Efficacy of methylene blue and curcumin mediated antimicrobial photodynamic therapy in the treatment of indirect pulp capping in permanent molar teeth.
This study aimed to evaluate the adhesive bond strength and antibacterial efficacy of methylene blue (MB)-mediated antimicrobial photodynamic therapy (aPDT) and curcumin (CUR)-mediated aPDT versus the conventional disinfectants, such as chlorhexidine gluconate (CHX) gel and sodium hypochlorite (NaOCl), for indirect pulp capping (IPC) treatment of permanent molars. One Hundred grossly carious human permanent molars were collected through non-traumatic extraction. All specimens were embedded in polyvinyl cross-sections to the cemento-enamel junction. The cavity preparation was conducted by grinding the samples using silicon carbide discs. After culturing Streptococcus mutans (S. mutans), a 10 µL of S. mutans suspension (106 colony forming units/mL) was transferred in each tooth cavity and anaerobically incubated for 48 h at 37 °C. All specimens were randomly divided into 5 groups: Group-I: samples treated IPC; Group-II: samples treated with 2% CHX gel; Group-III: samples treated with 6% NaOCl; Group-IV: irradiation of prepared cavity with MB-mediated aPDT; and Group-V: irradiation of prepared cavity with CUR-mediated aPDT. After disinfection methods, the universal adhesive was used, and all specimens were restored using giomer. Eventually, confocal laser scanning microscopy, shear bond strength (SBS), micro-tensile bond strength (μTBS), four-point bending strength (4P-BS) analyses were performed, and the data were analyzed statistically. At baseline, the highest SBS (48.8 ± 6.5 MPa), μTBS (54.3 ± 3.9 MPa), and 4P-BS (123 ± 32 MPa) scores were demonstrated by the samples treated with MB-mediated aPDT. However, after 12 months of storage, the highest SBS (42.3 ± 3.9 MPa) and μTBS (45.2 ± 6.6 MPa) scores were shown by samples treated with MB-mediated aPDT, while CUR-mediated aPDT treated samples demonstrated the highest 4P-BS scores (70 ± 18 MPa). Moreover, the highest antibacterial activity against S. mutans was shown by the samples treated with MB-mediated aPDT. The application of aPDT, especially MB-mediated, demonstrated superior SBS, μTBS, and 4P-BS values as well as antibacterial activity against S. mutans as compared to 2% CHX gel and 6% NaOCl as cavity disinfectants for IPC treatment of permanent molars.


Active dendrites: colorful wings of the mysterious butterflies.
Santiago Ramón y Cajal had referred to neurons as the 'mysterious butterflies of the soul.' Wings of these butterflies--their dendrites--were traditionally considered as passive integrators of synaptic information. Owing to a growing body of experimental evidence, it is now widely accepted that these wings are colorful, endowed with a plethora of active conductances, with each family of these butterflies made of distinct hues and shades. Furthermore, rapidly evolving recent literature also provides direct and indirect demonstrations for activity-dependent plasticity of these active conductances, pointing toward chameleonic adaptability in these hues. These experimental findings firmly establish the immense computational power of a single neuron, and thus constitute a turning point toward the understanding of various aspects of neuronal information processing. In this brief historical perspective, we track important milestones in the chameleonic transmogrification of these mysterious butterflies.


NMR structure of the conserved hypothetical protein TM0487 from Thermotoga maritima: implications for 216 homologous DUF59 proteins.
The NMR structure of the conserved hypothetical protein TM0487 from Thermotoga maritima represents an alpha/beta-topology formed by the regular secondary structures alpha1-beta1-beta2-alpha2-beta3-beta4-alpha3- beta5-3(10)-alpha4, with a small anti-parallel beta-sheet of beta-strands 1 and 2, and a mixed parallel/anti-parallel beta-sheet of beta-strands 3-5. Similar folds have previously been observed in other proteins, with amino acid sequence identity as low as 3% and a variety of different functions. There are also 216 sequence homologs of TM0487, which all have the signature sequence of domains of unknown function 59 (DUF59), for which no three-dimensional structures have as yet been reported. The TM0487 structure thus presents a platform for homology modeling of this large group of DUF59 proteins. Conserved among most of the DUF59s are 13 hydrophobic residues, which are clustered in the core of TM0487. A putative active site of TM0487 consisting of residues D20, E22, L23, T51, T52, and C55 is conserved in 98 of the 216 DUF59 sequences. Asp20 is buried within the proposed active site without any compensating positive charge, which suggests that its pK(a) value may be perturbed. Furthermore, the DUF59 family includes ORFs that are part of a conserved chromosomal group of proteins predicted to be involved in Fe-S cluster metabolism.


Transanal Suture Mucopexy for Hemorrhoids.
Core factors involved in the treatment of hemorrhoids include the engorgement of hemorrhoids, prolapse, recurrence, and pain. The goal of this study was to assess the safety, pain, and efficacy of the transanal suture mucopexy for the treatment of hemorrhoids. This was a retrospective study over a 13-year period. This procedure was performed, and data collected, from medical records at six centers in India. This study includes 5634 patients who had grade II to IV symptomatic hemorrhoids. Patients suffering from thrombosed hemorrhoids, inflammatory bowel disease, anal strictures, and anorectal carcinoma were excluded. Hemorrhoidal swelling was reduced by manual massage and a steep Trendelenburg position under saddle block. The reduced hemorrhoids were fixed to the muscles of the rectal wall using sutures. Each suture measured 0.5 to 1.0 cm in length; double-locking continuous sutures were used, along the complete circumference of the rectum, at 2 and 4 cm proximal to the dentate line. Pain assessed using the visual analog scale and hemorrhoid recurrence served as outcome measures. The transanal suture mucopexy procedure was performed for 5634 patients with symptomatic hemorrhoids. A dull pain compatible with a visual analog score of 2 to 3 was reported in 126 (2.2%) patients; in the remaining 5508 (97.8%) patients, the visual analog score was 1 to 2. Effective treatment without complications occurred for 5541 patients (98.65%). A recurrence rate of 1.3% was recorded in 5634 cases with a mean follow-up of 7 ± 6 years. Utilization of a self-illuminating proctoscope or Brinckerhoff or anal speculum is essential. Transanal suture mucopexy, designed with 2 suture rows, is a safe procedure with a short learning curve. It is associated with minimal pain, low recurrence rate, and fewer complications. See Video Abstract at http://links.lww.com/DCR/B841. ANTECEDENTES:Los factores centrales involucrados en el tratamiento de la enfermedad hemorroidal incluyen congestión de hemorroides, prolapso, recurrencia y dolor.OBJETIVO:Evaluar la seguridad, el dolor y la eficacia de la mucopexia transanal con sutura para el tratamiento de la enfermedad hemorroidal.DISEÑO:Estudio retrospectivo durante un período de 13 años.ESCENARIO:Este procedimiento se realizó y se recopilaron datos de expedientes médicos en seis centros en India.PACIENTES:Este estudio incluye 5634 pacientes con enfermedad hemorroidal sintomática grado II a IV. Se excluyeron pacientes que padecían hemorroides trombosadas, enfermedad inflamatoria intestinal, estenosis anales y carcinoma anorrectal.INTERVENCIONES:La inflamación hemorroidal se redujo mediante masaje manual y posición Trendelenburg profundo bajo bloqueo caudal. Las hemorroides reducidas se fijaron a los músculos de la pared rectal mediante suturas. Cada sutura midió 0.5 a 1.0 cm de longitud, se utilizaron suturas en surgete continuo de doble anclado, a lo largo de la circunferencia completa del recto, a dos y cuatro cm proximales a la línea dentada.PRINCIPALES MEDIDAS DE RESULTADO:El dolor se evaluó mediante la escala de puntuación analógica visual y se evaluó la presencia de recurrencia.RESULTADOS:El procedimiento de mucopexia transanal con sutura se realizó en 5634 pacientes con hemorroides sintomáticas. Se informó un dolor sordo compatible con una puntuación analógica visual de 2-3 en 126 (2.2%) pacientes; en los 5508 (97.8%) pacientes restantes, la puntuación analógica visual fue de 1-2. La mayoría (5541 pacientes [98.65%]) tuvo un tratamiento eficaz sin complicaciones. Se registró una tasa de recurrencia del 1.3% en 5634 casos con un seguimiento medio de 7 ± 6 años.LIMITACIONES:La utilización de un proctoscopio autoiluminado o de Brinckerhoff o espéculo anal es esencial.CONCLUSIÓN:La mucopexia transanal con sutura es un procedimiento seguro diseñado con dos filas de suturas asociadas con dolor mínimo y baja tasa de recurrencia con menos complicaciones. Tiene una curva de aprendizaje corta. Consulte Video Resumen en http://links.lww.com/DCR/B841. (Traducción-Dr. Jorge Silva Velazco).


Myelodysplastic syndrome with myelofibrosis and basophilia: detection of trisomy 8 in basophils by fluorescence in-situ hybridization.
We report a case of myelodysplastic syndrome (MDS) with myelofibrosis and pulmonary tuberculosis who had marked basophilia in the peripheral blood. A clonal karyotypic abnormality characterized by trisomy 8 was demonstrated by cytogenetic analysis. By correlation of cell morphology with results of fluorescence in situ hybridization using a chromosome 8 probe, we demonstrated that the basophils were not reactive but belonged to the neoplastic MDS clone.


[The influence of tripterygium hypoglaucum hutch on the HIF-1α expression in the CIA rat models].
To investigate the effect of tripterygium hypoglaucum hutch (THH) on the expression of hypoxi induciable factor (HIF-1α) in rats with collagen induced arthritis (CIA) model and its mechanism. Establish CIA model rat, group randomly, treat groups with gastric feeding at High, Medium and Low doses of THH once a day, with continuous medication for 30 days. Record arthritis index (AI) and joint pathology change. Detect HIF-1α mRNA and protein expression with PT-PCR and immunohistochemical staining. THH could inhibit paw swelling in CIA rats, reduce synovial proliferation and inflammatory response significantly. THH may mitigate joint inflammation of CIA model rat through reduction of HIF-1α expression.


