The health-related quality of life in patients with post-COVID-19 after hospitalization: a systematic review.
Symptoms in post-COVID-19 patients who require hospitalization can persist for months, significantly affecting their health-related quality of life (HRQoL). Thus, the present study aimed to discuss the main findings regarding HRQoL in post-COVID-19 patients who required hospitalization. An electronic search was performed in the MEDLINE, EMBASE, CINAHL, Web of Science, LILACS, and Scopus databases, without date and language restrictions, until July 2021. Twenty-four articles were included in the analysis. It seems that HRQoL partially improved soon after hospital discharge, although the negative impact on HRQoL may persist for months. The physical and mental aspects are affected because patients report pain, discomfort, anxiety, and depression. The HRQoL of COVID-19 infected patients was worse than that of uninfected patients. Additionally, HRQoL seemed worse in patients admitted to the intensive care unit than in those who remained in the ward. Improvements in HRQoL after hospital discharge are independent of imaging improvement, and there seems to be no association between HRQoL after hospital discharge and disease severity on hospital admission. Many factors have been identified as determinants of HRQoL, with women and advanced age being the most related to worse HRQOL, followed by the duration of invasive mechanical ventilation and the need for intensive care. Other factors included the presence and number of comorbidities, lower forced vital capacity, high body mass index, smoking history, undergraduate education, and unemployment. In conclusion, these findings may aid in clinical management and should be considered in the aftercare of patients.


[Fulguration of foci of atrial tachycardia in the adult].
Fulguration of the site generator of arrhythmia was attempted in three 31, 33 and 55 year-old patients presenting ectopic atrial tachycardias resistant to various antiarrhythmic medications. Episodes of atrial fibrillation and flutter were also documented in two of them. Two patients had a surgically corrected congenital cardiopathy:interatrial communication or pulmonary stenosis. Mapping of the endocardial emergence point was carried out with electrodes placed 1 cm apart, demonstrating the high atrial origin of the tachycardia, near the right atrium. The auriculogram preceded the earliest possible ectopic P wave by 20 to 70 ms; its multiphasic and prolonged morphology, suggested a local intra-atrial conduction disorder in the three cases. Cathodic shocks were delivered at this site without complications with cumulative energies of 720 J, 480 J and 320 J, respectively. The fulguration was ineffective and revealed other arrhythmic sites in two patients. Only patient n1 has been asymptomatic since 24 months under a treatment with Sotalol 160 mg which had been previously ineffective.


[Clinical analysis and surgical treatment of 14 cases of esophageal gastrointestinal stromal tumors].
To explore the clinical features and surgical management of esophageal gastrointestinal stromal tumors (GIST). The clinical data of patients with esophageal GISTs undergoing surgery at our hospital between January 1999 and April 2012 were retrospectively reviewed. Of 14 patients, the male: female ratio was 8:6; the median age of the patients was 42 years (range 33 - 63 years). Dysphagia was the most common symptom, and all cases were diagnosed postoperatively. The tumors were resected by enucleation or esophagectomy or endoscopic submucosal resection. The median follow-up was 43.5 months, ranging from 2 to 142 months, with all patients have no recurrence and metastasis. Esophageal GIST is rather rare. At present, surgical resection and postoperative diagnosis remain the mainstay for treatment of patients with esophageal GISTs in China.


Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis.
Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS. MEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622). Six trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD -0.00023, 95% CI -0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI -0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI -0.00096 to 0.00177) when Asian ratio of the population was elevated. We raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care. https://www.crd.york.ac.uk/prospero, identifier CRD42022299622.


Membrane Bound Peroxiredoxin-1 Serves as a Biomarker for In Vivo Detection of Sessile Serrated Adenomas.
Aim: Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAFV600E mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently labeled 7mer peptide KCCFPAQ was shown to detect SSAs in vivo. We aim to identify the target of this peptide. Results: Peroxiredoxin-1 (Prdx1) was identified as the binding partner of the peptide ligand. In vitro binding assays and immunofluorescence staining of human colon specimens ex vivo supported this result. Prdx1 was overexpressed on the membrane of cells with the BRAFV600E mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAFV600E mutation and human SSA specimens showed higher oxidative stress as well as elevated levels of Prdx1 on the cell membrane. Innovation and Conclusion: These results suggest that Prdx1 is overexpressed on the cell surface in the presence of oxidative stress and can serve as an imaging biomarker for in vivo detection of SSAs. Antioxid. Redox Signal. 36, 39-56.


Intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 are involved in protection mediated by CD3+TCR alpha beta- T cells at the early stage after infection with Listeria monocytogenes in rats.
To investigate the significance of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) in host defense against infection with intracellular parasites, we examined the effects of in vivo pretreatment with mAbs to ICAM-1 (1A29) and LFA-1 alpha (WT-1) on the protection against infection with Listeria monocytogenes in Fisher F344/N rats. Expression of ICAM-1 and LFA-1 alpha molecules on T cells in spleen, liver and peritoneal cavity of rats was down-regulated after i.p. administration with daily doses of 300 micrograms of either 1A29 or WT-1 for 10 days. The survival rate of rats inoculated with viable Listeria was significantly reduced by in vivo pretreatment with 1A29 together with WT-1 for 10 days but not by in vivo pretreatment with control mAb. The numbers of bacteria in the spleen in rats pretreated with both 1A29 and WT-1 were significantly increased on day 3 and day 6 after infection with 1 x 10(7) of viable Listeria corresponding to 1/30 of LD50 to normal rats. Thus, the resistance against listerial infection was severely impaired by combinational pretreatment with mAbs in ICAM-1 and LFA-1 alpha. As shown in our previous report, the early appearance of CD3+TCR alpha beta- T cells, presumably TCR gamma delta T cells, was evident in the peritoneal cavity and liver of control rats at the early stage after listerial infection, while this was suppressed at this stage in rats pretreated with both 1A29 and WT1.(ABSTRACT TRUNCATED AT 250 WORDS)


T-plastin is essential for basement membrane assembly and epidermal morphogenesis.
The establishment of epithelial architecture is a complex process involving cross-talk between cells and the basement membrane. Basement membrane assembly requires integrin activity but the role of the associated actomyosin cytoskeleton is poorly understood. Here, we identify the actin-bundling protein T-plastin (Pls3) as a regulator of basement membrane assembly and epidermal morphogenesis. In utero depletion of Pls3 transcripts in mouse embryos caused basement membrane and polarity defects in the epidermis but had little effect on cell adhesion and differentiation. Loss-of-function experiments demonstrated that the apicobasal polarity defects were secondary to the disruption of the basement membrane. However, the basement membrane itself was profoundly sensitive to subtle perturbations in the actin cytoskeleton. We further show that Pls3 localized to the cell cortex, where it was essential for the localization and activation of myosin II. Inhibition of myosin II motor activity disrupted basement membrane organization. Our results provide insights into the regulation of cortical actomyosin and its importance for basement membrane assembly and skin morphogenesis.


Fallopian tube carcinoma.
Primary adenocarcinoma of Fallopian tube is a rare gynecological malignancy affecting women in the fifth and sixth decades of their lives. The rarity of this type of carcinoma has prompted reports of individual cases rather than publication of a large series. One such case is reported in a 50-year-old nulliparous post-menopausal female. The age, low fertility index and presentation of the disease are in accordance with previous reports in the literature. The present case also fulfills the diagnostic criteria's applied to this tumor.


Identification of Francisella species and discrimination of type A and type B strains of F. tularensis by 16S rRNA analysis.
Tularemia is a zoonotic disease, occurring throughout the Northern Hemisphere. The causative agent, the bacterium Francisella tularensis, is represented by two main types. Type A is found in North America, whereas type B is mainly found in Asia and Europe and to a minor extent in North America. No routine technique for rapid diagnosis of tularemia has been generally applied. We have partially sequenced 16S rRNAs of two F. tularensis strains, as well as the closely related Francisella novicida. Of 550 nucleotides analyzed, only one difference in 16S rRNA primary sequence was found. This 16S rRNA analysis enabled the construction of oligonucleotides to be used as genus- and type-specific probes. Such probes were utilized for the establishment of a method for rapid and selective detection of the organism. This method allowed identification of Francisella spp. at the level of genus and also discrimination of type A and type B strains of F. tularensis. The analysis also permitted the detection of F. tularensis in spleen tissue from mice infected with the bacterium. The results presented will enable studies on the epizootiology and epidemiology of Francisella spp.


Measuring multimorbidity in research: Delphi consensus study.
To develop international consensus on the definition and measurement of multimorbidity in research. Delphi consensus study. International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021. Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels. 150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction. Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.


