Conditions potentially sensitive to a personal health record (PHR) intervention, a systematic review.
Personal Health Records (PHRs) are electronic health records controlled, shared or maintained by patients to support patient centered care. The potential for PHRs to transform health care is significant; however, PHRs do not always achieve their potential. One reason for this may be that not all health conditions are sensitive to the PHR as an intervention. The goal of this review was to discover which conditions were potentially sensitive to the PHR as an intervention, that is, what conditions have empirical evidence of benefit from PHR-enabled management. A systematic review of Medline and CINAHL was completed to find articles assessing PHR use and benefit from 2008 to 2014 in specific health conditions. Two researchers independently screened and coded articles. Health conditions with evidence of benefit from PHR use were identified from the included studies. 23 papers were included. Seven papers were RCTs. Ten health conditions were identified, seven of which had documented benefit associated with PHR use: asthma, diabetes, fertility, glaucoma, HIV, hyperlipidemia, and hypertension. Reported benefits were seen in terms of care quality, access, and productivity, although many benefits were measured by self-report through quasi-experimental studies. No study examined morbidity/mortality. No study reported harm from the PHR. There is a small body of condition specific evidence that has been published. Conditions with evidence of benefit when using PHRs tended to be chronic conditions with a feedback loop between monitoring in the PHR and direct behaviours that could be self-managed. These findings can point to other potentially PHR sensitive health conditions and guide PHR designers, implementers, and researchers. More research is needed to link PHR design, features, adoption and health outcomes to better understand how and if PHRs are making a difference to health outcomes.


Complete phenotypic characterization of apobec-1 knockout mice with a wild-type genetic background and a human apolipoprotein B transgenic background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of Apobec-1.
We have produced gene knockout mice by targeted disruption of the apobec-1 gene. As recently reported by Hirano et al. (Hirano, K.-I., Young, S. G., Farese, R. V., Jr., Ng, J., Sande, E., Warburton, C., Powell-Braxton, L. M., and Davidson, N. O. (1996) J. Biol. Chem. 271, 9887-9890), these animals do not edit apolipoprotein (apo) B mRNA or produce apoB-48. In this study we have performed a detailed analysis of the lipoprotein phenotypic effects of apobec-1 gene disruption that were not examined in the previous study. We first analyzed the plasma lipoproteins in knockout animals with a wild-type genetic background. Although there was no difference in plasma cholesterol between apobec-1(-/-), +/-, or +/+ mice, there was a marked (176%) increase in plasma apoB-100, from 1.8 +/- 1.2 mg/dl in apobec-1(+/+) mice to 2.7 +/- 0.6 mg/dl in apobec-1(+/-) and 5.0 +/- 1.4 mg/dl in apobec-1(-/-) mice. Plasma apoE was similar in these animals. By fast protein liquid chromatography (FPLC) analysis, there was a significant decrease in plasma high density lipoprotein (HDL) cholesterol in apobec-1(-/-) mice. We further fractionated the plasma lipoproteins into d < 1.006, 1.006-1.02, 1.02-1.05, 1.05-1.08, 1.08-1.10, and 1.10-1.21 g/ml classes, and found a marked (30-40%) reduction in the cholesterol and protein content in the (d 1.08-1.10 and 1.10-1.21) HDL fractions, corroborating the FPLC data. SDS-gel analysis revealed an absence of apoB-48, an increase in apoB-100 in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions, and a small decrease in apoA-I in the HDL fractions in the apobec-1(-/-) samples. We next raised the basal plasma apoB levels in the apobec-1(-/-) animals by cross-breeding them with human apoB transgenic (TgB) mice. The plasma apoB-100 was 3-fold higher in apobec-1(-/-)/TgB+/- mice (26.6 +/- 18.3 mg/dl) than in apobec-1(+/+)/TgB+/- mice (9.8 +/- 3.9 mg/dl, p < 0.05). The apobec-1(-/-)/TgB+/- mice had a plasma cholesterol levels of 170 +/- 28 mg/dl and triglyceride levels of 106 +/- 31 mg/dl, which are 80% and 58% higher, respectively, than the corresponding values of 94 +/- 21 mg/dl and 67 +/- 11 mg/dl in apobec+/+/TgB+/- mice. By FPLC, the apobec-1(-/-)/TgB+/- animals developed markedly elevated plasma LDL cholesterol (518.5 +/- 329.5 microg/ml) that is 373% that of apobec1(+/+)/TgB+/- mice (139.0 +/- 87.0 microg/ml) (p < 0.05). The elevated plasma triglyceride was accounted for mainly by a 97% increase in VLDL triglyceride in the apobec1(-/-)/TgB+/- mice. We conclude that apobec-1(-/-) animals have a distinctive lipoprotein phenotype characterized by significant hyperapoB-100 and HDL deficiency in mice with a wild-type genetic background. Furthermore, the abolition of apoB mRNA editing elevates plasma total cholesterol and LDL cholesterol in apobec-1(-/-) animals with a TgB background. Finally, to exclude the possibility that absence of apoB mRNA editing was a secondary effect of chronic Apobec-1 deficiency, we treated apobec-1(-/-) mice with a replication-defective mouse Apobec-1 adenoviral vector and found that we could acutely restore apoB mRNA editing in the liver. These experiments indicate that Apobec-1 is an essential component of the apoB mRNA editing machinery and absence of editing in the knockout animals is a direct consequence of the absence of functional Apobec-1.


Prior statin use is associated with improved outcomes in community-acquired pneumonia.
Statins have potent anti-inflammatory effects in laboratory studies of pulmonary inflammation. We investigated whether statin users had improved outcome when admitted with community-acquired pneumonia. We carried out a prospective observational study of patients admitted to the hospital with community-acquired pneumonia between January 2005 and November 2007. The use of statins, angiotensin-converting enzyme inhibitors, beta-blockers, and aspirin were recorded. The outcomes of interest were 30-day mortality, need for mechanical ventilation or inotropic support, and the development of complicated pneumonia. On multivariate logistic regression, statin use was associated with significantly lower 30-day mortality (adjusted odds ratio [AOR] 0.46, 95% confidence interval [CI], 0.25-0.85, P=.01) and development of complicated pneumonia (AOR 0.44, 95% CI, 0.25-0.79, P=.006). There was no effect on requirement of mechanical ventilation or inotropic support (AOR 0.93, 95% CI, 0.49-1.76, P=.8). Patients prescribed statins had more severe pneumonia (median Pneumonia Severity Index 4, interquartile range [IQR] 3-4) compared with patients not prescribed cardiovascular drugs (median Pneumonia Severity Index 3, IQR 2-4, P < .0001). Despite this, C-reactive protein levels on admission were significantly lower in patients prescribed statins (median 119 mg/L, IQR 46-215) compared with patients prescribed no cardiovascular drugs (182 mg/L, IQR 66-326, P < .0001). On multivariate logistic regression, statin use was independently protective against a C-reactive protein that failed to fall by 50% or more at day 4 (AOR 0.50, 95% CI 0.27-0.92, P=.02). Statin use is associated with reduced markers of systemic inflammation and improved outcomes in patients admitted with community-acquired pneumonia.


High-performance liquid chromatographic preparation of galactosyl-hydroxylysine, a specific bone collagen marker.
Galactosyl-hydroxylysine, a specific bone collagen marker, has been prepared directly from human urine samples by high-performance liquid chromatography (HPLC) on a preparative column. The compound is the didansyl derivative, as proved by HPLC and mass spectrometry under fast atom bombardment conditions. Since this compound is not commercially available, the procedure reported appears to be the simplest way to prepare it, which is necessary to measure the urinary excretion of this collagen metabolite by HPLC.


Comparing the risk for death with peritoneal dialysis and hemodialysis in a national cohort of patients with chronic kidney disease.
The influence of type of dialysis on survival of patients with end-stage renal disease (ESRD) is controversial. To compare risk for death among patients with ESRD who receive peritoneal dialysis or hemodialysis. Prospective cohort study. 81 dialysis clinics in 19 U.S. states. 1041 patients starting dialysis (274 patients receiving peritoneal dialysis and 767 patients receiving hemodialysis) at baseline. Patients were followed for up to 7 years and censored at transplantation or loss to follow-up. Cox proportional hazards regression stratified by clinic was used to compare the risk for death with peritoneal dialysis versus hemodialysis. Twenty-five percent of patients undergoing peritoneal dialysis and 5% of hemodialysis patients switched type of dialysis. After adjustment, the risk for death did not differ between patients undergoing peritoneal dialysis and those undergoing hemodialysis during the first year (relative hazard, 1.39 [95% CI, 0.64 to 3.06]), but the risk became significantly higher among those undergoing peritoneal dialysis in the second year (relative hazard, 2.34 [CI, 1.19 to 4.59]). After stratification, the survival rate was no different for patients who had the highest propensity of being initially treated with peritoneal dialysis. Results were consistent with adjustment based on a propensity score model and in sensitivity analyses that used as-treated models and models in which switches in type of dialysis were treated as treatment failures. Results were similar but stronger in analyses that were restricted to patients who were treated only in clinics offering both types of dialysis. Patients were not randomly assigned to their initial type of dialysis. Also, more patients undergoing peritoneal dialysis than hemodialysis switched type of dialysis over time, and the reason for switching was often a consequence of the technique. The risk for death in patients with ESRD undergoing dialysis depends on dialysis type. Further studies are needed to evaluate a possible survival benefit of a timely change from peritoneal dialysis to hemodialysis.


Mouse Models of Phaeohyphomycosis.
Infections by dematiaceous fungi especially phaeohyphomycosis are an emerging group of infectious diseases worldwide with a variety of clinical presentations. The mouse model is a useful tool for studying phaeohyphomycosis, which can mimic dematiaceous fungal infections in humans. Our laboratory has successfully constructed a mouse model of subcutaneous phaeohyphomycosis and found significant phenotypic differences between Card9 knockout and wild-type mice, mirroring the increased susceptibility to this infection observed in CARD9-deficient humans. Here we describe construction of the mouse model of subcutaneous phaeohyphomycosis and related experiments. We hope that this chapter can be beneficial for the study of phaeohyphomycosis and facilitate the development of new diagnostic and therapeutic approaches.


