Mechanisms of scale formation and carbon dioxide partial pressure influence. Part II. Application in the study of mineral waters of reference.
In the first part, we have designed a new model of evolution for the calco-carbonic system which includes the hydrated forms of CaCO3: CaCO3 amorphous, CaCO3 x 6H2O (ikaite) and CaCO3 x H2O (monohydrate) (J. Eur. Hydr. 30 (1999) 47). According to this model, it is the precipitation of one or other of these hydrated forms which could be responsible for the breakdown of the metastable state. After this first step, the precipitates evolve to dehydrated solid forms. Through the elaboration of computer programs in which the CaCO3(0) (aq) ion pair formation was considered, this model was compared to experimental data obtained by the critical pH method applied to synthetic solutions. In the present article, the same method was applied for four French mineral waters, at 25 degrees C under study. Three samples formed a precipitation during the sodium hydroxide addition. For these three cases, this precipitation began for the CaCO3 H2O saturation. The added volume of sodium hydroxide was more than what was required for neutralizing free CO2 initially in solution. These results indicate that during a spontaneous scaling phenomenon, the pH rises at the same time by loss of the initial free CO2 and of the one produced by the hydrogen carbonate ions decomposition. Then we calculated, at various temperatures for the three studied scaling waters: CO2 partial pressures and loss of total carbon corresponding to the solubility products of CaCO3 hydrated forms. The results show that the partial pressure monitoring of the carbon dioxide is important in managing the behavior of scaling waters.


A Systematic Review of Randomized Controlled Trials Comparing Renal Sympathetic Denervation Versus Sham Procedure for the Management of Uncontrolled Hypertension.
The efficacy of renal sympathetic denervation (RSD) in the treatment of uncontrolled hypertension (HTN) remains uncertain. A systematic review of randomized controlled trials was performed to evaluate the efficacy and safety of RSD for resistant HTN. PubMed, EMBASE, MEDLINE, Cochrane, Directory of Open Access Journals, CINAHL, and Google Scholar were searched from January 01, 2001, through July 30, 2020. Randomized controlled trials comparing RSD with the sham procedure for uncontrolled HTN were selected. The primary efficacy outcome was the reduction in ambulatory systolic blood pressure. We used random-effects models. Nine prospective clinical trials met the inclusion criteria. The ReSet and Symplicity HTN-3 Trial showed no significant changes because of discrepancies in complete circumferential ablation during RSD. The Relief study, The Radiance HTN solo, and the SPYRAL HTN OFF medical trials showed a significant reduction in systolic blood pressure in the group that had undergone the intervention compared with the sham group attributed to rigorous trial design. In conclusion, our systematic review suggests that efficacy of RSD seems to be superior to sham-controlled interventions provided circumferential denervation is performed. However, difference in efficacy is marginal.


SigTools: exploratory visualization for genomic signals.
With the advancement of sequencing technologies, genomic data sets are constantly being expanded by high volumes of different data types. One recently introduced data type in genomic science is genomic signals, which are usually short-read coverage measurements over the genome. To understand and evaluate the results of such studies, one needs to understand and analyze the characteristics of the input data. SigTools is an R-based genomic signals visualization package developed with two objectives: (i) to facilitate genomic signals exploration in order to uncover insights for later model training, refinement and development by including distribution and autocorrelation plots; (ii) to enable genomic signals interpretation by including correlation and aggregation plots. In addition, our corresponding web application, SigTools-Shiny, extends the accessibility scope of these modules to people who are more comfortable working with graphical user interfaces instead of command-line tools. SigTools source code, installation guide and manual is freely available on http://github.com/shohre73.


Hypothesis: senile purpura is a prognostic feature in elderly patients.
In a consecutive series of 1125 elderly Chinese patients admitted acutely into the geriatric unit of a general hospital over a 6-month period, 53 (5%) had senile purpura (SP). The prevalence of SP increased exponentially with age and was higher in men than in women. The mean hospital stay of patients with SP was significantly longer than in the non-SP group. SP may have prognostic significance in the elderly.


[News in the management of calcium and phosphorus metabolism disorders for patient treated by hemodialysis].
Bone metabolism is very frequently disturbed in end stage renal failure hemodialyzed, with secondary hyperparathyroidism development but also serious potential cardiovascular consequences. New treatments will be available very soon in Europe such as new phosphate binders, vitamin D2 analogues or calcimimetics to fight against such medical diseases, with the hope of less risk for vascular complications. The real place of such new medical opportunities needs to be determined. Moreover, studies with morbidity and mortality end-points are waited before estimating the real importance of these new therapeutic tools.


CeO2 nanocrystallines ensemble-on-nitrogen-doped graphene nanocomposites: one-pot, rapid synthesis and excellent electrocatalytic activity for enzymatic biosensing.
Ceria nanomaterials for heterogeneous catalysis have attracted much attention due to their excellent properties and have been extensively applied in recent years. But the poor electron conductivity and the aggregation behavior severely affect their electrocatalytic performances. In this paper, we prepared a novel catalyst based on CeO2 nanocrystallines (CeO2 NCs) ensemble-on-nitrogen-doped graphene (CeO2-NG) nanocomposites through a one-step heat-treatment without the need of the precursor. The results confirmed that the high dispersion of CeO2 NCs with the uniform size distribution of about 5nm on the surface of nitrogen-doped graphene (NG) sheets could be easily obtained via the one-step procedure and the resultant CeO2-NG nanocomposites were an excellent electrode material possessing outstanding electrochemical features for electron transfer. Luminol, an important electroactive substance, was further chosen to inspect the electrocatalytic properties of the as-prepared CeO2-NG nanocomposites. The studies showed that the presence of the NG in CeO2-NG nanocomposites could facilitate the electrochemical redox process of luminol. Compared with pristine CeO2 NCs, the synthesized CeO2-NG nanocomposites can enhance the electrochemiluminescence (ECL) intensity by 3.3-fold and decrease the onset ECL potential for about 72mV in the neutral condition. Employing above superiority, selecting cholesterol oxidase (ChOx) as the model oxidase, a facile ECL method for cholesterol detection with the CeO2-NG nanocomposites as the matrix to immobilize enzyme ChOx was developed. The results demonstrated CeO2-NG nanocomposites exhibited excellent performances in terms of sensitivity and catalytic activities, indicating that NG-based nanomaterials have great promise in electrocatalytic and enzymatic biosensing fields.


Using the Severity of Dependence Scale to examine cannabis consumers with impaired control in Canada.
The 2018 Cannabis Act legalizing the production, sale, and use of cannabis for non-medical purposes renewed interest in the importance of ongoing and more detailed monitoring of cannabis consumption and consequences. Some cannabis users will experience impaired control over their use of cannabis, putting them at risk for cannabis use disorder (CUD, sometimes called addiction) and other harms. Including the Severity of Dependence Scale (SDS) in the annual Canadian Community Health Survey (CCHS) would allow for monitoring of one of the more harmful consequences of cannabis use in the post-legalization period. Data from the nationally representative 2019-2020 CCHS were used to examine cannabis consumers with and without impaired control. Respondents who used cannabis in the past year were categorized according to their SDS scores: those with impaired control (SDS ≥ 4) versus those without impaired control (SDS < 4). Cross-tabulations were used to examine the sociodemographic, mental health, health behaviour and cannabis exposure characteristics of those with impaired control. Multivariable logistic regression models assessed associations between these characteristics and the risk of impaired control. The prevalence of self-reported cannabis-related problems experienced by consumers-with and without impaired control-is also presented. In 2019-2020, 4.7% of past-year cannabis consumers scored ≥ 4 on the SDS and were considered to have impaired control. Multivariable logistic regression suggested that the odds of having impaired control remained higher for people who were male, were aged 18 to 24 years, were single or never married, were from lower-income households, were diagnosed with an anxiety or a mood disorder, started consuming cannabis at age ≤ 15, and consumed at least monthly. A better understanding of the characteristics of cannabis consumers experiencing impaired control (a correlate of future CUD or addiction) could help with the development of more effective education, prevention and treatment strategies.


Correction: Tagger-A Swiss army knife for multiomics to dissect cell type-specific mechanisms of gene expression in mice.
[This corrects the article DOI: 10.1371/journal.pbio.3000374.].


Health Literacy Within a Diverse Community-Based Cohort: The Multi-Ethnic Study of Atherosclerosis.
Health literacy has yet to be described in a non-clinical, racially diverse, community-based cohort. Four questions assessing health literacy were asked during annual phone encounters with Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2016 and 2018 (n = 3629). We used prevalence ratios (PRs) with 95% confidence intervals (CIs) to characterize how demographic and acculturation factors related to limited health literacy. Models adjusted for age, sex, and race/ethnicity, and race/ethnicity-stratified models were also examined. Limited health literacy was prevalent in 15.4% of the sample. Participants who were older, female, lower-income, or less acculturated were at greater risk for having limited health literacy. Chinese, Hispanic, and Black participants were more likely than White participants to have limited health literacy. Patterns were similar when stratified by race/ethnicity. Within MESA limited health literacy was common, particularly among Chinese and Hispanic participants, with some of the variance explained by differences in acculturation.


Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP.
Combined administration of nomifensine, a DA reuptake inhibitor, and MPTP completely prevented the long-term (30 days post-treatment) striatal DA depletions induced by MPTP in mice. Cotreatment with desipramine and clomipramine or fluoxetine, inhibitors of NE and 5-HT, respectively had no effect on DA neurotoxicity of MPTP. The findings indicate that MPTP (or MPP+) is a substrate for the specific DA reuptake system and may explain, in part, its selective toxic effects on DA neurons.


Fenestration of the epithelium lining the roof of the fourth cerebral ventricle in amphibia.
Scanning electron microscopy of the caudal end of the roof of the fourth cerebral ventricle in four amphibian species shows that numerous pores occur between the ependymal cells. These pores have diameters ranging from 5--100 micron; they permit bluk flow of cerebrospinal fluid out of the ventricular system into the subarachnoid space.


