Long-term followup of renal morphology and function in children with recurrent pyelonephritis.
Renal morphology and function were evaluated in 161 children with recurrent pyelonephritis with or without vesicoureteral reflux and with or without scarred or small kidneys. The patients were followed for 1 to 21 years. Renal function was determined by glomerular filtration rate and effective renal plasma flow by clearances of inulin and paraaminohippuric acid. Of 105 children with normal kidneys originally small or scarred kidneys developed in 37, of whom 22 had grade III or greater vesicoureteral reflux, while small kidneys developed in 13 of 29 children with renal scarring originally. Of the 37 children with normal kidneys originally renal parenchymal scarring developed in 14 after the age of 4 to 5 years. Glomerular filtration rate was already < -2 standard deviations of that of controls in 51% of the patients at the first and in 53% at the last investigation of renal function. Of these patients with a glomerular filtration rate of < -2 standard deviations 69% had small or parenchymally reduced kidneys most of whom had the first pyelonephritis episode before age 3 years. Patients with small kidneys had a lower glomerular filtration rate than those with normal sized kidneys, whether scarred or not. The low glomerular filtration rate and its subsequent further reduction were related to kidney size and not to the presence or degree of vesicoureteral reflux. However, in individual patients the rate of functional deterioration could not be predicted from the radiological findings. Patients with bilateral small kidneys seemed to show the greatest decrease in glomerular filtration rate during followup as did those with grade III or greater reflux undergoing surgery bilaterally and those patients also had a lower glomerular filtration rate at the last investigation compared to patients not undergoing surgery. In conclusion, renal functional damage seems to occur early in the course of the disease and seems to be related to kidney size but there is a further slow progression with reduction in renal function which occurs, although this is difficult to predict from the radiological changes in individual patients. Therefore, patients with recurrent pyelonephritis should be followed regularly by glomerular filtration rate determination using an accurate method.


Synthesis, chromatographic resolution and chiroptical properties of carboxyibuprofen stereoisomers: major metabolites of ibuprofen in man.
The chromatographic resolution of the four stereoisomers of carboxy-ibuprofen, a major metabolite of ibuprofen in man, was achieved using a Chiralpak AD chiral stationary phase (CSP) (J.T. Baker, Milton, Keynes, UK). The elution order of the stereoisomers was determined to be 2'S,2R;2'R,2R;2'R,2S;2'S,2S by a combination of stereoselective synthesis of diastereoisomeric mixtures and analysis of the two diastereoisomers isolated from human urine following the administration of (S)-ibuprofen. The individual stereoisomers were isolated by semipreparative chiral phase chromatography and characterized by circular dichroism spectroscopy.


Assay of N-nitrosamines in foodstuffs produced in the USSR by gas-liquid chromatography with a thermal energy analyser.
The content of volatile N-nitrosamines in over 4000 samples of domestic foodstuffs of plant and animal origin were studied. It was found that 88% of the samples studied contained N-nitrosamines, the greatest amounts being detected in some samples of malt and beer, fish products and some meat products. The impact of food processing technologies on the formation of N-nitrosamines is discussed. Possibilities of preventing the accumulation of N-nitrosamines during the process of food production are discussed.


Opiate receptor sensitivity in depressed patients before and after clomipramine treatment.
To measure opiate receptor sensitivity, the effects of naloxone on beta-endorphin and cortisol serum levels were determined before and after 3 weeks of clomipramine treatment (75 mg/day i.v.) in 12 patients with major depressive disorder. The opiate antagonist significantly increased both hormonal levels. The only significant endocrine differences between pre- and post-treatment were basal and maximal cortisol levels, which were elevated before antidepressant therapy. The rise in the cortisol or beta-endorphin serum level after naloxone injection was not affected by clomipramine treatment. There was no significant relationship between depression score and basal or stimulated endocrine variables. These data do not indicate a distinct effect of antidepressants on opiate receptor sensitivity.


Human Umbilical Cord Mesenchymal Stromal Cell Treatment of Severe COVID-19 Patients: A 3-Month Follow-Up Study Following Hospital Discharge.
Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% ± 8.46% and 59.45% ± 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% ± 8.00% and 58.97% ± 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 ± 3.69 vs. 31.9 ± 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 ± 0.88 vs. 1.00 ± 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.


Demonstration of the Rhesus haplotype CdE (r-y) in the genotype of 48 subjects from 8 families. Genotype CdE/CdE (r-yr-y) in 2 members of the same family.
Forty-eight individuals heterozygous for CdE (R-Y) haplotype were identified in the pedigrees of 8 kindreds containing 128 members. Two homozygotes CdE/CdE (r-yr-y) were found in a large inbred kindred. Our study among French blood donors of the Seine-Maritime region demonstrated that about one of two individuals possessing the Rhesus phenotype CcdEd (rh'rh') carried the CdE (r-y) haplotype.


Chemotherapy-related bilateral dermatitis associated with eccrine squamous syringometaplasia: reappraisal of epidemiological, clinical, and pathological features.
A characteristic cutaneous eruption related to the use of cytostatic chemotherapeutic drugs has been described in the literature. This condition appears to be characterized by an erythematous eruption, primarily affecting the intertriginous areas bilaterally, together with eccrine squamous syringometaplasia as the main histologic feature. We sought to establish the epidemiologic, clinical, and histologic characteristics of this poorly defined chemotherapy drug-related eruption. Retrospective data were collected from 21 consecutive patients with this clinical and histopathologic pattern who attended an oncology center between January 1999 and September 2009. Two skin biopsy specimens were obtained from all patients, with the first being taken within 24 hours of onset, and the second 72 to 96 hours after onset. The patients analyzed were predominantly female (72%), with a mean age of 52 years (range 10-69 years). The lesions presented clinically as bilateral erythematous plaques affecting both axillae (95%), groin (88%), and side aspects of the neck (48%). The main histologic feature in all cases was eccrine squamous syringometaplasia, characterized by the transformation of the eccrine cuboidal epithelium into two or more layers of squamous cells with intercellular bridges. The onset of the eruption appeared within 30 days (range 2-30 days) after the initiation of the cytostatic agent infusion. The lesions resolved with desquamation and postinflammatory hyperpigmentation. The same cutaneous pattern recurred in up to 50% of patients in whom the oncologist reintroduced the cytostatic treatment. Small sample size was a limitation. We suggest the term "chemotherapy-related bilateral dermatitis associated with eccrine squamous syringometaplasia" to describe this distinctive entity, which is primarily associated with pegylated liposomal doxorubicin infusions and chemotherapeutic regimens used in autologous bone-marrow transplantation.


Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors.
The Wee1 kinase inhibitor adavosertib abrogates cell-cycle arrest, leading to cell death. Prior testing of twice-daily adavosertib in patients with advanced solid tumors determined the recommended phase II dose (RPh2D). Here, we report results for once-daily adavosertib. A 3 + 3 dose-escalation design was used, with adavosertib given once daily on days 1 to 5 and 8 to 12 in 21-day cycles. Molecular biomarkers of Wee1 activity, including tyrosine 15-phosphorylated Cdk1/2 (pY15-Cdk), were assessed in paired tumor biopsies. Whole-exome sequencing and RNA sequencing of remaining tumor tissue identified potential predictive biomarkers. Among the 42 patients enrolled, the most common toxicities were gastrointestinal and hematologic; dose-limiting toxicities were grade 4 hematologic toxicity and grade 3 fatigue. The once-daily RPh2D was 300 mg. Six patients (14%) had confirmed partial responses: four ovarian, two endometrial. Adavosertib plasma exposures were similar to those from twice-daily dosing. On cycle 1 day 8 (pre-dose), tumor pY15-Cdk levels were higher than baseline in four of eight patients, suggesting target rebound during the day 5 to 8 dosing break. One patient who progressed rapidly had a tumor WEE1 mutation and potentially compensatory PKMYT1 overexpression. Baseline CCNE1 overexpression occurred in both of two responding patients, only one of whom had CCNE1 amplification, and in zero of three nonresponding patients. We determined the once-daily adavosertib RPh2D and observed activity in patients with ovarian or endometrial carcinoma, including two with baseline CCNE1 mRNA overexpression. Future studies will determine whether CCNE1 overexpression is a predictive biomarker for adavosertib.


Complexin cross-links prefusion SNAREs into a zigzag array.
Complexin prevents SNAREs from releasing neurotransmitters until an action potential arrives at the synapse. To understand the mechanism for this inhibition, we determined the structure of complexin bound to a mimetic of a prefusion SNAREpin lacking the portion of the v-SNARE that zippers last to trigger fusion. The 'central helix' of complexin is anchored to one SNARE complex, while its 'accessory helix' extends away at ~45° and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion. We expected the accessory helix to compete with the v-SNARE for t-SNARE binding but found instead that the interaction occurs intermolecularly. Thus, complexin organizes the SNAREs into a zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion.


Site-specific transgenesis by Cre-mediated recombination in Drosophila.
Transposons such as P elements are routinely used to stably transfer exogenous DNA (transgenes) into the Drosophila genome. Transgene insertion events, however, are essentially random and are subject to 'position effects' from nearby endogenous regulatory elements. Here we describe a microinjection-based system that uses Cre-mediated recombination to insert transgenes into precise genomic 'landing sites'. The system is simple and efficient, and will permit precise comparisons between multiple transgenic constructs.


From University to Court: The Reversal of Stahl's Positions on Gold-Making.
Georg Ernst Stahl, an influential chymical-medical author of the late seventeenth and early eighteenth centuries, first believed in alchemical transmutation and reversed his position over the course of his career. This essay begins by placing Stahl's early teaching in alchemy in a larger background in which German princes and academics shared intense interest in gold-making. Then, tracing Stahl's intellectual development, it shows that he developed an increasing reservation about alchemy, though he remained open to the possibility of transmutation during his tenure at Halle. Finally, this essay shows that Stahl's service to King Friedrich Wilhelm I was an important context for his later public denunciation of alchemy. An analysis of Stahl's career shift from a university professor to a royal physician at court thus sheds light on the reversal of his positions.