Histoplasmosis in the acquired immune deficiency syndrome.
This report describes the experience with disseminated histoplasmosis in seven of 15 patients with the acquired immune deficiency syndrome (AIDS) diagnosed in Indianapolis since 1981. Three were homosexual, two were intravenous drug addicts, one was the spouse of another patient with AIDS and disseminated histoplasmosis, and the seventh was a hemophiliac. Six had associated infections: candidiasis in three, Pneumocystis carinii pneumonia, recurrent mucocutaneous herpes simplex infection, and disseminated Mycobacterium avium infection in two each, and disseminated infection with an unidentified mycobacterium in one. Clinical diseases suggested sepsis in four. Histoplasma fungemia occurred in five, but the diagnosis was established first by visualization of organisms in blood or bone marrow in three. Results of Histoplasma serologic tests were positive in each. Three died before receiving 50 mg of amphotericin B, three had prompt improvement with amphotericin B, and one was treated with ketoconazole to prevent dissemination. However, two of the three patients treated with amphotericin B had relapses after a 35 mg/kg course, and the third died within a month following therapy. Disseminated histoplasmosis is a major opportunistic infection in patients with AIDS from endemic areas. AIDS should be strongly considered in otherwise healthy persons with disseminated histoplasmosis, especially if risk factors for AIDS are present. Amphotericin B is not curative in these patients.


Delayed maturation of skin window macrophages in myelodysplastic syndromes.
Blood monocyte differentiation to macrophages was examined in nine patients with primary myelodysplastic syndromes using the skin window technique. Emigrated cells were stained cytochemically for acid phosphatase reaction after 1, 2, 4, 7, 9, 12 and 23 h. Compared to age-matched controls, seven patients showed a significant delay in lysosomal enzyme acquisition, which is associated with macrophage differentiation. Our results with this in-vivo assay demonstrate an involvement of the monocyte/macrophage system in primary myelodysplastic syndromes and show that patients often have a disturbance in macrophage differentiation.


High-intensity interval training in patients with intermittent claudication.
Provision, uptake, adherence, and completion rates for supervised exercise programs (SEP) for intermittent claudication (IC) are low. A shorter, more time-efficient, 6-week, high-intensity interval training (HIIT) program may be an effective alternative that is more acceptable to patients and easier to deliver. The aim of this study was to determine the feasibility of HIIT for patients with IC. A single arm proof-of-concept study, performed in secondary care, recruiting patients with IC referred to usual-care SEPs. Supervised HIIT was performed three times per week for 6 weeks. The primary outcome was feasibility and tolerability. Potential efficacy and potential safety were considered, and an integrated qualitative study was undertaken to consider acceptability. A total of 280 patients were screened: 165 (59%) were eligible, and 40 (25%) were recruited. The majority (n = 31; 78%) of participants completed the HIIT program. The remaining nine patients were withdrawn or chose to withdraw. Completers attended 99% of training sessions, completed 85% of sessions in full, and performed 84% of completed intervals at the required intensity. There were no related serious adverse events. Maximum walking distance (+94 m; 95% confidence interval, 66.6-120.8 m) and the SF-36 physical component summary (+2.2; 95% confidence interval, 0.3-4.1) were improved following completion of the program. Uptake to HIIT was comparable to SEPs in patients with IC, but completion rates were higher. HIIT appears feasible, tolerable, and potentially safe and beneficial for patients with IC. It may provide a more readily deliverable, acceptable form of SEP. Research comparing HIIT with usual-care SEPs appears warranted.


Humanized immune system (HIS) mice as a tool to study human NK cell development.
The study of human hematopoiesis is conditioned by access to nondiseased human tissue samples that harbor the cellular substrates for this developmental process. Technical and ethical concerns limit the availability to tissues derived from the fetal and newborn periods, while adult samples are generally restricted to peripheral blood. Access to a small animal model that faithfully recapitulates the process of human hematopoiesis would provide an important tool. Natural killer (NK) cells comprise between 10% and 15% of human peripheral blood lymphocytes and appear conserved in several species. NK cells are implicated in the recognition of pathogen-infected cells and in the clearance of certain tumor cells. In this chapter, we discuss NK cell developmental pathways and the use of humanized murine models for the study of human hematopoiesis and, in particular, human NK cell development.


Neoadjuvant chemoradiotherapy is superior to chemotherapy alone in surgically treated stage III/N2 non-small-cell lung cancer: a retrospective single-center cohort study.
There is lack of consensus whether neoadjuvant chemoradiotherapy (CHT/RT) is superior to neoadjuvant chemotherapy (CHT) alone in patients with potentially resectable stage III/N2 non-small-cell lung cancer (NSCLC). We retrospectively evaluated clinical parameters and outcomes in patients with clinical stage III/N2 NSCLC treated with neoadjuvant CHT/RT versus CHT followed by surgery. Nearest-neighbor propensity score (PS) matching was used to correct for pretreatment differences. A total of 84 patients were enrolled. Thirty-four (40%) and 50 (60%) patients received CHT/RT or CHT followed by curative-intent surgery, respectively. Overall 90-day mortality and morbidity were 0% versus 0.04% and 21% versus 18%, respectively, with no significant difference between the CHT/RT and the CHT-alone cohorts (P = 0.51 and P = 0.70). In the PS-matched cohort, complete pathological response was recorded in 25% after CHT/RT versus 0% after CHT at the time of surgery. Patients receiving neoadjuvant CHT/RT exhibited significantly better 5-year disease-free survival (DFS) [45% versus 16% CHT group; hazard ratio (HR) 0.43, P = 0.04]; 5-year overall survival (OS) was 75% after CHT/RT and 21% after CHT (HR 0.37, P = 0.001). CHT/RT more often induced pathological mediastinal downstaging (P = 0.007), but CHT/RT remained the only independent factor for DFS and OS and did not depend on mediastinal downstaging. In this retrospective PS-matched long-term analysis, neoadjuvant CHT/RT conferred improved DFS and OS compared with CHT alone in stage III/N2 NSCLC. These highly challenging results require confirmation in well-designed randomized controlled trials conducted at highly specialized thoracic oncology centers.


Nationwide Analysis of the Outcomes and Mortality of Hospitalized Infants with Concomitant Diagnosis of COVID-19.
Coronavirus disease 2019 (COVID-19) generally causes milder illness in the pediatric population. However, infants represent a higher-risk population with evolving symptomatology and severity. There is a paucity of large population-based data on the impact of COVID-19 on hospitalized infants. In this large cohort study, the National Inpatient Sample database was queried for all infant hospital admissions between January and December 2020 in the United States, with and without a diagnosis of COVID-19 based on ICD-10-CM U07. The mortality and morbidity of infants with and without COVID-19 were evaluated. Parent-reported race and outcomes were also analyzed. A weighted total of 3,754,236 infants who were hospitalized were identified, of which 4,265 patients (0.11%) had a concomitant diagnosis of COVID-19. Infants with COVID-19 had similar mortality and extracorporeal membrane oxygenation utilization. Infants with concomitant COVID-19 had a higher rate of respiratory failure, congestive heart failure, acute kidney injury, and coagulopathy. Compared with Caucasian infants and Asian infants, Hispanic and African American infants were more likely to have COVID-19 hospital admissions than hospitalizations without COVID-19 diagnosis. Patients with lower median household income represented the majority of the COVID-19 hospitalization. The infants with COVID-19 were more likely to have Medicaid or Medicare insurance and less likely to have private insurance. In this large cohort of hospitalized infants with COVID-19, the infection was associated with complications, including respiratory failure and endotracheal intubations but not associated with a higher risk for mortality. Infants from racial minorities and lower socioeconomic strata carry the highest burden of COVID-19 infection. · Infants with COVID-19 represent a higher-risk group with evolving symptomatology and severity.. · Infants with COVID-19 had similar mortality rates and extracorporeal membrane oxygenation utilization as those without COVID-19.. · Racial minorities and lower socioeconomic strata carry the highest burden of COVID-19 infection..


Meal-Induced Symptoms in Children with Dyspepsia-Relationships to Sex and the Presence of Gastroparesis.
To test the hypothesis that in children with dyspepsia, prospective symptom severity following ingestion of a meal would correlate with percent gastric retention, and those ultimately diagnosed with gastroparesis would report worse symptoms. Prospective, single-center study with 104 children with dyspepsia completing a prospective dyspepsia symptom questionnaire before and after eating a standardized Tougas meal during gastric emptying scintigraphy. Main outcomes included correlation between gastric retention and symptoms and comparison of symptom severity between those with and without gastroparesis. Fifty-two children (50%) had gastroparesis (gastroparesis: 12.5 ± 2.9 years, 65% female; nongastroparesis: 13.0 ± 2.9 years, 60% female; all P > .05). Bloating was the only symptom significantly worse in youth with gastroparesis. For the entire cohort, bloating and fullness correlated with percent retention. However, in those with gastroparesis, only nausea correlated with retention (4 hours.; rs = 0.275, P < .05). Girls with gastroparesis had significantly worse symptoms (except satiety) when compared with boys with gastroparesis (P < .05). Overall in children, there is little difference in symptom severity between children with gastroparesis vs normal emptying based on current standards. However, girls with gastroparesis have worse symptoms vs boys with gastroparesis, underscoring a need for further studies into the role of sex in gastroparesis symptoms. In all children, both bloating and fullness correlated modestly with gastric retention, and nausea correlated in those with gastroparesis.


Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient.
Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.


Effect of histamine H2 and H3 receptor modulation in the septum on post-training memory processing.
We compared the effects of modulating the postsynaptic histamine receptor subtype 2 (H2) and inhibitory presynaptic autoreceptor subtype 3 (H3) on memory processing in the septum. Mice were partially trained on footshock avoidance in a T-maze. Immediately after training, saline or a drug solution was infused into the septum. One week later, retention was tested by continuing training until the mice made five avoidance responses in six consecutive trials. The results indicate that dimaprit, an H2 agonist, facilitated retention (25 and 50 pg) with a U-shaped dose-response curve typical of drugs acting at postsynaptic receptors. Cimetidine, an H2 antagonist, impaired retention (15-50 ng). The H3 agonist. imetit, impaired retention (25-200 ng), while the H3 antagonist, thioperamide, facilitated retention (10-400 ng). An unusual feature of the dose-response curve for thioperamide was that it did not appeal to yield a U-shaped curve as occurs with drugs acting postsynaptically, but facilitated retention to approximately the same degree from 50 to 400 ng. As histamine neurons project to various limbic system structures involved in memory processing, it may play an important role in regulating the activity of structures such as the septum, hippocampus and amygdala.


