Prognostic significance of percent positive biopsies in clinically organ-confined prostate cancer treated with permanent prostate brachytherapy with or without supplemental external-beam radiation.
The purpose of this paper was to evaluate the relationship between the percentage of positive biopsies and the biochemical outcome in hormone-naive patients undergoing permanent prostate brachytherapy with or without supplemental external-beam radiation therapy. Four hundred thirteen hormone-naive patients underwent prostate brachytherapy for clinical T1c-T2b NxM0 (1997 American Joint Committee on Cancer classification) adenocarcinoma of the prostate gland from April 1995 through June 2001. The median patient age was 66.9 years, and the median pretreatment prostate-specific antigen value was 6.8 ng/mL. The median follow-up was 52 months. Patients were stratified by percentage of positive biopsy results into the following cohorts: < 34%, 34%-50%, and > 50%. The influences of percentage of positive biopsy results, patient age, clinical T stage, Gleason score, pretreatment prostate-specific antigen value, risk group, prostate volume, supplemental external-beam radiation therapy, isotope, percentage of prescribed dose covering 90% of the target volume (D90), and volume receiving 100%, 150%, and 200% of the prescribed dose (V100/150/200) were evaluated. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. For all 413 patients, the 7-year actuarial freedom from biochemical progression rate was 99.4%, 94.3%, and 89.2% when stratified by percentage of positive biopsy results in the < 34%, 34%-50%, and > 50% groups, respectively. When low-, intermediate-, and high-risk patients were stratified by percentage of positive biopsy results, a nonsignificant trend for increased biochemical progression was noted with increasing positive biopsy results. In multivariate analysis, percentage of positive biopsy results and pretreatment prostate-specific antigen value were the only significant predictors of biochemical outcome. The median postimplantation prostate-specific antigen value for all biochemically disease-free patients was < 0.1 ng/mL, regardless of risk group or percentage of positive biopsy results cohort. Multivariate analysis demonstrated that percentage of positive biopsy results and pretreatment prostate-specific antigen value were statistically significant predictors of 7-year biochemical progression-free survival. However, the relatively small absolute differences in biochemical outcome based on percentage of positive biopsy results may be a result of radiation dose escalation with the utilization of generous periprostatic treatment margins.


A 53-Year-Old Woman With Seizure and Cavitary Lung Mass.
A 53-year-old woman with no significant past medical history came to her local ED after a witnessed generalized tonic-clonic seizure. CT scan imaging of the head revealed a left frontal lobe hypodensity concerning for a mass with surrounding edema. In the previous month, she had undergone ambulatory evaluation for a subacute cough that had more recently become productive of bloody sputum. Outpatient chest radiography had demonstrated a new right lung opacity, shown on subsequent CT scan imaging to be a right upper lobe (RUL) consolidation. She was prescribed a course of doxycycline, after which sputum expectoration improved but a nonproductive cough remained. Repeat thoracic imaging was pending at the time the seizure occurred. The patient had no history of chronic lung disease or recurrent infections. There were no constitutional symptoms. She did not take any home medications on a regular basis. She was a lifetime nontobacco user. She denied use of alcohol and illicit drugs. She had previously worked in a medical office but was now spending most of her time helping her husband take care of their house and property in Kingston, New York, a town of about 23,000 people in the Hudson River Valley. She was born in the United States and had not traveled recently. She had no pets. There was no history of recent dental procedures. She was transferred to our institution for neurosurgical evaluation.


Genetic heterogeneity in HER2 testing may influence therapy eligibility.
Prospective studies have demonstrated that approximately 20% of HER2 testing may be inaccurate. When carefully validated testing is conducted, available data do not clearly demonstrate the superiority of either IHC or fluorescence in situ hybridization (FISH) as a predictor of benefit from anti-HER2 therapy. In addition, the interpretation of the findings of HER2 tests according to international guidelines is not uniform. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) recently published practice guidelines for a definition of HER2 amplification heterogeneity that can give rise to discrepant results between IHC and FISH assays for HER2. In this article, we compare the HER2 status of 291 non consecutive breast cancers. The status is determined by both IHC and FISH approaches, using a specific FISH strategy to investigate genetic heterogeneity. Our data demonstrate that HER2 amplified cells may be found as diffuse, clustered in a specific area or section, intermingled with non-amplified cells or confined to metastatic nodules. The correct evaluation of ratio value in the presence of genetic heterogeneity and of polysomy contributes to the accurate assessment of HER2 status and potentially affects the selection of appropriate anti-HER2 therapy. By taking into account the presence of different genetic cell populations, the immunotherapy eligibility criteria for HER2 FISH scoring proposed in the CAP (2009) and SIGU guidelines identify an additional subset of cases for trastuzumab or lapatinib therapy compared to the ASCO/CAP (2007) guidelines.


Immunohistochemical localization to pyloric antral G cells of peptides derived from porcine preprogastrin.
Antibodies to the peptides (designated cryptic A and B) that flank the G34 region of pig progastrin were used in immunohistochemical studies of the gastrointestinal tract. In elution and restaining experiments, the same cells were revealed by the cryptic peptide antibodies, and by antibodies specific for C-terminus of G17 and N-terminus of G34. The cells reacting with the cryptic peptide antibodies were localized predominantly to antral mucosa. They were found in pig, ferret, dog and cat but not in man, guinea pig, rat or mouse; presumably in the latter species there are amino acid substitutions in the cryptic peptides that influence immunoreactivity with the present antibodies. The results indicate that progastrin production occurs only in G cells in the gut, and that a single population of cells produces all the predicted regions of progastrin.


Monoclonal gammopathies of undetermined significance.
The monoclonal gammopathies include multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis (AL), and Waldenström's macroglobulinemia (WM). At Mayo Clinic, almost 60% of patients with a monoclonal gammopathy have MGUS. MGUS is characterized by the presence of a serum monoclonal protein value <3 g/dL, fewer than 10% plasma cells in the bone marrow, no or a small amount of monoclonal protein in the urine, and absence of lytic bone lesions, anemia, hypercalcemia, or renal insufficiency related to the plasma-cell proliferative process. During long-term follow-up of 241 patients with MGUS seen at Mayo Clinic from 1956 to 1970, MM, WM, AL, or a related disorder developed in 64. To confirm the findings, we conducted a population-based study on MGUS in the 11 counties of southeastern Minnesota from 1960 to 1994. The risk of progression to a malignant plasma-cell disorder was 1% per year.


Hexa-aqua-dodeca-μ2-iodido-octahedro-hexa-tantalum diiodide tetra-hydrate.
In the crystal structure of the cluster salt, [Ta6I12(H2O)6]I2·4H2O, the octa-hedral {Ta6} cluster core is μ2-coordinated by twelve iodido ligands (inner ligand sphere) whereas the six aqua ligands coordinate each at the six outer positions. The discrete, inversion-symmetric cluster complex is double-positively charged, and two iodide anions are present in the crystal structure as counter-ions. In addition, four water mol-ecules are co-crystallized. Hydrogen bonds between the cluster unit, the iodide anions and co-crystallized water mol-ecules stabilize the charge-assisted packing in the crystal structure.


Autosomal dominant hypoparathyroidism with intracranial calcification outside the basal ganglia.
We describe a family with autosomal dominant hypoparathyroidism. The 3 affected individuals had no detectable serum parathyroid hormone on radioimmunoassay. The propositus presented with seizures and on CT scan had bilateral basal ganglion calcification and calcification in the frontal lobes. His similarly affected mother had even more intracerebral calcification. The latter manifestation has not been described previously in autosomal dominant hypoparathyroidism.


LV lead fixation in a coronary vein may be the cause and result of thrombosis.
A recently implanted left ventricular lead was fixated in the coronary sinus due to thrombosis while attempting to reposition the lead because of phrenic nerve stimulation.


Kinetic modeling and experiments on removal of COD/nutrients from dairy effluent using chlorella and co-culture.
A sustainable and cost-effective approach of waste water management is biological treatment for reducing organic carbon, nitrate, and phosphate content. Co-culturing of algae with bacteria in wastewater leads to higher biomass yield and improvement in COD/nutrients removal compared to the single strain counterparts. In this study, a mathematical modeling framework is proposed to predict the dynamic behavior of microbial co-culture in dairy waste water. Initially, the model has been developed to predict the biomass growth and COD/nutrients removal with discrete cultures (algae and bacteria). As an extension of the single strain kinetic model, Lotka-Volterra model was formulated to explore the symbiotic relationship between algae and bacteria in a co-culture and the impact of the interactions on the COD/nutrients removal efficiency and growth dynamics. Supporting experiments were carried out in 6 parallel sets (3 sets with triplicates) with standalone algae (Chlorella vulgaris, CV), bacteria (activated sludge), and co-culture in real-time dairy liquid effluent in lab flasks and predicted values from modeling were validated against experimental findings. Statistical analysis confirms reasonably good agreement between the model predictions and experimental findings indicating a positive synergistic effect of the algae-bacterial co-culture on COD removal.


Representing performance of horizontal flow treatment wetlands: The Tanks In Series (TIS) and the Plug Flow with Dispersion (PFD) approaches and their application to design.
Horizontal flow wetlands have been designed using the so-called P-k-C* approach, which has been largely embraced by the treatment wetlands literature. P is meant to represent the equivalent number of apparent tanks in series (hydraulic factor), but also incorporates the loss of biodegradability as the wastewater undergoes treatment (kinetic factor). For design purposes, literature proposes fixed values of P. The proposal of this paper is to decouple hydraulics from kinetics and use the traditional concept of N or NTIS (number of tanks in series) as a function of geometric relationships of the wetland to be designed, leaving kinetic elements to be dealt with solely by the first-order removal rate coefficient (k). From the literature, a database with 41 wetlands with data from tracer studies was used, and a novel regression-based equation was derived relating N with the ratio length/depth of horizontal wetlands. This equation can be used at the design stage for estimating N and, hence, the output concentration of the pollutant using the traditional structure of the TIS model, with a possible inclusion of background concentration (C*). The paper presents all relevant equations, including those from the plug-flow with dispersion model (PFD), and it is shown how to convert from one hydraulic model to the other, what is also believed to be a novel approach in the treatment wetland literature. Finally, the area-based removal rate coefficients (kA) proposed by Kadlec and Wallace (2009) for designs of horizontal wetlands treating domestic wastewater based on the P-k-C* approach are converted into kA values for the TIS model in the paper.