Long-term outcome of severe acute kidney injury survivors followed by nephrologists in a developing country.
This study aimed to evaluate the long-term outcome of patients after a severe episode of acute kidney injury (AKI) on survival and progression to chronic kidney disease (CKD) and to identify risk factors associated with these outcomes. We performed a prospective study that evaluated the long-term outcome of 509 AKI stage 3 patients who were followed by nephrologists in a Brazilian University Hospital from 2004 to 2013. Age was 60.2 years (47.5-71) and the follow-up time was 25 months (12-44). The late mortality was 38.1% and age (HR 2.89, 95% CI=1.88 to 4.46, P < 0.0001), diabetes (HR 1.46, 95% CI=1 0.02 to 2.16, P < 0.047), liver disease (HR 2.95, 95% CI=1.19 to 7.3, P = 0.02) and creatinine (Cr) at the time of hospital discharge (HR 1.21, 95% CI=1.04 to 1.41, P = 0.01) were associated with poor long-term survival. At the moment of hospital discharge, 52.1% of patients had complete recovery of renal function, 39.7% had partial recovery and 8.3% had not recovered renal function. After 36 months, 43.5% of patients progressed to CKD, and 5.3% needed for chronic dialysis. Factors associated with progression to CKD were age (HR 1.02, 95% CI=1.008 to 1.035, P = 0.009), CKD (HR 1.05 95% CI=1.007 to 1.09, P = 0.04), diabetes (HR 1.12, CI 1.008-1.035, P = 0.009) and number of AKI episodes (HR 1.65, 95% CI=1.19 to 2.2, P = 0.0023). This study showed that AKI patients have high mortality after hospital discharge and age, diabetes, liver disease, and Cr value at the time of discharge were factors associated with long-term mortality. The risk factors for this progression to CKD were age, the presence of diabetes and the number of AKI episodes.


Structural polymorphism of coiled-coils from the stalk domain of SARS-CoV-2 spike protein.
Spike trimer plays a key role in SARS-CoV-2 infection and vaccine development. It consists of a globular head and a flexible stalk domain that anchors the protein into the viral membrane. While the head domain has been extensively studied, the properties of the adjoining stalk are poorly understood. Here, we characterize the coiled-coil formation and thermodynamic stability of the stalk domain and its segments. We find that the N-terminal segment of the stalk does not form coiled-coils and remains disordered in solution. The C-terminal stalk segment forms a trimeric coiled-coil in solution, which becomes significantly stabilized in the context of the full-length stalk. Its crystal structure reveals a novel antiparallel tetramer coiled-coil with an unusual combination of a-d and e-a-d hydrophobic core packing. Structural analysis shows that a subset of hydrophobic residues stabilizes different coiled-coil structures: trimer, tetramer, and heterohexamer, underscoring a highly polymorphic nature of the SARS-CoV-2 stalk sequence.


A 43 kDa form of the GTP-binding protein Gi3 in human erythrocytes.
Purified preparations of human erythrocyte G-proteins contain a 43 kDa pertussis toxin substrate which appears to be the alpha-subunit of a heterotrimeric GTP-binding protein. The 43 kDa protein is recognized by antisera that are sequence-specific for peptides encoding a sequence common to all 39-53 kDa G-protein alpha-subunits. G alpha o-specific antiserum did not recognize 43 or 40-41 kDa alpha-subunits. AS/6, which recognizes the alpha i proteins, recognized 43 kDa as well as 40-41 kDa proteins. Of the three antisera specific for individual members of the alpha i family, only the Gi3-specific antiserum recognized the 43 kDa erythrocyte G-protein. However, 40-41 kDa forms of all three alpha is are present. These observations indicate that human erythrocytes contain a novel 43 kDa form of Gi3.


Metaphit antagonizes phencyclidine-induced hypothermia in the rat.
The acute administration of phencyclidine (PCP) causes hypothermia in the rat. Metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]-piperidine) is a derivative of PCP that has been shown to irreversibly acylate PCP receptors in vitro and in vivo and can antagonize the behavioral and electrophysiological effects of PCP in the rat. The purpose of the present study was to determine whether pretreatment with metaphit can block the hypothermic effects of PCP in the rat. Metaphit or PCP (1.0 mumol/rat) were injected into the lateral ventricles of rats, and 24 hr later the subjects were challenged with PCP (20.0 mg/kg s.c.). Pretreatment with metaphit blocked PCP-induced hypothermia; however, pretreatment with PCP did not affect the subsequent hypothermic response to PCP. These results indicate that the antagonism of PCP-induced hypothermia by metaphit was a specific effect and not due to PCP receptor desensitization.


Patterns of shading tolerance determined from experimental light reduction studies of seagrasses.
A review and analysis of the experimental literature on seagrass shading evaluated the relationships among experimental light reduction, experimental duration, additional modifying factors and common meadow-scale seagrass response metrics to determine whether there were consistent statistical relationships. Modifying factors included study latitude, field site depth, season of experiment initiation, rhizome connectivity (severed, intact), experiment type (field, mesocosm), and seagrass life history strategy. Highly significant, best fit linear regression models were found for both biomass and shoot density reduction that included light reduction, duration and other modifying variables, although unexplained variation in the data were high. Duration of light limitation affected extent of response for both metrics, and unexplained variance was greatly reduced by analysis of data from durations >60d for shoot density and for >60d <120d for biomass. Life history strategy was also a significant factor in three of four regression models. While the slopes of the responses were relatively similar for biomass and shoot density, unexplained variation was generally greater for shoot density than biomass in models for data pooled across species. There were highly significant, best fit regression models found for both biomass and shoot density for both genus and species level analyses, with the extent and duration of light reduction the most important model factors. Season of experiment, rhizome status, latitude, and experiment type all were also included in multiple models. Biomass regression models again tended to have lesser unexplained variation than shoot density models. Life history was invariant within genus and species, and separate analyses for data divided among Colonizing, Opportunistic, and Persistent strategies found relatively similar, best fit regression models among strategies. However, the mean percent reduction of both biomass and shoot density was generally lower for the Persistent strategy than for the other two life histories, suggesting a greater buffering capacity against effects of light reduction for such species. Overall, biomass based models explained more of the variance in seagrass response to light reduction than shoot density, and may be the preferred response variable for meadow-scale impact assessments. The relationships observed may inform management decisions by helping define the scope of expected responses of seagrasses in general to the range of factors that may reduce light availability to seagrasses.


Subcutaneous Injectable Drugs Hypersensitivity and Desensitization: Insulin and Monoclonal Antibodies.
Injectable drugs, including monoclonal antibodies, are becoming crucial components in the management of chronic diseases. The most common side effects are local reactions at the site of administration. With the increased and prolonged use of these medications, we are seeing increased reports of hypersensitivity reactions. The aim of this article is to discuss the signs and symptoms of these reactions as well as management, which may involve desensitization for 3 commonly encountered injectable drugs: tumor necrosis factor-α inhibitors (etanercept and adalimumab), insulin, and omalizumab.


Correlating multi-functional role of cold shock domain proteins with intrinsically disordered regions.
Cold shock proteins (CSPs) are an ancient and conserved family of proteins. They are renowned for their role in response to low-temperature stress in bacteria and nucleic acid binding activities. In prokaryotes, cold and non-cold inducible CSPs are involved in various cellular and metabolic processes such as growth and development, osmotic oxidation, starvation, stress tolerance, and host cell invasion. In prokaryotes, cold shock condition reduces cell transcription and translation efficiency. Eukaryotic cold shock domain (CSD) proteins are evolved form of prokaryotic CSPs where CSD is flanked by N- and C-terminal domains. Eukaryotic CSPs are multi-functional proteins. CSPs also act as nucleic acid chaperons by preventing the formation of secondary structures in mRNA at low temperatures. In human, CSD proteins play a crucial role in the progression of breast cancer, colon cancer, lung cancer, and Alzheimer's disease. A well-defined three-dimensional structure of intrinsically disordered regions of CSPs family members is still undetermined. In this article, intrinsic disorder regions of CSPs have been explored systematically to understand the pleiotropic role of the cold shock family of proteins.


The performance of computer-aided detection when analyzing prior mammograms of newly detected breast cancers with special focus on the time interval from initial imaging to detection.
The clinical role of CAD systems to detect breast cancer, which have not been on cancer containing mammograms not detected by the radiologist was proven retrospectively. All patients from 1992 to 2005 with a histologically verified malignant breast lesion and a mammogram at our department, were analyzed in retrospect focussing on the time of detection of the malignant lesion. All prior mammograms were analyzed by CAD (CADx, USA). The resulting CAD printout was matched with the cancer containing images yielding to the radiological diagnosis of breast cancer. CAD performance, sensitivity as well as the association of CAD and radiological features were analyzed. 278 mammograms fulfilled the inclusion criteria. 111 cases showed a retrospectively visible lesion (71 masses, 23 single microcalcification clusters, 16 masses with microcalcifications, in one case two microcalcification clusters). 54/87 masses and 34/41 microcalcifications were detected by CAD. Detection rates varied from 9/20 (ACR 1) to 5/7 (ACR 4) (45% vs. 71%). The detection of microcalcifications was not influenced by breast tissue density. CAD might be useful in an earlier detection of subtle breast cancer cases, which might remain otherwise undetected.


Female sex street workers and sexually transmitted infections: their knowledge and behaviour in Italy.
This study assessed knowledge and sexual behaviour regarding sexually transmitted infections (STIs) among female sex street workers in the area of Milan, Italy. A questionnaire was administered covering socio-demographic characteristics; knowledge about STIs; sexual behaviour. A total of 241 female sex street workers were interviewed. A vast majority knew AIDS and syphilis, whereas the knowledge about other STIs was unsatisfactory. Only 11.7% knew that STIs are transmitted by sexual intercourse with HIV seropositive partners, by unprotected sexual intercourse, and that kissing was not a mode of transmission. This knowledge was significantly higher in female sex street workers with a higher number of years in sex work and among those who received information from physicians and associations about STIs. The mean score of fear for contracting STIs was 7.5 and being younger, practicing prostitution for shorter period of time, and requiring more information about STIs were significantly associated with this fear. 'Ever condom use' was 100% during anal intercourse with clients; whereas only one woman reported vaginal and oral intercourse without condom. Only 15.2, 16.7, and 30% of those engaged in vaginal, oral, and anal intercourse with a non-paying sexual partner used condoms all the times. Overall, 83.5% of female sex street workers used a condom every time with clients or non-paying partners and those with fewer clients and partners routinely were more likely to use it. Interventions for preventing STIs and for improving the level of knowledge of STIs among female sex street workers are strongly needed.


