Characterization and gene expression profiling of five human embryonic stem cell lines derived in Taiwan.
Human embryonic stem cell (hESC) lines have been derived from the inner cell mass of blastocysts. Five hESC lines have been derived from 32 discarded blastocysts in Taiwan, and these lines have since been continuously cultured on mitotically inactivated mouse embryonic fibroblasts as feeder in the hESC medium for more than 44 passages and underwent freezing/thawing processes. All of five hESC lines expressed characteristic undifferentiated hESC markers such as SSEA-4, TRA-1-81, alkaline phosphatase, TERT, transcription factors POU5F1 (OCT4), and NANOG. The hESC lines T1 and T3 possess normal female karyotypes, whereas lines T4 and T5 are normal male, but line T2 is male trisomy 12 (47XY,+12). The hESC lines T1, T2, T3, and T5 were able to produce teratomas in SCID mice, and line T4 could only form embryoid bodies in vitro. Global gene expression profiles of single colonies of these five hESC lines were analyzed using Affymetrix human genome U133 plus 2.0 GeneChip. The results showed that 4,145 transcripts, including 19% of unknown functions, were detected in all five hESC lines. Comparison of the 4,145 genes commonly expressed in the five hESC lines with those genes expressed in teratoma produced by hESC line T1 and placenta revealed 40 genes exclusively expressed in all five hESC lines. These 40 genes include the previously reported stemness genes such as POU5F1 (OCT4), NANOG, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 responsible for self-renewal and pluripotent differentiation. The global gene expression analysis also indicated that the TGFβ/activin branch components inhibin BC, ACVR2A, ACVR1 (ALK2), TGFBR1 (ALK5), and SMAD2 were found to be highly expressed in undifferentiated states of these five hESC lines and decreased upon differentiation. The epigenetic states and expression of 32 known imprinted genes in these five hESC lines and/or differentiated derivatives were also investigated. In short, the hESC nature of these five hESC lines is supported by the undifferentiated state, extensive renewal capacity, and pluripotency, including the ability to form teratomas and/or embryoid bodies; and these cell lines will be useful for research on human embryonic stem cell biology and drug development/toxicity testing. The epigenetic states and expression of imprinted genes in hESC lines should be thoroughly studied after extended culture and upon differentiation in order to understand epigenetic stability in hESC lines before their clinical applications.


Relapsing Rhodococcus equi infection in a heart transplant recipient successfully treated with long-term linezolid.
We report a heart transplant recipient with Rhodococcus equi and Cryptococcus neoformans infection. Despite an initially relapsing course and the acquisition of resistance in vivo, the patient responded to 5 months of linezolid and 6 months of fluconazole. This is the 1st R. equi infection to be cured with linezolid in a heart transplant recipient.


Association between dietary protein intake and skeletal muscle mass in older Korean adults.
We investigated the association of low and high daily protein intakes on skeletal muscle mass status in Korean adults aged 60 years and older. This cross-sectional study used data from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. The participants' dietary protein intake was assessed using the 24-h dietary recall method and was classified as low (< 0.8 g/kg body weight/day), moderate (0.8-1.2 g/kg/day), and high (> 1.2 g/kg/day). Amount of skeletal muscle mass was measured using whole-body dual-energy X-ray absorptiometry. Low skeletal muscle mass was defined as appendicular skeletal muscle mass index < 7.0 kg/m2 in men and < 5.4 kg/m2 in women. The study included data from 4585 participants (2022 men and 2563 women). All skeletal muscle parameters in women and total lean mass in men decreased as the amount of protein consumed daily increased. However, there was no association between high or low protein intake and low skeletal muscle mass in men or women. No association was found between the amount of daily protein intake and skeletal muscle mass status in older Korean adults. Gender-specific further studies focussing on the interactions of dietary protein intake under specific conditions including physical activity status and the daily distribution of protein intake and the quality and source of the protein are needed to evaluate the impact of protein intake status on muscle health in older Koreans.


Public health job advertisements in Australia and New Zealand: a changing landscape.
To describe available public health jobs in Australia and New Zealand by comparing recent job advertisements. We screened vacancies from 14 online job boards for public health jobs in late 2018. Data collected included information on job titles, sector, contract tenure, location and salary. We compared our findings with those of a job advertisements study from 2005. We found 333 public health job advertisements in Australia and New Zealand. Common roles included project officers, researchers and managers. Nearly 40% of jobs asked for a 'tertiary' degree, with an additional 20% requiring a PhD degree. A qualification in public health was considered essential in 13% of job advertisements. Median annual salary range was $95,000-$111,365. There is not one specific public health job. Instead, such jobs are diverse in role, sector, qualification level required and the salary they confer. Implications for public health: There is a demand for skilled workers to perform increasingly complex public health functions, but this may eventually be outpaced by graduate supply. Furthermore, while salaries are considerable, long-term positions are not, and this has implications for the sustainability of the public health workforce.


It's not just about abortion: incorporating intersectionality in research about women of color and reproduction.
Intersectionality was first articulated in the 1970s and 1980s by women of color scholars, such as Deborah King, Patricia Hill Collins, Kimberle Crenshaw, Cherrie Moraga, Gloria Anzualdua, and Nira Yuval-Davis, and has now become a core concept in women's and gender studies. It is generally understood within feminist circles that researchers must address the interlocking effects of identities, oppressions, and privileges to fully understand the range and complexity of women's experiences. Women (and men) not only experience the effects of gender in their lives, but they are also affected by their race, ethnicity, class, sexual orientation, and (dis)ability, among other aspects of their identities. These identities do not operate separately from one another, but work in tandem to shape the social, cultural, economic, and political conditions of individuals and social groups. In sum, intersectionality is not about identity politics, but is about the social, cultural, political, and economic processes that affect our lives.


Whole-Body Fluorescence Imaging in the Near-Infrared Window.
Fluorescence imaging is one of the most widely used in vivo imaging methods for both fundamental research and clinical practice. Due to the reduced photon scattering, absorption, and autofluorescence in tissues, the emerging near-infrared (NIR) imaging (650-1700 nm) can afford deep tissue imaging with high spatiotemporal resolution and in vivo report the anatomical structures as well as the physiological activities in a whole-body level. Here, we give a brief introduction to fluorescence imaging in the first NIR (NIR-I, 650-950 nm) and second NIR (NIR-II, 1000-1700 nm) windows, summarize the recently developed NIR fluorophores and their applications in whole-body vascular system imaging, precision cancer theranostics, and regenerative medicine. Finally, the clinical applications and future prospects of in vivo NIR fluorescence imaging are also discussed.


Successful Bridging to Allogeneic Hematopoietic Stem Cell Transplantation by Azacitidine and Venetoclax in a Case of Acute Myeloid Leukemia With t(3;3)(q21.3;q26.2) Developed Early After Orthotopic Heart Transplantation.
A 48-year-old male patient developed acute myeloid leukemia (AML) with t(3;3)(q21.3;q26.2) chromosomal mutation 8 months after orthotopic heart transplantation from a human leukocyte antigen-unmatched brain-dead donor for cardiac sarcoidosis. He had sequelae of stroke and chronic renal failure at the time of AML diagnosis. He received 3 cycles of azacitidine and venetoclax induction therapy and achieved complete hematological remission with incomplete count recovery without causing severe complications, including infection. He sequentially underwent allogeneic peripheral blood stem cell transplantation from a HLA-8/8 matched, ABO-blood matched, unrelated female donor and successfully achieved donor cell engraftment. His transplanted heart was viable, and the coronary vessels were not damaged even after allogeneic peripheral blood stem cell transplantation. Although AML relapsed afterward, azacytidine/venetoclax was a tolerable bridging therapy even for early-onset AML after heart transplantation.


Kushiyaki-related Streptococcus suis meningitis with ventriculitis: A case report.
Streptococcus suis causes a zoonotic disease that commonly manifests as meningitis. People handle pork or its derivatives are at a high risk of infection. Handwashing and donning personal protective equipment are the practical preventive measures.


Numerical simulation of cooling rates in vitrification systems used for oocyte cryopreservation.
Oocyte cryopreservation is of key importance in the preservation and propagation of germplasm. Interest in oocyte cryopreservation has increased in recent years due to the application of assisted reproductive technologies in farm animals such as in vitro fertilization, nuclear transfer and the need for the establishment of ova/gene banks worldwide. However, the cryopreservation of the female gamete has been met with limited success mainly due to its small surface-area:volume ratio. In the past decade, several vitrification devices such as open pulled straws (OPS), fine and ultra fine pipette tips, nylon loops and polyethylene films have been introduced in order to manipulate minimal volumes and achieve high cooling rates. However, experimental comparison of cooling rates presents difficulties mainly because of the reduced size of these systems. To circumvent this limitation, a numerical simulation of cooling rates of various vitrification systems immersed in liquid nitrogen was conducted solving the non-stationary heat transfer partial differential equation using finite element method. Results indicate the nylon loop (Cryoloop®) is the most efficient heat transfer system analyzed, with a predicted cooling rate of 180,000°C/min for an external heat transfer coefficient h= 1000 W/m(2)K when cooling from 20 to -130°C; in contrast, the open pulled straw method (OPS) showed the lowest performance with a cooling rate of 5521°C/min considering the same value of external heat transfer coefficient. Predicted cooling rates of Miniflex® and Cryotop® (polyethylene film system) were 6164 and 37,500°C/min, respectively, for the same heat transfer coefficient.


