Increase in chloride ion permeability across the nerve cell membrane after the endogenous antigen S-100 incorporation.
36Cl fluxes through microdissected Deiters' neuronal membranes have been studied in a microchamber device simulating the extra- and intracellular compartments. GABA stimulates Cl- permeability through the membranes by 24%. Also, S-100/Ca2+ incorporation into the Deiters' membrane increases 36Cl- permeation to a similar extent. The two effects do not appear to be additive. This circumstance is interpreted as indicating that S-100/Ca2+ exerts its effects via postsynaptic GABAA receptor complexes.


The neuroendocrine system of normal human appendix, ileum and colon, and in neurogenic appendicopathy.
Epithelial endocrine cells containing 5-hydroxytryptamine, substance P, somatostatin, enteroglucagon and vasoactive intestinal polypeptide-immunoreactivity were localized by immunocytochemistry in the mucosa of normal appendices, ileum and proximal colon, and in neurogenic appendicopathy. In neurogenic appendicopathy a large number of proliferating nerves were visualized independently of neurotransmitters by immunostaining for neuron-specific enolase. A large number of nerve fibers were shown to contain substance P-immunoreactivity and to be of intrinsic origin. Stromal endocrine cells containing 5-hydroxytryptamine, somatostatin- and possibly substance P-immunoreactivity, were observed in substantial numbers in neurogenic appendicopathy. Substance P may be involved as a neurotransmitter and/or as a paracrine/endocrine peptide in the pathogenesis of spastic contractions and abnormal peristalsis of the appendix, which are characteristic of neurogenic appendicopathy. Stromal endocrine cells may be considered to be the origin of certain carcinoids in the appendix.


Notes from the field: Acute pesticide-related illness resulting from occupational exposure to acrolein - Washington and California, 1993-2009.
Acrolein is an aquatic herbicide used in the western United States to prevent impaired water flow in irrigation canals. Despite its toxicity, few cases of acrolein-related illness have been reported in the literature. On August 15, 2012, an irrigation district notified the Washington State Department of Labor & Industries (L&I) of acrolein-related illness in one of its pesticide applicators. L&I inspected the site and interviewed the exposed worker, coworkers, and employer. The Washington State Department of Health assisted by obtaining medical records, interviewing the patient and hospital staff, and reviewing information obtained from L&I. To look for additional cases, CDC reviewed data from the SENSOR-Pesticides program* and the California Department of Pesticide Regulation for 1993-2009, the most recent years of data availability, and identified seven additional cases of acute acrolein-related illness.


Tight modiolar proximity and feasibility of slim modiolar cochlear implant electrode array insertion in diverse etiologies of hearing loss.
To report on our experience with the slim modiolar electrode (SME) especially focusing on the wide range of etiologies including inner ear anomalies, tumors, ossifications, and even revision surgeries. All the cochlear implantation cases performed from June 2018 to September 2019 by a single surgeon was prospectively recruited. The molecular/radiological etiology of hearing loss, intraoperative outcomes, and radiographic studies of cases where the SME was implanted was reviewed to evaluate compatibility of SME for the wide range of etiologies. For cases where SME replaced the other electrode as a revision, audiologic assessment was also made. Among the 99 ears implanted during the study period, the SME was successfully implanted in 86 ears. These SME cases comprised inner ear anomaly/cochear nerve deficiency (n = 21) including cochlear hypoplasia type IV with the modiolus, intracochlear schwannoma (n = 1), far advanced otosclerosis (n = 1) and 7 revision cases. The SME was successfully used in 7 revision surgeries to replace the existing electrode. Shorter spiral diameter and decreased intracochlear position index for SME was found compared with their previous electrodes. Four out of the 6 patients who received revision implantation showed better speech perception after their surgeries. The SME can be implanted in any cases unless the integrity of the modiolus is totally compromised. Due to its slim design and tight modiolar-hugging feature, good functional outcome can also be anticipated. Additionally, it is suitable for revision surgeries possibly allowing better hearing outcomes which may be attributed to its closer proximity to the modiolus.


Novel glucosylceramide synthase inhibitor based prodrug copolymer micelles for delivery of anticancer agents.
In order to improve the efficacy of chemotherapy for cancers, we have developed a novel prodrug micellar formulation to co-deliver ceramide-generating anticancer agents and ceramide degradation inhibitor (PPMP). The prodrug nanocarrier is based on a well-defined POEG-b-PPPMP diblock copolymer. The hydrophilic block of POEG-b-PPPMP is POEG, and the hydrophobic block is composed of a number of PPMP units, which could work synergistically with loaded anticancer drugs. POEG-b-PPPMP was readily synthesized via a one-step reversible addition-fragment transfer (RAFT) polymerization from a PPMP monomer. The newly synthesized polymers were self-assembled into micelles and served as a carrier for several hydrophobic anticancer drugs including DOX, PTX and C6-ceramide. POEG-b-PPPMP prodrug polymer exhibited intrinsic antitumor activity in vitro and in vivo. In addition, POEG-b-PPPMP prodrug polymer was comparable to free PPMP in selectively enhancing the production of pro-apoptotic ceramide species as well as down-regulating the mRNA expression of GCS. DOX-loaded POEG-b-PPPMP micelles exhibited an excellent stability of 42 days at 4 °C. Moreover, DOX loaded in POEG-b-PPPMP micelles showed higher levels of cytotoxicity than DOX loaded in a pharmacologically inert polymer (POEG-b-POM) and Doxil formulation in several tumor cell lines. Consistently, in a 4T1.2 murine breast cancer model, the tumor inhibition followed the order of DOX/POEG-b-PPPMP > DOX/POEG-b-POM ≥ Doxil > POEG-b-PPPMP > POEG-b-POM. Our data suggest that POEG-b-PPPMP micelles are a promising dual-functional carrier that warrants more studies in the future.


