Dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats.
We investigated the impact of dietary restriction on the basal rate of somatotrope renewal in the pituitary gland. Bromodeoxyuridine (BrdU), a thymidine analog, was administered continuously for 1 week in male F344 rats at 3, 8 and 20 months of age (mo), fed ad libitum (AL) or diet restricted from 1.5 mo (DR). Combined immunostainings for BrdU and GH visualized newly formed somatotropes as well as pituitary cells in tissue sections. The rate of incorporation of BrdU by anterior pituitary cells (BrdU-labeled nuclei/100 nuclei) was not influenced by the dietary regimen or age. The fraction of BrdU-labeled somatotropes relative to all labeled cells precipitously decreased to the same level in both dietary groups between 3 and 8 mo, although the fraction was greater in DR rats at 3 mo. In AL rats, the fraction decreased further between 8 and 20 mo, while it stabilized in DR rats. Our results suggested that dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats. Although one must also estimate the effects of dietary restriction on apoptotic cell death in pituitary cells, the present study provides evidence that dietary restriction modulates somatotropes cell turnover and preserves the cell population for GH secretion during aging.


Does bladder augmentation stabilize serum creatinine in urethral valve disease? A series of 19 cases.
This study evaluates the results of bladder augmentation (BA) in 19 boys with posterior urethral valves, especially as regards its efficacy in stabilizing serum creatinine. In the period 1995-2005, 188 patients with urethral valves were surgically managed. Nineteen of these had undergone BA as a part of their surgical management after initial endoscopic valve ablation in 15 and diversion in four boys. The mean serum creatinine at the time of BA was 2.11 mg/dl. BA stabilized the serum creatinine in 14 but failed to do so in five boys. A serum creatinine level of more than 2mg/dl at the time of BA was associated with a significantly worse rate of success. BA as part of an undiversion procedure in three boys was unsuccessful. In an economic milieu where renal transplantation is not available for the majority of deserving children, careful selection is required before BA is considered as a surgical solution for the valve bladder. BA, when otherwise indicated, has been beneficial in children with pre-augmentation creatinine up to 2 mg/dl.


Predictors of sexual function in pregnant Iranian adolescents.
Human sexual activity is one of the main aspects of life. The present study intended to determine the status of sexual function in pregnant adolescents at their second trimester of pregnancy and its predictive factors. This cross-sectional research studied 136 adolescents aged 15-19 years in their 24th-30th gestational weeks. All eligible pregnant adolescents in all 80 health centers of Tabriz, Iran were considered as the study samples. The data were collected using a socio-demographic questionnaire, the Female Sexual Function Index (FSFI) and the Conflict Tactics Scale (CTS2). A general linear model was used to determine the relationships between sexual function and socio-demographic characteristics and intimate partner violence (IPV). The frequency of sexual dysfunction in pregnant adolescents was about 65%. The mean [standard deviation (SD)] of total sexual function score was 25.3 (5.9) from the attainable score of 2-36. The pregnant adolescents obtained the lowest and the highest mean scores in the sexual desire and sexual satisfaction subscales, respectively. Shorter marital duration and IPV were sexual function predictors. Considering the high prevalence of sexual dysfunction in pregnant adolescent, and the impact of IPV on sexual function, midwives should take the necessary actions in identifying and consulting this disorder and IPV in their prenatal visits.


The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation.
With a 15% incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and is a poor prognostic factor. Immune checkpoint inhibitors (ICIs) as salvage therapy have modest activity in BTC. There are limited data on the efficacy of ICIs according to KRAS mutation in BTC. We evaluated the efficacy of ICIs in BTC patients with or without KRAS mutations. Retrospective observational study. We conducted molecular profiling in BTC patients who received ICIs as salvage therapy. The expression of programmed death ligand 1 (PD-L1) on tumor cells was assessed using immunohistochemistry. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to KRAS mutation and PD-L1 expression. A total of 62 patients were included in this analysis. The median age was 68.0 years; 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% received fluoropyrimidine plus oxaliplatin (FOLFOX) before ICI. The median number of lines of prior chemotherapy was 2.5. The KRAS mutation was found in 13 patients (19.1%), and 28 patients (45.2%) showed 1% or more of tumor cells out of visible tumor cells positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS with ICI were 5.6 [interquartile range (IQR): 3.3-8.0] and 3.8 (IQR: 3.0-4.5) months, respectively. There were no statistically significant differences in PFS with ICIs according to KRAS mutation (mutant type versus wild type) and PD-L1 expression (positive versus negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS compared with patients with KRAS mutation and PD-L1 negativity (10.1 versus 2.6 months, p = 0.047). This finding was not shown in patients with wild-type KRAS. Our analysis suggested that PD-L1 expression might be a useful biomarker for ICIs in BTC patients with KRAS mutation but not in those with wild-type KRAS.


Lack of association between peripheral neuropathy and HTLV-I infection in west Africa. Epidemiological, serological and nerve biopsy study.
Patients (n = 1166) with various neurological disorders hospitalized in Dakar, Abidjan, Lomé and Ouagadougou were examined prospectively over a 42-month period. Seropositivity for HTLV-I alone was found to be 1.8%, which is comparable to that estimated for the general population in Africa. Eighteen of the patients with TSP and only 5 with PN were HTLV-I positive, but co-infections were found in 30-40% of cases. Discrete and unspecific lesions were observed on light and electron microscopic examination of peripheral nerve biopsies from 11 patients. Since spastic paraparesis emerges as the disorder containing the largest number of HTLV-I-positive individuals, it may be premature to conclude that HTLV-I is a causal agent in PN. Nevertheless, their rarity and the frequency of retroviral co-infections distinguish these cases of African HTLV-I-associated myelopathy from comparable cases observed in other parts of the world.


Physiological and genome-wide RNA-sequencing analyses identify candidate genes in a nitrogen-use efficient potato cv. Kufri Gaurav.
Nitrogen (N) is an important nutrient for plant growth. However, its excess application leads to environmental damage. Hence, improving nitrogen use efficiency (NUE) of plant is one of the plausible options to solve the problems. Aim of this study was to identify candidate genes involved in enhancing NUE in potato cv. Kufri Gaurav (N efficient). Plants were grown in aeroponic with two contrasting N regimes (low N: 0.75 mM, and high N: 7.5 mM). Higher NUE in Kufri Gaurav was observed in low N based on the parameters like NUE, NUpE (N uptake efficiency), NUtE (N utilization efficiency) and AgNUE (agronomic NUE). Further, global gene expression profiles in root, leaf and stolon tissues were analyzed by RNA-sequencing using Ion Proton™ System. Quality data (≥Q20) of 2.04-2.73 Gb per sample were mapped with the potato genome. Statistically significant (P ≤ 0.05) differentially expressed genes (DEGs) were identified such as 176 (up-regulated) and 30 (down-regulated) in leaves, 39 (up-regulated) and 105 (down-regulated) in roots, and 81 (up-regulated) and 694 (down-regulated) in stolons. The gene ontology (GO) terms like metabolic process, cellular process and catalytic activity were predominant. Our RT-qPCR analysis confirmed the gene expression profiles of RNA-seq. Overall, we identified candidate genes associated with improving NUE such as superoxide dismutase, GDSL esterase lipase, probable phosphatase 2C, high affinity nitrate transporters, sugar transporter, proline rich proteins, transcription factors (VQ motif, SPX domain, bHLH) etc. Our findings suggest that these candidate genes probably play crucial roles in enhancing NUE in potato.


Arsenic in cooked rice: effect of chemical, enzymatic and microbial processes on bioaccessibility and speciation in the human gastrointestinal tract.
Rice, used as staple food for half of the world population, can easily accumulate arsenic (As) into its grain, which often leads to As contamination. The health risk induced by presence of As in food depends on its release from the food matrix, i.e., its bioaccessibility. Using an in vitro gastrointestinal simulator, we incubated two types of cooked rice (total As: 0.389 and 0.314 mg/kg). Arsenic bioaccessibility and speciation changes were determined upon gastrointestinal digestion. Washing with deionized water and cooking did not result in changes of As speciation in the rice although the arsenic content dropped by 7.1-20.6%. Arsenic bioaccessibility of the cooked rice in the small intestine ranged between 38 and 57%. Bioaccessibility slightly increased during digestion in the simulated small intestine and decreased with time in the simulated colon. Significant speciation changes were noted in the simulated colon, with trivalent monomethylarsonate (MMA(III)) becoming an important species.


Computer-aided information system to support direct patient care. The application of a hand-held data collector in a department of medicine.
In the pilot study, described herein, we have tried to develop a computerized system to assist and improve medical and nursing care. Our major goal was to bring the computer to the patient's bedside. This was achieved by a Hand-Held Data Collector, which is easy to carry and operate, and has a big enough memory. In this preliminary study, we have developed appropriate software specifically designed to reflect the daily activities and needs of a department of medicine. Using this software, we have demonstrated that all 'clinical events' and routine tasks of the department can be managed via the Hand-Held Data Collector.


Unusual presentation of appendiceal abscess on barium contrast studies.
The defect of an appendiceal abscess on a barium enema is most often seen on the medial aspect of the cecum. However, the site of involvement may vary depending on the location of the appendix. This paper illustrates some of the unusual radiographic findings that were found on barium enemas in six pediatric patients with appendiceal abscess that were not involving the medial cecum.


Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine.
This study has compared the effect of repeated administration of charcoal and cholestyramine on the elimination of piroxicam. Eight young adults were given piroxicam as a single dose of 20 mg, on 3 separate occasions. On one of the occasions charcoal was also given. On another occasion cholestyramine was also administered. The mean elimination half-life after piroxicam alone was 53.1 h. This was reduced to 40.0 h by charcoal administration and to 29.6 h after administration of cholestyramine. In the second phase of the study 7 elderly subjects received piroxicam 20 mg for 14 days on two occasions. Cholestyramine administration at the end of one of the periods reduced the mean elimination half-life of piroxicam from 52.3 h to 27.3 h.