[Evaluation of HIV-related continuing education programs for established physicians].
Neither the HIV-specialists, the cooperating specialists, nor the family physicians are required to have special qualifications to treat HIV-infected patients. CME-courses don't consider the very different fields of interest of the participants or that the transfer of knowledge is quite important to ensure the quality of medical care. Questionnaires regarding HIV related topics were distributed in nine HIV-CME courses (9/93-5/94) of the DAGNA (German association of panel physicians treating HIV-infected patients) in cooperation with the society of physicians of Germany and the association of public health insurances. The satisfaction of the participants, the topics with regard to their relevance for the task group, the importance for the daily routine, and didactic manners were investigated. Feed-back: 41%. Although the general impression of most participants was "quite satisfying" (87%) there was some critic regarding special aspects. The rating of the courses depended on the level of qualification. Specialists in internal medicine rated the relevance for their medical practice, the topics and the possibility of contribution more positive than other specialists or general practitioners (GP). In general, there was a great difference regarding the rating of the courses among the participants because of their individual level of qualification and knowledge. In order to take the different levels of qualification and demands for topics into account there must be graduated courses: specialists, experts, elementary and beginner courses. The basic courses should contain not only the lectures but also the possibility of an active contribution of the participants. Adequate guidelines have to be developed.


Strange taste and mild lithium intoxication.
So far, it has not been emphasised that lithium can lose or change taste in some patients. This report addresses such side effect of lithium. A 61-year-old bipolar patient experienced taste changes while increasing lithium levels up to 1.28 mEq/l and the taste changes returned to normal after lithium discontinuation. The present findings suggest that changes in tastes may be a symptom of mild lithium intoxication.


Suicidal ideation is associated with nighttime wakefulness in a community sample.
Nocturnal wakefulness is a risk factor for suicide and suicidal ideation in clinical populations. However, these results have not been demonstrated in general community samples or compared to sleep duration or sleep quality. The present study explored how the timing of wakefulness was associated with suicidal ideation for weekdays and weekends. Data were collected from 888 adults aged 22-60 as part of the Sleep and Healthy Activity, Diet, Environment, and Socialization study. Suicidal ideation was measured by the Patient Health Questionnaire-9, while timing of wakefulness was estimated from the Sleep Timing Questionnaire. Binomial logistic regressions estimated the association between nocturnal (11 pm-5 am) and morning (5 am-11 am) wakefulness and suicidal ideation. Nocturnal wakefulness was positively associated with suicidal ideation on weekdays (OR: 1.44 [1.28-1.64] per hour awake between 11:00 pm and 05:00 am, p < 0.0001) and weekends (OR: 1.22 [1.08-1.39], p = 0.0018). Morning wakefulness was negatively associated with suicidal ideation on weekdays (OR: 0.82 [0.72-0.92] per hour awake between 05:00 am and 11:00 am, p = 0.0008) and weekends (OR: 0.84 [0.75-0.94], p = 0.0035). These associations remained significant when adjusting for sociodemographic factors. Additionally, nocturnal wakefulness on weekdays was associated with suicidal ideation when accounting for insomnia, sleep duration, sleep quality, and chronotype (OR 1.25 [1.09-1.44] per hour awake, p = 0.002). Wakefulness at night was consistently associated with suicidal ideation. Additionally, morning wakefulness was negatively associated with suicidal ideation in some models. Although these findings are drawn from a non-clinical sample, larger longitudinal studies in the general population are needed to confirm these results.


[Assessment of the success of orthodontic treatment from the viewpoint of general dentistry].
Using internationally accepted indices, the authors studied the caries and gingivities frequency as well as the oral hygiene in 112 successfully treated orthodontic patients 35 months or thereabout after termination of the treatment and retention. The results obtaines are compared with those from an adequate control group and statistically evaluated. The general dental condition and the degree of oral rehabilitation of the orthodontic patients was better than those of the subjects in the control group.


Human population differentiation is strongly correlated with local recombination rate.
Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental F(ST) shows negative correlation with recombination rate, with F(ST) reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P<<10(-12)). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and F(ST) has a qualitatively different relationship for F(ST) between African and non-African populations and for F(ST) between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history.


Clinical interventions addressing nonmedical health determinants in Medicaid managed care.
We aimed to examine how interventions addressing social determinants of health (SDH) have been adopted in the context of Medicaid managed care organizations (MMCOs), which serve a large proportion of patients with social and economic barriers to good health. We designed a systematic literature review to examine how SDH interventions have been adopted in MMCOs. The review included published articles from PubMed, Scopus, and Business Source databases, as well as review articles published in the gray literature and articles recommended by the study's National Advisory Committee to identify interventions describing how MMCOs have invested in interventions that address patients' SDH. To be included in the review, an article had to describe an intervention that was based in the United States, be supported financially by an MMCO, focus on at least 1 SDH, and be integrated into clinical care delivery. Twenty-five programs were identified in either commercial Medicaid or Medicaid-only MCOs that involved interventions integrated into clinical care and related to SDH. Interventions varied widely in terms of target populations and target SDH, and rarely included rigorous evaluations. The majority of programs described "case management services" that did not clearly distinguish between the delivery of medical and social interventions. Despite a growing interest in clinical interventions that address SDH, little information is available in the published literature about the extent to which these interventions have been adopted by MMCOs, where they are likely to have early traction based both on capitated funding structures and the low-income populations served.


Diagnostic performance of controlled attenuation parameter for predicting steatosis grade in chronic hepatitis B.
A novel controlled attenuation parameter (CAP) using the signals acquired by the FibroScan® has been developed as a method for evaluating steatosis. The aim of this study is to assess the performance of the CAP for the detection and quantification of steatosis in patients with chronic hepatitis B (CHB). 136 subjects with CHB underwent liver biopsy and FibroScan® within 60 days. CAP was evaluated retrospectively using raw FibroScan® data. Steatosis was graded as follows: S0 (steatosis < 10% of hepatocytes), S1 (10 to < 30%), S2 (30 to < 60%) or S3 (≥ 60%). Performance was evaluated by area under the receiver operating characteristic (AUROC) curve. Proportions of each steatosis grade (S0-S3) were 78, 10, 9 and 3%, respectively. Using univariate analysis, liver stiffness measurement (LMS) significantly correlated with fibrosis (τ = 0.43; P < 10-10), sex, necro-inflammatory activity, steatosis, age, NASH, and perisinusoidal fibrosis, and with liver fibrosis (P < 10-8) and perisinusoidal fibrosis (P = 0.008) using multivariate analysis. CAP correlated with steatosis (τ = 0.38, P < 10-7), body mass index, NASH, fibrosis and perisinusoidal fibrosis using univariate analysis, but only steatosis (P < 10-10) and perisinusoidal fibrosis (P = 0.002) using multivariate analysis. AUROCs for LSM were: 0.77 (0.69-0.85), 0.87 (0.80-0.95), and 0.93 (0.83-1.00), respectively, for fibrosis stages F ≥ 2, F ≥ 3 and F = 4. AUROCs for CAP were: 0.82 (0.73-0.92), 0.82 (0.69-0.95), and 0.97 (0.84-1.00) for ≥ S1, ≥ S2 and S3 steatosis, respectively. In conclusión CAP is a novel, accurate non-invasive tool and may be suitable for detecting and quantifying steatosis in CHB patients.


[Fluorescence in situ hybridization detection of peripheral lymphocyte and ultrastructural study of the testicular tissue in a 48,XXYY syndrome patient].
To investigate the pathogenesis of male sterility in 48,XXYY syndrome patient. The peripheral lymphocyte was detected by dual-color fluorescence in situ hybridization. The bioptic testicular tissues were pathologically sectioned and ultra-thin sections were examined by electron-microscopy. The pathological findings revealed extremely severe dysgenesis of the badly damaged testicular tissue. Only a few convoluted seminiferous tubules were found, in which no spermatogenic cell or sperm of any range could be viewed. The ultrastructural observations showed the thickened interstitial vascular walls of the testicular tissue and severe hyperplasia of the collagen fibers in the basilemma and lumens of the blood vessels. The structure of the testicle in the 48,XXYY syndrome patient has severe fibrous hyperplasia, leading to the non-specific thickening of the barrier and serious damage to the blood-testis barrier, which in turn produce significant disturbance and pathological changes in the process of the spermatogenic cell formation. The whole interrelated loops account mainly for the male sterility.


Clinical outcome of rumination syndrome in adults without psychiatric illness: a prospective study.
This prospective study was conducted to characterize the clinical features of adult rumination syndrome, in the absence of psychiatric illness, by applying newly modified clinical criteria, and to elucidate factors influencing outcomes after treatment. Twenty-one adult patients diagnosed with rumination syndrome at a tertiary referral center over a 2-year period were enrolled in the study. All patients received supportive psychotherapy and medical treatment. Changes in symptom parameters were analyzed using a pretreatment and a post-treatment questionnaire. Patients were classified into three groups according to symptomatic outcome: improved group, sustained group and aggravated group. The duration of treatment was longer in the improved group than in the sustained or aggravated groups (P = 0.018). Esophageal manometry testing demonstrated non-transmitted contractions of the esophageal body in 10 patients (47.6%) and low amplitude contractions in eight patients (38.1%). Mean lower esophageal sphincter (LES) pressure was 9.8 +/- 2.6 mmHg. Baseline LES pressure in the improved group was higher than in the other groups (P = 0.001). Ambulatory 24-h esophageal pH monitoring showed pathological acid reflux in six patients (28.6%). All pathological acid reflux occurred in post-rumination periods. Scintigraphic testing of gastric emptying revealed that the mean retention rate at 120 min was 34.2 +/- 2.5% of initial contents, and delayed emptying was noted in three patients (14.3%). Rumination syndrome is often accompanied by heterogeneous conditions such as postprandial gastroesophageal reflux, various abnormalities in esophageal manometric tests and delayed gastric emptying. Medical treatment and supportive psychotherapy can be effective in otherwise normal adult patients, especially in patients who comply with long durations of treatment and who demonstrate higher baseline LES pressures.


