NMR studies of Azotobacter vinelandii and Pseudomonas putida seven-iron ferredoxins. Direct assignment of beta-cysteinyl carbon NMR resonances and further proton NMR assignments of cysteinyl and aromatic resonances.
Ferredoxins are proteins which contain iron and inorganic sulfide and are capable of electron transport. They are found in a wide range of organisms, from anaerobic bacteria, to plants and mammals. Although NMR spectroscopy has been used to study ferredoxins since the 1970s, little important structural or biochemical information has resulted from these investigations. The major difficulty has been the effect of the paramagnetic iron-sulfur clusters on the peptide resonances, hindering nuclear Overhauser effect (NOE) studies and causing broad line widths. These effects are most pronounced on resonances arising from the nuclei closest to the iron-sulfur center. Unfortunately, these are likely to be the most interesting nuclei, as they report the events and geometry in the vicinity of the active sites. In this paper, the first direct assignment of beta-cysteinyl 13C resonances for any iron-sulfur protein is reported for the spectrum of Pseudomonas putida ferredoxin. These resonances are of special significance, as they arise from the atoms on the protein closest to the iron centers, with the exception of the directly bound cysteinyl sulfur atoms. In addition, cysteinyl and ring system 1H NMR resonance assignments are made for the spectra of P. putida ferredoxin and Azotobacter vinelandii ferredoxin I.


Effect of a high affinity aluminosilicate sorbent on prevention of aflatoxicosis in growing pigs.
Adding 0.5% hydrated sodium calcium aluminosilicate to diets formulated with aflatoxin-contaminated corn significantly reduced the detrimental effects of the mycotoxin on live weight gains and feed intake. Hepatocellular changes normally associated with aflatoxin consumption could not be detected histopathologically in liver sections from pigs fed contaminated diets plus the aluminosilicate sorbent.


Molecular genetic alterations in thyroid transcription factor 1-negative lung adenocarcinoma in cytology specimens: A subset with aggressive behavior and a poor prognosis.
Patients with thyroid transcription factor 1 (TTF1)-negative pulmonary adenocarcinoma (ADC) have been reported to have a worse prognosis and to lack epidermal growth factor receptor (EGFR) mutations. This study describes a series of cytology specimens from patients with clinically confirmed pulmonary carcinoma negative for TTF1. A search for TTF1-negative ADC from 2010 to 2017 was performed. Each patient's clinical history, pathology specimens, and molecular results were noted. Two hundred ten patients with TTF1-positive pulmonary ADC formed the control group. Fifty specimens were identified from 50 patients (26 females and 24 males). The median age was 58.5 years. The smoking history was as follows: 38 smokers/former smokers (76%), 10 nonsmokers (20%), and 2 patients with an unknown status (4%). Thirty-nine patients (78%) had no previous history of malignancy. The clinical stages were as follows: stage I or II (n = 2 [4%]), stage III (n = 9 [18%]), stage IV (n = 37 [74%]), and unknown (n = 2 [4%]). Patients' mean survival was 10.3 months. Molecular results were available in 43 cases. Twenty-seven cases (63%) had no mutation identified; when they were compared with the control group, TTF1-negative patients had overall shorter survival (P = .0047), even though no statistically significant difference was seen on the clinical stage. Known mutations were less frequent (P = .0095) in TTF-negative tumors (KRAS mutations, n = 11 [25%]; anaplastic lymphoma kinase [ALK], n = 3 [7%]; and EGFR, n = 2 [5%]). This was particularly true for EGFR mutations (P = .047). However, ALK rearrangements were present at an increased frequency in the TTF1-negative group (P = .018). Patients with TTF1-negative lung ADC have worse overall survival, a lower frequency of known mutations, and a higher frequency of ALK alterations.


Emerging properties of nuclear RNP biogenesis and export.
RNA biology has recently seen an explosion of data due to advances in RNA sequencing, proteomic, and RNA imaging technologies. In this review, we highlight progress that has been made using these approaches in the area of nuclear RNP biogenesis and export. Excitingly, the ability to collect quantitative data at the 'omics' scale combined with measurements of transcription, decay, and transport kinetics is providing the information needed to address RNP biogenesis at a systems level. We believe this to be a necessary and critical next step that will lead to a better understanding of how RNP quality, diversity, and fate emerge from a defined set of nuclear RNP assembly and maturation steps.


Transcriptomic analysis of human breast cancer cells reveals differentially expressed genes and related cellular functions and pathways in response to gold nanorods.
Breast cancer is the leading cause of cancer deaths in women. Recent advances in nanomedicine have shown that gold nanorods (AuNRs), as multifunctional drug delivery and photothermal therapeutic agents, have potential for use in cancer therapy. However, the effect of AuNRs on the transcriptome of breast cancer cells is unknown. In the present study, cells of the triple-negative human breast cancer cell line MDA-MB-231, which has high metastatic activity, were treated with AuNRs for transcriptomic analysis using RNA-seq technology. In total, 3126 genes were found to be up-regulated and 3558 genes were found to be down-regulated in AuNR-treated MDA-MB-231 cells. These differentially expressed genes presumably take part in multiple biological pathways, including glycolysis and regulation of the actin cytoskeleton, and impact a variety of cellular functions, including chemoattractant activity. The distinct gene expression profile of MDA-MB-231 cells treated with AuNRs provides a foundation for further screening and validation of important genes involved in the interaction between AuNRs and MDA-MB-231 cells.


Prevalence of Salmonella spp. on Canadian pig farms using liquid or dry-feeding.
The objective of this study was to determine whether the shedding and antibody titre to Salmonella was lower for pig herds provided liquid-feed compared to those on traditional dry rations. Twenty liquid-feeding farms and 61 dry-feeding farms were selected. The amount of antibodies to Salmonella in sera from 15 finisher pigs on each of 80 Ontario swine farms was analyzed by means of enzyme-linked immunosorbent assay (ELISA). In addition, the presence of Salmonella on the 20 liquid-feeding farms and 21 of the dry-feeding farms was assessed by culture of 15 fecal samples taken directly from finisher pigs and five pooled pen-fecal samples at each farm. A cut-off of OD% 10 was used. The Salmonella sero-prevalence differed between the two groups of farms. At least one pig tested sero-positive on 98% of the dry-feeding farms and 84% of the liquid-feeding farms (P<0.05). A multi-variable mixed linear regression model with the farm as a random variable and farm factors as the fixed effects was fitted. Crude optical density (OD) of the individual pig was considered as the continuous dependent variable. Dry-feeding and antimicrobial daily usage was associated with crude OD (P<0.05). In addition, crude OD increased with increasing herd size (P<0.05). Salmonella was isolated from 25 out of 420 fecal samples (6%) from dry-feeding farms compared to three out of 400 samples (0.8%) from liquid-feeding farms. Eight of the dry-feeding farms (38%) tested positive compared to only three of the liquid-feeding farms (15%). Salmonella was also recovered from the pen environment on five dry-feeding farms but were not isolated from the facilities using liquid-feeding. Salmonella Typhimurium was isolated from four farms in the dry-feed group and on one farm with liquid-feeding. The one S. Typhimurium isolate from the liquid-feeding farm exhibited no antimicrobial resistance, but those from dry-feeding farms were resistant to four or more antimicrobial agents. The results of the logistic regression, with farm as a random effect showed that dry-feeding [OR=2.7 (1.1-15.1)] and continuous flow system [OR=2.3 (1.2-12.7)] increased risk of finding Salmonella in the individual pig. These findings indicate that liquid-feeding and all-in all-out management of the grower-finisher barns can reduce the Salmonella prevalence.


Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation.
Persistent activation of nuclear factor B (NF-κB) is very important in the modulation of macrophages cellular response to microbial infections. The deubiquitinase USP14, which is critical for ubiquitin-mediated proteasomal degradation of proteins, is known to be involved in cancer, neurological diseases, and aging. However, the mechanism by which USP14 regulates inflammation remains unclear. Here, we demonstrated that decreasing the deubiquitinase activity of USP14 resulted in reduced lipopolysaccharides (LPS)-mediated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 release in THP-1 and RAW264.7 cells. Meanwhile, USP14 knockdown by siRNA showed the same effects, with no cytotoxicity in THP-1 cells. Moreover, inhibiting the deubiquitinase activity of USP14 or USP14 knockdown resulted in decreased ERK1/2 and IκBα phosphorylation, increased amounts of the NF-κB inhibitor IκBα, and reduced NF-κB p65 transport from the cytoplasm into nucleus. These findings suggested that USP14 induces NF-κB activity and ERK1/2 phosphorylation triggered by microbial infection.


Impact of Novel Hormonal Agents (Abiraterone, Enzalutamide) on the Development of Visceral and/or Brain Metastases in Patients With Bone-metastatic Castration-resistant Prostate Cancer.
The overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients has improved since 2011 with the use of novel hormonal agents (NHAs). The incidence of brain metastases (mets) has been reported to increase since 2004 with the use of docetaxel, but not the incidence of visceral mets. Our objective was to study whether the use of NHAs increases the risk of developing visceral or brain mets (VBMs). mCRPC patients with mets limited to bone (bmCRPC), treated at Tours University Hospital between 2007 and 2015, were included retrospectively. The primary endpoint was to determine whether treatment with NHAs was associated with an increased incidence of VBMs. Secondary endpoints included the search for putative predictive factors to develop VBMs. On 187 bmCRPC patients included, 65 developed VBMs. VBM incidence increased in bmCRPC patients alive after 2011, compared to patients who died before (39.7 vs. 24.6%, P = .04). Meanwhile, their median OS increased from 16.3 months to 28.5 months (P = .01). The longer was the treatment with NHAs, the lower was the risk of VBMs (HR = 0.96, 95% CI [0.94; 0.99]), whereas age < 70 years (HR = 3.33, 95% CI [1.50; 7.40]) and low PSA level at diagnosis (HR = 1.58, 95% CI [1.16; 2.15]) increased this risk. Though retrospective, our results showed an increased incidence of VBMs in bmCRPC patients after 2011. However, this was not associated with NHA exposure duration. The role of NHA exposure remains unclear and needs further investigation.


