Tumor Frameshift Mutation Proportion Predicts Response to Immunotherapy in Mismatch Repair-Deficient Prostate Cancer.
Genomic biomarkers that predict response to anti-PD1 therapy in prostate cancer are needed. Frameshift mutations are predicted to generate more neoantigens than missense mutations; therefore, we hypothesized that the number or proportion of tumor frameshift mutations would correlate with response to anti-PD1 therapy in prostate cancer. To enrich for response to anti-PD1 therapy, we assembled a multicenter cohort of 65 men with mismatch repair-deficient (dMMR) prostate cancer. Patient characteristics and outcomes were determined by retrospective chart review. Clinical somatic DNA sequencing was used to determine tumor mutational burden (TMB), frameshift mutation burden, and frameshift mutation proportion (FSP), which were correlated to outcomes on anti-PD1 treatment. We subsequently used data from a clinical trial of pembrolizumab in patients with nonprostatic dMMR cancers of various histologies as a biomarker validation cohort. Nineteen of 65 patients with dMMR metastatic castration-resistant prostate cancer were treated with anti-PD1 therapy. The PSA50 response rate was 65%, and the median progression-free survival (PFS) was 24 (95% confidence interval 16-54) weeks. Tumor FSP, more than overall TMB, correlated most strongly with prolonged PFS and overall survival (OS) on anti-PD1 treatment and with density of CD8+ tumor-infiltrating lymphocytes. High FSP similarly identified patients with longer PFS as well as OS on anti-PD1 therapy in a validation cohort. Tumor FSP correlated with prolonged efficacy of anti-PD1 treatment among patients with dMMR cancers and may represent a new biomarker of immune checkpoint inhibitor sensitivity. Given the modest efficacy of immune checkpoint inhibition (ICI) in unselected patients with advanced prostate cancer, biomarkers of ICI sensitivity are needed. To facilitate biomarker discovery, a cohort of patients with DNA mismatch repair-deficient (dMMR) prostate cancer was assembled, as these patients are enriched for responses to ICI. A high response rate to anti-PD1 therapy in these patients was observed; however, these responses were not durable in most patients. Notably, tumor frameshift mutation proportion (FSP) was identified as a novel biomarker that was associated with prolonged response to anti-PD1 therapy in this cohort. This finding was validated in a separate cohort of patients with nonprostatic dMMR cancers of various primary histologies. This works suggests that FSP predicts response to anti-PD1 therapy in dMMR cancers, which should be validated prospectively in larger independent cohorts.


Extraction and characterisation of pigment from Yanzhiguo [Prunus napaulensis (Ser.) Steud.].
Yanzhiguo [Prunus napaulensis (Ser.) Steud] belongs to Rosaceae family and is consumed as wild fruit, pulp and juice. However, its potential for extracting natural pigment has not yet been explored. Herein, the components in the fresh Yanzhiguo pulp were preliminarily analyzed by liquid chromatography coupled to mass spectrometry. And, the optimal pre-treatment conditions were established for further extraction of Yanzhiguo pigment based on the a* value. Then, by combining the data from single-factor experiments and response surface methodology, the optimal extraction process was established as: 35% EtOH, a liquid-solid ratio of 200:1 mL g-1, an extraction time of 65 min, and an extraction temperature of 100 °C. Moreover, it was found that the a* value and yield had high fitness except when extracted into ethanol (EtOH) with different concentrations. Meanwhile, our result demonstrated Yanzhiguo pigment had high stability in general environments with carmine (a synthetic pigment) as control, except for extreme environments such as direct (hot) sunlight, high temperature (75 °C) and strong alkaline (pH ≥ 11). Also, Yanzhiguo pigment exhibited good antioxidant activity. Our results contribute to more information on Yanzhiguo pigment and promote its application by providing efficient extraction technology.


Efficient visible-light-driven hydrogen evolution and Cr(VI) reduction over porous P and Mo co-doped g-C3N4 with feeble N vacancies photocatalyst.
Developing highly efficient and inexpensive photocatalysts without noble metals, yet remarkably enhancing hydrogen production and Cr(VI) reduction activity, is highly needed. Here, the effective photocatalytic H2 evolution under visible light from an Eosin Y (EY)-sensitized (P, Mo)-g-C3Nx system by avoiding any noble metal co-catalyst is reported by the first time. Meanwhile, the optimized sample also displays the excellent performance in photocatalytic hexavalent chromium (Cr(VI)) reduction. In addition, this composite exhibits delectable stability for photocatalytic activities, no significant decay of activity is being observed after 16h reaction for photocatalytic H2 evolution (8h for Cr(VI) reduction). It is believed that this work will open up a new route for fabricating high-performance and inexpensive photocatalysts for hydrogen production and Cr(VI) reduction.


Decreased expression of Hsp27 and Hsp70 in transformed lymphoblastoid cells from patients with spinocerebellar ataxia type 7.
Spinocerebellar ataxia type 7 (SCA7) is caused by an expansion of unstable CAG repeats within the coding region of the novel gene, ataxin-7, on chromosome 3. This disease is also associated with an accumulation of abnormal proteins, including expanded polyglutamine-containing proteins, molecular chaperones, and the ubiquitin-proteasome system. In this study, two SCA7 lymphoblastoid cell lines (LCLs) with 100 and 41 polyglutamine repeats were utilized to examine the effects of polyglutamine expansion on heat shock proteins. Interestingly, under basal conditions, Western blot and immunocytochemical analysis showed a significant decrease of Hsp27 and Hsp70 protein expression in cells containing expanded ataxin-7, as compared with that of the normal LCL. On the other hand, the protein levels of Hsp60 and Hsp90 were not significantly altered in the mutant LCLs. Results from semi-quantitative RT-PCR indicated that the differences in Hsp70 protein levels were due to transcriptional defects while the reduction of Hsp27 in the mutant cells was not caused by transcriptional defects. Our results further demonstrated that despite of defective protein expression of Hsp27 and Hsp70, a normal heat shock response was observed in lymphoblastoid cells expressing mutant ataxin-7. Taken together, our results indicated that expanded ataxin-7 that leads to neurodegeneration significantly impaired the expression of Hsp27 and Hsp70 protein, which may be, at least in part, responsible for the toxicity of mutant ataxin-7 proteins and ultimately resulted in an increase of stress-induced cell death.


Impacts of land surface model and land use data on WRF model simulations of rainfall and temperature over Lake Tana Basin, Ethiopia.
The Weather Research and Forecasting (WRF) model is one of the regional climate models for dynamically downscaling climate variables at finer spatial and temporal scales. The objective of this study was to evaluate the performance of WRF model for simulating temperature and rainfall over Lake Tana basin in Ethiopia. The WRF model was configured for six experimental setups using three land surface models (LSMs): Noah, RUC and TD; and two land use datasets: USGS and updated New Land Use (NLU). The performances of WRF configurations were assessed by comparing simulated and observed data from March to August 2015. The result showed that temperature and rainfall simulations were sensitive to LSM and land use data choice. The combination of NLU with RUC and TD produced very small cold bias (0.27 °C) and warm bias (0.20 °C) for 2m maximum temperature (Tmax) and 2m minimum temperature (Tmin), respectively. WRF model with RUC and NLU captured well the observed spatial and temporal variability of Tmax, while TD and NLU for Tmin. Moreover, rainfall simulation was better with NLU; especially NLU and Noah configuration produced the smallest mean bias (2.39 mm/day) and root mean square error (6.6 mm/day). All the WRF experiments overestimated light and heavy rainfall events. Overall, findings showed that the application of updated land use data substantially improved the WRF model performance in simulating temperature and rainfall. The study would provide valuable support for identifying suitable LSM and land use data that can accurately predict the climate variables in the Blue Nile basin.


Attitudes of French adolescents toward sexuality.
Three hundred and eighty-six French adolescents from 16 to 18 years of age (145 boys and 241 girls) were questioned about sexuality. The five questions used covered their opinions on: abortion, masturbation, sexual intercourse during adolescence, homosexuality and marriage. The comparison of their responses to the five questions was expected to bring out the differences in their reactions in these areas. In fact, the results revealed that the subjects were not concerned to the same degree by the five questions. It was also observed that few adolescents were completely "liberal" and even fewer completely "conservative". The importance of socio-cultural factors, especially religion, associated with the attitudes of the subjects appeared undeniable. Some interesting differences in attitudes expressed by the two sexes were brought out.


Effect of laser and environmental parameters on reducing microbial contamination of stainless steel surfaces with Nd:YAG laser irradiation.
The effect of laser (pulse repetition frequency, pulse energy and exposure time) and environmental parameters (pH, NaCl concentration and wet or dry samples) of Nd:YAG laser decontamination of stainless steel inoculated with Escherichia coli, Staphylococcus aureus and Listeria monocytogenes was investigated. Stainless steel discs were inoculated with the bacterial samples and exposed to laser energy densities to about 900 J cm(-2). These inactivation curves allowed selection of laser parameters for two-level multifactorial designed experiments, the results of which allowed comparisons to be made between effects of individual and combined parameters on the laser inactivation efficiency. Escherichia coli was inactivated most effectively as a wet film with L. monocytogenes and S. aureus showing similar response. For the multifactorial experiments all laser parameters were significant and were smallest for S. aureus as a wet film. pH and NaCl concentration had little effect on the efficacy of laser inactivation but dry or wet states and all laser parameters were significant. Such systems may prove to be applicable in industrial processes where stainless steel may be contaminated with acidic solutions or salt, e.g. in the food industry with laser inactivation seeming to be independent of these parameters. Parameters have been identified that allow optimization of the treatment process.


