The effect of enterprise financialization on green innovation: evidence from Chinese A-share non-financial listed enterprises.
The financialization of entity enterprises brings both benefits and risks for economic development. In the context of green economy transformation, exploring the impact of enterprise financialization on green innovation deserves more focus. This paper takes the A-share non-financial listed companies from 2007 to 2021 as the research sample to examine how corporate financialization affects green innovation. The results reveal that the enterprise financialization is negatively associated with green innovation, which is more significant for the short-term financialization. Further analysis shows that external supervision governance (institutional investors and analysts' attention) can alleviate the hindering effect of corporate financialization on green innovation. The mechanism tests confirm that enterprise financialization prevents enterprise green innovation by increasing enterprise risk-taking level and reducing R&D investment (capital input and labor input). Heterogeneity analysis reports that higher consumer eco-friendly preference and consumption level can ease the hindering effect of corporate financialization on corporate green innovation. This paper can provide inspiration for enterprises to reasonably arrange asset investment and how to stimulate enterprises' enthusiasm for green innovation, thus powering the green development of the real economy.


An Aldolase-Based New Pathway for Bioconversion of Formaldehyde and Ethanol into 1,3-Propanediol in Escherichia coli.
Formaldehyde (HCHO) is a reactive one-carbon compound that is interesting for biosynthesis. The assimilation of HCHO depends on the catalysis of aldolase. Here, we present a novel synthetic pathway in E. coli to convert HCHO and ethanol into 1,3-propanediol (PDO) using a deoxyribose-5-phosphate aldolase (DERA). DERA condenses HCHO and acetaldehyde to form 3-hydroxypropionaldehyde, the direct precursor of PDO formation. This new pathway opens up the possibility to synthesize an appealing C3 compound from a C1 compound and a C2 compound without carbon loss in contrast to all the other known PDO synthetic pathways where typically 30-50% of the carbons are lost as CO2 and other byproducts. The pathway is successfully demonstrated by elaborating three metabolic modules. First, DERA from Thermotoga maritima was found to be efficient for the aldol condensation and PDO production module. For the module of acetaldehyde supply from ethanol, an alcohol dehydrogenase from Hansenula polymorpha was selected. For the HCHO supply module, the control of HCHO concentration and its utilization were shown to be important for achieving the assimilation of HCHO in recombinant E. coli cells. By deleting the gene frmA for endogenous conversion of HCHO to formate and controlling HCHO at a level of about 0.6 mM, the concentration and yield of PDO were increased from initially 5.67 mM (0.43 g/L) and 0.057 mol/mol to 17.35 mM (1.32 g/L) and 0.096 mol/mol in bioconversion of ethanol and HCHO with resting E. coli cells. Further engineering of DERA and the HCHO supply module is necessary to realize the potential of this promising metabolic pathway.


[The toxicological, hygienic and clinical aspects of the action of low levels of organic solvents].
The article presents experimental data showing that Average Shift Concentration (ASC) and Maximal Single Concentration (MSC) for some solvents (tetrachloromethane, tetrachloroethane, dimethylformamide, benzene) are expedient to be justified. Clinical and hygienic materials proved significant health parameters (nervous system, peripheral blood) and urine levels of main metabolites to depend on chlorbenzene and toluene concentrations influencing the workers. Having analyzed the results, the authors recommended following hygienic norms in the air of workplace: for chlorbenzene ASC--50 mg/cu m, MSC--100 mg/cu m; biologic MAC for urine 4-chlorcatechol--0.05 g/l; for toluene ASC--50 mg/cu m, MSC--150 mg/cu m; biologic MAC for urine hippuric acid--1.5 g/l. The article shows some features of ASC and MSC practical application.


Breast reduction surgery and breast cancer risk: does reduction mammaplasty have a role in primary prevention strategies for women at high risk of breast cancer?
Prophylactic bilateral mastectomy has been demonstrated to reduce breast cancer incidence in women with a high inherited susceptibility to breast cancer. For the majority of high-risk women, however, bilateral prophylactic mastectomy is not an acceptable option for primary prevention of breast cancer. Several epidemiological follow-up studies have indicated that there may be a substantial reduction in breast cancer risk among women who have undergone breast reduction surgery. The authors reviewed the evidence from these studies, with emphasis on the problems inherent in interpreting the results of nonexperimental studies of elective medical procedures. Although such observational studies cannot demonstrate definitively that reduction mammaplasty reduces the risk of breast cancer, the evidence from these studies is sufficiently strong to warrant the evaluation of breast reduction surgery as an option for primary prevention in clinical studies of women at increased risk of breast cancer. The availability of a more acceptable surgical option for primary prevention of breast cancer could increase the number of women willing to choose risk reduction surgery and thus may result in an overall reduction in breast cancer mortality among high-risk women.


Eveningness associates with smoking and sleep problems among pregnant women.
Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness-eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.


Electron microscopy of histologically difficult to diagnose gynecologic neoplasms.
The ultrastructural characteristics useful in identifying a selected series of histologically difficult to diagnose malignant neoplasms of the human gynecological sphere are presented. The results are discussed in relation to routine diagnosis and when appropriate, to their pathogenic origin.


The Dishwater Menace: Healthy Drinking Spaces and the Public Good in Post-Prohibition Ontario.
This paper examines inter-bureaucracy tension, negotiation, and resolution in the case of the oversight of beverage room sanitation in Ontario in the 1930s and 1940s. Both the Liquor Control Board of Ontario (LCBO) and various public health authorities claimed authority over the health status of public drinking spaces. But the LCBO had legislative priority. The ensuing debates regarding health and cleanliness linked issues of beverage room glass sanitation to a biopolitical approach to public drinking. Developing a more scientifically sophisticated approach to beverage glass cleaning required a balancing of administrative priorities. Perfect sanitation was expensive and complicated, and the LCBO's mandate demanded attention to the financial viability of beverage rooms. The LCBO needed to forge a trade off between safety and viability, while maintaining a public drinking system that dissuaded illegal drinking. The subsequent compromise in beverage room glass sanitation tied contemporary chemical sanitizers to the challenging economics of depression-era beverage room management.


[Clinical evaluation of roxatidine acetate hydrochloride injection as preanesthetic medication].
The effects of single intravenous administration of roxatidine acetate hydrochloride 75 mg on the volume and pH of gastric juice were investigated in 43 patients undergoing elective surgery under general anesthesia. The drug was given 1 hour before anesthesia. The percentages of patients with gastric pH above 2.5 and gastric juice volume under 25 ml were 95.3% and 97.7% at the time of induction of anesthesia and at the time of extubation, respectively. As for overall assessment on gastric secretion, 93.0% was judged as very effective. In 2 cases, pricking sensations were observed at the time of injection, but these symptoms disappeared without any treatment within a few minutes. No other adverse reactions nor abnormal laboratory test findings were observed. In conclusion, roxatidine acetate hydrochloride administered intravenously 1 hour prior to anesthesia is thought to be useful to prevent acid aspiration pneumonitis.


Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury.
Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ. A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI.


Translational and rotational diffusion of SF6 in zeolite NaY.
Temperature dependence of equilibrium as well as dynamical properties of SF(6) in zeolite NaY have been investigated by molecular dynamics simulation. By about 200 K, SF(6) begins to have increased mobility. Strong orientational preference is exhibited by SF(6) during its passage through the 12-ring window, the bottleneck for diffusion. The preference is for orientation with C(3) followed by C(2) and then C(4) molecular symmetry axis perpendicular to the window plane. Translational motion is diffusive with an activation energy of 5.5 kJ/mol. Rotational-diffusion coefficient has an activation energy of 2.83 kJ/mol. Rotational motion is facile within the alpha-cage. Translational motion is hindered during passage through the 12-ring window when C(4) is perpendicular to the window plane. Orientational correlation functions P(1) and P(2) around C(2), C(3) and C(4) are reported. Only the long time decay of C(4) shows oscillations. This is attributed to the hindered rotation during intercage migration while passing through the 12-ring window.


Reconciling patient and provider priorities for improving the care of critically ill patients: A consensus method and qualitative analysis of decision making.
Providers have traditionally established priorities for quality improvement; however, patients and their family members have recently become involved in priority setting. Little is known about how to reconcile priorities of different stakeholder groups into a single prioritized list that is actionable for organizations. To describe the decision-making process for establishing consensus used by a diverse panel of stakeholders to reconcile two sets of quality improvement priorities (provider/decision maker priorities n=9; patient/family priorities n=19) into a single prioritized list. We employed a modified Delphi process with a diverse group of panellists to reconcile priorities for improving care of critically ill patients in the intensive care unit (ICU). Proceedings were audio-recorded, transcribed and analysed using qualitative content analysis to explore the decision-making process for establishing consensus. Nine panellists including three providers, three decision makers and three family members of previously critically ill patients. Panellists rated and revised 28 priorities over three rounds of review and reached consensus on the "Top 5" priorities for quality improvement: transition of patient care from ICU to hospital ward; family presence and effective communication; delirium screening and management; early mobilization; and transition of patient care between ICU providers. Four themes were identified as important for establishing consensus: storytelling (sharing personal experiences), amalgamating priorities (negotiating priority scope), considering evaluation criteria and having a priority champion. Our study demonstrates the feasibility of incorporating families of patients into a multistakeholder prioritization exercise. The approach described can be used to guide consensus building and reconcile priorities of diverse stakeholder groups.


