressin can restore this rhythm and lead to dry nights. The reasons for this aberrant circadian AVP rhythm are not established. Furthermore, not all children with enuresis and nocturnal polyuria can be successfully treated with desmopressin suggesting that factors beyond renal water handling can be implicated such as natriuresis, hypercalciuria, and sleep-disordered breathing. The advances in the research of the genetic background of the condition may shed further light on the enuresis pathophysiology.


The Prognosis of Progressive Multifocal Leukoencephalopathy in HIV/AIDS Patients Undergoing Highly Active Antiretroviral Treatment: A Systematic Review.
Progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system (CNS), is most commonly associated with advanced HIV infection. Although the severe neurological conditions - PML and progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS) - are linked to HIV, little is known about their characteristics in the era of established antiretroviral therapy (ART). The aim of this systematic review, which was performed by adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, was to determine the prognosis of PML in patients with HIV. We gathered and examined articles, including case-control and cohort studies, systematic reviews, and meta-analyses that were published between January 1, 2013, and May 2023. These articles were compiled from the following databases: Pubmed, Pubmed Central, Google Scholar, Wiley Library, and ScienceDirect. A total of 519 records were found from these databases for our systematic review after applying the proper filters. They were then further screened and put through quality appraisal tools, which ultimately led to the selection of 10 articles for the final analysis. This research offers crucial insights into the clinical consequences of PML in HIV patients receiving highly active antiretroviral therapy (HAART).


Rural-urban differences in family and paid caregiving utilization in the United States: Findings from the Cornell National Social Survey.
While rates of family caregiving and paid caregiving are increasing, how often they occur together ("shared care") and whether utilization varies geographically are unknown. We examined differences in family and paid caregiving utilization by rurality and region in the United States. The 2020 Cornell National Social Survey is an annual cross-sectional telephone-based survey of a random sample of 1,000 US adults. Participants were asked if they have been a family caregiver, including if they provided care alongside a paid caregiver. Rural-Urban Commuting Area Codes and Census areas classified rurality and region. The association between residence and the prevalence of caregiving was determined with multivariable Poisson regression. Among 857 participants with geographic and caregiving data, 11.8% (n = 101) were rural dwellers and 34.2% were family caregivers. Rural residence (vs urban) was associated with a higher prevalence of family caregiving (PR: 1.59 [1.22, 2.06]), and Western residence (vs Northeast) was associated with a lower prevalence of family caregiving (PR: 0.63 [0.46, 0.87], P = .01). Forty percent of family caregivers shared care with a paid caregiver. There was no significant difference in shared care by rural residence in unadjusted (31.8% rural vs 43.1% urban, P = .22) or adjusted models (PR: 0.85 [0.51, 1.41], P = .53). Although family caregiving was more prevalent in rural areas and certain regions, shared care did not differ by rurality or region. Studies are needed to understand why rural residents do more family caregiving without additional support from paid caregivers, and what the implications are for caregivers and care recipients.


Production and characterization of a bovine T cell-specific monoclonal antibody identifying a mature differentiation antigen.
A monoclonal antibody (MAb), BLT-1, with specificity for bovine mature T cells was prepared by somatic cell hybridization of myeloma NS-1 and spleen cells from BALB/c mice hyperimmunized with bovine T lymphocytes. The MAb reacted with over 92% of nylon wool-nonadherent lymphocytes (T cells) but not with nylon wool-adherent EAC-positive lymphocytes (B cells) in the indirect immunofluorescence assay. It is an IgM, with kappa-light chains, which fixed complement well and killed over 95% of mature T cells in complement-mediated cytotoxicity assays. It reacted with the same proportions of peripheral lymphoid cells (peripheral blood, lymph nodes, and spleen) as the polyclonal goat anti-bovine thymocyte serum (GABTS), but only with 25% of GABTS-positive thymocytes. Immunoperoxidase staining of frozen tissue sections showed that the BLT-1-positive cells were located in the medulla of the thymus and in the T lymphocyte areas of lymph nodes. Western immunoblotting assays showed that the BLT-1-reactive membrane antigen is a 22,000 m.w. protein which was inducible in bovine thymocytes with bovine thymic hormones, thymosin fraction 5, thymosin alpha 1, and thymopentin ORF-18150, indicating that it is a mature T lymphocyte differentiation antigen. The thymosin alpha 1 and thymopentin were found to show additive effects on mature T cell antigen expression by bovine thymocytes.


Matter - a current picture.
A century ago, a two-part review by W. C. McC. Lewis entitled "The Structure of Matter" appeared in this journal, surveying the achievements that had been made to date in that field. Topics included the value of Avogadro's constant, the dimensions of a molecule, equations of state for non-ideal gases, then-current theories relating electron configurations to the Periodic Law, the then-new nuclear atom model of Rutherford, and the first findings from X-ray crystallographic studies of matter, a field then in its nascent phase. This article is a sequel to that work. As a vast quantity of research has been addressed to the topic in the intervening period, the view presented here can at best be selective and idiosyncratic. Nonetheless, it attempts to capture some of the important strides in 'matter science', broadly defined, over the past century, highlight some recent areas of interest or novelty, and give a picture of some of the mysteries that remain.


Correction: Determination of aflatoxin M1 using an aptamer-based biosensor immobilized on the surface of dendritic fibrous nano-silica functionalized by amine groups.
Correction for 'Determination of aflatoxin M1 using an aptamer-based biosensor immobilized on the surface of dendritic fibrous nano-silica functionalized by amine groups' by Houman Kholafazad kordasht et al., Anal. Methods, 2019, 11, 3910-3919, DOI: 10.1039/C9AY01185D.


Fundus albipunctatus in a patient with achondroplasia.
We describe a patient with achondroplasia who presented with defective night vision due to fundus albipunctatus. We found no previous report of the association in a search of the literature.


Direct synthesis of water-dispersible FePt nanoparticles capped with L-cysteine.
A direct synthetic route of FePt nanoparticles (NPs) has been developed. Reduction of platinum acethylacetonate (Pt(acac)2) and thermal decomposition of iron carbonyl (Fe(CO)5) in the presence of L-cysteine produced fcc FePt NPs with a mean diameter of 2.9 nm. Capping of the FePt NPs with L-cysteine is accomplished by a thiolate linkage between the amino acid and the NP surfaces, which renders them water-dispersible rather than in organic solvents. SQUID magnetization study demonstrated that the FePt NPs exhibited superparamagnetic behavior at 300 K. For the structural model of the FePt NPs, the Fe K-edge and Pt L(III)-edge XAFS results suggest that most of the Pt atoms are preferentially located in the core region, the Fe atoms are preferentially located in the shell region.


Reactivity of fibrinogen and fibrinopeptide A containing fibrinogen fragments with antisera to fibrinopeptide A.
Two antisera used in the radioimmunoassay for human fibrinopeptide A (FPA) which appear to have different immunochemical specificities have been tested for cross-reactivity with fibrinogen and with three fragments of fibrinogen which contain the FPA sequence. These fragments were the three-chain, NH2-terminal disulfide knot (N-DSK) produced by CNBr cleavage of fibrinogen, the reduced, carboxymethyl Aalpha chain portion of the N-DSK, and fragment E produced by plasmin digestion of fibrinogen. One antiserum (R-2) showed high specificity for free FPA and less than 2% cross-reactivity with fibrinogen or the FPA-containing fragments. The other antiserum (R-33) possessed a much higher degree of cross-reactivity with the FPA-containing fragments. Synthetic and native fibrinopeptides were found to be indistinguishable in the assay system with either antiserum. As a result of these studies, an hypothesis has been developed concerning the nature of the antigenic determinants on FPA which favor measurement of free FPA and limit cross-reactivity with larger, FPA-containing peptides.


