Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission.
Female mosquitoes inject saliva into vertebrate hosts during blood feeding. This process transmits mosquito-borne human pathogens that collectively cause ~1,000,000 deaths/year. Among the most abundant and conserved proteins secreted by female salivary glands is a high-molecular weight protein called salivary gland surface protein 1 (SGS1) that facilitates pathogen transmission, but its mechanism remains elusive. Here, we determine the native structure of SGS1 by the cryoID approach, showing that the 3364 amino-acid protein has a Tc toxin-like Rhs/YD shell, four receptor domains, and a set of C-terminal daisy-chained helices. These helices are partially shielded inside the Rhs/YD shell and poised to transform into predicted transmembrane helices. This transformation, and the numerous receptor domains on the surface of SGS1, are likely key in facilitating sporozoite/arbovirus invasion into the salivary glands and manipulating the host's immune response.


Efficacy of patient selection criteria for obesity surgery in a non-high-dependency unit/intensive care unit facility.
Publicly funded obesity surgery remains underfunded in Australia. One barrier to expansion is the perception that perioperative care requires critical care facilities. This study evaluates the effectiveness of patient selection criteria in avoiding unplanned patient transfer and adverse outcomes in obesity surgery performed at a facility without a high-dependency unit/intensive care unit (HDU/ICU). Retrospective analysis was performed on patients undergoing obesity surgery between January 2017 and March 2020 in a centre with specific screening criteria. Criteria included: body mass index <48 for males and <52 for females with up to three stable comorbidities from a selected list. Revision sleeve or bypass procedures were contraindicated. Primary outcome was patient transfer to our main campus. Secondary outcomes included return to theatre (RTT), readmission and death. Outcomes were compared to laparoscopic cholecystectomies (LC) performed at the same centre. A total of 387 obesity surgery procedures were performed; 372 patients (96%) were discharged without complication. Fifteen (3.9%) were transferred to the main campus, eight were admitted to ICU and two required re-operation. Twelve (3.1%) were readmitted within 30 days of discharge, five required re-operation. Transfer, 30-day readmission and 30-day emergency department presentation rates were similar in comparison to LC. RTT during index admission (0.5% vs. 3.0%; p = 0.006) and during 30-day post-operative period (1.8% vs. 4.4%; p = 0.025) was lower in the obesity surgery group. Carefully selected screening criteria allow obesity surgery to be performed at a well-supported non-HDU/ICU facility with few complications and acceptable rates of unplanned patient transfer.


Is there a protein ligase?
Results obtained from experiments dealing with mammalian, bacterial, phage and mitochondrial protein biosynthesis as well as certain enzymatically performed amino acid replacement studies on Kunitz trypsin inhibitor strongly suggest that protein ligation may be occuring in vivo. Amino acid substitution experiments prove the reversibility of endopeptidase reactions, and protein ligation is the reverse of endopeptidase reaction. These experiments are discussed in detail and the suggestion is made that ligation may also be useful in the repair of certain essential proteins which may become damaged.


N-Acetyl Cysteine and Glutathione in Health and Cancer-Pharmacogenomics, Research, and Clinical Practice: Hypothesis and Review.
Glutathione (GSH) is a major intracellular antioxidant capable of scavenging free radicals and detoxifying electrophiles from endogenous and exogenous sources via the free thiol group. GSH plays an important role in a multiple cellular process, including cell differentiation, proliferation, and apoptosis. Pharmacogenomics has demonstrated its important role as a key element in cellular health. The study intended to examine the benefits of using GSH pharmacogenomics as a therapy to prevent side effects and interactions with antineoplastic agents in the diagnosis and treatment of malignancies. The research team performed a narrative review using the Google scholar and PubMed electronic databases. In summary, the involvement of GSH in the carcinogenesis and drug resistance of tumor cells is clear and well understood, but further studies, aimed at understanding the GSH-driven molecular pathways, might be crucial to designing new therapeutic strategies to fight cancer progression, overcoming chemoresistance, using in combination with immunotherapies, and preventing or minimizing their negative side effects.


Developing and evaluating a pediatric asthma severity computable phenotype derived from electronic health records.
Extensive data available in electronic health records (EHRs) have the potential to improve asthma care and understanding of factors influencing asthma outcomes. However, this work can be accomplished only when the EHR data allow for accurate measures of severity, which at present are complex and inconsistent. Our aims were to create and evaluate a standardized pediatric asthma severity phenotype based in clinical asthma guidelines for use in EHR-based health initiatives and studies and also to examine the presence and absence of these data in relation to patient characteristics. We developed an asthma severity computable phenotype and compared the concordance of different severity components contributing to the phenotype to trends in the literature. We used multivariable logistic regression to assess the presence of EHR data relevant to asthma severity. The asthma severity computable phenotype performs as expected in comparison with national statistics and the literature. Severity classification for a child is maximized when based on the long-term medication regimen component and minimized when based only on the symptom data component. Use of the severity phenotype results in better, clinically grounded classification. Children for whom severity could be ascertained from these EHR data were more likely to be seen for asthma in the outpatient setting and less likely to be older or Hispanic. Black children were less likely to have lung function testing data present. We developed a pragmatic computable phenotype for pediatric asthma severity that is transportable to other EHRs.


Calculation of subunit stoichiometry of large, multisubunit proteins from amino acid compositions.
The subunit stoichiometry of a large, multisubunit protein can be determined from the molar amino acid compositions (i amino acids) of the protein and its subunits. The number of copies of the subunits (1, 2, ... j) is calculated by solving all possible combinations of simultaneous equations in j unknowns (i!/j!(i - j)!). Calculations carried out using the published amino acid compositions determined by analysis and the compositions calculated from the sequences for two proteins of known stoichiometry provided the following results: Escherichia coli aspartate transcarbamoylase (R6C6, Mr = 307.5 kDa), R = 5.6 to 6.6 and C = 5.8 to 6.3, and spinach ribulose-bisphosphate carboxylase (L8S8, Mr = 535 kDa), L = 7.3 to 9.1 and S = 5.6 to 10.6. Calculations were also carried out with the amino acid compositions of two much larger proteins, the E. coli pyruvate dehydrogenase complex, Mr = 5280 kDa, subunits E1 (99.5 kDa), E2 (66 kDa), and E3 (50.6 kDa), and the extracellular hemoglobin of Lumbricus terrestris, Mr = 3760 kDa, subunits M (17 kDa), D1 (31 kDa), D2 (37 kDa), and T (51 kDa); the results for PDHase were E1 = 20 to 24, E2 = 18 to 31, E3 = 21 to 33 and those for Lumbricus hemoglobin were M = 34 to 46, D1 = 13 to 19, D2 = 13 to 18, and T = 34 to 36. Although the sample standard deviations of the mean values are generally high, the proposed method works surprisingly well for the two smaller proteins and provides physically reasonable results for the two larger proteins.


Enhancing visual motion discrimination by desynchronizing bifocal oscillatory activity.
Visual motion discrimination involves reciprocal interactions in the alpha band between the primary visual cortex (V1) and mediotemporal areas (V5/MT). We investigated whether modulating alpha phase synchronization using individualized multisite transcranial alternating current stimulation (tACS) over V5 and V1 regions would improve motion discrimination. We tested 3 groups of healthy subjects with the following conditions: (1) individualized In-Phase V1alpha-V5alpha tACS (0° lag), (2) individualized Anti-Phase V1alpha-V5alpha tACS (180° lag) and (3) sham tACS. Motion discrimination and EEG activity were recorded before, during and after tACS. Performance significantly improved in the Anti-Phase group compared to the In-Phase group 10 and 30 min after stimulation. This result was explained by decreases in bottom-up alpha-V1 gamma-V5 phase-amplitude coupling. One possible explanation of these results is that Anti-Phase V1alpha-V5alpha tACS might impose an optimal phase lag between stimulation sites due to the inherent speed of wave propagation, hereby supporting optimized neuronal communication.


Prognostic factors and patterns of recurrence after emergency management for obstructing colon cancer: multivariate analysis from a series of 2120 patients.
At equal TNM stage, obstructing colon cancer (OCC) is associated with worse prognosis in comparison with uncomplicated cancer. Our aim was to identify prognostic factors of overall (OS) and disease-free survival (DFS) in patients treated for OCC. From 2000 to 2015, 2325 patients were treated for OCC in French surgical centers, members of the French National Surgical Association (AFC). Patients with palliative management were excluded. The main endpoints were OS and DFS. A multivariate analysis, using Cox proportional hazards regression model, was performed to determine independent prognostic factors. The cohort included 2120 patients. The median of follow-up was 13.2 months. In multivariate analysis, age > 75 years, ASA score ≥ 3, ECOG score ≥ 3, right-sided colon cancer, presence of synchronous metastases, anastomotic leakage, and absence of adjuvant chemotherapy were independent OS factors. Age > 75 years, ASA score ≥ 3, right-sided colon cancer, presence of synchronous metastases, and absence of postoperative chemotherapy were independent factors of poor OS after exclusion of patients who died postoperatively. Age ≥ 75 years, ASA score ≥ 3, ECOG score ≥ 3, right-sided colon cancer, lymph node involvement, presence of vascular, lymphatic or perineural invasion, less than 12 harvested lymph nodes, and absence of adjuvant chemotherapy were independent DFS factors. Management of OCC should take into account prognostic factors related to the patient (age, comorbidities), tumor location, and tumor stage. Adjuvant chemotherapy administration plays an important role. For patients undergoing initial defunctionning stoma, neoadjuvant chemotherapy could be an option to improve prognosis.


