Up-regulation of miR-130b expression level and down-regulation of miR-218 serve as potential biomarker in the early detection of human osteosarcoma.
Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity that principally emerges in children and adolescents. MiRNAs regulate a variety of normal physiologic processes and are involved in tumorigenesis and development of multiple malignancies, including OS. This study was aimed to evaluate the clinical significance of miR-130b and miR-218 in osteosarcoma patient. We utilized quantitative real-time PCR to evaluate the level of miR-130b and miR-218 expressions in OS patients and normal tissues and their relationship with clinicopathological features and survival in OS patients. QRT-PCR indicated that miR-130b expression in tumor tissues was strongly elevated than adjacent non-tumor tissues (P < 0.001), while the level of miR-218 expression in osteosarcoma tissues was down-regulated than adjacent non-tumor tissues (P < 0.001). We evaluated the clinical significance of miR-130b and miR-218 in osteosarcoma. Clinical correlation analysis showed that increased expression of miR-130b and decreased expression of miR-218 were significantly associated with advanced tumor stage (x (2) = 6.285, P < 0.009; x (2) = 7.172, P < 0.007), distant metastasis (x (2) = 5.528; P < 0.001; x (2) = 4.617, P < 0.001) and size of tumor (x (2) = 5.01, P = 0.013; x (2) = 4.271, P = 0.019). Taken together, our data indicated that high miR-130b level and low level of miR-218 are associated with poor clinicopathological characteristics. Furthermore, miR-130b may play a key role in the progression of osteosarcoma.


Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect.
Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC50 value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (λmax). Binding is governed by entropy driven factor (24.8 cal mol(-1) K(-1)) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study.


Loss of ryanodine receptor calcium-release channel expression associated with overactive urinary bladder smooth muscle contractions in a detrusor instability model.
To investigate the changes in spontaneous bladder smooth muscle contractions that occur during detrusor instability (DI), and to test the possibility that altered function or expression of ryanodine receptors (RyRs) could account for the increased bladder contractions. After 8 weeks of partial bladder outlet obstruction, DI was confirmed in female experimental rats by filling cystometry. Muscle strips were dissected from freshly isolated bladders, and isometric tension recorded in strips from DI and normal bladders. The contractions were recorded during electrical stimulation or exposure to various agents. Western blot analysis was used to determine RyR expression in DI and normal bladder muscle. In DI bladder muscle, spontaneous contractile activity persisted in the presence of blockers for known neurotransmitter receptors in the bladder wall. The RyR blocker ryanodine significantly increased the spontaneous contractile frequency in normal bladder strips, but failed to affect spontaneous contractions in DI muscle. Caffeine inhibited spontaneous contractile activity in both the DI and normal strips. After administering the l-type Ca(2+) channel antagonist nimodipine, the myogenic contractile activity was abolished in normal strips; in contrast, in DI strips, the amplitude of contractions was reduced but the frequency of contractions was unchanged. Western blot analysis showed that RyR expression was lower in DI muscle than in normal bladder muscle. These results provide the first characterization of a loss of regulation of spontaneous contractile activity by RyRs in DI muscle associated with a significant decrease in RyR expression. RyRs in normal detrusor muscle act as negative-feedback regulators of spontaneous contractile activity, presumably by releasing Ca(2+) that activates Ca(2+)-dependent K(+) channels to decrease contractility. This mechanism might be weakened in DI muscle, resulting in spontaneous contractile overactivity.


De novo assembly and characterization of the Chinese three-keeled pond turtle (Mauremys reevesii) transcriptome: presence of longevity-related genes.
Mauremys reevesii (Geoemydidae) is one of the most common and widespread semi-aquatic turtles in East Asia. The unusually long lifespan of some individuals makes this turtle species a potentially useful model organism for studying the molecular basis of longevity. In this study, pooled total RNA extracted from liver, spleen and skeletal-muscle of three adult individuals were sequenced using Illumina Hiseq 2500 platform. A set of telomere-related genes were found in the transcriptome, including tert, tep1, and six shelterin complex proteins coding genes (trf1, trf2, tpp1, pot1, tin2 and rap1). These genes products protect chromosome ends from deterioration and therefore significantly contribute to turtle longevity. The transcriptome data generated in this study provides a comprehensive reference for future molecular studies in the turtle.


Ethnobotanical study of medicinal plants in Adwa District, Central Zone of Tigray Regional State, Northern Ethiopia.
Medicinal plants have been used for ages in Ethiopia. Some 887 plant species have been documented to heal human and livestock health problems. Documenting the traditional use of medicinal plants is a vital step in obtaining information on bioactive chemicals, preserving indigenous knowledge and ultimately interesting, medicinal plant species. We conducted this study with the aim of documenting the ethnobotanical knowledge associated with medicinal plant use in Adwa District, Northern Ethiopia. The study was conducted from September 2018 to December 2019. A total of 393 informants (242 males and 151 females) were selected. Data were collected using semi-structured interviews, guided walks and group discussions. We calculated informant consensus factors (ICF) and fidelity level (FL) and performed ranking and paired comparisons. Data were analysed using descriptive statistics, including independent sample t test and ANOVA. Overall, we documented 127 medicinal plants belonging to 105 genera, under 54 families to be used by local people to address 43 human and 15 livestock ailments. Families Fabaceae and Solanaceae were the most important ones with 11 (8.66%) species each. Herbs were the dominant growth form (55 species), followed by shrubs (39). The most frequently used plant parts were leaves (24.27%) followed by roots (14%). The most important preparation method was crushing and pounding (42.7%) followed by fumigation (smoke and vapour) (23, 11.1%). The common route of administration was via skin application (67 or 32%) followed by oral (63, 27%). ICF showed that tonsillitis had the higher value (0.95). Cucumis ficifolius A. Rich. was the most preferred medicinal plant (36) treating abdominal pain, followed by Kalanchoe quartiniana A. Rich. for blackleg (34). Adwa District is relatively rich in medicinal plant diversity and traditional knowledge on use, preparation and application of the medicinal flora. However, agricultural expansion (51%), overgrazing (43%) and drought (37%) were mentioned most when informants were asked about the threats to medicinal plants in Adwa District. Hence, on-site and off-site medicinal plant conservation would help protect medicinal plants in the district.


Aldehyde dehydrogenase 2 genetic variations may increase susceptibility to Parkinson's disease in Han Chinese population.
Genetic variations of ALDH2, encoding aldehyde dehydrogenase-2 which regulates aldehyde oxidation in the brain, have been recently suggested to impact on the association of pesticide exposure with Parkinson's disease (PD). However, the link between ALDH2 polymorphism and PD remains elusive. In the present study, tag-single nucleotide polymorphisms of ALDH2, including rs4767944, rs441, and rs671, were extracted and analyzed in a Chinese cohort consisting of 584 PD patients and 582 controls. Results from genotyping analyses showed that rs4767944 (p = 0.002), but not rs441 and rs671, were associated with PD. The C allele of rs4767944 served a risk factor toward PD. Further analysis presented a significant association between haplotype frequencies and the risk for PD, primarily driven by the preponderance of the C-T-A (p = 0.03) or C-T-G (p = 0.003) haplotype of rs4767944, rs441, and rs671 in PD patients. In conclusion, these novel results suggest an association between PD susceptibility and ALDH2 genetic variations.


Effectiveness of SPECT/CT Imaging for Sentinel Node Biopsy Staging of Primary Cutaneous Melanoma and Patient Outcomes.
Coregistered SPECT/CT can improve accuracy of sentinel node biopsy (SNB) for staging melanoma. This benefit has implications for pathology services and surgical practice with increased diagnostic and surgical workload. The purpose of this study was to investigate the effectiveness of SPECT/CT imaging. SNB data were collected over a 10-year period. Preoperative SLN mapping was performed by using planar lymphoscintigraphy (LSG) for all patients (n = 1522) and after October 2015, patients underwent a second co-registered SPECT/CT scan (n = 559). The patients were stratified according to the imaging protocol. The number of nodes and nodal basins were assessed. The reasons for cancellation also were assessed. A total of 95% (1446/1522) of patients underwent a successful SNB procedure. Significantly more sentinel nodes were identified by the SPECT/CT protocol (3 vs. 2; p < 0.0001). More patients were cancelled in the SPECT/CT cohort (9.3% vs. 2.5%; p < 0.0001). Head & neck, lower limb, and AJCC IB primaries were significantly less likely to proceed to SNB. SPECT/CT identified significantly more positive SNBs (20.9% vs. 16.5%; p = 0.038). SPECT/CT imaging was associated with improved disease-free (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.0); p = 0.048) and disease-specific survival (HR = 0.48; 95% CI: 0.3-0.78; p = 0.003). Patients who did not proceed to SNB had a significantly increased nodal relapse rate (23.5% vs. 6.8%; HR = 3.4; 95% CI: 1.9-6.2; p < 0.0001) compared with those who underwent SNB. This large cohort study confirms the increased accuracy of SPECT/CT for identifying SLN metastases, which would appear to have a significant therapeutic benefit, although an increased risk of cancellation of the SNB procedure on the day of surgery.


Production of narrative discourse in aphasia.
The study described the abilities of a group of 15 moderately impaired aphasics and 15 normals to produce narrative discourse. The experimental tasks included telling stories, summarizing stories, and giving morals to stories. The data were analyzed in terms of sentential grammar, discourse grammar, and subjective ratings of content and clarity of language. The results showed that aphasics produced well-structured discourse. The language of the aphasics' discourse was reduced in both complexity and amount, as compared to that produced by normals. The reduction of language reflected selective reduction of hierarchically organized information. The findings of the study confirm the results of previous research on mildly impaired aphasics, which also showed preservation of discourse structure with selective reduction of information.