Use of digital video for documentation of microscopic features of tissue samples.
Digital photography is commonly used to document microscopic features of tissue samples, but it relies on the capture of arbitrarily selected representative areas. Current technologic advances permit the review of an entire sample, some even replicating the use of a microscope. To demonstrate the applicability of digital video to the documentation of histologic samples. A Canon Elura MC40 digital camcorder was mounted on a microscope, glass slide-mounted tissue sections were filmed, and the unedited movies were transferred to a Apple Mac Pro computer. Movies were edited using the software iMovie HD, including placement of a time counter and a voice recording. The finished movies can be viewed in computers, incorporated onto DVDs, or placed on a Web site after compression with Flash software. The final movies range, on average, between 2 and 8 minutes, depending on the size of the sample, and between 50 MB and 1.6 GB, depending on the intended means of distribution, with DVDs providing the best image quality. Digital video is a practical methodology for documentation of entire tissue samples. We propose an affordable method that uses easily available hardware and software and does not require significant computer knowledge. Pathology education can be enhanced by the implementation of digital video technology.


Quantitative analysis of 11-dehydrocorticosterone and corticosterone for preclinical studies by liquid chromatography/triple quadrupole mass spectrometry.
The activity of the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type-1 (11βHSD1) is altered in diseases such as obesity, inflammation and psychiatric disorders. In rodents 11βHSD1 converts inert 11-dehydrocorticosterone (11-DHC) into the active form, corticosterone (CORT). A sensitive, specific liquid chromatography/tandem mass spectrometry method was sought to simultaneously quantify total 11-DHC and total and free CORT in murine plasma for simple assessment of 11βHSD1 activity in murine models. Mass spectrometry parameters were optimised and a method for the chromatographic separation of CORT and 11-DHC was developed. Murine plasma was prepared by 10:1 chloroform liquid-liquid extraction (LLE) for analysis. Limits of quantitation (LOQs), linearity and other method criteria were assessed, according to bioanalytical method validation guidelines. Reliable separation of 11-DHC and CORT was achieved using an ACE Excel 2 C18-AR (2.1 × 150 mm; 2 μm) fused core column at 25°C, with an acidified water/acetonitrile gradient over 10 min. Analytes were detected by multiple reaction monitoring after positive electrospray ionisation (m/z 345.1.1 ➔ 121.2, m/z 347.1 ➔ 121.1 for 11-DHC and CORT, respectively). The LOQs were 0.25 and 0.20 ng/mL for 11-DHC and CORT, respectively. This LC/MS method is suitable for the reliable analysis of 11-DHC and CORT following simple LLE of murine plasma, bringing preclinical analysis in line with recommendations for clinical endocrinology and biochemistry.


Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma.
MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p < 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment. Graphical abstract.


Individual cognitive training of reading disability improves word identification and sentence comprehension in adults with mild mental retardation.
Reading therapy has been shown to be effective in treating reading disabilities (RD) in dyslexic children, but little is known of its use in subjects with mild mental retardation (MR). Twenty adult volunteers, with both RD and mild MR, underwent 60 consecutive weeks in a cognitive remediation program, and were compared with 32 untreated control subjects. The experimental group showed a significant improvement in word identification, as measured by oral production (p=0.0004) or silent reading (p=0.023), and sentence comprehension (p=0.0002). Adults with MR appear to benefit from new approaches in the field of RD.


Relevance to the higher order structure may govern auditory statistical learning in neonates.
Hearing is one of the earliest senses to develop and is quite mature by birth. Contemporary theories assume that regularities in sound are exploited by the brain to create internal models of the environment. Through statistical learning, internal models extrapolate from patterns to predictions about subsequent experience. In adults, altered brain responses to sound enable us to infer the existence and properties of these models. In this study, brain potentials were used to determine whether newborns exhibit context-dependent modulations of a brain response that can be used to infer the existence and properties of internal models. Results are indicative of significant context-dependence in the responsivity to sound in newborns. When common and rare sounds continue in stable probabilities over a very long period, neonates respond to all sounds equivalently (no differentiation). However, when the same common and rare sounds at the same probabilities alternate over time, the neonate responses show clear differentiations. The context-dependence is consistent with the possibility that the neonate brain produces more precise internal models that discriminate between contexts when there is an emergent structure to be discovered but appears to adopt broader models when discrimination delivers little or no additional information about the environment.


Fast vergence eye movements are disrupted in Parkinson's disease: A video-oculography study.
Blurred near vision is a common non-motor symptom in patients with Parkinson's disease (PD), however detailed characterization of vergence eye movements (VEM) is lacking. Convergence and divergence were examined in 18 patients with PD and 18 control subjects using infrared video-oculography. VEM metrics analyzed included latency, velocity and accuracy, in vertical and horizontal planes. The latency of convergence and divergence was significantly increased in PD subjects. Additionally, divergence was slow and hypometric, while other convergence metrics were similar to controls. We provide evidence in favor of disrupted VEM in PD.


The influence of the side chain on sterol side-chain cleavage in rat adrenal glands.
The cholesterol side-chain cleavage enzyme system of rat adrenal cortex, the enzyme catalyzing a rate-limiting step of adrenal steroidogenesis, was shown to metabolize a series of cholesterol analogues to pregnenolone. In the presence of Ca2+, rat adrenocortical mitochondria converted the analogue with two less methylene groups (C25) than cholesterol into pregnenolone at a faster rate than cholesterol. The analogues with one or three less methylene groups (C26 or C24) were metabolized at a similar rate to cholesterol. Lengthening the non-polar side chain produced analogues that did not appear to be metabolized. Studies of the metabolism of these analogues in isolated rat adrenocortical carcinoma cells showed that the C24 and C25 analogues were converted into pregnenolone much more efficiently than was cholesterol or the C26 sterol. The experimental findings are explained in terms of the differing ability of each exogenously added sterol to gain access to the active site of the sterol side-chain cleavage enzyme by passage through the membranes of the adrenal cell.


[Chemotherapy].
The progress of cancer chemotherapy has made a large contribution to the significant improvement of cure rate in patients with hematological malignancy including malignant lymphoma. Interpatient variability characterizes the disposition of many drugs. In the case of drugs with a wide therapeutic index, such variability is unlikely to affect either clinical efficacy or toxicity. With anticancer drugs, however, there is much less margin for error, due to their very narrow therapeutic index. Therefore, it is crucially important to understanding the mechanism of action, pharmacokinetics and pharmacodynamics of each anticancer drug in order to give chemotherapy in safety. Overview of the pharmacological functions of anticancer agent using in malignant lymphoma is the subject of this chapter.


Current landscape in US schools for bystander CPR training and AED requirements.
Out-of-hospital cardiac arrest is a public health crisis affecting about 356,000 adults and 23,000 children annually in the US with 90% fatality. Early bystander CPR and AED application improve survival. Less than 3% of the US population is CPR trained annually. Since 20% of the US population is at school daily, these represent ideal places to target CPR training. Having standardized state school CPR and AED laws will help with training. We performed a systemic search of the state-specific laws for school AED and CPR requirements within the US. We used PubMed and Google search using keywords: school CPR mandates, US laws for CPR in schools, US state laws for AED implementation, and gaps in US school CPR and AED. We searched for mandates for schools in other countries for comparison. The state laws for CPR training for high school graduation and AED requirements in US. schools are highly variable, and funding for AEDs is inadequate, especially in schools in lower socio-economic zip codes. Recent AED legislative efforts focus mainly on athletic areas and don't adequately address school size, number of buildings, non-athletic areas, and engagement of student-led advocacy efforts. To improve OHCA survival, we identified potential solutions to consolidate efforts and overcome the barriers-standardize state laws, involve student bodies, increase funding, and allocate appropriate resources. The CPR/AED education needs to start earlier in schools and be part of the standard curriculum rather than implemented as a stopgap check-box mandate.


Relationship Between Rapid Skin Clearance and Quality of Life Benefit: Post Hoc Analysis of Japanese Patients with Moderate-to-Severe Psoriasis Treated with Ixekizumab (UNCOVER-J).
Ixekizumab has demonstrated rapid onset of action, high levels of skin clearance, and improvements in quality of life in patients with moderate-to-severe psoriasis, including plaque, erythrodermic, or generalized pustular psoriasis. This was a post hoc analysis of UNCOVER-J, a phase 3, multicenter, single-arm, open-label study of ixekizumab for treatment of Japanese patients with psoriasis. The objective was to assess the proportion of patients who achieved Dermatology Life Quality Index (DLQI) (0,1) and Itch Numeric Rating Scale (NRS) (0) at weeks 4 and 12 according to Psoriasis Area and Severity Index (PASI) percentage improvement levels. All intent-to-treat patients with plaque, erythrodermic, or generalized pustular psoriasis were analyzed. A total of 91 patients were treated with ixekizumab and included in the analysis. Rapid improvements in PASI at weeks 4 and 12 were associated with improvements in DLQI (0,1) response at week 4 and at week 12. Complete skin clearance (PASI 100) achieved either at week 4 or week 12 was associated with a higher Itch NRS (0) response at week 12. Patients with rapid improvement in clinical symptoms of psoriasis had better patient outcomes than those with slower responses. These findings highlight the clinical importance of achieving a fast response in patients with psoriasis, which may lead to better treatment outcomes. ClinicalTrials.gov identifier, NCT01624233.