Austrian syndrome: The deadly triad.
Austrian syndrome is a rare triad of endocarditis, meningitis, and pneumonia caused by Streptococcus pneumonia described by Robert Austrian in 1956. The incidence has reduced since the introduction of beta-lactam therapy in the early 1940s. Additionally, the introduction of the pneumococcal vaccination in 1977 further decreased the incidence of infection. Streptococcal endocarditis could potentially be very aggressive and life threatening despite appropriate therapy. It has a high mortality rate nearing 30 % even after proper antibiotics and surgical intervention. Therefore, an early recognition is crucial for early intervention and mortality reduction. We present a patient with Austrian syndrome who had a poor outcome despite proper management that is attributed to late presentation and delayed treatment.


The role of procalcitonin in identifying high-risk cancer patients with febrile neutropenia: A useful alternative to the multinational association for supportive care in cancer score.
The Multinational Association for Supportive Care in Cancer (MASCC) risk index has been utilized to determine the risk for poor clinical outcomes in patients with febrile neutropenia (FN) in an emergency center (EC). However, this index comprises subjective elements and elaborated metrics limiting its use in ECs. We sought to determine whether procalcitonin (PCT) level (biomarker of bacterial infection) with or without lactate level (marker of inadequate tissue perfusion) offers a potential alternative to MASSC score in predicting the outcomes of patients with FN presenting to an EC. We retrospectively identified 550 cancer patients with FN who presented to our EC between April 2018, and April 2019, and had serum PCT and lactate levels measured. Compared with patients with PCT levels <0.25 ng/ml, those with levels ≥0.25 ng/ml had a significantly higher 14-day mortality rate (5.2% vs. 0.7%; p = 0.002), a higher bloodstream infection (BSI) rate, and a longer hospital length of stay (LOS). Logistic regression analysis showed that patients with PCT levels ≥0.25 ng/ml and lactate levels >2.2 mmol/L were more likely to be admitted and have an LOS >7 days, BSI, and 14-day mortality than patients with lower levels. PCT level was a significantly better predictor of BSI than MASSC score (p = 0.003) or lactate level (p < 0.0001). Procalcitonin level is superior to MASCC index in predicting BSI. The combination of PCT and lactate levels is a good predictor of BSI, hospital admission, and 14-day mortality and could be useful in identifying high-risk FN patients who require hospital admission.


Maternal diet during pregnancy and risk of brain tumors in children.
Nine studies of childhood brain tumors and maternal diet during pregnancy have focused on foods related to the N-nitroso-compound(NOC) hypothesis. An association between frequent consumption of cured meat by pregnant women and increased risk is a consistent finding in most of the studies. The data on fruit and vegetable consumption are less consistent, but suggest decreased risk. Studies that assess all aspects of maternal diet during pregnancy are needed to determine whether the observed associations remain after adjustment for other aspects of diet. Such comprehensive studies also may elucidate other dietary factors that affect the risk of brain tumors in children.


Performance assessment framework for groundwater treatment plants in Arid Environments: a case of Buraydah, Saudi Arabia.
In arid environmental regions, such as the Kingdom of Saudi Arabia (KSA), each and every drop of groundwater needs to be efficiently utilized to meet growing water demands. Ground water treatment plants (WTPs) are regularly being monitored by the municipalities to ensure safe water supply. However, analyzing large data to assess the performance of a WTP has always been a daunting task for plant's management. Most of existing performance assessment frameworks were developed for surface WTPs. In this research, an assessment framework using performance-based water quality indices (P WQI) is developed to facilitate senior management of ground WTPs for effective decision-making. The framework is also implemented on a case study of Buraydah, Qassim, Saudi Arabia. Five most important water quality parameters (WQPs) have been selected to assess the performance of different components of the WTP, including raw water, pre-treatment, ultrafiltration, sand filtration, reverse osmosis, and final product. Depending on the relative importance of WQPs for a specific treatment process, different weighting schemes have been developed for each treatment process using fuzzy analytical hierarchical process (FAHP) to address the possible uncertainties in data and imprecision in expert opinion. Subsequently, fuzzy weighted sum method (FWSM) is employed to develop aggregated P WQI for assessing average monthly performance during the year 2016. Study results show that all the units consistently performed "high," and the plant is meeting drinking water quality standards throughout the year. Hypothetical scenario analysis revealed robustness of the developed framework by showing lacking performance in case failure of different units.


[Behavior of various serum enzymes following ligation of the superior mesenteric artery in the rat (preliminary report)].
In rats, shortly after ligation of superior mesenteric artery serum enzyme activities are found significantly altered. Those changes concern aspartate aminotransferase (GOT), alanine aminotransferase (GPT), lipase, alpha amylase, and isocitrate dehydrogenase as well as glutamate dehydrogenase. The causes are discussed. The authors emphasize that the assessment of serum enzymes possibly gives some help in diagnosing acute intestinal ischemias in early stages.


Multicenter evaluation of the bovine mesenteric vein bioprostheses for hemodialysis access in patients with an earlier failed prosthetic graft.
The number of patients requiring hemodialysis increases each year, with a large cohort of patients still requiring prosthetic grafts for hemodialysis. All available prosthetic vascular access grafts have predictable failure rates, leading to a large group of patients with multiple failed access grafts. This report evaluates use of mesenteric vein bioprosthesis (MVB) as a conduit for patients who have failed at least one earlier synthetic vascular access graft. Two-hundred seventy-six access grafts were implanted in patients who had at least one earlier failed synthetic graft. Of these grafts, 183 were MVB and 93 were synthetic. Graft histories were obtained from 128 of the 183 patients who received the MVB, representing a nonrandomized historic data set of previously failed grafts as an internal control group (INT). Patency was determined by Kaplan-Meier analysis, and the Cox proportional hazards model was used for multivariate analysis of factors predictive of effect. Primary patency at 12 months was 35.6% MVB versus 28.4% synthetic grafts. At 24 months, secondary patency was 60.3% MVB, 42.9% synthetic, and 18.0% INT (p < 0.0001, log- rank). Complication rates, including dilation, seroma, infection, and thrombosis, were all notably lower for the MVB compared with synthetic grafts by Cox regression (p < 0.001). Intervention rate per patient year was lower in the MVB group (0.97 versus 1.37) compared with synthetic grafts (p = 0.003). MVB provided superior secondary graft patency compared with both historic graft data or newly implanted nonrandomized synthetic implants. A considerable reduction in thrombosis, infection, and interventions was observed with the MVB graft. These results suggest that MVB offers a safe alternative to patients who have a history of failing synthetic access grafts and may represent an option for extending vascular access to this patient population.


Platysma flap using dual skin paddles.
The platysma myocutaneous flap is rarely reported as an option for reconstruction in the head and neck. In our experience it is a reliable flap that is easy to raise, has a limited risk of morbidity at the donor site, and allows for early recommencement of oral function. We report a patient with an unusually aggressive orocutaneous fistula that complicated the simple extraction of teeth. We modified the platysma flap to provide two independent skin paddles so we could reconstruct both the intraoral and cutaneous defects simultaneously with a good clinical outcome.


Retracted: Inhibition of miR-23a-3p promotes osteoblast proliferation and differentiation.
Retraction: 'Inhibition of miR-23a-3p promotes osteoblast proliferation and differentiation', by Yi Dai, Chunyan Zheng, Hao Li, J Cell Biochem. The above article, published online on 06 November 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.29497), has been retracted by agreement between the the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.


Autologous cartilage and fibrin sealant may be superior to conventional fat grafting in preventing physeal bone bridge formation - a pilot study in porcines.
The article compares physeal recovery after insertion of autologous cartilage and a conventional fat graft in a standardized porcine physeal gap model. Presence of a bone bridge was the primary outcome. Ten porcines in two groups of five were included in a paired design. A standardized physeal gap in the distal femur was made in all animals. One group (n = 5) was randomized for deposition of autologous cartilage and a Tisseel® or Tisseel® alone. The autologous cartilage was harvested from the femoral articular surface. The other group was randomized for fat grafting or no grafts at all. All animals were housed for 14 weeks. Magnetic resonance imaging (MRI) was performed at 14 weeks prior to euthanasia. The physis was harvested for histology. MRI - Three bone bridges were seen in the fat grafted gaps. All empty gaps formed a bone bridge. No gaps filled with autologous cartilage and Tisseel® resulted in bone bridges. One gap filled with Tisseel® only caused a bone bridge. Histology - The cartilage grafted gaps recovered with physeal-like cartilaginous tissue in histological analysis. Fat grafts seems ineffective in preventing bone bridges. The use of autologous cartilage may be superior to the current treatment. However, donor site complications were not investigated. The study serves as a proof of concept study and requires further investigation. III.


An epithelial cell line with elongated myoid morphology derived from bovine mammary gland. Expression of cytokeratins and desmosomal plaque proteins in unusual arrays.
Cells of a clonal line (BMGE + HM) selected from bovine mammary gland epithelial cell cultures are described which, after reaching confluence, do not assume typical epithelioid morphology, but form elongated cells with long slender processes extending over the surfaces of other cells. However, cells of this line which display non-epithelioid morphology and are exceptionally rich in actin microfilaments are identified as epithelial cells by their synthesis of cytokeratins and desmosomal plaque proteins, as demonstrated by immunofluorescence and immunoelectron microscopy and by gel electrophoresis of cytoskeletal proteins. The cells do not produce vimentin and desmin filaments. The specific cytokeratin polypeptides of these myoid cells are identical to those present in normal epithelioid BMGE + H cells but are arranged in unusual arrays of meshworks of finely dispersed, non-fasciated filaments and granular structures. Desmosomal plaque proteins, notably desmoplakins, are abundant, but the electron microscopic appearance of the desmosomes is abnormal in that most of them are associated with a second accessory plaque formed at a distance of 0.1-0.15 micron from the normal desmosomal plaque. Both cytokeratin filaments and desmosomal structures are found throughout the whole cytoplasm, including the extended cell processes. The existence of an epithelial cell line with such an unusual morphology demonstrates the importance of non-morphological criteria in identifying epithelium-derived cells. Our findings also indicate that dramatic differences of cell shape and organization of epithelial cells need not necessarily be associated with changes in the expression of specific cytoskeletal proteins. The possible origin of this cell line from myoepithelial cells is discussed.