Intermittent hypoglossal nerve palsy caused by a calcified persistent hypoglossal artery: an uncommon neurovascular compression syndrome.
Neurovascular compression is assumed to cause symptoms like trigeminal neuralgia, hemifacial spasm and vestibular paroxysmia. We present a patient with recurrent episodes of transient dysarthria due to isolated right hypoglossal nerve (HN) palsy. We describe the first case of a calcified persistent hypoglossal artery (PHA) as the putative cause of a hypoglossal neurovascular compression syndrome. Our patient received a daily low-dose medication of carbamazepine resulting in complete relief of symptoms. In conclusion, PHA is not only an anatomic variation but also a possible cause of a neurovascular compression syndrome leading to intermittent HN palsy.


Repeat Resection and Intraoperative Radiotherapy for Malignant Gliomas of the Brain: A History and Review of Current Techniques.
The degree of primary resection of malignant brain gliomas (MBGs) has correlated positively with progression-free and overall survival. The indications for surgery and reoperation in MBG relapse remain controversial. Surgery will not be curative and should be followed by adjuvant treatment. We reviewed the reported studies with respect to repeat resection and the various methods of intraoperative radiotherapy for MBGs from the initial experience with high-energy linear accelerators in Japan to modern, integrated brachytherapy solutions using solid and balloon applicators. Because of the findings from our review, we have begun to research into the use of intraoperative balloon brachytherapy for recurrent MBGs.


Tuberculosis: health care and surveillance in prisons.
To identify tuberculosis-related health care and surveillance actions in Prison Health Units. Cross-sectional study, of quantitative, exploratory and descriptive character. We visited 13 Teams of Prison Health, and nurses and technicians were interviewed regarding epidemiological surveillance instruments, physical structure and materials. Search for respiratory symptoms in admission was reported by 6 (46.2%) of the teams, and the smear microscopy was the most requested test. The Logbook of Respiratory Symptoms and the Logbook for Monitoring Tuberculosis Cases were used in 7 (53.8%) institutions. Two of them (15.4%) had a location for sputum collection and 1 (7.7%) had a radiographer. The Directly Observed Therapy was reported in 7 (53.8%) units. Health care actions related to the search for respiratory symptoms and Directly Observed Therapy should be expanded, as well as surveillance actions and recording in official documents of the National Tuberculosis Control Program.


Changes in subchondral bone structure and mechanical properties do not substantially affect cartilage mechanical responses - A finite element study.
Subchondral bone structure has been observed to change in osteoarthritis (OA). However, it remains unclear how the early-stage OA changes affect the mechanics (stresses and strains) of the osteochondral unit. In this study, we aim to characterize the effect of subchondral bone structure and mechanical properties on the osteochondral unit mechanics. A 3-D finite element model of the osteochondral unit was constructed based on a rabbit femoral condyle μCT data and subjected to creep loading in indentation. Trabecular bone volume fraction, subchondral bone plate thickness, and equilibrium modulus were varied (including experimentally observed changes in early OA) to characterize the effect of these parameters on the osteochondral unit mechanics. At the end of the creep phase, the maximum principal strain at the bone surface of the cartilage-bone interface was decreased by 50% when the trabecular bone volume fraction was reduced from 48% to 28%. The maximum principal stress at the same location was decreased by 36% when plate thickness was reduced by 100 μm (-31%). In cartilage, small changes in the mechanics were seen near the cartilage-bone interface with a considerably thinner (-31%) plate. The changes in trabecular bone volume fraction, subchondral bone thickness and plate equilibrium modulus did not substantially affect the cartilage mechanics. Our results suggest that experimentally observed changes that occur in the subchondral bone structure in early OA have a minimal effect on cartilage mechanics under creep indentation loading; clear changes in the cartilage mechanics were seen only with an unrealistically soft subchondral bone plate.


Data-driven test strategy for COVID-19 using machine learning: A study in Lahore, Pakistan.
We aimed at giving a preliminary analysis of the weakness of a current test strategy, and proposing a data-driven strategy that was self-adaptive to the dynamic change of pandemic. The effect of driven-data selection over time and space was also within the deep concern. A mathematical definition of the test strategy were given. With the real COVID-19 test data from March to July collected in Lahore, a significance analysis of the possible features was conducted. A machine learning method based on logistic regression and priority ranking were proposed for the data-driven test strategy. With performance assessed by the area under the receiver operating characteristic curve (AUC), time series analysis and spatial cross-test were conducted. The transition of risk factors accounted for the failure of the current test strategy. The proposed data-driven strategy could enhance the positive detection rate from 2.54% to 28.18%, and the recall rate from 8.05% to 89.35% under strictly limited test capacity. Much more optimal utilization of test resources could be realized where 89.35% of total positive cases could be detected with merely 48.17% of the original test amount. The strategy showed self-adaptability with the development of pandemic, while the strategy driven by local data was proved to be optimal. We recommended a generalization of such a data-driven test strategy for a better response to the global developing pandemic. Besides, the construction of the COVID-19 data system should be more refined on space for local applications.


Dietary habits and mammographic patterns in patients with breast cancer.
Between 1983 and 1986, dietary history interviews were conducted with 238 women aged 50-65 years who had surgery for stage I-II breast cancer. Diagnostic mammograms were coded in line with Wolfe's criteria in N1, P1, P2, and Dy patterns. Women with Dy pattern reported significantly higher intake of total fat, monounsaturated fatty acids (FA), polyunsaturated FA, n-3 FA, n-6 FA in per cent of energy (E%), and alpha-tocopherol in mg/10 MJ. Fat intake was lowest in women with N1 pattern and highest in those having Dy pattern. Patients having ER-rich cancers and Dy pattern reported significantly higher intake of total fat, monounsaturated FA, polyunsaturated FA, n-6 FA (E%), and alpha-tocopherol (mg/10 MJ), as well as significantly lower intake of carbohydrate (E%) and calcium (g/10 MJ). In the stepwise multivariate analysis, the multivariate-odds ratio (OR) for having P2 + Dy patterns was 1.06 (95% confidence interval (CI), 1.02-1.12) for each increment in E% of total fat. In women with ER-rich tumors this OR was 1.09 (95% CI, 1.02-1.16). The highest self-reported body mass index (BMI) was observed in women with N1 + P1 patterns. OR for having P2 + Dy patterns was 0.91 (95% CI, 0.83-0.98) for each increment in 1 kg/m2 of BMI. The results suggest that dietary habits affect the mammographic parenchymal pattern in women with breast cancer and that a high fat intake is associated with a higher proportion of mammograms with Dy pattern in such patients.


[Heterotopic ossification in cancer of the stomach. An experimental contribution to a clinical phenomenon (author's transl)].
Heterotopic ossifications are found frequently in rats with nitrosoguanidine-induced carcinomas of the gastric stump. The following steps of differentiation of the desmal ossification in the stump carcinomas are demonstrated: 1. Osteoblasts. 2. Osteoid. 3. Woven Bone reticular network. 4. Lamellar bone. The islands of metaplastic bone cells are predominantly located in the invasive marginal area of the carcinoma of the gastric stump. The histology is similar to that one seen in stomach cancer of men. Therefore, the here described model seems to be suitable for further study of the metaplastic bone formation in the gastrointestinal tract.


The Adverse Effects Profile of Teprotumumab.
Teprotumumab therapy for thyroid eye disease (TED) patients represents a major step forward. It targets and inhibits the insulin-like growth factor-1 receptor (IGF-1R), and its effectiveness is based on its interconnectedness with the thyrotropin receptor. However, IGF-1R has a ubiquitous expression and several adverse effects have been reported with teprotumumab use. Describing these adverse effects for better understanding is the purpose of this review. We reviewed the oncological studies in which teprotumumab was initially used. Subsequently we reviewed the clinical trials for TED and then the case series and case reports associated with teprotumumab use since it is US Food and Drug Administration approval (January 2020). We focused on common and/or serious adverse effects reported with the use of teprotumumab. We described the common occurrence of hyperglycemia (10%-30% incidence), its risk factors and suggested management. Hearing changes are described, a broad spectrum from mild ear pressure to hearing loss (sensorineural mechanism). Risk factors, suggested monitoring, and possible upcoming therapies are reviewed. We also reviewed data on fatigue, muscle spasms, hair loss, weight loss, gastrointestinal disturbances, menstrual changes, and infusion reactions. We noted some discrepancies between adverse effects in oncological studies vs studies focused on TED, and we aimed to explain these differences. The use of teprotumumab should consider patient's values and preferences in balancing the expected benefit with these potential risks. Future drugs targeting IGF-1R should investigate these adverse effects for a possible class effect. Combination therapies with different agents hopefully will be identified that maximize benefits and minimize risks.


Risk factors for intrauterine growth restriction in a socio-economically disadvantaged region.
Risk factors for pregnancies being complicated by the birth of a small-for-gestational age (SGA) infant were analysed in a socio-economically disadvantaged area, with separate analysis for population-based and customized-based birth weight percentiles. A retrospective case-controlled study of all singleton pregnancies resulting in the birth of an infant with a birth weight < 10 population-based centile, born in the Northern suburbs of metropolitan Adelaide, between 1998 and 2003. Significant risk factors in the univariate analysis were subsequently checked with multivariate analysis. The analyses confirm marked differences between population-based and customized-birth weight centiles. Patterns of risk factors show clear differences in risk factors for these two different SGA groups. Univariate analyses of all (nulliparous and multiparous women) customized SGA infants shows us the following odds ratio's (OR); unemployment OR 2.06, 95% confidence interval (CI) 1.46-2.92, being a single mother OR 1.90, CI 1.76-2.05, smoking OR 3.24, CI 2.32 - 4.54, recreational drug use OR 2.40, CI 1.55-3.70, mental health problems OR 1.52, CI 1.04-2.23, domestic violence OR 3.42, CI 1.26-9.29, being healthy OR 0.43, CI 0.30-0.61, preeclampsia OR 1.73, CI 1.01-2.97, and BMI < 30 OR 0.63 CI 0.43-0.93. Length of pregnancy interval had no relationship whatsoever with the risk of being delivered of an SGA infant. Multivariate analyses for customized SGA showed five factors with an OR > 2 (95% CI not crossing 1), including unemployment, smoking, maternal age > 34 years, not being healthy and preeclampsia, while different paternity, age 25-34 compared to age < 25 were also found to be significant risk factors. Higher systolic blood pressure was found to convey significant protection. When studying risk factors for pregnancies complicated by the birth of an SGA infant, both population-derived and customized growth centiles should be utilized. This study confirms the importance of smoking as a major risk factor, our data also show major protection being conveyed by having a regular job and being generally healthy. Pregnancy interval did not have any relationship with the birth of SGA infants, while paternity change was identified as a clear risk factor. Although genuine preeclampsia persists as a clear risk factor, higher systolic blood pressure appears to convey protection.