Whole organ sheep kidney tissue engineering and in vivo transplantation: Effects of perfusion-based decellularization on vascular integrity.
During the past decade, increased efforts have been made to develop alternative management options instead of dialysis and homograft renal transplantation for end-stage renal disease. State-of-the-art methods employ tissue engineering to produce natural acellular scaffolds that could resolve the concern of allograft rejection and obviate the need for immunosuppressive therapy. Complete decellularization of kidney with intact extracellular matrix is crucial for in vivo compatibility and success of transplantation. Herein, we evaluate the efficacy of two different whole organ decellularization protocols, vasculature integrity, and in vivo transplantation of sheep kidneys. Eight sheep kidneys were decellularized by perfusion-based method utilizing two different protocols (Protocol 1: 1% Triton X-100 and 0.5% SDS vs. Protocol 2: 1% SDS). The samples were evaluated by histopathology in terms of decellularization and extracellular matrix preservation. Computerized tomography angiography was performed to evaluate vasculature. Subsequently, both methods were transplanted in four sheep and monitored for vascular integrity and extravasations in short-term. Scaffolds obtained from both protocols were entirely decellularized. However; the extracellular matrix was better preserved in protocol 1 compared to protocol 2. In addition, the vascular integrity was intact in decellularized scaffolds treated with Triton X-100 plus SDS (protocol 1). After transplantation, the samples treated with protocol 2 showed extravasation of fluid in the interstitial space while the samples treated with protocol 1 showed intact extracellular matrix and vasculature. This study demonstrated the efficacy of well-preserved acellular scaffold and vasculature network in post renal transplant outcome in a sheep model. These results have potential to pave the road for further investigations in acellular whole organ transplantation.


Tau in physiology and pathology.
Tau is a microtubule-associated protein that has a role in stabilizing neuronal microtubules and thus in promoting axonal outgrowth. Structurally, tau is a natively unfolded protein, is highly soluble and shows little tendency for aggregation. However, tau aggregation is characteristic of several neurodegenerative diseases known as tauopathies. The mechanisms underlying tau pathology and tau-mediated neurodegeneration are debated, but considerable progress has been made in the field of tau research in recent years, including the identification of new physiological roles for tau in the brain. Here, we review the expression, post-translational modifications and functions of tau in physiology and in pathophysiology.


Selectivity of the intrinsic sympathomimetic activity of the beta-adrenergic blocking drug bucindolol.
We studied the comparative effects of beta-adrenergic blockade with propranolol (PROP) and bucindolol (BUC), a beta-adrenergic agonist having both alpha-adrenergic blocking properties and intrinsic sympathomimetic activity (ISA) on airway and cardiovascular responses, in 38 mongrel dogs in situ. Intravenous infusion of 0.6 mg/kg + 6 micrograms/kg/min BUC and 2.0 mg/kg + 20 micrograms/kg/min PROP caused identical shifts in the isoproterenol (ISO) EC50 for chronotropic and hypotensive arterial blood pressure responses. After PROP administration, resting heart rate (HR) decreased from 188 +/- 15 to 142 +/- 12 beats/min (p less than 0.02); BUC caused no decrease in HR. In contrast, the effects of BUC and PROP on mean arterial blood pressure response to ISO were similar. No change in bronchomotor tone was observed after bolus injection of either BUC or PROP. Beta-Adrenergic relaxation to ISO and alpha-adrenergic contraction to norepinephrine (NE) were studied simultaneously in tracheal and bronchial airways using chronotropically equivalent beta-adrenoceptor blocking doses of PROP and BUC. Comparable inhibition of ISO-induced airway relaxation after contraction with 120 micrograms/kg/min i.v. serotonin was demonstrated in both PROP (n = 5) and BUC (n = 5) groups (p less than 0.01 for doses greater than 5 X 10(-11) mol/kg). Similarly, both BUC (n = 5) and PROP (n = 5) blocked beta-adrenergic relaxation and caused identical alpha-adrenergic airway contraction to intravenous NE. We conclude that the ISA of the beta-adrenergic blocking drug BUC can be demonstrated on the spontaneous rate of the heart but not on the activity of bronchial smooth muscle. BUC neither augments ISO-induced relaxation nor inhibits NE-induced contraction of airways after effective chronotropic blockade.


Light-enhanced bioaccumulation of molybdenum by nitrogen-deprived recombinant anoxygenic photosynthetic bacterium Rhodopseudomonas palustris.
As molybdenum (Mo) is an indispensable metal for plant nitrogen metabolisms, accumulation of dissolved Mo into bacterial cells may connect to the development of bacterial fertilizers that promote plant growth. In order to enhance Mo bioaccumulation, nitrogen removal and light illumination were examined in anoxygenic photosynthetic bacteria (APB) because APB possess Mo nitrogenase whose synthesis is strictly regulated by ammonium ion concentration. In addition, an APB, Rhodopseudomonas palustris, transformed with a gene encoding Mo-responsive transcriptional regulator ModE was constructed. Mo content was most markedly enhanced by the removal of ammonium ion from medium and light illumination while their effects on other metal contents were limited. Increases in contents of trace metals including Mo by the genetic modification were observed. Thus, these results demonstrated an effective way to enrich Mo in the bacterial cells by the culture conditions and genetic modification.


Assessment of technical heterogeneity among diagnostic tests to detect germline risk variants for hematopoietic malignancies.
To determine the degree of testing consistency among commercially available diagnostic assays for hereditary hematopoietic malignancies (HHMs). Next-generation sequencing assays designed for the diagnosis of HHMs were studied to determine which genes were sequenced, their ability to detect variant types relevant for HHMs, and clinical-grade characteristics such as price, turnaround time, and tissue types accepted. Commercial assays varied in price (USD 250-4702), number of genes sequenced (12-73), and average turnaround time (14-42 days). A number of nongermline tissue types were accepted despite the tests being designed for germline diagnostic purposes. Multiple genes with well-characterized roles in HHM pathogenesis were omitted from more than one-third of panels intended for the evaluation of HHMs. Only 4 of 82 genes were consistently covered across all HHM diagnostic panels. The assays were highly variable in their sensitivity for structural alterations relevant to HHMs, such as copy-number variants. A high degree of diagnostic heterogeneity exists among commercially available HHM diagnostic assays. Many of these assays are incapable of detecting the full spectrum of HHM-associated variants, leaving patients vulnerable to the consequences of underdiagnosis, missed opportunities for screening, and the potential for donor-derived malignancies.


Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes.
Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology, function and disease. While numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts, few target osteocytes specifically, particularly mature osteocytes. Our goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5' and 3' regions of the Sost gene (Sost ERT2 Cre). Four founder lines were crossed with the Ai9 Cre reporter mice. One founder line showed high and specific activity in mature osteocytes. Bones and organs were imaged and fluorescent signal quantitated. While no activity was observed in 2 day old pups, by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or 'leaky' with age. The percentage of positive osteocytes increased following tamoxifen injection, especially in males, with 43% to 95% positive cells compared to 19% to 32% in females. No signal was observed in any bone surface cell, bone marrow, nor in muscle with or without tamoxifen injection. No spontaneous signal was observed in any other organ. However, with tamoxifen injection, a few positive cells were observed in kidney, eye, lung, heart and brain. All other organs, 28 in total, were negative with tamoxifen injection. However, with age, a muscle phenotype was apparent in the Sost-ERT2 Cre mice. Therefore, although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes, the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.


Hormone replacement therapy in Germany: determinants and possible health-related outcomes. Results of National Health Surveys from 1984 to 1999.
To explore the determinants of hormone replacement therapy (HRT) use and possible health-related outcomes in Germany. 827 current HRT users (age range 31-78 years, who had taken HRT products in the last 7 days before the medical interview) and 2371 age-matched nonusers were identified from five population-representative National Health Surveys performed from 1984 to 1999 in Germany. Cross-sectional comparisons between HRT users and nonusers were performed for socioeconomic factors and possible health-related outcomes. Regression models were used to obtain odds ratios of HRT use. HRT use increased dramatically from 3% in 1984/1985 to 21% in 1998/1999 among German women aged 40-69. Regression analysis and comparison between HRT users and nonusers suggested that HRT use was closely associated with socioeconomic factors and personal lifestyle that may favor better health. In HRT users, however, we did not observe any health-related benefits in satisfaction with life or health. While HRT users appeared superior to nonusers with respect to the glycemic status, histories of cardiovascular diseases, despite a favorable lipid profile, occurred not less than in the group of nonusers. In the settings of our cross-sectional studies in Germany HRT did not improve users' health benefits and did not show cardioprotective effects. The better glycemic status should be balanced against the higher risks of cardiovascular diseases and breast cancer.


Red Shift in Optical Excitations on Layered Copper Perovskites under Pressure: Role of the Orthorhombic Instability.
The red shift under pressure in optical transitions of layered compounds with CuCl6 4- units is explored through first-principles calculations and the analysis of available experimental data. The results on Cu2+ -doped (C2 H5 NH3 )2 CdCl4 , that is taken as a guide, show the existence of a highly anisotropic response to pressure related to a structural instability, driven by a negative force constant, that leads to an orthorhombic geometry of CuCl6 4- units but with a hole displaying a dominant 3z2 -r2 character (z being the direction perpendicular to the layer plane). As a result of such an instability, a pressure of only 3 GPa reduces by 0.21 Å the longest Cu2+ -Cl- distance, lying in the layer plane, while leaving unmodified the two other metal-ligand distances. Owing to this fact, it is shown that the lowest d-d transition would experience a red shift of 0.34 eV while the first allowed charge transfer transition is also found to be red shifted but only by 0.11 eV that reasonably concurs with the experimental value. The parallel study on Jahn-Teller systems CdCl2 :Cu2+ and NaCl:Cu2+ involving tetragonal elongated CuCl6 4- units shows that the reduction of the long axis by a pressure of 3 GPa is three times smaller than that for the layered (C2 H5 NH3 )2 CdCl4 :Cu2+ compound. Accordingly, the optical transitions of such systems, which involve a positive force constant, are much less sensitive to pressure than in layered compounds. The origin of the red shift under pressure undergone by the lowest d-d and charge transfer transitions of (C2 H5 NH3 )2 CdCl4 :Cu2+ is discussed in detail.


The morphologic diagnosis of analgesic (phenacetin) abuse.
A number of different morphologic characteristics were examined to determine their relative values in establishing a purely morphologic diagnosis of phenacetin abuse. These included hyperpigmentation of the skin, the costal cartilages, the liver, and the renal tubules, and capillarosclerosis of the lower urinary tract. Hyperpigmentation of the skin, liver, and renal tubules cannot be used in the diagnosis of phenacetin abuse. Massive brown pigmentation of the costal cartilages in patients under 60 years of age suggests phenacetin abuse, but even this morphologic parameter, when used alone, is insufficient to establish a definite diagnosis. Capillarosclerosis in the lower urinary tract does, however, permit one to diagnose phenacetin abuse with certainty, as it is found exclusively in this condition.