[Literature research of the hepatotoxicity of glucoside tripterygium total and its synergism and toxicity reducing effects].
Correlated literatures of the liver injury induced by glucoside tripterygium total (GTT) and of its synergism and toxicity reducing effects were retrieved to study the correlation between the dosage, the time point of GTT and the liver injury. The monomer or active ingredients of animals and plants with the hepatoprotective effect were included. The mechanisms of action between GTT and these drugs were analyzed. The mechanism for GTT induced liver injury and its synergism and toxicity reducing mechanisms, as well as the preventive measures were discussed, thus providing evidence-based basis for safe clinical application of GTT.


Cost-effectiveness of Different Post-retained Restorations.
Dentists can choose between metal and fiber post systems to provide post-retained restorations. The risk of tooth loss and other complications differs between different post systems, as do the initial treatment costs. We aimed to assess the cost-effectiveness of (1) cast metal (MC), (2) preformed metal (MP), (3) glass fiber (GF), and (4) carbon fiber (CF) post-retained restorations. A mixed public-private payer's perspective within German healthcare was taken. Risks of complications were extracted from systematic reviews. Costs were estimated by using fee items and 2016 material costs. A Markov model was constructed to follow up an endodontically treated molar receiving a post-retained crown in an initially 50-year-old patient during his lifetime. Monte Carlo microsimulations were performed to assess lifetime costs and tooth retention time. MPs were least costly (€692€), retaining teeth for 26.7 years. GFs were more costly (€745€), retaining teeth for 27.6 years. MCs were minimally more effective but also more costly than GFs (€774€). CFs were less effective and most expensive (€825€, 26.7 years). For payers willing to invest more than €60€ per tooth retention year, GF was cost-effective. Payers willing to invest an additional €670€ found MC to be cost-effective. These findings were found robust in sensitivity analyses. For payers not willing to invest additional money for longer tooth retention, MP seemed most suitable to retain restorations. For payers with additional willingness to pay, GF seemed suitable, retaining teeth for longer. MC was only cost-effective under very high willingness to pay. CF is not recommendable on the basis of their cost-effectiveness.


Quinone binding sites of cyt bc complexes analysed by X-ray crystallography and cryogenic electron microscopy.
Cytochrome (cyt) bc1, bcc and b6f complexes, collectively referred to as cyt bc complexes, are homologous isoprenoid quinol oxidising enzymes present in diverse phylogenetic lineages. Cyt bc1 and bcc complexes are constituents of the electron transport chain (ETC) of cellular respiration, and cyt b6f complex is a component of the photosynthetic ETC. Cyt bc complexes share in general the same Mitchellian Q cycle mechanism, with which they accomplish proton translocation and thus contribute to the generation of proton motive force which drives ATP synthesis. They therefore require a quinol oxidation (Qo) and a quinone reduction (Qi) site. Yet, cyt bc complexes evolved to adapt to specific electrochemical properties of different quinone species and exhibit structural diversity. This review summarises structural information on native quinones and quinone-like inhibitors bound in cyt bc complexes resolved by X-ray crystallography and cryo-EM structures. Although the Qi site architecture of cyt bc1 complex and cyt bcc complex differs considerably, quinone molecules were resolved at the respective Qi sites in very similar distance to haem bH. In contrast, more diverse positions of native quinone molecules were resolved at Qo sites, suggesting multiple quinone binding positions or captured snapshots of trajectories toward the catalytic site. A wide spectrum of inhibitors resolved at Qo or Qi site covers fungicides, antimalarial and antituberculosis medications and drug candidates. The impact of these structures for characterising the Q cycle mechanism, as well as their relevance for the development of medications and agrochemicals are discussed.


Longitudinal study of antimyelin T-cell reactivity in relapsing-remitting multiple sclerosis: association with clinical and MRI activity.
In multiple sclerosis (MS), T-cells are considered to be critical in coordinating an immunopathological cascade that results in myelin damage. We investigated whether clinical disease activity or brain inflammatory activity as measured by magnetic resonance imaging (MRI) was associated with changes in autoreactive T-cell reactivities in MS patients. To this end, a longitudinal study was performed in which T-cell-related immune parameters and clinical parameters (including MRI) were monitored in seven relapsing-remitting (RR) MS patients and two healthy controls with bimonthly intervals over a period of 18 months. The serial evaluation of antimyelin (MBP, PLP, MOG) T-cell responses revealed highly dynamic shifts and fluctuations from one pattern to another in a patient-dependent manner. In some of the patients, changes in T-cell-related immune variables were found to concur with MRI activity and generally preceded clinical relapses. These alterations include: increased number of myelin-reactive IFN-gamma secreting T-cells, detection of clonally expanded myelin-reactive T-cells, elevated proinflammatory and decreased antiinflammatory cytokine production, upregulation of ICAM-1 membrane expression and highly increased serum levels of soluble VCAM-1. However, not all exacerbations and MRI changes were associated with changes in antimyelin reactivity. Some of the observed immune alterations were also detected in the healthy controls, indicating that additional regulatory mechanisms-which may be defective in MS-play a role in the downregulation of potentially pathological T-cell responses. In conclusion, this study provides further support for an important role of myelin-reactive T-cells in the pathogenesis of MS. In addition, the observed dynamic changes in the antimyelin T-cell reactivity pattern may be a major obstacle for the development of antigen-specific immunotherapies.


Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals.
Arsenic is an environmental and occupational toxin. Dermatologic toxicities due to arsenic exposure are well-documented and include basal cell and squamous cell carcinomas. However, the mechanism of arsenic-induced skin cancer is not well-understood. Recent studies indicate that arsenic exposure results in the generation of reactive oxygen species (ROS) and oxidative stress. Here, we examined the chemical nature of the specific ROS, studied the interrelationship among these species, and identified the specific species that is responsible for the subsequent DNA damage in a spontaneously immortalized keratinocyte cell line. We detected the formation of O(2)(*)(-) and H(2)O(2) in keratinocytes incubated with arsenite [As(III)] but not with arsenate. As(III)-induced DNA damage was detected in a concentration-dependent manner and evident at low micromolar concentrations. Catalase, an H(2)O(2) scavenger, eliminated H(2)O(2) and reduced the As(III)-mediated DNA damage. Superoxide dismutase, by enhancing the production of H(2)O(2) and (*)OH, significantly increased the As(III)-mediated DNA damage. Sodium formate, a competitive scavenger for (*)OH, and deferoxamine, a metal chelator, both reduced the DNA damage. These results suggest that exposure to arsenite generates O(2)(*)(-) and H(2)O(2), and (*)OH, derived from H(2)O(2), is responsible, at least in part, for the observed DNA damage. These findings demonstrate arsenic-induced formation of specific ROS and provide the direct evidence of (*)OH-mediated DNA damage in keratinocytes, which may play an important role in the mechanism for arsenic-induced skin carcinogenicity.


Cohesion induced by a rotating magnetic field in a granular material.
We report experiments on a magnetic cohesive granular material made of steel spheres in the millimeter range. A magnetic field magnetizes the spheres, so that an interaction force between grains appears. A rotating magnetic field is applied parallel to plane of the quasi-two-dimensional cell containing the spheres so that only the time averaged force between two particles will be considered. Both maximum angle of stability and angles of repose are measured. The maximum angle of stability is found to depend linearly on the interaction force. Another noticeable feature is the lack of dependence of the maximum angle of stability on the initial height of the heap. We show that the angle of repose is less sensitive to the magnetic interaction force than the maximum of stability. At last, we discuss the importance of using a rotating field rather than a constant one. In particular, we report some measurements of both the maximum angle of stability and the angle of repose in constant field, which show a strong dependence of the angles of avalanche on the direction of the field.


[Genetic analysis of migraine headache: a review].
Recent advances in genetic analysis of migraine headache are reviewed. Point mutations of P/Q -type Ca2+ channel alpha1 subunit(CACNA1A) gene and Na-K ATPase, alpha2 (ATP1A2) gene have been identified in the familial hemiplegic migraine (FHM-1 and FHM-2, respectively). Mutations in notch-3 gene cause the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an autosomal dominant inherited disorder often accompanying with migraine like headache. Serotonin (5-HT) related genes, dopamine D2 receptors (DRD2) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and angiotensin converting enzyme (ACE) gene have been noticed as the susceptible genes for migraine pathogenesis. Genetic study of migraine is promising and will provide further understanding of the migraine pathophysiology. Discovery of the responsible or susceptible genes will open an avenue to develop new therapeutic strategy.


Plasma clearance rates of coagulation factors VIII and IX in factor-deficient individuals.
The plasma clearance rates of factors IX and VIII were determined in patients with hemophilia A and B who had received factor replacement by prolonged, continuous infusion of factor concentrates. The clearance rates were calculated by dividing the factor infusion rates by the steady-state plasma factor activities corrected for base-line factor activities. The mean factor IX clearance rate in eight factor IX-deficient patients was 233 mL/h (range 159 to 340 mL/h). The mean normalized clearance rate was 3.4 mL/h/kg. The mean factor VIII clearance rate in eight factor VIII-deficient patients was 294 mL/h (range 229 to 361 mL/h) and the mean normalized rate was 5.0 mL/h/kg. Both factors show linear relationships between the factor infusion rates and the steady-state plasma factor activities achieved.


Monitoring the T-cell receptor repertoire at single-clone resolution.
The adaptive immune system recognizes billions of unique antigens using highly variable T-cell receptors. The alphabeta T-cell receptor repertoire includes an estimated 10(6) different rearranged beta chains per individual. This paper describes a novel micro-array based method that monitors the beta chain repertoire with a resolution of a single T-cell clone. These T-arrays are quantitative and detect T-cell clones at a frequency of less than one T cell in a million, which is 2 logs more sensitive than spectratyping (immunoscope), the current standard in repertoire analysis. Using T-arrays we detected CMV-specific CD4+ and CD8+ T-cell clones that expanded early after viral antigen stimulation in vitro and in vivo. This approach will be useful in monitoring individual T-cell clones in diverse experimental settings, and in identification of T-cell clones associated with infectious disease, autoimmune disease and cancer.


