Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study.
Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the biological basis of frailty has been difficult to establish. In this study, we aimed to assess the possible association between different OS and inflammatory biomarkers and frailty. This cross-sectional analysis was performed among 2,518 subjects participating in a large population-based cohort study on aging conducted in Germany. Frailty was assessed as proposed by Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:M146-M156]. OS biomarkers, biological antioxidant potential (BAP), derivate of reactive oxygen metabolites (d-ROM) and total thiol levels (TTL), and an established biomarker of inflammation C-reactive protein (CRP) were measured by spectrophotometry and immunoturbidimetry. Logistic regression models were performed to assess the relationship between the OS biomarkers and frailty status. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to quantify the associations. Mean levels of d-ROM, TTL, and CRP differed between frail and non-frail participants (p values <0.0001). Comparing highest and lowest quartiles of the biomarkers, statistically significant positive associations with frailty were observed for d-ROM (OR: 2.02, 95% CI: 1.25-3.25) and CRP (OR: 3.15, 95% CI: 2.00-4.96), respectively, after controlling for age and sex. An inverse statistically significant association with frailty was observed for TTL (OR: 0.42, 95% CI: 0.25-0.69). The strong associations with OS biomarkers and CRP support a major role of OS and inflammation in the development of frailty, which should be followed up in further longitudinal studies on frailty.


Effect of long-term normalization of serum complement levels on the course of lupus nephritis.
We compared the long-term outcome of patients with lupus nephritis in whom normalization of complement levels (CH50) was sustained by adjustment of immunosuppressive therapy to those patients with persistently low complement levels despite similar immunosuppression in whom therapy was adjusted solely on the basis of clinical disease activity. Thirty-nine female patients with lupus nephritis recruited from 1972 to 1979 were prospectively studied (mean follow-up, 116.7 +/- 11 months). Entry criteria included initial renal biopsy, low CH50, and elevated anti-DNA antibody levels. A second biopsy was performed in 24 patients after an interval of 40.6 +/- 5 months. Treatment was started with prednisone (1 mg/kg/day). Azathioprine at a dose of 1.5 to 2.0 mg/kg/day was added if complement was not normalized by prednisone alone. Twenty-five of 39 patients had normal complement levels within six months (Group 1), and immunosuppressive therapy was tapered but continuously readjusted to the lowest dosage that preserved normal CH50 and maintained clinical remission. Eight of these 25 patients subsequently became persistently hypocomplementemic due to inadequate drug intake (Group 1B), whereas the complement levels continued to be controlled in the other 17 patients (Group 1A). Despite similar therapy, the remaining 14 patients did not achieve normalization of complement within the initial six months of therapy, and therefore future treatment decisions were based solely on clinical symptoms (Group 2). Renal pathologic lesions were classified according to World Health Organization criteria and a semi-quantitative chronicity index. During the first six months, there were no significant differences in clinical or histologic features between patients in whom complement levels were controlled and patients in whom complement levels were not controlled. After a mean observation period of 10 years, however, patients with consistent normalization of complement (Group 1A) did much better than patients with only short-term complement control (Group 1B) or persistent hypocomplementemia (Group 2). Both groups with low complement levels had a similar outcome with significantly worse kidney and patient survival. Life-table analysis demonstrated that the differences in outcome between complement-controlled and complement-uncontrolled groups became apparent only after five or more years of follow-up. Patients with a low chronicity score on initial biopsy whose complement level was controlled did uniformly well with no renal failure or death. (ABSTRACT TRUNCATED AT 400 WORDS)


Hormone replacement therapy for prevention and treatment of osteoporosis.
Estrogen therapy is clearly effective in the prevention and treatment of osteoporosis. Several estrogens and routes of administration are available. A progestin is required to protect the endometrium if the patient has a uterus. The duration of treatment required is unknown but probably is > or = 10 years for prevention and may be life-long, which is the requirement for patients with established disease. A regimen of patient monitoring can be easily established and must become routine for all patients on long-term treatment.


Site-Based Comparative Analysis of Sample Collection Through Direct Biopsy and Nasal Swabs for Early Diagnosis of Post-COVID Rhinomaxillary Fungal Infection Using Potassium Hydroxide Mounting: A Retrospective Cohort Study.
To perform site-based comparative analysis for samples collected from the nasal region and oral cavity subjected to microscopic detection of fungal hyphae in KOH mount in a group of patients with rhinomaxillary mucormycosis. Forty patients fulfilled eligibility criteria. The diagnostic outcome of detection of fungal hyphae from the KOH samples obtained was the primary endpoint of the study. Based on this, the samples were grouped into three groups viz-oral, nasal and both. The secondary outcome was to check if there was any diagnostic delay in these three groups of patients. The mean number of days for delayed diagnosis for oral site involvement was 56.33 ± 37.53, for nasal involvement was 32.86 ± 19.53 and for both oral and nasal involvement was 22.00 ± 12.94. This difference was statistically significant at p = 0.03. The mean delay in diagnosis was significantly less when both oral and nasal regions are involved as compared to the only oral region involved at P = 0.01. To avoid the chance of delayed diagnosis or false-negative results, it is best to collect samples from both nasal tissues and the most representative site in the dentoalveolar segment depending on the extensiveness of the disease.


Reaction of nitrite with ascorbate and its relation to nitrosamine formation.
In this study of the nitrosation of morpholine in the presence of ascorbic acid, the amount of ascorbate required to inhibit completely the formation of nitrosomorpholine depended on whether oxygen was present in the system. The nitric oxide (produced during the oxidation of ascorbate by nitrous acid) might have reacted with oxygen to yield additional oxidizing equivalents, or oxygen might have directly oxidized the ascorbate semiquinone intermediate produced in the initial step of oxidation reaction. A pH- dependent induction period observed during the nitrosation of morpholine in the presence of ascorbate and excess nitrite was accounted for by the kinetics of the reactions.


Characterization of immune response in mice to plasmid DNA encoding human sperm associated antigen 9 (SPAG9).
To examine the immunogenicity of the plasmid DNA encoding human sperm associated antigen 9 (hSPAG9), the cDNA corresponding to hSPAG9 was cloned in mammalian expression vector pcDNA 3.1 down stream of cytomegalovirus promoter. Immunization of female BALB/cJ mice with pcDNA-hSPAG9 plasmid DNA in saline by intramuscular (i.m.), by adsorbing onto gold microcarriers (delivered by gene gun) and by recombinant hSPAG9 (r-hSPAG9) protein generated antibody response against Escherichia coli expressed r-hSPAG9 protein and native SPAG9 in human sperm. Although mice immunized with r-hSPAG9 protein exhibited highest antibodies titres (P<0.001), the difference in the antibody titres seen by the two modes of plasmid DNA delivery were not significant (P>0.05). A dominant IgG1 isotype response was observed in mice immunized with pcDNA-hSPAG9 plasmid DNA delivered by gene gun as compared to a mixed IgG1-IgG2a isotype response in mice immunized with r-hSPAG9 protein and pcDNA-hSPAG9 plasmid DNA delivered by i.m. Further, antibodies generated by pcDNA-hSPAG9 plasmid DNA localized acrosomal compartment of human sperm and inhibited sperm adherence to or penetration in zona-free hamster egg penetration test. These studies for the first time, demonstrate the feasibility of generating an immune response to sperm specific hSPAG9 protein by DNA vaccine and that antibodies thus generated recognize native SPAG9 in human sperm.


Hormonal profile of diabetic men and the potential link to prostate cancer.
Previous studies suggest men with diabetes may be at reduced risk for prostate cancer as compared to men without diabetes. To investigate potential biological mechanisms, hormonal profiles of diabetic men and non-diabetic controls were compared. In the Health Professionals Follow-Up Study, plasma levels of C-peptide, testosterone, sex-hormone binding globulin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were determined in 171 diabetic men and 3,001 non-diabetic controls. Multiple linear regression analysis was conducted and least square means were calculated for hormones of interest. Plasma levels of several hormones either < or =1, 1.1-6, 6.1-14.9, or > or =15 years after diagnosis with diabetes were examined. As time since diabetes diagnosis increased, plasma levels of C-peptide and IGFBP-3 significantly decreased (p for trend: C-peptide =.05, IGFBP-3 =.03). While testosterone and SHBG levels both significantly increased with increasing time since diabetes diagnosis (p for trend: testosterone =.02, SHBG =.002), the ratio of testosterone to SHBG decreased, suggesting a reduction in bioavailable testosterone. Plasma IGF-1 levels were lower in diabetics than non-diabetics, but no significant time trend was noted. This study of hormonal profiles of diabetic versus non-diabetic men identified changes in diabetic men that may be consistent with reduced prostate cancer risk.


Breast Cancer Mortality among Women with a BRCA1 or BRCA2 Mutation in a Magnetic Resonance Imaging Plus Mammography Screening Program.
Annual breast magnetic resonance imaging (MRI) plus mammography is the standard of care for screening women with inherited BRCA1/2 mutations. However, long-term breast cancer-related mortality with screening is unknown. Between 1997 and June 2011, 489 previously unaffected BRCA1/2 mutation carriers aged 25 to 65 years were screened with annual MRI plus mammography on our study. Thereafter, participants were eligible to continue MRI screening through the high-risk Ontario Breast Screening Program. In 2019, our data were linked to the Ontario Cancer Registry of Cancer Care Ontario to identify all incident cancers, vital status and causes of death. Observed breast cancer mortality was compared to expected mortality for age-matched women in the general population. There were 91 women diagnosed with breast cancer (72 invasive and 19 ductal carcinoma in situ (DCIS)) with median follow-up 7.4 (range: 0.1 to 19.2) years. Four deaths from breast cancer were observed, compared to 2.0 deaths expected (standardized mortality ratio (SMR) 2.0, p = 0.14). For the 489 women in the study, the probability of not dying of breast cancer at 20 years from the date of the first MRI was 98.2%. Annual screening with MRI plus mammography is a reasonable option for women who decline or defer risk-reducing mastectomy.