Renal, hematologic and infectious complications in multiple myeloma.
Renal failure is a common complication in patients with multiple myeloma. It is generally due to tubular light-chain damage, and it is reversible in about 50% of patients. The reversibility rate depends on the degree of light-chain nephropathy. The initial therapy should consist of dexamethasone- or cyclophosphamide-based regimens. High-dose therapy/autologous transplant may be of benefit in selected patients. Early plasma exchange may be useful in patients who have severe renal failure but do not yet require dialysis. Renal replacement with dialysis is a worthwhile measure in patients with end-stage renal failure. Anemia is the most common hematologic complication. About 70% of anemic patients respond to recombinant human erythropoietin (rHuEPO), resulting not only in an increase in the hemoglobin level but also in an improvement in the quality of life. The hemoglobin level should ideally be maintained at around 12 g/dL. Infection is the main cause of morbidity and mortality in patients with myeloma. The highest risk of infection is within the first 2 months of initiation of therapy as well as in patients with renal failure and in those with relapsed and refractory disease.


The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives.
As the most important component of the stromal cell population in the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are crucial players in tumor initiation and progression. The interaction between CAFs and tumor cells, as well as the resulting effect, is much greater than initially expected. Numerous studies have shown that noncoding RNAs (ncRNAs) play an irreplaceable role in this interplay, and related evidence continues to emerge and advance. Under the action of ncRNAs, normal fibroblasts are directly or indirectly activated into CAFs, and their metabolic characteristics are changed; thus, CAFs can more effectively promote tumor progression. Moreover, via ncRNAs, activated CAFs can affect the gene expression and secretory characteristics of cells, alter the TME and enhance malignant biological processes in tumor cells to contribute to tumor promotion. Previously, ncRNA dysregulation was considered the main mechanism by which ncRNAs participate in the crosstalk between CAFs and tumor cells. Recently, however, exosomes containing ncRNAs have been identified as another vital mode of interaction between these two types of cells, with a more direct and clear function. Gaining an in-depth understanding of ncRNAs in CAFs and the complex regulatory network connecting CAFs with tumor cells might help us to establish more effective and safer approaches for cancer therapies targeting ncRNAs and CAFs and offer new hope for cancer patients.


Calcified ganglioneuroma of the bladder.
Ganglioneuromas involving the genitourinary tract are extremely rare but are potentially serious tumors. We describe a patient, known to have von Recklinghausen's disease, who presented with a calcified ganglioneuroma of the bladder demonstrated by intravenous urography, sonography, and computed tomography.


Clinical trial with testosterone undecanoate for male fertility control.
The newly available orally effective testosterone undecanoate (TU) was investigated as a possible means for male fertility control. One of 7 normal volunteers exposed to 80 mg TU three times a day for 10-12 weeks became azoospermic, the remaining showed slightly suppressed or unaffected sperm counts. The insufficient suppression of spermatogenesis in 6 out of 7 subjects may be due to the fact that testosterone levels are only sufficiently high to suppress gonadotropins for some hours after ingestion of the drug.


Cigarette taxes, prices, and disparities in current smoking in the United States.
Increasing cigarette taxes has been the cornerstone of tobacco control policy. Recent work has argued that raising cigarette taxes alone may no longer be an effective strategy for lowering smoking rates. We largely confirm these findings but also find that increases in price continue to predict lower smoking participation in most model specifications. We argue that raising cigarette prices via taxation remains an effective public health policy. We discuss the advantages of homogeneous tax environments and minimum price laws for eliminating opportunities for consumers to offset tax increases by searching for lowest taxes.


Design and validation of a questionnaire for the evaluation of educational experiences in the metaverse in Spanish students (METAEDU).
The aim of this study is to design and validate an instrument that allows the evaluation of educational experiences and formative assessment in the metaverse from a holistic perspective. Hence, a research design based on the development of a scale has been used. Three hundred and sixty-two Spanish secondary school students participated in the study, selected through purposive sampling. The instrument created has been subjected to an analysis of content validity, validity by expert judgment, construct validity, and reliability. For data analysis, the SPSS and AMOS programs have been used. An exploratory factor analysis and a confirmatory factor analysis have been performed to determine the construct validity. In addition, the Cronbach's alpha has been calculated to verify the internal consistency of the tool. The results reveal several findings that position the resulting questionnaire as a valid and reliable instrument to evaluate educational experiences and practices in the metaverse. In short, this study has led to the development of a comprehensive evaluation tool at the service of educators or any institution interested in implementing its educational praxis within the metaverse, a field of research that has yet to be explored.


Computed tomographic angular measurements using a bone-centered three-dimensional coordinate system are accurate in a femoral torsional deformity model and precise in clinical canine patients.
In small animal orthopedics, angular measurements in the canine femur are often applied in clinical patients with bone deformities and especially in complex and severe cases. Computed tomography (CT) has been shown to be more precise and accurate than two-dimensional radiography, and several methods are described. Measurement techniques evaluated in normal bones must prove accuracy in deformed bones in clinical settings. The goals of our study were to evaluate the accuracy of canine femoral torsion angle measurements in a femoral torsional deformity model and to test repeatability and reproducibility of canine femoral neck inclination, torsion, and varus angle measurements in CT datasets of dogs applying a CT-based technique using a three-dimensional (3D) bone-centered coordinate system. For precision testing, femoral torsion, femoral neck inclination, and femoral varus angles were measured in CT data of 68 canine hind limbs by two operators, and their results were compared. For accuracy testing, a femoral torsional deformity model was preset from 0° to +/-90° with a goniometer and scanned. Torsion angles were measured in the CT data and compared to the preset value. In the femoral torsion model, the Bland-Altman plots demonstrated a mean difference of 2.11°, and the Passing-Bablok analysis demonstrated a correlation between goniometer and CT-based measurements. In the clinical CT scans, intra- and interobserver agreement resulted in coefficients of variation for repeated measurements (%) between 1.99 and 8.26 for the femoral torsion, between 0.59 and 4.47 for the femoral neck inclination, and between 1.06 and 5.15 for the femoral varus angles. Evaluation of femoral malformations with torsional deformities is the target area of this technique. Further studies are required to assess its value in different types, degrees, and combinations of osseous deformities and to establish normal reference values and guidelines for corrective osteotomies. Based on the results of this study, the accuracy of the torsion angle measurements and the precision of inclination, torsion, and the varus angle measurements were considered acceptable for clinical application.


Gambling activities of young Australians: developing a model of behaviour.
As more gambling venues open in Australia, youth gambling as problem behaviour has been identified. The aim of this study was to assess youth gambling in a population with easy access to gambling, and to evaluate the adequacy of a model for predicting adolescent gambling frequency and problem gambling. The model comprised a combination of the Theory of Reasoned Action (TRA) (Ajzen & Fishbein, 1980), personality variables (venturesomeness, impulsiveness), and cognitive bias variables derived from Weinstein's (1980) propositions concerning unrealistic optimism about future life events. A sample of 1017 school- and university-based adolescents indicated relatively low frequencies of gambling and low scores on the problem gambling scale, with males scoring higher than females on both measures. The TRA was supported with about 30% of the variance of each of gambling behaviour and problem gambling accounted for by intentions, attitudes, and subjective norms. Personality factors added significantly to the prediction of gambling. The cognitive bias variables, although independently not statistically significant, further contributed to prediction.


Bleeding-Related Complications and Readmission Rates Associated With Fibrin Sealant Use in Patients Undergoing Coronary Artery Bypass Graft Surgery in the United States.
To compare the clinical and economic outcomes of EVICEL (Ethicon, Inc., Somerville, NJ) and TISSEEL (Baxter Healthcare Corporation, Westlake Village, CA) use in patients undergoing primary coronary artery bypass graft (CABG) surgery. Retrospective database analysis. Premier prospective hospital database (June 2009 through March 2014) covering approximately 20% of hospital discharges in the United States. Adults undergoing primary CABG surgery who received either EVICEL or TISSEEL on the day of surgery (index date). Two intervention groups were formed, EVICEL and TISSEEL. Clinical outcomes compared included postoperative bleeding complications (International Classification of Diseases, Ninth Revision, Clinical Modification code: 998.1) and number of blood transfusions received on the index day. Economic outcomes compared included hospital length of stay, hospital costs, and 30-day readmission rates. Propensity-score matching was used to control for patient and hospital characteristics. A total of 129,014 primary CABG surgery patients were identified; 986 patients (mean age: 64 years, 73% male) received EVICEL and 6,340 patients (mean age: 65 years, 75% male) received TISSEEL on the index day. After propensity-score matching, patients who received EVICEL compared with TISSEEL had significantly fewer postoperative bleeding complications (3.0% v 5.0%, p = 0.0197), index-day blood transfusion rates (19% v 34%, p<0.0001), readmission rates (18% v 32%, p<0.0001), and costs ($40,736 [standard deviation $19,465] v $46,005 [standard deviation $24,049], p<0.0001). Results from a sensitivity analysis using a generalized linear model to control for other hemostatic agent use also favored EVICEL over TISSEEL. Results from this real-world retrospective database analysis showed fewer bleeding complications and lower costs in patients undergoing primary CABG surgery who received EVICEL compared with TISSEEL.


Influence of soil reaction on diversity and antifungal activity of fluorescent pseudomonads in crop rhizospheres.
The diversity and antifungal activity of fluorescent pseudomonads isolated from rhizospheres of tea, gladiolus, carnation and black gram grown in acidic soils with similar texture and climatic conditions were studied. Biochemical characterisation including antibiotic resistance assay, RAPD and PCR-RFLP studies revealed a largely homogenous population. At soil pH (5.2), the isolates exhibited growth with varying levels of siderophore production, irrespective of crop rhizospheres. Two isolates with maximum chitinase production showed antagonism. The bacterial populations in general lacked the ability to produce deleterious traits such as cellulase, pectinase and hydrogen cyanide. However, increased pH levels beyond 5.2 caused reduction in metabolite production with reduced antifungal activity. The homogeneity of the bacterial population irrespective of crop rhizospheres together with decreased secondary metabolite production at higher pH levels reinstated the importance of soil over host plant in influencing rhizosphere populations. The studies also yielded acid tolerant chitinase producing antagonistic fluorescent pseudomonads.