Accurate measurements of the effects of deuteration at backbone amide positions on the chemical shifts of ¹⁵N, ¹³Cα, ¹³Cβ, ¹³CO and ¹Hα nuclei in proteins.
An approach towards accurate NMR measurements of deuterium isotope effects on the chemical shifts of all backbone nuclei in proteins ((15)N, (13)Cα, (13)CO, (1)Hα) and (13)Cβ nuclei arising from (1)H-to-D substitutions at amide nitrogen positions is described. Isolation of molecular species with a defined protonation/deuteration pattern at successive backbone nitrogen positions in the polypeptide chain allows quantifying all deuterium isotope shifts of these nuclei from the first to the fourth order. Some of the deuterium isotope shifts measured in the proteins ubiquitin and GB1 can be interpreted in terms of backbone geometry via empirical relationships describing their dependence on (φ; ψ) backbone dihedral angles. Because of their relatively large variability and notable dependence on the protein secondary structure, the two- and three-bond (13)Cα isotope shifts, (2)ΔCα(NiD) and (3)ΔCα(Ni+1D), and three-bond (13)Cβ isotope shifts, (3)ΔCβ(NiD), are useful reporters of the local geometry of the protein backbone.


Methotrexate chemosensitivity by ATP luminescence in human leukemia cell lines and in breast cancer primary cultures: comparison of the TCA-100 assay with a clonogenic assay.
Chemosensitivity assays are widely used to predict the ability of tumor cell lines to respond to potential or existing cytotoxic drugs. In this study we have compared the cell cloning assay first described by Salmon and Hamburger with a recently developed assay which measures viable cell number by ATP luminescence. Methotrexate (MTX) was chosen as the test agent, since cell lines with varying degrees of sensitivity to this agent were readily available. The results shown good correlation between the two assays, both of which are able to discriminate between the various cell lines used. MTX inhibition of primary breast carcinomas and cell lines shows a steep dose-response curve with a threshold concentration above which increasing dose does not increase sensitivity. In solid tumors, the plateau is usually reached at a level well below 100% inhibition. The ATP luminescence assay allows discrimination of MTX sensitivity between breast carcinomas and has considerable technical advantages over the cloning assay.


Visualizing single-molecule conformational transition and binding dynamics of intrinsically disordered proteins.
Intrinsically disordered proteins (IDPs) play crucial roles in cellular processes and hold promise as drug targets. However, the dynamic nature of IDPs remains poorly understood. Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level. We use the device to study c-Myc interaction with Max and/or small molecule inhibitors. We observe the self-folding/unfolding process of c-Myc and reveal its interaction mechanism with Max and inhibitors through ultrasensitive real-time monitoring. We capture a relatively stable encounter intermediate ensemble of c-Myc during its transition from the unbound state to the fully folded state. The c-Myc/Max and c-Myc/inhibitor dissociation constants derived are consistent with other ensemble experiments. These proof-of-concept results provide an understanding of the IDP-binding/folding mechanism and represent a promising nanotechnology for IDP conformation/interaction studies and drug discovery.


Mechanical functioning of peripheral nerves: linkage with the "mushrooming" effect.
Biomechanical properties of nerve have been studied extensively. All neural matrix tissues have been suggested to be the main load-bearing component. Based on the ultrastructure it has been proposed that the architecture of the epineurium allows some degree of extensibility of the nerve. A role of the perineurium could be to withstand the positive endoneurial pressure. The hypothesis is that the mechanical behaviour of nerves is dependent on an interaction between the core swelling pressure and restraint by the outer sheath. Loss of this balance will alter that behaviour. To test this, rat sciatic nerves were subjected to mechanical loading at in vivo and ex vivo tension. Retraction of nerve segments was measured after excision and after incubation at 37 degrees C or freezing. Swelling properties of the nerve were measured by immersion in water or PBS (phosphate buffer solution) with intact or opened epineurium. Results showed a significant decrease in strength and stiffness with an increase in strain of the nerve after excision, compared to in vivo. Retraction was on average 11%. Freezing or incubation at 37 degrees C did not alter retraction. The swelling properties of the nerve demonstrated a significant difference between intact and opened epineurium and similar results for water and PBS, indicating that epineurium is a constraint and that the nerves are underhydrated. The proposed model for the intact nerve is a continuous connective tissue tube surrounding and constraining an inner swelling pressure of the neural core. Loss of integrity of the nerve has detrimental effects on its biomechanical properties.


