Application of facial neuromuscular electrical stimulation (fNMES) in psychophysiological research: Practical recommendations based on a systematic review of the literature.
Facial neuromuscular electrical stimulation (fNMES), which allows for the non-invasive and physiologically sound activation of facial muscles, has great potential for investigating fundamental questions in psychology and neuroscience, such as the role of proprioceptive facial feedback in emotion induction and emotion recognition, and may serve for clinical applications, such as alleviating symptoms of depression. However, despite illustrious origins in the 19th-century work of Duchenne de Boulogne, the practical application of fNMES remains largely unknown to today's researchers in psychology. In addition, published studies vary dramatically in the stimulation parameters used, such as stimulation frequency, amplitude, duration, and electrode size, and in the way they reported them. Because fNMES parameters impact the comfort and safety of volunteers, as well as its physiological (and psychological) effects, it is of paramount importance to establish recommendations of good practice and to ensure studies can be better compared and integrated. Here, we provide an introduction to fNMES, systematically review the existing literature focusing on the stimulation parameters used, and offer recommendations on how to safely and reliably deliver fNMES and on how to report the fNMES parameters to allow better cross-study comparison. In addition, we provide a free webpage, to easily visualise fNMES parameters and verify their safety based on current density. As an example of a potential application, we focus on the use of fNMES for the investigation of the facial feedback hypothesis.


Semantic and psychometric validation of the Brazilian Portuguese version (PASE-P) of the Psoriatic Arthritis Screening and Evaluation questionnaire.
PASE (Psoriatic Arthritis Screening and Evaluation) was developed in the English language to screen for inflammatory arthritis among patients with psoriasis. It is 15 item self administered questionnaire with a score from 15 to 75. A higher score indicates a greater risk for inflammatory joint disease. The purpose of this study was to translate, adapt and validate this questionnaire into Brazilian Portuguese (PASE-P). 465 patients diagnosed with psoriasis (158 with psoriatic arthritis confirmed by a rheumatologist according to the CASPAR criteria and 307 without) were evaluated in dermatology clinics. We performed the analysis of semantic equivalence in eight steps. For psychometric equivalence, we evaluated the data quality, reliability, construct validity, well-known groups and discriminant characteristics of the items, as well as a ROC curve to determine optimal PASE-P cutoff points in case identification and their sensitivity / specificity. The final version presented excellent reproducibility (CCI = 0.97) and reliability (Cronbach's alpha> 0.9). A cut-off point of 25 distinguished between patients with and without psoriatic arthritis, with sensitivity of 69.5 and specificity of 86.8. PASE-P proved to be culturally valid and reliable to screen for psoriatic arthritis in Brazilian patients with psoriasis.


Urogenital Chlamydia trachomatis infections among ethnic groups in Paramaribo, Suriname; determinants and ethnic sexual mixing patterns.
Little is known about the epidemiology of urogenital Chlamydia trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese, Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia, including the role of ethnicity, and identified transmission patterns and ethnic sexual networks among clients of two clinics in Paramaribo, Suriname. Participants were recruited at two sites a sexually transmitted infections (STI) clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men and nurse-collected vaginal swabs were obtained for nucleic acid amplification testing. Logistic regression analysis was used to identify determinants of chlamydia. Multilocus sequence typing (MLST) was performed to genotype C. trachomatis. To identify transmission patterns and sexual networks, a minimum spanning tree was created, using full MLST profiles. Clusters in the minimum spanning tree were compared for ethnic composition. Between March 2008 and July 2010, 415 men and 274 women were included at the STI clinic and 819 women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age, ethnicity, and recruitment site were significantly associated with chlamydia in multivariable analysis. Participants of Creole and Javanese ethnicity were more frequently infected with urogenital chlamydia. Although sexual mixing with other ethnic groups did differ significantly per ethnicity, this mixing was not independently significantly associated with chlamydia. We typed 170 C. trachomatis-positive samples (76%) and identified three large C. trachomatis clusters. Although the proportion from various ethnic groups differed significantly between the clusters (P = 0.003), all five major ethnic groups were represented in all three clusters. Chlamydia prevalence in Suriname is high and targeted prevention measures are required. Although ethnic sexual mixing differed between ethnic groups, differences in prevalence between ethnic groups could not be explained by sexual mixing.


Uptake of Silver-Containing Nanoparticles in an Estuarine Plant: Speciation and Bioaccumulation.
Understanding the bioaccumulation of silver-containing nanoparticles (Ag-NPs) with different species, concentrations, and sizes in estuarine plants is critical to their related environmental risk. Herein, the distribution of Ag-NPs in tidewater, sediments, and plants (Scirpus triqueter) of field-constructed mesocosm was investigated, where tidewater was exposed to Ag0-NPs and Ag+ at environmentally relevant concentrations. Particle number concentrations (PNCs) and sizes of Ag-NPs with various species were analyzed using a multistep selective dissolution method followed by the single-particle- inductively coupled plasma mass spectrometry technique. After 30 days of exposure, more than half of Ag0-NPs were dissolved to Ag+ and about 1/4 of Ag+ were transformed into Ag0-/AgCl-NPs in tidewater. Ag-NPs in stems exposed to Ag0-NPs were found to be dominated by metallic Ag, while Ag+ exposure led to more Ag2S-NPs in stems. In roots, 71% and 51% of Ag-NPs were found as Ag2S-NPs for Ag0-NPs and Ag+ treatment groups, respectively. Plant stems had a significantly higher enrichment of Ag-NPs than roots. Based on both random forests and structure equation models, it is suggested that salinity of tidewater can regulate Ag0-NPs in tidewater indirectly by influencing AgCl-NPs in tidewater and further affect the total PNCs of Ag-NPs in plant stems. Moreover, elevated sulfate-reducing bacteria (SRB) result in more Ag2S-NPs in rhizosphere sediments, thereby enhancing the bioaccumulation of Ag-NPs by roots.


[Do prothrombin time, transaminases, and platelet count predict the severity of fibrosis in viral liver diseases?].
The goal of our study is to assess the performance of a score combining 3 serological parameters (PT, platelets and transminases) in predictive hepatic fibrosis. The study involved 54 patients, 29 of which resulted in distributing them according to the score of Metavir into 2 groupes: Group A with mild fibrosis (F1,F2) and group B with severe fibrosis (F3,F4). PT, platelets and transminase values in serum were assessed for all patients. The total score of the 3 biological parameters combined, was significantly more elabled in the severe fibrosis group than in the mild fibrosis group (P = 0.01) but it was not of much importance in 30% of cases as it did not allow to classify the patients with certainty in group A or in group B. This score does not seem to grant exemption from needle liver biopsy, but it can be improved by the association of other direct markers of fibrosis.


Surgical approaches to malignant tumors of the nasal septum.
Malignant tumors of the nasal septum are rare, probably not more than 300 having been reported. Most of these tumors are epidermoid carcinomas; the second most common histologic type is melanoma. Unless diagnosed and treated early, these tumors are lethal. We report five cases, four carcinomas and one melanoma. We recommend a combined approach with early, wide surgical excision and postoperative irradiation therapy. Surgical considerations must include functional and cosmetic restoration as well as adequate excision of the tumor. Prosthetic appliances can be quite helpful in patients with large resections.


Bioactive and mechanically strong Bioglass-poly(D,L-lactic acid) composite coatings on surgical sutures.
New coating processes have been investigated for degradable (Vicryl) and nondegradable (Mersilk) sutures with the aim to develop Bioglass coated polymer fibers for wound healing and tissue engineering scaffold applications. First, the aqueous phase of a Bioglass particle slurry was replaced with a poly(D,L-lactic acid) (PDLLA) polymer dissolved in solvent dimethyle carbonate (DMC) to act as third phase. SEM observations indicated that this alteration significantly improved the homogeneity of the coatings. Second, a new coating strategy involving two steps was developed: the sutures were first coated with a Bioglass-PDLLA composite film followed by a second PDLLA coating. This two-step process of coating has addressed the problem of poor adherence of Bioglass particles on suture surfaces. The coated sutures were knotted to determine qualitatively the mechanical integrity of the coatings. The results indicated that adhesion strength of coatings obtained by the two-step method was remarkably enhanced. A comparative assessment of the bioactivity of one-step and two-step produced coatings was carried out in vitro using acellular simulated body fluid (SBF) for up to 28 days. Coatings produced by the two-step process were found to have similar bioactivity as the one-step produced coatings. The novel Bioglass/PDLLA/Vicryl and Bioglass/PDLLA/Mersilk composite sutures are promising bioactive materials for wound healing and tissue engineering applications.


Disruptions to School and Home Life Among High School Students During the COVID-19 Pandemic - Adolescent Behaviors and Experiences Survey, United States, January-June 2021.
Youths have experienced disruptions to school and home life since the COVID-19 pandemic began in March 2020. During January-June 2021, CDC conducted the Adolescent Behaviors and Experiences Survey (ABES), an online survey of a probability-based, nationally representative sample of U.S. public- and private-school students in grades 9-12 (N = 7,705). ABES data were used to estimate the prevalence of disruptions and adverse experiences during the pandemic, including parental and personal job loss, homelessness, hunger, emotional or physical abuse by a parent or other adult at home, receipt of telemedicine, and difficulty completing schoolwork. Prevalence estimates are presented for all students and by sex, race and ethnicity, grade, sexual identity, and difficulty completing schoolwork. Since the beginning of the pandemic, more than half of students found it more difficult to complete their schoolwork (66%) and experienced emotional abuse by a parent or other adult in their home (55%). Prevalence of emotional and physical abuse by a parent or other adult in the home was highest among students who identified as gay, lesbian, or bisexual (74% emotional abuse and 20% physical abuse) and those who identified as other or questioning (76% and 13%) compared with students who identified as heterosexual (50% and 10%). Overall, students experienced insecurity via parental job loss (29%), personal job loss (22%), and hunger (24%). Disparities by sex and by race and ethnicity also were noted. Understanding health disparities and student disruptions and adverse experiences as interconnected problems can inform school and community initiatives that promote adolescent health and well-being. With community support to provide coordinated, cross-sector programming, schools can facilitate linkages to services that help students address the adverse experiences that they faced during the ongoing COVID-19 pandemic. Public health and health care professionals, communities, schools, families, and adolescents can use these findings to better understand how students' lives have been affected during the pandemic and what challenges need to be addressed to promote adolescent health and well-being during and after the pandemic.


