Inhibition of cAMP formation by EGF in thyroid follicles is mediated by intracellular Ca++.
The mechanism of cAMP-inhibition by EGF was studied in isolated porcine thyroid follicles. EGF inhibited TSH-induced cAMP-formation maximally by 40%, this effect remained up to 1 h of pre-incubation. The calcium-ionophore A 23 187 also inhibited cAMP-formation, but its effect was relieved after 1 h. The phorbolester TPA had a biphasic influence on cAMP-formation, with a transient increase (5 min) before a sustained inhibition (60 min); the inhibitory effect was mimicked by the diacylglycerol 1-oleoyl-2-acetyl-glycerol. Exogenous arachidonic acid had only a small and transient inhibitory effect on cAMP-formation. We conclude, that EGF inhibits cAMP-formation by a raise of intracellular Ca++, as well as by the direct activation of proteinkinase C, indicating, that a phosphorylated product could be a mediator for the inhibition of adenylate cyclase.


On the role of patient.
Modern, highly technical health care systems increasingly remove patients from active participation in managing their own medical treatment. This is particularly true when serious or life-challenging illness occurs. Health psychology has much to contribute in the debate over the degree of patient self-determination necessary to achieve optimal treatment outcomes. Psychologists may directly influence this process through their professional contact with medical patients and their families. Through researching the behavioral skills of medical consumership, identifying the elements of effective patient-physician interaction, and encouraging physicians-in-training to adopt a propatient partnership attitude, psychology adds new dimensions to the provision of health care. This paper reviews some of the issues faced by patients with life-challenging illnesses through the writer's personal experience, and seeks to identify the requisite actions for informed, participatory involvement on the part of patients.


Precise investigation of the axial ligand substitution mechanism on a hydrogenphosphato-bridged lantern-type platinum(III) binuclear complex in acidic aqueous solution.
Detailed equilibrium and kinetic studies on axial water ligand substitution reactions of the "lantern-type" platinum(III) binuclear complex, [Pt(2)(mu-HPO(4))(4)(H(2)O)(2)](2)(-), with halide and pseudo-halide ions (X(-) = Cl(-), Br(-), and SCN(-)) were carried out in acidic aqueous solution at 25 degrees C with I = 1.0 M. The diaqua Pt(III) dimer complex is in acid dissociation equilibrium in aqueous solution with -log K(h1) = 2.69 +/- 0.04. The consecutive formation constants of the aquahalo complex () and the dihalo complex () were determined spectrophotometrically to be log = 2.36 +/- 0.01 and log = 1.47 +/- 0.01 for the reaction with Cl(-) and log = 2.90 +/- 0.04 and log = 2.28 +/- 0.01 for the reaction with Br(-), respectively. In the kinetic measurements carried out under the pseudo-first-order conditions with a large excess concentration of halide ion compared to that of Pt(III) dimer (C(X)()- >> C(Pt)), all of the reactions proceeded via a one-step first-order reaction, which is a contrast to the consecutive two-step reaction for the amidato-bridged platinum(III) binuclear complexes. The conditional first-order rate constant (k(obs)) depended on C(X)()- as well as the acidity of the solution. From kinetic analyses, the rate-limiting step was determined to be the first substitution process that forms the monohalo species, which is in rapid equilibrium with the dihalo complex. The reaction with 4-penten-1-ol was also kinetically investigated to examine the reactivity of the lantern complex with olefin compounds.


[Retroperitoneal fibrosis and Castleman disease in two patients with high IgG4 levels].
With the cumulative increase in the number of autoimmune pancreatitis cases, the disease is now widely accepted as a symptom of IgG4-related systemic disease. We recently experienced two cases of retroperitoneal fibrosis and Castleman disease presenting high IgG4 levels without evident pancreatic lesions. Both patients were successfully treated with steroid therapy. It is necessary to acknowledge that retroperitoneal fibrosis and Castleman disease, with or without pancreatic lesions, may have aspects of IgG4-related systemic disease and that the measurement of serum IgG4 and tissue immunostaining for IgG4 should be considered for diagnosing and treating the conditions.


Mental healthcare for psychiatric inpatients during the COVID-19 epidemic.
During this 2019 coronavirus disease (COVID-19) pneumonia epidemic, some experts have expressed concern for the mental healthcare of different types of population groups. However, hospitalised patients with severe mental illness are seemingly overlooked. Psychiatric patients are still a vulnerable group who need to obtain more attention and respect, particularly during the COVID-19 outbreak in China. In this commentary, we briefly introduce the situation of hospitalized patients with severe mental illness and suggest some effective measures that should be rapidly undertaken to reverse current challenges.


Hepatitis B vaccine and risk of acute myocardial infarction among individuals with diabetes mellitus.
A pre-licensure clinical trial of a two-dose cytosine phosphoguanine adjuvanted hepatitis B vaccine (HEPLISAV-B® [Dynavax, USA]; HepB-CpG vaccine) found an unanticipated numerical imbalance in acute myocardial infarction (AMI) compared to recipients of a three-dose aluminum adjuvanted hepatitis B vaccine (ENGERIX-B® [GlaxoSmithKline, Belgium]; HepB-alum vaccine). A post-licensure study was required to compare AMI rates among recipients of HepB-CpG vaccine and HepB-alum vaccine. Individuals with diabetes mellitus (DM), who are at higher risk of AMI, comprise more than half of the post-licensure study cohort. To inform the ongoing post-licensure study, we examined the association between AMI and receipt of HepB-alum vaccine in individuals with DM. We conducted a case-control study nested in a cohort of individuals with DM ages ≥40 years at Kaiser Permanente Southern California using electronic health records. AMI cases from 2012 to 2017 were identified by principal discharge diagnosis and matched 1:1 with randomly selected controls. The adjusted odds ratio (aOR) for receipt of ≥1 HepB-alum vaccine dose was compared for AMI cases and controls using conditional logistic regression. We subsequently performed the same matched case-control analysis stratified by year. Of 8138 matched case-control pairs, 17.4% of cases and 15.0% of controls received HepB-alum vaccine. The aOR of HepB-alum vaccination comparing cases and controls was 0.97 (95% confidence interval 0.87-1.08). Similarly, there was no significant association between HepB-alum vaccine and AMI in any of the study years. HepB-alum vaccination was not associated with AMI in individuals with DM. This finding will provide contextual insight for the ongoing post-licensure study of HepB-CpG vaccine.


A review of the role of serotonin system genes in obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that causes the patient to experience intrusive thoughts and/or to carry out repetitive, ritualized behaviors that are time consuming and impairing. OCD is familial and heritable. The genetic factors responsible for pathogenesis, however, remain largely unknown despite the numerous candidate gene studies conducted. Based on efficacy of serotonin reuptake inhibitors (SRIs) in treating OCD, serotonin system genes have been a dominant focus in OCD candidate gene studies. We review the most commonly studied candidate serotonin system gene variants (specifically in SLC6A4, HTR2A, HTR1B, and HTR2C) and their association with OCD. Although findings to date are mixed, serotonin transporter polymorphism 5-HTTLPR and HTR2A polymorphism rs6311 (or rs6313) are most consistently associated with OCD. Mixed findings may be the result of genetic complexity and phenotypic heterogeneity that future studies should account for. Homogenous patient subgroups reflecting OCD symptom dimensions, OCD subtypes, and sex should be used for gene discovery.


High genetic stability of the region coding for the structural proteins of yellow fever virus strain 17D.
The genome of the Pasteur 17D-204 vaccine strain of yellow fever virus has been cloned into pBR327. The inserts of recombinant plasmids were analysed by restriction cleavage pattern and compared with that of the genome of another substrain previously cloned and sequenced. Ten of the overlapping inserts were found to contain the sequence of the complete genome. We have sequenced approximately 3680 bases of the 5' region which codes for the C, M and E structural proteins and the NS1 non-structural protein. This sequence is the same as that reported previously, indicating a remarkable stability of these two vaccine substrains.


Amyotrophic Lateral Sclerosis: New Perpectives and Update.
Amyotrophic lateral sclerosis (ALS), Charcot's disease or Lou Gehrig's disease, is a term used to cover the spetrum of syndromes caracterized by progressive degeneration of motor neurons, a paralytic disorder caused by motor neuron degeneration. Currently, there are approximately 25,000 patients with ALS in the USA, with an average age of onset of 55 years. The incidence and prevalence of ALS are 1-2 and 4-6 per 100,000 each year, respectively, with a lifetime ALS risk of 1/600 to 1/1000. It causes progressive and cumulative physical disabilities, and leads to eventual death due to respiratory muscle failure. ALS is diverse in its presentation, course, and progression. We do not yet fully understand the causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. In this chapter, we will discuss the diagnosis, treatment, and how to cope with impaired function and end of life based on of our experience, guidelines, and clinical trials. Nowadays ALS seems to be a more complex disease than it did two decades - or even one decade - ago, but new insights have been plentiful. Clinical trials should be seen more as experiments on pathogenic mechanisms. A medication or combination of medications that targets more than one pathogenic pathway may slow disease progression in an additive or synergistic fashion.