Catalytically active human telomerase mutants with allele-specific biological properties.
Expression of the catalytic subunit of human telomerase, hTERT, extends human primary fibroblast life span. Such life span extension has generally been reported to be accompanied by net telomere lengthening, which led to the hypothesis that it is the telomere lengthening that causes the life span extension. Here we show that hTERT+C and hTERT-FlagC, mutant telomerase proteins with either 10 additional residues or a FLAG epitope added to the hTERT C-terminus, confer significant but limited life span extension to IMR90 human primary lung fibroblasts. However, as the cells continue to grow for >100 population doublings past their normal senescence point, bulk telomere length continues to erode to lengths much shorter than those seen at the senescence of control telomerase-negative cells. Expression of hTERT+C immortalized IMR90 cells transformed by three different oncogenes. Again, bulk telomeres became much shorter than those of the control cells at crisis. Additional hTERT mutants were constructed and analyzed similarly. Enzymatically active hTERT-N125A+T126A, like other previously reported conserved GQ domain mutants and C-terminally HA-tagged hTERT, failed to extend life span. Another GQ domain mutant, hTERT-E79A, was indistinguishable from wild-type hTERT in its cell growth effects, but there was no net telomere lengthening. These results uncover further hTERT allele-specific phenotypes that uncouple telomerase activity, net telomere lengthening and life span extension.


Giant sigmoidal diverticulum: report of a case and review of the literature.
A case report of giant sigmoidal diverticulum and a review of the relevant medical literature are presented. Only 20 cases have previously been reported. Diagnosis is dependent on a gradually enlarging mass, usually found on physicial examination. Radiologic study usually confirms the diagnosis and differentiates this condition from others, such as intestinal duplication, emphysematous cholecystitis, cholecysto-enteric fistulas, etc. The treatment is prophylactic. It is important to undertake early surgical intervention before the condition progresses to perforation or other complications.


Fabrication of one-dimensional Fe3O4/P(GMA-DVB) nanochains by magnetic-field-induced precipitation polymerization.
One-dimensional (1D) magnetic Fe(3)O(4)/P(GMA-DVB) peapod-like nanochains have been successfully synthesized by magnetic-field-induced precipitation polymerization using Fe(3)O(4) as building blocks and P(GMA-DVB) as linker. The Fe(3)O(4) microspheres without surface modification can be arranged with the direction of the external magnetic field in a line via the dipolar interaction between Fe(3)O(4) microspheres and linked permanently via P(GMA-DVB) coating during precipitation polymerization. The length of peapod-like nanochains can be controlled by magnetic field intensity, and the thickness of polymer shell can be tuned by the amount of monomers. Magnetic measurement revealed that these 1D peapod-like nanochains showed highly magnetic sensitivity. In the presence of magnetic field, 1D magnetic Fe(3)O(4)/P(GMA-DVB) peapod-like nanochains can be oriented and aligned along the direction of external magnetic field.


Molecular detection of Babesia and Theileria from crossbred cattle in Sirajganj and Rangpur districts of Bangladesh.
Babesia and Theileria are potential threats to the livestock industry, causing considerable economic losses. These tick-borne blood parasites are more prevalent in crossbred cattle than local cattle in Bangladesh. To confirm the species of Babesia and Theileria in crossbred cattle from the northern part of Bangladesh using conventional and molecular tools. A total of 385 crossbred cattle blood samples were subjected to DNA extraction and PCR. For molecular detection, B. bigemina rhoptry-associated protein 1a, B. bovis spherical body protein-4, and Theileria spp. 18S rRNA were used as the marker genes. Using PCR, only 72 (18.7%) samples were found piroplasm positive, of which 12.2% Theileria, 4.7% Babesia, and 1.8% mixed infections. Both Babesia (7.3%), Theileria (7.7%) and mixed (2.8%) infections were detected in Sirajganj, and only Theileria (20.4%) was detected in Rangpur district. By PCR and nPCR we detected B. bigemina and T. annulata in Sirajganj district, and Theileria sp. in Rangpur district. The target gene sequences of isolated pathogens confirmed B. bigemina and T. annulata, and Theileria sp from these samples. Blood smears of all samples were also examined microscopically for Babesia and/or Theileria spp. and 14.3% of samples were found positive, of which 5.9% Babesia and 8.3% Theileria. Generally, the pathogens detected in Sirajgang and Rangpur were genetically related to South Asia, particularly South East Asian isolates. These findings provide information for a better understanding of the epidemiology of Babesia and Theileria as well as to improve the approaches for diagnosis and control of tick-borne diseases in Bangladesh.


High initial bowel resection rate and very-early-onset inflammatory bowel disease - A challenge in a low-prevalence area.
Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD). The incidence in children and adolescents has risen since the 21st century globally, including Taiwan. The study aimed to disclose the characteristics and outcome of pediatric IBD (pIBD) patients in a tertiary center for the past two decades. We retrospectively reviewed the charts of pIBD children from 2000 to 2018 in a tertiary center in Northern Taiwan. Demographics, presentations, diagnostic modalities, treatment, and outcomes were analyzed. A total of 38 cases were enrolled, including 27 CD and 11 UC patients. An almost 3-folds increase in incidence after 2010 was observed. Twelve cases (32%) were early-onset, and six of them (16%) were very-early-onset; four of them were detected with single-gene mutations [XIAP, TTC7A (2 siblings), and ZAP70]. Eleven CD patients (40.7%) received bowel resection at the onset, and another two (7.4%) had bowel resection years after the diagnosis. Initial bowel resection was associated with fibrostenotic/penetrating behavior, early-onset disease, and growth failure. This study demonstrated an increased incidence of pIBD in the past two decades in Taiwan, a low-prevalence region. The initial high bowel resection rate in CD was related to the fibrostenotic and/or penetrating behavior, younger age at diagnosis, and growth failure.