5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy.
Fifty-one patients with metastatic adenocarcinoma received Folinic Acid (FA) combined with 5-Fluorouracil (5FU) in a Phase I-II clinical trial. Two different schedules were used: (a) bolus infusion--5FU 7-12 mg/kg/d I.V. d1-5, FA 1.6 mg/kg/d I.V. d1-5; (b) continuous infusion--5FU 600-1200 mg/m2/d I.V. d1-4, FA 60 mg/m2/d I.V. d1-4. Mucositis and myelosuppression were dose-limiting, with recommended dose levels of 5FU for further trials being 10 mg/kg/d I.V. d1-5 and 1000 mg/m2/d I.V. d1-4 on the bolus and continuous infusion schedules, respectively. Forty-one evaluable patients with measurable disease were treated. Thirty-six had metastatic colorectal carcinoma, and 14/36 patients responded (CR-1, PR-13), including responses in three patients who had previously failed 5FU treatment alone. In the two patients with unknown primary sites and three with gastric cancer, no response were seen. 5FU and FA have activity equivalent to 5FU alone, and the responses in patients receiving prior 5FU suggest it may be superior. The possibility that toxicity may be enhanced does exist. Further trials of these two agents are warranted.


Inhibition by lead ion of Electrophorus electroplax (Na+ + K+)-adenosine triphosphatase and K+-p-nitrophenylphosphatase.
Inorganic lead ion in micromolar concentrations inhibits Electrophorus electroplax microsomal (Na+ + K+)-adenosine triphosphatase ((Na+ + K+)-ATPase) and K+-p-nitrophenylphosphatase (NPPase). Under the same conditions, the same concentrations of PbCl2 that inhibit ATPase activity also stimulate the phosphorylation of electroplax microsomes in the absence of added Na+. Enzyme activity is protected from inhibition by increasing concentrations of microsomes, ATP, and other metal ion chelators. The kinetics follow the pattern of a reversible noncompetitive inhibitor. No kinetic evidence is elicited for interactions of Pb2+ with Na+, K+, Mg2+, ATP, or p-nitrophenylphosphate. Na+- ATPase, in the absence of K+, and (Na+ + K+)-NPPase activity at low [K+] are also inhibited. ATP inhibition of NPPase is not reversed by Pb2+. The calculated concentrations of free [Pb2+] that produce 50% inhibition are similar for ATPase and NPPase activities. Pb2+ may act at a single independent binding site to produce both stimulation of the kinase and inhibition of the phosphatase activities.


A qualitative analysis of case managers' use of harm reduction in practice.
The harm reduction approach has become a viable framework within the field of addictions, yet there is limited understanding about how this approach is implemented in practice. For people who are homeless and have co-occurring psychiatric and substance use disorders, the Housing First model has shown promising results in employing such an approach. This qualitative study utilizes ethnographic methods to explore case managers' use of harm reduction within Housing First with a specific focus on the consumer-provider relationship. Analysis of observational data and in-depth interviews with providers and consumers revealed how communication between the two regarding the consumer's substance use interacted with the consumer-provider relationship. From these findings emerged a heuristic model of harm reduction practice that highlighted the profound influence of relationship quality on the paths of communication regarding substance use. This study provides valuable insight into how harm reduction is implemented in clinical practice that ultimately has public health implications in terms of more effectively addressing high rates of addiction that contribute to homelessness and health disparities.


Estrogen modifies an electrocommunication signal by altering the electrocyte sodium current in an electric fish, Sternopygus.
Many species of electric fish emit sexually dimorphic electrical signals that are used in gender recognition. In Sternopygus, mature females produce an electric organ discharge (EOD) that is higher in frequency and shorter in pulse duration than that of mature males. EOD pulse duration is determined by ion currents in the electrocytes, and androgens influence EOD pulse duration by altering the inactivation kinetics of the electrocyte sodium current. We examined whether estrogen modulates the female-specific EOD and, if so, whether it regulates EOD pulse duration by acting on the same androgen-sensitive ion current in the electrocytes. We implanted gonadectomized Sternopygus with either empty SILASTIC capsules (control), one capsule filled with estradiol-17beta (E2; low dose), or three capsules of E2 (high dose). Twelve days after implantation, E2-treated fish had plasma E2 levels approximately 3.3-fold (low dose) or approximately 7.1-fold (high dose) higher than controls. After implantation, both E2-treated groups had higher EOD frequency and shorter EOD pulse duration than controls and their own preimplantation values. Through immunocytochemistry, we identified immunoreactive estrogen receptors in the nuclei of electrocytes, indicating that these cells are directly responsive to estrogen. In addition, voltage-clamp studies showed that E2 affected the electrocyte ion currents kinetics: the sodium inactivation time constant was significantly lower in E2-treated fish than in controls. Thus, sexual dimorphism in the electrocommunication signal results, at least in part, from estrogens and androgens acting in opposite directions on the same ion current in the electrocytes.


The inhibitory mechanism of 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx) formation by ultraviolet-gallic acid (UV-GA) during the oil-frying process of squid.
The inhibitory effect of ultraviolet-gallic acid (UV-GA) on carbonyl valence and intermediates and precursors of 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx) was investigated to futher clarify the inhibitory mechanism for safety control the quality of oil-fried squid. Ultraviolet C-treated gallic acid (UVC-GA) and ultraviolet B-treated gallic acid (UVB-GA) were produced by ultraviolet 225 nm of band C and 300 nm of band B, respectively. The MeIQx contents in oil-fried squid were significantly higher, and UVC-GA and UVB-GA could significantly inhibit the MeIQx formation and the formation rates of carbonyl valence and precursors (threonine (Thr), creatinine, and glucose). The UVB-GA inhibited formaldehyde formation, while UVC-GA significantly reduced the formaldehyde, acetaldehyde, and 2,5-dimethyl pyrazine contents. In conculsion, UV-GA reduced carbonyl produced from the lipid oxidation to further weaken the catalysis of carbonyl, rendering the MeIQx precursor degrading into the intermediates during Strecker degradation. Thus, the MeIQx formation was inhibited.


Formate dehydrogenase from methylotrophic bacterium Pseudomonas sp. 101: gene cloning and expression in Escherichia coli.
Using two degenerate 20- and 23-mer oligonucleotide probes, the gene encoding NAD(+)-dependent formate dehydrogenase (FDH) (EC 184.108.40.206) was shown to lie within a 3.5 kb PstI fragment of the chromosomal DNA of methylotrophic bacterium Pseudomonas sp. 101. A phasmid library was prepared in the lambda pSL5 vector with partial EcoRI-digested DNA from Pseudomonas sp. 101. The 12 clones selected contained three types of phasmid: lambda pFDH1, lambda pFDH2 and lambda pFDH3 (with inserts of 15, 17.6 and 18.5 kb respectively). The inserts contained the same 15 kb EcoRI and 3.5 kb PstI fragments and included the complete FDH gene. Further subcloning of the insert resulted in plasmid pFDH2 and a 2.32 kb HindIII-BgIII fragment. Active enzyme was expressed in Escherichia coli TG1 (pFDH2) strain under control of a lac promoter.


Cone pigments in acute posterior multifocal placoid pigment epitheliopathy.
We measured cone pigment density and kinetics with a reflection retinal densitometer during the evolution and resolution of posterior pole lesions in a 17-year-old patient with acute posterior multifocal placoid pigment epitheliopathy. Three weeks after onset, density was markedly reduced and regeneration complex and nonexponential. Pigment density increased, and kinetics returned to normal as the disease resolved.


Photocatalytic water oxidation by persulphate with a Ca2+ ion-incorporated polymeric cobalt cyanide complex affording O2 with 200% quantum efficiency.
Incorporation of a small amount of Ca2+ ions into a polymeric cobalt cyanide complex to form Cax[CoII(H2O)2]1.5-x[CoIII(CN)6] resulted in a significant enhancement of activity for photocatalytic water oxidation in a buffer solution (pH 7.0) containing [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) as a photocatalyst and Na2S2O8 as an electron acceptor to achieve a quantum efficiency of 200%.


Profiles of antibiotic resistance genes in an inland salt-lake Ebinur Lake, Xinjiang, China: The relationship with antibiotics, environmental factors, and microbial communities.
Lakes in arid northwestern China, as the main pollutant-holding water bodies in the typical ecologically fragile areas, are facing the unknown risk of exposure to antibiotics and antibiotic resistance genes (ARGs). In this study, five ARGs and one mobile genetic element (intI1) and their relation with antibiotics, microbial communities and water quality were investigated in Ebinur Lake Basin, a typical salt-lake of China. Quantitative PCR analysis indicated that ARGs decreasing order in both surface water and sediment was sul1 >sul2 >tetW>ermB>qnrS, which means sulfonamide resistance genes were the main pollution ARGs. Macrolide antibiotics were the predominant antibiotics in the surface water and sediment in winter, while sulfonamides and quinolones accounted for a high proportion in summer. There was a non-corresponding relationship between ARGs and antibiotics. Moreover, the relationship between ARGs and microbial communities were defined. Sulfonamide resistance genes were carried by a greater diversity of potential host bacteria (76 genera) than other ARGs (9 genera). And their positive correlation with intI1 (p < 0.05) which promotes their migration and provides possibility of their co-occurrence in bacterial populations (e.g., Nitrospira). Bacterial genera were the main driver of ARGs distribution pattern in highly saline lake sediment. Environmental factors like salinity, total nitrogen and organic matter could have a certain influence on the occurrence of ARGs by affecting microorganisms. The results systematically show the distribution and propagation characteristics of ARGs in typical inland salt-lakes in China, and preliminarily explored the relationship between ARGs and antibiotics, resistance genes and microorganisms in lakes in ecologically fragile areas.