A new species of Copa (Araneae: Corinnidae: Castianeirinae) from dry forests in the north west of Madagascar.
A new species of the castianeirine spider genus Copa Simon, 1885, is described from northwestern Mahamavo region in Madagascar. Copa sakalava sp. nov. () is illustrated and diagnosed against continental Afrotropical congeners.


Stoichiometric interactions between cyanobacterial clock proteins KaiA and KaiC.
We determined the stoichiometry of KaiA-KaiC interactions. Using immunoblotting and two-dimensional Native- and SDS-PAGE (2DNS-PAGE) analysis, we demonstrated that the reaction products of KaiA-KaiC interactions in the presence of ATP consisted of only phosphorylated KaiC whereas in the presence of the unhydrolyzable analogue 5'-adenylylimidodiphosphate (AMPPNP) they consisted of KaiA and KaiC. In the presence of ATP, the KE (molar ratio of KaiA dimer to KaiC hexamer giving half saturation in the enhancement of KaiC phosphorylation) was 0.25, and IAsys affinity biosensor analysis demonstrated that 1 molecule of KaiA dimer interacted with 1 molecule of KaiC hexamer. In the presence of AMPPNP, the ratio of KaiA dimer to KaiC hexamer in KaiA-KaiC complexes was determined to be 2 by 2DNS-PAGE, Native-PAGE/Scatchard plot, and IAsys analyses. These results suggest that 2 molecules of KaiA dimer can interact with 1 molecule of KaiC hexamer, and that interactions of at least 1 molecule of KaiA dimer with 1 molecule of KaiC hexamer are enough to enhance the phosphorylation of KaiC by KaiA at an almost saturated level.


Maternal urine phthalate metabolite exposure and miscarriage risk: a nested case-control study of the Zunyi Birth Cohort.
Phthalates (PAEs) are widespread persistent organic pollutants and endocrine disruptors. However, the associations between PAE exposure and the risk of miscarriage in humans are unclear, and an insufficient number of studies have evaluated the possible threshold or dose-dependent effects of first trimester PAE exposure on miscarriage risk. Our research measured the levels of mono-methyl phthalate (MMP), mono-ethyl phthalate, mono-isobutyl phthalate, MiBP mono-butyl phthalate (MBP), mono-octyl phthalate, mono-benzyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in maternal urine collected in early gestation between 150 pregnancies ending in miscarriage and 150 pregnancies with live birth. We also estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PAE as a continuous variable or quartile. A restrictive cubic splines was used to assess dose-dependent effects after controlling for maternal characteristics (e.g., age, educational level). we identified monotonically increasing dose-dependent effects of MEHHP and MMP on the risk of miscarriage. The largest effect estimates were approximately threefold higher for the highest MBP (OR = 2.57; 95% CI = 1.32-5.01) or MMP quartile (OR = 3.57; 95% CI = 1.82-7.00) and two-fold higher for the highest MEHHP quartile (OR = 2.12; 95% CI = 1.10-4.11). Our research preliminarily obtained possible thresholds of MBP, MEHHP, and MMP which were 18.07, 2.38, and 0.80 µg/g Cr for the risk of miscarriage, respectively. First-trimester exposure to MBP, MEHHP, and MMP exceeding certain thresholds increases the risk of miscarriage.


α-Catenin links integrin adhesions to F-actin to regulate ECM mechanosensing and rigidity dependence.
Both cell-cell and cell-matrix adhesions are regulated by mechanical signals, but the mechanobiological processes that mediate the cross talk between these structures are poorly understood. Here we show that α-catenin, a mechanosensitive protein that is classically linked with cadherin-based adhesions, associates with and regulates integrin adhesions. α-Catenin is recruited to the edges of mesenchymal cells, where it interacts with F-actin. This is followed by mutual retrograde flow of α-catenin and F-actin from the cell edge, during which α-catenin interacts with vinculin within integrin adhesions. This interaction affects adhesion maturation, stress-fiber assembly, and force transmission to the matrix. In epithelial cells, α-catenin is present in cell-cell adhesions and absent from cell-matrix adhesions. However, when these cells undergo epithelial-to-mesenchymal transition, α-catenin transitions to the cell edge, where it facilitates proper mechanosensing. This is highlighted by the ability of α-catenin-depleted cells to grow on soft matrices. These results suggest a dual role of α-catenin in mechanosensing, through both cell-cell and cell-matrix adhesions.


Utilization of machine learning to test the impact of cognitive processing and emotion recognition on the development of PTSD following trauma exposure.
Though lifetime exposure to traumatic events is significant, only a minority of individuals develops symptoms of posttraumatic stress disorder (PTSD). Post-trauma alterations in neurocognitive and affective functioning are likely to reflect changes in underlying brain networks that are predictive of PTSD. These constructs are assumed to interact in a highly complex way. The aim of this exploratory study was to apply machine learning models to investigate the contribution of these interactions on PTSD symptom development and identify measures indicative of circuit related dysfunction. N = 94 participants admitted to the emergency room of an inner-city hospital after trauma exposure completed a battery of neurocognitive and emotional tests 1 month after the incident. Different machine learning algorithms were applied to predict PTSD symptom severity and clusters after 3 months based. Overall, model accuracy did not differ between PTSD clusters, though the importance of cognitive and emotional domains demonstrated both key differences and overlap. Alterations in higher-order executive functioning, speed of information processing, and processing of emotionally incongruent cues were the most important predictors. Data-driven approaches are a powerful tool to investigate complex interactions and can enhance the mechanistic understanding of PTSD. The study identifies important relationships between cognitive processing and emotion recognition that may be valuable to predict and understand mechanisms of risk and resilience responses to trauma prospectively.


Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model.
Marbofloxacin is a third-generation fluoroquinolone developed solely for veterinary medicine with a broad spectrum of antibacterial activity against some Gram-positive and most Gram-negative bacteria, including the bovine respiratory tract pathogen, Pasteurella multocida. The objective of our study was to elucidate the pharmacokinetics and pharmacodynamics of marbofloxacin in a Pasteurella multocida infected murine lung model, and to estimate the magnitudes of pharmacokinetics-pharmacodynamics parameters associated with various effects. The pharmacokinetic studies revealed marbofloxacin kinetics in infected mice were linear over a dose ranging from 1.25 to 10 mg/kg of body weight. The protein binding in the plasma of neutropenic infected mice was 29.77 %. The magnitudes of the ratio of the free-drug area under the concentration-time curve over 24 h to MIC (fAUC 0-24h/MIC) associated with static effect, a 2 log10 reduction and a 3 log10 reduction of bacterial counts were 40.84, 139.34, and 278.08 h, respectively. Based on the dose range study, marbofloxacin exhibited concentration-dependent killing and the fAUC/MIC was the PK/PD index that correlated best with efficacy (R(2) = 83 %). On the basis of a bactericidal effect goal of fAUC 0-24h/MIC of 278.08 h, if marbofloxacin is used for the treatment of P. multocida serious lung infection with an MIC90 of 0.12 μg/ml, the current dose (2 mg/kg) would fail to achieve a bactericidal effect. It would benefit from higher doses (4 ~ 6 mg/kg) than those commonly used in clinical practice.


Efficient de novo synthesis of resveratrol by metabolically engineered Escherichia coli.
Resveratrol has been the subject of numerous scientific investigations due to its health-promoting activities against a variety of diseases. However, developing feasible and efficient microbial processes remains challenging owing to the requirement of supplementing expensive phenylpropanoic precursors. Here, various metabolic engineering strategies were developed for efficient de novo biosynthesis of resveratrol. A recombinant malonate assimilation pathway from Rhizobium trifolii was introduced to increase the supply of the key precursor malonyl-CoA and simultaneously, the clustered regularly interspaced short palindromic repeats interference system was explored to down-regulate fatty acid biosynthesis pathway to inactivate the malonyl-CoA consumption pathway. Down-regulation of fabD, fabH, fabB, fabF, fabI increased resveratrol production by 80.2, 195.6, 170.3, 216.5 and 123.7%, respectively. Furthermore, the combined effect of these genetic perturbations was investigated, which increased the resveratrol titer to 188.1 mg/L. Moreover, the efficiency of this synthetic pathway was improved by optimizing the expression level of the rate-limiting enzyme TAL based on reducing mRNA structure of 5' region. This further increased the final resveratrol titer to 304.5 mg/L. The study described here paves the way to the development of a simple and economical process for microbial production of resveratrol.


Developmental expression and androgenic regulation of the mRNA for major secretory proteins of the rat epididymis.
The concentration of the mRNAs for two pairs of androgen-dependent secretory proteins of the rat epididymis has been measured by filter hybridization with cDNA during the course of post-natal development and following castration and androgen replacement of adult animals. The rate of synthesis of the secretory proteins, measured in an in vitro incubation system, was also ascertained during post-castration involution of the epididymis and during subsequent androgen replacement. The mRNAs for the proteins were first detected at 20 days of age and their levels increased rapidly to reach near adult levels between 30 and 40 days. In the caput epididymidis the levels of the mRNAs declined rapidly during the first week after castration and became undetectable by 16 weeks. Administration of testosterone propionate to animals castrated for 16 weeks reinduced the levels of mRNAs to maximum values by 1 week, but for one pair of proteins the reinduced maximum was only 30% of precastration values. This result, in conjunction with other information, is suggestive that this pair of proteins is under multihormonal control. In the cauda epididymidis, the kinetics of change in mRNA level during androgen withdrawal and replacement were slower than in the caput. In all instances, changes in the rate of synthesis of the secretory proteins followed by observed changes in their level of mRNA, suggesting an absence of androgenic control of translation in the epididymidis.


Orthogonal electrogram sensing.
Intracardiac electrogram sensing is the afferent limb of demand pacing systems. Under- and over-sensing at the ventricular level has been demonstrated in almost 50% of implanted unipolar pulse generators, and atrial electrogram sensing problems are more common. A unique dedicated sensor employing noncontacting and circumferentially placed orthogonal electrodes was tested at both the atrial and ventricular levels. Electrograms demonstrated voltages similar to those recorded from contacting electrodes, but with complete far-field rejection of signals from the opposite chamber. Orthogonal electrograms allowed for activation sequencing and capture verification as well.