Strategies to improve insurance coverage for infertility services.
Various studies repeatedly have demonstrated that in the United States, only a minority of couples with infertility receive medical treatment and even fewer receive such treatment from specialists. Primarily couples of higher socioeconomic status receive such treatment. It is therefore obvious that a lack of insurance coverage greatly contributes to this country's disproportionately low utilization of fertility services compared with other developed nations. Such low utilization raises significant ethical and economic issues. For example, if the treatment of infertility is to be perceived as the treatment of a disease stage (a notion widely supported in our professional community), then how can we defend the fact that services are principally available only to the affluent? Moreover, by having access to only a fraction of the potential national market for infertility services, the national overhead for these services is distributed over only a fraction of potential buyers, greatly increasing unit costs. In short, obtaining a larger market for our services through better insurance coverage would solve ethical quandaries and, at the same time, reduce fertility costs on a unit level. How, then, can such improved insurance coverage be achieved? A number of possible strategies come to mind.


Muscle strength in the triceps surae and objectively measured customary walking activity in men and women over 65 years of age.
1. Objective measurements of the maximal voluntary strength of triceps surae and the amount and speed of customary walking have been made in 56 men and 66 women aged over 65 years, who were living independently. 2. Strength was measured using a dynamometer based upon a hydraulic system (Bourdon tube). Walking was assessed, for amount using a mechanical accelerometer (pedometer) over a week, and for speed using a self-paced test for normal walking over 100 m on the level. The reliability and validity of these methods has been described. 3. The men were significantly stronger (1128 +/- 206 vs 873 +/- 177 N) even after adjustment for body weight; their amount of walking was similar to that of women, but they walked significantly faster (4.8 +/- 0.6 vs 4.2 +/- 0.6 km/h). Men were significantly more active in leisure pursuits (as assessed by questionnaire). 4. Significant associations between strength and chosen normal walking speed were found for both sexes (r = 0.41, P less than 0.001 for men and r = 0.36, P less than 0.01 for women). The amount of walking (daily stepscore as a mean from 7 consecutive days recorded) was significantly but less strongly correlated with strength (r = 0.30, P less than 0.05) in the men only. 5. Multiple regression analysis showed that in men neither age nor amount of walking had any further effect in addition to speed, but in women age had an additional effect (multiple R = 0.48). 6. An association has been demonstrated which raises the possibility of reversing loss of muscle strength through increased daily activity.


Burn Care in Low-Resource and Austere Settings.
More than 95% of the 11 million burns that occur annually happen in low-resource settings, and 70% of those occur among children. Although some low- and middle-income countries have well-organized emergency care systems, many have not prioritized care for the injured and experience unsatisfactory outcomes after burn injury. This chapter outlines key considerations for burn care in low-resource settings.


Nε-(carboxymethyl)lysine Concentration in Debris from Carotid Artery Stenting Correlates Independently with Signal Intensity on T1-Weighted Black-Blood Magnetic Resonance Images.
Because magnetic resonance imaging (MRI) focuses on the morphological characteristics of carotid artery plaques, its diagnostic value with respect to plaque vulnerability is limited. We examined the correlation between Nε-(carboxymethyl)lysine (CML), a main chemical structure of advanced glycation end-products, and the vulnerability of plaques visualized on MRI scans. We enrolled 43 patients who had undergone carotid artery stenting (CAS) for carotid artery stenosis; all underwent MRI studies, including black-blood MRI and diffusion-weighted imaging (DWI). The signal intensity ratio (SIR) of plaques to adjacent sternocleidomastoid muscle (P/M) on T1- and T2-weighted images (T1WI, T2WI) was calculated. Protein samples were extracted from debris trapped by a filter device. The concentrations of CML and myeloperoxidase (MPO) were measured by solid-phase enzyme-linked immunosorbent assay. The patients were classified into 2 groups based on their SIR-P/M on T1WI and T2WI scans. We observed a higher incidence of post-CAS DWI lesions in patients with a higher than a lower SIR-P/M on T1WI; the CML and MPO concentrations in their CAS debris were also higher. No such differences were seen in patients with a higher or lower SIR-P/M on T2WI scans. The concentration of CML in CAS debris correlated independently with the SIR-P/M on T1WI of the carotid plaques, and was related to the concentration of MPO in CAS debris. Our findings suggest CML as a candidate molecular imaging probe for the identification of vulnerable plaques.


Extracorporeal membrane oxygenation induced cardiac dysfunction in newborn lambs.
Extracorporeal membrane oxygenation (ECMO) is routinely used to support cardiopulmonary failure in infants and children. Suboptimal outcomes for primary cardiac support suggest a need for investigation of the impact of ECMO on the heart. Twenty-four newborn lambs received a brief period of ECMO support to investigate the hypothesis that ECMO produces cardiac dysfunction in newborn lamb. Dorset newborn lambs, 4-7 days of age, were exposed to ECMO for 5 min at a 100 ml/kg flow rate and quickly weaned off. Measurements included echocardiographic mean left ventricular (LV) velocity of circumferential fiber shortening corrected for heart rate (mVCFc), LV shortening fraction, and peak systolic wall stress plus hemodynamic measurement of LV maximum rate of pressure change with time (LV dp/dt max), maximum rate of pressure change divided by developed pressure (LV dp/dtP), right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, LV peak and end-diastolic pressure, and aortic pressure. These measures were also obtained after an exposure to 5 min of ECMO and immediate disconnect for 5 min, followed by ECMO administration for 1 h again, followed by discontinuation of ECMO. LV mVCFc is decreased after exposure to 5 min of ECMO support despite a decrease in LV peak systolic wall stress that provides afterload reduction. LV mVCFc is inversely related to peak systolic wall stress at a significance level of p < 0.0001. The time period after initiation of ECMO is a significant factor in the model (p = 0.0097). Time [baseline] was different from the other time points with p = 0.0010. Average mVCFc at baseline is 1.27 ± 0.35 and decreases to 1.01 ± 0.42 after 5 min of ECMO that is then withdrawn. Peak systolic wall stress decreases from 36.0 ± 13.1 at baseline to 29.8 ± 12.1 after 5 min of ECMO. LV dp/dt max decreases from 1,769 ± 453 mmHg/s at baseline to 1,311 ± 513 mmHg/s after exposure to 5 min of ECMO (p = 0.0005). Baseline LV dp/dt max is different from each point after start of ECMO. Diastolic LVdp/dt min increased from -1,340 ± 477 mmHg/s to -908 ± 393 mmHg/s at 5 min. Echocardiographic mVCFc, when considered in isolation or as a function of LV peak systolic wall stress, shows diminished LV function after ECMO. Hemodynamic measurement of LV dp/dt max and LV dp/dt min confirms the observation. Separation of the humoral from mechanical effect of ECMO with the short exposure to the extracorporeal circuit shows that an immediate decrement of LV function occurs at initiation of ECMO, a finding that has not been stressed with previous studies of extracorporeal support. This implies a potentially outcome-limiting deleterious effect for the patient who requires ECMO support for the heart rather than the lungs. We should continue to strive to understand and ameliorate this deleterious effect of the extracorporeal circulation circuit.


Uptake of host cell transforming growth factor-beta by Trypanosoma cruzi amastigotes in cardiomyocytes: potential role in parasite cycle completion.
The cytokine transforming growth factor-beta (TGF-beta) plays various functions in the control of Trypanosoma cruzi infectivity and in the progression of Chagas' disease. When we immunostained T. cruzi-infected cardiomyocytes (after either in vivo or in vitro infections) for TGF-beta, we observed stronger immunoreactivity in parasites than in host cells. TGF-beta immunoreactivity evolved during parasite cycle progression, with intense staining in amastigotes versus very faint staining in trypomastigotes. TGF-beta was present on the surface of amastigotes, in the flagellar pocket, and in intraparasitic vesicles as revealed by electron microscopy. However, no ortholog TGF-beta gene could be identified in the genome of T. cruzi by in silico analysis or by extensive polymerase chain reaction and reverse transcriptase-polymerase chain reaction studies. Immunoreactive TGF-beta was most probably taken up by the parasite from the host cell cytoplasm because such an internalization process of biotinylated TGF-beta could be observed in axenic amastigotes in vitro. These observations represent the first example of a novel mechanism by which a primitive unicellular protozoan can use host cell TGF-beta to control its own intracellular life cycle.


Two-dimensional micro-separation technique for proteins and peptides, combining isoelectric focusing and gel gradient electrophoresis.
The two-dimensional combination of gel electrofocusing and gel gradient electrophoresis yields separate information about differences in net charge and molecular weight of macro-ions. A micro-version of this technique is described. The first dimension electrofocusing run is performed in cylindrical polyacrylamide gel of capillary size, using xylene cyanole FF as a reliable marker dye to indicate the final separation stage when proteins reach their isoelectric points. In the second-dimension run the focused proteins are separated in a continuous slab gel gradient of less than stamp size with total acrylamide concentration ranging from ca. 1% to more than 40%. Spreading of peaks in the gradient slab gel is shown to be related to the approach of protein to its pore limit in the gel. This spreading is a useful indicator of the final position of a protein in the gel if molecular weights are estimated according to the separation pattern in the gradient gel. The method described has been developed for the separation of proteins extracted from large single cells (i.e., neurons of the mollusc Aplysia californica.