Total antioxidant capacity of seminal plasma is different in fertile and infertile men.
To determine if the total antioxidant capacity of seminal plasma is different in fertile and infertile men. An enhanced chemiluminescence assay applied to seminal plasma from groups of fertile and infertile men. The Assisted Conception Unit, Royal Maternity Hospital, Belfast. Men of proven fertility whose partners had an ongoing pregnancy resulting from IVF and male partners of couples attending our subfertility clinic. Total antioxidant capacity was significantly higher in seminal plasma from fertile men than from that of infertile men with normozoospermic samples that exhibited reactive oxygen species or asthenozoospermic samples with or without reactive oxygen species activity. Seminal plasma from infertile men has lower antioxidant levels than that of fertile men, particularly of patients whose semen have poor sperm motility. The presence of reactive oxygen species activity in sperm of infertile groups also is associated with lower levels of chain-breaking antioxidants in seminal plasma.


Four new species of the spider genus Synagelides Strand, 1906 from South China (Araneae, Salticidae).
Four new species of the jumping spider genus Synagelides Strand, 1906 from Guizhou and Yunnan, China are described: Synagelidesangustus sp. nov. (♀), S.latus sp. nov. (♂♀), S.subagoriformis sp. nov. (♂♀), and S.triangulus sp. nov. (♀). Photographs of the habitus and copulatory organs and a distributional map are provided.


Sequence variation of bovine elastin mRNA due to alternative splicing.
Poly A+ RNA, isolated from a single 210 day fetal bovine nuchal ligament, was used to synthesize cDNA by the RNase H method, using AMV reverse transcriptase for first strand synthesis and DNA polymerase I for the second strand. The cDNA was inserted into lambda gt10 using EcoRI linkers, and recombinant phage containing elastin sequences were identified by hybridization with a 1.3 kb sheep elastin cDNA clone, pcSELI (Yoon, K. et al., Biochem. Biophys. Res. Comm. 118: 261-265, 1984). Three clones containing the largest inserts of 2.9, 2.8, and 2.6 kb were selected for further study. The complete sequence analysis of the 3 clones was correlated with the sequence of 10.2 kb of the bovine elastin gene. The analyses: (i) showed that the cDNA encompassed the great majority of the translated sequence, (ii) ordered the tryptic peptides of porcine tropoelastin, (iii) determined new amino acid sequences not previously found in the porcine peptides and (iv) demonstrated that alternative splicing of the primary transcript leads to significant variation in the sequence of the translated portion of the mRNA.


Intracranial dural metastasis from uterine leiomyosarcoma with orbital extension.
Intracranial metastases from uterine leiomyosarcoma are very rare and have been found mainly in the brain (17 cases); on the other hand, metastases to the skull, dura and orbit are really exceptional. The authors report the case of a 57-year-old woman who presented with a 6-week history of right proptosis, left hemiparesis, intracranial hypertension and torpor 8 months after surgery for uterine leiomyosarcoma. CT scan showed a very large right frontal tumor with both intracranial and intraorbital extension. At operation the tumor was found to arise from the dura of the right anterior cranial fossa; complete removal of the intracranial tumor mass and partial removal of the intraorbital component were performed. However, early tumor regrowth was observed 45 days after operation and death occurred 2 months later. Pathologic examination showed a high-grade sarcoma with smooth muscle differentiation and high mitotic activity. Immunohistochemical staining revealed positivity for actin and vimentin and negativity for S-100 protein, cytocheratin and desmin. This is the first reported case of uterine leiomyosarcoma metastatic to the dura of the anterior cranial fossa with intracranial and intraorbital extension. An aggressive surgical resection is the best treatment of intracranial metastatic leiomyosarcoma, because of the scarce response to radiotherapy and chemotherapy. However, the outcome is poor, with early recurrence.


Innervation of the corpus allatum in the Colorado potato beetle as revealed by retrograde diffusion with horseradish peroxidase.
The application of horseradish peroxidase for tracing the cells innervating the corpus allatum in adult Leptinotarsa decemlineata, using simple instruments, is described. The corpus allatum in this insect appears to be innervated by a single group of about eight cells. The size and position of these cells indicate that they belong to the L-type lateral neurosecretory cells. The axons from each of these cells split into two pathways: one pathway arborizes extensively in the dorsal part of the brain adjacent to the pars intercerebralis whereas the other passes unbranched through the neuropil of the protocerebral lobe and corpus cardiacum into the corpus allatum. Additional cell groups in the pars intercerebralis which were stained when the corpus cardiacum was also contaminated with horseradish peroxidase are illustrated. The possible involvement of the lateral neurosecretory cells in the regulation of juvenile hormone biosynthesis is discussed.