Accumulation profiles of PrP(Sc) in hemal nodes of naturally and experimentally scrapie-infected sheep.
In classical scrapie, the disease-associated abnormal isoform (PrP(Sc)) of normal prion protein accumulates principally in the nervous system and lymphoid tissues of small ruminants. Lymph nodes traffic leukocytes via lymphatic and blood vasculatures but hemal nodes lack lymphatic vessels and thus traffic leukocytes only via the blood. Although PrP(Sc) accumulation profiles are well-characterized in ovine lymphoid tissues, there is limited information on such profiles in hemal nodes. Therefore, the objective of this study was to compare the follicular accumulation of PrP(Sc) within hemal nodes and lymph nodes by prion epitope mapping and western blot studies. Our studies found that PrP(Sc) accumulation in 82% of animals' abdominal hemal nodes when PrP(Sc) is detected in both mesenteric and retropharyngeal lymph nodes collected from preclinical and clinical, naturally and experimentally (blood transfusion) scrapie-infected sheep representing all three major scrapie-susceptible Prnp genotypes. Abdominal hemal nodes and retropharyngeal lymph nodes were then used to analyze immune cell phenotypes and PrP(Sc) epitope mapping by immunohistochemistry and PrP(Sc) banding patterns by western blot. Similar patterns of PrP(Sc) accumulation were detected within the secondary follicles of hemal nodes and retropharyngeal lymph nodes, where cellular labeling was mostly associated with macrophages and follicular dendritic cells. The pattern of PrP(Sc) accumulation within hemal nodes and retropharyngeal lymph nodes also did not differ with respect to epitope mapping with seven mAbs (N-terminus, n = 4; globular domain, n = 2; C-terminus, n = 1) in all three Prnp genotypes. Western blot analysis of hemal node and retropharyngeal lymph node homogenates revealed identical three banding patterns of proteinase K resistant PrP(Sc). Despite the anatomical difference in leukocyte trafficking between lymph nodes and hemal nodes, the follicles of hemal nodes appear to process PrP(Sc) similarly to lymph nodes.


The radiological management of malignant biliary obstruction.
Percutaneous transhepatic biliary drainage has become widely accepted as a safe and effective palliative therapy for malignant biliary obstruction. The results of drainage were reviewed over a 3-year period and patients divided by the response to decompression as measured by change in serum bilirubin. Patients with good response survived an average of 198 days, while patients with a poor response survived an average of 12 days. No procedural mortality was encountered. However, despite the generally good results, a 30-day mortality rate of 28% was seen, with good responders having a mortality of 10% and poor responders a mortality of 88%. Patients with hepatic metastatic disease as documented by liver-spleen scan, ultrasonography or computed tomography do poorly, surviving an average of 39 days, despite a good biochemical response. The success of percutaneous biliary decompression has allowed surgeons to select cases for cholecystenterostomy from the group of good responders. A more selective clinical approach is suggested for radiologists on the basis of these results.


Analgesic activity of new pyrazine CH and NH acids and their hydrophobic and electron donating properties.
Analgesic efficacy was determined by the hot plate method for a group of 17 new pyrazine and 3 non-pyrazine CH and NH acids. The biological data were quantitatively related to the hydrophobicity of the compounds, expressed by fragmental constant, and to the orbital energy of the highest occupied molecular orbital, calculated quantumchemically. It has been found that the higher the electron donating properties, the more active is the agent, provided that its hydrophobicity allows it to reach its site of action. The results obtained support the charge transfer model for the biological interaction of analgesic agents.


Visualization of glucocorticoid receptor in the brain of green fluorescent protein-glucocorticoid receptor knockin mice.
Glucocorticoids exert various neuroendocrinological effects, including stress response, in the central nervous system via glucocorticoid receptor (GR). GRs are transported from the cytoplasm to the nucleus upon ligand binding, and then exert the transcriptional activity. Although it is important for unraveling the actual property of the GR in vivo, subcellular dynamics of the GR are still unclear within the brain tissue in which the neuronal circuitry is maintained. To address this issue, we generated green fluorescent protein (GFP)-GR knockin mice, whose GR has been replaced by a GFP-GR fusion protein that is functionally indistinguishable from endogenous GR. In fixed brain sections of the GFP-GR knockin mice, the distribution of the green fluorescence was similar to that of GR immunoreactivity. By subtracting autofluorescence using fluorescent emission fingerprinting method with confocal laser scanning microscope, nuclear localization of GFP-GR was identifiable in the hippocampal CA3 subregion, where subcellular localization of the GR has been unsolved compared with other areas. To examine the subcellular trafficking of GFP-GR in vivo, we performed adrenalectomy on the GFP-GR knockin mice. GFP-GR was translocated from the nucleus to the cytoplasm and neurites two days after adrenalectomy. Furthermore, laser scanning cytometry by which fluorescence intensity in situ can be quantitatively measured revealed the entire GFP-GR expression level was increased. We then examined the dynamic changes in the subcellular localization of GFP-GR in living hippocampal neurons both in dissociated culture and in tissue slices. GFP-GR was localized in not only the perikarya but also neurites in the absence of ligand, and nuclear translocation following ligand treatment was observed. This is the first report visualizing subcellular trafficking of the GR in the mouse brain in more physiological condition. The present results propose new avenues for the research of the GR dynamics both in vitro and in vivo.


The NAM2 proteins from S. cerevisiae and S. douglasii are mitochondrial leucyl-tRNA synthetases, and are involved in mRNA splicing.
We have cloned and sequenced the NAM2 gene of Saccharomyces douglasii, which is a homologue of the NAM2 gene of Saccharomyces cerevisiae. The wild-type S.douglasii gene possesses the suppressor functions of the mutant S. cerevisiae NAM2-1 allele, being able to cure a mitochondrial b14 maturase deficiency. By sequence comparisons and direct measurements we have demonstrated that the NAM2 genes encode mitochondrial leucyl tRNA synthetases (EC 184.108.40.206.). Using a derivative of the NAM2 gene, where the expression of the gene is under the control of the UAS GAL10, we have shown that the processing of the pre-mRNA from the two mosaic genes oxi3 and cob-box is impaired when transcription of the gene is repressed. These results lead us to conclude that the mitochondrial leucyl tRNA synthetase is involved in protein synthesis and mRNA splicing. Sequence comparisons show that the mitochondrial and Escherichia coli leucyl tRNA synthetases are highly homologous; however, significant features which may be important for the splicing functions of the mitochondrial enzymes are absent from the bacterial enzyme.


Timing for maximum anaesthetic effect of topical cream during early infant circumcision (EIC) in Rakai, Uganda.
The objective of this study is to determine the optimal timing for device-based infant circumcision under topical anaesthesia. We include infants aged 1-60 days who were enrolled in a field study of the no-flip ShangRing device at four hospitals in the Rakai region of south-central Uganda, between 5 February 2020 and 27 October 2020. Two hundred infants, aged 0-60 days, were enrolled, and EMLA cream was applied on the foreskin and entire penile shaft. The anaesthetic effect was assessed every 5 min by gentle application of artery forceps at the tip of the foreskin, starting at 10 min post-application until 60 min, the recommended time to start circumcision. The response was measured using the Neonatal Infant Pain Scale (NIPS). We determined the onset and duration of anaesthesia (defined as <20% of infants with NIPS score >4) and maximum anaesthesia (defined as <20% of infants with NIPS score >2). Overall, NIPS scores decreased to a minimum and reversed before the recommended 60 min. Baseline response varied with age, with minimal response among infants aged 40 days. Overall, anaesthesia was achieved after at least 25 min and lasted 20-30 min. Maximum anaesthesia was achieved after at least 30 min (except among those aged >45 days where it was not achieved) and lasted up to 10 min. The optimal timing for maximum topical anaesthesia occurred before the recommended 60 min of waiting time. A shorter waiting time and speed may be efficient for mass device-based circumcision.


Selective and nonselective nonsteroidal anti-inflammatory drugs in perianesthesia pain management.
Despite advances in pain management techniques, there remains room for further improvement in optimizing postoperative patient comfort. Although nonsteroidal anti-inflammatory drugs (NSAIDs) that are more selective in the inhibition of the cyclooxygenase (COX) enzyme have become more popular over recent years, the use of traditional nonselective NSAIDs remains efficacious in reducing postoperative pain. Both nonselective and selective NSAIDs have an important role in perianesthesia pain management. This article reviews the benefits and risks of both nonselective NSAIDs and COX-2 NSAIDs in the perianesthesia period.


Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation.
Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation. Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less. The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02). Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating postoperative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes.


Vir90, a virulence-activated gene coding for a Bordetella pertussis iron-regulated outer membrane protein.
Bordetella pertussis undergoes phenotypic changes modulated by the bvgAS locus, which regulates the expression of many genes related to virulence and immunogenicity. We previously reported the N-terminal sequence of a 90 kDa bvg-regulated outer membrane protein (OMP) of B. pertussis (SWISS-PROT accession No. p81549), a novel potential virulence factor that we named Vir90. The open reading frames (ORFs) which potentially code for Vir90 in B. pertussis, B. parapertussis and B. bronchiseptica were identified by computer analysis of the genomic sequences available for the three Bordetella species. Nucleotide sequence analysis of the vir90 upstream region revealed the presence of a putative promoter, a BvgA binding site and a putative Fur binding site. The B. pertussis Vir90 protein showed significant homology with ferrisiderophore receptors from Gram-negative bacteria. An antiserum raised against Vir90His recombinant protein recognized the 90-kDa protein in immunoblots of OMPs from these three virulent Bordetella species. The accumulation of the Vir90 protein increased 4-fold under low iron growth conditions. Therefore, the vir90 gene is expressed in the tested species and its expression is regulated positively by the BvgAS system and negatively under high iron concentration, likely by Fur.