High prevalence of Mycoplasma genitalium in women presenting for termination of pregnancy.
Sexually transmitted infections increase the risk of postoperative complications after termination of pregnancy. Mycoplasma genitalium is sexually transmitted and associated with adverse clinical outcomes in both males and females. The prevalence of M. genitalium is not yet known in New Zealand women or among women presenting for termination of pregnancy. This study involved prospective data collection at a public hospital clinic for termination of pregnancy. Participants were 300 under 25-year-old women presenting for termination of pregnancy. The study aimed to describe the prevalence of M. genitalium in women presenting for termination of pregnancy using real-time polymerase chain reaction (PCR) testing. Women provided a vaginal swab that was sent to the laboratory for PCR detection of M. genitalium. Data collection included age, ethnicity, previous pregnancy history, gestational age, procedure type, results of STI tests performed on referral for a termination of pregnancy (C. trachomatis, N. gonorrhoeae, T. vaginalis and bacterial vaginosis) and use of antimicrobials in the past 3 weeks. M. genitalium was detected in 26 women (8.7%). Rates of infection did not differ significantly by patient characteristics such as age, ethnicity or previous pregnancies. Infection with M. genitalium was not significantly associated with bacterial vaginosis or C. trachomatis infection. To our knowledge, this is the first prospective study designed to determine the prevalence of M. genitalium in women presenting for termination of pregnancy. Given the high proportion of cases observed in this study, further research is needed to determine the clinical significance of M. genitalium in postoperative termination of pregnancy complications.


Pediatric bilateral ureteral stone successfully removed using single-use flexible ureteroscopy with a holmium: YAG laser.
A 12-year-old boy received steroid for his minimal change nephrotic syndrome for 10 years, and bilateral renal and ureteral stones and hydronephrosis were observed. Single-use flexible ureteroscopy is usable for pediatric lithotripsy with Ho: YAG laser.


Response hierarchy models and their application in health and medicine: understanding the hierarchy of effects.
Successful patient engagement pursuits naturally require healthcare providers to possess a detailed understanding of their target audiences, with one of the most important processes to comprehend being the manner in which they learn about particular establishments and decide to extend their patronage. While health services patronage pathways vary between and among consumers, general patronage patterns exist which can provide enlightenment regarding this important process. Achieving knowledge on this front can help healthcare providers maximize opportunities to engage audiences and acquire all-important market share. The discipline of marketing, in part, focuses on customer engagement practices and, in describing the patronage process, it often uses what are referred to as response hierarchy models. Also known as hierarchy of effects models, these representations can help healthcare providers to understand the course through which individuals become customers of given establishments, aiding them particularly in devising appeals that can accelerate the patronage process. This particular article describes response hierarchy models, presents examples, and discusses the benefits that they offer healthcare institutions in their efforts to engage patients. As institutional viability and vitality are predicated on abilities to successfully attract and retain patients, healthcare establishments must direct keen attention toward developing associated skills. This necessitates that health and medical providers possess a detailed understanding of their target audiences, notably including the stages through which they pass on their way to becoming patrons. Response hierarchy models present the patronage process, depicting given stages, permitting insights which can assist healthcare providers in their quests to hasten desired exchange and capture market share.


Anatomic and functional characteristics of the rat ileal pouch.
The definitive operation for chronic ulcerative colitis (UC) and familial adenomatous polyposis is total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Mild inflammation (pouchitis) is omnipresent in pouches and becomes severe in 50% of UC patients with IPAA. The etiology of pouchitis is likely due to combined genetic, microbial, and immunologic factors. Epithelial cell exposure to surgical trauma and/or to changes in intestinal bacterial composition may account for the inflammatory infiltrate. Progress in understanding pouchitis is restricted by the lack of suitable animal models. An ileal pouch-rectal anastomosis [IPRA] in rats was developed to reproduce a model of human IPAA and clinical, gross and histologic criteria were determined. Many shared features with human ileal pouch were observed. IPRA is an important in vivo model to study mechanisms of repair, defense and immunity that may contribute to pouchitis.


Clinicopathologic features of the mixed epithelial and mesenchymal type metaplastic breast carcinoma with myoepithelial differentiation in a subset of six cases.
Metaplastic carcinoma (MC) of the breast, consisting of epithelial and mixed epithelial-mesenchymal tumors, are extremely rare human neoplasms. They are mostly detected between the 5th and 7th decade and have an unfavorable prognosis. Therefore, it is of utmost important to find out the behavior and also the immunohistochemical (IHC) profile of these tumors. In the current study, the aim was to examine 6 cases of MC with detailed clinico-pathological variables of cancer, follow-up and IHC profile of several antigens. The following immunohistochemical markers were used: MNF116, vimentin, CD10, smooth muscle actin (SMA), estrogen/progesterone receptors and HER-2/neu. The mean age was 39.1 the mean size was 3.3 cm. 83% of the cases had spindle cell sarcoma-like areas. Two of six cases also had a chondrosarcoma-like component. The epithelial component was invasive ductal carcinoma in all. MNF116, vimentin, CD10, and SMA expressions were as follows: mesenchymal cells: 33%, 100%, 50%, 83%, epithelial cells: 100%, 50%, 33%, 0%. All were triple negative. 66.6% presented with the axillary lymph node metastases. The mean follow-up period was 51 months, 50% died of the disease. Two had distant metastases to the lung. Our series which only included mixed epithelial-mesenchymal type metaplastic carcinoma of the breast showed myoepithelial differentiation with a worse prognosis.


NFK prevent postoperative abdominal adhesion through downregulating the TGF-β1 signaling pathway.
Postoperative abdominal adhesions (PAAs) represent a frequent condition occurring in more than 90% of patients undergoing abdomen and pelvic surgeries, which can cause chronic abdominal pain, female infertility, and repeated bowel obstruction, requiring repetitive surgical interventions causing morbidity and mortality, as well as high costs. It is therefore of paramount clinical importance and significance to develop practical and reliable strategies for preventing the occurrence of PAAs. In this study, we demonstrated that Nianfukang (NFK, composed of polyethylene glycol 1450 and diclofenac sodium) is highly effective in preventing PAAs, likely by reducing leukocytes and inflammatory factors in the abdominal cavity, and inhibiting intestinal fibrosis in a rat model of PAAs induced by postoperative cecum scraping. We further uncovered that NFK downregulates the expression of TGF-β1, a key factor for adhesion formation, to suppress the TGF-β1/TGF-βRIII/Smad2 signaling pathway, thereby inhibiting the proliferation and migration of fibroblasts and provided evidences for the involvement of the TGF-β1/TGF-βRIII/Smad2 axis in the prevention of PAAs in normal human colon fibroblast CCD-18Co. Our findings support NFK as a potential anti-adhesive product that has the advantages of significant effectiveness, safety profile, and low cost, as well as clear mechanism of action.


Comparison of various short noise exposures in albino and pigmented guinea pigs.
Albino and pigmented guinea pigs were exposed to 20 kHz at 120 dB SPL for exposure durations of 30, 7.5, 6.5, 5 and 3.25 min. In a second series of experiments, the two shortest exposures were repeated after an interval of 6 or 24 h. Sensory hair cell loss was assessed 3 weeks post-exposure by surface preparations and quantified as percentage cell loss per segment per row, total numbers of outer and inner hair cells lost and the area of total outer hair cell damage. A variable but discrete area of damage resulted from these exposures. The main differences between the two strains were that in albino guinea pigs fewer ears were damaged after the shortest single exposures and generally more damage occurred after repeated exposures. However, no differences were detected in either strain when the interval between repeated exposures was changed.


The aetiology of optic atrophy in Nigerians--a general hospital clinic study.
This study aimed at reviewing cases presenting with optic atrophy at the eye clinic of the University College Hospital, Ibadan, Nigeria with a view to identifying some of the diagnostic problems. The study was a retrospective review of 100 cases selected by systematic random sampling method of a total of 6160 patients presenting with optic atrophy to the eye clinic over 6 years (April 1990 to March 1996). Diagnosis was based on ophthalmoscopic appearance of optic disc corroborated with visual field studies. The mean age of the patients was 40.8 years. The male to female ratio was 2:1 bilateral. Eighty percentages were bilateral, whereas 20% were unilateral. Only in 38% of cases could the cause of the optic atrophy be identified. The most frequently diagnosed were cranio-orbital neoplasms (8%), those referable to trauma (8%), hydrocephalus (7%), retinitis pigmentosa (3%) and post infectious (2%). Other causes include toxins, congenital, seizure disorders, birth asphyxia and papilloedema. In 62% of cases, the aetiology cannot be satisfactorily elicited. Some suggestions have been made to overcome some of these diagnostic problems.


Disposable biosensor based on platinum nanoparticles-reduced graphene oxide-laccase biocomposite for the determination of total polyphenolic content.
A disposable amperometric biosensor was developed for the detection of total polyphenolic compounds from tea infusions. The biosensor was designed by modifying the surface of a carbon screen-printed electrode with platinum nanoparticles and reduced graphene oxide, followed by the laccase drop-casting and stabilization in neutralised 1% Nafion solution. The obtained biosensor was investigated by scanning electron microscopy and electrochemical techniques. It was observed that platinum nanoparticles-reduced graphene oxide composite had synergistic effects on the electron transfer and increased the electroactive surface area of the carbon screen-printed electrode. The constructed analytical tool showed a good linearity in the range 0.2-2 μM for caffeic acid and a limit of detection of 0.09 μM. The value of Michaelis-Menten apparent constant was calculated from the electrochemical version of Lineweaver-Burk equation to be 2.75 μM. This disposable laccase biosensor could be a valuable tool for the estimation of total polyphenolic content from tea infusions.


DAPLE orchestrates apical actomyosin assembly from junctional polarity complexes.
Establishment of apicobasal polarity and the organization of the cytoskeleton must operate coordinately to ensure proper epithelial cell shape and function. However, the precise molecular mechanisms by which polarity complexes directly instruct the cytoskeletal machinery to determine cell shape are poorly understood. Here, we define a mechanism by which the PAR polarity complex (PAR3-PAR6-aPKC) at apical cell junctions leads to efficient assembly of the apical actomyosin network to maintain epithelial cell morphology. We found that the PAR polarity complex recruits the protein DAPLE to apical cell junctions, which in turn triggers a two-pronged mechanism that converges upon assembly of apical actomyosin. More specifically, DAPLE directly recruits the actin-stabilizing protein CD2AP to apical junctions and, concomitantly, activates heterotrimeric G protein signaling in a GPCR-independent manner to favor RhoA-myosin activation. These observations establish DAPLE as a direct molecular link between junctional polarity complexes and the formation of apical cytoskeletal assemblies that support epithelial cell shape.


Latent anaphylactic sensitivity of infants to cow's milk proteins. Histamine release from blood basophils.
Approximately 25% of infants tested released greater than 9% of their blood basophil histamine content in the presence of cow's milk proteins, indicating a degree or level of latent anaphylactic sensitivity to these allergens. Approximately 10% of infants show a considerably higher level of sensitivity (14-63% histamine release). These findings fulfil an essential tenet of the modified anaphylactic hypothesis for cot-death.


