Commercial pesticides for urban applications induced population growth and sub-cellular alterations in Raphidocelis subcapitata (Chlorophyceae) at concerning environmental concentrations.
Information regarding the safety and environmental risks of pesticides intended for urban use remains limited. This study aimed to assess the effects of four common pesticides on the microalga Raphidocelis subcapitata: DIAZINON® 25% C. E., Roundup®, URBACIN® 20C. E., and VAPODEL® 20% C. E., which are commercial formulations of diazinon, glyphosate, dichlorvos, and cypermethrin, respectively. According to 96-h inhibition of population growth bioassays, the four pesticide toxicities exemplified the following order: DIAZINON® (diazinon) > Roundup® (glyphosate) > VAPODEL® (dichlorvos) > URBACIN® (cypermethrin). Increasing pesticide concentrations elicited alterations in the specific growth rates (µmax). The macromolecule contents and photosynthetic pigments increased in groups exposed to the highest concentrations of DIAZINON® 25%, Roundup®, and URBACIN® 20 compared to the control group, despite these treatments inducing lower population growth rates. VAPODEL® 20% induced higher growth rates and lower macromolecule content compared to the control. Since active ingredients were not quantified, certain comparisons may prove limiting, but it is important to assess the effects of the whole mixtures in the form that they enter the environment, especially for urban-intended applications or generic formulations with higher additive contents. Finally, this study demonstrated that commercial pesticide formulations designed for urban applications might pose a threat to freshwater microalgae due to their underestimated toxic potential, but further studies are required.


Neuroimaging of mass lesions of the pineal region in infancy and childhood.
Mass lesions of the pineal gland, quadrigeminal plate, posterior third ventricle and midbrain are grouped together as pineal region lesions. The various methods of neuroimaging should not only help to localise and circumscribe these lesions, but should also suggest their quality and nature, i.e. cystic parts, delineation and possible histology. Also, the pathomorphological pattern with respect to the position of the aqueduct and the direction of growth towards the third ventricle and trigone of the lateral ventricle plays an important role in deciding which approach is possible and most suitable. Of major importance are the deep vascular structures and the vasculature of the lesion itself. The study is based on 24 cases of the pediatric age group from a total of 52 observed cases.


Afforestation suppresses soil nitrogen availability and soil multifunctionality on a subtropical grassland.
Microbes simultaneously drive multiple functions (multifunctionality) that support human well-being. However, the structure and function of microbial communities and their impact on soil multifunctionality following grassland afforestation remains unknown, thus hindering our ability to formulate conservation policies. We compared soil bacterial and fungal communities, soil abiotic properties, and soil nitrogen (N) function and multifunctionality in the afforested sites that were previously grassland, on a subtropical plateau in China. We also explored the degree to which the niche complementarity effect and the selection effect of microbes are linked to soil N function and multifunctionality. We found that afforestation of grassland significantly decreased pH, available N concentration and density, and soil multifunctionality. However, afforestation significantly increased C (carbon) limitation and shifted soil microbes from being limited by N to, instead, being co-limited by N and P (phosphorus). The significant decrease in available N was primarily driven by soil microbes. In shaping soil N availability, the effect of bacterial diversities was stronger than that of fungal diversities, and the effect of fungal functional diversities was stronger than that of bacterial functional diversities. The effect of functional diversities was greater than that of all the significant changes in the functions and, also, the significant changes in the N-related functions. These results further emphasized that functional niche complementarity dominated soil N availability. In addition, bacterial taxonomic diversities showed positive effects of niche complementarity on soil multifunctionality; ultimately, the losses in bacterial taxonomic diversities derived from the increases in C limitation and the shifts in NP limitation combined to impaired soil multifunctionality. Our results suggested that the optimization of soil microbial functional diversities might increase soil N availability, and that minimizing losses of soil microbial taxonomic diversities by optimizing soil abiotic environments might improve soil multifunctionality.


Modulation of human NK cells by interferon and prostaglandin E2.
Our studies have shown that stimulation of human natural killer (NK) cells by poly I:C does not depend on or require monocytes. In contrast, the presence of monocytes in a mixed population of mononuclear cells stimulated by poly I:C suppresses NK activity. The suppression can be partially overcome if indomethacin (10(-6) M) is added to the culture during stimulation. Culture supernatants from poly I:C stimulated monocytes do not have detectable levels of anti-viral activity but contained appreciable amounts of PGE2. Our results offer an explanation as to how NK cells may protect themselves from suppression by PGE2. We have demonstrated that IFN-activated NK cells become resistant to PGE2-mediated suppression; moreover the suppression does not require cells other than the large granular lymphocytes, the major effector cell type for NK. Taken together, the data suggest that stimulation of NK cells is dependent on and regulated by the relative levels of interferon produced by lymphocytes and PGE2 produced by monocytes.


Evidence for the recruitment of autophagic vesicles in human brain after stroke.
Autophagy is a homeostatic process for recycling proteins and organelles that is increasingly being proposed as a therapeutic target for acute and chronic neurodegenerative diseases, including stroke. Confirmation that autophagy is present in the human brain after stroke is imperative before prospective therapies can begin the translational process into clinical trials. Our current study using human post-mortem tissue observed an increase in staining in microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1 (SQSTM1; also known as p62) and the increased appearance of autophagic vesicles after stroke. These data confirm that alterations in autophagy take place in the human brain after stroke and suggest that targeting autophagic processes after stroke may have clinical significance.


Anti-N-methyl-D-aspartate receptor encephalitis in adults: a systematic review and analysis.
To analyze predictors of treatment outcome for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in adults. We performed a comprehensive literature search of PubMed, PsycInfo, and OVID. We included 424 patients from case reports and case series. Demographics, anti-NMDAR antibodies, prodromal and presenting symptoms, diagnostic workup, and treatment variables were recorded. Inferential analyses were performed in the subset (n = 299) of those with known treatment outcomes. Multivariate multinomial logistic regression analysis for treatment outcome compared full recovery versus partial recovery and full recovery versus death. Treatment outcomes consisted of 34.67% full recovery (n = 147), 30.90% partial recovery (n = 131), 4.95% death (n = 21), and 29.48% unknown (n = 125). Speech/language abnormality and abnormal electroencephalogram (EEG) were each significantly associated with a higher relative risk for a full recovery. Treatment with intravenous immunoglobulin and plasmapheresis were each significantly associated with a higher relative risk for partial recovery. The analysis comparing death to full recovery found that catatonia was significantly associated with a lower relative risk for death. Increased age, orofacial dyskinesia, and no tumor removal were each significantly associated with a higher relative risk for death. Increased age, orofacial dyskinesia, and no tumor removal were associated with a higher relative risk for death in anti-NMDAR encephalitis in adults. Clinicians should monitor and appropriately treat anti-NMDAR encephalitis with these findings to minimize the risk of death.


Jumping translocations of 1q in Burkitt lymphoma and acute nonlymphocytic leukemia.
"Jumping translocations" have been observed mostly in cultured cells. Reports of such translocations in hematologic malignancies are few, and the associated clinical picture is unclear. We report three cases of hematologic malignancies with various unbalanced translocations (so-called jumping translocation) involving trisomy of the long arm of chromosome 1. The first case was a 13-year-old boy with Burkitt lymphoma who showed a very aggressive clinical course. The second case was a 10-month-old girl with acute nonlymphocytic leukemia [ANNL, French-American-British (FAB) classification M0] who had high risk factors, including hyperleukocytosis with a peripheral white blood cell (WBC) count of 300,000/microliters, and who died 7 months after diagnosis. The third case was a 6-year-old boy with Burkitt-like leukemia whose first remission lasted only 1 month. Only 10 cases with jumping translocations, including two cases with Burkitt-like leukemia/lymphoma, have been reported previously. This rare phenomenon may occur with increased frequency in Burkitt-like leukemia/lymphoma and may be an adverse prognostic factor.


Independent and combined effects of physical activity and body mass index on the development of Type 2 Diabetes - a meta-analysis of 9 prospective cohort studies.
The aim of this harmonized meta-analysis was to examine the independent and combined effects of physical activity and BMI on the incidence of type 2 diabetes. Our systematic literature review in 2011 identified 127 potentially relevant prospective studies of which 9 fulfilled the inclusion criteria (total N = 117,878, 56.2 % female, mean age = 50.0 years, range = 25-65 years). Measures of baseline physical activity (low, intermediate, high), BMI-category [BMI < 18.4 (underweight), 18.5-24.9 (normal weight), 25.0-29.9 (overweight), 30+ (obese)] and incident type 2 diabetes were harmonized across studies. The associations between physical activity, BMI and incident type 2 diabetes were analyzed using Cox regression with a standardized analysis protocol including adjustments for age, gender, educational level, and smoking. Hazard ratios from individual studies were combined in a random-effects meta-analysis. Mean follow-up time was 9.1 years. A total of 11,237 incident type 2 diabetes cases were recorded. In mutually adjusted models, being overweight or obese (compared with normal weight) and having low physical activity (compared with high physical activity) were associated with an increased risk of incident type 2 diabetes (hazard ratios 2.33, 95 % CI 1.95-2.78; 6.10, 95 % CI: 4.63-8.04, and 1.23, 95 % CI: 1.09-1.39, respectively). Individuals who were both obese and had low physical activity had 7.4-fold (95 % CI 3.47-15.89) increased risk of type 2 diabetes compared with normal weight, high physically active participants. This harmonized meta-analysis shows the importance of maintaining a healthy weight and being physically active in diabetes prevention.


G-CSF protects dopaminergic neurons from 6-OHDA-induced toxicity via the ERK pathway.
Granulocyte colony-stimulating factor (G-CSF) is known to have various functions such as induction of survival, proliferation and differentiation of hematopoietic cells. Recently, this factor has also been shown to exhibit neuroprotective effects in rat ischemic brain. In the present study, we first demonstrated that both G-CSF and G-CSF receptor were expressed in dopaminergic neurons in the adult substantia nigra and mesencephalic cultures, suggesting that G-CSF might exert its neuroprotective effects in dopaminergic neurons. Pretreatment with G-CSF protected dopaminergic neurons from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. Investigation of the underlying mechanisms showed that the extracellular-regulated kinase (ERK), but not Janus kinase/signal transducer(s) and activator(s) of transcription (JAK/STAT), was activated following G-CSF treatment. Moreover, G-CSF also increased phosphorylation of Bad, and restored 6-OHDA-induced decrease in Bcl-xL level. The 6-OHDA-caused caspase-3 activation in dopaminergic neurons was inhibited by G-CSF. Inhibition of ERK abrogated G-CSF-mediated Bad phosphorylation, Bcl-xL expression, activated caspase-3 reduction, and the protection of dopaminergic neurons. Taken together, G-CSF prevents dopaminergic neurons from 6-OHDA-induced toxicity via ERK pathway followed by inhibiting the apoptosis-execution process. These results suggest that G-CSF might have a therapeutic potential in Parkinson's disease.