Active recombinant thioredoxin h protein with antioxidant activities from sweet potato (Ipomoea batatas [L.] Lam Tainong 57) storage roots.
Recombinant thioredoxin h (Trx2) overproduced in Escherichia coli (M15) was purified by Ni2+-chelated affinity chromatography. The molecular mass of Trx2 is approximately 1.4 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Total antioxidant status, 1,1-diphenyl-2-picrylhydrazyl (DPPH) staining, reducing power method, Fe2+-chelating ability, ferric thiocyanate (FTC) method, and protection of calf thymus DNA against hydroxyl radical-induced damage were studied. The thioredoxin h protein with a concentration of 12.5 mg/mL exhibited the highest activity (expressed as 0.37 +/- 0.012 mM ABTS* radical cation being cleared) in a total antioxidant status test. In the DPPH staining thioredoxin h appeared as white spots when it was diluted to 50 mg/mL (a final amount of 15 microg). Like the total antioxidant status, the reducing power, Fe2+-chelating ability, FTC activity, and protection against hydroxyl radical-induced calf thymus DNA damage were found with the thioredoxin h protein. It was suggested that thioredoxin h might contribute to its antioxidant activities against hydroxyl and peroxyl radicals.


A racemic synthesis of an AB-ring system of hexacyclinic acid.
[structure: see text] An AB-ring system of the polyketide natural product hexacyclinic acid has been synthesized in racemic form. The key steps were an intramolecular Diels-Alder cyclization of an ester tethered 1,3-nonadiene-8-yne, which generated the B-ring, and a samarium diiodide mediated reductive annulation, which was used to form the A-ring.


Nifuroxazide Has Better Efficacy Than Probiotic Treatment in Adult Patients with Acute Diarrheal Syndrome.
Acute gastroenteritis remains an extremely common problem among the general population. In Western countries, an average person will probably face one or two episodes of gastrointestinal infections every year. The aim of this study was to compare the efficacy of nifuroxazide and probiotic preparation containing lactic acid bacteria in the treatment of acute diarrheal syndrome. The study was prospective, comparative study. Patients who suffered from acute infective diarrhoea for ≤72 hours and had ≥3 unformed stools per day, with no administration of antibiotics during 10 days before enrolment were divided into two groups: nifuroxazide group and the lactic acid probiotic group. All patients received therapies four times a day for three days. Data was collected at the baseline visit (before the initiation of the treatment) and two follow-up examinations on the third and seventh day from the treatment start. The study included 61 patients, 36 in nifuroxazide group and 25 in probiotic group. Nifuroxazide group compared to probiotic group showed faster improvement of patients' condition with lower number of stools three and seven days after therapy start (p=0.001 and p<0.001 respectively) and faster stool consistency normalization. On the seventh day from therapy start medium mushy stool consistency was observed in the majority of patients in nifuroxazide group (n=31, 86%) and only in small number of patients in probiotic group (n=5, 20%). Patients were feeling better and there was a trend of reporting better therapy efficacy in nifuroxazide group. Subjective assessment of therapy tolerability was also better in nifuroxazide group. Compliance to therapy and recommended dietary regime was similar between groups and there were no significant differences between groups regarding age, gender, elevated body temperature, abdominal pain, cramps, nausea and vomiting. Although probiotics are sometimes used in the treatment of acute diarrheal syndrome, nifuroxazide has better efficacy and greater patients' satisfaction. Nifuroxazide can be recommended as the first choice empirical treatment in adult patients with the acute diarrheal syndrome.


Analog optical computing based on a dielectric meta-reflect array.
In this Letter, we realize the concept of analog computing using an engineered gradient dielectric meta-reflect-array. The proposed configuration consists of individual subwavelength silicon nanobricks, in combination with a fused silica spacer and silver ground plane, realizing a reflection beam with full phase coverage of 2π degrees, as well as an amplitude range of 0 to 1. Spectrally overlapping electric and magnetic dipole resonances, such high-index dielectric metasurfaces can locally and independently manipulate the amplitude and phase of the incident electromagnetic wave. This practically feasible structure overcomes substantial limitations imposed by plasmonic metasurfaces such as absorption losses and low polarization conversion efficiency in the visible range. Using such CMOS-compatible and easily integrable platforms promises highly efficient ultrathin planar wave-based computing systems that circumvent the drawbacks of conventional bulky lens-based signal processors. Based on these key properties and the general concept of spatial Fourier transformation, we design and realize broadband mathematical operators such as the differentiator and integrator in the telecommunication wavelengths.


The oxidation of NN-dimethyl-p-phenylenediamine by oxidizing agents and by caeruloplasmin.
1. The oxidation of NN-dimethyl-p-phenylenediamine (DPD) by inorganic oxidants and by caeruloplasmin was studied. Some experiments were also made with NNN'N'-tetramethyl-p-phenylenediamine (TPD). 2. E(mM) (550) of the first free radical oxidation product of DPD (DPD(+)) was 9.8 and E(mM) (563) of the corresponding product of TPD (TPD(+)) was 12.5. 3. The non-enzymic decomposition of DPD(+) was studied with respect to temperature, pH, concentration and DPD/DPD(+) ratio, thus defining conditions for enzyme experiments under which DPD(+) extinction at 550mmu was proportional to enzyme activity. 4. Rates of oxidation of DPD to DPD(+) by caeruloplasmin were constant over a range of DPD concentrations. At low DPD concentrations a lag period occurred, which was eliminated by addition of DPD(+). 5. A lag period was not observed with TPD, but at low TPD concentrations the rate of TPD(+) formation was greater when TPD(+) was added. This suggests that TPD(+) may compete weakly as a substrate with TPD and may be oxidized further by the enzyme before a non-enzymic reaction with TPD to form more TPD(+). 6. With DPD sulphate or acetate or TPD sulphate as substrate, Lineweaver-Burk plots were curved. With DPD hydrochloride the chloride ion caused inhibition at higher concentrations, opposing the curvature. 7. Curved Lineweaver-Burk plots were interpreted in terms of two types of substrate binding site with different K(m) values but similar V(max.) values. 8. The apparent thermodynamic changes associated with enzyme-substrate-complex formation at the sites with higher K(m) suggest that considerable conformational change may occur on binding at these sites. 9. With substrate concentrations at which only the low-K(m) sites are involved 2mol. of DPD(+)/mol. of caeruloplasmin are formed before a steady state is established. At higher substrate concentrations up to 3.2mol. of DPD(+)/mol. of caeruloplasmin are formed at this initial stage. 10. Results are discussed in relation to caeruloplasmin structures in which (a) two valence-changing and two permanently cuprous copper atoms are more accessible than the remaining four copper atoms or (b) binding of substrate at one site hinders access of substrate to another site.


Liquid chromatographic determination of aspartame in dry beverage bases and sweetener tablets with confirmation by thin layer chromatography.
A liquid chromatographic method is described for the determination of aspartame in dry beverage bases and sweetener tablets. The sample was mixed with the mobile phase, the pH was adjusted to within +/- 0.1 pH unit of the mobile phase, and the sample was diluted to volume with the mobile phase. The solution was filtered and a 10 microL aliquot was injected onto a C18 reverse phase column. Aspartame was quantitated with an ultraviolet detector. Recoveries of aspartame ranged from 94 to 111%. The dry beverage bases contained 5-13% aspartame and the sweetener tablets contained 19% aspartame. The presence of aspartame was confirmed by using thin layer chromatography.