Health-seeking behavior and transmission dynamics in the control of influenza infection among different age groups.
It has been found that health-seeking behavior has a certain impact on influenza infection. However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified. The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak. A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection. A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change. The age-specific overlapping percentage was estimated to be 40%-43%, 55%-60%, and 19%-35% for child, teenage and adult, and elderly age groups, respectively. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%. The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection.


A core promoter element downstream of the TATA box that is recognized by TFIIB.
We have defined a core promoter element downstream of the TATA box that is recognized by TFIIB. This involves a DNA-binding domain in TFIIB that is distinct from the helix-turn-helix motif (which recognizes an element upstream of the TATA box). The TFIIB recognition element we describe regulates transcription in a manner that is promoter context-dependent, particularly with respect to the TFIIB recognition element that is located upstream of the TATA box. Thus TFIIB can recognize two distinct sequence elements that flank the TATA box, employing independent DNA-binding motifs and cooperating in the regulation of transcription.


Fokker-Planck analysis of stochastic coherence in models of an excitable neuron with noise in both fast and slow dynamics.
We provide a detailed and quantitative Fokker-Planck analysis of noise-induced periodicity (stochastic coherence, also known as coherence resonance) in both a discrete-time model and a continuous-time model of excitable neurons. In particular, we show that one-dimensional models can explain why the effects of noise added to the fast and slow dynamics of the models are dramatically different. We argue that such effects should occur in any excitable system with two or more distinct time scales and need to be taken into account in experiments investigating stochastic coherence.


COMPARATIVE POPULATION GENETIC STRUCTURE OF A PARASITE (FASCIOLOIDES MAGNA) AND ITS DEFINITIVE HOST.
The population genetic structure of the American liver fluke, Fascioloides magna, and its definitive host the white-tailed deer, Odocoileus virginianus, was examined in South Carolina. Flukes were significantly more common in deer from river-swamp habitat than upland areas and prevalence increased with host age. The distribution of flukes among deer occurred as a negative binomial with the mean dispersion parameter, k, equal to 0.17 and the range from 0.10 to 1.11 within local areas. Significant spatial genetic differentiation was observed for flukes and deer. Patterns of genetic distance in flukes were not concordant with those of the definitive host nor were they related to geographic distance between sample locations. Spatial genetic differentiation among flukes reflected the tendency for individual hosts to harbor multiple individuals from a limited number of parasite clones. The large population size of the parasite and movements of the definitive host tend to counteract factors that lead to spatial differentiation.


Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis.
To evaluate the effectiveness of photobiomodulation in the treatment of oral mucositis. Systematic review and meta-analysis encompassing in the electronic databases: LILACS, MEDLINE, EMBASE, COCHRANE, SCOPUS, WEB OF SCIENCE, and CINAHL and in http://clinicaltrials.gov . Eligibility criteria were randomized, non-randomized, and observational studies that used photobiomodulation for the treatment of oral mucositis. The endpoints were reduction in the severity of oral mucositis, duration of lesions, and pain reduction. For data analysis, the Review Manager 5.4 program was used. A total of 316 studies were identified, 297 in the electronic databases and 19 in http://clinicaltrials.gov . After removing duplicates, 260 studies were selected for title and abstract reading, of which 223 were excluded. A total of 37 studies were chosen for full reading, of which 6 were included in the review, totaling 299 patients. The treatment used was photobiomodulation. The patients were divided into two groups: the laser group used only photobiomodulation or associated with other therapies, and the control group did not use photobiomodulation. For the endpoint reduction in the severity of oral mucositis (OM), the chance of reduction of the OM was greater in the laser group as compared to the control group. For the endpoints duration of OM lesions and pain reduction, it was not possible to carry out a meta-analysis due to the high heterogeneity between studies. In the interpretation of the meta-analysis, the reduction in the severity of oral mucositis was greater in the group that received photobiomodulation. Photobiomodulation was effective in the treatment of oral mucositis.


Oogenesis in four species of Piscicola (Hirudinea, Rhynchobdellida).
Piscicola has a pair of elongated sac-shaped ovaries. Inside the ovaries are numerous small somatic cells and regularly spherical egg follicles. Each follicle is composed of three types of cells: many (average 30) germ cells (cystocytes) interconnected by intercellular bridges in clones (cysts), one intermediate cell, and three to five outer follicle cells (envelope cells). Each germ cell in a clone has one intercellular bridge connecting it to the central anucleate cytoplasmic mass, the cytophore. Each cluster of germ cells is completely embedded inside a single huge somatic follicle cell, the intermediate (interstitial) cell. The most spectacular feature of the intermediate cell is its development of a system of intracytoplasmic canals apparently formed of invaginations of its cell membrane. Initially the complex of germ cell cluster + intermediate cell is enclosed within an envelope composed of squamous cells. As oogenesis progresses the envelope cells gradually degenerate. All the germ cells that have terminated their mitotic divisions are of similar size and enter meiotic prophase, but one of the cystocytes promptly starts to grow faster and differentiates into the oocyte, whereas the remaining cystocytes withdraw from meiosis and become nurse cells (trophocytes). Numerous mitochondria, ER, and a vast amount of ribosomes are transferred from the trophocytes via the cytophore toward the oocyte. Eventually the oocyte ingests all the content of the cytophore, and the trophocytes degenerate. Little vitellogenesis takes place; the oocyte gathers nutrients in the form of small lipid droplets. At the end of oogenesis, an electron-dense fibrous vitelline envelope appears around the oocyte, among short microvilli. At the same time, electron-dense cortical granules occur in the oocyte cortical cytoplasm; at the end of oogenesis they are numerous, but after fertilization they disappear from the ooplasm. In the present article we point out many differences in the course of oogenesis in two related families of rhynchobdellids: piscicolids and glossiphoniids.


[Improvement of osseointegration of titanium dental implant surfaces modified with strontium-substituted hydroxyapatite].
To explore the osteogenic activity of a micro-arc oxidation (MAO)-treated strontium (Sr)-substituted hydroxyapatite (Sr-HA) coating developed to enhance the osseointegration of titanium dental implants, and to investigate the strengthening mechanisms of bone bonding of crystalline hydroxyapatite (HA) with incorporation of strontium in vivo. The morphology and phase component of the oxidized film of Sr-HA and HA coated implants were examined by SEM and X-ray diffraction (XRD). Then, twenty-four implants were inserted into the metaphysis of rabbits tibias and femurs using polyfluorochrome sequential labeling. Four and 12 weeks following the surgery, the morphology and chemical composition of the bone-implant interfaces were evaluated by histological examination and energy-dispersive X-ray. The XRD patterns showed that diffraction peaks of HA shift to lower 2θ values with Sr-addition, which resulted in decreases in lattice energy and then crystallinity. Sr-HA coating presented a microporous structure in the SEM observation. Meanwhile, Sr-HA coating exhibited osteogenic activity at the early stage of bone healing period and new bone mineral apposition ratio [(4.75 ± 0.46) microm/d] was significantly higher than that of the control group [(3.21 ± 0.44) microm/d]. An apatite layer was observed at the interface of bone-Sr-HA coating in light microscopy observation and energy-dispersive X-ray analysis. Then the apatite layer was precipitated and formed new bone which became mature bone and bonded tightly to the Sr-HA. Strontium-substituted hydroxyapatite coating shows high biological activity, which can accelerate the formation of apatite layer, hence the osteogenic ability.


New classifications of monotonicity investigation for discrete operators with Mittag-Leffler kernel.
This paper deals with studying monotonicity analysis for discrete fractional operators with Mittag-Leffler in kernel. The $ \nu- $monotonicity definitions, namely $ \nu- $(strictly) increasing and $ \nu- $(strictly) decreasing, are presented as well. By examining the basic properties of the proposed discrete fractional operators together with $ \nu- $monotonicity definitions, we find that the investigated discrete fractional operators will be $ \nu^2- $(strictly) increasing or $ \nu^2- $(strictly) decreasing in certain domains of the time scale $ \mathbb{N}_a: = \{a, a+1, \dots\} $. Finally, the correctness of developed theories is verified by deriving mean value theorem in discrete fractional calculus.