The Utility of Blind Pap Tests in Young Adults with Developmental Delay: A Pilot Study.
There are no guidelines specific to women with developmental delay who may not be able to tolerate a Papanicolaou (Pap) test in the office setting. The purpose of this study was to assess the utility of a less invasive method, a blind Pap for women with developmental delay, compared to the traditional Pap test performed in pediatric and adolescent gynecology (PAG) patients. Retrospective cohort pilot study. Outpatient PAG clinics and the inpatient PAG service at a single institution. PAG patients who underwent a traditional Pap test and developmentally delayed PAG patients who underwent a blind Pap test. Patients were 26 years of age or less between July 2007 and March 2019. Charts were reviewed to identify those who underwent a traditional Pap test (with a speculum and direct visualization) versus a blind Pap test (with a vaginal swab without a speculum). Descriptive statistics and Wilcoxon rank and Fisher exact tests compared specimen adequacy, presence of the endocervical/transformation zone (EC/TZ), and cytology results. Of 328 PAG patients identified, 314 patients had a traditional Pap test (control), and 14 patients had a blind Pap test (4.3%). The majority of Pap tests were satisfactory in both groups. The EC/TZ component was present in 279 (90%) specimens within the traditional Pap test group and 8 (57%) in the blind Pap test group (P = .002). The traditional Pap test group results varied, with most (81.9%) being negative for intraepithelial lesion or malignancy. All BP group pathology findings were negative for intraepithelial lesion or malignancy. Our study demonstrated an ability to perform a Pap test in a less invasive manner than a traditional Pap test. Although all blind Pap test specimens were adequate, only in 57% was the EC/TZ component reported to be present, compared to 90% of the traditional Pap test specimens.


Tail pinch increases acetylcholine release in rat striatum even after toluene exposure.
The effect of tail pinch on acetylcholine release in the striatum of freely moving rats was studied by microdialysis immediately after inhalation exposure to toluene (2000 ppm, 2 h) or exposure to air only. It has recently been found that toluene increases extracellular dopamine levels while decreasing acetylcholine release, and that dopamine uptake inhibition increases both extracellular dopamine levels and acetylcholine release, suggesting that toluene decreases acetylcholine release by a dopamine-independent mechanism. The present experiment was an attempt to study if a behaviourally induced increase of extracellular dopamine differs from that induced by toluene in affecting striatal acetylcholine release. Acetylcholine released increased during tailpinch in the unexposed as well as the toluene exposed group. No difference between the two groups in the acetylcholine release response to tailpinch was demonstrated. The result supports the conclusion that acute toluene exposure decreases acetylcholine release via a dopamine independent mechanism, and suggests that toluene exposure does not affect the striatal acetylcholine response to an acute stressful stimulus.


Circ_0000566 contributes oxygen-glucose deprivation and reoxygenation (OGD/R)-induced human brain microvascular endothelial cell injury via regulating miR-18a-5p/ACVR2B axis.
Circular RNAs (circRNAs) exert regulatory roles in cerebrovascular disease. Human brain microvascular endothelial cells (HBMECs) participated in brain vascular dysfunction in ischemic stroke. Herein, the functions of circ_0000566 in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced HBMECs were investigated. The expression of circ_0000566, miR-18a-5p, and Activin receptor type 2B (ACVR2B) was measured via quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were utilized to detect cell viability and cell apoptosis. Western blot assay was employed to measure the levels of apoptotic-related proteins and ACVR2B. The secretion of IL-1β, IL-6, and TNF-α was detected via corresponding kits. The relationship between miR-18a-5p and circ_0000566 or ACVR2B was examined via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0000566 and ACVR2B were highly expressed, while miR-18a-5p was down-regulated in OGD/R-treated HBMECs. OGD/R treatment promoted HBMECs apoptosis and inflammation and suppressed cell viability, which could be attenuated by silencing of circ_0000566. Circ_0000566 acted as a miR-18a-5p sponge to contribute to OGD/R-induced HBMECs injury. ACVR2B served as a direct target of miR-18a-5p, and ACVR2B overexpression might abolish the inhibitory role of miR-18a-5p on OGD/R-treated HBMEC injury. Circ_0000566 sponged miR-18a-5p to regulate OGD/R-induced HBMECs injury via regulating ACVR2B expression.


Neurosonographic assessments of corpus callosum related structures in growth-restricted fetuses.
The aim of this study was to evaluate whether corpus callosum length (CCL), corpus callosum-fastigium length (CCFL) and the angle between CCL-CCFL (CCFA) were altered in growth-restricted fetuses. This prospective case-control study was conducted in a tertiary center. A total of 80 singleton fetuses were included in the study, classified as 36 late-onset growth-restricted fetuses and 44 adequate-for-gestational-age fetuses. All biometric measurements and Doppler assessments of umbilical artery, middle cerebral artery, and ductus venosus were performed via the trans-abdominal route. CCL, CCLF, and CCFA were assessed via the trans-vaginal route. Late-onset growth-restricted fetuses showed significantly reduced CCL and CCFL. There was no statistically significant differences in terms of CCFA. Moderate-high correlations between CCL and biparietal diameter, head circumference, abdominal circumference, FL and gestational age were detected (r: 0.482 p: 0.000; r: 0.537 p: 0.000; r: 0.488 p: 0.000; r: 0.519 p: 0.000; and r: 0.472 p: 0.000, respectively). This study adds to the literature that CCFA has not changed despite the decrease in CCL and CCFL in late-onset fetal growth restriction that might be a result of the redistribution of cerebral blood flow. To clarify the prognostic implications of these results in terms of neural and cognitive functions in postnatal life, there is a need for larger prospective studies.


Structural and functional characterization of soluble endoglin receptor.
Endoglin, an accessory membrane receptor of transforming growth factor-beta (TGF-beta)1, modulates the cellular response to TGF-beta via its interaction with type I and II TGF-beta receptors. It has been considered a promising target for the development of therapeutics and cancer markers. We have established stable CHO cell lines that efficiently secrete soluble endoglin (s-endoglin) fused with human growth hormone. Two oligomeric forms were observed in a homogeneous preparation of s-endoglin, as a dimer and a tetramer. The dimeric s-endoglin enhanced TGF-beta responsiveness in U937 cells, thus proving its potential for therapeutic applications. Small angle X-ray scattering (SAXS) experiments revealed elongated conformations of both dimeric and tetrameric s-endoglins in solution, suggesting that s-endoglin might undergo conformational adaptations upon TGF-beta binding. The current results provide important references and material for high-resolution structural studies and for medical applications of s-endoglin.


Experimental rubeosis of the iris in rabbits.
Rabbits were subjected to vascular injuries in an attempt to cause ocular ischemia and rubeosis. Occlusion of the ipsilateral common carotid artery showed fluorescein angiographic evidence of iris ischemia, but no rubeosis. Occlusion of two or more vortex veins caused iris ischemia, vasodilation, and angiographically visible neovascular capillaries on the iris. Histology confirmed the presence of thin-walled, superficial neovascular channels. The stimultaneous occlusion of the carotid artery and of two or more ipsilateral vortex veins also produced angiographic and histologic evidence of iris ischemia and neovascularization. These results confirm that venous flow impairment is a more efficient stimulus to neovascularization than ischemia due to arterial insufficiency. Nevertheless, in none of the animals could a neovascular response comparable to human rubeosis be elicited, and it is concluded that vascular lesions to the anterior segment are not an adequate model to study rubeosis.


Effect of robotic-assisted gait training on objective biomechanical measures of gait in persons post-stroke: a systematic review and meta-analysis.
Robotic-Assisted Gait Training (RAGT) may enable high-intensive and task-specific gait training post-stroke. The effect of RAGT on gait movement patterns has however not been comprehensively reviewed. The purpose of this review was to summarize the evidence for potentially superior effects of RAGT on biomechanical measures of gait post-stroke when compared with non-robotic gait training alone. Nine databases were searched using database-specific search terms from their inception until January 2021. We included randomized controlled trials investigating the effects of RAGT (e.g., using exoskeletons or end-effectors) on spatiotemporal, kinematic and kinetic parameters among adults suffering from any stage of stroke. Screening, data extraction and judgement of risk of bias (using the Cochrane Risk of bias 2 tool) were performed by 2-3 independent reviewers. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria were used to evaluate the certainty of evidence for the biomechanical gait measures of interest. Thirteen studies including a total of 412 individuals (mean age: 52-69 years; 264 males) met eligibility criteria and were included. RAGT was employed either as monotherapy or in combination with other therapies in a subacute or chronic phase post-stroke. The included studies showed a high risk of bias (n = 6), some concerns (n = 6) or a low risk of bias (n = 1). Meta-analyses using a random-effects model for gait speed, cadence, step length (non-affected side) and spatial asymmetry revealed no significant differences between the RAGT and comparator groups, while stride length (mean difference [MD] 2.86 cm), step length (affected side; MD 2.67 cm) and temporal asymmetry calculated in ratio-values (MD 0.09) improved slightly more in the RAGT groups. There were serious weaknesses with almost all GRADE domains (risk of bias, consistency, directness, or precision of the findings) for the included outcome measures (spatiotemporal and kinematic gait parameters). Kinetic parameters were not reported at all. There were few relevant studies and the review synthesis revealed a very low certainty in current evidence for employing RAGT to improve gait biomechanics post-stroke. Further high-quality, robust clinical trials on RAGT that complement clinical data with biomechanical data are thus warranted to disentangle the potential effects of such interventions on gait biomechanics post-stroke.


Non-linear least squares analysis of phase diagrams for non-ideal binary mixtures of phospholipids.
A computer program for non-linear least squares minimization has been applied to construct temperature-composition phase diagrams for several binary systems of different phospholipids based on their calorimetric data. The calculated phase diagram is guided to fit the calorimetric data with two adjustable parameters that describe the non-ideal mixing of lipid components in the gel and liquid-crystalline phases. The parameter estimation procedure is presented to show that the computer program can be used not only to generate phase diagrams with characteristic shapes but also to numerically estimate the lipid-lipid pair interactions between the mixed and the like pairs in the two-dimensional plane of the bilayer in both the gel and liquid-crystalline states. The binary lipid systems examined include dimyristoylphosphatidylcholine/1-palmitoyl-2-stearoylphosphatidylchol ine, 1-capryl-2-behenoylphosphatidylcholine/1-behenoyl-2-lauro ylphosphatidylcholine, and 1-stearoyl-2-caprylphosphatidylcholine/dimyristoylphosphatidylchol ine.