Electrooptical properties of reduced protein-sodium dodecyl sulfate complexes.
Two independent electrooptical properties, the specific Kerr constants and the electric birefringence relaxation times, of the saturated sodium dodecyl sulfate complexes of a series of reduced polypeptides of known molecular weight are reported. Both the Kerr constants and the relaxation times are unique functions of the molecular weight of the polypeptide chain. The specific Kerr constants depend upon the square of the polypeptide molecular weight. The relaxation times of the complexes, which are proportional to the rotational diffusion constants, are dependent on the molecular weight to approximately the first power. The latter finding is inconsistent with the compact prolate ellipsoid model for sodium dodecyl sulfate-protein complexes proposed by Reynolds and Tanford ((1970) J. Biol. Chem. 245, 5161) in which the cross section is constant and the length depends on linearly on molecular weight; for this model the relaxation times would depend on approximately the 2.5 power of the molecular weight in the range of sizes investigated. Combination of the present results with other properties in the literature rules out a number of other models characterized by compactness and near inflexibility. No firm conclusions can be drawn as to the suitability of the free-draining flexible model of Shirahama, Tsujii, and Takagi ((1974) J. Biochem. (Tokyo) 75, 309).


Binocular measurement method for a continuous casting slab based on the one-dimensional probabilistic Hough transform and local sub-pixel sifting.
Due to the low measurement accuracy of the continuous casting slab model caused by difficulty in detecting ideal corners, a binocular measurement method based on the one-dimensional probabilistic Hough transform and local sub-pixel sifting is proposed. First, the one-dimensional probabilistic Hough transform based on inclination angle voting and the Freeman chain code is used to detect the line segments of the exterior outline. Next, sub-pixel points are extracted in each region of interest (ROI) by using Zernike moments, and sifted in the overlapping area of adjacent ROIs. Then the orthogonal total least squares (TLS) method is applied to fitting sub-pixel edges. Finally, after the key points are matched, three-dimensional localization and measurement are completed according to the binocular vision measurement principle. The experimental results show that the minimum relative error and average relative error of length reach 0.3401% and 0.3945%, respectively, satisfying the measurement requirement. Compared with scale-invariant feature transform (SIFT) and the oriented FAST and rotated BRIEF (ORB), the measurement error of the proposed algorithm is reduced by 80.01% and 74.63%, respectively. Compared with another edge fitting method based on k-means clustering and least squares fitting, its measurement error is reduced by 34.11%, and the time consumption is shortened by 39.07%, verifying its excellent performance in accuracy and efficiency.


Protective effects of nebivolol from oxidative stress to prevent hypertension-related target organ damage.
Hypertension is one of the leading risk factors for morbidity and mortality in patients with cardiovascular and cerebrovascular diseases and renal impairment. It also leads to target organ damage (TOD), which worsens organ function and the patient's clinical status. Reactive oxygen species (ROS)-mediated oxidative stress may contribute significantly to TOD in patients with hypertension. NO (nitric oxide) is a paracrine factor derived from endothelial cells that has been shown to alleviate ROS-mediated oxidative damage. Nebivolol is a third-generation β-blocker with vasodilator activity, both actions contributing to decreased blood pressure in hypertensive patients. Its vasodilatory function is mediated by the endothelial l-arginine NO pathway. Nebivolol increases the bioavailability of NO in the vasculature. Its efficacy and safety profile is comparable to other commonly used antihypertensive agents. In this article, we review the current literature to understand TOD secondary to oxidative stress in patients with hypertension and the role of nebivolol in its prevention. A better understanding of the underlying mechanisms by which nebivolol reduces ROS-mediated TOD will not only help in the development of targeted therapies but may also improve health outcomes in hypertensive patients.


[Problems posed by therapeutic trials in vascular acrosyndromes].
Vascular acrosyndromes are mainly subjective clinical phenomena that are difficult to classify, are related to the patient's background, and require a particularly strict protocol for the evaluation of their therapy. An essential criterion is the homogeneity of groups treated, the Raynaud's phenomenon having to be separated into idiopathic Raynaud's disease, digital arteritis and scleroderma. Functional subjective disturbances have to be rated by the patients themselves, while taking into account the conditions of daily life and of climate. Clinical trials must be double-blind against placebo after a pre-inclusion study. They must be conducted entirely during cold spells for Raynaud's phenomena. Static measurements are of limited value amongst functional exploratory techniques, dynamic tests (vascular reactivity to cold) providing more valid data on the action of medication.


Monoclonal antibodies to leukocyte integrins CD11a/CD18 and CD11b/CD18 or intercellular adhesion molecule-1 inhibit chemoattractant-stimulated neutrophil transendothelial migration in vitro.
Intercellular adhesion molecule-1 (ICAM-1) is present on the endothelium and binds to one or more members of the CD11/CD18 family of leukocyte surface integrins. To assess the role of these molecules in mediating chemotaxis of neutrophils across the endothelium, an in vitro model consisting of monolayers of human umbilical vein endothelial cells (HUVEC) grown on amniotic connective tissue was used. Neutrophils placed on the apical sides of these cultures migrated across the endothelium in response to chemoattractants added basally. Monoclonal antibodies (MoAbs) to CD11a, CD11b, and CD18 on the neutrophils inhibited this migration by 52% +/- 11%, 29% +/- 19%, and 90% +/- 7%, respectively. An MoAb to ICAM-1 inhibited transendothelial chemotaxis of the leukocytes by 55% +/- 16%. Inhibition was mediated by binding of the MoAb to ICAM-1 on the HUVEC, rather than by any direct effect of the antibody on the neutrophils. When used in combination, MoAbs to CD11a and to CD11b inhibited migration in a nearly additive fashion. A similar additive effect was observed when MoAbs to CD11b and to ICAM-1 were used together. In contrast, MoAbs to CD11a and to ICAM-1 produced no more inhibition when used in combination than when added singly. These results show that ICAM-1, CD11a/CD18, and CD11b/CD18 all participate in controlling migration of neutrophils across endothelial monolayers in response to chemotactic agents.


Optimizing sentinel surveillance in temporal network epidemiology.
To help health policy makers gain response time to mitigate infectious disease threats, it is essential to have an efficient epidemic surveillance. One common method of disease surveillance is to carefully select nodes (sentinels, or sensors) in the network to report outbreaks. One would like to choose sentinels so that they discover the outbreak as early as possible. The optimal choice of sentinels depends on the network structure. Studies have addressed this problem for static networks, but this is a first step study to explore designing surveillance systems for early detection on temporal networks. This paper is based on the idea that vaccination strategies can serve as a method to identify sentinels. The vaccination problem is a related question that is much more well studied for temporal networks. To assess the ability to detect epidemic outbreaks early, we calculate the time difference (lead time) between the surveillance set and whole population in reaching 1% prevalence. We find that the optimal selection of sentinels depends on both the network's temporal structures and the infection probability of the disease. We find that, for a mild infectious disease (low infection probability) on a temporal network in relation to potential disease spreading (the Prostitution network), the strategy of selecting latest contacts of random individuals provide the most amount of lead time. And for a more uniform, synthetic network with community structure the strategy of selecting frequent contacts of random individuals provide the most amount of lead time.


Three grades of subjective experiences in schizophrenia: their phenomenology and implications for initial treatment.
Subjective experiences (SEs) in schizophrenia are sometimes neglected in operationalized diagnostics because schizophrenic patients often distort reality. Nevertheless, they sometimes report the peculiar nature of their experiences in a form of SEs. Two cases are presented to show the characteristic forms of SEs, which represent awareness of disturbed experiences of reality. They correspond to SEs in the third grade (SE3s), while SEs in the first grade consist of general subjective symptoms regarding mental and nervous conditions and those in the second grade indicate awareness of deficits in mental functions. Showing an intermediate nature between real and imaginary, SEs as well as first-rank symptoms perplex patients in the initial stage of the illness. Labeling SE3s as symptoms might successfully reduce the distress and anxiety of patients and be helpful in introducing them to long-lasting pharmacotherapy.


Infectious Disease Outbreak and Post-Traumatic Stress Symptoms: A Systematic Review and Meta-Analysis.
Background: As one of the most widely researched consequence of traumatic events, the prevalence of post-traumatic stress symptoms (PTSS) among people exposed to the trauma resulting from infectious disease outbreak varies greatly across studies. This review aimed at examining the pooled prevalence of PTSS among people exposed to the trauma resulting from infectious disease outbreak, summarizing the possible causes of the inconsistencies in the current estimates. Methods: Systematic searches of databases were conducted for literature published on PubMed, EMBASE, Web of Science, the Cochrane Library, PsycArticles, and Chinese National Knowledge Infrastructure (CNKI) until 14 October 2020. Statistical analyses were performed using R software (registration number: CRD42020182366). Results: About 106 studies were included. The results showed that the pooled prevalence of PTSS among the general population exposed to the trauma resulting from infectious disease outbreak was 24.20% (95% CI: 18.54-30.53%), the pooled prevalence of PTSS among healthcare workers was 24.35% (95% CI: 18.38-1.51%), the pooled prevalence of PTSS among patients with infectious disease was 28.83% (95% CI: 18.53-44.86%), and the pooled prevalence of PTSS among suspected cases of infectious disease was 25.04% (95% CI: 18.05-34.73%). Mortality rate was a significant contributor to heterogeneity. Conclusions: Evidence suggests that PTSS were very common among people exposed to the trauma resulting from infectious disease outbreak. Health policymakers should consider both short-term and long-term preventive strategy of PTSS.