Markers of inflammation and oxidative stress in peritoneal dialysis: a comparison between high and low peritoneal transporters.
High transport status is reported to be associated with increased mortality in peritoneal dialysis (PD). It has been hypothesized that this might be a result of a state of chronic inflammation and increased oxidative stress. We performed this pilot study to explore this hypothesis. Based on the standard peritoneal equilibration test, PD patients were divided in two transporter groups: LOW (Low + Low average) and HIGH (High + High Average). Markers of inflammation and oxidative stress were compared between the two groups, including C-reactive protein (CRP), plasma apoptogenic potential, monocyte HLA DR expression, Advanced Oxidative Protein Products (AOPP) and reactive carbonyl residues (RCO). Of 42 patients (34 male/8 female) studied, 8 patients were LOW and 34 were HIGH transporters. Median values of CRP (1.39 vs. 0.62 mg/L), plasma apoptogenic potential (15 vs. 14.5%), AOPP (118.36 vs. 113.86 micromol/L) and RCO (1.72 vs. 1.13 nmol/mg protein) were similar among LOW and HIGH transporters. However HIGH transporters had significantly lower monocyte HLA DR expression (mean fluorescent intensity (MFI) -197.89 vs. 124.98 units, p=0.02) compared with LOW transporters. Stable chronic PD patients with high peritoneal transport status have reduced monocyte HLA-DR expression, a biomarker of increased risk for infections. This could potentially contribute to a higher risk of mortality in this group.


Women and young adults suffer most from other people's drinking.
Research on alcohol-related harm has predominantly focused on harm suffered by the drinker and priority has been given to health-related harms. In comparison, studies on alcohol's harms to others than the drinker are scarce. This study sought to examine the human sufferings from other people's drinking both in the public and in the private sphere. The data of our study come from the Finnish Drinking Habits Survey carried out by face-to-face interviews from two separate simple random samples among Finns aged 15-69. In 2000 the response rate was 78% (n = 1932) and in 2008 74% (n = 2725). Women experience much more negative consequences from others' drinking than men do in both public and private spaces. Regarding public places, people under the age of 30 experience harm most frequently. In the private sphere, harms experienced by women were more prevalent and more serious in character. Women carry a notably heavier burden of problems related to other peoples' drinking.


Safety issues and drug-drug interactions with commonly used quinolones.
Quinolones are widely used antimicrobials with good efficacy and favourable safety. Recently, forms of quinolone toxicity such as peripheral neuropathy, retinal detachment or QTc-prolongation have attracted attention. Data on different aspects of direct quinolone toxicity are reviewed and consider risk factors and predisposing structural properties. Indirect forms of quinolone toxicity such as Clostridium difficile infections or adverse reactions associated with drug-drug interactions are also discussed. Finally, the role of transporters in the pharmacokinetics of these antimicrobials and their utilisation in critically ill patients are illustrated. A MEDLINE PubMed search for articles published in English from January 1960 to June 2014 was completed using the terms: quinolone, quinolone-induced toxicity, quinolone pharmacokinetics, quinolone and critically ill, drug-drug interactions. Quinolones exhibit an important component of the antibiotic arsenal. Although several adverse events have been associated with their use, taking into consideration risk factors, contraindications and potential drug-drug interactions can drastically reduce the respective risks.


Immune-enhancing enteral formulas: are they beneficial in critically ill patients?
Over the last decade there has been considerable interest in the use of specific nutrients to alter the metabolic response to injury and infection, to improve immune function, and to prevent or reverse the severe catabolism and wasting of the lean body mass that accompanies critical illness. In this review, representative animal studies and, when available, human studies examining the potential benefits of these individual nutrients are summarized. The overview of basic investigations is by no means all-inclusive, and the emphasis of this manuscript is a review of the currently available clinical trials examining the potential benefits of combinations of these individual immunity-enhancing nutrients in human patients.


Reasons for removal of rigid internal fixation devices in craniofacial surgery.
Despite the widespread use of rigid fixation techniques in craniofacial surgery, there is a paucity of studies in the literature that serve to better define the reasons for the subsequent removal of plates and screws. The current study appears to be the first to attempt to assess these issues among a broad range of craniofacial surgery patients. Fifty-five patients who underwent hardware removal following craniofacial surgery at the University of Michigan Medical Center between 1989 and 1995 were retrospectively studied via an in-depth chart review. Common reasons for hardware removal included palpable/prominent hardware in 19 patients (34.5%), loosening of plates and screws in 14 patients (25.5%), pain in 14 patients (25.5%), infection in 13 patients (23.6%), wound dehiscence/exposure of hardware in 11 patients (20%), and removal at the time of secondary procedures in 5 patients (9.1%). It is hoped that this study will serve as a tool to define more completely the risk of needing subsequent hardware removal among craniofacial surgery patients treated with rigid internal fixation.


[Health services research: innovation transfer in clinical research].
Clinical research in Germany suffers from a structural crisis caused by inappropriate input, suboptimal output and low efficiency. The situation is aggravated by fixed DRG-based payments, fix charges for education and research and reductions in governmental funding. Both healthcare system and clinical research in Germany are characterized by a profound sectorization, followed by resource competition between basic science and patient-oriented research. Basic biomedical research in Germany is widely accepted in the international context, but there is a lack of research on the transfer of basic science to clinical trials and everyday healthcare. According to international examples, the 1999 systematology of the Deutsche Forschungs-Gemeinschaft (DFG), a German research foundation, has to be expanded to the dimension of innovation transfer. Clinical translational research focuses on the transfer of basic science to clinical trials, and outcomes research, also known as health services research, describes the transfer of results from clinical trials (efficacy) to clinical application (effectiveness). Outcomes research is interdisciplinary, multiprofessional and patient-oriented. The so-called effectiveness gap between efficacy and effectiveness is determined by patient-sided, professional, organizational and system factors. Outcomes research provides university-based medical research centers with the opportunity to join other stakeholders of the healthcare system and to integrate the universities' scientific standard with its own further development. It is suggested that this widened perspective plays a key role in settling the crisis of clinical research in Germany.


Increased risk for diabetes development in subjects with large variation in total cholesterol levels in 2,827,950 Koreans: A nationwide population-based study.
Recent studies suggest a role for hyperlipidemia in the development of diabetes. The aim of this study is to analyze the relationship between variations of total cholesterol (TC) levels and the risk for type 2 diabetes development from a Korean nationwide population-based database. We examined the General Health Check-up sub-dataset of the Korean National Health Insurance Service (NHIS) of 2,827,950 participants who had at least three health check-ups between 2002 and 2007, and were not reported to have diabetes during that time. The variations of TC levels between the examinations were calculated as follows: [Formula: see text]. The examinees were divided into 10 groups according to TC variation, and the hazard ratio for diabetes development from 2007 to 2013, were analyzed. During the follow-up period, 3.4% of the participants had developed diabetes. The hazard ratio (HR) for diabetes development relative to the overall risk in the whole study population started to be higher than 1.0 from eighth decile of TC variation. The highest decile group showed an increased HR for diabetes development after adjustment for confounding variables (1.139; 95% confidence interval 1.116~1.163). These results were similar regardless of the use of anti-hyperlipidemic medication and baseline TC levels. The participants with a large variation in TC levels showed an increased risk for diabetes development, independent of the use of anti-hyperlipidemic medications. These results suggest a relationship between fluctuations in lipid levels and the development of type 2 diabetes.


Charged amino acid variability related to N-glyco -sylation and epitopes in A/H3N2 influenza: Hem -agglutinin and neuraminidase.
The A/H3N2 influenza viruses circulated in humans have been shown to undergo antigenic drift, a process in which amino acid mutations result from nucleotide substitutions. There are few reports regarding the charged amino acid mutations. The purpose of this paper is to explore the relations between charged amino acids, N-glycosylation and epitopes in hemagglutinin (HA) and neuraminidase (NA). A total of 700 HA genes (691 NA genes) of A/H3N2 viruses were chronologically analyzed for the mutational variants in amino acid features, N-glycosylation sites and epitopes since its emergence in 1968. It was found that both the number of HA N-glycosylation sites and the electric charge of HA increased gradually up to 2016. The charges of HA and HA1 increased respectively 1.54-fold (+7.0 /+17.8) and 1.08-fold (+8.0/+16.6) and the number of NGS in nearly doubled (7/12). As great diversities occurred in 1990s, involving Epitope A, B and D mutations, the charged amino acids in Epitopes A, B, C and D in HA1 mutated at a high frequency in global circulating strains last decade. The charged amino acid mutations in Epitopes A (T135K) has shown high mutability in strains near years, resulting in a decrease of NGT135-135. Both K158N and K160T not only involved mutations charged in epitope B, but also caused a gain of NYT158-160. Epitope B and its adjacent N-glycosylation site NYT158-160 mutated more frequently, which might be under greater immune pressure than the rest. The charged amino acid mutations in A/H3N2 Influenza play a significant role in virus evolution, which might cause an important public health issue. Variability related to both the epitopes (A and B) and N-glycosylation is beneficial for understanding the evolutionary mechanisms, disease pathogenesis and vaccine research.