Purification and properties of 5'-nucleotidase from the membrane of Vibrio costicola, a moderately halophilic bacterium.
Two different Mg2+-dependent adenosine 5'-triphosphate-hydrolyzing activities were detected in membranes of Vibrio costicola, a novel 5'-nucleotidase and an N,N'-dicyclohexylcarbodiimide-sensitive adenosine triphosphatase. The former and the latter had different requirements for Mg2+ and were selectively assayed in the membranes by using, respectively, 20 and 2 mM Mg2+. The two enzymes were extracted with a combination of Triton X-100 and octylglucoside, separated on a diethylaminoethyl cellulose column, and purified on glycerol gradients. The purified 5'-nucleotidase consisted of one major polypeptide of 70,000 daltons when analyzed on polyacrylamide gels in the presence of sodium dodecyl sulfate. The purified 5'-nucleotidase was similar in substrate specificities, divalent cation specificities, and pH profiles to the membrane-bound N,N'-dicyclohexylcarbodiimide-insensitive nucleotide-phosphohydrolyzing activity. The enzyme hydrolyzed nucleoside 5'-tri, 5'-di, and 5'-monophosphates at comparable rates. Inorganic pyrophosphate, p-nitrophenyl phosphate, glucose 6-phosphate, beta-glycerophosphate, adenosine 5'-diphosphate glucose, adenosine 3'-monophosphate, and cyclic adenosine 3',5'-monophosphate were not hydrolyzed, either im membranes or by the purified 5'-nucleotides. Actions of NaCl and KCl on the activity of the 5'-nucleotidase were studied. The enzyme was activated by both NaCl and KCl; the activation profiles however, were different for the membrane-bound and purified 5'-nucleotidase. The purified enzyme, unlike the membrane-bound enzyme, was markedly stimulated by high concentrations of NaCl (up to 3 M).


Tuning the Upconversion Luminescence Lifetimes of KYb2 F7 :Ho(3+) Nanocrystals for Optical Multiplexing.
Conventional luminescent color coding is limited by spectral overlap and the interference of background fluorescence, thus restricting the number of distinguishable identities that can be used in practice. Here, we demonstrate the possibility of generating diverse time-domain codes, specially designed for a single emission band, using lanthanide-doped upconversion nanocrystals. Based on the knowledge of concentration quenching, the upconversion luminescence kinetics of KYb2 F7 : Ho(3+) nanocrystals can be precisely controlled by modifying the dopant concentration of Ho(3+) ions, resulting in a tunable emission lifetime from 75.8 to 1944.5 μs, which suggests the practicality of these time-domain codes for optical multiplexing.


Ambipolar Conjugated Polymers with Ultrahigh Balanced Hole and Electron Mobility for Printed Organic Complementary Logic via a Two-Step CH Activation Strategy.
High mobility ambipolar conjugated polymers are seriously absent regardless their great potential for flexible and printed plastic devices and circuits. Here, ambipolar polymers with ultrahigh balanced hole and electron mobility are developed via a two-step CH activation strategy. Diketopyrrolopyrrole-benzothiadiazole-diketopyrrolopyrrole (DBD) and its copolymers with thiophene/selenophene units (short as PDBD-T and PDBD-Se) are used as examples. PDBD-Se exhibits highly efficient ambipolar transport with hole and electron mobility up to 8.90 and 7.71 cm2 V-1 s-1 in flexible organic field-effect transistors, presenting a milestone for ambipolar copolymer screening. Based on this performance metrics and good solubility, PDBD-Se is investigated as inkjet-printable semiconductor ink for organic complementary logic circuits. Under ambient processing, maximum hole and electron mobilities reach 6.70 and 4.30 cm2 V-1 s-1 , respectively. Printed complementary inverter and NAND gates with transition voltages near VDD /2 are fabricated, providing an easy-handling, general material for printed electronics and logic.


Time to Review the Role of Surrogate End Points in Health Policy: State of the Art and the Way Forward.
The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. Market access and coverage decisions are, however, often based on surrogate end points, biomarkers, or intermediate end points, which aim to substitute and predict patient-relevant outcomes that are unavailable because of methodological, financial, or practical constraints. We provide a summary of the present use of surrogate end points in health care policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policymakers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although the use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and health care systems.


Yucca: an efficient algorithm for small-molecule docking.
In this paper, we present a new algorithm, which is based on an efficient heuristic for local search, for rigid protein-small-molecule docking. We tested our algorithm, called Yucca, on the recent 100-complex benchmark, using the conformer generator OMEGA to generate a set of low-energy conformers. The results showed that Yucca is competitive both in terms of algorithm efficiency and docking accuracy.


A prospective hospital-based study of the clinical impact of non-severe acute respiratory syndrome (Non-SARS)-related human coronavirus infection.
In addition to the human coronaviruses (HCoVs) OC43 and 229E, which have been known for decades to cause infection in humans, 2 new members of this genus have recently been identified: HCoVs NL63 and HKU1. Their impact as a cause of respiratory tract disease in adults at risk for complications needs to be established. We prospectively assessed the clinical impact of coronavirus infection (excluding cases of severe acute respiratory syndrome) among hospitalized adults. All patients with respiratory disease for whom bronchoalveolar lavage was performed were screened by reverse-transcriptase polymerase chain reaction for the presence of all 4 HCoVs. HCoV was identified in 29 (5.4%) of 540 bronchoalveolar lavage fluid specimens from 279 subjects (mean age, 51 years; 63% male). HCoV OC43 was identified most frequently (12 isolates), followed by 229E (7 isolates), NL63 (6 isolates), and HKU1 (4 isolates). In all, 372 (69%) of 540 bronchoalveolar lavage fluid specimens were negative for bacteria, and 2 persons were coinfected with other respiratory viruses. Transplantation was the most common underlying condition. Of the 29 patients who had HCoV identified in their bronchoalveolar lavage fluid specimens, 9 (31%) were hospitalized in the intensive care unit, 22 (76%) presented to the hospital with acute respiratory symptoms, 16 (55%) presented with cough and/or sputum, 13 (45%) presented with dyspnea, 16 (55%) had experienced prior respiratory infection, and 18 (62%) had a new infiltrate that was visible on chest radiograph. The most frequent final diagnosis was a lower respiratory tract infection. The recently discovered HCoVs NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infection. Our study also suggests that coronaviruses contribute to respiratory symptoms in most cases.