A national study of medical student clinical skills assessment.
This study describes comprehensive standardized patient examinations in medical schools nationally. We surveyed 121 medical school curriculum deans regarding their use of standardized patient assessments. Questions addressed examination characteristics, funding sources, and collaborations. A total of 91 of 121 curriculum deans responded (75% response rate). The majority (84%) of respondents report conducting a comprehensive clinical skills assessment during the third or fourth year of medical school. Most programs are funded with dean's office monies. Although many collaborate with other institutions for examination development, the majority of schools score and remediate students independently. Two-thirds of all respondents (61/91) report that the new standardized patient licensing requirement elevates the importance of in-house clinical skills examinations. Most medical schools now conduct comprehensive clinical skills assessments after the core clerkships, and collaboration is common. These results suggest increasing emphasis on clinical and communication skills competency and opportunities for collaborative research.


Spontaneous Rectus Sheath Hematoma: Factors Predictive of Conservative Management Failure.
To evaluate radiographic, laboratory, and clinical factors associated with conservative management (CM) failure in spontaneous rectus sheath hematoma (RSH). Retrospective review of 72 patients with spontaneous RSH between 2006 and 2017 was performed. Patients were initially managed conservatively and then divided into 2 groups based on decision to embolize. No differences were found between embolization (n = 32) and CM (n = 40) groups in age (67.5 vs 69.5 y; P = .79), sex (31% vs 38% male; P = .58), body mass index (27.7 vs 25.7 kg/m2; P = .20), or medical comorbidities. Univariate analyses compared initial hemoglobin level, change in hemoglobin level, coagulation parameters, transfusion requirements, hematoma volume, and active extravasation on computed tomographic (CT) angiography between groups. Multivariable logistic regression identified factors predictive of CM failure. A scoring system was then created to predict CM failure. CM failed in 32 of 72 patients. Multivariable regression identified active extravasation on CT angiography (P = .02), hematoma volume (P = .01), and packed red blood cell (pRBC) transfusion of ≥ 4 U (P = .03) as predictors of embolization. A scoring system using these factors along with maximum rate of hemoglobin decrease yielded a sensitivity of 100% and specificity of 98% in determining need for embolization. CM for RSH was more likely to fail in patients with active extravasation on CT angiography, larger hematoma volume, pRBC transfusion of ≥ 4 U, and higher rate of hemoglobin decrease. Using these parameters, a scoring system was created that achieved high sensitivity and specificity in identifying patients who would require embolization.


Single-microvessel occlusion produces lamina-specific microvascular flow vasodynamics and signs of neurodegenerative change.
Recent studies have highlighted the importance of understanding the architecture and function of microvasculature, and dysfunction of these microvessels may underlie neurodegenerative disease. Here, we utilize a high-precision ultrafast laser-induced photothrombosis (PLP) method to occlude single capillaries and then quantitatively study the effects on vasodynamics and surrounding neurons. Analysis of the microvascular architecture and hemodynamics after single-capillary occlusion reveals distinct changes upstream vs. downstream branches, which shows rapid regional flow redistribution and local downstream blood-brain barrier (BBB) leakage. Focal ischemia via capillary occlusions surrounding labeled target neurons induces dramatic and rapid lamina-specific changes in neuronal dendritic architecture. Further, we find that micro-occlusion at two different depths within the same vascular arbor results in distinct effects on flow profiles in layers 2/3 vs layer 4. The current results reveal laminar-scale regulation distinctions in microinfarct response and raise the possibility that relatively greater impacts on microvascular function contribute to cognitive decline in neurodegenerative disease.


Planar bilayer membranes made from phospholipid monolayers form by a thinning process.
We investigated the manner in which planar phospholipid membranes form when monolayers are sequentially raised. Simultaneous electrical and optical recordings showed that initially a thick film forms, and the capacitance of the film increases with the same time course as the observed thinning. The diameter of fully thinned membranes varies from membrane to membrane and a torus is readily observed. The frequency-dependent admittance of the membrane was measured using a wide-bandwidth voltage clamp whose frequency response is essentially independent of capacitative load. The membrane capacitance dominates the total admittance and the membrane dielectric is not lossy. The specific capacitance of membranes of several mixtures was measured. A schematic diagram of the formation of these membranes is presented.


Reduced urinary serotonin excretion after intake of high doses of hypoxanthine.
Two healthy volunteers were treated with hypoxanthine 3 x 1 g and allopurinol 3 x 100 mg daily for 1 week. During this treatment serum oxypurine concentration and urinary oxypurine excretion increased as expected. No side effects were observed except for some mild daytime drowsiness and lethargy. Measurements of urinary serotonin (5-HT) excretion showed decreases to as much as 60% below initial values. Decreased urinary 5-HT excretion was also found in a patient with incomplete Lesch-Nyhan syndrome during treatment with high doses of hypoxanthine. His neurological symptoms improved slightly. The results suggest that high doses of hypoxanthine exert a nonspecific sedative effect on both patients with Lesch-Nyhan syndrome and healthy controls. The cause is probably a reduced synthesis or release of 5-HT.


Optimization of operating parameters for sludge process reduction under alternating aerobic/oxygen-limited conditions by response surface methodology.
Batch tests were employed to estimate the optimal conditions for excess sludge reduction under an alternating aerobic/oxygen-limited environment using response surface methodology. Three key operating parameters, initial mixed liquor suspended solids (initial MLSS), HRT (hydraulic retention time) and reaction temperature (T), were selected, and their interrelationships studied by the Box-Behnken design. The experimental data and ANOVA analysis showed that the coefficient of determination (R(2)) was 0.9956 and the adjR(2) was 0.9912, which demonstrates that the modified model was significant. The optimum conditions were predicted to give a maximal ΔMLSS yield of 226 mg/L at an initial MLSS of 10,021 ± 50 mg/L, an HRT of 9.1h and a reaction temperature of 29°C. The prediction was tested by triplicate experiments, where a ΔMLSS yield of 233 mg/L was achieved under the chosen optimal conditions. This excellent correlation between the predicted and measured values provides confidence in the model.


Misinterpretations of Significance Testing Results Near the P-Value Threshold in the Urologic Literature.
Background The outcome of a statistical test is to accept or reject a null hypothesis. Reporting a metric as "trending toward significance" is a misinterpretation of the p-value. Studies highlighting the prevalence of statistical errors in the urologic literature remain scarce. We evaluated abstracts from 15 urology journals published within the years 2000-2021 and provided a quantitative measure of a common statistical mistake-misconstruing the function of null hypothesis testing by reporting "a trend toward significance." Materials and methods We performed an audit of 15 urology journals, looking at articles published from January 1, 2000, to January 1, 2022. A word recognition function in Microsoft Excel was utilized to identify the use of the word "trend" in the abstracts. Each use of the word "trend" was manually investigated by two authors to determine whether it was improperly used in describing non-statistically significant data as trending toward significance. Statistics and data analysis were performed using Python libraries: pandas, scipy.stats, and seaborn. Results This study included 101,134 abstracts from 15 urology journals. Within those abstracts, the word "trend" was used 2,509 times, 572 uses of which were describing non-statistically significant data as trending toward significance. There was a statistically significant difference in the rate of errors between the 15 journals (p < 0.01). The highest rate of improper use of the word "trend" was found in Bladder Cancer with a rate of 1.6% (p < 0.01) of articles. The lowest rate of improper use was found in European Urology, with a rate of 0.3% (p < 0.01). Our analysis found a moderate correlation between the number of articles published and the number of misuses of the word "trend" within each journal and across all journals every year (r = 0.61 and 0.70, respectively). Conclusion The overall rate of p-value misinterpretation never exceeded 2% of articles in each journal. There is significance in the difference in misinterpretation rates between the different journals. Authors' utilization of the word "trend" describing non-significant p-values as being near significant should be used with caution.


Does conal prime CANAL more than cinal? Masked phonological priming effects in Spanish with the lexical decision task.
Evidence for an early involvement of phonology in word identification usually relies on the comparison between a target word preceded by a homophonic prime and an orthographic control (rait-RATE vs. raut-RATE). This comparison rests on the assumption that the two control primes are equally orthographically similar to the target. Here, we tested for phonological effects with a masked priming paradigm in which orthographic similarity between priming conditions was perfectly controlled at the letter level and in which identification of the prime was virtually at chance for both stimulus onset asynchronies (SOAs) (66 and 50 msec). In the key prime-target pairs, each prime differed from the target by one vowel letter, but one changed the sound of the initial c, and the other did not (cinal-CANAL vs. conal-CANAL). In the control prime-target pairs, the primes had the identical vowel manipulation, but neither changed the initial consonant sound (pinel-PANEL vs. ponel-PANEL). For both high- and low-frequency words, lexical decision responses to the target were slower when the prime changed the sound of the c than when it did not, whereas there was no difference for the controls at both SOAs. However, this phonological effect was small and was not significant when the SOA was 50 msec. The pattern of data is consistent with an early phonological coding of primes that occurs just a little later than orthographic coding.