B-type natriuretic peptide plasma concentration in acutely poisoned patients.
B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles upon ventricular myocyte stretch. BNP plasma concentration is useful in cardiology especially for identifying patients with congestive heart failure (CHF), as a prognostic marker of acute coronary syndromes and independent predictor of sudden cardiac death. Its value in clinical toxicology is unclear. As toxins frequently produce deleterious effects on the cardiovascular system we have decided to carry out the pilot study on BNP plasma levels in acutely poisoned patients. The 117 patients (65 males and 52 females) treated at the Department of Clinical Toxicology Jagiellonian University Medical College in Kraków in 2004 were included. 42 of them were intoxicated with ethanol, 35 with pharmaceuticals (mostly tricyclic antidepressants), 13 with CO. The mean age of examined group was 34.07 +/- 12.08 year. The control group consisted of 54 healthy volunteers and employees of the Department (mean age; 32.7 +/- 11.74). A significantly higher BNP concentration was found in poisoned patients than in the control group. The highest BNP plasma concentration was noted in pharmaceutical poisoned patients. Mean BNP concentration in poisonings of minor severity (grade 1) was significantly lower then in moderate (grade 2) or severe (grade 3) poisonings. BNP plasma measurement as an additional marker of cardiac disturbances in clinical toxicology practice may be suggested.


Insights on the (Auto)Photocatalysis of Ferritin.
Traditionally, ferritin has been considered a photocatalyst capable of photo-oxidizing organic molecules and transferring electrons to external electron acceptors when irradiated by UV-visible light. We have designed new approaches to resolve the uncertainties regarding its photocatalytical mechanism. Experiments with an Fe(II) chelator, an electrochromic indicator, and recombinant ferritin proteins indicate that the excited electrons at the conduction band of the ferritin core do not cross the protein shell. Instead, irradiation causes the electrons to reduce the ferrihydrite core to produce Fe(II) ions. These Fe(II) ions exit the protein shell to reduce electron acceptors. In the absence of electron acceptors or chelators, Fe(II) re-enters ferritin.


Carbon-core silver-shell nanodots as sensitizers for phototherapy and radiotherapy.
Spherical carbon nanoparticles (carbon nanodots) with a silver shell were investigated as potential sensitizing agents. The cytotoxicity of the combination of ultraviolet radiation or x-rays with the nanodots was examined in cancer cells in vitro. The cell viability decreased following the exposure to the radiation. The carbon nanodots enhanced the radiation effects by significantly reducing the amount of surviving cells compared to that of the cells exposed only to the radiation. Carbon-core silver-shell nanodots can be proposed as a bimodal sensitization platform for biological and medicinal applications employing non-ionizing or ionizing radiation.


A reanalysis of curvature in the dose response for cancer and modifications by age at exposure following radiation therapy for benign disease.
To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy(-1) of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.


Oocytes from women of advanced reproductive age do not appear to have an increased risk of zona pellucida hardening.
To test the hypothesis that very advanced reproductive age leads to an increased risk of zona pellucida hardening by comparing fertilization rates and rates of failed fertilization with conventional oocyte insemination vs intracytoplasmic sperm injection (ICSI). Women aged > or = 45 were given the option of ICSI vs conventional oocyte insemination in circumstances where there was no male factor present. They were advised of the theoretical benefit of ICSI overcoming zona hardening but also advised that ICSI might lower pregnancy rates and is more costly. There were 364 cycles evaluated and 74% chose ICSI. The failed fertilization rates were similar--28.4% (66/232) for ICSI vs 26.5% (35/132) for conventional insemination. The fertilization rates were similar 56.0% with ICSI vs 50.9% with conventional oocyte insemination. Based on similar fertilization and failed fertilization rates in women aged > or = 45 undergoing IVF-ET, zona hardening does not appear to be a consequence of reproductive aging.


Pharmacotherapy for male breast cancer.
Breast cancer in males is uncommon, occurring at approxiamtely 1% of the rate of female breast cancer. Male breast carcinomas tend to be highly positive for hormone receptors, including oestrogen, progesterone and androgen receptors. Owing to this, hormone therapy is recommended as the primary treatment modality. Adjuvant therapy is recommended for male breast cancers with large size or positive axillary nodes. For metastatic disease, options for therapy include tamoxifen, orchiectomy, anti-androgens with or without luteinising hormone releasing hormone analogues or combination chemotherapy. The newer hormonal treatments, such as the selective aromatase inhibitors or novel antioestrogens, have not yet been well studied in male breast cancer but have potential for efficacy in this disease.


Shoulder pyarthrosis: a concomitant process.
Thirty cases of glenohumeral pyarthrosis are reported. Systemic immune compromise and local tissue abnormalities were each present in 74% of the adult patients. Both were present in 52%. Most adult patients were debilitated by chronic diseases. Diagnosis was frequently delayed due to mild symptoms and minimal, nonspecific laboratory findings. Poor results correlated with treatment delay. Shoulder pyarthrosis occurred ipsilateral to forearm arteriovenous dialysis fistulas in four patients. Postoperative shoulder pyarthroses were eradicated only in patients with clinically intact immune systems. Three patients (10%) with intact rotator cuffs had unsuspected associated subacromial bursa abscesses. Evaluation of suspected glenohumeral pyarthrosis should include evaluation of the subacromial bursa.


Negative media portrayal of palliative care: a content analysis of print media prior to the passage of Voluntary Assisted Dying legislation in Victoria.
Key misunderstandings of palliative care exist in the community, with media being reported as a key source underpinning knowledge. This retrospective media analysis of consecutive articles sought to examine the portrayal of palliative care in the Australian print media, focussing on the 2 years (2016-2018) coverage preceding the Voluntary Assisted Dying legislation in Victoria, Australia. Summative content analyses revealed coverage of palliative care was frequently (74%) in the context of a discussion of euthanasia. Only small numbers of articles described the activities of palliative care, and even fewer its potential beneficial impact, while a quarter (26%) described palliative care was inadequate to relieve suffering. These findings suggest that current coverage of palliative care in the media may contribute to negative public views and misconceptions. An opportunity exists to enhance media coverage, and in turn, improve the public understanding of care in serious illness.


Rapamycin and trametinib: a rational combination for treatment of NSCLC.
Mammalian target of rapamycin (mTOR) is one of the most commonly activated pathways in human cancers, including lung cancer. Targeting mTOR with molecule inhibitors is considered as a useful therapeutic strategy. However, the results obtained from the clinical trials with the inhibitors so far have not met the original expectations, largely because of the drug resistance. Thus, combined or multiple drug therapy can bring about more favorable clinical outcomes. Here, we found that activation of ERK pathway was responsible for rapamycin drug resistance in non-small-cell lung cancer (NSCLC) cells. Accordingly, rapamycin-resistant NSCLC cells were more sensitive to ERK inhibitor (ERKi), trametinib, and in turn, trametinib-resistant NSCLC cells were also susceptible to rapamycin. Combining rapamycin with trametinib led to a potent synergistic antitumor efficacy, which induced G1-phase cycle arrest and apoptosis. In addition, rapamycin synergized with another ERKi, MEK162, and in turn, trametinib synergized with other mTORi, Torin1 and OSI-027. Mechanistically, rapamycin in combination with trametinib resulted in a greater decrease of phosphorylation of AKT, ERK, mTOR and 4EBP1. In xenograft mouse model, co-administration of rapamycin and trametinib caused a substantial suppression in tumor growth without obvious drug toxicity. Overall, our study identifies a reasonable combined strategy for treatment of NSCLC.


[Penetration of ampicillin and oxacillin into the tissues of rats with aseptic inflammation].
Penetration of 2 penicillins with different indices of serum protein binding in the tissues of rats with aseptic inflammation was studied. The pharmacokinetics of both penicillins in the blood serum (total preparation) did not differ. However, the level of the ampicillin free fraction was much higher than that of oxacillin. In the inflammation exudate and inflamed tissues, the maximum concentrations of free ampicillin and the area below its pharmacokinetic curve were also higher than those of oxacillin. The rate of elimination of both antibiotics from the exudate was the same. The period of half elimination of the drugs from the exudate and inflamed tissue was significantly higher than the period of their half elimination from the blood serum. High positive correlation between the ampicillin levels in the blood serum and inflamed and intact tissues was shown. As for oxacillin, positive correlation between its levels in the blood serum and inflamed tissue was observed.


Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and SYCP2 align by homology but fail to synapse and have possible impaired specificity of chromatin loop attachment.
The targeted deletion of the meiotic chromosome core component MmSYCP3 results in chromosome synaptic failure at male meiotic prophase, extended meiotic chromosomes, male sterility, oocyte aneuploidy and absence of the MmSYCP2 chromosome core component. To test the functions of SYCP2 and SYCP3 proteins in the cores, we determined the effect of their deletion on homology recognition by whole chromosome painting and the effect on chromatin loop attachment to the cores with endogenous and exogenous sequences. Because we observed that the alignment of cores is between homologs, it suggested that alignment is not a function of the chromosome core components but might be mediated by chromatin-chromatin interactions. The alignment function therefore appears to be separate from intimate synapsis function of homologous cores that is observed to be defective in the SYCP3-/- males. To examine the functions of the SYCP2 and 3 core proteins in chromatin loop attachment, we measured the loop sizes of the centromeric major satellite chromatin and the organization of an exogenous transgene in SYCP3+/+ and SYCP3-/- males. We observed that these satellite chromatin loops have a normal appearance in SYCP3-/- males, but the loop regulation of a 2-Mb exogenous lambda phage insert appears to be altered. Normally the insert fails to attach to the core except by flanking endogenous sequences, but in the absence of SYCP2 and SYCP3, there appears to be multiple attachments to the core. This suggests that the selective preference for the attachment of mouse sequences to the chromosome core in the wild-type male is impaired in the SYCP3-/- male. Apparently the SYCP2 and SYCP3 proteins function in the specificity of chromatin attachment to the chromosome core.