Spectrum of p53 tumor suppressor gene mutations and breast cancer survival.
p53 mutation is associated with poor prognosis in breast cancer patients. Mutations in different structural and functional domains of p53 have different effects on its biological activities. Nevertheless, few studies have examined the full spectrum of p53 gene mutations in relation to breast cancer survival. To evaluate the prognostic significance of the types, localizations, and multiplicity of p53 gene mutations in breast cancer patients. Prospective cohort study of a consecutive series of 271 women with histologically confirmed primary breast cancer who underwent breast resection at the Jackson Memorial Hospital, Miami, FL, between 1984 and 1986. Main outcome measures. Ten year overall and breast-cancer-specific deaths. After adjustment for tumor stage, treatment regimen, and the number of mutations, patients with p53 mutations had significantly greater breast-cancer-specific mortality than did patients without p53 mutations (hazard ratio = 2.86; 95% confidence interval: 1.15-7.11). Further analysis of mutation characteristics showed that patients with the following mutations had significantly poorer breast cancer disease-free survival: silent/missense mixed mutations (7.95; 1.28-49.62), nonsense mutations (9.43; 1.29-69.12), transitions (3.79; 1.46-9.88), mutations in which guanine changed (3.32; 1.01-10.35), and mutations on exon 7 (6.46; 1.78-23.45). Breast-cancer-specific and all-cause mortality are increased in female breast cancer patients with the following p53 mutation characteristics: silent and missense mixed mutations, transitional mutations, mutations in which guanine changed, mutations on exon 7, or multiple mutations occurring within 60 codons. These findings indicate that not just p53 mutation per se but the full spectrum (i.e., different types, locations, and numbers) of p53 mutation needs to be examined when it is used as a prognostic marker of survival in breast cancer patients.


Craniofacial Anthropometry of Healthy Turkish Young Adults: Outer Canthal, Inner Canthal, Palpebral Fissure, and Interpupillary Distances.
This study aims to examine the values of the orbital region in Turkish young adults by the two-dimensional photogrammetry. Anthropometric measurements of the eye and eyelid-related parameters were taken from 100 female and 100 male volunteer Turkish young adults, ranging in age from 18 to 25 years. Endocanthion (en), exocanthion (ex), and pupil (p) were identified on the photograph and the distances between these points were measured with the ImageJ program. The average values of the en-en, ex-en (R), ex-en (L), p-p, and ex-ex were found as 32.92 ± 2.84, 32.48 ± 2.06, 32.22 ± 2.01, 65.32 ± 3.77, and 97.75 ± 5.09 mm, respectively. There were statistically significant differences between the genders in all parameters. Although there are many studies examining these parameters, comprehensive studies are needed in different populations and in many cases. In this study, we believe that the results obtained for Turkish young adults can be used as reference values.


Development and validation of a computer-based measure of symmetry and arranging behavior in obsessive-compulsive disorder: a preliminary study.
While compulsive ordering and arranging, and a preoccupation with symmetry are common presentations of obsessive-compulsive disorder (OCD), little attention has been given to these types of symptoms in the assessment of patients with OCD. The goal of the present study was to develop and evaluate psychometric properties for the objective and quantitative measurement of compulsive symptoms related to symmetry and arranging. Thirty-five normal volunteers performed computer-simulated environment tasks under four different conditions with or without a target and distraction. Primary dependent variables included several indices of time and manipulation of arranging behaviors. We evaluated the validity of the task by comparing the novel behavioral measures with standardized measures such as the Symmetry, Ordering and Arranging Questionnaire (SOAQ), Obsessive Compulsive Inventory-Revised (OCI-R), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), and Quality of Life Scale (WHOQOL). We found a significant positive correlation between the arrangement time (time to complete the task) with the SOAQ score and the "ordering" subscore of the OCI-R. In addition, the number of manipulations was positively correlated with the SOAQ score and the "ordering" subscore of the OCI-R. There were no significant correlations between behavioral parameters and other scales measuring constructs less relevant to the symptoms of OCD related to ordering/symmetry. There was only a significant main effect of the target on the arrangement time. This study demonstrates the good convergent and discriminant validity of this task as a novel behavioral measure for the assessment of arranging compulsion symptoms. We can infer from the results that subjects are likely to spend more time in compulsive arranging when the target for the task is given.


Impaired formation of desmosomal junctions in ADPKD epithelia.
Mutations in polycystin-1 (PC-1) are responsible for autosomal dominant polycystic kidney disease (ADPKD), characterized by formation of fluid-filled tubular cysts. The PC-1 is a multifunctional protein essential for tubular differentiation and maturation found in desmosomal junctions of epithelial cells where its primary function is to mediate cell-cell adhesion. To address the impact of mutated PC-1 on intercellular adhesion, we have analyzed the structure/function of desmosomal junctions in primary cells derived from ADPKD cysts. Primary epithelial cells from normal kidney showed co-localization of PC-1 and desmosomal proteins at cell-cell contacts. A striking difference was seen in ADPKD cells, where PC-1 and desmosomal proteins were lost from the intercellular junction membrane, despite unchanged protein expression levels. Instead, punctate intracellular expression for PC-1 and desmosomal proteins was detected. The N-cadherin, but not E-cadherin was expressed in adherens junctions of ADPKD cells. These data together with co-sedimentation analysis demonstrate that, in the absence of functional PC-1, desmosomal junctions cannot be properly assembled and remain sequestered in cytoplasmic compartments. Taken together, our results demonstrate that PC-1 is crucial for formation of intercellular contacts. We propose that abnormal expression of PC-1 causes disregulation of cellular adhesion complexes leading to increased proliferation, loss of polarity and, ultimately, cystogenesis.


Escape deficits induced by uncontrollable foot-shock in recombinant inbred strains of mice.
Although uncontrollable stressors reliably induce numerous behavioral disturbances, considerable interindividual variability exists in this respect. Inasmuch as genetic factors may be fundamental in determining vulnerability to stressor effects, the present investigation assessed alterations in escape performance following exposure to uncontrollable foot-shock in the BALB/cByJ and C57BL/6ByJ mice and seven recombinant inbred strains. Exposure to uncontrollable foot-shock disrupted shuttle escape performance in a strain-specific manner; however, any differences due to gender were not particularly remarkable. The profile of stressor effects in the recombinant strains (i.e., performance deficits greater, lesser or intermediate to the progenitor strains) suggest that the stressor effects on escape performance may be subserved by two or more genetic determinants. The findings are related to central mechanisms that may potentially account for strain differences.


Surgical approaches to the distal radius.
Fractures of the distal radius are among the most common fractures seen. They encompass a myriad of presentations and fracture patterns that often benefit from various open reduction and internal fixation techniques-including volar plating, dorsal plating, radial plating, intramedullary nailing, and fragment-specific fixation. In order to obtain optimal reduction of these fractures, surgeons require a thorough understanding of the anatomy and various surgical exposures. The distal radius is surrounded by a soft tissue envelope rich in vascularity and cutaneous innervation. The osseous surface consists of two articular surfaces and three cortical sides covered almost entirely by soft tissue. Approaches to the distal radius can be broadly divided into volar, radial, and dorsal. Visualization of the articular surface can be accomplished best arthroscopically. Arthroscopy can be performed alone or in conjunction with other open approaches to the distal radius. This article will review the pertinent anatomy and various surgical approaches in order to facilitate the surgeon's ability to safely expose a distal radius fracture.


Genome-wide profiling reveals cancer-related genes with switched alternative polyadenylation sites in colorectal cancer.
Alternative polyadenylation (APA) is an important post-transcriptional regulation in eukaryotic cells. It plays considerable roles in many biological processes and diseases, such as cell differentiation, proliferation and cancer. Colorectal cancer (CRC) is one of the most common malignancies worldwide, which is among the top five in incidence and mortality of all cancers in China. Although there have been some studies on the APA of CRC, the normal and carcinoma samples used for genome-wide profiling were not matched. The purpose of this study was to obtain genes with switched 3'-untranslated region (UTR) that may be associated with intracellular regulation of CRC by analyzing APA patterns of strict control groups from clinical patients. CRC and matched normal tissues were acquired from surgical specimens from three CRC patients. Their libraries of 3'-terminal fragments of mRNA with poly(A) tails were constructed by 3T-seq technology and sequenced by Illumina Hiseq X Ten. APA patterns of cancer and matched normal tissues were analyzed by bioinformatics analysis, and a representative gene, GPI, was verified by quantitative reverse transcription PCR. Overall, we identified 35,076 poly(A) sites in total. Compared to the matched normal tissues, we detected 350, 405 and 375 genes with significantly APA-mediated 3'-UTR alteration in cancer tissues of three patients, respectively. Forty-seven genes with switched 3'-UTR were shared in all three patients. In addition, most of these genes have shortened 3'-UTRs, some of which were associated with cancers, such as GPI. Our studies found several genes with switched 3'-UTR in CRC patients, which may provide some important clues for more in-depth study of the cellular regulation in CRC from the perspective of post-transcriptional regulation. It may also help in the search for new biomarkers of CRC.


Amino acid mutations of the infectious clone from Chinese EIAV attenuated vaccine resulted in reversion of virulence.
The Chinese equine infectious anemia virus (EIAV) donkey-leukocyte attenuated vaccine (DLV) provides a unique natural model system by which attenuated mechanism and immunological control of lentivirus replication may be studied. We analyzed the critical consensus mutations that occurred during the viral passages in vitro and in vivo for vaccine's preparation. Based on the full-length infectious clone pLGFD3 (EIAV vaccine background) and according to mutations displayed during viral attenuation, we successfully constructed an infectious clones pLG5-3-l in which gag and env genes were point-mutated by overlap PCR mutagenesis strategy. pLG5-3-l was proved to have the ability of effective replication in vitro cells culture systems by Reverse Transcriptase Assay and virion observation under electron microscopy. Results of the in vivo experiments indicated that marked differences occurred between the mutated virus and their parental virus in clinical manifestation and plasma viral replication during 6-month observation period. In contrast to asymptom of animals infected with pLGFD3-V, the mutated virus (pLG5-3-l-V) developed typical clinical progression in the corresponding experimentally infected animals. The results of the distinct differences in clinical profiles and viral dynamics before and after mutation of EIAV infectious clone will help to understand the protective mechanism of Chinese EIAV vaccine and shed light on novel HIV vaccine design.