Evaluation of newly developed wearable ear canal thermometer, mimicking the application to activities on sports and labor fields.
We evaluated the reliability of a newly developed wearable ear canal thermometer based on three different experiments, in which ear canal and rectal temperature (Tear and Trec, respectively) were simultaneously monitored. In Experiment 1, participants sat at 28 °C and 50% relative humidity (RH), during which fanning or 41 °C lower legs water immersion was conducted. In Experiment 2, participants conducted a 70-min treadmill exercise (4 km/h, 0.5% slope) at 35 °C and 50% RH with intermittent fanning. In Experiment 3, participants completed a 20 min treadmill exercise (6 km/h, 5% slope) at 35 °C and 65% RH. Bland-Altman analysis for Tear and Trec showed the difference of - 0.2-0.3 °C and the limit of agreement of the mean ± 0.3-0.6 °C. The intraclass correlation coefficient was 0.44-0.83. The results may suggest that the ear canal thermometer is useful to assess core body temperature in sports and/or labor fields.


Social capital, trust in the health-care system and self-rated health: the role of access to health care in a population-based study.
This paper investigates the relationship between institutional trust in the health-care system, i.e. an institutional aspect of social capital, and self-rated health, and whether the strength of this association is affected by access to health-care services. The 2004 public health survey in the Scania region of Sweden is a cross-sectional study; a total of 27,963 respondents aged 18-80 years answered a postal questionnaire, which represents 59% of the random sample. Logistic regression model was used to investigate the association between institutional trust and self-rated health. Multivariate analyses of self-rated health were performed in order to investigate the importance of possible confounders (age, country of origin, education, economic stress, generalized trust in other people, and care-seeking behaviour) on this association. A 28.7% proportion of the men and 33.2% of the women reported poor self-rated health. A total of 15.0% and 58.3% of the respondents reported "very high" and "rather high" trust in the health-care system, respectively. Almost one-third of all respondents reported low institutional trust. Respondents born outside Sweden, with low/medium education, low generalized trust and low institutional trust had significantly higher odds ratios of poor self-rated health. Multiple adjustments for age, country of origin, education, economic stress, and horizontal trust had some effect on the significant relationship between institutional trust and poor self-rated health, for both men and women, but the additional introduction of care-seeking behaviour in the model substantially reduced the odds ratios. In conclusion, low trust in the health-care system is associated with poor self-rated health. This association may be partly mediated by "not seeking health care when needed". However, this is a cross-sectional exploratory study and the causality may go in both directions.


Analysis of left ventricular function from multiple gated acquisition cardiac blood pool imaging. Comparison to contrast angiography.
Global ventricular function was evaluated by both multiple gated cardiac blood pool scans (MUGA) and contrast ventriculograms in a group of 17 patients with suspected coronary artery disease. The contrast ventriculograms were analyzed frame by frame to generate a volume versus time curve for each patient, while the tracer data were analyzed by two methods: 1) the standard method, in which the left ventricle is identified on the end-diastolic frame and the background corrected activity under the region of interest obtained from the entire cardiac cycle, and displayed as a time versus activity curve; and 2) by a semi-automatic method in which the computer applies a threshold detection program to define the ventricular borders, and activity in the chamber at each point in the cardiac cycle is defined after background correction. The tracer data in each patient were analyzed independently by four observers. The tracer data correlated with the contrast data on a point by point basis r = 0.87 for the standard method, and 0.93 for the semi-automatic technique. An F test of variance revealed the semi-automatic method superior to the standard approach (P less than 0.05).


Exercise-Induced Acute Kidney Injury in a Police Officer with Hereditary Renal Hypouricemia.
Hereditary renal hypouricemia is characterized by hypouricemia with hyper-uric acid clearance due to a defect in renal tubular transport. Patients with hereditary renal hypouricemia have a higher risk of exercise-induced acute kidney injury (EAKI) and reduced kidney function. Although the best preventive measure is avoiding exercise, there are many kinds of jobs that require occupational exercise. A 27-year-old male police officer suffered from stage 3 AKI after performing a 20-m multistage shuttle run test. His mother had previously been diagnosed as having renal hypouricemia at another facility. The patient had reported having hypouricemia during a health check at a previous police station, but his serum uric acid concentration was within the normal range at our hospital. After treatment, he recovered from EAKI and exhibited low serum uric acid and hyper-uric acid clearance. Since the patient desired to continue his career requiring strenuous exercise, it was difficult to establish a preventive plan against the recurrence of EAKI. Patients with hereditary renal hypouricemia who must undergo strenuous occupational anaerobic exercise are at higher risk of developing EAKI than other workers. The risks of EAKI among patients with hypouricemia should be considered when undergoing physical occupational training.


[A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients].
Occult HBV infection is defined by positive HBV DNA in individuals with undetectable levels of HBsAg. The objective of this study was to assess the prevalence of occult HBV infection in HIV-infected patients. Serum samples were obtained from 105 HBsAg-negative HIV patients who were hospitalized and were not given anti-virus treatment at Shanghai Public Health Clinical Center. Microparticle enzyme immunoassay (MEIA) was used to detect HBV serologic markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). ELISA was used to detect HCV antibody. CD4+ T cell count was examined with flow cytometry. Nested PCR was used to amplify surface protein region of HBV. 32 (30.5%) patients (27 men, 5 women) were HBV DNA positive in the 105 HBsAg-negative HIV-infected patients (92 men and 13 women). 22 patients (including 5 patients with HBV DNA +) were in 16-30 years group, 44 patients (including 15 patients with HBV DNA +) were in 3149 years group and 39 patients (including 12 patients with HBV DNA +) were in 50-75 years group. 5 patients were negative for all HBV serologic markers and 27 patients detected with at least one of anti-HBc, anti-HBe or anti-HBs. 14 patients (29.8%) with HBV DNA + in 47 HIV-infected patients were coinfected with HCV, 18 patients (31.0%) were HBV DNA + in 58 HIV-monoinfected patients. The median absolute CD4+ T cell count was 145.1 cells/microl (4-623 cells/microl), 26 patients (34.7%) were HBV DNA + in 75 AIDS patients with CD4+ T cell <200 cells/microl and 6 patients (20.0%) HBV DNA + in 30 HIV-infected patients with CD4+ T cell >200 cells/microl. No statistical significant association could be established between the above factors. It is found that occult HBV did occur in HIV-infected patients. No statistical significant association could be established between occult HBV infection and gender, age, HBV serologic markers, coinfected HCV and CD4+ T cell count.


Differences in the key parameters of the individual versus relay swimming starts.
The purpose of the present study was twofold: (i) to compare the kinematic characteristics of individual and relay swimming starts; and (ii) to relate the kinematic variables to 5 m performance for both starts. Twelve elite-level swimmers performed 2 × 25 m at maximal effort (one with an individual and one with a relay start randomly). Two-dimensional direct linear transformation algorithms were used to calculate swimmers' centre of mass (CM) kinematics during each subphase. The results indicated moderate to much faster 5 m, 10 m 15 and 15 m times (29.4, 10.7 and 6.5%) for relay than individual starts as well as the differences at specific parameters, but no differences in take-off horizontal velocity between start techniques. Large correlations to performance times were found in block time, horizontal take-off velocity, take-off velocity and entry angle (r = 0.77 to 0.83) 20 for individual start, but in changeover time, take-off height and entry distance (r = 0.69 to 0.90) for relay start. Differences on swim start regulations between individual and relay events were in line with different key parameters related to start performances in each event. This should be considered by swimmers and coaches when addressing the starting improvement.


The interconnection between independent reactive control policies drives the stringency of local containment.
The lack of medical treatments and vaccines upon the arrival of the SARS-CoV-2 virus has made non-pharmaceutical interventions the best allies in safeguarding human lives in the face of the COVID-19 pandemic. Here we propose a self-organized epidemic model with multi-scale control policies that are relaxed or strengthened depending on the extent of the epidemic outbreak. We show that optimizing the balance between the effects of epidemic control and the associated socio-economic cost is strongly linked to the stringency of control measures. We also show that non-pharmaceutical interventions acting at different spatial scales, from creating social bubbles at the household level to constraining mobility between different cities, are strongly interrelated. We find that policy functionality changes for better or worse depending on network connectivity, meaning that some populations may allow for less restrictive measures than others if both have the same resources to respond to the evolving epidemic.


Effect of Zingiber officinale essential oil on Fusarium verticillioides and fumonisin production.
The antifungal activity of ginger essential oil (GEO; Zingiber officinale Roscoe) was evaluated against Fusarium verticillioides (Saccardo) Nirenberg. The minimum inhibitory concentration (MIC) of GEO was determined by micro-broth dilution. The effects of GEO on fumonisin and ergosterol production were evaluated at concentrations of 500-5000 μg/mL in liquid medium with a 5mm diameter mycelial disc of F. verticillioides. Gas chromatography-mass spectrometry showed that the predominant components of GEO were α-zingiberene (23.9%) and citral (21.7%). GEO exhibited inhibitory activity, with a MIC of 2500 μg/mL, and 4000 and 5000 μg/mL reduced ergosterol biosynthesis by 57% and 100%, respectively. The inhibitory effect on fumonisin B1 (FB1) and fumonisin B2 (FB2) production was significant at GEO concentrations of 4000 and 2000 μg/mL, respectively. Thus, the inhibition of fungal biomass and fumonisin production was dependent on the concentration of GEO. These results suggest that GEO was able to control the growth of F. verticillioides and subsequent fumonisin production.