Lipids mediate supramolecular outer membrane protein assembly in bacteria.
β Barrel outer membrane proteins (OMPs) cluster into supramolecular assemblies that give function to the outer membrane (OM) of Gram-negative bacteria. How such assemblies form is unknown. Here, through photoactivatable cross-linking into the Escherichia coli OM, coupled with simulations, and biochemical and biophysical analysis, we uncover the basis for OMP clustering in vivo. OMPs are typically surrounded by an annular shell of asymmetric lipids that mediate higher-order complexes with neighboring OMPs. OMP assemblies center on the abundant porins OmpF and OmpC, against which low-abundance monomeric β barrels, such as TonB-dependent transporters, are packed. Our study reveals OMP-lipid-OMP complexes to be the basic unit of supramolecular OMP assembly that, by extending across the entire cell surface, couples the requisite multifunctionality of the OM to its stability and impermeability.


Effect of short-course glucocorticoid application on patients with chronic rhinosinusitis with nasal polyps.
Local and systemic glucocorticoids are mainstay therapies for chronic rhinosinusitis. With respect to local glucocorticoids, nasal spray is used extensively, but some patients do not benefit from short-course treatment. Recently, some clinicians have focused on the effects of high-dose local glucocorticoids in chronic rhinosinusitis with nasal polyps (CRSwNP), such as treatment using nasal irrigation, transnasal nebulization, and nose-dripping therapy (nasal drop) with high-dose budesonide. However, there are little data comparing the effect of short-course high-dose local glucocorticoids with regular nasal spray and oral steroids in the treatment of preoperative CRSwNP patients. Furthermore, the appropriate use of different types of glucocorticoids in different endotypes of CRSwNP remains unclear. This randomized controlled clinical research study was performed at a single academic center. Patients who satisfied the criteria of chronic rhinosinusitis with bilateral nasal polyps were randomly assigned in a 1:1:1 ratio to receive oral methylprednisolone, 24 mg/d and budesonide nasal spray, 256 μg/d, or intranasal budesonide suspension, 1 mg/d and budesonide nasal spray, 256 μg/d, or budesonide nasal spray, 256 μg/d for one week. Symptoms, endoscopic scores, and tissue and blood inflammatory cells were recorded before and after the study. Adverse events were recorded by clinicians. A total of 127 patients with CRSwNP underwent randomization. The total nasal symptoms scores (TNSS) decreased significantly in all groups compared to those at baseline. The assessment of the reduction in TNSS demonstrated that the change was significantly greater in the nasal drop group than in the nasal spray group (-7.47 vs -4.10, P = 0.032), and it was also greater in the oral steroid group than in the nasal spray group (-7.30 vs -4.10, P = 0.039). A similar trend also appeared in the reduction in Sinonasal-Outcome Test 22 (SNOT-22). After treatment, a significantly reduction in NP score was observed in the nasal drop group (-0.82) and oral steroid group (-0.85) compared with that in the nasal spray group (-0.10), and there was no significant difference between the nasal drop and oral steroid groups (P = 0.98). While calculating the percentage of patients who were sensitive to glucocorticoid treatment, there was 10.26% in the nasal spray group, 47.37% in the nasal drop group, and 52.50% in the oral steroid group that were sensitive to glucocorticoid treatment. The reduction in NP score was more significant in patients with eosinophilic CRSwNP in the nasal drop group and oral steroid group than in the nasal spray group. However, in patients with non-eosinophilic CRSwNP, the change in NP size was similar in the different treatment groups. Budesonide suspension nasal drop can significantly improve the quality of life and reduce the endoscopic score following short-course treatment, and the treatment effect of nasal drop was better than that of regular nasal spray. Budesonide nasal suspension can be used as a regular treatment for eosinophilic CRSwNP and can be an alternative choice for patients with a high percentage of tissue eosinophil infiltration who cannot use oral glucocorticoids.


Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells.
Vacuole membrane protein 1 (Vmp1) is described as a cancer-relevant cell cycle modulator, but the function of this protein and its mode of action in tumor progression are still unknown. In this study, we show that the VMP1 mRNA level is significantly reduced in kidney cancer metastases as compared to primary tumors. Further, VMP1 expression is also decreased in the invasive breast cancer cell lines HCC1954 and MDA-MB-231 as compared to the non-invasive cell lines MCF-12A, T-47D and MCF-7. We show for the first time that Vmp1 is a plasma membrane protein and an essential component of initial cell-cell contacts and tight junction formation. It interacts with the tight junction protein Zonula Occludens-1 and colocalizes in spots between neighboring HEK293 cells. Downregulation of VMP1 by RNAi results in loss of cell adherence, and increases the invasion capacity of the non-invasive kidney cancer cell line Caki-2. In conclusion, our findings establish Vmp1 to be a novel cell-cell adhesion protein and that its expression level determines the invasion and metastatic potential of cancer cells.


CT of the urinary tract: turning attention to radiation dose.
Expanding applications and uses of CT have fueled concerns about possible increases in the risk of radiation-induced cancer. This article reviews several strategies for optimizing the radiation dose necessary for adequate CT imaging of the urinary tract.


Genetic determinants of von Willebrand factor plasma levels and the risk of stroke: the Rotterdam Study.
High von Willebrand factor (VWF) plasma levels are associated with an increased risk of stroke. VWF levels are strongly heritable. A previous meta-analysis of five large genome-wide association studies identified single-nucleotide polymorphisms (SNPs) within eight genetic loci as determinants of VWF levels. Whether these SNPs are associated with stroke risk is not known. The aim of our study was to investigate the association between genetic determinants of VWF levels and stroke risk. The study was part of the Rotterdam Study, a large population-based cohort study among subjects aged ≥ 55 years. A total of 5763 participants for whom DNA was available, and who were free of stroke at baseline, were eligible for analysis. VWF antigen (VWF:Ag) levels were measured in 3379 eligible participants. Within each of the eight loci, one top SNP was defined. The association between the eight SNPs and the risk of stroke was analyzed. Then, a genetic score, based on these eight SNPs, was constructed, and its total contribution to VWF plasma levels and stroke risk was investigated. None of the eight SNPs was individually associated with stroke risk. A higher genetic score was significantly associated with a higher VWF:Ag level, but was not associated with an increased risk of stroke. Eight SNPs that strongly determine VWF levels are not associated with stroke risk, either individually, or combined in a genetic score.


Corrigendum: The fate of sulfonamide resistance genes and anthropogenic pollution marker intI1 after discharge of wastewater into a pristine river stream.
[This corrects the article DOI: 10.3389/fmicb.2023.1058350.].


Preoperative biomedical risk and depressive symptoms are differently associated with reduced health-related quality of life in patients 1year after cardiac surgery.
To examine whether preoperative biomedical risk and depressive symptoms were associated with physical and mental components of health-related quality of life (HRQoL) in patients 1year after cardiac surgery. Seventy-five patients completed a psychological evaluation, including the Center for Epidemiological Study of Depression scale, the 12-item Short-Form Physical Component Scale (SF-12-PCS) and Mental Component Scale (SF-12-MCS), the Instrumental Activities of Daily Living questionnaire for depressive symptoms and HRQoL, respectively, before surgery and at 1-year follow-up. Preoperative depressive symptoms predicted the SF-12-PCS (beta=-.22, P<.05) and SF-12-MCS (beta=-.30, P<.04) scores in patients 1year after cardiac surgery, whereas the European System for Cardiac Operative Risk Evaluation was associated with SF-12-PCS (beta=-.28, P<.02), but not SF-12-MCS (beta=.01, P=.97) scores postoperatively. The current findings showed that preoperative depressive symptoms are associated with poor physical and mental components of HRQoL, whereas high biomedical risk predicts reduced physical, but not mental, functioning in patients postoperatively. This study suggests that a preoperative assessment of depressive symptoms in addition to the evaluation of common biomedical risk factors is essential to anticipate which patients are likely to show poor HRQoL after cardiac surgery.


Prognostic importance of coincidental coronary artery calcification on FDG-PET/CT oncology studies.
Coronary artery calcification (CAC) on body CT imaging is considered a coincidental finding in cancer patients. In order to determine the significance of CAC in cancer patients we evaluated the prognostic utility of CAC detected on oncology FDG-PET/CT studies. A retrospective study was performed of consecutive FDG-PET/CT studies from January to March 2011. CAC was identified on the CT portion of FDG/PET-CT studies. Chart review documented statin use, the Framingham risk score (FRS) (includes age, diabetes, hypertension, dyslipidemia and smoking), the primary malignancy and metastases. The primary end point was a composite of death and cardiovascular (CV) events (non-fatal myocardial infarction (MI), PCI or coronary artery bypass surgery (CABG)). 266 patients had a median follow up of 41 months (95% CI 31-56 months). CAC was noted in 140 patients. Based on CAC, potentially 84 patients would have had a change in statin prescribing (p < 0.01). CAC was associated with the primary end point on univariable and multivariable analysis (OR 2.6 (95% CI 1.42-4.77) (p < 0.01). On univariable Kaplan-Meier survival analysis, CAC was associated with decreased survival only in the absence of metastases (p < 0.01). Cox proportional hazard modelling demonstrated CAC was associated with mortality and cardiac events in patients without metastases, whereas FRS was not (For CAC: HR 1.69 (95% CI 1.22-2.35), p = 0.002). CAC is commonly detected with oncology FDG-PET/CT. In cancer patients CAC was associated with an increased risk of clinical events. CAC reduced survival free time in patients without metastases. CAC might therefore be considered more than a coincidentaloma in patients without metastases.