Updated meta-analysis on HER2 polymorphisms and risk of breast cancer: evidence from 32 studies.
Several studies have been performed to investigate the association of the HER2 Ile655Val polymorphism and breast cancer risk. However, the results were inconsistent. To understand the precise relationship, a meta-analysis was here conducted. A search of PubMed conducted to investigate links between the HER2 Ile655Val polymorphism and breast cancer, identified a total of 32 studies, of which 29, including 14,926 cases and 15,768 controls, with odds ratios (ORs) with 95% confidence intervals were used to assess any association. In the overall analysis, the HER2 Ile655Val polymorphism was associated with breast cancer in an additive genetic model (OR=1.136, 95% CI 1.043-1.239, p=0.004) and in a dominant genetic (OR=1.118, 95% CI 1.020-1.227, p=0.018), while no association was found in a recessive genetic model. On subgroup analysis, an association with breast cancer was noted in the additive genetic model (OR=1.111, 95% CI: 1.004-1.230, p=0.042) for the Caucasian subgroup. No significant associations were observed in Asians and Africans in any of the genetic models. In summary, our meta-analysis findings suggest that the HER2 Ile655Val polymorphism is marginally associated with breast cancer susceptibility in worldwide populations with additive and dominant models, but not a recessive model.


pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.
The chloroquine resistance transporter, PfCRT, of the human malaria parasite Plasmodium falciparum is sensitive to acidic pH. Consequently, PfCRT operates at 60% of its maximal drug transport activity at the pH of 5.2 of the digestive vacuole, a proteolytic organelle from which PfCRT expels drugs interfering with heme detoxification. Here we show by alanine-scanning mutagenesis that E207 is critical for pH sensing. The E207A mutation abrogates pH-sensitivity, while preserving drug substrate specificity. Substituting E207 with Asp or His, but not other amino acids, restores pH-sensitivity. Molecular dynamics simulations and kinetics analyses suggest an allosteric binding model in which PfCRT can accept both protons and chloroquine in a partial noncompetitive manner, with increased proton concentrations decreasing drug transport. Further simulations reveal that E207 relocates from a peripheral to an engaged location during the transport cycle, forming a salt bridge with residue K80. We propose that the ionized carboxyl group of E207 acts as a hydrogen acceptor, facilitating transport cycle progression, with pH sensing as a by-product.


Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 3): Novel Analytical Methods Based on Raman Spectroscopy for the Characterization of Deposits and Deposition Phenomena of Creams Containing 20% (w/w) Urea.
In drug formulations for external application, variations in the state of pharmaceutical agents within the base formulation may affect the transfer of agents to the skin. Here, we use Raman spectroscopic methods to acquire more detailed information on the state of the active pharmaceutical ingredients within an externally applied formulation. The combination of wide-field Raman spectroscopy with an experimental method in which drug formulations are applied to glass surfaces provided a new method for characterizing the state of pharmaceutical agents within drug formulations. Here, we demonstrate the usefulness of this new method, called application to glass-wide-field Raman spectroscopy (AG-WRS). In addition to allowing rapid and easy wide-field observations, the use of WRS allows Raman imaging in a manner that is insensitive to variations in the thickness of the formulations applied to sample slides. We consider two types of urea-compound creams with different crystal deposition rates, using AG-WRS to characterize the post-application time-evolving state of deposited crystals. Differences in the base pharmaceutical produce different spectra for the deposits, indicating that the deposits differ in composition and structure. In addition, we use microscopic laser Raman measurements to demonstrate that the process of crystal formulation differs significantly for formulations with different compositions. Our results demonstrate that the combination of AG-WRS with existing analytical techniques such as powder X-ray diffraction or thermal analysis yields more detailed and timely post-application information on the state of pharmaceuticals in external application. We believe this will be a valuable analytical tool for future studies related to the development of external application.


Medication errors in an internal medicine department. Evaluation of a computerized prescription system.
Evaluation of a computerized physician order entry in an Internal Medicine Department, with a unit-dose distribution system. Pharmacy Department, Internal Medicine Department. S. Francisco Xavier Hospital, Lisbon, Portugal. This study was carried out in December 2001 and January 2002. After two years experience of the CPOE system, medication errors were evaluated prospectively, in an internal medical department of a 360-bed academic hospital. Data were collected once a week. Pharmacists reviewed all medical prescriptions as part of their routine work. Medication errors detected were recorded on a data collection form with a design based on the types of errors as defined by the American Society of Hospital Pharmacists (ASHP). Completed forms were reviewed and medication errors were classed according to ASHP guidelines. A total of 2268 orders were monitored (162 patients). In these orders, 73 medication errors (22.4% of the patients) were detected and documented (59 prescribing errors and 14 monitoring errors). The most common prescribing errors were deficiencies related to the right class but wrong drug (28.3%): omeprazole vs. ranitidine/sucralfate in stress ulcer prophylaxis; incorrect dose (30%) and unclear orders (13.3%). Errors related to incorrect frequency of administration (5%); maintenance of IV route (5%); duplicated drug therapy (11.7%); drug interactions (1.7%) and length of therapy (3.3%) were also detected. The 14 monitoring errors detected were failures to review a prescribed regimen for appropriateness and detection of problems. Computerized prescription order entry has demonstrated effectiveness in eliminating medication errors related to transcribing and patient identification. Nevertheless, medication errors related to prescription and monitoring still occur. The use of clinical decision support systems and pharmacist involvement is vital to achieve maximum medication safety and reduce medication error rates.


Pancreas transplantation under alemtuzumab (Campath-1H) and tacrolimus: Correlation between low T-cell responses and infection.
Alemtuzumab induction and tacrolimus-based immunosuppression has been effective in pancreas transplantation. Despite the encouraging results of this minimalistic approach to immunosuppression, infection still remains a significant cause of morbidity. The Cylex ImmuKnow [corrected] assay was used in this study to compare pancreas recipient clinical states (stable, rejection, infection) with T cell responses. Blood samples were taken from pancreas recipients pretransplant and at approximately three-month intervals posttransplant for analysis of T cell responses. When possible, T cell responses were also quantified during changes in clinical status (infection or rejection). A range between 100-300 ng/ml adenosine triphosphate (ATP) was found in stable patients (mean 194+/-123, n = 51) with good graft function and no infection or rejection. A low T cell response was highly correlated with infectious states. The fourteen patients with infections/posttransplant lymphoproliferative disease had a mean ATP of 48 ng/ml. Risk hazard analysis showed that patients with ATP levels <100 ng/ml were four to seven times more susceptible to infection compared to stable patients. Four patients with rejection showed a T cell response of 550 ng/ml ATP, which was statistically significant compared to stable patients, although the sampling numbers (9) were too small to be conclusive. The Cylex ImmuKnow [corrected] assay is a valuable tool to more precisely modulate immunosuppression in pancreas transplant patients. In particular, the assay is extremely useful in detecting overly immunosuppressed patients vulnerable to infections.


First Psychometric Properties of the Dutch Interview for Diagnostic Assessment of Autism Spectrum Disorder in Adult Males Without Intellectual Disability.
For autism spectrum disorder (ASD) in adults there are several diagnostic instruments available with a need for consideration of the psychometric properties. This study aimed to conduct a first psychometric evaluation of a new diagnostic ASD instrument, the NIDA (Dutch Interview for Diagnostic assessment of ASD in adults) in 90 adult males without intellectual disability (age 18-65 years) in the Netherlands: 30 with ASD, 30 with a Personality Disorder and 30 nonpatient controls. The interrater agreement ranged from 0.79 to 1.00, the convergent validity including sensitivity and specificity ranged from 0.76 to 1.00, and we observed an adequate concurrent criterion-related validity. These promising findings can serve as foundation for future psychometric NIDA studies in a more diverse population. TRIAL REGISTRATION: The Netherlands National Trial Register NTR6391. Registered 04 May 2017.