Eruptive syringomas: Summary of ninety cases and a brief literature review.
Eruptive syringomas is a rare variant of syringoma, which is a benign adenoma differentiated from the terminal ducts of the eccrine glands. Nowadays, it's widely valued because of obvious skin lesions, large scope of influence, and high misdiagnosis rate. We aim to explore the clinical features of eruptive syringomas and the current research progress. We firstly summarized the clinical features of 90 cases of eruptive syringomas. Then, the chi-square test was used to analyze the relationship between the onset site of eruptive syringomas and age, as well as gender. Finally, we briefly reviewed the previous literature. During 12 years, 90 cases of eruptive syringomas were diagnosed in our hospital, including 28 males (31.1%) and 62 females (68.9%). The average diagnosed age was 28.8. Patients from 20 to 40 years old is 63 (70%), which is the most. 60 (66.7%) patients had the course for more than 1 year. Among onset sites, the neck, chest, and abdomen were in the top three. The chi-square test showed that there were no significant differences in the onset sites of patients aged ≤ 20 and >20 years old (p-value = 0.181), as well as male and female (p-value = 0.363). We found that more female than male was affected, and the most common onset sites were the neck, chest, and abdomen. Neither age nor gender was significantly associated with onset site distribution. Our study provides some data support for the research of eruptive syringomas.


Locked nucleic acid: modality, diversity, and drug discovery.
Over the past 20 years, the field of RNA-targeted therapeutics has advanced based on discoveries of modified oligonucleotide chemistries, and an ever-increasing understanding of how to apply cellular assays to identify oligonucleotides with improved pharmacological properties in vivo. Locked nucleic acid (LNA), which exhibits high binding affinity and potency, is widely used for this purpose. Our understanding of RNA biology has also expanded tremendously, resulting in new approaches to engage RNA as a therapeutic target. Recent observations indicate that each oligonucleotide is a unique entity, and small structural differences between oligonucleotides can often lead to substantial differences in their pharmacological properties. Here, we outline new principles for drug discovery exploiting oligonucleotide diversity to identify rare molecules with unique pharmacological properties.


Inhibitory effects of various beverages on ritodrine sulfation by recombinant human sulfotransferase isoforms SULT1A1 and SULT1A3.
Ritodrine is known to undergo extensive presystemic sulfation in the intestinal mucosa, and its bioavailability is as low as 30%. Accordingly, inhibition of intestinal sulfation may lead to an increase in the bioavailability of ritodrine. In this study, we aimed to investigate the activities of ritodrine sulfation by SULT1A1, which is expressed predominantly in the liver, and SULT1A3, which is expressed predominantly in the intestine, as well as the inhibitory effects of beverages on their activities. We investigated ritodrine sulfation by using recombinant human sulfotransferase (SULT) 1A1 and SULT1A3 in an in vitro study. Next, we investigated the inhibitory effects of grapefruit juice, orange juice, green tea, and black tea on ritodrine sulfation. Sulfation of ritodrine by SULT1A3 was much higher than that by SULT1A1, suggesting that the bioavailability of ritodrine may be limited by intestinal SULT1A3. The ritodrine sulfation activities of SULT1A1 and SULT1A3 were significantly inhibited by all beverages examined at a concentration of 10%. Green tea and black tea exhibited potent inhibition; even at a concentration of 5%, they both inhibited SULT1A1 by 100% and SULT1A3 by >or=95%. Our results suggest that concomitant ingestion of beverages such as green tea and black tea may increase the bioavailability of orally administered ritodrine, and perhaps other beta2-agonists, and lead to an increase in the clinical effects or adverse reactions.


A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor.
Monoclonal antibody vpg15 detects a 24-kDa cell surface protein on feline cells permissive for infection with feline immunodeficiency virus (FIV). The antibody blocks infection of FIV-susceptible cells, and expression of the vpg15 marker is decreased in FIV-infected cells in vitro. These results suggest that the antibody may recognize an FIV receptor distinct from CD4.


Simulation of circadian rhythm generation in the suprachiasmatic nucleus with locally coupled self-sustained oscillators.
In mammals, circadian rhythms are driven by a pacemaker located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The firing rate of neurons within the SCN exhibits a circadian rhythm. There is evidence that individual neurons within the SCN act as circadian oscillators. Rhythm generation in the SCN was therefore modeled by a system of self-sustained oscillators. The model is composed of up to 10000 oscillatory elements arranged in a square array. Each oscillator has its own (randomly determined) intrinsic period reflecting the widely dispersed periods observed in the SCN. The model behavior was investigated mainly in the absence of synchronizing zeitgebers. Due to local coupling the oscillators synchronized and an overall rhythm emerged. This indicates that a locally coupled system is capable of integrating the output of individual clock cells with widely dispersed periods. The period of the global output (average of all oscillators) corresponded to the average of the intrinsic periods and was stable even for small amplitudes and during transients. Noise, reflecting biological fluctuations at the cellular level, distorted the global rhythm in small arrays. The period of the rhythm could be stabilized by increasing the array size, which thus increased the robustness against noise. Since different regions of the SCN have separate output pathways, the array of oscillators was subdivided into four quadrants. Sudden deviations of periodicity sometimes appeared in one quadrant, while the periods of the other quadrants were largely unaffected. This result could represent a model for splitting, which has been observed in animal experiments. In summary, the multi-oscillator model of the SCN showed a broad repertoire of dynamic patterns, revealed a stable period (even during transients) with robustness against noise, and was able to account for such a complex physiological behavior as splitting.


Performance of automated multiplex polymerase chain reaction (mPCR) using synovial fluid in the diagnosis of native joint septic arthritis in adults.
This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis. Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study. Of 72 patients, 42 (58%) were deemed to have septic joints. The sensitivity of mPCR and synovial fluid culture was 38% and 29%, respectively. No significant differences were found between the AUCs of both techniques (p = 0.138). A strong concordance of 89% (Cohen's kappa: 0.65) was shown. The mPCR failed to detect Staphylococcus aureus (n = 1) and Streptococcus pneumoniae (n = 1; no primer included in the mPCR), whereas the synovial fluid culture missed six microorganisms (positive mPCR: S. aureus (n = 2), Cutibacterium acnes (n = 3), coagulase-negative staphylococci (n = 2)). The automated mPCR showed at least a similar performance to the synovial fluid culture (the current benchmark) in diagnosing septic arthritis, having the great advantage of a shorter turnaround time (within five hours). Cite this article: Bone Joint J 2019;101-B:288-296.


Partial amino acid sequence analysis of rabbit MHC class II molecules isolated from two-dimensional polyacrylamide gels.
Partial N-terminal amino acid sequence analyses were performed on rabbit MHC class II molecules eluted from 2-D electrophoretic gels. Rabbit spleen cells were biosynthetically labelled with 3H-phenylalanine, 3H-tyrosine and 35S-methionine and class II molecules were immunoprecipitated with a monoclonal antibody, 2C4. The immunoprecipitates were electrophoresed on 2-D gels and as many as 15 spots were observed. Individual spots corresponding to alpha and beta chains were eluted from unfixed gels following visualization of the spots by autoradiography of 35S-Met labelled polypeptides. Ten eluted polypeptides were subjected to amino acid sequence analysis to locate Phe and Tyr residues. Comparison of these partial sequences with sequences of human class II molecules indicated that each of six beta chains and three of four alpha chains were homologous to human DQ molecules; one of the alpha chains appeared homologous to DR alpha or DP alpha. The assignment of alpha or beta chain to the polypeptides was confirmed by radiosequence of molecules labelled with 35S-Cys residues. Thus, by a relatively simple procedure, individual MHC class II polypeptides in spleen cell lysates have been separated from each other and partial amino acid sequences have been obtained.


Identification of ATP6V0A4 as a potential biomarker in renal cell carcinoma using integrated bioinformatics analysis.
Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cancer, and is associated with a high mortality rate, which is related to high rates of tumor recurrence and metastasis. The aim of the present study was to identify reliable molecular biomarkers with high specificity and sensitivity for ccRCC. A total of eight ccRCC-related expression profiles were downloaded from Gene Expression Omnibus for integrated bioinformatics analysis to screen for significantly differentially expressed genes (DEGs). Reverse transcription-quantitative (RT-q)PCR, western blotting and immunohistochemistry staining assays were performed to evaluate the expression levels of candidate biomarkers in ccRCC tissues and cell lines. In total, 255 ccRCC specimens and 165 adjacent normal kidney specimens were analyzed, and 344 significant DEGs, consisting of 115 upregulated DEGs and 229 downregulated DEGs, were identified. The results of Gene Ontology analysis suggested a significant enrichment of DEGs in 'organic anion transport' and 'small molecule catabolic process' in biological processes, in 'apical plasma membrane' and 'apical part of the cell' in cell components, and in 'anion transmembrane transporter activity' and 'active transmembrane transporter activity' in molecular functions. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were significantly enriched in the 'phagosome', the 'PPAR signaling pathway', 'complement and coagulation cascades', the 'HIF-1 signaling pathway' and 'carbon metabolism'. Next, 7 hub genes (SUCNR1, CXCR4, VCAN, CASR, ATP6V0A4, VEGFA and SERPINE1) were identified and validated using The Cancer Genome Atlas database. Survival analysis showed that low expression of ATP6V0A4 was associated with a poor prognosis in patients with ccRCC. Additionally, received operating characteristic curves indicated that ATP6V0A4 could distinguish ccRCC samples from normal kidney samples. Furthermore, RT-qPCR, western blotting and immunohistochemistry staining results showed that ATP6V0A4 was significantly downregulated in ccRCC tissues and cell lines. In conclusion, ATP6V0A4 may be involved in tumor progression and regarded as a potential therapeutic target for the recurrence and metastasis of ccRCC.