Factors related to the waiting time for scheduling an oral biopsy in Brazil: a multilevel analysis.
Timely diagnosis of oral cancers is critical, and performing biopsies of oral lesions with suspected malignancy is a crucial step in achieving this goal. The waiting time for the diagnosis may be related to the progression and prognosis of malignant neoplasms. The aim of this observational, cross-sectional, national-level study was to identify the factors associated with the waiting time for scheduling an oral biopsy, based on the identification of its need. We used secondary data from the Brazilian public health system, obtained from the 2nd cycle of the National Program to Improve Access and Quality of Dental Specialty Centers (PMAQ-CEO). The study outcome was the waiting time for scheduling an oral biopsy, starting from the identification of the need for the exam. We analyzed individual and contextual variables using multilevel statistical analysis. In 51.8% of DSC the waiting time for scheduling a biopsy was non-immediate; in 58.1% of CEOs, the sum of the weekly workload of dentists working in the Stomatology specialty is up to 20 h per week; in terms of coverage, 67.1% of the CEOs have only municipal coverage and 34.0% are references for up to 12 oral health teams in primary health care; only the coverage variable remained significant in the multivariate model (p < 0.05). Of the contextual variables, none of the variables remained significant (p > 0.05). When these were analyzed together, only the coverage remained significant (p < 0.05); CONCLUSION: Our analysis indicates that the waiting time for scheduling an oral biopsy is longer in CEOs that cover only one municipality and is not related to contextual factors.


Ultrastructural changes in rat hypothalamic neurosecretory cells and their associated glia during minimal dehydration and rehydration.
A quantitative ultrastructural study was performed to determine the changes in the neurosecretory neurons of the supraoptic (SON) and circularis (NC) nuclei following 4-24 h of water deprivation (WD) and subsequent rehydration (12 and 24 h). In both nuclei, the amount of direct soma-somatic contact increased throughout WD, apparently by retraction of fine glial processes from between the cells. Rehydration reversed these changes. The number of smaller (less than 1600 A) neurosecretory granules (NSG's) decreased in both nuclei at 4 h of WD but returned to control levels by 24 h of WD and remained so during rehydration. Larger (less than 1600 A) NSG's decreased in number at 4 h of WD in SON and then returned to control levels by 24 h of WD and remained the same throughout rehydration. In NC, these NSG's did not change in number with WD, but significantly increased between 12 and 24 h of rehydration. No cells with dilated rough endoplasmic reticulum were seen in NC during this study. In SON, however, the percentage of such cells increased at 4 and 12 h of dehydration only to decrease to control levels at 24 h of dehydration and throughout rehydration. Lysosomes decreased at 4 h of dehydration in SON and returned to control levels thereafter. In NC, lysosomes tended to decrease with dehydration and increase with rehydration. These findings indicate that detectable morphological changes take place in the course of alterations in hydration state that are well within the physiological range.


Light, leaf age, and leaf nitrogen concentration in a tropical vine.
Tropical vines in the Araceae family commonly exhibit alternating periods of upward and downward growth, decoupling the usual relationship between decreasing light environment with increasing age among the leaves on a shoot. In this study I examined patterns of light, leaf specific mass, and leaf nitrogen concentration in relation to leaf position, a measure of developmental age, in field collected shoots of Syngonium podophyllum. These data were analyzed to test the hypothesis that nitrogen allocation parallels within-shoot gradients of light availability, regardless of the relationship between light and leaf age. I found that leaf nitrogen concentration, on a mass basis, was weakly correlated with leaf level light environment. However, leaf specific mass, and consequently nitrogen per unit leaf area, were positively correlated with gradients of light within the shoot, and either increased or decreased with leaf age, providing support for the hypothesis that nitrogen allocation parallels gradients of light availability.


Favourable effect of flunarizine on the recovery from hemiparesis in rats with intracerebral hematomas.
In 25 rats, an intracerebral hematoma was created in the foreleg area of the motor cortex by injection of 50 microliters blood. After the lesion, 13 were treated with flunarizine and 12 with the solvent. Neurological testing was performed by measuring the running time on a rotating platform. In animals with hemiparesis, the flunarizine group (n = 7) showed a significantly (P less than 0.05) better recovery than the control group (n = 8). No significant differences occurred in animals without neurological deficits (flunarizine: n = 6, control: n = 4). So the effect of the drug is not due to a non-specific activation; it may partially cure neurological deficits caused by intracerebral hematoma.


Purification of lactose synthetase a protein from human milk and demonstration of its interaction with alpha-lactalbumin.
A fairly simple procedure for isolating lactose synthetase A protein from human milk in 36% yield is described. The A protein has a molecular weight of about 40,000. Its interaction with alpha-lactalbumin in the presence of N-acetylglucosamine has been demonstrated by affinity chromatography and gel filtration.


Parasitological examination for presence of hookworms (Uncinaria spp.) in northern elephant seals (Mirounga angustirostris) at Año Nuevo State Reserve, California (2012).
Northern elephant seals (Mirounga angustirostris Gill, 1866), inhabiting rookeries on the mainland of Año Nuevo State Reserve in central California, were investigated in 2012 for presence of hookworms (Uncinaria spp.). Material collected and examined for hookworms included: blubber (n = 15), stomach and intestines (n = 21) from dead pups; feces from the rectum of weaned pups (n = 23); sand containing apparent feces in areas of weaned pups (n = 28) and sand without apparent feces in areas of weaned pups (n = 54); milk from females (n =23) at 5 days and about 23 to 26 days postpartum; and placenta from one female. Evidence of hookworm presence was not detected in any of the samples examined. Possible reasons why hookworms were not found in northern elephant seals on the mainland of Año Nuevo State Reserve are discussed.


Dysbaric cerebral air embolism in Hawaii.
Cerebral air embolism is a major cause of death and disability among sport scuba divers. To better define the epidemiologic and clinical manifestations of this infrequently encountered disorder, the records of all recompression treatments in Hawaii from 1976 through 1979 were reviewed. Forty-two cases of dysbaric air embolism (DAE) were identified on the basis of clinical criteria, accounting for 18% of the patients undergoing recompression treatment for diving-related disorders during this four-year period. In 22 patients (52%), DAE was part of a dysbarism syndrome that involved one or more forms of decompression sickness and/or in which DAE could not be differentiated from neurologic decompression sickness. The presenting signs and symptoms varied, with asymmetric multiplegia being the most common finding. Two patients died, giving a case fatality rate of 5% for those who survived until reaching the recompression chamber. Overall, 78% of the cases manifested either complete (61%) or substantial (17%) recovery with recompression and adjunctive medical measures. Traditional concepts of dysbaric cerebral air embolism are not adequate to explain the spectrum of clinical manifestations encountered in this condition.


Management of combined hepatocellular carcinoma-cholangiocarcinoma.
To review the recent consensus on the nomenclature, clinical features, diagnosis, and treatment of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA). cHCC-CCA is a primary liver carcinoma with varying degrees of hepatocytic and cholangiocytic cytology and architecture within the same tumor. The diagnosis of cHCC-CCA can only be established based on histologic examination. Surgical resection should be considered in patients with resectable tumors who do not have underlying liver disease or clinically significant portal hypertension. While treatment by liver transplantation (LT) is controversial due to the high risk of post LT recurrence, LT should remain as a potentially curative option in a highly selected group of patients. Little data exist for the outcome of other treatments. High quality multicenter prospective studies should be conducted to better understand this rare, but increasingly recognized tumor.


Endoscopic retrograde cholangiopancreatography results three days after a failed pre-cut.
deep cannulation of the common bile duct is essential in endoscopic retrograde cholangiopancreatography (ERCP). However, cannulation is not possible in approximately 20 % of the cases with the usual techniques. Pre-cutting is an alternative that allows cannulation in difficult cases although its success is not guaranteed. Repeating the ERCP within three days of a failed pre-cut is an acceptable option. to determine if an ERCP performed three days after a failed pre-cut papillotomy allows the bile duct to be cannulated without increasing complication rates. patients who underwent an ERCP plus pre-cut were included, in whom the common bile duct could not be cannulated and who also underwent a new ERCP three days after the initial pre-cut. The primary objective was a successful biliary cannulation in the second ERCP and the secondary objective were the complications of the initial pre-cut. forty patients with an average age of 65 years were identified and 57 % were male. The indications for ERCP were choledocholithiasis in 95 %, biliary fistula in 2.5 % and pancreatic neoplasia in 2.5 %. The ERCP was repeated three days later in 92.5 % of the cases and the biliary cannulation was successful in 78.3 %. a new ERCP performed within three days of a failed pre-cut is justifiable since it has a significant success rate. Bile duct cannulation is achieved in three out of four patients, with an acceptable percentage of complications.


A statistical table for the degree of coexistence between two species.
The well known Jaccard's association coefficient has been calculated on perfectly random infinite samples of different n size and a statistical table with the corresponding probability values is presented.


Geographical genetic variation in the gene encoding VP3 from the Alberta isolate of epizootic hemorrhagic disease virus.
The complete nucleic acid and deduced amino acid sequences of gene segment 3 and the encoded VP3 from the North American, Alberta isolate of epizootic hemorrhagic disease virus serotype 2 (EHDV-2) are reported. Complementary DNA corresponding to segment 3 was 2768 nucleotides in length with an open reading frame of 2697 base pairs which encoded a VP3 polypeptide of 899 amino acid residues. Sequence comparison with genome segment 3 and VP3 from the Australian strain of EHDV-2 indicated genotypic and phenotypic homologies of 79% and 94%, respectively. Two North American field isolates of EHDV-2, as well as EHDV-1 (New Jersey isolate), had virtually identical homology to the Alberta isolate. Sequence analysis delineated North American EHDV strains as members of a genetically homologous and geographically distinct group of orbiviruses (topotype). The data support the hypothesis that geographic isolation between North American and Australian orbiviruses has permitted the viral topotypes to maintain their genetic distinctness.