A Multi-Hospital Survey of Current Practices for Supporting Recovery From Sepsis.
Sepsis survivors are at increased risk for morbidity and functional impairment. There are recommended practices to support recovery after sepsis, but it is unclear how often they are implemented. We sought to assess the current use of recovery-based practices across hospitals. Electronic survey assessing the use of best practices for recovery from COVID-related and non-COVID-related sepsis. Questions included four-point Likert responses of "never" to "always/nearly always." Twenty-six veterans affairs hospitals with the highest (n = 13) and lowest (n = 13) risk-adjusted 90-day sepsis survival. Inpatient and outpatient clinician leaders. None. For each domain, we calculated the proportion of "always/nearly always" responses and mean Likert scores. We assessed for differences by hospital survival, COVID versus non-COVID sepsis, and sepsis case volume. Across eight domains of care, the proportion "always/nearly always" responses ranged from: 80.7% (social support) and 69.8% (medication management) to 22.5% (physical recovery and adaptation) and 0.0% (emotional support). Higher-survival hospitals more often performed screening for new symptoms/limitations (49.2% vs 35.1% "always/nearly always," p = 0.02) compared with lower-survival hospitals. There was no difference in "always/nearly always" responses for COVID-related versus non-COVID-related sepsis, but small differences in mean Likert score in four domains: care coordination (3.34 vs 3.48, p = 0.01), medication management (3.59 vs 3.65, p = 0.04), screening for new symptoms/limitations (3.13 vs 3.20, p = 0.02), and anticipatory guidance and education (2.97 vs 2.84, p < 0.001). Lower case volume hospitals more often performed care coordination (72.7% vs 43.8% "always/nearly always," p = 0.02), screening for new symptoms/limitations (60.6% vs 35.8%, p < 0.001), and social support (100% vs 74.2%, p = 0.01). Our findings show variable adoption of practices for sepsis recovery. Future work is needed to understand why some practice domains are employed more frequently than others, and how to facilitate practice implementation, particularly within rarely adopted domains such as emotional support.


Amlodipine besylate-excipients interaction in solid dosage form.
This article studies the compatibility of amlodipine besylate in its solid formulations with various drug excipients. The various factors affecting amlodipine besylate stability were studied using high-performance liquid chromatography (HPLC). It has been found that binary 1:1 mixtures of amlodipine besylate and an excipient are stable at 65 degrees C and 40 degrees C/75% RH. Further investigations were conducted to study the stability of amlodipine besylate in multicomponent mixtures, including mixtures with actual formulations. The study reveals that mixtures of lactose, magnesium stearate, and water induce some instability on amlodipine besylate. The major degradation product confirmed by HPLC-mass spectrometry is amlodipine besylate glycosyl. This is in conformity with the well-known Maillard reaction between primary amines and lactose. Thus, lactose-free amlodipine formulations are recommended from the safety, quality, efficacy, and process cost points of view.


Primary carcinoma of the liver: clinical course and therapeutic results.
A Finnish series of 53 patients with primary carcinoma of the liver has been examined with a view to establishing the clinical course, the therapeutic results, and the factors which might influence the prognosis. Four tumors were resected, with one 6-year survival. All patients with no effective treatment were dead within 1 year from diagnosis. Thirty-seven nonresected patients with primary liver carcinoma were treated with chemotherapy and/or hepatic irradiation with mean survival time of 9.1 months after diagnosis. The best palliation in these patients was achieved by the combination treatment of chemotherapy and hepatic irradiation; the mean survival time was 13.8 months and, considering only the responders, 18.3 months. The laparotomy finding of 46 cases revealed that 67% of patients were without extrahepatic metastases of primary liver carcinoma at the time of diagnosis. At autopsy that figure was 44%. These data demonstrate that primary liver carcinoma is surprisingly often localized in the liver, but yet survival in these patients seems to be only occasionally favorably influenced by recent therapies, except hepatic resection, which remains the treatment of choice when feasible. Perhaps for primary carcinoma of the liver, the combination treatment of chemotherapy and hepatic irradiation gives better palliation than either one of these therapies alone.


Cognitive therapy for the prevention of suicide attempts: a randomized controlled trial.
Suicide attempts constitute a major risk factor for completed suicide, yet few interventions specifically designed to prevent suicide attempts have been evaluated. To determine the effectiveness of a 10-session cognitive therapy intervention designed to prevent repeat suicide attempts in adults who recently attempted suicide. Randomized controlled trial of adults (N = 120) who attempted suicide and were evaluated at a hospital emergency department within 48 hours of the attempt. Potential participants (N = 350) were consecutively recruited from October 1999 to September 2002; 66 refused to participate and 164 were ineligible. Participants were followed up for 18 months. Cognitive therapy or enhanced usual care with tracking and referral services. Incidence of repeat suicide attempts and number of days until a repeat suicide attempt. Suicide ideation (dichotomized), hopelessness, and depression severity at 1, 3, 6, 12, and 18 months. From baseline to the 18-month assessment, 13 participants (24.1%) in the cognitive therapy group and 23 participants (41.6%) in the usual care group made at least 1 subsequent suicide attempt (asymptotic z score, 1.97; P = .049). Using the Kaplan-Meier method, the estimated 18-month reattempt-free probability in the cognitive therapy group was 0.76 (95% confidence interval [CI], 0.62-0.85) and in the usual care group was 0.58 (95% CI, 0.44-0.70). Participants in the cognitive therapy group had a significantly lower reattempt rate (Wald chi2(1) = 3.9; P = .049) and were 50% less likely to reattempt suicide than participants in the usual care group (hazard ratio, 0.51; 95% CI, 0.26-0.997). The severity of self-reported depression was significantly lower for the cognitive therapy group than for the usual care group at 6 months (P= .02), 12 months (P = .009), and 18 months (P = .046). The cognitive therapy group reported significantly less hopelessness than the usual care group at 6 months (P = .045). There were no significant differences between groups based on rates of suicide ideation at any assessment point. Cognitive therapy was effective in preventing suicide attempts for adults who recently attempted suicide.


A Concise Synthesis of the Repeating Unit of Capsular Polysaccharide Staphylococcus aureus Type 8.
The first synthesis of the repeating unit of S. aureus capsular polysaccharide type 8 is described. The repeating unit is an unusual trisaccharide sequence of three uncommon sugars, all connected via 1,2-cis linkages. The synthetic trisaccharide was equipped with capping methyl groups at the points of propagation of the polysaccharide sequence.


trans-Tetra-aqua-bis-[bis-(pyridin-3-yl)methanone-κN]manganese(II) bis-(perchlorate).
In the title complex, [Mn(C(11)H(8)N(2)O)(2)(H(2)O)(4)](ClO(4))(2), the Mn(2+) ion is located on an inversion center with the slightly distorted N(2)O(4) octa-hedral coordination sphere comprising N-atom donors from two monodentate trans-related bis-(pyridin-3-yl)methanone ligands and four water ligands. The two perchlorate anions are linked to the mononuclear complex mol-ecule through water O-H⋯O hydrogen bonds while inter-complex water O-H⋯N(pyridine) inter-actions form an infinite chain structure extending along the b axis. The perchlorate anions also function as inter-unit links through water O-H⋯O hydrogen bonds which, together with water O-H⋯O(carbon-yl) inter-actions, give a three-dimensional framework structure.


African-American women's exclusion of women and inclusion of kin and males into their social networks: a mistrust of women issue?
In a previous study, a small group of rural African American women were found to have negative attitudes of mistrust of women, which influenced the size and composition of their social network. The purpose of this study was twofold: (1) to describe the size, gender, and kin composition of the social network of a larger sample of rural and small-city African American women and (2) to psychometrically evaluate the Brown Attitude toward Women (BATW) scale. Two hundred rural and small town women (both drug users and non-users) completed a paper and pencil survey. A large percentage (from 44-75%) of women completing the survey held negative attitudes toward other women, which were reasons they gave for excluding women from their social networks. The women's mistrust of other women appears to contribute to their small network size. Women with smaller social networks tended to include a larger percentage of males and kin within their networks. Research and clinical implications of this phenomenon are discussed.


Classification of atopic dermatitis phenotypes according to allergic sensitization by cluster analysis.
A cluster study to classify atopic dermatitis (AD) phenotypes into subgroups is required to better understand and manage the disease owing to the heterogeneity of its clinical features. This study aimed to identify the phenotypic subgroups of childhood AD according to allergic sensitization. In 258 children with AD, hierarchical cluster analysis based on specific immunoglobulin (Ig) E sensitization revealed four distinct clusters. Cluster A (n = 71) revealed no IgE sensitization, whereas cluster B (n = 28) showed sensitization to egg white only. Cluster B was highly associated with early-onset AD (<3 months) and a family history of atopic diseases. Cluster C (n = 68) and D (n = 91), sensitized to multiple foods and inhalants, respectively, showed a higher prevalence of skin infection within the last 1 year than others. Cluster D was related to late-onset AD (>12 months) and had more atopic comorbidities. In addition, cluster D showed the most severely impaired health-related quality of life and more frequent use of immunosuppressants. Therefore, childhood AD can be classified into 4 clusters based on the allergic sensitization status, and clinical phenotypes and treatment strategy may be different according to clusters.