Effect of Previous SARS-CoV-2 Infection on Antibody Response to a Single Immunization with the Pfizer BNT162b mRNA Vaccine Among Healthcare Workers in Foggia, Italy.
Data have suggested that SARS-CoV-2 infection causes an antibody response at least as strong as one BNT162b2 vaccine dose. Nevertheless, some aspects require further investigation to better understand the immunogenicity of one vaccine dose among infected individuals. Thus, we evaluated how previous SARS-CoV-2 infection may influence the humoral immunity after a single Pfizer BNT162b mRNA vaccine dose in a sample of healthcare workers (HCWs). As part of the routine surveillance activity conducted among HCWs of the Policlinico Riuniti Foggia Hospital (Apulia region, Italy), we conducted a retrospective serosurvey in the period January-March 2021. We compared specific antibody titres (anti-spike IgGs measured by enzyme-linked immunoassay, ELISA) after SARS-CoV-2 infection and after the first dose of the BNT162b2 vaccine, analysing the impact of sex, age, time since infection, and presence of symptoms on the humoral response. We included in the study 58 HCWs (mean age 44.1 years, 48.2% male) with anti-spike IgG titres available before and after the first BNT162b2 vaccine dose. Among these, we observed higher titres in previously infected cases (N = 21) than in COVID-19-naïve subjects (N = 37) (medians 1510 vs. 0.68; p < 0.001). A statistically significant difference in anti-spike IgG titres was also observed among previously infected HCWs before vaccine dose in comparison with post-dose infection-naïve HCWs (medians 18.37 vs. 0.68, p < 0.001). Among infected individuals, no differences by sex, age, or time since infection were reported (p > 0.05). Post-dose titres of symptomatic and asymptomatic infected HCWs slightly differed (medians = 1900 vs. 1090; p = 0.048). Our data support the viable hypothesis of a single-dose vaccine regimen in individuals with a history of COVID-19, but no conclusion on duration of protection in this group can be drawn from our study.


Effectiveness of neoadjuvant chemotherapy with cisplatin and irinotecan followed by surgery on small-cell carcinoma of the esophagus: A case report.
Small-cell carcinoma of the esophagus (SCCE) is a rare disease with aggressive progression and a poor prognosis. A standard treatment strategy for SCCE is yet to be established. A 40-year-old woman with dysphagia was admitted to our hospital. A clinical diagnosis of SCCE (T3N1N0 stage IIIA) was established. She was initially treated with chemotherapy using cisplatin (CDDP) and irinotecan (CPT-11). After two courses of treatment, the primary lesion in the esophagus was not detectable by esophageal endoscopy. Likewise, swelling of the right recurrent nerve lymph node present prior to treatment could not be detected. The chemotherapy resulted in a complete response. One month after the conclusion of chemotherapy, radical esophagectomy with three-field lymph node dissection was performed. Histopathological examination of the excised specimen revealed no residual tumor or lymph node metastasis. The patient was discharged from hospital 29 days after surgery with no complications. The patient is alive and has remained cancer-free for 48 months after the surgery. Systemic chemotherapy for SCCE in combination with surgery was treated after surgery in most reports. Neoadjuvant chemotherapy is advantageous from three viewpoints, namely achievement of downstaging, increasing complete resection rates, and a better completion of treatment compared with postoperative chemotherapy. Neoadjuvant chemotherapy following esophagectomy could be a useful treatment option for patients with limited disease (LD) of SCCE. We report a case of SCCE achieving a pathologically complete response with neoadjuvant chemotherapy using CDDP and CPT-11, and long-term survival followed by surgery.


A hospital outbreak of antibiotic-resistant Streptococcus pneumoniae.
We report six patients colonised with a multiply resistant strain of Streptococcus pneumoniae.


Estimating the contribution of occupational solar ultraviolet exposure to skin cancer.
Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. Outdoor workers are at particular risk because they spend long working hours outside, may have little shade available and are bound to take their lunch at their workplace. Despite epidemiological evidence of a doubling in risk of squamous cell carcinoma (SCC) in outdoor workers, the recognition of skin cancer as an occupational disease remains scarce. To assess occupational solar UV doses and their contribution to skin cancer risk. A numerical model (SimUVEx) was used to assess occupational and lunch break UV exposure, and to characterize exposure patterns and anatomical distribution. Risk of SCC was estimated from an existing epidemiological model. Horizontal body locations received 2.0-2.5 times more UV than vertical locations. The dose associated with having lunch outdoors every day was similar to that from doing outdoor work 1 day per week, but only half that of a seasonal worker. Outdoor work is associated with an increased risk of SCC and also with frequent acute episodes. Occupational solar exposure contributes greatly to overall lifetime UV dose, resulting in an excess risk of SCC. The magnitude of the estimated excess in risk supports the recognition of SCC as an occupational disease.


Identification of novel potent bicyclic peptide deformylase inhibitors.
Screening of our compound collection using Staphylococcus aureus Ni-Peptide deformylase (PDF) afforded a very potent PDF inhibitor with an IC(50) in the low nanomolar range but with poor antibacterial activity (MIC). Three-dimensional structural information obtained from Pseudomonas aeruginosa Ni-PDF complexed with the inhibitor suggested the synthesis of a variety of analogues that would maintain high binding affinity while attempting to improve antibacterial activity. Many of the compounds synthesized proved to be excellent PDF-Ni inhibitors and some showed increased antibacterial activity in selected strains.


[The effect of cefaclor, doxycycline and other oral antibiotics on phagocytosis of polymorphonuclear granulocytes and PHA-induced stimulation of blood lymphocytes in man].
The influence of the orally applicable antibacterial agents, cefaclor (Panoral), doxycycline, erythromycin, and cotrimoxazole on phagocytosis by human neutrophil granulocytes was investigated. Further, the influence of cefaclor, erythromycin, and doxycycline on PHA stimulation of human blood lymphocytes was studied. Doxycycline (1 mg/ml) had strongly suppressive effects on phagocytosis, whereas cefaclor (1 mg/ml cotrimoxazole (0.1 mg/ml), and erythromycin (0.1 mg/ml) did not suppress phagocytosis. PHA-induced lymphocyte stimulation was strongly inhibited by doxycycline (10 micrograms/ml), whereas cefaclor (10 micrograms/ml) did not suppress at all. Erythromycin (10 micrograms/ml) exerted some inhibition (average 12.6%). These results are discussed with respect to immunoneutrality of antibacterial agents.


Determination of amiodarone and desethylamiodarone in human plasma by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry with an ion trap detector.
A sensitive and specific high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS-MS) method has been developed for the simultaneous determination of amiodarone and desethylamiodarone in human plasma. After the addition of the internal standard tamoxifen, plasma samples were extracted using Oasis MCX solid-phase extraction cartridges. The compounds were separated on a 5 microm Symmetry C18 (Waters) column (150 x 3.0 mm, internal diameter) with a mobile phase of acetonitrile-0.1% forrmic acid (46:54, v/v) at a flow-rate of 0.5 ml/min. The overall extraction efficiency was more than 89% for both compounds. The assay was sensitive down to 1 microg/l for amiodarone and down to 0.5 microg/l for desethylamiodarone. Within-run accuracies for quality-control samples were between 95 and 108% of the target concentration, with coefficients of variation <8%. The proposed method enables the unambiguous identification and quantitation of amiodarone and desethylamiodarone in both clinical and forensic specimens.


The energetic costs of stereotyped behavior in the paper wasp, Polistes dominulus.
Polistes wasps engage in many behavioral interactions. Although there has been debate over the meaning of these interactions, these stereotypical behaviors can be used to determine a colony's linear dominance hierarchy. Due to the implicit relationship between behavioral and reproductive dominance, behavioral interactions are commonly used to distinguish the reproductively dominant alpha foundress from the beta foundress. It has been suggested that in order to maintain reproductive control, the alpha foundress is forced to remain at a physiologically constrained activity limit. This, in turn, may allow aggressive interactions to be used as determinants influencing reproductive partitioning between cooperating individuals. Energetic costs can place important limitations on behavior, but the energetic cost of the interactions has not previously been measured. To address this, we measured the CO(2) production of 19 non-nestmate pairs displaying interactive and noninteractive behavior. The rate of energy used during interaction behavior was positively associated with published rankings of aggression. However, our results indicate that interactions are not very energetically costly in Polistes, particularly when compared to the likely cost of foraging. These data suggest that maintaining reproductive dominance is not very energetically expensive for the dominant and that the dominant foundress expends energy at a lower rate than the subordinate foundress.


Abnormal cortisol profile during psychosocial stress among patients with schizophrenia in a Chinese population.
Accumulating evidence suggests that hypothalamic-pituitary-adrenal axis dysfunction might play an important role in the pathophysiology of schizophrenia. The aim of this study was to explore the cortisol response to psychological stress in patients with schizophrenia. In this study, patients with schizophrenia (n = 104) and healthy volunteers (n = 59) were asked to complete psychological stress challenge tasks, which included the Paced Auditory Serial Addition Task and Mirror-Tracing Persistence Task, and pre- and post-task saliva samples were collected to measure cortisol levels. Emotions and psychopathology were assessed by the Positive and Negative Affect Schedule and Positive and Negative Syndrome Scale. The results showed (1) that the cortisol response and negative emotions in patients with schizophrenia differed significantly from those in healthy volunteers, (2) there were significant interactions between the sampling time and diagnosis for saliva cortisol levels, (3) there were significant interactions between the scoring time and diagnosis for the negative affect score of the PANAS, and (4) the changes in salivary cortisol levels and negative affect scores before and after the psychological stress challenge tasks were not correlated with clinical symptoms in patients with schizophrenia. These findings indicated an abnormal cortisol profile in patients with schizophrenia, which might be a biological characteristic of the disease.


Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome.
MCT8 deficiency is a rare genetic leukoencephalopathy caused by a defect of thyroid hormone transport across cell membranes, particularly through blood brain barrier and into neural cells. It is characterized by a complex neurological presentation, signs of peripheral thyrotoxicosis and cerebral hypothyroidism. Movement disorders (MDs) have been frequently mentioned in this condition, but not systematically studied. Each patient recruited was video-recorded during a routine outpatient visit according to a predefined protocol. The presence and the type of MDs were evaluated. The type of MD was blindly scored by two child neurologists experts in inherited white matter diseases and in MD. Dystonia was scored according to Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). When more than one MD was present, the predominant one was scored. 27 patients were included through a multicenter collaboration. In many cases we saw a combination of different MDs. Hypokinesia was present in 25/27 patients and was the predominant MD in 19. It was often associated with hypomimia and global hypotonia. Dystonia was observed in 25/27 patients, however, in a minority of cases (5) it was deemed the predominant MD. In eleven patients, exaggerated startle reactions and/or other paroxysmal non-epileptic events were observed. MDs are frequent clinical features of MCT8 deficiency, possibly related to the important role of thyroid hormones in brain development and functioning of normal dopaminergic circuits of the basal ganglia. Dystonia is common, but usually mild to moderate in severity, while hypokinesia was the predominant MD in the majority of patients.