Exploring physical literacy in children aged 8 to 12 years old: a cross-cultural comparison between China and Greece.
The concept of physical literacy (PL) has been advocated as a crucial determinant for increasing the quality and quantity of movement and physical activity (PA). Children's PL has been rarely compared across countries, although it has shown low levels in many countries. This study aimed to explore and compare children's PL from China and Greece. A total of 327 Chinese (47.1% boys) and 295 Greek children (48.1% boys) aged 8 to 12 years participated in this study. Children's PL was objectively assessed by the Chinese and Greek version of the Canadian Assessment of Physical Literacy, 2nd edition, which consists of four domains: Daily Behavior, Physical Competence, Motivation and Confidence, and Knowledge. and Understanding. Univariate analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) on total PL and domain scores were conducted in both countries, respectively. MANOVA revealed significant differences in total PL and distribution scores between two countries (Pillais' trace = 0.260, F = 53.855, p < 0.001, η2 = 0.260), with Greek children scoring better than Chinese. Nevertheless, most children failed to present an adequate PL level as they were mostly in the "progressing" stage. The chi-square denoted that the distribution of Chinese and Greek participants across the CAPL-2 interpretive categories was statistically different for total PL (χ2 [3] = 18.726, p < 0.001, Cramer's V = 0.174), with more Greek children being classified as "achieving" and "excelling". The variance between Chinese and Greek children may be attributed to cultural differences in the context of PA, such as PE policies and settings. The relatively low level of PL shown in both countries echoes the global trend of the declining PA among children, with an increasing amount of their time spent in a sedentary lifestyle. These findings highlight the need to consider children's cultural factors and pedagogical strategies in terms of developing their PL. Future research is required to explore the impact of cultural background on PL development among children and appropriate strategies to migrate their influence.


Evaluation of the automated 'Enzymen-Test Anti HIV-1 + 2' and 'Enzymen-Test Anti HIV-1/2 selective' for the combined detection and differentiation of anti-HIV-1 and anti-HIV-2 antibodies.
A new, modular automated ELISA (test 1) for HIV-1 and HIV-2 antibody detection and differentiation (Enzymun-Test Anti HIV-1 + 2; anti HIV 1/2 selective, Boehringer Mannheim) was compared with 3 alternative enzyme immunoassays (Abbott recombinant HIV-1/HIV-2 3rd generation EIA, Abbott (test 2); Enzygnost HIV 1 + 2, Behringwerke (test 3); and Wellcozyme HIV recombinant, Murex (test 4)) and Western blot (New LAV I Blot and New LAV II Blot; Diagnostics Pasteur). 380 serum samples from HIV-1 and HIV-2 seropositive patients at different stages of disease, high risk individuals, patients with conditions unrelated to AIDS and from healthy blood donors were used in this evaluation along with 6 seroconversion panels, 6 serum dilution series and 'tricky' sera (repeatedly positive results in ELISA, but negative or undeterminate in Western blot; n = 67). Using the Western blot as reference assay, the overall sensitivity of the four ELISAs was 100%. Test 4 showed the highest sensitivity for antibody detection in seroconversion and dilution series. A high specificity was achieved with test 1 (100%) and test 2 (99.4%). A relatively high rate of false positive results were obtained with test 2 (n = 12) and test 3 (n = 10) by testing 'tricky' sera or samples obtained from healthy blood donors. In comparison to Western blot, a clear differentiation between HIV-1 and HIV-2 antibody serum samples was achieved with the Enzymun-Test. The results of the present study show that the Enzymun-Test provides reliable selective HIV-1 and HIV-2 antibody detection at a cost which is significantly lower than the costs of Western blot tests. Furthermore, the evaluation of test 1 suggests, that it is a highly specific assay for HIV antibody detection.


Interferon and interferon inactivators in patients with acquired immune deficiency syndrome and Kaposi's sarcoma. A preliminary report.
The interferon system has been implicated in the diagnosis and potential treatment of acquired immune deficiency syndrome (AIDS). In our study of AIDS patients we have identified the presence of circulating serum interferon inactivator(s). These interferon inactivators were not detected in AIDS prodrome patients or in patients with classical Kaposi's sarcoma. The evidence suggests that interferon inactivators may play a role in the clinical manifestation of AIDS.


Efficacy of oltipraz in preventing acetaminophen-induced liver injury in mice.
Oltipraz (OPZ) is a synthetic dithiolethione with potential as a cancer chemopreventive agent, which can work by inducing detoxification enzymes. OPZ is an activator of nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting its involvement in enzyme induction and possible protection against drug-induced liver injury. In this study, we present OPZ-mediated protection of mice against acetaminophen (APAP)-induced liver injury and discuss its possible contributing factors. Overnight-fasted male CD-1 mice were administered APAP intraperitoneally, and some mice were administered OPZ 16 h before APAP. Hepatotoxicity was assessed by measuring serum alanine aminotransferase leakage and histopathological evaluation. The hepatic mRNA expressions of CYP2E1, glutamate cysteine ligase (GCL), and NAD(P)H:quinone oxidoreductase (NQO1) were measured by real-time reverse-transcription polymerase chain reaction. OPZ protected mice from APAP-induced liver injury in a dose-dependent manner, but did not alter hepatic glutathione (GSH) content or GCL expression in control mice, indicating that its hepatoprotective effect is not due to changes in basal GSH levels. OPZ did not affect CYP2E1 expression or APAP-induced early GSH depletion, suggesting it does not inhibit the metabolic activation of APAP to produce N-acetyl-p-benzoquinone imine. In contrast, after GSH depletion, OPZ accelerated hepatic GSH recovery. APAP significantly increased GCL expression during liver injury, but OPZ treatment only led to additional NQO1 expression. This suggests that NQO1 is responsible for the enhanced GSH recovery and protection against APAP-induced liver injury seen in OPZ-treated mice. In summary, OPZ protects against APAP-induced liver injury by inducing NQO1 expression and resulting in improved GSH recovery.


Pseudo-QT prolongation, artifactual electrocardiographic patterns produced by transduction of cardiovascular motion.
Four cases are presented in which focal electrocardiographic artifacts mimicked QT segment prolongation with giant T and U waves. Displacement of the recording electrode by a subjacent cardiovascular impulse was the cause of this distortion. The artifacts could be reproduced at the bedside by intentional changes in patient posture and electrode stability. Phasic variation in electrode contact with the electrolyte gel and skin, or intermittent contact between the heart and chest wall, causes shifts in the electrical properties of the recording system which may distort the recorded waveforms during the repolarization phase of the electrocardiogram.


The human rights-based approach to sustainable development: Lessons from recent African investment treaty practice.
This paper provides a non-exhaustive analysis of the human rights-based approach to sustainable development (HRBA to SD) contained in the Draft Pan African Investment Code (Draft PAIC), the Southern African Development Community Model BIT (SADC Model BIT), and 37 Bilateral Investment Treaties (BIT) concluded by African countries between 2017 and 2021. The analysis was conducted through an analytical framework that breaks down the investors' human rights responsibility into five key analytical elements: the duty-bearer, the content of human rights obligation, the legal force of the standards, the enforcement of the human rights obligation and the legitimacy of the HRBA to SD. This paper shows that the HRBA has resulted in the linking of investment protection, the incorporation of mandatory human rights, and the promotion of SD goals in some African investment instruments. The paper also suggests that the HRBA to SD has limited influence on treaty practice, as it is adopted by a limited number of intra-African BITs. It appears that the HRBA as adopted in African investment treaty practice has a moderate influence on achieving SD objectives. This article is a valuable contribution to the literature on sustainable development, on "Africanization of international investment law", and on the responsibility of corporations in relation to human rights.


Plasmonic Ag decorated graphitic carbon nitride sheets with enhanced visible-light response for photocatalytic water disinfection and organic pollutant removal.
Photocatalytic disinfection with high performance is thought to be a promising way for water purification. Herein, plasmonic Ag doped urea-derived graphitic carbon nitride (g-C3N4) composites were fabricated via in-situ photo-deposition at room temperature as the visible-light photocatalyst. Scan electron microscopy and transmission electron microscopy images showed the uniform dispersion of Ag nanoparticles on the surface of g-C3N4 sheet, which facilitated the synergistic effect of antibacterial performance from Ag and photocatalytic property from Ag/g-C3N4 composites. Photocatalytic water disinfection against Escherichia coli with visible light was performed to demonstrate the improved photocatalytic property with assistance of Ag. The 3-Ag/g-C3N4 exhibited the best bactericidal performance by inactivating all bacteria within 120 min with damaged cell membranes of Escherichia coli observed by scan electron microscopy and transmission electron microscopy images. Photoluminescence spectra, steady-state surface photovoltage spectra, photocurrent response, and electrochemical impedance spectra results revealed that Ag nanoparticles inhibited the recombination of photo-generated e- and h+ pairs and further reinforced the photocatalytic performance of g-C3N4. Scavenger experiments indicated that h+ produced on valence band of g-C3N4 dominated the photocatalytic disinfection process against Escherichia coli. This work further proved Ag/g-C3N4 showed great potential in photocatalytic water disinfection under visible-light irradiation.