Access to gem-Difluoroalkenes via Organic Photoredox-Catalyzed gem-Difluoroallylation of Alkyl Iodides.
An organic photoredox-catalyzed gem-difluoroallylation of α-trifluoromethyl alkenes with alkyl iodides via C-F bond cleavage for the synthesis of gem-difluoroalkene derivatives is reported. This transition-metal-free transformation utilized a readily available organic dye 4CzIPN as the sole photocatalyst and employed a common chemical N,N,N',N'-tetramethylethylenediamine as the radical activator of alkyl iodides via halogen-atom transfer. In addition, a variety of iodides, including primary, secondary, and tertiary alkyl iodides, were tolerated and provided good to high yields.


In vivo imaging of the effect of LPS on arterial endothelial cells: molecular imaging of heat shock protein 60 expression.
Bacterial endotoxins are known as stress factors for endothelial cells. In 20 normocholesterolemic New Zealand White (NZW) rabbits, endothelial stress was induced by intravenous (i.v.) injection of lipopolysaccharide (LPS), while eight NZW rabbits were sham-treated or served as untreated controls. In vivo molecular imaging was performed using co-registered computer tomography and positron emission tomography 24 h after i.v. injection of (124)I-labeled monoclonal anti-HSP60 or (124)I-radiolabelled isotype control antibodies. Compared to control animals, in vivo images of rabbit aortae revealed significantly increased endothelial binding of (124)I-labeled anti-HSP60 antibodies upon LPS, especially at sites of aortal branching. This was confirmed by immunohistochemistry and autoradiography data. Our results showed, as proof-of-principle, that HSP60-expression in normocholesterolemic rabbits is significantly increased after induction of endothelial stress and that non-invasive in vivo molecular imaging of early aortal HSP60-expression using (124)I-labeled anti-HSP60 monoclonal antibodies is possible.


Evaluation of leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins for in vitro fertilization or gamete intrafallopian transfer.
A prospective randomized trial was conducted to compare the efficiency of two ovarian stimulation protocols for in vitro fertilization-embryo transfer or gamete intrafallopian transfer. Protocol 1 consisted of clomiphene citrate and human menopausal gonadotropin (hMG) with 55 cycles of 42 patients being evaluated. Protocol 2 had 38 cycles of 34 patients receiving a gonadotropin-releasing hormone agonist (GnRH-a) and hMG. The incidence of a spontaneous luteinizing hormone surge was 38.2% in protocol 1 and 0% in protocol 2. Both protocols had a similar cancellation rate. The total clinical pregnancy rates per oocyte retrieval for patients receiving protocol 1 and protocol 2 were 19.5% and 10.3%, respectively. The difference was not statistically significant. Therefore, as first-line ovulation induction agents, it cannot be concluded that either protocol demonstrates a clear superiority over the other and further trials of the GnRH-a/hMG combination are indicated.


Chemiluminescence-based detection: principles and analytical applications in flowing streams and in immunoassays.
The present paper provides the principles of chemiluminescence (CL) and its powerful applications in analytical chemistry, mainly in the area of flow injection analysis, column liquid chromatographic and capillary electrophoretic separating systems, and its potential in immunoassays. CL is light produced by a chemical reaction. The most common advantages of chemiluminescent reactions are the relatively simple instrumentation required, the very low detection limits and wide dynamic ranges, which have contributed to the interest of CL detection in flow injection analysis, high performance liquid chromatography, including miniaturized systems, and, most recently, the exploding area of capillary electrophoresis. The latter powerful microanalytical separation technique offers high numbers of theoretical plates and relatively short analysis times requiring only small sample volumes, the migrating system comprising aqueous buffer solutions. In non-isotopic immunoassays, covering a great variety of applications in human and veterinary medicine, forensic medicine, agriculture and food industry, the radioisotope is replaced by a fluorescence or chemiluminescent label. The use of CL as a detection principle permits quantitative determination of various compounds at low concentrations. Disadvantages of the CL-based technique may include lack of sufficient selectivity and sensitivity to various physicochemical factors.


Otitis media, auditory sensitivity, and language outcomes at one year.
The relationship among otitis media, auditory sensitivity, and emerging language was examined in a group of 1-year-old children who were prospectively followed since birth. Pneumatic otoscopy was used to document the otologic status of the children's ears at each medical visit. There were 13 babies with normal ratings in each ear at 80% more of their visits (designated as "otitis free") and 12 babies with bilaterally positive otoscopy results at 30% or more of their first year visits (designated "otitis positive"). In comparison to the otitis free infants, the group of otitis positive babies demonstrated reduced auditory sensitivity as measured by auditory brain stem response (ABR) and poorer expressive language abilities. However, differences in receptive language were not detected. These results suggest that otitis media may have an impact on auditory sensitivity and developing language as early as 1 year of age.


Evaluation of radionuclide concentrations and average annual committed effective dose due to medicinal plants and soils commonly consumed by pregnant women in Osukuru, Tororo (Uganda).
The intention of the study was to establish the activity concentrations and the annual committed effective dose due to ingestion of medicinal plants and soils by pregnant women and their probable effects to infants. The samples of medicinal plants and soils were collected from Osukuru, Tororo District (Uganda). The naturally occurring radionuclides investigated were 226Ra, 232Th and 40K and their activity concentrations were determined using NaI gamma detector. In the medicinal plants, the average activity concentrations of 226Ra, 232Th and 40K were found to be 6.04 Bq/kg, 9.65 Bq/kg and 359.59 Bq/kg respectively. African Basil registered the highest activity concentration of 226Ra of 10.02 Bq/kg, spider plant had the highest activity concentration of 232Th of 18.60 Bq/kg whereas the pumpkin registered the highest activity concentrations of 40K of 437.92 Bq/kg. The average activity concentrations of 226Ra, 232Th and 40K in 'medicinal soils' were 68.87 Bq/kg, 78.20 Bq/kg and 477.44 Bq/kg respectively. The soils from the anthills registered the highest activity concentration of 226Ra and 40K while the one from bricks registered the highest activity concentration of 232Th. The annual committed effective dose due to the ingestion of medicinal plants varied from 0.096 to 0.297 mSv/y with an average of 0.194 mSv/y in infants, 0.016-0.040 mSv/y with an average of 0.029 mSv/y for individuals of age range 12-17 years and 0.007-0.018 mSv/y with an average of 0.013 mSv/y for individuals older than 17 years. Whereas the annual committed effective dose due to the ingestion of 'medicinal soils' varied from 1.28 to 1.65 mSv/y with an average of 1.46 mSv/y in infants, 0.23-0.30 mSv/y with an average of 0.26 mSv/y (12-17 years) and 0.07-0.09 mSv/y with an average of 0.08 mSv/y for individuals older than 17 years. In medicinal plants, the annual committed effective dose for the all age groups examined were below 0.3 mSv/y (maximum world permissible as reported UNSCEAR, 2000) while that due to the ingestion of 'medicinal soils' had values higher 0.3 mSv/y in infants. The results of this study show that there is inherent danger to the infants in consuming soils during pregnancy and this should be discouraged.


Drug abuse of Finnish male prisoners in 1995.
The purpose of the present research was to estimate the extent and variety of abuse of illegal drugs, use and misuse of hypnotics and sedatives and anabolic steroids in the Finnish prison population. The study was undertaken during October-November 1995 at four prisons, three of which were closed institutions and one an open prison; one of the three closed institutions was a juvenile prison. There was a total of 707 inmates in the prisons selected for the study. Questionnaires were given personally to all prisoners in the open prison and in the young prisoners' division in the juvenile prison, but in two large central prisons only some divisions were selected for the study. The questionnaires were completed by 354 prisoners; 75 prisoners refused to respond. A total of 27.7% of subjects reported taking illegal drugs while in their current prison and 70.1% had sometimes used them. Of those who were drug-free before their first imprisonment, 21.7% began using drugs in prison. At present hypnotics and sedatives were reported as in use by 41.8% of subjects, one-third as prescribed drugs and about 10% illicitly. A total of 3.7% of subjects reported taking anabolic steroids in the current prison. Cannabis and amphetamine were the most common illegal drugs reported. Intravenous drug use was reported by 19.2% of the respondents at some point in their lives, and 10.7% of prisoners had injected drugs in their current prison. Use of illegal drugs and misuse of drugs were significantly higher among young prisoners (< or = 25 years of age).


Egg donor self-reports of ovarian hyperstimulation syndrome: severity by trigger type, oocytes retrieved, and prior history.
To evaluate self-reported survey data provided by US oocyte donors on their experiences with ovarian hyperstimulation syndrome and possible correlations between OHSS severity and number of oocytes retrieved, trigger type, and prior OHSS history. An 85-question retrospective survey was administered online. Survey questions included demographic information, reasons for donating, immediate per-cycle experiences and outcomes, perceptions of informed consent, and perceived impact of donation on long-term health. Quantitative Data for this study was collected between February 2019 and September 2020 via QualtricsXM (January 2019), an online survey platform. Follow-up interviews were also conducted. Participants were recruited via fertility clinics, egg donation agencies, and online forum. The research was approved by the University of California, San Francisco Institutional Review Board (#14-14765). Of 420 initiated US oocyte donor online surveys, 289 (68%) respondents provided detailed information on per cycle experiences with ovarian hyperstimulation syndrome, number of oocytes retrieved, and trigger type over a total of 801 cycles. On cycles where donors reported receiving GnRH agonist triggers (n = 337), they reported milder OHSS compared to cycles with hCG or dual triggers. Among donors undergoing multiple retrieval cycles, the severity of OHSS in second cycles was strongly associated with OHSS severity in first cycles. Self-reported OHSS in oocyte donors is lower in GnRH antagonist stimulation protocols combined with GnRHa trigger and in cycles where donors reported fewer than 30 oocytes retrieved. Donors who reported severe OHSS on a prior cycle were significantly more likely to experience severe OHSS on a subsequent cycle.