Prioritizing population-based nutrition-related interventions to prevent and control hypertension in Iran: a multi-criteria decision-making approach.
Numerous nutrition-related policy options and strategies have been proposed to tackle hypertension and other risk factors of non-communicable diseases (NCDs). In this study, we developed a comparative analysis using a multi-criteria decision-making (MCDM) model for prioritizing population-based nutrition-related interventions to prevent and control hypertension in Iran. We employed a combination of Delphi technique and Analytic Hierarchy Process (AHP) method as the methodological tool to prioritize decision alternatives using multiple criteria. The prominent assessment criteria and intervention strategies were derived using a literature review, focus group discussion (n = 11), and a 2-round modified Delphi technique with specialists and experts involved in different stages of health policy-making (round 1: n = 50, round 2: n = 46). Then, the AHP was used to determine the weightage of the selected interventions and develop the decision-making model. The sensitivity analysis was performed to test the stability of the priority ranking. Nine alternative interventions were included in the final ranking based on eight assessment criteria. According to the results, the most priority interventions to prevent and control hypertension included reformulation of food products to contain less salt and changing the target levels of salt in foods and meals, providing low-sodium salt substitutes, and reducing salt intake through the implementation of front-of-package labeling (FOPL). The results of the sensitivity analysis and a comparison analysis suggested that the assessment model performed in this study had an appropriate level of robustness in selecting the best option among the proposed alternatives. MCDM techniques offer a potentially valuable approach to rationally structuring the problem, along with the opportunity to make explicit the judgments used as part of the decision-making model. The findings of this study provide a preliminary evidence base to guide future decisions and reforms aiming to improve appropriate population-based interventions for tackling hypertension and other risk factors of NCDs.


Physical properties of model biological lipid bilayers: insights from all-atom molecular dynamics simulations.
The physical properties of lipid bilayers are sensitive to the specific type and composition of the lipids that make up the many different types of cell membranes. Studying model bilayers of representative heterogeneous compositions can provide key insights into membrane functionality. In this work, we use atomistic molecular dynamics simulations to characterize key properties in a number of bilayer membranes of varying composition. We first examine basic properties, such as lipid area, volume, and bilayer thickness, of simple, homogeneous bilayers comprising several lipid types, which are prevalent in biological membranes. Such lipids are then used in simulations of heterogeneous systems representative of bacterial, mammalian, and cancer membranes. Our analysis is especially focused on depth-dependent, transmembrane profiles; in particular, we calculate lateral pressure and dipole potential profiles, two fundamental properties which play key roles in a large number of biological functions.


Bacillus anthracis CapD, belonging to the gamma-glutamyltranspeptidase family, is required for the covalent anchoring of capsule to peptidoglycan.
Several examples of bacterial surface-structure anchoring have been described, but they do not include polyglutamate capsule. Bacillus anthracis capsule, which is composed only of poly-gamma- d-glutamate, is one of the two major virulence factors of the bacterium. We analysed its anchoring. We report that the polyglutamate is anchored directly to the peptidoglycan and that the bond is covalent. We constructed a capD mutant strain, capD being the fourth gene of the capsule biosynthetic operon. The mutant bacilli are surrounded by polyglutamate material that is not covalently anchored. Thus, CapD is required for the covalent anchoring of polyglutamate to the peptidoglycan. Sequence similarities suggest that CapD is a gamma-glutamyltranspeptidase. Furthermore, CapD is cleaved at the gamma-glutamyltranspeptidase consensus cleavage site, and the two subunits remain associated, as necessary for gamma-glutamyltranspeptidase activity. Other Gram-positive gamma-glutamyltranspeptidases are secreted, but CapD is located at the Bacillus surface, associated both with the membrane and the peptidoglycan. Polyglutamate is hydrolysed by CapD indicating that it is a CapD substrate. We suggest that CapD catalyses the capsule anchoring reaction. Interestingly, the CapD(-) strain is far less virulent than the parental strain.


Consumers' intention-based influence factors of renewable energy adoption in Pakistan: a structural equation modeling approach.
As the adoption of renewable energy (RE) is a complex and intricate procedure affected by a wide range of factors, it prompts traction among researchers to examine these influence factors. The aim of this study is to scrutinize the factors affecting consumers' intention to adopt RE for household use in Pakistan. The current research has contributed through expanding the structural framework of the theory of planned behavior by incorporating three novel factors (perception of self-effectiveness, perception of neighbor's participation, and belief about RE benefits) to have a deep insight into the factors that motivate or inhibit consumers to adopt RE. Outcomes are based on the primary data compiled from 353 households in the five main cities of Pakistan accompanying an inclusive survey. The state-of-the-art structural equation modeling was utilized to test and analyze the proposed hypotheses. The results signify that the influencing factors such as perception of self-effectiveness, awareness of RE, and perception of neighbor's participation impart a positive effect on consumers' intention to adopt RE, whereas cost of RE generation has an opposite effect. Interestingly, environmental concern and belief about RE benefits found to have neutral effects. Research results emphasize the need to enhance public awareness, reform policy structure, transform social norms, and highlight the benefits that RE provides, all through an integrative and coherent way.


Secondary metabolites from the endophytic fungi Penicillium polonicum and Aspergillus fumigatus.
Two new compounds, rhodostegone (1) from endophytic fungus Penicillium polonicum and cyclo-(l-Val-l-Leu) (2) from Aspergillus fumigatus, together with six known diketopiperazines (3-8), were isolated. The structures of these compounds were characterized through a combination of extensive IR, MS, NMR, and CD analysis.


Exercise-induced changes in triceps surae tendon stiffness and muscle strength affect running economy in humans.
The purpose of the present study was to investigate whether increased tendon-aponeurosis stiffness and contractile strength of the triceps surae (TS) muscle-tendon units induced by resistance training would affect running economy. Therefore, an exercise group (EG, n = 13) performed a 14-week exercise program, while the control group (CG, n = 13) did not change their training. Maximum isometric voluntary contractile strength and TS tendon-aponeurosis stiffness, running kinematics and fascicle length of the gastrocnemius medialis (GM) muscle during running were analyzed. Furthermore, running economy was determined by measuring the rate of oxygen consumption at two running velocities (3.0, 3.5 ms(-1)). The intervention resulted in a ∼7 % increase in maximum plantarflexion muscle strength and a ∼16 % increase in TS tendon-aponeurosis stiffness. The EG showed a significant ∼4 % reduction in the rate of oxygen consumption and energy cost, indicating a significant increase in running economy, while the CG showed no changes. Neither kinematics nor fascicle length and elongation of the series-elastic element (SEE) during running were affected by the intervention. The unaffected SEE elongation of the GM during the stance phase of running, in spite of a higher tendon-aponeurosis stiffness, is indicative of greater energy storage and return and a redistribution of muscular output within the lower extremities while running after the intervention, which might explain the improved running economy.


A prospective evaluation of magnetic resonance imaging, computed tomography, and mediastinoscopy in the preoperative assessment of mediastinal node status in bronchogenic carcinoma.
Computed tomography, magnetic resonance imaging, chest roentgenography, and mediastinoscopy were compared prospectively as staging modalities to assess mediastinal node status in 84 patients with presumed operable bronchogenic carcinoma. Computed tomography was associated with a sensitivity of 71.0%, a specificity of 87.7% and an overall accuracy of 82.1%. Magnetic resonance imaging did not provide any advantage over computed tomography in the assessment of mediastinal node status. The accuracy of computed tomography was not dependent on cell type of the primary tumor. Although chest roentgenography had a sensitivity of 80.7%, the overall accuracy of 57.1% was unacceptably low. The sensitivity (87.1%), specificity (100%), positive (100%) and negative (93.0%) predictive values, and accuracy (95.2%) of mediastinoscopy exceeded those observed with all other modalities. We continue to recommend mediastinoscopy as the most accurate staging investigation in the routine management of patients with bronchogenic carcinoma.


Does NADH play a central role in energy metabolism in Helicobacter pylori?
The complete genome sequence of Helicobacter pylori reveals an unusual NADH-quinone oxidoreductase (NDH-1 or Complex I) that might lack the NADH-binding domain. H. pylori also lacks various NADH-generating enzymes. What are the consequences for electron transfer to H. pylori NDH-1 and could NADPH be involved?


[Patient education and breast cancer].
The therapeutic education program set up at the Institut Universitaire du Cancer (University Cancer Institute) in Toulouse accompanies the treatment pathway of breast cancer patients. It includes nine collective workshops. From work organization to application, professionals and patients are closely involved.


Prenatal Diagnosis of COL4A1 Mutations in Eight Cases: Further Delineation of the Neurohistopathological Phenotype.
Increasing number of mutations responsible for vascular lesions, leading to ischemic or hemorrhagic stroke in young adults, has been identified in the recent years. It has been demonstrated in both mice and humans, that mutations in COL4A1 gene promote cerebral hemorrhages. In humans, both adults and children may be affected, and the spectrum has been broadened recently to neonates and fetuses. We present a cohort of eight COL4A1 mutated fetuses in which cerebral hemorrhages were detected by ultrasound leading to elective terminations of pregnancy. Our neuropathological studies demonstrated a strikingly similar pathological pattern, dominated by supra- and infratentorial multifocal hemorrhagic lesions of various abundance and age in the vicinity of enlarged small vessels having a discontinuous wall. This was constantly associated with a spectrum of supratentorial post-ischemic damages of the grey and white matters. Morphometric studies of brain vessels confirmed vascular dilation and hypervascularization in both grey and white matters and severe attenuation of the smooth-muscle actin staining in the white matter. These observations add to the rare human neuropathological phenotype of COL4A1 mutations. Its recognition is mandatory to enhance the number of tested patients in the future, as well as the genetic counseling of parents.


Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis.
Diagnosis and management of latent tuberculosis (TB) infections are one of the challenges of eradicating pulmonary TB. A critical aspect of controlling pulmonary TB spread is early diagnosis. One TB biological marker type under evaluation is microRNAs (miRNAs). Mycobacterium tuberculosis infection causes epigenetic changes. The upregulation of miRNA-29a-3p suppresses the immune response by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells, increasing susceptibility to pulmonary TB. This study aimed to assess miRNA-29a-3p expression as a biomarker of active and latent pulmonary TB infection. This case-control study included 50 individuals with active TB, 33 household contacts with a positive IFN-γ release assay (IGRA), and 30 healthy controls. An enzyme-linked immunosorbent assay-based IGRA was used to determine latent pulmonary TB infection in household contacts. Quantitative real-time PCR was used to quantify miRNA-29a-3p expression. Data analysis used analyses of variance and receiver operating characteristic (ROC) curves. miRNA-29a-3p expression differed significantly between active TB, latent TB, and healthy participants (controls; p = <0.001. ROC curve analysis showed that miRNA-29a-3p expression had 86% sensitivity and 73% specificity with an area under the ROC curve (AUC) of 0.763 (95% confidence interval [CI]: 0.668-0.858). The miRNA-29a-3p ROC curve had 84.8% sensitivity and 70% specificity with an AUC of 0.808 (95% CI: 0.698-0.919) for latent TB. Additionally, miRNA-29a-3p expression was significantly correlated with active (p < 0.0001) and latent (p < 0.0001) pulmonary TB. However, miRNA-29a-3p expression was not significantly correlated with INF-γ levels in patients with active (R = 0.005; p = 0.62) and latent (R = 0.010; p = 0.38) pulmonary TB or healthy controls (R = 0.060; p = 0.19). miRNA-29a-3p expression was increased in patients with active and latent pulmonary TB. Therefore, miRNA-29a-3p represents a potential biomarker for latent and active pulmonary TB. However, IFN-γ levels were not correlated with miR-29a-3p expression.