Phenotype-genotype correlations in patients with GNB1 gene variants, including the first three reported Japanese patients to exhibit spastic diplegia, dyskinetic quadriplegia, and infantile spasms.
We report the first three Japanese patients with missense variants in the GNB1 gene. Patients exhibited severe dyskinetic quadriplegia with cortical blindness and epileptic spasms, West syndrome (but with good outcomes), and hypotonic quadriplegia that later developed into spastic diplegia. Whole-exome sequencing revealed two recurrent GNB1 variants (p.Leu95Pro and p.Ile80Thr) and one novel variant (p.Ser74Leu). A recent investigation revealed large numbers of patients with GNB1 variants. Functional studies of such variants and genotype-phenotype correlation are required to enable future precision medicine.


Health-Related Decision-Making in HIV Disease.
Individuals living with HIV show moderate decision-making deficits, though no prior studies have evaluated the ability to make optimal health-related decisions across the HIV healthcare continuum. Forty-three HIV+ individuals with HIV-associated neurocognitive disorders (HAND+), 50 HIV+ individuals without HAND (HAND-), and 42 HIV- participants were administered two measures of health-related decision-making as part of a comprehensive neuropsychological battery: (1) The Decisional Conflict Scale (DCS), and (2) The Modified UCSD Brief Assessment for Capacity to Consent (UBACC-T). Multiple regression analyses revealed that HAND was an independent predictor of both the DCS and the UBACC-T, such that the HAND+ sample evidenced significantly poorer scores relative to comparison groups. Within the HIV+ sample, poorer health-related decision-making was associated with worse performance on tests of episodic memory, risky decision-making, and health literacy. Findings indicate that individuals with HAND evidence moderate deficits in effectively comprehending and evaluating various health-related choices.


Efficiency and safety evaluation of prophylaxes for venous thrombosis after gynecological surgery.
In this study, we investigate the incidence of venous thrombosis (VT), and evaluate the effectiveness and safety of 3 major thromboprophylaxes and the potential risk factors for VT in women undergoing surgery for a gynecological malignancy. We performed a randomized controlled trial of 307 patients undergoing laparoscopic surgery for gynecological malignancies at a single institution from January 2016 to October 2017. Patients were divided into 3 groups: one receiving a half dose of low-molecular-weight heparin sodium injection (FLUXUM, Alfa Wassermann, Italy) delivered by injection, one receiving a full dose of FLUXUM, and a third group receiving an Argatroban injection. None of the patients in our study developed a pulmonary embolism, bleeding, or infectious complications. There were no statistical differences in the rate of deep venous thrombosis (DVT) (0%, 0%, and 2.38%) and the superficial venous thromboembolism (SVT) (15.66%, 8.97%, and 18.6%) among the 3 groups. None of the patients developed symptomatic VT. The effect of treatment on alanine aminotransferase and aspartate aminotransferase differed between the groups, with a minimal effect in the Argatroban group, and all 3 methods resulted in minimal impairment of renal function. Decreased hemoglobin, elevated levels of D-dimer, and prothrombin time were closely related to thrombogenesis. In conclusion, the incidence of postoperative thrombosis in gynecological malignancy among these Chinese people is not as low as we had originally presumed. Argatroban is not more effective than Parnaparin as a direct thrombin inhibitor, but it has less influence on liver function, which is beneficial for patients undergoing chemotherapy. Hemoglobin, D-dimer, and prothrombin time may be used to predict or detect thrombogenesis.


Differences in the risk of severe falls between patients aged <65 years and patients aged ≥65 years at a psychiatric hospital based on 12-year incident reports.
This study compared age differences in risk factors for falls requiring treatment in psychiatric patients. An incident database was used to compare fall incidents in patients aged less than 65 years and those aged greater than or equal to 65 years. Approximately 30% of fallers were less than 65 years. Mental status and medication were the main risk factors. Decreased activities of daily living were associated with the most falls in patients greater than or equal to 65 years. Fall risk differed between the two age groups. Medication may play a major role in falls among patients less than 65 years.


Inhibition of the casein-kinase-1-ε/δ/ prevents relapse-like alcohol drinking.
During the past decade, it has been shown that circadian clock genes have more than a simple circadian time-keeping role. Clock genes also modulate motivational processes and have been implicated in the development of psychiatric disorders such as drug addiction. Recent studies indicate that casein-kinase 1ε/δ (CK1ε/δ)--one of the components of the circadian molecular clockwork-might be involved in the etiology of addictive behavior. The present study was initiated to study the specific role of CK1ε/δ in alcohol relapse-like drinking using the 'Alcohol Deprivation Effect' model. The effect of CK1ε/δ inhibition was tested on alcohol consumption in long-term alcohol-drinking rats upon re-exposure to alcohol after deprivation using a four-bottle free-choice paradigm with water, 5%, 10%, and 20% ethanol solutions, as well as on saccharin preference in alcohol-naive rats. The inhibition of CK1ε/δ with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats. The impact of the treatment was further characterized using nonlinear regression analyses on the daily profiles of drinking and locomotor activity. We reveal that CK1ε/δ inhibition blunted the high daytime alcohol intake typically observed upon alcohol re-exposure, and induced a phase shift of locomotor activity toward daytime. Only the highest dose of PF-670462 shifted the saccharin intake daily rhythm toward daytime during treatment, and decreased saccharin preference after treatment. Our data suggest that CK1 inhibitors may be candidates for drug treatment development for alcoholism.


