A family-level floristic inventory and analysis of medicinal plants used in Traditional African Medicine.
Floristic diversity patterns of medicinal plants in sub-Saharan Africa are compared to global patterns to gain insights into the selection of plants used in Traditional African Medicine. To answer two questions: Firstly, is the selection of medicinal plants used in Traditional African Medicine in sub-Saharan Africa based on availability or is it biased towards certain plant families? Secondly, does the floristic composition of African medicinal plants differ from the global pattern and from other healing systems of the world? Data edited and summarized from recent reviews and on-line databases were compiled into an inventory of all vascular plant families of the world, showing the global numbers of species per family, the numbers of African taxa per family, the numbers of African medicinal plant species per family and the numbers of commonly traded African medicinal plants. These data were subjected to linear regression analyses, as well as Bayesian analysis and Imprecise Probability calculation (using the Imprecise Dirichlet model). At least 4576 vascular plant species from 1518 genera are used in Traditional African Medicine in sub-Saharan Africa, representing 192 families (out of 254 African families). Traditional African Medicine is dominated by Fabaceae (567 spp., 156 genera), Rubiaceae (318 spp., 99 genera), Asteraceae (314 spp., 112 genera), Malvaceae (202 spp., 46 genera), Euphorbiaceae (197 spp., 47 genera), Apocynaceae (167 spp., 68 genera), Lamiaceae (142 spp., 37 genera), Acanthaceae (106 spp., 40 genera), Asparagaceae (90 spp., 18 genera) and Poaceae (85 species, 47 genera). Regression analysis of the African medicinal flora shows that the Fabaceae (576 medicinal species/residual +136), Malvaceae (202/+105), Rubiaceae (318/+85), Lamiaceae (142/+55), Euphorbiaceae (197/+54) and Combretaceae (72/+49) are overused, while Aizoaceae (10/-136), Orchidaceae (34/-127), Iridaceae (16/-101) and Poaceae (85/-87) are underused. Bayesian and IDM analysis showed that a large number of smaller families are also overused and underused. Commonly traded African medicinal plants species are mostly from Fabaceae (27 species), Apocynaceae (16), Burseraceae (12) and Rubiaceae (9). The selection of African medicinal plants appears to be based on availability (for some families) and apparently cultural and other criteria, such as the presence of alkaloids, terpenoids and volatile compounds for others (e.g., Fabaceae, Apocynaceae and Burseraceae). In terms of commercialised species in international trade, Traditional African Medicine differs from the global pattern (and other healing systems) in the dominance of Fabaceae and Apocynaceae and the relatively low numbers of Asteraceae, Lamiaceae, Apiaceae and Rosaceae.


Explaining Disaster and Pandemic Preparedness at the Nexus of Personal Resilience and Social Vulnerability: An Exploratory Study.
The purpose of this research was a pilot examination to identify and assess relationships among social vulnerability, personal resilience, and preparedness for a sample of US residents living in the Gulf South, who had experienced climate-related disaster (e.g., hurricanes) and the COVID-19 pandemic. Binary logistic regression was conducted using primary survey data collected in 2020 (n = 744) to identify statistically significant explanatory variables of sociodemographic characteristics and resilience, measured by the CD-RISC 10, of climate-related disaster, and pandemic preparedness. Results indicate that respondents who identified as white, had more education, were in a relationship, and spoke English as a first language, as well as respondents who had exhibited greater resilience, were more likely to prepare for a climate-related disaster. Respondents who spoke English as a first language, had more education, and greater resilience were found to be statistically significant explanatory variables of pandemic preparedness. Respondents who prepared for disaster were also more likely to prepare for the pandemic. These findings provide insights into protective factors related to preparedness, including linkages between resilience and preparedness that can aid public health professionals in supporting resilience and preparedness efforts for impacted communities.


An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of two widely marketed tryptamine-derived NPDs, namely alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine.


Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(-receptor) antibodies.
Migraine preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs) has a positive effect on patients' health-related quality of life (HRQoL). The German treatment guidelines recommend discontinuing successful treatment with CGRP(-receptor) mAbs after 6-12 months. We aimed to evaluate headache-specific and generic HRQoL for three months after discontinuation of CGRP(-receptor) mAb treatment. We conducted a prospective, longitudinal cohort study, including patients with migraine after 8-12 months of therapy with a CGRP(-R) mAb and before a planned discontinuation attempt. HRQoL was assessed at the time of the last mAbs injection (V1), eight weeks later (V2), and sixteen weeks later (V3). For headache-specific HRQoL, we used the Headache Impact Test-6 (HIT-6). Generic HRQoL was determined with the EuroQol-5-Dimension-5-Level (ED-5D-5L) form, and the Short-Form 12 (SF-12), which comprises a Physical Component Summary (PCS-12) and a Mental Component Summary (MCS-12). Questionnaires' total scores were compared across the three observation points using nonparametric procedures. The study cohort consisted of n = 61 patients (n = 29 treated with the CGRP-receptor mAb erenumab and n = 32 with the CGRP mAbs galcanezumab or fremanezumab). The HIT-6 sum score was 59.69 ± 6.90 at V1 and increased by 3.69 ± 6.21 at V3 (p < 0.001), indicating a greater headache impact on patients' lives. The mean total EQ-D5-L5 score declined from 0.85 ± 0.17 at V1 by - 0.07 ± 0.18 at V3 (p = 0.013). Both Mental and Physical Component Scores of the SF-12 worsened significantly during treatment discontinuation: The PCS-12 total score decreased by - 4.04 ± 7.90 from V1 to V3 (p = 0.013) and the MCS-12 score by - 2.73 ± 9.04 (p = 0.003). Changes in all questionnaires' scores but the MCS-12 were already significant in the first month of the drug holiday (V2). Our results show a significant decline in headache impact and generic HRQoL of migraine patients after treatment discontinuation of a CGRP(-R) mAb. The observed deterioration is above the established minimally clinically important differences for each of the questionnaires and can therefore be considered clinically meaningful. Monitoring HRQoL during a discontinuation attempt could facilitate the decision whether or not to resume preventive treatment with CGRP(-R) mAbs.


Management of anesthesia during dynamic cardiomyoplasty.
To review experience with anesthetic management in ten patients undergoing dynamic cardiomyoplasty (CMPL), a new surgical technique that serves as an alternative to heart transplantation. Retrospective clinical study. Cardiothoracic operating room at a university hospital. Ten male functional New York Heart Association (NYHA) class III and IV patients, aged 39 to 60 years, awaiting heart transplantation, 7 of whom were diagnosed with dilated cardiomyopathy, 3 with postischemic cardiomyopathy. Under general anesthesia, the latissimus dorsi muscle was harvested and rotated into the chest through a window in the second rib. The muscle was then wrapped around the heart. Starting from the second postoperative week, the latissimus dorsi was stimulated to provide assistance to a failing heart. The mean left ventricular ejection fraction (LVEF) of the 10 patients was 24.89% +/- 9.17% (range 10% to 37%). No intraoperative death occurred. Two patients died of multiple organ failure and an apparent arrhythmia on the 15th and 25th postoperative days, respectively. The rest of the patients regained good working capacity postoperatively, as evidenced by improvement in NYHA grade. Nevertheless, the LVEF improved in only one patient. No significant differences were evident between preoperative and postoperative blood values, hemodynamic data, or spirometry. Dynamic CMPL is a considerable challenge for the anesthesiologist because these patients have poor cardiac reserve preoperatively and do not benefit from the procedure in the first two postoperative weeks. To date, CMPL seems to be an important alternative to heart transplantation because experience has shown an improvement in the quality of life with low intraoperative and postoperative complications.


Reproducibility of residual cancer burden for prognostic assessment of breast cancer after neoadjuvant chemotherapy.
The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden assessment is highly reproducible, with reproducible long-term prognostic significance.


Patients' poor communication with their doctors in the first visit of the gynecological endocrinology outpatient clinics.
To investigate patients' communication with their gynecologists in the first visit of the gynecological endocrinology outpatient clinics. We developed a questionnaire to evaluate 379 women' expectations of their first visit, information-giving about illness, and understanding of the consultation they encountered from April to August 2010. Descriptive statistics and multiple linear regression analysis were used to analyze the data. Before the first visit, 55% (208/379) of participants hoped to get the doctors' special attention, and 60% (227/379) of patients expected a very satisfying consultation. During the consultation, only 34% (129/379) of patients provided their case history clearly according to physicians' inquiry, 21% (81/379) of patients understood the examination and 28% (105/379) of patients understood the therapeutic regime after doctors' explanation. Correlation analysis showed that sociodemographic characteristics such as young age (under 20 years old), low level of education (primary school or less), and lack of medical knowledge affected patients' information-giving about illness and understanding of their first visit (all ps < 0.05). Patients expected a patient-centered doctor-patient communication in gynecological endocrinology outpatient clinics. They could not communicate well with their doctors, which was affected by age, education, and medical background.


Pediatric renal lymphangiectasia: importance of recognition and accurate renal imaging.
Renal lymphangiectasia is a rare diagnosis. It is also referred to as renal lymphangioma, renal lymphangiomatosis, peripelvic lymphangiectasia, renal peripelvic multicystic lymphangiectasia, and hygroma renale. The presentation varies, and the diagnosis depends on accurate radiologic interpretation. We present the radiologic images of a pediatric patient who was diagnosed with renal lymphangiectasia after being evaluated for suspected nonaccidental trauma to emphasize the importance of identifying this entity by the characteristic radiologic findings.


Development of a protein-ligand extended connectivity (PLEC) fingerprint and its application for binding affinity predictions.
Fingerprints (FPs) are the most common small molecule representation in cheminformatics. There are a wide variety of FPs, and the Extended Connectivity Fingerprint (ECFP) is one of the best-suited for general applications. Despite the overall FP abundance, only a few FPs represent the 3D structure of the molecule, and hardly any encode protein-ligand interactions. Here, we present a Protein-Ligand Extended Connectivity (PLEC) FP that implicitly encodes protein-ligand interactions by pairing the ECFP environments from the ligand and the protein. PLEC FPs were used to construct different machine learning models tailored for predicting protein-ligand affinities (pKi∕d). Even the simplest linear model built on the PLEC FP achieved Rp = 0.817 on the Protein Databank (PDB) bind v2016 'core set', demonstrating its descriptive power. The PLEC FP has been implemented in the Open Drug Discovery Toolkit (https://github.com/oddt/oddt). Supplementary data are available at Bioinformatics online.