Portable EEG monitoring for older adults with dementia and chronic pain - A feasibility study.
Given the reduced ability of people with dementia to self-report pain, this study examined the feasibility of using a portable electroencephalography (EEG) headband (MUSE 2) as a pain measurement tool for long-term care residents with dementia. Ten minutes of resting-state EEG was acquired by MUSE 2 from people with dementia experiencing ongoing pain (n = 3) and without current pain (n = 1) over three days. The MUSE 2 was acceptable and feasible for use in people with dementia while challenges regarding software, data collection and analysis in using this device are reported. Compared to the resident not experiencing pain, EEG signals of residents with ongoing pain showed different EEG patterns, and this could be a potential biomarker to support pain measurement in people with dementia. Further research with larger sample size is warranted to verify study results.


[Vitaprost Forte in the treament of patients with benign prostatic hyperplasia: pathogenetic basics and clinical results].
The review is dedicated to the history of creation, biological effects and clinical use of prostatic peptides. Pathogenetic basics of using peptide drugs in prostatic disease are discussed. The results of clinical trials of efficiency of drug Vitaprost Forte in patients with benign prostatic hyperplasia are shown.


Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy.
Despite the ability of radical prostatectomy to eradicate prostate carcinoma, biochemical evidence of recurrent prostate carcinoma may be seen in approximately 40% of patients 15 years after they undergo surgery. Localization of recurrent disease after radical prostatectomy is difficult and may greatly influence subsequent clinical management. The authors examined the utility of indium 111 ((111)In)-capromab pendetide immunoscintigraphy to detect recurrent prostate carcinoma radiographically in men with early biochemical evidence of failure (serum prostate specific antigen [PSA] < or = 4.0 ng/mL) and assessed the minimum serum PSA level necessary for imaging recurrent disease. Between May 1987 and August 1995, 255 hormone-naïve men with a mean (+/- standard deviation) age of 65 years +/- 7 years who underwent radical prostatectomy for clinically localized prostate carcinoma were followed without adjuvant therapy until early PSA recurrence in this multicenter study. Preoperatively, all patients had negative bone scans and pathologically negative lymph nodes, and they did not undergo hormonal ablation, chemotherapy, or radiation therapy preoperatively or postoperatively until the (111)In-capromab pendetide scan was performed. All men in this study had postoperative serum PSA levels < or = 4.0 ng/mL at the time of radionuclide imaging. All men underwent imaging with the capromab pendetide scan to localize recurrent disease, and charts were reviewed to document clinical evidence of recurrence. Pathologic findings included mean Gleason scores of 6.7 +/- 1.2; pathologic tumors classified as pT2a (18%), pT2b (26%), pT3a (38%), pT3b (16%), and pT4a (2%); a pathologic lymph node status of pN0 (100%); positive surgical margins (44%); and perineural invasion (42%). Capromab pendetide uptake was seen in 72% of 255 men throughout a range of patients' postoperative serum PSA levels (0.1-4.0 ng/mL), with 31% of men having local uptake (prostatic fossa) only. Of 151 men who underwent additional imaging studies, 16 of 139 men (12%) and 15 of 92 men (16%) showed evidence of recurrent disease by bone scintigraphy and computed tomography scans, respectively. Gleason score, pathologic stage, perineural invasion, and margin status were not correlated significantly with the (111)In-capromab pendetide scan. Capromab pendetide imaging can localize early PSA recurrence and may guide appropriate treatment after patients undergo radical prostatectomy. No minimum serum PSA value was needed to potentially detect radiographic disease after surgery. Further confirmatory studies and long-term follow-up of this cohort documenting response to salvage therapy are needed to validate these imaging findings.


Influence of castration on incorporation of exogenous peroxidase into "synaptic" vesicles of the median eminence. II. The perivascular part of the palisade zone in male rats.
In the median eminence of male rats, nerve profiles in the immediate vicinity of portal capillaries have been divided into 4 categories on the basis of their vesicular content: profiles a with agranular "synaptic" vesicles of about 50 nm, b with similar agranular vesicles and also with granular vesicles of mainly 60-140 nm, c with granular vesicles alone and d without vesicles. Twenty-four hours after castration, the percentage of profiles of category a was significantly increased when compared with sham-operated animals, whereas the percentage of profiles of category b was significantly decreased. After intravenous injection of exogenous peroxidase, especially the nerve profiles located in direct contact with the outer basement membrane of the portal capillaries contained peroxidase positive "synaptic" vesicles. Injection off peroxidase after castration resulted in a significant increase in the percentage of nerve profiles containing both peroxidase positive and peroxidase negative "synaptic" vesicles (category a). It is suggested that, in certain nerve terminals, castration may lead to release off the content of granular vesicles, which may contain gonadotropin releasing factor. This release then may cause that nerve terminals with agranular vesicles and granular vesicles (category b) change in their vesicular content and are therefore classified as terminals with only agranular vesicles (category a). An increased turnover rate in the ultrastructurally affected terminals may be reflected in increased uptake of exogenous peroxidase. The observations imply that certain neurones projecting to portal capillaries in the median eminence are, directly or indirectly, sensitive to changes in the level of gonadal steroids.


Conformational change upon product binding to Klebsiella pneumoniae UDP-glucose dehydrogenase: a possible inhibition mechanism for the key enzyme in polymyxin resistance.
Cationic modification of lipid A with 4-amino-4-deoxy-L-arabinopyranose (L-Ara4N) allows the pathogen Klebsiella pneumoniae to resist the antibiotic polymyxin and other cationic antimicrobial peptides. UDP-glucose dehydrogenase (Ugd) catalyzes the NAD⁺-dependent twofold oxidation of UDP-glucose (UPG) to produce UDP-glucuronic acid (UGA), a requisite precursor in the biosynthesis of L-Ara4N and bacterial exopolysaccharides. Here we report five crystal structures of K. pneumoniae Ugd (KpUgd) in its apo form, in complex with UPG, UPG/NADH, two UGA molecules, and finally with a C-terminal His₆-tag. The UGA-complex structure differs from the others by a 14° rotation of the N-terminal domain toward the C-terminal domain, and represents a closed enzyme conformation. It also reveals that the second UGA molecule binds to a pre-existing positively charged surface patch away from the active site. The enzyme is thus inactivated by moving the catalytically important residues C253, K256 and D257 from their original positions. Kinetic data also suggest that KpUgd has multiple binding sites for UPG, and that UGA is a competitive inhibitor. The conformational changes triggered by UGA binding to the allosteric site can be exploited in designing potent inhibitors.


Generalized Violence as a Threat to Health and Well-Being: A Qualitative Study of Youth Living in Urban Settings in Central America's "Northern Triangle".
El Salvador, Guatemala, and Honduras rank among the top 10 countries experiencing violence in the world, despite not being at war. Although there is abundant literature on generalized violence in this "northern triangle" of Central America as a driver of out-migration to the United States, very little is known about the perspectives and experiences of youth who do not migrate. This study aimed to elicit the emic perspectives of youth residing in the region on how the day-to-day generalized violence produces a pervasive threat to the overall health and human security of youth as well as the key protective factors and resiliencies at work. We conducted two separate waves of qualitative research in 2015 and 2018 over a 6-month period, which included 60 in-depth interviews and six focus groups among Salvadoran, Guatemalan and Honduran youth living in urban areas. Qualitative thematic analysis revealed two meta-themes: (1) 'Lack of health,' defined as not experiencing peace within the family, the community, and the country' and (2) 'Resilience.' Thematic clusters that reflect the first meta-theme are: (1) violence as a common occurrence; (2) living in fear and insecurity; (3) victimization; and (4) lack of state protection and services. Thematic clusters for the second meta-theme are: (1) a positive future outlook and a commitment to education; (2) transnational and local family network support; and (3) engagement in community-based youth groups. To interpret the findings, we adopt the Latin American Social Medicine and Collective Health (LASM-CH) approach that prioritizes perspectives from the region. Generalized violence is conceptualized as a systemic phenomenon that is generated and reproduced through the complex interactions of structural inequities and unequal power relations. The findings of this study provide new insights into the implementation of a different approach to address the generalized violence, insights that may guide multi-sectoral health policies and interventions both in the region and transnationally.


Thyroid hormone autoantibodies in primary Sjögren syndrome and rheumatoid arthritis are more prevalent than in autoimmune thyroid disease, becoming progressively more frequent in these diseases.
To verify the greater prevalence of circulating thyroid hormone autoantibodies (THAb) in primary Sjogren syndrome (SS) vs Hashimoto's thyroiditis (HT) and Graves' disease (GD), we measured THAb in the serum of patients with these 3 diseases who were sampled from 1998-1999 (no.=20, 88, 25) and 1990-1992 (no.=13, 75, 31). Patients with rheumatoid arthritis (RA) (no.=23 and 16) and other collagenoses (no.=20 and 16) were also studied. A third series of patients with these 5 diseases was studied from 1975-1982, and data have been taken into account. THAb were detected using a specific radioimmunoprecipitation method, and their presence was correlated with the presence of TG antibodies (TGAb). We found that IgG antibodies against T3, T4 or both were present with these prevalences in the 1975-1982, 1990-1992 and 1998-1999 series: HT=1, 4, 20%; GD=2, 6, 32%; SS=20, 31, 50%; RA=0, 12, 26%; other collagenoses=0, 0, 0%. The majority of the Sjogren or arthritis cases positive for THAb were negative for TGAb, while the opposite was true for the 2 autoimmune thyroid diseases. We conclude that prevalence of THAb in the 2 non-thyroid autoimmune diseases is greater than in the 2 thyroid autoimmune diseases. In addition, prevalence of THAb is increasing over time regardless of disease. Molecular similarity between extra-thyroid connective proteins (specifically associated to primary SS and RA) and iodinated regions of TG, and an increased preponderance of environmental factors as triggers of autoimmune diseases might account for our findings.


The influence of context on residents' evaluations: effects of priming on clinical judgment and affect.
Different lines of research have suggested that context is important in acting and learning in the clinical workplace. It is not clear how contextual information influences residents' constructions of the situations in which they participate. The category accessibility paradigm from social psychology appears to offer an interesting perspective for studying this topic. We explored the effect of activating medically irrelevant mental concepts in one context, so-called 'priming', on residents' interpretations as reflected in their judgments in another, work-related context. Obstetric-gynecologic residents participated in two unrelated-tasks experiments. In the first experiment residents were asked to indicate affect about a change in a routine procedure after performing an ostensibly unrelated 'priming' task which activated the concept of either ineffective coping or effective coping. The second experiment concerned residents' patient management decisions in a menorrhagia case after 'priming' with either action or holding off. Contextually activated mental concepts lead to divergent affective and cognitive evaluations in a subsequent medical context. Residents are not aware of this effect. The strength of the effect varies with residents' level of experience. Context influences residents' constructions of a work-related situation by activating mental concepts which in turn affect how residents experience situations. Level of experience appears to play a mediating role in this process.