Tracking and controlling the spatiotemporal spread of SARS-CoV-2 Omicron variant in South Africa.
South Africa is the focus of the current epidemic caused by Omicron. Understanding the spatiotemporal spread of Omicron in South Africa and how to control it is crucial to global countries. To explore the spatiotemporal spread of Omicron in 9 provinces in South Africa, a province-level geographic prediction model of COVID-19 symptom onset risk, is proposed. It has been found that i) The spatiotemporal spread was relatively slow during the first stage and following the emergence of Omicron in Gauteng. The spatial spread of Omicron accelerated after it had become the dominant variant, and continued to spread from Gauteng to the neighboring provinces and main transport nodes. ii) Compared with current Alert Levels 1-4 in all provinces, the imposition of lockdown in the high-onset-risk Gauteng together with the Alert Level 1 in other 8 provinces, was found to more effectively control the spread of Omicron in South Africa. Moreover, it can reduce the spread of the Omicron epidemic in the provinces where main international airports are located to other parts of the world. iii) Due to declining vaccine efficiency over time, even when the daily vaccination rates in each province increased by 10 times, the daily overall onset risk was only reduced by 0.34%-7.86%. Our study has provided a comprehensive investigation concerning the spatiotemporal dynamics of Omicron and hence provided scientific findings to enable a contribution which will assist in controlling the spatiotemporal spread of Omicron by integrating the prevention measures and vaccination.


Classification, Biological Characteristics and Cultivations of Ganoderma.
Species of Ganoderma (Ling-zhi) have been widely researched and cultivated due to their highly prized medicinal value, which is famous as a traditional Chinese medicine. The aims of this chapter are to (1) review the historical taxonomy of the family Ganodermataceae, (2) provide an account of the genera and species of Ganoderma together with the distributions and habitats, (3) evaluate morphological features and phylogenetic methods to define the genera and species and (4) present two commonly used cultivated methods (wood-log cultivation and substitute cultivation) for Ganoderma.


Interaction of bovine seminalplasmin with Escherichia coli RNA polymerase in the presence of rifampicin.
The interaction of bovine seminalplasmin and rifampicin with E. coli RNA polymerase was studied using fluorescence spectroscopy. Both seminalplasmin and rifampicin are known to be the inhibitors for the initiation of RNA synthesis in E. coli. Rifampicin quenced the intrinsic fluorescence of RNA polymerase and seminalplasmin when excited at 280 nm. However, excess of seminalplasmin reversed the quenching of RNA polymerase fluorescence by rifampicin. Upon addition of rifampicin to the seminalplasmin-RNA polymerase complex, no change in fluorescence spectrum was observed. It appeared that although rifampicin could form complexes with RNA polymerase and seminalplasmin alone, no binding domain was available for rifampicin in the RNA polymerase-seminalplasmin complex. These observations are discussed in the light of the 'initiation site' of E. coli RNA polymerase.


The potential of 3D models and augmented reality in teaching cross-sectional radiology.
What was the educational challenge?The complexity and variability of cross-sectional imaging present a significant challenge in imparting knowledge of radiologic anatomy to medical students.What was the solution?Recent advancements in three-dimensional (3D) segmentation and augmented reality (AR) technology provide a promising solution. These advances allow for the creation of interactive, patient-specific 3D/AR models which incorporate multiple imaging modalities including MRI, CT, and 3D rotational angiography can help trainees understand cross-sectional imaging.How was the solution implemented?To create the model, DICOM files of patient scans with slice thicknesses of 1 mm or less are exported to a computer and imported to 3D Slicer for registration. Once registered, the files are segmented with Vitrea software utilizing thresholding, region growing, and edge detection. After the creation of the models, they are then imported to a web-based interactive viewing platform and/or AR application.What lessons were learned that are relevant to a wider global audience?Low-resource 3D/AR models offer an accessible and intuitive tool to teach radiologic anatomy and pathology. Our novel method of creating these models leverages recent advances in 3D/AR technology to create a better experience than traditional high and low-resource 3D/AR modeling techniques. This will allow trainees to better understand cross-sectional imaging.What are the next steps?The interactive and intuitive nature of 3D and AR models has the potential to significantly improve the teaching and presentation of radiologic anatomy and pathology to a medical student audience. We encourage educators to incorporate 3D segmentation models and AR in their teaching strategies.


Construction of a pH-responsive, ultralow-dose triptolide nanomedicine for safe rheumatoid arthritis therapy.
Rheumatoid arthritis (RA) is a chronicautoimmune disease, marked by joint swelling and pain, articular synovial hyperplasia, as well as cartilage and bone destruction. Triptolide (TP) is an anti-inflammatory molecule but its use to treat RA is limited due to poor solubility and extremely high toxicity. In this study, by encapsulating TP into a star-shaped amphiphilic block copolymer, POSS-PCL-b-PDMAEMA, we engineered a pH-sensitive TP-loaded nanomedicine (TP@NPs) to simultaneously reduce the toxicity of TP and improve its therapeutic efficacy. TP@NPs shows a uniform spherical structure with a hydrodynamic diameter of ~92 nm and notable pH-responsiveness. In vitro TP@NPs showed reduced cytotoxicity and cell apoptosis of treated RAW264.7 cells compared to free TP. And in vivo intravenous injection of indocyanine green-labeled NPs into a collagen-induced arthritis model in mice showed that the engineered compound had potent pharmacokinetic and pharmacodynamic profiles, while exhibiting significant cartilage-protective and anti-inflammatory effects with a better efficacy and neglible systemic toxicity even at an ultralow dose compared to free TP. These results suggest that TP@NPs may be a safe and effective therapy for RA and other autoimmune diseases.


Perinatal Understanding of Mindful Awareness for Sleep (PUMAS): A single-arm proof-of-concept clinical trial of a mindfulness-based intervention for DSM-5 insomnia disorder during pregnancy.
Cognitive-behavioral therapy is effective for prenatal insomnia, but unresolved cognitive arousal limits patient outcomes. Therapies aimed at reducing cognitive arousal may benefit pregnant women with insomnia. This proof-of-concept trial evaluated Perinatal Understanding of Mindful Awareness for Sleep (PUMAS, which combines mindfulness with behavioral sleep strategies) on insomnia, depression, and cognitive arousal. A single-arm trial of 12 pregnant women with DSM-5 insomnia disorder (n = 5/12 with comorbid depression) who received six sessions of PUMAS delivered individually via telemedicine. Pretreatment and posttreatment outcomes included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), pre-sleep arousal scale's cognitive factor (PSASC; nocturnal cognitive arousal), perinatal-focused rumination (appended to PSASC), and Glasgow sleep effort scale. Eleven of 12 patients completed all sessions. Intent-to-treat analyses revealed a 10.83-point reduction in ISI (Cohen's dz = 3.05), resulting in 83.3% insomnia remission. PUMAS produced large reductions in EPDS (Cohen's dz = 2.76 in depressed group), resulting in all five baseline depressed patients remitting from depression. PUMAS produced large reductions in nocturnal cognitive arousal, perinatal-focused rumination, and sleep effort (all Cohen's dzs>2.00). Patients were highly satisfied with PUMAS and identified the telemedicine format and meditation app as positive features of its delivery. Patients rated sleep restriction and guided meditations as the most helpful treatment components. Prenatal insomnia patients were highly engaged in PUMAS, which produced large acute reductions in insomnia, depression, and cognitive arousal. These findings support the concept and feasibility of PUMAS for pregnant women with insomnia who present with or without comorbid depression. NCT04443959.


[Effects of millimetric electromagnetic waves on regional blood flow and effectiveness of multimodal therapy of patients with pulmonary tuberculosis].
The impact of millimetric electromagnetic radiation (MER) on the natural history of the disease was studied in 54 patients with various types of pulmonary tuberculosis. The patients were treated using wavelengths of 6.4 and 7.1 mm on a YAVOR device. Following 10 sessions of MER therapy used in combination with specific drugs, caverns were found to close in 50% of patients at months 2-3 of therapy and in the controls at months 5-6. Infiltrative changes at the site of lesion resolved at weeks 2-3 of MER exposure, but in the controls at months 1-2 of drug therapy. In 5 (10%) out of 54 patients, regional blood flow parameters became normal, 27 (50%) patients were ascertained to have a partial improvement and 22 (40%) had no changes. No changes were seen in the controls as long as 2 weeks either.


Enhancement of simultaneous gold and copper recovery from discarded mobile phone PCBs using Bacillus megaterium: RSM based optimization of effective factors and evaluation of their interactions.
Bioleaching of Au from mobile phone printed circuit boards (MPPCBs) was studied, using Bacillus megaterium which is a cyanogenic bacterium. To maximize Au extraction, initial pH, pulp density, and glycine concentration were optimized via response surface methodology (RSM). Bioleaching of Cu, an important inhibitor on Au recovery, was also examined. To maximize Au recovery, the optimal condition suggested by the models was initial pH of 10, pulp density of 8.13g/l, and glycine concentration of 10g/l. Under the optimal condition, approximately 72% of Cu and 65g Au/ton MPPCBs, which is 7 times greater than the recovery from gold mines, was extracted. Cu elimination from the MPPCBs having a rich content of Au did not cause a significant effect on Au recovery. It was found that when the ratio of Cu to Au is high, Cu elimination can considerably improve Au recovery. B. megaterium could extract the total Au from PCBs containing 130g Au/ton MPPCBs.


Hydroxyethyl starch for perioperative goal-directed fluid therapy in 2020: a narrative review.
Perioperative fluid management - including the type, dose, and timing of administration -directly affects patient outcome after major surgery. The objective of fluid administration is to optimize intravascular fluid status to maintain adequate tissue perfusion. There is continuing controversy around the perioperative use of crystalloid versus colloid fluids. Unfortunately, the importance of fluid volume, which significantly influences the benefit-to-risk ratio of each chosen solution, has often been overlooked in this debate. The volume of fluid administered during the perioperative period can influence the incidence and severity of postoperative complications. Regrettably, there is still huge variability in fluid administration practices, both intra-and inter-individual, among clinicians. Goal-directed fluid therapy (GDFT), aimed at optimizing flow-related variables, has been demonstrated to have some clinical benefit and has been recommended by multiple professional societies. However, this approach has failed to achieve widespread adoption. A closed-loop fluid administration system designed to assist anesthesia providers in consistently applying GDFT strategies has recently been developed and tested. Such an approach may change the crystalloid versus colloid debate. Because colloid solutions have a more profound effect on intravascular volume and longer plasma persistence, their use in this more "controlled" context could be associated with a lower fluid balance, and potentially improved patient outcome. Additionally, most studies that have assessed the impact of a GDFT strategy on the outcome of high-risk surgical patients have used hydroxyethyl starch (HES) solutions in their protocols. Some of these studies have demonstrated beneficial effects, while none of them has reported severe complications. The type and volume of fluid used for perioperative management need to be individualized according to the patient's hemodynamic status and clinical condition. The amount of fluid given should be guided by well-defined physiologic targets. Compliance with a predefined hemodynamic protocol may be optimized by using a computerized system. The type of fluid should also be individualized, as should any drug therapy, with careful consideration of timing and dose. It is our perspective that HES solutions remain a valid option for fluid therapy in the perioperative context because of their effects on blood volume and their reasonable benefit/risk profile.