Underestimation of foraging behaviour by standard field methods in malaria vector mosquitoes in southern Africa.
Defining the anopheline mosquito vectors and their foraging behaviour in malaria endemic areas is crucial for disease control and surveillance. The standard protocol for molecular identification of host blood meals in mosquitoes is to morphologically identify fed mosquitoes and then perform polymerase chain reaction (PCR), precipitin tests, or ELISA assays. The purpose of this study was to determine the extent to which the feeding rate and human blood indices (HBIs) of malaria vectors were underestimated when molecular confirmation by PCR was performed on both visually fed and unfed mosquitoes. In association with the Southern Africa International Centers of Excellence in Malaria Research (ICEMR), mosquito collections were performed at three sites: Choma district in southern Zambia, Nchelenge district in northern Zambia, and Mutasa district in eastern Zimbabwe. All anophelines were classified visually as fed or unfed, and tested for blood meal species using PCR methods. The HBIs of visually fed mosquitoes were compared to the HBIs of overall PCR confirmed fed mosquitoes by Pearson's Chi-Square Test of Independence. The mosquito collections consisted of Anopheles arabiensis from Choma, Anopheles funestus s.s., Anopheles gambiae s.s. and Anopheles leesoni from Nchelenge, and An. funestus s.s. and An. leesoni from Mutasa. The malaria vectors at all three sites had large human blood indices (HBI) suggesting high anthropophily. When only visually fed mosquitoes tested by PCR for blood meal species were compared to testing those classified as both visually fed and unfed mosquitoes, it was found that the proportion blooded was underestimated by up to 18.7%. For most Anopheles species at each site, there was a statistically significant relationship (P < 0.05) between the HBIs of visually fed mosquitoes and that of the overall PCR confirmed fed mosquitoes. The impact on HBI of analysing both visually fed and unfed mosquitoes varied from site to site. This discrepancy may be due to partial blood feeding behaviour by mosquitoes, digestion of blood meals, sample condition, and/or expertise of entomology field staff. It is important to perform molecular testing on all mosquitoes to accurately characterize vector feeding behaviour and develop interventions in malaria endemic areas.


Evaluation of the effect of pancreatic volume on mortality in patients with acute pancreatitis.
Pancreatic volume is enlarged in acute pancreatitis. This study aimed to evaluate whether there was a difference in pancreatic volume between survivors and non-survivors with acute pancreatitis using computer-generated 3D imaging. This single-center retrospective observational cohort study was conducted between January 2015 and December 2020. The hospital automation system was used to get the patients diagnosed with acute pancreatitis by using International Classification of Diseases (ICD) (ninth edition, code 577.0 or 10th version, code K 85.0) codes. The patients' pancreatic volumes, computed tomography severity index (CTSI), and modified computed tomography severity index (mCTSI) scores were calculated using the data obtained from the hospital automation system. The pancreatic volumes of the patients were measured using the computer-generated 3D imaging method. Pancreatic volume, CTSI, and mCTSI were then statistically compared in terms of mortality prediction by using the receiver operating characteristic (ROC) analysis. Of the 143 patients, 57.34% were female and 42.66% were male. The cut-off value of pancreatic volume in determining mortality was>81.5 cm3 OR:17.43 (%95 CI: 2.2-138.1) Cohen's d:1.126, at which it had 92.3% sensitivity, 60.0% specificity, 18.8% positive predictive value, and 98.7% negative predictive value. As a result of the ROC analysis of pancreatic volume in mortality prediction, the area under curve (AUC) value was determined as 0.787 [95% confidence interval (CI): 0.711-0.851]. The ROC analysis of the CTSI and mCTSI scores in mortality prediction revealed AUC values of 0.822 (95%CI: 0.750-0.881) and 0.955 (95%CI: 0.907-0.983) respectively. Although CTSI scores pancreatic enlargement and mCTSI scores pancreatic necrosis and inflammation, the pancreatic volume value is not clearly scored in both. In this study population, pancreatic volume above 81.5 cm was associated with increased mortality. Both CTSI and mCTSI scores outperformed pancreatic volume in predicting mortality.


Most lay people can correctly identify indigenous venomous snakes.
We attempted to determine how accurately members of the public can identify venomous snakes. Six different snakes indigenous to southern California were displayed in cages for 265 people to view at a street fair. These included 4 nonvenomous snakes and 2 venomous snakes. People were asked whether the snake was venomous and the name of the snake, if they knew it. Overall, people recognized whether a snake was venomous or nonvenomous 81% of the time. They were most accurate at identifying rattlesnakes as being venomous (95%) but incorrectly identified nonvenomous snakes as being venomous 25% of the time. Men were more accurate than women, and adults were more accurate than children. Subjects were less well able to identify the exact species of snakes. The results suggest that there may be no need to capture, kill, or bring a snake to the hospital for identification, at least in this geographic area.


Functional conservation of MIKC*-Type MADS box genes in Arabidopsis and rice pollen maturation.
There are two groups of MADS intervening keratin-like and C-terminal (MIKC)-type MADS box genes, MIKC(C) type and MIKC* type. In seed plants, the MIKC(C) type shows considerable diversity, but the MIKC* type has only two subgroups, P- and S-clade, which show conserved expression in the gametophyte. To examine the functional conservation of MIKC*-type genes, we characterized all three rice (Oryza sativa) MIKC*-type genes. All three genes are specifically expressed late in pollen development. The single knockdown or knockout lines, respectively, of the S-clade MADS62 and MADS63 did not show a mutant phenotype, but lines in which both S-clade genes were affected showed severe defects in pollen maturation and germination, as did knockdown lines of MADS68, the only P-clade gene in rice. The rice MIKC*-type proteins form strong heterodimeric complexes solely with partners from the other subclade; these complexes specifically bind to N10-type C-A-rich-G-boxes in vitro and regulate downstream gene expression by binding to N10-type promoter motifs. The rice MIKC* genes have a much lower degree of functional redundancy than the Arabidopsis thaliana MIKC* genes. Nevertheless, our data indicate that the function of heterodimeric MIKC*-type protein complexes in pollen development has been conserved since the divergence of monocots and eudicots, roughly 150 million years ago.


Changes in metabolism and vestibular function depend on gravitational load in mice.
The vestibular system is known to participate in controlling posture and metabolism. Different gravitational environments, including microgravity or hypergravity, cause plastic alteration of the vestibular system, and plasticity is important for adaptation to a novel gravitational environment. However, it is unclear whether the degree of change in vestibular-related physiological function depends on gravitational loading. To examine this, we used a hypergravity environment including 1.33 G, 1.67 G, and 2 G for 29 days. We found that a gravitational threshold induces physiological changes, including vestibular-related posture control and metabolism in mice. Body mass did not return to the preloading level in 1.67 G and 2 G mice. A significant drop in food intake, observed on the first day of hypergravity load, disappeared in all mice after longer exposure. However, a reduction in water intake was sustained in 2 G mice but not 1.33 G and 1.67 G mice. Body temperature did not return to the preloading level in 2 G mice by the final day. A decrease in the skill of the righting reflex was observed in 2 G mice but not 1.33 G and 1.67 G mice. In conclusion, this study showed that hypergravity-induced changes in metabolism and vestibular function depended on the amount of gravitational loading. The 2 G load affected vestibular-related posture control and metabolism considerably, compared with 1.33 G and 1.67 G loads.NEW & NOTEWORTHY It is unclear whether the degree of change in vestibular-related physiological function depends on gravitational loading. Present study showed that exposure to hypergravity-induced degrees of change in metabolism and vestibular function depended on the gravitational loading. The response of body mass depended on the gravitational loading size. Especially in 2 G environment, water intake, body temperature, and vestibular function were influenced. These changes could involve plastic alteration of vestibular-related autonomic and motor functions.


Ultrasound measurement of the transverse diameter of the fetal thymus in pregnancies complicated by the preterm prelabor rupture of membranes.
To determine whether the measurement of the transverse diameter of the fetal thymus is of value in the identification of either histologic chorioamnionitis or funisitis in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). The transverse diameter of the fetal thymus was measured in 216 fetuses from PPROM pregnancies. A small thymus was defined as a transverse thymic diameter below the fifth percentile according to a previously published nomogram. The placenta, the fetal membranes, and the umbilical cord were assessed for the presence of inflammation. A small thymus was identified in 69% (150/216) of fetuses. A small thymus was present in 80% (106/133) and 88% (36/41) of women with histologic chorioamnionitis or funisitis, respectively. The presence of a small thymus had a sensitivity of 79%, specificity of 47%, positive predictive value of 71%, negative predictive value of 59% for the identification of chorioamnionitis (p < 0.0001; odds ratio 3.5) and a sensitivity of 88%, specificity of 35%, positive predictive value of 24%, and negative predictive value of 92% in the identification of funisitis (p = 0.004; odds ratio 4.4). The sonographic finding of a small thymus is a sensitive indicator of histologic chorioamnionitis or funisitis; low specificity excludes it as a possible clinical implication in the management of PPROM pregnancies.


Faulty development of cortical neurons in the Snell dwarf cerebrum.
In the Snell dwarf motor cortex, area 6 of Caviness, the cell number, the stratification of neurons and the portion of layer-widths were absolutely identical to those of the controls. By means of the Golgi-Cox method modified by Ramon-Moliner, however, the pyramidal neuron was found to have small perikarya, short primary dendrites with sparse branchings, and a low spine density on the dendrites. The corpus callosum of the dwarf contained a reduced number of fibers compared to that of the controls, and the staining for myelin basic protein revealed a considerable reduction of positive-fibers of radiation in this area. The content of Thy-1 antigen in the cerebrum, cerebellum and brainstem, was significantly lower than that of controls, but the monoamine content was normal in the cerebrum and brainstem. From these results, it appears that the Snell dwarf cerebrum shows retarded neuronal growth; a reduction in size of neurons, an underdevelopment of axons and dendrites, and a retarded maturation of spine, in addition to arrested glial proliferation. At present, it is unclear which hormone deficient in these mutants, growth hormone or thyroxine, is the essential potentiator for neuronal growth.