In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis.
Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein-receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3'-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.


Metformin-related lactic acidosis in patients with acute kidney injury.
Metformin is nowadays considered as first-line therapy in individuals with non-insulin dependent diabetes mellitus (NIDDM). Metformin-related lactic acidosis (MALA) occurs more frequently after inappropriate use especially in patients with acute kidney injury (AKI) or chronic kidney disease (CKD). Thus, its prescription in these patients is contraindicated, while the role of dialysis is under evaluation. We describe two cases of severe metformin-related lactic acidosis with underlying acute kidney injury, which were treated with dialysis. In both cases, lactic acidosis occurred on a background of acute decline in renal function, possibly due to drug accumulation. It is interesting that metformin was contraindicated in one case. Lactic acidosis is a rare but potentially fatal adverse effect of metformin, particularly in patients with AKI, which should always be considered in clinical practice. Dialysis seems to contribute significantly to the management of this life-threatening condition and the improvement in outcome.


Comparing geographic information system-based estimates with trauma center registry data to assess the effects of additional trauma centers on system access.
Geographic information systems (GISs) are often used to analyze trauma systems. Geographic information system-based approaches can model access to a trauma center (TC), including estimates of transport time and population coverage, when accurate trauma registry and emergency medical systems (EMS) data are not available. We hypothesized that estimates of trauma system performance calculated using a standard GIS method with public data would be comparable with trauma registry data. A standardized GIS-based method was used to estimate metrics of TC access in a regional trauma system in which the number of TCs increased from one to three during a 3-year period. Registry data from the index TC in the system were evaluated for different periods during this evolution. The number of admissions to the TC in different periods was compared with changes predicted by the GIS-based model, and the distribution of observed ground-based transportation times was compared with the predicted distribution. With the addition of two TCs to the system, the volume of patients transported by ground to the index TC decreased by 30%. However, the model predicted a 68% decrease in population having the shortest predicted transport time to the index TC. The model predicted the geographic trend seen in the registry data, but many patients were transported to the index TC even though it was not the closest center. Observed transport times were uniformly shorter than predicted times. The GIS-based model qualitatively predicted changes in distribution of trauma patients, but registry data highlight that field triage decisions are more complex than model assumptions. Similarly, transport times were systematically overestimated. This suggests that model assumptions, such as vehicle speed, based on normal traffic may not fully reflect emergency medical systems (EMS) operations. There remains great need for metrics to guide policy based on widely available data. Epidemiological, level III.


Haplotype analysis of QTLs governing early seedling vigor-related traits under dry-direct-seeded rice (Oryza sativa L.) conditions.
The eventual shifting of cultivation method from puddle transplanted rice to direct-seeded rice (DSR) to save water prompted researchers to develop DSR-suitable varieties. To achieve this, identification of molecular markers associated with must-have traits for DSR, especially early seedling vigour related traits is crucial. In the present investigation, the haplotype analysis using flanking markers of three important quantitative trait loci (QTLs) for early seedling vigour-related traits viz., qSV-6a (RM204 and RM402) for root length; qVI (RM20429 and RM3) for seedling vigour index; qGP-6 (RM528 and RM400) for germination percentage revealed that the marker alleles were found to show significant associations with qVI and qGP-6 QTLs. The majority of genotypes with high early seedling vigour are with qVIHap-1 (220 and 160 bp) and qGPHap-1 (290 and 290 bp). The rice genotypes with superior haplotypes for early seedling vigour are BMF536, BMF540, BMF525, MM129 and MDP2. In conclusion, here we demonstrated that the markers RM20429 and RM3 are associated with seedling vigour index whereas RM528 and RM400 are associated with germination percentage. Therefore, these markers can be utilized to develop varieties suitable for DSR conditions through haplotype-based breeding. In addition, the rice genotypes with superior haplotypes can be of immense value to use as donors or can be released as varieties also under DSR conditions.


Acute left anterior descending artery occlusion in a hemophiliac A patient during recombinant factor VIII infusion: treatment with coronary angioplasty.
Acute myocardial infarction in association with the replacement of recombinant factor VIII in hemophiliacs has not been documented. We describe the use of PTCA in a hemophiliac A patient who developed acute myocardial infarction during factor VIII replacement. Because surgery in hemophiliac A patients remains hazardous, PTCA seems to be an attractive alternative.


Developing and validating learning domains, competencies, and evaluation items for global health clinical immersion practicums for graduate-level nursing programs.
To develop and validate learning domains, competencies, and evaluation tool for graduate-level experiential nursing global health programs. Standard competencies have not been synthesized and delineated nor have evaluation tools been developed for global health programs at the graduate level. A combination of a documentary literature review and expert consensus panel to validate results was used as a design for this study. The NLM and CINAHL databases were searched for articles published between 2007 - 2017 relevant to graduate-level global health nursing programs. Data were extracted and coded, from which themes regarding learning domains, competencies and evaluation items were derived. We then used a three-step expert panel to refine and form a statistical representation (>0.78 agreement on importance, relevance and clarity) of the learning domains, competencies, and evaluation items. Relevant articles (N = 26) were included for the documentary review, 18 concerning learning domains of global health immersion programs and eight concerning interdisciplinary global health competencies specific to nursing. These learning relationships were then formatted into a table subdivided between learning categories for expert panel consensus. After expert panel review, a compendium of learning domains, competencies, and evaluation items resulted. Global health clinical learning practicums are essential for graduate-level preparation of nurses. Learning domains, competencies, and evaluation tools need to be adopted and empirically tested by international and national nursing associations. The results of this study need further testing to aid these associations.


Haemangio-endothelioma of the orbit.
A case of infantile orbital haemangio-endothelioma was successfully treated with corticosteroids. Roentgenological and histological findings before and after treatment are described. It is suggested that an haemangio-endothelioma may be transformed into a cavernous angioma.


Special problems in ophthalmic subspecialties.
A study of 276 medicolegal cases disclosed the number in various ophthalmic subspecialties. The medical reasons for filing these claims were usually based upon omission or commission of acts fundamental to good basic ophthalmology, not the omission of sophisticated procedures. Among the lesions were that physicians should plan for the care of emergencies, use few types of drugs, order roentgenograms if suspicions arise, use consultants, stay well within one's level of competence, and document everything.


Attraction of phlebotomine sand flies to baited and non-baited horizontal surfaces.
Female phlebotomine sand flies (Diptera: Psychodidae) transmit leishmaniasis as they engorge on vertebrate blood required for egg production. Phlebotomus (Phlebotomus) papatasi (Scopoli, 1786), the vector of Leishmania major (Yakimoff & Schokhor, 1914), the causative agent of cutaneous leishmaniasis (CL) were not attracted to large horizontal sticky traps (LHSTs) unless these were baited with CO2 derived from dry ice or from fermenting sugar/yeast mixture (SYM). Attraction of P. papatasi males by CO2 may indicate their tendency to mate on or near the blood-host. Male P. (Larroussius) orientalis (Parrot, 1936), the vector of visceral leishmaniasis (VL) in Ethiopia, were collected on LHSTs in large numbers. Although the number of females remained low, augmentation with SYM, increased the number of females by 800% while the number of males increased by only about 40%. Apparently, male P. orientalis utilize the horizontal surfaces for forming mating swarms. P. (Paraphlebotomus) sergenti (Parrot, 1917), is the vector of CL caused by Leishmania tropica. Although approximately twice as many P. sergenti males were caught on LHSTs as females, it appears that LHSTs were attractive to both sexes. Use of SYM baits is potentially useful for monitoring phlebotomine sand flies in places where dry ice is unobtainable or prohibitively expensive. LHSTs can provide an inexpensive alternative to CDC traps for monitoring some species of sand flies. Unfortunately, the numbers of female sand flies, crucial for estimating transmission of Leishmania, is usually low on LHSTs.


Common bile duct necrosis after cardiac catheterization.
A case of necrosis of the entire extrahepatic biliary tract after cardiac catheterization is presented. The axial blood supply to these structures makes them susceptible to ischemic injury.


NGB 2904 and NGB 2849: two highly selective dopamine D3 receptor antagonists.
N-(4-[4-¿2, 3-dichlorophenyl¿-1-piperazinyl]butyl)-3-fluorenylcarboxamide and N-(4-[4-¿2, 3-dichlorophenyl¿-1-piperazinyl]butyl)-2-biphenylenylcarboxamide were prepared in several steps from 2,3-dichloroaniline. These compounds were identified as highly selective dopamine D3 receptor antagonists.


Determinants of Effort Intolerance in Patients With Heart Failure: Combined Echocardiography and Cardiopulmonary Stress Protocol.
The purpose of this study was to assess individual mechanisms of effort intolerance in patients with heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), or normal cardiac function using combined echocardiography and cardiopulmonary stress testing. Combined stress echocardiography and cardiopulmonary tests visualize cardiac chambers in 4 well-defined activity levels (rest, unloaded, anaerobic threshold, and peak), allowing noninvasive assessment of cardiac function, hemodynamics, and arterial venous oxygen content difference (AVo(2)Diff) during all stages. Left ventricular volumes, stroke volume (SV), S', E/e', oxygen consumption (Vo(2)), and AVo(2)Diff were measured in all effort stages using ramp semirecumbent cycle prolonged (≥8 min) exercise in 45 consecutive subjects evaluated for effort intolerance (14 normal cardiac function, 16 HFpEF, and 15 HFrEF patients; age 56.5 ± 16 years; 73% male). In HFpEF and HFrEF, the changes in Vo2 were attenuated (between group p = 0.003; group by time interaction p < 0.0001), as well as peak heart rate (p = 0.0001; p = 0.0001) and SV (p = 0.006; p = 0.0001). End-diastolic volume to E/e' ratio (measure of compliance) was superior in HFrEF and normal patients at baseline but worsened in HFpEF and HFrEF at peak exercise (8.3 ± 4 vs. 11.6 ± 5 vs. 19.1 ± 8; p = 0.004; p = 0.01). Functional mitral regurgitation worsened even during the unloaded stage, mostly in patients with HFrEF, but also in several patients with HFpEF. In multivariable analysis, heart rate response (p = 0.007), and AVo(2)Diff (p < 0.0001) were the most significant independent predictors of effort capacity; SV was not. Combined tests are feasible and allow noninvasive evaluation of effort intolerance. In HFpEF and HFrEF patients, exercise intolerance is predominantly due to chronotropic incompetence and peripheral factors. Combined stress echocardiography and cardiopulmonary tests may have potential for clinical management and selection of patients for trials.