Effect of Tadalafil on Prevention of Urethral Stricture After Urethral Injury: An Experimental Study.
To evaluate the preventive effect of phosphodiesterase type 5 inhibitor (tadalafil) on the formation of urethral stricture after urethral injury. A total of 28, 4-month-old male New Zealand rabbits were included and divided into 3 groups. Group 1 was a sham group with 8 rabbits that underwent only urethroscopy. Group 2 was a nontreatment group with 10 rabbits that underwent urethral electrocoagulation without any treatment. Group 3 was the treatment group with 10 rabbits that underwent urethral electrocoagulation with systemic tadalafil treatment. After 30 days of follow-up, urethroscopy and retrograde urethrography were performed to evaluate the morphological changes in the urethra. The urethra tissues were examined with standard light microscopy by a histologist, and apoptosis was evaluated by the terminal dUTP nick end-labeling assay. Urethral diameters in group 1, group 2, and group 3 were 9.14 ± 0.73 mm, 3.52 ± 1.2 mm, and 7.68 ± 1.14 mm, respectively. The differences in urethral diameters were statistically significant between groups (P < .01). Collagen deposition in submucosal connective tissue was significantly less in the tadalafil group vs the nontreatment group. The numbers of apoptotic cells in submucosal connective tissue were also quantitatively higher in urethral stricture groups compared to the sham group. Tadalafil treatment had a protective effect against the formation of urethral stricture in rabbit model. This treatment can be a promising opportunity for urethral stricture and must be supported by clinical studies.


Modeling time evolving COVID-19 uncertainties with density dependent asymptomatic infections and social reinforcement.
The COVID-19 pandemic has posed significant challenges in modeling its complex epidemic transmissions, infection and contagion, which are very different from known epidemics. The challenges in quantifying COVID-19 complexities include effectively modeling its process and data uncertainties. The uncertainties are embedded in implicit and high-proportional undocumented infections, asymptomatic contagion, social reinforcement of infections, and various quality issues in the reported data. These uncertainties become even more apparent in the first 2 months of the COVID-19 pandemic, when the relevant knowledge, case reporting and testing were all limited. Here we introduce a novel hybrid approach SUDR by expanding the foundational compartmental epidemic Susceptible-Infected-Recovered (SIR) model with two compartments to a Susceptible-Undocumented infected-Documented infected-Recovered (SUDR) model. First, SUDR (1) characterizes and distinguishes Undocumented (U) and Documented (D) infections commonly seen during COVID-19 incubation periods and asymptomatic infections. Second, SUDR characterizes the probabilistic density of infections by capturing exogenous processes like clustering contagion interactions, superspreading, and social reinforcement. Lastly, SUDR approximates the density likelihood of COVID-19 prevalence over time by incorporating Bayesian inference into SUDR. Different from existing COVID-19 models, SUDR characterizes the undocumented infections during unknown transmission processes. To capture the uncertainties of temporal transmission and social reinforcement during COVID-19 contagion, the transmission rate is modeled by a time-varying density function of undocumented infectious cases. By sampling from the mean-field posterior distribution with reasonable priors, SUDR handles the randomness, noise and sparsity of COVID-19 observations widely seen in the public COVID-19 case data. The results demonstrate a deeper quantitative understanding of the above uncertainties, in comparison with classic SIR, time-dependent SIR, and probabilistic SIR models.


Possibilities and limitations of microsurgery in patients with meningiomas of the sellar region.
Problems associated with the operative technique and operative results in 40 patients who underwent surgical removal of a meningioma in the sellar region are analysed. Attention must be paid not only to the possibilities and limitations of microsurgery but also to general aspects such as hypothalamic and pituitary function.


Impact of the novel coronavirus (COVID-19) pandemic on sleep.
The COVID-19 pandemic has led to significant changes in daily routines and lifestyle worldwide and mental health issues have emerged as a consequence. We aimed to assess the presence of sleep disturbances during the lockdown in the general population. Cross-sectional, online survey-based study on adults living through the COVID-19 pandemic. The questionnaire included demographics and specific questions assessing the impact of the pandemic/lockdown on sleep, daytime functioning and mental health in the general population. Identification of sleep pattern changes and specific sleep-related symptoms was the primary outcome, and secondary outcomes involved identifying sleep disturbances for predefined cohorts (participants reporting impact on mental health, self-isolation, keyworker status, suspected COVID-19 or ongoing COVID-19 symptoms). In total, 843 participants were included in the analysis. The majority were female (67.4%), middle aged [52 years (40-63 years)], white (92.2%) and overweight to obese [BMI 29.4 kg/m2 (24.1-35.5 kg/m2)]; 69.4% reported a change in their sleep pattern, less than half (44.7%) had refreshing sleep, and 45.6% were sleepier than before the lockdown; 33.9% had to self-isolate, 65.2% reported an impact on their mental health and 25.9% were drinking more alcohol during the lockdown. More frequently reported observations specific to sleep were 'disrupted sleep' (42.3%), 'falling asleep unintentionally' (35.2%), 'difficulties falling'/'staying asleep' (30.9% and 30.8%, respectively) and 'later bedtimes' (30.0%). Respondents with suspected COVID-19 had more nightmares and abnormal sleep rhythms. An impact on mental health was strongly associated with sleep-related alterations. Sleep disturbances have affected a substantial proportion of the general population during the COVID-19 pandemic lockdown. These are significantly associated with a self-assessed impact on mental health, but may also be related to suspected COVID-19 status, changes in habits and self-isolation.


Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo.
Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies.


Initial attendance and retention in adult healthcare as criteria for transition success among organ transplant recipients.
Adolescent and young adult (AYA) solid organ transplant recipients experience worsening medical outcomes during transition to adult healthcare. Current understanding and definitions of transition success emphasize first initiation of appointment attendance in adult healthcare; however, declines in attendance over time after transfer remain possible, particularly as AYAs are further removed from their pediatric provider and assume greater independence in their care. The current study assessed health-care utilization, medical outcomes, and transition success among 49 AYA heart, kidney, or liver recipients recently transferred to adult healthcare. Differences in outcomes were examined along two transition success criteria: (1) initial engagement in adult healthcare within 6 or 12 months of last pediatric appointment and (2) retention in adult healthcare over 3 years following last pediatric appointment. Growth curve modeling examined change in attendance over time. Successful retention in adult healthcare was significantly related to more improved clinical outcomes, including decreased number and duration of hospitalizations and greater medication adherence, as compared to initial engagement. Significant declines in appointment attendance over 3 years were noted, and individual differences in declines were not accounted for by age at transfer or time since transplant. Findings underscore support for AYAs after transfer, as significant declines in attendance were noted after initiating adult care. Clinical care teams should examine transition success longitudinally to address changes in health-care utilization and medical outcomes. Attention to interventions and administrative support aimed at maintaining or increasing attendance and identifying risk factors and intervention for unsuccessful transition is warranted.


Risk factors and outcomes following revascularization for chronic mesenteric ischemia.
Revascularization for chronic mesenteric ischemia is an infrequent vascular procedure whose objective long-term patency results have been described in relatively few patients. We reviewed our experience with such procedures and report on the objective and symptomatic long-term results. We retrospectively reviewed a consecutive series of 42 patients who underwent mesenteric arterial reconstruction of 66 vessels during an 11-year period from 1986 to 1997. All patients were treated for symptomatic chronic mesenteric ischemia. The results support the clinical efficacy and durability of visceral artery bypass procedures for patients with symptomatic chronic mesenteric ischemia. Patency rates for females were better than for males independent of graft type.


Changes in aggression and locomotor behaviors in response to zinc is accompanied by brain cell heterogeneity and metabolic and circadian dysregulation of the brain-liver axis.
Zinc is an essential nutrient for life, but over-accumulation can result in toxicity. Anthropogenic activities can increase zinc concentrations in aquatic environments (e.g., to ∼0.46-1.00 mg/L), which are above the safe level of 0.1 mg/L. We investigated the behavior and physiology of zebrafish (Danio rerio) in response to environment-related exposure to zinc chloride at 0.0 (Ctrl), 1.0 (ZnCl2-low) and 1.5 (ZnCl2-high) mg/L for 6 weeks (the zinc conversion ratio of zinc chloride is ∼0.48 and the nominal (measured) values were: Ctrl, 0 (∼0.01); ZnCl2-low, 0.48 (∼0.51); ZnCl2-high, 0.72 (∼0.69) mg/L). Low-zinc exposure resulted in significantly increased locomotion and fast moving behaviors, while high-zinc exposure resulted in significantly increased aggression and freezing frequency. Single cell RNA-seq of neurons, astrocytes, and oligodendrocytes of the brain revealed expression of genes related to ion transport, neuron generation, and immunomodulation that were heterogeneously regulated by zinc exposure. Astrocyte-induced central nervous system inflammation potentially integrated neurotoxicity and behavior. Integrated analyses of brain and hepatic transcriptional signatures showed that genes (and pathways) dysregulated by zinc were associated with sensory functions, circadian rhythm, glucose and lipid metabolism, and amyloid β-protein clearance. Our results showed that environment-related zinc contamination can be heterogeneously toxic to brain cells and can disturb coordination of brain-liver physiology. This may disrupt neurobehavior and cause a neurodegeneration-like syndrome in adult zebrafish.


The PRISMA Symposium 3: lessons from beyond Europe. why invest in research and service development in palliative care? An Australian perspective.
Hospice and palliative care services need to be able to compete with finite health care resources. To compete for such funding, the sector needs to continuously improve the evidence base that demonstrates improved outcomes, or else funding will continue to be at the level of a "social good" rather than as services that deliver improved health outcomes. Three questions need to be answered for policy makers and health funders: 1) Why invest health care spending in hospice and palliative care?, 2) Why invest research monies in hospice and palliative care clinical research and health service development?, and 3) How can emerging evidence be more effectively implemented to improve patient outcomes? No single measure captures the net benefit of hospice and palliative care services. By patient-defined parameters, hospice and palliative care services have demonstrated benefits, including physical symptom control. To meet patients' concerns, greater emphasis needs to be placed on maintaining physical independence for a longer period of time. Targeted investment of research funding can deliver further improvements in patient outcomes and models of service delivery. Rigorous studies are feasible and necessary if each patient is going to receive the best possible support. Benchmarking and service development strategies can deliver improved patient outcomes. With routine point-of-care data collection and feedback loops to individual services, patient-valued outcomes and resourcing can be improved in hospice and palliative care. Public-good investments in hospice and palliative care research are vital to building the evidence base for improving the quality of care offered.