The threat of reduced efficacy of anthelmintics against gastrointestinal nematodes in sheep from an area considered anthelmintic resistance-free.
The worldwide increased difficulty to combat gastrointestinal nematode (GIN) infection in sheep, due to progressing anthelmintic resistance (AR), calls for an enhanced and standardized implementation of early detection of AR. This study provides a snapshot of the current AR status against benzimidazoles and macrocyclic lactones in southern Italy, generated with standardized techniques. On 10 sheep farms, the efficacy of albendazole (ALB) and either eprinomectin (EPR) or ivermectin (IVM) was evaluated based on the faecal egg count reduction test (FECRT) performed with the Mini-FLOTAC. For each tested drug, 40 sheep were rectally sampled at D0 and sampled again 14 days after the treatment (D14). The FECRT was calculated from individual samples and pooled samples which consist of 5 individual samples. Efficacy was classified as 'reduced, 'suspected' and 'normal'. Coprocultures were set for D0 and D14 faecal samples of each group. From farms with FECR < 95%, an in vitro egg hatch test (EHT) and a follow-up FECRT using fenbendazole (FBZ) were conducted. Based on the FECR, high efficacy (from 95.7% to 100%) was observed for ALB and IVM in eight farms (Farms 3-10). On Farm 1 and Farm 2, the efficacy for the macrocyclic lactones was classified as 'normal', but 'reduced' efficacy was observed for ALB on Farm 1 (FECR = 75%) and 'suspected' efficacy on Farm 2 (FECR = 93.3%) with the predominant GIN genus Trichostrongylus followed by Haemonchus at D14. The FEC results of pooled samples strongly correlated with those of individual samples, for FEC at D0 (rs = 0.984; P < 0.0001) and at D14 (rs = 0.913; P < 0.0001). The classifications of efficacy in Farm 1 (FECR = 86.0%) and Farm 2 (FECR = 93.0%) in the follow-up FECRT with FBZ coincide with the main FECRT trial. The in vitro EHT confirmed AR in both farms (Farm 1: 89%; Farm 2: 74%). In regions like southern Italy, where the negative impacts from AR have played a minor role, efficient monitoring of AR is important in order to evaluate potential risks and being able to promptly respond with countermeasures.


Engraftment following T cell-depleted bone marrow transplantation. III. Differential effects of increased total-body irradiation on semiallogeneic and allogeneic recipients.
Three different doses of total-body irradiation (TBI) (1100, 1300, 1500 cGy) have been analyzed as conditioning regimens for semiallogeneic B6AF1 (H-2b X H-2a) and allogeneic A/J (H-2a) recipients of T cell-depleted C57BL6 (H-2b) bone marrow transplants. Recipient survival and engraftment of both donor erythrocytes and lymphocytes were examined in each group. The large majority of allogeneic mice prepared with 1100 cGy rejected their grafts, which resulted in poor survival (less than 30%); improved survival (up to 80%) and complete donor engraftment were noted as the TBI dose was increased. By contrast, survival in semiallogeneic B6AF1 recipients was independent of TBI dose and was greater than 80% in all groups. Outright failure of marrow grafts (less than 10% donor hematopoiesis) did not occur in these recipients, but mixed chimerism (simultaneous occurrence of both donor and host cells) was frequently observed at lower TBI doses. Complete (greater than 90%) donor engraftment was noted for erythrocytes but not for lymphocytes. Possible mechanisms accounting for these differences between semiallogeneic and allogeneic recipients of marrow transplants are discussed.


FT-IR-based method for rutin, quercetin and quercitrin quantification in different buckwheat (Fagopyrum) species.
The present study explores an alternative method for antioxidants determination in buckwheat (Fagopyrum) samples. Buckwheat contains different amounts of the antioxidants rutin, quercetin and quercitrin in different plant parts. Buckwheat seeds are most commonly used as food; however, preparations from the herb can also be used as a rich source of rutin. Infrared spectroscopy was used for individual and sum quantification of rutin, quercetin and quercitrin in whole and ground flowers and leaves of seven different buckwheat species. Correlation coefficients R of calibration and independent validation set for rutin, quercetin and quercitrin were 1.00 and 0.98, 0.94 and 0.99, 0.99 and 0.95, respectively. Some of the developed models had accuracy comparable to the reference HPLC method. Additionally many different parameters that give an important insight into the FTIR technique are discussed (different plant parts, whole and ground untreated samples, 3 different resolutions, 7 spectra pre-treatments, using individual or averaged spectra, reducing spectral data input, considering additional non-spectral data). The implemented technique used no sample preparation, is non-destructive and uses very little amounts of sample. Result show that infrared spectroscopy can be a fast and environmentally friendly alternative technique for routine analysis of main flavonoids in aerial parts of buckwheat.


Amblyopia revisited: evidence for the heterogeneity of the syndrome.
Functional amblyopia has been considered as a homogeneous syndrome for the last decade or so, mainly on the basis of animal experiments. Recently, important differences have been shown to exist between strabismic and anisometropic as well as deprivation amblyopia. Even strabismic amblyopia may be subdivided in different classes. These statements are supported with experimental and clinical data. Clinical relevance of the heterogeneity of amblyopia is discussed particularly in the view of the concept of its cure.


Brain imaging in psychiatry - a study of 435 psychiatric in-patients at a university clinic.
The use of brain imaging in psychiatry still lacks clear guidelines. We investigated the referral practice, outcome and predictive factors of neuroimaging in a Swiss psychiatric university clinic. Medical files were reviewed retrospectively for 435 consecutively hospitalized patients who were subjected to neuroimaging. The association between the sociodemographic and clinical characteristics and the scan results was analyzed using bivariate and multivariate analyses. Of overall examinations, 69.4% were normal, 16.3% equivocal and 14.3% abnormal; 2.9% of scans ordered for screening only showed pathology. Neurologic signs and advanced age of patients predicted abnormal scan findings, whereas other variables such as EEG results showed no significant association. Our results support the need for clear indications for using brain imaging in psychiatric in-patients. Focal neurologic signs and advanced patient age seems to predict abnormal scan results. However, these criteria are not sufficiently sensitive to predict significant scan findings in all patients.


A kinematic and kinetic analysis of the hip and knee joints in patients with posterior tibialis tendon dysfunction; comparison with healthy age-matched controls.
The biomechanical abnormalities in patients with posterior tibial tendon dysfunction (PTTD) have been described, but few studies have investigated biomechanical chains of adjacent joints. Therefore, we examined the gait pattern of the lower extremity in subjects with PTTD, focusing on the hip and knee joints. We compared 19 PTTD patients (average age: 67.1) with 30 age-matched control subjects (average age: 65.1). Gait analysis was performed with a nine-camera motion-capture system and four force plates, using the Vicon Plug-In-Gait and Vicon Nexus software. Temporal-spatial parameters were compared between PTTD and control subjects, and motion and ground reaction force data were compared between the affected limb, the contralateral limb, and the right limb in control subjects. Subjects with PTTD had increased stance phase ratio and decreased stride length, cadence, and gait speed. The limbs of subjects with PTTD showed increased knee internal rotation at lording response, which was biased to abduction in the knee joint during the gait cycle, and irregular hip flexion and knee extension moment in the terminal stance, even under control of gait speed. We believe that the subjects with PTTD have an increased risk of knee osteoarthritis in both the affected and contralateral limbs.


Studies on the early changes in acute isoniazid neuropathy in the rat.
Large single doses if isoniazid by mouth (1--2g/kg) have been shown to produce in rats Wallerian degeneration visible with the light microscope from the third day onwards. By contrast, changes in axons are seen from 24 h onwards by electron microscopy. The earliest ultrastructural changes are associated with vacuoles appearing between axon and Schwann cells. These are large and focal, and often compress the axon. The adjacent axon may show changes in smooth ER, and in microtubular arrangement. Alterations in smooth membranes and in mitochondria are visible in Schwann cell cytoplasm, not necessarily related to the vacuole formation and axonal features. It is suggested that INH neuropathy is essentially a multifocal axonal lesion.


Results and morbidity of percutaneous nephrolithotripsy.
The medical records of the first 210 patients treated with percutaneous nephrolithotripsy at Duke University Medical Center were reviewed. Eleven patients were treated for bilateral stones for a total of 221 renal units. The procedure failed in 6 patients (2.7%). Stone fragments were retained in 55 patients (24.9%), with unplanned fragments in 41 cases (18.6%). Open surgery was subsequently performed in 4 patients (1.8%). There were no nephrectomies or deaths in our patients. Percutaneous nephrolithotripsy is a highly successful method for removal of upper tract stones and has a complication rate no higher than that of open surgical procedures.


Prevalence and correlates of non-suicidal self-injury among lesbian, gay, bisexual, and transgender individuals: A systematic review and meta-analysis.
The current review presents a meta-analysis of the existing empirical literature on the prevalence of non-suicidal self-injury (NSSI) among lesbian, gay, bisexual, and transgender (LGBT) individuals, as well as on correlates of NSSI within sexual and gender minority populations. Eligible publications (n = 51) were identified through a systematic search of PsycINFO, MEDLINE, and Embase, supplemented by a search of references of prior reviews on this topic. NSSI prevalence rates were quite elevated among sexual (29.68% lifetime) and gender (46.65% lifetime) minority individuals compared to heterosexual and/or cisgender peers (14.57% lifetime), with transgender (46.65% lifetime) and bisexual (41.47% lifetime) individuals being at greatest risk. Even among these group findings, sexual minority youth emerged as an especially vulnerable population. Moreover, current evidence suggests these rates and differences between LGBT and heterosexual and/or cisgender peers have not declined over time. These findings may in some measure be due to the existence of LGBT-specific risk correlates combined with general risk correlates being more severe among sexual and gender minority populations. Additional research, particularly employing a longitudinal design, is needed in this area to advance efforts to reduce risk for NSSI among sexual and gender minority individuals.