The endothelial cell cytoskeleton modulates extravascular polymorphonuclear leukocyte accumulations in vivo.
Actin microfilaments, key elements in the endothelial cell (EC) cytoskeleton, have been noted in in vitro studies to play a modulating role in the diapedesis of polymorphonuclear leukocytes (PMN). The role of the cytoskeleton in PMN diapedesis in vivo was the subject of this study. Small skin abrasions were produced in rabbits. Cytoskeletal manipulation was accomplished by local application of phalloidin which promotes microfilament assembly or cytochalasin B which causes their disassembly, prior to addition of a chemotaxin. When the initial treatment to the abrasion site was saline, the secondary addition of more saline resulted in PMN accumulations, expressed as PMN/mm3 of 36 +/- 19, while 10(-4) M cytochalasin B led to 91 +/- 32 (P less than 0.05). Secondary addition of chemotaxins or histamine also led to significant PMN accumulations of 169 +/- 54 with 10(-8) M leukotriene (LT) B4, 318 +/- 85 with zymosan-activated plasma (ZAP), and 158 +/- 48 with 10(-4) M histamine. When the initial treatment was 10(-8) M phalloidin, PMN accumulations were reduced to 31 +/- 22 with cytochalasin B (P less than 0.05 relative to saline as initial treatment); 63 +/- 43 with LTB4 (P less than 0.05); 137 +/- 48 with ZAP (P less than 0.05); and 51 +/- 35 with histamine (P less than 0.05). In contrast, initial blister treatment with cytochalasin B rather than saline increased PMN accumulations in response to LTB4, 291 +/- 71 (P less than 0.05), and histamine, 270 +/- 56 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology.
The role of infection in the pathogenesis of preterm labor and delivery, and the specific mechanisms through which this association is demonstrated are presented. Cellular and biochemical changes that initiate parturition in the setting of infection are discussed, particularly prostaglandins and cytokines.


Dissection of complex traits of tomato in the post-genome era.
We present the main advances of dissection of complex traits in tomato by omics, the genes identified to control complex traits and the application of CRISPR/Cas9 in tomato breeding. Complex traits are believed to be under the control of multiple genes, each with different effects and interaction with environmental factors. Advance development of sequencing and molecular technologies has enabled the recognition of the genomic structure of most organisms and the identification of a nearly limitless number of markers that have made it to accelerate the speed of QTL identification and gene cloning. Meanwhile, multiomics have been used to identify the genetic variations among different tomato species, determine the expression profiles of genes in different tissues and at distinct developmental stages, and detect metabolites in different pathways and processes. The combination of these data facilitates to reveal mechanism underlying complex traits. Moreover, mutants generated by mutagens and genome editing provide relatively rich genetic variation for deciphering the complex traits and exploiting them in tomato breeding. In this article, we present the main advances of complex trait dissection in tomato by omics since the release of the tomato genome sequence in 2012. We provide further insight into some tomato complex traits because of the causal genetic variations discovered so far and explore the utilization of CRISPR/Cas9 for the modification of tomato complex traits.


Plasmacytoma of the proximal humerus.
This is the case report of a 67-year-old man who developed a solitary lytic lesion of the proximal humerus. Through further studies that included MR imaging of the affected upper extremity and biopsy, a final diagnosis of plasmacytoma was given. We present the clinical, imaging, and histologic findings and review the general characteristics of this neoplastic condition.


Trends in risk factors for lifestyle-related diseases by socioeconomic position in Geneva, Switzerland, 1993-2000: health inequalities persist.
We report on trends in risk factors for lifestyle-related diseases among socioeconomic position (SEP) groups. We continuously surveyed the adult population of Geneva, Switzerland, for 8 years (1993-2000) with independent, cross-sectional surveys of representative samples (4207 men and 3987 women aged 35-74 years). Age-adjusted linear regression slopes estimated annual risk factor trends. Interaction terms were tested for trend differences between SEP groups. Overall, low-SEP persons had the worst risk factor profiles. Eight-year trends indicate that (1) number of pack-years smoked decreased by half a pack-year among high-SEP female current smokers only; (2) obesity prevalence more than doubled from 5% to 11% among high-SEP men only; (3) systolic and diastolic blood pressures decreased similarly in all SEP groups; (4) unsaturated-to-saturated dietary fat ratio declined in the low-SEP group only; and (5) physical inactivity and current/former cigarette smoking prevalences remained unchanged in all SEP groups. Smoking, obesity, high blood pressure, and physical inactivity are more prevalent among low-SEP persons. Most socioeconomic risk factor differences remained stable in the 1990s. Thus, social inequalities in chronic disease morbidity and mortality will persist in the next decades.


More Flavor for Flavonoid-Based Interventions?
Poor diets are associated with obesity and a decline in cognitive function. Flavonoids are plant compounds that have been associated with improved metabolic parameters in obesity and reversal of cognitive decline. Given that microbial flavonoid conversion is important for bioactivity, flavonoid-derived neuroactive compounds may be functionally crucial in the gut microbiome-brain axis.


Partial Resuscitative Endovascular Balloon Occlusion of the Aorta Limits Ischemia-Reperfusion Injury After Simulated Aeromedical Evacuation.
One of the advantages of partial Resuscitative Endovascular Balloon Occlusion of the Aorta (pREBOA) compared to the original model is the mitigation of reperfusion injury. The safety and efficacy of pREBOA have not been demonstrated in the setting of aeromedical evacuation. We hypothesized that the pREBOA would result in less ischemia-reperfusion injury after altitude exposure. Twenty-four swine underwent femur fracture with hemorrhage for 20 min, followed by resuscitative endovascular balloon occlusion of the aorta (REBOA) deployment to Zone 1 and were randomized to pREBOA-PRO (Prytime Medical Devices Inc) full inflation, partial inflation, or sham inflation and then an altitude exposure of ground level or 8000 ft for 15 min. The primary endpoint was to examine if the balloon functioned at altitude. Our secondary endpoint was investigating evidence of ischemia-reperfusion by hemodynamic instability, electrolyte derangements, and acidosis. Comparisons were made by ANOVA. After deflation, the partially inflated group maintained a higher mean arterial pressure (MAP) compared to fully inflated group (P = 0.026). Full REBOA pigs were more tachycardic compared to sham pREBOA at ground (P < 0.001) and this was exacerbated at altitude (P < 0.001). Full REBOA pigs were more acidotic than sham and pREBOA at ground pigs (P = 0.0006 and P = 0.0002, respectively). Altitude increased the acidosis in full REBOA pigs, resulting in a greater base deficit (P < 0.0001), lactate (P < 0.0001), and IL-6 (P = 0.006). PREBOA resulted in less severe ischemia-reperfusion injury at both altitude and ground, while full balloon inflation at altitude exacerbated acidosis and ischemia-reperfusion injury. Efforts should therefore be made to utilize partial balloon occlusion when employing the REBOA catheter.


Pathognomonic aspect of germinoma on CT scan.
Bilateral visual impairment, associated with amenorrhea, diabetes insipidus and mental deterioration were observed in a 28 year old woman. CT scan revealed bilateral symmetrical infiltrative processes surrounding the ventricular system, which was confirmed by postmortem examination. Histologically the lesion was a germinoma.


Corrigendum: Diversity and heterogeneity in human breast cancer adipose tissue revealed at single-nucleus resolution.
[This corrects the article DOI: 10.3389/fimmu.2023.1158027.].


Formation of carnosine-Cu(II) complexes prevents and reverts the inhibitory action of copper in P2X4 and P2X7 receptors.
To further analyze the action of copper on brain synaptic mechanisms, the brain dipeptide carnosine (beta-alanyl-L-histidine) was tested in Xenopus laevis oocytes expressing the rat P2X4 or P2X7 receptors. Ten micromolar copper halved the currents evoked by ATP in both receptors; co-application of carnosine plus copper prevented the metal induced-inhibition with a median effective concentration of 12.1 +/- 3.9 and 12.0 +/- 5.5 microm for P2X4 and P2X7, respectively. Zinc potentiated only the P2X4 ATP-evoked currents; carnosine had no effect over this metal. The relative potency and selectivity of classical metal chelators to prevent the copper inhibition was compared between carnosine and penicillamine (PA), bathophenanthroline (BPh) or L-histidine (His). Their rank order of potency in P2X4 and P2X7 receptors was carnosine = PA = His > BPh > Glycine (Gly) and carnosine = BPh = His > PA > Gly, respectively. The potency to prevent the zinc-induced potentiation in the P2X4 receptor was BPh > PA > His; carnosine, Gly and beta-alanine were inactive. Whereas 1-100 microm carnosine or His alone did not modify the ATP-evoked currents, 10-100 microm PA augmented and 100 microm BPh decreased the ATP-evoked currents. Carnosine was able to revert the copper-induced inhibition restoring the maximal ATP gated current in a concentration-dependent manner. Electronic spectroscopy confirm the formation of carnosine-Cu(II) complexes, mechanism that can account for the prevention and reversal of the copper inhibition, revealing its potential in copper intoxication treatment.


Mapping optogenetically-driven single-vessel fMRI with concurrent neuronal calcium recordings in the rat hippocampus.
Extensive in vivo imaging studies investigate the hippocampal neural network function, mainly focusing on the dorsal CA1 region given its optical accessibility. Multi-modality fMRI with simultaneous hippocampal electrophysiological recording reveal broad cortical correlation patterns, but the detailed spatial hippocampal functional map remains lacking given the limited fMRI resolution. In particular, hemodynamic responses linked to specific neural activity are unclear at the single-vessel level across hippocampal vasculature, which hinders the deciphering of the hippocampal malfunction in animal models and the translation to critical neurovascular coupling (NVC) patterns for human fMRI. We simultaneously acquired optogenetically-driven neuronal Ca2+ signals with single-vessel blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-fMRI from individual venules and arterioles. Distinct spatiotemporal patterns of hippocampal hemodynamic responses were correlated to optogenetically evoked and spreading depression-like calcium events. The calcium event-related single-vessel hemodynamic modeling revealed significantly reduced NVC efficiency upon spreading depression-like (SDL) events, providing a direct measure of the NVC function at various hippocampal states.