Tubal choriocarcinoma presented as ruptured ectopic pregnancy: a case report and review of the literature.
Tubal choriocarcinoma is an extremely rare but highly malignant trophoblastic tumor, which may be either gestational or non-gestational in origin. Due to atypical clinical manifestations and symptoms similar to ectopic pregnancy, it is easily to be confused with ectopic pregnancy. In addition, inadequate understanding of this rare disease by clinicians often leads to misdiagnosis or missed diagnosis, which in turn results in delayed treatment or even tumor metastasis. This report summarized a case of a woman who was finally diagnosed as tubal choriocarcinoma through the follow-up of serum β hCG levels and histopathological results after undergoing salpingectomy for being misdiagnosed as ectopic pregnancy. Five courses of adjuvant chemotherapy (5-fluorouracil, actinomycin-D, vinorelbine regime) have been administered to the patient in the prevention of any recurrences. During 1-year follow-up, the patient was asymptomatic and presented no evidence of recurrence. Tubal choriocarcinoma is easily to be confused with ectopic pregnancy. By analyzing this case and previous related cases, we aimed to provide references for clinicians in the diagnosis and treatment of tubal choriocarcinoma.


Profile of siRNAs derived from green fluorescent protein (GFP)-tagged Papaya leaf distortion mosaic virus in infected papaya plants.
We used green fluorescent protein (GFP)-tagged Papaya leaf distortion mosaic virus (PLDMV-GFP) to track PLDMV infection by fluorescence. The virus-derived small interfering RNAs (vsiRNAs) of PLDMV-GFP were characterized from papaya plants by next-generation sequencing. The foreign GFP gene inserted into the PLDMV genome was also processed as a viral gene into siRNAs by components involved in RNA silencing. The siRNAs derived from PLDMV-GFP accumulated preferentially as 21- and 22-nucleotide (nt) lengths, and most of the 5'-terminal ends were biased towards uridine (U) and adenosine (A). The single-nucleotide resolution map revealed that vsiRNAs were heterogeneously distributed throughout the PLDMV-GFP genome, and vsiRNAs derived from the sense strand were more abundant than those from the antisense strand. The hotspots were mainly distributed in the P1 and GFP coding region of the antisense strand. In addition, 979 papaya genes targeted by the most abundant 1000 PLDMV-GFP vsiRNAs were predicted and annotated using GO and KEGG classification. Results suggest that vsiRNAs play key roles in PLDMV-papaya interactions. These data on the characterization of PLDMV-GFP vsiRNAs will help to provide insight into the function of vsiRNAs and their host target regulation patterns.


Characterization of (6-4) photoproduct DNA photolyase.
Pyrimidine (6-4) pyrimidone photoproduct is the second most abundant UV photoproduct in DNA. Recently, it was reported that Drosophila melanogaster cell-free extracts restored the biological activity of (6-4) photo-product-containing DNA in a light-dependent reaction (Todo, T., Takemori, H., Ryo, H., Ihara, M., Matsunaga, T., Nikaido, O., Sato, K., and Nomura, T. (1993) Nature 361, 372-374) concomitant with the loss of (6-4) photoproduct antigenic sites and (6-4) photoproduct-caused alkali-labile sites. In the present study we show that the (6-4) photoproduct but not its Dewar isomer is the substrate for the enzyme, that the enzyme has an action spectrum peak at 400 nm, and that the efficiency of repair per incident photon is very low compared with cyclobutane pyrimidine dimer photolyases. Furthermore, we provide evidence that the (6-4) photoproduct photolyase converts the photoproduct to unmodified bases probably through an oxetane intermediate.


[Extrapyramidal syndrome in idiopathic hemochromatosis. Significance of laboratory chemical, neurophysiologic and imaging procedures (CCT, MRT)].
In any patient with unexplained basal ganglia symptoms or dementia, the possibility of idiopathic hemochromatosis (IHC) should be considered. The findings of magnetic resonance tomography, discussed in this case report, lead to the conclusion that IHC is very likely to induce these syndromes. This is of clinical importance as IHC can be successfully treated by phlebotomy.


Non-communicable diseases and risk of tuberculosis in Korea.
It is possible that the increasing burden of non-communicable diseases (NCDs) and their risk factors are an obstacle to the reduction of tuberculosis (TB) incidence in the Republic of Korea. To estimate population-attributable fractions (PAF) of NCDs and their risk factors related to TB in Korea. The prevalence of diabetes mellitus (DM), current smoking, heavy drinking and undernutrition was estimated from the Korean National Health and Nutrition Examination Survey (KNHANES) conducted in 2013. Estimates of effect for risk factors were obtained from meta-analyses. The PAF was calculated based on these data. The PAF of DM, current smoking, heavy drinking and undernutrition was 20.0%, 18.8%, 18.4% and 9.6%, respectively. Current smoking has the highest PAF among men, while undernutrition was the highest among women. Current smoking and heavy drinking were significantly attributed to TB among the younger population, while DM was the most common responsible factor among the older population. Major risk factors such as current smoking and DM were more prevalent in the lower income level population. NCDs and their risk factors play an important role at the population level in TB epidemics in Korea. Collaborative TB and NCD activities in TB control should therefore be intensified.


Rare earth elements in soil around coal mining and utilization: Contamination, characteristics, and effect of soil physicochemical properties.
REEs are emerging contaminants, and soils nearby coal and coal ash with high REEs composition are vulnerable to REEs contamination. Besides, coal industry can alter surrounding soil characteristics. However, there is information paucity about REEs contamination and geochemical behaviors along with soil characteristics around coal industrial areas, which are essential for understanding their toxicity and mobilization. The study was conducted in soils surrounding Kriel coal-fired power plant (KCM) and Greenside coal mining in Witbank (GSCM), South Africa. Multivariate statistical analysis, pollution and fractionation indices, and BCR sequential extraction were applied. The ∑REEs in the soils were compared to ∑REEs abundance in the upper earth's crust (UEC), and slightly higher ∑REEs was found in KCM but slightly lower in GSCM. Generally, LREEs are abundant. The soil REEs were normalized using the Post-Archean Australian Shale (PAAS) and Eu and Gd in KCM and Gd in GSCM were >1. Contamination assessment revealed that the soils are slightly to moderately contaminated by REEs. ∑REEs in KCM was significantly correlated with soil particle sizes of 2.00-50.00 μm, Al2O3, Fe2O3, and MnO, while with 2.00-3.00 μm and Al2O3 in GSCM. Fractionation characteristics showed a positive Ce anomaly, with positive linear regressions with Fe2O3 and MnO. In contrast, a negative Eu anomaly was found with positive linear regressions with Al, Ca, and Mg-oxides. Oxidizable fractioned REEs accounted for 32.33% of the ∑REEs in GSCM and 35.85% in KCM, and their high EF suggests enrichment that could be due to coal mining and utilization. Most soil physicochemical properties appear to be negatively correlated with the exchangeable REEs. Overall, the soils are contaminated by REEs and the REEs characteristics are considerably influenced by major elements oxide, U, and Th contents. Therefore, more attention should be paid to REEs contamination and impacts around coal mining and utilization.


Expression of p63, TTF-1 and Maspin in Non-Small Cell Lung Carcinoma and Their Effect on the Prognosis and Differential Diagnosis.
Lung cancer is still the leading cause of cancer mortality. Antiapoptotic genes and protease inhibitors play an important role in the development of lung cancer. p63, TTF-1 and maspin expression and their role in the differential diagnosis, overall survival, progression-free survival and other clinicopathological characteristics of the patients were investigated in 80 surgically-resected non-small cell lung carcinomas. The maximal tumor diameter range was 1.5-11 cm (mean: 4.06±1.8 cm). Forty-five (56.3%) tumors were adenocarcinoma, 23 (28.8%) squamous cell carcinoma, four (5%) large cell carcinoma, six (7.5%) large cell neuroendocrine carcinoma, one (1.2%) sarcomatoid carcinoma while one was (1.2%) both adenocarcinoma and squamous cell carcinoma. The patients with advanced TNM stage and a tumor diameter more than 3 cm had markedly poor survival. Immunohistochemically, p63 staining was present in 87.5% of squamous cell carcinomas, 4.3% of adenocarcinomas, 25% of large cell carcinomas, and 16.7% of large cell neuroendocrine carcinomas. Similarly, maspin was positive in 66.7% of squamous cell carcinomas and 17.4% of adenocarcinomas. The TTF-1 staining rate was higher in adenocarcinomas (84.8%). There was no immunoreactivity in squamous cell carcinomas (p < 0.001). We found that p63 and TTF-1 had no significant effect on survival in either tumor group (p > 0.05) while maspin has a negative prognostic effect in adenocarcinoma (p=0.048). This study suggests that p63 and TTF-1 are reliable markers in non-small cell lung carcinoma and can be used in differential diagnosis. Maspin has been identified as a prognostic marker in adenocarcinoma. However, more studies are required to elucidate the significance of maspin.


Environmental management aspects for TBT antifouling wastes from the shipyards.
Tributyltin (TBT)-based antifouling paints have been successfully used for over 40 years to protect a ship's hull from biofouling. However, due to its high toxicity to marine organisms, the International Maritime Organization (IMO), in 1990, adopted a resolution recommending governments to adopt measures to eliminate antifouling paints containing TBT. High concentrations of TBT are detected in the vicinity of ports and shipyards. TBT is also usually detected in the sediment, in which it accumulates. This study reviews recent literature for the best management practices (BMPs) in order to minimize the environmental effects of TBT. The paper focuses on the evaluation of the available techniques for the removal of TBT from shipyard wastes and from the sediment. The most effective treatment methods are highlighted. BMPs include recycling of abrasive materials, use of cleaner abrasive materials, reuse of spent abrasive materials, substitution of hydroblasting by vacuum blasting or containment or ultra-high-pressure water blasting and confinement of pollution by enclosure and containment systems. The treatment of the TBT wastes by conventional biological wastewater treatment processes is probably not suitable, because the concentrations of TBT found in shipyards' wastewaters are toxic to microorganisms. Advanced technologies such as activated carbon adsorption and dissolved air flotation, in combination with filtration and coagulation-clarification, photodegradation and electrochemical treatment, are required to remove TBT. However, advanced methods should be further optimized to meet the regulatory limit of 200 ng/L. To date, only one published work examines the efficiency of incineration for the treatment of solid sandblast wastes. Regarding the treatment of sediment, land deposition of the less polluted fraction of sediment is a feasible option. Such treatment must take into account the risk of contamination of groundwater and the surroundings, and it requires extended areas of land. Other treatment methods, such as thermal and electrochemical treatment, are promising options but due to the large amounts of dredged material, they have high capital and operational costs.