Influence of different post-processing methods on the dimensional accuracy of 3D-printed photopolymers for dental crown applications - A systematic review.
To perform a systematic review that provides an overview of the current literature on the influence of different post-processing methods on the accuracy of additive-manufactured (3D-printed) photopolymer crown materials, and whether more research is needed. The search used three online databases, Ovid (MEDLINE), Scopus and Web of Science which were screen for publications that involved assessing dimensional accuracy in post-processing of 3D printed dental crown materials. Publications that were literature reviews, abstracts, written in a language different from English, or publications that did not assess dimensional accuracy were excluded. The included articles were published between 1995 and 2023. After the removal of duplicates using Endnote, 135 studies remained for further screening, 13 were selected for full-text analysis, and 7 studies were included in the systematic review. A total of 7 articles were examined and categorised based on several factors, such as the type of material, number of specimens per group, print layer thickness, print angle of specimens, 3D printer used, properties of the specimens studied, and the method of analysing the accuracy of the specimens. It was found that post-processing washing times outside the prescribed instruction for use (IFU) may have an impact on the physical and biocompatibility characteristics of the material. Studies focusing on inert mediums during post-processing require more detailed investigation. The use of different post-curing conditions does not significantly affect the materials dimensional accuracy.


Desmoplastic fibroma of the hand: case report.
We present a patient who had a desmoplastic fibroma at the base of the metacarpal of his long finger. The operation to remove the lesion and to reconstruct the metacarpal is described. The history of the experiences with this lesion is reviewed.


[Seroepidemiologic study of rubella in childbearing women in Aragon, Spain (2003-2007)].
To quantify and identify the rubella-susceptible population in Aragon according to sociodemographic variables, with the aim of assessing compliance with the 5% limit set by the World Health Organization (WHO). Rubella serology tests performed in women of childbearing age in the Miguel Servet Hospital from 2003 to 2007 were studied. A descriptive analysis of seronegativity was performed by age, years of study, and WHO region (for 2007). A logistic regression was performed with the independent variables of age and geographical origin. We studied 13,136 women. The mean age was 31.2 years. During the study period, 5% were susceptible to rubella (95%CI: 4.63-5.37). In 2003, 8.8% were seronegative and the highest percentage (12.3%) was found in women aged 15 to 19 years. The percentage of seronegativity was higher in foreign-born women (7.7%), especially those from Asia, than in Spanish women (3.3%; p<0.05). Postpartum preventive strategies should be established to prevent possible rubella outbreaks and cases of congenital rubella syndrome.


Mixed hematopoietic chimerism and transplantation tolerance.
Durable transplantation tolerance can be reliably achieved by inducing engraftment of hematopoietic cells in recipients initially depleted of T-lymphocytes. Engraftment of donor pluripotent hematopoietic stem cells (PPHSC) produces mixed hematopoietic chimeras in which both host and donor cells coexist and are tolerant of each other. The major mechanism of tolerance in these chimeras is central, intrathymic clonal deletion, which is induced and maintained by immigration of both host and donor marrow-derived cells to the host thymus, ensuring the ongoing central deletion of donor- and host-reactive cells. In this article, approaches developed in our laboratory to induce stable mixed hematopoietic chimerism and specific central deletional allogeneic and xenogeneic tolerance without toxic or myeloablative host conditioning are reviewed.


Comprehensive survey of the VxGΦL motif of PP2Cs from Oryza sativa reveals the critical role of the fourth position in regulation of ABA responsiveness.
Regulation of abscisic acid (ABA) signaling is crucial in balancing responses to abiotic stresses and retaining growth in planta. An ABA receptor (PYL/RCAR) and a protein phosphatase (PP2C), a co-receptor, form a complex upon binding to ABA. Previously we reported that the second and fourth positions in the VxGΦL motif of PP2Cs from Oryza sativa are critical in the interaction of PP2Cs with PYL/RCARs. Considering substantial effects of the VxGΦL motif on ABA signaling outputs, further comprehensive characterization of residues in the second and fourth positions are required. Here we surveyed the second and fourth positions of the VxGΦL motif by combination of biochemical, structural and physiological analyses. We found that the fourth position of the VxGΦL motif, highly conserved to small hydrophobic residues, was a key determinant of the OsPP2C50:OsPYL/RCAR interactions across subfamilies. Large hydrophobic or any hydrophilic residues in the fourth position abrogated ABA responsiveness. Analysis of crystal structures of OsPP2C50 mutants, S265L/I267V ("LV"), I267L ("SL") and I267W ("SW"), in complex with ABA and OsPYL/RCAR3, along with energy calculation of the complexes, uncovered that a bulky hydrophobic residue in the fourth position of the VxGΦL motif pushed away side chains of nearby residues, conferring side-chain rotameric energy stress. Hydrophilic residues in this position imposed solvation energy stress to the PP2C:PYL/RCAR complex. Germination and gene expression analyses corroborated that OsPP2C50 AS and AK mutants modulated ABA responsiveness in Arabidopsis. Our results suggest that ABA responsiveness could be fine-tuned by the fourth position of the VxGΦL motif on PP2Cs. KEY MESSAGE: We comprehensively surveyed the VxGΦL motif to find that the fourth position, highly conserved to small hydrophobic residues, was critical in regulating ABA responsiveness.


Facile and direct detection of human papillomavirus (HPV) DNA in cells using loop-mediated isothermal amplification (LAMP).
Human papillomavirus (HPV)-mediated cancers, particularly cervical and oropharyngeal cancer, lead to hundreds of thousands of deaths worldwide each year. Simple, straightforward, and cost-effective detection of HPV DNA from patients with these malignancies or at risk for developing cancer can improve outcomes for patients, serving as a tool for early detection, monitoring treatment response, and assessment of cancer recurrence. Loop-mediated isothermal amplification (LAMP) is a simple and robust method for the detection and amplification of DNA in a single tube, utilizing the Bst strand-displacing DNA polymerase. We developed a workflow utilizing LAMP for the visual detection of HPV DNA in oral rinses. We demonstrate that LAMP is able to easily discriminate between two of the high-risk HPV subtypes, HPV16 and HPV18. We then utilized LAMP to visually detect HPV DNA directly from cells in oral rinses, mimicking a clinical inspired scenario of detecting HPV DNA in clinical samples. Our results suggest that LAMP is a robust, colorimetric assay method for the detection of HPV DNA in complex cellular samples, and further development is warranted to bring LAMP into the clinic.


The mycobacteriology laboratory and new diagnostic techniques.
Use of the most rapid and reliable laboratory tests for mycobacterial detection, identification, and susceptibility testing is important for TB control. In 1993, CDC experts made recommendations regarding optimal methods of mycobacterial testing (i.e., stains for AFB, culture, identification, and susceptibility testing of M. tuberculosis) and turnaround times for reporting results. Various technical advances have enhanced the diagnostic capability of the laboratory and/or improved laboratory efficiency since then. The commercial NAA tests for direct detection of MTBC have the greatest potential to impact patient care. To assist physicians, CDC experts have published recommendations concerning use of the NAA tests for management of patients with suspected TB, with emphasis on the MTD assay, which is approved for both AFB smear-positive and smear-negative specimens. With regard to mycobacterial culture, totally automated, nonradiometric systems are commercially available. For mycobacterial identification, various molecular techniques have been developed, but at present, they are used predominantly in research or large reference laboratories. Molecular tests also have proved useful for better understanding the epidemiology of TB and investigating episodes of suspected laboratory cross-contamination. With regard to mycobacterial susceptibility testing, use of the new automated culture systems for testing MTBC is under evaluation, but only one such system has been approved for this purpose. In addition, laboratory guidelines for susceptibility testing of MTBC and certain NTM have recently been published by the NCCLS.


Differential exposure to N-ethyl N-nitrosourea during pregnancy is relevant to the induction of glioma and PNSTs in the brain.
Exposure to N-nitroso compounds (NOCs) during pregnancy has been associated with an increase in brain tumors in the progeny. This study investigated the brain tumorigenic effect of N-ethyl N-nitrosourea (ENU) after differential exposure of rats during pregnancy. Sprague Dawley rats were exposed to a single dose of ENU (80 mg/kg) in three different circumstances: 1) at first, second or third week of gestation; 2) at the 15th embryonic day (E15) in consecutive litters and 3) at E15 in three successive generations. Location and characterization of the offspring's brain tumors were performed by magnetic resonance imaging and histopathological studies. Finally, tumor incidence and latency and the animals' survival were recorded. ENU-exposure in the last two weeks of pregnancy induced intracranial tumors in over 70% of the offspring rats, these being mainly gliomas with some peripheral nerve sheath tumors (PNSTs). Tumors appeared in young adults; glioma-like small multifocal neoplasias converged on large glioblastomas in senescence and PNSTs in the sheath of the trigeminal nerve, extending to cover the brain convexity. ENU-exposure at E15 in subsequent pregnancies lead to an increase in glioma and PNST incidence. However, consecutive generational ENU-exposure (E15) decreased the animals' survival due to an early onset of both types of tumors. Moreover, PNST presented an inheritable component because progeny, which were not themselves exposed to ENU but whose progenitors were, developed PNSTs. Our results suggest that repeated exposure to ENU later in pregnancy and in successive generations favours the development of intracranial gliomas and PNSTs in the offspring.


Complete killing of Caenorhabditis elegans by Burkholderia pseudomallei is dependent on prolonged direct association with the viable pathogen.
Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. Much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis. In this study, we showed that different isolates of B. pseudomallei have divergent ability to kill the soil nematode Caenorhabditis elegans. The rate of nematode killing was also dependent on growth media: B. pseudomallei grown on peptone-glucose media killed C. elegans more rapidly than bacteria grown on the nematode growth media. Filter and bacteria cell-free culture filtrate assays demonstrated that the extent of killing observed is significantly less than that observed in the direct killing assay. Additionally, we showed that B. pseudomallei does not persistently accumulate within the C. elegans gut as brief exposure to B. pseudomallei is not sufficient for C. elegans infection. A combination of genetic and environmental factors affects virulence. In addition, we have also demonstrated that a Burkholderia-specific mechanism mediating the pathogenic effect in C. elegans requires proliferating B. pseudomallei to continuously produce toxins to mediate complete killing.