Risk avoidance, offsetting community effects, and COVID-19: Evidence from an indoor political rally.
The Centers for Disease Control and Prevention (CDC) deem large indoor gatherings without social distancing the "highest risk" activity for COVID-19 contagion. On June 20, 2020, President Donald J. Trump held his first mass campaign rally following the US coronavirus outbreak at the indoor Bank of Oklahoma arena. In the weeks following the event, numerous high-profile national news outlets reported that the Trump rally was "more than likely" the cause of a coronavirus surge in Tulsa County based on time series data. This study is the first to rigorously explore the impacts of this event on social distancing and COVID-19 spread. First, using data from SafeGraph Inc, we show that while non-resident visits to census block groups hosting the Trump event grew by approximately 25 percent, there was no decline in net stay-at-home behavior in Tulsa County, reflecting important offsetting behavioral effects. Then, using data on COVID-19 cases from the CDC and a synthetic control design, we find little evidence that COVID-19 grew more rapidly in Tulsa County, its border counties, or in the state of Oklahoma than each's estimated counterfactual during the five-week post-treatment period we observe. Difference-in-differences estimates further provide no evidence that COVID-19 rates grew faster in counties that drew relatively larger shares of residents to the event. We conclude that offsetting risk-related behavioral responses to the rally-including voluntary closures of restaurants and bars in downtown Tulsa, increases in stay-at-home behavior, displacement of usual activities of weekend inflows, and smaller-than-expected crowd attendance-may be important mechanisms. The online version contains supplementary material available at 10.1007/s11166-021-09359-4.


Effects of bradykinin on the survival of multiterritory perforator flaps in rats.
Bradykinin, a vasoactive peptide, has many biological functions. For example, it accelerates angiogenesis. Thus, we studied the effects of bradykinin on the survival of perforator flaps. Averagely, 50 male Sprague-Dawley rats were divided into control and bradykinin groups and underwent procedures to the multiterritory perforator flap. Areas of flap survival were tested 7 days later. Flap perfusion was evaluated by laser Doppler imaging. We assessed the extent of autophagy by determining LC3-II/I, Beclin 1, and p62. Flap angiogenesis was assessed by immunohistochemistry and H&E staining. We measured the level of vascular endothelial growth factor (VEGF) protein using western blot. We assessed oxidative stress by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels. The apoptotic index was also evaluated by western blot, and we determined nitric oxide (NO) production using an NO assay kit. The bradykinin group exhibited significantly larger areas of flap survival, higher blood supply, and more neovascularization. The bradykinin group also had higher SOD activity, higher VEGF expression and NO content, and reduced MDA compared to the control group. Rats treated with bradykinin also had lower levels of apoptosis and autophagy relative to the control group. Our results suggest that bradykinin promotes the survival of multiterritory perforator flaps by increasing angiogenesis, promoting the release of NO, suppressing apoptosis, reducing oxidative stress, and inhibiting autophagy.


Drop in one-to-one nursing linked with infant mortality.
A REDUCTION in one-to-one nursing in neonatal intensive care units has been linked in a new study to a higher death rate.


Entomological aspects and the role of human behaviour in malaria transmission in a highland region of the Republic of Yemen.
The Republic of Yemen has the highest incidence of malaria in the Arabian Peninsula, yet little is known of its vectors or transmission dynamics. A 24-month study of the vectors and related epidemiological aspects of malaria transmission was conducted in two villages in the Taiz region in 2004-2005. Cross-sectional blood film surveys recorded an overall malaria infection rate of 15.3 % (250/1638), with highest rates exceeding 30 % in one village in May and December 2005. With one exception, Plasmodium malariae, all infections were P. falciparum. Seven Anopheles species were identified among 3407 anophelines collected indoors using light traps (LT) and pyrethrum knockdown catches (PKD): Anopheles arabiensis (86.9 %), An. sergentii (9 %), An. azaniae, An. dthali, An. pretoriensis, An. coustani and An. algeriensis. Sequences for the standard barcode region of the mitochondrial COI gene confirmed the presence of two morphological forms of An. azaniae, the typical form and a previously unrecognized form not immediately identifiable as An. azaniae. ELISA detected Plasmodium sporozoites in 0.9 % of 2921 An. arabiensis (23 P. falciparum, two P. vivax) confirming this species as the primary malaria vector in Yemen. Plasmodium falciparum sporozoites were detected in An. sergentii (2/295) and a single female of An. algeriensis, incriminating both species as malaria vectors for the first time in Yemen. A vector in both wet and dry seasons, An. arabiensis was predominantly anthropophilic (human blood index = 0.86) with an entomological inoculation rate of 1.58 infective bites/person/year. Anopheles sergentii fed on cattle (67.3 %) and humans (48.3; 20.7 % mixed both species), but only 14.7 % were found in PKDs, indicating predominantly exophilic behaviour. A GIS analysis of geographic and socio-economic parameters revealed that An. arabiensis were significantly higher (P < 0.001) in houses with televisions, most likely due to the popular evening habit of viewing television collectively in houses with open doors and windows. The predominantly indoor human biting vectors recorded in this study could be targeted effectively with LLINs, indoor residual spraying and/or insecticide-treated window/door curtains reinforced by education to instil a perception that effective and affordable malaria prevention is achievable.


The role of guidance in delivering cardiac resynchronization therapy: A systematic review and network meta-analysis.
Positioning the left ventricular lead at the optimal myocardial segment has been proposed to improve cardiac resynchronization therapy (CRT) response. We performed a systematic review and network meta-analysis evaluating echocardiographic and clinical response delivered with different guidance modalities compared to conventional fluoroscopic positioning. Randomized trials with ≥6 months follow-up comparing any combination of imaging, electrical, hemodynamic, or fluoroscopic guidance were included. Imaging modalities were split whether one modality was used: cardiac magnetic resonance (CMR), speckle-tracking echocardiography (STE), single-photon emission computed tomography, cardiac computed tomography (CT), or a combination of these, defined as "multimodality imaging." Twelve studies were included (n = 1864). Pair-wise meta-analysis resulted in significant odds of reduction in left ventricular end-systolic volume (LVESV) >15% (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.05-2.13, P = .025) and absolute reduction in LVESV (standardized mean difference [SMD] -0.25, 95% CI -0.43 to -0.08, P = .005) with guidance. CMR (OR 55.3, 95% CI 4.7-656.9, P = .002), electrical (OR 17.0, 95% CI 2.9-100, P = .002), multimodality imaging (OR 4.47, 95% CI 1.36-14.7, P = .014), and hemodynamic guidance (OR 1.29-28.0, P = .02) were significant in reducing LVESV >15%. Only STE demonstrated a significant reduction in absolute LVESV (SMD -0.38, 95% CI -0.68 to -0.09, P = .011]. CMR had the highest probability of improving clinical response (OR 17.9, 95% CI 5.14-62.5, P < .001). Overall, guidance improves CRT outcomes. STE and multimodality imaging provided the most reliable evidence of efficacy. Wide CIs observed for results of CMR guidance suggest more powered studies are required before a clear ranking is possible.


Antimicrobial activity of terpenoids from Trichodesma amplexicaule Roth.
T. amplexicaule Roth. has been investigated phytochemically for biologically active constituents from the benzene extract. This yielded a mixture of terpenoids: beta-sitosterol, alpha-amyrin, lupeol, hexacosanoic acid, ceryl alcohol and hexacosane. The sequential extracts, isolated terpenoids and reference antibiotics were screened for their possible bioactivities against selected pathogenic bacteria, Escherichia coli, Staphylococcus aureus and fungi, Aspergillus flavus and Penicillium chrysogenum etc. Out of the sequential extracts, the benzene extract was more potent against S. aureus (IZ = 10.36) and R. phaseoli (IZ = 10.69). The inhibition zones of isolated terpenoids were also recorded and the activity index was calculated and it was found that hexacosane was more active (IZ = 13.39) against E. coli and hexacosanoic acid had greater activity against A. flavus (IZ = 11.56). The present study deals with antimicrobial screening of sequential extracts and isolated terpenoids.


Erythropoietin processing in erythropoietic system and central nervous system.
We describe possible functions of carbohydrates attached to growth factors and strategies to examine the functions, concentrating on erythropoietin, a major regulator of erythropoiesis. Erythropoietin in erythropoiesis functions as an endocrine hormone; it is produced by kidney cells and transferred into the circulation to hemopoietic sites. In the brain, erythropoietin acts on neurons in a paracrine fashion. Comparison of glycosylation has been made between kidney and brain erythropoietins.


[Venous thromboembolism: What other risk factors in a North African population? A study of 276 cases].
Venous thromboembolism is a multicausal disease. Understanding interactions between risk factors is the key to advance knowledge about the etiology of venous thrombosis. These interactions are still unclear. In addition to traditional risk factors, there is data about many other risk factors, recorded with few populations based prospective epidemiologic studies or punctually reported. Interactions between these risk factors remain unclear. The aim of our work is to identify and analyze combinations of risk factors. This is a retrospective, single-center study, which investigates the etiology of venous thromboembolism, on the records of patients hospitalized in internal medicine for venous thrombosis, over a period of 12 years. We selected 276 cases. The average age was 51 years. At least, we found one traditional risk factors in 87 % of cases, 34 patients had no traditional risk factors. Suspected risk factors were found in 81 % of cases and there was at least one punctually reported factor in 34 % of cases. The combination of risk factors mostly found was association of traditional and suspected risk factors. In more than 50 % of patients, we noted at least, more than one traditional or one suspected risk factors. Among 18 patients presenting only suspected risk factors, there was at least combination of 3 risk factors per patient. The role of suspected risk factors in the occurrence of venous thrombosis was not negligible in this work. Our data suggest a hypothesis that it's through their association that suspected risk factors might be able becoming comparable to traditional risk factors.