Developmental changes in DNAse I digestibility and RNA template activity of neuronal nuclei relative to the postnatal appearance of a short DNA repeat length.
Neurons of the rat cerebral hemispheres are known to undergo a postnatal shift to a short DNA repeat length. In the present study we report that rat neuronal nuclei are more sensitive to digestion with DNAse I when isolated at a developmental stage after the shift in neuronal DNA repeated length compared to nuclei isolated before the shift. This observation may suggest that a decondensation of neuronal chromatin accompanies the postnatal shift in DNA repeat length. We have also found that neuronal nuclei isolated after the shift to a short DNA repeat length demonstrate an increased ability to synthesize RNA in vitro.


Psychosocial issues and sleep quality among seafarers: a mixed methods study.
Seafarers, especially those working for a prolonged period of time, are exposed to a high number of social, psychological and physical stressors including irregular working hours. This study aims to identify important aspects of Asian seafarers' psychosocial wellbeing and quality of sleep that could affect safety and health of the seafarers in long voyage tankers. In this mixed method study, psychological health issues were investigated through semi-structured interviews with 17 Asian male seafarers. Participants were selected through purposive sampling. In the quantitative phase, 179 seafarers completed the Pittsburgh Sleep Quality Index (PSQI) on sleep quality. From the interviews, three categories consisting of six themes emerged, including sleep abnormalities, inevitable stressors, and lack of social communication. The majority of the seafarers believed that their quality of sleep was affected by their physical work environment and by issues raised by their families. As reasons for stress at sea, they mentioned the nature of the occupation and the psychosocial work environment. Most participants pointed out that lack of social communications had adverse effects on both their work lives on board and their private lives at home. In the quantitative phase, the response rate was 81.4%. Mean PSQI index was 5.9 (SD 2.6 and range from 2 to 14). Sleep impairment was higher in academic than non-academic individuals (p < 0.001). Sleep abnormalities and lack of social communication should be considered as modifiable risk factors for seafarers' psychosocial well-being at sea.


Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects.
Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha1A-adrenergic receptor (alpha1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level. A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha1A-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours. Our data suggest that the alpha1A-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha1A-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.


Mechanical and electromyographic responses during the 3-min all-out test in competitive cyclists.
While the 3-min all-out test is an ideal exercise paradigm to study muscle fatigue during dynamic whole-body exercise, so far it has been used mainly to provide insight into the bioenergetic determinants of performance. To shed some light into the development of peripheral muscle fatigue during the 3-min all-out test, we investigated the time course of muscle-fibre conduction velocity (MFCV). Twelve well-trained cyclists (23 ± 3 yrs) performed an incremental test, a 3-min all-out familiarization trial and a 3-min all-out test. Surface electromyographic signals were detected from the vastus lateralis muscle of the dominant limb. MFCV decreased with power output, though with a somewhat different time course, and the two parameters were strongly correlated (r = 0.87; P < 0.001). A modest decrease in MFCV (17.7 ± 4.8%), probably due to the endurance characteristics of the subjects, may help explain why a relatively high power output (79 ± 8% of the peak power output of the incremental test; 60 ± 14% of the difference between this peak value and the gas exchange threshold) was still maintained at the end of the test. These findings suggest that muscle fatigue substantially affects performance in the 3-min all-out test, expanding on the traditional bioenergetic explanation that performance is limited by rate and capacity of energy supply.


Subcortical Cognition: The Fruit Below the Rind.
Cognitive neuroscience has highlighted the cerebral cortex while often overlooking subcortical structures. This cortical proclivity is found in basic and translational research on many aspects of cognition, especially higher cognitive domains such as language, reading, music, and math. We suggest that, for both anatomical and evolutionary reasons, multiple subcortical structures play substantial roles across higher and lower cognition. We present a comprehensive review of existing evidence, which indeed reveals extensive subcortical contributions in multiple cognitive domains. We argue that the findings are overall both real and important. Next, we advance a theoretical framework to capture the nature of (sub)cortical contributions to cognition. Finally, we propose how new subcortical cognitive roles can be identified by leveraging anatomical and evolutionary principles, and we describe specific methods that can be used to reveal subcortical cognition. Altogether, this review aims to advance cognitive neuroscience by highlighting subcortical cognition and facilitating its future investigation.


Index of the transmissible common liability to addiction: heritability and prospective associations with substance abuse and related outcomes.
Substance use disorders (SUDs) are highly comorbid and exhibit a relatively late onset. As such, many behaviors and personality traits present prior to the initiation of substance use can be used to predict later SUDs. The transmissible liability index (TLI) is a quantitative measure of such behaviors that indexes the common liability to SUDs. We examined the predictive utility and heritability of the TLI in a large community twin sample. Using the Minnesota Twin Family Study (N=2510), we estimated TLI scores from mother, child, and teacher reports of symptom and personality measures assessed at age 11. We then estimated the genetic and environmental contributions to the association between TLI scores at age 11 and composite measures of substance abuse and behavioral disinhibition (antisocial behavior) at age 17. For both male and female twins, TLI scores were highly heritable (.76) and exhibited moderate associations with adolescent substance abuse (r=.29) and behavioral disinhibition (r=.40). Genetic factors accounted for the association between TLI scores and the adolescent outcomes. Findings support the utility of the TLI as a measure of the inherited, common liability to SUDs.


Choroidal thickness in patients with systemic arterial hypertension: a systematic review and meta-analysis.
The global burden of hypertension is constantly increasing with adverse cardiovascular and ocular sequelae. The association between elevated blood pressure and choroidal thickness (CT), as assessed via optical coherence tomography (OCT), is poorly understood. Studies including hypertensive adults and normotensive controls undergoing OCT were evaluated for inclusion in this meta-analysis. The primary endpoint was CT difference between hypertensive and normotensive adults. We conducted a systematic review and after searching 1011 results from MEDLINE, ClinicalTrials.gov, medRxiv and Cochrane Library, six studies were deemed eligible and were pooled according to a random-effect model. A statistically significant reduction in choroidal thickness was found in hypertensive adults (n = 454) as compared with normotensive controls (n = 365) [mean difference: -0.77; 95% confidence intervals: (-1.20, -0.34); p = 0.0004]. The main limitations of this meta-analysis are the relatively small population included and the high statistical heterogeneity (I 2 = 87%) among the various studies. Of note, after excluding one study the heterogeneity was markedly reduced. Choroidal thickness is reduced among hypertensive subjects compared with normotensive controls. This finding mandates further examination in the context of long-term clinical outcomes.


Estradiol impairs epithelial CXCL1 gradient in the cervix to delay neutrophil transepithelial migration during insemination.
Female reproductive mucosa must allow allogenic sperm survival whereas at the same time, avoid pathogen infection. To preserve sperm from neutrophil attack, neutrophils disappear from the vagina during the ovulatory phase (high estradiol); although the mechanisms that regulate neutrophil influx to the vagina during insemination remain controversial. We investigated the sex hormone regulation of the neutrophil migration through the cervix during insemination and revealed that ovulatory estradiol dose fades the CXCL1 epithelial expression in the ectocervix and fornix; hence, retarding neutrophil migration and retaining them in the epithelium. These mechanisms spare sperm from neutrophil attack to preserve reproduction, but might compromise immunity. However, luteal progesterone dose promotes the CXCL1 gradient expression to restore neutrophil migration, to eliminate sperm and prevent sperm associated pathogen dissemination. Surprisingly, these mechanisms are hormone dependent and independent of the insemination. Thus, sex hormones orchestrate tolerance and immunity in the vaginal lumen by regulating neutrophil transepithelial migration in the fornix and ectocervix.


Effects of a Community-Level Intervention on Alcohol-Related Motor Vehicle Crashes in California Cities: A Randomized Trial.
This trial assesses the effects of a community-level alcohol prevention intervention in California on alcohol-related motor vehicle crashes. The study is a group RCT with cities as the unit of assignment to condition and as the unit of analysis. A total of 24 California cities with populations between 50,000 and 450,000 were chosen at random and roughly matched into pairs before randomly assigning 12 each to the intervention and control conditions. The intervention, aimed at reducing excessive drinking among adolescents and young adults, included driving under the influence sobriety checkpoints, saturation patrols, and undercover operations to reduce service of alcohol to intoxicated patrons in bars, all including high visibility so the public would be aware of them. A measure of overall intervention intensity or dosage was created. The outcome was a monthly percentage of all motor vehicle crashes that were single vehicle nighttime crashes for drivers aged 15-30 years. Multilevel analyses were conducted to examine intervention effects on alcohol-related crashes among drivers aged 15-30 years. Crash data were obtained in 2018 with data preparation and analysis conducted in 2019. Intent-to-treat analyses indicated a 17% reduction in the percentage of alcohol-involved crashes among drivers aged 15-30 years relative to controls, which translates to about 310 fewer crashes. Dosage was found to have a statistically significant effect on crashes among this age group, although not in the expected direction. Enhanced alcohol enforcement operations involving both community health and law enforcement agencies can help to reduce alcohol-impaired driving and related consequences among young people. Including measures of intervention dosage raises interesting questions about the understanding of the impact of the community intervention. Future studies should continue to further develop implementation strategies that may more effectively and efficiently reduce community alcohol-related harm.


Studies on the ionophorous antibiotics. VIII. Effects of monovalent and divalent cation ionophores on blood platelets.
The effects of a monovalent cation ionophore etheromycin (CP-38295) and a divalent cation ionophore lysocellin on blood platelets function have been investigated. When platelets were incubated with 3 micronM of each ionophore, the simultaneous induction of secretion of stored serotonin and efflux of intracellular calcium occurred, but there was no detectable influx of extracellular calcium. With increasing concentrations, these compounds caused platelet aggregation accompanied by increased influx of external calcium. These results are consistent with the hypothesis that the liberation of calcium from the intracellular store mediated the platelet secretion reaction.