Effect of Instrumentation Length and Instrumentation Systems: Hand Versus Rotary Files on Apical Crack Formation - An In vitro Study.
Stresses generated during root canal instrumentation have been reported to cause apical cracks. The smaller, less pronounced defects like cracks can later propagate into vertical root fracture, when the tooth is subjected to repeated stresses from endodontic or restorative procedures. This study evaluated occurrence of apical cracks with stainless steel hand files, rotary NiTi RaCe and K3 files at two different instrumentation lengths. In the present in vitro study, 60 mandibular premolars were mounted in resin blocks with simulated periodontal ligament. Apical 3 mm of the root surfaces were exposed and stained using India ink. Preoperative images of root apices were obtained at 100x using stereomicroscope. The teeth were divided into six groups of 10 each. First two groups were instrumented with stainless steel files, next two groups with rotary NiTi RaCe files and the last two groups with rotary NiTi K3 files. The instrumentation was carried out till the apical foramen (Working Length-WL) and 1 mm short of the apical foramen (WL-1) with each file system. After root canal instrumentation, postoperative images of root apices were obtained. Preoperative and postoperative images were compared and the occurrence of cracks was recorded. Descriptive statistical analysis and Chi-square tests were used to analyze the results. Apical root cracks were seen in 30%, 35% and 20% of teeth instrumented with K-files, RaCe files and K3 files respectively. There was no statistical significance among three instrumentation systems in the formation of apical cracks (p=0.563). Apical cracks were seen in 40% and 20% of teeth instrumented with K-files; 60% and 10% of teeth with RaCe files and 40% and 0% of teeth with K3 files at WL and WL-1 respectively. For groups instrumented with hand files there was no statistical significance in number of cracks at WL and WL-1 (p=0.628). But for teeth instrumented with RaCe files and K3 files significantly more number of cracks were seen at WL than WL-1 (p=0.057 for RaCe files and p=0.087 for K3 files). There was no statistical significance between stainless steel hand files and rotary files in terms of crack formation. Instrumentation length had a significant effect on the formation of cracks when rotary files were used. Using rotary instruments 1 mm short of apical foramen caused lesser crack formation. But, there was no statistically significant difference in number of cracks formed with hand files at two instrumentation levels.


[Bioretention Media Screening for the Removal of Phosphorus in Urban Stormwater].
Urban runoff is an increasingly important source of excess phosphorus (P) to local receiving waters. Bioretention, a promising technology for urban stormwater pollution treatment, was investigated to determine whether the mixture of purple soil and sand could adsorb sufficient P at low concentrations in urban stormwater. The TP concentrations of urban runoff from variously impervious areas in Chongqing City ranged from 0. 04 to 7. 00 mg . L-1 (mean ± S. D. = 0. 75 mg . L-1 ± 1. 08 mg . L-1); the TDP concentrations ranged from 0. 02-0. 46 mg . L-1 ( mean ± S. D. = 0. 15 mg . L-1 ± 0. 10 mg . L-1). The media adsorption benchmark was determined for a bioretention facility sized at 10% of the 100% impervious catchment area and having 10 years of capacity according to annual rainfall pattern and the runoff TDP range. The media benchmark for adsorption was calculated as 7. 5 mg . kg-1 at soluble P concentration of 0. 30 mg . L-1 which provided the necessary stormwater treatment. The oxalate-extractable aluminum and iron content influenced the P sorption capacity for neutral and acid purple soils. A strong positive linear relationship was observed between the oxalate ratio [OR = (Alox + Feox)/Pox] and media P sorption capacity. The media mixture of 20% purple soil and 80% sand showed excellent P removal, meeting the developed benchmark for adsorptive behavior. The media mixture in a large-scale (60 cm) column consistently produced soluble reactive phosphorus effluent event with mean concentrations <0. 05 mg . L-1. The media mixture of purple soil and sand can be used as a bioretention media to treat low-concentration phosphorus in urban runoff under various hydrologic and pollutant concentration conditions.


Xylazine toxicity--literature review and report of two cases.
Xylazine is a veterinary sedative, analgesic or general anesthetic. Its pharmaceutical action results in sympathetic discharge via stimulation of alpha-2-adrenoceptors. In humans, toxicity consists of central nervous system depression, bradycardia and hypotension. The dosages known to produce toxicity in humans vary from 40 mg up to 2400 mg. Because of decomposition, xylazine blood concentrations in two homicide victims were unknown; however, the concentrations in the brain, liver, and kidneys were much higher in the 23-year-old female versus the 33-year-old male victim. A bottle of xylazine found on the crime scene had a concentration of 100 mg/mL. This 50 mL bottle had 32 mL remaining. Therefore at some point in time 18 mL had been utilized. The amount of available milligrams of xylazine (1800 mg) were enough to cause toxicity in both the woman and the man. Of interest was the fact that the partially skeletonized heads were found remote from the torsos, however, the concentration of xylazine in the body tissues provided a toxicological match of which head belonged to which body. Xylazine toxicity in humans and its relationship to these homicides will be the focus of this report.


Prognostic significance of α-fetoprotein in gastric adenocarcinoma.
α-fetoprotein (AFP)-producing gastric carcinoma is a rare type of gastric cancer. Compared with other types, it is more aggressive and prone to liver metastases. To investigate the prognostic characteristics of AFP in patients with gastric adenocarcinoma. Our study included 391 patients diagnosed with gastric adenocarcinoma, who were admitted between 2006 and 2019. For all patients, demographic characteristics, location of the lesion, levels of AFP, CEA, and CA19-9, pathology diagnosis, results of operation, and survival status were recorded. In our study, 68.3% of the patients were male, and the mean age was 62.76 years. In 66 (16.9%) patients, AFP level (cut-off = 8.2 ng/dl) was higher than normal. A total of 26 cases were with AFP > 100 ng/ml. 92.3% of cases with positive AFP gastric cancer were stage 4, and liver metastasis was detected in 80.8%. No significant difference was found between groups with AFP levels of < 100 ng/ml and ≥ 100 ng/ml in terms of gender, location of the lesion, or stage of the tumour. An AFP value higher than 100 ng/ml was significantly associated with liver metastasis, pathological diagnoses, and metastasis status. There was a significant difference in mortality between AFP > 100 ng/ml and age. Predictors with high predictive value are needed for early diagnosis and screening of gastric cancer. We thought that comprehensive studies on this subject would contribute to the literature and reduce the mortality and economic losses by determining the prognosis of gastric cancer.


Changes in rat uterine and cervical phospholipase A2 activity following progesterone agonist or antagonist administration at term.
Our previous study revealed that a fall in plasma progesterone (P(4)) level was associated with a transient increase in cytosolic phospholipase A(2) (PLA(2)) activity and prostaglandin F(2)alpha level in the rat uterus and cervix during natural parturition. This study determined the changes in the PLA(2) activities during modulated occurrence of delivery by P(4) antagonist or agonist late in pregnancy. In rats undergoing P(4) antagonist-induced preterm delivery, the PLA(2) activities of both uterine and cervical cytosol significantly decreased 12 h after the challenge and tended to be attenuated within 72 h. The plasma P(4) level altered in a similar pattern. Blockade of delivery by chronic treatment with P(4) agonist was not associated with changes in uterine PLA(2) activity compared with that in normally delivering rats, although there was a persistent rise in cervical PLA(2) activity. The obtained data indicates that the PLA(2) activities in rat uterine and cervical cytosol are not regulated solely by P(4) and that delivery can occur without activation of this enzyme.


[Color Doppler imaging and measurements of intraovarian and intrauterine vascularization on basal ultrasound examination in spontaneous ovulatory and anovulatory cycles].
Any organs functioning directly depends on vascularization. It applies also to the uterus and ovary which go through changes of vascularization during a menstruation cycle. The aim of this investigation was to determine differences in intrauterine and ovarian stromal arterioral blood flow on basal ultrasound examination (day 2-4) between spontaneous ovulatory and anovulatory cycles. This prospective clinical investigation included 205 patients divided into two groups: with ovulatory and with anovulatory cycles. Resistance to ovarian arterioral stromal blood flow was significantly lower in the patients with ovulatory cycles (pulsatile index--PI 0.97 +/- 0.4 vs 1.93 +/- 1.37; p = 0.001737; and (resistance index - RI 0.55 +/- 0.12 vs 0.68 +/- 0.14; p = 0.040033). There. were no statistically significant differences in arcuate arterioral blood flow in the pateints with ovulatory and anovulatory cycles (PI 1.21 +/- 0.34 vs 61 +/- 0,61 p = 0.136161 and RI 0.64 +/- 0.11 vs 0.74 +/- 0.07; p = 0.136649). The patients with ovulatory cycles had lower uterine radial arterioral blood flow than the patients with anovulatory cycles (PI 1.001 +/- 0.22 vs 1.61 +/- 0.23 p = 0.007501 and RI 0.55 +/- 0.08 vs 0.71 +/- 0.12; p = 0,0460113). The patients with ovulatory cycles had lower subendometrial arterioral blood flow resistance (PI 0.69 0.19 vs 1.385 +/- 0.09; p = 0.00622 and RI 0.44 +/- 0.09 vs 0.65 +/- 0.02; p = 0.027458). Color Doppler ultrasuond imaging and measurements of intrauterine and ovarian stromal arterioral blood flow on basal ultrasound examination (day 2-4), showed lower resistance to blood flow in ovulatory than in anovulatory cycles.


2-Oxoglutarate-dependent dioxygenases in the biosynthesis of simple coumarins.
Coumarins are natural plant products that have been the subject of extensive phytochemical and pharmacological research studies in the past few decades. The core structure of coumarins is derived from the respective cinnamates via ortho-hydroxylation of the aromatic ring, trans/cis isomerization, and lactonization. Various substitution patterns of coumarins have been reported, whereas the biosynthesis of coumarins remains elusive. Ortho-hydroxylation is a key step in simple coumarin biosynthesis as a branch point from the lignin biosynthetic pathway. 2-Oxoglutarate-dependent dioxygenases (2OGDs) from plants convert cinnamate derivatives into simple coumarins through the process of ortho-hydroxylation. This review describes the 2OGDs involved in coumarin biosynthesis and their substrate specificities.


