Performance of the Harris functional for extended basis sets at the Hartree-Fock and density functional levels.
The Harris functional is a noniterative variational procedure that uses an input charge density to produce an energy that is surprisingly accurate compared to the converged Kohn-Sham self-consistent result. We adapted and generalized this functional for the Hartree-Fock closed- and open-shell cases as well as examined its use for hybrid density functional methods such as B3LYP. Analysis of extended basis set calculations shows that at the B3LYP level an input density formed from a double zeta + polarization orbital basis is accurate enough to reproduce the energy of triple zeta + double polarization + diffuse orbital basis. For large molecules this translates into a computational speed that can be an order of magnitude faster. In the case of Hartree-Fock calculations a "bootstrapping technique" that employs successive applications of the Harris functional can further reduce computational times while retaining sufficient accuracy.


Electrochemical monitoring of the interaction of doxorubicin with nicotinamide and Fe(III) ions under aerobic and anaerobic conditions.
The interaction of doxorubicin with Fe(III) ions and nicotinamide (NA) has been followed by square-wave voltammetry, cyclic voltammetry and UV-VIS. spectroscopy techniques at aerobic and anaerobic conditions. Fe(III)-doxorubicin complex gives a 1-electron reversible step at -0.494 V and a shoulder at 580 nm. Further, the Fe(III)-doxorubicin complex was found to be more stable at aerobic conditions. In the presence of NA, an intermediate (NA-Fe(III)-DQ) forms at -0.462 V under aerobic conditions. Because of the formation of this intermediate, nicotinamide may reduce the cardiotoxic effect of doxorubicin and cause to its detoxification.


Drug-induced PML: a global agenda for a global challenge.
The occurrence of severe adverse events such as progressive multifocal leukoencephalopathy (PML) has the potential to limit the benefits of highly efficacious medicines being developed to fulfill unmet clinical needs across therapeutic areas. Following an Expert meeting in London in July 2011 (http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500111562.pdf), a research agenda, highlighting methodological, clinical, and communication elements, to mitigate the risk and improve the management of drug-induced PML has been agreed upon.


[Meta-analysis on the relationship of chlamydia pneumonia infection and coronary heart disease].
To determine the relationship of chlamydia pneumonia (CP) infection and coronary heart disease (CHD). Studies published before 2004 that had reported on correlations between CHD and CP were collected. Studies were sorted into four sorts according to different testing methods. We determined to use either fixed effect model or random effect model according to the result of heterogeneity test. Meta-analysis was done by RevMan 4.2. Totally 29 studies were included into the review. The odd ratio (OR) to review all literature enzyme-linked immunosorbent assay (ELISA), dot-immunogdd filtration assay (DIGFA), and micro-immunofluorescence (MIF) was 4.00 (3.07, 5.22), 2.86 (1.89, 4.32), 14.89 (1.46, 151.57), and 4.46 (3.15, 6.32). CP infection is associated with CHD, CP infection may be one of the risk factors of CHD.


Prevalence of overweight and obesity in children and adolescents aged 2-16 years.
To estimate the prevalence of obesity and overweight in children and adolescents in our city and to investigate the associated factors. A cross-sectional study of 1317 children and adolescents aged 2-16 years. Multistage probability sampling was used to select three groups of subjects: 411 aged 12 to 16 years, 504 aged 6 to 12 years, and 402 aged 2 to 6 years. Body mass index was calculated, and obesity and overweight were diagnosed using the threshold levels of the International Obesity Task Force for children and adolescents. Parents were asked about eating habits, health, social, and demographic aspects. Results are given as percentages (95% confidence interval). The relationship between obesity and overweight and the different variables was studied using multiple logistic regression. The adjusted odds ratio (OR) was calculated. Among children and adolescents aged 2-16 years, 9.5% (8.0%-11.0%) were obese and 22.4% (23.3%-24.6%) were overweight. Of subjects aged 12-16 years, 8.5% (5.9%-11.2%) were obese and 20.5% (16.7%-24.3%) were overweight. In the groups aged 6-12 years and 2-6 years, rates of obesity and overweight were 11.6% (8.9% -14.3%) and 31.0% (27.0-35.0) and 8.0% (5.4%-10.6%) and 13.6% (10.3%-16.9%) respectively. Obesity or overweight was associated to age (OR 1.21; P<0.001), maternal obesity (OR 10.99; P= 0.008), a birthweight higher than 4kg (OR 2.91; p 0.002), and formula feeding (OR 1.82; P= 0.005). Obesity and overweight in children and adolescents are highly prevalent problems in our city.


Computed-tomography-directed stereotaxis for movement disorder with postoperative magnetic resonance imaging confirmation.
Movement disorders may respond dramatically to properly placed lesions in thalamic and subthalamic areas. Proper location of lesions may be verified postoperatively by magnetic resonance imaging (MRI). Herein is reported a case of stereotactically placed bilateral lesions under computed tomography control using the Leksell apparatus, with successful clinical outcome, and the verification of lesion placement by subsequent MRI images.


Entropy of left ventricular late gadolinium enhancement and its prognostic value in hypertrophic cardiomyopathy a new CMR assessment method.
As a novel metric, entropy generated from late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can be utilized to assess tissue heterogeneity. However, it is unknown if it can be utilized for risk stratification in hypertrophic cardiomyopathy (HCM). In addition, it is unknown if LGE entropy correlates with LGE mass%, which is commonly utilized for fibrosis assessment. This research was done to investigate these issues. Patients with HCM who underwent 3.0-T CMR between January 2015 and January 2020 were prospectively enrolled and classified into low- and high-risk groups according to the AHA/ACC risk stratification guideline for 2020. The LGE entropy was automatically estimated using a generic Python package algorithm. On CMR imaging, the LGE mass% was determined using the CVI 42 software. Endpoint events included sudden cardiac death (SCD), hospital readmission owing to heart failure, and implantable cardioverter defibrillator (ICD) treatment for ventricular arrhythmias. A total of 109 HCM participants (70 males) were included. During the follow-up (23 ± 7 months), the patients in the high-risk group had higher LGE entropy (p < 0.001) and LGE mass% (p < 0.001) than those in the low-risk group, and patients with endpoint events had higher LGE entropy (p < 0.001) and LGE mass% (p < 0.001) than those without endpoint events. In all participants, there was a link between LGE entropy and LGE mass%, according to the Spearman rank correlation analysis (p < 0.001; r = 0.667). In ROC analysis, the area under the curve (AUC) of LGE entropy was 0.893 (95% CI, 0.794-0.993; P<0.001), AUC of LGE mass% was 0.826 (95% CI, 0.737-0.914; P<0.001), AUC of LVEF was 0.610 (95% CI, 0.473-0.748; P = 0.117) and AUC of 2020 AHA/ACC guideline for risk stratification was 0.716 (95% CI, 0.617-0.815; P = 0.002). According to Kaplan-Meier curves, HCM with a higher LGE entropy (≥cutoff value (<5.873) or ≥ thied tertile (5.540)) were more likely to experience the endpoint events. Following adjustment for the 2020 AHA/ACC guideline for risk categorization, LGE mass%, or decreased LVEF, Cox analysis showed that LGE entropy was independently linked with endpoint events. The variability and extent of LGE pictures can be reflected by LGE entropy, which is a reliable, usable, and repeatable metric for risk classification in HCM. It is a prognostic indicator of endpoint events that is independent of other risk indicators.


Preoperative upper gastrointestinal testing can help predicting long-term outcome after gastric banding for morbid obesity.
Gastric banding (GB) is one of the most popular bariatric procedures for morbid obesity. Apart from causing weight loss by alimentary restriction, it can interfere with functions of the esophagus and upper stomach. The aim of this study was to evaluate if the results of extensive preoperative upper GI testing were correlated with long-term outcome and complications after GB. Using a prospectively maintained computerized database including all the patients undergoing bariatric operations in both our hospitals, we performed a retrospective analysis of the patients who underwent complete upper gastrointestinal (GI) testing (endoscopy, pH monitoring, and manometry) before GB. One hundred thirty-four patients underwent complete testing before GB. Abnormal pH monitoring (increased total reflux time, increased diurnal reflux time, increased number of reflux episodes) predicted the development of complications and especially pouch dilatation and food intolerance. The mean De Meester score was higher among patients who developed complications than in the remaining ones (25.4 vs 17.7, P=0.03). High lower esophageal sphincter pressure also predicted progressive long-term food intolerance. Endoscopic findings were not predictive of the long-term outcome. There is some association between the function of the upper digestive tract and long-term complications after gastric banding. Abnormal pH monitoring predicts overall long-term complications, especially food intolerance with or without reflux, and pouch dilatation, and a high lower esophageal sphincter pressure predicts long-term food intolerance. Extended upper gastrointestinal testing with endoscopy, 24-h pH monitoring, and esophageal manometry is probably worthwhile in selecting patients for gastric banding.


Dynamically expressed single ELAV/Hu orthologue elavl2 of bees is required for learning and memory.
Changes in gene expression are a hallmark of learning and memory consolidation. Little is known about how alternative mRNA processing, particularly abundant in neuron-specific genes, contributes to these processes. Prototype RNA binding proteins of the neuronally expressed ELAV/Hu family are candidates for roles in learning and memory, but their capacity to cross-regulate and take over each other's functions complicate substantiation of such links. Honey bees Apis mellifera have only one elav/Hu family gene elavl2, that has functionally diversified by increasing alternative splicing including an evolutionary conserved microexon. RNAi knockdown demonstrates that ELAVL2 is required for learning and memory in bees. ELAVL2 is dynamically expressed with altered alternative splicing and subcellular localization in mushroom bodies, but not in other brain regions. Expression and alternative splicing of elavl2 change during memory consolidation illustrating an alternative mRNA processing program as part of a local gene expression response underlying memory consolidation.