Prevalence and associated factors of depression and anxiety among nurses during the outbreak of COVID-19 in China: A cross-sectional study.
Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and has caused traumatic experience for nurses worldwide. However, the prevalence of depression and anxiety symptoms in nurses, and how psychosocial factors influence nurses in this public crisis are unknown. To determine the effect of COVID-19 on the mental health of nurses and the prevalence of anxiety and depression symptoms among nurses in China during the outbreak. A cross-sectional study. A total of 3,228 nurses in Sichuan Province and Wuhan City were selected by convenience sampling. All participants were invited to complete the questionnaire through WeChat from January 27 to February 3, 2020. A self-reported questionnaire combining depression and anxiety scale was used to collect data anonymously. Binary and multivariate logistic regression was applied to measure the odds of psychosocial factors of anxiety and depression and perceived health, respectively. The total incidence of depression (34.3%) and anxiety (18.1%) during the COVID-19 outbreak was lower than that during the SARS outbreak; however, the rate of depression in our study (47.1%) was high and similar in a recent study (50.4%) about the health care workers exposed to COVID-19 in China. The results indicated that COVID-19-related stress, relationship quality with family, and demographic characteristics were associated with depression, anxiety, and perceived health status. Furthermore, the prevalence of depression was similar between nurses working in low-risk COVID-19 wards was as high as working in high-risk COVID-19 wards (OR, 1.078; 95% CI, 0.784-1.481). Our study revealed the high prevalence of depression and anxiety among nurses during the outbreak of COVID-19. COVID-19 factors and psychosocial factors were associated with mental health of nurses. The results suggest that hospitals should implement effective mental health promotion programs focused on occupational safety and family support to improve the well-being of nurses.


Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes.
Type 1 diabetes (T1D), an autoimmune disease, occurs most commonly in children. Identifying altered gene expression in peripheral blood mononuclear cells (PBMCs) of T1D may lead to new strategies for preserving or improving β-ell function in patients with T1D. The Gene Expression Omnibus database was searched for microarray studies in PBMCs of T1D. Subsequently, gene expression datasets from multiple microarray studies were integrated to obtain differentially expressed genes (DEGs) between T1D and normal controls (NC). Gene function analysis was performed to determine the functions of the DEGs identified. Four microarray studies were available for analysis, including 199 T1D samples and 74 NC samples. Analysis revealed 695 genes that were significantly differentially expressed in PBMCs from T1D compared with NC samples, with 450 upregulated and 245 downregulated. Signal transduction (gene ontology [GO]: 0007165; false discovery rate [FDR] = 1.54 × 10-7 ) and protein binding (GO: 0005515; FDR = 2.93 × 10-24 ) were significantly enriched for the GO categories of biological processes and molecular functions, respectively. The most significant pathway in the Kyoto Encyclopedia of Genes and Genomes analysis was arachidonic acid metabolism (FDR = 1.44 × 10-3 ). Protein-protein interaction network analysis showed that the significant hub proteins contained immature colon carcinoma transcript 1 (ICT1; degree = 214; clustering coefficient [C] = 4.39 × 10-5 ), zinc finger and BTB domain containing 16 (ZBTB16; degree = 112; C = 8.04 × 10-4 ), and SERTA domain containing 1 (SERTAD1; degree = 38; C = 0.0014). This integrated analysis will help develop improved therapies and interventions for T1D by identifying novel drug targets.


Survivorship Navigation for Young Women With Early-Stage Breast Cancer.
Young women treated for breast cancer experience unique concerns in follow-up. We developed a program to direct young breast cancer survivors to a dedicated survivorship visit and evaluated their experience. Early-stage breast cancer patients diagnosed under age 45 within 1 year of completing breast surgery, chemotherapy and/or radiation therapy were systematically referred for a survivorship visit. Patients completed a one-time, post-visit survey about their experience. Sixty-nine out of 89 (78%) eligible patients attended a survivorship visit, and 40 of those 69 (58%) completed the post-visit survey. Most respondents learned about the survivorship clinic after completing treatment (30/40; 75%) and reported the survivorship visit occurred at an appropriate time in their follow-up care (26/40; 65%). Of the 34 respondents who reported receiving a treatment summary and survivorship care plan, 30 indicated it would be helpful when visiting their primary care provider (88.2%). Participants reported gaining valuable knowledge about cancer treatment (28/38; 73.7%), side effects (32/39; 82.1%), and cancer surveillance (30/40; 75%), and discussed emotional health (32/40; 80%), exercise (38/40; 95%), and ongoing cancer surveillance (32/37; 86.5%). Several reported intentions to make changes to their follow-up oncology care (8/20; 40%), exercise routines (16/30; 53.3%), and emotional health care (15/22; 68.2%). Survivorship visit navigation is feasible for young breast cancer patients. These visits can influence knowledge gained and intended future health plans and behaviors. Systematic approaches to survivorship care may improve the physical and mental health of cancer survivors. Future health care delivery research focused on survivorship is warranted.


Preservation of the quality and fertility potential of post-thawed rooster sperm using MitoQ.
Cryopreservation of rooster spermatozoa is an efficient procedure to spread qualified semen samples for reproductive goals in commercial flocks, but the freeze-thawing process reduces the quality and fertility potential of post-thawed sperm cells. This study was aimed to investigate the effect of the mitochondria-targeted antioxidant MitoQ on rooster sperm quality and fertility potential preservation during freeze-thawing process. Semen samples were collected and diluted in the Lake medium, assigned into five equal aliquots, supplemented with 0, 1, 10, 100 and 1000 nM MitoQ, and cryopreserved in liquid nitrogen. After thawing, sperm motility, membrane functionality, abnormal morphology, mitochondria active potential, acrosome integrity, viability, apoptosis status, lipid peroxidation, DNA fragmentation, ROS concentration and fertility potential were evaluated. According to the results, freezing extender supplementation with 10 and 100 nM MitoQ presented higher (P ≤ 0.05) total motility, progressive motility, average path velocity, membrane functionality, mitochondria active potential, acrosome integrity and viability compared to the other groups. On the other hand, lipid peroxidation, apoptosis rate, DNA fragmentation and ROS concentration were lower (P ≤ 0.05) in groups received 10 and 100 nM MitoQ compared to other groups. Moreover, fertility rate was higher in groups received 10 and 100 nM MitoQ compared to control group. Therefore, MitoQ is able to preserve quality parameters and fertility potential of post-thawed spermatozoa in rooster and it could be an effective additive for supplementation of rooster's semen cryopreservation medium during reproductive programs.


Synthesis, characterization of copper(II), cobalt(II), nickel(II), zinc(II) and cadmium(II) complexes of [7-hydroxy-4-methyl-8-coumarinyl]glycine and a comparitive study of their microbial activities.
A new Mannich base, [7-hydroxy-4-methyl-8-coumarinyl]glycine [MCGH(2)], has been prepared by the condensation of 7-hydroxy-4-methyl-coumarin with glycine and formaldehyde. Its conformational changes on complexation with transition metal ions [copper(II), cobalt(II), nickel(II), zinc(II) and cadmium(II)] have been studied on the basis of elemental analysis, conductivity measurements, spectral (infrared, (1)H NMR, electronic, EPR), magnetic and thermogravimetric studies. The infrared spectral studies of all the complexes reveal that the ligand has coordinated through -NH and two hydroxyl groups. The conductance data of the complexes suggest them to be non-electrolytes. Fluorescence property of the ligand and its metal complexes was studied and concluded that the ligand MCGH(2) can be a potential candidate for the determination of zinc(II) and cadmium(II) at room temperature by fluorimetric method. The antimicrobial activity of all the compounds was studied against Gram negative (Escherichia coli) and Gram positive (Bacillus cirroflagellosus) bacteria and fungi, Aspergillus niger and Candida albicans. It was observed that the coordination of metal ion has a pronounced effect on the microbial activities of the ligand. All the metal complexes have shown higher antimicrobial effect than the free ligand.


Novel TRPV4 variant causes a severe form of metatropic dysplasia.
We present a girl born with a frontal bossing, short neck, bell-shaped thorax, short limbs with prominent joints, and a tail-like coccygeal appendage. Genetic screening of TRPV4 identified a novel de novo heterozygous missense variant. We believe the variant causes the severe form of metatropic dysplasia in this patient.


Enhanced recovery of Arcobacter spp. using NaCl in culture media and re-assessment of the traits of Arcobacter marinus and Arcobacter halophilus isolated from marine water and shellfish.
The genus Arcobacter is a relatively poorly known group of bacteria, and the number of new species and sequences from non-culturable strains has increased considerably in recent years. This study investigates whether using media that contain NaCl might help to improve the recovery of Arcobacter spp. from marine environments. To this aim, 62 water and shellfish samples were analysed in parallel, with both a commonly used culture method (enrichment in Arcobacter-CAT broth followed by culture on Blood Agar) and a new one that supplements the Arcobacter-CAT enrichment broth with 2.5% NaCl (w/v) followed by culturing on Marine Agar. The new method yielded ca. 40% more positive samples and provided a higher diversity of known (11 vs. 7) and unknown (7 vs. 2) Arcobacter species. Among the 11 known species recovered, Arcobacter marinus and Arcobacter halophilus were isolated only by this new method. No more strains of these species have been isolated since their original descriptions, both of which were based only on a single strain. In view of that, the phenotypic characteristics of these species are re-evaluated in the present study, using the new strains. Strains of A. halophilus had the same phenotypic profile as the type strain. However, some strains of A. marinus differed from the type strain in that they did not hydrolyse indoxyl-acetate, becoming, therefore, the first Arcobacter species to show a varying ability to hydrolyse indoxyl-acetate. This study shows to what extent a simple variation to the culture media can have a big influence on positive samples and on the community of species recovered.