Spatial velocity of the dynamic vectorcardiographic loop provides crucial insight in ventricular dysfunction.
Vectorcardiogram (VCG) represents the trajectory of the tip of cardiac vectors in three dimensional space with varying time. It is a recurring, near-periodic pattern of cardiac dynamics that is constructed by drawing the instantaneous vectors from a zero reference point according to direction, magnitude and polarity in the space. Being a three dimensional entity, it is more informative and more sensitive than conventional ECG as an evaluation tool of the physiology of cardiac dynamics, because of its extra degree of freedom. Accordingly, it is possible to find out even a minute and early electrophysiological alteration in diseases. Each cardiac cycle primarily consists of three loops in VCG corresponding to P, QRS, and T wave activities. The morphological assessment of the QRS loop was carried out in three dimensional space in order to analyze the spatial vectors of the ventricles and their patho-physiological correlation in various cardiac diseases. Spatial Velocity (SV) is a virtual velocity that represents the rate of movement of the tip of the cardiac vector through space, coordinated by three orthogonal leads, and can be estimated by using simple mathematical formula. It is the rate of change in amplitude and the directionality of instantaneous vectors in seriatim in the three dimensional space to quantify their the temporo-spatial characteristic pattern. We propose to evaluate this novel VCG descriptor SV, in normal individuals and patients of ventricular dysfunction. The possible mechanisms consistent with the patho-physiological basis of ventricular dysfunction or heart failure with altered SV would enrich the current understanding of the disease. Heart failure is the final common pathway of multitude of cardiac pathologies. Despite etiological heterogeneity, there are common mechanisms involved in the complex electrophysiological alteration of the failing myocardium. The changes observed as a consequence of ventricular dysfunction involve ion channel remodeling, intercellular uncoupling, myocardial ischemia, alterations in calcium handling, remodeling of the extracellular matrix, the presence of scars, activation of the sympathetic & the renin-angiotensin-aldosterone system, dilatation as well as stretch of viscous etc. The source modulation of the depolarization wave and its propagation in the heart and body fluid volume conductor also influence the visual pattern of cardiac vectors. In addition, patients with heart failure receive pharmacological or non-pharmacological therapies that also influence the electrophysiological changes. We hypothesize that the spatial velocity of ventricular depolarization and repolarization vectors of the VCG loop alters with a characteristic pattern in the patients with ventricular dysfunction and can differentiate healthy individuals from patients with ventricular dysfunction and also differentiate various categories, gradations and severity stratifications of the patients with ventricular dysfunction.


Correlation of cone beam computed tomography (CBCT) findings in the maxillary sinus with dental diagnoses: a retrospective cross-sectional study.
This study was conducted to assess the coincidence of mucosal hyperplasia in the maxillary sinus and related clinical diagnoses of posterior maxillary teeth found in cone beam computed tomography (CBCT) scans. A total of 204 patients who underwent CBCT examinations between 2006 and 2008 were evaluated retrospectively. Clinical and CBCT findings were correlated using patient records. Absolute frequencies, odds ratios (OR), and 95% confidence intervals (95% CI) were calculated for statistical evaluations. There was a pronounced association between periodontitis and radiological signs of sinusitis. Basal mucosal wall thickening was more likely in patients with decayed and non-vital teeth compared to patients with sound teeth (OR = 5.2; 95% CI = 1.2-23.1). Basal mucosal wall thickening was also more likely than total mucosal thickening (OR = 10.4; 95% CI = 2.6-42.2). Patients with decayed and endodontically treated teeth were more likely to exhibit involvement of the basal wall (OR = 9.2; 95% CI = 3.3-25.2) than were patients with healthy teeth. CBCT examinations revealed a correlation between basal mucosal thickening in the maxillary sinus and decayed posterior maxillary teeth or periodontitis. Chronic symptoms involving the sinuses are one of the most common reasons for patients to consult physicians. One reason for chronic orofacial pain is the prevalence of undiagnosed sinus conditions.


[Isolation of lipofuscin from the bovine myocardium].
The paper describes the procedure of lipofuscin isolation from bovine myocardium with the use of 15-45% (weight/volume) linear gradient of sucrose density and differential centrifugation. Two coloured populations of lipofuscin granules with different density have been distinguished. Electron microscopic studies of the isolated lipofuscin have revealed the homogeneity of fractions and good maintenance of the granules. The electron microscopic, absorptive and luminescent spectral properties of lipofuscin preparations correspond to its properties in situ. The isolation of lipofuscin preparations suggests the possibility of studying the chemical composition and intramolecular structure of the granules.


Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory.
A complex array of inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically affects memory processes is not well understood. We find that a small subclass of type 1 cannabinoid receptor (CB1R)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D1 receptor (D1R) signaling to GABAergic transmission. Mice lacking CB1Rs in D1-positive cells (D1-CB1-KO) display impairment in long-term, but not short-term, novel object recognition memory (NOR). Re-expression of CB1Rs in hippocampal D1R-positive cells rescues this NOR deficit. Learning induces an enhancement of in vivo hippocampal long-term potentiation (LTP), which is absent in mutant mice. CB1R-mediated NOR and the associated LTP facilitation involve local control of GABAergic inhibition in a D1-dependent manner. This study reveals that hippocampal CB1R-/D1R-expressing interneurons control NOR memory, identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral outcomes.


Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides-Where Are We Now.
Peptide receptor radionuclide therapy (PRRT) has been one of the most successful and exciting examples of theranostics in nuclear medicine in recent decades and is now firmly embedded in many treatment algorithms for unresectable or metastatic neuroendocrine neoplasms (NENs) worldwide. It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of somatostatin receptors that can be selectively targeted. This review article outlines the scientific basis of PRRT in treatment of NENs and describes its discovery dating back to the early 1990s. Early treatments utilizing Indium-111, a γ-emitter, showed promise in reduction in tumor size and improvement in biochemistry, but were also met with high radiation doses and myelotoxic and nephrotoxic effects. Subsequently, stable conjugation of DOTA-peptides with β-emitting radionuclides, such as Yttrium-90 and Lutetium-177, served as a breakthrough for PRRT and studies highlighted their potential in eliciting progression-free survival and quality of life benefits. This article will also elaborate on the key trials which paved the way for its approval and will discuss therapeutic considerations, such as patient selection and administration technique, to optimize its use.


Simple technique for identifying the linea alba in lower abdominal incisions.
Identification of the true midline in infra-umbilical longitudinal incisions is often difficult. Traditional methods of identification can be unreliable. An alternative technique for identifying the linea alba, based on the attachments of the median umbilical ligament, is presented. The technique is both reliable and reproducible in identifying the midline. This technique is recommended as a means of avoiding muscle incision and facilitating wound closure.


Efficacy and Safety of Targeted High-Intensity Medium-Band (304-312 nm) Ultraviolet B Light in Pediatric Vitiligo.
Phototherapy is a commonly used treatment for vitiligo that has demonstrated safety and efficacy. High-intensity targeted ultraviolet B (UVB) light (304-312 nm) delivered using a phototherapy device is a useful therapeutic option because it can induce repigmentation in a short time without global exposure to radiation, but information regarding this device in children is limited. We performed a retrospective analysis of 95 patches of vitiligo in 27 children treated using a targeted phototherapy device. Phototherapy was administered twice a week. After the first 10 treatment sessions, 82 (86.3%) patches demonstrated some repigmentation and 36.8% achieved 50% or more repigmentation. After a mean of 20.4 treatment sessions, 86 patches (90%) demonstrated some repigmentation and 53.7% achieved 50% or more repigmentation. Responses varied depending on the anatomic location of the lesions. Better responses were usually observed on the face and trunk, whereas the extremities typically showed little response. Repigmentation was better in patients with active vitiligo than in those with stable vitiligo, with responses better with a disease duration of 1 year or less than in those with a duration of more than 1 year. There was no statistically significant difference in repigmentation between those with segmental and generalized vitiligo. The only short-term local side effect was mild erythema that required a decrease in dosage in six patients. Targeted high-intensity medium-band UVB phototherapy alone can produce clinical improvement in pediatric vitiligo and is well tolerated.


First case of fatal bacteremia due to Nocardia neocaledoniensis.
Nocardia neocaledoniensis is an uncommon cause of human-infections. Few cases are reported in the literature. We describe the first case of bacteremia caused by N. neocaledoniensis. This article underlines the importance of mass spectrometry for easy and rapid identification of such bacterium.


Chimeric antigen receptor T cells: a novel therapy for solid tumors.
The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.


Trans-mucosal platforms for dental implants: Strategies to induce muco-integration and shield peri-implant diseases.
Trans-mucosal platforms connecting the bone-anchored implants to the prosthetic teeth are essential for the success of oral rehabilitation in implant dentistry. This region promotes a challenging environment for the successfulness of dental components due to the transitional characteristics between soft and hard tissues, the presence of bacteria, and mechanical forces. This review explored the most current approaches to modify trans-mucosal components in terms of macro-design and surface properties. This critical review article revised intensely the literature until July 2023 to demonstrate, discuss, and summarize the current knowledge about marketable and innovative trans-mucosal components for dental implants. A large number of dental implant brands have promoted the development of several implant-abutment designs in the clinical market. The progress of abutment designs shows an optimistic reduction of bacteria colonization underlying the implant-abutment gap, although, not completely inhibited. Fundamental and preclinical studies have demonstrated promising outcomes for altered-surface properties targeting antibacterial properties and soft tissue sealing. Nanotopographies, biomimetic coatings, and antibiotic-release properties have been shown to be able to modulate, align, orient soft tissue cells, and induce a reduction in biofilm formation, suggesting superior abilities compared to the current trans-mucosal platforms available on the market. Future clinical implant-abutments show the possibility to reduce peri-implant diseases and fortify soft tissue interaction with the implant-substrate, defending the implant system from bacteria invasion. However, the absence of technologies translated to commercial stages reveals the need for findings to "bridge the gap" between scientific evidences published and applied science in the industry.


Comprehensive pore structure characterization of silica monoliths with controlled mesopore size and macropore size by nitrogen sorption, mercury porosimetry, transmission electron microscopy and inverse size exclusion chromatography.
The porosity of monolithic silica columns is measured by using different analytical methods. Two sets of monoliths were prepared with a given mesopore diameter of 10 and 25 nm, respectively and with gradated macropore diameters between 1.8 and 7.5 microm. After preparing the two sets of monolithic silica columns with different macro- and mesopores the internal, external and total porosity of these columns are determined by inverse size-exclusion chromatography (ISEC) using polystyrene samples of narrow molecular size distribution and known average molecular weight. The ISEC data from the 4.6 mm analytical monolithic silica columns are used to determine the structural properties of monolithic silica capillaries (100 microm I.D.) prepared as a third set of samples. The ISEC results illustrate a multimodal mesopore structure (mesopores are pores with stagnant zones) of the monoliths. It is found by ISEC that the ratio of the different types of pores is dependent on the change in diameter of the macropores (serve as flow-through pores). The porosity data achieved from the mercury penetration measurement and nitrogen adsorption as well of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) pictures are correlated with the results we calculated from the ISEC measurements. The ISEC results, namely the multimodal pore structure of the monoliths, reported in several publications, are not confirmed analyzing the pore structures of the different silica monoliths using all other analytical methods.


Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23 stability.
Here, we show that Nucleophsomin/B23 provides lysine 263 as a critical binding site for ATP. Mutagenesis of lysine 263 to asparagine (K263N) disrupts B23 from ATP binding. While B23 WT exclusively localizes to the nucleolus, the B23-K263N is redistributed from the nucleolus to the nucleoplam. Notably, the K263N mutant is unstable, and displayed rapid degradation. Alteration of K263 induced B23 instability through increased ubiquitination and proteaosomal degradation. Moreover, mutation of K263 impedes the mitogenic effect of B23 in PC12 cells. Thus, K263 is a critical site for ATP binding and required for B23 stability, confining B23 in the nucleolus.


Interstitial deletion and ring chromosome derived from 16q.
An interstitial deletion of 16q was identified in an infant with failure to thrive, dysmorphic facies, and congenital heart defects. The mother of this infant had a similar deletion of 16q with ring formation of a fragment presumed to be derived from the deleted portion of 16q. We discuss these cases and compare them to other reports of 16q deletions.


Prenatal diagnosis of duodenal atresia: does it make any difference?
The outcome of infants with duodenal atresia diagnosed antenatally is compared with that of infants diagnosed after birth. The incidence of neonatal morbidity was higher and preoperative conditions were poorer in the second group.


Measurement of venous leg ulcers with a laser-based three-dimensional method: comparison to computer planimetry with photography.
A lack of reproducible and practical methods to assess venous leg ulcer healing is a major problem encountered by investigators evaluating various treatments. We aimed to compare a new laser-based three-dimensional (3D) measuring device with computer planimetry with photography for the assessment of venous leg ulcers, and to estimate the reliability of measurements by the methods. Sixty measurements of perimeter and area of 15 venous leg ulcers, < 10 cm in diameter (eight patients; six females; mean age 71 years; range 52-90 years), were made with both methods. Two independent investigators performed the measurements at the first visit and 2-4 weeks later. The precision and accuracy of the methods were determined and compared. The accuracies for computer planimetry with photography in comparison with the laser-based 3D measuring method were 8.4% for perimeter and 16.0% for area measurements. The precisions of ulcer area and perimeter measurements did not differ significantly between the two methods (p=0.993 and 0.201, respectively). The main advantage of the laser-based measuring method is the 3D ulcer measurement with a precision of 7.5%, which also takes into account distortions created by the limb convexity. The system is accurate, inexpensive, user-friendly, and appropriate for everyday practice.


Osseous metastases from carcinomas of the colon and rectum.
Of 765 patients with disseminated metastatic carcinoma of the colon and rectum treated at Memorial Sloan-Kettering Cancer Center during the ten-year period 1960--1970, 53 (6.9 per cent) had skeletal metastases. Of these, 14 (1.8 per cent) had osseous metastases only. In one case the osseous lesion was the first symptom of a cancer of the sigmoid colon, and one patient had metastasis in the fibula from a primary rectal cancer. In our series the incidences of osseous metastases were 8.9 per cent from rectal carcinoma and 5.1 per cent from colonic carcinoma. The mean period from manifestation of skeletal metastasis to death was 13.2 months.


Inhibitory effect of antidepressants on B16F10 melanoma tumor growth.
Antidepressant drugs, like fluoxetine, a selective serotonin reuptake inhibitor, desipramine, a nonselective noradrenaline reuptake inhibitor, and mirtazapine, an antagonist of noradrenaline α2 auto- and heteroreceptors, are widely used for the treatment of depressive symptoms in cancer patients. Since these antidepressants have different activities targeting the immune system, they might also modulate tumor growth in cancer patients. In the present study, we investigated the effects of administration of antidepressant drugs: fluoxetine, desipramine and mirtazapine on B16F10 melanoma tumor growth. These drugs were administered intraperitoneally (ip) for 17 days after subcutaneous injection of B16F10 melanoma cells to male C57BL/6J mice. Fluoxetine significantly inhibited melanoma solid tumor growth and desipramine tended to decrease this parameter whereas mirtazapine had no effect. The inhibitory effect of fluoxetine on melanoma growth was associated with an increased mitogen-induced T cell proliferation which may at least partly participate in the mechanism of the antitumor effect of this antidepressant. It appears that the inhibitory effect of fluoxetine on tumor growth is not related with changes in cytokine levels except for IL-10.


Socio-economic differences in public opinion regarding water fluoridation in Queensland.
To describe public opinion relating to the fluoridation of drinking water in a sample of the Queensland population. Data were collected by means of a computer-assisted telephone interview survey from a sample of the Queensland population. Descriptive statistics and logistical regression were used to examine associations between variables. Seventy per cent of the total sample supported water fluoridation of their local supply. More than 71% of the total sample agreed that water fluoridation was safe. People living in areas of higher socio-economic/relative socio-economic advantage were more likely to support the addition of fluoride to local drinking water and agree that it was safe. Opinions about fluoridation varied by respondent age and gender. General support was found in this sample of the Queensland population for fluoridation of drinking water. In Queensland, fluoridation of the water supply is now a political decision. Information about public opinion on fluoridation may assist decision makers in the final determination.


Multiscale modeling in the framework of biological systems and its potential for spaceflight biology studies.
A central tenet of systems biology is that biological systems are greater than the sum of their component parts. Spaceflight is associated with hazards including radiation exposure and microgravity which impact different echelons of biological organizations spanning molecular, cellular, organ, and organismal levels. These insults lead to physical damage, including muscle and bone loss, neurological damage, and impaired immunity. Mitochondrial dysfunction and biological alterations occurring during spaceflight have been reported. The health challenges presented by long-term space travel must be addressed and appropriate countermeasures developed to protect astronauts. Increasing quantity of multiomics data are being generated from cells and model organisms flown in space, with physiological data from astronauts. Systems biology approaches leveraging mathematical reasoning and computational modeling are required to characterize these components in a holistic fashion. In this review, we provide an historic perspective on multiscale biological systems modeling, followed by a discussion on its utility for spaceflight biology research.


High prevalence of Clostridium botulinum types A and B in honey samples detected by polymerase chain reaction.
A test protocol for reliable detection of Clostridium botulinum types A and B spores in honey by polymerase chain reaction (PCR) was developed and used for a prevalence survey of C. botulinum spores in 190 honey samples. The inhibiting effects of honey on microbial growth and PCR analysis were overcome by using a method of supernatant filtration (SF) in the preparation of the samples before enrichment and PCR. By using this method, an inoculum of 0.1 spore of C. botulinum/g honey could be detected. In the prevalence survey, spores of C. botulinum were detected in 8 (7%) of the 114 Finnish and in 12 (16%) of the 76 imported honey samples. The quantity of spores in PCR-positive samples varied from less than 18 to 140 spores/kg. Neurotoxin gene sequences corresponding to C. botulinum type A were detected in 17 samples and proteolytic type B in 12 samples by PCR analysis. Both types A and B were detected in nine samples. Strains of C. botulinum type A were isolated from 14 and type B from 2 of the 20 PCR-positive samples. This is the first report of type A spores of C. botulinum being detected and isolated in Fennoscandia.


A technique for arthroscopic mattress suture placement.
Many techniques and instrument systems have been developed for performing arthroscopic Bankart repair and arthroscopic rotator cuff repair. These procedures often use multiple simple sutures placed in the repaired tissue. The use of a mattress suture design allows for inversion or eversion of the repaired tissue, greater repair strength, and provides a greater area of soft tissue apposition to bone. Described is a technique for arthroscopic mattress suture placement. We have used this technique primarily for arthroscopic Bankart repair and arthroscopic rotator cuff repair. Suture material of any type may be used with this technique.


Long-Segment Intradural Extramedullary Teratoma of Dorsolumbar Spinal Cord in an Adolescent: A Rare Tumor with Review of Literature.
Spinal intradural extramedullary teratomas are rare tumors arising from more than one germ cell layers and are more common in children than in older age groups. Teratomas are more commonly seen in intracranial compartment and are extremely rare in the spine. They are difficult to diagnose pre-operatively and the definitive diagnosis is usually done by histopathologic evaluation. Intraspinal teratomas should be considered in the differential diagnosis of any intradural extramedullary tumor of the spine. We reviewed the literature and reported a rare case of intradural extramedullary teratoma in an adolescent located in dorsolumbar spine without any history of prior spinal procedure.


Mitochondrial matrix P53 sensitizes cells to oxidative stress.
A mitochondrial matrix-specific p53 construct (termed p53-290) in HepG2 cells was utilized to determine the impact of p53 in the mitochondrial matrix following oxidative stress. H₂O₂ exposure reduced cellular proliferation similarly in both p53-290 and vector cells, and p53-290 cells demonstrating decreased cell viability at 1mM H₂O₂ (~85% viable). Mitochondrial DNA (mtDNA) abundance was decreased in a dose-dependent manner in p53-290 cells while no change was observed in vector cells. Oximetric analysis revealed reduced maximal respiration and reserve capacity in p53-290 cells. Our results demonstrate that mitochondrial matrix p53 sensitizes cells to oxidative stress by reducing mtDNA abundance and mitochondrial function.


A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial.
Most women develop MS before menopause. Menopausal hot flashes can worsen MS symptoms, and could be relieved with hormone therapy. Our objective was to evaluate feasibility, tolerability and symptom response of Duavee® (bazedoxifene + conjugated estrogen) in a Phase Ib/IIa double-blind randomized controlled clinical trial. We randomized 24 peri/postmenopausal women with MS and symptomatic hot flashes 1:1 to Duavee® versus placebo. Evaluations occurred at baseline and 2 months. Groups were balanced for age (mean 51.2 ± 3.6 years), EDSS [median 3 (IQR:2.5, 4.5)], and MS duration. 21/24 participants completed the study. Enrollment was protracted (34 months), partially due to concerns about hormone therapy safety. treatment group participants reported greater satisfaction and fewer missed doses; one participant (placebo) developed new MRI lesions; liver function testing remained normal for all patients. Hot Flash Related Daily Interference scale at 2 months was lower in treatment vs. placebo group [median (IQR) of 4 (0.5, 14) vs. 9 (0, 33)]. Between-group differences were not statistically significant. Despite perceived benefits in MS, estrogens have perceived risks that represent a hurdle to enrollment. With appropriate education and screening of participants, the favorable study retention (87%) and treatment satisfaction observed in the current study support the feasibility of a longer, powered trial to evaluate whether a proven treatment for menopausal symptoms, Duavee®, could also improve MS-related function in menopausal women with MS.