Lactic acid bacteria isolated from Chinese traditional fermented milk as novel probiotic strains and their potential therapeutic applications.
Lactic acid bacteria (LAB) are believed to have health-promoting properties to the host and can be used in therapeutics interventions; intriguingly, they have the property to produce bio-preservatives substances. Therefore, this study aimed to mine probiotics and evaluate their safety, functional properties, and cholesterol-lowering capability. Seven potential probiotic strains were compared from 56 LAB strains isolated from traditional Chinese fermented milk. The results showed that all tested strains are tolerant to gastric acidity (45.5-83.26) and bile salts (11.92-92.91%) and have antibacterial activity against Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922. Likewise, it lowered the cholesterol levels in vitro by live cells (26.57-45.76%) and dead cells (29.53-50.97%) with remarkable aggregation ability (13.8-43.71%). Antioxidant properties and produce short chain fatty acids (SCFAs) were strain-dependent features. Upon assessment of the safety, Enterococcus faecium NWAFU-BIO-AS14 exhibited virulence factors genes (VFs) of (mur-2ed, odc, and tet(K)) and + hemolysis activity. While Enterococcus faecium NWAFU-BIO-A-B24 and Limosilactobacillus fermentum NWAFU-BIO-B-S6 have VFs of (odc, vanC2, and ant(6)-Ia). Limosilactobacillus fermentum NWAFU-BIO-D-B2 has only (odc). Thus, they are not considered as safe probiotics. In contrast, Lactiplantibacillus plantarum NWAFU-BIO-BS29, Companilactobacillus crustorum NWAFU-BIO-AS16, and Lactobacillus gallinarum NWAFU-BIO-D-S7 are the safest and best strains, respectively, due to the absence of 16 VFs and their sensitivity to antibiotics such as kanamycin, erythromycin, tetracycline, gentamycin, vancomycin, streptomycin, chloramphenicol, and ampicillin. Accordingly, these strains have a high potentiality to be used as starter cultures or safely applied as perfect probiotics in functionals food and feed. The online version contains supplementary material available at 10.1007/s13205-022-03403-z.


PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through 14-3-3 zeta phosphorylation.
We investigated placental apoptosis and the expression of and interactions between 14-3-3 and Bcl-2 family proteins during preeclampsia. In addition, we explored the mechanism of Bax dissociation from 14-3-3, hypothesizing that PKC-mediated phosphorylation of 14-3-3 results in dissociation of Bax from 14-3-3 proteins, and leads to apoptosis. Placental samples from 10 women with preeclampsia and 10 normotensive control patients were analyzed using M30-specific immunohistochemistry to assess placental apoptosis. Biochemical markers of cellular apoptosis, such as cleaved caspase-3, Bax, Bcl-2, 14-3-3, and PKC were followed by Western blotting. Interaction of 14-3-3 proteins with Bax and with PKC was assessed by immunoprecipitation. M30-positive cells were widespread in the preeclamptic placentas. The levels of cleaved caspase-3, Bax, 14-3-3 zeta, phospho-(Ser)-14-3-3, and PKC delta were significantly higher in the preeclamptic placentas than in normal placentas. Preeclampsia was also associated with weaker interactions between 14-3-3 zeta and Bax and stronger interactions between 14-3-3 zeta and PKC delta. Our results suggest that PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through the phosphorylation of 14-3-3 zeta. This finding may at least in part explain the apoptosis-inducing activity of PKC delta, revealing the important role of PKC delta in the development of apoptosis-related diseases such as preeclampsia.


Verification of myocardial contrast two-dimensional echocardiographic assessment of perfusion defects in ischemic myocardium.
Myocardial contrast two-dimensional echocardiography was used in 21 closed chest dogs to assess its ability to delineate the extent of underperfused acutely ischemic myocardium. An agitated saline-Renografin echocardiographic contrast agent was injected into the left main coronary artery after left anterior descending coronary artery occlusion, and the size of the contrast echo-free area characterizing the perfusion defect was outlined in short-axis cross sections of the left ventricle. In 13 dogs, monastral blue dye was injected after 45 minutes of coronary artery occlusion and before sacrifice to provide anatomic delineation of underperfused zones in equivalent sections. Perfusion defects assessed by contrast two-dimensional echocardiography correlated well with those delineated by monastral blue dye (r = 0.91). Contrast echocardiographic study was also performed in eight other dogs at 5 hours of occlusion, after which infarct size was measured with triphenyl-tetrazolium-chloride. Contrast echocardiographic outline of the perfusion deficiency correlated but slightly overestimated the extent of necrosis (r = 0.88). It is concluded that contrast two-dimensional echocardiography can detect and outline the underperfused "risk area" during acute coronary artery occlusion, and may also permit assessment of the extent of myocardial infarction.


Septic arthritis in immunocompetent and immunosuppressed hosts.
Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.


Vaginal Rejuvenation with Acellular Dermal Matrix.
Female genital cosmetic surgery consists of multiple procedures, usually including labiaplasty, clitoral prepuce reduction, labia majora augmentation, and vaginoplasty. The reasons for women to undergo these surgeries can be categorized as functional and aesthetic ones. In this study, we introduced the modified vaginoplasty with acellular dermal matrix (ADM) and briefly reviewed our experience in the combination of multiple procedures to achieve the optimal effect.


Chemistry of plants from Crete: stachyspinoside, a new flavonoid glycoside and iridoids from Stachys spinosa.
The new flavonoid glycoside stachyspinoside (1), and the three iridoids, 7-O-acetyl-8-epi-loganic acid (2), ajugol (3) and harpagide (4) were isolated from Stachys spinosa. The structures of these compounds were established on the basis of mass spectrometry (ESMS and tandem MS), one- and two-dimensional nuclear magnetic resonance experiments (COSY, COSY LR, HMQC, TOCSY and HMBC) as well as simple chemical derivatization.


Public perception of pharmacists: Film and television portrayals from 1970 to 2013.
To determine the percentage of pharmacists portrayed in a positive, negative, or neutral light in films and television shows available in the United States from January 1970 to July 2013. Secondary objectives were to evaluate pharmacist characters as heroes, villains, or victims; assess pharmacist characters' demographics; and determine the presence of pharmacist characters in medical-themed television shows. Retrospective, observational, descriptive study. A review of available U.S. film and television from January 1970 to July 2013 at an academic institution. 214 television episodes or films that contained at least one pharmacist portrayal. Electronic inquiries requesting submissions of known pharmacist portrayals were distributed to pharmacy professionals in national and state-affiliated pharmacy organizations and to faculty, staff, and students at the University of South Carolina. Electronic databases and search engines (Internet Movie Database [IMDb], Bing, and Google) were consulted and used to further research possible pharmacist portrayals. The study investigators developed an algorithm incorporating social norms, common pharmacist practices, and viewer perceptions to determine positive, negative, or neutral status for each pharmacist portrayal. Year and genre of media, demographics of identified pharmacist characters, portrayal status of identified pharmacist characters, and number of pharmacist characters and appearances per each television show reviewed. In the films and television shows reviewed, there were 231 pharmacist portrayals, with 160 unique pharmacist characters. Of the 231 portrayals, 145 (63%) were negative, 30 (13%) were positive, and 56 (24%) were neutral. Of the 160 unique characters, 121 (76%) were male, 120 (75%) were Caucasian, and 86 (54%) were younger than 50 years old. The name of the character was provided for 70 (44%) of the pharmacists portrayed. The portrayal of pharmacists in U.S. film and television is primarily negative. Pharmacists and pharmacy organizations are encouraged to be vocal proponents of the profession and educate trainees on the importance of an enhanced public perception.


Dosimetric Predictors of Genitourinary Toxicity From a Phase I Trial of Prostate Bed Stereotactic Body Radiation Therapy.
Our purpose was to analyze dose-volume parameters associated with genitourinary (GU) toxicity from a phase I clinical trial of prostate bed stereotactic body radiation therapy. Patients were treated in escalating dose levels of 35, 40, and 45 Gy, over 5 fractions. Data from all 26 patients enrolled in the protocol were analyzed using multiple dose-volume cut points for multiple GU organs at risk. Univariate logistical regression and Fisher exact test were used to assess statistical significance associated with incidence of toxicity. The median follow-up was 36 months for all patients. Acute GU toxicity was mild and resolved spontaneously. Eight out of 26 patients (30.7%) developed late GU toxicity of grade 2 or higher. Two patients developed grade 3 ureteral stenosis, 1 in the 35 Gy arm and the other in the 45 Gy arm. Three patients developed grade 2 or higher hematuria/cystitis, and 3 developed grade 2 or higher incontinence. Incidence of grade 3 ureteral stenosis was related to the absolute volume of bladder wall receiving greater than 20, 25, and 30 Gy (P < .01). Grade 2 cystitis and hematuria were related to the volume of bladder wall receiving 20 Gy less than 34% and 35 Gy less than 25% (18.8% vs 60% and 23.8% vs 80%, respectively, P < .05). Incontinence was related to mean urethral dose less than 35 Gy and 25 Gy (4.3% vs 66.7% and 0% vs 37.5%, respectively, P < .05) and volume of urethra receiving 35 Gy less than 24% (8.3% vs 50%, P < .05). This is the first analysis to report dose-volume thresholds associated with late GU toxicity in patients receiving prostate bed stereotactic body radiation therapy. We recommend limiting the bladder wall receiving 25 Gy to less than 18 cubic centimeters to reduce the risk for late grade 3 ureteral stenosis.