Advance care planning among residents in long-term care.
This study was conducted to determine whether two types of advance directives exist for individuals residing in long-term care facilities. Findings were based on data from the Medical Expenditure Panel Study-Nursing Home Component (MEPS-NHC), a survey using a two-stage stratified probability sample of nursing homes and residents to produce valid national estimates of the nursing home population in the United States. The two types of advance directives included basic, i.e., living will or do-not-resuscitate (DNR) order, and progressive (do-not-hospitalize order or orders restricting feeding, medication, or other treatment). Approximately 59 percent of long-term care residents had a basic advance directive, 9 percent have a progressive directive, and 60 percent have some type of directive. Logistic regression results indicate that the factors associated with the likelihood of each type of directive differ considerably, and only two variables (African American ethnicity and less time in the facility) were associated with a reduced likelihood of having either type of directive. Our results indicate that the two proposed types of advance directives are distinct with regard to the variables predicting each.


Daily hemofiltration in severe heart failure.
Heart failure of class IV NYHA has a very severe prognosis. Its most frequent electrolytic alterations are hyponatremia, hypokalemia, and hypomagnesemia which can cause serious arrhythmias and sudden death. The regulation of the electrolytic equilibrium by means of pharmacological therapy becomes impossible in patients with severe heart failure resistant to strong doses of diuretics in the oligo-anuric phase. This study focused on the use of daily hemofiltration in a group of patients suffering from cardiac insufficiency of class IV NYHA. The results have been evaluated over 1 year.


Single, context-specific glycans can target misfolded glycoproteins for ER-associated degradation.
The endoplasmic reticulum (ER) maintains an environment essential for secretory protein folding. Consequently, the premature transport of polypeptides would be harmful to the cell. To avert this scenario, mechanisms collectively termed "ER quality control" prevent the transport of nascent polypeptides until they properly fold. Irreversibly misfolded molecules are sorted for disposal by the ER-associated degradation (ERAD) pathway. To better understand the relationship between quality control and ERAD, we studied a new misfolded variant of carboxypeptidase Y (CPY). The molecule was recognized and retained by ER quality control but failed to enter the ERAD pathway. Systematic analysis revealed that a single, specific N-linked glycan of CPY was required for sorting into the pathway. The determinant is dependent on the putative lectin-like receptor Htm1/Mnl1p. The discovery of a similar signal in misfolded proteinase A supported the generality of the mechanism. These studies show that specific signals embedded in glycoproteins can direct their degradation if they fail to fold.


Computed tomography in bacterial meningitis of childhood.
The hospital records of 85 children with bacterial meningitis were reviewed and a subset of 25 children who underwent computed tomography of the head were identified. The major stated indications for computed tomography were fever (8 patients), seizures (4 patients), signs of increased intracranial pressure (4 patients), focal neurologic dysfunction (3 patients) and recurrent meningitis (2 patients). Abnormal findings were demonstrated by computed tomography in 20 of 25 patients but in 8 patients consisted solely of nonspecific dilatation of spaces containing cerebrospinal fluid or of basilar enhancement. The yield of information that was useful either diagnostically or therapeutically was low; positive findings of obvious clinical relevance were present in only 2 cases. Computed tomography provides an accurate means of diagnosing intracranial complications of bacterial meningitis. It must be used conservatively, however, to limit expense and radiation exposure and enhance the yield of potentially relevant information. Computed tomography is indicated for children with persistent neurologic dysfunction, persistently positive cerebrospinal fluid cultures or recurrent meningitis, whereas it is of little value for children with prolonged fever alone.


Native point defects on hydrogen-passivated 4H-SiC (0001) surface and the effects on metal adsorptions.
With the continued expansion of silicon carbide's (SiC) applications, atomistic understanding on the native point defects of its surfaces, particularly on those of the hydrogen-passivated (HP) 4H-SiC (0001) surface, becomes imperative. Using first-principles calculations, the structures and formation energies of several typical native point defects (e.g., ISi, IC, VSi, VC, and SiC) on the (0001) HP-surface of 4H-SiC were systematically explored, including the effects of the unit cell size, environmental condition, charge state, and hydrogen incorporation. Furthermore, their adsorptions of Ag (Mo) atom on these defective sites were systematically investigated. The formation energies of these defects in the HP-surface, clean surface, and bulk SiC were concluded together with their thermodynamic concentrations in the HP-surface estimated. The influences of these defects to metal (Ag, Mo) adsorptions of HP-surfaces were concluded. Based on these conclusions, the wettability improvement between the metal liquid and ion (Ag or Mo) implanted SiC substrates in the previous studies can be well understood at the atomistic scale. This study provides a theoretical guideline to SiC surface modification for the production of metal-SiC composites, brazing of SiC with metals, fabrication of electronic devices, or the growth of two dimensional nanofilms.


Management of hyperglycemia in minority children with type 2 diabetes mellitus.
This paper discusses management of hyperglycemia in minority children with type 2 diabetes mellitus (DM). Over the past several years the incidence of type 2 DM in minority children and adolescents has markedly increased. Intensive management of children with type 2 DM includes exercise, diet, insulin therapy, oral drug (metformin) therapy, and combination insulin-oral drug therapy. The results of a study of the efficacy of treatment modalities in 35 African-American children are presented. In the study, the patients were divided into two groups, one treated with diet or metformin therapy (20 children) and the other with insulin or a combination of insulin and metformin (15 children). All of the children in the study were negative for antibodies to glutamic acid decarboxylase. Plasma glucose and serum C-peptide concentrations were measured at 0, 30, 60, 90, and 120 min after ingestion of a liquid meal (Sustacal) (7 ml/kg with a maximum of 360 ml). The increase of C-peptide (ACP) in response to the mixed meal was calculated by peak minus fasting C-peptide. ACP was significantly higher in those children treated with diet/metformin than in those treated with insulin/insulin and metformin combination therapy (4.6 +/- 1.9 vs 21 +/- 1.6, p <0.01). Mean HbA1c at one-year follow up was lower for the diet/metformin patients than in the insulin/insulin and metformin group (7.0 +/- 2.8 vs 11.4 +/- 3.7, p <0.01). Our results indicate that in children with type 2 DM, there is more severe pancreatic beta-cell dysfunction in the group of children requiring insulin therapy.


Use of Statins and the Risk of Incident Diabetes: A Retrospective Cohort Study.
Even though several landmark statin trials have demonstrated the beneficial effects of statin therapy in both primary and secondary prevention of cardiovascular disease, several studies have suggested that statins are associated with a moderate increase in risk of new-onset diabetes. These observations prompted the US FDA to revise statin labels to include a warning of an increased risk of incident diabetes mellitus as a result of increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose. However, few studies have used US-based data to investigate this statin-associated increased risk of diabetes. The primary objective of our study was to examine whether the use of statins increases the risk of incident diabetes mellitus using data from the Thomson Reuters MarketScan (®) Commercial Claims and Encounters Database. This study was a retrospective cohort analysis utilizing data for the period 2003-2004. The study population included new statin users aged 20-63 years at index who did not have a history of diabetes. The proportion (3.4 %) of statin users (N = 53,212) who had incident diabetes was higher than the proportion (1.2 %) of non-statin users (N = 53,212) who had incident diabetes. Compared with no statin use and controlling for demographic and clinical covariates, statin use was significantly associated with increased risk of incident diabetes (hazard ratio 2.01; 99 % confidence interval 1.74-2.33; p < 0.0001). In addition, risk of diabetes was highest among users of lovastatin, atorvastatin, simvastatin, and fluvastatin. Diabetes risk was lowest among pravastatin and rosuvastatin users. Because the potential for diabetogenicity differs among different statin types, healthcare professionals should individualize statin therapy by identifying patients who would benefit more from less diabetogenic statin types.


Oligomeric pseudorotaxanes adopting infinite-chain lattice superstructures.
It's just an illusion: Above a critical chain length, where oligomers contain five or more recognition units, apparently infinite donor-acceptor polypseudorotaxanes are formed in the solid state (see picture). X-ray crystallographic analyses of three different examples have shown that although the oligomeric chains are undoubtedly discrete and monodisperse, they nevertheless appear to be infinite in the crystal.


A structured mechanistic model of the kinetics of enzymatic lysis and disruption of yeast cells.
A structured, mechanistic model has been built for the kinetics of yeast cell lysis by microbial cell lytic enzymes, based on an understanding of the two-layer yeast cell wall structure and the properties of yeast-lytic enzyme systems. The model predicts the release of protein, peptides and carbohydrates from four cell structures: the outer and inner wall layers, the cytosol and organelles or proteins present in particles; it also predicts organelle or particle lysis or solubilization and the breakdown of released proteins to peptides. Applications of the model to design and optimization of selective product release are discussed.


[Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis].
To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.