Accumulation and conversion of β-carotene and astaxanthin induced by abiotic stresses in Schizochytrium sp.
Astaxanthin is a kind of ketone carotenoid belonging to tetraterpenoids with an excellent antioxidant activity and it is widely used in nutrition and health-care industries. This study aimed to explore the effect of different abiotic stresses on carotenoid production in Schizochytrium sp. Firstly, the characteristics of carotenoid accumulation were studied in Schizochytrium sp. by monitoring the change of carotenoid yields and gene expressions. Then, different abiotic stresses were systematically studied to regulate the carotenoid accumulation. Results showed that low temperature could advance the astaxanthin accumulation, while ferric ion could stimulate the conversion from carotene to astaxanthin. The glucose and monosodium glutamate ratio of 100:5 was helpful for the accumulation of β-carotene. In addition, micro-oxygen supply conditions could increase the yield of β-carotene and astaxanthin by 25.47% and 14.92%, respectively. This study provided the potential regulation strategies for carotenoid production which might be used in different carotenoid-producing strains.


Two species and a genus new for Thailand, with description of a new species of Neurolarthra Fischer (Hymenoptera: Braconidae: Alysiinae).
Neurolarthra Fischer, 1976, is a small braconid genus with two described species. The genus is revised using morphological characters and a phylogenetic analysis of COI sequence data; GenBank accession numbers of seven COI sequences from two species are included. A new species from Thailand is described and illustrated: N. karensharkeyae Yao n. sp. Neurolarthra Fischer and N. procera are reported for the first time from Thailand. A key to species of the genus Neurolarthra is presented.


Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection.
Semen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen-induced alterations are likely short-lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations. We assessed stored genital specimens from 152 HIV-negative KwaZulu-Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two-year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate-specific antigen (PSA) by ELISA, whereas Y-chromosome DNA (YcDNA) detection and quantification were conducted by RT-PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA-YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T-cell frequencies were assessed in cytobrushes by flow-cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits. Here, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA-YcDNA+ and 67% (433/651) were PSA-YcDNA-. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV-2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier-related proteins (MMP-2, TIMP-1 and TIMP-4) and activated CD4+CCR5+HLA-DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA-DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro-inflammatory cytokines (including IL-6, TNF-α, IP-10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021). More recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV-associated microbes, which declined by three to fifteen days of post-exposure. Although transient, semen-induced alterations may have implications for HIV susceptibility in women.


TP53 codon 72 polymorphism and type 2 diabetes: a case-control study in South Indian population.
TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor suppressive function requires an activation and stabilization of TP53 in response to cell stressors. However, besides its cancer-preventive functions, TP53 is also known to be involved in diverse cellular processes including metabolism, reproduction, stem cell renewal and development. Indeed, several lines of evidence strongly suggest that TP53 plays crucial role in diabetes. A number of studies have evaluated the association of genetic alterations (single nucleotide variations) in TP53 gene with the development of diabetes. However, the results have not been consistent. The aim of this study was to evaluate whether the C/G polymorphism at codon 72 (Pro72/Arg72), located in exon 4 of TP53, is associated with type 2 diabetes in South Indian population. A total of 74 type 2 diabetic patients and 54 non-diabetic subjects were screened. None of the three genotypes, namely C/C (Pro/Pro), C/G (Pro/Arg), and G/G (Arg/Arg) was found to be significantly associated with type 2 diabetes in our study group. The findings of this study indicate that TP53 codon 72 polymorphism is not associated with increased risk of type 2 diabetes in South Indian population. Further studies with a large cohort size would be necessary to corroborate the observations of this study. Nevertheless, this study represents the first genetic analysis of TP53 variants in South Indian type 2 diabetic patients.


Coronavirus Disease 2019 (COVID-19) Learning Online: A Flipped Classroom Based on Micro-Learning Combined with Case-Based Learning in Undergraduate Medical Students.
During the coronavirus disease 2019 (COVID-19) pandemic, medical colleges in China had to use online teaching. This study explored the effect of COVID-19 knowledge learning online in a flipped classroom based on micro-learning combined with case-based learning (CBL). There were 74 undergraduate medical students who were randomly grouped to an observation group and a control group with 37 participants in each virtual classroom on the Network Teaching Platform. Students learning in the control group utilized face-to-face lecture with PowerPoint pre-provided, while students learning in the observation group were conducted in a flipped classroom based on micro-learning combined with CBL. We compared the effect of both formats of COVID-19 knowledge learning online and the impact on clinical practice attitude in two groups. All 74 students (100%) responded pretest, posttest and retention test, and completed the questionnaire online. Both formats significantly improved COVID-19 knowledge acquisition at the conclusion of online COVID-19 curriculum. Students' knowledge test scores including total score and scores of five knowledge dimensions of COVID-19 were significantly higher in the observation group than those in the control group (P<0.05). Compared with students in the control group, students in the observation group performed better in retention test and had a significantly more positive clinical practice attitude (P<0.05 in all items). A flipped classroom based on micro-learning combined with CBL showed greater effectiveness in COVID-19 knowledge gain in undergraduate medical students and made their attitude toward clinical practice more positive.


Tracking multiple conformations occurring on angstrom-and-millisecond scales in single amino-acid-transporter molecules.
Most membrane protein molecules undergo conformational changes as they transition from one functional state to another one. An understanding of the mechanism underlying these changes requires the ability to resolve individual conformational states, whose changes often occur on millisecond and angstrom scales. Tracking such changes and acquiring a sufficiently large amount of data remain challenging. Here, we use the amino-acid transporter AdiC as an example to demonstrate the application of a high-resolution fluorescence-polarization-microscopy method in tracking multistate conformational changes of a membrane protein. We have successfully resolved four conformations of AdiC by monitoring the emission-polarization changes of a fluorophore label and quantified their probabilities in the presence of a series of concentrations of its substrate arginine. The acquired data are sufficient for determining all equilibrium constants that fully establish the energetic relations among the four states. The KD values determined for arginine in four individual conformations are statistically comparable to the previously reported overall KD determined using isothermal titration calorimetry. This demonstrated strong resolving power of the present polarization-microscopy method will enable an acquisition of the quantitative information required for understanding the expected complex conformational mechanism underlying the transporter's function, as well as those of other membrane proteins.


In vitro studies of gonadal organogenesis in the presence and absence of H-Y antigen.
In a very strict sense, the primary (gonadal) sex of mammals is determined not so much by the presence or absence of the Y but the expression or nonexpression of the evolutionary extremely conserved plasma membrane H-Y antigen. The central somatic blastema of embryonic indifferent gonads contains one cell lineage characterized by the possession of S-F differentiation antigen that differentiates into testicular Sertoli cells in the presence of H-Y and into ovarian follicular (granulosa) cells in its absence. This cell lineage appears to play the most critical role in gonadal differentiation. Whether or not testicular Leydig cells and ovarian theca cells are similarly derived from the common cell lineage has not been determined. Nevertheless, if given H-Y antigen, presumptive theca-cell precursors of the fetal ovary acquire hCG (LH?)-receptors-the characteristic of fetal Leydig cells.


CircSHOC2 Knockdown Alleviates High Glucose-Induced Vascular Endothelial Cell Pyroptosis via Targeting miR-145/FOXO1 Axis In Vitro Condition.
Emerging evidence indicates that pyroptosis participates in the pathogenic process of vascular endothelial cells in cardiovascular system complications of diabetes. The roles of circular RNAs (circRNAs) in high glucose (HG)-induced vascular endothelial cells are still unclear. Here, our research investigated the function and mechanism of circRNA circSHOC2 in pyroptosis of vascular endothelial cells. Results indicated that circSHOC2 was up-regulated in HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, cellular assays indicated that circSHOC2 silencing repressed HG-induced HUVECs pyroptosis. Moreover, circSHOC2 targeted miR-145 through miRNA sponge, and FOXO1 functioned as downstream target of miR-145. In conclusion, these findings suggested the potential roles of circSHOC2 on HG-induced vascular endothelial cells in vitro condition, providing new insights for cardiovascular system complications of diabetes.


A genome-wide atlas of co-essential modules assigns function to uncharacterized genes.
A central question in the post-genomic era is how genes interact to form biological pathways. Measurements of gene dependency across hundreds of cell lines have been used to cluster genes into 'co-essential' pathways, but this approach has been limited by ubiquitous false positives. In the present study, we develop a statistical method that enables robust identification of gene co-essentiality and yields a genome-wide set of functional modules. This atlas recapitulates diverse pathways and protein complexes, and predicts the functions of 108 uncharacterized genes. Validating top predictions, we show that TMEM189 encodes plasmanylethanolamine desaturase, a key enzyme for plasmalogen synthesis. We also show that C15orf57 encodes a protein that binds the AP2 complex, localizes to clathrin-coated pits and enables efficient transferrin uptake. Finally, we provide an interactive webtool for the community to explore our results, which establish co-essentiality profiling as a powerful resource for biological pathway identification and discovery of new gene functions.