Chronic total occlusion recanalization for myocardial infarction.
An 84-year-old patient with prior coronary artery bypass surgery presented with non-ST segment elevation acute myocardial infarction. The culprit lesion was at the distal anastomosis of a saphenous vein graft (SVG) to the right posterior descending artery. The proximal right coronary artery was chronically occluded. Because of significant disease both proximal and distal to the SVG anastomosis, percutaneous intervention of the SVG carried high risk for acute vessel closure. The native right coronary artery chronic total occlusion was successfully recanalized, enabling complete revascularization of the right coronary artery. The SVG was then occluded using an Amplatzer vascular plug.


The ASB2β Ubiquitin-interacting motif is involved in its monoubiquitination.
ASB2 proteins are E3 ubiquitin (Ub) ligases that ubiquitinate filamins. There are two ASB2 splice variants, ASB2α and ASB2β. ASB2β has a ubiquitin-binding motif (UIM) at the N-terminal region but ASB2α does not. Here, we provide the first evidence that ASB2β but not ASB2α is monoubiquitinated and that this monoubiquitination involves the UIM. Myc-tagged ASB2β and hemagglutinin (HA)-tagged Ub were co-expressed in HEK293 cells using the pCMV expression vector. Immunoprecipitation with an anti-Myc antibody followed by immunoblotting with anti-Myc and anti-HA antibodies showed an additional ASB2β protein band that had both a Myc and a HA tag. The molecular weight of this protein was larger than that of ASB2β, and the difference in molecular weight between these two proteins corresponded to the molecular weight of monoubiquitin, strongly implying that monoubiquitinated ASB2β is produced in cells. ASB2β with mutations in the UIM motif; either Glu·Asp·Glu27-29Ala·Ala·Ala mutations (ASB2β M1) or a Ser38Ala mutation, (ASB2β M2) were not monoubiquitinated, suggesting the importance of the UIM for ASB2β monoubiquitination. Furthermore, an ASB2β mutant that lacked a SOCS box (ASB2β ΔC) and did not show E3 Ub ligase activity was monoubiquitinated to the same extent as the wild-type ASB2β. In contrast, an ASB2β mutant that lacked the UIM-containing domain (ASB2β ΔN) was not monoubiquitinated. These results suggest that ASB2β but not ASB2α might be monoubiquitinated and that the ASB2β UIM motif, but not its E3 Ub ligase activity, plays a pivotal role in this monoubiquitination.


Performance and mechanisms of immobilization remediation for Cd contaminated water and soil by hydroxy ferric combined acid-base modified sepiolite (HyFe/ABsep).
In order to simultaneously improve the remediation capability of Cd contaminated water and soil, hydroxy iron-ABsep (HyFe/ABsep) was synthesized by a two-step modified (acid-base composite treatment, and hydroxy group was by using NaOH and Fe (NO3)3·9H2O). Results showed that HyFe/ABsep had developed pores and a rougher surface morphology, and the salt-soluble ion content was increased, surface-loaded iron species was mainly composed of FeOOH. Adsorption process of Cd2+ by HyFe/ABsep conformed best to the preudo-second-order model and Redlich-Paterson models, respectively. The behavior over a whole range of adsorption was consistent with chemical adsorption being the rate-controlling step and the theoretical maximum adsorption capacity obtained for the HyFe/ABsep was 220.9 mg·g-1 at 298 K, which was 4.87 times than Sep. HyFe/ABsep also had a more excellent passivation effect on available Cd in soil, being 36.83%-48.46% under the treatments of 0.5%-4% HyFe/ABsep, The structure and morphology of HyFe/ABsep were characterized through SEM-EDS, TEM, FTIR, XRD and XPS indicated that the mainly mechanisms of Cd sorption may include precipitates, ion exchange and complexation of active silanol groups. Therefore, HyFe/ABsep can employ as an effective agent for immobilization remediation of Cd contaminated water and soil.


Nonlinear terms produced by passing amplitude-modulated sinusoids through a hair cell transducer function.
We derive mathematically the output of Corey and Hudspeth's hair cell transducer function for the following cases: (1) the input is a single carrier whose output is modulated by the sum of two sinusoids; (2) the input is the sum of two carriers, each of which is amplitude-modulated by a single sinusoid. The theoretical results are similar to the results of an experiment in which field potentials were recorded from the human scalp while one ear was stimulated with auditory waveform (1) and with auditory waveform (2) of the cases above.


Microbes from mature compost to promote bacterial chemotactic motility via tricarboxylic acid cycle-regulated biochemical metabolisms for enhanced composting performance.
This study aims to reveal the underlying mechanisms of mature compost addition for improving organic waste composting. Composting experiments and metagenomic analysis were conducted to elucidate the role of mature compost addition to regulate microbial metabolisms and physiological behaviors for composting amelioration. Mature compost with or without inactivation pretreatment was added to the composting of kitchen and garden wastes at 0%, 5%, 10%, 15%, and 20% (by wet weight) for comparison. Results show that mature compost promoted pyruvate metabolism, tricarboxylic acid (TCA) cycle, and oxidative phosphorylation to produce heat and energy to accelerate temperature increase for composting initiation and biological contaminant removal (>78%) for pasteurization. Energy requirement drives bacterial chemotactic motility towards nutrient-rich regions to sustain organic biodegradation. Nevertheless, when NADH formation exceeded NAD+ regeneration in oxidative phosphorylation, TCA cycle was restrained to limit continuous temperature increase and recover high intracellular NAD+/NADH ratio to secure stable oxidation reactions.


A historical perspective on cerebral palsy as a concept and a diagnosis.
Sigmund Freud was the first to write about cerebral palsy as a nosographic category, uniting various infantile motor deficits of brain origin. He did not ascribe more than a temporary value to the term (infantile) cerebral palsy, but it has become--and still is--an indispensable part of the nosographic system. Nevertheless, it is still easier to explain what cerebral palsy is not than to define it precisely.


Combined brachial plexus and spinal cord trauma.
The clinical features of combined injuries of the brachial plexus and spinal cord in 31 patients are described. Diagnosis of the brachial plexus lesion was delayed in 17 instances, and the reasons for this are discussed. Early diagnosis is important so that definitive treatment and long-term plans can be instituted without delay. This dual lesion constitutes a very severe disability; as a direct result of their brachial plexus paralysis, 9 paraplegics did not achieve their predicted level of independence. Possible mechanisms of injury are suggested. Motorcycle accidents are particularly likely to cause these injuries, and a plea is made for further legislation to reduce the risks of injuries to young motorcyclists.


Geriatric care needs and HMO technology. A theoretical analysis and initial findings from the National Medicare Competition Evaluation.
More than 770,000 Medicare beneficiaries were enrolled in 1986 in HMOs that have very little experience in providing health care to elderly patients. A general framework for assessing the effects of HMO as compared with fee-for-service delivery systems for the elderly is needed to guide the many studies of quality of care that are underway and will ensue. The following paper addresses the development of such a framework through analysis of the "fit" between the health care needs of the elderly and HMO technology and examination of initial findings from the National Medicare Competition Evaluation--a major project currently underway.


Biologically relevant lyotropic liquid crystalline phases in mixtures of n-octyl β-D-glucoside and water. Determination of the phase diagram by fluorescence spectroscopy.
When mixed with water, n-octyl β-D-glucoside forms self-assembled nanostructures, several of which are liquid crystalline and all of which depend on the water/glucoside ratio and temperature. For practical use of these phases, a detailed understanding of the conditions under which they exist (i.e., the isobaric phase diagram) is required. We use the fluorescence of the dye molecule prodan as a new approach to probe the phases formed in these mixtures. The prodan fluorescence signal depends on the polarity of its environment and thus the phase(s) in which the dye exists. Visual inspection of the total fluorescence signal can qualitatively determine the phases present, including coexisting phases. Temperature-induced phase changes are also detected from variations observed in the prodan fluorescence spectrum. The sensitivity of this new technique allows the single- and multiple-phase regions to be mapped carefully for the first time.


Effectiveness of Injury Prevention Programs With Core Muscle Strengthening Exercises to Reduce the Incidence of Hamstring Injury Among Soccer Players: A Systematic Review and Meta-Analysis.
Muscles in the hamstring group are frequently injured in sporting activities. Injury prevention programs (IPPs), including eccentric training of the hamstrings, have proven to be of great value in decreasing the injury rate of hamstring muscles. To examine the effectiveness of IPPs that include core muscle strengthening exercises (CMSEs) in reducing hamstring injury rates. This systematic review with meta-analysis was based upon the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted for relevant studies published from 1985 to 2021 using the following databases: Cochrane Library, MEDLINE, AMED, PubMed, Web of Science, and Physiotherapy Evidence Database (PEDro). The initial electronic search found 2694 randomized controlled trials (RCTs). After removing duplicate entries, 1374 articles were screened by their titles and abstracts, and 53 full-text records were assessed, of which 43 were excluded. The remaining 10 articles were reviewed in detail, from which 5 studies met our inclusion criteria and were included in the current meta-analysis. Systematic review and meta-analysis of RCTs. Level 1a. Two researchers independently completed the abstract review and performed full-text reviews. A third reviewer was consulted to reach a consensus if any discrepancies were noted. Details were recorded about the participants, methodological aspects, eligibility criteria, intervention data, and outcome measures, including age; number of subjects in the intervention/control group; number of injuries in each group; and the duration, frequency, and intensity of the training conducted in the intervention. The pooled results of 4728 players and 379,102 exposure hours showed 47% hamstring injury reduction per 1000 h of exposure in the intervention group compared with the control group with an injury risk ratio of 0.53 (95% CI [0.28, 0.98], P = 0.04). The results indicate that CMSEs incorporated with IPPs reduce susceptibility and risk of hamstring injuries in soccer players.


Acute noise stress, ACTH administration, and blood pressure alteration.
Two groups of male Wistar rats were submitted to a single noise exposure (2640 Hz, 30 W, 102 dB, 15 min) (St group) or to a single dose of ACTH (1.5 IU/100 g b.wt.) (Ac group), respectively. A control group of nontreated rats (Co group) was used. Blood pressure (BP) was measured using an indirect tail cuff method and corticosterone (B) levels were measured by specific RIA. Haematocrit (Hc) and blood pH values were also evaluated. Acute treatments of both noise exposure and ACTH administration produced corticosterone hypersecretion and blood pressure elevation, with lower haematocrit and higher blood pH values than those found in the Co group. No differences were found between St and Ac treatments.