Hepatic arginase activity in intra- and extrauterine larvae of the ovoviviparous salamander. Salamandra salamandra (L.) (Amphibia, Urodela).
The hepatic arginase activity of Salamandra salamandra was determined at three different stages of intra- and extrauterine larval development and at fully metamorphosed juveniles. The highest enzymatic activity was found in intrauterine larvae in November, the lowest in intrauterine larvae in June of the following year. These data can be correlated with the ureotelism of intrauterine larvae previously described and are discussed with respect to the metabolism of larval and juvenile fire salamanders.


Real-World Dispensing Patterns of Inhalation Medication in Young Adult Asthma: An Inception Cohort Study.
The Global Initiative for Asthma (GINA) suggests a step-wise approach for pharmacological treatment of asthma. Valid study of real-world treatment patterns using dispensing databases includes proper measurement of medication adherence. We aim to explore such patterns by applying a time-varying proportion of days covered (tPDC)-based algorithm. We designed a retrospective inception cohort study using the University of Groningen IADB.nl community pharmacy dispensing database. Included were 19,184 young adults who initiated asthma medication anywhere between 1994 and 2021, in the Netherlands. Main treatment steps were defined as: 1 - SABA/ICS-formoterol as needed, 2 - low dose ICS, 3 - low dose ICS + LABA or tiotropium, or intermediate dose ICS, 4 - intermediate to high dose ICS + LABA or tiotropium, triple therapy, or high dose ICS, 5 - treatment prescribed by a specialist. Changes in treatment steps were determined using a time-varying proportion of days covered (tPDC)-based algorithm. Individual drug treatment trajectories were visualized over time using a lasagna plot. At initiation, of the 19,184 included individuals, 52%, 7%, 15%, 16%, and 10% started treatment in steps 1 to 5, respectively. The median (IQR) follow-up time was 3 (1-7) years. Median (IQR) number of switches was 1 (0-3). Comparing starting step to last observed step, 37% never switched between treatment steps, 20% of individuals stepped down and 22% stepped up. The low proportion of treatment switches between steps indicates that tailoring of treatment to patients' needs might be suboptimal. The tPDC-based algorithm functions well in translating dispensing data into continuous drug-utilization data, enabling a more granular assessment of treatment patterns among asthma patients.


Arabinosylcytosine downregulates thymidine kinase and induces cross-resistance to zidovudine in T-lymphoid cells.
The aim of this study was to determine molecular mechanism(s) responsible for the reduced thymidine kinase activity (TK) observed earlier in an arabinosylcytosine (araC) resistant lymphoid cell line (H9-araC cells), which was obtained following continuous cultivation of H9 cells in the presence of 0.5 microM araC. Compared to H9 cells, in H9-araC cells TK1 and TK2 gene expressions were reduced to 17.7% and 2.5%, respectively, and the cellular AZT accumulation was diminished to 35.8%. These cells were also found cross-resistant to azidothymidine (>42-fold). There was no significant difference in the expression of MDR1, MRP4 or TK protein. The lack of correlation between the expressions of TK protein and TK1 and TK2 suggests that post-translational factors may also play a role in the reduced TK activity in H9-araC cells. These findings suggest that araC affects TK expression at the genetic level.


Superior temporal gyrus volumes in maltreated children and adolescents with PTSD.
The structure and function of the superior temporal gyrus (STG), a structure involved in receptive and nonverbal auditory and language processing, is understudied in posttraumatic stress disorder (PTSD). Event-related potential abnormalities were previously reported in PTSD, implicating the existence of dysfunction in the primary auditory cortex and adjacent anterior auditory cortex of the STG in adult PTSD. Anatomic magnetic resonance imaging (MRI) volumetric analysis of the superior temporal gyrus were performed in 43 maltreated children and adolescents with PTSD and 61 nonmaltreated healthy control subjects. Unadjusted STG gray matter volumes were larger in maltreated subjects with PTSD than in control subjects, whereas STG white matter volumes were smaller in maltreated subjects with PTSD than in control subjects. After adjusting for differences in cerebral volume, right, left, and total superior temporal gyrus volumes were relatively larger in PTSD subjects compared with control subjects. After covarying for differences in cerebral gray matter volumes, regression analysis showed that PTSD subjects had significantly greater STG gray matter volumes in most, and in particularly right-sided STG measurements. Furthermore, findings of significant side-by-diagnosis interactions for STG and STG gray but not white matter STG volumes suggest that there is a more pronounced right > left asymmetry in total and posterior STG volumes but a loss of the left > right asymmetry seen in total, anterior, and posterior STG gray matter volumes in PTSD subjects compared with control subjects. These STG findings may suggest developmental alterations in maltreatment-related pediatric PTSD.


Usage of the HINTS exam and neuroimaging in the assessment of peripheral vertigo in the emergency department.
Dizziness is a common presenting symptom in the emergency department (ED). The HINTS exam, a battery of bedside clinical tests, has been shown to have greater sensitivity than neuroimaging in ruling out stroke in patients presenting with acute vertigo. The present study sought to assess practice patterns in the assessment of patients in the ED with peripherally-originating vertigo with respect to utilization of HINTS and neuroimaging. A retrospective cohort study was performed using data pertaining to 500 randomly selected ED visits at a tertiary care centre with a final diagnostic code related to peripherally-originating vertigo between January 1, 2010 - December 31, 2014. A total of 380 patients met inclusion criteria. Of patients presenting to the ED with dizziness and vertigo and a final diagnosis of non-central vertigo, 139 (36.6%) received neuroimaging in the form of CT, CT angiography, or MRI. Of patients who did not undergo neuroimaging, 17 (7.1%) had a bedside HINTS exam performed. Almost half (44%) of documented HINTS interpretations consisted of the ambiguous usage of "HINTS negative" as opposed to the terminology suggested in the literature ("HINTS central" or "HINTS peripheral"). In this single-centre retrospective review, we have demonstrated that the HINTS exam is under-utilized in the ED as compared to neuroimaging in the assessment of patients with peripheral vertigo. This finding suggests that there is room for improvement in ED physicians' application and interpretation of the HINTS exam.


Hypoxia and breast cancer: prognostic and therapeutic implications.
Hypoxia affects many important processes in tumour progression and is a key feature in the tumour microenvironment that needs to be taken into account when evaluating prognostics and therapeutic options for cancer patients. Hypoxia-regulating proteins, i.e. hypoxia inducible factors (HIFs), and associated gene products have been linked to certain tumour behaviours and might be useful as prognostic and predictive markers. Recently, hypoxia-driven gene products have been launched as novel cancer treatment targets with the potential to increase tumour-specific effects. Breast cancer consists of a multitude of different diseases with certain common characteristics, but also clearly disparate behaviours and genetic alterations. In this review we will summarise the role of hypoxia in breast cancer and specifically outline the importance of hypoxia and HIF-1alpha regarding prognostic and treatment-specific implications. (Part of a Multi-author Review).


Incidental primary breast cancer detected on PET-CT.
The purpose of this study is to determine the incidence of primary breast cancer (PBC) detected on (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in patients with a known diagnosis of non-mammary malignancies. A database search was performed to identify patients with non-mammary malignancies who had undergone staging with FDG PET-CT at a single institution between September 2005 and September 2011 and with the word "breast" reported in the PET-CT dictation. Additional breast imaging studies, clinical data, and the final histopathology of the breast lesions were correlated with the PET-CT images. Of 1951 patients who underwent PET/CT, 440 incidental breast lesions were identified in 438 patients. Of these 440 lesions, 195 (45 %) were benign, 160 (37 %) malignant, and 85 (19 %) missing data. A total of 25 PBCs were diagnosed; with a median size of 1.8 cm (range 0.8-10.7 cm); and a median SUVmax of 4.4 (range 1.7-17.6). There were 19 invasive ductal cancers, 1 invasive lobular cancer, 2 papillary cancers, 1 tubular cancer, 1 sarcomatoid cancer, and 1 ductal carcinoma in situ. Eight patients had regional nodal disease. Mammography revealed the PBC in 19 of 23 tumors (83 %), sonography in 22 of 23 (96 %). Six percent (25 of 440) of incidental breast lesions identified on FDG PET-CT represent PBCs; more than half were at an early stage and potentially curable.


Cystic duct cyst: type VI in Todani's classification.
Regarding the article recently published by Junquera E et al. that referenced our work, we agree with the authors that the cystic duct cyst (CDC) is type VI according to Todani's classification, which describes five different types of biliary cysts.


Inhibition of high affinity L-glutamic acid uptake into rat cortical synaptosomes by the conformationally restricted analogue of glutamic acid, cis-1-aminocyclobutane-1,3-dicarboxylic acid.
The action of two cyclobutane derivatives of L-glutamic acid on the high affinity uptake of L-glutamic acid was investigated using a preparation of synaptosomes from rat cerebral cortex. cis-1-Aminocyclobutane-1,3-dicarboxylic acid (also known as trans-2,4-methanoglutamic acid) potently inhibited L-glutamic acid uptake (IC50 30 microM), whereas trans-1-aminocyclobutane-1,3-dicarboxylic acid (also known as cis-2,4-methanoglutamic acid), a potent N-methyl-D-aspartate (NMDA) agonist, was inactive. Analysis of the kinetics of L-glutamic acid uptake in the presence and absence of cis-1-aminocyclobutane-1,3-dicarboxylic acid (CACB) suggests that it may act as a competitive inhibitor (Ki 8 microM). CACB may be substrate for the L-glutamic acid high-affinity uptake carrier since preincubation of CACB with the synaptosomal preparation increased its potency in inhibiting L-glutamic acid uptake. The conformationally restricted structure of CACB may be indicative of the conformations of L-glutamic acid that interact with the high affinity uptake carrier.