Human β-defensin-3 and nuclear factor-kappa B p65 synergistically promote the cell proliferation and invasion of oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is a usual oral cancer. Therefore, it's essential to identify targets for its early diagnosis and therapy. This research aimed to explore the roles of human β-defensin-3 (hBD-3) and nuclear factor-kappa B (NF-κB) p65 in the pathogenesis and progression of OSCC. The connection between NF-κB p65 and the carcinogenesis of oral cancer was analyzed by immunohistochemical staining. The relative expressions of hBD-3 and NF-κB p65 in OSCC cells were evaluated by qRT-PCR and Western blot. Afterward, hBD-3 was knocked down, and NF-κB p65 was overexpressed. The cell viability and invasion were tested via CCK-8 and Transwell experiment, and the expression of hBD-3, NF-κB p65, and its downstream molecules was evaluated by Western blot. The expression of NF-κB p65 was increased with the aggravation of the oral submucosal fibrosis. HBD-3 and NF-κB p65 were high-expressed in OSCC cells. The viability and invasion abilities of OSCC cells that knocked down hBD-3 were markedly decreased, while they were restored by the overexpression of NF-κB p65. The expressions of NF-κB p65 and c-myc were diminished while IκB and p21 were raised with the knockdown of hBD-3. After overexpression of NF-κB p65, the expression of hBD-3 and IκB did not change markedly, while c-myc was increased and p21 was decreased dramatically. HBD-3 and NF-κB p65 facilitate the proliferation and invasion of OSCC cells, and hBD-3 may promote this process by governing the expression of NF-κB p65 and its downstream c-myc and p21.


Non-redundant functions of group 2 innate lymphoid cells.
Protective immunity relies on the interplay of innate and adaptive immune cells with complementary and redundant functions. Innate lymphoid cells (ILCs) have recently emerged as tissue-resident, innate mirror images of the T cell system, with which they share lineage-specifying transcription factors and effector machinery1. Located at barrier surfaces, ILCs are among the first responders against invading pathogens and thus could potentially determine the outcome of the immune response2. However, so far it has not been possible to dissect the unique contributions of ILCs to protective immunity owing to limitations in specific targeting of ILC subsets. Thus, all of the available data have been generated either in mice lacking the adaptive immune system or with tools that also affect other immune cell subsets. In addition, it has been proposed that ILCs might be dispensable for a proper immune response because other immune cells could compensate for their absence3-7. Here we report the generation of a mouse model based on the neuromedin U receptor 1 (Nmur1) promoter as a driver for simultaneous expression of Cre recombinase and green fluorescent protein, which enables gene targeting in group 2 ILCs (ILC2s) without affecting other innate and adaptive immune cells. Using Cre-mediated gene deletion of Id2 and Gata3 in Nmur1-expressing cells, we generated mice with a selective and specific deficiency in ILC2s. ILC2-deficient mice have decreased eosinophil counts at steady state and are unable to recruit eosinophils to the airways in models of allergic asthma. Further, ILC2-deficient mice do not mount an appropriate immune and epithelial type 2 response, resulting in a profound defect in worm expulsion and a non-protective type 3 immune response. In total, our data establish non-redundant functions for ILC2s in the presence of adaptive immune cells at steady state and during disease and argue for a multilayered organization of the immune system on the basis of a spatiotemporal division of labour.


Prediction of liquid chromatographic retention for differentiation of structural isomers.
A liquid chromatography (LC) retention time prediction software, ACD/ChromGenius, was employed to calculate retention times for structural isomers, which cannot be differentiated by accurate mass measurement techniques alone. For 486 drug compounds included in an in-house database for urine drug screening by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOFMS), a retention time knowledge base was created with the software. ACD/ChromGenius calculated retention times for compounds based on the drawn molecular structure and given chromatographic parameters. The ability of the software for compound identification was evaluated by calculating the retention order of the 118 isomers, in 50 isomer groups of 2-5 compounds each, included in the database. ACD/ChromGenius predicted the correct elution order for 68% (34) of isomer groups. Of the 16 groups for which the isomer elution order was incorrectly calculated, two were diastereomer pairs and thus difficult to distinguish using the software. Correlation between the calculated and experimental retention times in the knowledge base tested was moderate, r(2)=0.8533. The mean and median absolute errors were 1.12 min, and 0.84 min, respectively, and the standard deviation was 1.04 min. The information generated by ACD/ChromGenius, together with other in silico methods employing accurate mass data, makes the identification of substances more reliable. This study demonstrates an approach for tentatively identifying compounds in a large target database without a need for primary reference standards.


Inhibitors of cannabinoid receptor 1 suppress the cellular entry of Lujo virus.
Lujo virus (LUJV), which belongs to Mammarenavirus, family Arenaviridae, has emerged as a pathogen causing severe hemorrhagic fever with high mortality. Currently, there are no effective treatments for arenaviruses, including LUJV. Here, we screened chemical compound libraries of Food and Drug Administration (FDA)-approved drugs and G protein-coupled receptor-associated drugs to identify effective antivirals against LUJV targeting cell entry using a vesicular stomatitis virus-based pseudotyped virus bearing the LUJV envelope glycoprotein (GP). Cannabinoid receptor 1 (CB1) antagonists, such as rimonabant, AM251 and AM281, have been identified as robust inhibitors of LUJV entry. The IC50 of rimonabant was 0.26 and 0.53 μM in Vero and Huh7 cells, respectively. Analysis of the cell fusion activity of the LUJV GP in the presence of CB1 inhibitors revealed that these inhibitors suppressed the fusion activity of the LUJV GP. Moreover, rimonabant, AM251 and AM281 reduced the infectivity of authentic LUJV in vitro, suggesting that the antiviral activity of CB1 antagonists against LUJV is mediated, at least in part, by inhibition of the viral entry, especially, membrane fusion. These findings suggest promising candidates for developing new therapies against LUJV infections.


Fastbreak: a tool for analysis and visualization of structural variations in genomic data.
Genomic studies are now being undertaken on thousands of samples requiring new computational tools that can rapidly analyze data to identify clinically important features. Inferring structural variations in cancer genomes from mate-paired reads is a combinatorially difficult problem. We introduce Fastbreak, a fast and scalable toolkit that enables the analysis and visualization of large amounts of data from projects such as The Cancer Genome Atlas.


Measles outbreak in a French Roma community in the Provence-Alpes-Côte d'Azur region, France, May to July 2017.
To analyse a measles outbreak in a Roma community. We describe a community-wide outbreak of genotype D8 measles that took place in southeastern France, between May and July 2017, along with the control measures adopted. We identified a total of eighteen cases, between six months and 24 years old. All cases were unvaccinated or incompletely vaccinated and belonged to a sedentary French Roma community. Most of them (67%) were hospitalised, with three cases (17%) of severe measles including one death of a 16-year-old girl who had previously received oral corticosteroids. The latter was the only lethal case notified in France during the year 2017. Control measures included intensification of surveillance, isolation of cases, and a large vaccination campaign in this Roma community. During the outbreak period, there was no case of healthcare-associated measles transmission. A broad adherence to vaccination through the mediating role of both the chief of the community and the pastor allowed reaching completed vaccination coverage of 90%. Efforts should be concentrated to enhance access to health services for minorities such as the Roma community characterized by low vaccination coverage. A trustful relationship with leaders of the community is essential to ensure adherence to vaccination. In France, attributable mortality to measles is low and concerns mainly unvaccinated and immunodepressed patients.


Genotypic characterization of hepatitis C virus and its significance in patients with chronic liver disease from Northern India.
The characterization of hepatitis C virus (HCV) strains has important prognostic, therapeutic, and epidemiologic implications. The present study was intended to determine the HCV genotypes from Northern India in chronic liver disease (CLD) patients. The response to therapy in various subtypes was also evaluated in patients with chronic hepatitis. Furthermore, the genotypes were correlated with the biochemical and histopathologic parameters to assess the severity of liver disease. Five milliliter of blood sample was collected aseptically from 98 patients with CLD due to hepatitis C. Genotyping was performed by restriction fragment length polymorphism and type-specific polymerase chain reaction, followed by direct sequencing. The HCV genotypes depicted were 1a (6.12%), 1b (8.16%), 1c (8.16%), 3a (17.34%), 3b (6.12%), 3a + 3b (40.81%), 3a + 1b (7.14%), and an unclassified type of 6.12%. The present study revealed that HCV genotype 3 is the predominant one, with 40.81% (40/98) being a mixed type of 3a with 3b and identification of newer subtype 1c. HCV subtypes 1a, 3a, and 3b are responding to therapy, whereas 1b (40%, 2/5), 1c (66.67%, 2/3), 3g (33.3%, 1/3), 3a + 3b (41.6%, 5/12), and mixed type 3a + 1b (66.67%, 4/6) are poor responders to therapy. The biochemical profiles were higher in mixed type followed by types 3 and 1, whereas the histologic parameters revealed that the severity of liver disease was more in mixed type followed by types 1 and 3, which also showed poor response to therapy.


Physiologic Timeline of Cranial-Base Suture and Synchondrosis Closure.
Fusion of cranial-base sutures/synchondroses presents a clinical conundrum, given their often unclear "normal" timing of closure. This study investigates the physiologic fusion timelines of cranial-base sutures/synchondroses. Twenty-three age intervals were analyzed in subjects aged 0 to 18 years. For each age interval, 10 head computed tomographic scans of healthy subjects were assessed. Thirteen cranial-base sutures/synchondroses were evaluated for patency. Partial closure in greater than or equal to 50 percent of subjects and complete bilateral closure in less than 50 percent of subjects defined the fusion "midpoint." Factor analysis identified clusters of related fusion patterns. Two hundred thirty scans met inclusion criteria. The sutures' fusion midpoints and completion ages, respectively, were as follows: frontoethmoidal, 0 to 2 months and 4 years; frontosphenoidal, 6 to 8 months and 12 years; and sphenoparietal, 6 to 8 months and 4 years. Sphenosquamosal, sphenopetrosal, parietosquamosal, and parietomastoid sutures reached the midpoint at 6 to 8 months, 8 years, 9 to 11 months, and 12 years, respectively, but rarely completed fusion. The occipitomastoid suture partially closed in less than or equal to 30 percent of subjects. The synchondroses' fusion midpoints and completion ages, respectively, were as follows: sphenoethmoidal, 3 to 5 months and 5 years; spheno-occipital, 9 years and 17 years; anterior intraoccipital, 4 years and 10 years; and posterior intraoccipital, 18 to 23 months and 4 years. The petro-occipital synchondrosis reached the midpoint at 11 years and completely fused in less than 50 percent of subjects. Order of fusion of the sutures, but not the synchondroses, followed the anterior-to-posterior direction. Factor analysis suggested three separate fusion patterns. The fusion timelines of cranial-base sutures/synchondroses may help providers interpret computed tomographic data of patients with head-shape abnormalities. Future work should elucidate the mechanisms and sequelae of cranial-base suture fusion that deviates from normal timelines.