Purification and properties of a pantetheine-hydrolyzing enzyme from pig kidney.
A microsomal glycoprotein that catalyzes the hydrolysis of pantetheine to pantothenate and cysteamine was solubilized and purified to homogeneity as determined by sodium dodecyl sulfate electrophoresis. The enzyme from pig kidney cortex was solubilized on exposure to butanol and purified by heat treatment, ammonium sulfate fractionation, hydrophobic chromatography, and hydroxyapatite chromatography. The purified enzyme (Mr = 57,000) has a specific activity of 14 mumol of pantothenate produced per min/mg of protein, a value 35 times that previously reported. A method for localizing enzymatic activity on polyacrylamide gels is presented, and enzyme activity, protein, and carbohydrate are shown to migrate identically by electrophoresis on nondenaturing polyacrylamide gels. Amino acid analysis indicated an absorbance index E1%1cm (280 nm) of 11.3, and carbohydrate analysis revealed the presence of galactose, mannose, fucose, glucose, galactosamine, and sialic acid for a total carbohydrate composition of 11.8%. The enzymatic hydrolysis of various pantetheine analogs indicated the enzyme had a high specificity for the pantothenate moiety but a low specificity for the cysteamine portion.


Asaia lannaensis sp. nov., a new acetic acid bacterium in the Alphaproteobacteria.
Asaia lannaensis sp. nov. was described for two strains isolated from flowers of the spider lily collected in Chiang Mai, Thailand. The isolates produced acetic acid from ethanol on ethanol/calcium carbonate agar, differing from the type strains of Asaia bogorensis, Asaia siamensis, and Asaia krungthepensis, but did not grow in the presence of 0.35% acetic acid (v/v). The new species is the fourth of the genus Asaia, the family Acetobacteraceae.


Decision rules for hypertension screening: application in a poor community with endemic hypertension.
Data from a hypertension screening project involving 4,272 black residents of a rural southern community were analyzed to determine the effects of a set of admission-decision rules on the case load of a proposed hypertension clinic. Four decision rules were investigated: conjunctive (diastolic high or systolic high); disjunctive (diastolic and/or systolic high); additive (sum of diastolic and systolic high); and systolic only. Most information relevant to admission to treatment came from knowledge of systolic blood pressures, even though knowledge of the diastolic pressure is essential in individual diagnosis. Incremental increases in the minimum blood pressure necessary for admission to treatment from 140/90 mm Hg to 160/95 mm Hg resulted in a one-third reduction in the number of patients treated, a 24% reduction in personnel utilization per patient, and a 34% reduction in drug costs; but in an estimated 14% increase in the attack rate for morbid events in men.


Recent Advances in Lewis Base-Catalysed Chemo-, Diastereo- and Enantiodivergent Reactions of Electron-Deficient Olefins and Alkynes.
Lewis base catalysis provides powerful synthetic strategies for the selective construction of carbon-carbon and carbon-heteroatom bonds. Thus continuous efforts have been deployed to develop effective methodologies involving Lewis base catalysis. The nucleophilicity and steric hindrance of Lewis base catalyst often plays a major role in catalytic reactivity and selectivity in the reaction. In the past decades, tremendous progress has been made in the divergent construction of valuable motifs under Lewis base catalysis. In this review, we provide a comprehensive and updated summary of Lewis base-catalysed chemo-, diastereo- and enantiodivergent reaction, as well as the related mechanism will be highlighted in detail.


Evaluation of the optimal combinations of modulation factor and pitch for Helical TomoTherapy plans made with TomoEdge using Pareto optimal fronts.
Modulation factor (MF) and pitch have an impact on Helical TomoTherapy (HT) plan quality and HT users mostly use vendor-recommended settings. This study analyses the effect of these two parameters on both plan quality and treatment time for plans made with TomoEdge planning software by using the concept of Pareto optimal fronts. More than 450 plans with different combinations of pitch [0.10-0.50] and MF [1.2-3.0] were produced. These HT plans, with a field width (FW) of 5 cm, were created for five head and neck patients and homogeneity index, conformity index, dose-near-maximum (D2), and dose-near-minimum (D98) were analysed for the planning target volumes, as well as the mean dose and D2 for most critical organs at risk. For every dose metric the median value will be plotted against treatment time. A Pareto-like method is used in the analysis which will show how pitch and MF influence both treatment time and plan quality. For small pitches (≤0.20), MF does not influence treatment time. The contrary is true for larger pitches (≥0.25) as lowering MF will both decrease treatment time and plan quality until maximum gantry speed is reached. At this moment, treatment time is saturated and only plan quality will further decrease. The Pareto front analysis showed optimal combinations of pitch [0.23-0.45] and MF > 2.0 for a FW of 5 cm. Outside this range, plans will become less optimal. As the vendor-recommended settings fall within this range, the use of these settings is validated.


Nicotine and acute stress: effects of nicotine versus nicotine withdrawal on stress-induced hemoconcentration and cardiovascular reactivity.
This study was designed to assess the effects of nicotine and nicotine withdrawal on stress-induced hemoconcentration and cardiovascular reactivity during acute stress in smokers. Forty-six smokers (>or=10 cigarettes per day) were tested twice, once while wearing a 21 mg nicotine patch for 12h and once while wearing a placebo patch (nicotine withdrawal). Calculated plasma volume, hemoglobin, hematocrit, HR, SBP, DBP, cardiac output, stroke volume, and total peripheral resistance were assessed during a 10-min baseline period, 6-min Paced Auditory Serial-Addition Task (PASAT), and a 2-min cold pressor (CP). No differences between conditions were found for any of the hematological measurements. Participants demonstrated greater HR and SBP increases to the PASAT during the nicotine withdrawal condition. For CP, participants showed greater HR and DBP increases and SV decreases during the nicotine withdrawal condition. Data from affective state ratings indicated that participants reported more negative affect during the psychological challenges during nicotine withdrawal conditions. Negative affective state may further lead to enhanced cardiovascular reactivity. These results demonstrate that although nicotine and nicotine withdrawal significantly have differential effects on cardiovascular functioning, the same differential condition effects do not appear to exist for stress-induced hemoconcentration.


Correction to: A pilot study of improved psychological distress with art therapy in patients with cancer undergoing chemotherapy.
An amendment to this paper has been published and can be accessed via the original article.


Art-based interventions during pregnancy to support women's wellbeing: An integrative review.
The transition to motherhood is a dynamic experience. Antenatal care and education are designed to support women during pregnancy, however childbearing women often report a further need for emotional and social support beyond preparation for birth. Broadening routine antenatal care to included art-based interventions may offer women an opportunity to explore important aspects of the transition to motherhood. The aim of this integrative review is to synthesise research regarding the use of art-based interventions with women during pregnancy. A systematic integrative review of the current evidence-base was conducted. A multi-database keyword search was implemented, and a total of six articles met inclusion criteria. Results were analysed using an inductive thematic analysis framework. Six studies met the inclusion criteria. Three major themes were generated: art-based engagements supported women to express complex emotion, fostered a sense of connection and strengthened personal resourcefulness. Creative expression provided an opportunity to explore important aspects of the motherhood experience including, complex emotion, identity and bonding with the unborn child. Being in a group enhanced the health effects of art-making and the social connection felt supportive when role and identity was evolving. Whilst research on the current topic is emergent, preliminary results suggest that facilitated art-based programs are valuable for pregnant women. Art-based experiences offer women a unique opportunity to explore the full dimensionality of the transition to motherhood which can contribute to improved health and wellbeing. These findings suggest that art-based programs may serve to complement existing antenatal care models.


Improving the growth rate of Escherichia coli DH5alpha at low temperature through engineering of GroEL/S chaperone system.
GroEL/S is a molecular chaperone system in Escherichia coli which not only assists the folding of intracellular proteins but also affects the cellular activity against the change of environmental condition. Here we show that the growth rate of E. coli DH5alpha can be improved at low temperature by expressing a GroEL/S variant achieved through irrational protein engineering approach. The GroELS variant (GroELS(var)) accelerating the growth of E. coli DH5alpha was screened through enrichment culture of the mutant libraries obtained by random mutagenesis. E. coli DH5alpha harboring the groELS(var) gene exhibited approximately 1.5-2 times higher growth rate compared to the strain with wild-type GroELS at 15-30 degrees C. At 10 degrees C, a temperature that the growth of E. coli DH5alpha almost stops, the GroELS(var) triggered the growth of E. coli DH5alpha. We identified that seven nucleotides of groELS gene and six amino acids of the GroELS were changed through the mutagenesis and screening. Site directed mutagenic analysis revealed that H360 in GroEL(var) is the most crucial residue determining the activity of GroELS(var) and more than one of the other residues in GroEL(var) may be additionally involved in the activity of GroELS(var). The improvement of growth rate induced by the GroELS(var) was observed only in the strain DH5alpha and not detected in other E. coli strains, such as BL21, BW25113, codon+, JM110, Top10, and XL1-blue.


U-shaped associations between glycated albumin and obesity and role of IL-10 in hyperacute ischemic stroke.
There is growing interest in the use of new biomarkers such as glycated albumin (GA). In contrast to glycated hemoglobin (HbA1c), GA showed an inverse correlation with prestroke obesity status, but data are limited for ischemic stroke (IS). We explored the association between GA and body mass index (BMI) and investigated inflammatory cytokines to support the academic background. In total, 155 patients with hyperacute IS (HIS) between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to BMI quartiles. Levels of inflammatory cytokines, including IL-1β, IL-10, IL-6, TNF-α, and TNF-R1, were determined by ELISA using a ProcartaPlex multiplex immunoassay. The mean age of the 155 patients was 68 ± 12 years, and 67.1% were men. The lowest BMI group had higher GA levels (GA 2 T and 3 T = 80%) (p-value=0.017), and these U-shaped associations were maintained only for small vessel occlusion etiology (p-value= 0.004). Plasma IL-10 levels were positively correlated with BMI and showed a U-shaped pattern (p-value= 0.001). GA levels and BMI had U-shaped associations with HIS. IL-10, which acts as a protective cytokine for cardiovascular disease, may play a novel role in this association. Although GA is an emerging favorable clinical marker of cardiovascular outcomes, obesity status should be considered when interpreting these associations.