Exploring the Pattern of Early COVID-19 Transmission Caused by Population Migration Based on 14 Cities in Hubei Province, China.
Relevant studies show that population migration has a great impact on the early spread of infectious diseases. Therefore, it is important to explore whether there is an explicit relationship between population migration and the number of confirmed cases for the control of the COVID-19 epidemic. This paper mainly explores the impact of population migration on early COVID-19 transmission, and establishes a predictive nonlinear mathematical model to predict the number of early cases. Data of confirmed cases were sourced from the official website of the Municipal Health Committee, and the proportions of migration from Wuhan to other cities were sourced from the Baidu data platform. The data of confirmed cases and the migration proportions of 14 cities in Hubei Province were collected, the COVID-19 cases study period was determined as 10 days based on the third quartile of the interval of the incubation period, and a non-linear mathematical model was constructed to clarify the relationship between the migration proportion and the number of confirmed COVID-19 cases. Finally, eight typical regions were selected to verify the accuracy of the model. The daily population migration rates and the growth curves of the number of confirmed cases in the 14 cities were basically consistent, and Pearson's correlation coefficient was 0.91. The specific mathematical expression of 14 regions is . In each of the fourteen cities, The nonlinear exponential model structure is as follows:. It was found that the R 2 values of the fitted mathematical model were greater than 0.8 in all studied regions, excluding Suizhou (p < 0.05). The established mathematical model was used to fit eight regions in China, and the correlations between the predicted and actual numbers of confirmed cases were greater than 0.9, excluding that of Hebei Province (0.82). The study found that population migration has a positive and significant impact on the spread of COVID-19. Modeling COVID-19 risk may be a useful strategy for directing public health surveillance and interventions. Restricting the migration of the population is of great significance to the joint prevention and control of the pandemic worldwide.


Demonstration of giant and anular nexus in the psoriatic epidermis.
In the psoriatic skin, nexus were most prominent in the upper layers of the viable epidermis, using the Alcian blue-Lanthanum technique. There, they reached double and manifold the length (giant nexus) of those in normal epidermis. According to the villous transformation of the epidermal cell surface in psoriasis, the nexus showed a great variation in their shape. Undulating nexus were seen beside invagination--and anular nexus. On ther other hand, nexus were lacking in the deepest layers of the psoriatic epidermis in contrast to normal epidermis. From these findings it seems that the intercellular communication by specialized low resistant junctions is reduced in the deepest layers of the psoriatic epidermis. In the upper epidermal layers, however, the extensive formation and the variable configuration of the nexus express a high synthetic activity and a well developed intercellular information in these areas of the psoriatic epidermis.


Effect of position changing on bilirubin levels during phototherapy.
Turning of infants during phototherapy for hyperbilirubinemia is practiced in many nurseries. However, there is little research evidence in support of this practice. This study examined the effect of turning on serum total bilirubin concentration and on the duration of phototherapy. We first conducted a pilot study in term infants requiring phototherapy using transcutaneous bilirubinometry in order to determine the time required to clear the skin of bilirubin. This "blanching time" was found to be approximately 150 minutes. We then conducted a randomized study comparing turning the baby during phototherapy with care in the supine position only. Thirty term infants were enrolled in the study (turned - 14; supine - 16). No differences were found between the groups in baseline data, such as birth weight, gestational age, age at start of phototherapy, or type of feeds. Infants in the supine group showed a significantly larger drop in serum total bilirubin concentration and required a shorter duration of phototherapy. We conclude that infants should be nursed supine during phototherapy. Based on these results, we propose a modification to the traditional model of bilirubin kinetics during phototherapy.


Perceptuo-motor dysfunction in the child with hemiplegia.
Eighteen children with hemiplegia were examined by means of standard neurological and other, specialized, sub-tests to define the extent of their perceptuo-motor dysfunction. Particular attention was paid to auditory language function, praxis, visuo-spatial skills, body schema, tactile defensiveness and inattention. The side of the hemiplegia was not found to predispose to any specific dysfunction, with the exception of inattention which was seen only in those with left-sided hemiplegia. Children with a history of familial sinistrality had a higher incidence of speech problems, particularly in the area of auditory language and speech delay. The results are discussed in the light of therories of plasticity and cerebral organization.


Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis.
In a variety of recent studies in animals with chronic renal diseases, investigators have found a tight correlation between the elevation in glomerular pressures and flows versus glomerular hypertrophy. To investigate a possible causal link between the glomerular hyperfunction and hypertrophy, we studied the functional and morphological sequelae of nephrectomy and those of unilateral ureteral diversion (UD) into the peritoneal cavity (that is, removal of renal clearance function while keeping the kidney tissue in situ). In all nine experimental groups of 54 Munich-Wistar rats, 2/3 of the renal mass was removed from the left kidney by ligation of two or three branches of the left renal artery. In addition, right nephrectomy (NPX) was performed in Groups 1B, 2B and 3B or UD in Groups 1C, 2C and 3C. The right kidney was left untouched in control groups, Groups 1A, 2A and 3A. Micropuncture measurements and histological studies were performed at four days (Groups 1A, 1B and 1C), two weeks (Groups 2A, 2B and 2C) or four weeks (Groups 3A, 3B and 3C). At both four days and two weeks, NPX and UD groups had marked and comparable degrees of glomerular hypertension, hyperperfusion and hyperfiltration compared to the control group in the left kidney.(ABSTRACT TRUNCATED AT 250 WORDS)


Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice.
GM-CSF takes part in the cytokine network regulating the metabolism of extracellular matrix (ECM) during atherogenesis. Since data also point to an effect of GM-CSF on the vascular ECM in general, the vascular collagenous matrix was studied in wild-type and GM-CSF-deficient mice. Histological examination revealed a disorganized vascular ECM in GM-CSF-deficient mice involving the collagenous matrix and elastic fiber system. As shown by electron microscopy, collagen bundles were disrupted and reduced. The diameter of fibrils varied widely. mRNA expression of collagens and related molecules was studied. Fibrillar collagens were markedly reduced, alpha1(I)procollagen to 16.5% of control levels alpha1(III)procollagen was abolished whereas the expression level of network-forming alpha1(VIII)procollagen was not altered. As shown by in situ hybridization, the number of collagen-expressing cells was reduced. Matrix metalloproteinases and their inhibitor 1 were not affected by GM-CSF deficiency. Our studies demonstrate that GM-CSF plays a major role in the cytokine network regulating the metabolism of vascular collagens. GM-CSF deficiency leads to an altered composition of the vascular collagenous matrix, i.e., reduced amount of fibrillar collagen, altered ratio of fibrillar and network-forming collagen, and failures in the fibrillogenesis. We suggest that GM-CSF is a basic requirement for the maintenance of vessel wall integrity and resilience.


A limited survey of fumonisins in corn and corn-based products in Asian countries.
Natural occurrence of fumonisins B1 (FB1) and B2 (FB2), a promoter for hepato-carcinogenesis, was investigated in corn and corn - based products sampled in Japan, Nepal, and China by high - performance liquid chromatographic method. From the 9 imported corn kernel and 6 gluten feed samples, FB1 was detected in 8 corn (0.6 ∼ 4.1μg/g) and all gluten feed (0.3 ∼ 2.4μg/g) samples, while FB2 was found in the same corn (0.3 ∼ 10μg/g) and 3 gluten feed (0.8 ∼ 8.5μg/g) samples. ELISA analysis also revealed the contamination of aflatoxin B1 in 2 corn and all gluten feed samples along with fumonisins. Of 17 corn grit samples, 14 and 5 samples were contaminated with fumonisin B1 and B2, with maximum levels of 2.6 and 2.8μg/g, respectively. As for corn-based foodstuffs marketed in Japan, no significant contamination of fumonisins was observed. Among 24 corn kernel samples in Nepal, 12 and 7 samples were positive for FB1 and FB2, and averaged to 0.6 and 1.6μg/g, respectively. One sample showed the highest fumonisin contents as 4.6 and 5.5μg/g, respectively. In corn samples harvested at Shanghai and Beijing, China, FB1 and FB2 were detected in various concentrations. Mycological survey has also revealed the presence of a fumonisin - producing fungus in a crop field of Japan. These findings have for the first time demonstrated high levels of contamination of fumonisins in corn and corn - based products in Asian countries. Natural co - occurrence of fumonisins and aflatoxin B1 was also detected in raw materials for mixed feed.


The angiotensin converting enzyme (ACE) inhibitor, captopril disrupts the motility activation of sperm from the silkworm, Bombyx mori.
Angiotensin I-converting enzyme (also known as peptidyl dicarboxypeptidase A, ACE, and EC 184.108.40.206), which is found in a wide range of organisms, cleaves C-terminal dipeptides from relatively short oligopeptides. Mammalian ACE plays an important role in the regulation of blood pressure. However, the precise physiological functions of insect ACE homologs have not been understood. As part of our effort to elucidate new physiological roles of insect ACE, we herein report a soluble ACE protein in male reproductive secretions from the silkmoth, Bombyx mori. Seminal vesicle sperm are quiescent in vitro, but vigorous motility is activated by treatment with either a glandula (g.) prostatica homogenate or trypsin in vitro. When seminal vesicle sperm were pre-incubated with captopril, a strong and specific inhibitor of mammalian ACE, and then stimulated to initiate motility by the addition of the g. prostatica homogenate or trypsin, the overall level of acquired motility was reduced in an inhibitor-concentration-dependent manner. In the course of this project, we detected ACE-related carboxypeptidase activity that was inhibited by captopril in both the vesicular (v.) seminalis of the noncopulative male reproductive tract and in the spermatophore that forms in the female bursa copulatrix at the time of mating, just as in an earlier report on the tomato moth, Lacanobia oleracea, which belongs to a different lepidopteran species (Ekbote et al., 2003a). Two distinct genes encoding ACE-like proteins were identified by analysis of B. mori cDNA, and were named BmAcer and BmAcer2, respectively [the former was previously reported by Quan et al. (2001) and the latter was first isolated in this paper]. RT-qPCR and Western blot analyses indicated that the BmAcer2 was predominantly produced in v. seminalis and transferred to the spermatophore during copulation, while the BmAcer was not detected in the adult male reproductive organs. A recombinant protein of BmAcer2 (devoid of a signal peptide) that was expressed in Escherichia coli cells exhibited captopril-sensitive carboxypeptidase activities. Our findings show that the BmAcre2 gene encodes a secreted ACE protein included in the Bombyx seminal plasma. In particular, the silkworm ACE protein in the seminal fluid might be involved in the signaling pathway that leads to the activation and regulation of sperm motility.