Prognostic implications of large volume residual disease in patients with advanced stage epithelial ovarian cancer.
Thirty-two patients with Stage III or IV epithelial ovarian cancer and residual tumor volumes in excess of 2 cm in diameter after initial debulking were treated with platinum and cyclophosphamide chemotherapy. Twenty-seven patients (84%) received at least six courses of chemotherapy. Six patients developed grade 3 or 4 hematologic toxicity and one patient died with granulocytopenia and sepsis. The actuarial survival of the total group of patients was 78% at 12 months, 27% at 24 months, and 11% at 36 month. Of patients with residual disease 2-4 cm in diameter, 82% were alive 12 months after diagnosis and 46% were alive at 24 months. In contrast, patients with greater than 4 cm residual disease had a 12-month survival of 73% and a 24-month survival of only 7%. The size of residual tumor after surgery remains a very important prognostic factor in patients treated with platinum-based combination chemotherapy. Reoperation with further tumor debulking should be considered in ovarian cancer patients referred for chemotherapy with large volume residual disease to maximize response to combination chemotherapy.


C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor's carboxy-terminus.
The colony-stimulating factor-1 (CSF-1) receptor is a protein-tyrosine kinase that regulates the proliferation and differentiation of monocyte and macrophage precursors. Binding of CSF-1 to its receptor results in activation of the kinase domain and autophosphorylation on a number of tyrosine residues. Phosphorylated tyrosine residues function as binding sites for SH2 domain-containing signaling proteins. It is known that activated receptors are internalized and degraded, but the mechanics of this process remain largely unknown. Recently, evidence has started to emerge that the ubiquitin-protein ligase c-Cbl is involved in CSF-1 receptor degradation. In addition, there is evidence that the CSF-1 receptor carboxy-terminus is involved in down regulation of the receptor. Here we show that the c-Cbl tyrosine kinase-binding (TKB) domain binds in vitro and in vivo to the CSF-1 receptor. Binding is dependent on the receptor's protein-kinase activity. Deletion of the carboxy-terminus or mutation of Tyr 973 blocks binding. We further provide evidence that the CSF-1 receptor's carboxy-terminus is a substrate for autophosphorylation. Our observations are consistent with a model in which receptor autophosphorylation at Tyr 973 creates a binding site for c-Cbl. Association of c-Cbl with the receptor leads to ubiquitination, followed by receptor degradation.


The adolescent and liver transplantation.
The outcome of liver transplantation is usually reported in terms of graft and patient survival, medical and surgical complications, and quality of life, but when it comes to transplanted adolescents such conventional parameters are unable to give a full account of their life with a new liver, and their transition from adolescence to adulthood is a time when they are particularly vulnerable. Adolescents with liver transplants have excellent survival rates, over 80% of them surviving more than 10 years. Graft loss is most often associated with complications such as chronic rejection, hepatic artery thrombosis, and biliary complications. Calcineurin inhibitors may have various side effects, including hypertension and nephrotoxicity. Liver-transplanted adolescents are also exposed to viral infections, among which Epstein-Barr virus is very common and associated with the onset of post-transplant lymphoproliferative disorders. Growth retardation may also be an issue in some liver transplant recipients. Future studies will determine the best way to assess the functional immune status of adolescents with a transplanted liver with a view to ensuring the best treatment to induce tolerance without the complications of excessive immunosuppression. Schooling may be disrupted due to adolescent transplant recipients' poor adherence. Non-adherence is associated with a poor medical outcome. Both physical and psychosocial functioning is reportedly lower among young liver transplant recipients than in the general population.


Steady-state operation of a biofilter coupled with photocatalytic control of bacterial bioaerosol emissions.
Bioaerosols are emitted during the biological treatment of water, soil, and air pollutants. The elimination of these pollutants has become a priority due to their detrimental effects on human health. Advanced oxidation technologies have been used to control bioaerosol emissions specially to improve indoor air quality. This investigation was focused on evaluating the biofiltration of ethyl acetate vapors in terms of removal efficiency and bioaerosol emission. Also, a continuous photocatalytic process to inactivate bioaerosols emitted from the biofilter was assessed as a post-treatment. The photocatalysis was developed with ZnO and TiO2 immobilized onto Poraver glass beads. Flow cytometry (FC) coupled with fluorochromes was used to characterize and quantify bioaerosol emissions in terms of live, dead, and injured cells. Ethyl acetate removal efficiencies were maintained in a steady state with values of 100% under 60-g m-3 h-1 inlet load (IL). Biomass concentration in the biofilter reached values up to 228 mgbiomass gperlite-1 at day 56 of operation, but the spontaneous occurrence of predatory mites diminished biomass concentration by 33%. Bioaerosols emitted during the steady-state operation of the biofilter were composed mainly by bacteria (~ 94%) and in a less extent of fungal spores (0.29-6%). The most efficient photocatalytic system comprised TiO2/Poraver with 78% inactivation of bioaerosols during the first 2 h of the process, whereas the ZnO/Poraver system showed null activity (~ 0%) of inactivation. FC results show that the main mechanism of inactivation of TiO2/Poraver was cell death.


Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns.
Wound healing is a dynamic process that could be accelerated by growth factors. We investigated the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on burn healing in a randomised placebo-controlled trial. We recruited 600 patients with superficial or deep second-degree burns. Patients received 150 AU/cm2 daily topical rbFGF (n=300) or placebo (n=300) plus vehicle. We assessed healing by photography, punch-biopsy, and clinical examination. All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group. Superficial and deep second-degree burns treated with rbFGF healed in a mean of 9.9 (SD 2.5) days and 17.0 (4.6) days, respectively, compared with 12.4 (2.7) and 21.2 (4.9) days (p=0.0008 and p=0.0003, respectively). No adverse effects were seen locally or systemically with rbFGF. rbFGF effectively decreased healing time and improved healing quality. Clinical benefits would be shorter hospital stays and the patient's skin quickly becoming available for harvesting and grafting.


Hemadsorption in patients requiring V-A ECMO support: Comparison of Cytosorb versus Jafron HA330.
ECMO support is associated with the development of a systemic hyper-inflammatory response, which may become quite significant and extreme in some cases. We hypothesize that Cytosorb or Jafron therapy may benefit patients on V-A ECMO in terms of levels of inflammatory markers such as IL-6, complications, and overall outcomes. We conducted a retrospective study of prospectively collected data in a single tertiary care center between January 2021 and April 2022. At the time of the analysis of this article, 20 patients on V-A ECMO had cytokine adsorption while on ECMO support: Cytosorb group (n = 10), Jafron group (n = 10). In 10 ECMO-supported patients cytokine adsorption was not used, this group served as a control group, which may be quite significant in some cases. Evaluation of the level of inflammatory markers (IL-1, 6, 8; CRP, Leukocyte, Lactate, PCT, NT-proBNP, TNF-α) was performed. There was statistically significant longer CPB time, aortic cross-clamp time and ICU stay in cytokine adsorption groups than in the control group, but there were no differences between subgroups with different types of haemoadsorption used. Moreover, in the control group mortality rate was higher than in the cytokine adsorption groups (60% vs. 20%, p = 0.02). All patients had an elevation of inflammatory markers in the perioperative and immediate postoperative periods. After 72 h of intensive care, blood inflammation markers had a tendency to decline. At the time of writing, hemadsorption in patients requiring V-A ECMO support represents a good therapeutic effect. This effect is permanent for the whole period of extracorporeal cytokine hemadsorption application for both CytoSorb and Jafron HA330 devices.


[Evaluation of high frequency hearing thresholds in smokers].
We investigated whether high frequency hearing thresholds differed between smokers and nonsmokers. The study was carried out in 50 individuals including 20 nonsmokers (mean age 29 years; range 25 to 37 years) and 30 smokers (mean age 34 years; range 25 to 50 years). The smokers group was comprised of individuals who had been smoking at least a pack a day for more than 10 years. High frequency hearing thresholds (8-18 kHz) were compared between the two groups. The mean hearing thresholds of smokers at 16 kHz were 50.66 dB HL and 49.50 dB HL in the left and right ears, respectively; the corresponding figures for nonsmokers were 31.00 dB HL and 33.25 dB HL, respectively (p=0.005). The mean hearing thresholds of smokers and nonsmokers at 18 kHz were 57.33 dB HL and 41.25 dB HL for the left ears, and 59.33 dB HL and 42.52 dB HL for the right ears, respectively (p=0.005). Analyses between the two groups after exclusion of subjects over 40 years of age showed significant differences at 16 kHz and at 18 kHz for the left ears, and at 18 kHz for the right ears (p=0.005). Our results suggest that smoking can be considered one of the factors that plays a role in high frequency hearing loss.


Evaluation of left ventricular function based on simulated systolic flow dynamics computed from regional wall motion.
Left ventricular (LV) chamber flow is undoubtedly influenced by the time-dependent regional motion of the LV wall. In an attempt to obtain diagnostic parameters based on LV chamber flow, we computed the LV chamber, two-dimensional systolic velocity and pressure distribution for two right anterior oblique (RAO) ventriculograms: one normal, one with ischemic coronary artery disease, and several simulations with prescribed abnormal wall motion. The flow fields are obtained by solving the discretized two-dimensional Navier-Stokes equations for viscous, incompressible unsteady flow using the finite analytic method. These solutions were used as a basis for two LV assessment parameters: (1) local pressure gradient near the LV wall, and (2) the central ejection region (CER), defined as the region of flow domain in which the obtained velocity field vectors are aligned +/- 5 degrees from the LV long axis. A CER coefficient, R, derived from the location and orientation of the CER within the LV cavity, is defined such that R = 0 for a heart which produces no CER, and R = 1 for a heart whose contraction is perfectly even along the entire RAO LV outline. The computed local pressure gradients in the ischemic heart near the apical wall region were reduced compared with those computed in the normal heart. An observable decrease in magnitude of the pressure gradients in the apical region for increasing severity of abnormal wall motion was also indicated. However, the prescribed abnormal wall motion simulations generated reduced pressure gradients in regions of abnormal wall motion and normal regions as well. Therefore, the local wall pressure gradient may not be suitable for localization of coronary occlusion but for presence of disease only. The time-averaged CER coefficient was 0.709 for the normal heart and 0.453 for the diseased heart. The CER shifted toward the region of LV wall which exhibits the abnormal motion, and the CER coefficient decreased with increasing severity of abnormal wall motion. The CER coefficient provides a qualitative and quantitative measure of global function that regional wall motion analysis cannot provide, and is a parameter which is sensitive to regional and temporal abnormalities and the resulting compensatory actions which cannot be detected by global parameters.