A comparison of robotic and laparoscopic minimally invasive adrenalectomy for adrenal malignancies.
Although guidelines recommend open adrenalectomy for most resectable adrenal malignancies, minimally invasive adrenalectomies are performed. Robotic adrenalectomies have become more popular recently, but there is a paucity of literature comparing laparoscopic and robotic resections. Patients who underwent a planned minimally invasive adrenalectomy for adrenal malignancies (adrenocortical carcinoma, malignant pheochromocytoma, other carcinoma) were identified in the National Cancer Database. The primary outcome was the conversion rate from minimally invasive to open. Other post-operative outcomes and survival were compared. 416 patients (76.5%) underwent a laparoscopic adrenalectomy and 128 (23.5%) underwent a robotic operation. Demographics and clinical characteristics were similar. Approximately 19% of tumors resected by a minimally invasive approach were > 10 cm. The intra-operative conversion rate was decreased among robotic adrenalectomies relative to laparoscopic on univariate (7.8% vs. 18.3%, p = 0.005) and multivariable (odds ratio 0.39, p = 0.01) analyses. Using marginal standardization, there was a stepwise increase in the conversion rate as tumor size increased (< 5, 5-10, > 10 cm) for laparoscopic (7.5%, 18.0%, 33.2%) and robotic (3.1%, 8.3%, 17.3%) adrenalectomies. Operations which required conversion had a greater margin positivity rate, greater length of stay, and an association with poor overall survival. In contrast to most clinical guidelines, minimally invasive adrenalectomies are being performed on large malignant tumors. A laparoscopic approach was associated with a greater conversion rate and subsequent poor outcomes. If a surgeon is not planning an open adrenalectomy, but adrenal malignancy is a possibility, robotic adrenalectomy may be the preferred approach for resectable adrenal tumors.


AMP deaminase from dogfish erythrocytes: purification and some properties.
The AMP deaminase from erythrocytes from the dogfish, Scyliorhinus caniculus, L., was purified by chromatography on cellulose-phosphate and DEAE-cellulose. The 1300-fold purified enzyme was highly unstable. At low substrate concentrations, a sharp pH optimum was found at pH 6.7. At higher substrate concentrations, the highest activity was found between pH 6.8 and 7.2. The substrate saturation curve was hyperbolic in the presence of monovalent cations. The binding of inorganic phosphate showed cooperativity. Overall the kinetic properties of AMP deaminase from erythrocytes from dogfish are very similar to that described for other species.


An electrically controlled drug delivery system based on conducting poly(3,4-ethylenedioxypyrrole) matrix.
As numerous therapeutic agents are not well tolerated when administrated systemically, localized and controlled delivery can help to decrease their toxicity by applying an optimized drug concentration at extended exposure time. Among different types of drug delivery systems, conjugated polymers are considered as promising materials due to their biocompatibility, electrical conductivity and ability to undergo controllable redox reactions. In this work poly(3,4-ethylenedioxypyrrole), PEDOP, matrix is described for the first time as a reservoir of a model drug, ibuprofen (IBU). Drug immobilization process is performed in situ, during the electrochemical polymerization of 10 mM EDOP in the presence of 5-50 mM IBU. The loading efficiency of polymer matrix is dependent on IBU concentration and reaches 25.0±1.3 μg/cm2. The analysis of PEDOP-IBU chemical structure based on Raman spectroscopy, energy dispersive spectroscopy and surface morphology data provided by scanning electron microscopy shows that IBU is accumulated in the structure of matrix and evidently influences its morphology. IBU is then released in a controlled way under the influence of applied potential (-0.7 V vs. Ag/AgCl). It is demonstrated that the judicious choice of the synthesis conditions leads to a tailored loading efficiency of PEDOP matrix and to a tunable drug release.


Correlation between handgrip and isokinetic strength of shoulder muscles in elite sitting volleyball players.
The aim of this study was to examine the relationships between isometric handgrip (HG) strength and isokinetic strength data of the glenohumeral rotator muscles. Twelve (Female = 50%) Brazilian Sitting Volleyball (SV) national team players volunteered. Measures of maximal grip strength were obtained by a HG dynamometer Jamar® and isokinetic measures of peak torque (PT) and total work (TW) during shoulder rotations movements were obtained with a Biodex isokinetic dynamometer at speed of 60°/s and 180°/s. Pearson correlation coefficients between isometric HG and isokinetic strength data ranged between 0.23 and 0.72 for the PT and between 0.3 and 0.76 for the isokinetic TW. Results presented positive relationships between HG isometric strength and isokinetic strength of external rotators of the shoulder in SV players. We can suggest that in the absence of isokinetic dynamometers, HG isometric strength measurements could be used to measure strength levels of the external rotator muscles of elite SV players' shoulder, particularly in the TW values.


Six years' experience with screening of a diethylstilbestrol-exposed population.
The physician population delivering obstetric care in Philadelphia between 1950 and 1970 was contacted to ascertain their use of diethylstilbesterol (DES) during pregnancy. Of the 31.8% of the physicians who responded to the questionnaire, 71.8% used DES during pregnancy and 12.7% desired assistance in review of their records. During the 6 years from the initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Of these 830 patients 61.7% were found to have cervicovaginal abnormalities, and 65.9% of the patients showed either adenosis or evidence of the prior existence of vaginal adenosis. Eight patients were treated for clear cell adenocarcinoma. Two cases were detected while asymptomatic. Seven of the patients are living with no evidence of cancer, and two of these have survived over 5 years.


Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5-mediated repression of B-cell-specific genes.
PU.1 and Pax5 are important regulators of immunoglobulin heavy-chain (IgH) gene expression in B lineage cells. We have previously shown that PU.1 can potentiate the transcription of an IgH HS1,2 enhancer-linked reporter gene, and that Pax5 represses the same enhancer in transient transfection assays. Here we report that PU.1, like Pax5, can recruit and physically interact with a member of the Groucho family of co-repressors, Grg4. As a consequence, PU.1 in conjunction with Pax5 represses enhancer function in a position-dependent manner when Grg4 is recruited. Interestingly, Grg4 levels decrease following B-cell activation, suggesting temporal regulation of Grg4. Moreover, the joining-chain promoter, with an activity pattern and architecture resembling HS1,2 can also be repressed by the combinatorial action of Pax5/PU.1/Grg4. These data indicate that Pax5 depends on PU.1, acting in cis, for stable recruitment of Grg co-repressors to B-cell-specific genes.


Spatiotemporal distribution and socioeconomic disparities of dengue, chikungunya and Zika in two Latin American cities from 2007 to 2017.
To assess the presence, pattern and magnitude of socioeconomic inequalities on dengue, chikungunya and Zika in Latin America, accounting for their spatiotemporal distribution. Using longitudinal surveillance data (reported arboviruses) from Fortaleza, Brazil and Medellin, Colombia (2007-2017), we fit Bayesian hierarchical models with structured random effects to estimate: (i) spatiotemporally adjusted incidence rates; (ii) Relative Concentration Index and Absolute Concentration Index of inequality; (iii) temporal trends in RCIs; and (iv) socioeconomic-specific estimates of disease distribution. The spatial analysis was conducted at the neighbourhood level (urban settings). The socioeconomic measures were the median monthly household income (MMHI) for Brazil and the Socio-Economic Strata index (SES) in Colombia. There were 281 426 notified arboviral cases in Fortaleza and 40 887 in Medellin. We observed greater concentration of dengue among residents of low socioeconomic neighbourhoods in both cities: Relative Concentration Index = -0.12 (95% CI = -0.13, -0.10) in Fortaleza and Relative Concentration Index = -0.04 (95% CI = -0.05, -0.03) in Medellin. The magnitude of inequalities varied over time across sites and was larger during outbreaks. We identified a non-monotonic association between disease rates and socioeconomic measures, especially for chikungunya, that changed over time. The Relative Concentration Index and Absolute Concentration Index showed few if any inequalities for Zika. The socioeconomic-specific model showed increased disease rates at MMHI below US$400 in Brazil and at SES-index below level four, in Colombia. We provide robust quantitative estimates of socioeconomic inequalities in arboviruses for two Latin American cities. Our findings could inform policymaking by identifying spatial hotspots for arboviruses and targeting strategies to decrease disparities at the local level.


Banded applications are highly effective in minimising herbicide migration from furrow-irrigated sugar cane.
Runoff from farm fields is a common source of herbicide residues in surface waters in many agricultural industries around the world. In Queensland, Australia, the runoff of PSII inhibitor herbicides (in particular diuron and atrazine) is a major concern due to their potential impact on the Great Barrier Reef. This study compared the conventional practice of broadcast application of herbicides in sugarcane production across the whole field with the banded application of particular herbicides onto raised beds only using a shielded sprayer. This study found that the application of two moderately soluble herbicides, diuron and atrazine, to only the raised beds decreased the average total load of both herbicides moving off-site by >90% compared with the conventional treatment. This was despite the area being covered with the herbicides by the banded application being only 60% less than with the conventional treatment. The average total amount of atrazine in drainage water was 7.5% of the active ingredient applied in the conventional treatment compared with 1.8% of the active ingredient applied in the banded application treatment. Similarly, the average total amount of diuron in drainage water was 4.6% of that applied in the conventional treatment compared with 0.9% of that applied in the banded application treatment. This study demonstrates that the application of diuron and atrazine to raised beds only is a highly effective way of minimising migration of these herbicides in drainage water from furrow irrigated sugarcane.


Women and Politics: Coverage of 2021 Parliamentary Election Campaign in the Albanian Online Media.
This study aims to analyze the online media coverage of political discourse and portrayal of women, as political candidates and voters, during the electoral campaign of 2021 in Albania and raises two research questions with regard to this, employing a gender perspective. The study uses a qualitative methodology. Media content analysis is employed for the analysis of 1420 online articles, from 15 portals, 7 TVs, and 8 newspapers. The results show that political candidates are the subject of a gendered portrayal in media. Women receive less amount of time, more focus on personal life versus professional, and on "soft" issues; young candidates are on focus for being "surprise" or "clean" candidates; political party leaders follow the same gendered discourse, the narrative of political candidates' interest, and objectives for women voters relates to their traditional role; women candidates' looks and appearance are targeted in the media; and sexist language promotes hate speech and derogatory comments. To add to this picture, some women candidates promote the gender stereotypes' game to appeal to their electorate, while there is almost no reflection by the media on the problematics of gender portraying during the electoral campaign.