Migraine history and response to lasmiditan across racial and ethnic groups.
The robust enrollment in SPARTAN and SAMURAI provided the opportunity to present post-hoc descriptive details on migraine disease characteristics and treatment outcomes after treatment with lasmiditan, a selective serotonin (5-HT1F) receptor agonist, in racial and ethnic subgroups. Descriptive data from racial (White [W](n = 3471) and Black or African American [AA](n = 792)) and ethnic (Hispanic or Latinx [HL](n = 775) and Non-Hispanic or Latinx [Non-HL](n = 3637)) populations are presented on pooled data from two double-blind, placebo-controlled, randomized Phase 3 studies (SAMURAI [NCT02439320] and SPARTAN [NCT2605174]). Patients were treated with lasmiditan (50 (SPARTAN only), 100, or 200 mg) or placebo for a single migraine attack of moderate-to-severe intensity. Efficacy data were recorded in an electronic diary at baseline, 30, 60, 90, and 120 min. Safety was evaluated and reported by occurrences of adverse events. Clinical characteristics were generally similar across populations. W participants had longer migraine history than AA participants, and Non-HL participants had more migraine disability than HL participants. In the lasmiditan single-attack studies, AA participants waited longer than W participants to take study drug. A higher proportion of HL participants rated baseline migraine severity as severe compared to Non-HL participants. Response to lasmiditan was similar across racial and ethnic groups, including pain response, freedom from most bothersome symptom and migraine-related disability, and safety and tolerability. Across multiple outcomes, AA and HL participants tended to report more positive outcomes. There were few differences in demographic and clinical characteristics across racial and ethnic groups. Similar lasmiditan efficacy and safety outcomes were observed in AA versus W participants, and in HL versus Non-HL participants. Small observed differences may be driven by a tendency toward a more positive response observed across all treatment groups by AA and HL participants.


Toxicity of manganese to various life stages of selected marine cnidarian species.
Manganese (Mn) pollution in marine waters is increasing and sensitivities to this metal vary widely among marine species. The aims of this study were to characterise Mn chemistry in seawater, and evaluate the toxic effects of Mn on various life stages of two scleractinian corals - the branching sp. Acropora spathulata and massive sp. Platygyra daedalea, and the anemone Exaiptasia pallida. Analytical and theoretical characterisation experiments showed that 97-100% of Mn (II) additions ≤ 200 mg/L in seawater were soluble over 72 h and largely assumed labile complexes. Concentrations estimated to reduce coral fertilisation success by 50% (5.5-h EC50) were 237 mg/L for A. spathulata and 164 mg/L for P. daedalea. A relatively low 72-h LC50 of 7 mg/L was calculated for A. spathulata larvae. In a pilot test using fragments of adult A. spathulata, intact coral tissue rapidly sloughed away from the underlying skeleton at very low concentrations with a 48-h EC50 of just 0.7 mg/L. For E. pallida, survival, tentacle retraction and reproduction were unaffected by prolonged high exposures (12-d NOEC 54 mg/L). This study provides important data supporting the derivation of separate water quality guidelines for Mn in systems with and without coral - a decision recently considered by Australian and New Zealand authorities. It demonstrates the high sensitivity of coral larvae and adult colonies to Mn and the potential risks associated with relying on other early life stage tests and/or E. pallida as ecotoxicological representatives of critically important scleractinian corals.


Risperidone: clinical outcome predictors and cost-effectiveness in a naturalistic setting.
Although risperidone seems to be a safe and effective treatment for the management of psychotic symptoms, its acquisition cost is considerably higher than that of conventional antipsychotics, and its precise role in managing psychiatric illnesses has yet to be defined. The purpose of this investigation was to examine the relationship of patient demographic variables to therapeutic outcomes and to analyze the financial impact of risperidone on the treatment of psychotic symptoms. Subjects included in this 2-year, retrospective cohort, intent-to-treat analysis were all patients initiated on risperidone therapy at an inpatient psychiatric treatment facility. Clinical outcomes were assessed from the absolute change in hospitalized days, total number of psychotropic medications prescribed, and historic Clinical Global Impression severity scores. Logistic regression analysis was conducted to analyze the potential relationship to certain demographic variables to therapeutic response. The cost-benefit analysis compared the direct treatment costs incurred by the institution before and after risperidone initiation. Of the 66 patients originally started on risperidone, 57 completed a therapeutic trial. A clinical response was evident in 54 percent of these patients overall. Logistic regression analysis identified previous treatment intolerance and a negative history of substance abuse as predictive of therapeutic success with risperidone (p = .0006 and p = .01, respectively). Hospitalization rates declined by 43 percent among treatment responders and by 1.3 percent among nonresponders resulting in a net annual savings of $147,962. Risperidone may be efficacious in many patients who had previously failed antipsychotic trials. Patients who had been unable to tolerate traditional antipsychotics and those who lacked a documented history of substance abuse were uniquely responsive to risperidone treatment. The significant decline in hospitalized days that was observed among responsive patients seems to indicate that risperidone may be a cost-effective approach to the management of psychotic symptoms.


Longitudinal analysis of antibody decay in convalescent COVID-19 patients.
Determining the sustainability of antibodies targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for predicting immune response against the Coronavirus disease 2019 (COVID-19). To quantify the antibody decay rates among the varying levels of anti-nucleocapsid (anti-N) Immunoglobulin G (IgG) in convalescent COVID-19 patients and estimate the length of time they maintained SARS-CoV-2 specific antibodies, we have collected longitudinal blood samples from 943 patients over the course of seven months after their initial detection of SARS-CoV-2 virus by RT-PCR. Anti-N IgG levels were then quantified in these blood samples. The primary study outcome was the comparison of antibody decay rates from convalescent patients with high or low initial levels of antibodies using a mixed linear model. Additional measures include the length of time that patients maintain sustainable levels of anti-N IgG. Antibody quantification of blood samples donated by the same subject multiple times shows a gradual decrease of IgG levels to the cutoff index level of 1.4 signal/cut-off (S/C) on the Abbott Architect SARS-CoV-2 IgG test. In addition, this study shows that antibody reduction rate is dependent on initial IgG levels, and patients with initial IgG levels above 3 S/C show a significant 1.68-fold faster reduction rate compared to those with initial IgG levels below 3 S/C. For a majority of the donors naturally occurring anti-N antibodies were detected above the threshold for only four months after infection with SARS-CoV-2. This study is clinically important for the prediction of immune response capacity in COVID-19 patients.


Diagnosis of legionnaires' disease by urinary antigen and DNA detection: a case report.
A 38-year-old male patient who was admitted to a private hospital in Kuala Lumpur presented with fever, symptoms of respiratory infection and diarrhoea. On admission, he was febrile, toxic looking, dehydrated with hypotension and tachycardia. No clinical signs of respiratory infection were detected on admission. Initially he was treated as a case of septicaemia with fluid therapy and intravenous antibiotic (Perfloxacin). Subsequently, he was noticed to have pneumonia in the right lower zone of the lung. His sputum, stool and blood were sent for culture and the results were negative. Sputum culture for Legionella and serological tests for Mycoplasma and Legionella were also reported negative. Sandwich ELISA performed on his urine sample detected Legionella pneumophila antigen. L. pneumophila mip gene was also detected in his urine by polymerase chain reaction. The patient was commenced on Erythromycin and he responded favourably to the treatment. The present case shows that L. pneumophila should not be overlooked as one of the causative agents of pneumonia and rapid techniques of urinary antigen and DNA detection should be utilized to make an early diagnosis of the infection.


The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment.
Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity. This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin. Exposure is classified as direct-women taking ribavirin during pregnancy or the 6 months prior to conception-or indirect-women exposed through sexual contact, 6 months prior to or during pregnancy, with a man who is taking or has taken ribavirin in the past 6 months. Women are followed until delivery and infants for 1 year. When enrollment is complete, birth defect rates will be compared with the Metropolitan Atlanta Congenital Defects Program's published rate of 2.67. Using data collected since inception in 2003 through February 2016, preliminary rates were calculated. The registry has enrolled 272 pregnant women, with 180 live births: there were seven birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence interval (CI) 3.4-16.2)] and four birth defect cases among 95 indirectly exposed women [4/95 (4.2%) (95% CI 1.2-10.4)]. Of the 11 infants, nine had structural defects and two had chromosomal anomalies. Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen. Based on the patterns of birth defects reported, preliminary findings do not suggest a clear signal of human teratogenicity for ribavirin. However, the current sample size is insufficient for definitive conclusions, and ribavirin exposure should be avoided during pregnancy and during the 6 months prior to pregnancy, in accordance with prescribing information. ClinicalTrials.gov identifier: NCT00114712.


Post-extrasystolic potentiation and the force-frequency relationship: differential augmentation of myocardial contractility in working myocardium from patients with end-stage heart failure.
We studied post-extrasystolic potentiation (PESP) and frequency potentiation (FP) of human working myocardium isolated from the ventricles of 10 patients with end-stage heart failure (CHF) and 17 non-failing controls (CTL). The contractility index was peak isometric tension developed in vitro by trabeculae carneae (CTL n = 34, CHF n = 31); programmed electrical stimulation was used to initiate as well as alter the timing relationship of the contractile events. While holding constant the total number of contractions per unit of time, we compared the augmentation of contractile performance that occurred upon doubling the stimulation frequency (FP) to that of changing the stimulation pattern (PESP). In the CTL group we found that FP and PESP differed in their ability to augment cardiac contractile performance, PESP being more effective; 105 +/- 13% for PESP vs. 34 +/- 11% (mean +/- S.E.M.) for FP. In the CHF group, the inotropic response to PESP was similar to CTL; in contrast, the relative efficacy of FP (3 +/- 3%) compared to PESP (81 +/- 14%) was markedly diminished. Studies with positive inotropic agents revealed that the percent change in contractility induced by FP and PESP depends upon the relative inotropic state of the heart; however, the contractile response to PESP always equaled or exceeded those produced by clinically relevant concentrations of inotropic agents, particularly in CHF muscles. Agents that increase intracellular levels of adenosine 3',5'-cyclic monophosphate reversed the FP abnormalities seen in the CHF group, suggesting that deficient production of this second messenger in heart failure may cause the abnormal force-frequency relationship in failing myocardium. We conclude that the differential responses of myopathic muscle to PESP and FP may be caused by abnormal restitution processes during diastole. Our results suggest that PESP may be an effective therapeutic modality for patients with severe heart failure who have failed to adequately respond to inotropic drugs, and may serve as a useful indicator of cardiac contractile reserve in these patients.