Nephrotic syndrome following allogeneic stem cell transplantation associated with increased production of TNF-alpha and interferon-gamma by donor T cells.
Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the immunological complications of stem cell transplantation (SCT) including graft-versus-host disease (GVHD). In this report of a patient undergoing allogeneic SCT for AML, serial cytokine measurements by real-time PCR revealed increased production of interferon-gamma (IFN-gamma) and TNF-alpha, but not interleukin (IL)-4 in purified T cells following withdrawal of immunosuppression. Cytokine changes were contemporaneous with the onset of nephrotic syndrome (NS), a rare manifestation of GVHD. These findings indicate that serial cytokine monitoring may allow for the prediction of GVHD during immunosuppression withdrawal and lend further insight into the pathogenesis of NS. Bone Marrow Transplantation (2003) 32, 447-450. doi:10.1038/sj.bmt.1704151


Lab-scale study on the application of In-Adit-Sulfate-Reducing System for AMD control.
In a study of the 29 operating passive systems for acid mine drainage (AMD) treatment, 19 systems showed various performance problems. Some systems showed very low efficiency even without visible leakage or overflow. Though systems show fairly good efficiency in metal removal (mainly iron) and pH control, sulfate removal rates were very low which indicates the possibility of very poor sulfate reductions by Sulfate Reducing Bacteria (SRB). As an alternative method, In-Adit-Sulfate-Reducing System (IASRS), the method of placing the SAPS inside the adit, to have temperature constant at about 15 degrees C, was suggested. Lab-scale model experiments of IASRS were carried out. The models 1 and 2 were run at 15 degrees C and 25 degrees C, respectively. The model 1 contained about a half of COD in the beginning of the operation than that of model 2. Metal removal ratios were higher than 90% in both systems. Both systems showed the sulfate removal ratios of 23% and 27%, respectively, which were still considerably low, even though higher than those of presently operating systems. However, since the synthetic AMD used was very low in pH (2.8) and very high in sulfate concentration, if some suggested modifications were applied to the standard design, it is presumed that the sulfate removal ratio would have increased.


Family Refusal of Heart Valve Donation.
Impairment of the heart valves can occur due to many diseases that cause deterioration of the contractile function and harm the body, making it necessary for the heart valves to be transplanted. This study's objective was to analyze families' refusal to donate heart valves between 2001 and 2020. This was a cross-sectional study conducted in accordance with the Terms of Family Authorization for Donation of Organs and Tissues from patients diagnosed with brain death by an Organ Procurement Organization in the state of São Paulo. The variables analyzed were sex, age, cause of death, hospital type (private or public), and refusal to donate heart valves. Data analysis was performed using Stata software version 15.0 (StataCorp, LLC, College Station, Tex, United States) in a descriptive and inferential way. A total of 236 people (9.65%) refused to specifically donate heart valves of their relatives, the majority of whom were between 41 and 59 years old. Most potential donors had suffered a stroke and had been in a private hospital. From 2001 to 2009, there was a decreasing trend in males and the age group from 0 to 11 years old, whereas there was an increasing trend in those aged 60 years or older and in the general population. Between 2010 and 2020, there was a downward trend in the 41- to 59-year-old age group and the general population. The specific refusal to donate heart valves was associated with age, diagnosis, and whether the institution was public or private.


SMC protein RecN drives RecA filament translocation for in vivo homology search.
While the molecular repertoire of the homologous recombination pathways is well studied, the search mechanism that enables recombination between distant homologous regions is poorly understood. Earlier work suggests that the recombinase RecA, an essential component for homology search, forms an elongated filament, nucleating at the break site. How this RecA structure carries out long-distance search remains unclear. Here, we follow the dynamics of RecA after induction of a single double-strand break on the Caulobacter chromosome. We find that the RecA-nucleoprotein filament, once formed, rapidly translocates in a directional manner in the cell, undergoing several pole-to-pole traversals, until homology search is complete. Concomitant with translocation, we observe dynamic variation in the length of the filament. Importantly in vivo, the RecA filament alone is incapable of such long-distance movement; both translocation and associated length variations are contingent on action of structural maintenance of chromosome (SMC)-like protein RecN, via its ATPase cycle. In summary, we have uncovered the three key elements of homology search driven by RecN: mobility of a finite segment of RecA, changes in filament length, and ability to conduct multiple pole-to-pole traversals, which together point to an optimal search strategy.


Benign dermoscopic features in melanoma.
Various dermoscopic features are usually associated with benign melanocytic lesions. Our objective was to determine frequency and extension of benign dermoscopic features (BDF) in melanoma. Retrospective review of dermoscopic images of a consecutive series of 516 histopathologically proven melanomas collected in 6 years in Graz. Correlation of BDF with mean Breslow thickness, with presence/absence of associated benign nevus component and with the pre-operative clinico-dermoscopic diagnosis, as reported on the original histopathologic reports. In addition to melanoma specific criteria, 42% of melanomas showed BDF. In 12.3% cases, the benign features occupied more than the half of the lesion. The BDF typical pigment network, homogeneous pattern and regular globules/cobblestone pattern had the highest frequency. BDF were associated with relatively thinner melanomas (mean Breslow thickness of 0.51 mm). The presence of BDF was observed in 67.1% of histopathologically documented nevus-associated melanoma and in 35.7% of melanoma de novo. A pre-operative clinico-dermoscopic diagnosis of melanoma was achieved in only 54.1% of cases displaying BDF. A significant proportion of melanomas may exhibit BDF. Clinicians should be aware of the presence of BDF in melanoma as possible diagnostic pitfall.


Metabolic response to hypoxia in European sea bass (Dicentrarchus labrax) displays developmental plasticity.
Several physiological functions in fish are shaped by environmental stimuli received during early life. In particular, early-life hypoxia has been reported to have long-lasting effects on fish metabolism, with potential consequences for fish life history traits. In the present study, we examine whether the synergistic stressors hypoxia (40% and 100% air saturation) and temperature (15° and 20°C), encountered during early life, could condition later metabolic response in European sea bass (Dicentrarchus labrax) juveniles. Growth rate and metabolic parameters related to carbohydrate and lipid metabolism in the liver were investigated at the juvenile stage under normoxic and chronic hypoxic conditions. Juvenile growth rates were significantly lower (p<1×10-6) under hypoxic conditions and were not improved by prior early-life exposure to hypoxia. Growth was 1.3 times higher (p<5×10-3) in juveniles reared at 15°C during the larval stage than those reared at 20°C, suggesting that compensatory growth had occurred. Early-life exposure to hypoxia induced higher (p<2×10-6) glycogen stores in juveniles even though there was no apparent regulation of their carbohydrate metabolism. In the liver of juveniles exposed to chronic hypoxia, lower glycogen content combined with stimulation of phosphoenolpyruvate carboxykinase gene expression and higher lactate concentration indicated a stimulation of the anaerobic glycolytic pathway. Furthermore, hypoxia only induced lower (p<1×10-3) lipid content in the liver of juveniles that had experienced 15°C at the larval stage. The present study provides evidence that environmental conditions experienced during early life shape the metabolic traits of D. labrax with potential consequences for juvenile physiological performance.


Correction to: Comparison of the Effect of Exercise on Late-Phase LTP of the Dentate Gyrus and CA1 of Alzheimer's Disease Model.
The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. "Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004" should have been included on the paper.


Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study.
In our previous study investigating effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients' data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin. Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR, n = 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR; n = 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared. Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (-43.8 and 17.9 mg/dL; both p < 0.05). Luseogliflozin significantly lowered "lowest glucose" (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (-19.2 and -24.0 mg/dL; both p < 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (-15.50 mg/dL; p < 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h; p < 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups. Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose. Taisho Pharmaceutical Co., Ltd, Tokyo, Japan. JapicCTI-142548.


Determination of 35 sulfonamides in pork by magnetic molecularly imprinted polymer-based dispersive solid-phase extraction and ultra-performance liquid chromatography photodiode array method.
Sulfonamide residues in foods of animal origin are potential risks to consumer health, so it is very important to inspect them. Among the previously reported instrumental methods, the best method can only be used to determine at most 22 sulfonamides. Thus, an instrumental method capable of determining more sulfonamide species is desirable. In this study, sulfadoxine was used as a template to synthesize a type of magnetic molecularly imprinted polymer that could recognize 35 sulfonamides. After characterization, this composite was used to develop a dispersive solid-phase extraction method for extraction and purification of the 35 sulfonamides in pork, followed by determination using an ultra-performance liquid chromatography photodiode array method. This composite exhibited high adsorption capacity (11.01-19.21 μg mg-1 ) and high recovery (>89.01%), and could be reused at least ten times. Due to the enrichment effect during sample preparation (enrichment factor 22-66), the limits of detection for determination of the 35 drugs in pork were in the range of 0.08-0.53 ng g-1 . The detection results for some real pork samples were consistent with a liquid chromatographic-tandem mass spectrometric method. After comparison, the present method showed generally better performances than the previously reported sample preparation methods and instrumental methods for detection of sulfonamides. The method developed in the present study could be used as a practical tool for routine detection of sulfonamide residues in pork samples. © 2022 Society of Chemical Industry.


Pathologic conditions of the lower cranial nerves IX, X, XI, and XII.
The glossopharyngeal, vagus, spinal accessory, and hypoglossal cranial nerves can be affected by an acute or chronic process that has an impact on the way the patient presents clinically. Knowledge of nerve pathways and relations to surrounding structures is fundamental when evaluating patients who have lower cranial nerve symptoms. A systematic "segment-based" approach helps to narrow the differential diagnosis Pathologic conditions that cause lower cranial nerve symptoms are presented.