Stimulation-induced Ca(2+) influx at nodes of Ranvier in mouse peripheral motor axons.
In peripheral myelinated axons of mammalian spinal motor neurons, Ca(2+) influx was thought to occur only in pathological conditions such as ischaemia. Using Ca(2+) imaging in mouse large motor axons, we find that physiological stimulation with trains of action potentials transiently elevates axoplasmic [C(2+)] around nodes of Ranvier. These stimulation-induced [Ca(2+)] elevations require Ca(2+) influx, and are partially reduced by blocking T-type Ca(2+) channels (e.g. mibefradil) and by blocking the Na(+)/Ca(2+) exchanger (NCX), suggesting an important contribution of Ca(2+) influx via reverse-mode NCX activity. Acute disruption of paranodal myelin dramatically increases stimulation-induced [Ca(2+)] elevations around nodes by allowing activation of sub-myelin L-type (nimodipine-sensitive) Ca(2+) channels. The Ca(2+) that enters myelinated motor axons during normal activity is likely to contribute to several signalling pathways; the larger Ca(2+) influx that occurs following demyelination may contribute to the axonal degeneration that occurs in peripheral demyelinating diseases. Activity-dependent Ca(2+) signalling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca(2+)] indicator revealed that during repetitive action potential stimulation, [Ca(2+)] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca(2+)] elevations (∼ 0.1 μm with stimulation at 50 Hz, 10 s) were blocked by removal of Ca(2+) from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca(2+) channels and reverse mode Na(+)/Ca(2+) exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca(2+)] elevations, which now included a prominent contribution from L-type Ca(2+) channels. These results suggest that the peri-nodal axolemma of motor axons includes multiple pathways for stimulation-induced Ca(2+) influx, some active in normally-myelinated axons (T-type channels, NCX), others active only when exposed by myelin disruption (L-type channels). The modest axoplasmic peri-nodal [Ca(2+)] elevations measured in intact motor axons might mediate local responses to axonal activation. The larger [Ca(2+) ] elevations measured after myelin disruption might, over time, contribute to the axonal degeneration observed in peripheral demyelinating neuropathies.


Prediction of seebeck coefficient for compounds without restriction to fixed stoichiometry: A machine learning approach.
The regression model-based tool is developed for predicting the Seebeck coefficient of crystalline materials in the temperature range from 300 K to 1000 K. The tool accounts for the single crystal versus polycrystalline nature of the compound, the production method, and properties of the constituent elements in the chemical formula. We introduce new descriptive features of crystalline materials relevant for the prediction the Seebeck coefficient. To address off-stoichiometry in materials, the predictive tool is trained on a mix of stoichiometric and nonstoichiometric materials. The tool is implemented into a web application (http://info.eecs.northwestern.edu/SeebeckCoefficientPredictor) to assist field scientists in the discovery of novel thermoelectric materials. © 2017 Wiley Periodicals, Inc.


The Tubing, Hitch and Lasso, Intussusception Anchor (THALIA) Technique: A Novel Approach to Fixate the Penile Implant Reservoir.
Penile implant reservoir herniation or migration after inflatable penile prosthesis (IPP) placement may occur with standard or submuscular placement. Additionally, fixating the tubing in patients with retained reservoirs may be helpful for future prosthetic surgeons. We describe a novel technique to fixate IPP reservoirs in the preferred position. We present our preferred technique to fixate IPP reservoirs to prevent migration or herniation. We evaluated our success in preventing reservoir herniation or migration. 35 cases successfully underwent our new technique. 30 cases involved reservoirs that were thought to be at a high risk for migration. 5 cases were performed in non-infected retained reservoir scenarios where a reasonable attempt at removal either failed or was considered high risk. No immediate reservoir or infectious complications occurred. Mean follow-up was 5 months. The technique extended the case time by 5-10 minutes. Our novel technique is feasible, and although further follow-up and power are needed, fixating the pump tubing may reduce reservoir complications. Yang D, Heslop D, Houlihan M, et al. The Tubing, Hitch and Lasso, Intussusception Anchor (THALIA) Technique: A Novel Approach to Fixate the Penile Implant Reservoir. J Sex Med 2021;18:224-229.


Membrane defects in paramyotonia congenita (Eulenburg).
Membrane potentials, current-voltage relationships, and component conductances were determined in resting excised external intercostal muscle fibers from five patients with paramyotonia congenita. At 37 degrees C all investigated parameters were normal. At 27 degrees C the resting potentials decreased to about -40 mV, and the fibers were inexcitable. At this stage the membrane currents were much larger than in normal fibers owing to increases in the membrane conductances for Na and Cl ions. The earlier finding that in the cold the Na permeability is abnormally large was confirmed. The Cl permeability was shown to be normal even in the cold. The decrease of the resting potential and the changes in the current-voltage relationship at 27 degrees C could be prevented by the use of the Na channel blocker tetrodotoxin (TTX) or by bathing the fibers in a Na-free solution. Our previous conclusion that the Cl conductance at 27 degrees C was also increased when TTX was present was not confirmed. Exposure of a muscle bundle to 7 mmol/l potassium did not lead to excessive depolarization and paralysis.


Osteopontin increases the proliferation of neural progenitor cells.
We examined the role of osteopontin in the proliferation of neural progenitor cells in vitro. Osteopontin increased the proliferation of neural progenitor cells in the presence of FGF2 as measured by cell proliferation assay and bromodeoxy uridine incorporation studies. In addition, immunoblot analysis demonstrated an increase in the phosphorylation of retinoblastoma protein with a concurrent increase in the content of phospho-Akt and cyclin D1. These results indicate that osteopontin can upregulate the content of phospho-Akt, cyclin D1 and phospho-Rb to subsequently enhance the proliferation of neural progenitor cells in the presence of FGF2.


TLR2 as a Therapeutic Target in Bacterial Infection.
Toll-like receptor (TLR) 2 recognizes and responds to threats early in bacterial infections and can influence the downstream immune response to the host's benefit or detriment. Therapeutic modulation of TLR2 signaling represents an underutilized opportunity to moderate the immune response to infection to promote an improved outcome for the host.


Behavioral versus process consultation interventions in school settings.
Teachers experiencing difficulties in managing disruptive, acting-out children in two parochial first-grade classes were provided either behavioral or process consultation. The behavioral intervention included discussions of behavior modification principles, feedback concerning contingent praise, and individualized behavioral interventions. In contrast, the process consultant used clarifying, supportive, and reflective responses to help the teacher better understand classroom difficulties and enhance her ability to work with problem children. Results of the interventions indicated that during consultation sessions and follow-up, problem behaviors were significantly reduced and attention to desirable behaviors significantly increased. The results were observed in three problem children in the classroom provided with behavioral consultation, and there only. Both teachers rated problem children as being less disruptive following program involvement. Significant positive relations were found between directly observed and teacher ratings of problem behaviors.


Technique for liver separation using the modified liver hanging maneuver (LHM) in a case of thoraco-omphalopagus conjoined twins.
Conjoined twins are rare, high-stakes cases requiring complex management. This report presents thoraco-omphalopagus conjoined twins who shared parts of liver and abdominal wall. The main obstacle in separating these patients was liver fusion. Two-year-old female conjoined twins presented with liver fusion between segments 2 and 3 in twin A and segments 2 and 4A in twin B. Liver separation was performed using the modified liver hanging maneuver. After separating the triangular ligaments and surrounding adhesions, a 12-Fr Foley catheter was inserted under the fused liver, suspending it upward and producing a clear separation plane. Liver separation required only 32 min. No notable bleeding or bile leakage was observed. The liver hanging maneuver was originally used as an adjunct technique for liver tumor hepatectomy. We used this technique to separate the fused livers in conjoined twins. The advantages of LHM include potentially reducing excess manipulation, which may result in parenchyma and vascular pedicle injury, and facilitating bleeding control, thereby reducing the operation time. The liver hanging maneuver using a conventional Foley catheter is a simple and useful method for separating fused livers in conjoined twins.


The Emerging Role of Epicardial Ablation.
Sosa and colleagues first described a percutaneous approach (via the subxiphoid area) to access the pericardial space in 1996. Epicardial mapping and ablation is increasingly used for the treatment of supraventricular and ventricular arrhythmias and represents an adjunctive approach for challenging arrhythmias to improve procedural success rates. Epicardial ablation should be considered not only after the failure of an endocardial ablation but often as a first-line approach. Complications may occur during percutaneous access and epicardial ablation, and these might be reduced or avoided by improved operator skills and experience. New tools to access the epicardial space are being evaluated.


Coordination molecular hats binding acetonitrile via C-H...pi interactions.
The [M(3)L(3)](3+) metallo-macrocycles with syn, syn, syn conformation, self-assembled from crown ether functionalized 1,10-phenanthroline Pd(II) nitrates with naphthanoimidazole, bind a solvent CH(3)CN within the naphthanoimidazolate-built cavity through C-H...pi interactions in the crystalline state.


House dust mite control measures for asthma: systematic review.
The major allergen in house dust comes from mites. We performed a systematic review of the randomized trials that had assessed the effects of reducing exposure to house dust mite antigens in the homes of people with mite-sensitive asthma, and had compared active interventions with placebo or no treatment. Fifty-four trials (3002 patients) were included. Thirty-six trials assessed physical methods (26 mattress covers), 10 chemical methods and eight a combination of chemical and physical methods. Despite the fact that many trials were of poor quality and would be expected to exaggerate the reported effect, we did not find an effect of the interventions. For the most frequently reported outcome, peak flow in the morning (1565 patients), the standardized mean difference was 0.00 (95% confidence interval (CI) -0.10 to 0.10). There were no statistically significant differences in number of patients improved (relative risk 1.01, 95% CI 0.80-1.27), asthma symptom scores (standardized mean difference -0.04, 95% CI -0.15 to 0.07) or in medication usage (standardized mean difference -0.06, 95% CI -0.18 to 0.07). Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended.


Usefulness of the Rapid Office Strain Assessment (ROSA) tool in detecting differences before and after an ergonomics intervention.
Most ergonomics studies on office workstations evaluate the effects of an intervention only by subjective measures such as musculoskeletal pain and discomfort. Limited evidence has been provided regarding risk factor reduction in office environments through standardized methods assessments. The Rapid Office Strain Assessment (ROSA) tool can provide an estimation of risk factor exposure for office workers as a means by which the outcome of interventions can be quantified. The aim of the study was to evaluate if ROSA scores reflect changes in risk factors after an ergonomics intervention among office workers. Office workers (n = 60) were divided into two groups. The experimental group received a workstation intervention and the control group received no intervention. Changes in ROSA scores were compared before and after the intervention in both groups. Statistically significant reductions in the ROSA final and section scores occurred after the intervention in the experimental group with (mean reduction of 2.9, 0.8 and 1.6 points for sections A, B and C, respectively). In contrast, no differences were detected in the control group (mean increase of 0.1 point for sections A and C and mean reduction of 0.1 point for Section B). These findings show that ROSA scores reflect changes in risk factors after an ergonomics intervention in an office environment. Consequently, this tool can be used for identifying and controlling risk factors among computer workers, before and after interventions.