[Partial results of an investigation of the state of dentition of the Czechoslovak population with regard to targets of WHO for the year 2000].
In 1987 a nation-wide survey of the state of dentition of Czechoslovak population in age groups of 2-65 years and above was made. The paper presents the results in the age category of 5-6 years, 12 years, 18 years, 35-44 and 65 year and more, with regard to criteria defined for WHO targets for the year 2000. Data for the CSSR, SSR and CSSR are presented separately.


Association of subjective social status with epigenetic aging among Black and White women.
Subjective social status (SSS), an individual's assessment of their own social status in relation to others, is associated with health and mortality independently of objective SES; however, no studies have tested whether SSS influences epigenetic aging. The current study examines if SSS is associated with epigenetic age acceleration in both Black and White women, independently of objective SES measured during both childhood and adulthood. For 9- and 10-year-old Black and White girls, parental education and annual household income was obtained. At ages 39-42, 361 participants (175 Black, 186 White) reported their current education, household income, and SSS, and provided saliva to assess age acceleration using the GrimAge epigenetic clock. Linear regression estimated the association of SSS with epigenetic age acceleration, controlling for objective SES (current education, current income, parents' education, income during childhood), smoking, and counts of cell types. When all objective SES variables were included in the model, SSS remained significantly associated with epigenetic age acceleration, b = - 0.31, p = .003, ß = - 0.15. Black women had significantly greater age acceleration than White women, (t(359) = 5.20, p > .001, d = 0.55) but race did not moderate the association between SSS and epigenetic age acceleration. Women who rated themselves lower in SSS had greater epigenetic age acceleration, regardless of income and education. There was no difference by race for this association.


Evidence for intramitochondrial complementation between deleted and normal mitochondrial DNA in some patients with mitochondrial myopathy.
Twenty-three patients with mitochondrial myopathies and mitochondrial DNA deletions in muscle were studied by means of deletion mapping and sequencing, histochemistry and polarography. Histochemistry showed significantly less focal cytochrome oxidase deficiency relative to number of ragged red fibres when the deletion did not involve reading frames for cytochrome oxidase subunits. Polarography in such patients showed defects exclusively involving complex I, in contrast to the others with larger deletions who generally had more diffuse respiratory chain defects. Analysis of other published histochemical data showed similar findings to our own. It is concluded that translation of a proportion of deleted mitochondrial DNAs occurs in at least some patients with mitochondrial DNA deletions, implying that deleted and normal mitochondrial genomes share transfer RNAs within mitochondria in such cases.


Remediation of recalcitrant pollutants in water solution using visible light responsive cerium-doped tungsten trioxide nanoparticles.
In order to attain a solar energy-driven photocatalyst for wastewater remediation, cerium-doped WO3 (W1-xCexO3 with x = 0, 0.02, 0.04, 0.06, and 0.08) nanoparticles have been synthesized via a chemical co-precipitation technique. X-ray diffraction (XRD) analysis confirmed that W1-xCexO3 nanoparticles retained their monoclinic structure even after doping. The presence of the vast number of defects produced in the WO3 lattice was corroborated by Raman spectroscopy. Scanning electron microscopy confirmed the spherical shape of the nanoparticles with particle size range 50-76 nm. The optical band gap of W1-xCexO3 nanoparticles decreases from 3.07 to 2.36 eV with an increase in x, as confirmed by UV-Vis spectroscopy. Photoluminescence (PL) spectroscopy confirmed that the minimum rate of recombination was observed for W1-xCexO3 with x = 0.04. Degradation efficiency was explored for methyl violet (MV) and rhodamine-B (Rh-B) with 0.01 g of photocatalyst in a photoreactor chamber having a 200-W xenon lamp as a visible source of light. The results showed that the maximum photo-decolorization towards MV (94%) and rhodamine-B (79.4%) was observed in x = 0.04 sample in just 90 min because of its least recombination rate, highest adsorption capacity, and optimum band edge positions. Intriguingly, it has been observed that the modification with cerium in WO3 nanoparticles enhances the photocatalytic activity by narrowing the band gap and by efficaciously lowering the recombination rate due to electron entrapment by defects produced in the lattice.


Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) as Possible Prognostic Markers for Patients Undergoing Resection of Adrenocortical Carcinoma.
Adrenocortical cancer (ACC) is a rare disease with a poor outcome, and robust prognostic factors remain unclear. High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as markers of host inflammation have been found to be associated with decreased long-term outcomes in several tumour types, but have been scarcely analysed in ACC. Patients who underwent resection of their ACC between 2000 and 2020 were identified; therapeutic, operative and outcome data were analysed. Pre-operative NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. Fifty-seven patients (30F:27 M) with an overall median age of 53 years [range: 18-86] presented with tumours of median size 11.5 cm [range: 3.0-22.0], of whom 26 (46%) were hormonally active. Majority of patients underwent an open resection (n = 48; 84%); more than half (n = 30; 53%) underwent multi-organ excision. Median NLR was 4.63 and median PLR was 186.21; these values were used for median split analyses (low vs. high). There were no differences with regard to age, sex or tumour characteristics and peri-operative data between the two groups (all p > 0.05). Overall, median recurrence-free survival (RFS) was 26 months (3-year: 45%) on Kaplan-Meier analysis. On univariate analyses, a high NLR did not influence RFS [HR = 1.57 (95%-CI: 0.73-2.38); p = 0.25], but patients with a high PLR had an increased risk of developing recurrence [HR = 2.39 (95%-CI: 1.08-5.31); p = 0.03]. The median overall survival (OS) was 33 months (3 years: 79%) on Kaplan-Meier analysis. Both a high NLR [HR = 2.24 (95%-CI: 1.07-4.70); p = 0.03] and a high PLR [HR = 4.02 (95%-CI: 1.80-8.98); p = 0.001] were strongly associated with a shorter OS on unadjusted analyses. Elevated pre-operative NLR and PLR are associated with shorter OS, while higher PLR was also associated with a shorter RFS for patients undergoing curative intent resection of ACC.


A method for improved detection of 8-isoprostaglandin F2α/β and benzodiazepines in wastewater.
Wastewater-based epidemiology is a tool incorporating biomarker analysis that can be used to monitor the health status of a population. Indicators of health include endogenous oxidative stress biomarkers and hormones, or exogenous such as alcohol and nicotine. 8-Iso-prostaglandin F2α/β is a biomarker of endogenous metabolism that can be used to measure oxidative stress in a community. Benzodiazepines are a harmful subclass of anxiolytics either prescribed or sourced illegally. The analysis of oxidative stress markers and uptake of benzodiazepines in wastewater may provide information about distress in the community. A method has been applied to detect 8-isoPGF2α/β and the illicit benzodiazepines clonazolam, flubromazolam and flualprazolam in addition to other prescribed benzodiazepines in wastewater. These substances have been sold as counterfeit pharmaceutical products, such as Xanax, which was formulated to include alprazolam. Deconjugation was initially performed on wastewater samples, followed by liquid-liquid extraction for isoprostanes and solid phase extraction for benzodiazepines to determine the total levels of these analytes. Limits of quantification were in the range of 0.5-2 ng/L for all the analytes except 8-isoPGF2α/β which was 50 ng/L. Stability, recovery and matrix effect studies were also conducted. Finally, this method was applied to influent wastewater from South Australia which showed the prevalence of 8-isoPGF2α/β and benzodiazepines.


Arsenic uptake by two vegetables grown in two soils amended with As-bearing animal manures.
Organoarsenicals are widely used as growth promoters in animal feed, resulting in unabsorbed arsenic (As) left in animal manures. A pot experiment was conducted to investigate the growth and As uptake of amaranth (Amaranthus tricolor Linn, a crop with an axial root system) and water spinach (Ipomoea aquatica Forsk, a crop with a fibrous root system) grown in a paddy soil (PS) and a lateritic red soil (LRS) amended with 2% and 4% (w/w) As-bearing chicken manure and pig manure, respectively. Soils without any fertilizers were the controls. The biomass, As contents and total As uptake of the shoots, As transfer factors (TFs) from roots to shoots and the root/shoot (R/S) ratios of water spinach were significantly higher than those of amaranth (p<0.0015). The biomass, total As uptake and R/S ratios showed significant difference for soil types (p<0.0031). Manure amendments increased the biomass of both vegetables, reduced the As contents in amaranth but increased those in water spinach. The As contents were negatively correlated with the biomass in amaranth, but positive correlation was observed for water spinach. The total As uptake by amaranth was decreased in PS and insignificantly affected in LRS by manure application, but that by water spinach was significantly increased in both soils. We suggest that the higher As uptake by water spinach might be related to its root structure and R/S ratio. Heavy application of As-bearing animal manures should be avoided in water spinach.


Can oviposition on marine litter pose a threat to marine fishes?
Marine litter colonization is widely investigated as an important pathway for the dispersal of potentially invasive species. However, this phenomenon may be impacting marine biota in other ways as well. In this viewpoint, we express our concerns regarding the potential loss of viable eggs of numerous oviparous fishes deposited on marine litter when large-scale stranding events occur. Our concerns are supported by personal observations of stranded marine litter harboring fresh and viable egg capsules (Sympterygia sp.) and eggs (Family: Blenniidae), as well as reports in the literature. The loss of viable eggs from oviparous fishes is widely overlooked and poorly understood. Based on these knowledge gaps, we make a call for research and propose several research priorities to understand the impact of these events.


Once-weekly, high-dose stereotactic body radiotherapy for lung cancer: 6-year analysis of 60 early-stage, 42 locally advanced, and 7 metastatic lung cancers.
To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy(10)). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy(10). Respiration gating was used in 46%. The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older, debilitated, and with comorbidities. Elderly patients and/or patients medically unfit for combined modality therapy with locally advanced disease can find an effective palliative alternative in SBRT.