Concentration-dependence of aniline-induced methemoglobinemia in dogs: a derivation of an acute reference concentration.
Four male Beagle dogs per group were head-only exposed to aniline vapor in concentrations ranging from 15.8 to 493.6 mg/m3. Each exposure session was for 4h. Additionally, one group of dogs was both head-only and whole-body exposed to approximately 241 mg/m3 to better appreciate the contribution of dermal uptake on methemoglobin (MetHb) induction. The exposure paradigm chosen was comparable to a dose-escalation type of study, however, providing adequate recovery periods between each exposure session to exclude 'carry-over' effects from one exposure session to another. This was verified by the determination of standard hematology endpoints before and after each exposure session. The time- and concentration-dependence of MetHb was analyzed as the key endpoint. The results of this study show that MetHb was maximal around the end of the 4 h exposure period. Significantly increased MetHb was observed at concentrations equal and above 30.3 mg/m3 at a duration of exposure of at least 60 min. The extent of MetHb formation observed in some hyperventilating dogs suggests that the dosing-rate is important for the outcome of test. Whole body exposed dogs displayed markedly higher MetHb values when compared to head-only exposed dogs. Taking into account the entire concentration-time-effect relationship 23.6 and 20.6 mg/m3 were estimated to be the threshold concentrations to cause 0.8% MetHb following a 4 and 8h exposure period, respectively. The C(n)xt analysis of MetHb formation is consistent with a concentration-dependent restoration kinetics of MetHb suggesting that results from high level exposures cannot readily be extrapolated to low-level exposures. In summary, this study demonstrates that for aniline, an agent known to be bioactivated by a hepatic first-pass metabolism, the rate of delivery and uptake appears to be decisive for the extent of MetHb formation. Carry-over effects related to erythrotoxicity or Heinz body formation were not observed at any exposure level.


Ligand biological activity predicted by cleaning positive and negative chemical correlations.
Predicting ligand biological activity is a key challenge in drug discovery. Ligand-based statistical approaches are often hampered by noise due to undersampling: The number of molecules known to be active or inactive is vastly less than the number of possible chemical features that might determine binding. We derive a statistical framework inspired by random matrix theory and combine the framework with high-quality negative data to discover important chemical differences between active and inactive molecules by disentangling undersampling noise. Our model outperforms standard benchmarks when tested against a set of challenging retrospective tests. We prospectively apply our model to the human muscarinic acetylcholine receptor M1, finding four experimentally confirmed agonists that are chemically dissimilar to all known ligands. The hit rate of our model is significantly higher than the state of the art. Our model can be interpreted and visualized to offer chemical insights about the molecular motifs that are synergistic or antagonistic to M1 agonism, which we have prospectively experimentally verified.


New insights into the aryl hydrocarbon receptor as a modulator of host responses to infection.
The host response to infection is known to be influenced by many factors, including genetics, nutritional status, age, as well as drug and chemical exposures. Recent advances reveal that the aryl hydrocarbon receptor (AhR) modulates aspects of the innate and adaptive immune response to viral, bacterial, and parasitic organisms. Although many of these observations were made using the high affinity but poorly metabolized AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), not all of the effects are detrimental to the host. Sometimes AhR activation, even with TCDD, was beneficial and improved host resistance and survival. A similar dichotomy is observed in infected AhR-deficient mice, wherein absence of functional AhR sometimes, but not always, alters host resistance. When examined in their totality, current data indicate that AhR controls multiple regulatory pathways that converge with infection-associated signals and depending on the context (e.g., type of pathogen, site of infection), lead to distinct outcomes. This creates numerous exciting opportunities to harness the immunomodulatory action of AhR to transform host responses to infection. Moreover, since many of the mechanisms cued in response to infectious agents are pivotal in the context of other diseases, there is much to be learned about AhR's cellular targets and molecular mechanisms of action.


Plasmodium vivax: isolation of mature asexual stages and gametocytes from infected human blood by colloidal silica (Percoll) gradient centrifugation.
The densities of human erythrocytes infected with P. vivax obtained from infected patients were determined by isopycnic centrifugation in continuous gradients of Percoll. The approximate densities of erythrocytes infected with rings were 1.086 to 1.1, trophozoites (amoeboid stages) 1.053 to 1.086, schizonts and gametocytes 1.053 to 1.056 and of the other cellular elements of blood, uninfected erythrocytes, 1.086 to 1.1, polymorphonuclear leucocytes 1.073 to 1.086 and mononuclear cells 1.062 to 1.073 g/ml. Based on these values, a one-step gradient of 47% Percoll was devised to separate erythrocytes infected with the more mature stages (trophozoites, schizonts and gametocytes) from uninfected erythrocytes. By this method it is possible to obtain parasitaemias of 88% to 98% from blood with starting parasitaemias of less than 0.7%. This method is therefore being routinely used for immunological, biochemical and molecular biological studies on P. vivax.


Utility of solution electrochemistry mass spectrometry for investigating the formation and detection of biologically important conjugates of acetaminophen.
On-line formation and detection of glutathione and cysteine conjugates of acetaminophen were accomplished by the interfacing of a coulometric electrochemical cell with a thermospray mass spectrometer in a flow-injection experiment using a liquid chromatographic pump. Formation of the conjugates occurred only after acetaminophen was oxidized electrochemically by a two-electron transfer to N-acetyl-p-benzoquinoneimine and reacted in a mixing tee with either glutathione or cysteine. The newly formed conjugate was detected by thermospray mass spectrometry by observing the [M + H]+ ion for the acetaminophen-glutathione conjugate at m/z 457, or the [M + H]+ ion for the acetaminophen cysteine conjugate at m/z 271. Both the glutathione and cysteine conjugates produced a common fragment ion at m/z 184. The on-line reaction of glutathione and electrochemically generated N-acetyl-p-benzoquinoneimine was monitored at varying pH. At pH 8.5 the ion intensity for the acetaminophen-glutathione conjugate was greater than at lower pH, indicating that lower proton concentration enhanced the reaction of glutathione with N-acetyl-p-benzoquinoneimine. This on-line electrochemical-thermospray mass spectrometric method demonstrated that acetaminophen conjugates may be formed and detected in the time frame of 1 s.


What causes steroid cataracts? A review of steroid-induced posterior subcapsular cataracts.
Prolonged use of glucocorticoids is a significant risk factor for the development of posterior subcapsular cataract. This places restrictions on the use of glucocorticoids in the treatment of systemic and/or ocular inflammatory conditions as well as in organ transplantation. The mechanisms responsible for the opacification are unknown and no effective treatment, other than surgical removal of the lens, is available. Difficulties in establishing suitable in vivo or in vitro models have limited research in this area. Nevertheless, several mechanisms, based on observations with other types of cataracts, have been proposed. In this review, these mechanisms are evaluated in light of the evidence available. A novel mechanism is also proposed, in which steroids do not directly act on the lens but rather affect the balance of ocular cytokines and growth factors.


Practice guidelines for community-based parenteral anti-infective therapy.
Practice guidelines for community-based parenteral anti-infective therapy (CoPAT) have recently been formulated in several countries. These guidelines emphasize the importance of teamwork and the interdisciplinary nature of CoPAT, and they use similar criteria for patient selection and evaluation, anti-infective agent selection and administration, and clinical monitoring. There are now guidelines or standards addressing the roles and responsibilities of the physician, nurse, and pharmacist in the delivery of CoPAT, and home care standards that address issues such as drug storage and preparation, treatment planning, and monitoring of ongoing care.


Rapid and accurate determination methods based on data fusion of laser-induced breakdown spectra and near-infrared spectra for main elemental contents in compound fertilizers.
Compound fertilizer occupies a dominant position in the structure of fertilizer products in China. The contents of nitrogen, phosphorus and potassium are the key indicators affecting the fertilization efficiency and the price of compound fertilizers. Laser-induced breakdown spectroscopy (LIBS) and near-infrared spectroscopy (NIRS) are two rapid analytical techniques suitable for online monitoring of the above components in compound fertilizer. However, accurate LIBS analysis needs to overcome matrix effects and interference from environmental elements, and NIRS also has the limitation of not being able to directly detect inorganic components in compound fertilizers. The combination of LIBS and NIRS techniques, namely LIBS-NIRS data fusion, has the potential to reduce interferences in the detection of single spectroscopic techniques and further improve the analysis accuracy. This study compared the LIBS-NIRS data fusion methods under different optimization conditions, and found that CARS-OPF (competitive adaptive reweighted sampling combined with outer product fusion) and CARS-EWF (competitive adaptive reweighted sampling combined with equal weight fusion) are two effective intermediate data fusion methods which can achieve better quantitative analysis results than single spectroscopic methods. The root mean square errors of prediction (RMSEP) for nitrogen, phosphorus, and potassium contents in compound fertilizers by using CARS-OPF are 0.901, 0.693, and 1.52, respectively, and the RMSEP for those indicators by using CARS-EWF are 0.934, 0.719, and 1.60, respectively. In these two methods, the LIBS and NIRS characteristic variables of compound fertilizers are firstly screened by CARS algorithm, and then intermediate data fusion was carried out by using equal weight fusion or outer product fusion. Redundant variables in the original data can be well removed in the data fusion process to ensure the accuracy of the analysis. Therefore, the combined methods of LIBS-NIRS based on CARS-OPF and CARS-EWF could be well applied to the rapid and accurate detection of main elemental contents in compound fertilizers.