Cultural and educational disparities in the use of primary and preventive health care services among midlife women in Israel.
This study aimed to assess rates of primary and preventive healthcare use among women in midlife from different cultural origins and to identify sociodemographic and health characteristics that could explain cultural differences in health care utilization. Data were collected for the Women's Health in Midlife National Study in Israel, in which women aged 45-64 were randomly selected according to age and ethnic/origin group strata: Long-term Jewish residents (n = 540), immigrants from the former Soviet Union (n = 151), and Arab women (n = 123). Interviews included measures of primary and preventive visits, clinical screening services (mammogram, Pap smear, bone density), health and lifestyle, and sociodemographics. Long-term residents reported more preventive visits and screening tests and lower use of primary care, compared with immigrants and Arab women. In multivariate analyses, cultural group, education, self-rated health, and health motivation were significantly associated with utilization of primary and preventive care. Ethnic/origin group differences were mostly related to cultural differences and not to financial barriers or medical factors. For example, among the more traditional group, namely, Arab women, low use of preventive gynecologic care seemed to be related to the lack of physicians of the same culture and gender. The findings underscore the importance of the primary care physician, especially in minority groups, as a provider who can identify at-risk groups and serve as a gateway to health promotion. The findings also suggest that the lack of female providers may be one explanation for the low utilization of gynecologic services among women from traditional cultures.


Possible adrenal involvement in hydroxyurea toxicity defense mechanisms.
Changes in blood biochemistry, resembling adrenocortical hyperfunction, induced by oral administration with hydroxyurea (HYD) at a dosage of 800 mg/Kg/d for 5 days (K+ and total protein decrease, total cholesterol increase) are not modified or enhanced (total protein) by adrenalectomy. Adrenalectomy dramatically enhanced the decrease of WBC and neutrophils normally induced by HYD. Replacement therapy with corticosterone attenuated and/or delayed the above changes. Normally-functioning adrenocortical tissue may play a role in protection against HYD haematological toxicity in the rat and the drug-induced hypothalamus pituitary mediated adrenocortical activation seems to represent a mechanism capable of counteracting drug toxicity.


Assessing the climate change mitigation potential from food waste composting.
Food waste is a dominant organic constituent of landfills, and a large global source of greenhouse gases. Composting food waste presents a potential opportunity for emissions reduction, but data on whole pile, commercial-scale emissions and the associated biogeochemical drivers are lacking. We used a non-invasive micrometeorological mass balance approach optimized for three-dimensional commercial-scale windrow compost piles to measure methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2) emissions continuously during food waste composting. Greenhouse gas flux measurements were complemented with continuous oxygen (O2) and temperature sensors and intensive sampling for biogeochemical processes. Emission factors (EF) ranged from 6.6 to 8.8 kg CH4-C/Mg wet food waste and were driven primarily by low redox and watering events. Composting resulted in low N2O emissions (0.01 kg N2O-N/Mg wet food waste). The overall EF value (CH4 + N2O) for food waste composting was 926 kgCO2e/Mg of dry food waste. Composting emissions were 38-84% lower than equivalent landfilling fluxes with a potential net minimum savings of 1.4 MMT CO2e for California by year 2025. Our results suggest that food waste composting can help mitigate emissions. Increased turning during the thermophilic phase and less watering overall could potentially further lower emissions.


Effects of Oil Types and Fat Concentrations on Production Performance, Egg Quality, and Antioxidant Capacity of Laying Hens.
In this study, soybean oil, lard and mixed oils were added to the feed in two concentrations (1.5% and 3% of each), resulting in six experimental groups. The control group was fed with a base diet without additions, and used to compare the effects of feeding on production performance and egg quality of laying hens. The results demonstrated that: (1) the 3% supplemented-oils or lard group showed a decrease in laying rate; (2) 1.5% and 3% added-lard significantly increased the total amount of unsaturated fatty acids in eggs, compared to the control group; (3) 1.5% and 3% soybean oil increased the content of mono/polyunsaturated fatty acids, cholesterol, phospholipids and choline in eggs; (4) glutathione peroxidase (GPx) and superoxide dismutase (SOD) contents were increased in all groups, being the most evident in the lard-treated group; (5) all experimental groups showed an increase in the content of essential and non-essential amino acids in albumen; (6) 3% oils, especially the mixed oils, damaged the structure of globules of cooked egg yolks. Therefore, the use of 1.5% soybean oil in the feed diet of Hyline brown hens resulted in the most adequate oil to ensure animal health and economic significant improvements in this experiment.


Autosterilization of Contaminated and Devascularized Bone Fragments Through a Subcutaneous Bone Pouch.
The purpose of this article was to present results of cases using a subcutaneous bone pouch technique and to assess the potential "autosterilization" effect that occurs when these contaminated free bone fragments are placed in nontraumatized tissue. Retrospective review of prospectively collected data. Community-Based Level 1 Trauma Center. Eight patients were consented for the described technique, and data were collected over an 8-year period. Placement of fragments into a surgically created subcutaneous pouch in a nontraumatized tissue zone, followed by delayed, cultured, and attempted reimplantation at the initial injury site. Culture results after extraction of bone fragments from subcutaneous bone pouch and clinical outcomes after reimplantation into initial open fracture site. All 8 cases undergoing this technique resulted in healing of the subcutaneous bone pouch without signs or symptoms of infection at the time of attempted reimplantation or fragment removal. Four of the 8 cases had successful reimplantation and union at the open fracture site. Preserving devascularized bone fragments in a subcutaneous pouch in a region of nontraumatized tissue appears to be a safe procedure that allows for an "autosterilization" type of process to occur. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


[Impact and risks of cost cutting programs on the quality of hospital care in Switzerland].
Cost-minimization programs in Switzerland either in the public or the private sector have impact on quality and accessibility of the health care system. Rationalization may induce in fact hidden rationing of care and increases the workload of the health care workers involved. The relation of hospital staffing to inpatient quality of care are important issues. The reduction of funds may place patients at risk, due to lower staffing levels. Patient to nurses ratio have a substantial effect on inpatient mortality and nurse burnout. Research in Switzerland is needed to define the measurement of the nursing case mix on the basis of discharge data and to elucidate the factors influencing the staffing levels of nurses and the mix of nursing personnel in hospitals. Due to reduced funding the ability of hospitals to handle emergency cases may be compromised. The impact on quality and risks of unreflected cost minimization programs in hospitals but also the whole health care system are important and worth of public notice. Possible solutions for a health care reform in Switzerland are outlined and discussed.


Treatment of metastatic breast cancer during pregnancy: we need to talk!
Metastatic breast cancer during pregnancy is a challenging situation. The literature yield in this topic is poor given the rarity of the disease. Management strategies should be discussed in a multidisciplinary manner and each case have to be counselled separately and informed about the pros and cons of different treatment options. Here, we report a case of metastatic breast cancer initially diagnosed during pregnancy. We discuss the clinical course and dilemmas governing the management decisions.


Low density lipoprotein receptor-related protein 1 mediated endocytosis of β1-integrin influences cell adhesion and cell migration.
The low density lipoprotein receptor-related protein 1 (LRP1) has been shown to interact with β1-integrin and regulate its surface expression. LRP1 knock-out cells exhibit altered cytoskeleton organization and decreased cell migration. Here we demonstrate coupled endocytosis of LRP1 and β1-integrin and the involvement of the intracellular NPxY2 motif of LRP1 in this process. Mouse embryonic fibroblasts harboring a knock in replacement of the NPxY2 motif of LRP1 by a multiple alanine cassette (AAxA) showed elevated surface expression of β1-integrin and decreased β1-integrin internalization rates. As a consequence, cell spreading was altered and adhesion rates were increased in our cell model. Cells formed more focal adhesion complexes, whereby in vitro cell migration rates were decreased. Similar results could be observed in a corresponding mouse model, the C57Bl6 LRP1 NPxYxxL knock in mice, therefore, the biochemistry of cellular adhesion was altered in primary cortical neurons. In vivo cell migration experiments demonstrated a disturbance of neuroblast cell migration along the rostral migratory stream. In summary, our results indicate that LRP1 interacts with β1-integrin mediating integrin internalization and thus correlates with downstream signaling of β1-integrin such as focal adhesion dynamics. Consequently, the disturbance of this interaction resulted in a dysfunction in in vivo and in vitro cell adhesion and cell migration.


Idiopathic perforation of the biliary tract in infancy and childhood.
The case of a 25-day-old Saudi boy with spontaneous perforation of the biliary tract is reported. The mode of presentation and treatment are described and the literature on the subject reviewed.


Immunohistochemical assay for detection of K-ras protein expression in metastatic colorectal cancer.
The monoclonal antibodies (mAbs) that target the epidermal growth factor receptor (EGFR) had expanded the range of treatment options for metastatic colorectal cancer. However, such type of treatment was shown to be ineffective if there is K-ras mutation. In most previous studies K-ras gene mutation was mainly assessed by PCR. Our work is designed to detect K-ras protein expression by immunohistochemistry (IHC) aiming to reach a preliminary method that could be confirmed by PCR and considered an alternative way for the detection of K-ras aberration. We are also aiming to find a relation between K-ras protein expression and K-ras gene mutation. Paraffin embedded tissue samples from 26 metastatic colorectal cancer (mCRC) patients were analyzed for K-ras protein expression by IHC using Rap1A polyclonal antibody. Staining patterns were subjectively assessed and correlated with clinicopathological features. The results were statistically evaluated using the Chi-square test. K-ras cytoplasmic positivity was observed in 42.3% of cases. The positivity was either strong in 26.9% or moderate in 15.4%. With respect to adenocarcinoma variants, 50% of cases were positive for K-ras protein expression while all mucinous and signet ring types were negative. The positivity was noted in 50% of moderately differentiated GII colorectal carcinomas as compared with 38.9% in poorly differentiated GIII. Positive staining was observed in 40% of cases with positive lymph node metastasis while in the absence of nodal metastasis the positivity was 45.5%. No significant correlation was found between clinicopathological parameters and K-ras staining results. IHC may compliment PCR in the detection of K-ras mutation.