Effect of Vitamin D on YKL-40: Rat Hypercholesterolemia Model.
YKL-40 is considered to be associated with cardiovascular disease (CVD). In this study, the effect of serum 25(OH) vitamin D [25(OH)VitD] differences between groups on YKL-40 was evaluated on a hypercholesterolemia rat model. Thirty-two male rats (wistar albino) were equally divided into 4 groups. The first group was the control group; the second group was high-cholesterol (H-CH) adequate vitamin D (VitD) group (H-AdeVD). The third group was the H-CH deficient VitD group (H-DefVD), and the last group was designed with the H-CH supplement VitD (H-SupVD). The feeding process consisted of 2 stages. At the first stage (5 months), the H-DefVD group was fed on VitD deficient chow, while the other groups (control, H-AdeVD, H-SupVD) were fed on standard chow. At the second stage (3 months), the H-AdeVD and the H-SupVD groups were fed on the H-CH chow, whereas the H-DefVD group was fed on the H-CH-VitD deficient chow. Moreover, the H-SupVD group was given 100 IU/kg/day VitD along with the H-CH chow. Compared with the control group, interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and YKL-40 values in the H-DefVD groups increased significantly (p<0.001, p<0.001, p=0.009, p=0.005; sequentially). It can be concluded that VitD can suppress the YKL-40, thus, it will prevent CVD development in rat. Therefore, further clinical studies related with human will reveal the effect of VitD and YKL-40 on CVD development.


Increased clearance of phenytoin as the presenting feature of infectious mononucleosis.
A 19-year-old man with posttraumatic seizures under good control with phenytoin, 500 mg/day, presented with three seizures. His blood level of phenytoin, previously in a therapeutic range, was 4.2 microgram/ml. No systemic or laboratory evidence of infectious mononucleosis was found. Ten days later, the blood picture became compatible with infectious mononucleosis, at which time his phenytoin clearance returned to normal.


Association of circulating C-reactive protein and high-sensitivity C-reactive protein with components of sarcopenia: A systematic review and meta-analysis of observational studies.
Sarcopenia, a multi-faceted skeletal muscle disorder in the older population, has poor health outcomes. Some previous observational studies investigated the association between circulating inflammatory markers and sarcopenia components to evaluate chronic inflammation as a risk factor for sarcopenia in the elderly population. Nevertheless, the association between circulating C-reactive protein (CRP) and hs-CRP, as the recognized markers of systemic inflammation and components of sarcopenia, is unclear. This meta-analysis aimed to investigate the association of muscle strength, muscle mass, and muscle function with two serum inflammatory markers, circulating C-reactive protein (CRP) and high-sensitive CRP (hs-CRP). We assessed all observational studies across different electronic databases including PubMed, Scopus, and Google Scholar using keywords such as "muscle strength", "muscle mass", "muscle function", CRP and hs-CRP from inception until the 30th of July 2019. Only studies that investigated the association between components of sarcopenia and CRP or hs-CRP levels were included. Participants' country, age, sex, BMI, and screening tool for sarcopenia were retrieved. The correlations between muscle strength, muscle mass, and muscle function with CRP, and hs-CRP were expressed as the correlation coefficient (r) with 95% confidence intervals (CIs). Begg's test and Egger's test were conducted to evaluate risk of publication bias in this study. Initially, we found fifty-nine studies for the qualitative synthesis. Ultimately, nineteen adult cross-sectional studies comprising 14,650 subjects were included in the meta-analysis. Of them, fourteen studies measured the correlation between CRP or hs-CRP and muscle strength. There were significant inverse correlation between CRP and hs-CRP concentrations with muscle strength (ES (z) = -0.22; 95% CI = -0.34 to -0.09; P < 0.001), (ES (z) = -0.22; 95% CI = -0.34 to -0.09; P < 0.001), respectively. No publication bias was found between muscle strength and CRP (P = 0.53) or hs-CRP (P = 0.62) respectively. Among diagnostic components of sarcopenia, impairment of muscle strength was independently associated with both inflammatory biomarkers. However, future cohort studies are essential to clarify the causal correlation.


Cell cytoskeleton and proliferation study for the RANKL-induced RAW264.7 differentiation.
Although document studies (including ours) have been reported the achieved in vitro osteoclastic cellular model establishment from the RAW264.7 cell lineage, there was no study directly reported that American Type Culture Collection (ATCC) cell bank has various RAW264.7 cell lineages. Besides that, for our knowledge there was only one study compared the two different RAW264.7TIB-71 and RAW264.7CRL-2278 cell lineages for their osteoclastic differentiation, and they concluded that the RAW264.7CRL-2278 demonstrated to generate much osteoclast than RAW264.7TIB-71 . However, on the contrary to their results we noticed the fusion of RAW264.7TIB-71 in our previous studies was much compromising. Therefore, we try to explore the two cell lineages for their properties in osteoclastic differentiation with an in-depth cellular cytoskeletal study. Our current study has showed that comparing to the RAW264.7CRL-2278 , RAW264.7TIB-71 demonstrated a much higher efficacies for RANKL-stimulated osteoclastic differentiation. Besides that, in our depth cytoskeletal studies, we found that the RANKL-induced RAW264.7TIB-71 cells could finally differentiate into mature osteoclasts. However, regardless the various pre-treatment conditions, there was no mature osteoclast formed in RANKL-induced RAW264.7CRL-2278 cell lineage.


The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia.
Using I131 VLDL selectively labelled in the B-apoprotein and I125 LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72-83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21-28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.


Synchronous regulation of VH and CH allotypes among Ig molecules in multi-heterozygous rabbits suppressed with anti-VH allotype antibody: emergence of IgA from suppression prior to IgG and IgM.
Heterozygous rabbits of genotype a1n81f73g74/a2n82f71g75 were suppressed at birth for the VH region a1 allotype. At 8 weeks of age, quantitative analysis of serum IgG, IgM, and IgA molecules showed that the VHa1 specificity was effectively suppressed in the three classes of Ig and that the suppression was extended to the CH region n81 specificity on mu-chains as well as to the CH region f73 and g74 specificities on alphaf and alphag chains. At 26 weeks of age, analysis of serum IgG and IgM molecules showed that a1 was still suppressed to approximately the same extent in both Ig classes and the suppression was still extended to the CH region n81 specificity. However, at 26 weeks, the percentage of molecules with a1 specificity had doubled among serum and colostral IgA molecules and this increase was extended to the CH region f73 and g74 specificities. Thus, the suppressed allotypes reappeared first among IgA molecules. Our data are consistent with a regulatory mechanism which controls and synchronizes the expression of the VHa and the CH allotypes expressed on the same heavy chain. The order of the re-expression of the suppressed allotypes with respect to Ig class may allow further definition of selective regulatory mechanisms for the synthesis of Ig classes.


High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) impacts activities of daily living of patients with post-stroke cognitive impairment: a systematic review and meta-analysis.
To systematically evaluate the impact of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on activities of daily living (ADLs) of patients with post-stroke cognitive impairment (PSCI). Relevant studies published as of November 2022 (English and Chinese) were searched in Web of Science, PubMed, Embase, Cochrane Library, OVID, China Science and Technology Journal Database (VIP), Wanfang, Chinese National Knowledge Infrastructure (CNKI), and SinoMed databases. Randomized controlled trials (RCTs) that used HF-rTMS for the treatment of ADLs in patients with PSCI were included in this meta-analysis. Two reviewers independently screened literature, extracted the data, evaluated the risk of bias using the Cochrane Risk of Bias Tool, and cross-checked. Forty-one RCTs involving 2855 patients with PSCI were included. In 30 RCTs, the experimental group received HF-rTMS in addition to the interventions used in the control group. In 11 RCTs, the experimental group received HF-rTMS while the control group received sham-rTMS. Barthel Index (BI), Modified Barthel Index (MBI), and Functional Independence Measure (FIM) were higher in the HF-rTMS group than in the control group, whereas scores of Blessed Behavior Scale was lower in the HF-rTMS group than in the control group. All P < 0.05. In 36 studies, the stimulation sites were on the dorsolateral prefrontal cortex (DLPFC). HF-rTMS can ameliorate ADLs of patients with PSCI and has a better rehabilitation effect on PSCI.


Noninvasive Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography for the Diagnosis of Lesion-specific Ischemia.
Fractional flow reserve derived from coronary computed tomography angiography (FFRCT) has emerged as a powerful tool for the assessment of flow-limiting coronary stenoses. To date, FFRCT is the only noninvasive imaging modality for the depiction of lesion-specific ischemia and large prospective multicenter studies have established its high diagnostic value. The nature of FFRCT allows the prediction of functional outcome of coronary stenting, which will expand the role of cardiac computed tomography in the evaluation and management of coronary artery disease.


Growth hormone responses to clonidine and GRF in spontaneously hypertensive rats: neuroendocrine evidence for an enhanced responsiveness of brain alpha 2-adrenoceptors in genetical hypertension.
Clonidine induces growth hormone (GH) release in rat. According to previous investigations this effect is mediated by postsynaptic alpha 2-adrenoceptors in the hypothalamus exerting a stimulatory influence on the recently discovered GH releasing factor (GRF). In the present study it is demonstrated that spontaneously hypertensive rats (SHR) of the Wistar-Kyoto strain display enhanced GH responses to clonidine as compared to normotensive Wistar-Kyoto control rats. In contrast, the GH responses to GRF are similar in hypertensive and normotensive animals. These findings indicate that brain alpha 2-adrenoceptors are more responsive in SHR than in normotensive controls. Since the enhanced GH responses to clonidine were observed also in young, prehypertensive SHR they are probably not secondary to the elevated blood pressure. The possible importance of an altered alpha 2-adrenergic neurotransmission for the development of elevated blood pressure in SHR is discussed.


In vivo and in vitro measurements of P32-uptake in the ocular tissue in cases of malignant melanoma.
In vivo and in vitro measurements of radioactive phosphorus uptake after intravenous injection of P32 in 26 cases of malignant melanoma of the choroid is reported. The specific radioactivity of dissected ocular tissue after enucleation is described. No statistically significant relationship between the radioactive phosphorus uptake and the histologically differentiated cell type was found. It was possible to demonstrate the P32 uptake as a function of the mass of the tumor.


Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis.
To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HBeAg/anti-HBe status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HBeAg-positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum sIL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.