Artificial intelligence performance in image-based ovarian cancer identification: A systematic review and meta-analysis.
Accurate identification of ovarian cancer (OC) is of paramount importance in clinical treatment success. Artificial intelligence (AI) is a potentially reliable assistant for the medical imaging recognition. We systematically review articles on the diagnostic performance of AI in OC from medical imaging for the first time. The Medline, Embase, IEEE, PubMed, Web of Science, and the Cochrane library databases were searched for related studies published until August 1, 2022. Inclusion criteria were studies that developed or used AI algorithms in the diagnosis of OC from medical images. The binary diagnostic accuracy data were extracted to derive the outcomes of interest: sensitivity (SE), specificity (SP), and Area Under the Curve (AUC). The study was registered with the PROSPERO, CRD42022324611. Thirty-four eligible studies were identified, of which twenty-eight studies were included in the meta-analysis with a pooled SE of 88% (95%CI: 85-90%), SP of 85% (82-88%), and AUC of 0.93 (0.91-0.95). Analysis for different algorithms revealed a pooled SE of 89% (85-92%) and SP of 88% (82-92%) for machine learning; and a pooled SE of 88% (84-91%) and SP of 84% (80-87%) for deep learning. Acceptable diagnostic performance was demonstrated in subgroup analyses stratified by imaging modalities (Ultrasound, Magnetic Resonance Imaging, or Computed Tomography), sample size (≤300 or >300), AI algorithms versus clinicians, year of publication (before or after 2020), geographical distribution (Asia or non Asia), and the different risk of bias levels (≥3 domain low risk or < 3 domain low risk). AI algorithms exhibited favorable performance for the diagnosis of OC through medical imaging. More rigorous reporting standards that address specific challenges of AI research could improve future studies. This work was supported by the Natural Science Foundation of China (No. 82073647 to Q-JW and No. 82103914 to T-TG), LiaoNing Revitalization Talents Program (No. XLYC1907102 to Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (No. M0268 to Q-JW and No. M0952 to T-TG).


Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease.
Cilnidipine, a dual L-/N-type calcium channel blocker, dilates both efferent and afferent arterioles and is renoprotective. Our multi-center, open-labeled, and randomized trial compared the antiproteinuric effect of cilnidipine with that of amlodipine in hypertensive patients with kidney disease. A group of 339 patients, already receiving renin-angiotensin system inhibitor treatment, were randomly assigned to cilnidipine or amlodipine. The primary endpoint was a decrease in the urinary protein to creatinine ratio. After 1-year of treatment, systolic and diastolic blood pressures were significantly reduced in both groups which did not differ between them. The urinary protein to creatinine ratio significantly decreased in the cilnidipine compared to the amlodipine group. Cilnidipine exerted a greater antiproteinuric effect than amlodipine even in the subgroup whose blood pressure fell below the target level. This study suggests that cilnidipine is superior to amlodipine in preventing the progression of proteinuria in hypertensive patients when coupled with a renin-angiotensin system inhibitor.


Fertility potential in 5α-reductase type 2 deficient males.
Males with 5α-reductase deficiency experience oligospermia or azoospermia, resulting in fertility problems. The aim of the present systemic review was to assess the fertility status of males with 5α-reductase type 2 deficiency and explore how reproduction can be achieved in these patients. An extensive search of two databases (Pubmed and SCOPUS) was performed. Studies with original clinical data in patients with 5α-reductase deficiency evaluating the impact of the disease on semen quality and quantity and pregnancy outcomes through assisted or natural conception methods were eligible to be included in this systematic review. A total of nine cases were identified based on the eligibility criteria, all of which included reports of successful reproduction in males with 5α-reductase type 2 deficiency. In five individuals, assisted reproduction technology was used to achieve conception, highlighting its importance in solving the fertility problems that males with 5α-reductase deficiency are facing. Potential future fertility is a further indication for assigning the male gender in diagnosed newborns. In order to achieve this, the development of a management plan starting at birth is crucial for these patients, so that spermatogenesis and potential fertility can be preserved. In adulthood, semen analysis and mutation screening may also help in guiding these patients to select the correct fertilization method for their individual genetic and phenotypic characteristics.


Transmissibility and transmission of respiratory viruses.
Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R0) or secondary attack rate is heterogeneous for the same virus. Respiratory viruses can be transmitted via four major modes of transmission: direct (physical) contact, indirect contact (fomite), (large) droplets and (fine) aerosols. We know little about the relative contribution of each mode to the transmission of a particular virus in different settings, and how its variation affects transmissibility and transmission dynamics. Discussion on the particle size threshold between droplets and aerosols and the importance of aerosol transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is ongoing. Mechanistic evidence supports the efficacies of non-pharmaceutical interventions with regard to virus reduction; however, more data are needed on their effectiveness in reducing transmission. Understanding the relative contribution of different modes to transmission is crucial to inform the effectiveness of non-pharmaceutical interventions in the population. Intervening against multiple modes of transmission should be more effective than acting on a single mode.


Direct demonstration and quantification of long-range DNA looping by the lambda bacteriophage repressor.
Recently, it was proposed that DNA looping by the lambda repressor (CI protein) strengthens repression of lytic genes during lysogeny and simultaneously ensures efficient switching to lysis. To investigate this hypothesis, tethered particle motion experiments were performed and dynamic CI-mediated looping of single DNA molecules containing the lambda repressor binding sites separated by 2317 bp (the wild-type distance) was quantitatively analyzed. DNA containing all three intact operators or with mutated o3 operators were compared. Modeling the thermodynamic data established the free energy of CI octamer-mediated loop formation as 1.7 kcal/mol, which decreased to -0.7 kcal/mol when supplemented by a tetramer (octamer+tetramer-mediated loop). These results support the idea that loops secured by an octamer of CI bound at oL1, oL2, oR1 and oR2 operators must be augmented by a tetramer of CI bound at the oL3 and oR3 to be spontaneous and stable. Thus the o3 sites are critical for loops secured by the CI protein that attenuate cI expression.


Atractylodin alleviates cancer anorexia-cachexia syndrome by regulating NPY through hypothalamic Sirt1/AMPK axis-induced autophagy.
Cancer anorexia-cachexia syndrome (CACS) is a complex syndrome associated with loss of muscle and adipose tissue and weight loss, and is a major lethal factor in the later stages of cancer. The mechanism of action of CACS is not fully understood and there are no drugs specifically approved for its treatment. Atractylodin, the main active component of Atractylodes lancea, is widely used in the treatment of digestive disorders and has the ability to reduce IL-1, IL-6 and TNF-α levels. Our results showed that gavage with Atractylodin increased body weight, muscle and fat weight and reduced tumor weight and volume as well as abnormally high serum concentrations of the muscle atrophy-causing cytokines IL-1β, IL-6 and TNF-α in CACS model mice. RT-PCR data revealed that Atractylodin promoted the expression of the pro-feeding NPY and suppressed the expression of the anorexia POMC in the hypothalamus. Western blot results showed that Atractylodin promoted the expression of Sirt1 and p-AMPK in the hypothalamus, accompanied by an increase in autophagy. Furthermore, the Sirt1 inhibitor EX527 or AMPK inhibitor Compound C (CC) reversed Atractylodin-induced beneficial effects in CACS model mice. In hypothalamic cells subjected to glucose deprivation, Atractylodin increased NPY mRNA expression by enhancing AMPK-modulated autophagy; while EX527 or Compound C blunted Atractylodin-induced autophagy enhancement effect in vitro. In conclusion, Atractylodin can be used as an anti-cachexia drug and the underlying mechanism may involve the promotion of NPY expression by Sirt1/AMPK-regulated autophagy.


An evaluation of the performance of XLD, DCA, MLCB, and ABC agars as direct plating media for the isolation of Salmonella enterica from faeces.
To compare the performance of four media, singly and in combination, as direct plating media for the isolation of Salmonella enterica from human faeces. Two thousand four hundred and nine routine, faecal samples received by four laboratories were inoculated on to xylose lysine desoxycholate (XLD), desoxycholate citrate (DCA), mannitol lysine crystal violet brilliant green (MLCB), and alpha-beta chromogenic (ABC) agars using standardised protocols, reagents, and data collection. Isolates of presumptive salmonellae were identified using standard laboratory techniques and the results were analysed statistically. Direct plating recovered 46 of the 60 possible isolates of Salmonella spp recovered via enrichment broth. No isolates were recovered from direct plating that were not recovered via selenite enrichment. MLCB gave the highest isolation rate individually (84.8%) and amounts of competing flora (CF) did not affect the recognition of colonies. ABC proved highly specific, but insensitive, and isolation rates were adversely affected by any amount of CF. Isolation rates from XLD and DCA were only affected when the CF load was heavy. DCA was least specific, with only 9.01% of picks positive and greatest number of confirmatory tests. XLD and MLCB, in combination, gave the highest isolation rate. Where the earlier results of direct plating may be advantageous, XLD and MLCB provide the optimal combination. For non-typhi salmonellae, MLCB is the best, single direct plating medium. For routine diagnostic work, XLD is most effective.


Continuous intra-arterial blood pH monitoring in rabbits with acid-base disorders.
The acid-base balance of arterial blood is important for the clinical management of seriously ill patients, especially patients with acute lung injury or acute respiratory distress syndrome. We developed a novel fluorosensor for continuous blood pH monitoring and evaluated its performance both in vitro and in vivo in rabbits with acid-base disorders. The pH sensor is made of N-allyl-4-piperazinyl-1, 8-napthalimide and 2-hydroxyethyl methacrylate, which were bonded at the distal end of the optical fiber. The fluorescence intensity increased as the pH decreased with good reproducibility, selectivity and linearity in the pH range of 6-8. The pH measurement precision was 0.03 ± 0.03 pH units with a bias of -0.02 ± 0.04 (n = 105) and -0.00 ± 0.05 pH units (n=189) in rabbits with metabolic and respiratory acid-base orders, respectively. The optical pH sensor can accurately measure pH fluctuations with a fast response and is a promising candidate for continuous in-line measurements of blood pH in critical care patients.