Thyroid Hormones in Hemolymph of Red King Crabs from the Barents Sea.
Only a few studies have reported the presence and levels of thyroid hormones in invertebrates. At the same time, the administration of these hormones has been shown to be a profitable method for inducing growth in crustaceans. Knowledge of thyroid hormone concentrations is required to involve this approach in crustacean aquaculture. For this reason, we examined hemolymph samples of the invasive red king crab Paralithodes camtschaticus from the Barents Sea population for the levels of triiodothyronine (T3) and thyroxine (T4). Radioimmunoassays indicated that T3 ranged from 0.26 to 1.55 μg dL-1, whereas T4 varied from 52 to 203 μg dL-1. Adult crabs demonstrated higher levels of T3 than juveniles, while juvenile crabs had higher levels of T4 in comparison to larger conspecifics. The thyroxine levels were consistent throughout the study period. In contrast, significant seasonal variations were found for T3. In immature crabs, the maximum concentration was found in October, whereas in adult crabs, the highest level of T3 was registered in August. Most likely, these results are explained by changes in physiological conditions of the crabs associated with their molting calendar and migration activity. Our data may have important implications for aquaculture of Paralithodes camtschaticus in the Barents Sea.


A review on the use of lichens as a biomonitoring tool for environmental radioactivity.
Lichens have been widely used as a biomonitoring tool to record the distribution and concentration of airborne radioactivity and pollutants such as metals. There are limitations, however: although pollutants can be preserved in lichen tissues for long periods of time, not all radioactive and inert elements behave similarly. The chemical species of elements at the source, once captured, and the mode of storage within lichens play a role in this biomonitoring tool. Lichens are a symbiotic association of an algal or cyanobacterial partner (photobiont) with a fungal host (mycobiont). Lichens grow independently of the host substrates, including rocks, soils, trees and human-made structures. Lacking a root system, lichen nutrient or contaminant uptake is mostly through direct atmospheric inputs, mainly as wet and dry deposition. As lichens grow in a large variety of environments and are resilient in harsh climates, they are adapted to capture and retain nutrients from airborne sources. The context of this review partially relates to future deployment of small modular reactors (SMRs) and mining in remote areas of Canada. SMRs have been identified as a future source of energy (electricity and heat) for remote off-grid mines, potentially replacing diesel fuel generation facilities. For licensing purposes, SMR deployment and mine development requires capabilities to monitor background contaminants (natural radioactivity and metals) before, during and after deployment, including for decommissioning and removal. Key aspects reviewed herein include: (1) how lichens have been used in the past to monitor radioactivity; (2) radiocontaminants capture and storage in lichens; (3) longevity of radiocontaminant storage in lichen tissues; and (4) limitations of lichens use for monitoring radiocontaminants and selected metals.


Synthesis and evaluation of a new phosphorylated ribavirin prodrug.
Ribavirin is an important broad-spectrum antiviral drug. However, its utilization can be limited by its potential to cause hemolytic anemia as well as its variability in dosing levels and efficacy outcomes. To overcome these issues, we report on a new alkoxyalkylphosphodiester prodrug of ribavirin (2) that is designed to release the active ribavirin-monophosphate species selectively in nucleated cells while limiting its exposure in anucleated red blood cells (RBCs). Prodrug 2 displays improved in vitro antiviral activity against the hepatitis C virus replicon and influenza virus. Unlike ribavirin, prodrug 2 does not significantly decrease ATP levels in RBCs. Prodrug 2 demonstrates decreased uptake in RBCs but increased uptake in HepG2 hepatocytes when compared to ribavirin. In vivo, prodrug 2 is orally bioavailable and well-tolerated in rats in which it is processed to ribavirin and accumulates in the liver. These results indicate that prodrug 2 has the potential for safer, lower, less frequent, and less variable administration than ribavirin.


COVID-19 reinfection: A multicenter retrospective study in Saudi Arabia.
There are limited direct data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) long-term immune responses and reinfection. This study aimed to evaluate the rate, risk factors, and severity of COVID-19 reinfection. This retrospective cohort study included five hospitals across Saudi Arabia. All subjects who were presented or admitted with positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) tests were evaluated between March 2020 and August 2021. Reinfection was defined as a patient who was infected followed by clinical recovery, and later became infected again 90 days post first infection. The infection was confirmed with a positive SARS-CoV-2 (RT-PCR). Four hundred and seventeen recovered cases but with no reinfection were included as a control. A total of 35,288 RT-PCR-confirmed COVID-19 patients were observed between March 2020 and August 2021. Based on the case definition, (0.37%) 132 patients had COVID-19 reinfection. The mean age in the reinfected cases was 40.95 ± 19.48 (range 1-87 years); Females were 50.76%. Body mass index was 27.65 ± 6.65 kg/m2; diabetes and hypertension were the most common comorbidities. The first infection showed mild symptoms in 91 (68.94%) patients; and when compared to the control group, comorbidities, severity of infection, and laboratory investigations were not statistically different. Hospitalization at the first infection was higher, but not statistically different when compared to the control group (P = 0.093). COVID-19 reinfection is rare and does not carry a higher risk of severe disease. Further studies are required, especially with the continuously newly emerging variants, with the unpredictable risk of reinfection.


Facial palsy following cochlear implantation.
Owing to its anatomical location, the facial nerve (FN) is at risk of damage during cochlear implantation, especially during posterior tympanotomy. The aim of this study was, therefore, to evaluate the risk of FN palsy following cochlear implantation surgery via mastoidectomy and posterior tympanotomy approach (facial recess). This is a retrospective study. The data bank of patients who received a cochlear implant between 2000 and 2012 was analyzed. 3403 surgeries were done during this period. Records of the patients who had suffered from FN palsy were evaluated and the type of FN palsy, the severity, time of onset, and need for revision surgery were recorded. 0.76 % (26/3403) of the patients had FN palsy and were, therefore, included in the study. 76.9 % (20/26) subjects were 18 years or older. 0.15 % (5 subjects) suffered from immediate FN palsy and 0.62 % (21 subjects) from delayed FN palsy. Intraoperative FN injury was documented in only three subjects of the immediate FN palsy group. In two subjects with immediate FN palsy, the FN was intraoperatively exposed but not injured, despite these individuals' experiencing FN palsy. In 100 % of the immediate onset FN palsy group a part of the FN was exposed during surgery, whereas it was exposed only in 9.5 % of the delay onset FN palsy group. Although the FN was bone protected in 19 subjects, they had FN palsy. Most of the subjects presented House-Brackmann grade III or IV (69.2 %). All of the subjects were treated initially with a conservative therapy, only 42.3 % (11 subjects) underwent revision surgery. The recovery rate was 80.8 % (in immediate onset palsy 40 %, in delayed onset palsy 90.5 %). Cochlear implantation entails only a minimal risk of FN palsy and that FN palsy is chiefly a transient problem.


Small and large artery elasticity indices in peripheral arterial occlusive disease (PAOD).
In peripheral arterial occlusive disease (PAOD), arterial compliance of the central arteries has been reported to be reduced. It is, however, not clear whether, in PAOD, decreased arterial compliance is also accompanied by similar changes in the peripheral arteries. Therefore the aim of the study was to determine the large (C1) and small (C2) artery elasticity indices in PAOD and their relations to its well-accepted characteristics (ankle-brachial index, ABI; pulse pressure, PP; absolute claudication distance, ACD). A total of 43 patients with PAOD (mean age 68 +/- 9 years; ABI of the limiting leg 0.65 +/- 0.14; SBP (systolic blood pressure) 149 +/- 20 mmHg, and ACD 488 +/- 187 m) were enrolled as well as 16 control subjects of comparable age (69 +/- 4 years) and blood pressure (SBP 147 +/- 27 mmHg). All subjects underwent non-invasive pulse wave analysis in order to determine arterial compliance of the aorta and major side branches (C1) and of the distal circulation (C2), using a modified Windkessel model. In PAOD, both C1 (1.41 +/- 0.56 ml/mmHg) and C2 (0.023 +/- 0.012 ml/mmHg) were comparable to values in an age and blood pressure-matched control group (C1, 1.25 +/- 0.66 ml/mmHg; C2, 0.027 +/- 0.008 ml/mmHg). C1 was significantly correlated with ACD (r = 0.36, p = 0.02), PP (r = -0.33, p < 0.02) and only borderline with ABI (r = 0.28, p = 0.07). C2 was correlated with PP (r = -0.38, p < 0.01), ABI (r = 0.36, p < 0.02) but not with ACD. Large (C1) and small (C2) artery elasticity indices in PAOD were decreased but comparable to values in an elderly group with isolated systolic hypertension. Moreover, C1 and C2 correlated with markers (ABI and PP) of severity of vascular disease.


Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced autophagy of mouse Leydig TM3 cells in vitro.
As a plasticizer, plastic softener, and flame-retardant, tri-ortho-cresyl phosphate (TOCP) is and has been widely used in industry and reported to have a toxic effect on the male reproductive system in animals besides neurotoxicity and immunotoxicity. We have reported that TOCP inhibits spermatogenesis and induces autophagy of rat spermatogonial stem cells, but it is still unknown whether TOCP induces autophagy of mouse Leydig cells and its potential mechanism. Cell viability was observed by MTT assay. Level of testosterone was measured by radioimmunoassay. Apoptosis was observed by AnnexinV-FITC/PI assay. The contents of LC3, Atg5-Atg12, and Beclin 1 were detected by Western blotting analysis. Autophagosomes were investigated by transmission electron microscopy. The contents of MDA and GSH and the activities of SOD, GSH-PX, total antioxidant status (TAS) and total oxidant status (TOS) were measured by oxidative stress kits. The present study shows that TOCP markedly inhibited viability and testosterone output of mouse Leydig TM3 cells but had no effect on apoptosis. However, TOCP significantly increased both LC3-II and the ratio of LC3-II to LC3-I and the contents of autophagy proteins Atg5 and Beclin 1. Transmission electron microscopy (TEM) showed that TOCP increased autophagic vacuoles of the cytoplasm, indicating that TOCP could induce autophagy of the cells. TOCP significantly induced oxidative stress of mouse Leydig TM3 cells. H2O2 also inhibited viability and induced autophagy of the cells; however, inhibition of oxidative stress by N-acetyl-L-cysteine (NAC) could rescue the inhibition of cell viability and induction of autophagy by TOCP. The results show oxidative stress might be involved in TOCP-induced autophagy of mouse Leydig TM3 cells.