Modulation of human platelet adenylate cyclase by prostacyclin (PGX).
Prostacyclin (PGX) (57)-9-deoxy-6,9alpha-epoxy-delta5-PGF1alpha has been found to be a potent stimulator of cAMP accumulation in platelets than PGE1. The prostacyclin stimulation of platelet cAMP accumulation can be antagonized by the prostaglandin endoperoxide PGH2, and a PGH2-induced platelet aggregation is antagonized by prostacyclin. A model of platelet homeostasis is proposed that suggests platelet aggregation is controlled by a balance between the adenylate cyclase stimulating activity of prostacyclin, and the cAMP lowering activity of PGH2.


Flexor tendon injuries.
Flexor tendon injuries have constituted a large portion of the literature in hand surgery over many years. Yet many controversies remain and the techniques of surgery and therapy are still evolving. The anatomical and finer technical considerations involved in treating these injuries have been put forth and discussed in detail including the rehabilitation following the flexor tendon repair. The authors consider, recognition and mastery of these facts form the foundation for a successful flexor tendon repair. The trend is now towards multiple strand core sutures followed by early active mobilization. However, the rehabilitation process appears to be one of the major determinant of the success following a flexor tendon repair. Early mobilization is essential for all the flexor tendon repairs as it is proved to improve the quality of the repaired tendon. The art of achieving the harmony between a stronger repair and unhindered gliding of the repair site through the narrow flexor tendon sheath simultaneously can be mastered with practice added to the knowledge of the basic principles.


Identification and characterization of human snoRNA core promoters.
Small nucleolar RNAs (snoRNAs) represent one of the largest groups of functional non-protein coding RNAs currently known in eukaryotic cells. The processing of intron encoded snoRNAs has been well documented; however, the transcriptional regulation of snoRNA genes is still poorly understood, most likely due to the lack of characterization of snoRNA promoters. Here we used a computational approach to predict core promoters for 131 human snoRNAs. Majority of putative snoRNA promoters are supported by DNase I hypersensitivities, RNA polymerase II ChIP-seq peaks, or CAGE tag clusters. Based on the genomic organizations of predicted human snoRNA promoters, we propose five transcriptional models of those snoRNA genes; we also found evidence that some intronic human snoRNAs might have their own promoters. The present study is the first in silico screening of human snoRNAs promoters; and we anticipate the data will facilitate further molecular characterization of transcriptional control of human snoRNA genes.


Incisional Blepharoplasty for the Asian Eye.
The goal of Asian blepharoplasty is to create a lid crease configuration that resembles the natural-appearing crease found in other Asians. Because the Asian upper eyelid contains more prominent preseptal fat resulting in greater lid fullness, soft tissue work in blepharoplasty of the Asian eye is even more diverse and essential than that of whites in order for there to be the sustainability of the eyelid crease. Hence, Asian blepharoplasty should be performed specifically following the orbital anatomy of Asians. This article details the incisional method of blepharoplasty to create natural-appearing creases for Asians with single eyelids.


Effects of aging and dietary n-3 fatty acids on rat brain phospholipids: focus on plasmalogens.
The aging brain undergoes modifications in the lipid composition of cell membranes and especially in plasmalogens. These phospholipids represent between one-half and two-thirds of the ethanolamine phospholipids in the brain. They are known to facilitate membrane fusion and act as endogenous antioxidants. During normal aging and in some pathological conditions, plasmalogen and DHA levels fall. In this context, we aimed to evaluate the influence of n-3 FA intake on plasmalogens in the brain during aging. Littermates from two generations of n-3-deficient rats were fed an n-3-deficient diet or an equilibrated diet containing either alpha-linolenic acid alone (alpha-LNA) or with two doses of DHA (0.3 or 0.6% w/w). After weaning, 9 mon of diet, or 21 mon of diet, plasmalogen levels were assessed, and the sn-2 substitutions of plasmenylethanolamines were analyzed in the cortex, striatum, and hippocampus. Our results showed that plasmalogen contents were not influenced by the diet. Plasmalogen levels were significantly decreased in aged rats compared with adults, whereas DHA levels increased in the hippocampus and remained stable in the cortex and striatum. DHA levels were significantly and similarly increased in total phospholipids and especially in plasmenylethanolamines after 9 mon of diet containing alpha-LNA alone or combined with DHA. This study showed that each structure sustained specific age-induced modifications. Dietary n-3 FA may not oppose the physiological decrease in brain plasmalogen levels during aging. Moreover, alpha-LNA appears to be equally as potent as preformed DHA at replacing DHA in the brain of our rat model.


Mediastinal hemangioma arising in setting of partial anomalous pulmonary venous drainage to azygous vein in a 57-year-old woman.
Partial anomalous pulmonary venous drainage (PAPVD) to the azygous vein and benign posterior mediastinal hemangioma in adults are both rare entities in isolation. The coexistence of these two lesions in the same patient has not been reported. We describe a unique case of PAPVD to the azygous vein in an adult woman, where the anomalous left inferior pulmonary vein transited first through a large hemangioma, and then eventuated in the azygous vein.


Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis.
Bulbar involvement in amyotrophic lateral sclerosis (ALS) is often related to a worse prognosis on account of the higher risk of pulmonary aspiration and undernutrition due to dysphagia. The aim of our study was to assess the effects of enteral feeding by percutaneous endoscopic gastrostomy (PEG) in a long-term follow-up of ALS patients. We report the results of PEG in 31 ALS patients with bulbar involvement. The patients were observed at 3-monthly intervals over a period of 2 years after PEG. All the data were compared with those obtained from a control group of 35 ALS patients who refused PEG. Mortality did not differ significantly between the two groups of patients during the first 6 months of observation, whereas after this period it was lower in the PEG group. In the patients who had had PEG, the body mass index showed a mild but statistically significant improvement after tube insertion while in the control group it decreased significantly. The findings of this study demonstrate that PEG can improve survival in elderly and young ALS patients with bulbar involvement; it enhances their quality of life and helps their integration in their social and family surroundings. We think that PEG should be included symptomatic treatment of all ALS patients with bulbar involvement from the onset of symptoms.


[Comparison of the effects of alpha and beta ecdysone on a diploid clone of cultured Drosophila melanogaster cells in vitro: induction of proteins and morphological changes].
The specific induction of a similar (class of) protein(s) by alpha or beta-ecdysone in the cells of a "sensitive" clone of Drosophila melanogaster cultured in vitro was shown by polyacrylamide gel electrophoresis. However, differences can be seen in the action of the two hormones. (1) The threshold concentration is about 10 times higher for alpha-ecdysone (10 nM) than for beta-ecdysone (1 nM). (2) Beyond this threshold (i.e. 100 nM) the rate of induction is greater for beta-ecdysone (less than or equal to 24 h) than for alpha-ecdysone (larger than or equal to 48 h). The morphological modifications and the protein induction are seen simultaneously after 1 day of 100 nM beta-ecdysone treatment. On the contrary, a dissociation of these two phenomena is noted with the same concentration of alpha-ecdysone.


Deconstructing the role of the exposome in youth suicidal ideation: Trauma, neighborhood environment, developmental and gender effects.
Environment (E) is pivotal in explaining variability in brain and behavior development, including suicidal ideation (SI) and behavior. It is therefore critical to systematically study relationships among environmental exposures (i.e., exposome) and suicidal phenotypes. Here, we evaluated the role of individual-level adversity and neighborhood environment and their interaction (E x E) in association with youth SI. Sample included youth (N = 7,054, ages 11-21) from the Philadelphia Neurodevelopmental Cohort, which investigated clinical phenotypes in a diverse US community population. We examined cross-sectional associations of environmental exposures with lifetime history of SI (n = 671), focusing on interactions between individual-level exposures to assaultive trauma (n = 917) and neighborhood-level socioeconomic status (SES) quantified using geocoded Census data. Models included potential confounds and overall psychopathology. Results showed that assaultive trauma was strongly associated with SI (OR = 3.3, 95%CI 2.7-4, p < .001), while low SES was not (p = .395). Both assault and low SES showed stronger association with SI in females, and in early adolescence (all E X gender/age interactions, p < .05). In traumatized youths, lower SES was associated with less SI, with no SES effects on SI in non-traumatized youths (Assault X SES interaction, Wald = 8.19, p = .004). Associations remained significant controlling for overall psychopathology. No single SES variable emerged above others to explain the moderating effect of SES. These findings may suggest a stress inoculation effect in low SES, where youths from higher SES are more impacted by the deleterious trauma-SI association. Determining which environmental factors contribute to resilience may inform population specific suicide prevention interventions. The cross-sectional study design limits causal inferences.


The impact of increasing land productivity on groundwater dynamics: a case study of an oasis located at the edge of the Gobi Desert.
Intensification of agricultural systems may result in overexploitation of water resources in arid regions because enhanced productivity of crops is often associated with increased actual evapotranspiration (AET). The aim of this study was to quantify the effect of increased regional AET on the groundwater level in a case study of the oasis located within the Shiyang River Basin near the edge of the Gobi Desert. The results of the study show that regional AET increased during the period from 1981 to 2010 due to increasing oasis area and air temperature. The water losses due to AET exceeded the water supply from the mountainous discharges of the basin by the end of this period, leading to groundwater overexploitation in the oasis area. This case study shows the importance of considering the effect of climate change on water losses associated with increasing agricultural production for the sustainable agricultural development of arid regions.


Evaluation of a Virus-like Nanoparticle Porcine Circovirus Type-2 (PCV2) Capsid Protein Fused with the Pig Immunoglobulin Fc Fragment as a Novel Vaccine Candidate against PCV2 in Mice.
Porcine circovirus Type 2 (PCV2) is a primary etiological pathogen of post-weaning multi-systemic wasting syndrome (PMWS). The capsid protein of PCV2 is the crucial immunogenic protein which can induce antibody generation and immune responses. However, there is still a lack of efficient PCV2 vaccines with high immunogenicity. In the current study, we developed a novel engineered PCV2 capsid (∆1-41aa)-pFc fusion protein (PCFP), which comprised a truncated capsid protein of PCV2 and a porcine IgG Fc fragment, fused to the capsid protein of PCV2 at the C-terminus. We found that this novel fusion protein could auto-assemble into virus-like nanoparticles with an estimated mean diameter of 22.6 nm, characterized by transmission electron microscopy. Immunization of BALB/c mice with this fusion protein significantly increased the production levels of anti-PCV2-capsid protein antibody in serum. Besides, the virus-like nanoparticles, PCFP was demonstrated to induce efficient cellular immune responses in mice, as evident by the high specific T cell reactivity to the PCFP fusion protein and the high production of the immune cytokines IFN-γ and IL-10 in an ex vivo re-stimulation system. Collectively, these findings demonstrate that the PCV2 truncated capsid subunit Fc-fusion protein can induce both cellular and humoral immune responses, and it displays great application potential.