Etiologic distribution of isolated abducens nerve palsy: Analysis of 807 patients and literature review.
The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated abducens nerve palsy by recruiting patients from all departments in a referral-based university hospital. We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies. The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes. The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.


The Stomach: a Rare Site for Metastatic Solid Pseudopapillary Neoplasm of the Pancreas.
Metastatic solid pseudopapillary neoplasms of the pancreas are rare, and the stomach is also a rare site for metastases. We present a case of a lady with solid pseudopapillary neoplasm of the pancreas who previously had a distal pancreatectomy but subsequently had multiple hepatic, adrenal peritoneal and nodal metastases. She developed dyspepsia and on oesophagogastroduodenoscopy, was found to have gastric metastases as well. We believe this is the first reported case of metastatic solid pseudopapillary neoplasm of the pancreas to the stomach.


Microwave irradiation: an important tool to functionalize fullerenes and carbon nanotubes.
Microwave irradiation is an important tool in the functionalization of fullerenes and carbon nanotubes. These are compounds with excellent properties that make them useful for the development of optoelectronic organic devices. The applications of microwaves in the chemistry of these materials are reviewed.


Supramaximal test results of male and female speed skaters with particular reference to methodological problems.
Six male and six female elite speed skaters were tested during two bicycle ergometer tests: a 30 s sprint test and a 2.5 min supra maximal test. During the 2.5 min test oxygen consumption was measured every 30 s. The males showed 30-31% higher mean power output values both during the sprint test (1103 versus 769 Watt) and during the 2.5 min test (570 versus 390 Watt). Maximal oxygen consumption was 31% higher for the males than for the females (5.10 versus 3.50 1.min-1). However, when expressed per kilogram lean body weight (LBM), power output and oxygen consumption was equal for both sexes. Differences between present and previous results are most likely due to methodological problems with the estimation of load during the supra maximal test. Subjects appear to experience difficulties in distributing their power output over the 2.5 min if they are tested for the first time. For experienced skaters and cyclists, fixed levels of 19 W.kgLBM-1 as initial load setting for the sprint test and 8 W.kg LBM-1 for the 2.5 min test are recommended.


Assessment of peri-extubation pain by visual analogue scale in the adult intensive care unit: a prospective observational study.
This prospective observational study was undertaken in order to assess pain experienced by intensive care unit patients at the time of extubation and to identify factors associated with pain of at least moderate intensity. Prospective observational study. Intensive care unit at a university hospital. During a 1-year period the presence, severity and clinical predictors of orofacial and/or chest pain among patients undergoing removal of endotracheal tubes was assessed. Pain was evaluated using a visual analogue scale (VAS). Of 332 extubated patients, 203 could be evaluated. During the peri-extubation period, pain was significantly associated with a SAPS II score more than 36 ( p=0.03) and duration of mechanical ventilation (MV) of 6 days or more ( p=0.002), whereas intubation in the operating room was associated with less pain ( p=0.001). Pain of at least moderate intensity (VAS score >30 mm) was reported by 73% of patients and pain of severe intensity (VAS score >50 mm) was reported by 45% of patients. MV duration of 6 days or more was the only independent risk factor for pain of at least moderate intensity (OR 2.4, 95% CI 1.03-5.4, p=0.04). We also observed that pain had resolved 1 h after extubation in the majority of patients. Our results suggest that, in intensive care unit patients, peri-extubation pain is frequent and should be considered for treatment, especially in patients with longer intubation.


14-3-3 regulates the nuclear import of class IIa histone deacetylases.
Class IIa histone deacetylases (HDACs) form complexes with a class of transcriptional repressors in the nucleus. While screening for compounds that could block the association of HDAC4 with the BTB domain-containing transcriptional repressor Bach2, we discovered that phorbol 12-myristate 13-acetate (PMA) induced the cytoplasmic retention of HDAC4 mutants lacking a nuclear export signal (NES). Although PMA treatment and PKD overexpression has been proposed to facilitate the nuclear export of class IIa HDACs by creating 14-3-3 binding sites containing phosphoserines, our experiments using HDAC mutants demonstrated that PMA greatly reduces nuclear import. PMA treatment repressed the NLS activity in a manner dependent on 14-3-3 binding. These results suggest that nuclear HDAC4 is not tethered in the nucleus, but instead shuttles between the nucleus and the cytoplasm. Phosphorylation-induced 14-3-3 binding biases the balance of nucleo-cytoplasmic shuttling toward the cytoplasm by inhibiting nuclear import.


Predictors of maternal parenting self-efficacy for infants and toddlers: A Jordanian study.
This study aimed to investigate the predictors of maternal parenting self-efficacy when the children concerned are in the early years of life. A descriptive-analytical research study was carried out among 213 women who were in the early months of the postpartum period and attending healthcare facilities in Irbid, Jordan. The State Anxiety Inventory (SAI) and the Maternal Parenting Self-Efficacy (PMP S-E) tool were used to collect the data. A significant correlation was found between the scores in self-efficacy and the quality of marriage relations (B = 3.56, P = 001), family income (B = 1.97, P = .05), employment (B = 4.027, P = .027), education (B = 2.48, P = .004), and living with extended family (B = 5.28, P = .02). The findings of this study show that MPSE is significantly associated with various predictors. These predictors are the mother's education, income, whether she lives with extended family, her quality of marriage, and her employment. Maternal anxiety was found not to be a predictor for MPSE and this may explain other factors such as social support and living with extended family. It is essential for nurses to understand maternal parenting self-efficacy, therefore, including the concept of maternal parenting self-efficacy in nursing curricula can help raise awareness of this important concept. Understanding maternal parenting self-efficacy is necessary for nurses to evaluate the mothers' parenting self-efficacy.


Nonodontogenic Cysts of the Jaws and Treatment in the Pediatric Population.
Nonodontogenic cysts within the jaws are not a common presentation in the pediatric population. Cysts within the pediatric population tend to be developmental and odontogenic in nature. Although nonodontogenic cysts of the jaws are relatively uncommon, it is imperative the clinician understand their clinical behavior and management because failure to do so can result in increased patient morbidity. The nonodontogenic cysts of the jaws that are most often encountered are the central giant cell granuloma, traumatic bone cavity, aneurysmal bone cyst, nasopalatine duct cyst, and nasolabial cyst. This article reviews common clinical findings, radiographic features, histopathologic features, and current treatments of nonodontogenic cysts.


Detection in vivo of protein-DNA interactions within the lac operon of Escherichia coli.
Studies of the sequence-specific binding of proteins to DNA have so far relied on in vitro experiments using cloned restriction fragments containing the relevant DNA sequences. We have applied the genomic sequencing technique of Church and Gilbert to show that the interactions observed in vitro occur in vivo. We use this approach to study the binding of regulatory proteins to the lac operon in vivo and detect changes in the reactivity (inhibition or enhancement) of guanines to methylation by dimethyl sulphate caused by the proximity of proteins to the N-7 atom of these guanines. We can detect the simultaneous binding of the catobolite gene activator protein (CAP) and the Lac repressor to their specific recognition sequences, and following induction of the lac operon we observe effects that are related to RNA polymerase binding or RNA elongation. We have successfully used oligonucleotide probes as short as 17 bases to display genomic sequence.


Relationship between percent positive biopsies and biochemical outcome after permanent interstitial brachytherapy for clinically organ-confined carcinoma of the prostate gland.
Recently, the percentage of positive prostate biopsies has been reported to be statistically significant in predicting the biochemical outcome after either radical prostatectomy or 3-dimensional conformal external beam radiotherapy. In this study, we evaluated the impact of the percentage of positive prostate biopsies in predicting the 5-year biochemical outcome for patients with clinically organ-confined prostate cancer undergoing permanent interstitial brachytherapy. Two hundred sixty-two hormone naive patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins, using either 103Pd or 125I for clinical T1b/T2b NXM0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. The actual percentage of positive biopsies (number of positive biopsies/total number of biopsies) was determinable for 255 of the 262 patients. Of the evaluated cases, 133 patients were implanted with 103Pd and 122 patients with 125I. The median patient age was 68 years (range 48-81). The median follow-up was 38.6 months (range 6-73). Follow-up was calculated from the day of implantation. Patients were stratified by the percentage of positive biopsies into the following groups: <34%, 34-50%, and >50%. Additional clinical parameters evaluated included patient age, clinical T-stage, Gleason score, pretreatment prostate specific antigen (PSA), risk group, and prostate volume. Low-risk patients were staged as clinical T1c/T2a, Gleason score < or =6, and pretreatment PSA < or =10 ng/mL, intermediate-risk patients presented with one unfavorable prognostic parameter, and high-risk patients presented with two or more unfavorable prognostic parameters (clinical stage T2b, PSA >10 ng/mL, Gleason score > or =7). Treatment parameters included the use of supplemental external beam radiation and choice of isotope. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology consensus definition. For the 255 evaluated patients, the 5-year actuarial biochemical no evidence of disease survival rate was 92.5%. For patients with low, intermediate, and high-risk disease, 95.8%, 98.1%, and 79.4% of patients were free of biochemical failure, respectively. When each risk group was stratified into the percent positive biopsy categories of <34%, 34-50%, and >50%, no statistical difference was found in biochemical outcome for the biopsy subgroups. In multivariate analysis, none of the clinical or treatment parameters predicted for failure in the low-risk group; only Gleason score was predictive for intermediate-risk patients and only PSA for high-risk patients. In the overall population, PSA and Gleason score were both found to be predictors of biochemical failure, but not risk group, clinical stage, or percentage of positive biopsies. There was no significant dependence between the percent positive biopsy group and the Kaplan-Meier biochemical survival rates for any of the various subgroups of clinical and treatment parameters, except for clinical stage T1c-T2a (p = 0.006). The median postimplant PSA was 0.2 ng/mL for patients with either low-risk disease or <34% positive biopsies and 0.1 ng/mL for all other risk groups or percent positive biopsy subgroups. Although a significant trend was found for biochemical failure with increasing percent positive biopsies in the overall population, our results suggest that the percentage of positive biopsies is not statistically significant in predicting the 5-year biochemical disease-free outcome for patients with low, intermediate, and high-risk disease undergoing permanent prostate brachytherapy. Only the Gleason score in intermediate-risk patients and the pretreatment PSA level in high-risk patients was predictive of biochemical failure. We believe this relative lack of significance for the percentage of positive biopsies is a result of dose escalation far exceeding other radiotherapy modalities and the ability to aggressively treat the periprostatic region compared with radical prostatectomy by way of the accurate placement of periprostatic seeds.