Cutting edge: receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells.
Immunization with heat shock proteins (HSPs) induces Ag-specific CTL responses. The specificity of the immune response is based on peptides associated with HSPs. To investigate how exogenous HSP/peptide complexes gain access to the MHC class I-restricted Ag presentation pathway, we incubated the monocytic cell line P388D1 and the dendritic cell line D2SC/1 with gold-labeled HSPs gp96 and HSC70. We show that HSPs bind specifically to the surface of these APCs and are internalized spontaneously by receptor-mediated endocytosis, demonstrating the existence of specific receptors for HSPs on these cells. In addition, we observe colocalization of internalized HSPs and surface MHC class I molecules in early and late endosomal structures. These findings provide possible explanations for the immunogenicity of HSP/peptide complexes and for the transfer of HSP-associated peptides onto MHC class I molecules.


Immunopharmacological studies of new 3-benzoyl-4-mercaptobutyric acids. Immunomodulating effects.
A number of D-penicillamine (PA) derivatives (3-benzoyl-4-mercaptobutyric acids) having acetylthio groups on an alpha or beta position of a carboxylic acid, were synthesized and examined for their immunological effects compared with PA. New PA derivatives suppressed adjuvant-induced arthritis (AA) in SD rats and enhanced AA in Lewis rats like PA. Suppressive effects of 2-acetylthiomethyl-3-(4-methyl-benzoyl)propionic acid (compound II-3) on AA in SD rats was most potent among PA derivatives and PA. II-3 enhanced type II collagen-induced arthritis in rats more effectively than PA, and it slightly prolonged the survival time of NZBXNZW hybrid (BWF1) mice. Hemolytic plaque forming cells in the spleen cells of BDF1 and aged Balb/c mice were potentiated but those of BWF1 were suppressed by both compounds. In in vitro experiments, both compounds enhanced lymphocyte transformation. On the contrary, II-3 had no effect on the acute inflammatory response, delayed type hypersensitivity and IgE antibody response. The abnormal release of lysosomal enzymes from the peritoneal macrophages of aged MRL/l mice were suppressed by both compounds. These results suggest that II-3 is an immunomodulator like PA but more effective than PA. II-3 may be clinically effective for rheumatoid arthritis.


Congenital Acinar Cystic Transformation of the Pancreas with Proximal Jejunal Atresia and Hepatic Iron Overload: An Autopsy Case.
Introduction: Acinar cystic transformation (ACT) of the pancreas is characterized by multiple cysts lined by dual ductal and acinar-type of epithelium. ACT is typically a disease of adulthood and has not been described in a neonate. Case report: Autopsy of this term 3-day old male demonstrated cystic transformation of the entire pancreas measuring 42 mm in its largest dimension. The main pancreatic duct was patent. The numerous variable-sized cysts were lined by both ductal (CK7-positive) and acinar (trypsin-positive) epithelium. Congenital hemochromatosis of the liver, complete proximal jejunal atresia, gangrene of the post-atretic jejunum, and subglottic stenosis were associated features. Discussion/Conclusion: ACT may occur in the neonate in association with other abnormalities.


Heterotrimeric G protein mediated regulation of proteinase production in Aspergillus nidulans.
Extracellular proteinase production induced by carbon starvation was studied in a series of heterotrimeric G protein signaling pathway mutants of Aspergillus nidulans. All the mutants tested--including deltafadA (Galpha), deltasfaD (Gbeta), deltagpgA (Ggamma) and deltasfgA (regulator of FadA signaling)--showed an elevated proteinase production after glucose depletion. Our results strongly support the view that during growth, FadA/SfaD/GpgA G protein signaling inhibits proteinase production via both Galpha and Gbetagamma subunits, and all conditions, which are not sufficient to support vegetative growth and, hence, inhibit this type of G protein signaling, elevate extracellular proteinase activities.


Modulation detection by normal and hearing-impaired listeners.
In five normally hearing subjects and seven subjects with damaged cochleas, detection thresholds for sinusoidal frequency modulation (FM) and amplitude modulation (AM) were measured using 1 s stimuli with a 500 Hz carrier frequency (Fc) at a 'comfortable' loudness (given by subject-dependent SPLs and SLs). The modulation frequency (Fmod) was 2 Hz or 10 Hz. FM (but not AM) detection was poorer in the hearing-impaired group, especially when the hearing loss at Fc exceeded 50 dB. Fmod had a different effect on FM and AM detection. The corresponding interaction was essentially identical for the two groups of subjects. Previous studies strongly suggested that normal listeners use mainly neural phase-locking cues for the detection of FM when Fmod = 2 Hz, but mainly tonotopic cues when Fmod = 10 Hz. The present results suggest that cochlear damages reduce the usefulness of these two types of cues to an approximately equal degree.


The Effects of COVID-19 Lockdown on Social Connectedness and Psychological Distress in U.S. Adults with Chronic Diseases.
Lockdown measures enacted in 2020 to control the spread of COVID-19 led to increases in the prevalence of mental health problems. Due to their high-risk status, individuals with chronic diseases may be at increased risk and disproportionately adversely affected by the COVID-19 pandemic. The investigators examined associations between having a high-risk chronic condition, social connectedness, and general distress and COVID-19-specific distress among U.S. adults during the COVID-19 lockdown. Baseline measures of a longitudinal survey collected at the beginning of the pandemic (April to June 2020) were analyzed to identify factors associated with loss of social connectedness from pre- to post-lockdown. The associations between social connectedness and both general and COVID-19-specific psychological distress were adjusted for certain high-risk chronic illnesses and interaction effects. The sample available for analysis included 1354 subjects (262 high-risk chronic diseases and 1092 without chronic illness). Those reporting the loss of social connectedness were younger (median = 39 vs. 42) and more likely to be unemployed because of the pandemic (19.4% vs. 11.0%). Adjustment for interaction demonstrated a stronger negative association between social connectedness change and the psychosocial impact of COVID-19 for those with high-risk illness(es) (change in connectedness*chronic illness OR = 0.88, 95%CI: 0.79-0.98, p = 0.020). These findings inform our understanding of the distribution and intersection of responses to public health lockdown orders in the U.S. and build further evidence of the importance of social connectedness on psychological distress.


Atom-type assignment in molecules and clusters by perturbation theory-A complement to X-ray structure analysis.
An approach to distinguish elements with similar atomic numbers in molecules and clusters is presented and applied to experimentally synthesized and structurally characterized mixed-metallic compounds. By first treating a homogenized reference system constructed from the original compound and applying first-order perturbation theory it is possible to find the most stable distribution of the atom types to the atomic sites in a very efficient way. This work is focused on the appropriate choice of homogenized reference systems and on applications treating experimentally synthesized compounds. With these examples is shown that the method is a helpful complement to X-ray crystal structure analysis.


Estimating the prevalence of dementia using multiple linked administrative health records and capture-recapture methodology.
Obtaining population-level estimates of the incidence and prevalence of dementia is challenging due to under-diagnosis and under-reporting. We investigated the feasibility of using multiple linked datasets and capture-recapture techniques to estimate rates of dementia among women in Australia. This work is based on the Australian Longitudinal Study on Women's Health. A random sample of 12,432 women born in 1921-1926 was recruited in 1996. Over 16 years of follow-up records of dementia were obtained from five sources: three-yearly self-reported surveys; clinical assessments for aged care assistance; death certificates; pharmaceutical prescriptions filled; and, in three Australian States only, hospital in-patient records. A total of 2534 women had a record of dementia in at least one of the data sources. The aged care assessments included dementia records for 79.3% of these women, while pharmaceutical data included 34.6%, death certificates 31.0% and survey data 18.5%. In the States where hospital data were available this source included dementia records for 55.8% of the women. Using capture-recapture methods we estimated an additional 728 women with dementia had not been identified, increasing the 16 year prevalence for the cohort from 20.4 to 26.0% (95% confidence interval [CI] 25.2, 26.8%). This study demonstrates that using routinely collected health data with record linkage and capture-recapture can produce plausible estimates for dementia prevalence and incidence at a population level.


Getting stuck in depression: the roles of rumination and emotional inertia.
Like many other mental disorders, depression is characterised by psychological inflexibility. Two instances of such inflexibility are rumination: repetitive cognitions focusing on the causes and consequences of depressive symptoms; and emotional inertia: the tendency for affective states to be resistant to change. In two studies, we tested the predictions that: (1) rumination and emotional inertia are related; and (2) both independently contribute to depressive symptoms. We examined emotional inertia of subjective affective experiences in daily life among a sample of non-clinical undergraduates (Study 1), and of affective behaviours during a family interaction task in a sample of clinically depressed and non-depressed adolescents (Study 2), and related it to self-reported rumination and depression severity. In both studies, rumination (particularly the brooding facet) and emotional inertia (particularly of sad/dysphoric affect) were positively associated, and both independently predicted depression severity. These findings demonstrate the importance of studying both cognitive and affective inflexibility in depression.