Bipolar diagnosis in China: Evaluating diagnostic confidence using the Bipolarity Index.
Diagnosis of bipolar disorder is inherently difficult. The goal of this study was to examine the utility and psychometric properties of the Bipolarity Index (BPx) in a population of patients treated in China. At nine Chinese health facilities participating in CAFÉ-BD, clinicians completed a standardized affective disorder evaluation for consecutive patients (N=615) with a clinical diagnosis of MDD and BPD and scored the Bipolarity Index. The investigators constructed ROC curves to determine the optimal cut off points to discriminate subjects in three clinical diagnostic groups: bipolar disorder (BPD), major depressive disorder (MDD) and healthy (no psychiatric diagnosis) controls (HC). This study is registered with ClinicalTrials.gov, number NCT02015143. 1) The cut-off score between the MDD and BPD groups was 42.0, with a sensitivity of 0.957 and specificity of 0.881 (Z=63.064, P<0.001); the cut-off score between the MDD and BPD II groups was 34.0, with a sensitivity of 0.810 and specificity of 0.855 (Z=20.174, P<0.001); and the cut-off score between the BPD II and BPD I groups was 57.0, with a sensitivity of 0.680 and specificity of 0.772 (Z=9.636, P<0.001). 2) Five domains contributed to the discrimination results. State-related domains (episode characteristics and course of illness) made greater contributions than trait-related domains (age of onset, family history, and treatment response). The data are purely descriptive. The BPD II sample and the family history dataset were small. Our finding indicates good reliability and validity for the Chinese version of the BPx, which encourages its use as a measure of diagnostic confidence for bipolar spectrum disorders. Further prospective study is necessary to determine if the BPx is useful in identifying subgroups among MDD subjects at high risk for conversion to BPD.


A new sequence-specific endonuclease (Bsp) from Bacillus sphaericus.
A new restriction endonuclease has been isolated from Bacillus sphaericus R. The purification procedure includes Bio-Gel filtration, (NH4)2SO4 fractionation and phosphocellulose chromatography. After the phosphocellulose step the enzyme preparation is free of non-specific nucleases. Bsp cleaves double-stranded DNA with the same specificity as Bacillus subtilis (Bsu) and Haemophilus aegyptius (HaeIII) restriction endonucleases, as concluded from digests and double-digests of phiX174 replicative form DNA with Bsu and Bsp. The 5'-terminal nucleotide of the cleavage products was shown to be C. Bacillus sphaericus R produces Bsp in extremely large quantities and the enzyme can be easily purified in high yield.


Immune Therapy for Sarcomas.
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care. Preclinical and clinical efforts to enhance immune function against sarcoma will be reviewed. Interventions to enhance immune function against sarcoma have included regional therapy (surgery, cryoablation, radiofrequency ablation, electroporation, and radiotherapy), cytokines, macrophage activators (mifamurtide), vaccines, natural killer (NK) cells, T cell receptor (TCR) and chimeric antigen receptor (CAR) T cells, and efforts to decrease inflammation. The latter is particularly important because of new knowledge about factors influencing expression of checkpoint inhibitory molecules, PD1 and CTLA-4, in the tumor microenvironment. Since these molecules can now be blocked using anti-PD1 and anti-CTLA-4 antibodies, how to translate this knowledge into more effective immune therapies in the future as well as how to augment effectiveness of current interventions (e.g., radiotherapy) is a challenge. Barriers to implementing this knowledge include cost of agents that release immune checkpoint blockade and coordination of cost-effective outpatient sarcoma treatment. Information on how to research clinical trial eligibility criteria and how to access current immune therapy trials against sarcoma are shared, too.


Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.
Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.


Uterine geometry by Wing Sound and hysterography versus direct measurements.
Selecting an IUD that fits the uterine dimensions is believed to be a keystone in improving IUD performance. This study included 15 women admitted for hysterectomy with no gross pelvic pathology distorting the uterine cavity and no contraindication to hysterography. Before hysterectomy the uterine cavity dimensions were measured using the Wing Sound II device and hysterography. After hysterectomy, direct measurements of the same dimensions were performed. The correlation between the Wing Sound II device measurements and those obtained by the direct method was highly significant except for the fundal transverse dimension where the correlation was moderately significant. On the other hand, hysterography measurements had a moderately significant correlation with those obtained by the direct method, except for the fundal transverse dimensions and the total uterine length where the correlation was insignificant. The Wing Sound II device is a simple, safe and accurate tool for studying uterine geometry on an outpatient basis.


A fourth-year medical school rotation in quality, patient safety, and population medicine.
Quality improvement and population medicine are skills that are increasingly important for physicians to possess. Methods to achieve foundational acquisition of these skills in medical school have not been well described in the past. The primary goal of this project is to provide hands-on, experiential learning in full-cycle population-based care. A description is given of a 4-week, team-based, rapid-cycle quality improvement project embedded in a required fourth-year medical school rotation. Over the course of 4 years a nonspecialty generic Ambulatory Care rotation was converted to a population-based learning rotation. For the last 3 years this rotation has required students to participate in teams of three to four students to assess, plan, implement, and evaluate a quality improvement project. Between 2008 and 2010 a total of 510 students completed the rotation. During this time the project component of the rotation received a 53% average rating of "excellent" or "above average." Qualitative evaluation indicates the project to be an acceptable and worthwhile educational experience for medical students, adding new insights and occasionally career-changing perspectives. Although experiential team-based quality improvement projects are a new format for learning in the medical school environment, it can be implemented in a format that is acceptable and beneficial to future physicians and healthcare systems.


Stimulation of autophagy improves vascular function in the mesenteric arteries of type 2 diabetic mice.
What is the central question of this study? What is the role of autophagy in vascular dysfunction in type 2 diabetes? What is the main finding and its importance? Autophagy is decreased in the mesenteric arteries of type 2 diabetic mice, and stimulation of autophagy using rapamycin and trehalose improves vascular function, which is associated with normalization of myogenic response and endothelium-dependent relaxation. Vascular dysfunction is a major complication in type 2 diabetes (T2D). It has been suggested that dysregulation of autophagy is associated with various cardiovascular diseases. However, the relationship between autophagy and vascular dysfunction in T2D remains unclear. Thus, we examined whether reduced autophagy is involved in vascular dysfunction and whether stimulation of autophagy could improve vascular function in diabetes. Ten- to twelve-week-old male type 2 diabetic (db- /db- ) mice and their control (db- /db+ ) mice were treated with rapamycin or trehalose. Mesenteric arteries (MAs) were mounted for arteriography and their diameter was measured. Western blot analysis and immunofluorescence staining were assessed. Myogenic response (MR) was significantly increased, whereas endothelium-dependent relaxation (EDR) was significantly attenuated in the MAs of diabetic mice. These results were associated with increased expression of LC3II, p62 and beclin-1 in diabetic mice. Treatment with autophagy stimulators significantly reduced the potentiation of MR and improved EDR in the diabetic mice. Furthermore, autophagy stimulation normalized expression of LC3II, p62 and beclin-1 in the diabetic mice. In addition, phosphorylation level of endothelial nitric oxide synthase was decreased in diabetic mice and was restored by rapamycin and trehalose. T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications.


Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: implication for breast carcinogenesis.
Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogenesis. Breast reduction tissues from young women and teenagers, representative of USA's high breast cancer incidence population, were studies using immunocytochemistry and targeted PCR arrays in order to learn whether a marker of chronic oxidative-stress [protein adducts of 4-hydroxy-2-nonenal (4HNE)] can identify where molecular changes relevant to carcinogenesis might be taking place prior to any histological changes. 4HNE-immunopositive (4HNE+) mammary epithelial cell-clusters were identified in breast tissue sections from most women and from many teenagers (ages 14-30 y) and, in tissues from women ages 17-27 y with many vs. few 4HNE+ cells, the expression of 30 of 84 oxidative-stress associated genes was decreased and only one was increased > 2-fold. This is in contrast to increased expression of many of these genes known to be elicited by acute oxidative-stress. The findings validate using 4HNE-adducts to identify where molecular changes of potential relevance to carcinogenesis are taking place in histologically normal mammary epithelium and highlight differences between responses to acute vs. chronic oxidative-stress. We posit that the altered gene expression in 4HNE+ tissues reflect adaptive responses to chronic oxidative-stress that enable some cells to evade mechanisms that have evolved to prevent propagation of cells with oxidatively-damaged DNA and to accrue heritable changes needed to establish a cancer.


The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation.
The CSF-1 receptor (CSF-1R) regulates CNS microglial development. However, the localization and developmental roles of this receptor and its ligands, IL-34 and CSF-1, in the brain are poorly understood. Here we show that compared to wild type mice, CSF-1R-deficient (Csf1r-/-) mice have smaller brains of greater mass. They further exhibit an expansion of lateral ventricle size, an atrophy of the olfactory bulb and a failure of midline crossing of callosal axons. In brain, IL-34 exhibited a broader regional expression than CSF-1, mostly without overlap. Expression of IL-34, CSF-1 and the CSF-1R were maximal during early postnatal development. However, in contrast to the expression of its ligands, CSF-1R expression was very low in adult brain. Postnatal neocortical expression showed that CSF-1 was expressed in layer VI, whereas IL-34 was expressed in the meninges and layers II-V. The broader expression of IL-34 is consistent with its previously implicated role in microglial development. The differential expression of CSF-1R ligands, with respect to CSF-1R expression, could reflect their CSF-1R-independent signaling. Csf1r-/- mice displayed increased proliferation and apoptosis of neocortical progenitors and reduced differentiation of specific excitatory neuronal subtypes. Indeed, addition of CSF-1 or IL-34 to microglia-free, CSF-1R-expressing dorsal forebrain clonal cultures, suppressed progenitor self-renewal and enhanced neuronal differentiation. Consistent with a neural developmental role for the CSF-1R, ablation of the Csf1r gene in Nestin-positive neural progenitors led to a smaller brain size, an expanded neural progenitor pool and elevated cellular apoptosis in cortical forebrain. Thus our results also indicate novel roles for the CSF-1R in the regulation of corticogenesis.