Six Cases of Hemoptysis with Angiogenesis from Non-Bronchial Systemic Arteries.
BACKGROUND Although bronchial arteries are the most common cause of hemoptysis, other systemic arteries can cause hemoptysis and are potential pitfalls for successful embolization. CASE REPORT We present 6 cases of hemoptysis showing vascularization from systemic arteries other than bronchial arteries that presented to our department between 2013 and 2020. Chronic inflammatory diseases such as tuberculosis and pulmonary aspergillosis were the underlying diseases in 4 of the 6 cases. In all 6 cases, the lesions were close to the pleura. The abnormal non-bronchial systemic arteries were the internal thoracic artery in 4 cases, intercostal artery in 2 cases, lateral thoracic artery in 2 cases, and the subclavian, thyrocervical, and inferior phrenic arteries in 1 case each, all of which formed a shunt with the pulmonary artery. Additionally, depending on the location of the lesion, the non-bronchial systemic arteries near the lesion proliferated into the lung parenchyma through the adherent pleura. CONCLUSIONS When lesions are in contact with the pleura, various non-bronchial systemic arteries near the lesion can develop in the pulmonary parenchyma via the adherent pleura, which can cause hemoptysis. In patients with hemoptysis, it may be useful to evaluate chest contrast-enhanced computed tomography and angiography, while always accounting for the potential involvement of non-bronchial systemic arteries to ensure a safer and more reliable treatment.


Construction of a microrobot system using magnetotactic bacteria for the separation of Staphylococcus aureus.
Magnetotactic bacteria exhibit superiority over other bacteria in fabricating microrobots because of their high motility and convenient controllability. In this study, a microrobot system is constructed using magnetotactic bacteria MO-1 and applied in pathogenic separation. The feasibility of this approach is demonstrated using Staphylococcus aureus. The MO-1 magnetotactic bacterial microrobots are fabricated by binding magnetotactic bacteria MO-1 with their rabbit anti-MO-1 polyclonal antibodies. The efficient binding of MO-1 magnetotactic bacterial microrobots to Staphylococcus aureus is corroborated by phase contrast microscopic and transmission electron microscopic analyses. Further, a microfluidic chip is designed and produced, and the MO-1 microrobots are magnetically guided toward a sample pool in the chip. In the sample pool, Staphylococcus aureus samples are loaded on the microrobots and then carried away to a detection pool in the chip, suggesting the microrobots have successfully carried and separated pathogen. This study is the first to demonstrate bacterial microrobots carrying pathogens and more importantly, it reflects the great potential of using magnetotactic bacteria to develop magnetic-guided, auto-propelled microrobots for pathogen isolation.


Improved Stability of Layered and Porous Nickel-Rich Cathode Materials by Relieving the Accumulation of Inner Stress.
The commercial application of high-capacity LiNi0.8 Co0.1 Mn0.1 O2 is impeded by its inferior cycling stability, which has been attributed to structural instability caused by stress accumulation during both calcination and cycling. A porous structure was deliberately introduced into nickel-rich material particles to relieve such stress. Cross-sectional SEM and mercury penetration tests confirmed the successful construction of a porous structure. Ex situ TEM and powder XRD confirmed that the porous structure reduced the stress concentration regions in uncycled nickel-rich material by providing a buffer space. In addition, the porous structure helps the permeation of the electrolyte and alleviates the stress accumulation during cycling, endowing the nickel-rich cathode materials with enhanced rate capability and suppressed phase transition. This strategy can be extended for the synthesis of diverse nickel-rich cathode materials to improve their cycling stability.


Metal-free α-CH amination of ethers with hypervalent sulfonylimino-λ3-bromane that acts as an active nitrenoid.
Hypervalent N-triflylimino-λ(3)-bromane undergoes direct and regioselective α-C-H amination of ethers at room temperature under transition metal-free conditions. Kinetic results, substituent and deuterium isotope effects suggest an asynchronous concerted organonitrenoid transition state with some hydride transfer character, analogous to that for alkane C-H insertions.


Comprehensive lysine acetylomes emerging from bacteria to humans.
Recent proteomic studies reveal that 5-10% of mammalian and bacterial proteins undergo lysine acetylation, a post-translational modification that adds an acetyl group to the ɛ-amino group of lysine residues. Many of these proteins are not canonical targets, such as histones and transcription factors, suggesting that this modification plays a much wider role than previously appreciated. These studies also suggest that lysine acetylomes are at least comparable with (if not larger than) phosphoproteomes. Although many of the newly identified acetylation events still require validation, they constitute an important framework for further research and the development of new drugs useful in treating a variety of pathologies. Herein, we summarize these proteomic studies and highlight recent reports linking lysine acetylation to heterochromatin assembly, sister chromatid cohesion, cytoskeleton dynamics, autophagy, receptor signaling, RNA processing and metabolic control.


Moving towards successful exon-skipping therapy for Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is an X chromosome-linked lethal muscular disorder with progressing muscle wasting and weakness caused by mutations in the gene encoding a subsarcolemmal protein dystrophin. For a long time, there was no effective cure; however, advances in molecular biology have allowed the development of radical treatment approaches. Among them, exon-skipping therapy using antisense oligonucleotides is very promising, because it corrects the reading frame of the dystrophin-encoding gene and restores protein expression, resulting in the conversion of DMD to a clinically milder form, Becker muscular dystrophy (BMD). However, clinical trials in exon-skipping therapy did not provide satisfactory results, which may be attributed to inefficient exon skipping, low expression level of restored dystrophin and inadequate methods of muscle function evaluation. To date, exon-skipping approaches have particularly focused on the correction of the gene-reading frame. However, the problem is that the relationship between the resultant and expected phenotypes in terms of definite symptomatic improvement has not yet been elucidated. In other words, previously conducted clinical trials have not been planned based on the comprehensive assessment of genotype-phenotype relationship in BMD, which demonstrates a broad range of symptom severity depending on the functional activity of the truncated dystrophin. The analysis I present in this review strongly suggests that the development of exon-skipping therapy and its clinical trials should be based on large-cohort studies of BMD.


Platelet monoamine oxidase activity in elderly depressed outpatients.
Platelet monoamine oxidase (MAO) activity was assayed in 42 unmedicated, elderly, RDC depressed, unipolar outpatients over 60 years of age, 17 nondepressed controls, and 17 younger volunteers without psychiatric illness. Elderly depressed women (n = 22) had significantly higher MAO activity than sex- and age-comparable controls. No significant relationships between MAO activity and duration of current depressive episode, duration of illness, or family history of affective disorder were obtained. These results extend to elderly female outpatients the finding that depression is associated with increased platelet MAO activity, exceeding the normal age-related increase.


Comparison of different laser-based enucleation techniques for benign prostate hyperplasia: A systematic review and meta-analysis.
To summarize the current evidence on different laser-based enucleation techniques for benign prostate hyperplasia and compare the efficacy and safety of en-bloc, two-lobe and three-lobe techniques. Through a systematical search of multiple scientific databases in March 2021, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines, whose protocol was registered with PROSPERO(CRD42021240684). A total of 9 studies were included. All three laser enucleation techniques had no statistically significant difference in terms of enucleated prostate weight, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), transient UI (TUI), persistent UI (PUI) and early postoperative complications. A shorter enucleation time was associated with the en-bloc technique compared to three technique (MD: -8.26, 95%CI: -12.73--3.79, p = 0.0003), whereas no significant difference was found in en-bloc versus two-lobe technique (MD:0.97,95%CI: -0.30-2.24,p = 0.13) and two-lobe versus three-lobe technique (MD: -3.19, 95%CI: -7.45-1.06, p = 0.14). A higher enucleation rate was associated with the en-bloc and two-lobe technique (MD: 0.05, 95%CI: 0.00-0.10, p = 0.03; MD: 0.09, 95%CI: 0.01-0.17, p = 0.03, respectively). A superior QoL was related to the two-lobe enucleation technique compared to three-lobe technique (MD: 0.22, 95%CI: 0.06-0.39, p = 0.009), whereas no meaningful difference was found in the group of en-bloc versus two-lobe (MD: -0.12, 95%CI: -0.62-0.37, p = 0.62) and group of en-bloc versus three-lobe (MD: -0.14, 95%CI: -0.56-0.29, p = 0.52). En-bloc and two-lobe laser-based enucleation techniques are feasible and safe alternative to three-lobe technique with comparable surgical outcomes and similar functional outcomes. A superior enucleation efficiency was associated with En-bloc and the two-lobe techniques compared to the three-lobe technique.


Characterization and phylogenetic analysis of the complete mitochondrial genome of Aphis spiraecola (Hemiptera: Aphididae).
Aphis spiraecola is an important pest of citrus and transmits a number of plant viruses. Here, we sequenced and annotated the complete mitochondrial genome (mitogenome) of A. spiraecola. This mitogenome was 15,465 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and 2 ribosomal RNA unit genes (rRNAs). Gene order was conserved and identical to that of Drosophila yakuba and to most other previously sequenced Aphididae. The whole mitogenome exhibited heavy AT nucleotide bias (81.8%). All 13 PCGs were initiated by the ATN (ATG, ATT and ATA) codon. Except for cox1 and nad4 which end with the incomplete codon T-, all PCGs terminated with the stop codon TAA. Phylogenetic analysis showed that A. spiraecola got together with the same genus species Aphis gossypii and Aphis craccivora with high support value, and Aphis had a close relationship with Schizaphis and Rhopalosiphum.