Toxicity assessment of microcystin-leucine arginine in planarian Dugesia japonica.
Microcystin-leucine arginine (MC-LR), a representative cyanobacterial toxin, poses an increasing and serious threat to aquatic ecosystems. Despite investigating its toxic effects in various organisms and cells, the toxicity to tissue regeneration and stem cells in vivo still needs to be explored. Planarians are ideal regeneration and toxicology research models and have profound implications in ecotoxicology evaluation. This study conducted a systemic toxicity evaluation of MC-LR, including morphological changes, growth, regeneration, and the underlying cellular and molecular changes after MC-LR exposure, which were investigated in planarians. The results showed that exposure to MC-LR led to time- and dose-dependent lethal morphological changes, tissue damage, degrowth, and delayed regeneration in planarians. Furthermore, MC-LR exposure disturbed the activities of antioxidants, including total superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, and total antioxidant capacity, leading to oxidative stress and DNA damage, and then reduced the number of dividing neoblasts and promoted apoptosis. The results demonstrated that oxidative stress and DNA damage induced by MC-LR exposure caused apoptosis. Excessive apoptosis and suppressed neoblast activity led to severe homeostasis imbalance. This study explores the underlying mechanism of MC-LR toxicity in planarians and provides a basis for the toxicity assessment of MC-LR to aquatic organisms and ecological risk evaluation.


Higher-Order VLP-Based Protein Macromolecular Framework Structures Assembled via Coiled-Coil Interactions.
Hierarchical organization is one of the fundamental features observed in biological systems that allows for efficient and effective functioning. Virus-like particles (VLPs) are elegant examples of a hierarchically organized supramolecular structure, where many subunits are self-assembled to generate the functional cage-like architecture. Utilizing VLPs as building blocks to construct two- and three-dimensional (3D) higher-order structures is an emerging research area in developing functional biomimetic materials. VLPs derived from P22 bacteriophages can be repurposed as nanoreactors by encapsulating enzymes and modular units to build higher-order catalytic materials via several techniques. In this study, we have used coiled-coil peptide interactions to mediate the P22 interparticle assembly into a highly stable, amorphous protein macromolecular framework (PMF) material, where the assembly does not depend on the VLP morphology, a limitation observed in previously reported P22 PMF assemblies. Many encapsulated enzymes lose their optimum functionalities under the harsh conditions that are required for the P22 VLP morphology transitions. Therefore, the coiled-coil-based PMF provides a fitting and versatile platform for constructing functional higher-order catalytic materials compatible with sensitive enzymes. We have characterized the material properties of the PMF and utilized the disordered PMF to construct a biocatalytic 3D material performing single- and multistep catalysis.


Associations of sleep duration and fruit and vegetable intake with the risk of metabolic syndrome in Chinese adults.
To understand the adverse association of short sleep duration and insufficient fruit and vegetable intake (FVI) with and their combined effect on metabolic syndrome (MetS) in Chinese adults.This cross-sectional study analyzed 7052 adults aged 18∼64 years old in 2009, with fasting blood samples collected. Participants were divided into short/normal/long sleep duration groups and sufficient/insufficient FVI groups in accordance with self-reported information. Metabolic syndrome was defined by National Cholesterol Education Program's Adult Treatment Panel III criteria.The prevalence of MetS among the study subjects was 21.74%. Participants were classified into short (<7 h/d), normal (7∼9 h/d), and long (>9 h/d) groups according to their daily sleep duration. Participants with less than 500 g of FVI per day was considered as insufficient FVI. After adjusting for confounders, the negative effect of short sleep duration on MetS was statistically significant, with an OR of 1.29 (95%CI = 1.06∼1.56); and high fasting glucose levels were significantly associated with insufficient FVI. Compared with subjects with normal sleep duration and sufficient FVI, participants with short sleep time and insufficient FVI had the highest risk of MetS (OR = 1.37, 95% CI: 1.04-1.66).This study revealed that insufficient FVI and short sleep duration were significantly associated with an increased risk of MetS among Chinese adults. Increasing FVI and normal sleep duration during Chinese adults could be significant targets for reducing the prevalence of MetS.


Management of varicella in neonates and infants.
In countries where vaccination is not implemented, varicella is a common ubiquitous disease offering a broad range of clinical presentations. Whereas mother-to-child perinatal transmission of varicella zoster virus (VZV) can lead to disseminated life-threatening diseases in unimmunised newborns, postnatal acquisition will be generally a source of milder infections. The pattern and severity of the disease are known to be partly determined by the timing of VZV acquisition during pregnancy with the highest risk period located around delivery. Management of youngest children after contact with a varicella case remains difficult for clinicians not only because of unawareness of varicella natural history and risks factors for serious complications, but also because of the lack of consensus from experts available in the literature. This state of uncertainty often leads to overconsumption of healthcare resources with systematic hospitalisation and unjustified antiviral intravenous therapies. After a concise literature review, this article proposes pragmatic recommendations considering newborns in various scenarios following a contact with VZV, taking into account the timing and mode of virus transmission, the maternal immunological status, the baby's gestational age and the presence of other underlying conditions.


The Tower of London Test: different scoring criteria for diagnosing Alzheimer's disease and mild cognitive impairment.
The Tower of London (TOL) is used for evaluating planning skills, which is a component of the executive functions. Different versions and scoring criteria were developed for this task, and some of them present with different psychometrical properties. This study aimed to evaluate two specific scoring methods of the TOL in diagnosing Mild Cognitive Impairment and probable Alzheimer's disease. The TOL total scores from 60 patients of each diagnosis were compared with the performance of 60 healthy-aged controls using receiver operating characteristics analysis and multinomial logistic regression. Krikorian method better diagnosed Alzheimer's disease, while Portellas's was better at discriminating healthy controls from Mild Cognitive Impairment, but were not efficient at comparing this last group with Alzheimer's patients. Regression analysis indicates that in addition to screening tests, TOL improves the classification of the three groups. The results suggest the two scoring methods used for this task may be useful for different diagnostic purposes.


An unprecedented 3-D SHG MOF material of silver(I) induced by chiral triple helices.
An unprecedented 3-D SHG-active metal-organic framework (MOF) of silver(I), Ag-Amidn (1) (HAmidn: 2-amino-4,5-imidazoledicarbonitrile), has been successfully prepared by employing the new single ligand. The cooperative coordination of the imidazole and carbonitrile N atoms leads to the chiral triple helices accounting for the noncentrosymmetric space group, which are linked together to form a rare 10(3) topological structure. Ag-Amidn (1) with high thermal stability and insolubility may be considered as a potential second-order NLO material.


Herbal and dietary supplement disclosure to health care providers by individuals with chronic conditions.
Very little is known about herbal and dietary supplement disclosure in adults with chronic medical conditions, especially on a national level. To examine herbal and dietary supplement disclosure to conventional health care providers by adults with chronic medical conditions. Data on herbal and dietary supplement use (N = 5456 users) in the previous year were used from the 2002 National Health Interview Survey. Bi-variable analyses compared characteristics between herbal and dietary supplement disclosers and nondisclosers. Multivariable logistic regression identified independent correlates of herbal and dietary supplement disclosure. Overall, only 33% of herbal and dietary supplement users reported disclosing use of herbal and dietary supplements to their conventional health care provider. Among herbal and dietary supplement users with chronic conditions, less than 51% disclosed use to their conventional health care provider. Hispanic (adjusted odds ratio and 95% confidence interval = 0.70 [0.52, 0.94]) and Asian American (adjusted odds ratio and 95% confidence interval = 0.54 [0.33, 0.89]) adults were much less likely than non-Hispanic white Americans to disclose herbal and dietary supplement use. Having less than a high school education (adjusted odds ratio and 95% confidence interval = 0.61 [0.45, 0.82]) and not having insurance (adjusted odds ratio and 95% confidence interval = 0.77 [0.59, 1.00]) were associated with being less likely to disclose herbal and dietary supplement use. Herbal and dietary supplement disclosure rates are low, even among adults with chronic conditions. These findings raise concerns about the safety of herbal and dietary supplements in combination with allopathic care. Future studies should focus on educating physicians about crosscultural care as well as eliciting information about herbal and dietary supplement use.


Colloid interaction energies for physically and chemically heterogeneous porous media.
The mean and variance of the colloid interaction energy (Φ*) as a function of separation distance (h) were calculated on physically and/or chemically heterogeneous solid surfaces at the representative elementary area (REA) scale. Nanoscale roughness was demonstrated to have a significant influence on the colloid interaction energy for different ionic strengths. Increasing the roughness height reduced the magnitude of the energy barrier (Φmax*) and the secondary minimum (Φ2min*). Conversely, increasing the fraction of the solid surface with roughness increased the magnitude of Φmax* and Φ2min*. Our results suggest that primary minimum interactions tend to occur in cases where only a portion of the solid surface was covered with roughness (i.e., isolated roughness pillars), but their depths were shallow as a result of Born repulsion. The secondary minimum was strongest on smooth surfaces. The variance in the interaction energy was also a strong function of roughness parameters and h. In particular, the variance tended to increase with the colloid size, the magnitude of Φ*, the height of the roughness, and especially the size (cross-sectional area) of the heterogeneity. Nonzero values of the variance for Φ2min* implied the presence of a tangential component of the adhesive force and a resisting torque that controls immobilization and release for colloids at this location. Heterogeneity reduced the magnitude of Φ* in comparison to the corresponding homogeneous situation. Physical heterogeneity had a greater influence on mean properties of Φ* than similar amounts of chemical heterogeneity, but the largest reduction occurred on surfaces with both physical and chemical heterogeneity. The variance in Φ* tended to be higher for a chemically heterogeneous solid.