Astrocytic Vesicle-based Exocytosis in Cultures and Acutely Isolated Hippocampal Rodent Slices.
Astrocytes are excitable neural cells that contribute to brain information processing via bidirectional communication with neurons. This involves the release of gliosignaling molecules that affect synapses patterning and activity. Mechanisms mediating the release of these molecules likely consist of non-vesicular and vesicular-based mechanisms. It is the vesicle-based regulated exocytosis that is an evolutionary more complex process. It is well established that the release of gliosignaling molecules has profound effects on information processing in different brain regions (e.g., hippocampal astrocytes contribute to long-term potentiation [LTP]), which has traditionally been considered as one of the cellular mechanisms underlying learning and memory. However, the paradigm of vesicle-based regulated release of gliosignaling molecules from astrocytes is still far from being unanimously accepted. One of the most important questions is to what extent can the conclusions obtained from cultured astrocytes be translated to in vivo conditions. Here, we overview the properties of vesicle mobility and their fusion with the plasma membrane in cultured astrocytes and compare these parameters to those recorded in astrocytes from acute brain hippocampal slices. The results from both experimental models are similar, which validates experiments on isolated astrocytes and further supports arguments in favor of in vivo vesicle-based exocytotic release of gliosignaling molecules. © 2017 Wiley Periodicals, Inc.


A fluorescent biosensor based on carbon quantum dots and single-stranded DNA for the detection of Escherichia coli.
To detect E. coli in food, a simple fluorescent biosensor based on single-stranded DNA (ssDNA) and carbon quantum dots (CQDs) was developed. The carbon quantum dots were synthesized using a superhydrothermal method with carrot juice as a carbon source. The fluorescence intensity of the CQDs was decreased by induced ssDNA attachment. In the presence of E. coli, ssDNA preferentially binds to E. coli through hydrogen bonding and its fluorescence is greater than that in the absence of E. coli. The results showed that the linear range of the sensor was 1 × 102-1 × 108 CFU mL-1 with a coefficient of determination (R2) of 0.9870. The detection limit for E. coli was 60 CFU mL-1.


Familial cerebral cavernomas due to a KRIT1 mutation presenting with epilepsy.
The authors present the case of a 25-year-old individual who presented acutely following a generalised tonic-clonic seizure. Brain MRI of the individual demonstrated the classical appearance of multiple cerebral cavernous haemangiomas (cavernomas). There was an autosomal dominant family history. Genetic testing identified a truncating mutation in the KRIT1 gene in the individual and confirmed the diagnosis of familial cerebral cavernomas as the cause of epilepsy in the family.


Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy.
Generalized lipodystrophy is characterized by adipose tissue absence, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with recombinant leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with recombinant leptin, and we have followed 15 on leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with recombinant leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with recombinant leptin demonstrated reduction in proteinuria and hyperfiltration.


[Intracellular Ca2+ distribution and its role in mouse oocytes maturation].
To determine the role of calcium and calmodulin in mouse oocyte maturation, we examined the distribution of intracellular calcium during mouse oocyte maturation by using Mira Cal Imaging System. The calcium was present homogeneously in oocytes with intact germinal vesicle (GV) and accumulated around the nuclear region after GV breakdown(GVBD). The high level of calcium disappeared 6 hours later after GVBD. In the presence of 50 mumol/L BAPTA/AM, we failed to observe this phenomena. All eggs treated with 20 mumol/L W7, an antagonist of calmodulin, 50 mumol/L BAPTA/AM, a calcium chelator, could not develop to metaphase II (MII), although GVBD was not affected. We also detected the activity of a cytoplasmic maturation-promoting factor (MPF). W7 and BAPTA/AM had no effects on the rise of MPF activity in the course of maturation. We suggest that compartment distribution of calcium around nuclear region plays an important role in mouse oocyte maturation.


[Afobazole increases cerebral blood flow in rats with global brain ischemia].
The selective anxiolytic drug afobazole administered in a dose of 5 mg/kg increased the cerebral blood flow in rats. The effect was more pronounced in rats with global reversible cerebral ischemia than in intact animals. The ischemia model was caused by occlusion of both common carotid arteries for 120 min with simultaneous reduction of the arterial pressure to 40-50 mm Hg through blood-letting. Afobazole also significantly increased the survival of rats with cerebral ischemia model caused by ligation of both common carotid arteries, which was evidence of the neuroprotector activity. Apparently, the ability of afobazole to improve the cerebral blood flow in ischemized rat brain is an important factor in realization of the neuroprotector activity.


Enhanced Four-Electron Selective Oxygen Reduction Reaction at Carbon-Nanotube-Supported Sulfonic-Acid-Functionalized Copper Phthalocyanine.
In the present work, the oxygen reduction reaction (ORR) is explored in an acidic medium with two different catalytic supports (multi-walled carbon nanotubes (MWCNTs) and nitrogen-doped multi-walled carbon nanotubes (NMWCNTs)) and two different catalysts (copper phthalocyanine (CuPc) and sulfonic acid functionalized CuPc (CuPc-SO3 - )). The composite, NMWCNTs-CuPc-SO3 - exhibits high ORR activity (assessed based on the onset potential (0.57 V vs. reversible hydrogen electrode) and Tafel slope) in comparison to the other composites. Rotating ring disc electrode (RRDE) studies demonstrate a highly selective four-electron ORR (less than 2.5 % H2 O2 formation) at the NMWCNTs-CuPc-SO3 - . The synergistic effect of the catalyst support (NMWCNTs) and sulfonic acid functionalization of the catalyst (in CuPc-SO3 - ) increase the efficiency and selectivity of the ORR at the NMWCNTs-CuPc-SO3 - . The catalyst activity of NMWCNTs-CuPc-SO3 - has been compared with many reported materials and found to be better than several catalysts. NMWCNTs-CuPc-SO3 - shows high tolerance for methanol and very small deviation in the onset potential (10 mV) between the linear sweep voltammetry responses recorded before and after 3000 cyclic voltammetry cycles, demonstrating exceptional durability. The high durability is attributed to the stabilization of CuPc-SO3 - by the additional coordination with nitrogen (Cu-Nx ) present on the surface of NMWCNTs.


Intracisternal Type A particles in murine pancreatic B cells. Immunocytochemical demonstration of increased antigen (p73) in genetically diabetic mice.
Intracisternal Type A particles (IAPs) are retroviruslike structures identified by a core protein antigen (p73) and found in mouse embryos, in many mouse tumor cells, and in pancreatic B cells of some strains of genetically diabetic mice. Using both peroxidase-antiperoxidase and protein A-gold immunocytochemical techniques to localize p73, the authors have observed differences in intracellular antigen distribution between MOPC-104E, a mouse tumor cell line rich in IAP, and B cells from genetically diabetic (db/db) mice of the CBA/LtJ and C57BL/KsJ strain. In MOPC-104E cells studied by electron microscopy, localization of protein A-gold complex label was almost exclusively limited to IAP and their sites of assembly on the rough endoplasmic reticulum. In contrast, p73 appeared widely distributed throughout the cytoplasm of B cells from hyperglycemic db/db mice but not normal littermate controls. In addition to distribution over budding IAP, label was also found dispersed through other cytoplasmic organelles involved in secretion, including Golgi complexes and secretory granules. Patch labeling of B cell surfaces was sometimes observed. An ultrastructural survey of islets isolated from normal mice of 7 inbred genetic backgrounds on which the "diabetes" (db) gene has been studied showed that constitutive ability to produce IAP was associated with strain susceptibility to severe diabetes (eg, C57BL/KsJ, DBA/2J, CBA/LtJ, and C3HeB/FeJ). Strains whose B cells failed to show constitutive expression in situ or glucose-inducible expression in cell culture were resistant to the diabetogenic action of db genes. The possibility is discussed that p73 may represent a "neoantigen" which sensitizes the diabetic mouse to reject, by autoimmune mechanisms, the B cells expressing it.


Evaluation of a commercially available luteinizing hormone test for its ability to distinguish between ovariectomized and sexually intact bitches.
To determine the value of a commercially available test for measurement of luteinizing hormone (LH) concentrations for its use in distinguishing between ovariectomized and sexually intact bitches. Prospective longitudinal cohort study. 101 sexually intact bitches and 199 ovariectomized bitches A commercial test kit was used to assay serum samples for LH concentration. A kappa test was used to assess the consistency of test interpretations. Sensitivity, specificity, predictive values, and consistency of test interpretation in the sample population and in 2 theoretical populations of bitches with differing frequencies of ovarian removal were determined. The test had excellent sensitivity (98%) but moderate specificity (78%) because of a high frequency of false-positive test results. This means that a single high serum LH concentration was not a reliable indicator of ovarian removal. However, a single low serum LH concentration was an excellent indicator that a bitch was sexually intact. The LH test results were positive within 10 days after ovarian removal and remained high in bitches from which ovaries had been removed > 5 years previously. Analysis of kappa values consistently revealed excellent agreement in test interpretation within and among evaluators and over a 6-hour time span. A single low LH test result confirms the need for ovariectomy in bitches prior to adoption. The test is applicable to bitches that have been ovariectomized prior to puberty and probably applies over the lifespan of the animal.