HPV vaccine knowledge, attitudes, and practices among New York State medical providers, dentists, and pharmacists.
Healthcare provider vaccine knowledge and attitudes influence delivery of a strong vaccine recommendation. We aim to describe HPV vaccine knowledge, attitudes, and recommendation or discussion practices (KAP) among New York State medical providers, dentists, and pharmacists. A survey to assess providers' KAP was distributed electronically to NYS members of medical organizations. Descriptive and inferential statistical methods were used to characterize provider KAP. Responses from 1637 surveys were included, from 864 (53%) medical providers, 737 (45%) dentists, and 36 (2%) pharmacists. 59% (509/864) of medical providers responded that they recommend HPV vaccine to patients, with 390/509 (77%) strongly recommending vaccine at 11-12 years. Medical providers were more likely to report recommending HPV vaccine for children ages 11-12 years if they strongly agreed that HPV vaccine prevents cancer 326/391 (83%) vs 64/117 (55%) and responded that HPV vaccination does not increase the risk of unprotected sex (386/494 (78%) vs 4/15 (25%)) (p < .05). Less than 1/3 of dentists reported discussing HPV vaccine with 11-26-year-old females (230/737, 31%) and males (205/737, 28%) at least "sometimes." Dentists were more likely to answer that they routinely discuss HPV vaccine with children ages 11-12 years if they responded that HPV vaccination does not increase sexual activity (70/73 (96%) vs 528/662 (80%), p < .001). Few pharmacists reported discussing HPV vaccine with 11-26-year-old females (6/36 (17%)) and males (5/36 (14%)) at least "sometimes." Gaps in HPV vaccine knowledge among providers still exist and may influence vaccine attitudes and recommendation or discussion practices.


Therapeutic management of the odontogenic keratocyst. An energetic approach with a conservative perspective and review of the current therapeutic options.
Odontogenic keratocysts (OKC) are cystic lesions appearing in the jaws, usually asymptomatic with a progressive growth into the bone. Many of them are diagnosed by a routine radiological examination. This study reports a 12-year-old girl that presented an asymptomatic large radiolucent unilocular lesion associated to the crown of 3.8 that caused displacement of the molar and the inferior alveolar canal. Differential diagnosis included OKC, unicystic ameloblastoma, ameloblastic fibroma, dentigerous cyst and orthokeratinized odontogenic cyst. Two surgical interventions were performed; first, a marsupialization, and 10 months after, the third molar extraction plus cyst enucleation, mucosa excision and the application of Carnoy's solution. The anatomopathological exam confirmed diagnosis of OKC. There was no evidence of recurrence after 2 years of follow-up. Marsupialization followed by surgical enucleation with mucosa excision and Carnoy's solution can help manage treatment of OKC, a lesion characterized by an aggressive behavior. Key words:Odontogenic keratocyst, mucosa excision, carnoy solution, third molar, tooth extraction.


Using Machine Learning to Uncover Hidden Heterogeneities in Survey Data.
Survey responses in public health surveys are heterogeneous. The quality of a respondent's answers depends on many factors, including cognitive abilities, interview context, and whether the interview is in person or self-administered. A largely unexplored issue is how the language used for public health survey interviews is associated with the survey response. We introduce a machine learning approach, Fuzzy Forests, which we use for model selection. We use the 2013 California Health Interview Survey (CHIS) as our training sample and the 2014 CHIS as the test sample. We found that non-English language survey responses differ substantially from English responses in reported health outcomes. We also found heterogeneity among the Asian languages suggesting that caution should be used when interpreting results that compare across these languages. The 2013 Fuzzy Forests model also correctly predicted 86% of good health outcomes using 2014 data as the test set. We show that the Fuzzy Forests methodology is potentially useful for screening for and understanding other types of survey response heterogeneity. This is especially true in high-dimensional and complex surveys.


[Screening for new binding proteins which interact with BM2 of influenza B virus with yeast two-hybrid system].
To explore the role of BM2 protein in the life cycle of influenza B virus. The authors screened human kidney MATCHMAKER cDNA library for new binding partners of BM2 of influenza B virus by using the yeast two hybrid system with truncated BM2 (26-109 aa) as the bait. Six positive plasmids encoding N-acetylneuraminate pyruvate lyase, angiopoietin 3, zinc finger protein 251, ribosomal protein S20, protein arginine N-methyltransferase 1 variant 1 (PRMT) and transcription factor-like 1 (TCFL1) were obtained. The results suggest that BM2 may play an important role in the life cycle of influenza B virus.


The prevalence of major depressive and bipolar disorders in Hungary. Results from a national epidemiologic survey.
In order to estimate the prevalence of affective disorders in Hungary a sample of the Hungarian adult population (18-64 years) selected at random was interviewed using the Diagnostic Interview Schedule (DIS) which generated DSM-III-R diagnoses. The lifetime rate for Major Depressive Disorder (MDD) was 15.1%, and for Bipolar Disorders (BD) 5.1%. The female-to-male ratio was 2.7 for MDD and nearly equal for BD. The 1-year and 1-month period prevalence rates were 7.1% and 2.6% for MDD and 0.9% and 0.5% for manic episodes. A higher rate of divorced or separated persons was found among individuals with a lifetime diagnosis of MDD. Besides these, the lifetime diagnosis of BD coexisted with higher rates of the never-married state. The highest hazard rate for the development of BD or MDD was in the range 15-19 years but in MDD another peak was also found in the range 45-50 years. The first peak was characteristic of the recurrent, and the other one of the single form of MDD. Insomnia, loss of energy, decreased interest, concentration problems were the most common symptoms during the depressive episode, independent of polarity. Higher rates of lifetime diagnosis of dysthymia and all kinds of anxiety disorder were revealed among persons with MDD. BD was associated with GAD (Generalized Anxiety Disorder), and panic disorder more often than chance.


The background brightness of the milky way near 2500 A between lparallel= 72 degrees and 126 degrees.
Data from a rocket experiment show details which were not known from ground-based observations.


The potential of Beclin 1 as a therapeutic target for the treatment of breast cancer.
Beclin 1 plays a crucial role in autophagy via the Beclin 1 interactome, and is involved in various biological processes such as protein sorting, chemokinesis, and cell death. Via these biologic functions, Beclin 1 contributes to both tumor suppression and tumor progression. Beclin 1 plays a key biologic function on cell homeostasis and affects tumorigenesis. In this review, detailing up-to-date knowledge on the tumorigenic role of Beclin 1, its implication in breast cancer, and its utility as a breast cancer-specific drug target is discussed. Because Beclin 1 is expressed in breast cancer cells, Beclin 1 could be a unique, effective drug target for the prevention and treatment of breast cancer. However, the expression of Beclin 1 varies according to cancer molecular subtypes, and Beclin 1 is involved in both breast cancer suppression and tumor progression; therefore, the decision of using a Beclin 1 inducer or inhibitor should be made based on breast cancer stage and subtype.


Treatment of atopic eczema with evening primrose oil: rationale and clinical results.
Recently a defect in the function of the enzyme delta-6-desaturase has been discussed as a major factor in the development of atopic eczema. Delta-6-desaturase is responsible for the conversion of linoleic acid to gamma linolenic acid. Several plants, including evening primrose, are known to be fairly rich in gamma linolenic acid. Hence, substitution of gamma linolenic acid in patients prone to developing atopic eczema seems like a feasible concept. During the last few years different clinical trials have been performed. Controlled trials following a parallel study design showed marked improvement in atopic eczema. Patients treated with the drug showed less inflammation, dryness, scaling and overall severity compared to controls. Although these findings have been supported by meta-analysis, there is still conflicting evidence in trials based on a crossover design alone, demonstrating a decrease in itching. At present, evening primrose oil in doses used for the treatment of atopic eczema is considered safe. However, still more trials addressing both efficacy and safety are needed to make a final decision.


Flowcytometric analysis of basophil counts in human blood and inaccuracy of hematology analyzers.
Differential leukocyte counts are of proven clinical value, but information about basophil counts in normal and disease conditions is scarce although basophils are regarded as key effector cells in allergy. To establish and validate flowcytometric methods for counting basophils in peripheral human blood, to determine reference values, and to examine the accuracy of two widely used hematology analyzers. Basophils were measured in whole blood by flowcytometry after staining with antibodies against the IL-3-receptor (CD123) or the eotaxin-receptor (CCR3) combined with other markers used for gating or validation purposes. The basophil percentages in 95 healthy adults showed an excellent correlation between the two independent flowcytometric methods, demonstrating that both are accurate and precise. The most robust maker is CCR3, which seems to be sufficient to specifically identify basophils. Normal values of relative and absolute blood basophils counts were 0.22-1.28% and 0.014-0.087 G/L (95% reference intervals), respectively. Basophil counts measured with two hematology analyzers Coulter GEN-S and ADVIA-120 showed no correlation between these instruments. Comparing the data obtained by flowcytometry and the analyzers demonstrate that basophil counts of the GEN-S are erratic, while the ADVIA-120 gives at least an estimation of true basophil numbers. We provide a solid description and validation of a novel and rapid method for the flowcytometric enumeration of basophil in whole blood. The fact that the most heavily used Hematology autoanalyzer gives completely erroneous results could explain why basophils counts have not yet received recognition as a clinically useful diagnostic marker.


Store-Operated Ca2+ Entry in Drosophila Primary Neuronal Cultures.
Intracellular calcium signals in neurons frequently derive from the stimulation of G protein-coupled receptors (GPCR) by neurotransmitters, neuropeptides, and neurohormones. GPCR stimulation in neurons leads to generation of inositol 1,4,5-trisphosphate (IP3), which in turn activates endoplasmic reticulum (ER)-localized IP3 receptors. The IP3 receptor (IP3R) is a ligand-gated Ca2+ channel, which releases Ca2+ from ER stores. In Drosophila neurons it has been shown that depletion of ER Ca2+ store is followed by store-operated Ca2+ entry (SOCE) through STIM and Orai, the ER Ca2+ sensor and the plasma membrane Ca2+ channel respectively. The elucidation of this Ca2+ signaling pathway in neurons has in part been possible due to the ease of genetic manipulation in Drosophila, which has allowed neuron-specific knockdown of various proteins of interest. This has been followed by standardization of conditions for culturing neurons from dissected brains of the relevant genotypes, such that they could be used for robust Ca2+ measurements by imaging with standard Ca2+ indicator dyes. Protocols for measurement of IP3-mediated Ca2+ release, passive depletion of ER Ca2+ store, and SOCE in primary cultures of Drosophila neurons are described here.