UBE2C overexpression in melanoma and its essential role in G2/M transition.
Ubiquitin‑conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression, and its aberrant expression has been implicated in various malignancies. However, its clinical and biological roles in malignant melanoma is still unclear. In this study, we found a significant high expression level of UBE2C in melanoma by an in silico analysis of The Cancer Genome Atlas (TCGA) database, which was further validated using fresh melanoma samples. The KM plotter showed that UBE2C level was statistically related to the overall survival (OS) of melanoma patients (p<0.01). RNA interference of UBE2C inhibited the growth of melanoma cells via deactivating ERK/Akt signaling pathways, and blocked the G2/M transition through downregulation of both the level and the activity of mitosis promoting factor (MPF), triggering the apoptosis of melanoma cells. Further, silencing of UBE2C significantly inhibited the xenografted tumor growth on nude mice, indicating an important role of UBE2C in melanoma growth in vivo. Together, our results show that UBE2C may serve as a novel prognostic biomarker as well as a potential therapeutic target for melanoma.


Malignant melanoma of the conjunctiva in children: a review of the international literature 1965-2006.
Conjunctival melanoma is rare in children. This article presents a comprehensive review and discusses the clinical significance of the published cases of malignant melanoma of the conjunctiva in children younger than 15 years. To obtain prior reports of conjunctival melanoma in children, a systematic search of the world literature was conducted. Additional studies were identified from the bibliographies of the retrieved articles, as well as from major ophthalmic textbooks. A review of the literature resulted in 28 reported cases of conjunctival melanoma in children younger than 15 years, and only 8 had adequate case details. Malignant melanoma of the conjunctiva is a rare condition in children. Limited knowledge for management and prognosis of this condition in children is largely due to its low occurrence.


The mediating role of social connectedness and hope in the relationship between group membership continuity and mental health problems in vulnerable young people.
There is growing evidence of a beneficial effect of social group processes on well-being and mental health. To investigate the role of group membership continuity in reducing mental ill-health among young people who were already vulnerable pre-pandemic, and to understand the social and psychological mechanisms of the benefits of group memberships for vulnerable young people. This study takes a cross-sectional design, using survey data from a sample of 105 young people aged 16-35 years, collected approximately 1 year after the global COVID-19 outbreak (January to July 2021). Correlational and path analyses were used to test the associations between group membership continuity and mental health problems (depression, anxiety, psychotic-like experiences) and the mediation of these associations by hope and social connectedness (in-person and online). To correct for multiple testing, the Benjamini-Hochberg procedure was implemented for all analyses. Indirect effects were assessed with coverage of 99% confidence intervals. Multiple prior group memberships were associated with preservation of group memberships during the COVID-19 pandemic. In-person social connectedness, online social connectedness and hope mediated the relationship between group membership continuity and mental health problem symptoms. The results suggest that clinical and public health practice should support vulnerable young people to foster and maintain their social group memberships, hopefulness and perceived sense of social connectedness as means of helping to prevent exacerbation of symptoms and promote recovery of mental health problems, particularly during significant life events.


An improved sensor for precision detection of in situ stem water content using a frequency domain fringing capacitor.
One role of stems is that of water storage. The water content of stems increases and decreases as xylem water potential increases and decreases, respectively. Hence, a nondestructive method to measure stem water content (StWC) = (volume of water) : (volume of stem), could be useful in monitoring the drought stress status of plants. We introduce a frequency domain inner fringing capacitor-sensor for measuring StWC which operates at 100 MHz frequency. The capacitor-sensor consists of two wave guides (5-mm-wide braided metal) that snugly fit around the surface of a stem with a spacing of 4-5 mm between guides. Laboratory measurements on analog stems reveals that the DC signal output responds linearly to the relative dielectric constant of the analog stem, is most sensitive to water content between the waveguides to a depth of c. 3 mm from the stem surface, and calibrations based on the gravimetric water loss of excised stems of plants revealed a resolution in StWC of < ± 0.001 v/ v. The sensor performed very well on whole plants with a 100-fold increased resolution compared with previous frequency domain and time domain reflectometry methods and, hence, may be very useful for future research requiring nondestructive measurements of whole plants.


Physiological accompaniments of human muscle fatigue.
Fatigue is defined as the failure of muscle to produce the initial peak force. This may be due to failure at one or more sites between the motor cortex, the motoneuron and the internal machinery of the muscle fibre. Issues of the topic under consideration include sensation of motor command during fatigue, voluntary activation of motoneuron pools and motor unit behaviour and electromyographic activity during fatigue. At one end of this motor chain there may be failure to generate an adequate descending voluntary drive to the motoneuron pool causing central fatigue and at the other a failure of excitation-contraction coupling. The contractile apparatus within the cell may also be abnormal. Changes in the central motor commands, the discharge of motoneurons and the output of muscle fibres during muscle fatigue are described.


The conformational landscape of myrtenol: The structure of the hydroxymethyl group and its robustness upon hydration.
The conformational landscape of myrtenol (2-pinen-10-ol) and its robustness upon hydration were investigated theoretically and experimentally by employing a synergic combination of quantum chemical calculations and Fourier transform microwave spectroscopy coupled to a supersonic jet expansion. Relaxed potential energy surfaces have been carried out, and the lowest energy conformers of the monomer were found to be associated with different geometries of the hydroxymethyl group from those previously reported [Sedo et al., J. Mol. Spectrosc. 356, 32 (2019)]. Geometry optimizations and harmonic vibrational frequency calculations allowed characterization of the equilibrium structure of the possible conformers of myrtenol. Among the nine predicted structures, four have been observed, analyzed, and identified. The controversy on the geometry was solved with the deuteration of the hydroxyl group, which led to the determination of substitution (rs) geometry, in agreement with the present theoretical results. Interestingly, the four observed conformers exhibit the same orientation of OH as in the allyl alcohol molecule. Furthermore, hydrogen bonding linking myrtenol to water was studied. One monohydrate has been observed and identified. Non-covalent interactions and natural bond orbital analysis were performed to depict the interactions responsible for the stabilization of the observed structure. We conclude that the structure of the hydroxymethyl group is robust and does not change upon hydration.


Development of a monoclonal antibody for the detection of anti-canine CD20 chimeric antigen receptor expression on canine CD20 chimeric antigen receptor-transduced T cells.
Chimeric antigen receptor (CAR) CAR-T cell therapy targeting CD20 can be a novel adoptive cell therapy for canine patients with B-cell malignancy. After injection of the CAR-T cells in vivo, monitoring circulating CAR-T cells is essential to prove in vivo persistence of CAR-T cells. In this study, we developed a novel monoclonal antibody against canine CD20 CAR, whose single-chain variable fragment was derived from the our previously reported anti-canine CD20 therapeutic antibody. Furthermore, we proved that this monoclonal antibody can detect therapeutic anti-canine CD20 chimeric antibody in the serum from healthy beagle dogs injected with the therapeutic antibody for safety study. This monoclonal antibody is a useful tool for monitoring both canine CD20-CAR-T cells and anti-canine CD20 therapeutic antibody for canine lymphoma.


Novel Single-Needle Approach for Retrocrural Celiac Plexus Blockade Using Fluoroscopic Guidance: A Case Report.
Celiac plexus neurolysis has been shown to be an effective analgesic option for patients with visceral pain related to intraabdominal malignancies. In the setting of significant tumor burden, the celiac plexus may be inaccessible, limiting the efficacy of the transcrural approach. This case report describes a novel single-needle approach to retrocrural celiac plexus blockade, allowing for rapid blockade with a needle trajectory contralateral to the aorta in a 73-year-old woman with altered anatomy secondary to advanced metastatic colorectal cancer.


Interacting effects of preoperative information and patient choice in adaptation to colonoscopy.
The aim of this study was to match patient information requirements by determining whether giving patients a choice for additional preprocedural audiovisual information modifies the effectiveness of this information on anxiety, worry, knowledge, and patient satisfaction. Patients scheduled to undergo colonoscopy were approached one week before their procedure. All patients received an information leaflet during their standard preanesthetic clinic visit. Patients were randomly assigned to a choice or no-choice condition. Patients in the choice condition were free to watch or not watch the video, people in the no-choice condition were further randomized to watch or not watch the video. Measures of anxiety and worry were completed before watching the video. Anxiety, worry, knowledge, and satisfaction were measured one week later just before the colonoscopy. One hundred sixty-six patients completed the study. Of those patients randomized to the choice condition, 69 percent wanted to watch the video. Those who chose not to watch the video were significantly more worried on the day of their procedure. Consistent with current evidence, watching the video was associated with improvements in short-term knowledge (F(1,161) = 4.8, P = 0.03). There was, however, no significant effect of the choice or video conditions on anxiety or patient satisfaction. There appears to be no additional benefits in terms of patient outcomes by allowing patients to choose whether they want additional audiovisual information. We suggest that all patients undergoing colonoscopy would benefit from watching such an educational video in the week before their procedure.


Can teacher-child relationships alter the effects of early socioeconomic status on achievement in middle childhood?
Using data from the NICHD SECCYD (N=1053), we used two-level hierarchical linear models with site fixed effects to examine whether teacher-child closeness and conflict moderated associations between two indicators of early socioeconomic status (maternal education and family income) and standardized measures of children's math and reading achievement at 54months, 1st, 3rd, and 5th grades. Children whose mothers had lower levels of education and conflictual relationships with teachers exhibited lower reading achievement, on average, across elementary school. At the same time, children with less educated mothers who experienced increases in teacher-child closeness and decreases in teacher-child conflict exhibited improvements in reading achievement across elementary school. Finally, low teacher-child closeness elevated the risk for poor math achievement posed by low family income. Implications for intervention design and development are discussed.