Comparative profiling of agr locus, virulence, and biofilm-production genes of human and ovine non-aureus staphylococci.
In a collaboration between animal and human health care professionals, we assessed the genetic characteristics shared by non-aureus staphylococci (NAS) infecting humans and dairy ewes to investigate their relatedness in a region concentrating half of the total National sheep stock. We examined by PCR 125 ovine and 70 human NAS for biofilm production, pyrogenic toxins, adhesins, autolysins genes, and accessory gene regulator (agr) locus. The microtiter plate assay (MPA) was used for the phenotypic screening of biofilm production. Ovine NAS included S. epidermidis, S. chromogenes, S. haemolyticus, S. simulans, S. caprae, S. warneri, S. saprophyticus, S. intermedius, and S. muscae. Human NAS included S. haemolyticus, S. epidermidis, S. hominis, S. lugdunensis, S. capitis, S. warneri, S. xylosus, S. pasteuri, and S. saprophyticus subsp. bovis. Phenotypically, 41 (32.8%) ovine and 24 (34.3%) human isolates were characterized as biofilm producers. Of the ovine isolates, 12 were classified as biofilm-producing while the remaining 29 as weak biofilm-producing. All 24 human isolates were considered weak biofilm-producing. Few S. epidermidis isolates harbored the icaA/D genes coding for the polysaccharide intercellular adhesin (PIA), while the bhp, aap, and embp genes coding biofilm accumulation proteins were present in both non-producing and biofilm-producing isolates. Fifty-nine sheep NAS (all S. epidermidis, 1 S. chromogenes, and 1 S. haemolyticus) and 27 human NAS (all S. epidermidis and 1 S. warneri) were positive for the agr locus: agr-3se (57.8%) followed by agr-1se (36.8%) predominated in sheep, while agr-1se (65.4%), followed by agr-2se (34.6%) predominated in humans. Concerning virulence genes, 40, 39.2, 47.2%, 52.8, 80 and 43.2% of the sheep isolates carried atlE, aae, sdrF, sdrG, eno and epbS respectively, against 37.1, 42.8, 32.8, 60, 100 and 100% of human isolates. Enterotoxins and tsst were not detected. Considerable variation in biofilm formation ability was observed among NAS isolates from ovine and human samples. S. epidermidis was the best biofilm producer with the highest prevalence of adhesin-encoding genes.


Depression and thoughts of self-harm and suicide among people living with dementia: results of a cross-sectional survey.
Depression is common among people with dementia. Despite most people with dementia living in the community, there have been few investigations of self-reported depressive symptoms and suicidal ideation among community-dwelling people with dementia in Australia. This study aimed to explore the proportion of people with mild, moderate and severe levels of depressive symptoms, and suicidal ideation among a sample of people living with dementia in Australia. Correlates of reporting depressive symptoms were also explored. Adults diagnosed with dementia by a medical professional who were English speaking and community-dwelling were asked to complete a paper and pencil survey. Those who were unable to provide independent consent were excluded. Depression was assessed using the Geriatric Depression Scale -15, and suicidal ideation was assessed using two study-specific items. Multivariable analyses examined quality of life, unmet needs and sociodemographic factors associated with having a score of five or more on the Geriatric Depression Scale-15. Ninety-four people participated in the study. Thirty-seven percent (n = 35) reported some level of depressive symptoms, with most of these (21%, n = 20) classified as having mild depressive symptoms. Five participants (5%) reported they had had thoughts of being better off dead or hurting themselves, while three (3%) reported having had a plan to end their life. For each additional unmet need, the odds of being depressed increased by 25%(P < 0.001). For each point increase in quality of life, the odds of being depressed decreased by 48% (P < 0.001). The high proportion of people with dementia who report depressive symptoms suggests the need to routinely assess depressive symptoms among this group. There may also be benefits in assessing unmet needs and addressing these where possible as part of an approach to reducing depression among people living with dementia in the community.


Physicochemical characteristics of non-electrolytes and their uptake by Brugia pahangi and Dipetalonema viteae.
The uptake of a diverse set of 14C-labelled non-electrolytes by Brugia pahangi and Dipetalonema viteae was measured relative to the free diffusion of tritiated water. Inulin was used as a non-absorbable surface marker to account for non-electrolyte adherent to the surface of the parasite which had not crossed the cuticle. B. pahangi and D. viteae took up the non-electrolytes to a similar degree; a comparison of tissue uptake indices gave a correlation coefficient of 0.99. Worm uptake could not be described by non-electrolyte octanol/aqueous partition coefficients alone. However, greater success was achieved using further descriptors and pattern recognition techniques for data analysis. The whole molecule descriptors log P, molar refraction, melting point, dipole moment and CNDO total energy were obtained from computer chemistry and the literature. Using a linear learning machine to relate uptake to these 5 physicochemical descriptors it was possible to successfully classify non-electrolytes as high or low uptake. Multivariate regression analysis of uptake versus these 5 parameters gave a correlation coefficient of 0.77. However, this was not statistically significant and therefore could not be used for quantitative predictions of substance uptake by worms. This illustrates the value of 'pattern recognition' techniques such as the linear learning machine. Using such 'pattern recognition' methods on a chemically related set of compounds it is anticipated that predictions of uptake can be achieved and improved upon. Such predictions could then be used in drug design.


Effect of a Neonatal Abstinence Syndrome Training Program on Nurses' Confidence and Ability to Use the Finnegan Scoring Tool.
To study the impact of an educational training program about neonatal abstinence syndrome (NAS) on the accuracy and reliability of NAS scoring by neonatal nurses when using the Finnegan Scoring Tool (FST), as well as the impact of training on nurses' confidence when using the FST. Pilot project based on the Plan-Do-Study-Act framework with a pretest-posttest design. Although nurses at this agency receive training on the FST as part of their unit orientation education, there is not currently a program for assessing their confidence and accuracy when using this tool over time. A convenience sample of registered nurses from the mother-baby (n = 11), NICU (n = 5), and pediatrics (n = 1) units. Nurses watched a video of a neonate, used the FST to score the neonate's withdrawal symptoms, and completed a rating of their self-confidence when using the tool before and after an educational training session and at a 2- to 4-week follow-up session. Participants improved to at least 90% interobserver reliability from the pretraining (64.7%) to posttraining (94.1%) assessments. No participants maintained 90% at follow-up. There appears to be a correlation between years of neonatal experience with tool confidence at pretraining (r = 0.52, N = 17, p < .04), posttraining (r = 0.52, N = 17, p < .03), and follow-up (r = 0.56, N = 17, p < .02) assessments. Pretraining reliability had a positive correlation to follow-up reliability (r = 0.51, p < .04). There was a statistically significant increase in confidence from before the training (mean = 2.06, standard deviation = 0.56) to after (mean = 2.47, standard deviation = .51; t[16] = -3.3, p < .004 [two-tailed]). Although participants reported feeling confident when using the scoring tool, they did not always accurately score symptoms. Participants reported positive buy-in and the need for additional training. Advanced training in NAS and the FST may help nurses improve NAS symptom detection and contribute to better neonatal health outcomes.


Clothing as a potential exposure source of trace elements during early life.
In recent years, the interest in determining the chemical composition of textile products has increased among the scientific community and regulatory agencies, driven by toxicological issues and environmental concerns. Chemical elements are naturally present in clothing as natural fibers or intentionally added during manufacture. Some of them show physical-chemical properties that allow their absorption through the skin. In addition, chronic situations increase the dermal exposure capacity. Because of age-specific behavioral characteristics and underdeveloped physiological function, children may be especially sensitive to exposure to trace elements. This study aimed to analyze the levels of twenty trace elements in 120 clothing items commercialized in Spain. Textile products for pregnant women and children <36 months old were included. The potential health implication of this dermal exposure in early life was also evaluated. Aluminum, zinc, and titanium showed the highest concentrations, with median levels of 27.6, 5.6, and 4.2 mg/kg, respectively. Since chromium is employed as a metal complex dye in synthetic fibers, high levels of this element were found in black polyester. Dermal exposure to titanium, which is a ubiquitous element in clothes made of synthetic fibers, was associated with a hazard quotient (HQ) higher than the threshold value (HQ > 1), with values of 1.13 for pregnant women and 1.22 for newborns. On the other hand, HQ values of other elements and cancer risks were lower than the recommended values. Assessing early-life exposure to toxic elements can help to identify potential sources and to prevent or reduce human exposure, mainly in vulnerable groups.


Second-hand tobacco smoke in prison: tackling a public health matter through research.
This action-research study conducted in a Swiss male post-trial detention centre (120 detainees and 120 staff) explored the attitudes of detainees and staff towards tobacco smoking. Tackling public health matters through research involving stakeholders in prisons implies benefits and risks that need exploration. The observational study involved multiple strands (quantitative and qualitative components, and air quality measurements). This article presents qualitative data on participants' attitudes and expectations about research in a prison setting. Semi-structured interviews were used to explore the attitudes of detainees and staff towards smoking before and after a smoke-free regulation change in the prison in 2009. Specific coding and thematic content analysis for research were performed with the support of ATLAS.ti. In total, 77 interviews were conducted (38 before the regulation change and 39 after the regulation change) with 31 detainees (mean age 35 years, range 22-60 years) and 27 prison staff (mean age 46 years, range 29-65 years). Both detainees and staff expressed satisfaction regarding their involvement in the study, and wished to be informed about the results. They expected concrete changes in smoke-free regulation, and that the research would help to find ways to motivate detainees to quit smoking. Active involvement of stakeholders promotes public health. Interviewing detainees and prison staff as part of an action-research study aimed at tackling a public health matter is a way of raising awareness and facilitating change in prisons. Research needs to be conducted independently from the prison administrators in order to increase trust and to avoid misunderstandings.