Constructing the quinonyl groups and structural defects in carbon for supercapacitor and capacitive deionization applications.
The structural defects and oxygen-containing functional groups of carbon materials as electrode materials for supercapacitors or capacitive deionization devices are critical to their electrochemical performance. The tuning of surface oxygen-containing functional groups and carbon defects during pyrolysis is key to achieve a high performance in ion storage. Herein, quinonyl-dominant defective porous carbon is prepared by a pyrolysis and cross-linking route using lavender stem and potassium acetate as precursor. Benefiting from the presence of abundant defect and surface quinonyl groups, porous carbon shows an ultra-high specific capacitance of 401 F g-1 (1 A g-1) and a high capacitance retention of 63% at a high current density of 100 A g-1 in a KOH solution. Meanwhile, as a capacitive deionization electrode material, it also exhibited a high adsorption capacity of 25.5 mg g-1 in 500 mg L-1 NaCl solution at 1.2 V. Theoretical density functional theory (DFT) calculation demonstrates that surface quinonyl groups and carbon defects can synergistically facilitate the adsorption of K+ and Na+ during the charge/discharge process. This work provides a new perspective for understanding the role of surface oxygen-containing groups and intrinsic defects of porous carbon materials in electrochemical energy storage and desalination applications.


First certain record of Demospongiae class (Porifera) alien species from the Mediterranean Sea.
In this paper, we identify some sponge specimens collected in the Faro Lake in Sicily, and belonging to Haliclona (Halicoclona) by using morphological analysis accompanied by molecular analysis through amplification of several molecular markers (18S and 28S rRNA, CO1 and ITS). The samples are identified as. H. (Halichoclona) vansoesti de Weerdt, de Kluijver & Gómez, 1999, a species native to the Caribbean, and therefore this is the first record of an alien species of the Demospongiae class (Porifera) from the Mediterranean Sea. This presence can be ascribed as results of global change (mainly global warming) that are affecting marine environment.


Association between birth weight and adolescent systolic blood pressure in a caucasian birth cohort differs according to skin type, CRH promoter or 11beta-HSD2 genotype.
To examine whether the inverse association between birth weight and blood pressure varies by skin pigmentation and/or related genotypes. 671 children from a predominantly caucasian birth cohort were followed-up to adolescence (mean (SD) age 14.4 (0.64)). Data on birth weight, socioeconomic status, maternal antenatal smoking, adolescent blood pressure and polymorphisms of candidate genes were obtained and analysed by multiple linear regression. An increase in birth weight of 1 kg was associated with an non-significant difference in adolescent systolic blood pressure of -0.53 mm Hg (95% CI -1.72 to 0.66) per kg after adjustment for child age and cohort entry criteria. The inverse association between birth weight and systolic blood pressure was stronger for those with darker skin (> or =2% melanin) (difference in effect, p = 0.02), those with more copies of the C allele of corticotropin-releasing hormone (CRH) +T1273C (p = 0.06), and those with more copies of the short (< or =236 bp) form of the 11beta-HSD2{CA}n(repeat) microsatellite (p = 0.03). These findings add to the evidence that cortisol-related pathways may account for at least part of the observed birth weight-blood pressure associations.


Discovering hidden brain network responses to naturalistic stimuli via tensor component analysis of multi-subject fMRI data.
The study of brain network interactions during naturalistic stimuli facilitates a deeper understanding of human brain function. To estimate large-scale brain networks evoked with naturalistic stimuli, a tensor component analysis (TCA) based framework was used to characterize shared spatio-temporal patterns across subjects in a purely data-driven manner. In this framework, a third-order tensor is constructed from the timeseries extracted from all brain regions from a given parcellation, for all participants, with modes of the tensor corresponding to spatial distribution, time series and participants. TCA then reveals spatially and temporally shared components, i.e., evoked networks with the naturalistic stimuli, their time courses of activity and subject loadings of each component. To enhance the reproducibility of the estimation with the adaptive TCA algorithm, a novel spectral clustering method, tensor spectral clustering, was proposed and applied to evaluate the stability of the TCA algorithm. We demonstrated the effectiveness of the proposed framework via simulations and real fMRI data collected during a motor task with a traditional fMRI study design. We also applied the proposed framework to fMRI data collected during passive movie watching to illustrate how reproducible brain networks are evoked by naturalistic movie viewing.


The effect of handling methods on subsequent plasma progesterone levels in sheep.
The mean progesterone concentration in the plasma of 10 adult Ethiopian Highland sheep obtained immediately after slaughter was 10.56 +/- 3.98 ng/ml. Samples were subsequently incubated at 4 degrees C, room temperature (19-22 degrees C) or 26 degrees C as either plasma or intact but citrated blood. Failure to separate plasma affected the progesterone content at 2-72 h at room temperature or 26 degrees C (p less than 0.01 - p less than 0.0001). Incubation temperature affected the plasma concentration at 18 h (p less than 0.05) and 24 h (p less than 0.001). Although progesterone values were generally higher in separated plasma, disparity with the values from plasma separated from incubated citrated blood was small (r = 0.76-0.98). Progesterone concentration declined haphazardly after collection but sometimes exceeded the initial readings. This kept the average concentration of progesterone in plasma separated immediately after collection fairly constant and within 15% of zero time samples during the first 48 h.


Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice.
The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.