Isolation and characterization of a temperature-sensitive mutant of Salmonella typhimurium defective in prolipoprotein modification.
A temperature-sensitive (ts) mutant of Salmonella typhimurium that accumulated unmodified murein prolipoprotein at 42 degrees C but not at 30 degrees C was identified. In vivo and in vitro studies of the biosynthesis of Braun's lipoprotein revealed that this mutant (SE5221) was defective in the glyceryl modification of prolipoprotein. The ts mutation was mapped to 60.6 min of the S. typhimurium chromosome and was linked to argA and cysH. A clone with a 1.4-kilobase S. typhimurium DNA insert that complemented the ts mutation and restored the prolipoprotein modification activity both in vivo and in vitro was isolated. DNA sequencing of the complementing region revealed an open reading frame encoding a protein with 291 amino acids lacking NH2-terminal signal sequence. This open reading frame is immediately 5' to the thyA gene and is allelic to umpA of Escherichia coli. Wild-type strains harboring the cloned gene exhibited elevated levels of prolipoprotein modification activity. At the non-permissive temperature, the mutation affected both growth and viability, and the mutant cells exhibited anomalous cell morphology. The ts phenotype was suppressed by the introduction of a lpp::Tn10 mutation. These results suggest that the cloned gene encodes prolipoprotein glyceryl transferase (lgt), and in the wild-type background, this prolipoprotein modification enzyme is essential for the growth and viability of S. typhimurium.


Hyperpolarized 3-helium MR imaging of the lungs: testing the concept of a central production facility.
The aim of this study was to test the feasibility of a central production facility with distribution network for implementation of hyperpolarized 3-helium MRI. The 3-helium was hyperpolarized to 50-65% using a large-scale production facility based at a university in Germany. Using a specially designed transport box, containing a permanent low-field shielded magnet and dedicated iron-free glass cells, the hyperpolarized 3-helium gas was transported via airfreight to a university in the UK. At this location, the gas was used to perform in vivo MR experiments in normal volunteers and patients with chronic obstructive lung diseases. Following initial tests, the transport (road-air-road cargo) was successfully arranged on six occasions (approximately once per month). The duration of transport to imaging averaged 18 h (range 16-20 h), which was due mainly to organizational issues such as working times and flight connections. During the course of the project, polarization at imaging increased from 20% to more than 30%. A total of 4 healthy volunteers and 8 patients with chronic obstructive pulmonary disease were imaged. The feasibility of a central production facility for hyperpolarized 3-helium was demonstrated. This should enable a wider distribution of gas for this novel technology without the need for local start-up costs.


Review article: stem cells in human reproduction.
The derivation of human embryonic stem (hES) cells heralds a new era in stem cell research, generating excitement for their therapeutic potential in regenerative medicine. Pioneering work of embryologists, developmental biologists, and reproductive medicine practitioners in in vitro fertilization clinics has facilitated hES cell research. This review summarizes current research focused on optimizing hES cell culture conditions for good manufacturing practice, directing hES cell differentiation toward trophectoderm and germ cells, and approaches used to reprogram cells for pluripotent cell derivation. The identification of germ stem cells in the testis and the recent controversy over their existence in the ovary raise the possibility of harnessing them for treating young cancer survivors. There is also the potential to harvest fetal stem cells with pluripotent cell-like properties from discarded placental tissues. The recent identification of adult stem/progenitor cell activity in the human endometrium offers a new understanding of common gynecological diseases. Discoveries resulting from research into embryonic, germ, fetal, and adult stem cells are highly relevant to human reproduction.


Marital therapy when one spouse has a primary affective disorder.
The authors explain why marital disharmony when one spouse has a primary affective disorder is difficult to treat but suggest that such couples can be treated successfully if the therapist is flexible and sets realistic goals. Because of the variability of the disease and the many unsubstantiated etiologies associated with it, the authors recommend a modified general system theory approach to treatment that includes a combination of psychotherapy and somatotherapy.


Assessing the detection, reporting and investigation of adverse events in clinical trial protocols implemented in Cameroon: a documentary review of clinical trial protocols.
International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee.


Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3-13C]Glucose Breath Tests.
This study aimed to evaluate changes in glucose metabolism at the early stage and onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Specifically, after the oral administration of [1, 2, 3-13C]glucose, the levels of exhaled 13CO2, which most likely originated from pyruvate decarboxylation and tricarboxylic acid, were measured. Eight OLETF rats and eight control rats (Long-Evans Tokushima Otsuka [LETO]) were administered 13C-glucose. Three types of 13C-glucose breath tests were performed thrice in each period at 2-week intervals. [3-13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule, which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13CO2 excretion in OLETF rats was delayed in all three breath tests compared to that in control rats, suggesting that OLETF rats had a lower glucose metabolism than control rats. In addition, overall glucose metabolism increased with age in both groups. The utilization of [2-13C]glucose was suppressed in OLETF rats at 6-12 weeks of age, but they showed higher [3-13C]glucose oxidation than control rats at 22-25 weeks of age. In the [1-13C]glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC180) were observed between OLETF and LETO rats of any age. Glucose metabolism kinetics were different between the age groups and two groups of rats; however, these differences were not significant based on the overall AUC180 of [1-13C]glucose. We conclude that breath 13CO2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats.


Regulation of Nanoliposome Rigidity and Bioavailability of Oligomeric Proanthocyanidin with Phytosterols Containing Different C3 Branches.
The rigidity of nanoliposomes significantly influences their physical stability and in vitro and in vivo behaviors (e.g., cellular uptake, blood circulation, biodistribution, etc.). This study aimed to quantify the rigidity of the nanoliposomes composed of phytosterol with varying C3 branches and phospholipids (DPPC, DOPC) using atomic force microscopy. Young's modulus, determined by the Shell model, effectively differentiated between mechanical differences in nanoliposomes with varying components and component structure and phase states. FTIR results indicated that P-SG exhibited the highest Young's modulus (175.98 ± 10.53 MPa) due to the hydrogen bond between the glucose residue of steryl glycosides (SGs) and the phospholipid polar head. However, the rigidity of DOPC nanoliposomes was not significantly different due to the unsaturated bond. The addition of oligomeric proanthocyanidin (OPC) did not change the order of rigidity among the nanoliposomes, with P-SG-OPC having the highest Young's modulus (126.27 ± 2.06 MPa). In the simulated gastrointestinal tract experiment, P-SG-OPC exhibited the greatest stability, with minimal particle aggregation. Cellular uptake experiments revealed that DPPC nanoliposomes with high rigidity had optimal endocytosis, while DOPC nanoliposome uptake was independent of rigidity. In melanin production inhibition tests, the inhibitory effect correlated directly with Young's modulus and P-SG-OPC had the best inhibitory effect on melanin generation. Our findings in this study provide valuable insights into the design and optimization of nanoliposomes for the efficient delivery of active substances, offering potential solutions for improving the efficacy of drug delivery systems.


Genetic characterization of Bombyx mori (Lepidoptera: Bombycidae) breeding and hybrid lines with different geographic origins.
The domesticated silkworm Bombyx mori L. comprises a large number of geographical breeds and hybrid lines. Knowing the genetic structure of those may provide information to improve the conservation of commercial lines by estimating inbreeding over generations and the consequences of excessive use of those lineages. Here, we analyzed the genetic diversity of seven breeds and eight hybrid lines from Eastern Europe and Asia using highly polymorphic microsatellites markers to determine its genetical impact on their use in global breeding programs. No consistent pattern of deviation from Hardy-Weinberg equilibrium was found for most breed and hybrids; and the absence of a linkage disequilibrium also suggests that the strains are in equilibrium. A principal coordinate analysis revealed a clear separation of two silkworm breeds from the rest: one (IBV) originated from India and the other one (RG90) from Romania/Japan. The tendency of the other breeds from different geographic origins to cluster together in a general mix might be due to similar selection pressures (climate and anthropogenic factors) in different geographic locations. Phylogenetic analyses grouped the different silkworm breeds but not the hybrids according to their geographic origin and confirmed the pattern found in the principal coordinate analysis.


Reference standardization and triglyceride interference of a new homogeneous HDL-cholesterol assay compared with a former chemical precipitation assay.
A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy, and cholesterol and triglyceride interference. In addition, its analytical performance was compared with that of a phosphotungstic acid (PTA)/MgCl2 precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were < or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4 mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5% and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H concentrations were increasingly positively biased with increasing triglyceride concentrations. The method comparison between HDL-H and HDL-P yielded the following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL-H amply meets the 1998 NCEP recommendations for total error; its precision is superior compared with that of HDL-P, and its average bias remains below +/-5% as long as triglyceride concentrations are < or = 10 g/L and in case of moderate hypercholesterolemia.


Death related to midazolam overdose during endoscopic retrograde cholangiopancreatography.
We report a midazolam-related death that occurred during endoscopic retrograde cholangiopancreatography (ERCP). The acute intoxication due to midazolam overdose was confirmed by high-pressure liquid chromatography (HPLC) analysis of the blood samples taken from the patient in the intensive care unit (2.8 microg/ml) and postmortem (2.4 microg/ml). The case strongly emphasizes the necessity of the precautions that should be taken when midazolam is intravenously administered.


Ground versus earth, there is a difference.
Investigations of injuries and fires caused by electrical circuits and equipment can result in incorrect conclusions when grounding systems are neglected. The term ground is loosely used in electrical jargon as any zero reference point for voltage measurement. Power systems are usually grounded to the earth. Other electrical systems are sometimes grounded to the same earth through a low impedance circuit. Residential grounding systems are described and a simple method is proposed for the investigator's use in evaluating the grounding system for potential shock or equipment damage hazards.