Low n-6/n-3 Gestation and Lactation Diets Influence Early Performance, Muscle and Adipose Polyunsaturated Fatty Acid Content and Deposition, and Relative Abundance of Proteins in Suckling Piglets.
Elevated omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) ratios in swine diets can potentially impose a higher risk of inflammatory and metabolic diseases in swine. A low ratio between the two omega PUFAs has beneficial effects on sows' and piglets' production performance and immunity status. At present, there are few studies on how sow nutrition directly affects the protein and fat deposition in suckling piglets. Two groups of sows were fed diets with high or low n-6/n-3 polyunsaturated ratios of 13:1 (SOY) and 4:1 (LIN), respectively, during gestation and lactation. Longissimus dorsi muscle and adipose tissue from newborn piglets, nourished only with sow's milk, were subjected to fatty acid profiling by gas chromatography-mass spectrometry (GC-MS) and to proteomics assays based on nano-liquid chromatography coupled to high-resolution tandem mass spectrometry (nLC-HRMS). Fatty acid profiles on both muscle and adipose tissues resembled the magnitude of the differences between fatty acid across diets. Proteomic analysis revealed overabundance of 4 muscle and 11 adipose tissue proteins in SOY compared to LIN in both piglet tissues. The detected overabundance of haptoglobin, an acute-phase protein, and the stimulation of protein-coding genes and proteins related to the innate immune response and acute inflammatory response could be associated with the pro-inflammatory role of n-6 PUFAs.


Action potentials in gland cells of rat pituitary pars intermedia: inhibition by dopamine, an inhibitor of MSH secretion.
1. Cells were dissociated from rat pituitary pars intermedia, maintained in culture, and subjected to electrophysiological study.2. Recorded membrane potentials varied widely (range - 18 to about - 80 mV). They were relatively insensitive to changes in external Na but were rapidly and reversibly lowered by excess K.3. Action potentials were elicited by passing current through intracellular recording electrodes. They were reversibly blocked by tetrodotoxin (TTX, 2 x 10(-6)M) or by removal of Na from the recording solution and thus appeared to be Na spikes. Cells yielding action potentials in response to depolarization had relatively high membrane potentials (about - 65 mV) which may be representative of the true resting membrane potential of pars intermedia cells.4. Spontaneous action potentials were recorded extracellularly from nearly all the many isolated pars intermedia cells studied with a microsuction electrode. Their amplitude was reduced by TTX (0.1-2 x 10(-6)M). Electron microscopic examination of cells producing action potentials showed them to be hormone-containing parenchymal (gland) cells.5. Dopamine (10(-6)M), a presumed physiological inhibitor of secretion of melanocyte stimulating hormone (MSH) from pars intermedia cells, decreased the frequency of spontaneous action potentials but not their amplitude. Similar effects were seen with noradrenaline (10(-6)M), another inhibitor of MSH secretion, whereas isoprenaline and 5-hydroxytryptamine (5-HT), which do not inhibit MSH secretion, had no effect.6. Action potentials may be involved in stimulus-secretion coupling in pars intermedia cells.


Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma.
Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC). The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8+ T cells in combination with an αPD-1 antibody on Hepa1-6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8+ T cells in combination with αPD-1 antibody significantly enhanced the function of CD8+ T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8+ T cells and significantly decreased the number of FoxP3+ regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups. The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs. The data of this study are available from the corresponding author on reasonable request.


Laser-assisted cell microdissection using the PALM system.
Laser-assisted microdissection has enabled the collection of morphologically defined cell populations from a tissue section. The PALM Robot MicroBeam laser microdissection system provides a robust system for the retrieval of specified cells (including single cells). Due to the fragile nature of DNA, and in particular RNA, robust protocols are required to obtain reliable data from a limited number of cells (1-10.000 cells). This chapter describes the application of the PALM MicroBeam system to isolate RNA and DNA from cells in a complex tissue for subsequent molecular analysis. Protocols for successful analysis of RNA from 500 to 1000 cells, including steps to produce cDNA for subsequent polymerase chain reaction analysis, are given. The cDNA could also be used as a template for linear amplification in order to perform gene array analysis. Furthermore, a protocol for genomic analysis of p53 mutations from single cells is given. The described procedures emphasize preparation of tissue, laser microdissection including catapulting of cells, and extraction of RNA and DNA. Downstream experiments for validation are also shown.


Methane emissions from Icelandic landfills - A comparison between measured and modelled emissions.
This study compares methane (CH4) emissions from five Icelandic landfills, quantified using tracer gas dispersion to modelled emission rates using the IPCC FOD model. The average CH4 emission rates measured from the investigated landfills were 475.4 kg CH4 h-1 (Álfsnes landfill), 32.5 kg CH4 h-1 (Fíflholt), 40.8 kg CH4 h-1 (Gufunes), 9.8 kg CH4 h-1 (Kirkjuferjuhjáleiga) and 78.4 kg CH4 h-1 (Stekkjarvík). At three of the landfills (Álfsnes, Fíflholt and Kirkjuferjuhjáleiga), the modelled emission was higher than the measured emission by factors ranging from 1.1 to 4.8, neglecting any CH4 oxidation in the cover soils. Even though CH4 oxidation might play a role at some of the investigated landfills, and thus reduce the gap between modelled and measured emissions, it is likely that the model overestimated CH4 generation due to uncertainties in input model parameters. Assuming that the measured emissions at the five landfills are representative of all the waste disposed in Iceland from 2007 to 2016, the measured emission should be extrapolated to 817 kg CH4 h-1, which is relatively close to the modelled national emission of 936 kg CH4 h-1 in 2017. This study showed that the application of the IPCC FOD model at national level is appropriate for estimating landfill CH4 emissions in Iceland. CH4 emissions from landfills in Iceland can be reduced by expanding or implementing gas collection or biocover systems for optimised microbial oxidation.


Postural tachycardia syndrome in children and adolescents.
Postural tachycardia syndrome is a chronic condition with frequent symptoms of orthostatic intolerance or sympathetic activation and excessive tachycardia while standing, without significant hypotension. Orthostatic symptoms include dizziness, lightheadedness, blurring of vision, near faints, weakness in legs, poor concentration, nausea, and headaches. Somatic symptoms include fatigue, sleep disorder, widespread pain, abdominal pain, and menstrual irregularities. Psychological problems may overlap with physical complaints. This review discusses the normal physiology of orthostatic change, different pathophysiological mechanisms of postural tachycardia syndrome, including hypovolemia, venous pooling, autonomic neuropathy, and hyperadrenergic responses. In addition, an outline for management tailored to the patient's clinical syndrome is presented, along with concluding thoughts on future research needs.


The Effect of Dupilumab on Intractable Chronic Rhinosinusitis with Nasal Polyps in Japan.
Dupilumab, which blocks the shared receptor component for interleukin-4 and interleukin-13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers. Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co-primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund-Mackay CT (LMK-CT) scores. Symptoms, sense of smell, health-related quality of life, and safety were assessed during the 52-week treatment period. Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: -3.1, P < .0001; Arm B: -2.1, P = .0011); NC score (Arm A: -1.2, P < .0001; Arm B: -0.9, P < .0001); and LMK-CT (Arm A: -5.1, P = .0005; Arm B: -2.8, P = .0425). The most common treatment-emergent adverse event in dupilumab and placebo-treated patients was nasopharyngitis. Dupilumab provided rapid, significant, and clinically meaningful improvements for patients with CRSwNP in Japan. Dupilumab was well tolerated, and safety and efficacy were consistent with the overall study population. 2 Laryngoscope, 131:E1770-E1777, 2021.


Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms.
Vagus nerve stimulation (VNS) is an effective adjunctive treatment for intractable epilepsy. However, the optimal range of device duty-cycles [on/(on + off times)] is poorly understood. The authors performed a multicenter, randomized trial of three unique modes of VNS, which varied primarily by duty-cycle. The results indicate that the three duty-cycles were equally effective. The data support the use of standard duty-cycles as initial therapy.


Echocardiography. Principles of interpretation.
Echocardiography offers the clinician an opportunity to image the heart noninvasively. Both M-mode and cross-sectional echocardiography can be used to measure cardiac dilation and hypertrophy and to quantitate myocardial function. Knowledge of normal echocardiographic anatomy is essential for understanding changes that occur in disease.


Multifarious analytical capabilities of the UV/Vis protein fluorescence in blood plasma.
Autofluorescence of blood plasma has been broadly considered as a prospective disease screening method. However, the assessment of such intrinsic fluorescence is mostly phenomenological, and its origin is still not fully understood, complicating its use in the clinical practice. Here we present the detailed evaluation of analytical capabilities, variability, and formation of blood plasma protein fluorescence based on the open dataset of excitation-emission matrices measured for ∼300 patients with suspected colorectal cancer, and our supporting model experiments. Using high-resolution size-exclusion chromatography coupled with comprehensive spectral analysis, we demonstrate, for the first time, the dominant role of HSA in the formation of blood plasma fluorescence in the visible spectral range (excitation wavelength >350 nm), presumably caused by its oxidative modifications. Furthermore, the diagnostic value of the tryptophan emission, as well as of the tyrosine fluorescence and visible fluorescence of proteins is shown by building a tree-based classification model that uses a small subset of physically interpretable fluorescence features for distinguishing between the control group and cancer patients with >80% accuracy. The obtained results extend current understanding and approaches used for the analysis of blood plasma fluorescence and pave the way for novel autofluorescence-based disease screening methods.


The association of female sex with management and mortality in patients with Staphylococcus aureus bacteraemia.
The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia. This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males. Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillin-resistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14-42] vs. 28 [interquartile range 14-45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85-1.13]). Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk.


Duplication of the blood glucose curve of an OGTT in dogs by a prospectively programmed I.V. infusion: infusion pattern and IRI response.
In conscious dogs the peripheral venous blood glucose profile of an OGTT (1.0 g/kg) was individually duplicated by a computed i.v. glucose infusion. The correspondence reached between both tests was demonstrated by the correlation between the paired increments of the reactive blood glucose concentration areas. The average total dose needed for duplication was 0.52 +/-0.04 g/kg (no. = 11). There was a more rapid and greater IRI increase in OGTT than in the infusion test. When 1.0 g glucose per kg was given according to the same pattern by a computed infusion, the integrated areas both of blood glucose and of IRI was twice that in OGTT. We concluded that the IRI increase in OGTT reinforced by enteral mechanisms favors the direct hepatic uptake of absorbed glucose. This could also protect the body from an excessive insulin release provoked by the entire oral load if it reached the peripheral circulation.