External validation of the Vascular Study Group of New England carotid endarterectomy risk predictive model using an independent U.S. national surgical database.
Previously, we described a Vascular Study Group of New England (VSGNE) risk predictive model to predict composite adverse outcomes (postoperative death, stroke, myocardial infarction, or discharge to extended care facilities) after carotid endarterectomy (CEA). The goal of this study was to externally validate this model using an independent database. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) CEA-targeted database (2010-2014) was used to externally validate the risk predictor model of adverse outcomes after CEA previously created using the VSGNE carotid database. Emergent cases and those in which CEA was combined with another operation were excluded. Cases in which a discharge destination cannot be determined were also excluded. To assess the predictive power of our VSGNE prediction score within this sample, a receiver operating characteristic curve was constructed. Risk scores for each NSQIP patient were also computed using beta weights from the VSGNE CEA model. To further assess the construct validity of our VSGNE prediction score, the observed proportion of adverse outcomes was examined at each level of our prediction scale and within five roughly equally sized risk groups formed on the basis of our VSGNE prediction scores. In this database, 10,889 cases met our inclusion criteria and were used in this analysis. The overall rate of adverse outcomes in this cohort was 8.5%. External validation of the VSGNE model on this sample showed moderately good predictive ability (area under the curve = 0.745). Patients in progressively higher risk groups, based on their VSGNE model scores, exhibited progressively higher rates of observed adverse outcomes, as predicted. The VSGNE CEA risk predictive model was externally validated on an NSQIP CEA-targeted sample and showed a fairly accurate global predictive ability for adverse outcomes after CEA. Although this model has a good population concordance, the lack of cut point indicates that individual risk prediction requires more evaluation. Further studies should be geared toward identification of variables that make this risk predictive model more robust.


Pseudo-aneurysm of the profunda femoris artery as a late complication of hip fracture in a patient with myelodysplasia.
We report a pseudo-aneurysm of the profunda femoris artery that resulted in intermittent bleeding and pain 6 weeks following dynamic hip screw fixation of an intertrochanteric hip fracture. Early diagnosis by angiogram could have minimised significant patient morbidity in this case.


Cyclodialysis induced persistent hypotony: surgical management with vitrectomy and endotamponade.
To report novel surgical approaches to the management of persistent hypotony after cyclodialysis. Retrospective review of the medical records of six eyes of six patients with persistent hypotony after traumatic cyclodialysis. The diagnosis accuracy of cyclodialysis was documented by ultrasound biomicroscopy in five patients. The other one underwent an anterior segment optical coherence tomography. The authors performed pars plana vitrectomy and silicone oil-assisted endotamponade in four patients. The remaining eyes underwent a gas tamponade after pars plana vitrectomy. Preoperative visual acuity (Snellen scale) ranged from count fingers to 20/50. The patients' visual acuity improved after the surgery. The intraocular pressure ranged from 2 mmHg to 6 mmHg (mean, 3.33 mmHg) before surgery. The authors did achieve an intraocular pressure normalization postoperatively. After surgery, the ciliary body was completely reattached in all cases. A slight angle recession was documented in one eye. The management of cyclodialysis clefts requires a stepwise approach. In cases where conservative management fails, wide ranges of options have been reported. Based on our results, we consider that silicone oil-assisted or gas-assisted endotamponade, after pars plana vitrectomy, can be an effective alternative approach to the cyclodialysis.


Feasibility of Problem Adaption Therapy in a Diverse, Frail Older Adult Population (PATH-MHS).
The purpose of the Problem Adaptation Therapy - Montefiore Health System (PATH-MHS) pilot program was to demonstrate the feasibility and effectiveness of PATH across a culturally, educationally, and functionally diverse cohort of older adults. Clinicians referred 145 participants with depression and cognitive impairment to PATH-MHS. We completed analyses of the change in depression, disability and the association between baseline characteristics and remission of depression. Most participants were Hispanic or Non-Hispanic Black and 54.7% (76) were primary Spanish speakers. Overall, there were significant decreases in the mean PHQ-9 and WHODAS 2.0 scores. In logistic regression models, neither age, education, gender, race/ethnicity, language nor long-term care status was significantly associated with remission of depression. This study demonstrates that we were able to engage a diverse, cognitively impaired, and frail cohort of older adults in PATH-MHS with significant reductions in depression and disability.


[Epidemiology: concepts and diagnosis of diabetes mellitus].
A review is presented of present concepts about diabetes mellitus and the several etiopathogenic mechanisms. Diagnostic criteria and classification are summarised. Some epidemiological data and their implications on prevention are reviewed.


Dizocilpine does not prevent the development of tolerance to the anxiolytic effects of diazepam in rats.
The non-competitive NMDA receptor antagonist, dizocilpine (0.25 mg/kg), has previously been shown to block the development of tolerance to the sedative effects of diazepam (2 mg/kg). Since there is considerable evidence that different mechanisms underlie the development of tolerance to the sedative and anxiolytic effects of diazepam, the present experiment examined whether dizocilpine would block the development of tolerance to diazepam's anxiolytic effects. Rats tested after an acute dose of diazepam (2 mg/kg) showed an anxiolytic effect, measured by an increase in the time spent in social interaction, whereas those tested after 21 days of treatment had scores equal to the control group. This development of tolerance was not blocked by concomitant administration of dizocilpine (0.25 mg/kg). Thus, these results provide further evidence that the mechanism underlying tolerance to the anxiolytic effects of diazepam is different from that underlying tolerance to the sedative effects.


[Ways to improve training of the populace for rendering medical first aid to casualties in extreme situations].
The article presents the results of population' training for rendering the first medical aid in the cases of extreme situations, fulfillment of the normative document requirements on the problem The study was conducted in All-Russian Center for Disaster Medicine "Zaschita" of Russian Health Ministry. It is shown that after publication of normative documents the rescuer and special contingent training has improved, at the same time the training of other population groups doesn't meet the requirements. The current programs and forms of population education, insufficient number of educational time and pore material and technical basis don't provide the necessary knowledge and skills on rendering the first medical aid in the cases of extreme situations. Basing on the study the following documents were developed: the unified program "The First medical aid", the test program to control the students' knowledge, the methodical manuals for teachers and students and the standards of class equipping.


The link between language and action in aging.
Many studies have demonstrated the existence of a link between action verb processing and action. However, little is known about the changes in this relationship with aging. To assess this point, we compare the performances of younger and older people during a priming task consisting of judging whether an image contains a human after listening to an action verb. In accordance with previous literature, the results showed that younger people were faster to detect the presence of a human in the image in congruent conditions, namely, when the action verb and the image refer to the same action. However, this effect was not present in older adults' participants. These findings suggest that the link between action and language decreases with age. We discuss these findings in the context of the embodied view of cognition.


Impact of socioeconomics and race on clinical follow-up and trial enrollment and adherence in cerebral cavernous malformation.
Cerebral cavernous malformation (CCM) affects more than a million Americans but advanced care for symptomatic lesions and access to research studies is largely limited to referral academic centers MATERIALS AND METHODS: A cohort of CCM patients screened for research studies at an accredited center of excellence for CCM was analyzed. Demographics, lesion location, history of hemorrhage, insurance type and area of deprivation index (ADI) were collected. Primary outcomes were clinical follow-up within a year from initial evaluation, and enrollment and adherence in clinical trials among eligible subjects RESULTS: A majority (52.8%) of CCM patients evaluated had a high socioeconomic status (SES) (ADI 1-3), and only 11.5% were African American. Patients who had a symptomatic bleed were more likely to follow-up (p=0.01), and those with brainstem lesion were more likely to enroll/adhere in a clinical trial (p=0.02). Rates of clinical follow-up were similar across different ADI groups, insurance coverage and race. Patients who were uninsured/self-paying, and African Americans were more likely to decline/drop from clinical trials (OR 2.4, 95% CI 0.46-10.20 and OR 2.2, 95% CI 0.33-10.75, respectively), but differences were not statistically significant CONCLUSIONS: Access of disadvantaged patients to center of excellence care and research remains limited despite geographic proximity to their community. Patients with lower SES and African Americans are as likely to follow-up clinically, but there were trends of differences in enrollment/adherence in clinical trials. Mitigation efforts should target systemic causes of low access to specialized care among uninsured and African American patients.


A four-year follow-up controlled study of stress response and symptom persistence in Brazilian children and adolescents with attention deficit disorder and hyperactivity (ADHD).
This study evaluated children and adolescents with Attention Deficit Disorder andHyperactivity Disorder (ADHD), reassessing them at a four-year follow-up. Their cortisol response to a stress stimulus was measured twice. ADHD symptom persistence, development of comorbidities, and psychostimulant usage were also reassessed. The initial sample consisted of 38 ADHD patients and 38 healthy controls, age ranging 6-14. At the follow-up, there were 37 ADHD patients and 22 healthy controls, age ranging 10-18. ADHD was classified as persistent if the patients fulfilled all DSM IV criteria for syndromic or subthreshold or had functional impairment. Salivary cortisol samples were collected prior to the application of a cognitive stressor (Continuous Performance Test - CPT), and at three time intervals afterwards at baseline and at the follow-up. Their reassessment showed that 75% had persistent symptoms, psychiatric comorbidities (oppositional defiant and behavioral disorders), functional and academic impairement. Only seven patients were on medication. The ADHD group's cortisol levels were lower than those measured four years earlier, but cortisol concentrations were similar for both ADHD and control groups at the four-year follow-up. The cortisol results suggest that HPA axis reactivity could be a marker differentiating ADHD from ADHD with comorbidities.