The structural organization of the septate and gap junctions of Hydra.
The septate junctions and gap junctions of Hydra were studied utilizing the extracellular tracers lanthanum hydroxide and ruthenium red. Analysis of the septate junction from four perspectives has shown that each septum consists of a single row of hexagons sharing common sides of 50-60 A. Each hexagon is folded into chair configuration. Two sets of projections emanate from the corners of the hexagons. One set (A projections) attaches the hexagons to the cell membranes at 80-100-A intervals, while the other set (V projections) joins some adjacent septa to each other. The septate junctions generally contain a few large interseptal spaces and a few septa which do not extend the full length of the junction. Basal to the septate junctions the cells in each layer are joined by numerous gap junctions. Gap junctions also join the muscular processes in each layer as well as those which connect the layers across the mesoglea. The gap junctions of Hydra are composed of rounded plaques 0.15-0.5 micro in diameter which contain 85-A hexagonally packed subunits. Each plaque is delimited from the surrounding intercellular space by a single 40-A band. Large numbers of these plaques are tightly packed, often lying about 20 A apart. This en plaque configuration of the gap junctions of Hydra contrasts with their sparser, more widely separated distribution in many vertebrate tissues. These studies conclude that the septate junction may possess some barrier properties and that both junctions are important in intercellular adhesion. On a morphological basis, the gap junction appears to be more suitable for intercellular coupling than the septate junction.


Cellular Mechanism Underlying Hydrogen Sulfide Mediated Epithelial K+ Secretion in Rat Epididymis.
As a novel gasotransmitter, hydrogen sulfide (H2S) elicits various physiological actions including smooth muscle relaxation and promotion of transepithelial ion transport. However, the pro-secretory function of H2S in the male reproductive system remains largely unclear. The aim of this study is to elucidate the possible roles of H2S in modulating rat epididymal intraluminal ionic microenvironment essential for sperm storage. The results revealed that endogenous H2S-generating enzymes cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) were both expressed in rat epididymis. CBS located predominantly in epithelial cells whilst CSE expressed primarily in smooth muscle cells. The relative expression level of CBS and CSE escalated from caput to cauda regions of epididymis, which was paralleled to the progressively increasing production of endogenous H2S. The effect of H2S on epididymal epithelial ion transportation was investigated using short-circuit current (I SC), measurement of intracellular ion concentration and in vivo rat epididymal microperfusion. Our data showed that H2S induced transepithelial K+ secretion via adenosine triphosphate-sensitive K+ (KATP) channel and large conductance Ca2+-activated K+ (BKCa) channel. Transient receptor potential vanilloid 4 (TRPV4) channel-mediated Ca2+ influx was implicated in the activation of BKCa channel. In vivo studies further demonstrated that H2S promoted K+ secretion in rat epididymal epithelium. Inhibition of endogenous H2S synthesis caused a significant decrease in K+ concentration of cauda epididymal intraluminal fluid. Moreover, our data demonstrated that high extracellular K+ concentration actively depressed the motility of cauda epididymal sperm in a pH-independent manner. Collectively, the present study demonstrated that H2S was vital to the formation of high K+ concentration in epididymal intraluminal fluid by promoting the transepithelial K+ secretion, which might contribute to the maintenance of the cauda epididymal sperm in quiescent dormant state before ejaculation.


Adult cortical dynamics.
There are many influences on our perception of local features. What we see is not strictly a reflection of the physical characteristics of a scene but instead is highly dependent on the processes by which our brain attempts to interpret the scene. As a result, our percepts are shaped by the context within which local features are presented, by our previous visual experiences, operating over a wide range of time scales, and by our expectation of what is before us. The substrate for these influences is likely to be found in the lateral interactions operating within individual areas of the cerebral cortex and in the feedback from higher to lower order cortical areas. Even at early stages in the visual pathway, cells are far more flexible in their functional properties than previously thought. It had long been assumed that cells in primary visual cortex had fixed properties, passing along the product of a stereotyped operation to the next stage in the visual pathway. Any plasticity dependent on visual experience was thought to be restricted to a period early in the life of the animal, the critical period. Furthermore, the assembly of contours and surfaces into unified percepts was assumed to take place at high levels in the visual pathway, whereas the receptive fields of cells in primary visual cortex represented very small windows on the visual scene. These concepts of spatial integration and plasticity have been radically modified in the past few years. The emerging view is that even at the earliest stages in the cortical processing of visual information, cells are highly mutable in their functional properties and are capable of integrating information over a much larger part of visual space than originally believed.


Photo-catalytic, anti-bacterial, and anti-cancer properties of phyto-mediated synthesis of silver nanoparticles from Artemisia tournefortiana Rchb extract.
Metal nanoparticles have largely been investigated due to their potential medicinal activities. This study demonstrates the biological properties of green-synthesized silver nanoparticles (AgNPs) by using Artemisia tournefortiana Rchb ethanol extract. Instrumentations such as ultraviolet-visible spectra analysis, high-resolution transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray analysis, X-ray diffraction, and Fourier transform infrared spectroscopy were used to reveal the synthesized AgNPs. Microscopic results showed that the particles were mostly spherical in shape, having an average diameter of 22.89±14.82nm. The antibacterial activity of the phyto-fabricated AgNPs was investigated by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The in vitro cytotoxicity effect was investigated against normal human embryonic kidney (HEK293) cells and human colon adenocarcinoma cancer (HT29) cells. The apoptotic cells were identified by annexin V/PI FITC staining, and morphological assessment. The expressions of Bax and Bcl2 were evaluated by quantitative real time PCR method. The phyto-synthesized AgNPs have shown increased cell apoptosis and demonstrated dose-dependent cytotoxicity in HT29 cancer cells. Moreover, the photocatalytic activity of the phyto-synthesized AgNPs was evaluated by degradation of Coomassie Brilliant Blue G-250 under UV light exposure and these fabricated Ag nanoparticles demonstrated efficacy in degrading the dye within 60min. Overall, the present results highlighted the antibacterial and anticancer properties of fabricated AgNPs, suggesting that phyto-synthesized silver nanoparticles could possess potent anti-pathogenic bacteria and anti-colon cancer activities.


Primary paraspinal lumbar hydatid disease: A known diagnosis in an unusual localization.
Hydatid disease is a parasitic infection caused by Echinococcus granulosus. Although the liver and lung are the most common sites of hydatid disease, it can also be seen in other organs due to migration via systemic circulation. Paraspinal lumbar hydatid disease without the involvement of other organs is extremely rare. We aimed to present the imaging and histopathological findings of a case with painful lumbar swelling that was later diagnosed as primary lumbar paraspinal hydatid disease. Hydatid disease should be considered as the differential diagnosis in patients with a lumbar paraspinal mass, particularly that containing multiple well-defined, round, small cysts, and in patients living in or traveling to endemic regions.


Neonatal basal ganglia and thalamic volumes: very preterm birth and 7-year neurodevelopmental outcomes.
BackgroundThis study aims to (i) compare volumes of individual basal ganglia nuclei (caudate nucleus, pallidum, and putamen) and the thalamus between very preterm (VP) and term-born infants at term-equivalent age; (ii) explore neonatal basal ganglia and thalamic volume relationships with 7-year neurodevelopmental outcomes, and whether these relationships differed between VP and term-born children.Methods210 VP (<30 weeks' gestational age) and 39 term-born (≥37 weeks' gestational age) infants underwent brain magnetic resonance imaging at term-equivalent age, and deep gray matter volumes of interest were automatically generated. 186 VP and 37 term-born children were assessed for a range of neurodevelopmental measures at age 7 years.ResultsAll deep gray matter structures examined were smaller in VP infants compared with controls at term-equivalent age; ranging from (percentage mean difference (95% confidence intervals) -6.2% (-10.2%, -2.2%) for the putamen, to -9.5% (-13.9%, -5.1%) for the caudate nucleus. Neonatal basal ganglia and thalamic volumes were positively related to motor, intelligence quotient, and academic outcomes at age 7 years, with mostly similar relationships in the VP and control groups.ConclusionVP birth results in smaller basal ganglia and thalamic volumes at term-equivalent age, and these smaller volumes are related to a range of 7-year neurodevelopmental deficits in VP children.


Germany's long-term care insurance model: lessons for the United States.
The implementation of public long term care (LTC) insurance in 1995 in Germany is an important public policy development that offers lessons for the U.S. The German LTC model is comprehensive and mandatory, covering 88 percent of its population, by equal premium contributions on wages from employees and employers. The new German system has uniform eligibility and benefit criteria, covers both institutional and home care, pays for family caregivers, is financially solvent, and is considered a success by the public. In contrast, the U.S. financing of LTC is largely private, with the government serving as the safety net for the majority of the LTC costs after individuals spend down their resources. This paper considers whether a German-type LTC system is feasible and affordable and discusses the issues and complexities of public LTC insurance, including cost containment, home care services, quality control, and administrative structure.