A new family of fucose-containing gangliosides isolated from human senile cataracts.
Gangliosides were isolated from human cataracts by solvent extraction, silicic acid chromatography, thin-layer chromatography and gas-liquid chromatography. A total of 11 resorcinol-positive bands were revealed by thin-layer chromatography. Bands 1, 5 and 7 were partially identified as hematoside. GM1 ganglioside and disialoganglioside by gas-liquid chromatography as the O-trimethylsilylated methylglycosides. In addition to galactose and glucose, fucose was found to be present in seven ganglioside fractions (bands 3, 4, 6 and 8-11). All these fucolipids contained N-acetylglucosamine in addition to sialic acid. Fucogangliosides G-3, G-4 and G-6 contained a 2:1 molar ratio of galactose to glucose, while G-8 had a galactose/glucose molar ratio of 1:1. Long-chain fatty acids constituted 60-77% of the total normal fatty acids in N-acetylgalactosamine-containing gangliosides, whereas the fucogangliosides contained primarily palmitate, although significant amounts of long-chain acids were also detected. The major long-chain base of the fucoganglioside was sphinganine (dihydrosphinogosine). The role of fucose-containing gangliosides in maintaining adhesions between lens membranes in cataracts is discussed with reference to glycosphingolipids in other tissues.


A model of clutch size determination in birds.
This paper tests the hypothesis that the timing and the size of bird clutches are determined by (1) a tendency to delay reproduction so that the female can store enough internal resources for laying a large clutch; (2) a tendency to breed early because survival of offspring late in the breeding season might be lower than early. These factors are approximated by linear functions in a model. The model predicts that there will be a correlation between early breeding females and those that have large clutches. This agrees with published data for several bird species. Predictions from the model are also made of clutch size and the impact on final clutch-size if one egg is removed or added during the laying. These predictions were compared with data from a crow (Corvus cornix) population and were supported if it is assumed that the formation of an egg is a relatively costly process. More precisely, the model is supported if the formation of an extra egg requires a delay of about four or five days before laying can begin.


Acromesomelic dysplasia with cardiac and neurologic abnormalities: an association by chance, new features of maroteaux type or a new syndrome?
We report a patient with acromesomelic dysplasia, cardiac and neurologic abnormalities. This may be a new syndrome or cardiac and neurologic features may be undescribed rare features of acromesomelic dysplasia.


Production and characterization of monoclonal antibodies directed against native epitopes of NhaA, the Na+/H+ antiporter of Escherichia coli.
Monoclonal antibodies (mAbs) recognizing native epitopes are an important tool for functional and structural studies of proteins, yet they have rarely been used with transport proteins. In an attempt to raise monoclonal antibodies against the NhaA Na+/H+ antiporter of Escherichia coli we encountered difficulties in the screening procedure, which is based on the standard enzyme-linked immunosorbent assay (ELISA). Here we report a rapid and efficient method of screening for anti-NhaA mAbs which recognize native epitopes of the antiporter. The method is based on the use of His-tagged protein, Ni2+-nitrilotriacetic acid coated plates and non-denaturing conditions in the assay. With this procedure four mAbs were obtained, three of which recognize the NhaA in its native conformation and one preferentially recognizes the denatured form. The latter mAb is Western blot positive, the others are Western blot negative and bind the detergent solubilized NhaA as assayed by gel filtration chromatography. Competition experiments show that the native epitopes are common to both the His-tagged and the wild-type protein. We suggest that in the standard ELISA the NhaA protein is not presented to the antibody in the native conformation whereas the His tag based protocol favors this presentation. Indeed, we could remarkably improve the low reactivity of the standard ELISA by coating the plates with anti-NhaA mAb and use it to present NhaA ('sandwich' ELISA or two antibodies assay). Remarkably, two of the mAbs (5H4, 2C5) which bind native NhaA inhibit drastically the deltapH driven 22Na uptake mediated by His-tagged NhaA reconstituted in proteoliposomes. Hence, these mAbs afford a new tool to study the structure/function relationship of the antiporter.


Controlled Synthesis, Chiral Assembly, and Circularly Polarized Luminescence of Poly(Phenyl Isocyanide)-Block-Polyfluorene Copolymers.
In this work, π-conjugated block copolymers consisting of poly(phenyl isocyanide) (PPI) and polyfluorene (PF) segments are facilely prepared by one-pot sequential polymerization of phenyl isocyanide (monomer 1) and 7-bromo-9,9-dioctylfluorene-2-boronic acid pinacol ester (monomer 2). The Pd(II)-terminated PPI is first prepared via polymerizing monomer 1 catalyzed with phenyl alkyne-Pd(II) complex and then utilized to initiate the controlled Suzuki cross-coupling polymerization of monomer 2, yielding various PPI-b-PF copolymers possessing controlled molar mass and narrow dispersity. Owing to the helical conformation of PPI segment and π-conjugated structure of PF segment, PPI-b-PF copolymers present distinctive optical property and fascinating chiral self-assembly behavior. During the self-assembly process, chirality transfer from helical PPI block to the supramolecular aggregates of helical nanofibers occurs to afford optically active helical nanofibers with high optical activity. Furthermore, the self-assembled helical nanofibers exhibit excellent circularly polarized luminescence performance.


How to interpret epicardial adipose tissue as a cause of coronary artery disease: a meta-analysis.
Experimental and clinical studies have suggested that epicardial adipose tissue (EAT) may cause coronary artery disease (CAD). A meta-analysis was conducted to investigate the relationship between EAT and CAD. A systematic literature search of Cochrane, Medline, Pubmed, Elsevier, Springerlink, Ovid, and Embase from their respective inceptions to August 2011 was conducted using specific search terms such as 'epicardial adipose tissue' and 'epicardial fat'. Data were extracted from applicable articles and mean differences or risk ratio, including 95% confidence intervals (CI), were calculated using RevMan 5.1 software. A total of 15 case-control studies and one case-sectional study (N=2872 patients) were identified. Compared with the non-CAD group, EAT thickness and volume were significantly higher in the CAD group (mean difference 1.57 mm, 95% CI: 0.74, 2.40, P<0.00001; mean difference 15.22 ml, 95% CI: 7.58, 22.87, P<0.0001). Patients in the higher EAT tertile (≥ 100 ml) were more likely to have CAD compared with those in the lower EAT tertile (<100 ml) (risk ratio 0.69, 95% CI: 0.52, 0.92, P=0.01). Patients with coronary plaque also had increased EAT volume compared with patients without coronary plaque (mean difference 24.90 ml, 95% CI: 9.99, 39.81 P=0.001). EAT volume was not different in patients whose coronary artery calcium scores were less than or equal to 10 or greater than 10 (mean difference -17.28 ml, 95% CI: -52.01, 17.44, P=0.33). On the basis of the current evidence, EAT seems to be an effective marker in the prediction of CAD.


Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.
Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood. In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM. A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003). Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.


Long-Term Effectiveness of Dupilumab in Patients with Atopic Dermatitis: Results up to 3 Years from the RELIEVE-AD Study.
Atopic dermatitis (AD) can require long-term therapy. Few real-world studies have evaluated long-term effectiveness from the patients' perspective. The aim of this study was to evaluate patient-reported outcomes (PROs) during long-term dupilumab treatment. Adults with moderate-to-severe AD who initiated dupilumab through the US manufacturer patient support program and participated in RELIEVE-AD (a prospective patient survey study with a 12-month follow-up) were recontacted 30-36 months post-initiation regardless of current dupilumab use. The online questionnaire consisted of PROs, including the Atopic Dermatitis Control Tool (ADCT), use of concomitant AD therapies, satisfaction with current therapy, global change in itch relative to before dupilumab initiation, non-itch skin symptoms (skin pain/soreness, hot/burning feeling, and sensitivity to touch), flares, Dermatology Life Quality Index, sleep problems, and the AD-specific Work Productivity and Activity Impairment Questionnaire. Of 698 patients who initiated dupilumab (baseline) and were recontacted, 425 completed the 30-36-month survey. Significant reductions from baseline were reported in concomitant AD therapy use (P < 0.05); 54.4% reported not using other AD medications vs. 12.8% at baseline. At 30-36 months, all results (non-itch skin symptoms, flares, sleep problems, health-related quality of life work/activity impairment, disease control, and treatment satisfaction) were similar to or incrementally better than the 12-month timepoint, with significant improvements vs. baseline (P < 0.001). Global change in itch was reported as "very much better" by 75.3% of respondents. Adequate disease control (score < 7 on ADCT) was reported by 80.7% of respondents, and 86.8% were satisfied with the treatment. In clinical practice settings, patient-reported benefits of dupilumab were maintained in survey respondents during long-term treatment up to 36 months while the use of concomitant AD therapies reduced.


Expression of transfected human CuZn superoxide dismutase gene in mouse L cells and NS20Y neuroblastoma cells induces enhancement of glutathione peroxidase activity.
The human CuZn superoxide dismutase (superoxide dismutase 1) a key enzyme in the metabolism of oxygen free-radicals, is encoded by a gene located on chromosome 21 in the region 21 q 22.1 known to be involved in Down's syndrome. A gene dosage effect for this enzyme has been reported in trisomy 21. To assess the biological consequences of superoxide dismutase 1 overproduction within cells, the human superoxide dismutase 1 gene and a human superoxide dismutase 1 cDNA were introduced into mouse L cells and NS20Y neuroblastoma cells. Both cell types expressed elevated levels (up to 3-fold) of enzymatically active human superoxide dismutase 1. These human superoxide dismutase 1 overproducers, especially neuronal cell lines, showed an increased activity in the selenodependent glutathione peroxidase. These data are consistent with the possibility that gene dosage of superoxide dismutase 1 contributes to oxygen metabolism modifications previously described in Down's syndrome.