From traumatic events and dissociation to body image and depression symptoms - in search of self-destruction syndrome in adolescents who engage in nonsuicidal self-injury.
The aim of the study was to analyze relationships between the variables: severity of depression symptoms, feelings towards one's own body, dissociation, the number and type of traumatic life events experienced by adolescents who engage in deliberate self-injury and are psychiatrically hospitalized. We examined 60 patients aged 13-17 (M = 15.48, SD = 1.19). More than a half (55%) were diagnosed with a mixed disturbance of emotions and conduct, 23.5% with depressive behavior disorders, 10% were diagnosed a depressive episode. The research tools: a socio-demographic survey; original Feelings Towards the Body Questionnaire created on the basis of Tomkiewicz's description; Kovacs's CDI; Scharfetter's Ego-Psychopathology questionnaire. The examined individuals have negative feelings toward their bodies, more than half of them experience severe depression symptoms. There are links between traumatic events, dissociation, body image and the severity of depression symptoms. The strongest links were found: between dissociation vis-a-vis the severity of depression symptoms and the feelings towards one's body; and between the severity of depression symptoms and the feelings towards one's body. Two thirds of the examined individuals attempted suicide. Various forms of direct self-destructive behaviors very often occur simultaneously. It also provokes reflection about the conditions under which self-inflicted injury does (or does not) prevent suicide attempts. Self-mutilation along with the interaction between clinical variables may form a self-destruction syndrome in various mental disorders and contribute to clinical pictures of these disorders, this should be taken into account in diagnosing and treatment of adolescents.


Ionic Conductivity of Polyelectrolyte Hydrogels.
Polyelectrolytes have many important functions in both living organisms and man-made applications. One key property of polyelectrolytes is the ionic conductivity due to their porous networks that allow the transport of water and small molecular solutes. Among polyelectrolytes, zwitterionic polymers have attracted huge attention for applications that involve ion transport in a polyelectrolyte matrix; however, it is still unclear how the functional groups of zwitterionic polymer side chains affect their ion transport and swelling properties. In this study, zwitterionic poly(carboxybetaine acrylamide), poly(2-methacryloyloxyethyl phosphorylcholine), and poly(sulfobetaine methacrylate) hydrogels were synthesized and their ionic conductivity was studied and compared to cationic, anionic, and nonionic hydrogels. The change of the ionic conductivity of zwitterionic and nonionic hydrogels in different saline solutions was investigated in detail. Zwitterionic hydrogels showed much higher ionic conductivity than that of the widely used nonionic poly(ethylene glycol) methyl ether methacrylate hydrogel in all tested solutions. For both cationic and anionic hydrogels, the presence of mobile counterions led to high ionic conductivity in low salt solutions; however, the ionic conductivity of zwitterionic hydrogels surpassed that of cationic and ionic hydrogels in high salt solutions. Cationic and anionic hydrogels showed much higher water content than that of zwitterionic hydrogels in deionized water; however, the cationic hydrogels shrank significantly with increasing saline concentration. This work provides insight into the effects of polyelectrolyte side chains on ion transport. This can guide us in choosing better polyelectrolytes for a broad spectrum of applications, including bioelectronics, neural implants, battery, and so on.


Multiple sclerosis: time for early treatment with high-efficacy drugs.
This review addresses current changes in the approach to treating patients with multiple sclerosis (MS). The widely practiced approach of utilizing agents with lower treatment efficacy (LETA) at onset with subsequent escalation has been challenged by new data suggesting that MS patients derive greater benefit when therapy is initiated with high-efficacy treatment agents (HETA). Several recent studies compared treatment efficacy and safety of early administration of HETA versus LETA. The results of randomized, double blind, phase III studies with LETA as a control arm and population-based larger and longer studies using propensity scoring, marginal structural modeling and weighted cumulative exposure analysis support the benefit of early treatment with HETA. Patients initiating their treatment with HETA, regardless of prognostic factors and MRI burden at baseline, showed significantly lower annualized relapse rate (ARR) and reduced disability progression in follow-up periods of up to 10-15 years. Moreover, the safety profile of recently approved HETA ameliorates concerns about off-target effects associated with a number of earlier high-efficacy drugs. Patient perception has also changed with an increasing preference for medication profiles that both improve symptoms and prevent disease progression. Accumulating data from randomized studies and the results of large population-based studies demonstrating short-term and longer-term patient benefits support the view that HETA should be more widely used. The adoption of early treatment with HETA capitalizes on a window of opportunity for anti-inflammatory drugs to maximally impact disease pathology and heralds a sea change in clinical practice toward pro-active management and away from a philosophy routed in generating clinical benefit as a consequence of treatment failure.


Design Rationale for Stimuli-Responsive, Semi-interpenetrating Polymer Network Hydrogels-A Quantitative Approach.
Stimuli-responsive semi-interpenetrating polymer network (semi-IPN) hydrogels form an important class of polymers for their tunable properties via molecular design. They are widely investigated for a diverse range of applications including drug delivery, sensors, actuators, and osmotic agents. However, in-depth studies on some of the critical design principles affecting diffusion/leaching of linear polymer from semi-IPN hydrogels are lacking. Herein, for the first time, by preparing a series of model semi-IPN hydrogels based on thermally responsive poly (N-isopropyl acrylamide) (PNIPAM) network and linear poly(sodium acrylate) (PSA), a systematic and quantitative study concerning linear polymer chain retention and swelling/deswelling kinetics is reported. The study shows that PSA retention is significantly affected not only by PSA molecular weight and concentration, but also by polymerization temperature, which could be linked to homogeneity and internal morphology of the hydrogel. Surprisingly, there is no obvious influence of crosslinking density of PNIPAM network toward PSA retention, while faster swelling and deswelling at higher crosslinking density are observed in terms of swelling rate constant and deswelling activation energy. These findings offer new insights on the factors affecting structural and physicochemical properties of such semi-IPN hydrogels, which should in turn serve as a general guideline for materials design.


Designing scaffolds of peptides for phage display libraries.
Phage display is a powerful method for the discovery of peptide ligands that are used for analytical tools, drug discovery, and target validations. Phage display technology can produce a huge number of peptides and generate novel peptide ligands. Recently, phage display technology has successfully managed to create peptide ligands that bind to pharmaceutically difficult targets such as the erythropoietin receptor. As a result of the structural analysis of their ligands, we found that the conformational design of peptides in library is important for selecting high-affinity ligands that bind to every target from a phage peptide library. Key issues concern constraints on the conformation of peptides on the phage and the development of chemically synthesized peptides derived from peptides on phage. This review discusses studies related to the conformation of peptides selected from phage display peptide libraries in addition to the conversion from peptides to non-peptides.


Interfacial restructuration of carbon nitride polymers for visible-light photocatalysis.
Photocatalyst surface restructuration is of immense practical importance for solar energy utilization. Herein, we present an ingenious strategy to bridge π-conjugated molecules into the framework of a polymeric semiconductor. This endows the catalyst with increased charge transfer and separation efficiency, resulting in an improved photoactivity. Moreover, the modified photocatalysts exhibit high structural stability and photoactivity. These results illustrate a novel method of integrating functional units to construct new photocatalysts for sustainable photocatalysis.


Sodium/glucose cotransporter 2 inhibitors for the treatment of type 1 diabetes: what are the latest developments?
Despite the improvements in insulin therapy, many patients with type 1 diabetes mellitus (T1DM) do not achieve glycemic targets. Hypoglycemia and weight gain are important barriers in reaching these targets. Sodium/glucose cotransporter 2 (SGLT2) inhibitors lack these side effects and have an insulin-independent mechanism of action. Therefore, they might be useful in patients with T1DM. The authors discuss the safety and efficacy of SGLT2 inhibitors in T1DM. Several randomized controlled trials have evaluated dapagliflozin, sotagliflozin and empagliflozin in this population whereas fewer data are available for other members of this class. In these studies, SGLT2 inhibitors reduced HbA1c levels and body weight without a greater risk of hypoglycemia. However, a higher incidence of diabetic ketoacidosis (DKA) was observed in patients treated with these agents. SGLT2 inhibitors improve glycemic control in patients with T1DM but this effect is modest. Even though weight loss and the neutral effect on the incidence of hypoglycemia are advantages of these agents, the increased risk of DKA is a cause of concern. Overall, SGLT2 inhibitors should be used with caution and only in carefully selected patients with T1DM who are motivated, adherent to treatment, well-trained in recognizing DKA and are closely followed-up.