Morphological findings in spontaneously hypertensive rats in comparison with findings after experimental renal hypertension.
The morphological findings in spontaneously hypertensive rats (SHR) were compared with the findings after experimental renal hypertension. In addition the effect of an arteriosclerogenic diet was investigated. Cardiac hypertrophy occurred in all types of hypertension. During the course of renal hypertension there was also hypertrophy of the tunica media of the arterial vessels of the heart, kidneys, mesenterium, and orta. Degenerative changes in the vascular walls occurred when nephrectomized rats were given a diet containing 2% cholesterol and 1% cholic acid. This produced intima lipoidosis after seven to eleven weeks. The intensity seemed to be dependent on the degree of hypertension and the duration of the experiment.


Sparse reconstruction of brain circuits: or, how to survive without a microscopic connectome.
Inside one voxel of a cubic millimeter of neocortex, fifty to hundred thousand neurons use 4 km of axonal cable to form three to fifteen hundred million synapses with each other. While in the human, such voxel is a small fragment of a cortical area, in the mouse an entire cortical area, like the primary auditory cortex, can be contained in a voxel of this size. This raises the fundamental question of what happens inside such a voxel? Are the circuits contained in this voxel, and their operations, different in every area, or are there general principles that are conserved across cortical areas and species? Such questions go to the heart of understanding how the neocortex wires itself and works. One proposal is to answer these questions by mapping the entire circuit at synaptic resolution to produce a 'connectome' - of the cortical column, or even of the entire brain. However, such a high-resolution connectome is self-evidently unachievable with the tools available and as a strategy it still leaves us short of understanding the 'principles of neural engineering'. We offer an alternative route that uses physiology and computational modeling as a means of generating 'predictive anatomy', where the questions about underlying structure are directed to fundamental principles of organization and operation of the cortical circuits. This approach involves 'sparse' rather than 'dense' reconstructions at light and electron microscope resolution to keep the questions well-matched to current experimental tools. Rather than providing a snap-shot of an entire wiring diagram, our strategy provides for a statistical description of the circuit and integrates theory, function, and structure in a common framework.


Balance recovery stepping responses during walking were not affected by a concurrent cognitive task among older adults.
Most of older adults' falls are related to inefficient balance recovery after an unexpected loss of balance, i.e., postural perturbation. Effective balance recovery responses are crucial to prevent falls. Due to the considerable consequences of lateral falls and the high incidence of falls when walking, this study aimed to examine the effect of a concurrent cognitive task on older adults' balance recovery stepping abilities from unannounced lateral perturbations while walking. We also aimed to explore whether cognitive performance accuracy is affected by perturbed walking and between task trade-offs. In a laboratory-based study, 20 older adults (> 70 years old) performed the following test conditions: (1) cognitive task while sitting; (2) perturbed walking; and (3) perturbed walking with a concurrent cognitive task. The cognitive task was serial numbers subtraction by seven. Single-step and multiple-step thresholds, highest perturbation achieved, 3D kinematic analysis of the first recovery step, and cognitive task performance accuracy were compared between single-task and dual-task conditions. Between task trade-offs were examined using dual-task cost (DTC). Single-step and multiple-step thresholds, number of recovery step trials, number of foot collision, multiple-step events and kinematic recovery step parameters were all similar in single-task and dual-task conditions. Cognitive performance was not significantly affected by dual-task conditions, however, different possible trade-offs between cognitive and postural performances were identified using DTC. In situations where postural threat is substantial, such as unexpected balance loss during walking, balance recovery reactions were unaffected by concurrent cognitive load in older adults (i.e., posture first strategy). The study was approved by the Helsinki Ethics Committee of Soroka University Medical Center in Beer-Sheva, Israel (ClinicalTrials.gov Registration number NCT04455607 , ID Numbers: Sor 396-16 CTIL; 02/07/2020).


Changing Indications for Pediatric Tracheotomy: An Urban Indian Study.
To review the changing indications, decannulation rates, complications and mortality in pediatric tracheotomies. Medical records of children who underwent primary or revision tracheotomy from April 2003 to December 2015 were retrospectively analyzed. Patient characteristics including age, sex, preoperative diagnosis and indications for tracheotomy. The complications, mortality and decannulation rates for the tracheotomies were studied. There were 101 patients who underwent tracheotomy over a period of 13 years. Out of these, complete data was available for 99 patients. There were 61 males and 38 females and the age of children who underwent tracheotomy on an average ranged from 2 months to 16 years. The indications were divided into five categories: airway obstruction, cardiopulmonary, craniofacial, neurological, and trauma. Out of the 99 patients, 92 patients underwent an elective tracheotomy while only 7 patients underwent an emergency tracheotomy. Fifty-eight patients could be successfully decannulated. 13 patients in our study died during the course of treatment, however, none of the deaths could be directly attributed to the tracheotomy. Three patients developed peristomal granulations requiring intervention, 1 patient had a severe stomal infection, and one patient had a tracheocutaneous fistula requiring surgical closure. Over the last few decades, widespread use of vaccinations and improved pediatric and neonatal intensive care has revolutionized child healthcare in developing countries like ours. This impact is reflected in our finding that neurological impairment has displaced obstructive airway (of infective etiology) as the most common indication for pediatric tracheotomy in the present era.


Complete genome of Polaromonas vacuolata KCTC 22033T isolated from beneath Antarctic Sea ice.
Polaromonas vacuolata KCTC 22033T is an obligate aerobic, Gram-negative, psychrophilic and rod-shaped bacterium isolated from beneath the sea ice off the coast of the Palmer Peninsula, Anvers Islands, Antarctica. P. vacuolata is the type species of Polaromonas genus and the first example of gas vacuolate Betaproteobacteria isolated from marine habitats. Here, we report a complete genome of P. vacuolata KCTC 22033T, which consists of 3,837,686 bp (G + C content of 52.07%) with a single chromosome, 3461 protein-coding genes, 56 tRNAs and 6 rRNA operons. Genomic analysis revealed the presence of genes involved in bacterial adaptation under saline conditions, cold adaptation via the production of gas vesicles and cell adhesion proteins, and a photoheterotrophic lifestyle when challenged by starvation. Intriguingly, several of these genes were likely acquired from species outside the Polaromonas genus. The genomic information therefore describes the unique evolution and adaptation of P. vacuolata to its extraordinary habitat, i.e., beneath the Antarctic sea ice.


Effects of denervation and immobilisation during development upon [3H]ouabain binding by slow- and fast-twitch muscle of the rat.
The effect of innervation and of muscle inactivity upon the normal production of Na+-K+-ATPase sites, assayed by [3H]ouabain binding, in muscle surface membranes has been determined for the rat. In both slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles a large increase was found to occur in [3H]ouabain binding per unit weight of muscle over the first 3 weeks of life. Interruptions of development, brought about by fixation of muscles at different lengths at 5 days of age, had no significant effect upon [3H]ouabain binding by EDL. In contrast, fixation led to a decrease in binding in SOL. When fixed in a shortened position profound morphological changes occurred, although these were not apparent when SOL was fixed in a stretched position. Denervation of SOL at 5 days of age significantly reduced the age related increase in the density of [3H]ouabain binding, whilst denervation of EDL had little effect. It was concluded that normal development of SOL is dependent upon innervation and possibly the resulting muscle activity, whereas development of EDL was relatively independent of innervation.


Characterization of cytoplasmic secretory granules (PSG), in prostatic epithelium and their transformation-induced loss in dysplasia and adenocarcinoma.
Cytoplasmic clarity is a histological feature of normal prostatic secretory cells, but in this study, tissue fixation in strong (>2.5%) glutaraldehyde dramatically altered cytological staining. Secretory cytoplasm appeared red and granular on routine stains because of myriad intensely staining eosinophilic granules (PSG). Immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) showed their exclusive localization to the PSG. Electron microscopy confirmed these findings and also showed that after fixation in many agents, including formaldehyde, PSG appeared empty, accounting for the artefactual "clear cell" appearance on light microscopy. PSG were most densely concentrated apically in a bud-shaped luminal compartment in which cytokeratin was selectively absent. Normal exocrine secretion was visualized as detachment of apocrine buds or their in situ disintegration. Distinctively in dysplasia and almost all carcinomas, PSG were rare to absent, and proteases were free in the cytoplasm, often concentrated beneath the apical membrane. The apocrine compartment was absent, with no observed secretory mechanism. Tumor cells had dark amphiphilic cytoplasm after all fixatives. This provided a reliable method of distinguishing malignant from benign glands in tissues fixed in strong glutaraldehyde. Clear cell carcinomas, whose cytoplasm mimicked routinely fixed normal secretory cells, surprisingly had almost no PSG. Instead, their "granules" were lipid-filled vacuoles reflecting a secretory pathway not seen in normal cells, dysplasia, or the common "dark cell" carcinomas. These observations may define two distinctive biological pathways of prostate cancer evolution and may facilitate diagnostic decisions on needle biopsy samples.


WSSV proteins and DNA genome released by ultrasonic rupture can infect crayfish as effectively as intact virions.
Proteins and nucleic acids from ultrasonically ruptured white spot syndrome virus (WSSV) can infect crayfish and cause death as effectively as intact WSSV virions. In this study, ultrasound was used to rupture the virus and the resulting suspension was filtered through a 50 nm membrane. Analysis by PCR and SDS-PAGE showed that both viral genes (VP19, VP26, VP28 and DNA polymerase) and proteins (VP15, VP19, VP26 and VP28) were present in the filtered solution. Electron microscopy showed that there were no intact virions in the filtered solution. When crayfish were injected with the filtered solution or with intact WSSV, the mortality in each group was 100 %. The same result was seen when crayfish were challenged orally with the filtered solution and intact WSSV. The filtered solution of ultrasonically ruptured virus, which contains viral proteins and residual DNA genome, can thus infect the host as effectively as intact virions. When the solution of viral proteins and residual DNA genome was digested with DNase I and then injected into crayfish, the survival rate was 100 %. We also found that, although viral proteins (except VP15) in the solution of ruptured virus were destroyed by treatment with DNase I, DNase I did not destroy the structural proteins of intact virions. A remaining viral protein in the DNase I-treated solution protects the DNA genome from degradation and we concluded that this protein is VP15, which is a DNA-binding protein. Our study highlights the extreme danger in producing vaccines from proteins obtained by ultrasonic rupture of viruses sincethe viral DNA genome is difficult to degrade and, if present, will lead to viral infection.