Integrating preventive health services within community health centers: lessons from WISEWOMAN.
Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) provides low-income, underserved women ages 40-64 with risk factor screening and lifestyle intervention and referral services to prevent cardiovascular disease (CVD). Integrating WISEWOMAN's services with the culturally appropriate medical care and support services offered by community health centers may improve the program's ability to reduce CVD burden among underserved women. We conducted a formative assessment of the perceived opportunities, challenges, and strategies associated with integrating WISEWOMAN into community health center settings. A panel of stakeholders that included health center and WISEWOMAN representatives was convened in 2002, and a semistructured discussion guide was used to elicit perspectives about integration. We also conducted an in-depth review of WISEWOMAN's history of collaboration with health centers in North Carolina. Stakeholders perceived a clear need for integrating WISEWOMAN within health center settings, indicating that centers have few other resources to expand preventive services delivery and offer effective lifestyle interventions for underserved populations. Perceived barriers to integration included competing demands on health center resources, difficulties hiring staff for new programs, and administrative burdens associated with data collection and reporting. Experiences within North Carolina's WISEWOMAN project demonstrate, however, that lifestyle interventions can be designed in ways that facilitate integration by health centers. Integration strategies need to be tailored to the resources, skills, and capacities available within health centers. As health centers and WISEWOMAN projects gain more experience in collaborating, additional research should be conducted to identify how best to achieve integration within specific institutional and community contexts.


An approach to the study of primitive thrombocythemia (PT) megakaryocytes by means of Fourier transform infrared microspectroscopy (FT-IR-M).
Chronic myeloid leukemia (CML), polycythemia vera (PV), idiopathic myelofibrosis (IM) and primary thrombocythemia (PT) are myeloproliferative diseases of clonal origin. Megakaryocyte series are commonly involved in these disorders. In a previous paper of us, megakaryocytes (MKs) from PV and PT patients were shown to be more pathological with respect to the MKs from CML. This paper describes a Fourier transform infrared microspectroscopy (FT-IR-M) study analyzing the cytoplasm and nucleus areas of MKs from thrombocythemic patients which exhibited numerous giant cells (from 100 to 190 microm in diameter). The size of these cells makes it possible to analyze the cell parts using FT-IR-M technique. The infrared determinations on 10 single MKs for each case examined in these two different cell regions revealed spectral differences with a high degree of reproducibility. Finally, the spectra of whole MKs from normal donors and from thrombocythemic patients were also compared.


Antiaging effects of astaxanthin-rich alga Haematococcus pluvialis on fruit flies under oxidative stress.
The microalga Haematococcus pluvialis (HP) is the best natural producer of astaxanthin (AX), which is a potent antioxidant with broad health benefits. The present study investigated the antiaging potential of HP biomass using the fruit fly Drosophila melanogaster as the animal model. The results showed that in wild-type flies the treatment of HP induced the early mortality at a concentration of 20 mg/mL, which was associated with the decreased enzymatic activities of CuZn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) as well as the down-regulation of SOD1, SOD2, and catalase (CAT) at the transcriptional level. In SOD(n108) mutant flies, the supplementation of HP (10 or 20 mg/mL) significantly extended their lifespan and ameliorated the age-related decline in locomotor function. Further studies suggested that HP may play a role as a complement to the defective endogenous antioxidant system to exert such lifespan elongation effects. These results, taken together, strongly support the antiaging properties of HP and its therapeutic rather than preventive potential against aging-related diseases.


The bonded amalgam restoration--a review of the literature and report of its use in the treatment of four cases of cracked-tooth syndrome.
Recent interest in amalgam as a restorative material has been directed toward the development of the bonded amalgam restoration. The literature regarding the theoretical and clinical aspects of this technique is reviewed. Four cases of successful treatment of cracked-tooth syndrome with the bonded amalgam restoration are presented.


Solitary breast metastasis to the ampulla and distal common bile duct.
The indications for pancreaticoduodenectomy have continued to expand over the past 10 to 15 years. This is in large part due to improved diagnostic studies, endoscopic retrograde cholangiopancreaticogram and computed tomography, and decreases in hospital perioperative morbidity and mortality. One third of breast cancer patients will develop metastatic disease usually to the liver, lung, or bone (World J Surg 1994;18:98-111). However, the presentation of painless jaundice due to a single metastatic lesion to the distal common bile duct from ductal adenocarcinoma of the breast is extremely rare. In this case report and review of the literature, we discuss the indications and emerging evidence that pancreaticoduodenectomies can now be performed for localized metastatic disease.


Moral Courage: Student Registered Nurse Anesthetist Experiences on the Operating Team.
Lack of moral courage may lead to moral stress for healthcare personnel and to unethical behavior or adverse events for patients. Hospital operating room (OR) teams include surgeons, OR nurses, Certified Registered Nurse Anesthetists (CRNAs), anesthesiologists, and student registered nurse anesthetists (SRNAs). Due to the multidisciplinary work in a stressful, high-technology and high-risk environment, the OR is the context for most of the unethical behavior reported in hospitals. The purpose of this study was to explore SRNA experiences of moral courage in the OR. We used a critical incident technique, utilizing 40 SRNA narratives of situations including moral courage/lack of moral courage. The narratives were analyzed using thematic analysis. Findings indicate that unethical behavior potentially leading to patient safety or work environment issues could be avoided when OR personnel showed moral courage by speaking up for patients or for colleagues. Lack of moral courage was indicated by tacit acceptance of unethical behavior or lack of collaboration. SRNAs need not only to learn about the CRNAs' professional obligations and tasks but also to develop moral courage to be able to respond to unethical behavior or communication in the OR. Hence, students should be introduced to such issues during their education.


Asymmetry in the Kuramoto model with nonidentical coupling.
Synchronization and desynchronization of coupled oscillators appear to be the key property of many physical systems. It is believed that to predict a synchronization (or desynchronization) event, the knowledge on the exact structure of the oscillatory network is required. However, natural sciences often deal with observations where the coupling coefficients are not available. In the present paper we suggest a way to characterize synchronization of two oscillators without the reconstruction of coupling. Our method is based on the Kuramoto chain with three oscillators with constant but nonidentical coupling. We characterize coupling in this chain by two parameters: the coupling strength s and disparity σ. We give an analytical expression of the boundary s_{max} of synchronization occurred when s>s_{max}. We propose asymmetry A of the generalized order parameter induced by the coupling disparity as a new characteristic of the synchronization between two oscillators. For the chain model with three oscillators we present the self-consistent inverse problem. We explore scaling properties of the asymmetry A constructed for the inverse problem. We demonstrate that the asymmetry A in the chain model is maximal when the coupling strength in the model reaches the boundary of synchronization s_{max}. We suggest that the asymmetry A may be derived from the phase difference of any two oscillators if one pretends that they are edges of an abstract chain with three oscillators. Performing such a derivation with the general three-oscillator Kuramoto model, we show that the crossover from the chain to general network of oscillators keeps the interrelation between the asymmetry A and synchronization. Finally, we apply the asymmetry A to describe synchronization of the solar magnetic field proxies and discuss its potential use for the forecast of solar cycle anomalies.


mRNA N6-methyladenosine methylation of postnatal liver development in pig.
N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in the regulation of post-transcriptional protein coding gene expression. Liver is a vital organ and plays a major role in metabolism with numerous functions. Information concerning the dynamic patterns of mRNA m6A methylation during postnatal development of liver has been long overdue and elucidation of this information will benefit for further deciphering a multitude of functional outcomes of mRNA m6A methylation. Here, we profile transcriptome-wide m6A in porcine liver at three developmental stages: newborn (0 day), suckling (21 days) and adult (2 years). About 33% of transcribed genes were modified by m6A, with 1.33 to 1.42 m6A peaks per modified gene. m6A was distributed predominantly around stop codons. The consensus motif sequence RRm6ACH was observed in 78.90% of m6A peaks. A negative correlation (average Pearson's r = -0.45, P < 10-16) was found between levels of m6A methylation and gene expression. Functional enrichment analysis of genes consistently modified by m6A methylation at all three stages showed genes relevant to important functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. Genes with higher m6A methylation and lower expression levels at any particular stage were associated with the biological processes required for or unique to that stage. We suggest that differential m6A methylation may be important for the regulation of nutrient metabolism in porcine liver.


A cysteine-rich LIM-only protein mediates regulation of smooth muscle-specific gene expression by cGMP-dependent protein kinase.
Vascular smooth muscle cells (VSMCs) undergo phenotypic modulation, changing from a differentiated, contractile to a de-differentiated, synthetic phenotype; the change is associated with decreased expression of smooth muscle (SM)-specific genes and loss of cGMP-dependent protein kinase (PKG), but transfection of PKG into de-differentiated VSMCs restores SM-specific gene expression. We show that small interference RNA-mediated down-regulation or pharmacologic inhibition of PKG reduced SM-specific gene expression in differentiated VSMCs and provide a mechanism for cGMP/PKG regulation of SM-specific genes involving the cysteine-rich LIM-only protein CRP4. PKG associated with CRP4 and phosphorylated the protein in intact cells. CRP4 had no intrinsic transcriptional activity, but exhibited adaptor function, because it acted synergistically with serum response factor (SRF) and GATA6 to activate the SM-alpha-actin promoter. cGMP stimulation of the promoter required PKG and CRP4 co-expression with SRF and GATA6. A phosphorylation-deficient mutant CRP4 and a CRP4 deletion mutant deficient in PKG binding did not support cGMP/PKG stimulation of the SM-alpha-actin promoter. In the presence of wild-type but not mutant CRP4, cGMP/PKG enhanced SRF binding to a probe encoding the distal SM-alpha-actin promoter CArG (CC(AT)(6)GG) element. CRP4 and SRF associated with CArG elements of endogenous SM-specific genes in intact chromatin. Small interference RNA-mediated down-regulation of CRP4 prevented the positive effects of cGMP/PKG on SM-specific gene expression. In the presence of CRP4, cGMP/PKG increased SRF- and GATA6-dependent expression of endogenous SM-specific genes in pluripotent 10T1/2 cells. Thus, CRP4 mediates cGMP/PKG stimulation of SM-specific gene expression, and PKG plays an important role in regulating the phenotype of VSMCs.


siRNA conjugate delivery systems.
Small interfering RNA (siRNA) has been chemically conjugated to a variety of bioactive molecules, lipids, polymers, peptides, and inorganic nanostructured materials to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver siRNAs to the target cells and tissues, many different siRNA bioconjugates were synthesized and characterized, and their gene silencing efficiencies were tested in vitro and in vivo. In this review, recent developments of siRNA bioconjugates are summarized.