Development of phantom materials with independently adjustable CT- and MR-contrast at 0.35, 1.5 and 3 T.
Quality assurance in magnetic resonance (MR)-guided radiotherapy lacks anthropomorphic phantoms that represent tissue-equivalent imaging contrast in both computed tomography (CT) and MR imaging. In this study, we developed phantom materials with individually adjustable CT value as well as [Formula: see text]- and [Formula: see text]-relaxation times in MR imaging at three different magnetic field strengths. Additionally, their experimental stopping power ratio (SPR) for carbon ions was compared with predictions based on single- and dual-energy CT. Ni-DTPA doped agarose gels were used for individual adjustment of [Formula: see text] and [Formula: see text] at [Formula: see text] and 3.0 T. The CT value was varied by adding potassium chloride (KCl). By multiple linear regression, equations for the determination of agarose, Ni-DTPA and KCl concentrations for given [Formula: see text] [Formula: see text] and CT values were derived and employed to produce nine specific soft tissue samples. Experimental [Formula: see text] [Formula: see text] and CT values of these soft tissue samples were compared with predictions and additionally, carbon ion SPR obtained by range measurements were compared with predictions based on single- and dual-energy CT. The measured CT value, [Formula: see text] and [Formula: see text] of the produced soft tissue samples agreed very well with predictions based on the derived equations with mean deviations of less than [Formula: see text] While single-energy CT overestimates the measured SPR of the soft tissue samples, the dual-energy CT-based predictions showed a mean SPR deviation of only [Formula: see text] To conclude, anthropomorphic phantom materials with independently adjustable CT values as well as [Formula: see text] and [Formula: see text] relaxation times at three different magnetic field strengths were developed. The derived equations describe the material specific relaxation times and the CT value in dependence on agarose, Ni-DTPA and KCl concentrations as well as the chemical composition of the materials based on given [Formula: see text] and CT value. Dual-energy CT allows accurate prediction of the carbon ion range in these materials.


To study the effect of acute infrared radiation-induced alterations in human skin at cellular and molecular level using in vivo confocal Raman spectroscopy.
Solar radiations are classified in terms of wavelengths, including visible light, infrared, and ultraviolet. Infrared radiation (IR) accounts the largest proportion of solar radiations that cause oxidative stress-induced aging of human skin. This study investigates the biochemical changes in proteins, lipids, and DNA associated with acute exposure to IR radiations. In vivo confocal Raman spectroscopy was used to examine the forearms region of 20 healthy participants with phototype II skin, aged between 18 and 30 years, without IR incidence (T0), with IR incidence 30 minutes (T30) at day 1 and 30 minutes at day 2 (T60). One-way ANOVA and two-tailed t test along with post hoc Bonferroni correction were used to detect the existence of significant differences in the timestamps of stratum corneum, stratum basale, and dermis at all IR wavenumbers under test. An increase in the Raman peaks of stratum corneum lipids, decrease in stratum basal DNA peaks, and a shift in the amide I peak of collagen in the skin dermis were observed. One-way ANOVA results showed significant differences among timestamps of stratum corneum, stratum basale, and dermis at all wavenumbers under test (P < .001). Furthermore, paired timestamps also showed significant differences (P < .016) except at two wavenumbers 1293 cm-1 and 852 cm-1 in stratum corneum and basale layer clusters on timestamps (T0 & T30 and T30 & T60, P > .016). This study proved that confocal Raman spectroscopy is an useful technique for early evaluation of IR-induced skin changes.


Synergistic mechanism of coincidence of two subacute stent thromboses: Insights from multiple imaging observations.
In the drug-eluting stent era, stent thrombosis is uncommon but still a life-threatening complication after percutaneous coronary intervention. There are several types of risk factors associated with stent thrombosis, which could work synergistically to produce thrombus. We report the case of subacute stent thrombosis. A 66-year-old male was hospitalized due to ST-segment elevation myocardial infarction and received emergency percutaneous coronary intervention to the obtuse marginal branch and the posterolateral artery. Five days later, he complained of chest pain. Emergency coronary angiography was performed and revealed stent thromboses in both the obtuse marginal branch and the posterolateral artery. Remarkably, in this case, stent thromboses occurred in the obtuse marginal branch and the posterolateral artery simultaneously. Finally, we overcame this situation by stenting to the main branch of left circumflex artery. We speculated the precise mechanism of simultaneously occurring two subacute stent thromboses through multiple intracoronary imaging modalities. In this case, we hypothesized that the combination of the protrusion of obtuse marginal branch stent to the main branch of left circumflex artery, blood flow turbulence due to the ulcer, and relatively high thrombogenicity of acute coronary syndrome lesion synergistically generated the thrombus. <Learning objective: Stent thrombosis following percutaneous coronary intervention is known as a life-threatening complication. To deal with this fatal complication appropriately, we should know the etiology of stent thrombosis. In this case, we revealed the effect of synergistic mechanism by enhanced thrombogenicity, malapposed struts, and blood flow turbulence by using multiple imaging modalities. Thus, we could decide to deploy the stent to the ulcer-like lesion of the main branch of the left circumflex artery.>.


Pre-analytical and analytical aspects affecting clinical reliability of plasma glucose results.
The measurement of plasma glucose (PG) plays a central role in recognizing disturbances in carbohydrate metabolism, with established decision limits that are globally accepted. This requires that PG results are reliable and unequivocally valid no matter where they are obtained. To control the pre-analytical variability of PG and prevent in vitro glycolysis, the use of citrate as rapidly effective glycolysis inhibitor has been proposed. However, the commercial availability of several tubes with studies showing different performance has created confusion among users. Moreover, and more importantly, studies have shown that tubes promptly inhibiting glycolysis give PG results that are significantly higher than tubes containing sodium fluoride only, used in the majority of studies generating the current PG cut-points, with a different clinical classification of subjects. From the analytical point of view, to be equivalent among different measuring systems, PG results should be traceable to a recognized higher-order reference via the implementation of an unbroken metrological hierarchy. In doing this, it is important that manufacturers of measuring systems consider the uncertainty accumulated through the different steps of the selected traceability chain. In particular, PG results should fulfil analytical performance specifications defined to fit the intended clinical application. Since PG has tight homeostatic control, its biological variability may be used to define these limits. Alternatively, given the central diagnostic role of the analyte, an outcome model showing the impact of analytical performance of test on clinical classifications of subjects can be used. Using these specifications, performance assessment studies employing commutable control materials with values assigned by reference procedure have shown that the quality of PG measurements is often far from desirable and that problems are exacerbated using point-of-care devices.


Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of alpha4 integrin.
Ultraviolet B (UVB) radiation affects the migration and function of epidermal Langerhans cells (LC) and causes immunosuppression of contact hypersensitivity. It is known that LC leaves the epidermis after exposure to UVB. To know the behavior of LC in the dermis after UVB radiation, we studied the effect of UVB radiation on the expression of integrin families on freshly isolated or cultured murine LC. We also examined whether UVB radiation affects the migration of LC to secondary lymphoid tissue chemokine (SLC/6Ckine). Integrin expressions of murine LC cultured in epidermal cell suspension were analyzed using flowcytometry. We used murine LC sorted flowcytometrically for binding assay to extracellular matrix and for migration assay to chemokine. Skin explant assay and immnohistochemical staining for 'cords formation' were performed as previously described. Twenty and 40 mJ/cm2 of UVB radiation down-regulated the expression of alpha4 integrin on 24 h-cultured LC, but not that of alpha6, beta1, or beta4 integrin. The number of cultured LC adhered to fibronectin, a ligand for alpha4 integrin, was decreased after UVB irradiation, while that to laminin, a ligand for alpha6 integrin, was not influenced. UVB radiation reduced the number of migrating LC to SLC. Furthermore, skin sheet explant experiments showed that UVB radiation inhibited the 'cords' formation in dermal vessels of the 48 h-cultured skin. These data suggest that UVB radiation may suppress the migration of LC from the dermis to lymphatic vessels. UVB radiation may downregulate the adherence of LC to dermal fibronectin and migration to SLC, and consequently suppress the migration of LC from the UVB-irradiated dermis to lymphatics.


Risk of fracture in patients with non-valvular atrial fibrillation initiating direct oral anticoagulants vs. vitamin K antagonists.
To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use. Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46-0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31-0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79-1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls. Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF.


Effects of pulsed copper exposures on early life-stage Pimephales promelas.
Effects of pulsed copper exposures were investigated using Pimephales promelas aged less than 24 h in short-term chronic testing (7 or 14 d) with moderately hard synthetic water. Concentrations tested were between the species mean chronic value (22 microg/L at a hardness of 100 mg/L as CaCO3) and the 7-d continuous exposure EC50 for survival (40 microg/L) to examine exposures that were not acutely toxic and representative of actual wastewater discharge permit exceedences. Factors tested included pulse duration, recovery time between pulses, and pulse frequency. Survival was the main endpoint affected in all treatments (analysis of variance, p < 0.05). Effects on fish biomass, independent of survival effects, were observed in only 2 of 86 treatments examined. Fish survival was negatively affected at average copper concentrations between 7 and 50% of the 7-d continuous exposure EC50. Exposures having a 48- to 96-h recovery time between pulses had less effect on fish survival than did treatments with shorter (12-24 h) or longer (>120 h) recovery times. Results suggest that the criteria averaging periods used in the United States, and the averaging periods typically used in wastewater discharge permit limits for copper, may not protect against effects of certain pulsed exposures.