Three-dimensional structure of the Y1 receptor agonist [Leu31, Pro34]NPY as determined by NMR and molecular modeling.
The solution structure of the Y1 receptor agonist, porcine [Leu31, Pro34]NPY, has been investigated by two-dimensional NMR and molecular modeling. A complete assignment of the NMR resonances was achieved and 201 inter-residue nuclear Overhauser enhancement spectroscopy (NOESY) connectivities could be identified, comprising several connectivities between the N- and C-terminal segments. A molecular model was calculated by distance geometry, simulated annealing and conjugate gradients energy minimization using the NOE constraints. The results indicate that, like NPY and other peptides of the family, [Leu31, Pro34]NPY adopts a folded hairpin structure with the terminal segments in close proximity. Analysis of the secondary chemical shifts for the CH(alpha)'s and of the temperature dependence of the NH chemical shifts combined with the NOE constraints indicates a tendency toward helix structure for the segment 18-30 and the presence of turn structure for the C-terminal segment (residues 31-36). Native NPY and [Leu31, Pro34]NPY have most of their structures in common but differ slightly in their C-terminal portion. Based on the structures of NPY and of its specific agonists, [Leu31, Pro34]NPY and NPY 13-36, conclusions can be drawn about the structural requirements for binding to the Y1 and Y2 receptor subtypes.


The effects of fatal hemorrhage on the cochlear vasculature.
The condition of the cochlear vasculature was evaluated in 7 normal guinea pigs subsequent to fatal aortic hemorrhage. The cochleas were prepared for histological analysis using a soft surface preparation technique. The data analysis revealed two statistically significant differences: an increase in the number of aggregations and plasma gaps in the vessel at the vestibular membrane ( VSVM ) and in the vessel of the spiral prominence ( VSSP ). In eight instances, a statistical tendency toward a difference was demonstrated. On the whole, the changes observed were small, scattered and inconsistent and were interpreted as indicative of no local circulatory response to hemorrhage. These findings suggest that the cochlear vasculature is either controlled by a marked autoregulation or that histological evidence of a sympathetically mediated vasoconstriction may be counteracted by an elevated PCO2 level causing vasodilation of the constricted inner ear vessels during a state of O2 deficiency. Further, it is proposed that these same mechanisms may also account for the relatively discrete changes seen in the vasculature following noise exposure.


"In a Religious Celebration"? The Religious Defense of LGBT Rights in U.S. Federal Courts.
This article advances scholarship on the relationship between sexuality, religion, and the law within the United States by analyzing case summaries and court opinions of the federal appellate cases decided between 1990 and 2020 that involve a religion-based claim being used to advance or defend gay and lesbian rights. Contrary to dominant public narratives that position religion uniformly in opposition to progressive sexual values, these cases show how Americans' religious beliefs and practices include diverse sexual identities. We find that the courts' reactions to such cases, however, illustrate the tension within legal discourse and hesitancy for the courts to equate religious and moral values with affirming LGBT identities, people, and rights. Our findings suggest that the courts and litigants define what religion is-and what it is not-by positioning it in relation to sexuality.


Bonding of silicone extra-oral elastomers to acrylic resin: the effect of primer composition.
Silicone elastomer is bonded to acrylic resin in many facial or oro-facial prostheses. The silicone elastomer/acrylic resin bond has been reported to be insufficient and primers have been used to enhance the bond. This study investigated the bond strength of silicone elastomer to acrylic resin using different types of primers. The extra-oral silicone elastomers studied were Cosmesil and Ideal. The "overlap-joint" model was used to evaluate the bond strength and the samples were stretched until fracture. The bonding surfaces were treated with a primer. The control primer was Cosmesil and the others a mixture of Cosmesil/Z-6020 and Cosmesil/A-174 in 50/50 v/v ratio. The bond strength ranged from 0.026 MPa to 0.219 MPa. The results obtained in this work led to the conclusion that the most critical parameter allowing the efficient performance of a primer is the compatibility and affinity of its composition with the selected silicone elastomer.


Reliability and construct validity of a composite pain scale for rabbit (CANCRS) in a clinical environment.
A composite pain scale for assessing and quantifying pain in rabbits (CANCRS) has been designed merging the Rabbit Grimace Scale (RbtGS) and a scale including clinical parameters (CPS). Construct validity and inter-rater reliability were assessed for CANCRS, for RbtGS and for CPS, in order to test their potential to detect pain in a clinical setting. Rabbits (n = 116) were either hybrids or purebreds and they were independently evaluated by two raters, who could be veterinarians (V) or veterinary medicine students (S). Score intervals determined four pain classes (No pain, Discomfort, Moderate pain and Severe pain) that matched presumptive pain classes associated with some pathological conditions. A chi-square test was used to assess the construct validity of the scales by checking how frequently scale results and presumptive pain classes matched. Sixty-nine patients were evaluated by one V and one S, whereas forty-seven rabbits were assessed by two V, in order to test inter-rater reliability. An intra-class correlation coefficient (ICC) was used to test reliability of the scales, whereas Cohen's kappa tested inter-rater agreement for each parameter of the CANCRS. Construct validity results show that CANCRS and RbtGS efficiently reveal pain (P ≤ 0.05), while CPS does not (p > 0.05). Inter-rater reliability was very good for both CANCRS and CPS (ICC 0.88 V-V, 0.94 between V-S; ICC 0.97 V-V, 0.91 V-S) and good for RbtGS (ICC 0.77 V-V, 0.88 V-S); therefore, CPS reproducibility was better between veterinarians and students than between veterinarians. Inter-rater agreement between veterinarians and veterinary medicine students was moderate to very good for all the parameters included in the CANCRS (Cohen's kappa >0,60). In conclusion, it is possible to state that the CANCRS has construct validity and it is a reliable tool for use in clinical practice, when coping with many rabbits with morphological differences. It is easy and fast to use and enriches the RbtGS with some clinical parameters that should be monitored during any clinical examination, allowing for capture of the multidimensional aspect of pain.


Intraepidermal injection of dissociated epidermal cell suspension improves vitiligo.
This study was initiated to evaluate the safety and effectiveness of intraepidermal injection of dissociated epidermal cells into the lesions of stable vitiligo patients. Autologous dissociated epidermal cell suspensions were injected intraepidermally into 10 stable vitiligo patients. None of the patients received adjuvant therapy. The response was evaluated as: marked (76-100%), moderate (51-75%), mild (26-50%) and minimal repigmentation (0-25%). Transmission electron microscopy was used to evaluate the transplanted cells and immunohistochemical staining with HMB-45 was performed to assess the repigmentation in vivo. In all cases, repigmentation started during the 4-week period after transplantation. Six months after transplantation, a marked repigmentation in four (40%), moderate repigmentation in two (20%) and mild repigmentation in two (20%) patients were observed. Two (20%) patients with white patches on their lids showed minimal repigmentation. No side effects were observed in any patients. Interestingly, repigmentation of gray hair in one patient, 4 months post transplantation was observed. Analysis of the ultrastructure of transplanted cells showed 1.5% of the cells had melanocyte morphology. HMB-45 positive cells were observed after cell transplantation. This method is an effective, simple and safe therapeutic option for stable vitiligo lesions.


Clinical features of small choroidal melanoma.
The detection and treatment of choroidal melanoma early in its natural course is critical to providing the patient with the best prognosis. Patients with small choroidal melanoma (< 4 mm thickness) develop metastasis in 16% of cases at 5 years follow up, whereas those with medium choroidal melanoma (4-8 mm thickness) and large choroidal melanoma (> 8 mm thickness) develop metastasis in 32 and 53%, respectively. The difficulty with early detection of choroidal melanoma relates to its clinical similarity to benign choroidal nevus. Factors that differentiate small choroidal melanoma from choroidal nevus can be remembered using the mnemonic TFSOM, indicating To Find Small Ocular Melanoma. The letters in this mnemonic represent T (Thickness >2 mm), F (subretinal Fluid), S (Symptoms), O (Orange pigment), and M (Margin touching optic disc). Choroidal melanocytic tumors that display 0 factors have 3% chance for growth at 5 years and most likely represent choroidal nevi. Tumors that display one factor have a 38% chance for growth and those with two or more factors show growth in over 50% of cases at 5 years. Most of those tumors with two or more risk factors probably represent small choroidal melanoma and early treatment is generally indicated. Therefore, ophthalmologists should be aware of the important factors that identify small choroidal melanoma so that early treatment and better life prognosis can be achieved for their patients.


Isolation of early hematopoietic cells, including megakaryocyte progenitors, in the ALDH-bright cell population of cryopreserved, banked UC blood.
ALDH-bright (ALDH(br)) cell populations sorted from freshly collected umbilical cord blood (UCB) on the basis of their high aldehyde dehydrogenase (ALDH) activity are highly enriched for HPC. HPC with low ALDH activity (ALDH(dim)) are primarily short-term progenitors, whereas progenitors that initiate long-term cultures or establish long-term grafts in xenograft models are ALDH(br). We examined the multilineage hematopoietic and platelet progenitor activities of ALDH(br) cells recovered from cryopreserved UCB units typically employed in the practice of clinical transplantation. Frozen UCB units were thawed, washed, immunomagnetically depleted of cells expressing glycophorin A and CD14, reacted for flow cytometric detection of ALDH, and sorted to yield ALDH(br) and ALDH(dim) populations. We measured surface Ag expression and viability of cells in the ALDH(br) and ALDH(dim) populations by flow cytometry and hematopoietic (CFC-H) and megakaryocytic (CFC-Mk) colony-forming cells in each population. ALDH(br) populations isolated from thawed UCB cells were highly enriched for CD34(+) and CD133(+) cells. Flow-sorted ALDH(br) populations were enriched 1116-fold in CFC-H, 10-fold in multilineage GEMM colonies and 2015-fold in CFC-Mk compared with the ALDH(dim) population. All progenitors giving rise to large Mk colonies were derived from ALDH(br) populations. ALDH(br) populations recovered from thawed, banked UCB with the method we describe have HPC activity and may be useful in the clinic to facilitate reconstitution of erythroid, myeloid and megakaryocytic blood elements.