Overlapping pathogenic de novo CNVs in neurodevelopmental disorders and congenital anomalies impacting constraint genes regulating early development.
Neurodevelopmental disorders (NDDs) and congenital anomalies (CAs) are rare disorders with complex etiology. In this study, we investigated the less understood genomic overlap of copy number variants (CNVs) in two large cohorts of NDD and CA patients to identify de novo CNVs and candidate genes associated with both phenotypes. We analyzed clinical microarray CNV data from 10,620 NDD and 3176 CA cases annotated using Horizon platform of GenomeArc Analytics and applied rigorous downstream analysis to evaluate overlapping genes from NDD and CA CNVs. Out of 13,796 patients, only 195 cases contained 218 validated de novo CNVs. Eighteen percent (31/170) de novo CNVs in NDD cases and 40% (19/48) de novo CNVs in CA cases contained genomic overlaps impacting developmentally constraint genes. Seventy-nine constraint genes (10.1% non-OMIM entries) were found to have significantly enriched genomic overlap within rare de novo pathogenic deletions (P value = 0.01, OR = 1.58) and 45 constraint genes (13.3% non-OMIM entries) within rare de novo pathogenic duplications (P value = 0.01, OR = 1.97). Analysis of spatiotemporal transcriptome demonstrated both pathogenic deletion and duplication genes to be highly expressed during the prenatal stage in human developmental brain (P value = 4.95 X 10-6). From the list of overlapping genes, EHMT1, an interesting known NDD gene encompassed pathogenic deletion CNVs from both NDD and CA patients, whereas FAM189A1, and FSTL5 are new candidate genes from non-OMIM entries. In summary, we have identified constraint overlapping genes from CNVs (including de novo) in NDD and CA patients that have the potential to play a vital role in common disease etiology.


[Emergency room management of multiple trauma : ATLS® and S3 guidelines].
Trauma management in the emergency room is an important part of the treatment chain of the severely injured. Important decisions with respect to diagnostics and treatment must be made under time pressure. Successful trauma management in the emergency room requires a hospital tailored treatment protocol. This written protocol needs consent from all participating disciplines and must be known by all members of the resuscitation team. The ATLS® and the recently published clinical practice guidelines on multiple trauma can be of help in order to establish or update such protocols. In order to continuously evaluate and improve performance in the emergency room local quality circles are needed that truly follow that aim. Important factors are reliability of agreement between the different disciplines and continuous communication of results to the team members. In order to be successful such quality circles need people that care.


The close relationship between growth factors and the nucleolar organizer regions in adenocarcinoma of the lung.
We examined immunohistochemically 111 cases of primary adenocarcinoma of the lung, for transforming growth factor alpha (TGF alpha) or epidermal growth factor (EGF), and argyrophilic nucleolar organizer regions (AgNORs). The presence of more than 75% positive cells for both growth factors was designated as a high-GF, while all others were considered to be a low-GF. If AgNORs counts were more than 5.00, it was considered to be a high-AgNORs group, while less than 5.00 was designated as a low-AgNORs group. In our 111 examined specimens, there were 51 (46%) cases of high-GF, and 64 (58%) with high AgNORs. The 5-year survival rates of the patients with a high-GF and low-GF were 34% and 57% (P < 0.05) respectively, while those with high-AgNORs and low-AgNORs were 21% and 81% (P < 0.001), respectively. In the cases of high-AgNORs, the 5-year survival rates of the patients with high-GF and low-GF were 0% and 36% (P < 0.05), respectively. However, in the cases of low-AgNORs, the 5-year survival rates of the patients with high-GF and low-GF were 83% and 79%, respectively. These data suggest that growth factors might be related to the biological malignancy of tumours with a high cell proliferation.


Human milk oligosaccharide lacto-N-tetraose: Physiological functions and synthesis methods.
Human milk oligosaccharides (HMOs) have attracted considerable attention due to their unique role in boosting infant health. Among the HMOs, lacto-N-tetraose (LNT) is a significant constituent associated with various health benefits, such as prebiotic effects, antiadhesive antimicrobials, antiviral protection, and immune modulators. LNT has received a "Generally Recognized as Safe" status by the American Food and Drug Administration and was approved as a food ingredient for infant formula. However, the limited availability of LNT poses a major challenge for its application in food and medicine. In this review, we first explored the physiological functions of LNT. Next, we describe several synthesis methods for production of LNT, including chemical, enzymatic, and cell factory approaches, and summarize the pivotal research results. Finally, challenges and opportunities for the large-scale synthesis of LNT were discussed.


Childhood vaccination timeliness following maternal migration to an informal urban settlement in Kenya.
Timely receipt of recommended vaccines is a proven strategy to reduce preventable under-five deaths. Kenya has experienced impressive declines in child mortality from 111 to 43 deaths per 1000 live births between 1980 and 2019. However, considerable inequities in timely vaccination remain, which unnecessarily increases risk for serious illness and death. Maternal migration is a potentially important driver of timeliness inequities, as the social and financial stressors of moving to a new community may require a woman to delay her child's immunizations. This analysis examined how maternal migration to informal urban settlements in Nairobi, Kenya influenced childhood vaccination timeliness. Data came from the Nairobi Urban Health and Demographic Surveillance System, 2002-2018. Migration exposures were migrant status (migrant, non-migrant), migrant origin (rural, urban), and migrant type (first-time, circular [previously resided in settlement]). Age at vaccine receipt (vaccination timeliness) was calculated for all basic vaccinations. Accelerated failure time models were used to investigate relationships between migration exposures and vaccination timeliness. Confounding was addressed using propensity score weighting. Over one-third of the children of both migrants and non-migrants received at least one dose late or not at all. Unweighted models showed the children of migrants had shorter time to OPV1 and DPT1 vaccine receipt compared to the children of non-migrants. After accounting for confounding only differences in timeliness for DPT1 remained, with the children of migrants receiving DPT1 significantly earlier than the children of non-migrants. Timeliness was comparable among migrants with rural and urban origins and among first-time and circular migrants. Although a substantial proportion of children in Nairobi's informal urban settlements do not receive timely vaccination, this analysis found limited evidence that maternal migration and migration characteristics were associated with delays for most doses. Future research should seek to elucidate potential drivers of low vaccination timeliness in Kenya.


Effects of dietary rumen-protected choline supplementation on colostrum yields, quality, and choline metabolites from dairy cattle.
Colostrum is a critical nutrient source that provides passive immunity to dairy calves. Choline is a trimethylated molecule that is frequently supplemented in the diet to periparturient dairy cows to support postpartum health and performance. Whereas choline and its metabolites have been characterized in milk, the effects of dietary rumen-protected choline (RPC) supplementation on choline metabolites in colostrum from dairy cattle have yet to be explored. Therefore, the objective of the present study was to assess the effects of dietary supplementation and dose of RPC on colostrum yields, quality, and choline metabolites. Parous Holstein cows were blocked by calving month and randomly assigned within block to receive 45 g/d (20.4 g/d of choline ions) of RPC (CHOL45, n = 22), 30 g/d (13.6 g/d of choline ions) of RPC (CHOL30, n = 20), or no RPC (control, n = 19) starting 24 d before expected calving. The effects of dietary supplementation and dose of RPC were assessed on colostrum yields, component yields, somatic cell score (SCS), quality (as assessed by Brix), and choline metabolites. Data were analyzed using a linear mixed model with the fixed effects of treatment, parity, and the 2-way interaction and the random effect of block. Regardless of dose, dietary RPC supplementation increased colostrum yields and protein yields. No effects of dietary RPC supplementation were found on colostrum component percentages, SCS, or colostrum quality. For choline metabolites, treatment interacted with parity for phosphocholine where colostrum from second-parity CHOL45 and CHOL30 cows had greater concentrations of phosphocholine than colostrum from second-parity control cows, but no treatment effect was seen in the colostrum from 3+ parity cows. Dietary choline supplementation, regardless of dose, increased trimethylamine N-oxide concentrations. Dietary choline supplementation did not affect the concentrations of choline, betaine, glycerophosphocholine, sphingomyelin, phosphatidylcholine, or total choline in colostrum. In conclusion, dietary choline supplementation increased phosphocholine concentrations in colostrum from second-parity cows, enhanced trimethylamine N-oxide concentrations, and increased colostrum yields without affecting colostrum quality.


On the genetics of the human serum paraoxonase (EC 22.214.171.124).
Incubation of the sera of 799 nonrelated persons with paraoxon led to varying degrees of inhibition of the serum cholinesterase (EC 22.214.171.124) with residual activity between 0% and 67.4% of the initial activity. This is the result of a differing paraoxonase (EC 126.96.36.199) activity. The residual activities show a trimodal distribution. The results of studies of 99 families with children show that an autosomal dominant herdity factor is most likely. Consideration of the constellations of the activity values within the families can thus yield a stochastic external criterion. This, together with the shape of the distribution of the individual values, gives good statistical estimates for the distributions and frequencies of the three groups obtained by an iteration technique. Tests of association that take account of group membership show that residual activity does not depend on the blood groups A, B, O, and Rh, or on age. A conclusive argument for our assumption of three activity groups is that the resulting group frequencies are consistent with the Hardy-Weinberg rule.