Corneal Topography for Intraocular Lens Selection in Refractive Cataract Surgery.
The purpose of this review is to evaluate the usefulness of corneal topography to select premium intraocular lenses (IOLs), including aspherical IOLs, toric IOLs, and multifocal IOLs, in refractive cataract surgery. Corneal topography can detect corneal regular astigmatism, corneal irregular astigmatism (higher-order aberrations [HOAs]) including spherical aberration, and corneal shape abnormalities after corneal refractive surgery. Surgeons can explain to the patients with significant corneal HOAs about its effect on postoperative visual function before surgery. Multifocal IOLs should not be selected for such eyes. For eyes with abnormal corneal shape, appropriate IOL power calculation formulae can be applied. In the case of toric IOLs, regular astigmatism and corneal HOAs should be checked. Before implanting an aspheric IOL, it is ideal to confirm spherical aberration of the cornea is not below the normal range. Because corneal HOAs, abnormal corneal shape after corneal refractive surgery, corneal regular astigmatism, and corneal spherical aberration increase postoperative refractive errors and poor vision quality with premium IOLs, corneal topography before cataract surgery is helpful in screening patients who are not appropriate candidates for premium IOLs.


[Therapy, therapist and client tested with the Latin square design].
A Latin square design is suggested for testing, 1) whether a specific therapy is effective, 2) whether the therapists involved differ in being successful and 3) whether selected clients react differentially (more or less) on that therapy. To avoid parametric implications, a modified Friedman-test is proposed for evaluating the suggested design nonparametrically.


Advanced interatrial block predicts clinical recurrence of atrial fibrillation after catheter ablation.
It has been demonstrated that advanced interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF); however, the impact of advanced IAB on recurrence of paroxysmal AF after catheter ablation is not clear. 204 consecutive patients with paroxysmal AF who underwent index circumferential pulmonary vein (PV) isolation were prospectively enrolled. In all patients, a resting electrocardiogram in sinus rhythm was evaluated for the presence of advanced IAB, defined as a P-wave duration >120ms and biphasic (±) morphology in the inferior leads. Advanced IAB was detected in 20.1% of patients. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30s beyond 3 months after the catheter ablation in the absence of any antiarrhythmic treatment. During the mean follow-up period of 13.9±6.2 months (range, 3-27 months), 62 patients (30.4%) developed recurrence of AF. The recurrence rate was higher in patients with advanced IAB than those without advanced IAB (46.3% vs. 26.4%, p=0.006). Cox regression analysis with adjustment for age, P-wave duration, CHADS2 score, and PV isolation identified advanced IAB (hazard ratio, 2.111; 95% confidence interval, 1.034-4.308; p=0.040) and left atrial diameter (hazard ratio, 1.051; 95% confidence interval, 1.004-1.100; p=0.034) as two independent predictors of recurrence of AF. Patients with advanced IAB were at an increased risk of AF recurrence after catheter ablation.


Exosomal long non-coding RNAs in the diagnosis and oncogenesis of pancreatic cancer.
Extracellular vesicles, specifically exosomes, play a significant role as an extracellular messenger through their transporting cargo. Of particular interest are the potential roles they play in pancreatic cancer, one of the leading causes of cancer-related mortality worldwide. Pancreatic Ductal Adenocarcinoma displays high chemo-resistance and metastatic ability, which may be influenced by cancer-derived exosomes carrying proteins, lipids and RNA. To date, among the most extensively examined exosomal molecular cargo there are long non-coding RNAs (lncRNAs) that, despite the increasing interest in their role and functions, are relatively poorly understood compared to other RNA transcripts. Nevertheless, we have witnessed an increasing interest for lncRNAs roles and functions in the past decade. For example, lncRNAs have been investigated as potential biomarkers for diagnosing pancreatic cancer and may have a role as therapeutics targets for precision medicine, but may also directly intervene in tumour progression features such as metastasis, epithelial to mesenchymal transition and resistance of cancer cells towards chemotherapy agents. The function of lncRNAs within various cancer exosomes is still undefined. In this review, we summarize the current knowledge on pancreatic cancer-derived exosome specific lncRNAs having prominent roles in genome integrity, pancreatic cancer progression and in other oncogenic hallmarks.


The effect of spatial frequency on steady-state accommodation.
Accommodation responses to sinusoidally modulated vertical gratings, at a vergence of -5.0 D, were measured over a 10 min period. Three spatial frequencies were employed: 1.67, 5.0 and 15 cycles degree-1. The results show that 1.67 and 5.0 cycles degree-1 elicit good accommodation responses which are temporally stable. All five subjects employed were unable to maintain an accurate accommodation response to a 15 cycles degree-1 grating. Consideration of the changes occurring in the retinal modulation with accommodative error indicates that spatial frequencies around 5.0 cycles degree-1 are the most useful for accommodation.


Robust optimization of uncertainty-based preventive maintenance model for scheduling series-parallel production systems (real case: disposable appliances production).
Industrial companies would attempt to keep themselves agile in the dynamic market. Given the competition among industries, lean methods are employed to reduce costs in the system. Among them, maintenance is significant to have a system available for manufacturing tasks. Maintenance is identified as the largest cost control tools in the equipment-driven industry. Implementing an effectual plan for preventive maintenance helps to be much more flexible and create an innovative solution for planning in the production. In this vein, this paper introduces an optimization model related to flexible flow-shop system scheduling in a series-parallel production system of disposable appliances by considering the preventive maintenance (PM) policy. By planning preventive maintenance, extra operation time is incurred to the system which may influence the cycle time and lead to lost sales and back orders. Therefore, the paper proposes a mathematical model to consider both operations times and availability of the whole production system to minimize the delays to reach an optimal sequence of processing. Since uncertainty exists in real industrial systems, the processing times are uncertain here. To handle uncertainty, robust optimization has been applied to solve the problem. In addition, a scenario-based genetic algorithm (SBGA) and Particle Swarm Optimization (PSO) algorithm have been developed to solve the proposed model. The results indicate the appropriate performance of the proposed approach in terms of time-saving leads to saving the cost of PM.


Towards the Inference of Social and Behavioral Determinants of Sexual Health: Development of a Gold-Standard Corpus with Semi-Supervised Learning.
Social and behavioral determinants of health (SBDH) are environmental and behavioral factors that are increasingly recognized for their impact on health outcomes. We describe ongoing research to extract SBDH related to sexual health from clinical documentation. Our work addresses several challenges. First, there is no standard set of SBDHs for sexual health; we describe our curation of 38 such SBDHs. Second, it is unknown how SBDH related to sexual health are expressed in clinical notes; we detail the characteristics of an annotated corpus. Third, SBDH documentations are rare; we describe the use of semi-supervised learning to accelerate the annotation process by identifying notes likely to document SBDH. Fourth, we describe preliminary results to infer an array of SBDH from clinical documentation using supervised learning.


Internal fixation of delayed union of fracture with chronic osteomyelitis due to Staphylococcus epidermidis: A case report.
The most feared and challenging complication in treating patients with musculoskeletal trauma is infection after fracture fixation, which can delay healing and, in turn, result in permanent functional loss of limbs or even amputation. Here, we describe a case in which a patient presented with stage 4 chronic osteomyelitis on the right tibia and fibula. To treat the late infection by eradicating or reducing the infection, it was recommended to replace the internal fixation with surgical debridement for 6 weeks and antibiotics for 6-12 weeks until the internal fixation device could be removed. Delayed union and chronic osteomyelitis are possible complications of IAFF.


Pseudohyperaldosteronism: pathogenetic mechanisms.
Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of plasma renin activity and aldosterone. Pseudohyperaldosteronism can be due to a direct mineralocorticoid effect, as with desoxycorticosterone, fluorohydrocortisone, fluoroprednisolone, estrogens, and the ingestion of high amounts of glycyrrhetinic acid. A block of 11-hydroxysteroid-dehydrogenase type 2 (11HSD2), the enzyme that converts cortisol into cortisone, at the level of epithelial target tissues of aldosterone, is involved in other cases. This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (apparent mineralocorticoid excess syndrome and some cases of low renin hypertension) or to an acquired reduction of the activity of the enzyme due to glycyrrhetinic acid, carbenoxolone, and grapefruit juice. In other cases saturation of 11HSD2 may be involved as in severe Cushing's syndrome and chronic therapy with some corticosteroids. Recently, an activating mutation of the mineralocorticoid receptor gene has been described. Another genetic cause of pseudohyperaldosteronism is the syndrome of Liddle, which is due to a mutation of the gene encoding for beta and gamma subunits of the sodium channels.


High Mycobacterium bovis genetic diversity in a low prevalence setting.
The genetic diversity among South African Mycobacterium bovis isolates from cattle was determined by genetic fingerprinting. The restriction fragment length polymorphism (RFLP) markers IS6110 and polymorphic GC-rich sequence (PGRS) as well as spoligotyping and determination of variable number of tandem repeats (VNTR) were used to characterize sub samples of 91 M. bovis field isolates. PGRS RFLP was the single most discriminatory method and combinations of typing methods, which included IS6110 and/or PGRS had the highest discriminatory power, able to reveal 29 distinct genotypes among 35 farms with no epidemiological link. Three of the farms were co-infected with two genetically unrelated strains. In contrast to reports from European and also other colonised countries on the African continent our findings are suggestive of a high genetic diversity of M. bovis in South Africa's cattle population, implying a variety of unrelated ancestor strains. Despite effective intervention through test-and-slaughter campaigns no indication of a 'founder effect' was apparent in the panel of isolates derived from all infected provinces.


Friedreich ataxia. II. Normal kinetics of lipoamide dehydrogenase.
Lipoamide dehydrogenase (LAD) kinetic values, Km and Vmax, were normal in 11 patients with Friedreich ataxia. Fibroblast activities of the pyruvate and alpha-ketoglutarate dehydrogenase complex, and LAD activities, were also normal. There was no reduction in oxidative decarboxylation of pyruvate, alpha-ketoglutarate, or several other substrates in intact fibroblasts. Methodologic differences may account for differences of opinion about putative abnormalities of the alpha-ketoacid dehydrogenase complexes.