An Excel-Based System to Manage Radiation Safety for the Family of Patients Undergoing 131I Therapy.
The purpose of this study was to develop spreadsheet workbooks that assist in the radiation safety counseling of 131I therapy patients and their families, providing individualized guidelines that avoid imposing overly conservative restrictions on family members and others. Methods: The mathematic model included biphasic patient radionuclide retention. The extrathyroidal component was a cylindric volume with a diameter corresponding to the patient's size and included patient self-absorption, whereas the thyroidal component was a point source whose transmission was reduced by self-absorption. A separate model in which the thyroid, extrathyroid, and bladder compartments fed serially from one to the next was developed to depict the radionuclide levels within the patient and to estimate the activity entering the environment at each urination. Results: The system was organized into a set of 4 workbooks: the first to be used with ablation patients prepared using thyrogen, the second with ablation patients prepared by deprivation, the third with hyperthyroid patients, and the fourth with the unusual hyperthyroid patient who finds the restrictions to be oppressive and returns 5-10 d after administration for a measurement and reassessment. The workbooks evaluated the radiation field strength external to the patient and indicated restrictions based on selected dose limits. To assist physicians in suggesting contamination precautions, the workbooks also evaluated the radioactivity present within the patient and the estimated discharge into the environment as a function of time. Conclusion: The workbooks that were developed assist the radiation safety counselor in individualizing radiation protection procedures for the family of patients undergoing 131I therapy. The workbook system avoids overly conservative assumptions while permitting selection of appropriate dose limits for each individual.


Microbial Translocation and B Cell Dysfunction in Human Immunodeficiency Virus Disease.
The gut mucosal barrier disrupted in HIV disease, resulting in increased systemic exposure to microbial products such as Lipo Polys Accharide (LPS). The association of enhanced microbial translocation and B cell dysfunction in HIV disease is not fully understood. High dose and short term exposure of microbial Toll-Like Receptor (TLR) agonists were used as vaccine adjuvants, however, low dose and long term exposure of TLR agonists could be harmful. The characteristics of B cell dysfunction in HIV disease included B cell, especially memory B cell depletion, enhanced levels of autoimmune antibodies and impaired vaccine or antigen responsiveness. This review discusses and explores the possibility of the effect of microbial translocation on memory B cell depletion and impaired vaccine responses in HIV infection. By determining the mechanisms of B cell depletion and perturbations in HIV disease, it may be possible to design interventions that can improve immune responses to vaccines, reduce selected opportunistic infections and perhaps slow disease progression.


Impulsivity as an underlying factor in the relationship between disordered eating and sexual behavior.
Previous research has reported associations between bulimia nervosa (BN), increased sexual activity, and impulsivity. However, most studies have examined these topics separately and have not examined the role of impulsivity in associations between bulimic and sexual behaviors. The current study sought to examine relationships between disordered eating, sexual behaviors, and impulsivity, as well as to investigate impulsivity as a third variable in these relationships. The participants were 500 female undergraduate students from a large midwestern university who completed self-report questionnaires of binge eating, the use of compensatory behavior, sexual behavior, and impulsivity. Compensatory behavior, but not binge eating, was significantly correlated with sexual experiences. Partial correlations indicated that impulsivity is a third variable that partially underlies this relationship. Compensatory behaviors and increased sexual activity likely represent risky behaviors that are influenced by impulsivity levels.


Another mechanism for creating diversity in gamma-aminobutyrate type A receptors: RNA splicing directs expression of two forms of gamma 2 phosphorylation site.
Diversity of gamma-aminobutyrate type A (GABAA) receptors has recently been proposed to be achieved by assembly of receptor subtypes from a multitude of subunits (alpha 1-6, beta 1-3, gamma 1-2, and delta) encoded by different genes. Here we report a further mechanism for creating GABAA receptor diversity: alternative RNA splicing. Two forms of bovine gamma 2 subunit cDNA were isolated (gamma 2S and gamma 2L) that differed by the presence or absence of a 24-base-pair (8-amino acid) insertion in the cytoplasmic domain between the third and fourth putative membrane-spanning regions. Polymerase chain reaction from RNA demonstrated that the two forms of gamma 2 subunit are expressed in bovine, human, and rat brain. Sequencing of genomic DNA clones encoding the gamma 2 subunit demonstrated that the 24-base-pair insert is organized as a separate exon. Analysis of the sequence of the 8-amino acid insert revealed that it contains a protein kinase C consensus phosphorylation site. Expression of the large cytoplasmic loop domains of gamma 2S and gamma 2L in Escherichia coli, followed by phosphorylation of the recombinant proteins by protein kinase C, demonstrated that gamma 2L, but not gamma 2S, could be phosphorylated. Thus the two forms of gamma 2 subunit differ by the presence or absence of a protein kinase C phosphorylation site. This mechanism for creating GABAA receptor diversity may allow differential regulation of the function of receptor subtypes.


Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting.
Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam-Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (-0·03 points [4·04]; -0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.


Antiviral therapy defiant mixed viral retinitis post hematopoietic allogeneic stem cell transplant.
Cytomegalovirus (CMV) retinitis is an uncommon presentation post allogeneic transplant and can be vision-threatening. Our case demonstrates the occurrence of polymerase chain reaction (PCR) proven mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogeneic stem cell transplant despite multiple prophylactic antiviral therapies, including letermovir, and in the documented absence of CMV DNAemia. A 21-year-old female with acute myeloid leukemia presented with mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogenic transplant. This presentation occurred despite ongoing standard prophylaxis for both of these viruses, as well as following two courses of treatment for CMV viremia, with a documented negative CMV PCR in the blood prior to the presentation with retinitis. The patient was treated with intravenous ganciclovir and subsequently transitioned to oral valganciclovir with durable resolution of the retinitis. We report a rare case of mixed viral retinitis occurring despite multiple antiviral prophylaxes including letermovir and with PCR-documented absence of preceding CMV viremia, in a post-allogeneic stem cell transplant patient, with PCR of the aqueous fluid demonstrating two viral populations. With very little existing literature on either mixed viral retinitis or CMV retinitis during letermovir prophylaxis, this case expands the literature on both topics. CMV retinitis is an uncommon potentially vision threatening presentation post hematopoietic stem cell transplant, and can occur due to early CMV reactivation, low CD4 count, and delayed CD4 lymphocyte recovery. Letermovir has poor CNS and retinal penetration. This case highlights the need for more research on secondary prophylaxis with letermovir.


Role of vasopressin in current anesthetic practice.
Arginine vasopressin (AVP), also known as antidiuretic hormone, is a peptide endogenously secreted by the posterior pituitary in response to hyperosmolar plasma or systemic hypoperfusion states. When administered intravenously, it causes an intense peripheral vasoconstriction through stimulation of V1 receptors on the vascular smooth muscle. Patients in refractory shock associated with severe sepsis, cardiogenic or vasodilatory shock, or cardiopulmonary bypass have inappropriately low plasma levels of AVP ('relative vasopressin deficiency') and supersensitivity to exogenously-administered AVP. Low doses of AVP and its synthetic analog terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in the treatment of refractory arterial hypotension in patients chronically treated with renin-angiotensin system inhibitors, cardiac arrest, or bleeding esophageal varices. In the perioperative setting, they represent attractive adjunct vasopressors in advanced shock states that are unresponsive to conventional therapeutic strategies.


Development and characterization of a rapid polymerizing collagen for soft tissue augmentation.
A liquid collagen has been developed that fibrilizes upon injection. Rapid polymerizing collagen (RPC) is a type I porcine collagen that undergoes fibrillization upon interaction with ionic solutions, such as physiological solutions. The ability to inject liquid collagen would be beneficial for many soft tissue augmentation applications. In this study, RPC was synthesized and characterized as a possible dermal filler. Transmission electron microscopy, ion induced RPC fibrillogenesis tests, collagenase resistance assay, and injection force studies were performed to assess RPC's physicochemical properties. An in vivo study was performed which consisted of a 1-, 3-, and 6-month study where RPC was injected into the ears of miniature swine. The results demonstrated that the liquid RPC requires low injection force (<7 N); fibrillogenesis and banding of collagen occurs when RPC is injected into ionic solutions, and RPC has enhanced resistance to collagenase breakdown. The in vivo study demonstrated long-term biocompatibility with low irritation scores. In conclusion RPC possesses many of the desirable properties of a soft tissue augmentation material. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 758-767, 2016.