Special Issue: "Electric, Magnetic, and Electromagnetic Fields in Biology and Medicine: From Mechanisms to Biomedical Applications".
The last decades have seen a huge increase in applications and devices using and emitting non-ionizing radiation, otherwise referred to as "electromagnetic fields" (EMF) [...].


Characteristics of persistent arthritis with refractory Kawasaki disease: a single-center retrospective study.
Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.


Activation of the alternative pathway of complement by monosodium urate crystals.
Monosodium urate crystals (MSU) have been shown to activate the alternative pathway of complement in a dose- and time-dependent fashion at 37 degrees C. Activation was maximal upon addition of 10-20 mg/ml monosodium urate crystals to C2-deficient human serum (C2D) or normal human serum containing 5 mM MgEGTA. Immunoelectrophoretic analysis of such treated sera demonstrated cleavage of C3 and factor B. Incubation of highly purified C3 and factor B with 10 mg/ml MSU did not, however, affect their immunoelectrophoretic pattern, suggesting that cleavage of either factor B or C3 in serum requires an intact alternative complement pathway. The fluid-phase control proteins, Factor H and Factor I, were not found to be diminished upon incubation of C2D serum or NHS containing MgEGTA with MSU. Thus activation appeared to be surface dependent and not a consequence of control protein depletion. It was also found, in agreement with earlier observations, that the classical complement pathway is activated, with concomitant depletion of C1 and C4. We conclude that MSU crystals activate both the classical and alternative pathways, and that such activation may participate in the pathogenesis of gouty arthritis.


Understanding the role of the blood brain barrier and peripheral inflammation on behavior and pathology on ongoing confined cortical lesions.
Inflammation in the Central Nervous System (CNS) is associated with blood brain barrier (BBB) breakdown during the early stages of Multiple Sclerosis (MS), indicating a facilitated entry of waves of inflammatory cells from the circulation to the CNS. In the progressive forms of MS, as the lesion becomes chronic, the inflammation remains trapped within the CNS compartment forming the slow evolving lesion, characterized by low inflammation and microglia activation at the lesions edges. The chronic expression of interleukin 1β (IL-1β) in the cortex induces BBB breakdown, demyelination, neurodegeneration, microglial/macrophage activation and impaired cognitive performance. The latter can be improved, as long as the BBB recovers and the lesion presents low inflammation. Here, we study the effects of peripheral inflammation on cortical central lesions after the restoration of the BBB, in order to elucidate the role of the peripheral inflammation on these lesions with intact BBB, as it occurs in the progressive forms of MS. Cortical lesions and peripheral inflammation were induced by the chronic expression of IL-1β using an adenovector. We performed histological, immunohistochemistry on brain tissue and behavioural analyses. The effects of the chronic expression of IL-1β in the cortex resolved within 56 days. However, peripheral and sustained inflammation re-opened the BBB, allowing the reappearance of the neuroinflammatory processes within the cortical lesions, increased demyelination and neurodegeneration, and an increase of the behavioral symptoms, such as cognitive impairment and anxiety-like symptoms. The early treatment of peripheral inflammatory processes should be considered in order to protect the brain from exacerbation of the ongoing neurodegenerative process.


Alignment and clustering strategies for GC×GC-MS features using a cylindrical mapping.
Comprehensive two-dimensional gas chromatography coupled to mass spectrometry is a powerful tool to analyze complex samples. For application of the technique in studies like biomarker discovery in which large sets of complex samples have to be analyzed, extensive preprocessing is needed to align the data obtained in several injections (analyses). We developed new alignment and clustering algorithms for this type of data. New in the current procedures is the consistent way in which the phenomenon referred to as wrap-around is treated. The data analysis problems associated with this phenomenon are solved by treating the 2D display as the surface of a three-dimensional cylinder. Based on this transformation we developed a new similarity metric for features as a function of both the cylindrical distance (reflecting similarity in chromatographic behavior) and of the mass spectral correlation (reflecting similarity in chemical structure). The concepts are used in warping and clustering, and include a protection against greedy warping. The methods were applied - for the purpose of an example - to the analysis of 11 replicates of a human urine sample concentrated by solid phase extraction. It is shown that the alignment is well protected against greedy warping which is important with respect to analytical qualities as robustness and repeatability. It is also demonstrated that chemically similar features are clustered together. The paper is organized as follows. First a brief introduction is provided addressing the background of the GC×GC-MS data structure followed by a theoretical section with a conceptual description of the procedures and details of the algorithms. Finally an example is given in the experimental section, illustrating the application of the procedures.


11beta-HSD1, inflammation, metabolic disease and age-related cognitive (dys)function.
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an intracellular amplifier of glucocorticoid action. By converting intrinsically inert glucocorticoids (cortisone, 11-dehydrocorticosterone) into their active forms (cortisol, corticosterone), 11beta-HSD1 increases glucocorticoid access to receptors. Glucocorticoid hormones modulate diverse physiological processes, linking circadian rhythms to food seeking, motivational and cognitive behaviours, as well as intermediary metabolism and immune responses. They are a key component of pathways that buffer the organism against stressful challenges. Here we review the part played in these processes by 11beta-HSD1, and discuss the promise of inhibitors of 11beta-HSD1 in alleviating disorders associated with cumulative stress.


Cyto-morphological features of parathyroid lesions: Fine-needle aspiration cytology series from an endocrine tumor referral center.
Descriptions of parathyroid cell cyto-morphology are limited. Fine-needle aspiration cytology (FNAC) with immunocytochemistry (ICC) or biochemical PTH measurements may help verify the parathyroid origin in extraordinary cases, although these methods are nowadays largely replaced by imaging techniques. We collected all available FNAC reports of parathyroid lesions from our department spanning 20 years, to characterize the clinical use of parathyroid FNAC, and to assess morphological correlates between cytology and subsequent histopathology. Twenty-eight cases with assessable cytological smears were found, of which 21 cases were surgically resected and 20 available for histological review (15 adenomas, 2 carcinomas, 2 atypical tumors and a single case with secondary hyperplasia). FNAC was predominantly performed to localize the diseased gland in cases with inconclusive imaging, in cases with a suspicion of intrathyroidal localization or in cases with persistent hypercalcemia following unsuccessful surgery. The diagnosis was verified using either PTH ICC and/or PTH measurements for most cases, and the procedure affected the clinical decision-making for the majority of patients in this selected cohort. Cytological differences between parathyroid adenomas and carcinomas were found, as only carcinomas showed pleomorphism with irregular nuclei and prominent nucleoli. Morphologically, no correlations to predominant cell types or growth patterns visualized at histological investigations among adenomas were noted, and biopsy artifacts were evident in 40% of cases. Parathyroid FNAC could be considered as a complementary analysis for a small group of selected patients, but benefits have to be weighed against the risk of biopsy artifacts in histological preparations.


Primary inner ear schwannomas: a case series and systematic review of the literature.
To describe the natural history of primary inner ear schwannomas (PIES) and evaluate management outcomes and relationship between PIES location, clinical presentation, and time to diagnosis. Retrospective chart review and systematic review of the literature. Vestibular schwannoma confined to or arising from the inner ear were included. PIES classification was based on anatomic subsite(s) involved. Detailed clinical history and outcomes were recorded. In a systematic review (1933-2011), including 14 patients from the authors' institution (1999-2009), a total of 72 studies comprising 234 patients were evaluated. Mean follow-up was 32.8 ± 39.1 months (range, 0-183 months). The cochlea was the most commonly involved subsite (51%). Hearing loss was the most frequent presenting symptom (99%). Vertigo and abnormal balance were more common among tumors involving the vestibular system (P < .01). Average delay between symptom onset and diagnosis was 7.0 ± 8.0 years (median, 5 years; range, 0-40 years). Recent onset hearing loss was more likely to elicit an earlier diagnosis (P = .01). The majority of patients were observed without treatment (53%). Tumor progression was seen in 52% of patients. PIES are rare tumors and most commonly involve the cochlea. Tumor location is often associated with clinical presentation and correlates with delay between symptom onset and diagnosis. A watch-and-scan approach is the management strategy of choice in the absence of intractable vertigo or extensive tumor growth. The majority of patients report stable or improved symptoms over time, regardless of treatment.


Overexpression of a TFIIIA-type zinc finger protein gene ZFP252 enhances drought and salt tolerance in rice (Oryza sativa L.).
We previously identified a salt and drought stress-responsive TFIIIA-type zinc finger protein gene ZFP252 from rice. Here we report the functional analysis of ZFP252 using gain- and loss-of-function strategies. We found that overexpression of ZFP252 in rice increased the amount of free proline and soluble sugars, elevated the expression of stress defense genes and enhanced rice tolerance to salt and drought stresses, as compared with ZFP252 antisense and non-transgenic plants. Our findings suggest that ZFP252 plays an important role in rice response to salt and drought stresses and is useful in engineering crop plants with enhanced tolerance to salt and drought stresses.


A chart audit study of the referral of obese patients to endocrinologists.
The aim of this study was to identify factors in primary care physicians' decisions to refer obese patients to an endocrine clinic. Charts of 83 referred obese patients were compared with randomly selected charts of 300 obese adults in the general ambulatory clinic files. The referral rate is estimated at 1% of obese patients in the clinical center and 0.25% of obese persons in the Lansing area. Referral of obese patients appears to depend primarily on degree of obesity and secondarily on suspicion of endocrine disease. Considerations limiting the usefulness of patient charts for studies of physicians' decision making are discussed.