Fractionation with ethanol of nucleic acids from viroid-infected plants.
A combination of high salt and low ethanol concentration allowed the fractionation of nucleic acids extracted from viroid-infected leaves. By adding 0.4-0.5 vol of ethanol to 1 vol of a solution in 2 M LiCl of nucleic acids (containing mainly DNA, 4S, 5S, 7S, and viroid RNAs), 85% of the DNA and 75% of the 4S RNA remained in solution, from where they could be recovered by increasing the ethanol concentration, whereas almost all 5S, 7S, and viroid RNAs precipitated. When this process was repeated three times a 95% elimination of the initial DNA and 4S RNA was achieved. The method can be of special interest in viroid purification considering that DNA and 4S RNA are the most abundant contaminants in the starting solution of nucleic acids. It is suggested that the highly ordered secondary structure of viroid RNA may be responsible for its particular behavior in the ethanol fractionation of nucleic acids.


The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene.
A cDNA clone YT35 , synthesized from poly(A)+ RNA of the human T cell tumor Molt 3, exhibits homology to the variable (V), joining (J), and constant (C) regions of immunoglobulin genes. We have isolated and sequenced the germ-line V and J gene segment counterparts to YT35 from a human cosmid library, and these failed to encode 14 nucleotides of the cDNA clone between the V and J regions. We postulate that these 14 nucleotides are encoded by a third gene segment analogous to the diversity (D) gene segments of immunoglobulin heavy chain genes. This T cell antigen receptor V gene appears to be assembled from three gene segments, V, D, and J, and accordingly most closely resembles immunoglobulin heavy chain V genes.


Significant factors influencing chronic postoperative inguinal pain: A conditional time-dependent observational cohort study.
Inguinal hernia (IH) repair is a common surgical procedure. Focus has shifted from recurrences to chronic postoperative inguinal pain (CPIP). To assess the natural course of CPIP and identify patient factors influencing the onset of CPIP, an observational registry-based study was performed. Data prospectively collected from the Club-Hernie national database was retrieved from 2011 until 2021. Patients who underwent elective surgery for inguinal hernia were divided in an irrelevant pain group and relevant pain group. Relevant pain at one year and two years were compared with patients with irrelevant pain at all-time points (preoperatively, one month, one year and two years). Quality of life questions were compared between relevant pain at one year and two years. 4.016 patients were included in the analysis. Mean age was 65.1 years, 90.3% of patients was male. Factors correlated with CPIP onset were age, gender, ASA, recurrent surgery, surgical technique, nerve handling and fixation type. Relevant pain at one month was a greater risk for CPIP than preoperative pain (12.3% vs 3.6%). In the majority of patients (83.2%) CPIP was ameliorated at two years. Hernia related complaints differed significantly between CPIP at one year and two years. Postoperative pain after one month was a greater risk factor for CPIP development than preoperative pain. CPIP at one year seems to have a different pain etiology than CPIP at two years. Patient and surgical factors influence the onset of CPIP at one year, however the natural course of these complaints shows great decline at two years, largely without reinterventions.


Slice cultures of the imprinting-relevant forebrain area MNH of the domestic chick: quantitative characterization of neuronal morphology.
The persistence of morphological features of neurons in slice cultures of the imprinting-relevant forebrain area MNH (mediorostral neostriatum and hyperstriatum ventrale) of the domestic chick was analysed at 7, 14, 21 and 28 days in vitro. After having been explanted and kept in culture the neurons in vitro have larger soma areas, longer and more extensively branched dendritic trees and lower spine frequencies compared to the neurons in vivo. During the analyzed culturing period, the parameters soma area, total and mean dendritic length, number of dendrites, number of dendritic nodes per dendrite and per neuron as well as the spine densities in different dendritic segments showed no significant differences between early and late periods. Highly correlated in every age group were the total dendritic length and the number of dendritic nodes per neuron, indicating regular ramification during dendritic growth. Since these morphological parameters remain stable during the first 4 weeks in vitro, this culture system may provide a suitable model to investigate experimentally induced morphological changes.


Butterfly larvae reduce host plant survival in vicinity of alternative host species.
Mortality of an annual plant. Collinsia torreyi, was increased in the vicinity of Pedicularis semibarbata plants. This was a consequence of feeding by Euphydryas editha, a herbivore which feeds on both plant species. Mortality of C. torreyi was better predicted by distance from P. semibarbata than by density of C. torreyi. Since not all herbivores are monophagous, interactions involving distance and density effects on plant survival and on vegetational diversity need to be considered with respect to plant and herbivore communities. Some of the complexities of one predator, two prey systems are discussed.


Absence of 7-acetyl taxol binding to unassembled brain tubulin.
The effect of taxol on microtubule proteins at 0 degrees C is controversial. In order to determine if taxol is unable to bind to unassembled tubulin, as has been hypothesized, the binding of [3H]acetyl taxol has been studied using equilibrium microdialysis. Ac-taxol bound to microtubules at 37 degrees C and the binding remained stable when the temperature was lowered to 0 degrees C. Ac-taxol bound also at 0 degrees C to microtubules stabilized with rhazinilam. In contrast, there was no binding of Ac-taxol to unassembled tubulin, either free tubulin at 0 degrees C or tubulin, complexed with several microtubule poisons, at 0 and 37 degrees C.


Influence of cell cycle phases on the electrical activity and hormone release in a transformed line of anterior pituitary cells.
Electrophysiological experiments have shown that about 50% of cultured GH3 cells (tumoral cell line, from the anterior pituitary gland) are inexcitable i.e. they do not display action potentials either spontaneously or when depolarized by a current pulse. We report here this inexcitability may be related to cellular kinetics. Thus we have studied the relationship between the various phases of the cell cycle, the electrophysiological properties of GH3/B6 cells and spontaneous or induced Prolactin and Growth Hormone (GH) release rates. Asynchronous populations of viable cells were stained with Hoechst 33 342 DNA fluorescent dye, and sorted using a flow cytometer into G1 and S phases. After selection intracellular potentials were recorded using a single glass micro-electrode; the basal or TRH stimulated rates of PRL and GH secretions were determined by RIA. Electrical properties of the cells i.e. resting potentials, input membrane resistance and excitability, reached a maximum for cells in G2+M phases. Only cells in G2+M displayed action potentials and TRH increased their secretion by 5 times for GH and by 6 times for PRL. In G1 and S phases the cells were electrically inactive and secretion rates remained at their basal levels. These findings demonstrate that the mechanism of stimulus secretion coupling is dependent upon the phases of the cell cycle.


Arginine as a general acid catalyst in serine recombinase-mediated DNA cleavage.
Members of the serine family of site-specific DNA recombinases use an unusual constellation of amino acids to catalyze the formation and resolution of a covalent protein-DNA intermediate. A recent high resolution structure of the catalytic domain of Sin, a particularly well characterized family member, provided a detailed view of the catalytic site. To determine how the enzyme might protonate and stabilize the 3'O leaving group in the strand cleavage reaction, we examined how replacing this oxygen with a sulfur affected the cleavage rate by WT and mutant enzymes. To facilitate direct comparison of the cleavage rates, key experiments used suicide substrates that prevented religation after cleavage. The catalytic defect associated with mutation of one of six highly conserved arginine residues, Arg-69 in Sin, was partially rescued by a 3' phosphorothiolate substrate. We conclude that Arg-69 has an important role in stabilizing the 3'O leaving group and is the prime candidate for the general acid that protonates the 3'O, in good agreement with the position it occupies in the high resolution structure of the active site of Sin.


Viral transmission risk factors in an Egyptian population with high hepatitis C prevalence.
Egypt has the world's highest prevalence of infection with hepatitis C virus (HCV), which is a major cause of hepatocellular carcinoma. The high HCV prevalence is largely attributed to the parenteral antischistosomal therapy (PAT) campaigns conducted from the 1950s through the 1980s; however, the primary modes of transmission in the post-PAT period are not well known. In this study we examined the associations between HCV prevalence and exposures to risk factors, including PAT, in a high HCV prevalence population. Using a cross-sectional design, we examined the associations between demographic characteristics and risk factors for HCV transmission and HCV positivity prevalence among a sample of Egyptian residents. Data were collected through an interview-administered survey, and the association estimates were determined using χ (2) and logistic regression. The highest HCV positivity prevalence was observed in cohorts born before 1960, and declined precipitously thereafter; whereas the proportion of subjects reporting PAT remained relatively stable. Being male, having a rural residence, and having received PAT were all associated with HCV positivity; however, PAT alone could not account for the high prevalence of HCV. In Egypt, PAT and other transmission factors yet to be identified, as well as cohorts born before the 1960s and infected with HCV, are most likely the main contributors to the current HCV endemic.


A functional role of S100A4/non-muscle myosin IIA axis for pro-tumorigenic vascular functions in glioblastoma.
Glioblastoma (GBM) is the most aggressive form of brain tumor and has vascular-rich features. The S100A4/non-muscle myosin IIA (NMIIA) axis contributes to aggressive phenotypes in a variety of human malignancies, but little is known about its involvement in GBM tumorigenesis. Herein, we examined the role of the S100A4/NMIIA axis during tumor progression and vasculogenesis in GBM. We performed immunohistochemistry for S100A4, NMIIA, and two hypoxic markers, hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9), in samples from 94 GBM cases. The functional impact of S100A4 knockdown and hypoxia were also assessed using a GBM cell line. In clinical GBM samples, overexpression of S100A4 and NMIIA was observed in both non-pseudopalisading (Ps) and Ps (-associated) perinecrotic lesions, consistent with stabilization of HIF-1α and CA9. CD34(+) microvascular densities (MVDs) and the interaction of S100A4 and NMIIA were significantly higher in non-Ps perinecrotic lesions compared to those in Ps perinecrotic areas. In non-Ps perinecrotic lesions, S100A4(+)/HIF-1α(-) GBM cells were recruited to the surface of preexisting host vessels in the vascular-rich areas. Elevated vascular endothelial growth factor A (VEGFA) mRNA expression was found in S100A4(+)/HIF-1α(+) GBM cells adjacent to the vascular-rich areas. In addition, GBM patients with high S100A4 protein expression had significantly worse OS and PFS than did patients with low S100A4 expression. Knockdown of S100A4 in the GBM cell line KS-1 decreased migration capability, concomitant with decreased Slug expression; the opposite effects were elicited by blebbistatin-dependent inhibition of NMIIA. S100A4(+)/HIF-1α(-) GBM cells are recruited to (and migrate along) preexisting vessels through inhibition of NMIIA activity. This is likely stimulated by extracellular VEGF that is released by S100A4(+)/HIF-1α(+) tumor cells in non-Ps perinecrotic lesions. In turn, these events engender tumor progression via acceleration of pro-tumorigenic vascular functions. Video abstract.