The influence of short-term pre-operative intravenous nutrition upon anthropometric variables, protein synthesis and immunological indices in patients with gastrointestinal cancer.
The influence of short-term pre-operative intravenous nutrition (IVN) upon protein synthesis in human liver and skeletal muscle was investigated in 30 patients with weight loss (>5 kg in preceding 3 months) who underwent resection of a neoplasm of the gastrointestinal tract. Patients were randomised to receive a normal hospital diet (HD group) or a hospital diet supplemented by intravenous nutrition (IVN groups; 0.18 gN/kg/24h as FreAmine III; 126kJ/24h as glucose) for either 3 (IVN(3)) or 7 days (IVN(7)) Nutritional assessment was undertaken by measurement of anthropometric, biochemical and immunological indices. In addition, the rates of protein synthesis in biopsies of liver and skeletal muscle, which were obtained at operation, were determined in vitro from the incorporation into protein of (14)C-leucine. Patients who received a hospital diet only (HD group) were in negative energy balance and continued to lose weight during the pre-operative period. The imbalance between caloric intake and expenditure was met from endogenous fuel stores with a reduction in fat-free mass and arm muscle area. Patients who received IVN maintained body weight and fat-free mass and had higher rates of protein synthesis in liver and skeletal muscle. In addition there was an increase in the plasma concentrations of prealbumin, haptoglobin and complement C3 together with a rise in the concentrations of the circulating immunoglobulins IgM and IgA. The majority of these changes occurred after only 3 days of IVN.


[Systematic selection of treatment, a model of psychotherapy based on the evidence. Background and development of a program of validation in Argentina].
Evidence suggests that while clinical practitioners generally value scientific validity, most clinical practices are supported by personal experience and belief. On the other hand, the Empirically Supported Therapies are rejected by most therapists who consider them inflexible and poorly adapted to each particular case. Larry Beutler et al, have developed a method based on scientific evidence called Systematic Treatment Selection (STS), that guides the clinician in the decisions about which are the most appropriate type of interventions for each particular patient. Fundación Aiglé and Centro Privado de Psicoterapias have developed a validation program with a local sample of three hundred patients. The following article will present the principal concepts of STS, as well as the steps and preliminary results of the validation program in Argentina.


Comparison of sensitivity, specificity, positive predictive value, and negative predictive value of stress testing versus 64-multislice coronary computed tomography angiography in predicting obstructive coronary artery disease diagnosed by coronary angiography.
Sixty-four-multislice coronary computed tomographic angiography (CTA) and coronary angiography were performed in 145 patients (mean age 67 +/- 10 years), and stress testing was performed in 47 of these patients to determine the sensitivity, specificity, positive predictive value, and negative predictive value of coronary CTA and of stress testing in diagnosing obstructive coronary artery disease (CAD) in patients with suspected CAD. In 145 patients, coronary CTA had 98% sensitivity, 74% specificity, 90% positive predictive value, and 94% negative predictive value in diagnosing obstructive CAD. In 47 patients, stress testing had 69% sensitivity, 36% specificity, 78% positive predictive value, and 27% negative predictive value for diagnosing obstructive CAD, whereas coronary CTA had 100% sensitivity, 73% specificity, 92% positive predictive value, and 100% negative predictive value for diagnosing obstructive CAD. In conclusion, coronary CTA has better sensitivity, specificity, positive predictive value, and negative predictive value than stress testing in diagnosing obstructive CAD.


A lncRNA-disease association prediction model based on the two-step PU learning and fully connected neural networks.
Long non-coding RNAs (lncRNAs) have been shown to play a regulatory role in various processes of human diseases. However, lncRNA experiments are inefficient, time-consuming and highly subjective, so that the number of experimentally verified associations between lncRNA and diseases is limited. In the era of big data, numerous machine learning methods have been proposed to predict the potential association between lncRNA and diseases, but the characteristics of the associated data were seldom explored. In these methods, negative samples are randomly selected for model training and the model is prone to learn the potential positive association error, thus affecting the prediction accuracy. In this paper, we proposed a cyclic optimization model of predicting lncRNA-disease associations (COPTLDA in short). In COPTLDA, the two-step training strategy is adopted to search for the samples with the greater probability of being negative examples from unlabeled samples and the determined samples are treated as negative samples, which are combined together with known positive samples to train the model. The searching and training steps are repeated until the best model is obtained as the final prediction model. In order to evaluate the performance of the model, 30% of the known positive samples are used to calculate the model accuracy and 10% of positive samples are used to calculate the recall rate of the model. The sampling strategy used in this paper can improve the accuracy and the AUC value reaches 0.9348. The results of case studies showed that the model could predict the potential associations between lncRNA and malignant tumors such as colorectal cancer, gastric cancer, and breast cancer. The predicted top 20 associated lncRNAs included 10 colorectal cancer lncRNAs, 2 gastric cancer lncRNAs, and 8 breast cancer lncRNAs.


Regulation of proteins in the VLA cell substrate adhesion family: influence of cell growth conditions on VLA-1, VLA-2, and VLA-3 expression.
Cell quiescence resulting from culture of normal human fibroblasts in low serum (0.5%) was associated with a subsequent gradual increase in the expression of the cell-surface glycoprotein VLA-1, and a corresponding decrease in the expression of extracellular matrix adhesion receptors VLA-2 and VLA-3. Quantitation using either flow cytometry or immunoprecipitation showed that both the VLA-1/VLA-2 and VLA-1/VLA-3 ratios increased 10- to 28-fold and were still rising when cells remained quiescent for 20-30 days. Although induced by cell quiescence, changes in the levels of VLA-1, VLA-2, and VLA-3 continued to occur well after cell proliferation had stopped and thus do not directly correlate with cell cycle transition events. Despite prolonged serum deprivation resulting in elevated VLA-1/VLA-2 and VLA-1/VLA-3 ratios, growth-arrested cells remained viable and were fully capable of proliferating when restimulated. The increases in VLA-1/VLA-2 and VLA-1/VLA-3 ratios observed on quiescent cells were readily reversible, since after restimulation with 10% serum, these ratios quickly returned within 1-2 days to a level near that found on normal exponentially grown cells. Elevation of VLA-1/VLA-2 and VLA-1/VLA-3 ratios is generally associated with quiescence and is not due just to serum deprivation since density arrest of cells at confluence had similar effects on these ratios.


Decreasing expression of HIF-1α, VEGF-A, and Ki67 with efficacy of neoadjuvant therapy in locally advanced cervical cancer.
Neoadjuvant chemotherapy (NACT) before radical hysterectomy has been widely used for locally advanced cervical cancer (LACC); However, its efficacy is yet to be determined. Effective and predictive biomarkers, which may aid in predicting the chemotherapy responses, were explored in this study. Initially, the expression of HIF-1α, VEGF-A, and Ki67 was detected in 42 paired (pre-NACT and post-NACT) LACC tissues, as well as 40 nonneoplastic cervical epithelial tissues by immunohistochemistry. Then, the correlation of the expression of HIF-1α, VEGF-A, Ki67 with the efficacy of NACT, as well as factors that affect the efficacy of NACT was analyzed. A clinical response occurred in 66.7% (28/42) of the patients, including 57.1% (16/28) with a complete response and 42.9% (12/28) with a partial response; While 33.33% (14/42) were non-responders, including 42.9% (6/14) with stable disease and 57.1% (8/14) with progressive disease. HIF-1α, VEGF-A, and Ki67 were overexpressed in LACC tissues compared to nonneoplastic tissues (P < .01, respectively); While the expression of HIF-1α, VEGF-A, and Ki67 was significantly decreased after NACT (P < .01, respectively). What's more, in the response group, HIF-1α, VEGF-A, and Ki67 expression were significantly decreased after chemotherapy in the post-chemotherapy cervical cancer tissues compared with the pre-chemotherapy cervical cancer tissues (all P < .05). Additionally, patients with lower histological grade and lower expression of HIF-1α, VEGF-A, and Ki67 were more responsive to NACT (P < .05, respectively); Moreover, the histological grade [P = .025, HR (95% CI): 0.133 (0.023-0.777)], HIF-1α [P = .019, HR (95% CI): 0.599 (0.390-0.918)], and Ki67 [P = .036, HR (95% CI): 0.946 (0898-0.996)] were independent risk factors affecting the efficacy of NACT in LACC. Expression of HIF-1α, VEGF-A, and Ki67 were significantly decreased after NACT, and decreasing expression of HIF-1α, VEGF-A, and Ki67 were related to good response to NACT, suggesting HIF-1α, VEGF-A, and Ki67 may be implicated in evaluating the efficacy of NACT in LACC.


Designing a Screening Program for Prevention of Avoidable Blindness in Iran through a Participatory Action Approach.
To design a screening program for prevention of blindness at the community level in Iran. In this qualitative study, the components and properties of the screening program were identified using a participatory action research method with focus group meetings (FGMs) with relevant health care providers and authorities. A content analysis approach was used for data analysis. In total, 18 stakeholders including six ophthalmologists with different sub-specialties participated in the five FGMs. The screening program aims to discover vision-threatening eye conditions in people aged 50 years and over. Primary health care workers deliver the program including vision tests and fundus imaging with the support of an ophthalmic technician. Retina specialists perform decision-making. Referral plans are interacted through an automated digital program. The screening environment, feedback, ethics and medical legal issues are other main components of the program. This study presents the initial concepts and components of a screening program for prevention of blindness in the adult population in Iran. The program has the potential to improve eye health at the community level and may potentially be replicated as a model for similar settings elsewhere.