[Malleolar fractures with ankle joint instability--experience with the positioning screw].
Malleolar fractures with an unstable ankle joint require additional stabilization. Different implants exist: We present the results of 135/155 patients treated with the so-called positioning screw. In 123 patients the positioning screw showed a spontaneous loosening with functional treatment and was therefore removed with the rest of the implants after eight to twelve months. In twelve cases the screw was broken. In 3/21 patients with the old 3.5 mm cortical screw with a core diameter of 1.9 mm in a correct position and in 9/113 patients with the new 3.5 mm cortical screw with inner core of 2.4 mm in an incorrect position. Positioning screws require early removal only if they fail to loosen or if a persistent limitation of dorsiflexion is still present after three months.


Surface-associated activation of plasminogen on gram-positive bacteria. Effect of plasmin on the adherence of Staphylococcus aureus.
In this article we review a novel type of plasminogen activation on staphylococcal and streptococcal cells. The activation mechanism implies a specific binding of glu-plasminogen to bacterial surface via the lysine-binding sites of plasminogen. Association of plasminogen with bacterial surfaces greatly enhances the t-PA mediated activation which takes place only poorly in solution. The end product, surface-associated plasmin, is enzymatically active, protected against high molecular weight plasmin inhibitors and capable of converting itself from glu-plasmin to the lys-form. The modification is associated with an increased affinity of the bound lys-plasmin towards the binding molecules on bacterial surface. This novel way of retaining plasmin on the surface may be important for the bacteria to invade and penetrate surrounding tissues. Our data on the effect of plasmin on staphylococcal adherence indicate that plasmin is not very effective in cleaning bacteria from surfaces coated with extracellular matrix components, fibronectin and fibrinogen.


Gene expression analysis of the ovary of hybrid females of Xenopus laevis and X. muelleri.
Interspecific hybrids of frogs of the genus Xenopus result in sterile hybrid males and fertile hybrid females. Previous work has demonstrated a dramatic asymmetrical pattern of misexpression in hybrid males compared to the two parental species with relatively few genes misexpressed in comparisons of hybrids and the maternal species (X. laevis) and dramatically more genes misexpressed in hybrids compared to the paternal species (X. muelleri). In this work, we examine the gene expression pattern in hybrid females of X. laevis x X. muelleri to determine if this asymmetrical pattern of expression also occurs in hybrid females. We find a similar pattern of asymmetry in expression compared to males in that there were more genes differentially expressed between hybrids and X. muelleri compared to hybrids and X. laevis. We also found a dramatic increase in the number of misexpressed genes with hybrid females having about 20 times more genes misexpressed in ovaries compared to testes of hybrid males and therefore the match between phenotype and expression pattern is not supported. We discuss these intriguing findings in the context of reproductive isolation and suggest that divergence in female expression may be involved in sterility of hybrid males due to the inherent sensitivity of spermatogenesis as defined by the faster male evolution hypothesis for Haldane's rule.


Robotic surgery for pelvic organ prolapse with complete bladder eversion.
Pelvic organ prolapse with complete bladder eversion is extremely rare. An 82-year-old woman was diagnosed with uterine prolapse 3 years ago and underwent occasional urethral catheter placement for difficulty in micturition. She presented with vulvar bleeding and prolapsed uterus from the vagina. Pelvic examination revealed uterine prolapse and a 65 × 65-mm red mass ventrally with urinary outflow. Contrast medium leakage from the vulvar mass and guidewire observed on antegrade pyeloureterography indicated pelvic organ prolapse with complete bladder eversion. Manual reduction of the everted bladder, robotic sacrocolpopexy, and bladder neck reconstruction was performed. However, eversion recurred 10 months postoperatively. Subsequently, robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed. There was no recurrence postoperatively. Robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed for complete bladder eversion.


A novel approach for quantification of the future unmet medical need in right ventricular dysfunction.
Although 'unmet medical need' (UMN) is an increasingly used term in the healthcare sector instrumental to the approximate value of drug discovery projects relevant to portfolio management, no standardized approach exists for its quantification. Especially in diseases with different comorbidities, high patient heterogeneity, and incomplete epidemiological data, it is difficult to judge the need for new therapies. The approach presented here combines an expert assessment of key UMN indicators related to the individual patient with a literature search to collect epidemiological data describing the corresponding patient population with its underlying heterogeneity. This assessment supports decision-making within the portfolio management process in larger research and development organizations.


Racers' attractive looks, popularity, and performance: how do speedboat racers react to fans' expectations?
Using a large sample of individual-level records in Japan speedboat racing where men and women racers participate, we investigated how racers' performance meets fans' pre-race expectations. To control for endogeneity bias, we measured the order of racers' attractiveness randomly determined in each race and then used this order as instrument for measuring racers' popularity. The fixed-effects IV estimations revealed the following. (1) Racers who are more attractive than their competitors tend to be more popular even after controlling for the condition of the race, racer ability, and other characteristics. (2) More popular men show better performance in the race even if the reward does not vary according to popularity; such tendency is not observed for women. This study contributes a novel setting for determining the expectation-enhancing effects of physical attractiveness.