Unmasking hypotension by beta lactam during dextran sulfate low-density lipoprotein apheresis.
The authors report, for the first time, potentially fatal adverse effects of combined treatment using beta lactam and low-density lipoprotein (LDL) apheresis with dextran sulfate adsorption. A 62-year-old man was receiving LDL apheresis because of peripheral artery disease. Cefmetazole was administered to treat infection of a leg ulcer. Although antibiotics alone did not cause any allergic reactions, he manifested circulatory collapse during LDL apheresis. Possible mechanisms for shock were discussed.


MORPHOMETRIC VARIABILITY IN CONTINENTAL AND ATLANTIC ISLAND POPULATIONS OF CHAFFINCHES (FRINGILLA COELEBS).
The magnitudes of phenotypic variances in peripherally isolated populations of common chaffinches (Fringilla coelebs) in the Azores, Madeira, and Canaries relative to their continental source populations in Iberia and Morocco have played a pivotal role in the formulation of competing hypotheses of phenotypic evolution in these isolates. Because Van Valen's niche variation hypothesis and Grant's model of island evolution were based on museum skins prone to measurement error and temporal variation, we re-examined the patterns of phenotypic variability using more precise skeletal measurements from freshly collected specimens. Levene's tests showed that univariate character variances were homogeneous in all island and continental populations, although there was a consistent trend for the magnitude of the variances to be lower for all characters in all Canary island populations. Multivariate Levene's tests, however, revealed significantly reduced total variances in the Hierro and Madeira populations compared to some Azores and continental populations. The Azores and continental populations did not differ in variability, and lower variances in the Canaries were not related to the presence or absence of the congeneric blue chaffinch (F. teydea), contrary to the predictions of Van Valen's niche variation hypothesis. Population variability was not inversely related to differentiation or isolation within the Azores or Canaries archipelagoes, opposite to the association reported by Grant. Our results also differ from both previous studies which reported much larger differences in population variabilities, and this likely reflects the use of heterogeneous samples of museum specimens, less precise external characters, and the use of tests sensitive to sample size. Differentiation among populations has been markedly greater in the Canary islands, implicating founder events and possibly historically stronger directional selection as determinants of this enhanced divergence relative to the Azores. These variance-reducing processes are unlikely to explain current lower levels of phenotypic variability because there has been sufficient time since colonization for replenishment of variability in polygenic characters. Average heterozygosities at putatively neutral allozyme loci are 1.6 times higher in the Azores compared to the Canaries, and support the view that effective population sizes are smaller in the latter archipelago. We argue that reduced variances in the Canary island populations represent lower equilibrium levels maintained by drift and mutation in populations with smaller long-term effective sizes, consistent with Lynch and Hill's neutral model of phenotypic evolution. Although episodes of selection in the past may have been interspersed with long periods of effective neutralism and drift, adaptationist hypotheses invoking a primary role for variance-reducing selection appear to be unwarranted.


Engineering a bzd cassette for the anaerobic bioconversion of aromatic compounds.
Microorganisms able to degrade aromatic contaminants constitute potential valuable biocatalysts to deal with a significant reusable carbon fraction suitable for eco-efficient valorization processes. Metabolic engineering of anaerobic pathways for degradation and recycling of aromatic compounds is an almost unexplored field. In this work, we present the construction of a functional bzd cassette encoding the benzoyl-CoA central pathway for the anaerobic degradation of benzoate. The bzd cassette has been used to expand the ability of some denitrifying bacteria to use benzoate as sole carbon source under anaerobic conditions, and it paves the way for future pathway engineering of efficient anaerobic biodegraders of aromatic compounds whose degradation generates benzoyl-CoA as central intermediate. Moreover, a recombinant Azoarcus sp. CIB strain harbouring the bzd cassette was shown to behave as a valuable biocatalyst for anaerobic toluene valorization towards the synthesis of poly-3-hydroxybutyrate (PHB), a biodegradable and biocompatible polyester of increasing biotechnological interest as a sustainable alternative to classical oil-derived polymers.


Mammographic density in relation to daidzein-metabolizing phenotypes in overweight, postmenopausal women.
Circulating hormones are associated with mammographic density, an intermediate marker of breast cancer risk. Differences in circulating hormones, including estrone and testosterone, have been observed in premenopausal women based on their capacity to metabolize daidzein, an isoflavone found predominantly in soybeans. Equol and O-desmethylangolensin (O-DMA) are products of intestinal bacterial metabolism of daidzein. There is interindividual variability in the capacity to produce daidzein metabolites; individuals can be equol producers or non-producers and O-DMA producers or non-producers. We tested the hypothesis that daidzein-metabolizing phenotypes are associated with mammographic density. Participants were recruited from among 92 sedentary, postmenopausal women, ages 50 to 75 years, who participated in a 1-year physical activity intervention. Pre-intervention mammographic density was determined using a computer-assisted, gray-scale thresholding technique. Fifty-five of these women consumed supplemental soy protein (>10 mg daidzein/d) for 3 days and collected a first-void urine sample on the fourth day to determine daidzein-metabolizing phenotypes. Equol and O-DMA concentrations were measured using gas chromatography-mass spectrometry. Associations between daidzein-metabolizing phenotypes and percent mammographic density were adjusted for age, maximum adult weight, gravidity, family history of breast cancer, and serum follicle-stimulating hormone and free testosterone concentrations. Mammographic density was 39% lower in equol producers compared with non-producers (P = 0.04). O-DMA producers had mammographic density 69% greater than non-producers (P = 0.05). These results suggest that particular intestinal bacterial profiles are associated with postmenopausal mammographic density, and these associations are not entirely explained by differences in reproductive or anthropometric characteristics or circulating hormones.


[Measurement of the Minimum Pressure in the Bronchial Cuff during One-lung Ventilation Using a Capnometer].
It is recommended to avoid overinflation of the bronchial cuff, leading to ischemic pressure damages to the respiratory mucosa and bronchial rupture. We investigated the minimum bronchial cuff pressure of 35 Fr double lumen tubes (DLTs) during one lung ventilation using a capnometer. We studied 50 patients who were scheduled to undergo thoracic surgery. General anesthesia was induced and the patients were intubated with 35 Fr left DLT. With a fiberoptic bronchoscope, the DLT was positioned appropriately. The bronchial cuff was inflated first with air 3-3.5 ml. Lung isolation was confirmed by auscultation. Measurements were performed with the patient in the lateral position. Ventilating one lung isolatedly for 5 minutes, we confirmed non ventilated condition with a capnometer displaying flat line. The bronchial cuff was deflated 0.5-ml steps just before displaying the respiratory pattern by the capnogram. The bronchial cuff pressure and volume were recorded at this point The minimum pressures of bronchial cuff (volume) for one lung ventilation are for male 5.46 ± 0.6 cmH2O (2.33?0.1 ml) and for female 1.5?0.5 cmH20 (1.09 ± 0.3 ml). These values are smaller than the recommended value (< 25 cmH2O). There was no case in which the collapse of the operated lung was insufficient. In this study, the bronchial pressure higher than 12 cmH2O was not necessary for one lung ventilation. If high intracuff pressure is necessary to seal the bronchus, there are possibilities of the incompatibility of the size of DLT and the herniation of the bronchial cuff to the proximal side. The method of confirmation of OLV using a capnometer can display the non ventilated condition on the monitor objectively. We can thus decrease troubles during operations.


Sulfinpyrazone C-glucuronidation is catalyzed selectively by human UDP-glucuronosyltransferase 1A9.
The uricosuric agent sulfinpyrazone (SFZ) is metabolized via C-glucuronidation, an uncommon metabolic pathway, in humans. The present study aimed to characterize SFZ glucuronidation by human liver microsomes (HLMs) and identify the hepatic forms of UDP-glucuronosyltransferase responsible for this pathway. Incubations of SFZ with HLMs formed a single glucuronide that was resistant to beta-glucuronidase and acid hydrolysis, consistent with formation of a C-glucuronide. Mass spectral analysis confirmed the identity of the metabolite as SFZ glucuronide (sulfinpyrazone beta-D-glucuronide; SFZG). SFZ C-glucuronidation by HLMs exhibited Michaelis-Menten kinetics, with mean (+/- S.D.) Km and Vmax values of 51 +/- 21 microM and 2.6 +/- 0.6 pmol/min . mg, respectively. Fifteen recombinant human UDP-glucuronosyltransferases (UGTs), expressed in HEK293 cells, were screened for their capacity to catalyze SFZ C-glucuronidation. Of the hepatically expressed enzymes, only UGT1A9 formed SFZG. UGTs 1A7 and 1A10, which are expressed in the gastrointestinal tract, also metabolized SFZ, but rates of metabolism were low compared with UGT1A9. SFZ glucuronidation by UGT1A9 exhibited "weak" negative cooperative kinetics, which was modeled by the Hill equation (S50 16 microM). The data indicate that UGT1A9 is the enzyme responsible for hepatic SFZ C-glucuronidation and that SFZ may be used as a substrate "probe" for UGT1A9 activity in HLMs.


Biochemical and Computational Insights on a Novel Acid-Resistant and Thermal-Stable Glucose 1-Dehydrogenase.
Due to the dual cofactor specificity, glucose 1-dehydrogenase (GDH) has been considered as a promising alternative for coenzyme regeneration in biocatalysis. To mine for potential GDHs for practical applications, several genes encoding for GDH had been heterogeneously expressed in Escherichia coli BL21 (DE3) for primary screening. Of all the candidates, GDH from Bacillus sp. ZJ (BzGDH) was one of the most robust enzymes. BzGDH was then purified to homogeneity by immobilized metal affinity chromatography and characterized biochemically. It displayed maximum activity at 45 °C and pH 9.0, and was stable at temperatures below 50 °C. BzGDH also exhibited a broad pH stability, especially in the acidic region, which could maintain around 80% of its initial activity at the pH range of 4.0-8.5 after incubating for 1 hour. Molecular dynamics simulation was conducted for better understanding the stability feature of BzGDH against the structural context. The in-silico simulation shows that BzGDH is stable and can maintain its overall structure against heat during the simulation at 323 K, which is consistent with the biochemical studies. In brief, the robust stability of BzGDH made it an attractive participant for cofactor regeneration on practical applications, especially for the catalysis implemented in acidic pH and high temperature.