Daikenchuto (TU-100) alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model: effects of gender and withdrawal.
Herbal medicines and natural products used for maintenance of health or treatment of diseases have many biological effects, including altering the pharmacokinetics and metabolism of other medications. Daikenchuto (TU-100), an aqueous extract of ginger, ginseng, and Japanese green pepper fruit, is a commonly prescribed Kampo (Japanese herbal medicine) for postoperative ileus or bloating. The effects of TU-100 on drug metabolism have not been investigated. In this study, we analyzed the effect of TU-100 on expression of key drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in murine liver and gastrointestinal tract using a dietary model. Liver, jejunum, and proximal colon were analyzed for phase I and II DMEs and DT mRNA expression by reverse transcription (RT) first by nonquantitative and followed by quantitative polymerase chain reaction (PCR) and protein expression. Liver, jejunum, and proximal colon expressed some identical but also unique DMEs and DTs. TU-100 increased the greatest changes in cytochrome (Cyp) 2b10 and Cyp3a11 and Mdr1a. Basal and TU-100 stimulated levels of DME and DT expression were gender-dependent, dose-dependent and reversible after cessation of TU-100 supplementation, except for some changes in the intestine. Quantitative Western blot analysis of protein extracts confirmed the quantitative PCR results.


Adiposity is associated with p53 gene mutations in breast cancer.
Mutations in the p53 gene are among the most frequent genetic events in human cancer and may be triggered by environmental and occupational exposures. We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations. Using tumor blocks from incident cases from a case-control study in western New York, we screened for p53 mutations in exons 2-11 using the Affymetrix p53 Gene Chip array and analyzed case-case comparisons using logistic regression. The p53 mutation frequency among cases was 28.1 %; 95 % were point mutations (13 % of which were silent) and the remainder were single base pair deletions. Sixty seven percent of all point mutations were transitions; 24 % of them are G:C>A:T at CpG sites. Positive p53 mutation status was associated with poorer differentiation (OR, 95 % CI 2.29, 1.21-4.32), higher nuclear grade (OR, 95 % CI 1.99, 1.22-3.25), and increased Ki-67 status (OR, 95 % CI 1.81, 1.10-2.98). Cases with P53 mutations were more likely to have a combined ER-positive and PR-negative status (OR, 95 % CI 1.65, 1.01-2.71), and a combined ER-negative and PR-negative status (OR, 95 % CI 2.18, 1.47-3.23). Body mass index >30 kg/m(2), waist circumference >79 cm, and waist-to-hip ratio >0.86 were also associated with p53 status; obese breast cancer cases are more likely to have p53 mutations (OR, 95 % CI 1.78, 1.19-2.68). We confirmed that p53 mutations are associated with less favorable tumor characteristics and identified an association of p53 mutation status and adiposity.


MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer.
Activation of mitogenic signaling pathways is a common oncogenic driver of many solid tumors including lung cancer. Although activating mutations in the mitogen-activated protein kinase (MAPK) pathway are prevalent in non-small cell lung cancers, MAPK pathway activity, counterintuitively, is relatively suppressed in the more aggressively proliferative small cell lung cancer (SCLC). Here, we elucidate the role of the MAPK pathway and how it interacts with other signaling pathways in SCLC. We find that the most common SCLC subtype, SCLC-A associated with high expression of ASCL1, is selectively sensitive to MAPK activation in vitro and in vivo through induction of cell-cycle arrest and senescence. We show strong upregulation of ERK negative feedback regulators and STAT signaling upon MAPK activation in SCLC-A lines. These findings provide insight into the complexity of signaling networks in SCLC and suggest subtype-specific mitogenic vulnerabilities.


Understanding the rural-urban disparity in acute respiratory infection symptoms among under-five children in Sub-Saharan Africa: a multivariate decomposition analysis.
Acute Respiratory Infections (ARIs) account for more than 6% of the worldwide disease burden in children under the age of five, with the majority occurring in Sub-Saharan Africa. Rural children are more vulnerable to and disproportionately affected by ARIs. As a result, we examined the rural-urban disparity in the prevalence of ARI symptoms and associated factors among children under the age of five in Sub-Saharan Africa. We used the most recent Demographic and Health Survey (DHS) data from 36 countries in Sub-Saharan Africa. The study included 199,130 weighted samples in total. To identify variables associated with ARIs symptoms, a multilevel binary logistic regression model was fitted. The Adjusted Odds Ratio (AOR) with a 95% CI was used to determine the statistical significance and strength of the association. To explain the rural-urban disparity in ARI prevalence, a logit-based multivariate decomposition analysis was used. Being female, ever breastfeeding, belonging to a poorer, better wealth status, and having better maternal educational status were significantly associated with lower odds of ARIs among under-five children. Whereas, small size or large size at birth, not taking vitamin A supplementation, being severely underweight, having diarrhea, didn't have media exposure, never had the vaccination, being aged 36-47 months, and being aged 48-59 months were significantly associated with higher odds of ARIs among under-five children. The multivariate decomposition analysis revealed that the difference in characteristics (endowment) across residences explained 64.7% of the overall rural-urban difference in the prevalence of ARIs, while the difference in the effect of characteristics (change in coefficient) explained 35.3%. This study found that rural children were highly affected by ARIs in SSA. To reduce the excess ARIs in rural children, public health interventions aimed at impoverished households, home births, and unvaccinated and malnourished children are crucial.


Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling.
Infiltrating macrophages are a key component of inflammation during tumorigenesis and progression. However, the role of macrophages in renal cell carcinoma (RCC), especially in the stage of RCC malignant progression, is still unclear. Here, we found the macrophages could be recruited more easily into RCC tissues than the surrounding non-tumor tissues. In vitro co-culture system also confirmed RCC cells had a better capacity to recruit macrophages via CXCL8 signaling than normal renal epithelial cells. The consequences of recruiting more macrophages may then increase RCC cells invasion abilities. Mechanism dissection revealed that infiltrating macrophages could function through induction of epithelial-mesenchymal transition and increased cancer stem cell-like populations via activation of AKT/mTOR signal, and then led to increasing RCC cells invasion. The orthotopically xenografted mouse model with RCC cells and macrophages also confirmed that infiltrating macrophages could increase RCC cells progression via AKT/mTOR signal. Together, our results reveal a new mechanism that macrophages in the RCC tumor microenvironment could increase RCC metastasis via activation of the AKT/mTOR signals. Targeting this newly identified signaling may help us to better inhibit RCC metastasis.


Outcomes of Cardiopulmonary Resuscitation and Predictors of Its Outcomes in the Emergency Department in King Saud Medical City, Saudi Arabia.
Cardiac arrest is a medical emergency marked by the cessation of cardiac mechanical activity and insufficient blood flow. CPR (cardiopulmonary resuscitation) is a life-saving method that involves restoring the essential functions of two vital organs: the heart and lungs. This study was conducted to identify the outcome of CPR in cardiac arrest patients presented to the emergency department (ED) and to identify predictors of CPR outcomes. This was a retrospective, descriptive study. All in-hospital cardiac arrest patients who underwent CPR in the King Saud Medical City (KSMC) ED between January 2017 and January 2020 were analyzed, with a sample size of 351 patients. Overall return of spontaneous circulation (ROSC) and survival to discharge (STD) were achieved in 106 (30.2%) and 40 (11.39%) patients, respectively. When assessing the predictors of ROSC, the analyses showed that patient age, pre-arrest intubation, the method used to deliver oxygen, and CPR duration were all statistically significant predictors for ROSC. Similarly, when assessing predictors associated with STD, the analyses showed that patient age, pre-arrest intubation, the method used to deliver oxygen, and CPR duration were positively associated with STD. Comparing the study's findings to those of similar studies, it shows a CPR outcome rate within the range of similar studies. It also highlights that CPR outcomes are highly associated with CPR duration (a maximum of 30 minutes), younger age, and endotracheal intubation.


Deficiency of aldose reductase attenuates inner retinal neuronal changes in a mouse model of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness where vascular abnormality and retinal dysfunction are reported. We showed earlier that genetic deletion of aldose reductase (AR), the rate-limiting enzyme in the polyol pathway, reduced the neovascularization through attenuating oxidative stress induction in the mouse oxygen-induced retinopathy (OIR) modeling ROP. In this study, we further investigated the effects of AR deficiency on retinal neurons in the mouse OIR. Seven-day-old wild-type and AR-deficient mice were exposed to 75 % oxygen for 5 days and then returned to room air. Electroretinography was used to assess the neuronal function at postnatal day (P) 30. On P17 and P30, retinal cytoarchitecture was examined by morphometric analysis and immunohistochemistry for calbindin, protein kinase C alpha, calretinin, Tuj1, and glial fibrillary acidic protein. In OIR, attenuated amplitudes and delayed implicit time of a-wave, b-wave, and oscillatory potentials were observed in wild-type mice, but they were not significantly changed in AR-deficient mice. The morphological changes of horizontal, rod bipolar, and amacrine cells were shown in wild-type mice and these changes were partly preserved with AR deficiency. AR deficiency attenuated the Müller cell gliosis induced in OIR. Our observations demonstrated AR deficiency preserved retinal functions in OIR and AR deficiency could partly reduce the extent of retinal neuronal histopathology. These findings suggested a therapeutic potential of AR inhibition in ROP treatment with beneficial effects on the retinal neurons.