Long-term follow-up of patients with asymptomatic occlusion of the internal carotid artery with good and impaired cerebral vasomotor reactivity.
Cerebral hemodynamic status might be prognostic for either the symptomatic or asymptomatic course of carotid occlusive disease. It is determined by evaluating cerebral vasomotor reactivity (VMR). We assessed VMR in asymptomatic patients with total occlusion of the internal carotid artery (ICA) and followed them to evaluate the role of impaired VMR in predicting ischaemic stroke (IS). Thirty-five patients (21 men, mean age ± SD 68 ± 7.5 years) with unilateral asymptomatic ICA occlusion were studied by transcranial Doppler and the Diamox test (intravenous 1.0 g acetazolamide) and followed for 48 months or until reaching the end-points of IS, transient ischaemic attack, or vascular death. VMR% was evaluated by recording the percent differences in peak systolic blood flow velocities in each middle cerebral artery at baseline and after Diamox administration. Based on VMR% calculations, 14 (40%) patients had good VMRs and 21 (60%) had impaired VMRs. The global annual risk of ipsilateral ischaemic events was 5.7%. The annual ipsilateral ischaemic event risk was 1.8% in patients with good VMRs, whilst it was 7.1% in patients with impaired VMRs. An impaired VMR was significantly correlated with ipsilateral IS (Kaplan-Meier log rank statistic, P = 0.04). Our results support the value of VMR assessment for identifying asymptomatic patients with carotid occlusion who belong to a high-risk subgroup for IS. New trials using extracranial-to-intracranial bypass surgery in patients with asymptomatic ICA occlusion and impaired VMRs are warranted.


Coordination versus Insertion: On the Interaction of 5 d-Transition Metal Carbonyl Clusters with Silver(I).
The title silver(I) complex salts [Ag{Re2 (CO)10 }{Re(CO)5 }2 ]+ [Al(ORF )4 ]- (AgRe4 ; ORF =-OC(CF3 )3 ) and [Ag{Ir4 (CO)12 }2 ]+ [Al(ORF )4 ]- (AgIr8 ) form upon reaction of Ag+ [Al(ORF )4 ]- and the transition metal carbonyls (TMCs) Re2 (CO)10 and Ir4 (CO)12 respectively. The solid-state structure of the AgRe4 cluster shows an unexpected asymmetric coordination motif, wherein the silver(I) cation has inserted into the Re-Re bond of one Re2 (CO)10 moiety, while the other dirhenium carbonyl coordinates only over one metal atom towards the silver(I) cation. The AgIr8 cluster is formed by the edge-on coordination of two Ir4 tetrahedra and the silver cation in a D2 symmetric fashion with a torsion angle of 46.5°. QTAIM analysis shows bond paths between the silver atom and the nearby metal atoms in all cases, whereas only the non-inserted Re2 (CO)10 moiety shows additional bond paths between the carbonyl ligands and the silver cation. In addition, the insertion of the Ag+ cation into the Re-Re bond in Re2 (CO)10 removes the bond path between the two rhenium atoms. The EDA-NOCV analysis suggests an increase of the interaction energy between the silver(I) cation and the respective metal carbonyls from the metal centered transition metal carbonyl (TMC) donors W(CO)6 <Re2 (CO)10 <Os3 (CO)12 <Ir4 (CO)12 . In all cases, the dominating orbital interaction is σ-donation [TMC]→Ag+ ←[TMC].


Lumbar herniated disc - endoscopic discectomy treatment.
The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


PAI-1 induction during kidney injury promotes fibrotic epithelial dysfunction via deregulation of klotho, p53, and TGF-β1-receptor signaling.
Renal fibrosis leads to chronic kidney disease, which affects over 15% of the U.S. population. PAI-1 is highly upregulated in the tubulointerstitial compartment in several common nephropathies and PAI-1 global ablation affords protection from fibrogenesis in mice. The precise contribution of renal tubular PAI-1 induction to disease progression, however, is unknown and surprisingly, appears to be independent of uPA inhibition. Human renal epithelial (HK-2) cells engineered to stably overexpress PAI-1 underwent dedifferentiation (E-cadherin loss, gain of vimentin), G2/M growth arrest (increased p-Histone3, p21), and robust induction of fibronectin, collagen-1, and CCN2. These cells are also susceptible to apoptosis (elevated cleaved caspase-3, annexin-V positivity) compared to vector controls, demonstrating a previously unknown role for PAI-1 in tubular dysfunction. Persistent PAI-1 expression results in a loss of klotho expression, p53 upregulation, and increases in TGF-βRI/II levels and SMAD3 phosphorylation. Ectopic restoration of klotho in PAI-1-transductants attenuated fibrogenesis and reversed the proliferative defects, implicating PAI-1 in klotho loss in renal disease. Genetic suppression of p53 reversed the PA1-1-driven maladaptive repair, moreover, confirming a pathogenic role for p53 upregulation in this context and uncovering a novel role for PAI-1 in promoting renal p53 signaling. TGF-βRI inhibition also attenuated PAI-1-initiated epithelial dysfunction, independent of TGF-β1 ligand synthesis. Thus, PAI-1 promotes tubular dysfunction via klotho reduction, p53 upregulation, and activation of the TGF-βRI-SMAD3 axis. Since klotho is an upstream regulator of both PAI-1-mediated p53 induction and SMAD3 signaling, targeting tubular PAI-1 expression may provide a novel, multi-level approach to the therapy of CKD.


Effects of novel anaerobic baffled biofilm membrane bioreactor configurations on membrane fouling mitigation and microbial community in treating liquor condensate.
A novel anaerobic baffled biofilm-membrane bioreactor (AnBB-MBR) was developed to treat industrial liquor condensate. In order to minimize membrane fouling, three different reactor configurations of R1:No media (anaerobic baffled MBR), R2:FF (Fixed Film AnBB-MBR) and R3:FF + MVB (Fixed Film and Moving Bed AnBB-MBR) were evaluated at the same operating hydraulic retention time of 3 days. The specific fouling rates of the ceramic membranes were 0.98, 0.84 and 0.5 kPa/L/m2 for R1:No media, R2:FF and R3:FF + MVB, respectively. The R2:FF and R3:FF + MVB reactors could mitigate the membrane fouling rates by 14.1% and 48.9%, compared to R1:No media due to biomass retention in the fixed film and mechanical scouring of the MVB. From the microbial community analysis, higher relative abundances of Methanosaeta were found in the biofilm whereas more Methanobacterium was found in the suspended sludge. Moreover, higher accumulations of humic and fulvic substances in the system could inhibit the methanogenic activity.


Evolution and disorder.
The evolution of disordered proteins or regions of proteins differs from that of ordered proteins because of the differences in their sequence composition, intramolecular contacts, and function. Recent assessments of disordered protein evolution at the sequence, structural, and functional levels support this hypothesis. Disordered proteins have a different pattern of accepted point mutations, exhibit higher rates of insertions and deletions, and generally, but not always, evolve more rapidly than ordered proteins. Even with these high rates of sequence evolution, a few examples have shown that disordered proteins maintain their flexibility under physiological conditions, and it is hypothesized that they maintain specific structural ensembles.


Creating 12-lead electrocardiogram waveforms using a three-lead bedside monitor to ensure appropriate monitoring.
How do you place the three electrodes to create waveforms for leads I, II, III, aVR, aVL, aVF, and V1-V6?


Vibrio vulnificus, an Underestimated Zoonotic Pathogen.
V. vulnificus, continues being an underestimated yet lethal zoonotic pathogen. In this chapter, we provide a comprehensive review of numerous aspects of the biology, epidemiology, and virulence mechanisms of this poorly understood pathogen. We will emphasize the widespread role of horizontal gene transfer in V. vulnificus specifically virulence plasmids and draw parallels from aquaculture farms to human health. By placing current findings in the context of climate change, we will also contend that fish farms act as evolutionary drivers that accelerate species evolution and the emergence of new virulent groups. Overall, we suggest that on-farm control measures should be adopted both to protect animals from Vibriosis, and also as a public health measure to prevent the emergence of new zoonotic groups.


[Not Available].
To determine the occult mortality in the extra-hospital setting. Retrospective study included patients who required health care using the Andalusian Emergency Services from January 2002 to June 2002 and who remained at home or were transferred to an Emergency department of a hospital in a normal ambulance as they were not considered to be in need of emergency assistance. Of the 562 patients who met the inclusion criteria of this study, 17 patients died after this care, which was an occult mortality of 3%, 8 of whom had remained at home. The occult mortality in this study is not insignificant; it affects all ages and is mainly due to respiratory disorders.


Technical contribution: use of continuous recording video monitoring of maintenance and pain behaviors in piglets after surgical castration to validate six continuous time sampling periods for behavior scoring.
Castration is a painful procedure routinely performed on piglets. Specific periods relative to castration and time sampling rules are used widely to quantify deviations in piglet's behavior associated with castration rather than assessing behavior for the entire trial period. However, very limited work has evaluated time sampling recording rules to quantify behavioral changes to piglets undergoing castration. Therefore, the objective of this study was to validate the accuracy of six continuous time sampling periods (5, 10, 15, 20, 30, and 45 min), to quantify piglet behavior post-castration when compared with a full 60-min observation period. Sixteen Yorkshire-Landrace x Duroc piglets were surgically castrated. Data were collected using continuous observation (recording rule) of each individual male piglet per litter for 60-min post-castration. The 60-min continuous behavioral data set was then subdivided into six data subsets for each defined continuous time sampling period (5, 10, 15, 20, 30, and 45 min). Data from each continuous time sampling period and the full period data were analyzed using both a generalized linear mixed model and linear regression analysis. For the generalized linear mixed model, 30- and 45-min continuous time sampling periods were not different (P > 0.05) when compared with the full observation period data for all behaviors. For the linear regression analysis, affiliative interaction, sitting, walking, huddled up, prostrated, scratching, spasms, and trembling behaviors met the pairwise comparison accuracy criteria: [1) the coefficient of determination (R2) was > 0.90, 2) the intercept did not differ from 0 (P > 0.05), and 3) the slope did not differ from 1 (P > 0.05)] at the 45-min continuous time sampling period compared to full observation period. Results from this study suggest that a 45-min continuous time sampling period would be necessary to accurately investigate piglet behavior during the acute pain sensitivity time post-castration when considering both maintenance and pain-associated behaviors.