De Novo Assembly and Annotation of the Complete Genome Sequence of Myxococcus xanthus DZ2.
We report the assembly and annotation of a high-quality genome sequence for Myxococcus xanthus strain DZ2 (GenBank accession number CP080538), created using a combination of short reads generated using DNBSEQ technology (BGI Genomics) and long high-fidelity (HiFi) reads generated using Pacific Biosciences (PacBio) technology.


In-Situ GISAXS Study of Supramolecular Nanofibers having Ultrafast Humidity Sensitivity.
Self assembled nanofibers derived from donor-acceptor (D-A) pair of dodecyl methyl viologen (DMV) and potassium salt of coronene tetracarboxylate (CS) is an excellent material for the development of organic electronic devices particularly for ultrafast response to relative humidity (RH). Here we have presented the results of in-situ grazing incidence small angle x-ray scattering (GISAXS) measurements to understand aridity dependent self reorganization of the nanofibers. The instantaneous changes in the organization of the nanofibers was monitored with different equilibrium RH conditions. Additionally formation of nanofibers during drying was studied by GISAXS technique - the results show two distinct stages of structural arrangements, first the formation of a lamellar mesophase and then, the evolution of a distorted hexagonal lattice. The RH dependent GISAXS results revealed a high degree of swelling in the lattice of the micelles and reduction in the distortion of the hexagonal structure with increase in RH. In high RH condition, the nanofibers show elliptical distortion but could not break into lamellar phase as observed during formation through drying. This observed structural deformation gives insight into nanoscopic structural changes of the micelles with change in RH around it and in turn explains ultrafast sensitivity in its conductivity for RH variation.


Cutaneous reflexes during rhythmic arm cycling are insensitive to asymmetrical changes in crank length.
The neural control of a movement depends upon the motor task performed. To further understand the neural regulation of different variations of the same type of movement, we created three dissimilar bilateral rhythmic arm cycling tasks by unilaterally manipulating crank length (CL). Modulation in the amplitude and sign of cutaneous reflexes was used as an index of neural control. Neurologically intact subjects performed three bilateral cycling trials at approximately 1 Hz with the ipsilateral crank arm at one of three different lengths. Cutaneous reflexes were evoked during each trial with trains (5 x 1.0 ms pulses at 300 Hz) of electrical stimulation delivered to the superficial radial nerve at the ipsilateral wrist. EMG recordings were made bilaterally from muscles acting at the shoulder, elbow, and wrist. Analysis was conducted after phase-averaging contingent upon the timing of stimulation in the movement cycle. CL variation created an asymmetrical cycling pattern and produced significant changes in the range of motion at the ipsilateral shoulder and elbow. Background EMG amplitude in muscles of the contralateral arm generally increased significantly as CL decreased. Therefore at a given phase in the movement cycle, the background EMG was different between the three cycling trials. In contrast, cutaneous reflex amplitudes in muscles of both arms were similar at each phase of the movement cycle between the different CLs trials at both early and middle latencies. This was particularly evident in muscles ipsilateral to nerve stimulation. We suggest that variations of arm cycling that primarily yield significant changes in the amplitude of muscle activity do not require significant task-specific change in neural control.


Unique genetic variants in dihydrolipoamide dehydrogenase (dld) gene confer strong resistance to phosphine in the rusty grain beetle, Cryptolestes ferrugineus (Stephens).
The rusty grain beetle, Cryptolestes ferrugineus, a major pest of stored commodities, has developed very high levels (>1000×) of resistance to the fumigant phosphine. Resistance in this species is remarkably stronger than reported in any other stored product pests demanding the need to understand the molecular basis of this trait. Previous genetic studies in other grain insect pests identified specific variants in two major genes, rph1 and rph2 in conferring the strong resistance trait. However, in C. ferrugineus, although the gene, rph1 was identified as cytochrome-b5-fatty acid desaturase, the rph2 gene has not been reported so far. We tested the candidate gene for rph2, dihydrolipoamide dehydrogenase (dld) using the recently published transcriptome of C. ferrugineus and identified three variants, L73N and A355G + D360H, a haplotype, conferring resistance in this species. Our sequence analysis in resistant strain and phosphine selected resistant survivors indicates that these variants occur either alone as a homozygote or a mixture of heterozygotes (i.e complex heterozygotes) both conferring strong resistance. We also found that one of the three variants, possibly L73N expressing "dominant" trait at low frequency in resistant insects. Comparison of dld sequences between Australian and Chinese resistant strain of this species confirmed that the identified variants are highly conserved. Our fitness analysis indicated that resistant insects may not incur significant biological costs in the absence of phosphine selection for 19 generations. Thus, we propose that the observed high levels of resistance in C. ferrugineus could be primarily due to the characteristics of three unique variants, L73N and A355G + D360H within dld.


Outcomes following liver transplant for alcohol-associated liver disease: comparing alcohol-associated hepatitis and cirrhosis.
Liver transplant (LT) is a highly effective therapy for refractory severe alcohol-associated hepatitis (SAH), but optimal selection criteria remain unknown. We aim to evaluate the outcomes of patients who received LT for alcohol-associated liver disease at our center following the introduction of updated selection criteria, including the removal of the minimum sobriety requirement. Data were collected on all patients who underwent LT for alcohol-associated liver disease from January 1, 2018, to September 30, 2020. Patients were divided into SAH and cirrhosis cohorts based on disease phenotype. One hundred twenty-three patients underwent LT for alcohol-associated liver disease, including 89 (72.4%) for cirrhosis and 34 (27.6%) for SAH. There was no difference in 1- (97.1 ± 2.9% vs. 97.7 ± 1.6%, p = 0.97) and 3-year (97.1 ± 2.9% vs. 92.4 ± 3.4%, p = 0.97) survival between SAH and cirrhosis cohorts. Return to alcohol use was more frequent in the SAH cohort at 1 year (29.4 ± 7.8% vs. 11.4 ± 3.4%, p = 0.005) and 3 years (45.1 ± 8.7% vs. 21.0 ± 6.2%, p = 0.005) including higher frequencies of both slips and problematic drinking. Unsuccessful alcohol use counseling (HR 3.42, 95% CI 1.12-10.5) and prior alcohol support meetings (HR 3.01, 95% CI 1.03-8.83) predicted a return to harmful alcohol use patterns in early LT recipients. Both duration of sobriety (c-statistic 0.32 (95% CI 0.34-0.43) and SALT score (c-statistic 0.47, 95% CI 0.34-0.60) were independently poor predictors of return to harmful drinking. Survival following LT was excellent in both SAH and cirrhosis cohorts. Higher rates of return to alcohol use highlight the importance of further individualized refinement of selection criteria and improved support following LT.


[The importance of the SCC antigen in the diagnosis and follow-up of cervix carcinoma. A cooperative study of the Gynecologic Tumor Marker Group (GTMG)].
SCC (squamous cell carcinoma) antigen is a subfraction of tumour antigen TA-4 isolated from cervical squamous cell carcinomas. Serum concentrations of SCC antigen were measured by radioimmunoassay in 382 control subjects, 70 women with cervical intraepithelial neoplasia (CIN), 517 with cervical carcinoma and 203 with other gynaecological carcinomas. Elevated SCC antigen levels (greater than 2.5 ng/ml) were found in 4% of normal controls, in 7% of women with CIN I-III, in 2%-23% with various forms of genital adenocarcinomas, in 55% with primary and in 76% of those with recurrent cervical squamous cell carcinoma. The positivity rate of the antigen was correlated with tumour stage (FIGO) and lymph node involvement of primary cervical squamous cell carcinomas. During long-term follow-up serum levels of SCC antigen were found to be concordant with tumour activity in 74% of cases. Patients with still elevated marker levels after therapy had twice the recurrence rate of women with normal serum values. Routine determination of SCC antigen during follow-up of cervical cancer is recommended.


Independent control of voluntary movements and associated anticipatory postural responses in a bimanual task.
When one hand loads the other arm, EMG responses in the stationary arm anticipate the load. This study used transcranial magnetic stimulation over each hemisphere to clarify the relationship between a voluntary movement on one side and the anticipatory postural response on the other. Subjects (n = 7) performed elbow flexion movements of one arm as a reaction-time task. Because subjects' arms were linked, flexion about one elbow resulted in extension force about the other, and an anticipatory response occurred in those elbow flexor muscles. After the 'go' signal and before the predicted onset of EMG, transcranial magnetic stimuli were delivered over one or other motor cortex. Stimulation contralateral to the reaction-time movement delayed the onset of voluntary EMG (46 ms in right biceps, 77 ms left) but did not alter the onset of EMG in the postural arm. Stimulation contralateral to the anticipatory postural response delayed only the postural EMG (left 96 ms, right 52 ms). Thus, the associated voluntary and postural responses were delayed independently by stimuli over their respective contralateral motor cortex. This suggests that, although timing of responses may be linked by an initial signal, the response from each motor cortex develops independently.


Bioactive polysaccharides from the stems of the Thai medicinal plant Acanthus ebracteatus: their chemical and physical features.
Crude water-soluble polysaccharides were isolated from Acanthus ebracteatus by hot water extraction followed by ethanol precipitation after pre-treatment with 80% ethanol. The crude polysaccharides were separated into neutral and acidic polysaccharides by anion-exchange chromatography. The neutral polysaccharide (A1001) was rich in galactose, 3-O-methylgalactose and arabinose, whereas the acidic polysaccharide (A1002) consisted mainly of galacturonic acid along with rhamnose, arabinose and galactose as minor components indicating a pectin-type polysaccharide with rhamnogalacturonan type I (RG-1) backbone. 3-O-Methylgalactose is also present in the acidic fraction. Both neutral and acidic fractions showed potent effects on the complement system using pectic polysaccharide PM II from Plantago major as a positive control. A small amount of 3-O-methylgalactose present in the pectin seemed to be of importance for activity enhancement in addition to the amount of neutral sugar side chains attached to RG-1. The relationship between chemical structure and effect on the complement system of the isolated polysaccharides is considered in the light of these data. The presence of the rare monosaccharide 3-O-methylgalactose may indicate that this can be used as a chemotaxonomic marker. The traditional way of using this plant as a medical remedy appears to have a scientific basis.