Bifidobacterium apri sp. nov., a thermophilic actinobacterium isolated from the digestive tract of wild pigs (Sus scrofa).
Fresh samples of intestinal contents of three wild pigs originating from the Central Bohemia region were examined for the presence of bifidobacterial strains. During the study, we isolated many fructose-6-phosphate phosphoketolase-positive, strictly anaerobic, irregular rod-shaped bacterial isolates. Three of them were preliminarily identified as representing a novel species of the genus Bifidobacterium because their 16S rRNA gene sequence similarity with the closest relatives of thermophilic bifidobacteria (Bifidobacterium boum DSM 20432T, Bifidobacterium thermophilum DSM 20210T, Bifidobacterium thermacidophilumsubsp. porcinum LMG 21689T, Bifidobacterium thermacidophilumsubsp. thermacidophilum DSM 15837T) was in the range of 97.9 - 98.4 %. All three bacterial isolates had identical 16S rRNA, dnaJ1, fusA, gyrB and rplB gene sequences. Isolate RP115T was chosen as a representative of the bacterial group and DNA G+C content (mol%) determination, biochemical tests and analyses of physiological and morphological characteristics, habitat and chemotaxonomic traits (peptidoglycan structure, cellular fatty acids and polar lipids profile) were performed. The DNA-DNA hybridization analyses of RP115T and species representing the group of thermophilic bifidobacteria revealed values in the range from 33 to 53 %. This fact, together with relatively low sequence similarities of particular phylogenetic markers among examined bacterial strains and the phenotyping and chemotaxonomy results obtained, indicated that the evaluated bacterial isolate should be classified as representing a separate taxon within the specific group of thermophilic bifidobacteria. The name Bifidobacterium apri (of boar) sp. nov. has been proposed for the representative strain RP115T (=CCM 8605T=DSM 100238T=LMG 28779T).


Smoking cessation aids and strategies: a population-based survey of former and current smokers in Norway.
In Norway, tobacco consumption is equally divided between combustible (cigarettes) and non-combustible (snus) tobacco. In the process of quitting, people who smoke can choose between several smoking cessation aids and strategies based on what is available on the market or what are recommended as cessation aids. A quit attempt may be planned or unplanned and consist of a gradual decline in consumption or an abrupt quitting. This study explores smoking cessation aids and strategies used at the latest quit attempt among people who have ever smoked. How prevalent is the use of various cessation aids and strategies, and do they correlate with each other? Are there any differences in successful quits depending on the use of a specific cessation aid or strategy? We used repeated cross-sectional representative surveys in Norway for 2017, 2018, 2019 and 2020. The analytic sample consists of people aged 20 years or older who have ever smoked daily, more precisely current daily smokers with at least one quit attempt (n = 476), and former daily smokers who quit in 2012 or later (n = 397). Participants answered questions on cessation aids and strategies used at their last quit attempt. Logistic regression analysis was used to estimate the associations between cessation aids and strategies and sociodemographic and smoking-related variables and successful quit attempts. Fifty-six percent of people who ever smoked daily reported any use of cessation aids, and nicotine replacement therapy (NRT), snus and e-cigarettes were the most commonly used cessation aids. Snus and web/mobile use was associated with successful quits, while NRT was associated with unsuccessful quit attempts. When exclusive use was separated from the combined use of several aids, only snus was associated with successful quits. Snus use was found to be a "stand-alone" cessation aid, and only weakly associated with the use of other cessation aids. Further investigation of cessation aid preferences is needed, especially among smokers with little or no contact with health services and/or for whom traditional cessation aids have no appeal.


Detection of Purple Sulfur Bacteria in Purple and Non-purple Dairy Wastewaters.
The presence of purple bacteria in manure storage lagoons is often associated with reduced odors. In this study, our objectives were to determine the occurrence of purple sulfur bacteria (PSB) in seven dairy wastewater lagoons and to identify possible linkages between wastewater properties and purple blooms. Community DNA was extracted from composited wastewater samples, and a conservative 16S rRNA gene sequence within and genes found in both purple sulfur and nonsulfur bacteria was amplified. Analysis of the genes indicated that all of the lagoons contained sequences that were 92 to 97% similar with . Sequences from a few lagoons were also found to be similar with other PSB, such as sp. (97%), (93-100%), and (95-98%). sequences amplified from enrichment and pure cultures were most similar to (93-96%). Carotenoid pigment concentrations, which were used as an indirect measure of purple bacteria levels in the wastewaters, were found to be positively correlated with salinity, nitrogen, total and volatile solids, and chemical oxygen demand; however, salinity could be the dominant factor influencing purple blooms. Due to the detection of PSB sequences in all lagoons, our findings suggest that the non-purple lagoons may have been purple in the past or may have the potential to become purple in the future.


Neurosarcoidosis Mimicking Normal Pressure Hydrocephalus.
Two female patients, aged 46 and 51, were referred to the National Hospital for Neurology and Neurosurgery with symptoms resembling normal pressure hydrocephalus (NPH) and with ventriculomegaly on the MRI. Both had a definite diagnosis of neurosarcoidosis (NS) on biopsy, and they underwent the medical and surgical management reserved for NPH. At follow-up, their presenting symptoms had resolved and they had clinically improved. Neurosarcoidosis can mimic NPH, and it should be excluded in patients presenting with NPH.


Association of oral health behavior and the use of dental services with oral health literacy among adults in Tehran, Iran.
To assess the association of oral health behavior (OHB) and the use of dental services with oral health literacy (OHL) among Iranian adults. This was a cross-sectional population study of a random sample of 1031 adults aged 18-65 in Tehran, Iran. We collected data on tooth brushing frequency, the consumption of sugary snacks and beverages, and time since last dental visit. To measure OHL, we used a validated OHL adults' questionnaire (OHL-AQ). In addition to descriptive analysis, we used multiple logistic regression models to assess the association of OHB and the most recent dental visit with OHL while controlling for socioeconomic and demographic factors. The participants' mean age was 36.3 (standard deviation 12.9), and 51% were women. Of the participants, 81.3% reported brushing their teeth daily (≥1/day), 37.6% consumed sugary snacks or beverages between meals less than once daily (<1/day), and 36.8% used dental services within the past 6 months. In the adjusted models, high OHL scores significantly correlated with daily (≥1/day) tooth brushing (odds ratio [OR] = 1.97, 95% confidence interval [CI]: 1.30-2.98), the consumption of sugary snacks or beverages (<1/day between meals) (OR = 1.56, 95% CI: 1.13-2.15) and the recent use of dental services (≤6 months) (OR = 1.59, 95% CI: 1.15-2.21), respectively. OHL relates significantly to improved OHB and the use of dental services. Oral health promotion programs should, therefore, take into account improvements in adults' OHL, particularly in countries with developing health-care services.


Three-field dissection or two-field dissection?--A proposal of new algorithm for lymphadenectomy.
There are no systematic criteria for cervical lymphadenectomy in esophageal carcinoma. We provide a new algorithm for deciding whether to use three-field dissection or two-field dissection. Ninety-eight patients underwent curative esophagectomies with three-field lymph node dissections for squamous cell carcinoma of the thoracic esophagus. We examined the outcomes and predictors for survival of these patients. Therefore, we devised a new decision tree for deciding whether to use three-field dissection or two-field dissection. The overall 5-year survival rate for the 98 patients was 41.3%. The number of positive nodes was the only significant predictor for survival in the multivariate Cox proportional hazard model. The outcomes of patients with positive supraclavicular/internal jugular nodes were poor. On the other hand, positive cervical paraesophageal nodes do not worsen prognosis. We provided a new algorithm for selecting procedure of lymphadenectomy based on the presence of lymph node metastases. This algorithm is decided by the number of positive nodes, the presence of cervical node metastasis and recurrent nerve node metastasis. According to this decision tree, there were a few patients who needed absolutely three-field dissections. The new algorithm may be helpful for deciding three-field dissection or two-field dissection for thoracic esophageal carcinoma.


Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. The 3 PPAR isotypes, PPAR-alpha, PPAR-gamma, and PPAR-delta, play a key role in the regulation of lipid and glucose metabolism. Obesity and the interrelated disorders of the metabolic syndrome have become a major worldwide health problem. In this review, we summarize the critical role of PPARs in regulating inflammation, lipoprotein metabolism, and glucose homeostasis and their potential implications for the treatment of obesity, diabetes, and atherosclerosis.


In-vivo microbiologic evaluation of polytetrafluoroethylene and cotton as endodontic spacer materials.
Spacers are commonly placed between the canal orifice and the temporary material between endodontic treatment appointments. This prevents the temporary restoration material from obstructing the canal orifices and allows for easy removal. Various endodontic spacers are currently used, including polytetrafluoroethylene (PTFE) tape. Previous in-vitro studies have demonstrated the advantages of using PTFE over using cotton; however, no in-vivo studies have demonstrated this. Hence, the purpose of this study was to evaluate which spacer showed less bacterial leakage between endodontic treatments. Fifty patients participated in the study and were randomly assigned to either the cotton or the PTFE group. Root canal treatments were completed in two appointments. Cotton and PTFE spacers were collected after a 2- to 4- week time interval between the first and second appointments. Samples were incubated on agar plates for 48 hours and then evaluated for presence of microbial growth. Colony forming units (CFUs) were counted for each of the samples. The results were analyzed using nonparametric statistical tests. Fifteen of the 24 cotton spacers and two of the 24 PTFE spacers were positive for bacterial growth. Cotton fibers exposed to the oral environment could potentially wick contaminants into the pulp chamber. The tendency of cotton to distort under masticatory forces may allow disruption of the temporary material's marginal seal. Based on the results of this study, the use of PTFE is strongly recommended over cotton as an endodontic spacer material. PTFE performed better than cotton in this in-vivo microbial study.