[Upper cervical intradural lipoma. Apropos of a case].
Intradural lipoma is a rare and slow growing tumor which represents 1% of all intra-spinal tumors. This tumor is often associated with dysraphism. It can be isolated without any associated vertebral or cutaneous malformations. Its clinical evolution is extremely slow and progressive. The fatty composition of this type of tumor allows easy detection by CT as well as by MRI. MRI permits: Reliable and direct assessment (in 3 different plans) of the extension of the lesion. An excellent post operative control.


Role of colony-forming tissue stem cells in the macula flava of the human vocal fold in vivo.
Our previous investigations showed that tissue stem cells in the maculae flavae (a stem cell niche) form colonies in vivo like stem cells in vitro. However, the roles of colony-forming cells in the maculae flavae in vivo have not yet been determined.This study investigated the metabolism of the colony-forming tissue stem cells in the maculae flavae of the human adult vocal fold. Histologic analysis of the human vocal folds. Three normal human adult vocal folds were investigated under transmission electron microscopy and light microscopy including immunohistochemistry. Mitochondrial cristae of the colony-forming cells in the maculae flavae were sparse. Hence, the microstructural features of the mitochondria suggested that their metabolic activity and oxidative phosphorylation were low. Colony-forming cells strongly expressed glucose transporter-1 and glycolytic enzymes (hexokinase II, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase A). The colony-forming cells did not express phosphofructokinase-1 but did express glucose-6-phosphate dehydrogenase indicating the cells relied more on the pentose phosphate pathway. Since the colony-forming cells expressed lactate dehydrogenase A, cells seemed to rely more on anaerobic glycolysis in an anaerobic microenvironment. The present study is consistent with the hypothesis that the colony-forming tissue stem cells in the maculae flavae of the human adult vocal fold seemed to rely more on anaerobic glycolysis using the pentose phosphate pathway for energy supply in vivo. Microstructural features of the mitochondria and expressed glycolytic enzymes of the colony-forming cells in the maculae flavae suggested that the oxidative phosphorylation activity was low.In an anaerobic microenvironment in vivo, there is likely a complex cross-talk regarding the metabolism between the colony-forming aggregated cells along the adhesion machinery and chemical signaling pathways, which reduces toxic oxygen species and is favorable to maintaining the stemness and undifferentiated states of the tissue stem cells. NA.


Hypoxia induces different responses of striatal high- and low- affinity dopamine uptake sites.
The dopamine (DA) uptake over a concentration range from 0.03 to 100 microM was studied in S1 fractions of the rat striatum prepared from control rats and those exposed for 14 h to hypobaric hypoxia. The uptake exhibited non-Michaelis-Menten kinetics, which were evaluated by applying an equation assuming two transport sites. The high-affinity uptake site was characterized by an apparent Michaelis-Menten constant of 0.47 microM and an apparent maximal transport rate of 113 pmol/mg protein/30 s. The respective constants of the low-affinity uptake site were 52.8 microM and 1490 pmol/mg protein/30 s. One hour after hypoxia kinetic constants of the high-affinity uptake were unchanged but the maximal transport rate of the low-affinity uptake was increased by 50%. The elevated low-affinity uptake capacity may represent a means of adaptation to hypoxia allowing a faster removal of high extracellular concentrations of DA.


Mass screening for glucose-6-phosphate dehydrogenase deficiency: improved fluorescent spot test.
New data on the reliability of the fluorescent spot test are presented. Improvements in the assay were established. Newborn mass screening for glucose-6-phosphate dehydrogenase (G-6-PD, EC 126.96.36.199) deficiency was performed with dried blood samples on filter paper (Guthrie-cards). Females, known to be heterozygote for G-6-PD deficiency were detected at a rate of approximately 30-70%, depending on the storage conditions of the samples. False positive results in male hemizygotes were eliminated.


Long-Arm Splinting Versus Above-Elbow Casting for Type 1 Supracondylar Fractures of the Humerus in Children: a Randomized Controlled Trial.
Type 1 supracondylar humerus (SCH) fractures tend to heal well when immobilized by above-elbow casting or long-arm splinting. There is no consensus as to whether one treatment method is more effective than the other for this injury. The purpose of this study was to compare the radiographic and functional outcomes of long-arm splinting and above-elbow casting as the definitive treatment for children with type 1 SCH fractures. The study was set up as a randomized controlled non-inferiority trial. Patients between three and 12 years old presenting with a type 1 SCH fracture were randomized into splint or cast groups, or an observational arm. Baumann's angle, functional assessment scores, and Flynn's criteria score were measured at initial injury and at six months post-injury. In total, 34 patients were enrolled in the study with 13 in the randomized arm and 21 in the observational arm. Due to lack of follow-up data at 6 months post-injury, five splint patients and 10 cast patients were included in the final cohort for data analysis. The average change in Baumann's angle at 6-month follow-up was 3° or less for each treatment arm. The splint group obtained excellent Flynn's criteria scores while the cast group reported good and excellent scores. Complications reported in the splint group included device breakdown, a conversion to above-arm cast, and significant itchiness. Preliminary findings suggest functional and radiological outcomes with splinting are non-inferior to casting; however, a larger sample size is required to more accurately compare the two modalities. This study was registered with the U.S. National Institutes of Health (ClinicalTrials.gov, #NCT01912365).


Only the Best of the Bunch-Sperm Preparation Is Not Just about Numbers.
In this Seminar, we present an overview of the current and emerging methods and technologies for optimizing the man and the sperm sample for fertility treatment. We argue that sperms are the secret to success, and that there are many avenues for improving both treatment and basic understanding of their role in outcomes. These outcomes encompass not just whether treatment is successful or not, but the wider intergenerational health of the offspring. We discuss outstanding challenges and opportunities of new technologies such as microfluidics and artificial intelligence, including potential pitfalls and advantages. This article aims to provide a comprehensive overview of the importance of sperm in fertility treatment and suggests future directions for research and innovation.


Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes.
Recent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population. Cross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1-2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445-8050], 6640 [5450-8470] and 7310 [5715-8935] per mm3, respectively; p for trend = 0.021) and the NLR (1.63 [1.28-2.13], 1.78 [1.38-2.25] and 2.14 [1.58-2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040-1.587]; ≥3 plaques, OR 1.377 [1.036-1.829]). The NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population.


Analysis of static balance performance and dynamic postural priority according to playing position in elite soccer players.
Balance performance and postural priority are important components of motor skill development. No published reports have investigated the differences in static balance abilities and postural priority among professional soccer players according to field position. We hypothesized that static balance as well as dynamic postural priority is influenced by playing position in professional soccer players. The study covered a group of 101 elite professional soccer players who were divided into six subgroups according to playing positions: goalkeepers (G) (n = 10), central defenders (CD) (n = 15), external defenders (ED) (n = 15), central midfielders (CM) (n = 23), external midfielders (EM) (n = 15) and forwards (F) (n = 23). All participants completed the Delos Postural System Test using the standard protocol. The tests were performed unilaterally on non-dominant (NL) and dominant leg (DL) under static conditions (with open and closed eyes) standing on a stable platform and under dynamic conditions on an unstable base. In the static test with open eyes (ST OE) there were no statistically significant differences between the legs and positions. In the static test with closed eyes (ST CE), the differences are statistically significant only between positions. Players on the CM position have significantly higher differences than G. In the dynamic postural priority test (DPPT) there is a difference between positions and legs. In fact, the statistically higher differentiation refers to players in the CM position relative to ED, CD, EM and F. We noticed a significantly greater difference in the NL compared to the DL. Static balance performance and postural priority varied with playing position in elite soccer players. Midfield players have better postural priority than players in other positions. Professional soccer players present greater balance postural priority on the non-dominant leg.


Matched pairs dosimetry: 124I/131I metaiodobenzylguanidine and 124I/131I and 86Y/90Y antibodies.
The technological advances in imaging and production of radiopharmaceuticals are driving an innovative way of evaluating the targets for antineoplastic therapies. Besides the use of imaging to better delineate the volume of external beam radiation therapy in oncology, modern imaging techniques are able to identify targets for highly specific medical therapies, using chemotherapeutic drugs and antiangiogenesis molecules. Moreover, radionuclide imaging is able to select targets for radionuclide therapy and to give the way to in vivo dose calculation to target tissues and to critical organs. This contribution reports the main studies published on matched pairs dosimetry with (124)I/(131)I- and (86)Y/(90)Y-labelled radiopharmaceuticals, with an emphasis on metaiodobenzylguanidine (MIBG) and monoclonal antibodies.


Contribution of self-motion perception to acoustic target localization.
The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit. The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans. Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied. During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.


Decoupling channel count from field of view and spatial resolution in single-sensor imaging systems for fluorescence image-guided surgery.
Near-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important. Conventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff. In this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer. We demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making. These results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.


Biophysical Reviews-A call to young biophysicists.
This Editorial for Volume 13, Issue 3 of Biophysical Reviews begins with a summary of the Issue contents. This is then followed by a discussion of some additional matters important to the journal. In particular, this Editorial offers some thoughts as to what constitutes a good scientific Commentary before announcing the call for nominations for the 'The 2022 Michèle Auger Award for Young Scientists' Independent Research'.