Pharmacokinetics of an intravenous and oral dose of enrofloxacin in white rhinoceros (Ceratotherium simum).
South Africa currently loses over 1000 white rhinoceros (Ceratotherium simum) each year to poaching incidents, and numbers of severely injured victims found alive have increased dramatically. However, little is known about the antimicrobial treatment of wounds in rhinoceros. This study explores the applicability of enrofloxacin for rhinoceros through the use of pharmacokinetic-pharmacodynamic modelling. The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin were evaluated in five white rhinoceros after intravenous (i.v.) and after successive i.v. and oral administration of 12.5 mg/kg enrofloxacin. After i.v. administration, the half-life, area under the curve (AUCtot ), clearance and the volume of distribution were 12.41 ± 2.62 hr, 64.5 ± 14.44 μg ml-1 hr-1 , 0.19 ± 0.04 L h-1 kg-1 , and 2.09 ± 0.48 L/kg, respectively. Ciprofloxacin reached 26.42 ± 0.05% of the enrofloxacin plasma concentration. After combined i.v. and oral enrofloxacin administration oral bioavailability was 33.30 ± 38.33%. After i.v. enrofloxacin administration, the efficacy marker AUC24 : MIC exceeded the recommended ratio of 125 against bacteria with an MIC of 0.5 μg/mL. Subsequent intravenous and oral enrofloxacin administration resulted in a low Cmax: MIC ratio of 3.1. The results suggest that intravenous administration of injectable enrofloxacin could be a useful drug with bactericidal properties in rhinoceros. However, the maintenance of the drug plasma concentration at a bactericidal level through additional per os administration of 10% oral solution of enrofloxacin indicated for the use in chickens, turkeys and rabbits does not seem feasible.


Virus-induced gene silencing is an effective tool for assaying gene function in the basal eudicot species Papaver somniferum (opium poppy).
Virus-induced gene silencing (VIGS) is an attractive method for assaying gene function in species that are resistant to conventional genetic approaches. However, VIGS has been shown to be effective in only a few, closely related plant species. Tobacco rattle virus (TRV), a bipartite RNA virus, has a wide host range and so in principle could serve as an efficient vector for VIGS in a diverse array of plant species. Here we show that a vector based on TRV sequences is effective at silencing the endogenous phytoene desaturase (PapsPDS) gene in Papaver somniferum (opium poppy). We show that this vector does not compromise the growth or reproduction of poppy and the plants did not display viral symptoms. The silencing of PapsPDS resulted in a significant reduction in PapsPDS mRNA and a concomitant photobleached phenotype. The ability to rapidly assay gene function in P. somniferum will be valuable in manipulation of the opiate pathway in this pharmaceutically important species. We suggest that our vacuum infiltration method used to deliver TRV-based vectors into poppy is a promising approach for expanding VIGS to diverse angiosperm species in which traditional delivery methods fail to induce VIGS. Furthermore, these studies demonstrate the utility of TRV-VIGS for probing gene function in a basal eudicot species that is phylogenetically distant from model plant species.


Effect of plasma proteins and buffer in flushing solutions on rat kidney preservation by cold storage.
The isolated rat kidney perfused at 37 C was used to evaluate the effect of adding plasma proteins to, and varying osmolality of, cold-storage flushing solutions with or without buffering. Addition of albumin improved immediate poststorage kidney function (glomerular filtration rate [GFR], fractional sodium reabsorption, and fractional protein clearance) of all flushing solutions tested after 6 hr and 24 hr of storage. At 6 hr, these improvements also correlated with less weight gain. Flushing solutions containing citrate and sulfate produced significantly better return of function after 24 hr of cold storage than Krebs' or Collins'-derived solutions. Osmolality was unimportant with solutions containing citrate. Collins' solution with reduced MgSO4 yielded better poststorage function than conventional solution. An all-citrate isotonic solution buffered with 15 mmol THAM preserved poststorage function at 48 hr better than a similarly buffered solution containing both citrate and sulfate. Loss of dry weight during storage and subsequent perfusion appeared to correlate, in these experiments, with loss of poststorage function. The isolated rat kidney provides discrimination among various flushing solutions. The technique might be useful in the assay of additional variables that might affect the quality of kidney preservation.


[Natural history of glandulocystic fundic polyposis in Gardner's syndrome].
The authors report 3 cases of fundic gland polyposis associated with Gardner's syndrome. Control endoscopies revealed fundic gland polyposis disappearance 14, 14, and 7 years respectively after discovery, and colectomy performed at ages 29, 30, and 32, respectively. This regression, described in autonomous fundic gland polyposis, is poorly documented in Gardner's syndrome. This phenomenon is not related to colectomy. However no explanation is currently available, and further studies are necessary to determine the factors related to the natural history of fundic gland polyposis in familial adenomatosis coli/Gardner's syndrome.


Infection control and care of the older person.
Elderly people are vulnerable to infections, particularly those linked with the use of antibiotics. Once infected, they may be a risk to others in hospital or primary care. Strict adherence to infection control measures is required in the care of these patients.


Longitudinal analysis of a demonstration rural outreach alcoholism program.
A longitudinal analysis of the nature and impact of the information and education activities of an alcoholism rural outreach program (ROP) located in a rural setting was conducted during 1973-1975 via annual community surveys and program records. The study focused on the kinds and amounts of activities conducted and on the impact of these activities on community attitudes toward and knowledge about alcohol and alcoholism as well as awareness of local resources. The community education efforts had the most impact on increasing community familiarity with treatment issues, but attitudes toward these resources as well as acceptance of the disease concept of alcoholism declined over the 3 yr of the program. Knowledge about alcohol and alcoholism also declined over time, but these scores were at chance levels during each of the three community surveys. Several factors appeared to limit the impact of the ROP: (1) trying to accomplish too many different tasks with a small staff and operating budget; (2) subcontracting the program to a local mental health center, which absorbed a large proportion of staff time for nonprogram activities; and (3) the choice of community education efforts.


A theoretical study on interaction of cyclopentadienyl ligand with alkali and alkaline earth metals.
Ab initio and density functional theory calculations are performed on half-sandwich (M-Cp) and sandwich (Cp-M-Cp) complexes of alkali and alkaline earth metals (M = Li, Na, K, Mg, and Ca) with cyclopentadienyl ligand (Cp). A comparison of dissociation energies demonstrates the ease of dissociation of the complex as ions in solvent phase and preference for dissociation as radicals in gas phase. Atoms in molecules analysis is used to characterize this cation-π interaction based on electron density values obtained at the cage critical point. The contribution of various components to the complex energy is estimated using reduced variational space analysis confirming maximum contribution from the coulomb exchange followed by contributions from polarization and charge transfer components of cyclopentadienyl ligand.


The Coaches' Efficacy Expectations of Youth Soccer Players with Different Maturity Status and Physical Performance.
This study aimed to report possible anthropometrical and physical performance differences between youth soccer players with different maturity status and to report the coaches' expectations, hypothesizing that coaches would expect more from players with advanced maturity. One hundred twenty-two (122) players completed a physical performance battery. Their maturity status was estimated and the coaches' efficacy expectations (CEEs) were assessed. Players with advanced maturation had better physical performance (F = 26.5-73.4; p < 0.01) and their CEEs for strength-related tasks were different according to the maturity status (F = 8.3-10.9; p < 0.01), but not for speed-related tests, nor for their general ability to play soccer. Normalized data showed significant differences between physical performance tests and their respective CEEs within each maturity group, especially in the Post-PHV group. This study confirms the physical advantages of players with advanced maturity while it shows controversial results of how maturation affects the coaches' perceptions and, indirectly, the coaches' identification and selection of talented players.


Statin-induced rhabdomyolysis in patient with renal failure and underlying undiagnosed hypothyroidism.
Rhabdomyolysis is a syndrome characterized by muscle necrosis which causes the release of myoglobin into the bloodstream. The manifestations of this syndrome range from asymptomatic elevation of serum muscle enzymes to life-threatening cases associated with extremely high enzyme levels, electrolyte imbalance, and acute renal failure. Symptoms of rhabdomyolysis include dark urine, muscle weakness, and fatigue. Statins are commonly used drugs for the prevention and management of dyslipidemia. We present an interesting and critical case on statin-induced rhabdomyolysis with renal failure and previously undiagnosed idiopathic hypothyroidism.