Adrenomedullin production in fibroblasts: its possible function as a growth regulator of Swiss 3T3 cells.
In addition to endothelial cells and vascular smooth muscle cells, we demonstrated that adrenomedullin (AM) is synthesized and secreted from fibroblasts, Swiss 3T3, Hs68, and NHLF cells, in a native and biologically active form. Synthesis and secretion of AM from these fibroblasts was regulated by inflammatory cytokines, such as tumor necrosis factor and interleukin-1, lipopolysaccharide, growth and differentiation factors, and hormones in a manner similar to that of vascular smooth muscle cells and endothelial cells. Tumor necrosis factor-alpha, interleukin-1beta, and dexamethasone elevated AM secretion, whereas transforming growth factor-beta1 and interferon-gamma suppressed it in these three fibroblasts. Swiss 3T3 cells were shown to express receptors specific for AM by both cAMP production and receptor binding assay, and AM was found to stimulate DNA synthesis of quiescent cells through the cAMP-mediated pathway. AM secreted from Swiss 3T3 cells was also confirmed to augment cAMP production and DNA synthesis in the cells themselves. These effects were inhibited by a neutralizing monoclonal antibody against AM. These findings raise the possibility that AM functions as a growth regulator in the case of Swiss 3T3 cells. As AM receptors are widely distributed, AM secreted from fibroblast may play a role as a local regulator in mesenchymal cells of inflammatory or wounded regions.


Designing hybrid web-based courses for accelerated nursing students.
Due to a heightened interest in accelerated nursing programs, enrollment in schools of nursing is rapidly increasing. Nursing programs need to find more creative ways to reach and teach older, technologically savvy adult learners, who have different learning needs than traditional undergraduate nursing students. These students present new challenges to nursing faculty. Larger class sizes, prior academic accomplishments, and a shorter time frame for assimilation of the nursing role provide opportunities for creative course delivery. This article discusses how a change in course design, specifically a hybrid Web-based course, can address these challenges.


[Activated clotting time post therapeutic anticoagulation with unfractionated heparin in patients undergoing elective percutaneous coronary intervention].
To investigate the activated clotting time (ACT) level after administration of guideline-recommended dose of unfractionated heparin (UFH) and to confirm the importance of ACT monitoring in percutaneous coronary intervention (PCI). We performed a retrospective study on 1 062 patients undergoing elective PCI in Peking Union Medical College Hospital from May 1, 2011 to December 31, 2012. All patients were administrated weight-adjusted UFH (70-100 U/kg) based on PCI guideline of ACCF/AHA/SCAI. Patients were divided into 3 groups: ACT < 300 s (598 cases), ACT 300-350 s (183 cases) and ACT > 350 s (281 cases). ACT level and factors that may affect UFH anticoagulation were analyzed. (1) The mean age was (63.0 ± 10.6) years and 751 (70.7%) patients were men. The mean weight was (70.5 ± 11.7) kg, and the mean UFH dose used was (100.7 ± 9.1) U/kg. (2) The median ACT was 285 (240-352) s after the UFH use. Pre-defined ACT target (300-350 s) was achieved only in 17.2% (183/1 062) patients. (3) Age, gender, height, weight, UFH/weight and the risk factors of coronary heart disease were similar among 3 groups (all P > 0.05). Multifactor linear correlation analysis showed that UFH/weight was related to ACT level (r = 0.07, P < 0.01), but other factors were not related to ACT level (all P > 0.05). (4) Among 598 patients with ACT < 300 s, 444 (74.2%) patients received additional UFH. No major bleeding events were observed in 1 062 patients. The incidence of minor bleeding and ischemic complications within 48 h after procedure were similar among 4 groups of ACT < 300 s with additional UFH, ACT < 300 s without additional UFH, ACT 300-350 s and ACT > 350 s (all P > 0.05). In this single-center study, only a small proportion of patients reached the ACT target after administration of weight-adjusted UFH. Our results supported the recommendation of ACT monitoring in current PCI guideline to improve efficacy and safety of UFH anticoagulation therapy.


There is no pulp necrosis or calcific metamorphosis of pulp induced by orthodontic treatment: biological basis.
To biologically explain why the orthodontic treatment does not induce pulp necrosis and calcific metamorphosis of the pulp, this paper presents explanations based on pulp physiology, microscopy and pathology, and especially the cell and tissue phenomena that characterize the induced tooth movement. The final reflections are as follows: 1) the orthodontic movement does not induce pulp necrosis or calcific metamorphosis of the pulp; 2) there is no literature or experimental and clinical models to demonstrate or minimally evidence pulp alterations induced by orthodontic movement; 3) when pulp necrosis or calcific metamorphosis of the pulp is diagnosed during orthodontic treatment or soon after removal of orthodontic appliances, its etiology should be assigned to concussion dental trauma, rather than to orthodontic treatment; 4) the two pulp disorders that cause tooth discoloration in apparently healthy teeth are the aseptic pulp necrosis and calcific metamorphosis of the pulp, both only induced by dental trauma; 5) the concussion dental trauma still requires many clinical and laboratory studies with pertinent experimental models, to increasingly explain its effects on the periodontal and pulp tissues.


Explaining a diagnosis of fibromyalgia in primary care: a scoping review.
Fibromyalgia is a common cause of chronic pain in the UK, with a huge individual and societal impact. Despite this, it remains difficult to diagnose and treat. The explanation of a fibromyalgia diagnosis can lead to difficult therapeutic relationships, with attitudinal issues and negative profiling of patients. This can lead to frustration, and have a harmful impact on health outcomes. To review how an explanation of a fibromyalgia diagnosis is provided in primary care in order to establish a model of best practice when educating patients on their diagnosis. Scoping review of articles written in English. MEDLINE, Embase, Web of Science, and grey literature were searched. Articles were extracted, reviewed, and analysed according to the inclusion criteria. In total, 29 records met the inclusion criteria. The following six overarching themes were identified: patient education; physician education; importance of the multidisciplinary team; importance of patient-centred care; the value of primary care; and useful resources. The literature illustrated that describing fibromyalgia using analogies to illustrate the pain sensitisation process can help patients understand their diagnosis better. This improves their willingness to accept management plans, particularly engagement with non-pharmacological therapies, which the literature suggested are best delivered within a multidisciplinary team. Key aspects of fibromyalgia should be explained to patients in order for them to gain a better understanding of their diagnosis. A 'one-size-fits-all' model for explaining the fibromyalgia diagnosis to patients is inappropriate because patients' experiences are individualised. Further research is required on whether different explanations impact patient outcomes.


Genetics of follicular lymphoma transformation.
Follicular lymphoma (FL) is an indolent disease, but 30%-40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL). The pathogenesis of this process remains largely unknown. Using whole-exome sequencing and copy-number analysis, we show here that the dominant clone of FL and transformed FL (tFL) arise by divergent evolution from a common mutated precursor through the acquisition of distinct genetic events. Mutations in epigenetic modifiers and antiapoptotic genes are introduced early in the common precursor, whereas tFL is specifically associated with alterations deregulating cell-cycle progression and DNA damage responses (CDKN2A/B, MYC, and TP53) as well as aberrant somatic hypermutation. The genomic profile of tFL shares similarities with that of germinal center B cell-type de novo DLBCL but also displays unique combinations of altered genes with diagnostic and therapeutic implications.


Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy.
The incidence of diabetes is increasing globally, with cardiovascular disease accounting for a substantial number of diabetes-related deaths. Although atherosclerotic vascular disease is a primary reason for this cardiovascular dysfunction, heart failure in patients with diabetes might also be an outcome of an intrinsic heart muscle malfunction, labelled diabetic cardiomyopathy. Changes in cardiomyocyte metabolism, which encompasses a shift to exclusive fatty acid utilization, are considered a leading stimulus for this cardiomyopathy. In addition to cardiomyocytes, endothelial cells (ECs) make up a significant proportion of the heart, with the majority of ATP generation in these cells provided by glucose. In this review, we will discuss the metabolic machinery that drives energy metabolism in the cardiomyocyte and EC, its breakdown following diabetes, and the research direction necessary to assist in devising novel therapeutic strategies to prevent or delay diabetic heart disease.


Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair.
Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.


Electrochemical immunosensor for point-of-care detection of soybean Gly m TI allergen in foods.
Soybean is a legume with high technological functionality, commonly used by the food industry as an ingredient in different products. However, soybean is an allergenic food whose undeclared presence in processed foods may represent a public health risk. In this work, it was developed an efficient electrochemical immunosensor, targeting the soybean trypsin inhibitor (Gly m TI) allergen using commercial anti-Gly m TI IgG, aiming at detecting/quantifying minute amounts of soybean in different food formulations. For this purpose, model mixtures of different foods (sausages, cooked-hams, biscuits) were prepared to contain known amounts of soybean protein isolate (100,000-0.1 mg kg-1) and submitted to specific thermal treatments (autoclaving, oven-cooking, baking). The electrochemical immunosensor allowed quantifying down to 0.1 mg kg-1 of soybean in the three food matrices, raw and processed (0.0012 mg of Gly m TI/kg of matrix). Accordingly, the immunosensor is suitable for detecting traces of soybean in raw, processed, and complex foods, thus protecting 99 % of soybean-allergic patients.


Anticancer properties of novel zinc oxide quantum dot nanoparticles against breast cancer stem-like cells.
Cancer stem cells (CSCs) play an essential role in cancer development, metastasis, relapse, and resistance to treatment. In this article, the effects of three synthesized ZnO nanofluids on proliferation, apoptosis, and stemness markers of breast cancer stem-like cells are reported. The antiproliferative and apoptotic properties of ZnO nanoparticles were evaluated on breast cancer stem-like cell-enriched mammospheres by MTS assay and flowcytometry, respectively. The expression of stemness markers, including WNT1, NOTCH1, β-catenin, CXCR4, SOX2, and ALDH3A1 was assessed by real-time PCR. Western blotting was used to analyze the phosphorylation of Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3). Markers of stemness were significantly decreased by ZnO nanofluids, especially sample (c) with code ZnO-148 with a different order of addition of polyethylene glycol solution at the end of formulation, which considerably decreased all the markers compared to the controls. All the studied ZnO nanofluids considerably reduced viability and induced apoptosis of spheroidal and parental cells, with ZnO-148 presenting the most effective activity. Using CD95L as a death ligand and ZB4 as an extrinsic apoptotic pathway blocker, it was revealed that none of the nanoparticles induced apoptosis through the extrinsic pathway. Results also showed a marked inhibition of the JAK/STAT pathway by ZnO nanoparticles; confirmed by downregulation of Mcl-1 and Bcl-XL expression. The present data demonstrated that ZnO nanofluids could combat breast CSCs via decreasing stemness markers, stimulating apoptosis, and suppressing JAK/STAT activity.