The unbinding of ATP from F1-ATPase.
Using molecular dynamics, we study the unbinding of ATP in F(1)-ATPase from its tight binding state to its weak binding state. The calculations are made feasible through use of interpolated atomic structures from Wang and Oster [Nature 1998, 396: 279-282]. These structures are applied to atoms distant from the catalytic site. The forces from these distant atoms gradually drive a large primary region through a series of sixteen equilibrated steps that trace the hinge bending conformational change in the beta-subunit that drives rotation of gamma-subunit. As the rotation progresses, we find a sequential weakening and breaking of the hydrogen bonds between the ATP molecule and the alpha- and beta-subunits of the ATPase. This finding agrees with the "binding-zipper" model [Oster and Wang, BIOCHIM: Biophys. Acta 2000, 1458: 482-510.] In this model, the progressive formation of the hydrogen bonds is the energy source driving the rotation of the gamma-shaft during hydrolysis. Conversely, the corresponding sequential breaking of these bonds is driven by rotation of the shaft during ATP synthesis. Our results for the energetics during rotation suggest that the nucleotide's coordination with Mg(2+) during binding and release is necessary to account for the observed high efficiency of the motor.


Comparison of the effects of some CYP3A and other enzyme inducers on replicative DNA synthesis and cytochrome P450 isoforms in rat liver.
The aim of this study was to investigate the mitogenic effects of some inducers of cytochrome P450 (CYP) isoforms in rat liver. Female Sprague-Dawley CD rats were treated with 100 mg/kg per day of either sodium phenobarbitone (NaPB), barbituric acid (BA), isoniazid (ISN), beta-naphthoflavone (BNF), pregnenolone-16alpha-carbonitrile (PCN), miconazole (MIC) or clotrimazole (CLOT), 75 mg/kg per day methylclofenapate (MCP), 50 mg/kg per day dexamethasone (DEX) and 500 mg/kg per day troleandomycin (TAO) by daily oral gavage for four days. Treatment with all compounds except BA, ISN and MIC, significantly increased relative liver weight. Administration of NaPB, PCN, DEX, MIC, CLOT and TAO all induced total CYP content, and by Western immunoblotting, levels of CYP3A isoforms in hepatic microsomal fractions. Apart from CLOT, all these compounds induced microsomal testosterone 6beta-hydroxylase activity. By measurement of marker enzyme activities and Western immunoblotting with antibodies to CYP1A2, CYP2B1/2 and CYP2E1, BNF, NaPB, ISN and MCP were shown to induce CYP1A2, CYP2B1/2, CYP2E and CYP4A isoforms, respectively. Replicative DNA synthesis was studied by implanting osmotic pumps containing 5-bromo-2'-deoxyuridine 1 day before the commencement of treatment with the enzyme inducers. Hepatocyte labelling index values were significantly increased by treatment with NaPB, PCN, MCP, CLOT and TAO, but not by BA, ISN, BNF, DEX and MIC. These studies demonstrate that while CYP2B and CYP4A enzyme inducers may stimulate replicative DNA synthesis, only some CYP3A enzyme inducers are mitogenic agents in rat liver.


Tonotopic organization of the human auditory cortex as detected by BOLD-FMRI.
Functional magnetic resonance imaging is a noninvasive and nonradioactive method for the detection of focal brain activity. In the present study the auditory cortex was investigated in nine normal subjects who were binaurally stimulated using pulsed sine tones of 500 Hz and 4000 Hz. The BOLD (blood oxygenation level dependent) signal change coincided with the stimulation paradigm and was detected in the plane of the superior temporal gyrus. The comparison of the spatial distribution of activated areas revealed a different behavior for the two frequencies. The present findings underline the existence of a frequency specific organization in the medio-lateral, fronto-occipital and cranio-caudal extension in both hemispheres of the auditory cortex in human. The activated areas for the high tone were found more frontally and medially orientated than the low tone stimulated areas. Furthermore, a slight cranio-caudal shift was observed for the higher frequency, more pronounced in the right than in the left temporal lobe. Finally, for most of the subjects investigated the BOLD activation area of the 500 Hz sine tone was larger than that of the 4000 Hz stimulation. Both frequencies showed a lateralization of signal response to the left temporal lobe.


Herbal remedies of Solidago--correlation of phytochemical characteristics and antioxidative properties.
In this study the correlation of phytochemical characteristics and antioxidative properties of classical herbal tea extracts-Infusum solidaginis, Decoctum solidaginis, Maceratum solidaginis-and tinctures prepared by various concentration of ethanol (40, 70, 96% v/v) have been examined for the release of flavonoids and their antioxidant activity. Quantitative and composition determination of flavonoids were carried out by spectrophotometry, high-performance liquid chromatography and capillary electrophoresis, respectively. Hydrogen-donating ability and reducing power properties were used to define in vitro radical scavenging activity of Solidago extracts, but integral antioxidative capacity was determined by luminometry (Photochem), calculating the ascorbic acid equivalents. Chlorogenic acid, quercetin-3-O-beta-D-rutinoside, quercetin-3-O-beta-D-galactoside, quercetin-3-O-beta-D-glucoside, quercetin-3-O-beta-D-rhamnoside, kaempferol-3-O-alpha-L-rhamnoside and quercetin were confirmed by retention times and UV spectra. Based on the dissolution rate, variance of flavonoid release and ascorbic acid equivalents it was concluded, that Tinctura solidaginis (70% v/v ethanol) and Infusum solidaginis are the most appropriate preparations.


The actions of 3,4-diaminopyridine in bullfrog sympathetic ganglia.
The effects of 3,4-diaminopyridine (3,4-DAP) on isolated sympathetic ganglia were studied by means of intracellular and extracellular recording techniques. 3,4-DAP in micromolar concentrations caused a single orthodromic stimulus to generate a brief burst of repetitive postganglionic discharges. Such stimulus-bound repetition (SBR) appeared to represent a presynaptic action of 3,4-DAP, as no repetitive firing could be evoked by antidromic or direct stimulation of ganglion cells. 3,4-DAP also increased the latency to the onset of the synaptic potential at concentrations paralleling those responsible for SBR. The actions of 3,4-DAP on synaptic transmission extended over a 10,000-fold concentration range, beginning with synaptic facilitation at micromolar concentrations (1-500 microM), and proceeding to depressant effects at millimolar concentrations (0.5-10 mM). The postganglionic repetitive discharges (SBR) induced by 3,4-DAP could be selectively suppressed by D-tubocurarine (D-Tc) or tetraethylammonium (TEA), at concentrations of these antagonists below those required to block transmission. 3,4-DAP had significant anti-curare effects, producing a four-fold shift of the D-Tc concentration-effect curve for transmission block. In contrast, 3,4-DAP neither antagonized nor enhanced the transmission block produced by TEA. These results are incompatible with traditional concepts of ganglionic blockade by D-Tc and TEA, and suggest the possibility of presynaptic sites of action in ganglion block.


Generation of two iPSC lines, (ICGi015-A and ICGi015-B), by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease.
Studying Parkinson's disease (PD), one of the most common neurodegenerative disorders worldwide, requires different model systems, including patient-specific induced pluripotent stem cell lines. With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of PD patient, carrying three SNPs, associated with PD development. The obtained iPSC lines express pluripotency markers and demonstrate the ability to in vitro differentiate into the three germ layers. These cell lines may be useful for studying molecular mechanisms of PD and for drug screening.


The relation between sarcomere energetics and the rate of isometric tension relaxation in healthy and diseased cardiac muscle.
Full muscle relaxation happens when [Ca2+] falls below the threshold for force activation. Several experimental models, from whole muscle organs and intact muscle down to skinned fibers, have been used to explore the cascade of kinetic events leading to mechanical relaxation. The use of single myofibrils together with fast solution switching techniques, has provided new information about the role of cross-bridge (CB) dissociation in the time course of isometric force decay. Myofibril's relaxation is biphasic starting with a slow seemingly linear phase, with a rate constant, slow kREL, followed by a fast mono-exponential phase. Sarcomeres remain isometric during the slow force decay that reflects CB detachment under isometric conditions while the final fast relaxation phase begins with a sudden give of few sarcomeres and is then dominated by intersarcomere dynamics. Based on a simple two-state model of the CB cycle, myofibril slow kREL represents the apparent forward rate with which CBs leave force generating states (gapp) under isometric conditions and correlates with the energy cost of tension generation (ATPase/tension ratio); in short slow kREL ~ gapp ~ tension cost. The validation of this relationship is obtained by simultaneously measuring maximal isometric force and ATP consumption in skinned myocardial strips that provide an unambiguous determination of the relation between contractile and energetic properties of the sarcomere. Thus, combining kinetic experiments in isolated myofibrils and mechanical and energetic measurements in multicellular cardiac strips, we are able to provide direct evidence for a positive linear correlation between myofibril isometric relaxation kinetics (slow kREL) and the energy cost of force production both measured in preparations from the same cardiac sample. This correlation remains true among different types of muscles with different ATPase activities and also when CB kinetics are altered by cardiomyopathy-related mutations. Sarcomeric mutations associated to hypertrophic cardiomyopathy (HCM), a primary cardiac disorder caused by mutations in genes encoding sarcomeric proteins, have been often found to accelerate CB turnover rate and increase the energy cost of myocardial contraction. Here we review data showing that faster CB detachment results in a proportional increase in the energetic cost of tension generation in heart samples from both HCM patients and mouse models of the disease.


Practical procedures for the delivery room resuscitation of micropreemies.
There are no standardized procedures for the resuscitation of micropreemies but respiratory and circulatory stabilization immediately after birth should be prioritized. Without aggressive support by positive pressure ventilation, establishing effective respiration among micropreemies is not possible. The first step in postnatal stabilization is initiated by positive airway pressure with a bag and mask. Once the heart rate increases above 100 beats/m, intratracheal intubation should be achieved because it is unusual for a micropreemie to breathe spontaneously or by non-invasive respiratory support for a protracted duration. Until further information is available, initial FiO2 should be between 0.3 and 0.6, and titrated to achieve SpO2 obtained from healthy term infants for the first 10 min of life. Temperature control of infants is also critical for successful resuscitation and heat-loss minimizing procedures should be used e.g. with insulating bags. After securing the intratracheal tube, the infants should be transferred to the NICU for further procedures, including pulmonary surfactant installation and umbilical cord catheterization. Procedures in a delivery room under a radiant warmer should be limited to the initial resuscitation. In NICUs, the infants should be placed into a closed incubator to maintain high environmental temperature and humidity as well as decrease exposure to intervention and noise. Increased number of staff will also be needed to stabilize the infants further in the NICU. Finally, appropriate equipment (e.g. appropriate sized laryngoscopes) should be made readily available, along with regular practical training and education, whether in person or through SIM courses which are essential for all staff to achieve competence in successful resuscitation of the newborn micropreemie.