Assessing the role of feed water constituents in irreversible membrane fouling of pilot-scale ultrafiltration drinking water treatment systems.
Fluorescence excitation-emission matrix (EEM) approach together with principal component analysis (PCA) was used for assessing hydraulically irreversible fouling of three pilot-scale ultrafiltration (UF) systems containing full-scale and bench-scale hollow fiber membrane modules in drinking water treatment. These systems were operated for at least three months with extensive cycles of permeation, combination of back-pulsing and scouring and chemical cleaning. The principal component (PC) scores generated from the PCA of the fluorescence EEMs were found to be related to humic substances (HS), protein-like and colloidal/particulate matter content. PC scores of HS- and protein-like matter of the UF feed water, when considered separately, showed reasonably good correlations with the rate of hydraulically irreversible fouling for long-term UF operations. In contrast, comparatively weaker correlations for PC scores of colloidal/particulate matter and the rate of hydraulically irreversible fouling were obtained for all UF systems. Since, individual correlations could not fully explain the evolution of the rate of irreversible fouling, multi-linear regression models were developed to relate the combined effect of HS-like, protein-like and colloidal/particulate matter PC scores to the rate of hydraulically irreversible fouling for each specific UF system. These multi-linear regression models revealed significant individual and combined contribution of HS- and protein-like matter to the rate of hydraulically irreversible fouling, with protein-like matter generally showing the greatest contribution. The contribution of colloidal/particulate matter to the rate of hydraulically irreversible fouling was not as significant. The addition of polyaluminum chloride, as coagulant, to UF feed appeared to have a positive impact in reducing hydraulically irreversible fouling by these constituents. The proposed approach has applications in quantifying the individual and synergistic contribution of major natural water constituents to the rate of hydraulically irreversible membrane fouling and shows potential for controlling UF irreversible fouling in the production of drinking water.


Intravesical instillation of ropivacaine reduces bladder spasms following paediatric ureteroneocystostomy.
Bladder spasms are a common cause of pain after surgical procedures that call for postoperative catheter drainage. Several therapeutic methods have been used to lessen these spasms but none have received widespread success. Twenty-six children were included in a prospective randomized trial to evaluate the safety and efficacy of daily intravesical instillation of ropivacaine as prophylactic treatment for bladder spasms following ureteroneocystostomy. Although six patients experienced mild transient pain during instillation, there was no systemic toxicity attributable to the ropivacaine. The average number of spasms per day fell by half in the instillation group (p<0.01). Intravesical instillation of ropivacaine is a feasible alternative prophylactic treatment for postoperative bladder spasms.


VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid.
Δ9,11 modifications of glucocorticoids (21-aminosteroids) have been developed as drugs for protection against cell damage (lipid peroxidation; lazaroids) and inhibition of neovascularization (anecortave). Part of the rationale for developing these compounds has been the loss of glucocorticoid receptor binding due to the Δ9,11 modification, thus avoiding many immunosuppressive activities and deleterious side effect profiles associated with binding to glucocorticoid and mineralocorticoid receptors. We recently demonstrated that anecortave acetate and its 21-hydroxy analog (VBP1) do, in fact, show glucocorticoid and mineralocorticoid receptor binding activities, with potent translocation of the glucocorticoid receptor to the cell nucleus. We concluded that Δ9,11 steroids showed novel anti-inflammatory properties, retaining NF-κB inhibition, but losing deleterious glucocorticoid side effect profiles. Evidence for this was developed in pre-clinical trials of chronic muscle inflammation. Here, we describe a drug development program aimed at optimizing the Δ9,11 chemistry. Twenty Δ9,11 derivatives were tested in in vitro screens for NF-κB inhibition and GR translocation to the nucleus, and low cell toxicity. VBP15 was selected as the lead compound due to potent NF-κB inhibition and GR translocation similar to prednisone and dexamethasone, lack of transactivation properties, and good bioavailability. Phamacokinetics were similar to traditional glucocorticoid drugs with terminal half-life of 0.35 h (mice), 0.58 h (rats), 5.42 h (dogs), and bioavailability of 74.5% (mice), and 53.2% (dogs). Metabolic stability showed ≥80% remaining at 1 h of VBP6 and VBP15 in human, dog, and monkey liver microsomes. Solubility, permeability and plasma protein binding were within acceptable limits. VBP15 moderately induced CYP3A4 across the three human hepatocyte donors (24-42%), similar to other steroids. VBP15 is currently under development for treatment of Duchenne muscular dystrophy.


Fibrin sealants and glues.
Fibrin sealants and fibrin glues have become effective instruments in the care of surgical patients. They have been used as an adjunct to hemostasis, wound healing, tissue adhesion, and drug delivery. In cardiac surgery, fibrin glues have emerged as valuable tools to improve hemostasis, decreased blood transfusions, improve tissue handling, and pretreat vascular grafts. Fibrin glues and sealants are now available commercially in the United States. This article will review the history, pharmacology, uses, and toxicity of fibrin sealants and fibrin glues.


Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients.
Pancreatic mucinous cystic neoplasms (MCNs) represent one of the precursor lesions of pancreatic ductal adenocarcinoma, and their detection has been facilitated by advances in preoperative imaging. Due primarily to the rarity of MCNs, however, there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation. A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes. To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma (MCN-AIC). All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed. Only cases with ovarian-type stroma verified by progesterone receptor staining were included. Preoperative features, histological findings and postoperative course were documented. Multivariate logistic regression was employed to investigate variables related to malignancy. Survival analysis was performed using the Kaplan-Meier curve, and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC. Among the 48 patients, 36 had benign MCNs, and 12 had malignant MCNs (1 high-grade atypical hyperplasia and 11 MCN-AIC). Age, tumour size, presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy. The follow-up period ranged from 12 mo to 120 mo, with a median overall survival of 58.2 mo. Only three patients with MCN-AIC died, and the 5-year survival rate was 70.1%. All 11 cases of MCN-AIC were stage I, and extracapsular invasion was identified as a prognostic factor for poorer outcomes. The risk factors independently associated with malignant transformation of MCNs included age, tumour size, presence of solid components or mural nodules, and pancreatic duct dilatation. Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.


Corrigendum: Receptor of advanced glycation end products deficiency attenuates cisplatin-induced acute nephrotoxicity by inhibiting apoptosis, inflammation and restoring fatty acid oxidation.
[This corrects the article DOI: 10.3389/fphar.2022.907133.].


Identify MicroRNA Targets Using AGO2-CLASH (Cross-linking, Ligation, and Sequencing of Hybrids) and AGO2-CLIP (Cross-Linking and Immuno-Precipitation) in Cells with or Without the MicroRNA of Interest Depleted.
MicroRNAs (miRNAs) are short noncoding RNAs and important players in the regulation of gene expression through post-transcriptional mechanisms. MicroRNAs regulate many cellular processes and are involved in disease progression. Identification of novel miRNA-to-target RNA connections can fill the gaps in the signaling pathways and suggest new therapeutic targets. MiRNA targets are often predicted by base-complementarity of their seed and flanking sequences with target sequences. Direct targets can also be identified by the physical interaction between the miRNA and the target RNA using immunoprecipitation of the Argonaute (AGO) protein, a component of the RNA-induced silencing complex, followed by ligation of AGO-associated miRNA and target RNA and next generation sequencing (CLASH). Databases describing these miRNA-RNA interactions have been generated from cells commonly studied or used. However, because the regulation by miRNAs varies among organs, tissues, cell types and species, identifying relevant targets in specific cells under conditions of interest may not be available. Here, the author describes simplified methods of AGO2-CLASH and AGO2-CLIP to identify miRNA targets by comparing primary cells derived from wild-type mice and those from specific miRNA knockout mice.


The male perspective: A mixed methods study of the impact, unmet needs and challenges of caring for women with breast cancer.
As a formative investigation toward the development of a supportive care intervention for male caregivers, this study explored the emotional impact, unmet needs and challenges experienced by men when caring for a woman with breast cancer. A cross-sectional mixed methods study, with an online survey and interviews. A total of 89 participants completed the survey, of whom 13 completed interviews. The majority (93%) of participants were husbands of care recipients; of the care recipients, 75% had early stage breast cancer and 45% were diagnosed over 5 years ago. Participants completed questionnaires assessing their emotional wellbeing, unmet needs and biopsychosocial challenges, with a sub-sample participating in subsequent interviews to elaborate on survey responses. Emotional difficulty was reported by <25% of the sample, and 83% reported experiencing at least one unmet need (M = 81.5, SD = 33.2). Of the 39 biopsychosocial challenges presented, 100%, 86% and 73% reported "ever experiencing," "currently experiencing," and "ever needing help," respectively. Interviewed participants echoed the most reported needs and challenges as changes to sex life, fear of recurrence and lack of practical information. Male cancer caregivers experience diverse challenges and require psychological support and practical information using both online and offline approaches to support their caregiving responsibilities. Healthcare professionals can support male caregivers by: being aware of their information and psycho-social needs; directing caregivers to online interventions for additional information; and facilitating the provision of online psycho-sexual and FCR support.


Peripapillary microvasculature in patients with diabetes mellitus: An optical coherence tomography angiography study.
To evaluate changes in peripapillary microvascular parameters in diabetes mellitus (DM) patients using optical coherence tomography angiography (OCTA). Seventy-one diabetic patients (40 in the no diabetic retinopathy [DR] group and 31 in the non-proliferative DR [NPDR] group) and 50 control subjects. OCTA (Zeiss HD-OCT 5000 with AngioPlex) 6 × 6 mm scans centered on the optic disc were analyzed. Peripapillary vessel density (VD), perfusion density (PD) in superficial capillary plexus (SCP) were automatically calculated. The average macular ganglion cell-inner plexiform layer (mGC-IPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the no DR and NPDR groups were significantly thinner than those of the control group. The no DR and NPDR groups showed lower peripapillary VD and PD in SCP compared with the control group. Using univariate regression analyses, the average mGC-IPL thickness, the pRNFL thickness, the no DR group and NPDR group were significant factors that affected the peripapillary VD and PD in SCP. Multivariate regression analyses showed that the grade of DR was a significant factor affecting the peripapillary VD and PD in SCP. OCTA revealed that peripapillary microvascular parameters in the no DR and NPDR groups were lower than those of normal controls. The peripapillary VD and PD in SCP were correlated with the mGC-IPL thickness, the pRNFL thickness, and the no DR and NPDR groups. Changes in peripapillary OCTA parameters may help with understanding the pathophysiology of DM and evaluating a potentially valuable biomarker for patients with subclinical DR.