Improving Proteoform Identifications in Complex Systems Through Integration of Bottom-Up and Top-Down Data.
Cellular functions are performed by a vast and diverse set of proteoforms. Proteoforms are the specific forms of proteins produced as a result of genetic variations, RNA splicing, and post-translational modifications (PTMs). Top-down mass spectrometric analysis of intact proteins enables proteoform identification, including proteoforms derived from sequence cleavage events or harboring multiple PTMs. In contrast, bottom-up proteomics identifies peptides, which necessitates protein inference and does not yield proteoform identifications. We seek here to exploit the synergies between these two data types to improve the quality and depth of the overall proteomic analysis. To this end, we automated the large-scale integration of results from multiprotease bottom-up and top-down analyses in the software program Proteoform Suite and applied it to the analysis of proteoforms from the human Jurkat T lymphocyte cell line. We implemented the recently developed proteoform-level classification scheme for top-down tandem mass spectrometry (MS/MS) identifications in Proteoform Suite, which enables users to observe the level and type of ambiguity for each proteoform identification, including which of the ambiguous proteoform identifications are supported by bottom-up-level evidence. We used Proteoform Suite to find instances where top-down identifications aid in protein inference from bottom-up analysis and conversely where bottom-up peptide identifications aid in proteoform PTM localization. We also show the use of bottom-up data to infer proteoform candidates potentially present in the sample, allowing confirmation of such proteoform candidates by intact-mass analysis of MS1 spectra. The implementation of these capabilities in the freely available software program Proteoform Suite enables users to integrate large-scale top-down and bottom-up data sets and to utilize the synergies between them to improve and extend the proteomic analysis.


Red algal Rubisco fails to accumulate in transplastomic tobacco expressing Griffithsia monilis RbcL and RbcS genes.
In C3 plants, the carbon fixation step catalyzed by ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) represents a major rate-limiting step due to the competing oxygenation reaction, which leads to the energy-intensive photorespiration and lowers the overall photosynthetic efficiency. Hence, there is great biotechnological interest in replacing the Rubisco in C3 crops with a more efficient enzyme. The Rubisco enzymes from red algae are among the most attractive choices due to their remarkable preference for carboxylation over oxygenation reaction. However, the biogenesis of Rubisco is extremely complex. The Rubisco enzymes in plants, algae, and cyanobacteria are made up of eight large and eight small subunits. The folding of the large subunits and the assembly of the large subunits with the small subunits to form a functional holoenzyme require specific chaperonin complexes and assembly factors. As a result, previous success in expressing foreign Rubisco in plants has been limited to Rubisco large subunits from closely related plant species and simpler bacterial enzymes. In our previous work, we successfully replaced the Rubisco in tobacco with a cyanobacterial enzyme, which was able to support the phototrophic growth of the transgenic plants. In this work, we used the same approach to express the Rubisco subunits from the red alga Griffithsia monilis in tobacco chloroplasts in the absence of the tobacco Rubisco large subunit. Although the red algal Rubisco genes are being transcribed in tobacco chloroplasts, the transgenic plants lack functional Rubisco and can only grow in a medium containing sucrose. Our results suggest that co-expression of compatible chaperones will be necessary for successful assembly of red algal Rubisco in plants.


Disruption of a gene predicted to encode a solute binding protein of an ABC transporter reduces transmission of Spiroplasma citri by the leafhopper Circulifer haematoceps.
Spiroplasma citri is transmitted from plant to plant by phloem-feeding leafhoppers. In an attempt to identify mechanisms involved in transmission, mutants of S. citri affected in their transmission must be available. For this purpose, transposon (Tn4001) mutagenesis was used to produce mutants which have been screened for their ability to be transmitted by the leafhopper vector Circulifer haematoceps to periwinkle plants. With one mutant (G76) which multiplied in leafhoppers as efficiently as S. citri wild-type (wt) strain GII-3, the plants showed symptoms 4 to 5 weeks later than those infected with wt GII-3. Thirty to fifty percent of plants exposed to leafhoppers injected with G76 remained symptomless, whereas for wt GII-3, all plants exposed to the transmission showed severe symptoms. This suggests that the mutant G76 was injected into plants by the leafhoppers less efficiently than wt GII-3. To check this possibility, the number of spiroplasma cells injected by a leafhopper through a Parafilm membrane into SP4 medium was determined. Thirty times less mutant G76 than wt GII-3 was transmitted through the membrane. These results suggest that mutant G76 was affected either in its capacity to penetrate the salivary glands and/or to multiply within them. In mutant G76, transposon Tn4001 was shown to be inserted into a gene encoding a putative lipoprotein (Sc76) In the ABCdb database Sc76 protein was noted as a solute binding protein of an ABC transporter of the family S1_b. Functional complementation of the G76 mutant with the Sc76 gene restored the wild phenotype, showing that Sc76 protein is involved in S. citri transmission by the leafhopper vector C. haematoceps.


Surgical Treatment of Crohn Colitis Involving More Than 2 Colonic Segments: Long-Term Outcomes From a Single Institution.
The incidence of primary Crohn colitis is uncommon and surgical treatment has remained controversial, although most patients with Crohn colitis eventually require surgical intervention. This study aims to compare the operative outcomes of patients who underwent segmental versus either total colectomy or total proctocolectomy for Crohn colitis and to assess potential risk factors associated with clinical and surgical recurrence-free survivals.This is a retrospective study of 116 patients who underwent primary surgery for Crohn colitis between August 1997 and July 2011. Patients were classified based on the type of surgery: segmental colectomy (SC group; n = 71) or either total colectomy or total proctocolectomy (TC group; n = 45).There were no significant differences in postoperative complications or the nutritional state between the SC and TC groups. Patients in TC group had a significantly higher clinical recurrence-free survival (CRFS). Among the 54 patients with multisegmental Crohn colitis, the TC group had a significantly increased CRFS and surgical recurrence-free survival (SRFS), compared with patients in the SC group (5-year CRFS: 82.0% ± 5.8% vs 22.2% ± 13.9%, P = 0.001; 5-year SRFS: 88.1% ± 5.0% vs 44.4% ± 16.6%, P = 0.001). By multivariate analysis of patients with multisegments involved, SC was a risk factor for SRFS and CRFS (hazard ratio [HR] = 4.637, 95% confidence interval [CI] = 1.387-15.509, P = 0.013 and HR = 32.407, 95% CI = 2.873-365.583, P = 0.005).TC patients have significantly increased CRFS and TC in patients with multisegment involvement may affect improved SRFS and CRFS. Among patients with multisegmental Crohn colitis, SC is an independent risk factor for CRFS and SRFS.


Effects of varying the load force range and frequency on force coordination in static manipulation.
A frequency associated deterioration of the hand grip (GF; normal component of force acting at the digits-object contact area) and load force (LF; the tangential component) coordination has been demonstrated in a variety of repetitive manipulation tasks. However, it remains unknown whether the effect originates from the task frequency per se, or from the rate of LF change (a prediction that could be derived from the minimum jerk hypothesis) which increases with both LF frequency and LF range. The aim of the study was to discern between the effects of LF frequency and LF range (which affects only the rate of LF) in static manipulation tasks. Subjects (N=15) exerted a sinusoidal LF pattern against an externally fixed instrumented handle at 5 different LF frequencies (0.67-3.33Hz) and ranges (6-30N). The results revealed weak and mainly non-significant effects of both LF range and frequency on GF scaling (GF/LF ratio). However, both GF-LF coupling (assessed by correlation coefficients) and GF modulation (change in GF relative to LF variation) demonstrated a prominent decrease associated with LF frequency, but not with LF range. The observed findings were interpreted by switching between hypothetical synergies of GF and LF producing muscles separately employed in the phases of the increasing and decreasing forces. From the practical aspect, however, the results suggest that the frequency, but not the LF range should be taken into account when designing rhythmic manipulation tasks, developing standard tests of hand function based on GF-LF coordination, or comparing the data from different studies.


Knowledge and management of diarrhea among underserved minority parents/caregivers.
Dehydration resulting from diarrhea continues to be a cause of morbidity, mortality, and increased health care costs in the United States. This study assesses parental knowledge of the causes and signs of diarrhea and dehydration. It also examines parental-care practices during an episode of diarrhea. A survey was given to 219 parents/caregivers of children less than 5 years of age who presented to a pediatric continuity clinic. A bilingual interviewer was used to administer the surveys to participants for assessing knowledge of causes, signs, and treatment of diarrhea; signs of dehydration; and care practices during an episode of diarrhea. A wide variation in the level of awareness of signs, causes, and treatment of diarrhea was detected. General knowledge of diarrhea was related positively to accessibility of health information, level of education, ethnicity, and experience with dehydration. General knowledge of diarrhea, adjusted for level of education, was higher in African Americans than in Hispanics. In children, dehydration from diarrhea may be prevented by increasing parents'/caregivers' general knowledge of diarrhea and dehydration and the appropriate usage of oral rehydration solutions. Intervention programs designed to increase parents'/caregivers' knowledge must be culturally sensitive and appropriate for diverse educational backgrounds and must assist in improving access to health-related information.