Operator-patient sex discordance and periprocedural outcomes of percutaneous coronary intervention (from the ORPKI Polish National Registry).
A recent study suggested that sex discordance between surgeons and patients negatively affects the outcomes of patients undergoing common surgical procedures. We sought to assess whether such an impact exists for periprocedural outcomes of percutaneous coronary intervention (PCI). From 2014 to 2020, data on 581,744 patients undergoing single-stage coronary angiography and PCI from 154 centers were collected. Patients were divided into four groups based on the patient and operator sex. Operator-patient sex discordance was defined as the procedure done by a male operator on a female patient or by a female operator on a male patient. Of 581,744 patients treated by 34 female and 782 male operators, 194,691 patients were sex discordant with their operator (female operator with male patient 12,479; male operator with female patient 182,212) while 387,053 were sex concordant (female operator with female patient 6,068; male operator with male patient 380,985). Among female patients, no difference in the risk of periprocedural complications, including death (0.65% vs. 0.82%; p = 0.10), between patients discordant versus concordant with operators was observed. Among male patients the risk of death (0.55% vs. 0.43%; p = 0.037) and bleeding at the puncture site (0.13% vs. 0.08%; p = 0.046) was higher in patients discordant with operators. However, the differences were no longer significant after adjustment for covariates. No detrimental effect of operator-patient sex discordance on periprocedural outcomes was confirmed in all-comer patients undergoing PCI. Some of the observed differences in outcomes were primarily related to the differences in baseline risk profile.


Reversal of Tetracycline Resistance in Escherichia coli by Noncytotoxic bis(Tryptophan)s.
Nine bis(tryptophan) derivatives (BTs) and two control compounds were synthesized and tested for antimicrobial activity against two Escherichia coli strains and a Staphylococcus aureus strain. The effects of linker type, shape, and conformational rigidity were manifested in dramatic differences in altering tetracycline potency when coadministered with that antibiotic. A reversal of resistance was observed for an E. coli strain having a TetA efflux pump. Survival of mammalian cells was assayed with good result.


Subsurface Drainage Nitrate and Total Reactive Phosphorus Losses in Bioenergy-Based Prairies and Corn Systems.
We compare subsurface-drainage NO-N and total reactive phosphorus (TRP) concentrations and yields of select bioenergy cropping systems and their rotational phases. Cropping systems evaluated were grain-harvested corn-soybean rotations, grain- and stover-harvested continuous corn systems with and without a cover crop, and annually harvested reconstructed prairies with and without the addition of N fertilizer in an Iowa field. Drainage was monitored when soils were unfrozen during 2010 through 2013. The corn-soybean rotations without residue removal and continuous corn with residue removal produced similar mean annual flow-weighted NO-N concentrations, ranging from 6 to 18.5 mg N L during the 4-yr study. In contrast, continuous corn with residue removal and with a cover crop had significantly lower NO-N concentrations of 5.6 mg N L when mean annual flow-weighted values were averaged across the 4 yr. Prairies systems with or without N fertilization produced significantly lower concentrations below <1 mg NO-N L than all the row crop systems throughout the study. Mean annual flow-weighted TRP concentrations and annual yields were generally low, with values <0.04 mg TRP L and <0.14 kg TRP ha, and were not significantly affected by any cropping systems or their rotational phases. Bioenergy-based prairies with or without N fertilization and continuous corn with stover removal and a cover crop have the potential to supply bioenergy feedstocks while minimizing NO-N losses to drainage waters. However, subsurface drainage TRP concentrations and yields in bioenergy systems will need further evaluation in areas prone to higher levels of P losses.


Objective response in amyloidosis treated with intermittent chemotherapy.
A 37-year-old woman with amyloidosis derived from light chain immunoglobulin had hepatosplenomegaly, elevated serum alkaline phosphatase values, and progressively destructive bony lesions. A 44-month intermittent course of chemotherapy with melphalan and prednisone resulted in regression, confirming the occasional efficacy of cytotoxic chemotherapy in this disease.


An exploration of how adolescents experience and reason their parents' comments on their weight, shape, and eating.
Disordered eating among adolescents is of increasing concern given associated physical and mental health sequelae. Cognitions underlying disordered eating are formed in childhood and adolescence. Parents are a significant presence during this period, so it is critical to understand how they influence their adolescent's eating cognitions and behaviors. Qualitative analysis using interpretative phenomenological analysis (IPA) methodology was employed to consider the lived experiences of 10 Australian adolescents (14-19 years), 60% female, as they engaged with their parents in a range of weight, shape, and eating communications. Our inductive IPA revealed three key themes representing adolescents' experiences and meaning-making: Parents as Influencers-adolescents acknowledged parents are influencers (objects) within a wider context of community and cultural norms (symbols) and can be protective for peer influence on body image ideals; Expression and Perception-the "what" (weight-talk as an object) and the "how" (objects as independent influences) of gendered parental communication related to health and fitness ideals and illustrated diverse interpretations of both verbal and non-verbal expression; and Fertile Soil and Maturity-the adolescent's characteristics and context influence perceptions of communication, a fear of deviating from norms, and an overarching focus on being "healthy" yet not always knowing what that was. Perception of bidirectional communication also offered valuable insights into potential dangers through family loyalty and in-group permissions. Findings highlight implications for the nuanced influence of parental communication and illustrate the pivotal role of parents within the bioecosystem of adolescent development.


[Radioactive gold treatment of primary carcinoma of the fallopian tube (author's transl)].
20 cases of primary carcinoma of the fallopian tube from 1958 to 1974 are reported. An operation was performed in all cases. A post-operative intra-peritoneal installation of radioactive gold was done in 14 cases. 6 patients which had radioactive gold treatment survived for more than 5 years. None of the patients survived for more than 5 years who did not have radioactive gold treatment. The positive effect on treatment of carcinoma of the fallopian tube of a complete operation with post-operative intra-peritoneal administration of radioactive gold is discussed in detail.


Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.
In 2008, an outbreak of canine distemper virus (CDV) infection in monkeys was reported in China. We isolated CDV strain (subsequently named Monkey-BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM receptors from dog, monkey and human origin, and analyzed the H gene of Monkey-BJ01-DV with other strains. The Monkey-BJ01-DV isolate replicated to the highest titer on Vero cells expressing dog-origin SLAM (10(5.2±0.2) TCID50/ml) and monkey-origin SLAM (10(5.4±0.1) TCID50/ml), but achieved markedly lower titers on human-origin SLAM cells (10(3.3±0.3) TCID50/ml). Phylogenetic analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related to other CDV strains obtained during recent CDV epidemics among species of the Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV, Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V, Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other animals at the same period. Our results suggested that the monkey origin-CDV-H protein could possess specific substitutions to adapt to the new host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect and replicate in host cells, but further adaptation may be required for efficient replication in host cells expressing the human SLAM receptor.


Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador.
To determine the role of cytochrome P450IBI (CYP1B1) mutations in causing primary congenital glaucoma (PCG) in a cohort of Native Americans from Quito, Ecuador. Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the CYP1B1 coding exons. The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in CYP1B1 were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/sequencing approach did not detect any large rearrangements or mutations outside the coding region. These findings suggest that mutations in CYPIBI are not a major cause of PCG in this population and that at least one additional locus for this condition is responsible for most cases. Further, the PCG phenotype did not correlate readily with the molecular basis of the disorder, suggesting that careful clinical analysis of the phenotype cannot predict the molecular basis of the disease with accuracy.


Specific IgG levels to wheat in wheat tolerant professional cyclists may depend on a homeostatic immune response to a high consumption of wheat.
Implication of IgG antibodies to wheat has been alleged in gastrointestinal symptoms. Precise data on the specific IgG levels in healthy subjects are lacking. Our objectives are to compare levels of IgG antibodies to wheat protein fractions in healthy non atopic or atopic subjects, and in healthy professional cyclist subjects, taking into account the quantitative consumption of wheat. 24 control subjects and 26 professional cyclist subjects were selected. ELISA was performed to 2 wheat commercial solutions and to 3 wheat protein fractions. No significant difference was observed between non atopic and atopic subjects. For wheat flour extract, physiological norm determined was 3.27 mg/L sIgG concentration +/- 1.25 CI (95% confidence intervals) for the professional cyclists (vs 1.56 mg/L +/- 0.91 CI in control subjects, p-value: 0.040). For gluten solution, physiological norm was 1.42 mg/L +/- 0.60 CI (vs 0.50 +/- 0.24 CI in control subjects, p-value: 0.010). Atopic and non atopic healthy adults have a similar level of sIgG to wheat. Increased levels of sIgG are observed correlatively with an excessive consumption, and could contribute to homeostasis of tolerance. Studies searching for a pathogenic role of sIgG in certain pathologies should take into account the quantitative consumption.