Therapeutic effect and apoptosis mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis.
To explore the effect and specific mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis, and aim to provide a new idea on treating the disease with traditional Chinese medicine based on syndrome differentiation. A total of 60 C57BL/6J male rats were included in the study. The model of Qi deficiency and blood stasis was established in 60 rats by using multiple-factor stimulation. About 10 rats were randomly taken to verify whether the model establishment was successful and the rest of 50 rats were divided into 5 groups with 10 rats each: blank control group, cisplatin group, low dose group, medium dose group and high dose group. The blank control group was treated with normal saline, and cisplatin group was treated with cisplatin while the other three groups were treated with lung-tonifying and expectorant decoction at different doses. The volume change in transplanted tumor, tumor inhibition rate, apoptosis rate, and expression of Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 in 5 groups were compared. The rapidest growth rate of transplanted tumor volume was observed in blank control group and the slowest in cisplatin group. The growth rate was gradually decreased with the increasing dose of lung-tonifying and expectorant decoction, and the difference in growth of tumor volume among groups was statistically significant (P < 0.05). The cisplatin group showed the highest tumor inhibition rate, with dose-dependent increase (P < 0.05). The apoptosis rate in low dose group was higher than blank control group but lower than high dose group (P < 0.05). The apoptosis rate in medium dose group was significantly higher than blank control group (P < 0.05). The apoptosis rate in high dose group was significantly higher than control group (P < 0.05). The positive expression rates of Bcl-2 and Bax in all groups showed statistically significant difference (P < 0.05), while expression of cleaved caspase-3 and cleaved caspase-9 in 5 groups was significantly different, with dose-dependent increase (P < 0.05). The lung-tonifying and expectorant decoction inhibits the proliferation of tumor cells by inducing and activating the cell apoptosis in treatment of lung cancer with Qi deficiency and blood stasis, probably with good clinical therapeutic effect.


Health Consequences of Weight Stigma: Implications for Obesity Prevention and Treatment.
Despite decades of research documenting consistent stigma and discrimination against individuals with obesity, weight stigma is rarely considered in obesity prevention and treatment efforts. In recent years, evidence has examined weight stigmatization as a unique contributor to negative health outcomes and behaviors that can promote and exacerbate obesity. This review summarizes findings from published studies within the past 4 years examining the relationship between weight stigma and maladaptive eating behaviors (binge eating and increased food consumption), physical activity, weight status (weight gain and loss and development of obesity), and physiological stress responses. Research evaluating the effects of weight stigma present in obesity-related public health campaigns is also highlighted. Evidence collectively demonstrates negative implications of stigmatization for weight-related health correlates and behaviors and suggests that addressing weight stigma in obesity prevention and treatment is warranted. Key questions for future research to further delineate the health effects of weight stigmatization are summarized.


Intravesical chemotherapy.
A total of 85 cases treated by intravesical administration of adriamycin (ADM) at Okayama University and other cooperating institutions were examined. Instillation of 50 mg adriamycin dissolved in 30 ml physiological saline was performed in two courses of 3 consecutive days, with a 4-day interval between the courses. The response rate was 70.6%. Following instillation therapy transurethral resection (TUR) was carried out in 69 cases (80%), segmental cystectomy in 7, and total cystectomy in 3. The follow-up period averaged 42 months, during which the recurrence rate was 57%; recurrence occurred within 18 months in 80% of these cases. Since the recurrence per patient-month x 100 was 3.348, the precise effect of intravesical chemotherapy in the prevention of recurrence was unclear. There were 9 cases of advanced disease (11% of the total, 18% of cases with recurrence). One patient with CIS (flat invasive tumor) seemingly achieved CR, but died 43 months after treatment due to metastatic disease. While this method is not always indicated in cases of CIS (flat invasive tumor), in cases in which it is indicated a drug causing only limited stimulation of the bladder mucosa should be used and long-term follow-up is essential.


Promoting adsorption performance and mechanical strength in composite porous gel film.
Starch is widely used to prepare biodegradable films due to its superior biocompatibility, low immunogenicity, and renewability. In this work, a novel K+/carrageenan porous-starch/casein gel film with high oil absorption was prepared using modified porous starch. Optimal gel stability and uniformity were obtained when adding 10 mg/mL k-carrageenan and 2 mg/mL K+ to 2 mg/mL microgels, with significantly reduced crystallinity and elasticity and increased tensile strength. The concentration of k-carrageenan was the main factor affecting gel strength and the hydrophilic and mechanical properties of the film. In addition, the film-forming solution showed excellent fluidity and spreading typical of non-Newtonian fluids. The film also exhibited a highly porous structure, as visualized by SEM and AFM, in line with a cumulative oil absorption rate of 87.5 % within 20 min, which was significantly higher than that obtained with glutinous rice starch. In conclusion, reinforcement of starch-based microgels as described in this study can maximize the film's adsorption performance and mechanical properties, with promising applications in skin care and beauty products.


Oxygen consumption and respiration during and after two yoga relaxation techniques.
Cyclic meditation (CM) is a technique which combines "stimulating" and "calming" practices, based on a statement in ancient yoga texts suggesting that such a combination may be especially helpful to reach a state of mental equilibrium. The oxygen consumption, breath rate and breath volume of 50 male volunteers (group mean age+/-SD, 27+/-6.3 years) were assessed before, during, and after sessions of CM and sessions of supine rest in the corpse posture (shavasana, SH). The sessions were one day apart and the order was alternated. The oxygen consumption, breath rate and breath volume increased during the "stimulating" practices of CM, returned to the baseline during the "calming" practices, and the oxygen consumption decreased by 19.3 percent below baseline values after CM. During the SH session the oxygen consumption, breath rate and breath volume reduced; however the decrease in oxygen consumption after SH was less than after CM (i.e., 4.8 percent). The results support the idea that a combination of yoga postures with supine rest (in CM) reduces the oxygen consumption more than resting supine alone does.


Pharmacokinetics and Pharmacodynamics of Two Formulations of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor in Healthy Chinese Subjects: An Open-Label, Randomized, Parallel-Design Bioavailability Study.
Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, pegfilgrastim) is a long-acting derivative of recombinant human granulocyte colony-stimulating factor with limited renal clearance and a longer half-life. It is used for the prevention of febrile neutropenia, owing to its capacity to promote neutrophil recovery. In this study, the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of 2 formulations of PEG-rhG-CSF were evaluated in healthy Chinese subjects. Twenty-four male subjects who received a single dose of subcutaneous PEG-rhG-CSF 100 µg/kg were randomized to either treatment A (3 mg/mL) or treatment B (1 mg/mL). Noncompartmental pharmacokinetic parameters of PEG-rhG-CSF were derived from serum concentration-time data. In addition, absolute neutrophil count (ANC) as a pharmacodynamic maker, immunogenicity through antidrug antibody testing, and safety were evaluated. The mean area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-t ) and the mean maximum concentration (Cmax ) of PEG-rhG-CSF after treatment A were 5070 ng·h/mL and 125 ng/mL, respectively; these values were comparable to those measured after treatment B (5340 ng·h/mL and 123 ng/mL, respectively). The mean value of area under the △ANC (baseline-adjusted ANC)-time curve and the maximum △ANC values were 4380 × 109 h/L and 33.1 × 109 /L, respectively, in the treatment A group, and 5170 × 109 h/L and 38.6 × 109 /L, respectively, in the treatment B group. The pharmacokinetic and pharmacodynamic profiles were similar for the 2 PEG-rhG-CSF formulations following a single dose of 100 µg/kg. The safety and immunogenicity profiles were also similar, with no significant differences. The dose adjustment of PEG-rhG-CSF was not considered necessary for formulation transformation.


Reassessing a cryptic history of early trilobite evolution.
Trilobites are an iconic Paleozoic group of biomineralizing marine euarthropods that appear abruptly in the fossil record (c. 521 million years ago) during the Cambrian 'explosion'. This sudden appearance has proven controversial ever since Darwin puzzled over the lack of pre-trilobitic fossils in the Origin of Species, and it has generally been assumed that trilobites must have an unobserved cryptic evolutionary history reaching back into the Precambrian. Here we review the assumptions behind this model, and suggest that a cryptic history creates significant difficulties, including the invocation of rampant convergent evolution of biomineralized structures and the abandonment of the synapomorphies uniting the clade. We show that a vicariance explanation for early Cambrian trilobite palaeobiogeographic patterns is inconsistent with factors controlling extant marine invertebrate distributions, including the increasingly-recognized importance of long-distance dispersal. We suggest that survivorship bias may explain the initial rapid diversification of trilobites, and conclude that the group's appearance at c. 521 Ma closely reflects their evolutionary origins.


Sustainable Routes for the Synthesis of Renewable Adipic Acid from Biomass Derivatives.
Adipic acid (AA) is a key industrial dicarboxylic acid intermediate used in nylon manufacturing. Unfortunately, the traditional process technology is accompanied by serious environmental pollution. Given the growing demand for adipic acid and the desire to reduce its negative impact on the environment, considerable efforts have been devoted to developing more green and friendly routes. This Review is focused on the latest advances in the sustainable preparation of AA from biomass-based platform molecules, including 5-hydroxymethylfufural, glucose, γ-valerolactone, and phenolic compounds, through biocatalysis, chemocatalysis, and the combination of both. Additionally, the development of state-of-the-art catalysts for different catalytic systems systematically is discussed and summarized, as well as their reaction mechanisms. Finally, the prospects for all preparation routes are critically evaluated and key technical challenges in the development of green and sustainable processes for the manufacture of AA are highlighted. It is hoped that the green adipic acid synthesis pathways presented can provide insights and guidance for further research into other industrial processes for the production of nylon precursors in the future.