One-off events? An empirical study of hackathon code creation and reuse.
Hackathons have become popular events for teams to collaborate on projects and develop software prototypes. Most existing research focuses on activities during an event with limited attention to the evolution of the hackathon code. We aim to understand the evolution of code used in and created during hackathon events, with a particular focus on the code blobs, specifically, how frequently hackathon teams reuse pre-existing code, how much new code they develop, if that code gets reused afterwards, and what factors affect reuse. We collected information about 22,183 hackathon projects from Devpost and obtained related code blobs, authors, project characteristics, original author, code creation time, language, and size information from World of Code. We tracked the reuse of code blobs by identifying all commits containing blobs created during hackathons and identifying all projects that contain those commits. We also conducted a series of surveys in order to gain a deeper understanding of hackathon code evolution that we sent out to hackathon participants whose code was reused, whose code was not reused, and developers who reused some hackathon code. 9.14% of the code blobs in hackathon repositories and 8% of the lines of code (LOC) are created during hackathons and around a third of the hackathon code gets reused in other projects by both blob count and LOC. The number of associated technologies and the number of participants in hackathons increase reuse probability. The results of our study demonstrates hackathons are not always "one-off" events as the common knowledge dictates and it can serve as a starting point for further studies in this area.


Bristle patterns, clones and cell competition along the anterior margin ofNotch wings ofDrosophila hydei.
The bristle pattern along the anterior margin ofNotch (N1-22.3) wings ofDrosophila hydei and the occurrence ofyellow (y 1-38.8) marked clones induced by X-ray irradiation during various larval stages are described. UnirradiatedN/N + wings show gaps ('notches') in the longitudinal bristle rows along the 1st longitudinal vein, with tufts of bristles particularly near gaps. X-ray irradiation increases the number and total length of the gaps. The patterning of bristles along the margin depends on theN (+) genotype of the induced clones. RecombinantN +/N + clones from irradiated wings show excessive growth with an autonomous wildtype bristle pattern. Characteristically, these clones do not respect the dorso-ventral compartment boundary along the wing margin, do not follow an exponential (2n) growth pattern, tend to fill the gaps with bristles and theiryellow medial row bristles are less often interspersed withy + bristles than described forN +/N + wings. HomozygousN appears to be a cell lethal condition inD. hydei as it is inD. melanogaster. When y clones were kept phenotypicallyNotch (viz.,N/N/N +) as the background cells, we found a lower number ofy bristles, a lower percentage of mosaic wings but also a reltive deficiency ofy + interspersions. The latter is discussed in relation to a possible clonal originof the notches.


Multicomponent Cardiac Rehabilitation and Cardiovascular Outcomes in Patients With Stable Angina: A Systematic Review and Meta-analysis.
To carry out a systematic review of the effect of cardiac rehabilitation (CR) and its components on cardiovascular outcomes in patients with stable angina. We searched the databases including Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from their inception up to November 1, 2017. The search was not restricted to time or publication status but was limited to the English language. Two independent investigators screened the identified studies and extracted the data in duplicate. We reviewed the included studies and, where possible, pooled their results and conducted meta-analyses. Risk of bias was assessed using Cochrane Collaboration tools. The search identified 7508 studies. Ten randomized trials including 4005 participants with the mean (SD) age of 59.6 (5.7) years were considered eligible for inclusion in our analyses. The results of meta-analyses of exercise-based CR for patients with stable angina revealed that CR improved exercise capacity (the difference between baseline and follow-up was 0.76 watt [0.49 to 1.02] higher in the CR group vs the non-CR group) and decreased angina frequency (standard mean difference, -0.27 [CI, -0.43 to 0.11]). No significant differences were noted in other outcomes, including quality of life. Mortality could not be adequately assessed because it was analyzed in only 1 exercise-based CR study. Our systematic review, involving a relatively small number of studies with low to moderate risk of bias and with considerable heterogeneity, found a significant decrease in angina frequency and increase in exercise capacity in patients with stable angina who participated in an exercise-based CR program. Studies involving the impact of components of CR are limited and generally report beneficial outcomes. Additional studies are needed to clarify the possible role of CR in the management of patients with stable angina.


Spatial distribution and risk factors for foot and mouth disease virus in Uganda: Opportunities for strategic surveillance.
Foot-and-mouth disease virus (FMDV) has a substantial impact on cattle populations in Uganda, causing short- and long-term production losses and hampering local and international trade. Although FMDV has persisted in Uganda for at least 60 years, its epidemiology there and in other endemic settings remains poorly understood. Here, we utilized a large-scale cross-sectional study of cattle to elucidate the dynamics of FMDV spread in Uganda. Sera samples (n = 14,439) from 211 herds were analyzed for non-structural protein reactivity, an indication of past FMDV exposure. Serological results were used to determine spatial patterns, and a Bayesian multivariable logistic regression mixed model was used to identify risk factors for FMDV infection. Spatial clustering of the disease was evident, with higher risk demonstrated near international borders. Additionally, high cattle density, low annual rainfall, and pastoralism were associated with increased likelihood of FMD seropositivity. These results provide insights into the complex epidemiology of FMDV in Uganda and will help inform refined control strategies in Uganda and other FMDV-endemic settings.


Coronary risk factors, knowledge and beliefs in 'blue collar' men attending general practice.
To describe risk factors, dietary knowledge and beliefs in Australian-born males of low socio-economic status (SES) in relation to coronary heart disease. Cross-sectional prevalence survey of 180 (99.7% of 185) selected attenders at a community health centre with a high proportion of low SES residents in Melbourne. Mean BMI and prevalence of obesity and smoking were higher than in national sample; age-weighted serum cholesterol somewhat lower. A majority believed that their diets were unhealthy and would continue to be so despite high perceived susceptibility to CHD. Seventy-two per cent wanted more dietary information and GPs were the most commonly nominated preferred source for this information. GPs have an important role in targeting this 'at risk' group in order to address the knowledge gaps and misconceptions identified in the study and to encourage appropriate behaviour and risk factor modification.


Development of the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES) for non-technical skills in cataract surgery.
Nontechnical skills (NTS) are fundamental for successfully managing intraoperative complications. We aimed to develop the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES); an NTS assessment system for posterior capsule rupture (PCR) during cataract surgery. A literature review and a focus group consisting of three cataract surgeons and one NTS researcher elicited the important NTS for the management of intraoperative cataract surgery complications. A novel taxonomy of NTS specific for PCR management was generated. Questionnaires were distributed to ophthalmologists in one UK training region. Delphi methodology was used to develop a final HUFOES draft. One further questionnaire was used to gain feasibility, educational impact and validity data. All HUFOES components achieved a mean importance rating of >8/10 and achieved high interrater agreement ratings (α = 0.953). Interrater agreement scores for HUFOES categories were: teamwork and communication (α = 0.819), leadership (α = 0.859), decision making (α = 0.753), situational awareness (α = 0.840) and professionalism (α = 0.890). In all, 92.8% (n = 13) rated HUFOES as specific for use, 85.7% (n = 12) agreed it contains appropriate assessment measures, 92.8% (n = 13) agreed that training with HUFOES would enhance preparation for PCR management and 78.6% (n = 11) declared HUFOES as the preferable training system for NTS in intraoperative ophthalmic emergencies when compared with the current gold standard. HUFOES has been developed and validated as a tool for the training and assessment of NTS in PCR. An NTS training programme integrated with HUFOES should be considered in order to enhance surgical NTS for managing intraoperative complications, and improve performance and outcomes following PCR.


Febrile seizures in one-five aged infants in tropical practice: Frequency, etiology and outcome of hospitalization.
Convulsive seizures are the common neurological emergencies in developing regions. The aim was to determine the prevalence, causes and outcome of seizures in childhood. Participants were children aged 1-5 years old, admitted consecutively with a history of febrile convulsions or were presented seizures with fever during hospitalization, in two pediatric university hospitals. The prospective study covered a period from January to December 2013. At admission, emergency care and resuscitation procedures were provided according to the national guidelines. The history included the number and a parental description of seizures. Children with epilepsy, any central nervous system infections and other disease were excluded. We have recorded 3647 children. Among them, 308 (8.4%) infants had presented with febrile seizures including 174 males and 134 females admitted to both pediatric hospitals (Tokoin University Teaching Hospitals: 206/3070, Campus University Teaching Hospitals: 102/577). Infants from 1 to 3 years age were the most common affected and constituted 65.9% of all patients. The months of September, December and January had recorded the high frequency of admission due to seizures. Regarding the seizures type, generalized tonic-clonic seizures were predominant (46.4%) followed by tonic seizures (17.2%) and status epilepticus in 9%. The etiologies were marked by falciparum malaria (52.3%), and other infections in 47.7%. At discharge, we have noted 11% (34/308) with neurodevelopmental disabilities, 6.7% of epilepsy and 9.7% (30/308) of death. The febrile seizure in child younger 5 years is an indicator of severe malaria in tropical nations. The campaign for "roll back malaria" must continue in developing countries to avoid long-term gross neurological deficits.


High-lysine maize: the key discoveries that have made it possible.
Forty-five years ago, a paper published by Mertz et al. (Science 145:279-280, 1964) initiated a revolution in the history of plant protein quality and affected dramatically the study of cereal crop storage proteins. The observation of the high lysine content of the endosperm of the opaque-2 (o2) maize mutant was a key factor in bringing about a new concept in the production of cereal seeds with a high nutritional value. It has been a long and very interesting road with astonishing results over these 45 years. We are now probably about to see the release of commercially engineered high-lysine maize lines. We have decided to pinpoint some key contributions to the science behind high-lysine plants and concentrated on the research done on maize, which is possibly the most complete and simple example to illustrate the advances achieved. However, studies on other plant species such as barley and model species such as tobacco are totally relevant and will be briefly addressed.