A novel approach to modelling transcriptional heterogeneity identifies the oncogene candidate CBX2 in invasive breast carcinoma.
Oncogenes promote the development of therapeutic targets against subsets of cancers. Only several hundred oncogenes have been identified, primarily via mutation-based approaches, in the human genome. Transcriptional overexpression is a less-explored mechanism through which oncogenes can arise. Here, a new statistical approach, termed oncomix, which captures transcriptional heterogeneity in tumour and adjacent normal (i.e., tumour-free) mRNA expression profiles, was developed to identify oncogene candidates that were overexpressed in a subset of breast tumours. Intronic DNA methylation was strongly associated with the overexpression of chromobox 2 (CBX2), an oncogene candidate that was identified using our method but not through prior analytical approaches. CBX2 overexpression in breast tumours was associated with the upregulation of genes involved in cell cycle progression and with poorer 5-year survival. The predicted function of CBX2 was confirmed in vitro, providing the first experimental evidence that CBX2 promotes breast cancer cell growth. Oncomix is a novel approach that captures transcriptional heterogeneity between tumour and adjacent normal tissue, and that has the potential to uncover therapeutic targets that benefit subsets of cancer patients. CBX2 is an oncogene candidate that should be further explored as a potential drug target for aggressive types of breast cancer.


Contribution of noradrenergic and serotonergic neurons to the circulatory effects of centrally acting clonidine and alpha-methyldopa in rabbits.
The effects of intracisternal clonidine (0.04, 0.2, and 1.0 microgram/kg) and of alpha-methyldopa (alpha-MD; 400 micrograms/kg) on mean arterial pressure (MAP) and heart rate (HR) were studied in conscious rabbits before, and 7 and 14 days after, intracisternal injection of (a) vehicle, (b) 6-hydroxydopamine (6-OHDA; 600 micrograms/kg), or (c) 5,6-dihydroxytryptamine (5,6-DHT; 633 micrograms/kg) (n = 6 per group). In the initial control experiment clonidine and alpha-MD produced similar falls in MAP and HR in each group; there was also good reproducibility of responses in vehicle-treated rabbits on the 3 experimental days. But after 6-OHDA or 5,6-DHT administration the circulatory effects of clonidine and alpha-MD were markedly attenuated. On day 14 after injection of 6-OHDA, the clonidine-induced falls in MAP and HR averaged 38 and 18%, respectively, of the control responses (p less than 0.001). On day 14 after 5,6-DHT administration, the falls in MAP and HR after clonidine administration were reduced to 27 and 13% of control, respectively (p less than 0.01), while the corresponding responses after alpha-MD administration were 39 and 61% of control (p less than 0.05). Neurochemical findings suggest that 6-OHDA affected noradrenergic (NA), dopaminergic (DA), but not serotonergic (5HT) neurons, and that 5,6-DHT affected 5HT but not NA and DA neurons. We conclude that the circulatory effects of clonidine and alpha-MD are mediated through both central NA and 5HT neurons.


[Newborn of diabetic mother. Glucose in amniotic fluid and clinical conditions (author's transl)].
Clinical and analytical data of sixteen newborns of insulin dependant mothers are studied. Relation between these data and newborn conditions as Apgar score and hypoglicemia are considered.


The endothelin peptides ET-1, ET-2, ET-3 and sarafotoxin S6b are co-mitogenic with platelet-derived growth factor for vascular smooth muscle cells.
We have investigated whether any of the three isoforms of endothelin (ET) ET-1, ET-2 and ET-3 or the structurally similar peptide sarafotoxin S6b is mitogenic on its own for rat vascular smooth muscle cells in culture. DNA synthesis was determined by a peroxidase-linked double antibody technique to detect bromodeoxyuridine incorporation into the nucleus and stained nuclei were counted by image analysis. None of the ET peptides or sarafotoxin S6b (up to 100 nM) was capable of initiating DNA synthesis in the absence of platelet derived growth factor (PDGF) or fetal calf serum. All the peptides potentiated the mitogenic effect of low concentrations of PDGF. ET-1 and ET-2 (10 nM) caused a 2-fold increase in the number of stained nuclei induced by 5 nM and 10 nM PDGF, whereas ET-3 and sarafotoxin S6b were less potent. These findings demonstrate that ET is a co-mitogen for rat vascular smooth muscle cells. The release of ET at sites of endothelial injury may therefore enhance the mitogenic action of locally acting PDGF on vascular smooth muscle cells and potentiate the proliferative response.


Promotion of skin wound healing using hypoimmunogenic epidermal cell sheets.
The physiological process of wound healing is dynamic, continuous, and intricate. Nowadays, full-thickness burn wounds are treated by autologous skin transplantation. Unfortunately, when substantial burns develop, there are fewer donor sites accessible, making it difficult to satisfy the requirement for large-scale skin transplants and increasing the risk of patient mortality. This study investigated the possibility of using a newly created hypoimmunogenic epidermal cell sheet to heal skin wounds. Transfection with lentivirus was used to generate Keratinocytes (KCs) that overexpress Indoleamine 2,3-Dioxygenase (IDO). Western blotting and quantitative polymerase chain reaction were used to measure IDO levels. To evaluate the function of IDO+ keratinocytes, CCK-8 and Transwell assays were performed. In cell sheet induction media, KCs and Fibroblasts (FBs) were cultured to yield epidermal cell sheets. The full-thickness skin excisions of BALB/c mice were transplanted with epidermal cell sheets. To assess the tumorigenicity of IDO+ keratinocytes, BALB/c nude mouse xenograft models were also used. CD3 and CD31 immunofluorescence labeling of wound tissue on day 12 to identify T lymphocyte infiltration and capillary development. ELISA measurement of IL-1 and TNF-α concentrations. IDO + keratinocytes dramatically enhanced the expression levels of IDO mRNA and protein, as well as the amount of kynurenine in the conditioned media of IDO+ keratinocytes, compared to the Control and NC groups. CD8+ T cell apoptosis was considerably greater in the IDO group than in the Control and NC groups. Nevertheless, the proliferation and migratory capabilities of IDO+ keratinocytes were not substantially different from those of the Control and NC groups. In vitro cultivation of the hypoimmunogenic epidermal cell sheet was effective. In vivo transplantation experiments demonstrated that IDO+ epidermal cell sheets can effectively promote wound healing without tumorigenicity, and IDO+ epidermal cell sheets may promote wound healing by decreasing the expression levels of inflammatory factors (TNF and IL-1) in wound tissue, decreasing CD3+ T lymphocytes, and increasing infiltration and new capillaries in wound tissue. In this study, we successfully constructed the hypoimmunogenic epidermal cell sheet and demonstrated that the hypoimmunogenic epidermal cell sheet could accelerate wound healing.


Cataleptic effects of gamma-hydroxybutyrate (GHB) and baclofen in mice: mediation by GABA(B) receptors, but differential enhancement by N-methyl-d-aspartate (NMDA) receptor antagonists.
Gamma-hydroxybutyrate (GHB) is a gamma-aminobutyric acid (GABA) analog that is used to treat narcolepsy but that is also abused. GHB has many actions in common with the GABA(B) receptor agonist baclofen, but their underlying GABA(B) receptor mechanisms may be different. The aim of this study is to further investigate a possible differential role of glutamate in GABA(B) receptor-mediated effects of GHB and baclofen. The experiments examined the effects of non-competitive antagonists at the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors on GHB-induced catalepsy and compared these effects with those on baclofen-induced catalepsy. In C57BL/6J mice, ketamine, phencyclidine (PCP), and dizocilpine (MK-801) all enhanced GHB-induced catalepsy. They did so with a potency order (i.e., MK-801 > PCP > ketamine) consistent with their relative potencies as NMDA antagonists but not as inhibitors of dopamine or organic cation transporters. Ketamine, PCP, and MK-801 enhanced catalepsy along inverted U-shaped dose-response curves likely because higher doses affected motor coordination, which limited their catalepsy-enhancing effects. Doses that were maximally effective to enhance GHB-induced catalepsy did not affect the cataleptic effects of baclofen. The finding that NMDA receptor antagonists enhance the cataleptic effects of GHB but not those of baclofen is further evidence that the GABA(B) receptor mechanisms mediating the effects of GHB and GABA(B) agonists are not identical. Differential interactions of glutamate with the GABA(B) receptor mechanisms mediating the effects of GHB and baclofen may explain why GHB is effective for treating narcolepsy and is abused, whereas baclofen is not.


Pharmacological aspects of selected herbs employed in hispanic folk medicine in the San Luis Valley of Colorado, USA: II. Asclepias asperula (inmortal) and Achillea lanulosa (plumajillo).
Interviews with Hispanic families in the San Luis Valley of Colorado revealed that several herbs, including Asclepias asperula (inmortal) and Achillea lanulosa (plumajillo), are popular ingredients in Hispanic folk medicine preparations. A review of the scientific literature indicates that related species of Asclepias asperula and Achillea lanulosa contain pharmacologically active compounds; these data serve as the focal point for continuing ethnopharmacologic investigation at the University of Colorado School of Pharmacy.


Age at menarche and weight concerns in relation to smoking trajectory and dependence among adolescent girls enrolled in a smoking cessation trial.
Many girls adopt dieting and other practices (i.e. cigarette smoking) to control weight during puberty. This analysis explored the relationship between age at menarche and onset of daily smoking, and whether this relationship was influenced by weight concerns among treatment seeking female adolescents. The sample consisted of 71 participants enrolled in a smoking cessation trial (age 15.2+/-1.3 years; 74.7% European American, baseline BMI 24.7+/-5.4, age at menarche 11.7+/-1.3 years, Fagerström Test for Nicotine Dependence score 7.0+/-1.2). Over 60% of participants reported weight concerns at baseline, based on responses to the Eating Disorders module from the Diagnostic Interview for Children and Adolescents. Linear regression analyses revealed a significant association between age at menarche and age of onset of daily smoking (beta=0.18+/-0.09, p=0.038). Having weight concerns did not modify the relationships between age at menarche and smoking trajectory/severity or abstinence. Findings support previous research showing that early maturation represents a risk factor for substance use. Further study in larger samples that include non-treatment-seeking adolescent female smokers is warranted.