Evolution and chemical diversity of the volatile compounds in Salvia species.
The plant essential oils are composed of volatile compounds and have significant value in preventing and treating neurological diseases, anxiety, depression, among others. The genus Salvia has been shown to be an important medicinal resource, especially the aerial parts of genus Salvia, which are rich in volatile compounds; however, the chemical diversity and distribution patterns of volatile compounds in Salvia species are still unknown. The work is performed to analyse the chemical diversity and distribution patterns of volatile compounds in genus Salvia. The genomic single nucleotide polymorphisms (SNPs) combined with gas chromatography-mass spectrometry (GC-MS) were used to explore the evolution and chemical diversity of Salvia volatile compounds. Initially, the genetic relationship of genus Salvia was revealed by phylogenetic tree that was constructed based on SNPs. And then, GC-MS was applied to explore the chemical diversity of volatile compounds. The results indicated that the volatile compounds were mainly monoterpenoids, sesquiterpenoids, and aliphatic compounds. The genomic SNPs divided species involved in this work into four branches. The volatile compounds in the first and second branches were mainly sesquiterpenoids and monoterpenoids, respectively. Species in the third branch contained more aliphatic compounds and sesquiterpenoids. And those in the fourth branch were also rich in monoterpenoids but had relatively simple chemical compositions. This study offered new insights into the phylogenetic relationships besides chemistry diversity and distribution pattern of volatile compounds of genus Salvia, providing theoretical guidance for the investigations and development of secondary metabolites.


Factors predictive of complex Mohs surgery cases.
Mohs surgery allows excision of skin cancer in a tissue-sparing fashion that minimizes recurrence risk. While the indications for Mohs surgery are well established, factors predictive of complex Mohs cases are less studied. To determine patient, tumor, and surgeon characteristics associated with complex Mohs cases. A retrospective review was performed for a 3-year period (7/2006-6/2009) to identify Mohs cases requiring ≥4 stages ("complex"), and a control population requiring ≤3 stages ("non-complex"). Surgical logs for four fellowship-trained Mohs surgeons were reviewed. 77 complex cases (51 academic practice vs. 26 private practice) were compared with 154 control cases (102 academic practice vs. 52 private practice). There were no significant differences in patient age, gender, immunosuppression, academic (2.7% complex) versus private practice (3.5% complex), or surgeons' years of experience. Factors associated with complexity included: recurrent tumors (p < 0.001; odds ratio (OR) 6.88; 95% confidence interval (CI) 2.8-17); basal cell carcinoma (BCC) with infiltrative or morpheaform histology (p = 0.0019; OR 3.0; 95% CI 1.5-6.3); tumors of the nose (p = 0.0168; OR 2.05; 95% CI 1.1-3.7), especially nasal tip (p = 0.0103; OR 3.68; 95% CI 1.3-10.6) and ear (p = 0.0178; OR 3.0; 95% CI 1.2-7.9), especially helix (p = 0.00744; OR 5.9; 95% CI 1.5-22.7); tumors with pre-operative size >1 cm (p = 0.018; OR 2.0; 95% CI 1.1-3.6); and tumors involving >1 cosmetic subunit (p = 0.0072; OR 5.0; 95% CI 1.5-16.7). Complex tumors had greater post-operative area (10.6 ± 1.3 vs. 3.6 ± 0.7 cm2; p < 0.0001), and more often required flap/graft repair (p < 0.0001; OR 6.9; 95% CI 3.7-13.1). A retrospective study representing a single geographic area. Mohs cases are similar in complexity whether in academic or private practice. Recurrent/aggressive histology tumors, tumors >1 cm, and tumors on the nose or ear are more likely to prove surgically complex. Advanced knowledge of these factors may be useful pre-operatively as Mohs surgeons plan their scheduled cases.


HIM-17 regulates the position of recombination events and GSP-1/2 localization to establish short arm identity on bivalents in meiosis.
The position of recombination events established along chromosomes in early prophase I and the chromosome remodeling that takes place in late prophase I are intrinsically linked steps of meiosis that need to be tightly regulated to ensure accurate chromosome segregation and haploid gamete formation. Here, we show that RAD-51 foci, which form at the sites of programmed meiotic DNA double-strand breaks (DSBs), exhibit a biased distribution toward off-centered positions along the chromosomes in wild-type Caenorhabditis elegans, and we identify two meiotic roles for chromatin-associated protein HIM-17 that ensure normal chromosome remodeling in late prophase I. During early prophase I, HIM-17 regulates the distribution of DSB-dependent RAD-51 foci and crossovers on chromosomes, which is critical for the formation of distinct chromosome subdomains (short and long arms of the bivalents) later during chromosome remodeling. During late prophase I, HIM-17 promotes the normal expression and localization of protein phosphatases GSP-1/2 to the surface of the bivalent chromosomes and may promote GSP-1 phosphorylation, thereby antagonizing Aurora B kinase AIR-2 loading on the long arms and preventing premature loss of sister chromatid cohesion. We propose that HIM-17 plays distinct roles at different stages during meiotic progression that converge to promote normal chromosome remodeling and accurate chromosome segregation.


[Isolation and properties of merodiploid strains with F-factor including the pts-region of the Escherichia coli K-12 chromosome].
A technique of hybridization of haploid methanol-utilizing yeast Pichia pinus MH4 is worked out using UV- and N-nitrosoguanidine-induced auxotrophic mutants. Vegetative diploid cultures are isolated. Tetrad analysis and random spore analysis have revealed a meiotic nature of spores, recombination of genetic material in the process of sporulation and the chromosomal nature of some mutations. A possibility to construct a genetic map of the yeast Pichia pinus MH4 is demonstrated on the basis of tetrad analysis. Three linkage groups are revealed. The life cycle in a homothalic haploid yeast, Pichia pinus, was demonstrated. They are capable to form zygotes and meiotic spores under conditions preventing vegetative growth.


The mitochondrial genomes of spontaneous orir petite mutants of yeast have rearranged repeat units organized as inverted tandem dimers.
We have investigated the structure and organization of the mitochondrial genomes of two related orir (ori-rearranged) spontaneous petite mutants of Saccharomyces cerevisiae. In these mutant genomes every repeat unit contains an inverted terminal duplication harboring a second (inverted) ori sequence, and tandem pairs of repeat units alternate with tandem pairs in inverted orientation. We have shown that orir genomes are organized as the genomes with inverted repeat units of ethidium bromide (EtBr)-induced petites, and we have clarified the mechanism by which such mutant mitochondrial genomes arise.


Preventing alloimmune rejection using circular RNA FSCN1-silenced dendritic cells in heart transplantation.
While heart transplantation is used as a standard treatment for heart failure, transplant rejection continues to pose a challenge. Recent evidence has shown that circular RNA (circRNA) is a new type of gene regulator in cell development. Our aim was to demonstrate that treatment with tolerogenic dendritic cells (Tol-DCs) generated by circular RNA FSCN1 (circFSCN1) silencing could prevent alloimmune rejection and prolong heart graft survival in heart transplantation. Bone marrow-derived DCs were transfected with circFSCN1 siRNA in vitro. The circFSCN1 level was measured by qRT-PCR. DC maturation was determined by flow cytometry. Mixed lymphocyte reactions (MLRs) were conducted to assess the function of DCs to activate T cells and to generate regulatory T cells (Tregs). In situ RNA hybridization and fluorescent microscopy were performed to detect the distribution of circFSCN1 in DCs. A heterotopic allogeneic murine heart transplantation was conducted where recipients were pre-treated with donor derived circFSCN1-silenced Tol-DCs. Heartbeat was monitored to assess immune rejection. Exonic circFSCN1 was highly expressed in the cytoplasm of mature DCs. Knockdown of circFSCN1 using siRNA arrested DCs at an immature state, impaired DC's ability to activate T cells and enhanced Treg generation. Treatment with circFSCN1-silenced Tol-DCs prevented alloimmune rejection, prolonged allograft survival, reduced fibrosis, and induced Tregs in vivo. Knockdown of circFSCN1 induces Tol-DCs and treatment with these Tol-DCs prevents alloimmune rejection and prolongs allograft survival. This is a promising therapeutic target to combat transplant rejection in heart transplantation and increases our understanding of circRNA in the immune system.


Pronounced therapeutic potential of oligonucleotides fixed on inorganic nanoparticles against highly pathogenic H5N1 influenza A virus in vivo.
This study describes the effective attack of oligonucleotides on the viral genome of highly pathogenic H5N1 influenza A virus (IAV) in vivo using for the first time the new delivery system consisting of biocompatible low-toxic titanium dioxide nanoparticles and immobilized polylysine-containing oligonucleotides with the native (ODN) and partially modified (ODNm) internucleotide bonds. Intraperitoneal injection of the TiO2•PL-ODN nanocomposite provided 65-70% survival of mice, while intraperitoneal or oral administration of TiO2•PL-ODNm was somewhat more efficient (~80% survival). The virus titer in the lung was reduced by two-three orders of magnitude. The nanocomposites are nontoxic to mice under the used conditions. TiO2 nanoparticles, unbound ODN, and the nanocomposite bearing the random oligonucleotide showed an insignificant protective effect, which indicates the ability of targeted oligonucleotides delivered in mice in the nanocomposites to site-specifically interact with complementary RNAs. The protection of oligonucleotides in nanocomposites by TiO2 nanoparticles and partial modification of the internucleotide bonds provides a continued presence of oligonucleotides in the body for the effective and specific action on the viral RNA. The proposed oligonucleotide delivery system can claim not only to effectively inhibit IAV genes but also to turn off other genes responsible for diseases caused by nucleic acids.


Morphometrical analysis of the kidney from nonobese diabetic (NOD) mice in the non-diabetic stage.
The kidneys of non-diabetic NOD and wild type ICR mice were examined morphometrically at 3 and 6 months of age. Kidney weights and diameter of renal corpuscles of non-diabetic NOD mice were less than those of ICR mice. No lesions were observed in glomeruli or uriniferous tubules. Renin-positive areas were more common in NOD mice than in ICR mice, but no differences were detected in the Western blot analyses.