Regional profile of developmental changes in the sensitivity of the N-methyl-D-aspartate receptor to polyamines.
The NMDA receptor exhibits increased sensitivity to stimulation during early development compared with the adult. In this study, we examined modulation of the NMDA receptor by polyamines during development to see if it correlates with differences in the functional responsiveness of the NMDA receptor. [3H]MK-801 binding was measured in discrete brain regions in the presence and absence of polyamines in 3-, 7-, 15-, 25-, and 60-day-old Sprague-Dawley rats. [3H]MK-801 binding increased between postnatal days 3 and 15, with adult levels of binding being reached between days 15 and 25. Spermidine (75 microM) caused maximal stimulation of [3H]MK-801 binding during early development, ranging from 250% in the thalamus to 450% in the caudate putamen at postnatal day 3. This effect gradually declined to levels seen in the adult by postnatal days 15-25. During all developmental stages, the stimulation seen was greater in the caudate putamen compared with the hippocampus. Diethylenetriamine (1 mM) exhibited similar developmental and regional heterogeneity in its effects on [3H]MK-801 binding, producing substantial stimulation of binding in the neonate, but not in the adult. The EC50 and Emax values for the stimulatory effect of spermidine were significantly higher at day 7 compared with the adult. Unlike spermidine and diethylenetriamine, there was no regional variation in the effects of the putative "polyamine site" inverse agonist 1,10-diaminodecane at any age and only a slightly attenuated inhibition at postnatal day 3 compared with the adult.(ABSTRACT TRUNCATED AT 250 WORDS)


Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications.
The terpenoids constitute the largest class of natural products and many interesting products are extensively applied in the industrial sector as flavors, fragrances, spices and are also used in perfumery and cosmetics. Many terpenoids have biological activities and also used for medical purposes. In higher plants, the conventional acetate-mevalonic acid pathway operates mainly in the cytosol and mitochondria and synthesizes sterols, sesquiterpenes and ubiquinones mainly. In the plastid, the non-mevalonic acid pathway takes place and synthesizes hemi-, mono-, sesqui-, and diterpenes along with carotenoids and phytol tail of chlorophyll. In this review paper, recent developments in the biosynthesis of terpenoids, indepth description of terpene synthases and their phylogenetic analysis, regulation of terpene biosynthesis as well as updates of terpenes which have entered in the clinical studies are reviewed thoroughly.


[Discrepancy between arthrography and arthrotomy with posterior lesions of the medial meniscus (author's transl)].
In 102 cases with arthrographic proven lesion of the medial meniscus clinical, radiological and operative results were correlated. In 10% the lesion could not be found by arthrotomy. These were all cases with lesions in the posterior part of the meniscus, mostly at the basis. It must be assumed, that the posterior portion of the medial meniscus cannot be judged completely by arthrotomy, especially if a ventral approach is used.


Predictors of failure after endocardial resection for sustained ventricular tachycardia.
This study was designed to identify characteristics that might be predictors of failure of surgical treatment alone (endocardial resection) for sustained ventricular tachycardia. Thirty-three consecutive patients with sustained ventricular tachycardia were studied by standard techniques preoperatively, intraoperatively, and 7 to 36 days postoperatively. Standard endocardial resection was guided by intraoperative mapping in all patients. Adjuvant cryoablation was used in areas that were not accessible to excision. Patients were divided into two groups on the basis of the results of the postoperative electrophysiologic study. Group I (14) were patients who still had ventricular tachycardia (failure) and Group II (19) were those who did not have ventricular tachycardia (success). On the basis of the postoperative electrophysiologic testing, the time from myocardial infarction to surgical treatment (less than 3 months) was a powerful predictor of failure of operation alone to prevent ventricular tachycardia (p less than 0.01). This may indicate a different mechanism of ventricular tachycardia in this group of patients. Another possible predictor of surgical failure was three-vessel disease. The site of origin of ventricular tachycardia, the use of cryoablation, the number of morphologies, and the amount of tissue resected were not significant predictors of success or failure. The result of the postoperative electrophysiologic study was also a strong prognostic predictor of subsequent arrhythmias.


The importance of atomic partial charges in the reproduction of intermolecular interactions for the triacetin - a model of glycerol backbone.
Lipids play a central role within the cell. They not only encompass it but are also engaged in many processes such as cellular transport and energy production. Despite ongoing advances in experimental studies, computer simulations are a viable method to trace their behavior at the atomic level and on an elusive time scale. In molecular modeling studies, the quality of the obtained results is associated with the considered force field and its parameters. In the present work, the authors have investigated the procedure of partial charges fitting on the example of a triacetin molecule, containing chemical moieties present in the glycerol backbone. The goal of the study was to validate assigned partial charges based on the quality of the torsion profiles using optimally assigned torsional coefficients and reproduction of the condensed phase properties of triacetin. We applied various approaches and noticed a significant improvement in the parameterization of triacetin compared to the original one. The results showed that it is important to take into account the intermolecular interactions in the partial charges fitting procedure to obtain good quality validation results.


Extreme rainfall trends of 21 typical urban areas in China during 1998-2015 based on remotely sensed data sets.
With the increase of population, many cities are growing in size at a phenomenal rate. Urbanization changes the urban underlying surface, influences the micro-climate, and sometimes affects the local precipitation process. In this study, we investigated the trends of extreme rainfall in China's 21 typical urban areas. Based on a series of daily rainfall and "Urban/built-up" dataset from TMPA 3B42 and MCD12Q1 products in China, trends in extreme precipitation, with the threshold defined as 95th (pre95p) and 99th (pre99p) percentiles of annual rain days during 1998-2015, have been assessed in China, and especially in 21 typical urban areas from 1998 to 2015. The tendency curves in extreme rainfall of different years are presented. In this period, more than 66% regions of China covered by TMPA 3B42 have increasing trends in extreme rainfall with pre95p threshold. The 21 typical urban areas showed different trends-in over half of these areas, upward tendencies in extreme rainfall were observed, particularly in Dalian, Beijing, and Chongqing. Seventeen urban areas showed increasing tendencies in pre95p extreme rainfall days, including Shanghai, Nanjing, Hangzhou, and Suzhou in the Yangtze River Delta region. The results also illustrate that southeastern coastal urban areas of China may have experienced decreasing occurrences in extreme rainfall.


Assessment of difficulties encountered in psychiatric follow-up studies.
To assess some of the socio-cultural reasons hindering psychiatric follow-up studies in Iran, 107 depressed patients were followed up for a period of about 3 years. Home visits were made, following two successive letters to which only five patients replied. Forty-five patients were interviewed, nine had moved, four refused interviewing, two were dead and the addresses or names of 47 were wrong. Wrong names and addresses, and behind them the illiteracy, change of address and the stigma of mental illness were the major causes of untraceability; the patients are inaccurate in giving their address and they may use one or another of their several names, surnames and nicknames. To make follow-up studies feasible, and as the patients and their relatives are the main sources of information, a more efficient registration system should be developed, with due respect to the characteristics of the population, to ensure having complete and correct names and addresses and to ensure patients' continual contact with the office.


QSAR study of flavonoid derivatives as p56lck tyrosinkinase inhibitors.
QSAR studies on 104 flavonoid derivatives as p56lck protein tyrosine kinase inhibitors were performed using hydration energy and logP as predictor parameters. The results obtained demonstrate in detail, which specify that hydration energy and hydrophobic parameters of the compounds play a significant role in developing QSAR models. The significance of presence and absence of substituents on particular position is successfully explored with the help of indicator parameters. The results are critically discussed on the basis of multiple linear regression parameters.


Successful Treatment of Corneal Opacification with Associated Thickened Epithelium by Simple Peeling: Acquired Corneal Subepithelial Hypertrophy (ACSH).
To study clinical and histopathological findings of corneal opacification caused by thickened epithelium leading to reduced vision and topographical changes and to evaluate the outcome of its removal. Twelve patients (17 eyes) with central, paracentral or peripheral corneal opacification were reviewed to obtain their visual acuity, describe their slit lamp (SL) appearance (depth, extent and density) and document their topographic changes before and after peeling of the epithelium under SL or surgical removal under the microscope. Specimens of six cases were available for histopathological examination and immunohistochemical staining. Most of the eye opacifications were secondary to corneal procedures in 10 [Penetrating keratoplasty (PKP) in 7 for congenital glaucoma, keratoconus or adherent leukoma - usually over graft-host junction -, Photorefractive keratectomy (PRK) in 2 and Phototherapeutic keratectomy in one], chronic inflammation following trachoma or non-specific causes (3), and herpetic scar (1). Three cases were considered to be idiopathic. All cases presented with decreased vision, astigmatism or changes in topography or refraction. Their vision, clinical symptoms and topography improved after treatment. Histopathologically, all six cases shared findings that are similar to what have been described as peripheral hypertrophic subepithelial corneal degeneration (PHSCD) rather than Salzmann's nodular degeneration. None of the cases showed inflammation or subepithelial pannus formation in the excised tissue. However, our cases did not fit into the diagnosis of PHSCD because of the location of the corneal opacification (being peripheral in 41% of the corneas, the presence of underlying primary etiologic factors in 82% of the eyes and the bilateral occurrence in 5 patients. Meticulous SL examination aided by corneal imaging may accurately diagnose and determine the depth of corneal opacification as a cause for reduced vision. Histopathologically, the removed tissue is similar to PHSCD, but cases differ in their clinical profile. Peeling the thickened epithelial/subepithelial tissue is curative in most patients, improves visual and clinical outcome and avoids unnecessary corneal grafting.


Vitamin B12b enhances the cytotoxicity of dithiothreitol.
It has been found previously that vitamin B12b amplifies significantly the cytotoxic effects of ascorbic acid by catalyzing the formation of reactive oxygen species, and the antioxidant dithiothreitol (DTT), in contrast to catalase, does not prevent the cytotoxicity. Therefore, in this study we examined whether B12b is able to enhance the cytotoxicity of DTT. It was revealed that B12b strongly increases the cytotoxic effect of DTT. Vitamin B12b added to DTT catalyzed the generation and drastic accumulation of hydrogen peroxide in culture medium to a concentration of 260 microM within 7 min. The extracellular oxidative burst induced by the combination of B12b and DTT (DTT + B12b) was accompanied by intracellular oxidative stress, the destabilization of lysosomes, and damage to DNA. The accumulation of DNA lesions led to the initiation of apoptotic cell death, including the activation of caspase-3 and the release of cytochrome c. The antioxidants pyruvate and catalase completely prevented the DTT + B12b-induced oxidative stress and cell death. The iron chelators desferrioxamine and phenanthroline prevented the geno- and cytotoxic action of the combination although they did not reduce the exogenous oxidative burst, indicating a key role for intracellular iron in the cytotoxicity of the combination. Thus, vitamin B12b dramatically enhances the cytotoxicity of DTT, catalyzing the generation of hydrogen peroxide and inducing extra- and intracellular oxidative stress, early destabilization of lysosomes, and iron-dependent DNA damage.