A Framework for Prediction of Oncogenomic Progression Aiding Personalized Treatment of Gastric Cancer.
Mutations in genes can alter their DNA patterns, and by recognizing these mutations, many carcinomas can be diagnosed in the progression stages. The human body contains many hidden and enigmatic features that humankind has not yet fully understood. A total of 7539 neoplasm cases were reported from 1 January 2021 to 31 December 2021. Of these, 3156 were seen in males (41.9%) and 4383 (58.1%) in female patients. Several machine learning and deep learning frameworks are already implemented to detect mutations, but these techniques lack generalized datasets and need to be optimized for better results. Deep learning-based neural networks provide the computational power to calculate the complex structures of gastric carcinoma-driven gene mutations. This study proposes deep learning approaches such as long and short-term memory, gated recurrent units and bi-LSTM to help in identifying the progression of gastric carcinoma in an optimized manner. This study includes 61 carcinogenic driver genes whose mutations can cause gastric cancer. The mutation information was downloaded from intOGen.org and normal gene sequences were downloaded from asia.ensembl.org, as explained in the data collection section. The proposed deep learning models are validated using the self-consistency test (SCT), 10-fold cross-validation test (FCVT), and independent set test (IST); the IST prediction metrics of accuracy, sensitivity, specificity, MCC and AUC of LSTM, Bi-LSTM, and GRU are 97.18%, 98.35%, 96.01%, 0.94, 0.98; 99.46%, 98.93%, 100%, 0.989, 1.00; 99.46%, 98.93%, 100%, 0.989 and 1.00, respectively.


Prevalence of mycoplasmas in the semen and vaginal swabs of Danish stallions and mares.
The reproduction rate of horses is one of the lowest within domestic livestock despite advances the veterinary medicine. Infertility in horses may be due mainly to the lack of suitable selection criteria in the breeding of horses. However, acquired infertility due to genital, bacterial infections may occur. Mycoplasmas have been implicated in genital disorders and infertility of many species including humans and horses. However, their role as commensals or pathogens of the genital tract of horses is still not determined. Bacteriological examinations made on the fossa glandis, urethra, penis and semen of stallions, showed the presence of different Mycoplasma species. Therefore our study aimed to find the prevalence of Mycoplasma species and a possible association with fertility problems in Danish riding horses. Eighty semen samples from stallions and 19 vaginal swab samples from mares were tested by PCR for presence of mycoplasmal DNA. The vaginal swab samples were also cultured in the Mycoplasma specific medium. None of the samples were positive for presence of genital mycoplasmas during the screen. The lack of genital mycoplasmas observed in this study may be due to a very extensive use of artificial insemination of modern sport horses.


Evaluation of the feeding preference between the aquatic macrophytes Egeria densa and Chara indica by the invasive mollusk Melanoides tuberculata.
This study evaluated the feeding preference of the invasive mollusk Melaniudes tuberculata between the aquatic macrophytes Egeria densa and Chara indica. The experiment consisted of twelve experimental units (glass aquariums) each of which contained three liters of water and three compartments. Fragments of E. densa and C. indica were placed in separate compartments within each unit; the third compartment, which did not contain macrophytes, was used as the control. Twenty Melanoides tuberculata individuals were placed in each unit and monitored hourly over the course of 24 hours for preferential movements. Physical and chemical water variables were measured at the beginning and end of the experiment. Habitat complexity was determined through collected macrophyte fragments and determined using the Fractop program. After 24 hours, the highest average number of individuals was observed in the treatment with Chara indica (ten individuals), which differed significantly from the treatment with E. densa (four individuals) and the control treatment (two individuals). The number of individuals between the E. densa and control treatment were similar. M. tuberculata showed a clear feeding preference for C. indica.


Determination of Mitochondrial Respiration and Glycolysis in Ex Vivo Retinal Tissue Samples.
Mitochondrial respiration is a critical energy-generating pathway in all cells, especially retinal photoreceptors that possess a highly active metabolism. In addition, photoreceptors also exhibit high aerobic glycolysis like cancer cells. Precise measurements of these metabolic activities can provide valuable insights into cellular homeostasis under physiological conditions and in disease states. High throughput microplate-based assays have been developed to measure mitochondrial respiration and various metabolic activities in live cells. However, a vast majority of these are developed for cultured cells and have not been optimized for intact tissue samples and for application ex vivo. Described here is a detailed step-by-step protocol, using microplate-based fluorescence technology, to directly measure oxygen consumption rate (OCR) as an indicator of mitochondrial respiration, as well as extracellular acidification rate (ECAR) as an indicator of glycolysis, in intact ex vivo retinal tissue. This method has been used to successfully assess metabolic activities in adult mouse retina and demonstrate its application in investigating cellular mechanisms of aging and disease.


[The well-established Dalbo-Rotex-retainer and the newly developed Ticap-system. Low-cost anchorage possibilities in the removable prosthesis].
Conventional retainers for removable prostheses are frequently used in the daily practice. Financial limits, physical and mental restrictions especially among elderly or disabled patients, and/or limited prognosis of abutment teeth may require simple and less expensive alternatives. For these indications the well-established Dalbo-Rotex-retainer and the newly developed Ticap-system are available. Both systems are options for the anchorage of removable prostheses. Their clinical use is presented; furthermore their advantages and restrictions are discussed.


[Influence of a triplex superimposed treatment on HBV replication and mutation during treating chronic hepatitis B].
To observe and evaluate the influence of a new antiviral treatment scheme on HBV replication and mutation during treating chronic hepatitis B. In the test group, lamivudine, IFN alpha-2b, Astragalus membranaceus were chosen as a triplex superimposed treatment scheme for treating the patients who were on the state of HBV high replication and involved in the clinical condition of chronic hepatitis B. The control group was treated with lamivudine alone. The observed parameters percentage of patients in whom HBV DNA became undetectable (serum HBV DNA<1.6 ng/L), HBeAg/anti-HBe seroconversion rate; HBV DNA serum level; HBV YMDD mutation rate and pre-C region mutation rate. Compared with that of the control group, HBV DNA undetectable rate of the test group increased markedly at weeks 12, 36, 48(P <0.05), HBeAg negative rate of the group increased markedly at week 36, 48(P <0.05), while anti-HBe positive rate increased only at week 48 (31.58 vs.19.23%, P <0.05). After 4 weeks of treatment, HBV DNA serum level of both the test group and the control group reduced very remarkably (P <0.01), and at week 48, reduced more significantly (P <0.001). Compared with the control group, HBV DNA serum level of the test group reduced notably at week 12 (P <0.05) and very notable at week 36 and 48(P <0.01). At week 12, the pre-C region mutation occurred in the test group, and at week 24, 36,48, the pre-C region and YMDD mutations occurred in both the test group and the control group. As to anti-viral treatment of chronic hepatitis B, the triplex superimposed treatment had better efficacy than lamivudine alone.


[Antibiotic prophylaxis with cefotaxime in gynecological endoscopy].
It is now well known that even short operations of limited scope lower the body's defences by influencing the immune system. As a result this leads to a change in microbial flora which encourages an increase in the number of Gram-negative, aerobic, anaerobic and enterococcal colonies. In order to prevent infective postoperative complications which might occur after endoscopic surgery, the authors suggest using a series of valuable recommendations which are reported in this paper. Among these the most important is antibiotic prophylaxis which is able to limit the episodes of infection, thus making a positive contribution to the postoperative iter. Cefotaxime was chosen by the authors since this molecule offers both reliable and efficacious prophylaxis as has also been shown by other studies in the obstetrics and gynecological field. The results obtained by this study fully concord with data reported in the literature.