Trends in gamma-hydroxybutyrate-related harms based on ambulance attendances from 2012 to 2018 in Victoria, Australia.
Although the prevalence of gamma-hydroxybutyrate (GHB) use is relatively low globally, harms related to the drug appear to be increasing. Few existing studies present reliable, representative, population-level data on GHB-related harms. The aim of this study was to investigate trends in acute GHB-related harms within an ambulance database in Australia. Cross-sectional, retrospective analysis of data on all GHB-related ambulance attendances in the state of Victoria, Australia during a 7-year period (January 2012-December 2018) MEASUREMENTS: Presentations were characterized based on patient demographics, transport to hospital, co-occurring substance use (i.e. GHB only, alcohol, methamphetamine, heroin, benzodiazepine and cannabis) and clinical presentation (e.g. symptoms of anxiety, psychosis, depression). There were 5866 GHB-related ambulance attendances between 2012 and 2018, with the prevalence rate increasing from 8.8 per 100 000 population in 2012 to a maximum of 21.7 per 100 000 population in 2017. Methamphetamine [odds ratio (OR) = 6.23, P < 0.001] and benzodiazepine-related (OR = 1.43, P < 0.001) co-occurrences; ages between 18-29 (OR = 6.58, P < 0.001) and 30-39 years (OR = 2.02, P < 0.001); and male gender (OR = 1.23, P < 0.001) were significant predictors of GHB-related attendances. There has been a 147% increase in the prevalence of GHB-related ambulance attendances in Victoria, Australia between 2012 and 2019, largely attributable to a growth in the proportions of people using gamma-hydroxybutyrate alone or concurrently with methamphetamine.


Tucker Tensor Regression and Neuroimaging Analysis.
Neuroimaging data often take the form of high dimensional arrays, also known as tensors. Addressing scientific questions arising from such data demands new regression models that take multidimensional arrays as covariates. Simply turning an image array into a vector would both cause extremely high dimensionality and destroy the inherent spatial structure of the array. In a recent work, Zhou et al. (2013) proposed a family of generalized linear tensor regression models based upon the CP (CANDECOMP/PARAFAC) decomposition of regression coefficient array. Low rank approximation brings the ultrahigh dimensionality to a manageable level and leads to efficient estimation. In this article, we propose a tensor regression model based on the more flexible Tucker decomposition. Compared to the CP model, Tucker regression model allows different number of factors along each mode. Such flexibility leads to several advantages that are particularly suited to neuroimaging analysis, including further reduction of the number of free parameters, accommodation of images with skewed dimensions, explicit modeling of interactions, and a principled way of image downsizing. We also compare the Tucker model with CP numerically on both simulated data and a real magnetic resonance imaging data, and demonstrate its effectiveness in finite sample performance.


Comparative studies of sheep immunoglobulins IgG1 and IgG2: amino acid sequence of carboxy-terminal cyanogen bromide fragments from their heavy chains.
Sheep immunoglobulin IgG1 and immunoglobulin IgG2 heavy chains were treated with cyanogen bromide. The fractions from the C-terminal end of the heavy chains were isolated and purified, and the amino acid sequences gamma1 and gamma2 heavy chains had the identical sequence: Met-His-Glx-Ala-Leu-His-Asx-His-Tyr-Thr-Glx-Lys-Ser-Ile-Ser-Lys-Pro-Pro-Gly. Comparison with the C-terminal peptides of other species, reported in the literature, suggests that the subclasses are the results of recent evolutionary processes. Residues at position 4 from the C-terminus may be phylogenetically related.


Monitoring water quality through citizen science while teaching STEM undergraduate courses during a global pandemic.
Due to the COVID-19 pandemic, many universities struggle to engage students while implementing a distance-based teaching/learning approach and to provide hands-on activities to students enrolled in STEM classes. Implementing service-focused activities that can be conducted by the students remotely can overcome these struggles. The goals of this study were to 1) implement citizen science activities focused on water quality using three commercially available low-cost test strips (2:1, 5:1, and 16:1) while teaching four undergraduate engineering courses at the University of Mississippi (UM) during a pandemic event, and 2) evaluate the acceptability and validate the results obtained. Eighty-five undergraduate students (citizen scientists) and five research scientists (control group) collected two water samples (with triplicates) after receiving detailed step-by-step written guidelines and video tutorials. One hundred twenty tap water samples were collected from private households across Lafayette County and its surrounding counties and multiple buildings on campus. Five laboratory fortified blank (LBF) samples were implemented to validate the results. While the academic background of the participants did not impact the results (p > 0.05), the results obtained using the different test strips were statistically different (p < 0.05). In fact, results obtained using the 2:1 and the 5:1 test strips were close to the LFBs, while, except for the higher concentration of Total Alkalinity (40 mg/L CaCO3), results obtained using the 16:1 test strips were significantly different than the LFBs. Results (in terms of pH, Nitrate, and Total Chlorine) obtained by the citizen scientists using the 2:1 and 5:1 test strips were consistent with those reported in the annual drinking water quality reports from UM and municipalities included in the investigated region. Overall, this activity was well received by the students. Approximately 75% of them agreed that this hands-on activity was a positive experience while struggling to attend face-to-face classes.


Coordinating smoking cessation treatment with menstrual cycle phase to improve quit outcomes (MC-NRT): study protocol for a randomized controlled trial.
Women experience greater difficulty achieving smoking abstinence compared to men. Recent evidence suggests that hormonal fluctuations during different phases of the menstrual cycle can contribute to lower smoking abstinence rates following a quit attempt among women. However, these findings are limited by small sample sizes and variability among targeted smoking quit dates. This clinical trial aims to clarify whether targeting the quit date to the follicular or luteal phase of the menstrual cycle can improve smoking abstinence. Participants will enroll in an online smoking cessation program providing nicotine replacement therapy (NRT) and behavioral support. We will randomize 1200 eligible individuals to set a target quit date: (1) during the mid-luteal phase, (2) during the mid-follicular phase, or (3) 15-30 days after enrollment with no regard to the menstrual cycle phase (usual practice). Participants will receive a 6-week supply of combination NRT consisting of a nicotine patch plus their choice of nicotine gum or lozenge. Participants will be instructed to start using NRT on their target quit date. Optional behavioral support will consist of a free downloadable app and brief videos focusing on building a quit plan, coping with cravings, and relapse prevention, delivered via e-mail. Smoking status will be assessed via dried blood spot analysis of cotinine concentration at 7 days, 6 weeks, and 6 months post-target quit date. We aim to overcome the limitations of previous studies by recruiting a large sample of participants and assigning target quit dates to the middle of both the follicular and luteal phases. The results of the trial can further elucidate the effects of the menstrual cycle on smoking cessation outcomes and whether it is beneficial to combine menstrual cycle phase timing strategies with accessible and low-cost NRT. ClinicalTrials.gov NCT05515354. Registered on August 23, 2022.


RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.
Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making.


Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases.
Pathogens related to systemic infections have been detected in the periodontal microbiota. The relationship amongst these pathogens, periodontal bacteria and periodontal clinical status is poorly understood. This study evaluated the association amongst red complex, A. actinomycetemcomitans (A.a) and non-oral pathogenic bacteria in subjects with good periodontal health (PH), gingivitis (G), chronic (CP) and aggressive (AP) periodontitis. Subgingival biofilm samples were obtained from 51 PH, 42 G, 219 CP and 90 AP subjects. The presence and levels of A.a, red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola), Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by DNA probes and DNA-DNA hybridization technique. CP and AP subjects presented significantly higher prevalence and levels of A.a, red complex and A. baumannii than G and PH individuals (p<0.01), whereas S. aureus was detected in lower frequency and counts in AP as compared to the other groups (p<0.001). The predictor variables age, prevalence of red complex, and the presence of A. baumannii and P. aeruginosa were strongly associated with the frequency of sites with PD and CAL ≥5 mm. Increasing age (OR 1.08), high frequency of red complex (OR 6.10), and the presence of A.a with P. aeruginosa (OR 1.90) were associated with periodontal disease (p<0.001). Subjects harbouring a high prevalence of A.a, A. baumannii, and red complex with P. aeruginosa were more likely to have AP than CP (p<0.001). Putative periodontal pathogens and non-oral bacteria alone or in association were strongly associated with periodontitis.


Complement C5a promotes antigen cross-presentation by Peyer's patch monocyte-derived dendritic cells and drives a protective CD8+ T cell response.
The complement fragment C5a is closely associated with adaptive immune induction in the mucosa. However, the mechanisms that control CD8+ T cell responses by C5a have not been extensively explored. This study reveals that C5/C5a in the Peyer's patch (PP) subepithelial dome increases upon oral Listeria infection. We hypothesize that C5aR+ PP cells play an important role in the induction of antigen-specific T cell immunity. Using single-cell RNA sequencing, we identify C5aR- and lysozyme-expressing dendritic cells (C5aR+ LysoDCs) in PP and examine their role in CD8+ T cell immune induction. Stimulation of C5aR+ LysoDCs by C5a increases reactive oxygen species levels, leading to efficient antigen cross-presentation, which elicits an antigen-specific CD8+ T cell response. In C5-deficient mice, oral co-administration of C5a and Listeria enhances Listeria-specific cytotoxic T cell levels. Collectively, these findings suggest a role of the complement system in intestinal T cell immunity.


Postnatal nitric oxide inhibition modifies neurotensin effect on ATPase activity.
We have previously showed that peptide neurotensin inhibits neuronal Na(+), K(+)-ATPase activity, an effect which involves high affinity neurotensin receptor. Nitric oxide (NO) acts as a neurotransmitter or as a neuromodulator when it is synthesized by neuronal nitric oxide synthase. Neurotensin effect on Na(+), K(+)-ATPase activity was evaluated in cortical synaptosomal membranes isolated from rats injected at 3, 4 and 5 postnatal days with saline (control) or N (ω)-nitro-L-arginine methyl esther (L-NAME), a nitric oxide synthase inhibitor. Assays were carried out at two stages: juvenile (35 days) and adult (56 days) ages. In an open field task, results recorded in juvenile rats markedly differed from those obtained in adult rats. The presence of neurotensin at 3.5 × 10(-8)-3.5 × 10(-6 )M concentration decreased 16-34% Na(+), K(+)-ATPase activity in membranes purified from control animals. At variance, the peptide failed to alter this enzyme activity in membranes obtained after L-NAME treatment. After administration of L-NAME, [(3)H]-ouabain binding to membranes isolated from adult male rats decreased 64% in the presence of 1.0 × 10(-6 )M neurotensin, a peptide concentration which only slightly decreased binding to membranes isolated from juvenile rats. It is postulated that early postnatal NO dysfunction may exert a permanent change in neurotensin system that influence later Na(+), K(+)-ATPase response to neurotensin.