Essential information for neurorecovery clinical trial design: trajectory of global disability in first 90 days post-stroke in patients discharged to acute rehabilitation facilities.
Many stroke recovery interventions are most beneficial when started 2-14d post-stroke, a time when patients become eligible for inpatient rehabilitation facilities (IRF) and neuroplasticity is often at its peak. Clinical trials focused on recovery need to expand the time from this plasticity to later outcome timepoints. The disability course of patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) enrolled in Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial with moderate-severe disability (modified Rankin Scale [mRS] 3-5) on post-stroke day4 who were discharged to IRF 2-14d post-stroke were analyzed. Among 1422 patients, 446 (31.4%) were discharged to IRFs, including 23.6% within 2-14d and 7.8% beyond 14d. Patients with mRS 3-5 on day4 discharged to IRFs between 2-14d accounted for 21.7% (226/1041) of AIS patients and 28.9% (110/381) of ICH patients, (p < 0.001). Among these AIS patients, age was 69.8 (± 12.7), initial NIHSS median 8 (IQR 4-12), and day4 mRS = 3 in 16.4%, mRS = 4 in 50.0%, and mRS = 5 in 33.6%. Among these ICH patients, age was 62.4 (± 11.7), initial NIHSS median 9 (IQR 5-13), day 4 mRS = 3 in 9.4%, mRS = 4 in 45.3%, and mRS = 5 in 45.3% (p < 0.01 for AIS vs ICH). Between day4 to day90, mRS improved ≥ 1 levels in 72.6% of AIS patients vs 77.3% of ICH patients, p = 0.3. For AIS, mRS improved from mean 4.17 (± 0.7) to 2.84 (± 1.5); for ICH, mRS improved from mean 4.35 (± 0.7) to 2.75 (± 1.3). Patients discharged to IRF beyond day14 had less improvement on day90 mRS compared with patients discharged between 2-14d. In this acute stroke cohort, nearly 1 in 4 patients with moderate-severe disability on post-stroke day4 were transferred to IRF within 2-14d post-stroke. ICH patients had nominally greater mean improvement on mRS day90 than AIS patients. This course delineation provides a roadmap for future rehabilitation intervention studies.


"Remember to take your medication": Prospective memory in Korsakoff's syndrome.
While event-based prospective memory refers to enacting intending action in response to a specific event or cue ("e.g., When I tell you there are 10 minutes left, please give me this stopwatch"), time-based prospective memory refers to enacting intending action in relation to a specific time ("In 10 minutes time, please ask me for a pencil"). Relative to event-based prospective memory, little is known about time-based prospective memory in Korsakoff's syndrome (KS). We used behavioral tasks to investigate event- and time-based prospective memory as well as episodic memory and executive function in patients with KS and control participants. Analysis demonstrated lower event- and time-based prospective memory in patients with KS than in control participants. Interestingly, we found lower time-based than event-based prospective memory in patients with KS. Further, significant correlations were observed between prospective memory and episodic memory and executive function in the patients. Prospective memory is important for everyday life tasks, and failures of prospective memory can endanger patients' safety. One clinical implication of our findings is the importance of including an evaluation of prospective memory in cognitive evaluation of KS.


Reactivation of HbF synthesis in normal adult erythroid bursts by IL-3.
Reactivation of HbF synthesis has been reported in normal adult erythroblast colonies ('burst') generated by erythroid progenitors (BFU-E) after seeding peripheral blood mononuclear cells (PBMC) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated by erythropoietin (Ep). Reactivation is almost totally suppressed when: (i) PMBC are grown in optimized FCS- culture or (ii) PBMC are first stringently depleted of monocytes and then plated in FCS+ medium (i.e. BFU-E growth in FCS+Mo- culture). In either case, addition of biosynthetic granulocyte-macrophage colony stimulating factor (GM-CSF) induces a dose-related increase of relative HbF synthesis up to the level in FCS+ culture. We report that, in FCS- culture of partially purified adult blood BFU-E, treatment with biosynthetic interleukin 3 (IL-3) causes a dose-related rise of relative HbF production in the bursts. A similar phenomenon is observed in FCS+ culture of highly purified BFU-E. The rise of HbF synthesis is seemingly mediated, at least in part, by a direct effect of IL-3 at BFU-E level. It is tentatively concluded that reactivation of HbF in vitro, as well as in a variety of in vivo conditions (i.e. stress erythropoiesis, marrow regeneration), may be at least in part mediated by IL-3 and GM-CSF.


Therapeutic effect of a temporary transpyloric stent in refractory post-surgical gastroparesis: a case report.
Gastroparesis is a syndrome characterized by delayed gastric emptying with associated symptoms. It was reported that the symptoms of diabetic gastroparesis had been greatly improved by transpyloric stent placement. However, the use of stents in benign conditions is considered to be contraindicated because of the increasing risk of complications, such as stent migration, reflux, perforation, bleeding, and, most importantly, new strictures caused by stent-induced tissue hyperplasia. While temporary placement of a self-expanding metallic stent (SEMC) can drastically reduce the risk of complications, few reports are available on the treatment of refractory PSG by temporary transpyloric stent. Does it have a long-term clinical effect after the stent being retrieved? After accepting partial resection of the lesser curvature in another hospital, a patient developed refractory gastroparesis. The symptoms hadn't been improved after long-term drug therapy and balloon dilation therapy. Four months after surgery, a fully covered SEMC was placed by endoscopy in our hospital. Gastroparesis had been greatly improved. Two weeks later, the transpyloric stent was retrieved and the patient didn't show recurrent symptoms. Follow-ups were arranged at 3 months, 6 months and 1 year respectively, and there was no evidence of recurrence was found. This case indicates that temporary transpyloric SEMC is a safe, effective and less invasive alternative for post-surgical gastroparesis patients.


Secular trends in the prevalence of type 2 diabetes in adults in China from 1995 to 2014: A meta-analysis.
The aim of the present study was to estimate trends in the prevalence of type 2 diabetes mellitus (T2DM) in adults in China. A systematic search was conducted for studies of T2DM prevalence in adults in China from 2000 to 2014. Pooled prevalence was calculated by a random-effects model. Subgroup and sensitivity analyses were performed. Chi-squared and Cochran-Mantel-Haenszel tests were used to assess differences among subgroups and pooled prevalence, respectively. Forty-six studies (data from 1995 to 2014; 1 463 079 adults) were included in the meta-analysis. The overall prevalence of T2DM was 7.9 %. The pooled prevalence overall and by location (urban and rural), gender (male and female), and age category (18-39, 40-59, and ≥60 years) was 4.5 %, 5.1 % and 3.0 %, 4.0 % and 4.2 %, and 1.4 %, 5.0 %, and 10.3 %, respectively, from 1995 to 1999; 6.6 %, 9.3 % and 5.6 %, 7.4 % and 7.5 %, and 1.8 %, 5.9 %, and 12.4 %, respectively, from 2000 to 2004; 10.3 %, 11.8 % and 6.8 %, 10.0 % and 8.6 %, and 2.8 %, 10.3 %, and 20.0 %, respectively, from 2005 to 2009; and 8.3 %, 12.5 % and 7.6 %, 8.6 % and 8.0 %, and 3.5 %, 8.5 %, and 15.3 %, respectively, from 2010 to 2014. The prevalence increased from 5.8 % to 11.6 % with per-capita gross domestic product and differed by diagnostic criteria. There was a trend of increasing prevalence of T2DM in adults in China from 1995 to 2009, with a decrease in 2010-14 and a greater increase over time in urban versus rural areas, males versus females, and older versus younger adults.


Postoperative outcomes in robotic gastric resection compared with laparoscopic gastric resection in gastric cancer: A meta-analysis and systemic review.
Robotic gastrectomy is a commonly used procedure for early gastric cancer and it also overcomes the limitation of laparoscopic. However, the complications of robotic gastrectomy (RG) still need to be assessed. Our study was designed to compare postoperative complications of RG with laparoscopic gastrectomy (LG). A meta-analysis and systemic review were prospectively collected using the PubMed, Cochrane Library, and MEDLINE database of published studies by comparing the RG and LG with gastric cancer up to December 2021. To evaluate the postoperative outcomes, odds ratios were calculated for Dichotomous data and the mean difference with 95% confidence interval (CI) was calculated for continuous data, and measured by the random-effect model. Thirty-two retrospective studies describing 13,585 patients (4484 RG and 9101 LG) satisfied the inclusion criteria. A statistically significant result was in blood loss (MD = -17.97, 95% Cl: -25.61 to 10.32, p < 0.001), Clavien-Dindo grade Ⅲ (odds ratio (OR) = 0.60, 95% CI: 0.48-0.76, p < 0.01), and harvested lymph node (MD = 2.62, 95% CI: 2.14-3.11, p < 0.001). There was no significant difference between robotic gastrectomy surgery (RGS) and laparoscopic gastrectomy surgery (LGS) regarding distal resection margin (DRM), proximal resection margin (PRM), conversion rate, anastomotic leakage, and overall complications. Having significant outcomes in Clavien-Dindo grade III, and blood loss, harvested lymph nodes are more common in RGS, and they also help in increasing the quality of life.


Positive regulation of additional sex comb-like 1 gene expression by the pluripotency factor SOX2.
Additional sex comb-like 1 (ASXL1) has been suggested to be an enhancer of trithorax and polycomb proteins, and functions as a dual co-regulator of retinoid acid (RA) signaling. However, the mechanism by which ASXL1 gene expression is regulated remains unresolved. Concomitant downregulation of both SOX2 and ASXL1 during the RA-induced differentiation of P19 cells prompted us to investigate the role of SOX2 in the regulation of ASXL1. Knockdown of SOX2 in SOX2-rich NT2 cells resulted in the reduction of ASXL1 expression, whereas SOX2 overexpression in SOX2-deficient H1299 cells increased ASXL1 expression. Using a cloned ASXL1-luciferase reporter, we demonstrated that SOX2 directly transactivates the ASXL1 promoter. Serial deletion and mutation studies mapped the SOX2 response element region in the ASXL1 promoter to -1600 to -1400 bp. We showed by chromatin immunoprecipitation assay that SOX2 directly binds to the ASXL1 promoter region. Finally, formation of embryonic bodies by ASXL1-depleted murine E14TG2a embryonic stem cells was significantly impaired, similar to SOX2-knockdown cells. From these results, we suggest that ASXL1 may be a direct target of SOX2 and may play a role in maintaining the pluripotency of stem cells.