Consequences of school closures due to COVID-19 in DRC, Nigeria, Senegal, and Uganda.
In 2020 and 2021, Governments across the globe instituted school closures to reduce social interaction and interrupt COVID-19 transmission. We examined the consequences of school closures due to COVID-19 across four sub-Saharan African countries: the Democratic Republic of Congo (DRC), Nigeria, Senegal, and Uganda. We conducted a qualitative study among key informants including policymakers, school heads, students, parents, civil society representatives, and local leaders. The assessment of the consequences of school closures was informed by the Diffusion of Innovations theory which informed the interview guide and analysis. Interview transcripts were thematically analysed. Across the four countries, schools were totally closed for 120 weeks and partially closed for 48 weeks. School closures led to: i) Desirable and anticipated consequences: enhanced adoption of online platforms and mass media for learning and increased involvement of parents in their children's education. ii) Desirable and unanticipated consequences: improvement in information, communication, and technology (ICT) infrastructure in schools, development and improvement of computer skills, and created an opportunity to take leave from hectic schedules. iii) Undesirable anticipated consequences: inadequate education continuity among students, an adjustment in academic schedules and programmes, and disrupted student progress and grades. iv) Undesirable unanticipated: increase in sexual violence including engaging in transactional sex, a rise in teenage pregnancy, and school dropouts, demotivation of teachers due to reduced incomes, and reduced school revenues. v) Neutral consequences: engagement in revenue-generating activities, increased access to phones and computers among learners, and promoted less structured learning. The consequences of school closures for COVID-19 control were largely negative with the potential for both short-term and far-reaching longer-term consequences. In future pandemics, careful consideration of the type and duration of education closure measures and examination of their potential consequences in the short and long term is important before deploying them.


[Head shaking test (HSN) using to diagnose vestibule damage].
There is described a transient nystagmus provoked by shaking the head in the horizontal plane for a few seconds in both normal subjects and patients that is called Head Shaking Test (HSN) as a diagnostic tool for vestibular dysfunction. HSN is generally accepted that is generated by an asymmetrical peripheral vestibular input and a central velocity storage mechanism, which integrate and extend the peripheral vestibular signals. Purposes 1. Creation of own modification method of stimulation and registration HSN 2. Estimation of HSN test value to show asymmetrical function of vestibular system 3. Establish possibility of HSN test to localization of damage vestibular system 4. Verification this test to use it as screening test Studied group was consisted of 111 subjects that consist of 68 women and 43 men with mean age 52,4 years. All patients and controls were submitted to audiological tests and vestibular examinations According to the results of the otoneurological tests, patients were divided into: 36 with peripheral vestibular disease, 37 with central vestibular disease, 6 with both peripheral and central vestibular disease and 32 control persons. Own modified HSN test was described. Frequency of movements was approximately 2 Hz determined by metronome. HSN was recorded using ENG apparatus produced by Hartmann. In the first study stage incidence of HSN-H and HSN-V related to localization of vestibular organ damage, symmetric and asymmetric reaction in tested. It was observed more incidence of HSN-H and HSN-V in patients with peripheral and central lesion of vestibular system than in control group. Estimation of HSN incidence related to kinetic test--acceleration-deceleration rotary test shows the same HSN frequency in compared groups, with symmetric or asymmetric reaction in rotary test. HSN frequency related to caloric test (canal paresis) showed statistic differences between normal and canal paresis reaction in caloric test. Analysis incidence of HSN-V revealed no significant differences between examined groups. In the second studied stage the sensitivity and specificity were examined. 1. It is possible to make HSN test using metronome and ENG recording 2. HSN test may be use to reveal asymmetry of vestibular function. 3. HSN is helpful to diagnose peripheral and central lesion to some extent. 4. HSN is not useful as screening test


High-Field Nuclear Magnetic Resonance Studies Reveal New Structural Landscape of Sulfur-Vulcanized Natural Rubber.
Despite intensive research efforts over the past 3 decades, the structural analysis of sulfur-vulcanized natural rubber (NR) remains challenging owing to the complexity and low population of its sulfur moieties. Herein, solid vulcanized NR samples and NR samples reacted with sulfur and other reactants in an organic solvent were analyzed by solid-state NMR with fast magic-angle spinning and solution NMR, respectively. The present high-field two-dimensional NMR analysis revealed six novel sulfur moieties in these samples, including cyclic sulfides, cyclic di/polysulfides, and crosslinked structures with a vinylidene group. While previous studies reported a variety of sulfur-crosslinked structures in NR, our analysis identified only two dominant types of crosslinked structures that matched those reported previously. Our NMR assignments for the crosslinked structures were inconsistent to a large extent with those presented in the previous studies; thus, in the current work, the crosslinked structures were reassigned using the new data. Based on quantitative NMR analysis, this study also provides the first tangible evidence that cyclic rather than crosslinked sulfides can be the dominant sulfur moieties in vulcanized NR. These results may drastically alter the previously established structural landscape of sulfur-vulcanized NR.


Modeling torque versus speed, shot noise, and rotational diffusion of the bacterial flagellar motor.
We present a minimal physical model for the flagellar motor that enables bacteria to swim. Our model explains the experimentally measured torque-speed relationship of the proton-driven E. coli motor at various pH and temperature conditions. In particular, the dramatic drop of torque at high rotation speeds (the "knee") is shown to arise from saturation of the proton flux. Moreover, we show that shot noise in the proton current dominates the diffusion of motor rotation at low loads. This suggests a new way to probe the discreteness of the energy source, analogous to measurements of charge quantization in superconducting tunnel junctions.


A confinement induced spectroscopic study of noble gas atoms using equation of motion architecture: Encapsulation within fullerene's voids.
A relativistic study of spectroscopic properties of the endohedral fullerenes Ng@C60q (where Ng = He, Ne and q=0,±1,±2 are the charges) associated with the C60 molecule has been done using the equation of motion coupled cluster (EOM-CC) methodology. Specific properties estimated are the transition energies, dipole oscillator strengths, and transition probabilities for the low-lying excitations 1s2(1S0) → 1snp (1P1) (n = 2, 3, 4) for He@C60q and 1s22s22p6 (1S0) → 1s22s22p5ns∕nd (1P1) (n = 3, 4) for Ne@C60q, which have been compared with those for the isolated atom to depict the confinement effect of the host molecule on the encapsulated atom. This is accomplished by introducing an effective potential to the atomic Hamiltonian induced by the fullerene moiety and its charge. The EOM-CC results have been compared with those estimated with the random phase approximation (and configuration interaction singles) to understand the effect of electron correlation under such confinement. The systematic and interesting behavior of the properties is highlighted indicating the effect of fullerene cage potential on the redistribution of electron density of the guest atom.