Control of magnetohydrodynamic stability by phase space engineering of energetic ions in tokamak plasmas.
Virtually collisionless magnetic mirror-trapped energetic ion populations often partially stabilize internally driven magnetohydrodynamic disturbances in the magnetosphere and in toroidal laboratory plasma devices such as the tokamak. This results in less frequent but dangerously enlarged plasma reorganization. Unique to the toroidal magnetic configuration are confined 'circulating' energetic particles that are not mirror trapped. Here we show that a newly discovered effect from hybrid kinetic-magnetohydrodynamic theory has been exploited in sophisticated phase space engineering techniques for controlling stability in the tokamak. These theoretical predictions have been confirmed, and the technique successfully applied in the Joint European Torus. Manipulation of auxiliary ion heating systems can create an asymmetry in the distribution of energetic circulating ions in the velocity orientated along magnetic field lines. We show the first experiments in which large sawtooth collapses have been controlled by this technique, and neoclassical tearing modes avoided, in high-performance reactor-relevant plasmas.


[Investigations on the percutaneous activity of a combination of heparin, allantoin and dexpanthenol in a specific ointment base, Antiinflammatory effect on UV-erythema in the guinea pig].
Compared to the ointment base, the application of a heparin-allantoin-dexpanthenol combination ointment (Hepathrombin ointment) to guinea pigs immediately after as well as 30 and 120 min prior to UV-irradiation effects more rapid regression of the erythema along with a reduction in erythema formation. After a pretreatment of 30 min, the temperature of the erythematous skin is also significantly lower. At a pretreatment of 120 min, no temperature differences can be observed between the ointment groups. This effect might result from a superimposition of the anti-erythematous/antiinflammatory effect of Hepathrombin along with a vasodilation effect on the deeper skin layers. The antiinflammatory effect of Hepathrombin is also discussed in connection with the mechanism of UV-induced erythema. The inhibition of UV-erythema by Hepathrombin underlines the rapid skin penetration of the active substances.


Light-weight lead aprons--light on weight, protection or labelling accuracy?
X-ray transmission tests were performed on a Green-Lite (Infab Corporation) apron/vest combination, and compared to a number of other apron/vest combinations routinely used at Christchurch Hospital as well as a sheet of 0.5 mm lead. The materials were X-rayed using the primary beam of a Philips Optimus 50 X-ray machine over an energy range of 50-125 kVp. The entrance and exit doses were recorded and percentage transmission calculated for each kVp. The Green-Lite apron/vest (labelled as 0.5 mm lead at 85 kVp) relies on the overlap at the front to provide the nominal 0.5 mm protection for both the vest and the apron. It performed significantly worse than 0.5 mm of lead and other 0.5 mm lead equivalent apron/vest combinations and provided between 0.3 and 0.39 mm lead equivalent protection depending on the energy used. Vests from other manufacturers all achieved 0.5 mm lead equivalence for a single layer of vest material over the range of energies tested and so were comparable to 1.0 mm lead when doubled. Some aprons relied on a double layer of material to achieve the 0.5 mm lead equivalence (which was not always made clear on the label), while others stated their lead equivalence for a single layer. This resulted in some confusion among wearers of the aprons as to which apron was better.


Correction: Inequalities in the Challenges Affecting Children and their Families during COVID-19 with School Closures and Reopenings: A Qualitative Study.
[This corrects the article DOI: 10.1093/phe/phac030.].


Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels.
Acid-sensing ion channels (ASICs) are voltage-independent proton-gated cation channels that are largely expressed in the nervous system as well as in some non-neuronal tissues. In rodents, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) can associate into homo- or hetero-trimers to form a functional channel. Specific polypeptide toxins targeting ASIC channels have been isolated from the venoms of spider (PcTx1), sea anemone (APETx2) and snakes (MitTx and mambalgins). They exhibit different and sometimes partially overlapping pharmacological profiles and are usually blockers of ASIC channels, except for MitTx, which is a potent activator. This review focuses on the use of these toxins to explore the structure-function relationships, the physiological and the pathophysiological roles of ASIC channels, illustrating at the same time the therapeutic potential of some of these natural compounds.


The relationships among overcommitment, effort-reward imbalance, safety climate, emotional labour and quality of working life for hospital nurses: a structural equation modeling.
Quality of working life (QWL) is a highly important issue for nurses. Nurses with lower QWL tend to have lower job performance and intention to stay. The aim of this study was to apply a theoretical model to examine the structural relationships among overcommitment, effort-reward imbalance (ERI), safety climate, emotional labour and QWL for hospital nurses. A cross-sectional study design and a simple random sampling method were used to recruit 295 nurses in a teaching hospital and used a structured questionnaire was used to collect data. Overall, the nurses' QWL was moderate. Our theoretical model showed a good model fit. Overcommintment had a significant direct positive effect on ERI (β = 0.35, p < 0.001) and indirect effects on safety climate (β = -0.149, p = 0.001), emotional labour (β = 0.105, p = 0.001) and QWL (β = -0.061, p = 0.004). Additionally, ERI not only had significant direct effects on safety climate (β = -0.42, p < 0.001), emotional labour (β = 0.30, p < 0.001) and QWL (β = -0.17, p < 0.001) but also indirectly affected QWL through safety climate (β = -0.304, p = 0.001) and emotional labour (β = -0.042, p = 0.005). Both safety climate (β = 0.72, p < 0.001) and emotional labour (β = -0.14, p = 0.003) showed significant direct effects on QWL. Our final model accounted for 72% of the variance in QWL. Our results highlight the necessity of improving the QWL of nurses. Policymakers and hospital administrators should develop policies and strategies that encourage nurses to exhibit an appropriate level of commitment, balance effort and reward, establish a climate of safety, and reduce emotional labour to improve the QWL of hospital nurses.


Health-related quality of life and oncologic outcomes after surgery in older adults with colorectal cancer.
Data regarding changes in functional status and health-related quality of life (HRQOL) before and after surgery are lacking. We identified colorectal cancer patients from the SEER-Medicare Health Outcomes Survey (MHOS) linked database to evaluate the association between HRQOL and survival. HRQOL survey data captured physical/mental health, activities of daily living (ADLs), and medical comorbidities. Patients who underwent surgery with HRQOL surveys prior to cancer diagnosis and ≥ 1 year after diagnosis were selected. Patient, disease, and HRQOL measures were analyzed in regard to overall survival (OS), disease-specific survival (DSS), and non-DSS. Of 590 patients included, 55% were female, 75% were Caucasian, and 83% had colonic primary. Disease extent was localized for 52%, regional for 41%, and distant for 7%. Median OS was 83 months. Decreased OS was independently associated with age ≥ 75 (HR 1.7, p < 0.0001), male sex (HR 1.4, p = 0.011), advanced disease (regional-HR 2.0, p < 0.0001; distant-HR 7.0, p < 0.0001), and decreased mental HRQOL (HR 1.4, p = 0.005). Decreased DSS was independently associated with advanced disease (regional-HR 4.1, p < 0.0001; distant-HR 16.5, p < 0.0001) and rectal primary (HR 1.6, p = 0.047). Decreased non-DSS was independently associated with age ≥ 75 (HR 2.2, p < 0.0001), male sex (HR 1.4, p = 0.03), decreased mental HRQOL (HR 1.4, p = 0.02), and increased comorbidities (HR 1.4, p = 0.04). The potential overall survival benefit of oncologic surgery is diminished by declines in physical and mental health. Early identification of older surgical patients at risk for functional and HRQOL declines may improve survival following colorectal cancer surgery.


Rapid determination of benzalkonium chloride in pharmaceutical preparations with flow injection liquid-liquid extraction.
Benzalkonium chloride was assayed by on-line extraction of the benzalkonium ion with picrate to chloroform. The absorbance of picrate was measured. The extractions were performed with a home-made flow injection extraction unit. Calibration curves (1.5-180 x 10(-4)% w/v) were straight lines (r = 0.9993) and the relative standard deviation of a series of injections was less than or equal to 2%. Pharmaceutical benzalkonium preparations, containing xylometazoline, timolol, phenylephrine or carbachol could also be assayed. The method was compared with a modified HPLC assay.


Electromyography of the external urethral sphincter in patients with prostatic hyperplasia.
We analyzed quantitatively the action potential of external urethral sphincter muscles by electromyography in 9 patients with benign prostatic hyperplasia and in 13 patients without micturition disturbances. In patients with benign prostatic hyperplasia the motor unit potentials had a mean amplitude of 290 plus or minus 40 microV., duration 5.0 plus or minus 0.1 msec. and phases 3.9 plus or minus 0.1. The control group values were 310 plus or minus 20 microV., 5.5 plus or minus 0.1 msec. and 3.8 plus or minus 0.1, respectively. There was a significant difference in duration, which was probably due to the difference in age of the 2 groups. An inverse relationship between age and duration was proved in the patients examined.


[The immunohistochemical changes of TGF-beta, type I and III collagen in corneal healing after photorefractive keratectomy].
To observe the immunohistochemical expression of transforming growth factor-beta (TGF-beta), type I and III collagen in monkey corneal healing after photorefractive keratectomy (PRK) and find whether TGF-beta is involved in the process of corneal healing and correlated with the syntheses of type I and III collagen. Three rhesus monkeys (6 eyes) were operated for myopic ablation of 10.0 diopters. The depth of ablation was 103 microm. Microscopy, transmission electron microscopy and immunohistochemistry were performed at 1, 3 and 6 months after PRK. TGF-beta staining was positive in the epithelium and a few fibroblasts under the epithelium at one month after the operation. The staining was negative at 6 months and in the control specimens. Postoperatively, type I and III collagen stainings were evident at 1, 3 and 6 months. Type I collagen staining was positive and type III was negative in the controls. TGF-beta is involved in the corneal healing after PRK, and perhaps correlated with the syntheses of type I and III collagen.