Identification of a Bacillus thuringiensis Q1 compound with algicidal activity.
Bacillus thuringiensis Q1, isolated from the eutrophic waters of the Haihe River in Tianjin, possesses remarkable algae dissolving character. We determined the lytic effect of B. thuringiensis Q1 fermentation broth, and it proved to be pH- and temperature-stable. Then, we investigated the structure of the algicidal compound by high performance liquid chromatography, gas chromatography tandem quadrupole mass spectrometry and fourier transform infrared spectroscopy, and identified as purine-derived C12H15O5N5. To further understand B. thuringiensis Q1, we performed genome sequencing and analysis. The genome was 5341610 bp, with 35.31% GC content. Some elements involved in algicidal activity, such as quorum sensing pathway and ABC transporter were predicted. Our results reveal that B. thuringiensis Q1 can be used for biological control of harmful algal blooms.


Multifocal hepatic abscesses in immunocompetent patient due to Bartonella henselae: Case report with review of literature.
To the best of our knowledge, this is the first case of multifocal hepatic abscesses in a young immunocompetent adult from India, which was successfully treated with hepatectomy and short course of oral antibiotic regimen. Publishing further such case reports will provide more clarity regarding the clinical significance of the disease, including associated risk factors and appropriate treatment.


Perceived segmentation of center from surround by only illusory contours causes chromatic lateral inhibition.
When a light and also its surrounding context slowly oscillate in chromaticity over time, the color appearance of the light depends on the relative phase of center and surround. The influence of the surround is generally accounted for by retinotopic center-surround organization, with the surround inhibiting signals from the center. The traditional neural account, however, cannot rule out lateral inhibition due to cortical mechanisms sensitive to object segmentation cues. Experiments here reveal that illusory contours are sufficient to separate a center from its surround. Observers adjusted the Michelson contrast of a matching disk to equal the perceived modulation depth of a central area within a surround. Both the central test and matching disk were maintained at constant luminance and modulated in-phase at 2Hz along one chromatic axis (L/(L+M) or S/(L+M)). The center was perceptually segmented from the surround by either a physical (retinotopic separation) or illusory (cortically represented) triangle contour. Segmentation of center from surround by the illusory contour strongly attenuated the perceived modulation depth for both chromatic axes. Further, the strength of attenuation was consistently greater with the illusory than the physically segmenting triangle. This cannot be accounted for by retinal center-surround antagonism; instead it points to a cortical neural representation of contours, with lateral inhibition following neural mechanisms sensitive to object segmentation cues.


Immune-induced expression of lipocalin-2 in brain endothelial cells: relationship with interleukin-6, cyclooxygenase-2 and the febrile response.
Interleukin (IL)-6 is critical for the febrile response to peripheral immune challenge. However, the mechanism by which IL-6 enables fever is still unknown. To characterise the IL-6-dependent fever generating pathway, we used microarray analysis to identify differentially expressed genes in the brain of lipopolysaccharide (LPS)-treated IL-6 wild-type and knockout mice. Mice lacking IL-6 displayed a two-fold lower expression of the lipocalin-2 gene (lcn2), and this difference was confirmed by real-time reverse transcriptase-polymerase chain reaction. Conversely, the induction of lipocalin-2 protein was observed in brain vascular cells following i.p. administration of recombinant IL-6, suggesting a direct relationship between IL-6 and lipocalin-2. Immunohistochemical analysis also revealed that LPS-induced lipocalin-2 is expressed by brain endothelial cells and is partly co-localised with cyclooxygenase-2 (Cox-2), the rate-limiting enzyme for the production of inflammatory induced prostaglandin E(2) (PGE(2) ), which is the key mediator of fever. The direct role of lipocalin-2 in fever was examined in LPS-challenged lipocalin-2 knockout mice. In both male and female mice, normal fever responses were observed at near-thermoneutral conditions (29-30 °C) but when recorded at normal room temperature (19-20 °C), the body temperature of lipocalin-2 knockout female mice displayed an attenuated fever response compared to their wild-type littermates. This difference was reflected in significantly attenuated mRNA expression of Cox-2 in the brain of lipocalin-2 knockout female mice, but not of male mice, following challenge with peripheral LPS. Our findings suggest that IL-6 influences the expression of lipocalin-2, which in turn may be involved in the control of the formation of Cox-2, and hence central PGE(2) -production. We have thus identified lipocalin-2 as a new factor in the pathway of inflammatory IL-6 signalling. However, the effect of lipocalin-2 on fever is small, being sex-dependent and ambient temperature-specific, and thus lipocalin-2 cannot be considered as a major mediator of the IL-6-dependent fever generating pathway.


False-negative upper extremity ultrasound in the initial evaluation of patients with suspected subclavian vein thrombosis due to thoracic outlet syndrome (Paget-Schroetter syndrome).
To assess the utilization and consequences of upper extremity Duplex ultrasound in the initial diagnostic evaluation of patients with suspected subclavian vein (SCV) thrombosis and venous thoracic outlet syndrome (VTOS). A retrospective single-center review was conducted for patients that underwent primary surgical treatment for VTOS between 2008 and 2017, in whom an upper extremity ultrasound had been performed as the initial diagnostic test (n = 214). Clinical and treatment characteristics were compared between patients with positive and false-negative ultrasound studies. There were 122 men (57%) and 92 women (43%) that had presented with spontaneous idiopathic arm swelling, including 28 (13%) with proven pulmonary embolism, at a mean age of 30.7 ± 0.8 years (range 14-69). Upper extremity ultrasound had been performed 23.8 ± 12.2 days after the onset of symptoms, with confirmation of axillary-SCV thrombosis in 169 patients (79%) and negative results in 45 (21%). Of the false-negative ultrasound study reports, only 8 (18%) acknowledged limitations in visualizing the central SCV. Definitive diagnostic imaging (DDI) had been obtained by upper extremity venography in 175 (82%), computed tomography angiography in 24 (11%), and magnetic resonance angiography in 15 (7%), with 142 (66%) undergoing catheter-directed axillary-SCV thrombolysis. The mean interval between initial ultrasound and DDI was 48.9 ± 14.2 days with no significant difference between groups, but patients with a positive ultrasound were more likely to have DDI within 48 hours than those with a false-negative ultrasound (44% vs 24%; P = .02). At the time of surgical treatment, the SCV was widely patent following paraclavicular decompression and external venolysis alone in 74 patients (35%). Patch angioplasty was performed for focal SCV stenosis in 76 (36%) and bypass graft reconstruction for long-segment axillary-SCV occlusion in 63 (29%). Patients with false-negative initial ultrasound studies were significantly more likely to require SCV bypass reconstruction than those with a positive ultrasound (44% vs 25%; P = .02). Duplex ultrasound has significant limitations in the initial evaluation of patients with suspected SCV thrombosis, with false-negative results in 21% of patients with proven VTOS. This is rarely acknowledged in ultrasound reports, but false-negative ultrasound studies have the potential to delay definitive imaging, thrombolysis, and further treatment for VTOS. Initial false-negative ultrasound results are associated with progressive thrombus extension and a more frequent need for SCV bypass reconstruction at the time of surgical treatment.


Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region.
The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region. We analyzed Wellcome Trust Case-Control Consortium genome-wide association study data for associations in the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 × 10(-3)) for replication and dependence analysis. The replication cohorts comprised 2857 patients with RA and 2994 controls from Spain, Netherlands, and Norway. We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were associated with RA in the combined analysis. Conditional analyses showed that none of these associations was independent of rs2476601. The SNP rs2476601 located in the PTPN22 gene is the sole common genetic variant associated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22 do not have a major influence in RA.


Genetic markers as instrumental variables.
The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists, statisticians, epidemiologists and social scientists. Although IV is commonly used in economics, the appropriate conditions for the use of genetic variants as instruments have not been well defined. The increasing availability of biomedical data, however, makes understanding of these conditions crucial to the successful use of genotypes as instruments. We combine the econometric IV literature with that from genetic epidemiology, and discuss the biological conditions and IV assumptions within the statistical potential outcomes framework. We review this in the context of two illustrative applications.


Transcriptome Profiling of Rust Resistance in Switchgrass Using RNA-Seq Analysis.
Switchgrass rust caused by Puccinia emaculata is a major limiting factor for switchgrass (Panicum virgatum L.) production, especially in monoculture. Natural populations of switchgrass displayed diverse reactions to P. emaculata when evaluated in an Ardmore, OK, field. To identify the differentially expressed genes during the rust infection process and the mechanisms of switchgrass rust resistance, transcriptome analysis using RNA-Seq was conducted in two pseudo-F1 parents ('PV281' and 'NFGA472'), and three moderately resistant and three susceptible progenies selected from a three-generation, four-founder switchgrass population (K5 × A4) × (AP13 × VS16). On average, 23.5 million reads per sample (leaf tissue was collected at 0, 24, and 60 h post-inoculation (hpi)) were obtained from paired-end (2 × 100 bp) sequencing on the Illumina HiSeq2000 platform. Mapping of the RNA-Seq reads to the switchgrass reference genome (AP13 ver. 1.1 assembly) constructed a total of 84,209 transcripts from 98,007 gene loci among all of the samples. Further analysis revealed that host defense-related genes, including the nucleotide binding site-leucine-rich repeat domain containing disease resistance gene analogs, play an important role in resistance to rust infection. Rust-induced gene (RIG) transcripts inherited across generations were identified. The rust-resistant gene transcripts can be a valuable resource for developing molecular markers for rust resistance. Furthermore, the rust-resistant genotypes and gene transcripts identified in this study can expedite rust-resistant cultivar development in switchgrass.