C/EBPalpha inactivation in FAK-overexpressed HL-60 cells impairs cell differentiation.
We previously demonstrated that focal adhesion kinase (FAK)-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli such as oxidative stress, ionizing radiation and TNF-receptor-induced ligand (TRAIL) compared with vector-transfected (HL-60/Vect) cells. Here, we show that HL-60/FAK cells are highly resistant to all-trans retinoic acid (ATRA)-induced differentiation, whereas original HL-60 or HL-60/Vect cells are sensitive. Treatment with ATRA at 1 muM for 5 days markedly inhibited the proliferation and increased the expression of differentiation markers (CD38, CD11b) in HL-60/Vect cells, but showed no such effect in HL-60/FAK cells. Electrophoretic mobility shift assay (EMSA) using an oligonucleotide for the c/EBP consensus binding sequence showed that c/EBPalpha was activated in ATRA-treated HL-60/Vect cells but not in HL-60/FAK cells, indicating that c/EBPalpha activation by ATRA was impaired in HL-60/FAK cells. In addition, the association of retinoblastoma protein (pRb) and c/EBPalpha after treatment with ATRA was seen in HL-60/Vect cells but not in HL-60/FAK cells. Further, hyperphosphorylation of pRb was observed in HL-60/FAK cells. Finally, the introduction of FAK siRNA into HL-60/FAK cells resulted in the recovery of sensitivity to ATRA-induced differentiation, confirming that the inhibition of HL-60/FAK differentiation resulted from both the induction of pRb hyperphosphorylation and the inhibition of association of pRb and c/EBPalpha.


Conformationally restricted nucleotides as a probe of structure-function relationships in RNA.
We introduce the use of commercially available locked nucleic acids (LNAs) as a functional probe in RNA. LNA nucleotides contain a covalent linkage that restricts the pseudorotation phase of the ribose to C3'-endo (A-form). Introduction of an LNA at a single site thus allows the role of ribose structure and dynamics in RNA function to be assessed. We apply LNA probing at multiple sites to analyze self-cleavage in the lead-dependent ribozyme (leadzyme), thermodynamic stability in the UUCG tetraloop, and the kinetics of recognition of U1A protein by U1 snRNA hairpin II. In the leadzyme, locking a single guanosine residue into the C3'-endo pucker increases the catalytic rate by a factor of 20, despite the fact that X-ray crystallographic and NMR structures of the leadzyme ground state reported a C2'-endo conformation at this site. These results strongly suggest that a conformational change at this position is critical for catalytic function. Functional insights obtained in all three systems demonstrate the highly general applicability of LNA probing in analysis of the role of ribose orientation in RNA structure, dynamics, and function.


Modeling the Ebolavirus Life Cycle with Transcription and Replication-Competent Viruslike Particle Assays.
Ebolaviruses are the causative agent of a severe hemorrhagic fever with high case fatality rates, for which no approved specific therapy is available. As biosafety level 4 (BSL4) agents, work with live ebolaviruses is restricted to maximum containment laboratories. Transcription and replication-competent viruslike particle (trVLP) systems are reverse genetics-based life cycle modeling systems that allow researchers to model virtually the entire ebolavirus life cycle outside of a maximum containment laboratory. These systems can be used to dissect the virus life cycle, and thus increase our understanding of virus biology, as well as for more applied uses such as the screening and development of novel antivirals, and thus represent powerful tools for work on ebolaviruses.


Generation of photon pairs by stimulated emission in ring resonators.
Third-order parametric downconversion (TOPDC) describes a class of nonlinear interactions in which a pump photon is converted into a photon triplet. This process can occur spontaneously or it can be stimulated by seeding fields. Here we show that stimulated TOPDC (StTOPDC) can be exploited for the generation of quantum correlated photon pairs. We model StTOPDC in a microring resonator, predicting observable pair generation rates in a microring engineered for third-harmonic generation, and we examine the peculiar features of this approach when compared with second-order spontaneous parametric downconversion and spontaneous four-wave mixing. We conclude that if the experimental difficulties associated with implementing StTOPDC can be overcome, it may soon be possible to demonstrate this process in resonant integrated devices.


Selective alterations of RNA in rat hippocampus after entorhinal cortex lesioning.
In vitro translation products from RNA of rat hippocampus after deafferentation by entorhinal cortex lesions were analyzed by two-dimensional gel electrophoresis. Although hippocampal total RNA yield was not affected 14 days after the lesion, analysis of the gels showed reproducible changes in the steady-state level of several transcripts. Glial fibrillary acidic protein RNA increased 2-fold over control hippocampi RNA. Moreover, seven other transcripts of unknown identity had increased prevalence in the denervated hippocampus. The changes, which ranged from 2- to 20-fold, involved mRNA encoding small slightly acidic polypeptides: 12 kDa (pI 5.6), 13 kDa (pI 6.1), 20 kDa (pI 5.8), 31 kDa (pI 5.7), 33 kDa (pI 5.7), 35 kDa (pI 5.6), and 53 kDa (pI 5.4). These results suggest new molecular markers for analyzing the complex mechanisms of synaptic reorganization in the dentate gyrus after deafferentation.


Echo acquisition during frequency-selective pulse trains for proton spectroscopy of metabolites in vivo.
Suppression of water and fat in proton spectra of rat skeletal muscle was achieved by acquisition of the spin echoes formed in the steady state after a series of frequency-selective composite pulses of constant amplitude, phase, and interpulse interval. The method enables observation of lactate in the presence of fat without resorting to difference spectroscopy, and on spectrometers which permit data acquisition immediately prior to a pulse, enables much faster data accumulation compared to standard echo sequences.


Concomitant Othello syndrome and impulse control disorders in a patient with Parkinson's disease: A case report.
Othello syndrome (OS) is characterized by delusional beliefs concerning the infidelity of a spouse or sexual partner, which may lead to extreme behaviors. Impulse control disorders refer to behaviors involving repetitive, excessive, and compulsive activities driven by an intense desire. Both OS and impulse control disorders in Parkinson's disease (PD) may be side effects of dopamine agonists. At present, there are only a few case reports and studies related to PD with concomitant OS and impulse control disorders. We describe a 70-year-old male patient with PD, OS, and impulse control disorders, who presented with a six-month history of the delusional belief that his wife was having an affair with someone. He began to show an obvious increase in libido presenting as frequent masturbation. He had been diagnosed with PD ten years earlier and had no past psychiatric history. In his fourth year of PD, he engaged in binge eating, which lasted approximately one year. Both OS and hypersexuality were alleviated substantially after a reduction of his pramipexole dosage and a prescription of quetiapine. Given its potential for severe consequences, OS should be identified early, especially in patients undergoing treatment with dopamine agonists.


Identification of candidate radioresistant genes in human squamous cell carcinoma cells through gene expression analysis using DNA microarrays.
Radiation therapy is currently the standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Individual OSCCs display a wide range of radiosensitivity (RS). To identify genes associated with radioresistance (RR) of OSCC and establish a useful method of predicting radio-therapeutic effectiveness, we examined the gene expression patterns of OSCC cell lines that exhibited different responses to ionizing radiation (IR) by clonogenic survival assay using an in-house cDNA microarray consisting of 2,201 human genes and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR). Microarray analysis showed overexpression of 7 genes in the radioresistant cell line, HSC2, and 2 genes in the radiosensitive cell line, HSC3. The changes in expression levels in 7 of 9 genes (Cytokeratin18, DTNBP1, ASNA1, Tcp20, Cyclophilin F, KIAA0218, and HBp17) were confirmed with QRT-PCR. Of these, the genetic alterations of Tcp20, whose expression was remarkably elevated in radioresistant HSC2 cells after IR, were investigated. The escalation of X-ray doses resulted in an enhanced Tcp20 expression level in HSC2 cells compared to radiosensitive HSC3 cells (P<0.05, Mann-Whitney U test). These results suggest that the identified genes, which include Tcp20, may play an important role in conferring RR to OSCC, and could also be useful in identifying cases of OSCC with more radioresistance.