Augmented polyol pathway activity and retinal pigment epithelial permeability in the diabetic BB rat.
In the present study we investigated the relationship between an augmented polyol pathway and the breakdown of the blood-retinal barrier in the spontaneously diabetic BB rat. Permeability experiments were performed in diabetic and age-matched non-diabetic BB rats in a longitudinal fashion using horseradish peroxidase. Increased permeability of horseradish peroxidase across the retinal pigment epithelium was noted after 6 months of diabetes. Abnormalities of the basal plasmalemmal infoldings of the retinal pigment epithelium were noted in the control animals and appeared to be exaggerated in diabetic rats. Simultaneous quantitative ultrastructural immunohistochemistry, using an affinity purified anti-BB rat aldose reductase antibody and protein-A gold, revealed a significant increase in the aldose reductase immunoreactivity of the retinal pigment epithelium in diabetic animals. These findings suggest that an augmented polyol pathway activity may play a role in the pathogenesis of the blood-retinal barrier breakdown at the level of the retinal pigment epithelium in the diabetic BB rat.


Relationship between plasma mexiletine levels at steady-state. Presence of ventricular arrhythmias and side effects.
The relationships between plasma mexiletine levels and the presence of ventricular arrhythmias and side effects were studied on patients from IMPACT (International Mexiletine and Placebo Antiarrhythmic Coronary Trial). 630 patients who had suffered a myocardial infarction were randomized between placebo and mexiletine. Plasma levels were measured 1 month after the beginning of treatment. Arrhythmia findings (presence or absence of premature ventricular contractions (PVCs), couplets, runs, bigeminy, trigeminy, multiformity and various combinations) were assessed from 24-h ambulatory ECG recordings. The empirical logistic transform was used for modeling the relationships. For all these variables, except the presence of PVCs, trigeminy and runs, the association with plasma level was significant: the higher the plasma level, the lower the rate of occurrence of the particular arrhythmia. This was true whether or not the patient had the arrhythmia at baseline. Analyses based on the same model showed a significant correlation between plasma level and tremor, constipation, sexual problems and the presence of at least one side effect. As the levels of mexiletine at which side effects become frequent are in the same range as those necessary to suppress arrhythmias, the therapeutic range is narrow and individual dose adjustment should preferably be made.


The liver as a self-organizing system. I. Theoretics of its representation.
The liver is described as a composite system consisting of a set of operative creodic microunits open to a continuous flow of matter, energy and informations. Its dynamics depend on two interactive and interrelated subsystems with actions described as homopoiesis and homeorhesis, making it an autoisodiasostic system. The system's emergent (equifinal) or emergence states, operative potential, diffusion and reaction phenomena and compensation states are also formally described. For readers not familiar with the language of general system theory, of system dynamics and of categorical analysis, a glossary of some terms is provided.


[Corrective surgery of thoracic anomalies in Poland syndrome. General review of 20 patients].
Breast and thoracic anomalies in Poland's syndrome, whether associated or not with hypoplasia of the upper limb, have no functional impairment. They present an important cosmetic disgrace. Several methods for correction were proposed: muscular transfer with or without implants. Each one has its advantages and drawbacks. We operated 20 adolescents and adults with this deformity: 13 females and 7 males. If the inferior bundle of the pectoralis major was always absent, other muscular anomalies such as aplasia of the latissimus dorsi may complicate the corrective procedure. The choice of the treatment depends upon the importance of the muscular and sometimes associated costal aplasia, in the young girl, the breast development and in both sexes the position of the nipple. The latissimus dorsi transfer may be considered as the most adapted technique for the pestoralis major replacement. The results are often disappointing due to the secondary muscular atrophy. A composite implant with a part for breast reconstruction and another to fill the subclavicular gap gives satisfactory results but it has the hazards of implants.


Hepatitis B virus C-gene variants.
The heterogeneity of hepatitis B virus (HBV) is increasingly believed to play a role in viral persistence, pathogenesis, and the type of response to antiviral therapy. One of the best studied parts of the HBV genome is the C-gene which codes for the nucleocapsid protein (HBc) and the e-antigen (HBeAg). Here we attempt to review the recent data on the sequence heterogeneity of this region and its possible implications.


Guanine nucleotide binding proteins in cultured renal epithelia: studies with pertussis toxin and aldosterone.
The GTP-binding proteins from cultured A6 epithelia were examined in isolated membrane preparations. Binding of [35S]GTPgammaS revealed a class of binding sites with an apparent Kd value of 100 nM and a Bmax of 220 pmol/mg protein. Short-term aldosterone treatment of the cells did not modify the binding kinetics, whereas pertussis toxin (PTX) decreased Bmax by 50%. The mRNA levels for Galphai-3, Galpha0, Galphas, and Galphaq were not increased after aldosterone. The patterns of small Mr G proteins and of PTX-ribosylated proteins were identical in membranes of both control and aldosterone-treated cells. Cross-linking of [alpha-32P]GTP, in control membranes, showed either no labeling or a faint band of Mr 59.5 kDa. This protein became prominent after aldosterone, and its labeling decreased with spironolactone. Thus short-term aldosterone does not promote increased expression of known heterotrimeric G proteins in epithelial membranes but activates resident PTX-sensitive Gi proteins and stimulates the expression of a specific GTP-binding protein of Mr 59.5 kDa.


A report on the present status of undergraduate urologic teaching in medical schools and some resulting recommendations.
At the request of the Education Council of the American Urological Association a survey of urologic teaching in America's medical schools was done. The most startling and distressing finding, based upon the study of 99 medical schools, was that more than half (52 per cent) of the schools do not require any clinical exposure to urology before graduation. Suggestions are offered, based upon the documented importance of urology in the delivery of primary care, for an approach to medical school curriculum committees to mandate the return of urology as a required subject in our schools.


Role of Individual, Family, and Community Resilience in Moderating Effects of Adverse Childhood Experiences on Mental Health Among Children.
Mental health outcomes such as attention-deficit/hyperactivity disorder (ADHD), behavior disorders, anxiety, depression, and adverse childhood experiences (ACEs) are common disorders among children in the United States. Little is known on how potential resilient factors may moderate the relationship between exposure to ACEs and mental health outcomes. This study examines associations between ACEs and resilience on mental health outcomes using the 2018 National Survey of Children's Health (N = 26,572). Logistic regression and interactions examined the association between ACEs, resilience, and mental health outcomes. ACE exposure and low resiliency were associated with an increased likelihood of mental health outcomes. There were significant interactions between exposure to ACEs and family resilience as well as significant interactions between ACE exposure and community resilience. On stratification, the presence of individual resilience and having all resilience measures decreased the odds of ADHD, behavioral disorders, anxiety, and depression and the presence of community resilience decreased the odds of depression among individuals who had experienced 4 or more ACEs. These results illustrate the need to promote resilience measures for tackling mental health problems and reducing the negative effect of trauma in children.


Theoretical methods for study of kinetics of models of the mitochondrial respiratory chain.
In earlier work, Hill and Chance obtained exact steady-state kinetic properties for partial models of the mitochondrial respiratory chain with two isopotential pools and one four-state "site enzyme" between the two pools. That work is extended here to full models of the respiratory chain with four isopotential pools and three four-state site enzymes between pairs of pools. Because of the complexity of the model, exact calculations are no longer possible. Instead, we show, by means of some examples, the feasibility of using Monte Carlo calculations on all cases and numerical solution of thousands of kinetic differential equations in many cases.


ZrO2-Ag2O nanocomposites encrusted porous polymer monoliths as high-performance visible light photocatalysts for the fast degradation of pharmaceutical pollutants.
This work reports a unique ZrO2-Ag2O heterojunction nanocomposite uniformly dispersed on a macro-/meso-porous polymer monolithic template to serve as simple and effective visible light-driven heterogeneous plasmonic photocatalysts for water decontamination. The monolithic photocatalysts' structural properties and surface morphology are characterized using various surface and structural characterization techniques. The photocatalytic performance of the proposed photocatalysts is evaluated by optimizing multiple operational parameters. The photocatalytic properties of the fabricated monolithic nanocomposite are monitored through time-dependent photocatalytic disintegration of norfloxacin drug, a widely employed antimicrobial, with considerable aquatic persistence. The analytical results conclude that a (60:40) ZrO2-Ag2O nanocomposite embedded polymer monolith exhibits superior photocatalytic activity for the complete mineralization of norfloxacin molecules under optimized conditions of solution pH (3.0), photocatalyst quantity (100 mg), pollutant concentration (15 mg/L), photosensitizers (2.0 mM KBrO3), visible light intensity (300 W/cm2 tungsten lamp) and irradiation time (≤ 1 h). The proposed new-age inorganic-organic hybrid visible light photo-catalysts with superior structural and surface properties exhibit brilliant performance and fast responsiveness for water decontamination applications, in addition to their excellent chemical stability, high durability, multi-reusability, and cost-effectiveness.


Phorbol myristate acetate--fate and usability in a human interleukin-1 assay.
Phorbol myristate acetate (PMA) has been widely used to produce interleukin-1 (IL-1) from monocytes (Mø) of various species, including man. Supernatants from cultures of human Mø, stimulated with PMA, 2 X 10(-6) M, contained IL-1-like activity, as judged by their high co-mitogenic effect on mitogen-stimulated human T-cells. However, a solution of PMA in culture medium was equally as active as the supernatants. By way of 3H-PMA it was demonstrated that the IL-1-like effect of PMA-induced supernatants was non-dialyzable, was coupled to proteins with a molecular weight greater than 70,000 Dalton and could be dependent mainly upon the PMA content. Thus, previous reports dealing with basic immunological as well as immunopharmacological aspects of IL-1, must be interpreted with caution if the conclusions have been based on results obtained with crude or high molecular weight forms of PMA-induced IL-1. It could be that PMA can be used as an IL-1 inducer. However, it must first be demonstrated that PMA does not interfere with the detection of IL-1 or, if so, that PMA has been removed sufficiently from the test material to avoid interference. Secondly, the specificity of PMA with respect to IL-1 inducing effect must be demonstrated under endotoxin-free culture conditions.