Characteristic differences in the abundance of tumor-infiltrating lymphocytes and intratumoral developing T cells in thymoma, with special reference to PD-1 expression.
Though programmed cell death-1 (PD-1) inhibitors mainly target tumor-infiltrating lymphocytes (TILs) expressing PD-1, developing T cells in thymus also express PD-1 in their process of maturation. To predict the therapeutic effect of PD-1 inhibitors for thymoma, it is necessary to clarify the proportions of TILs and intratumoral developing T cells. The expressions of CD4, CD8, and PD-1 on T cells were analyzed by flow cytometry in 31 thymomas. The amount of T cell receptor excision circles (TRECs), which can be detected in newly formed naïve T cells in the thymus, was evaluated using sorted lymphocytes from thymomas by quantitative PCR. The expressions of granzyme B (GZMB) and lymphocyte activation gene-3 (LAG-3) in PD-1 + CD8 T cells were analyzed by image cytometry using multiplex immunohistochemistry. The PD-1 + rate in both CD4 and CD8 T cells was significantly higher in type AB/B1/B2 than in type A/B3 thymomas. The amounts of TRECs in CD4 and CD8 T cells were significantly higher in type AB/B1/B2 than in type A/B3 thymomas and comparable to normal thymus. PD-1 expression at each stage of T cell development of type AB/B1/B2 thymomas was comparable to that of normal thymus. Both the percentages and cell densities of PD-1 + CD8 T cells expressing GZMB or LAG-3, which are known to contain tumor-reactive T cells, were significantly lower in type AB/B1/B2 thymomas. Most PD-1 + T cells in type AB/B1/B2 thymomas are intratumoral developing T cells and are not TILs.


Covariance of plasma free 3-methoxy-4-hydroxyphenethyleneglycol and diastolic blood pressure.
To test the acute effects of clonidine on plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), the major metabolite of brain norepinephrine (NE), and to examine the relationship between plasma MHPG and concurrently measured blood pressure variables, we performed a series of 31 double blind, placebo controlled, test days in which clonidine (1 and 5 micrograms/kg) or placebo was administered (p.o. at 9:00 a.m.) to six fasting normotensive male subjects. Three h following the 5 micrograms/kg clonidine dose, plasma MHPG reached a nadir significantly below both baseline and placebo levels (P less than 0.05). Mean MHPG concentrations were significantly correlated with diastolic blood pressure (sitting: r = 0.46, df = 88, P less than 0.00001; standing r = 0.49, df = 73, P less than 0.00001). Unexpectedly, this relationship was independent of clonidine dose and sampling time. Under drug-free conditions, the correlation between plasma free MHPG and diastolic blood pressure remained significant (sitting: r = 0.43, df = 40, P = 0.003; standing: r = 0.46, df = 33, P = 0.006). The findings are considered in light of evidence implicating brain NE systems in the regulation of blood pressure.


Evaluation of Fixational Behavior throughout Life.
To quantify development of gaze stability throughout life during short and long fixational tasks using eye tracking technology. Two hundred and fifty-nine participants aged between 5 months and 77 years were recruited along the study. All participants underwent a complete ophthalmological assessment. Fixational behavior during long and short fixational tasks was analyzed using a DIVE (Device for an Integral Visual Examination), a digital test assisted with eye tracking technology. The participants were divided into ten groups according to their age. Group 1, 0-2 years; group 2, 2-5 years; group 3, 5-10 years; group 4, 10-20 years; group 5, 20-30 years; group 6, 30-40 years; group 7, 40-50 years; group 8, 50-60 years; group 9, 60-70 years; and group 10, over 70 years. Gaze stability, assessed by logBCEA (log-transformed bivariate contour ellipse area), improved with age from 5 months to 30 years (1.27 vs. 0.57 deg2 for long fixational task, 0.73 vs. -0.04 deg2 for short fixational task), while fixations tend to be longer (1.95 vs. 2.80 msec for long fixational tasks and 0.80 vs. 1.71 msec for short fixational tasks). All fixational outcomes worsened progressively from the fifth decade of life. Log-transformed bivariate contour ellipse area (0.79, 0.83, 0.91, 1.42 deg2 for long fixational task and 0.01, 0.18, 0.28, 0.44 deg2 for short fixational task, for group 7, 8, 9, and 10 respectively). Stimuli features may influence oculomotor performance, with smaller stimuli providing prolonged fixations. Fixational behavior can be accurately assessed from 5 months of age using a DIVE. We report normative data of gaze stability and duration of fixations for every age group. Currently available technology may increase the accuracy of our visual assessments at any age.


Task-dependent audiovisual temporal sensitivity is not affected by stimulus intensity levels.
Flexibility and robustness of multisensory temporal recalibration is paramount for maintaining perceptual constancy of the surrounding natural world. Different environments impart various impediments, distances and routes that alter the propagation times of sight and sound cues comprising a multimodal event. One's ability to rapidly calibrate and account for these external variations allows for maintained perception of synchrony which is crucial for coherent and consistent perception. The two common paradigms used to compare precision of temporal processing between experimental and control groups, the simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks, often use supra-threshold stimuli. However, few studies have specifically examined the effects of normalizing stimulus intensities to participant's unisensory detection thresholds. The current project presented multiple combinations of auditory and visual stimulus intensity levels, based on individual detection thresholds, during a TOJ and a SJ task. While no effect of stimulus intensity was found on temporal sensitivity or perceived temporal synchrony, there was a significant difference in point of subjective simultaneity (PSS) measures between tasks. In addition, PSS estimates were audio-leading, rather than visual-leading as previously reported, suggesting that exposure to the particular combinations of stimulus intensity levels used influenced temporal synchrony perception. Overall, these results support the use of supra-threshold stimuli in TOJ and SJ tasks as a way of minimizing the confound from differences in unisensory processing.


Cyclic regulation of cytokinesis in amphibian eggs.
The effects of amphibian egg cytoplasm extracted at different times after activation and during the first four cleavages on cytokinesis were examined. Extracts of artificially activated or fertilized Xenopus or Pleurodeles eggs taken at the time of activation (T = 0) provoked precocious cleavage furrows in Pleurodeles eggs. Between T = 0.25 and T = 0.75 of the first cell cycle, the period corresponding to interphase, an inhibitory effect was found, and the division of injected eggs was delayed up to 30%. After T = 0.75, that is during mitosis, the cleavage induction effect was observed again. These enhancing and inhibitory effects were also found in the two fractions obtained following gel filtration of the cytoplasmic extracts. These experiments support the hypothesis that two antagonistic factors control cytokinesis. The inhibitory factor is active only during interphase, while the positive factor is present during mitosis and appears to regulate cytokinesis.


Mechanical zona pellucida removal of vitrified-warmed human blastocysts does not affect the clinical outcome.
Does complete mechanical removal of the zona pellucida modify the outcome of transfer of vitrified-warmed human blastocysts? In a prospective randomized controlled study, 419 couples were allocated to either zona pellucida-free (n = 209) or zona intact (n = 210) vitrified-warmed embryo transfer. Main outcome measures included clinical pregnancy, implantation and ongoing pregnancy rates. Transfer of zona pellucida-free blastocysts resulted in clinical pregnancy, implantation and ongoing pregnancy rates (35,9%, 33,9% and 32,1%, respectively), similar to those achieved with zona intact control embryos (39%, 36,4% and 33,1%, respectively). Total mechanical removal of the zona pellucida did not affect the tested parameters of clinical outcomes.


Experimental campaign on the mechanical properties of Canadian small clear spruce-pine-fir wood: Experimental procedures, data curation, and data description.
This article contains an experimental dataset related to the mechanical properties of Canadian small clear spruce-pine-fir wood. Motivated by the necessity of shading light on the orthotropic mechanical behavior of clear specimens of two of the most common wooden grades used for the manufacturing of cross-laminated timber panels in North America, a comprehensive experimental campaign on small clear spruce-pine-fir wood specimens, based on ASTM D143-22, has been conducted in the Department of Wood Science of the University of British Columbia. A total of 690 specimens from both visually-graded number 2 and machine-stress rated 2100fb 1.8E spruce-pine-fir wood were tested in compression, tension, and shear, following the directions parallel- and perpendicular-to-the-grain. For each test, the force and the deformation were recorded on-line through an MTS software before being stored in a hard drive disk unit as text files at the end of the test. Text files were then post-processed using a MATLAB routine to generate stress-strain data points, ultimate strength, and modulus of elasticity. Additionally, probability distributions of ultimate strength and modulus of elasticity of specimens were plotted. A Kolmogorov-Smirnov goodness-of-fit test was used to fit these data using either Burr, Gumbel, or Weibull distribution. In overall, the dataset presented in this work can be used in the finite-elements modelling of the structural behavior of timber connections or the local mechanical behavior of timber elements. This dataset can also be used to get a grasp and asses the variability in the mechanical properties of Canadian small clear spruce-pine-fir wood.


A bone replacement-type calcium phosphate cement that becomes more porous in vivo by incorporating a degradable polymer.
This study investigated whether mixing low viscosity alginic acid with calcium phosphate cement (CPC) causes interconnected porosity in the CPC and enhances bone replacement by improving the biological interactions. Furthermore, we hypothesized that low viscosity alginic acid would shorten the setting time of CPC and improve its strength. CPC samples were prepared with 0, 5, 10, and 20% low viscosity alginic acid. After immersion in acetate buffer, possible porosification in CPC was monitored in vitro using scanning electron microscopy (SEM), and the setting times and compressive strengths were measured. In vivo study was conducted by placing CPC in a hole created on the femur of New Zealand white rabbit. Microcomputed tomography and histological examination were performed 6 weeks after implantation. SEM images confirmed that alginic acid enhanced the porosity of CPC compared to the control, and the setting time and compressive strength also improved. When incorporating a maximum amount of alginic acid, the new bone mass was significantly higher than the control group (P = 0.0153). These biological responses are promising for the translation of these biomaterials and their commercialization for clinic applications.