Specificities and binding properties of eight monoclonal antibodies against carcinoembryonic antigen.
Eight different monoclonal antibodies against CEA were derived from fusions with spleen cells of mice immunized with highly purified CEA. All eight antibodies were IgG l, kappa and had isoelectric points between pH 6.5 and 7.5. They reacted strongly with native CEA, Smith degraded CEA (SI-stage) and CEAlow, only marginally with reduced and alkylated CEA and not at all with orosomucoid, indicating that they were directed against conformation dependent protein determinants. Two antibodies cross-reacted strongly with nonspecific cross-reacting antigen (NCA) while none of the antibodies cross-reacted with biliary glycoprotein I (BGP I). At least six different epitopes in the peptide moiety of CEA were recognized by this series of monoclonal antibodies. At least two of these appeared to occur twice in the molecule, possibly indicating that CEA contains two or more homology regions. The affinity constants of three of the CEA-'specific' antibodies were found to be very high, e.g. 1.2, 3.3, and 7.4 X 10(8) M-1, respectively.


Optimal parameters for laccase-mediated destaining of Coomassie Brilliant Blue R-250-stained polyacrylamide gels.
The data presented in this article are related to the research article entitled "Destaining of Coomassie Brilliant Blue R-250-stained polyacrylamide gels with fungal laccase" [1]. Laccase is a class of multicopper oxidases that can catalyze oxidation of recalcitrant dyestuffs. This article describes optimal parameters for destaining of polyacrylamide gels, stained with Coomassie Brilliant Blue R-250, with laccase from basidiomycete Cerrena sp. strain HYB07. Effects of laccase activity, mediator type and concentration, temperature and time on destaining of polyacrylamide gels were evaluated with respect to gel background intensity and protein band signals, and the optimal destaining effects were obtained with 15 U mL(-1) laccase and 2 μM ABTS at 37 °C after 2 h.


Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia.
Interferon (IFN)-gamma, the main cytokine responsible for immunological defense against Toxoplasma gondii, is essential in all infected tissues, including the central nervous system. However, IFN-gamma-activated microglia may cause tissue injury through production of toxic metabolites such as nitric oxide (NO), a potent inducer of central nervous system pathologies related to inflammatory neuronal disturbances. Despite potential NO toxicity, neurodegeneration is not commonly found during chronic T. gondii infection. In this study, we describe decreased NO production by IFN-gamma-activated microglial cells infected by T. gondii. This effect involved strong inhibition of iNOS expression in IFN-gamma-activated, infected microglia but not in uninfected neighboring cells. The inhibition of NO production and iNOS expression were parallel with recovery of neurite outgrowth when neurons were co-cultured with T. gondii-infected, IFN-gamma-activated microglia. In the presence of transforming growth factor (TGF)-beta1-neutralizing antibodies, the beneficial effect of the parasite on neurons was abrogated, and NO production reverted to levels similar to IFN-gamma-activated uninfected co-cultures. In addition, we observed Smad-2 nuclear translocation, a hallmark of TGF-beta1 downstream signaling, in infected microglial cultures, emphasizing an autocrine effect restricted to infected cells. Together, these data may explain a neuropreservation pattern observed during immunocompetent host infection that is dependent on T. gondii-triggered TGF-beta1 secretion by infected microglia.


X-ray image based COVID-19 detection using evolutionary deep learning approach.
Radiological methodologies, such as chest x-rays and CT, are widely employed to help diagnose and monitor COVID-19 disease. COVID-19 displays certain radiological patterns easily detectable by X-rays of the chest. Therefore, radiologists can investigate these patterns for detecting coronavirus disease. However, this task is time-consuming and needs lots of trial and error. One of the main solutions to resolve this issue is to apply intelligent techniques such as deep learning (DL) models to automatically analyze the chest X-rays. Nevertheless, fine-tuning of architecture and hyperparameters of DL models is a complex and time-consuming procedure. In this paper, we propose an effective method to detect COVID-19 disease by applying convolutional neural network (CNN) to the chest X-ray images. To improve the accuracy of the proposed method, the last Softmax CNN layer is replaced with a K -nearest neighbors (KNN) classifier which takes into account the agreement of the neighborhood labeling. Moreover, we develop a novel evolutionary algorithm by improving the basic version of competitive swarm optimizer. To this end, three powerful evolutionary operators: Cauchy Mutation (CM), Evolutionary Boundary Constraint Handling (EBCH), and tent chaotic map are incorporated into the search process of the proposed evolutionary algorithm to speed up its convergence and make an excellent balance between exploration and exploitation phases. Then, the proposed evolutionary algorithm is used to automatically achieve the optimal values of CNN's hyperparameters leading to a significant improvement in the classification accuracy of the proposed method. Comprehensive comparative results reveal that compared with current models in the literature, the proposed method performs significantly more efficient.


Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration.
Recent biochemical observations have suggested the abnormalities in the gamma-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCP i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of alpha 1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebellum (-15%) were significantly decreased. In addition, [(35)S]t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain.


Immune profiles to distinguish hospitalized versus ambulatory COVID-19 cases in older patients.
A fraction of patients with COVID-19 develops severe disease requiring hospitalization, while the majority, including high-risk individuals, experience mild symptoms. Severe disease has been associated with higher levels of antibodies and inflammatory cytokines but often among patients with diverse demographics and comorbidity status. This study evaluated hospitalized vs. ambulatory patients with COVID-19 with demographic risk factors for severe COVID-19: median age of 63, >80% male, and >85% black and/or Hispanic. Sera were collected four to 243 days after symptom onset and evaluated for binding and functional antibodies as well as 48 cytokines and chemokines. SARS-CoV-2-specific antibody levels and functions were similar in ambulatory and hospitalized patients. However, a strong correlation between anti-S2 antibody levels and the other antibody parameters, along with higher IL-27 levels, was observed in hospitalized but not ambulatory cases. These data indicate that antibodies against the relatively conserved S2 spike subunit and immunoregulatory cytokines such as IL-27 are potential immune determinants of COVID-19.


Molecular immune recognition of botulinum neurotoxin B. The light chain regions that bind human blocking antibodies from toxin-treated cervical dystonia patients. Antigenic structure of the entire BoNT/B molecule.
We recently mapped the regions on the heavy (H) chain of botulinum neurotoxin, type B (BoNT/B) recognized by blocking antibodies (Abs) from cervical dystonia (CD) patients who develop immunoresistance during toxin treatment. Since blocking could also be effected by Abs directed against regions on the light (L) chain, we have mapped here the L chain, using the same 30 CD antisera. We synthesized, purified and characterized 32 19-residue L chain peptides that overlapped successively by 5 residues (peptide L32 overlapped with peptide N1 of the H chain by 12 residues). In a given patient, Abs against the L chain seemed less intense than those against H chain. Most sera recognized a limited set of L chain peptides. The levels of Abs against a given region varied with the patient, consistent with immune responses to each epitope being under separate MHC control. The peptides most frequently recognized were: L13, by 30 of 30 antisera (100%); L22, by 23 of 30 (76.67%); L19, by 15 of 30 (50.00%); L26, by 11 of 30 (36.70%); and L14, by 12 of 30 (40.00%). The activity of L14 probably derives from its overlap with L13. The levels of Ab binding decreased in the following order: L13 (residues 169-187), L22 (295-313), L19 (253-271), and L26 (351-369). Peptides L12 (155-173), L18 (239-257), L15 (197-215), L1 (1-19) and L23 (309-327) exhibited very low Ab binding. The remaining peptides had little or no Ab-binding activity. The antigenic regions are analyzed in terms of their three-dimensional locations and the enzyme active site. With the previous localization of the antigenic regions on the BoNT/B H chain, the human Ab recognition of the entire BoNT/B molecule is presented and compared to the recognition of BoNT/A by human blocking Abs.


The effect of acute physical and mental stress on soluble cellular adhesion molecule concentration.
This study investigated the impact of acute physical and mental stress on serum concentrations of vascular cell adhesion molecule (VCAM)-1 and CX3CL1/fractalkine. Male volunteers (n=20; 21.3±0.55years of age) completed a graded treadmill test to exhaustion and a 20-minute mental stress task (Stroop Color-Word Test, mental arithmetic) on separate, non-consecutive days. Heart rate (HR) was measured at baseline and throughout exercise and mental stress. Blood was collected at baseline (PRE), immediately following (POST) and 30min after (POST30) exercise and mental stress. Soluble VCAM-1 and fractalkine were quantified in participant serum via enzyme-linked immunosorbent assays. Both treadmill exercise and the mental stress task significantly increased participant HR; although, exercise resulted in a substantially greater increase in participant HR compared to mental stress (197.82±11.99 vs. 38.67±3.10% [p<0.001]). VCAM-1 (815.74±139.55 vs. 738.67±131.59ng/mL [p=0.002]) and fractalkine (1.032±0.33 vs. 0.59±0.20ng/mL [p<0.001]) were significantly elevated in participant serum POST maximal exercise before returning to values similar to baseline at POST30. The acute mental stress task did not significantly alter serum VCAM-1 or fractalkine at any time point. In conclusion, maximal aerobic exercise results in a significant elevation of the soluble adhesion molecules VCAM-1 and fractalkine in the serum of adult males that does not occur following laboratory-induced mental stress. The findings of the current investigation may suggest a novel protective role for acute aerobic exercise in vascular health via exercise-induced CAM proteolysis.