Exploring an Existing Weight Management App for Use With Adolescents and Young Adults With Spina Bifida: Usability Study.
Adolescents and young adults with spina bifida (AYA-SBs) have unique user needs, given their variable and complex symptom profile. Owing to multiple barriers to prevention and intervention treatments for secondary conditions (eg, obesity), AYA-SBs may benefit from the use of behavioral intervention technologies (BITs). However, as BITs are often designed and tested with typically developing individuals, it is unclear if existing BITs may be usable for AYA-SBs. This study aimed to evaluate the usability of a high-quality, publicly available, weight management-focused mobile BIT (smartphone app) for AYA-SBs. Overall, 28 AYA-SBs attending a Young Men's Christian Association-based summer camp completed 4 structured usability tasks using a weight management app designed for the general public called My Diet Coach (Bending Spoons). Learnability was measured by (1) time to complete task, (2) number of user errors, and (3) correct entry of data when requested by the app. Satisfaction and general usability were measured via self-reported questionnaires and qualitative feedback following interactions with the app. The majority of the sample were able to complete the tasks, with increased completion rates and improved times on second attempts of the tasks (Ps<.05). Errors were common, and discrepancies emerged between quantitative and qualitative feedback such that self-reported measures indicated dissatisfaction but qualitative feedback was generally positive. Suggested improvements to the app included (1) tutorials, (2) simplifying the design, (3) more activity options for those who ambulate by wheelchair, and (4) notifications to prompt use. AYA-SBs were able to learn how to complete specific tasks independently on a weight management app, but design changes consistent with previously proposed user needs were recommended. Rather than designing entirely new BITs, it may be possible to adapt existing technologies to personalize BITs for specific populations such as AYA-SBs.


Antibodies as Carrier Molecules: Encapsulating Anti-Inflammatory Drugs inside Herceptine.
The human epidermal growth factor receptor 2 (HER2) is overexpressed in about a third of breast cancer patients, with a strong involvement of the cyclooxygenase-2 (COX-2) enzyme in the tumor progress. HER2 and COX-2 are consequently potential targets for inhibiting carcionogenesis. Herceptin (trastuzumab) is an antibody that partially blocks HER2-positive cancers at their initial stage. Unfortunately, the overall response rate to the single treatment with this antibody is still modest, and therefore, it needs to be improved by combining several chemotherapeutic agents. On the other hand, nonsteroidal anti-inflammatory drugs (NSAIDs) are designed to halt COX-2 functionality, so they might also exhort an anticancer activity. In this contribution, dual Herceptin-NSAID drugs are designed using theoretical tools. More specifically, blind docking, molecular dynamics, and quantum calculations are performed to assess the stability of 14 NSAIDs embedded inside Herceptin. Our calculations reveal the feasibility of improving the antitumor activity of the parent Herceptin by designing a dual HER2-targeting with Etofenamate. That coupling mode might be used to further rationalize new clinical strategies beyond classical antibody dosages.


Current Insights into the Potential Role of fMRI in Discovering the Mechanisms Underlying Obesity.
Obesity is becoming one of the major global health concerns. This chronic disease affects around 650 million people worldwide and is an underlying cause of a number of significant comorbidities. According to the World Health Organization (WHO) report on obesity from 2022, this disorder became the fourth leading cause of deaths in Europe. Thus, understanding the mechanisms underlying obesity is of essential importance to successfully prevent and treat this disease. The aim of this study was to review the current insights into the potential role of fMRI in discovering the mechanisms underlying obesity on the basis of recent scientific literature published up to December 2022 and searches of the PubMed, Google Scholar and Web of Science databases. The literature assessed indicated that a growing body of evidence suggests that obesity leads to changes in both structure and connectivity within the central nervous system. Emerging data from recent functional magnetic resonance imaging (fMRI) studies prove that obese individuals present an increased motivational drive to eat as well as impaired processing in reward- and control-related brain regions. Apart from this, it is clear that fMRI might be a useful tool in detection of obesity-induced changes within the central nervous system.


Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013.
Background. In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology. This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results. Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46-282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35-4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10-1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44-2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22-0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion. There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART.


Caveolin-1 expression in benign and malignant lesions of the breast.
Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens. Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data. No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers. In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.


Effect of trimethoprim administration on hepatic functions of albino rats.
The effects of chronic and high-dose administration of trimethoprim (TMP) i.p. for different periods on serum and hepatic functions of rats were studied at cellular and subcellular levels. Most of the parameters studied were unaffected after chronic administration of TMP (10 mg/kg/day) for 90 days except an increase in total lipid content of liver and liver microsomes. Administration of TMP in doses of 40 mg and 80 mg/kg/day for 21 days caused a significant increase in total lipid, cholesterol and transaminases activities of serum and liver. Protein, RNA and phospholipid contents of liver and microsomes decreased significantly while DNA content remained unchanged. Glycogen content of liver decreased significantly but alkaline phosphatase activity did not show any noticeable alteration. Histopathological findings showed fatty infiltration and distorted liver architecture. Administration of TMP in doses of 40 mg and 80 mg/kg/day for 14 days changed all the parameters and enzymes in a similar pattern but with less intensity. From the present study it is obvious that high doses of this drug cause harmful toxic effects on serum and hepatic function with liver injury whereas chronic administration has no effect so far.


Influence of body composition on risk factors for coronary heart disease in Thai women.
Height, body weight, body mass index (BMI), waist-to-hip circumference ratio (WHR), and body fat (BF were determined in 453 female Ramathibodi Hospital Staff, aged 19-61 years. These mean (±SEM) anthropometric parameters were 1.55+0.002 m, 55.1±0.4 kg, 23.0±0.2 kg/m2, 0.82±0.003, and 21.2±0.2 kg, respectively. The prevalences of overall obesity (BMI >= 25 kg/m2) and abdominal obesity (WHR>0.8) were 27.0 and 54.1 %, respectively. Their serum TC, LDL-C, TG, TC/HDL-C, LDL-C/HDL-C, apo B and FBG increased with overall obesity based on BMI or BF whereas opposite results were observed for serum HDLC and apo A-l levels. Except serum TC, LDL-C, and apo A-l levels, other biochemical parameters were also influenced by abdominal obesity based on WHR.


The first chondracanthid (Copepoda: Cyclopoida) reported from cultured finfish, with a revised key to the species of Chondracanthus.
A new species of the Chondracanthidae (Copepoda: Cyclopoida), Chondracanthus goldsmidi, is described based on material collected from the nasobranchial region of striped trumpeter (Latris lineata [Forster]) cultured at the Tasmanian Aqua-culture and Fisheries Institute, Marine Research Laboratories, Australia. This represents the first report of a chondracanthid copepod infecting cultured finfish and the first metazoan parasite from cultured striped trumpeter. Chondracanthus goldsmidi n. sp. can be distinguished from its female congeners by the absence of lateral processes on the head and the presence of 3 pairs of lateral trunk outgrowths, 3 middorsal body outgrowths (of which the first 2 are rounded), a small and subcylindrical antennule, and unornamented legs 1 and 2. A revised key to the 39 valid species of Chondracanthus is provided.


Pro-urokinase: a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect.
Highly purified pro-urokinase (pro-UK) or single-chain urokinase-type plasminogen activator (scu-PA) was treated with diisopropylfluorophosphate (1 mmol/L) to eliminate traces of two-chain UK activity. This preparation was found to retain a low activity against a chromogenic substrate (S2444), equivalent to 0.1% to 0.5% of the activity of its plasmin-activated derivative. Evidence is presented that the intrinsic activity of pro-UK (scu-PA) was sufficient to activate plasminogen on a fibrin plate or in buffer and was far more reactive against Lys-plasminogen than against Glu-plasminogen. The relative resistance of Glu-plasminogen to activation was overcome by the addition of lysine (25 mmol/L) to the reaction mixture. By contrast, in plasma, pro-UK (scu-PA) was stable and nonreactive for greater than 72 hours when incubated (37 degrees C). Pro-UK (scu-PA) did not form sodium dodecyl sulfate-stable inhibitor complexes, whereas complexation occurred rapidly with UK. Only at high concentrations of pro-UK (scu-PA) (greater than or equal to 250 IU/mL) did plasminogen activation in plasma occur. The relative inertness of pro-UK (scu-PA) in plasma, in contrast to its low-grade enzymatic activity in buffer, was attributed to the effect of inhibitors. The addition of EDTA or the removal of divalent cations by dialysis was associated with a lower threshold for nonspecific plasminogen activation by pro-UK (scu-PA) in plasma. Replacement of Ca++ but not other cations restored baseline conditions. In the presence of a clot, fibrin-selective plasminogen activation and clot lysis were triggered. Lysis was accompanied by less than 10% conversion of pro-UK (scu-PA) to two-chain UK, suggesting that the intrinsic activity of pro-UK (scu-PA) itself may have been responsible for fibrinolysis, although a contribution by the small amount of UK generated could not be excluded. Similarly, pro-UK (scu-PA) supported clot lysis for several days in the same plasma before the effect dissipated as a result of degradation to UK. When Glu-plasminogen in plasma was replaced by Lys-plasminogen, or when lysine was added to normal plasma, nonselective plasminogen activation and fibrinogenolysis occurred. It was concluded that under the experimental conditions, the fibrin specificity of pro-UK (scu-PA) can be explained by its selective activation of fibrin-bound plasminogen and is due to the latter's Lys-plasminogen-like conformation.(ABSTRACT TRUNCATED AT 400 WORDS)