Human cervicofacial mycetoma caused by Streptomyces griseus: First case report.
Streptomyces griseus causes subcutaneous mycetomas in felines and dolphins; however, human mycetoma caused by S. griseus has not previously been reported. Hereby, we report a case of a 50-year-old female presenting with swelling in the left upper cervical region and the left cheek that lasted for 6 months. The fine needle aspiration (FNA) performed on the swelling yielded purulent material; on microscopy, actinomycosis was diagnosed. On culturing, the pus grew S. griseus. To the best of our knowledge, this is the first reported case of human mycetoma caused by S. griseus.


Regrowth of granulocyte-macrophage progenitor cells (GM-CFC) in suspension cultures of bone marrow depleted of GM-CFC with 4-hydroperoxycyclophosphamide (4-HC).
The hematopoietic capacity of bone marrow treated with 4-hydroperoxycyclophosphamide (4-HC) was studied using long-term suspension cultures. It was shown that, in the presence of a previously established marrow adherent cell layer (ACL), the 4-HC treated bone marrow, deprived of GM-CFC, generates GM-CFC in long-term suspension cultures in vitro. The kinetics of GM-CFC reappearance in in vitro cultures indicate their origin from more primitive progenitors rather than from surviving GM-CFC. In the presented modification, the suspension culture system is useful in evaluating the transplantation potential of bone marrow purged in vitro with chemotherapeutic or biologic agents.


Silver nanoparticle-enriched diamond-like carbon implant modification as a mammalian cell compatible surface with antimicrobial properties.
The implant-bone interface is the scene of competition between microorganisms and distinct types of tissue cells. In the past, various strategies have been followed to support bony integration and to prevent bacterial implant-associated infections. In the present study we investigated the biological properties of diamond-like carbon (DLC) surfaces containing silver nanoparticles. DLC is a promising material for the modification of medical implants providing high mechanical and chemical stability and a high degree of biocompatibility. DLC surface modifications with varying silver concentrations were generated on medical-grade titanium discs, using plasma immersion ion implantation-induced densification of silver nanoparticle-containing polyvinylpyrrolidone polymer solutions. Immersion of implants in aqueous liquids resulted in a rapid silver release reducing the growth of surface-bound and planktonic Staphylococcus aureus and Staphylococcus epidermidis. Due to the fast and transient release of silver ions from the modified implants, the surfaces became biocompatible, ensuring growth of mammalian cells. Human endothelial cells retained their cellular differentiation as indicated by the intracellular formation of Weibel-Palade bodies and a high responsiveness towards histamine. Our findings indicate that the integration of silver nanoparticles into DLC prevents bacterial colonization due to a fast initial release of silver ions, facilitating the growth of silver susceptible mammalian cells subsequently.


Unsuspected primary cervical lymphoma presenting as "cervical fibroid": partial response to leuprolide acetate.
An unsuspected primary cervical lymphoma thought to be a cervical fibroid decreased in size dramatically after initiation of Leuprolide acetate prior to being correctly diagnosed during subsequent hysterectomy for uterine bleeding. This case represents the first reported successful use of Leuprolide acetate against a reticuloendothelial tumor.


A Review of Coronary Artery Thrombosis: A New Challenging Finding in COVID-19 Patients and ST-elevation Myocardial Infarction.
As the COVID-19 pandemic continues, more information on the nonrespiratory effects of the coronavirus is obtained. Cardiovascular complications, especially acute coronary syndromes, are rare. However, they prove to be effective factors in the mortality rate of COVID-19 subjects. Acute ST-elevation myocardial infarction with a special angiographic pattern in the form of extensive and multivessel thrombosis, regardless of atherosclerotic plaques, has posed a new therapeutic challenge. This has been associated with an increase in the incidence of stent thrombosis. Hypercoagulation, due to severe inflammation, is the main pathology of this phenomenon. Technically, percutaneous coronary intervention with aspiration thrombectomy and injectable antiplatelet are the mainstay of treatment for these patients. In addition, it is vital that appropriate antiplatelet and ischemia treatment after the intervention be taken into account.


The mannose receptor and other macrophage lectins.
The macrophage expresses a variety of cell surface lectins with activities that support specific functional roles and correspond to various differentiation states characteristic of this cell type. Recently, research has been carried out to investigate the mannose receptor, the advanced glycosylation end products receptor, the mannose-6-phosphate-receptor, the beta-glucan receptor, sialoadhesin and several galactose-specific binding proteins.


NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies.
Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) that further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders.


Bupleuri Radix Prevents the Recurrences of Resected Colonic Polyps by Affecting Angiogenin-2-Induced Protein Kinase B/Akt Signaling.
We aimed to explore the effects of Bupleuri Radix (BR) on the recurrence of resected colonic polyp (CP) by measuring angiogenin-2-induced protein kinase B (Ang PKB)/Akt signaling. The main ingredients of BR were extracted by using ethanol and measured by HPLC. One hundred twenty patients with CP >10 mm who underwent resected surgery were randomly allocated to an aspirin (AG) or a BR medicine (BG) group. The allocation ratio was 1 : 1 and the intervention duration was one year. The recurrence rate of resected CP was investigated and the plasma levels of Ang PKB/Akt and inflammatory cytokines were measured using ELISA kits. After one-year surgery, side effects were recorded. The relationship between the serum levels of the main compounds of BR and plasma levels of Ang PKB/Akt was analyzed. The main ingredients of CP are paeoniflorin, baicalin, saikosaponin A, and bupleurum saponin B2. Recurrence of resected CP was found in 17 patients from the AG group and eight patients from the BG group after one-year follow-up (p < 0.05). The levels of angiogenin-2 II and PKB/Akt in the AG group were higher than those in the BG group (p < 0.05). Meanwhile, BR treatment reduced the plasma levels of TNF-α, IL-1β, and IL-6, and increased the level of IL-10(p < 0.05). Inflammatory cytokines are important factors that affect the recurrence of resected CP. Serum paeoniflorin, baicalin, saikosaponin A, and bupleurum saponin B2 in BR had a strong negative relationship with the plasma levels of Ang PKB/Akt. BR significantly reduces the recurrence risk of resected CP by affecting Ang PKB/Akt signaling.


Early Holocene morphological variation in hunter-gatherer hands and feet.
The Windover mortuary pond dates to the Early Archaic period (6,800-5,200 years ago) and constitutes one of the earliest archaeological sites with intact and well-preserved human remains in North America. Unlike many prehistoric egalitarian hunter-gatherers, the Windover people may not have practiced a sex-based division of labor; rather, they may have shared the load. We explore how mobility and subsistence, as reconstructed from archaeological data, influenced hand and foot bone morphology at Windover. We took length and width measurements on four carpal bones, four tarsal bones, and load-bearing tarsal areas (calcaneus load arm, trochlea of the talus). We analyzed lateralization using side differences in raw length and width measurements. For other hypothesis testing, we used log transformed length-width ratios to mitigate the confounding effects of sexual dimorphism and trait size variation; we tested between-sex differences in weight-bearing (rear foot) and shock-absorbing (mid foot) tarsal bones and between-sex differences in carpal bones. We identified no significant between-sex differences in rear and midfoot areas, suggesting similar biomechanical stresses. We identified no significant between-sex differences in carpal bones but the test was under-powered due to small sample sizes. Finally, despite widespread behavioral evidence on contemporary populations for human hand and foot lateralization, we found no evidence of either handedness or footedness. The lack evidence for footedness was expected due its minimal impact on walking gait but the lack of evidence for handedness was surprising given that ethnographic studies have shown strong handedness in hunter-gatherers during tool and goods manufacture. The reconstructed activity patterns suggested both sexes engaged in heavy load carrying and a shared division of labor. Our results support previous findings-both sexes had stronger weight-bearing bones. Male shock-absorbing bones exhibited a trend towards greater relative width (suggesting greater comparative biomechanical stress) than females which may reflect the typical pattern of male hunter-gatherers engaging in walking greater distances at higher speeds than females. While there were no significant between-sex differences in carpal bones (supporting a shared work load model), females exhibited greater variation in index values, which may reflect a greater variety of and specialization in tasks compared to males. Because carpals and tarsals are so well-preserved at archaeological sites, we had surmised they might be useful proxies for activity in the absence of well-preserved long bones. Tarsals provide a stronger signal of past activity and may be useful in the absence of, or in addition to, preferred bones. Carpals, however, may not be useful as the effect size of biomechanical stress (in this study at least) is low and would require larger samples than may be possible at archaeological sites.


Prevalence of noncalcified coronary plaques by 64-slice computed tomography in patients with an intermediate risk for significant coronary artery disease.
In this prospective study, we investigated the prevalence and characteristics of clearly discernible noncalcified coronary plaques in a patient population with suspected significant coronary artery disease (CAD) by using 64-slice computed tomography (CT). The assessment of noncalcified coronary plaques by noninvasive strategies may be important to improve cardiovascular risk stratification. To rule out significant stenosis, high-resolution 64-slice coronary CT (0.6-mm collimation, 330-ms gantry rotation time) was performed in 161 consecutive patients with an intermediate risk for having CAD. Computed tomography data sets were evaluated for presence of coronary calcifications, noncalcified plaques, and/or lumen narrowing. Noncalcified coronary plaques were detected in 48 (29.8%) of 161 enrolled patients. Although noncalcified plaques together with coronary calcifications were present in 38 of 161 (23.6%) patients, the prevalence of noncalcified plaques as the only manifestation of CAD was 6.2% (10 of 161 patients). Patients with noncalcified plaques were characterized by significantly higher total cholesterol, low-density lipoprotein, and C-reactive protein levels as well as a trend for more diabetes mellitus. The majority of noncalcified plaques resulted in lumen narrowing of <50%. Of the remaining 113 patients, CAD and coronary calcifications were ruled out in 53 of 161 (32.9%) patients, whereas 60 of 161 (37.3%) patients presented with calcifications in the absence of noncalcified plaque. With the use of 64-slice CT, clearly discernible noncalcified atherosclerotic coronary plaques can be detected in a large group of patients with an intermediate risk for having CAD. The assessment of these plaques by CT angiography may allow for improved cardiovascular risk stratification.