Socio-Demographic Factors and Other Predictors of Pap Test Uptake Among Women: A Retrospective Study in Ghana.
The World Health Organization has reported a rise in cervical cancer in Ghana. Ghanaian women predominantly undergo opportunistic Pap smear screening for cervical cancer. Numerous studies have documented differences in the sociodemographic traits of participants undergoing Pap smear testing or screening, which correlates with their screening habits. This study aims to assess sociodemographic variables, including others that determine Pap test utilization at a single center in Ghana. A single-center survey was conducted by extracting data from the records of women who walked in for Pap smear testing. A telephone survey was also conducted among these women to document their barriers to utilizing the center. For data analysis, descriptive statistics and chi-square were utilized. A total of 197 participants' records were retrieved for the study. Most participants were market women (69.4%) and uneducated (71.4%). Their Pap smear screening records indicate that the majority (86%) had no history of cervical cancer screening, and only 3% tested positive for Pap smear test. Educational level, occupation and family history of cancer significantly correlated with participants' Pap smear history (p<0.05). However, most sociodemographic factors were not significant with the Pap test results of the participants (p>0.05). The perceived barrier identified by most participants was the need for more information (67.40%) on the test. This study revealed that sociodemographic and gynaecological factors do not correlate with Pap test results. However, education level, occupation, and family history of cancer were significantly associated with the history of Pap smear uptake. The most significant barrier hindering Pap smear services was the need for more information.


JNJ-10450232 (NTM-006), A novel non-opioid with structural similarities to acetaminophen, produces relatively long-lasting analgesia after a single dose in patients undergoing 3rd molar extraction.
JNJ-10450232 (NTM-006) is a non-opioid, non-NSAID analgesic and antipyretic compound with structural similarity to acetaminophen. Preclinical models show comparable analgesia relative to acetaminophen and no evidence of hepatotoxicity associated with overdose. Moreover, it was safe and generally well tolerated in a First-in-Human Study. This single-dose, single-center, inpatient, randomized, double-blind study in moderate-to-severe acute pain following third molar extraction compared efficacy and safety of 250 mg and 1000 mg JNJ-10450232 (NTM-006), 1000 mg acetaminophen, and placebo during the 24 h following administration. While onset of action of 1000 mg JNJ-10450232 (NTM-006) was relatively slower compared with acetaminophen, its duration of action was sustained up to 24 h being superior beginning 7 h after administration. No clinically important differences among treatment groups in nature or severity of adverse events were observed and no serious adverse events were reported. Increased bilirubin, potentially due to UGT1A1 inhibition and ingestion of blood from oral surgery, was the most commonly reported adverse event and the only event reported by ≥ 5% of subjects across treatment groups. These data support further evaluation of JNJ-10450232 (NTM-006) for the treatment of moderate-to-severe pain. CLINICALTRIALS.GOV ID: NCT02209181.


Absconding among admitted patients with bipolar affective disorder diagnosis in Uganda.
Hospitalization is often necessary for individuals with Bipolar affective Disorder (BAD) during severe manic or depressive episodes, as well as for stabilizing treatment regimens. However, a significant proportion of patients admitted for treatment of BAD abscond or leave the hospital without permission during their stay. In addition, patients managed for BAD may have unique characteristics that might force them into absconding. For example, the high prevalence of co-morbid substance use disorder - craving to use substances, suicidal behaviors - attempts to die by suicide, and cluster B personality disorders - characterized by impulsive acts. It is, therefore, essential to understand the factors contributing to absconding among patients with BAD, to facilitate designing strategies for preventing and managing this behavior. This study was based on a retrospective chart review of the inpatients diagnosed with BAD at a tertiary psychiatry facility in Uganda from January 2018 to December 2021. Approximately 7.8% of those with BAD absconded from the hospital. The likelihood of absconding among those with BAD increased with the use of cannabis [adjusted odds ratio (aOR) = 4.00, 95% confidence interval (CI) = 1.22-13.09, p-value = 0.022] and having mood lability [aOR = 2.15, 95% CI = 1.10-4.21, p-value = 0.025]. However, receiving psychotherapy during the admission (aOR = 0.44, 95 CI = 0.26-0.74, p-value = 0.002) and treatment with haloperidol (aOR = 0.39, 95% CI = 0.18-0.83, p-value = 0.014) reduced the likelihood of absconding. Absconding among patients with BAD is common in Uganda. Those with symptoms of affective lability and those with comorbid cannabis use tend to abscond more, while those who receive haloperidol and psychotherapy are less likely to abscond.


Characteristics of Pediatric Exposures to Antidementia Drugs Reported to a Poison Control System.
To characterize pediatric exposures to the antidementia drugs donepezil, memantine, rivastigmine, and galantamine by reviewing a poison control system's database. A retrospective review of a statewide poison control system's database identified cases of pediatric (less than 19 years of age) exposures to antidementia drugs over an 11-year period. Data collected included age, sex, drug(s) involved, route of exposure, reason for exposure, symptoms, and interventions. There were 189 cases identified (53% male, median age: 2.3 years, 99% unintentional exposures). Donepezil was the most commonly reported exposure (106 cases), followed by memantine (57), galantamine (18), oral rivastigmine (16), and transdermal rivastigmine (3). Coingestants were reported in 68 (36%) cases. Symptoms were reported in 38 (20%) cases. Gastrointestinal symptoms were most common (n = 21) followed by central nervous system depression (n = 15). Oral rivastigmine was associated with higher rates of symptoms. No bradycardia, seizures, or fasciculations were reported. Eighty-nine cases (47%) were evaluated at a health care facility, and 13 (7%) were admitted to a hospital. Oral rivastigmine exposures were associated with increased rate of health care facility evaluation. Activated charcoal was administered in 28 cases. Atropine was given only once, for drooling. There were no serious outcomes or deaths in this series. Reported pediatric exposures to antidementia drugs resulted in minimal morbidity and no mortality. Oral rivastigmine exposures were found to be associated with more symptoms and health care facility evaluations.


Transdermal permeation enhancement of N-trimethyl chitosan for testosterone.
The aim of this study was to evaluate the transdermal permeation enhancement of N-trimethyl chitosan (TMC) with different degrees of quaternization (DQ). TMCs with DQ of 40 and 60% (TMC40 and TMC60) were synthesized and characterized by (1)H NMR. Testosterone (TS) used as an effective drug, four different gels were prepared without enhancer, with 5% TMC40, 5% TMC60 or 2% Azone, respectively as enhancer. The effect of TMC60 on the stratum corneum was studied by Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) combined with the technique of deconvolution. The results showed that TMC60 could significantly affect the secondary structure of keratin in stratum corneum. In vitro permeation studies were carried out using Franz-diffusion cells and in vivo studies were performed in rabbits. Both in vitro and in vivo permeation studies suggested the transdermal permeation enhancement of TMCs. Compared to the TS gel without enhancer, TS gels with enhancers all showed significant enhancing effect on transdermal permeation of TS (P<0.05). Meanwhile, compared to 2% Azone, 5% TMC60 had a stronger enhancement (P<0.05) while 5% TMC40 had a similar effect (P>0.05). The results suggested that the enhancement of TMCs increased with the increase of DQ.


Tree dimensions: Maximizing the rate of height growth in dense stands.
To determine the effect of tree dimensions on the rate of height growth a model was constructed relating tree weight to total height and R, the ratio of crown weight to trunk weight. The model is based on the assumption that the trunk buckling safety factor is constant. If trees also maintain a constant R as they grow then the rate of height growth is maximized by R=0.17. In addition, the height growth rate increases as the buckling safety factor decreases. These predictions of optimal form for height growth are appropriate for shade intolerant, successional species growing in dense stands. Dimensional measurements of self thinning Populus tremuloides indicate near optimal dimensions for height growth. Trees ranging from 7 to 19 m in height had trunks which were only 50% thicker than the minimum required to prevent them from buckling under their own weight, and had a mean R of 0.13. This ratio of crown weight to trunk weight is significantly lower than the optimal value, but the predicted height growth rate for R=0.13 is 99% of that predicted for R=0.17.


[The characteristics of the realization of cytogenetic damage in mammalian and plant cells exposed to low doses of radiation].
A complicated character of the cytogenetic injury dependence upon radiation dose was revealed after low-level gamma irradiation of Vicia faba seedlings and Chinese hamster fibroblasts. The dependence was linear with low-level secondary exposure to 70 GeV protons. The authors discuss a threshold nature of induction of the cytogenetic damage repair responsible for a high outcome of damages under the effect of low-level gamma radiation.


Factors influencing acceptability of final disposal of incinerated ash and decontaminated soil from TEPCO's Fukushima Daiichi nuclear power plant accident.
TEPCO's Fukushima Daiichi nuclear power plant accident prompted extensive decontamination work. The decontaminated soil and incinerated ash generated by the process are scheduled for final disposal by March 2045 outside Fukushima Prefecture. The final disposal is unprecedented worldwide. Clarifying their acceptability will contribute to the final disposal of decontaminated soil and incinerated ash, as well as add knowledge about the perceived risk of low-concentration radioactive waste. A questionnaire survey was conducted to assess the psychological factors influencing final disposal acceptability. The results of the structural equation modeling demonstrated stable results, with risk perception decreasing acceptability, social benefits increasing acceptability, and personal benefits having limited impact. The initiative for the final disposal of decontaminated soil and incinerated ash can facilitate the reconstruction of Fukushima Prefecture after the disaster. Trust and intergenerational expectations are critical factors influencing the acceptability of this disposal. The responses were classified based on the relevance of moral norms using cluster analysis and moral foundations. The influence of each element on acceptability varied depending on the cluster. Trust was identified as the most influential factor in acceptability, regardless of the level of importance placed on moral norms.


Deflectometric method for the measurement of user power for ophthalmic lenses.
This paper presents a deflectometric technique to measure the power of an ophthalmic lens as perceived by the user. It is based on a calibrated camera acting as a pinhole in order to measure ray deflection along the same path as the visual axis when the lens is held in front of the eye. We have analyzed numerically the accuracy of our technique, and it has been compared experimentally with a commercial "lens mapper" and with the real user power calculated from the measured topography of the lens surfaces to state the reliability and accuracy of the presented technique.