Valence determination of manganese in battery cathode materials by high-resolution Mn Kalpha1 spectra.
High-resolution the Mn Kalpha1 X-ray fluorescence spectra (HRXRF) were measured for a variety of manganese compounds, the oxidation number (valence) of which was from II to VII. Plots of the valence against the full width at half maximum (FWHM) and the chemical shift of the Kalpha1 X-ray fluorescence spectra give a curve and a liniar relation, respectively. The coefficient of correlation (R2) for the latter plot was 0.989 between valency II and VII. More excellent linearlity from III to IV was obtained with R2 = 0.995, which enabled us to determine the oxidation number of manganese atom in a nickel ion doped spinel structure, LiMn2O4 (LiNixMn(2-x)O4, with 0.2 < x < 0.42). From the valence of manganese ion obtained from HRXRF, the oxidation number of nickel ion is concluded to be divalent.


Scaling Down Large-Scale Thawing of Monoclonal Antibody Solutions: 3D Temperature Profiles, Changes in Concentration, and Density Gradients.
Scale-down devices (SDD) are designed to simulate large-scale thawing of protein drug substance, but require only a fraction of the material. To evaluate the performance of a new SDD that aims to predict thawing in large-scale 2 L bottles, we characterised 3D temperature profiles and changes in concentration and density in comparison to 125 mL and 2 L bottles. Differences in diffusion between a monoclonal antibody (mAb) and histidine buffer after thawing were examined. Temperature profiles at six distinct positions were recorded with type T thermocouples. Size-exclusion chromatography allowed quantification of mAb and histidine. Polysorbate 80 was quantified using a fluorescent dye assay. In addition, the solution's density at different locations in bottles and the SDD was identified. The temperature profiles in the SDD and the large-scale 2 L bottle during thawing were similar. Significant concentration gradients were detected in the 2 L bottle leading to marked density gradients. The SDD slightly overestimated the dilution in the top region and the maximum concentrations at the bottom. Fast diffusion resulted in rapid equilibration of histidine. The innovative SDD allows a realistic characterisation and helps to understand thawing processes of mAb solutions in large-scale 2 L bottles. Only a fraction of material is needed to gain insights into the thawing behaviour that is associated with several possible detrimental limitations.


Epidemiological Study on Burnout in Spanish Dentists: Underlying Psychological Factors.
The aim of this work is to study the personality factors and coping styles of Spanish dentists when facing burnout syndrome, through epidemiological work. An epidemiological study of 1928 Spanish dentists was undertaken through an online survey, which registered the age and gender, and three questionnaires: NEO-FFI (personality traits), Brief COPE (coping styles), and MBI-HSS (burnout questionnaire). A multivariate analysis and an explanatory binary logistic regression model were used to estimate the presence of burnout. Neuroticism turned out to be the strongest indicator (OR 1.10; IC 95% 1.09-1.14), while extraversion (OR 0.93; IC 95% 0.91-0.95) and agreeableness (OR 0.94; IC95% 0.92-0.98) showed an inverse relationship with the occurrence of burnout, as did age (OR 0.9; IC95% 0.96-0.99). Conscientiousness (OR 1.0; IC95% 1.00-1.06) had a direct relationship with the presence of burnout. An avoidant coping style was the only indicative coping style (OR 1.04 IC95% 1.02-1.06). Approximately 70% of the dentists scored high on one of the three dimensions of burnout. No differences were found in the degree of burnout according to gender. Certain personality factors (neuroticism, extraversion, agreeableness, and conscientiousness), the avoidant coping style, and age are powerful indicators to attempt to forecast the presence of burnout syndrome in dentists.


Concomitant radiotherapy and transarterial chemoembolization reduce skeletal-related events related to bone metastases from renal cell carcinoma.
The purpose of this study was to compare the efficacy of radiotherapy (RT) combined with transcatheter arterial chemoembolization (TACE) with RT alone for the treatment of bone metastases from renal cell carcinoma (RCC). We included in this retrospective study 25 RCC patients (28 bone metastases), who were treated with RT at our institution. Patients were divided into two groups: patients treated with RT alone (monotherapy group; n = 17) and those treated with RT combined with TACE (combined therapy group; n = 11). The administered median RT dose was 30 Gy in 10 fractions. Anti-cancer agents used in TACE were cisplatin (median dose, 50 mg) and carboplatin (median dose, 240 mg) for patients with reduced renal function. We evaluated the objective response, post-RT-skeletal-related event (PR-SRE)-free rate, and adverse events associated with treatment for each group. The objective response rates for bone metastases in the monotherapy and combined therapy groups were 33% and 82%, respectively (p = 0.009). The 2-year PR-SRE-free rate in the monotherapy and combined therapy groups was 41.8% and 100%, respectively (p = 0.009). The objective response and PR-SRE-free rates were significantly superior in the combined therapy than in the monotherapy group. There were no significant differences in adverse events or survival between the two groups. RT combined with TACE is a promising treatment for bone metastases from RCC, as it results in higher objective response, and PR-SRE-free rates compared with RT alone. • Skeletal-related events (SREs) are common in patients with bone metastases from renal cell carcinoma (RCC). • Radiotherapy (RT) provides pain relief in patients with bone metastases from RCC, but rarely achieves objective response. • Combination of RT with transcatheter arterial chemoembolization results in higher objective response and post-RT-SRE-free rates compared with RT alone and is a promising treatment for bone metastases from RCC, as it.


Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea.
When DNA fragments from Micromonospora purpurea (the producer of gentamicin) were cloned in Streptomyces lividans, a gentamicin-resistant strain was obtained in which the ribosomes were highly resistant both to gentamicin and to kanamycin. Reconstitution analysis revealed that such resistance resulted from some property of their 16S RNA. Extracts from the clone contained methylase activity which acted on 16S RNA within E. coli 30S ribosomal subunits and rendered them resistant to gentamicin and kanamycin.


Extracorporeal membrane oxygenation for the treatment of adult sickle cell acute chest syndrome.
Sickle cell disease (SCD) is a hereditary haemoglobinopathy that results in polymerization of haemoglobin molecules and subsequent vaso-occlusion. A common cause of death in adults is acute chest syndrome (AChS) with resulting hypoxemic respiratory failure.Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used successfully in acutely reversible respiratory failure when conventional mechanical ventilation has been unable to adequately oxygenate and ventilate in a lung-protective fashion.We present an adult SCD patient with severe respiratory failure due to AChS, successfully treated with VV-ECMO. We also discuss some of the technical challenges and considerations when using ECMO in the SCD patient.


Triple reassortant H3N2 influenza A viruses, Canada, 2005.
Since January 2005, H3N2 influenza viruses have been isolated from pigs and turkeys throughout Canada and from a swine farmer and pigs on the same farm in Ontario. These are human/classical swine/avian reassortants similar to viruses that emerged in US pigs in 1998 but with a distinct human-lineage neuraminidase gene.


Examining Disparities and Excess Cardiovascular Mortality Before and During the COVID-19 Pandemic.
To investigate the patterns and demographic features of cardiovascular disease (CVD) death and subtypes myocardial infarction (MI), stroke, and heart failure in the pre-COVID-19 era (2018-2019) vs during the COVID-19 pandemic (2020-2021) in the United States. In this cross-sectional study, we used the US Multiple Cause of Death files for 2018 to 2021 to examine the trend of excess cause-specific deaths using International Classification of Diseases, Tenth Revision codes for CVD (I00 to I99), MI (I21 and I22), stroke (I60 to I69), and heart failure (I42 and I50). Our primary outcome was excess mortality from CVD and its 3 subtypes (MI, stroke, and heart failure) between prepandemic (2018-2019) and pandemic (2020-2021) years. We performed a subgroup analysis on race and month-to-month and year-to-year variation using χ2 analysis to test statistical significance. Overall, 3,598,352 CVD deaths were analyzed during the study period. There was a 6.7% excess CVD mortality, 2.5% MI mortality, and 8.5% stroke mortality during the COVID-19 pandemic (2020-2021) compared with the prepandemic era (2018-2019). Black individuals had higher excess CVD mortality (13.8%) than White individuals (5.1%; P<.001). This remained consistent across subtypes of CVD, including MI (9.6% vs 1.0%; P<.001), stroke (14.5% vs 6.9%; P<.001), and heart failure (5.1% vs -1.2%; P<.001). There has been a significant rise in CVD and subtype-specific mortality during the COVID-19 pandemic that has been persistent despite 2 years since the onset of the pandemic. Excess CVD mortality has disproportionately affected Black compared with White individuals. Further studies targeting and eliminating health care disparities are necessary.


An intact signal peptide on dengue virus E protein enhances immunogenicity for CD8(+) T cells and antibody when expressed from modified vaccinia Ankara.
Dengue is a global public health concern and this is aggravated by a lack of vaccines or antiviral therapies. Despite the well-known role of CD8(+) T cells in the immunopathogenesis of Dengue virus (DENV), only recent studies have highlighted the importance of this arm of the immune response in protection against the disease. Thus, the majority of DENV vaccine candidates are designed to achieve protective titers of neutralizing antibodies, with less regard for cellular responses. Here, we used a mouse model to investigate CD8(+) T cell and humoral responses to a set of potential DENV vaccines based on recombinant modified vaccinia virus Ankara (rMVA). To enable this study, we identified two CD8(+) T cell epitopes in the DENV-3 E protein in C57BL/6 mice. Using these we found that all the rMVA vaccines elicited DENV-specific CD8(+) T cells that were cytotoxic in vivo and polyfunctional in vitro. Moreover, vaccines expressing the E protein with an intact signal peptide sequence elicited more DENV-specific CD8(+) T cells than those expressing E proteins in the cytoplasm. Significantly, it was these same ER-targeted E protein vaccines that elicited antibody responses. Our results support the further development of rMVA vaccines expressing DENV E proteins and add to the tools available for dengue vaccine development.