Impact of imatinib or dasatinib coadministration on in vitro preantral follicle development and oocyte acquisition in cyclophosphamide-treated mice.
We investigated the impact of tyrosine kinase inhibitor (imatinib or dasatinib) coadministration with cyclophosphamide (Cp) on preantral follicle development in an in vitro mouse model. Seventy-three female BDF1 mice were allocated into four experimental groups: group A, saline; group B, Cp (25 mg/kg); group C, Cp (25 mg/kg) and imatinib (7.5 mg/kg); and group D, Cp (25 mg/kg) and dasatinib (7.5 mg/kg). Preantral follicles were isolated and cultured in vitro up to 12 days. Final oocyte acquisition and spindle integrity of metaphase II (MII) oocytes were assessed. Levels of 17β-estradiol and anti-Müllerian hormone (AMH) in the final spent media were measured by enzyme-linked immunosorbent assays, and the mRNA levels of Star, Sod1, Mapk3, and Casp3 in the final follicular cells were quantified by real-time polymerase chain reaction. The percentage of MII oocytes per initiated follicle, the proportion of MII oocytes with normal spindles, and the 17β-estradiol level were similar in all four groups. The median AMH level in group B (7.74 ng/mL) was significantly lower than that in group A (10.84 ng/mL). However, the median AMH levels in group C (9.96 ng/mL) and group D (9.71 ng/mL) were similar to that in group A. The mRNA expression levels of Star, Sod1, Mapk3, and Casp3 were similar in all four groups. Coadministration of imatinib or dasatinib with Cp could preserve AMH production capacity in this in vitro mice preantral follicle culture model, and it did not affect MII oocyte acquisition.


Paying for Happiness: Experimental Results from a Large Cash Transfer Program in Malawi.
This study analyzes the short-term impact of an exogenous, positive income shock on caregivers' subjective well-being (SWB) in Malawi using panel data from 3,365 households targeted to receive Malawi's Social Cash Transfer Program that provides unconditional cash to ultra-poor, labor-constrained households. The study consists of a cluster-randomized, longitudinal design. After the baseline survey, half of these village clusters were randomly selected to receive the transfer and a follow-up was conducted 17 months later. We find that the short-term impact of household income increases from the cash transfer leads to substantial SWB gains among caregivers. After a year's worth of transfers, caregivers in beneficiary households have higher life satisfaction and are more likely to believe in a better future. We examine whether program impacts on consumption, food security, resilience, and hopefulness could explain the increase in SWB but do not find that any of these mechanisms individually mediate our results.


Free-running circadian plasma cortisol rhythm in a blind human subject.
The plasma cortisol rhythm in man has been presumed to be an endogenous circadian rhythm, synchronized by some external stimulus to an exact 24-h period. Sleep/wake and 'social activity' cycles have been considered as candidates for this synchronizer. Previous studies have suggested that the dark/light phase shifts associated with the sleep-wake cycle may be the external synchronizer, rather than the sleep/wake cycle itself. A totally blind, but otherwise normal subject was studied for a period of 50 days. Her hourly sleep/wake status and hourly integrated mean plasma cortisol concentrations were determined, and the data were subjected to non-parametric mathematical analysis. The subject was found to have a free-running rhythm in plasma cortisol with a period of approximately 24.5 h. Her sleep/wake rhythm, determined by similar analysis, had a period of exactly 24 h. In addition to the dominant 24.5-h cortisol rhythm, there appeared to be a minor 24-h cortisol rhythm with a peak that coincided approximately with the time of awakening. It was not possible to determine whether this sleep/wake-related peak represented a minor component of the circadian rhythm, synchronized by some stimulus associated with sleep/wake activity, or merely an acute response to awakening itself. Nevertheless, the two rhythms exhibited 'beating' behaviour, resulting in maximal peak cortisol concentrations when they were in synchrony and minimal peak concentrations when they were not. It is concluded that environment dark/light phase shifts are the dominant synchronizer of the circadian rhythm in plasma cortisol concentrations in man, as they are for a variety of circadian rhythms in other living things.


Identification of a novel proline-rich peptide-binding domain in prolyl 4-hydroxylase.
Prolyl 4-hydroxylase (EC 18.104.22.168) catalyzes the hydroxylation of -X-Pro-Gly- sequences and plays a central role in the synthesis of all collagens. The [alpha(I)]2beta2 type I enzyme is effectively inhibited by poly(L-proline), whereas the [alpha(II)]2beta2 type II enzyme is not. We report here that the poly(L-proline) and (Pro-Pro-Gly)10 peptide substrate-binding domain of prolyl 4-hydroxylase is distinct from the catalytic domain and consists of approximately 100 amino acids. Peptides of 10-19 kDa beginning around residue 140 in the 517 residue alpha(I) subunit remained bound to poly(L-proline) agarose after limited proteolysis of the human type I enzyme tetramer. A recombinant polypeptide corresponding to the alpha(I) subunit residues 138-244 and expressed in Escherichia coli was soluble, became effectively bound to poly(L-proline) agarose and could be eluted with (Pro-Pro-Gly)10. This polypeptide is distinct from the SH3 and WW domains, and from profilin, and thus represents a new type of proline-rich peptide-binding module. Studies with enzyme tetramers containing mutated alpha subunits demonstrated that the presence of a glutamate and a glutamine in the alpha(II) subunit in the positions corresponding to Ile182 and Tyr233 in the alpha(I) subunit explains most of the lack of poly(L-proline) binding of the type II prolyl 4-hydroxylase. collagen/dioxygenases/peptide-binding domain/ proline-rich/prolyl hydroxylase


Enhancing deoxyribonucleic acid (DNA) detection sensitivity through microconcentration on patterned fluorocarbon polymer surface.
A microconcentration concept is proposed to enhance the sensitivity of deoxyribonucleic acid (DNA) hybridization due to evaporation of the hybridization solution on a patterned hydrophobic fluorocarbon polymer (FCP) surface. The combination of microconcentration and hybridization processes provides a tool to manipulate nanoliter solution. To fabricate a patterned DNA microarray with hydrophobic surrounding surface, a plasma polymerization and lift-off protocol was designed so that the process can be carried out in a standard microelectronic fabrication laboratory with minimal adjustments on the equipment. After microconcentration, a 1 microL hybridization solution can be concentrated to below 10 nL, which improves the hybridization sensitivity by a factor of 100.


Small-incision lenticule extraction in posterior polymorphic corneal dystrophy.
We present the case of a 37-year-old man with posterior polymorphic corneal dystrophy who had small-incision lenticule extraction surgery to correct myopic refractive errors. The subjective refraction was -2.62 in the right eye and -2.50 -0.25 × 80 in the left eye. Slitlamp biomicroscopy revealed a band-like lesion in the corneal endothelium of the right eye. The endothelial cell count was 1745 cells/mm(2) in the right eye and 2945 cells/mm(2) in the left eye. Small-incision lenticule extraction was performed to correct the myopic refractive errors in both eyes. Twelve months after surgery, the uncorrected distance visual acuity in both eyes was 20/20 and the posterior polymorphic corneal dystrophy lesion had not progressed. The case suggests that small-incision lenticule extraction surgery can be performed successfully and safely in patients with posterior polymorphic corneal dystrophy. None of the authors has a financial or proprietary interest in any material or method mentioned.


Study the effects of saffron on depression and lipid profiles: A double blind comparative study.
Depression is a one of the most prevalent psychiatric disorder. Despite several pharmacological treatments, still treating depression is a challenge. Herbal medicine that is better culturally accepted may play an important role in treatment of depression. In this double blind placebo controlled clinical trial, 40 patients that were suffering from major depression according to DSM-IV criteria were randomly allocated to take either fluoxetine and saffron (20 patients) or fluoxetine and placebo (20 patients). The patients of the two groups were evaluated with Beck depression scale at the beginning of the study and after four weeks. Lipid profile (total Triglyceride (TG) level, total cholesterol level, low density lipoprotein (LDL) level and high density lipoprotein (HDL) level) of the patients also was measured at the beginning and end of the trial. 30 patients (19 in saffron group and 11 in placebo group) completed the study. The two groups improved significantly in depression severity at the end of the study without significant difference (P: 0.560). The lipid profile of the two groups did not change significantly. Our study did not demonstrate antidepressive effects for saffron. We did not observe any lipid lowering effect in saffron group too. Of note is that our study is preliminary and larger studies with more patients and longer duration are needed to prove our results. IRCT 2013110915334.


Antifungal activity in seed coat extracts of woodland plants.
Aqueous extracts from seeds of four woodland ground flora species (Hyacinthoides non-scripta, Allium ursinum, Digitalis purpurea and Hypericum pulchrum) were tested for antifungal activity using a petriplate technique. Four species of fungi were investigated. The growth of three of these (Trichoderma viride, Rhizoctonia solani and Pythium sp.) was not affected by any of the seed coat extracts. The growth of Botrytis cinerea was inhibited by the seed coat extracts of Digitalis purpurea and Hypericum pulchrum but not by those of Hyacinthoides non-scripta or Allium ursinum. The buried seeds of Digitalis purpurea and Hypericum pulchrum can survive in woodland soils for long periods, whereas those of Hyacinthoides non-scripta and Allium ursinum are short-lived. The presence of antifungal agents in the seed coats of persistent species and their possible role in protecting seeds against fungal pathogens is discussed.


Application of virtual reality in dental implants: a systematic review.
A treatment approach that is widely used as a permanent and natural replacement for missing or extracted teeth is dental implants .VR is a computer-generated simulation that creates a three-dimensional (3D) image or environment. Advances in VR -based learning allow learners and students to practice and also help professionals plan a wide variety of surgical procedures, including the correct placement of dental implants. Therefore, in this systematic review, our aim was to investigate and evaluate the available virtual reality tools for dental implants and their effectiveness. Studies published up to 01/30/2023 which report the applications of using virtual reality technology in dental implants, were reviewed in three databases, including PubMed, Web of Science, and Scopus. All studies with evidence reporting the role of virtual reality technology in the field of dental implants were included in our analyses, written in English and published in peer-reviewed form, are included. Theoretical articles, and letters that did not provide original data, as well as studies that reported incomplete information, were excluded. Two reviewers independently assessed search results, extracted data, and assessed the quality of the included studies, and decisive agreement was reached by discussion and consultation with the third researcher. Narrative synthesis was undertaken to summarize and report the findings. Out of 1633 initial search results, nine were included in the present study based on the inclusion criteria. The focus of seven studies was on teaching and learning, and two studies have examined the implant planning procedure. The most commonly used hardware and software were head-mounted display and Unity3D, respectively. In almost all studies, the results showed that the use of virtual reality-based systems improves and enhances the skills of users, including dental students and specialists. Our findings showed that VR is an effective method for teaching and planning the implant process. Although the use of VR technology is limited for various reasons such as cost, it can increase the skills of dental professionals in performing dental implants.