Using cognitive modeling to examine the effects of competition on strategy and effort in races and tournaments.
We investigated the effects of two types of competition, races and tournaments (as well as an individual challenge and a do-your-best condition), on two different aspects of performance: effort and strategy. In our experiment, 100 undergraduate participants completed a simple cognitive task under four experimental conditions (in a repeated-measures design) based on different types of competitions and challenges. We used the Linear Ballistic Accumulator to quantify the effects of competition on strategy and effort. The results reveal that competition produced changes in strategy rather than effort, and that trait competitiveness had minimal impact on how people responded to competition. This suggests individuals are more likely to adjust their strategy in competitions, and the uncertainty created by different competition types influences the direction of these strategy adjustments.


Spectroscopic studies of cutaneous photosensitizing agents. XVII. Benzanthrone.
The photochemistry of benzanthrone (7H-benz[de]-anthracene-7-one) has been studied using electron paramagnetic resonance (EPR) in conjunction with the spin trapping technique and the direct detection of singlet molecular oxygen luminescence. Irradiation (lambda ex = 394 nm) of benzanthrone (BA) in aerated ethanol, dimethylsulfoxide or benzene resulted in the generation of superoxide (O2-.) which was trapped by 5,5-dimethyl-1-pyrroline-N-oxide. The ethoxy radical was also detected in ethanol. Photolysis of BA in deaerated basic ethanol led to the formation of BA anion radical, BA-., which was detected directly by ESR. This radical anion decayed back to BA with a unimolecular rate constant of 1.5 x 10(-3) s-1. The 1O2 quantum yields (lambda ex greater than 345 nm) for BA in ethanol, 90% ethanol and basic ethanol (0.1N NaOH) were 0.89, 0.88 and 0.28 respectively relative to Rose Bengal. The lower yield of 1O2 in basic ethanol may be attributable to the reaction of oxygen with BA-. (which is generated in higher yield at alkaline pH) to give O2-.. These findings suggest that on exposure to light BA can generate active oxygen species which may be responsible for the photocontact dermatitis caused by BA in industrial workers exposed to this chemical.


Hydrophobicity of several rhodium(II) carboxylates correlated with their biologic activity.
Rhodium(II) carboxylates differ greatly in antitumor activity and toxicity depending on the properties of the carboxylate group (methoxyacetate, propionate, butyrate, etc.) involved. The solubility characteristics of rhodium(II) carboxylates correlate well with both the antitumor activity and toxicity that these compounds display. The amount of rhodium which is adsorbed by tumor cells in vitro also correlates with the partition coefficient of the rhodium(II) compounds studied. Survival and toxicity studies show rhodium(II) pentanoate to possess the highest therapeutic index against the Ehrlich ascites tumor strain and also show that lengthening the carboxylate R chain beyond the pentanoate reduces the drugs' therapeutic efficacy.


Case report. Fungaemia due to Penicillium piceum, a member of the Penicillium marneffei complex.
Due to the inability of most Penicillium species to grow at 37 degrees C, systemic non-marneffei infections are very rare in the human host. We describe a case of fungemia due to Penicillium piceum in a female patient, who died a few days after repeated isolation of this fungus from blood cultures. The species is a member of the section Biverticillata of Penicillium, as was confirmed by rDNA Internal Transcribed Spacer (ITS) sequence data, and hence may share virulence factors with P. marneffei.


Onfalopagus parasitic fusioned twin: A case report.
The parasitic fetus is a kind of siamese twin, in which one of the twins is reabsorbed and some parts of the body can remain attached to the other twin. It is a very rare event, with a birth incidence that varies from 0.05 to 1.47 cases per 100,000. This paper reports the case of a parasitic twin diagnosed at 34 weeks of gestational age. Preoperative ultrasonography was performed and the absence of communication between vital organs and the parasite was observed, and surgery was scheduled at 10 days of life. A multidisciplinary team performed the surgical procedure and the child was discharged from the intensive care unit after 3 months. After diagnosis and birth, it is essential to investigate the anomalies found for future surgical programming, and cases of twins who do not share vital organs, for example, heart or brain, have higher survival rates. The treatment is surgical and the objective of the surgery must be resection of the parasite. The diagnosis still in the gestational period is essential to plan the best mode of delivery and neonatal care, as well as define the surgical schedule. The hospital must be tertiary and the presence of a multidisciplinary team is necessary to perform the surgery in order to present the highest success rates.


In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 3. Catalytic and regulatory properties of carbamylphosphate synthetase: channeling of carbamylphosphate to aspartate transcarbamylase.
The present work reports direct evidence for the channeling of carbamylphosphate from carbamylphosphate synthetase to aspartate transcarbamylase in the multifunctional protein that catalyzes the two first reactions of the pyrimidine pathway in Saccharomyces cerevisiae. This phenomenon is almost certainly related to the previously reported observation that the apparent in situ catalytic mechanism of aspartate transcarbamylase is altered by the association of this enzyme to carbamylphosphate synthetase. As a prerequisite of this investigation, the in situ catalytic and regulatory properties of carbamylphosphate synthetase were studied in the permeabilized cells of a strain that contains the wild-type multifunctional protein but is devoid of the carbamylphosphate synthetase specific for the arginine pathway.


Image in Hydatid Disease of the Central Nervous System.
Hydatid disease most frequently occurs in the liver. This article presents a case of spinal cord compression caused by vertebral hydatidosis with typical imaging characteristics and pathologic findings, which is rarely involved in the hydatidosis. The patient was successfully treated with surgical excision combined with antiparasitic therapy.


Measurement of 5-hydroxy-2-aminovaleric acid as a specific marker of metal catalysed oxidation of proline and arginine residues of low density lipoprotein apolipoprotein B-100 in human atherosclerotic lesions.
gamma-Glutamyl-semialdehyde (gammaGSA) is a major product of the metal catalysed oxidation of apolipoprotein B-100 (apoB-100) proline and arginine residues. On reduction, gammaGSA forms 5-hydroxy-2-aminovaleric acid (HAVA). This report describes the application of HAVA measurement to characterise the formation of gammaGSA in low density lipoprotein (LDL) recovered from human atherosclerotic lesions. HAVA concentrations were greatly increased in LDL from early (mean, 10.25; SD, 3.49 mol/mol apoB-100; p < 0.01), intermediate (mean, 11.18; SD, 2.37 mol/mol apoB-100; p < 0.01), and advanced (mean, 9.91; SD, 2.15 mol/mol apoB-100; p < 0.01) lesions, when compared with LDL from normal aortic tissue (mean, 0.05; SD, 0.01 mol/mol apoB-100). These findings support the hypothesis that pathways involving metal catalysed oxidation of LDL apoB-100 are of pathological importance in atherogenesis.


De novo major cardiovascular events in kidney transplant recipients: a comparative matched cohort study.
Although cardiovascular disease is known to be one of the leading causes of death after kidney transplantation (KT), evidence on the risk difference of de novo major adverse cardiovascular events (MACEs) in kidney transplant recipients (KTRs) compared with that in dialysis patients or the general population (GP) remains rare. We identified KTRs using the nationwide health insurance database in South Korea and then 1:1 matched them with the dialysis and GP controls without a pre-existing MACE. The primary endpoint was defined as de novo MACEs consisting of myocardial infarction, coronary revascularization and ischemic stroke. The secondary endpoints were all-cause mortality and death-censored graft failure (DCGF) in KTRs. We included 4156 individuals in each of the three groups and followed them up for 4.7 years. De novo MACEs occurred in 3.7, 21.7 and 2.5 individuals per 1000 person-years in the KTRs, dialysis controls and GP controls, respectively. KTRs showed a lower MACE risk {adjusted hazard ratio (aHR) 0.16 [95% confidence interval (CI) 0.12-0.20], P < .001} than dialysis controls, whereas a similar MACE risk to GP controls [aHR 0.81 (95% CI 0.52-1.27), P = .365]. In addition, KTRs showed a similar MACE risk compared with the GP group, regardless of age, sex and the presence of comorbidities, including hypertension, diabetes and dyslipidemia. Among KTRs, de novo MACEs were associated with an increased risk of all-cause mortality, but not with DCGF. De novo MACEs in KTRs were much lower than that in dialysis patients and had a similar risk to the GP, but once it occurred it caused elevated mortality risk in KTRs.


Historic racism in Kansas City affects Today's pediatric asthma burden.
Asthma morbidity is unequally distributed across populations throughout the United States, and reasons remain unclear. To assess how historical structural racism correlates with current day asthma disparities, we conducted a retrospective cohort study of 10,736 pediatric patients, ages 3-19 years, with two or more asthma encounters between October 2017-October 2019. Patient addresses were matched with historic Home Owners' Loan Corporation (HOLC) maps - which provide a measure of historic structural racism. Residential proximity to pollution sources served as an additional exposure measure. Healthcare utilization and asthma severity were studied against age, race, SES, geographic proximity to pollution, and HOLC grades. Patients living in historically divested neighborhoods and BIPOC patients were likely to require more acute care for asthma, even when adjusting for present day SES and residential proximity to pollution sources. This supports the assertion that historic structural racism influences present-day health.


Targeted polymeric therapeutic nanoparticles: Design and interactions with hepatocellular carcinoma.
Nanoparticles (NPs) have great potential as drug delivery systems or as drugs for treating certain diseases. We designed three NPs with different charges and modifications with PEG to treat tumors. PDLA-CS, PEG-PLGA-PLL, and PEG-PS/CaP NPs were designed and evaluated to assess NPs fate in vivo and efficacy for treating tumors. Comparison between PEG-modified and non-PEG-modified NPs showed that PEG-modified NPs increased K(+) efflux, easily escaped from lysosomes, affected the mitochondria, induced mitochondrial apoptosis, had longer circulation time, and easily targeted tumors. Non-PEG-modified NPs induce the endoplasmic reticulum apoptosis pathway. Comparison between positively and negatively charged NPs showed that negatively charged NPs have less effect on the K(+) efflux of normal cells and more effect on the mitochondrial apoptosis of tumor cells. Positively charged NPs accumulated within the tumors and the liver and lungs. These results provide a theoretical basis for future clinical applications.