Utility of Perioperative Laboratory Tests in Pediatric Patients Undergoing Spinal Fusion for Scoliosis.
Retrospective comparative study. We aimed to characterize the frequency of perioperative laboratory tests for posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and to assess whether test results affected clinical management. Perioperative laboratory tests for PSF including complete blood count, coagulation laboratory tests, basic metabolic panels (BMPs), and type and screen, are commonly ordered based on providers' discretion or existing order sets. Studies have shown unnecessary laboratory tests as financially and physically costly in adults; however, no studies have examined the necessity of common perioperative laboratory tests in pediatric spinal deformity surgery. Retrospective review of patients aged 10-18 years who underwent PSF for AIS at our center in the past three years. The clinical utility of perioperative laboratory tests was assessed based on detected incidence of anemia, blood transfusions, hematology/endocrinology/nephrology consultations, insulin administration, and postponed/canceled surgeries. A total of 234 patients were included (mean age 14.4 ± 1.8 years, 75% female). Of 105 (44.9%) patients with preoperative coagulation laboratory tests, 21 (20%) had abnormal results; however, none had subsequent hematology consultations or canceled/postponed surgeries. Postoperatively, only 5 (2.1%) patients and 30 (12.8%) patients had hemoglobin values less than 8 g/dL on postoperative day (POD) 1 and 2, respectively. Multivariate analysis identified POD1 hemoglobin ≤9.35 g/dL as the only predictor of hemoglobin <8 g/dL on POD2. Overall, there were 8 (3.4%) indicated blood transfusions postoperatively. Costs of unnecessary laboratory tests averaged $95.27 (range $49.72 to $240.27) per patient. Many perioperative laboratory orders may be unnecessary in pediatric spinal deformity surgery, subjecting patients to extraneous costs and needlesticks. In particular, preoperative coagulation laboratory tests, perioperative BMPs, and additional postoperative CBCs for those with hemoglobin >9.35 on POD1 may not be warranted. Level III, retrospective cohort study.


Pretreatment for alleviation of RO membrane fouling in dyeing wastewater reclamation.
Adsorption and coagulation were commonly used to alleviate reverse osmosis (RO) membrane fouling caused by dissolved organic matters (DOM), but the effects of changed composition and structure of DOM in dyeing wastewater after adsorption and coagulation on RO membrane fouling have seldom been studied. This study aimed at resolving the mechanism how the RO membrane fouling during dyeing wastewater treatment was alleviated by using adsorption and coagulation. The dyeing wastewater caused serious RO membrane fouling. Pretreatment with granular activated carbon (GAC), polyferric sulfate (PFS) and polyaluminum chloride (PACl) were conducted. It was shown that GAC could remove most of the DOM (95%) and preferred to adsorb protein, hydrophobic neutrals and fluorescent compounds. Both coagulants of PFS and PACl preferred to remove polysaccharides (the removal rate was 9-19% higher than that of DOM), high-MW compounds and these compounds with high fouling potential. Afterwards, the RO membrane fouling potential of the dyeing wastewater was tested. The GAC and PFS performed well to alleviate fouling. After GAC treatment, the decline rate of RO flux was similar to that of raw wastewater after 6-fold dilution. With pretreatment by PFS or PACl, the fouling potential of dyeing wastewater was much lower than that of raw wastewater after diluted to the same DOM content. Changes in polysaccharides content in the DOM had more effects on RO membrane fouling than that of proteins after these pretreatment. Although the DOM changed significantly after pretreatment, the fouling type was still intermediate blocking.


Life-threatening sepsis complicating heavy metal chelation therapy with desferrioxamine.
A case of severe Yersinia enterocolitica septicemia in a hemodialysis patient receiving desferrioxamine (DFX) therapy is reported. The association between systemic yersiniosis and DFX chelation therapy is reviewed. The increasing application of DFX chelation, in iron overload states and for aluminium overload in dialysis patients, provides an increasing number of patients at risk for this unusual drug side effect. An awareness of the association between Yersinia sepsis and DFX therapy allows appropriate therapeutic intervention which may prove lifesaving.


Metabolic-Associated Fatty Liver Disease (MAFLD) is associated with immune activation, increased epicardial fat volume, and steatohepatitis among people with HIV in a Thai cohort.
A change in terminology from fatty liver disease to metabolic-associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10-year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan-aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. The median age was 54 years (interquartile range [IQR] 52-60) and current CD4 count was 613 (IQR 467-804) cells/mm3 . A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non-alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6-6.6), and similar associations were also observed among different MAFLD categories. The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease.


Metabolism of natural and synthetic bioactive compounds in Cunninghamella fungi and their applications in drug discovery.
Investigation of xenobiotic metabolism is a key step for drug discovery. Since the in vivo investigations may be associated with harmful effects attributed to production of toxic metabolites, it is deemed necessary to predict their structure especially at the preliminary clinical studies. Furthermore, the application of microorganisms that are capable of metabolizing drugs mimic human metabolism and consequently may predict possible metabolites. The genus Cunninghamella has been proven to be a potential candidate, which mimics xenobiotic metabolism occurring inside the human body, including phase I and II metabolic reactions. Moreover, biotransformation with Cunninghamella showed chemical diversity, where a lot of products were detected in relation to the initial substrates after being modified by oxidation, hydroxylation, and conjugation reactions. Some of these products are more bioactive than the parent compounds. The current review presents a comprehensive literature overview regarding the Cunninghamella organisms as biocatalysts, which simulate mammalian metabolism of natural secondary and synthetic compounds.


Demographic and illness-related variables associated with HIV-related fatigue.
Fatigue is one of the most debilitating symptoms suffered by those with HIV infection, yet little is known about its correlates. The primary aims of this study were to describe the degree to which fatigue affects daily functioning and the demographic and illness-related predictors of fatigue. The sample (n = 128) was composed of primarily poor, unemployed people of color. Fatigue most often interfered with the ability to think quickly, perform household chores, exercise, work, engage in recreational activities, walk, plan activities, and think clearly. The consequences of fatigue were highest for lowered motivation, difficulty concentrating, increased drowsiness, losing patience, and interference with work, family, and social life. Multiple linear regression analyses showed statistically significant associations of employment status, monthly income, current antidepressant use, and number of years living with HIV infection as predictors of fatigue. These must be better understood to develop interventions to successfully ameliorate HIV-related fatigue.


The effect of stable bedding materials on dust levels, microbial air contamination and equine respiratory health.
The choice of bedding material affects the quality of air in a stable and, consequently, the respiratory health of horses and humans. The risk of respiratory problems can be mitigated by improving the quality of air in the stable. The choice of bedding material is particularly important in cold climate conditions where horses are kept indoors throughout the year. This study examined the impact of three bedding materials: straw (S), peat with shavings (PS), and crushed wood pellets (CWP). The investigated factors were air contamination, including dust contamination and microbial (bacterial and fungal) contamination, and the condition of the equine respiratory tract. The condition of the respiratory tract was evaluated based on the results of arterial blood biochemistry tests and endoscopic evaluations of the upper respiratory tract. Mechanical dust contamination was lowest for PS (1.09mg/m3) and highest for CWP (4.07mg/m3). Bacterial contamination (in CFU - colony forming units) was highest for PS (5.14log10CFU/m3) and lowest for CWP (4.81log10CFU/m3). Fungal air contamination was lowest for CWP (4.54log10CFU/m3) and highest for S (4.82log10CFU/m3) and PS (4.88log10CFU/m3). An analysis of physiological indicators revealed that all horses were clinically healthy regardless of the type of applied bedding. The type of bedding material did not exert a clear influence on arterial blood biochemistry or the results of endoscopic evaluations of the respiratory tract; however, the use of alternative for straw bedding materials improved endoscopy results.


Parieto-temporal alpha EEG band power at baseline as a predictor of antidepressant treatment response with repetitive Transcranial Magnetic Stimulation: a preliminary study.
The aim of this preliminary study was to determine the predictive value of absolute alpha band power measured during the rest EEG eyes closed task for responses to 20 sessions of high frequency repetitive transcranial stimulation (rTMS) in the left dorsolateral prefrontal cortex in patients with pharmacoresistant major depressive episode. 13 major depressive disorders (8 males) and 8 bipolar disorders (6 males) were included (mean age 58years). Spearman correlations between pretreatment alpha band power in height regions of analysis and absolute improvement in Beck Depression Inventory Short Form (ΔBDI-SF) were analyzed. The predictive value of alpha band power for classifying patients as responders and non-responders to rTMS was determined using Receiver Operating Characteristic (ROC) curve. Spearman correlation analysis revealed that ΔBDI-SF correlated significantly and negatively with alpha band power on the right (r=-.673, p=.001) and left parieto-temporal regions (r=-.638, p=.002). The area under the ROC curve for the right parieto-temporal was .815, p=.0037. The cut-off point that maximized both sensitivity and specificity was 1.49μV. Sensitivity, specificity, positive and negative predictive values were 100, 66, 80, 100% respectively. The population was small and lacked homogeneity concerning affective disorders (unipolar and bipolar disorder). The use of a self-rating subjective scale (BDI-SF) to measure the severity of depression could be criticized. Pretreatment alpha band power on parieto-temporal regions could be a predictor for response to rTMS in patients with homogenous demographic/clinical features. The association between electrical activity and the perfusion under each electrode need to be examined.


Synthesis and antiproliferative activity characterization of new imidazothiazolotriazine oxindolylidene derivatives containing various substituents in the oxindole ring.
Condensation of 1,3-diethyltetrahydroimidazo[4,5-е]thiazolo[3,2-b][1,2,4]triazine-2,7-dione with isatins followed by framework rearrangement in the thiazolotriazine moiety was used to synthesize two new series of oxindolylidenetetrahydroimidazo[4,5-е]thiazolo- [3,2-b][1,2,4]triazine-2,7-diones and oxindolylidenetetrahydroimidazo[4,5-е]thiazolo[2,3-c][1,2,4]triazine-2,8-diones containing various substituents in the oxindole moiety. The obtained compounds were tested for antiproliferative activity. The greatest activity was observed in the case of 1-alkyl-7-methyloxindolylidene derivatives of imidazo[4,5-е]thiazolo[2,3-c]triazine, which not only inhibited the growth of more than half of the studied cell lines, but also caused cell death in the SF-539 cell line (central nervous system cancer, mean growth percent -7.82%) and MDA-MB-435 (melanoma, -30.97 and -13.64%). The online version contains supplementary material available at 10.1007/s10593-022-03125-3.