Effect of Pupil Size and Binocular Viewing on Accommodative Gain in Emmetropia and Myopia.
To evaluate the differences in accommodative gain in response to different accommodative stimuli and determine the effects of pupil size, binocular viewing, and inherent eye refraction on accommodative gain. This study enrolled 47 healthy young adults (emmetropia: 21 eyes, myopia: 26 eyes). Refractive value and pupil size during accommodative stimulus were measured using an open-viewing type auto-refractor (Grand Seiko WAM-5500). The subject was continuously presented with six stimuli (0D, 1D, 2D, 3D, 4D, and 5D) in front of the eye. Measurements were performed under three conditions. Condition 1: Monocular status with complete occlusion of the non-viewing eye; Condition 2: Monocular status with occlusion of the non-viewing eye by translucent occluder; Condition 3: Binocular status. In the emmetropia group, there was no significant difference in accommodative gain between conditions 1 and 2 (p > .05), but conditions 2 and 3 were significantly different (p < .05). In the myopia group, accommodative gain was significantly different between conditions 1 and 2 with stimuli 3D, 4D, and 5D (p < .05), but conditions 2 and 3 were not significantly different (p > .05). The effects of pupil size and binocular viewing on accommodative gain differed between emmetropia and myopia.


Adaptation of trigeminal ganglion cells to periodic whisker deflections.
Trigeminal ganglion neurons in adult rats adapt to periodic whisker deflections in the range of 1-40 Hz, manifested as a reduction in spike counts to progressively later stimuli in a train of pulsatile or sinusoidal deflections. For high velocity, pulsatile deflections, adaptation is time- and frequency-dependent; as in the case of thalamic and cortical neurons, adaptation is greater at higher stimulus frequencies. With slower velocity, sinusoidal movements, trigeminal ganglion cells differ from central neurons, however, by exhibiting strong adaptation even at low frequencies. For both types of stimuli, effects in trigeminal ganglion neurons were more pronounced in rats maintained during the recording session under neuromuscular blockade than in non-paralysed animals. Results are consistent with previous findings in other systems that frequency-dependent adaptation of cutaneous primary afferent neurons is affected by mechanical properties of the skin. Such effects are likely to vary depending on the nature of the whisker stimuli and physiological states that affect skin viscoelasticity.


Increased Resistance to Carbapenems in Proteus mirabilis Mediated by Amplification of the blaVIM-1-Carrying and IS26-Associated Class 1 Integron.
Objective: The aim of the study was to decipher the mechanisms and associated genetic determinants responsible for increased carbapenem resistance among Proteus mirabilis clinical isolates. Methods: The entire genetic structure surrounding the β-lactam resistance genes was characterized by PCR, gene walking, and DNA sequencing. Results: A series of clinical P. mirabilis isolates were consecutively recovered from different patients at the Military hospital of Sofia, Bulgaria. They showed variable levels of resistance to carbapenems. All isolates produced the same carbapenemase VIM-1 that was chromosomally encoded. We showed that increased resistance to carbapenems was related to an increased number of blaVIM-1 gene copies. Conclusion: We showed here that increased carbapenem resistance in P. mirabilis may result from increased expression of the blaVIM-1 carbapenemase gene through multiplication of its copy number.


Direct signal transduction via functional interferon-alphabeta receptors in CD34+ hematopoietic stem cells.
Affinity purified, freshly isolated CD34+ progenitors were shown to express low levels of type I interferon (IFN) receptors (740 +/- 60 binding sites/cell, K(d) 0.7 +/- 0.04 nM) determined by Scatchard's analysis using a radiolabelled, neutralizing, monoclonal antibody directed against the IFNAR1 chain of the human type I IFN receptor. Treatment of freshly isolated (day 0), highly purified (>95% pure) CD34+ cells with recombinant IFN-alpha resulted in rapid tyrosine phosphorylation and activation of STAT1, Tyk2 and JAK1 as shown by Western immunoblotting. Similarly, IFN treatment was shown by confocal microscopy to result in rapid nuclear localization of the transcription factors IRF1 and STAT2, demonstrating the presence of functional IFN receptors on freshly isolated (day 0) CD34+ cells. The number of specific type I IFN receptor binding sites expressed on hematopoietic progenitor cells increased to some 1440 +/- 40 per cell after 11 days of cultivation of CD34+ cells in vitrosuggesting that receptor expression increases with cell differentiation. IFN-mediated signal transduction and the inhibitory effect of IFN-alpha on 7 or 14 days CFU-GM and BFU-E colony formation was abrogated in the presence of the anti-IFNAR1 mAb, indicating that IFN-alpha acts directly on the proliferation of human hematopoietic progenitor cells via receptor activated signal transduction without excluding the induction of other cytokines or growth factors by residual accessory cells.


[Primary hyperparathyroidism. Recent physiopathological data].
Recent advances in the physiology of the parathyroid hormone permit a better demonstration of the mechanisms of inappropriate hypersecretion which characterizes hyperparathyroidism, even through the etiology of primary forms still remains unknown. There have been also some progress achieved understanding and evaluating the impact od hypersecretion on target organs, especially bone and kidney. Some studies give an indication of the therapeutic modalities which would enable to reduce the excess of secretion, to counteract the effect of the hormone on its receptor sites or finally limit its consequences on osteopenia.


Altered Serum Immunological and Biochemical Parameters and Microbiota Composition in Patients With AN During Realimentation.
Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.


A Promising Modified Procedure for Upper Eyelid Retraction-Associated Graves' Ophthalmopathy: Transconjunctival Lateral Levator Aponeurectomy.
Upper eyelid retraction is a characteristic feature of thyroid eye disease, including Graves' orbitopathy. In this study, a new surgical technique for correction of lid retraction secondary to Graves' orbitopathy is described. Sixteen eyelids of patients older than 18 years old underwent surgical correction for moderate to severe lid retraction secondary to Graves' orbitopathy. In this procedure, levator aponeurectomy was performed via a transconjunctival approach. Upper marginal reflex distance (MRD1) was measured before the surgery and at 1 week, 3 months, and 6 months after the surgery. MRD1 was reduced significantly from preoperatively (mean: 7.84 mm) to 1 week after the surgery (mean: 3.59 mm) (P < 0.001). Three and six months after surgery, mean MRD1 was 5.09 mm and 5.10 mm, respectively, showing that lid retraction was improved significantly (P < 0.001). Lateral levator aponeurectomy via the transconjunctival approach is a simple, scar-less, quick procedure that has optimal stable outcome.


Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China.
Leprosy is a chronic infectious and neurological disease that is caused by infection of Mycobacterium leprae (M. leprae). A recent genome-wide association study indicated a suggestive association of LRRK2 genetic variant rs1873613 with leprosy in Chinese population. To validate this association and further identify potential causal variants of LRRK2 with leprosy, we genotyped 13 LRRK2 variants in 548 leprosy patients and 1078 healthy individuals from Yunnan Province and (re-)analyzed 3225 Han Chinese across China. Variants rs1427267, rs3761863, rs1873613, rs732374 and rs7298930 were significantly associated with leprosy per se and/or paucibacillary leprosy (PB). Haplotype A-G-A-C-A was significantly associated with leprosy per se (P=0.018) and PB (P=0.020). Overexpression of the protective allele (Thr2397) of rs3761863 in HEK293 cells led to a significantly increased nuclear factor of activated T-cells' activity compared with allele Met2397 after lipopolysaccharides stimulation. Allele Thr2397 could attenuate 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced autophagic activity in U251 cells. These data suggest that the protective effect of LRRK2 variant p.M2397T on leprosy might be mediated by increasing immune response and decreasing neurotoxicity after M. leprae loading. Our findings confirm that LRRK2 is a susceptible gene to leprosy in Han Chinese population.


Rydberg-valence interactions of CO, and spectroscopic evidence characterizing the C' 1Sigma+ valence state.
Rotationally cold absorption and two-photon ionization spectra of CO in the 90-100 nm region have been recorded at a resolution of 0.3-1.0 cm(-1). The analyses of up to four isotopomers seek to clarify the observations in regions where the Rydberg levels built on the ground state X (2)Sigma(+) of the ion interact with valence states of (1)Sigma(+) and (1)Pi symmetry. Previous observations of the 3ssigma, B (1)Sigma(+) Rydberg state, reviewed by Tchang-Brillet et al. [J. Chem. Phys. 96, 6735 (1992)], have been extended to energies above its avoided crossing with the repulsive part of the D(') (1)Sigma(+) valence state where resonances of varying intensities and widths have been attributed to the fully coupled 3ssigma or 4ssigma and D(') potentials, and where the B state approaches a second avoided crossing with the C(') (1)Sigma(+) valence state [Cooper and Kirby, J. Chem. Phys. 87, 424 (1987); 90, 4895 (1989); Chem. Phys. Lett. 152, 393 (1988)]. Fragments of a progression of weak and mostly diffuse bands, observed for all four isotopomers, have been assigned to the C(')<--X transition. The least-squares modeling of the 4p and 5p complexes reveals the 3ppi, E (1)Pi Rydberg state to be one of the perturbers, violating the Deltav=0 selection rule for Rydberg-Rydberg interactions on account of its rapid transition with increasing v from Rydberg to valence state. A second (1)Pi perturber, very loosely bound and clearly of valence type, contributes to the confusion in the published literature surrounding the 5p, v=0 complex.