A novel all-trans retinoic acid derivative regulates cell cycle and differentiation of myelodysplastic syndrome cells by USO1.
4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, has been demonstrated that it had a variety of anti-tumor effects by exerting regulation on cellular proliferation, apoptosis and differentiation. Here, we found that ATPR is critical for alleviating myelodysplastic syndrome (MDS) and acute myelogenous leukemia. USO1, vesicle transport factor, belongs to tether protein family and involved in endoplasmic reticulum to Golgi trafficking of protein which is important to tumorigenesis. How USO1 contribute to MDS remain elusive. USO1 is aberrantly activated in MDS and AML in vivo and vitro, aberration of which might be a dominant mechanism for MDS cell survival. During the ATPR-induced remission of MDS, in vitro, USO1 presents a time and concentration-dependent decrease. Silencing of USO1 promotes myeloid differentiation of MDS cells and inhibits MDS cellular proliferation while USO1 over-expression has the opposite effect, suggesting that reduction of USO1 enhances the sensitivity of SKM-1 cells to ATPR treatment. Mechanistically, USO1 exerts its oncogenic role by inactivating Raf/ERK signaling, while ATPR is access to revise it. Notably, the activity of Raf/ERK pathway is required for the development and maintenance of MDS cell proliferation. Collectively, our results demonstrate the USO1- Raf/ERK signaling axis in MDS and highlight the negative role of USO1 in ATPR-regulated remission of MDS.


Toll-like and adenosine receptor expression in injured skeletal muscle.
Many aspects of skeletal muscle regeneration are now considered to be controlled by the innate immune system, specifically macrophages, but the mechanisms for activation and modulation of the innate immune system during injury are not well understood. We analyzed the expression of toll-like receptors (TLRs) and adenosine receptors during traumatic skeletal muscle injury. mRNA expression and immunostaining of these receptors were evaluated in mouse skeletal muscle injured by freezing. Expression of nearly all mammalian TLRs was induced at 1 and/or 3 days postinjury with a common trend for higher expression at day 3. Injury also elicited a dramatic increase in the expression of adenosine receptors A(2B) and A(3) but not A(1) and A(2A) . Both receptor types may be potential targets for stimulation of skeletal muscle tissue regeneration and functional restoration after injury.


Analysis of pedigree data and whole-genome sequences in 12 cattle breeds reveals extremely low within-breed Y-chromosome diversity.
In this article, we analyzed pedigree information on males from 12 bovine breeds born in France between 2015 and 2019. We report an overall small number of paternal lineages with, for example, a minimal number of ancestors accounting for 95% of the Y-chromosome pool of their breed ranging from only 2 to 15 individuals. Then, we mined whole-genome sequence data from 811 sires (2 ≤ n ≤ 510 per breed) and built a median-joining network using 1411 SNPs. Most branches were breed-specific and in agreement with the geographic and genetic relatedness of these populations. The within-breed haplotype diversity was lower than expected based on genealogical information, which supports the existence of major male founder effects predating pedigree recording. In addition, we observed de novo mutation events among the descendants of the same ancestors, which are of interest to define paternal sub-lineages. Our results pave the way to future studies on the estimation of the effects of Y-chromosome haplotypes on male reproductive performances and on the conservation of Y-chromosome diversity.


Examining the direct and indirect effects of financial development on CO2 emissions for 88 developing countries.
The previous literature presents conflicting outcomes on the relationship between financial development and CO2 emissions. This study fixes this puzzle by testing both the direct and indirect effects of financial development on environmental pollution using Environmental Kuznets Curve (EKC) framework. Our empirical investigation relies upon difference and system generalized method of moments for a large sample of 88 developing countries during 2000-2014 period. The estimated outcomes, based on five different indicators of financial development, support the pollution inhibiting role of financial development for the selected countries. We also validate the existence of EKC hypothesis for the panel of economies. More importantly, the results of the indirect channels show that financial development also reduces the adverse effects of income, trade openness and FDI on the pollution emissions. Further, the validity of pollution heaven hypothesis (PHH), tested through trade openness and FDI variables, is also contingent upon the existence of weak financial structure. When financial development traverses certain limits, PHH ceases to exist for both these variables. Lastly, population size augments pollution emissions while human capital reduces the later. Based on these results, we propose some very important policy implications for the sample economies.


Quercetin handles cellular oxidant/antioxidant systems and mitigates immunosenescence hallmarks in human PBMCs: An in vitro study.
Immunosenescence, oxidative stress, and low vaccine efficacy are important symptoms of aging. The goal of our study was to test if quercetin had antiaging and stimulating effects on peripheral blood mononuclear cell (PBMC) immune cells in vitro in the presence of concanavalin a, PBMCs were isolated from healthy elderly and young people and cultured in a complete Roswell Park Memorial Institute 1640 medium supplemented with quercetin. Cell proliferation was assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide colorimetric assay after a 48-h incubation period. Spectrophotometric assays were used to assess oxidative biomarkers (proteins carbonyl [PC], malondialdehydes [MDA], and reduced glutathione [GSH]). The enzyme-linked immunosorbent assay method was used to determine the amount of interleukin (IL)-2 released. A Griess reagent was used to investigate inducible nitrite oxide synthase (iNOS) activity. When compared to young control cells, aged PBMCs had lower proliferation potency, lower IL-2 and NO release, and higher MDA and PC levels. Importantly, quercetin-treated aged PBMCs have a high proliferative response comparable to young cells, restored iNOS activity, and increased levels of GSH antioxidant defences. In comparison to untreated aged PBMCs, treated PBMCs have lower lipo-oxidative damage but higher PC levels. Quercetin may be used as a promising dietary vaccinal adjuvant in the elderly, it has significant effects in reducing immunosenescence hallmarks, as well as mitigating the lipo-oxidative stress in PBMCs cells.


Synthesis and characterization of radioisotope nanospheres containing two gamma emitters.
Silica-coated gold-silver alloy nanospheres prepared by Stöber's method were irradiated in a nuclear reactor to prepare radioisotope nanospheres for use as radiotracers. The radioisotope nanospheres included two gamma nuclides: (i) Au-198, emitting major photons with 0.412 MeV and (ii) Ag-108, emitting photons with 0.434 and 0.633 MeV. The nanospheres shell and core diameters were 100-112 nm and 20-50 nm, respectively, depending on their preparation. The gamma-emitting nanospheres could be used as tracers in high-temperature petrochemical and refinery processes in which conventional organic radioactive labels will decompose.


An unusual presentation of non-Hodgkins lymphoma: a case report.
Breast lymphoma is an uncommon disease with poor clinical outcome. The rarity of the disease is related to relatively small amount of lymphoid tissues in the breast. The prognosis usually depends on the stage at presentation. To highlight an uncommon presentation of Non-Hodgkin's Lymphoma. Non-Hodgkin's lymphoma can affect the breast. A high index of suspicion and prompt histological diagnosis are needed for effective management.


Calculating Thermodynamic Factors for Diffusion Using the Continuous Fractional Component Monte Carlo Method.
Thermodynamic factors for diffusion connect the Fick and Maxwell-Stefan diffusion coefficients used to quantify mass transfer. Activity coefficient models or equations of state can be fitted to experimental or simulation data, from which thermodynamic factors can be obtained by differentiation. The accuracy of thermodynamic factors determined using indirect routes is dictated by the specific choice of an activity coefficient model or an equation of state. The Permuted Widom's Test Particle Insertion (PWTPI) method developed by Balaji et al. enables direct determination of thermodynamic factors in binary and multicomponent systems. For highly dense systems, for example, typical liquids, it is well known that molecular test insertion methods fail. In this article, we use the Continuous Fractional Component Monte Carlo (CFCMC) method to directly calculate thermodynamic factors by adopting the PWTPI method. The CFCMC method uses fractional molecules whose interactions with their surrounding molecules are modulated by a coupling parameter. Even in highly dense systems, the CFCMC method efficiently handles molecule insertions and removals, overcoming the limitations of the PWTPI method. We show excellent agreement between the results of the PWTPI and CFCMC methods for the calculation of thermodynamic factors in binary systems of Lennard-Jones molecules and ternary systems of Weeks-Chandler-Andersen molecules. The CFCMC method applied to calculate the thermodynamic factors of realistic molecular systems consisting of binary mixtures of carbon dioxide and hydrogen agrees well with the NIST REFPROP database. Our study highlights the effectiveness of the CFCMC method in determining thermodynamic factors for diffusion, even in densely packed systems, using relatively small numbers of molecules.


The pattern of fractures of the facial skeleton in Kaduna, Nigeria. A survey of 1,447 cases.
A survey of 1,447 Nigerian patients with fractures of the facial skeleton is presented. The frequency and etiology of the fractures are described. Patients mainly affected were in the third decade of life. The male:female ratio is strikingly high, and the site distributions of the fractures are recorded and compared with those of other series. The cause of delay in reporting for treatment is examined, and the subsequent sequalae are outlined. Life-endangering injuries occurred in association with facial fractures. The necessity for teamwork between surgical specialists is emphasized. All fractures were treated by simple methods of fixation.