[Duration of breastfeeding in preterm infants followed at a secondary referral service].
Identify and analyze variables associated with shorter duration of breastfeeding in preterm infants. Retrospective cohort of premature infants followed up at secondary referral service in the period of 2010-2015. first appointment in the first month of corrected age and have undergone three or more consultations. Exclusion: diseases that impaired oral feeding. duration of breastfeeding. A total of 103 preterm infants were evaluated, accounting for 28.8% of the preterm infants born in the municipality in that period, with a power of study of 80%. Descriptive analysis, t-test, chi-square test, Kaplan-Meier curves and Cox regression were used. p-values<0.05 were considered significant. The median duration of breastfeeding among preterm infants was 5.0 months. The risk of breastfeeding discontinuation among preterm infants with gestational age <32 weeks was 2.6-fold higher than for those born at 32 weeks or more and the risk of breastfeeding interruption in preterm infants who were receiving breastfeeding supplementation in the first outpatient visit was 3-fold higher when compared to those who were exclusively breastfed in the first consultation. The median duration of breastfeeding in preterm infants was below the recommended one and discontinuation was associated with gestational <32 weeks and the fact that the infant was no longer receiving exclusive breastfeeding in the first outpatient visit. When these two variables were associated, their negative effect on the median duration of breastfeeding was potentiated.


The elastic constraint effect: a possible factor in renal perfusion.
An elastic constraint placed onto a distensible conduit modifies its perfusion characteristics. Surprisingly, a manifold increase in throughflow occurs as the resistance further downstream is increased. This flow anomaly occurs within a certain operating range of resistance settings.


No Clinical or Radiographic Difference Seen in Arthroscopic Bankart Repair With Knotted Versus Knotless Suture Anchors: A Randomized Controlled Trial at Short-Term Follow-Up.
The objective of this study was to compare the clinical and radiographic results of patients undergoing arthroscopic repair of labral lesions using knotted and knotless anchors. Sixty-four patients with anterior labral lesions (bone defects of the glenoid up to 13.5% or up to 20% if the instability severity index score was less than 4) and without other shoulder pathologies were randomly assigned to 2 groups, with 32 patients in each group. Clinical outcomes were assessed 6, 12, and 24 months after surgery by the Rowe score, Western Ontario shoulder instability index (WOSI), single assessment numeric evaluation (SANE), visual analog scale for pain (VASp), range of motion, and rate of postoperative recurrence. Postoperative magnetic resonance imaging (MRI) was performed, and the anterior and inferior labrum glenoid height indexes and anterior and inferior labral slopes were measured. The primary endpoint was the Rowe score at 24 months postoperatively. Fifty-one patients, 24 in the knotted group and 27 in the knotless group, completed 24 months of follow-up. At 24 months, the Rowe scores were 81.7 ± 19.9 points and 85.9 ± 14 points, respectively (P = .623); the WOSI scores were 509.2 ± 480.1 points and 555.9 ± 393.6 points, respectively (P = .533); the SANE scores were 90.7 ± 18.7 points and 89.2 ± 14.8 points, respectively (P = .427); and the VASp scores were 1.7 ± 2.5 points and 2.5 ± 2.7 points, respectively (P = .275). There was no significant difference in range of motion, postoperative recurrence, or MRI parameters between the groups. All subjects (100%) in both groups exceeded the minimal clinically important difference of 9.7 for the Rowe score (P > .999). Repair of Bankart's lesion through the use of knotted and knotless suture anchors yielded similar clinical and radiographic results on analysis at 24 months after operation. Level I. Randomized controlled clinical trial.


Hyperosmolar urea for elective midtrimester abortion. Experience in 1,913 cases.
Intra-amniotic hyperosmolar urea (59.7 per cent) augmented by intravenous oxytocin (332 millimicron per minute), prostaglandin F2alpha (20 mg.), prostaglandin F2alpha (10 mg.), or prostaglandin F2alpha (5 mg.) was utilized for 1,913 patients requesting elective midtrimester abortion. Injection-abortion intervals ranging from 13.70 to 21.49 hours were achieved with failure rates of 0.7 to 6.7 per cent. Despite frequent pre-existing medical conditions, the complication rate compared favorably with those of other methods for terminating midtrimester pregnancy such as saline amnioinfusion or dilatation and evacuation.


The pathophysiology of bone loss.
Aging is associated with a decline in cancellous and cortical bone mass and with a deterioration of microarchitecture in both skeletal compartments. These changes are more marked in women than men and are exaggerated in patients with fracture. With the insight gained from histomorphometry, we are beginning to understand the cellular mechanisms that underlie these changes. We recognize that deterioration in microarchitecture contributes to fracture risk, independently of bone mass. Techniques to assess bone microarchitecture noninvasively in a clinical setting are currently under development; it is likely that advances in this area will improve our ability to identify and manage patients with osteoporosis in the not too distant future.


Host-plant invasion by Rhizobium: the role of cell-surface components.
Rhizobia are soil bacteria that can become endosymbionts, reducing atmospheric nitrogen within nodules formed on the roots of legume plants. During tissue and cell invasion, bacterial cell-surface components adapt the bacterium to survive as an endophyte without eliciting host-defence responses. The structures of many of these components have been established recently, allowing their possible roles in invasion to be defined more clearly.


Placenta Accreta Spectrum Disorders: How to reduce maternal transfusion? A center experience on extraperitoneal retrograde hysterectomy.
Placenta Accreta Spectrum disorders (PASd) refer to the range of pathologic adherence of placenta associated with high maternal morbidity and mortality due to severe and sometimes life-threatening hemorrhage at the time of delivery. The aim of this study is to describe the surgical technique of extraperitoneal retrograde hysterectomy, which has allowed a reduction of blood transfusions compared to patients who underwent classical post-partum hysterectomy. We collected data from twelve patients with antenatal diagnosis of PASd treated between 2018 and 2021 with an extra-peritoneal hysterectomy using a posterior retrograde approach and we compared them to patients who underwent classical hysterectomy for suspected PASd, treated between 2007 and 2017. The classical hysterectomy group presented a higher frequency of blood and plasma transfusion compared to the extraperitoneal hysterectomy group. In particular, classical hysterectomy resulted in an independent risk factor for transfusion, with an increment of 6.6 times of risk. Even if future studies are required, we think that extraperitoneal hysterectomy could be a safe option in case of PASd, considering that classical hysterectomy compared to this approach increases, in our population, the risk of blood and plasma transfusion.


Erratum: Definitions of Severity in Treatment Seeking Studies of Febrile Illness in Children in Low and Middle Income Countries: A Scoping Review.
[This corrects the article DOI: 10.3389/ijph.2021.634000.].


Coexistence of infinitely many patterns and their control in heterogeneous coupled neurons through a multistable memristive synapse.
The phenomenon of hidden heterogeneous extreme multistability is rarely reported in coupled neurons. This phenomenon is investigated in this contribution using a model of a 2D FitzHugh-Nagumo neuron coupled with a 3D Hindmarsh-Rose neuron through a multistable memristive synapse. The investigation of the equilibria revealed that the coupled neuron model is equilibrium free and, thus, displays a hidden dynamics. Some traditional nonlinear analysis tools are used to demonstrate that the heterogeneous neuron system is able to exhibit the coexistence of an infinite number of electrical activities involving both periodic and chaotic patterns. Of particular interest, a noninvasive control method is applied to suppress all the periodic coexisting activities, while preserving only the desired chaotic one. Finally, an electronic circuit of the coupled neurons is designed in the PSpice environment and used to further support some results of the theoretical investigations.


Does prior use of antiplatelet therapy modify the effect of dual antiplatelet therapy in transient ischaemic attack/minor ischaemic stroke: A systematic review and meta-analysis.
The purpose was to determine whether prior use of antiplatelet therapy modifies the effect of dual antiplatelet therapy in patients with acute minor ischaemic stroke or transient ischaemic attack. A systematic review and meta-analysis of randomized controlled trials was performed comparing dual antiplatelet therapy to aspirin that reported subgroup analysis by prior antiplatelet use, adhering to the Cochrane Collaboration Guidelines. A fixed-effects meta-analysis was used to estimate a pooled treatment effect overall in subgroups with prior aspirin therapy and without prior aspirin therapy. Difference in treatment effect was assessed by testing p for interaction. The primary outcome measure was recurrent vascular events. Three eligible randomized controlled trials were identified, including 4831 participants with pre-existing antiplatelet use and 16,236 participants without pre-existing aspirin use. Recurrent vascular events occurred in 7.2% (95% confidence interval [CI] 4.3-10) of those without pre-existing aspirin use versus 7.3% (95% CI 4.1-10) of those receiving prior aspirin therapy. Effect of dual antiplatelet therapy on the primary outcome measure was consistent in participants with no prior aspirin use (odds ratio 0.75, 95% CI 0.66-0.84) compared to those taking aspirin before randomization (odds ratio 0.79, 95% CI 0.63-0.998) (p interaction = 0.66). The number needed to treat in the aspirin-naïve group was 55 (95% CI 37-107) compared to 66 (95% CI 32 to -746) in those on prior aspirin therapy. It was found that the effectiveness of dual antiplatelet therapy in patients with minor ischaemic stroke or high risk transient ischaemic attack does not significantly differ in patients with prior aspirin exposure; therefore there should be no influence on the decision to use dual antiplatelet therapy.


Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection: a cohort study.
Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection. Participants in this population-based cohort study underwent a structured interview, including history of CT infection, and subsequently cervical exfoliated cells were obtained for HPV DNA and CT DNA testing. Women with high-risk HPV DNA infection and no prevalent cervical disease constituted the overall study population (n=1390). A subgroup of women with persistent HPV infection (n=320) was also identified. All women were passively followed for development of cervical lesions in the national Pathology Data Bank. HRs and 95% CIs for CIN3+ during follow-up (up to 19 years) were estimated in an accelerated failure time model. Women who reported more than one CT infection had a statistically significantly increased risk of CIN3+ (high-risk HPV-positive, HR=2.51, 95% CI 1.44 to 4.37) (persistent HPV infection, HR=3.65, 95% CI 1.53 to 8.70). We found no association between CT DNA and subsequent risk of CIN3+ among women who were HPV-positive or had a persistent HPV infection at baseline. Repeated CT infections increased the risk of CIN3+ among women with prevalent as well as persistent high-risk HPV infection.