Impact of Trainee Involvement on Video-Assisted Thoracoscopic Lobectomy for Cancer.
Previous literature in other surgical disciplines regarding the impact of resident and fellow involvement on operative time and outcomes has yielded mixed results. The impact of trainee involvement on minimally invasive thoracic surgery is unknown. This study compared risk-adjusted differences in operative time and outcomes of video-assisted thoracoscopic lobectomy for cancer between cases performed with and without residents and fellows involved. All patients undergoing elective video-assisted thoracoscopic lobectomy for cancer between 2008 and 2018 were identified in the Veterans Affairs Surgical Quality Improvement Program database. Patients were stratified into 2 cohorts: cases with residents and fellows involved, and cases performed only by attending surgeons. Primary outcomes included operative time, postoperative hospital length of stay, and composite 30-day morbidity and mortality. Secondary outcomes included factors associated with high and low trainee operative autonomy. A total of 3678 patients met study inclusion criteria. In all, 1780 cases were performed with residents and fellows involved (median postgraduate year, 5; interquartile range, 4-7). Multivariate analysis showed that operative time was significantly shorter in resident- and fellow-involved cases compared with attending-only cases (mean [SD], 3.6 [1.4] versus 3.8 [1.6] hours; P < .001). There were no significant differences in composite 30-day morbidity and mortality (16.0% versus 17.1%; adjusted odds ratio = 0.93; 95% confidence interval, 0.77-1.11; P = .40) or length of stay. Substratification of trainees by postgraduate year resulted in similar findings. Cases performed in July through October and those in the Northeastern United States were associated with low autonomy. Current training paradigms in thoracic surgery are safe, and the involvement of motivated and skilled trainees with appropriate supervision may benefit operative duration.


[Arteriovenous malformations in the region of the ampulla of Galen. Anatomical and clinical aspects and the course of endovascular treatment (1979-1986). Apropos of 10 cases].
Technological progress has resulted in embolization being adapted as treatment of choice for arteriovenous malformations in the region of Galen's ampulla. To ensure recovery it is essential to conduct treatment at an early stage, to adapt it to the morphologic type of malformation and to investigate possible associated thrombosis requiring anticoagulant therapy. A shunt operation may be necessary if hydrocephalus fails to regress.


Planning for gene therapy.
In spite of some setbacks, gene therapy trials continue, while the UK government is putting in place plans to bring the potential power of genetics into mainstream public heathcare through its National Health Service.


Public disclosure of clinical trial results at Clinical Trial Registry of India- Need for transparency in research!
Since June 15, 2009, clinical trial registration in the Clinical Trial Registry-India (CTRI) has been made mandatory by the Drugs Controller General of India to improve transparency, accountability, conform to accepted ethical standards and reporting of all relevant results of registered trials. In this study, we planned to evaluate the compliance of Indian and global sponsors with clinical trials conducted in India in terms of reporting of clinical trial results at the CTRI. We included trials registered in the CTRI between January 2018 and January 2020. The CTRI and ClinicalTrials.gov registry was thoroughly searched for all completed interventional studies. A year-wise comparative analysis was performed to evaluate the number of clinical trials reporting results in both the registry. The reporting of completed interventional clinical trial results was 25/112 (22.32%) in year 2018, y, 8/105 (7.6%) in year 2019 and 17/140 (12.14%) in year 2020. There was significantly less reporting of results of Pharmaceutical company sponsored Interventional Studies-Indian at CTRI when compared with ClinicalTrials.gov registry for the year 2019 (odds ratio [OR]-0.17 (95% confidence interval [CI]: 0.08-0.36) and P < 0.0001) and year 2020 (OR-0.45 [95% CI: 0.24-0.82] and P < 0.01). The difference in results reported at CTRI was significantly low for Pharmaceutical company sponsored Interventional Studies-Global only for year 2019 (OR-0.09 [95% CI: 0.005-1.45] and P = 0.04) compared with ClinicalTrials.gov. There is a need to develop the culture of reporting clinical trial results in CTRI to strengthen the transparency in the research for overall benefit of public, health care professionals, and research community.


Venocclusive disease of the liver after allogeneic bone marrow transplantation in man.
One hundred and fifty-one consecutive patients underwent allogeneic bone marrow transplantation (B.M.T.) following high-dose chemotherapy and single dose total body irradiation (T.B.I.) for hematologic malignancies between September 1980 and December 1985. All patients included in this study were treated using a 60 Co beam to deliver a prescribed dose of 10 Gy to the mid-plane of the abdomen. Total body irradiation was performed the day before B.M.T. The mean instantaneous dose-rate was 3.5 cGy/min (range: 2.6 to 4.7). The real dose received was measured using thermoluminescent dosimeters (lithium borate). The difference between the doses delivered to the liver and to the mid-plane of the abdomen did not exceed 5%. The mean real dose delivered to the reference point was 10 Gy (range 8.3 to 11.7). Ninety five per cent of the patients received a dose ranging from 9.1 Gy to 10.9 Gy. High-dose cyclophosphamide was given to 126 patients with a "standard-risk" of relapse (60 mg/kg on day 5 and 4 before B.M.T.). Chemotherapy was intensified by the addition of other drugs in 25 patients with "higher-risk" of relapse. We analyzed the effect of the following pretransplant characteristics on the subsequent posttransplant development of V.O.D.: age, sex, ASAT and/or ALAT before conditioning regimen, diagnosis and status of malignant disease, history of liver disease, interval between diagnosis of hematologic malignancy and B.M.T., conditioning regimen (i.e., classical or intensified) and dose delivered to the liver during T.B.I. Seventeen patients were classified as having clinical V.O.D. giving a prevalence of 11.2%. In the first 2 months following B.M.T., death occurred respectively in 9 of 17 (53%) and 23 of 134 (17%) patients with and without clinical V.O.D. Univariate analysis showed that four characteristics were significantly related to an increased prevalence of V.O.D.: sex (11/62 females vs 6/89 males; p less than 0.05); history of liver disease (7/28 vs 10/117 patients without antecedent; p less than 0.01); ASAT and/or ALAT levels greater than 1.5 upper normal limit (11/49 vs 6/102 patients with levels less than 1.5; p less than 0.01) and intensified conditioning regimen (6/25 vs 11/126 patients with classical regimen; p less than 0.05). The conditioning regimen and history of liver disease were highly correlated to transaminases levels. Only two factors, transaminases levels and female sex, remained significantly associated with V.O.D. after multivariate analysis.


Measurement of porcine haptoglobin in meat juice using surface acoustic wave biosensor technology.
Aim of the study was the application of biosensor technique to measure the concentration of an acute phase protein (APP) within complex matrices from animal origin. For the first time, acute phase protein haptoglobin (Hp) was detected from unpurified meat juice of slaughter pigs by a label-free biosensor-system, the SAW-based sam®5 system. The system uses a sensor chip with specific antibodies to catch Hp while the mass-related phase shift is measured. The concentration is calculated as a function of these measured phase shifts. The results correlate very well with reference measurement results obtained by enzyme-linked immunosorbent assay (ELISA), R=0.98. The robust setup of the surface acoustic wave (SAW)-based system and its ability to measure within very short time periods qualifies it for large-scale analyses and is apt to identify rapidly pigs in the meat production process whose consumption would have an increased risk for consumers.


[Image processing of topographic EEG in epilepsy].
The processing of epileptic computerized topographical EEG (CTE) with the principle of image enhancement and point-by-point process was reported. The results indicated that the high potential distribution of CTE markedly reduced, the focus location was prominent and the mirror nearly disappeared after processing CTE image. The difference increased between the spike grey and the fast wave. This is advantageous to the surgical treatment of epileptic focus in brain.


Management of the cervical esophagus and hypofarinx perforations complicating anterior cervical spine surgery.
Five cases of esophageal or pharyngeal perforation diagnosed during or after anterior cervical spine surgery are presented. To outline a protocol for the early diagnosis and treatment of iatrogenic pharyngoesophageal perforations. Pharyngoesophageal perforations after anterior cervical spine surgery are uncommon or rarely reported complications. They may have serious functional consequences, including death, if they are not diagnosed promptly and treated effectively. These potentially fatal conditions require a surgical and medical therapy. Clinical course, diagnostic tools and guidelines for the management of five patients presenting esophagopharingeal perforations are illustrated. These five cases resulted in definitive healing of the laceration without functional consequences. We believe that awareness of these complications and their causes, prompt recognition of the symptoms and immediate and multimodality therapies are essential tools to achieve successful results.


The effect of the PKC inhibitor calphostin C and the PKC agonist phorbol 12-myristate 13-acetate on regulation of cytosolic Ca(2+) in mammalian skeletal muscle cells.
Protein kinase C (PKC) has been shown to exert broad actions in modulating Ca(2+) in cardiac myocytes, however, the effect of PKC in skeletal muscle cells is largely unknown. In this study, we examined the effect of the PKC inhibitor calphostin C (CC) and the PKC agonist phorbol 12-myristate 13-acetate (PMA) on intracellular Ca(2+) handling in C2C12 skeletal myotubes and skinned skeletal muscle fibers of the rat. CC (250 nM) significantly prolonged (P=0.01, n=6), and the PKC agonist PMA (500 nM; P=0.03, n=6) significantly shortened the decay phase of electrically induced Ca(2+) transients in C2C12 myotubes without affecting the amplitude or the time to peak of the transients. Skinned fiber studies showed that CC significantly inhibits SR Ca(2+) uptake in skeletal muscle cells. PMA had no effect. CC also increased the peak of ATP-induced Ca(2+) transients release by 94.2% (P<0.0001) in the presence of extracellular Ca(2+) and 54.5% (P=0.04) without external Ca(2+) via IP(3)-Ca(2+) release pathway in C2C12 myotubes, while PMA had no effect, suggesting that CC may modulate IP(3)-induced Ca(2+) release via a PKC-independent mechanism. CC at a concentration of 1 microM was able to induce a large sustained elevation in basal [Ca(2+)](i) that was blocked by Ca(2+) store depletion and the IP(3) receptor blocker 2-APB. These results indicate that PKC plays a role in modulation of SR function in skeletal muscle cells, and the PKC inhibitor CC may alter Ca(2+) handling via both PKC-dependent and PKC-independent pathways.


Sex-specific patterns of gene expression following influenza vaccination.
Sex-based variations in the immune response to the influenza vaccines was reported, however, the genetic basis responsible for the sex variations in the immune response toward the influenza vaccines remains unclear. Here, the genes responsible for sex-specific responses after vaccination with trivalent inactivated influenza virus were identified. These genes were enriched in virus response pathways, especially interferon signaling. A list of genes showing different responses to the vaccine between females and males were obtained next. Our results demonstrated that females generate stronger immune responses to seasonal influenza vaccines within 24 hours than males. However, most of these genes with variability between sexes had the opposite expression levels after three days, suggesting that males retained the immune responses longer than female. To summary, our study identified genes responsible for the sex variations toward influenza vaccination. Our findings might provide insights into the development of the sex-dependent influenza vaccines.