Persistence of placenta previa according to gestational age at ultrasound detection.
To evaluate gestational age at ultrasound detection of placenta previa as a predictor of previa persistence until delivery, and to estimate the effects of previa type, parity, and prior cesarean delivery on previa persistence. This was a retrospective cohort study of pregnancies with placenta previa detected during transabdominal or endovaginal ultrasound examination. Previa was categorized as complete if the placenta completely covered the internal cervical os or incomplete if the inferior placental edge partially covered or reached the margin of the os. Gestational age was grouped into 4-week intervals from 15 to 36 weeks. The outcome was cesarean delivery for persistent previa. Previa was detected during 940 ultrasound examinations in 714 pregnancies. Of those with placenta previa at 15-19 weeks, 20-23 weeks, 24-27 weeks, 28-31 weeks, and 32-35 weeks, previa persisted until delivery in 12%, 34%, 49%, 62%, and 73%, respectively. At each interval, complete previa was more likely to persist than incomplete previa, all P <.001. Prior cesarean delivery was an independent risk factor for persistent previa among women diagnosed with previa in the second trimester, P <.05. However, parity was not an independent risk factor for persistence at any gestational age interval after adjusting for prior cesarean delivery. Gestational age at ultrasound detection of placenta previa may be used to predict likelihood of previa persistence. After midpregnancy, risk of persistence appears to be higher than previously reported. Type of placentation and prior cesarean delivery are important factors that modify the risk that previa will complicate delivery.


Effects of day-to-day changes in root temperature on leaf conductance to water vapour and CO2 assimilation rates of Vigna unguiculata L. Walp.
Leaf gas exchange of Vigna unguiculata was influenced by short-term (day-to-day) changes in soil temperature and the response depended upon the aerial environment. When aerial conditions were constant at 30° C leaf temperature, high air humidity and moderate quantum flux, CO2 assimilation rate and leaf conductance increased with increases in soil temperature from 20 to 35° C, and this response was reversible. Decreases in CO2 assimilation rate and leaf conductance were observed at root temperatures above 30° C when root temperatures were increased from 20° C to 40° C and when air humidity was decreased in steps during the day. In contrast, varying soil temperatures between 20 to 35° C had no influence on gas exchange when shoots were subjected to a wide range of temperatures during each day.The gain ratio ∂A/τE remained constant at different air humidities when root temperature was less than or equal to 30° C indicating optimal gas exchange regulation, but changed with humidity at higher root temperatures. Leaf conductance responded independently from leaf water potential which remained relatively constant during individual experiments.The results indicate that plant responses to high root temperatures may have relevance to plant performance in semi-arid environments. They also illustrate the importance of controlling soil temperatures when studying the responses of potted plants in controlled aerial environments.


Which venous leg ulcers will heal with limb compression bandages?
To develop a simple prediction rule to identify patients in whom a venous leg ulcer will heal using a limb compression bandage (eg, Unna's boot). We performed a retrospective cohort study of patients with venous leg ulcers who received a limb compression bandage applied weekly. Prognostic factors were assessed from the patient's history before the start of treatment. The outcome of interest was a healed wound within 24 weeks of treatment. The final model was validated in another data set. Several accurate prognostic models were developed. The simplest model summed the size and duration of the wound before treatment, with 1 point given for a wound with an area >5 cm(2) and another if the wound was >6 months old. In the development data set, ulcers healed in 93% (110 of 118) of patients with a score of 0, but in only 13% (9 of 67) of those with a score of 2. In the validation data set, ulcers healed in 95% (19 of 20) of patients with a score of 0, and 37% (44 of 120) of those with a score of 2. This simple prognostic model can be used to discriminate between patients with a venous leg ulcer that will or will not heal within 24 weeks of care with a limb compression bandage. The model may be useful in determining which patients to treat with a limb compression, and which patients should be referred or considered for alternative treatments.


Aspirin dose increase from 75 to 150 mg suppresses red blood cell contribution to suboptimal platelet response to aspirin in patients with CAD.
To verify the hypothesis that erythrocytes play a role in suboptimal blood platelet response to acetylsalicylic acid (ASA, aspirin) in subjects with coronary artery disease (CAD). In a cross-over randomized controlled intervention study we evaluated blood platelet response to 30-day treatment with 75 mg/d or 150 mg/d of ASA (enteric coated) in CAD patients (n = 125). In vitro platelet response to collagen or arachidonic acid was monitored with impedance aggregometry and plasma thromboxane B2 was assayed immunoenzymatically. Blood morphology and several plasma biochemical parameters were determined using routine diagnostic procedures. CAD patients demonstrated lower blood platelet responsiveness to 75 mg/d of ASA compared to healthy subjects. The improved platelet responsiveness to 150 mg/d of ASA was particularly evident in "poor" responding patients. Positive correlations between platelet "poor" response to lower (75 mg/d) ASA dose and red blood cell count (Rs = 0.215; p < 0.04), haemoglobin (Rs = 0.232; p < 0.02) and haematocrit (Rs = 0.239; p < 0.02) were found in CAD patients. Association between "poor" platelet response with lower ASA dose was confirmed by conditional maximum likelihood logistic regression, which showed the independency between erythrocyte-derived parameters, as the risk factors for suboptimal platelet response to ASA, and other risk factors, like CRP or LDL-cholesterol. In "poor" ASA responders taking the higher ASA dose (150 mg/d) the correlation between platelets' response to ASA and erythrocyte-derived parameters was not significant. Red blood cell parameters are associated with suboptimal blood platelet response to ASA in patients with CAD. Such a platelet refractoriness to ASA may be effectively overcome by increasing the ASA dose.


Hypertonic saline increases gammadeltaT cell-mediated killing of activated neutrophils.
Hypertonic saline fluids used to resuscitate trauma patients can prevent neutrophil-mediated lung tissue damage, making them attractive alternatives to conventional resuscitation fluids. We have previously shown that gammadeltaT cells, a small T lymphocyte subset, reduce acute inflammatory lung damage by eliminating activated neutrophils that express heat shock protein 72 on the cell surface. Here, we studied whether these protective effects of hypertonic saline are related to improved gammadeltaT cell-mediated neutrophil killing. Laboratory investigation. University research laboratory. Human peripheral blood from healthy subjects--isolated gammadeltaT lymphocytes and neutrophils. Isolated blood cells were treated with different concentrations of hypertonic saline and endotoxin of Escherichia coli O111:B4 (lipopolysaccharide). In some experiments, gammadeltaT cells were activated by CD3 cross-linking or by phorbol-myristate acetate and ionomycin, or by phytohemagglutinin. Clinically relevant concentrations of hypertonic saline (20 mM) significantly augmented CD69 expression of gammadeltaT cells that were stimulated with 100 ng/mL lipopolysaccharide. Additionally, lipopolysaccharide induced a three- to five-fold increase in tumor necrosis factor-alpha and interleukin-10 expression by gammadeltaT cells. This response was completely abrogated by hypertonic saline. These data indicate that hypertonic saline can modulate gammadeltaT cell functions. Stimulation of neutrophils with 1-1,000 ng/mL lipopolysaccharide caused a greater than 3-fold increase in heat shock protein-72 expression on the cell surface, which was significantly augmented by hypertonic saline. In cocultures of gammadeltaT cells with autologous neutrophils, 15.6 +/- 3.4% of all neutrophils were killed within 120 min. In the presence of lipopolysaccharide (1 microg/mL), this percentage increased to 23.7 +/- 2.1%, and it was further increased to 31.8 +/- 3.1% when 20 mM hypertonic saline was added with lipopolysaccharide. Our findings suggest that hypertonic saline enhances the elimination of inflammatory neutrophils by gammadeltaT cells by augmenting heat shock protein-72 expression on the cell surface of neutrophils. Hypertonic saline resuscitation may therefore protect host tissues by enhancing neutrophil clearance from the lungs.


Effects of arterial hypoxia and beta-adrenoceptor blockade on cerebral blood flow and oxygen uptake following E. coli endotoxin in dogs.
Earlier studies in normoxia have shown that an endotoxin injection in dogs leads to an increase in cerebral metabolic rate of oxygen (CMRo2), a decrease in cerebral blood flow (CBF) and increased concentrations of monoamines in blood and cerebrospinal fluid (CSF). In animals pretreated with propranolol (PPL) the CMRo2 increase was abolished and thus beta-adrenoceptor mediated. Arterial hypoxia normally increases CBF without any influence on CMRo2. The aim of this study was to investigate the effects of moderate arterial hypoxia on CBF, CMRo2 and catecholamine concentrations in blood and CSF after endotoxin with and without pretreatment with PPL. Three groups of dogs were studied. Group 1: Six animals were subjected to arterial hypoxia without any other intervention. Group 2: Six animals were given an endotoxin injection (E. coli lipopolysaccharide O 111: B 4), before the induction of hypoxia. Group 3: Eight animals were pretreated with PPL per os, 12.5 mg.kg-1 twice a day for one week before the experiments, and the effects of arterial hypoxia were studied both before and after an intravenous injection of endotoxin. Two levels of hypoxia were studied; oxygen saturation in arterial blood aiming at 75 and 50%. Endotoxin was given intravenously in a dose of 1 mg.kg-1 bodyweight over a 5 minute period. After an endotoxin injection, the response to arterial hypoxia was an increase in CMRo2, in contrast to the unchanged CMRo2 without endotoxin. After pretreatment with PPL the increase in CMRo2 after endotoxin was prevented. The CBF reaction to hypoxia was uniformly an increase.(ABSTRACT TRUNCATED AT 250 WORDS)


COVID-19 outcomes in people living with HIV: Peering through the waves.
To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.