Glenohumeral Superior Translation and Subacromial Contract Pressure Are Both Improved With Superior Capsular Reconstruction: A Systematic Review and Meta-Analysis of Biomechanical Investigations.
To review cadaveric studies evaluating the biomechanical outcomes of superior capsular reconstruction (SCR) with different graft types for the treatment of irreparable rotator cuff (RTC) tears. PubMed, Cochrane, and Embase were queried in January 2022 to conduct this meta-analysis using the following key words: "superior capsule reconstruction," "superior capsular reconstruction," and "biomechanics." Articles were included if they reported glenohumeral superior translation or subacromial contact pressure following SCR in cadaveric RTC tears. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Number of shoulders, graft types, and biomechanical outcomes were recorded and analyzed with forest plots. Twelve studies (95 shoulders) were included in the statistical analysis. There was a significant reduction in glenohumeral superior translation following SCR compared with RTC tear across 10 studies (79 shoulders) with standardized mean difference (SMD) -2.48 mm; confidence interval (CI) -3.28 mm, -1.69 mm. The SMD between fascia lata graft and RTC tear was -3.84 mm (CI -4.82 mm, -2.86 mm) and between dermal allograft and RTC tear was -2.05 mm (CI -3.10 mm, -1.00 mm). There was a significant reduction in subacromial contact pressure following SCR compared with RTC tear across 5 studies (55 shoulders) with SMD -3.49 MPa (CI -4.54 MPa, -2.44 MPa). The SMD between fascia lata graft and RTC tear was -3.21 MPa (CI -5.08 MPa, -1.34 MPa) and between dermal allograft and RTC tear was -3.89 MPa (CI -5.91 MPa, -1.87 MPa). Independent of graft type, biomechanical studies suggest that SCR improves glenohumeral superior translation and subacromial contact pressure in comparison with RTC tear at time zero. There was no definitive evidence identified in this study to suggest a biomechanically superior SCR graft option. Investigating the biomechanical outcomes of several graft types for superior capsular reconstruction will help surgeons better understand the efficacies of different graft types for use in superior capsule reconstruction surgery.


Cervical and ocular vestibular evoked potentials in Machado-Joseph disease: Functional involvement of otolith pathways.
Machado-Joseph disease is defined as an autosomal dominant ataxic disorder caused by degeneration of the cerebellum and its connections and is associated with a broad range of clinical symptoms. The involvement of the vestibular system is responsible for several symptoms and signs observed in the individuals affected by the disease. We measured cervical and ocular vestibular evoked myogenic potentials in a sample of Machado-Joseph disease patients in order to assess functional pathways involved. Bilateral measures of cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) were obtained from 14 symptomatic patients with genetically proven Machado-Joseph disease and compared with those from a control group of 20 healthy subjects. Thirteen (93%) patients showed at least one abnormal test result; oVEMP and cVEMP responses were absent in 17/28 (61%) and 11/28 (39%) measures, respectively; and prolonged latency of cVEMP was found in 3/28 (11%) measures. Of the 13 patients with abnormal responses, 9/13 (69%) patients showed discordant abnormal responses: four with absent oVEMP and present cVEMP, two with absent cVEMP and present oVEMP, and three showed unilateral prolonged cVEMP latencies. Both otolith-related vestibulocollic and vestibulo-ocular pathways are severely affected in Machado-Joseph disease patients evaluated by VEMPs.


Highly efficient residue-selective labeling with isotope-labeled Ile, Leu, and Val using a new auxotrophic E. coli strain.
We recently developed a practical protocol for preparing proteins bearing stereo-selectively (13)C-methyl labeled leucines and valines, instead of the commonly used (13)C-methyl labeled precursors for these amino acids, by E. coli cellular expression. Using this protocol, proteins with any combinations of isotope-labeled or unlabeled Leu and Val residues were prepared, including some that could not be prepared by the precursor methods. However, there is still room for improvement in the labeling efficiencies for Val residues, using the methods with labeled precursors or Val itself. This is due to the fact that the biosynthesis of Val could not be sufficiently suppressed, even by the addition of large amounts of Val or its precursors. In this study, we completely solved this problem by using a mutant strain derived from E. coli BL21(DE3), in which the metabolic pathways depending on two enzymes, dihydroxy acid dehydratase and β-isopropylmalate dehydrogenase, are completely aborted by deleting the ilvD and leuB genes, which respectively encode these enzymes. The ΔilvD E. coli mutant terminates the conversion from α,β-dihydroxyisovalerate to α-ketoisovalerate, and the conversion from α,β-dihydroxy-α-methylvalerate to α-keto-β-methylvalerate, which produce the preceding precursors for Val and Ile, respectively. By the further deletion of the leuB gene, the conversion from Val to Leu was also fully terminated. Taking advantage of the double-deletion mutant, ΔilvDΔleuB E. coli BL21(DE3), an efficient and residue-selective labeling method with various isotope-labeled Ile, Leu, and Val residues was established.


N-Terminal protein modifications in an insect cell-free protein synthesis system and their identification by mass spectrometry.
To evaluate the ability of an insect cell-free protein synthesis system to generate proper N-terminal cotranslational protein modifications such as removal of the initiating Met, N-acetylation, and N-myristoylation, several mutants were constructed using truncated human gelsolin (tGelsolin) as a model protein. Tryptic digests of these mutants were analyzed by MALDI-TOF MS and MALDI-quadrupole-IT-TOF MS. The wild-type tGelsolin, which is an N-myristoylated protein, was found to be N-myristoylated when myristoyl-CoA was added to the in vitro translation reaction mixture. N-myristoylation did not occur on the Gly-2 to Ala mutant, in which the N-myristoylation motif was disrupted, whereas this mutant was found to be N-acetylated after removal of the initiating Met. Analyses of Gly-2 to His and Leu-3 to Asp mutants revealed that the amino acids at positions 2 and 3 strongly affect the susceptibility of the nascent peptide chain to removal of the initiating Met and to N-acetylation, respectively. These results suggest that N-terminal modifications occurring in the insect cell-free protein synthesis system are quite similar to those observed in the mammalian protein synthesis system. Thus, a combination of the cell-free protein synthesis system with MS is an effective strategy to analyze protein modifications.


The use of the DSM-III-R Checklist for initial diagnostic assessments.
The DSM-III-R Checklist is an efficient method for screening psychiatric patients for major psychiatric disorders while amassing a data base that can be used for later clinical and research activities. It yields valid diagnoses and key adjunctive symptoms. Patients enjoyed the interview, demonstrating an interest in the computer as well as a feeling of confidence in the complete review of symptoms. The psychiatry resident users in this project found the Checklist to be a valuable teaching instrument, a way to develop their thinking about symptoms and diagnostic rules, an efficient means of collecting an automated clinical data base, and a stimulus to pursue further research activities. Finally, the Checklist is an ideal diagnostic tool to amass a research data base and is currently being used in numerous studies by clinicians and nonclinicians.


Monoclonal antibodies against LHRH: development and immunoactivity in vivo and in vitro.
Mouse myeloma NS1-Ag4 cells were fused with spleen cells from a BALB/c mouse previously immunized with luteinizing hormone releasing hormone (LHRH) conjugated to serum bovine albumin (BSA). Fused cells were grown in HAT restrictive medium which was screened for LHRH binding ability via a primary binding assay employing [125I]LHRH and cold ethanol precipitation. One clone (hy-USASK/DSIL-LHRH-A1) was selected for further study. Cell culture fluid and ascites fluid bound 30% of [125I]LHRH at 1:4000 and 1:400,000 dilution respectively. A competitive inhibition assay using ascites fluid at 1:2,000,000 dilution and LHRH standards at 0.125-32.0 ng/ml was established. Initial studies using rabbit anti-mouse allotype sera in a horseradish peroxidase (HRP)-ELISA system indicate the antibody is IgG1. A dose of 0.5 ml ascites fluid containing LHRH antibody given intravenously (i.v.) on day 9 of gestation was effective in terminating pregnancy in rats. A 1 cm progesterone implant made of elastomer polymer and placed interperitoneally blocked this effect. Ascites fluid (4.5 ml) containing LHRH antibody, when infused i.v. into mature spayed female dogs induced a precipitous decline in mean luteinizing hormone (LH) levels and reduced LH pulsatility over 4 days. It was concluded that the mouse monoclonal antibody is specific for LHRH, and can interrupt reproductive events in vivo.


Chloroquine induces transitory attenuation of proliferation of human lung cancer cells through regulation of mutant P53 and YAP.
Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer-associated deaths worldwide. Though recent development in targeted therapy has improved NSCLC prognosis, yet there is an unmet need to identify novel causative factors and appropriate therapeutic regimen against NSCLCs. In this study, we identify key molecular factors de-regulated in NSCLCs. Analyze their expression by real-time PCR and immunoblot; map their localization by immuno-fluorescence microscopy. We further propose an FDA approved drug, chloroquine (CQ) that affects the function of the molecular factors and hence can be repurposed as a therapeutic strategy against NSCLCs. Available NSCLC mutation data reflects a high probabilistic chance of patients harboring a p53 mutation, especially a gain of function (GOF)-R273H mutation. The GOF-P53 mutation enables the P53 protein to potentially interact with non-canonical protein partners facilitating oncogenesis. In this context, analysis of existing transcriptomic data from R273H-P53 expressing cells shows a concomitant up-regulation of Yes-associated protein (YAP) transcriptional targets and its protein partner TEAD1 in NSCLCs, suggesting a possible link between R273H-P53 and YAP. We therefore explored the inter-dependence of R273H-P53 and YAP in NSCLC cells. They were found to co-operatively regulate NSCLC proliferation. Genetic or pharmacological inhibition of YAP and GOF-P53 resulted in sensitization of NSCLC cells. Further analysis of pathways controlled by GOF-P53 and YAP showed that they positively regulate the cellular homeostatic process- autophagy to mediate survival. We hence postulated that a modulation of autophagy might be a potent strategy to curb proliferation. In accordance to above, autophagy inhibition, especially with the FDA-approved drug- chloroquine (CQ) resulted in cytoplasmic accumulation and reduced transcriptional activity of GOF-P53 and YAP, leading to growth arrest of NSCLC cells. Our study highlights the importance of GOF-P53 and YAP in NSCLC proliferation and proposes autophagy inhibition as an efficient strategy to attenuate NSCLC tumorigenesis.