Melatonin aspiration: Treatment with flexible bronchoscopy.
A 68-year-old male with past medical history 84 pack year smoking history (quit in 2000), mild chronic obstructive pulmonary disease (COPD), adenocarcinoma of right upper lobe treated with surgery and chemoradiation, and melanoma resection in 2013 presented with a one-month history of cough with sputum production and progressive dyspnea on exertion. He did not improve with standard treatment of antibiotics and steroids. He underwent flexible bronchoscopy that revealed an aspirated pill. This was successfully removed in the same session with the flexible bronchoscope.


Internalization and re-expression of antigens of human melanoma cells following exposure to monoclonal antibody.
Modulation of the surface membrane of human Sk-Mel-28 melanoma cells by monoclonal antibody (MoAb) 96.5 recognizing p97 determinants was examined using direct radioimmunoassay and indirect fluorescent antibody-staining techniques. It was determined that the majority of 111In-labeled antibody that remained associated with cells after a 24-hr incubation at 37 degrees C had been internalized because MoAb 96.5 was no longer visible on the cell surface. A second treatment of these cells with the same antibody 24 hr later not only increased the cell-associated radioactivity, reflecting an increase of total antibody bound, but also rendered these cells membrane immunofluorescent again, indicating the re-expression of surface antigens. Autoradiographs of the electrophoretically analyzed membrane components of Sk-Mel-28 cells further demonstrated the appearance of newly synthesized 97-kDa proteins that were immunoprecipitable with MoAb 96.5. Taken together, the present findings suggest that p97 antigens undergo endocytosis in Sk-Mel-28 cells following exposure to MoAb 96.5. However, the same antigens were regenerated and expressed on the cell surface within a period of 24 hr. The re-expression of tumor cell surface antigen following initial internalization of the MoAb-antigen complex may have implications for diagnosis and therapy.


Influences of environmental conditions during infancy on final body stature.
In the following article we shall investigate the Second World War with its consequences on nutrition and other living conditions for the German population to try to determine whether lack of nutrition plus other deficiencies, which infants were subjected to in Germany during this time, had any influence on their adult stature. The following data formed the basis of our investigation: (1) nutrition of infants and school-aged children during the years 1939-1948; (2) stature and weight of 6-year-old boys between 1907 and 1948; (3) infant mortality between 1935 and 1950; (4) stature of 19-year-old men who were born between 1938 and 1951. From Figure 5 it can be seen that the mean stature of 19-year-old men born between 1938 and 1951 (except for those born in 1944 and 1945) rose steadily (secular acceleration). The plot of the yearly rate of acceleration (Fig. 6) reveals a minimum in 1944-1945, and follows a general downward, U-shaped trend (P less than 0.05). On the other hand, infant mortality between 1941 and 1949 follows an upward U-shaped trend (P less than 0.05). For the 6- to 8-month-old infants during 1945-1948 nutrition was far worse than that during the preceding years. It is even likely that the nutrition for the infants had already begun to decrease in quality in 1942. We find, therefore, a close correlation between the years of high infant mortality and the growth deficiencies of the men born during these years. Since we must assume that the nutritional situation for babies and infants worsened steadily after 1942 until it is apparent that a number of environmental factors directly influence human growth. The conclusion of our analysis is that a deficit of growth occurring after the end of the fourth year can be compensated fully. We conclude, furthermore, that the growth deficits which arise before the fourth year, on the other hand, cannot be compensated fully even if good or excellent environmental conditions follow.


Low-Power and Field-Free Perpendicular Magnetic Memory Driven by Topological Insulators.
Giant spin-orbit torque (SOT) from topological insulators (TIs) has great potential for low-power SOT-driven magnetic random-access memory (SOT-MRAM). In this work, a functional 3-terminal SOT-MRAM device is demonstrated by integrating the TI [(BiSb)2 Te3 ] with perpendicular magnetic tunnel junctions (pMTJs), where the tunneling magnetoresistance is employed for the effective reading method. An ultralow switching current density of 1.5 × 105 A cm-2 is achieved in the TI-pMTJ device at room temperature, which is 1-2 orders of magnitude lower than that in conventional heavy-metals-based systems, due to the high SOT efficiency θSH = 1.16 of (BiSb)2 Te3 . Furthermore, all-electrical field-free writing is realized by the synergistic effect of a small spin-transfer torque current during the SOT. The thermal stability factor (Δ = 66) shows the high retention time (>10 years) of the TI-pMTJ device. This work sheds light to the future low-power, high-density, and high-endurance/retention magnetic memory technology based on quantum materials.


High-yield isolation and subcellular proteomic characterization of nuclear and subnuclear structures from trypanosomes.
The vast evolutionary distance between the Opisthokonta (animals and yeast) and the excavata (a major group of protists, including Giardia and Trypanosoma) presents a significant challenge to in silico functional genomics and ortholog identification. Subcellular proteomic identification of the constituents of highly enriched organelles can alleviate this problem by both providing localization evidence and yielding a manageably sized proteome for detailed in silico functional assignment. We describe a method for the high-yield isolation of nuclei from the kinetoplastid Trypanosoma brucei. We also describe the subsequent purification of subnuclear compartments, including the nuclear envelope and nucleolus. Finally, using several proteomic strategies, we survey the proteome of a subcellular structure or organelle, using the nuclear pore complex as an example.


Effect of a Sepsis Screening Algorithm on Care of Children with False-Positive Sepsis Alerts.
To determine if implementation of an automated sepsis screening algorithm with low positive predictive value led to inappropriate resource utilization in emergency department (ED) patients as evidenced by an increased proportion of children with false-positive sepsis screens receiving intravenous (IV) antibiotics. Retrospective cohort study comparing children <18 years of age presenting to an ED who triggered a false-positive sepsis alert during 2 different 5-month time periods: a silent alert period when alerts were generated but not visible to clinicians and an active alert period when alerts were visible. Primary outcome was the proportion of patients who received IV antibiotics. Secondary outcomes included proportion receiving IV fluid boluses, proportion admitted to the hospital, and ED length of stay (LOS). Of 1457 patients, 1277 triggered a false-positive sepsis alert in the silent and active alert periods, respectively. In multivariable models, there were no changes in the proportion administered IV antibiotics (27.0% vs 27.6%, aOR 1.1 [0.9,1.3]) or IV fluid boluses (29.7% vs 29.1%, aOR 1.0 [0.8,1.2]). Differences in ED LOS and proportion admitted to the hospital were not significant when controlling for similar changes seen across all ED encounters. An automated sepsis screening algorithm did not lead to changes in the proportion receiving IV antibiotics or IV fluid boluses, department LOS, or the proportion admitted to the hospital for patients with false-positive sepsis alerts.


Systemic veterinary drugs for control of the common bed bug, Cimex lectularius, in poultry farms.
The common bed bug, Cimex lectularius L., is a hematophagous ectoparasite that was a common pest in poultry farms through the 1960s. Dichlorodiphenyltrichloroethane (DDT) and organophosphates eradicated most infestations, but concurrent with their global resurgence as human ectoparasites, infestations of bed bugs have been reappearing in poultry farms. Although the impact of bed bugs on chicken health has not been quantified, frequent biting and blood-feeding are expected to cause stress, infections and even anemia in birds. Bed bug control options are limited due to the sensitive nature of the poultry environment, limited products labeled for bed bug control and resistance of bed bug populations to a broad spectrum of active ingredients. Veterinary drugs are commonly used to control endo- and ectoparasites in animals. In this study, we evaluated the effects of two common veterinary drugs on bed bugs by treating the host with systemic antiparasitic drugs. We conducted dose-response studies of ivermectin and fluralaner against several bed bug strains using a membrane feeding system. Also, different doses of these drugs were given to chickens and two delivery methods (topical treatment and ingestion) were used to evaluate the efficacy of ivermectin and fluralaner on bed bug mortality. Using an artificial feeding system, both ivermectin and fluralaner caused high mortality in insecticide-susceptible bed bugs, and fluralaner was found to be effective on pyrethroid- and fipronil-resistant bed bugs. Ivermectin was ineffective in chickens either by the topical treatment or ingestion, whereas bed bugs that fed on chickens which had ingested fluralaner suffered high mortality when feeding on these chickens for up to 28 days post treatment. These findings suggest that systemic ectoparasitic drugs have great potential for practical use to control bed bug infestations in poultry farms. These findings also demonstrate the efficacy of fluralaner (and potentially other isoxazolines) as a potent new active ingredient for bed bug control.


Single-particle imaging of stress-promoters induction reveals the interplay between MAPK signaling, chromatin and transcription factors.
Precise regulation of gene expression in response to environmental changes is crucial for cell survival, adaptation and proliferation. In eukaryotic cells, extracellular signal integration is often carried out by Mitogen-Activated Protein Kinases (MAPK). Despite a robust MAPK signaling activity, downstream gene expression can display a great variability between single cells. Using a live mRNA reporter, here we monitor the dynamics of transcription in Saccharomyces cerevisiae upon hyper-osmotic shock. We find that the transient activity of the MAPK Hog1 opens a temporal window where stress-response genes can be activated. We show that the first minutes of Hog1 activity are essential to control the activation of a promoter. Chromatin repression on a locus slows down this transition and contributes to the variability in gene expression, while binding of transcription factors increases the level of transcription. However, soon after Hog1 activity peaks, negative regulators promote chromatin closure of the locus and transcription progressively stops.


l-Arginine-assisted one-pot synthesis of hierarchical Ag1Pt2 nanocorallines for surface-enhanced Raman spectroscopy.
The hierarchical multi-branched Ag1Pt2 nanocorallines (NCs) were prepared in a large scale by a rapid aqueous method, using l-arginine as the eco-friendly shape-directing agent. The product was mainly characterized by microscopy measurements, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The architectures exhibited superior surface-enhanced Raman scattering (SERS) with 4-nitrothiophenol (4-NTP), the enhancement factor (EF) of 1.3×105, a wide linear range of 10-100μM and a low detection limit of 0.01μM. Meanwhile, the SERS-active substrate was explored for the assay of 4-mercaptobenzoic acid (4-MBA) with significantly enhanced SERS performance. It means Ag1Pt2 NCs as a good Raman-active platform for sensing in food and environment analysis, owing to their rough surfaces and unique multi-branched structures.