Knockdown of HCG18 Inhibits Cell Viability, Migration and Invasion in Pediatric Osteosarcoma by Targeting miR-188-5p/FOXC1 Axis.
Understanding the underlying mechanisms of pediatric osteosarcoma (OS) migration and invasion is important for prognosis and treatment. We tried to measure the expression of long non-coding RNA HLA complex group 18 (HCG18) in OS and reveal its function in the malignant behaviors of OS cells. This study detected the expression of HCG18, miR-188-5p and forkhead box C1 (FOXC1) in OS tissues and cell lines by quantitative real-time PCR (qRT-PCR). The relevance between miR-188-5p and HCG18 or FOXC1 was affirmed by dual-luciferase reporter (DLR) assay. Cell viability was analyzed by MTT assay. Transwell assay was utilized to test cell invasion and migration. FOXC1 protein expression was detected by western blot. HCG18 expression was elevated in OS tissues, and enhanced HCG18 expression was related to metastasis. HCG18 silencing repressed the viability, migration and invasion of OS cells. Moreover, HCG18 interacted with miR-188-5p. MiR-188-5p up-regulation repressed cell viability, invasion and migration in OS cells. FOXC1, a known target of miR-188-5p, was negatively modulated by miR-188-5p. Furthermore, miR-188-5p inhibition or FOXC1 over-expression partially abolished the reduced of cell viability, invasion and migration mediated by HCG18 silencing in OS cell lines. This study revealed that HCG18 knockdown repressed the viability, invasion and migration of OS cells by targeting miR-188-5p and regulating FOXC1 expression. Thus, HCG18/ miR-188-5p/FOX may be a hopeful target for OS therapy.


Anti-Pr antibody induced cold autoimmune hemolytic anemia following pneumococcal vaccination.
While rare, vaccination-induced autoantibodies can occur outside of the pediatric population. This diagnosis should be considered after infectious and lymphoproliferative disorders are ruled out. Clinical management will depend on the individual case, but all patients should be monitored closely.


Efficacy of a dissolvable strip with calcium sodium phosphosilicate (NovaMin®) in providing rapid dentine hypersensitivity relief.
To evaluate the efficacy of a dissolvable strip containing 15% w/w calcium sodium phosphosilicate (CSPS) (Novamin®) in providing rapid relief from dentine hypersensitivity (DH). In this examiner-blind, proof-of-principle study, 120 healthy adults with DH were randomized 1:1 to the Test strip, professionally applied to facial surfaces of two selected teeth, or to No treatment. Sensitivity was assessed at baseline and 10min, 2h and 4h post-application in response to evaporative (air) and tactile stimuli (measured by Schiff sensitivity scale/a numeric rating scale and tactile threshold, respectively). Change from baseline was analyzed by ANCOVA. At 10min post-application, mean Schiff score change from baseline (primary endpoint) was statistically significant with the Test strip (-0.46; 95% confidence intervals [CI]: -0.563, -0.356; p<0.0001) but not with No treatment (-0.02; 95% CI: -0.119, 0.088; p=0.7664). The between-treatment group difference favored the Test strip (difference: -0.44; 95% CI: -0.591, -0.297; p<0.0001). Similar improvements with the Test strip were reported for all other evaporative (air) and tactile sensitivity endpoints (p<0.0001 vs no-treatment) at all timepoints (10min, 2h, 4h). Test strips were considered by most staff and participants slightly/moderately easy to apply (98%). Many participants rated the overall usage experience as "like moderately" (40%) or "like extremely" (20%). There were no treatment-related adverse events. This new CSPS-based technology may provide a novel treatment option for rapid relief from DH (Clinicaltrials.gov NCT02937623). A dissolvable strip containing 15% w/w calcium sodium phosphosilicate (CSPS) demonstrated significantly greater dentine hypersensitivity reductions following a single application compared with no treatment. Strips were well-liked by participants and generally well tolerated. A strip containing CSPS, which dissolves within 10min, may provide rapid relief from dentine hypersensitivity.


Tracking Zone-wise perturbation during unfolding of some globular proteins using Eu(III) complex of Tetracycline as a probe exhibiting Stark splitting.
Enhanced 'Antenna effect' of a suitably designed ternary complex of Eu(III), Tetracycline hydrochloride (TC) and globular proteins viz bovine serum albumin (BSA), human serum albumin (HSA) and β-lactoglobulin A (BLGA) in aqueous medium is employed to characterize the different partially unfolded states along with investigation of the micro- heterogeneous environment of the proteins during their stepwise unfolding. The zone-wise perturbation for the proteins upon denaturation by Urea and Guanidine hydrochloride (Gdn. HCl) is followed by the emission of Eu(III) through 'Antenna Effect' and that of the tryptophan (Trp) residues of the proteins as a function of denaturants both by steady state and time resolved emission study. With Gdn. HCl as denaturant, both BSA and BLGA show quenching of Eu(III) emission compared to pure protein while HSA exhibits an enhancement of antenna effect during unfolding as compared to that in its absence. In the presence of Urea, HSA and BSA show enhancement of antenna effect accompanied by Stark splitting of the 5D0→7F2 transition of Eu(III) although BLGA follows the similar pattern of quenching of Eu(III) emission as observed with Gdn. HCl without any Stark splitting. The proteins exhibit a two state transition with ΔGD values of ~ 2-3 kcal mol-1. Thus the use of Eu(III) emission as an efficient probe is advocating here to rationalize the microenvironment of the proteins during their stepwise unfolding.


Effects of season on placental, foetal and neonatal development in horses.
Seasonal changes in metabolic rate have been shown in horses and we hypothesized that this leads to the birth of smaller foals early in the year. Mares and their foals were assigned to three groups by day of foaling within the year (e.g. 1 January = day 1): Group 1 (n = 10) day 40-65, group 2 (n = 8) day 67-92, group 3 (n = 9) day 94-121. Groups did not differ with regard to parity. In foals, height at withers and body weight were determined on days 1-5 and weekly until 12 weeks of age. Chest circumference, distances fetlock to carpus, carpus to elbow, poll to nose and crown-rump length were determined on day 5 and weekly until 12 weeks of age. Placental weight (p < 0.05) and surface (p < 0.01) were lower in mares of group 1 than in groups 2 and 3. Foal weight and length measurements increased over time (p < 0.001). Height at withers was consistently lower in group 1 than in groups 2 and 3 (p < 0.05) while foal weight did not differ among groups. Fetlock to carpus, carpus to elbow (both p < 0.01) and poll to nose length (p < 0.05) were lower in group 1 than in groups 2 and 3. Neither gestation length nor sex ratio of foals differed among groups. In conclusion, foetal size is reduced when the final growth phase coincides with the winter months. This also impacts neonatal growth during the first three months of life.


Bone scintigraphy in breast cancer: a nine-year follow-up.
The results of skeletal scintigraphy performed at presentation in 465 women with histologically confirmed carcinoma of the breast were correlated with tumour size, node status, clinical course and survival during a follow-up of at least 2 years and up to 9 years. Skeletal metastases were eventually confirmed in 17.6% of the population under study, but were identified at presentation by scintigraphy in only half of these. The incidence of significant scintigraphic abnormalities ranged from 1.5% in patients with T0 and T1 node negative tumours to 20.3% in T4 node positive tumours. Patients with scintigraphic evidence of metastases had a significantly shorter survival than those without; 13.6% of the patients with an abnormality considered to be significant on the criteria employed in this study failed to develop confirmatory evidence of skeletal metastases during the period of follow-up. Alternative criteria are proposed which would substantially decrease the incidence of false positives without increasing the incidence of false negatives. Even so, it is concluded that there is no evidence that routine skeletal scintigraphy affects management of newly diagnosed patients with carcinoma of the breast. Unless an algorithm can be defined which requires the information provided by skeletal scintigraphy in order to determine clinical management, this investigation is not justified as a routine staging procedure and should be reserved for patients in whom there is a clinical suspicion of metastases and for clinical trials.


What outcomes should be measured in feline chronic kidney disease treatment trials? Establishing a core outcome set for research.
Chronic Kidney Disease (CKD) is an important cause of feline morbidity and mortality. There is currently no agreement on which outcomes are most important in CKD treatment trials to assist evidence-based decision making. Core Outcome Sets (COSs) originated in human healthcare and are an agreed set of outcomes to be measured and reported as a minimum in any trial conducted relating to a particular disease. To establish a COS for feline CKD, this study used a systematic review and two consensus methodologies (an electronic Delphi (eDelphi), and an in-person consensus meeting), with an international panel of key stakeholders. The systematic review identified 104 unique published parameters, which were rated by panellists in round 1 of the eDelphi. Panellists were also asked to suggest additional parameters. In round 2 these additional parameters were rated and any parameters not understood by >10 % of panellists in round 1 were redefined and re-rated. Parameters reaching consensus in rounds 1 and 2 were removed from round 3, when all remaining parameters were re-rated by panellists who could view their own previous rating alongside the median rating of the whole panel. To reach inclusion in the COS, parameters had to be rated 8 or 9 on a Likert scale of 1-9 (where 1 was not important and 9 was very important) by more than 80 % of panellists. In the consensus meeting, panellists discussed and re-rated borderline parameters and streamlined the final COS. Borderline parameters were those that had been closest to, but not achieved, the 80 % threshold for inclusion. The eDelphi panel (n = 73) rated 24/104 parameters highly enough for inclusion and proposed an additional 20 parameters, of which 3 reached the inclusion threshold. This totalled 27 parameters for inclusion. The consensus meeting panel (n = 16) rated an additional 6/20 borderline parameters highly enough for inclusion. During the streamlining process, 4 parameters were removed as one was considered not an outcome, and three were already addressed by other parameters. The remaining COS totalled 29 parameters. These were grouped into 9 core themes: clinical examination, quality of life, serum biochemistry, complete blood count, urinalysis, total amount of food eaten, CKD progression, survival time and cause of death. This is the first COS for feline medicine. In future treatment efficacy trials the COS will strengthen the evidence-base for this condition, by facilitating easier comparison of results between studies, and reduce research waste.