Endovascular Management of the Ascending Aorta: State of the Art.
Endovascular stent graft repair (EVAR) has revolutionized the management of aneurysms and dissections of the thoracic and abdominal aorta and is considered the first-line treatment in such pathologies. Initially designed for patients unfit for open repair, EVAR and thoracic endovascular aortic stent graft repair are associated with improved morbidity and mortality and a faster recovery process. The endovascular revolution of the aorta continues moving proximally, with fenestrated and branch stent grafts currently in clinical trials for the management of thoracoabdominal aortic aneurysms, and several branched thoracic devices are either approved or in trial for management of aortic arch pathologies. The final frontier in the endovascular management of the aorta is the aortic root and ascending aorta. The first early feasibility trial for management of type A aortic dissection has recently concluded with a multicenter phase 2 study slated for the spring of 2023. The following article updates the reader on the unique challenges of endovascular management of the ascending aorta and a look at the future technologies that will define this space.


Macroprolactinemia in a patient with infertility and hyperprolactinemia.
A significant number of patients with hyperprolactinemia have macroprolactinemia, a condition characterized by the preponderance of big-big prolactin with normal levels of free prolactin. As macroprolactin does not have biologic activity, such patients do not require further investigations or treatment for hyperprolactinemia. The case of a patient with hyperprolactinemia diagnosed during investigation of secondary infertility is presented. She was treated for over 2 years with dopamine agonists, with which her prolactin level normalized, but she remained infertile. Subsequent investigations demonstrated that she suffered from macroprolactinemia, not true hyperprolactinemia. The patient is currently not on dopamine agonist therapy, and although her total prolactin levels remain significantly elevated, her free prolactin levels have been in the normal range. Physicians should familiarize themselves with this entity and consider testing for it in patients with hyperprolactinemia to avoid an inappropriate diagnosis and unnecessary treatment.


A Critical Review of Miniaturised Percutaneous Nephrolithotomy: Is Smaller Better?
In an effort to reduce morbidity related to percutaneous nephrolithotomy (PCNL), some investigators have progressively introduced miniaturised approaches. The development of miniaturised nephroscopes facilitated widespread dissemination of these techniques and a significant expansion of the role of PCNL in endourology. To discuss the different techniques comprising modern PCNL and identify the pros and cons of each of them. Data for this review were identified through a search of PubMed, including studies published in the last 20 yr in core clinical journals in English. The search terms included "urolithiasis", "nephrolithiasis", or "urinary stones" in combination with "miniaturised PCNL", "mini-PCNL", "micro-PCNL", "minimally invasive PCNL", and "ultra-mini PCNL". Publications relevant to the subject were retrieved and critically appraised. The indications for miniaturised PCNL have not been standardised yet. Even though data in the literature reveal limitations and conflicting results, these techniques seem promising in terms of effectiveness and safety for the treatment of renal stones. The development of miniaturised scopes facilitated knowledge of the physics behind the vacuum cleaner effect generated during procedures, and greater efficacy of holmium laser generators and surgeon skill have led to progressive expansion of the indications for miniaturised techniques. Well-designed, randomised, multi-institutional studies are needed to better understand the indications for these miniaturised techniques before considering them a standard procedure for potential replacement of conventional PCNL. Miniaturised PCNL represents a valuable new tool in the armamentarium of modern endourologists, capable of offering good outcomes with lower complications rates compared to the standard technique and higher cost effectiveness compared to flexible ureteroscopy. Miniaturised percutaneous nephrolithotomy represents a safe and effective alternative to standard techniques for the treatment of renal stones. Each patient needs to be considered individually and tailored surgical treatment has to be offered.


[Pharmacotherapy of acute infant enteritis].
The management of acute diarrhea in infants with drugs is justified only where these drugs have specific interactions with the pathophysiologic mechanisms involved. Most of the infectious diarrheas are self-limited, many patients recover spontaneously. Antimicrobial drugs are only indicated if mucosal destruction takes place and symptoms of dysentery respectively inflammation are observed. Some authors propose to treat newborn and young infants in case of doubt. If antimicrobial drugs are given uncritically a selection of not obligatory microorganisms can occur, or the number of asymptomatic carriers increases. There is no confirmation that drugs like adsorbents (kaolin, pectin, charcoal) or lyophilized microorganisms have a therapeutic effect. In contrast morphine derivatives like loperamide act not only by slowing the intestinal motility but also by inhibiting the secretion mechanisms of the enterocyts. Nevertheless these drugs can not be recommended for infants since ileus symptoms have been observed.


When to use femoral vein injection for diagnosis of patent foramen ovale-Effect of a persistent eustachian valve on right atrial flow patterns during contrast transesophageal echocardiography.
Contrast echocardiography using agitated saline injected into the antecubital vein is the most common method used for the diagnosis of patent foramen ovale. We describe a case whereby the presence of a persistent eustachian valve and a "negative contrast sign" during contrast transesophageal echocardiography raised suspicion of a false-negative result. Femoral vein injection of contrast successfully demonstrated a patent foramen ovale. Femoral vein injection should be considered if this scenario is recognized because the eustachian valve directs blood preferentially from the inferior vena cava toward the interatrial septum and this route may prove to be more reliable.


Lack of Toll-like receptor 4 and 2 polymorphisms in Korean patients with bacteremia.
Toll-like receptors (TLRs) are pattern-recognition receptors that are important in innate immune responses to bacterial infection. The purpose of this study is to describe the prevalence of TLRs genetic variations in the bacteremic patients in Korea. A total of 154 patients with bacteremia and 179 healthy volunteers were included. The Asp299Gly and Thr399Ile allele of the TLR4 gene and Arg753Gln and Arg677Trp allele of the TLR2 gene were tested by PCR-RFLP. The DNA sequences were determined to confirm the PCR-RFLP results. Contrary to the expectation, no genetic polymorphisms were detected in both groups of this study, suggesting that it is very rare in Korean.


[Primary results of the reflexotherapy in the syndrome of irritable colon. Preliminary note5].
After stressing the uncertainties of classifying the syndrome exactly and the part played by psychosomatism in its aetiopathogenesis, some forms of acupuncture have been attempted as alternatives to psychodrugs and antispastic substances. 50 cases are examined in which diagnosis of irritable colon was confirmed by thorough clinical and laboratory examinations, use is also being made of appropriate computerizable tables.


Facilitators and barriers to adherence to medical recommendations among adolescents with cancer: A systematic review.
We aimed to systematically review barriers/facilitators of adherence among adolescents with cancer (aged 10-24 years), following a comprehensive approach to adherence that goes beyond medication-taking. Empirical studies published in English exploring determinants of adherence to medical recommendations among adolescents with cancer were identified in MEDLINE, PsycInfo, and Web of Science, up to October 2021. Records and full-text articles were reviewed by two independent reviewers, and results were classified according to the World Health Organization's (WHO) multidimensional adherence model. Eighteen studies were included. Despite heterogeneity in the definition and measurement of adherence, literature supported barriers/facilitators at patient, treatment, condition, healthcare team/system, and social/economic levels. Specifically, patient-related factors (i.e., psychological functioning and beliefs about disease and treatment) and social-related factors (i.e., family functioning) were major determinants of adolescent adherence. Few studies were conducted, and inconsistent findings were displayed for other dimensions (i.e., healthcare team/system, treatment, and condition-related factors). Adherence is a complex and multidetermined phenomenon. More research is needed to provide critical insights for policymakers and healthcare professionals in planning practices and interventions that effectively address meaningful barriers/facilitators of adolescents' adherence.


In vivo comparison of the inflammatory response induced by different vascular biomaterials.
Biomaterial implants induce a local inflammatory response. A comparison of the inflammatory cell response was made between several biomaterials commonly used as vascular prostheses. Disks of polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), aluminum, titanium, copper, and stainless steel were surgically placed into the peritoneum of mice. Recruited macrophage and neutrophil populations were measured after recovery from the disk surface and peritoneal lavage. Following peritoneal biomaterial implants, there was no difference in total neutrophil or macrophage recruitment between mice implanted with PET, PTFE, aluminum, or titanium disks. However, there was significant attenuation of total neutrophil and macrophage recruitment to stainless steel compared with the other implants. Similarly, there was no significant difference in the percentage of leukocytes adherent to the PET, aluminum, or titanium disks. Macrophage adherence to the stainless steel disks was attenuated by 19.1%, and the number of neutrophils was attenuated by 69.1% when compared with PET implant mice. Mice implanted with copper disks universally expired. Leukocyte recruitment did not differ between PET, PTFE, aluminum, or titanium disks, suggesting that these materials stimulate similar inflammatory responses. Stainless steel disks recruited both fewer neutrophils and fewer macrophages and support lower adherence of these cells than the other biomaterials. Copper incited an overwhelming and fatal response.


Metabolic crosstalk between membrane and storage lipids facilitates heat stress management in Schizosaccharomyces pombe.
Cell membranes actively participate in stress sensing and signalling. Here we present the first in-depth lipidomic analysis to characterize alterations in the fission yeast Schizosaccharomyces pombe in response to mild heat stress (HS). The lipidome was assessed by a simple one-step methanolic extraction. Genetic manipulations that altered triglyceride (TG) content in the absence or presence of HS gave rise to distinct lipidomic fingerprints for S. pombe. Cells unable to produce TG demonstrated long-lasting growth arrest and enhanced signalling lipid generation. Our results reveal that metabolic crosstalk between membrane and storage lipids facilitates homeostatic maintenance of the membrane physical/chemical state that resists negative effects on cell growth and viability in response to HS. We propose a novel stress adaptation mechanism in which heat-induced TG synthesis contributes to membrane rigidization by accommodating unsaturated fatty acids of structural lipids, enabling their replacement by newly synthesized saturated fatty acids.