Analysis and filtering of phase noise in an optical frequency comb at the quantum limit to improve timing measurements.
It is shown that the sensitivity of a highly sensitive homodyne timing measurement scheme with femtosecond (fs) lasers [Phys. Rev. Lett.101, 123601 (2008).] is limited by carrier-envelope-phase (CEO) noise. We describe the use of a broadband passive cavity to analyze the phase noise of a Ti:Sapphire oscillator relative to the standard quantum limit. This cavity also filters the lowest levels of classical noise at sidebands above 100 kHz detection frequency. Leading to quantum-limited CEO-phase noise at millisecond time scales, it can improve the sensitivity of the homodyne pulse timing measurement by 10 dB.


Temporal variation of coastal surface sediment bacterial communities along an environmental pollution gradient.
Terminal restriction fragment length polymorphism analysis (T-RFLP) was used to track the changes of bacterial community compositions (BCC) in coastal surface sediments along an environmental pollution gradient between 2004 and 2006. BCC in the chronically contaminated sites showed the largest deviation from those in the adjacent sites. Surprisingly, BCC at two contrasting environments (oceanic vs. river-influenced) were more similar. Unexpectedly, the BCC did not recover (when compared to oceanic control site) even after 5 years of pollution abatement initiatives in Victoria Harbour, Hong Kong. On the other hand, disposal of treated sewage for 5 years in one of the sites did not significantly affect the BCC. A striking seasonal variation in the BCC was observed at only the polluted sites. Although factors other than pollution gradients may explain the observed BCC patterns, the information presented here can be useful in predicting long-term effects of pollution on BCC. Furthermore, this study suggests that BCC analysis using T-RFLP is a faster, reliable and easier approach to monitor microbenthic community response to environmental pollution gradient in coastal sediments.


Evaluation of the subscapularis split created with passive rotation during arthroscopic dynamic anterior stabilization (DAS): A cadaveric study.
The purpose of the present study was to analyze the ability to create a subscapularis split by passive rotation of the arm during dynamic anterior stabilization (DAS) and to analyze the new geometry of the long head of the biceps LHB. The hypothesis was that this passive simple technique can create subscapularis split without additional dissection giving rise to new position of LHB with a new stabilization function. A technique of subscapularis split using the LHB was used in 12 fresh-frozen human cadaveric shoulders. A subscapularis split was created by passive rotation of the arm after the LHB is shuttled into the joint during DAS. The length of the subscapularis split, post-DAS position and length of the LHB, and the angulation of the LHB relative to bicipital groove were measured after DAS and if this new geometry can give a new dynamic effect on subscapularis muscle. The mean length of the subscapular split after maximal rotation was 20.4±6.0mm (range: 10-32mm). The mean elongation of the LHB was 0.6±1.4mm (range: -1 to +3mm). The final angle of the LHB relative to the bicipital groove was 45±5 degrees (range: 41 to 55 degrees). There is no need to create a distinct split prior to DAS. Additionally, DAS maintains the length-tension relationship of the LHB. The post-procedure medial angulation of the LHB relative to the bicipital groove may provide a lowering of the subscapularis, helping explain the anterior reinforcement of this technique. Basic science study, cadaver study.


Is it the time to expect long-term outcome data in addition to follow-up data for sleep apnea interventions?
Hunasikatti M. Is it the time to expect long-term outcome data in addition to follow-up data for sleep apnea interventions? J Clin Sleep Med. 2021;17(8):1519-1520.


COVID-19 mortality in California based on death certificates: disproportionate impacts across racial/ethnic groups and nativity.
To examine characteristics of coronavirus disease 2019 (COVID-19) decedents in California (CA) and evaluate for disproportionate mortality across race/ethnicity and ethnicity/nativity. COVID-19 deaths were identified from death certificates. Age-adjusted mortality rate ratios (MRR) were compared across race/ethnicity. Proportionate mortality rates (PMR) were compared across race/ethnicity and by ethnicity/nativity. We identified 10,200 COVID-19 deaths in CA occurring February 1 through July 31, 2020. The most frequently observed characteristics among decedents were age 65 years or above, male, Hispanic, foreign-born, and educational attainment of High School or below. MRR indicated elevated COVID-19 morality rates among Asian/Pacific Islander, Black, and Hispanic groups compared with the White group, with Black and Hispanic groups having the highest MRR at 2.75 (95%CI: 2.54-2.97) and 4.18 (95%CI: 3.99-4.37), respectively. Disparities were larger at younger ages. Similar results were observed with PMR, and patterns of age-racial/ethnic disparities remained in analyses stratified by education. Elevated PMR were observed in all ethnicity/nativity groups, especially foreign-born Hispanic individuals, relative to U.S.-born non-Hispanic individuals. These were generally larger at younger ages and persisted after stratifying by education. Differential COVID-19 mortality was observed in California across racial/ethnic groups and by ethnicity/nativity groups with evidence of greater disparities among younger age groups. Identifying COVID-19 disparities is an initial step toward mitigating disease impacts in vulnerable communities.


Emergent Bioanalogous Properties of Blockchain-based Distributed Systems.
We apply a novel definition of biological systems to a series of reproducible observations on a blockchain-based distributed virtual machine (dVM). We find that such blockchain-based systems display a number of bioanalogous properties, such as response to the environment, growth and change, replication, and homeostasis, that fit some definitions of life. We further present a conceptual model for a simple self-sustaining, self-organizing, self-regulating distributed 'organism' as an operationally closed system that would fulfill all basic definitions and criteria for life, and describe developing technologies, particularly artificial neural network (ANN) based artificial intelligence (AI), that would enable it in the near future. Notably, such systems would have a number of specific advantages over biological life, such as the ability to pass acquired traits to offspring, significantly improved speed, accuracy, and redundancy of their genetic carrier, and potentially unlimited lifespans. Public blockchain-based dVMs provide an uncontained environment for the development of artificial general intelligence (AGI) with the capability to evolve by self-direction.


A Puzzle of Life: Crafting Ribosomal Subunits.
The biogenesis of eukaryotic ribosomes is a complicated process during which the transcription, modification, folding, and processing of the rRNA is coupled with the ordered assembly of ∼80 ribosomal proteins (r-proteins). Ribosome synthesis is catalyzed and coordinated by more than 200 biogenesis factors as the preribosomal subunits acquire maturity on their path from the nucleolus to the cytoplasm. Several biogenesis factors also interconnect the progression of ribosome assembly with quality control of important domains, ensuring that only functional subunits engage in translation. With the recent visualization of several assembly intermediates by cryoelectron microscopy (cryo-EM), a structural view of ribosome assembly begins to emerge. In this review we integrate these first structural insights into an updated overview of the consecutive ribosome assembly steps.


Genetic polymorphism of drug metabolising enzymes in African populations: implications for the use of neuroleptics and antidepressants.
Metabolism of most drugs influences their pharmacological and toxicological effects. Drugs particularly affected are those with a narrow therapeutic window and that are subjected to considerable first-pass metabolism. Much of the interindividual and interethnic differences in effects of drugs is now attributable to genetic differences in their metabolism. Genetic polymorphisms have been described for many drug-metabolising enzymes in Caucasian and Oriental populations, the most well-characterised being those for cytochrome P450 2D6, cytochrome P450 2C19, glutathione S-transferases, and N-acetyl transferase 2. African populations have been studied to a lesser extent, but it is apparent that populations within Africa are heterogeneous with respect to these polymorphisms. In addition, although some allelic variants are common to all populations throughout the world (e.g., CYP2D6*5), some allelic variants are specific for an African population (e.g., CYP2D6*17). The polymorphisms give rise to enzymes with changed or no activity towards drug substrates. Two of the most important enzymes for metabolism of neuroleptics and other psychoactive drugs are CYP2D6 and CYP2C19. This article compares the current information on polymorphisms of these two enzymes in African and other populations and discusses the implications of these polymorphisms for neuropharmacotherapy.


Attitudes Scale on Alcohol, Alcoholism, and Persons With Alcohol Use Disorders.
The Attitudes Scale on Alcohol, Alcoholism, and Persons with alcohol use disorders ("Escala de Atitudes Frente ao Álcool, ao Alcoolismo e ao Persons with alcohol use disorders" [EAFAA]) is an instrument designed to measure attitudes toward alcohol, alcoholism, and persons with alcohol use disorders. It has been validated in Portuguese and Spanish. The purpose of this study was to examine the psychometric properties and factor structure of the American English version of the EAFAA (EAFAA-AEV). One hundred eighty-seven participants (nurses = 101 and nursing students = 86) completed the EAFAA-AEV. Confirmatory factor analysis resulted in a four-factor solution, supporting the original factor structure of the EAFAA. The scale has shown good internal consistency and reliability for the four factors. The total scale had a Cronbach's alpha of .85 and a McDonald's omega of .87. The EAFAA-AEV has similarly strong psychometric properties as the original version, suggesting that it is a reliable tool to identify attitudes toward alcohol and related issues among American-English-speaking nurses and nursing students.