Antidepressant transfer into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis.
Data regarding the ability of antidepressants to enter fetal, newborn and infant fluids have become gradually available, but mechanisms of antidepressant transfer remain poorly understood. Here we calculated penetration ratios in an array of matrices from combined samples of pregnant/breastfeeding women taking antidepressants. We performed a systematic literature search of PubMed and EMBASE to identify studies with concentrations of antidepressants from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal plasma concentration. When data from multiple studies were available, we calculated combined penetration ratios, weighting the study mean by study size. Eighty-five eligible studies were identified. For amniotic fluid, the highest penetration ratios were estimated for venlafaxine (mean 2.77, range 0.43-4.70 for the active moiety) and citalopram (mean 2.03, range 0.35-6.97), while the lowest ratios were for fluvoxamine (mean 0.10) and fluoxetine (mean 0.11, range 0.02-0.20 for the active moiety). For umbilical cord plasma, nortriptyline had the highest ratio (mean 2.97, range 0.25-26.43) followed by bupropion (mean 1.14, range 0.3-5.08). For breast milk, the highest ratios were observed for venlafaxine (mean 2.59, range 0.85-4.85), mianserin (mean 2.22, range 0.80-3.64) and escitalopram (mean 2.19, range 1.68-3.00). We observed considerable variability across antidepressants regarding their ability to enter fetal, newborn and infant fluids. Measuring antidepressant concentrations in a maternal blood sample can provide a reliable estimate of fetal/infant exposure, although further evidence for concentration-dependent effects is required.


Hypermethylation of genes in testicular embryonal carcinomas.
Testicular embryonal carcinoma (EC) is a major subtype of non-seminomatous germ cell tumours in males. Embryonal carcinomas are pluripotent, undifferentiated germ cell tumours believed to originate from primordial germ cells. Epigenetic changes during testicular EC tumorigenesis require better elucidation. To identify epigenetic changes during testicular neoplastic transformation, we profiled DNA methylation of six ECs. These samples represent different stages (stage I and stage III) of divergent invasiveness. Non-cancerous testicular tissues were included. Expression of a number of hypermethylated genes were examined by quantitative RT-PCR and immunohistochemistry (IHC). A total of 1167 tumour-hypermethylated differentially methylated regions (DMRs) were identified across the genome. Among them, 40 genes/ncRNAs were found to have hypermethylated promoters. Quantitative RT-PCR confirmed downregulation of 8 out of 9 of the genes. Among the confirmed genes, five were sex-linked genes, including X-linked genes STAG2, SPANXD/E and MIR1184, and Y-linked genes RBMY1A1/1B/1D and FAM197Y2P. RBMY1A is a testis-specific gene for spermatogenesis. RNF168 and USP13 are potential tumour suppressors. Expression of RBMY1A was lost in EC and seminoma as documented in the Protein Atlas. We confirmed downregulation of USP13 in EC by IHC. Our genome-wide analysis of testicular EC identified methylation changes in several previously unknown genes. This may provide insight of crosstalk between normal germ cell development and carcinogenesis.


Superparamagnetic core-shells anchored onto graphene oxide grafted with phenylethyl amine as a nano-adsorbent for extraction and enrichment of organophosphorus pesticides from fruit, vegetable and water samples.
A novel adsorbent composed of silica coated magnetic microparticles (Fe3O4@SiO2) and graphene oxide (GO) functionalized with phenylethyl amine (PEA) was synthesized and characterized using Fourier transform-infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), and CHN elemental analysis techniques. The adsorbent (Fe3O4@SiO2@GO-PEA) was then used in a magnetic solid phase extraction (MSPE) of six organophosphorous pesticides (OPPs) including methyl parathion, fenitrothion, methidathion, ethion, methyl azinphos and coumaphos prior to gas chromatography-nitrogen phosphorus detection (GC-NPD). The fabricated adsorbent combines the advantages of superior adsorption capability of modified GO and magnetic separability of magnetite microparticles to provide high adsorption capacity, and easy isolation from sample solutions. The main experimental parameters affecting the extraction recovery of OPPs including extraction time, pH, adsorbent dosage, salt concentration, and desorption conditions were investigated and optimized. Under the optimal conditions, linear responses were obtained in the concentration range of 0.06-200μgL(-1) with the determination coefficients (R(2)) between 0.9945 and 0.9996. The limits of detection were from 0.02 to 0.1μgL(-1) and the intraday and inter-day relative standard deviations (RSDs) were less than 4.8 and 6.4%, respectively. The method was successfully applied for determination of the OPPs in apple, grape, pear, bell pepper, celery and water samples. The obtained recoveries were in the range of 90.4-108.0% (RSDs=1.9-6.6%, n=3) for fruits and vegetables, and 94.6-104.2% (RSDs=2.0-4.8%, n=3) for water samples. The excellent extraction performance of the adsorbent can be attributed to its structure characteristics where the phenyl rings of PEA grafted on the GO nanosheets are accessible to interact effectively with OPPs via delocalized π-electron system.


First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.
Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.


Immunohistochemical Analysis and Electron Microscopy of Glial Cells in the Pancreas of Fetuses and Children.
Schwann cells forming peri-insular glial sheath of the pancreatic islets in some mammals can be involved in the pathogenesis of diabetes mellitus. Human pancreatic cells contain small elongated or oval cells of unknown origin with S100-immunopositive processes. We found that cells with processes located in pancreatic islets of human fetuses and children are similar to Schwann cells by their morphological and ultrastructural characteristics, immunopositive reaction for S100, and integration with nerve endings. In the pancreas of fetuses and children, Schwann cells are often seen in forming pancreatic islets and around the pancreatic ducts. The data suggests that Schwann cells can participate in the morphogenesis of human pancreatic islets.


Rapid identification of the copy number of α-globin genes by capillary electrophoresis analysis.
The current study aimed at the rapid identification of the copy number of α-globin genes for the diagnosis of α-thalassemia. To identify the copy number of α-globin genes in α-thalassemia, we developed a novel method using a multiplex polymerase chain reaction (PCR) in combination with the CE analysis. The proposed method provides a rapid detection of the common α-globin gene deletions. Sixty-six patients with α-thalassemia and 46 normal controls were included in the present study. The obtained results showed good correlation with those obtained by gap PCR. Moreover, a low amount of maternal cell contamination in the fetus specimen for the prenatal diagnosis of hemoglobin Barts hydrops fetalis as well as the rare multiplicated α-globin genes can be identified using this method. This method provides a convenient and efficient tool for the rapid identification of the copy number of α-globin genes in α-thalassemia and the individuals with α-globin gene multiplication.


Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Young Patients with Epithelial Ovarian Cancer: Analysis Based on SEER Program.
Currently, there is no clinical prediction model for young patients (≤ 45 years old) with epithelial ovarian cancer (EOC) based on large samples of clinical data. The purpose of this study was to construct nomograms using data extracted from the Surveillance, Epidemiology, and End Results (SEER) Program to predict the overall survival (OS) and cancer-specific survival (CSS) of patients and to further guide the choice of clinical treatment options. Data from a total of 6376 young patients with EOC collected from 1998 to 2016 were selected from the SEER database. These patients were randomly divided (7:3) into a training cohort (n = 4465) and a validation cohort (n = 1911). Cox and least absolute shrinkage and selection operator (LASSO) analyses were used to select the prognostic factors affecting OS and CSS, and the nomograms of OS and CSS were established. The performance of the nomogram models was assessed by C-index, area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Sample were chosen from patients who underwent surgery in Shengjing Hospital to set external validation. Kaplan-Meier curves were plotted to compare survival outcomes between subgroups. Nomograms showed good predictive power and clinical practicality. The internal and external validation indicated better performance of the nomograms than the American Joint Committee on Cancer (AJCC) staging system and tumor grade system. Significant differences were observed in the survival curves of different risk subgroups. We constructed predictive nomograms to evaluate the OS and CSS of young patients with EOC. The nomograms will provide an individualized evaluation of OS and CSS for suitable treatment of young patients with EOC.


Liver transplantation.
Liver replacement has become a viable treatment option for select patients with severe acute or chronic hepatic failure. Evaluation of potential candidates is discussed along with current techniques for donor organ retrieval, recipient implantation, and postoperative immunosuppression.


Methamphetamine Exposure in Adolescent Impairs Memory of Mice in Adulthood Accompanied by Changes in Neuroplasticity in the Dorsal Hippocampus.
Methamphetamine (METH) has been shown to alter learning and memory by affecting the neuroplasticity of the dorsal hippocampus, a key structure that undergoes extensive remodeling during adolescence. In this study, we investigated whether mid-to-late adolescent exposure to METH leads to long-lasting memory impairment. To do this, adolescents (35-48 postnatal days) were exposed to different doses of METH for 14 days and then evaluated by the Morris water maze (MWM), new object recognition test (NORT), and the Y-maze, to investigate the learning and memory abilities of mice in their adolescence and adulthood, respectively. We also detected the mRNA levels of genes associated with neuroplasticity in the dorsal hippocampus. The synaptic ultrastructure and the number of neurons and astrocytes in the dorsal hippocampus were also determined by transmission electron microscopy (TEM) and immunofluorescence (IF). Exposure to METH in mid-to-late adolescence impaired spatial memory retrieval ability and the long-term recognition memory of mice in their adulthood, but not in their adolescence. Of note, the impairment of memory capacity in adulthood was accompanied by molecular and structural changes in synapses in the dorsal hippocampus. Our results indicate that mice exposed to METH in mid-to-late adolescence have impaired memory ability in their adulthood; this may be the result of abnormal changes in the structural plasticity of the dorsal hippocampus; the causal relationship between changes in synaptic structural plasticity and memory impairment needs to be further confirmed. In summary, our study provides evidence for the detrimental consequences of adolescent addiction and the prevention of adolescent drug abuse.