Lived experience caring for a child with Covid-19 disease: A phenomenological study.
Caregivers of COVID-19 patients, including mothers with an infected child, are affected by adverse physical and psychological effects. Since mothers perform an important role in caring for a child with Covid-19, explaining their challenges and experiences positively affects the health conditions of children and society, in general. This study aimed to explain mothers' experiences with children diagnosed with COVID-19, who were referred to Bandar Abbas Children's Hospital. The present study was qualitative and used the Van-Manen method. The statistical population included 13 mothers with children hospitalized for coronary heart disease and COVID-19, who were selected by purposive sampling. Semi-structured interviews were implemented to collect data until saturation. Data analysis was performed using MAXQDA 10 software. Lincoln and Guba's criteria were used to evaluate the data's accuracy and strength. The mean age of mothers participating in the study was 37.92 ± 4.87. On the other hand, the mean age of children was 5.15 ± 2.07 years. Three main themes and 13 sub-themes were extracted from the data analysis. The main themes were "Inability to Caring", "Mental and Physical drain" and "Conflict of Roles and Responsibilities". In this study, when a child develops COVID-19 disease, the mother experiences a series of negative emotions, which lead to feelings of helplessness and inability to care for the child. Mental and physical manifestations strains were the most important issues that the mothers experienced. The majority of the participants need psychological support to cope with the disease. Therefore, it is recommended to make a proper design to psychologically and socially support these mothers, while alleviating the physical manifestations of their children's disease.


Polycyclic aromatic hydrocarbons (PAHs) in soils around oil refineries; Case study: Erbil and Kirkuk refineries, Iraq- A modelling approach.
Political tensions in Iraq have made attention to environmental issues not a priority for the authorities. Therefore, the influence of Kirkuk and Erbil refineries on contamination of the surrounding soil by polycyclic aromatic hydrocarbons (PAHs), were studied. 25 soil samples were collected and analyzed using high-performance liquid chromatography (HPLC), and their fate and health risk were investigated using Exposure Model for Soil-Organic Fate and Transport (EMSOFT) and the Monte Carlo Simulation (MCS) model. High ∑PAHs contamination (raged from 212.8 to 12,790.4 ppb), the dominance of pyrogenic sources, and high ecological risk were observed. The mean hazard index values for children (0.043) are higher than those for adults (0.02), while the incremental lifetime carcinogenic risk values for adults (8.50E-4) are greater than those for children (5.27E-4). Pyrene is the significant soil PAH from the depth of 3 cm downwards, while phenanthrene and fluorene are the major constituents of PAHs between the depth of 3 and 10 cm. Also, low molecular weight PAHs significantly decrease in soil layers over the time frame, and maximum PAHs concentrations belong to high molecular weight PAHs over 20 years. Using an appropriate monitoring system, as well as sound management decisions to reduce the emission of environmental pollution are needed. Also, it seems that the use of constant values for soil physicochemical parameters such as moisture and porosity, despite seasonal variations, may result in uncertainty for fate and transport modelling. Therefore, seasonal sampling and analysis of soil parameters, would be helpful. The online version contains supplementary material available at 10.1007/s40201-022-00809-y.


Nitric oxide evaluation in upper and lower respiratory tracts in nasal polyposis.
A decrease in nasal nitric oxide (NO) and an increase in exhaled NO have been demonstrated in patients with nasal polyposis (NP). The aims were to evaluate the flux of NO from the three compartments of the respiratory tract, namely, upper nasal, lower conducting and distal airways, and to search for relationships between NO parameters and indexes of upper and lower disease activity (bronchial reactivity and obstruction). The effect of medical treatment of polyposis was also evaluated. Seventy patients with polyposis were recruited. At baseline, pulmonary function tests (spirometry, plethysmography, bronchomotor response to deep inspiration using forced oscillation measurement of resistance of respiratory system, methacholine challenge, multiple flow rates of exhaled NO and nasal NO measurements) were performed together with an assessment of polyposis [clinical, endoscopic and computed tomography (CT) scores]. Statistical relationships were demonstrated between nasal NO flux and severity scores (clinical: rho=-0.31, P=0.015; endoscopic: rho=-0.57, P<0.0001; CT: rho=-0.46, P=0.0005), and between alveolar NO concentration and distal airflow limitation (FEF(25-75), rho=-0.32, P=0.011). Thirty-six patients were assessed after 11 [7-13] (median [interquartile]) months of medical treatment, demonstrating an improvement in clinical and endoscopic scores, an increase in nasal NO flux, a decrease in NO flux from conducting airways, an improvement in the mild airflow limitation (forced expiratory volume in 1 s, FEF(25-75), even in non-asthmatic patients) and a decrease in the bronchoconstrictor effect of deep inspiration. The medical treatment of NP improves both airway reactivity and obstruction, whatever the presence of asthma, suggesting a functional link between upper and lower airway functions.


Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler.
The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein.


Sensitivity of Radial Endobronchial Ultrasound-Guided Bronchoscopy for Lung Cancer in Patients With Peripheral Pulmonary Lesions: An Updated Meta-analysis.
Registry trials have found radial endobronchial ultrasound (r-EBUS) sensitivity to vary between institutions, suggesting that in clinical practice, r-EBUS sensitivity may be lower than reported in clinical trials. We performed a meta-analysis to update the estimates of r-EBUS sensitivity and to explore factors contributing to heterogeneity of results. A systematic review using PubMed was performed through July 2018 to determine the sensitivity of r-EBUS for lung cancer, and to construct a summary receiver operating characteristic curve. The DerSimonian and Laird method was used to weight results. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. Study quality was assessed using the QUADAS tool, and publication bias was tested using funnel plots. Fifty-one studies with a total of 7,601 patients were included. r-EBUS pooled sensitivity was 0.72 (95% CI, 0.70-0.75), and area under the sROC curve was 0.96 (95% CI, 0.94-0.97). Significant heterogeneity was observed (I2 = 76%; heterogeneity P < .01). We failed to demonstrate an association between sensitivity and air bronchus sign, average nodule size, use of fluoroscopy, virtual bronchoscopy, guide sheath, cancer prevalence, multicenter status, or consecutive enrollment. Rapid onsite cytology was associated with increased sensitivity (P = .01). The pooled pneumothorax rate was 0.7% (95% CI, 0.3%-1.1%). Funnel plots were asymmetrical, demonstrating sample size-related effects and possible publication bias. r-EBUS has an excellent safety profile, but there is significant between-study heterogeneity. Sample size-related effects and possibly publication bias have led to overly optimistic estimates of the sensitivity of r-EBUS.


Protective effects of γ-aminobutyric acid against H2O2-induced oxidative stress in RIN-m5F pancreatic cells.
γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and reported to maintain the redox homeostasis and insulin secretion function of pancreatic β cells. This study tested the hypothesis that GABA maintains cellular redox status, and modulates glycogen synthase kinase (GSK)-3β and antioxidant-related nuclear factor erythroid 2-related factor 2 (NRF2) nuclear mass ratio in the H2O2-injured RINm5F cells. RINm5F cells were treated with/without GABA (50, 100 and 200 μmol/L) for 48 h and then exposed to 100 μmol/L H2O2 for 30 min. Viable cells were harvested, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to detect reactive oxygen species (ROS) level; cellular redox status and insulin secretion were measured; cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; mitochondrial membrane potential (MMP) was detected by flow cytometry; relative genes levels were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); western blotting was used to determine protein expression of GSK-3β and p-GSK-3β (Ser9), and nuclear and cytoplasmic NRF2. H2O2 increased ROS production, and induced adverse affects in relation to antioxidant defense systems and insulin secretion. These changes were restored by treatment with 100 and 200 μmol/L GABA. In addition, 100 or 200 μmol/L GABA induced membrane depolarization and increased cell viability. These effects were mediated by Caspase-3, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) expression. Western blotting indicated that GABA inhibited GSK-3β by increasing p-GSK-3β (Ser9) level, and directed the transcription factor NRF2 to the nucleus. In rat insulin-producing RINm5F cells, GABA exerts its protective effect by regulating GSK-3β and NRF2, which governs redox homeostasis by inhibiting apoptosis and abnormal insulin secretion by exposure to H2O2.


A theory-based behavioural change communication intervention to decrease the provision of water to infants under 6 months of age in the Republic of Guinea.
In many countries, the provision of water in the early months of a baby's life jeopardises exclusive breast-feeding (EBF). Using a behavioural theory, this study assessed the impact of a behaviour change intervention on mothers' intention to act and, in turn, on the water provision in addition to breast milk to their infants under 6 months of age (IU6M) in two regions of Guinea. A quasi-experimental design. Data on individual and environmental factors of the theoretical framework, sociodemographic and outcomes were collected using validated questionnaires before and after the intervention. The outcomes examined were the intention to provide water to IU6M, the provision of water and EBF. Path analyses were performed to investigate pathways by which psychosocial and environmental factors influenced the water provision in addition to breast milk. Four health centres were assigned randomly to each study's arm (one control/CG and one intervention group/IG per region). The sample included 300 mothers of IU6M: 150 per group. In IG, the proportion of mothers providing water decreased from 61 % to 29 % before and after the intervention (P < 0·001), while no difference was observed in CG (P = 0·097). The EBF rate increased in IG (from 24·0 % to 53·8 %, P < 0·001) as opposed to CG (36·7 % to 45·9 %, P = 0·107). An association (P < 0·001) between the intention and the behaviour was observed in both groups. An intervention developed using a sound framework reduces the provision of water among IU6M and improves EBF.


Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. Several risk factors promote AF, among which diabetes mellitus has emerged as one of the most important. The growing recognition that obesity, diabetes and AF are closely intertwined disorders has spurred major interest in uncovering their mechanistic links. In this article we provide an update on the growing evidence linking oxidative stress and inflammation to adverse atrial structural and electrical remodeling that leads to the onset and maintenance of AF in the diabetic heart. We then discuss several therapeutic strategies to improve atrial excitability by targeting pathways that control oxidative stress and inflammation.