Promoting a well-dispersion of MoO3 nanoparticles on fibrous silica catalyst via one-pot synthesis for enhanced photoredox environmental pollutants efficiency.
The coexistence of pharmaceutical compounds and heavy metals in the aquatic environment has resulted in complications in the treatment process and thus, causing uproar among the citizens. The radical-based photocatalysis technology has aroused as an excellent method to eliminate both heavy metal and pharmaceutical compounds in the water. Herein, reported the utilization of the microemulsion technique for the preparation of nanoporous fibrous silica-molybdenum oxide (FSMo) towards simultaneous photocatalytic abatement of hexavalent chromium (Cr(VI)) and tetracycline (TC). The FESEM analysis showed the spherical morphology of the FSMo catalyst with dendrimeric silica fiber. The synthesized FSMo catalyst exhibited narrowed bandgap, high crystallinity, and well Mo element dispersion for enhanced photo-redox of Cr(VI) and TC. Remarkably, simultaneous remediation of the Cr(VI) and TC over FSMo demonstrated superior photocatalytic efficiency, 69% and 75%, respectively, than in the individual system, possibly due to the effective separation of photoinduced charges. The introduction of the Mo element to the silica framework via microemulsion technique demonstrated better dispersion of Mo compared to the incipient wetness impregnation method and thus, yielded higher photocatalytic activity towards simultaneous removal of TC and Cr(VI). Besides, quenching experiments revealed the electrons and holes as the active species that play a dominant role in the simultaneous photo-redox of Cr(VI) and TC. Lastly, the FSMo catalyst demonstrated high stability after four continuous cycles of simultaneous photocatalysis reactions, implying its potential as a suitable material for practical wastewater treatments.


Does outpatient treatment reduce hospital stay in schizophrenics?
The implementation of community mental health care for psychiatric patients in Mannheim, an industrial city of approximately 300,000 inhabitants, poses questions concerning the impact of outpatient treatment on the probability of rehospitalization. For this purpose the use of extramural facilities by a group of 148 patients with a diagnosis of schizophrenia was studied over a period of 18 months. Based on a model of utilization that allows for the removal of confounding effects the statistical analysis reveals that outpatient contacts with psychiatrists in practice or with an outpatient clinic indeed reduces time in hospital and also improves the psychopathological status of the patients.


An analysis of the reflex systemic vasodilator response elicited by lung inflation in the dog.
1. A maintained inflation of the lungs caused a reflex reduction in total systemic vascular resistance in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow and the arterial blood P(O2) and P(CO2) were maintained constant.2. The fall in systemic arterial perfusion pressure evoked by inflation of the lungs was accompanied by an increase in blood flow to the lower limbs and a reduction in their calculated vascular resistance. Since the fall in resistance occurred when the limb was perfused either at constant pressure or at constant blood flow, it must be due to vasodilatation.3. Lung inflation caused vasodilatation in skin, muscle, and in the splanchnic vascular bed. The responses in vertebral circulation were, however, small and variable.4. The vasodilator responses in the vascular territories studied were reflex in nature, being abolished by cutting the cervical vagosympathetic nerves, in which run the afferent fibres, or by interrupting the sympathetic pathways to the blood vessels.5. In the intact limb, muscle, skin and splanchnic vascular bed, the vasodilator responses to lung inflation were unaffected by atropine or propranolol, but were abolished by hexamethonium, dibenyline and bretylium tosylate, indicating that they were due predominantly to a reduction in the activity in sympathetic adrenergic vasoconstrictor fibres.


GnRH antagonist in the adjuvant treatment of a recurrent ovarian granulosa cell tumor: a case report.
Ovarian granulosa cell tumors (GCT) are usually treated by surgery and chemotherapy. Successful response to GnRH agonists as an adjuvant therapy has previously been reported. In this case of recurrent GCT, we used a GnRH antagonist. A 78-year-old woman underwent surgery for an ovarian granulosa cell tumor (pT1a N0 Mx). Six months later, laparotomy revealed an inoperable recurrence of the tumor. Experimental treatment with a GnRH antagonist was not clearly successful. This is in contrast to the previously proven benefit of GnRH agonist therapy in this type of malignancy and to the positive response elicited by GnRH antagonists in epithelial ovarian tumors. GnRH antagonist therapy had no demonstrable efficacy in the treatment of a poorly differentiated and aggressive recurrent granulosa cell tumor.


Association between serum beta-human chorionic gonadotropin and inflammation, oxidative stress in pregnancy-induced hypertension.
The aberrant increase of circulating beta-human chorionic gonadotropin (β-HCG) at early stages of pregnancy can be used to predict gestational hypertension. However, the association of β-HCG and inflammation, oxidative stress in pregnancy-caused hypertensive disorder on perinatal stage remains unclear. A case-controlled study was performed, with 133 adult pregnant women participated in their perinatal stage. Participants in this research included 45 with mild preeclampsia, 40 with severe preeclampsia and 48 without hypertension. Higher circulating β-HCG level was correlated with severer pregnancy-induced hypertension. Independent contribution of inflammatory factors including interleukin-6, tumor necrosis factor-α and interferon-γ and oxidative stress factors including thiobarbituric acid reactive substance and total antioxidant capacity to severe pregnancy-induced hypertension was significant (P < 0.001). The correlation of circulating β-HCG levels with inflammatory and oxidative stress markers in patients with pregnancy-induced hypertension in perinatal stage was statistically significant.


SIRPbeta1 is expressed as a disulfide-linked homodimer in leukocytes and positively regulates neutrophil transepithelial migration.
Signal regulatory proteins (SIRPs) comprise a family of cell surface signaling receptors differentially expressed in leukocytes and the central nervous system. Although the extracellular domains of SIRPs are highly similar, classical motifs in the cytoplasmic or transmembrane domains distinguish them as either activating (beta) or inhibitory (alpha) isoforms. We reported previously that human neutrophils (polymorphonuclear leukocytes (PMN)) express multiple SIRP isoforms and that SIRPalpha binding to its ligand CD47 regulates PMN transmigration. Here we further characterized the expression of PMN SIRPs, and we reported that the major SIRPalpha and SIRPbeta isoforms expressed in PMN include Bit/PTPNS-1 and SIRPbeta1, respectively. Furthermore, although SIRPalpha (Bit/PTPNS-1) is expressed as a monomer, we showed that SIRPbeta1 is expressed on the cell surface as a disulfide-linked homodimer with bond formation mediated by Cys-320 in the membrane-proximal Ig loop. Subcellular fractionation studies revealed a major pool of SIRPbeta1 within the plasma membrane fractions of PMN. In contrast, the majority of SIRPalpha (Bit/PTPNS-1) is present in fractions enriched in secondary granules and is translocated to the cell surface after chemoattractant (formylmethionylleucylphenylalanine) stimulation. Functional studies revealed that antibody-mediated ligation of SIRPbeta1 enhanced formylmethionylleucylphenylalanine-driven PMN transepithelial migration. Co-immunoprecipitation experiments to identify associated adaptor proteins revealed a 10-12-kDa protein associated with SIRPbeta1 that was tyrosine-phosphorylated after PMN stimulation and is not DAP10/12 or Fc receptor gamma chain. These results provide new insights into the structure and function of SIRPs in leukocytes and their potential role(s) in fine-tuning responses to inflammatory stimuli.


Increased postprandial glycaemia, insulinemia, and lipidemia after 10 weeks' sucrose-rich diet compared to an artificially sweetened diet: a randomised controlled trial.
The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear. To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postprandial metabolic profiles after 10 weeks. Healthy overweight subjects were randomised to consume drinks and foods sweetened with either sucrose (∼2 g/kg body weight) (n = 12) or artificial sweeteners (n = 11) as supplements to their usual diet. Supplements were similar on the two diets and consisted of beverages (∼80 weight%) and solid foods (yoghurts, marmalade, ice cream, stewed fruits). The rest of the diet was free of choice and ad libitum. Before (week 0) and after the intervention (week 10) fasting blood samples were drawn and in week 10, postprandial blood was sampled during an 8-hour meal test (breakfast and lunch). After 10 weeks postprandial glucose, insulin, lactate, triglyceride, leptin, glucagon, and GLP-1 were all significantly higher in the sucrose compared with the sweetener group. After adjusting for differences in body weight changes and fasting values (week 10), postprandial glucose, lactate, insulin, GIP, and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake, postprandial lactate, insulin, GIP, and GLP-1 levels were still significantly higher on the sucrose-rich diet. A sucrose-rich diet consumed for 10 weeks resulted in significant elevations of postprandial glycaemia, insulinemia, and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects.


Environmental impact assessment of post-combustion CO2 capture technologies applied to cement production plants.
Decarbonizing the cement manufacturing sector presents an interesting and pressing challenge as it is one of the largest energy consumers in industry (i.e., 7%), emitting considerable amounts of anthropogenic carbon dioxide (i.e., 7%). This paper performs a technical and environmental assessment of decarbonisation of cement production through process modelling and simulation, thermal integration analysis, and Life Cycle Assessment (LCA). Integration of three post-combustion capture methods for a conventional cement plant with an annual productivity of one million tons and a carbon capture rate of 90% is evaluated in comparison to the reference case without carbon capture and storage (CCS). Mass and energy balances derived from simulations are used for the assessment of three innovative capture systems: reactive gas-liquid absorption using Methyl-Di-Ethanol-Amine, reactive gas-solid adsorption using calcium looping (CaL) technology and membrane separation. For the LCA study, a "cradle-to-gate" approach is carried out using GaBi software, according to the ReCiPe impact assessment method. The general conclusion is that integrating the CCS methods into the cement production process leads to a decrease in global warming potential (GWP) in the range of 69.91%-76.74%. Of the CCS technologies analysed, CaL technically outperforms the others as it requires 34% less coal and provides 1.6 times higher gross energy efficiency. From an environmental perspective, CaL integration ranks first, with the lowest scores in six of the nine impact categories and a GWP reduction of 76.74% compared to the baseline scenario without CCS.


Efference copies: Context matters when ignoring self-induced motion.
Across the animal kingdom, efference copies of neuronal motor commands are used to ensure our senses ignore stimuli generated by our own actions. New work shows that the underlying motivation for an action affects whether visual neurons are responsive to self-generated stimuli.


Infection by a dimorphic fungus Sporothrix schenckii in an immunocompromised patient.
Infections caused by dimorphic fungi, rarely observed in a temperate climate, may cause chronic infections in immunocompromised patients. We describe a case of sporotrichosis in a 50-year-old woman, who underwent mastectomy due to breast carcinoma, followed by radiation and chemotherapy. She developed skin lesions, localized along the lymphatics. Discharge samples repeatedly yielded a characteristic growth of the dimorphic fungus Sporothrix schenckii. The isolate was resistant to all commonly used antifungal agents, except for itraconazole. Therapy with this antifungal agent resulted in disappearance of the clinical symptoms.