Thermoresponsive comb-shaped copolymer-Si(100) hybrids for accelerated temperature-dependent cell detachment.
Well-defined comb-shaped copolymer-Si(100) hybrids were prepared, via successive surface-initiated atom transfer radical polymerizations (ATRPs) of glycidyl methacrylate (GMA) and N-isopropylacrylamide (NIPAAm), for accelerated cell detachment at a lower temperature. The Si-C bonded comb copolymer consisted of a well-defined (nearly monodispersed) poly(glycidyl methacrylate) (P(GMA)) main chain, a well-defined NIPAAm polymer (P(NIPAAm) block, and well-defined P(NIPAAm) side chains. The ring opening reaction of epoxy groups of the P(GMA) main chain with 2-chloropropionic acid resulted in the immobilization of the alpha-chloroester groups (the ATRP initiators for the NIPAAm side chains) and the concomitant formation of hydroxyl groups. P(NIPAAm) acted as the thermoresponsive side chains of the comb copolymer for control of cell adhesion and detachment, while the P(GMA) main chain with hydroxyl groups provided a local hydrophilic microenvironment. The unique microstructure of the comb copolymer brushes facilitated cell recovery at 20 degrees C (below the lower critical solution temperature (LCST) of P(NIPAAm)) without restraining cell attachments and growth at 37 degrees C. The accelerated detachment of cells indicated that the underlying hydrophilic environment of the comb copolymer brushes contributed to speedy hydration of the P(NIPAAm) segments below the LCST. The thermoresponsive comb copolymer-Si(100) hybrids are potentially useful as adhesion modifiers for cells in silicon-based biomedical devices.


The lipidome as a composite biomarker of the modifiable part of the risk of breast cancer.
The potential for dietary fat to prevent breast cancer makes identification of defined molecules a mandatory step. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, we have used the fatty acid composition of white adipose tissue as biomarker of past lipid intake. When considered separately, candidate fatty acids identified as favourable on the basis of their association with breast cancer risk have usually led to inconsistent results in dietary intervention studies carried out in rats. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions, which finally determines the lipidome, the lipid profile that is found in individuals. We reappraised the role of the complete lipid profile through a comprehensive study of adipose tissue fatty acids obtained in patients with benign or malignant breast tumors. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low n-6/n-3 fatty acid ratio was associated with decreased breast cancer risk. The lipidome may provide the opportunity to quantify the modifiable part of the risk of breast cancer. The lipidome may be used as a template for designing proper dietary modifications in order to delay the occurrence of breast cancer. Which dietary modifications should be undertaken in order to bring a pertinent change to the lipidome with respect to the risk of breast cancer is currently unknown. The lipidome may allow the individualization of a high risk population of women, who may be targeted for a dietary prevention of breast cancer. The setting and validation of a high-throughput lipidomic station with analytical capabilities fitted to the need of mass screening is required. These two locks must be resolved before a primary prevention of breast cancer by diet could be contemplated.


A survey of neurologists' views on epilepsy surgery and medically refractory epilepsy.
There is a 20-year delay between the diagnosis of epilepsy and surgical treatment. The aim of this study was to describe the different views held by neurologists regarding refractory epilepsy that may contribute to the delay in referring patients for epilepsy surgery. Neurologists in Michigan were mailed a 10-item survey inquiring about their definition of medically refractory epilepsy and their decision-making process in referring patients for epilepsy surgery. Eighty-four neurologists responded (20%). The majority defined medically refractory epilepsy as failure of three monotherapy antiepileptic drug (AEDs) trials and at least two polytherapy trials. Nineteen percent responded that all approved AEDs had to fail before a patient could be defined as medically refractory. Eighty-two percent of the respondents had referred patients for epilepsy surgery. Almost 50% were not satisfied with the level of communication from epilepsy centers. One-third reported serious complications resulting from surgery. These findings suggest that further education and improved communication from comprehensive epilepsy centers may shorten the time to referral and ultimately improve the lives of patients with epilepsy.


B- and N-doped carbon dots by one-step microwave hydrothermal synthesis: tracking yeast status and imaging mechanism.
Carbon dots (CDs) are widely used in cell imaging due to their excellent optical properties, biocompatibility and low toxicity. At present, most of the research on CDs focuses on biomedical application, while there are few studies on the application of microbial imaging. In this study, B- and N-doped carbon dots (BN-CDs) were prepared from citric acid, ethylenediamine, and boric acid by microwave hydrothermal method. Based on BN-CDs labeling yeast, the dead or living of yeast cell could be quickly identified, and their growth status could also be clearly observed. In order to further observe the morphology of yeast cell under different lethal methods, six methods were used to kill the cells and then used BN-CDs to label the cells for imaging. More remarkably, imaging of yeast cell with ultrasound and antibiotics was significantly different from other imaging due to the overflow of cell contents. In addition, the endocytosis mechanism of BN-CDs was investigated. The cellular uptake of BN-CDs is dose, time and partially energy-dependent along with the involvement of passive diffusion. The main mechanism of endocytosis is caveolae-mediated. BN-CDs can be used for long-term stable imaging of yeast, and the study provides basic research for applying CDs to microbiol imaging.


Monoclonal antibodies and fusion proteins in medicine.
Humanized antibodies and decoy receptors have been introduced in clinical practice to treat malignancies and systemic autoimmune disease because they ablate specific cells or disrupt pathogenic processes at distinct points. Reported clinical responses offer hope to treatment-resistant patients, particularly those with lymphomas and rheumatic diseases. Side effects from the use of biologic agents include lymphokine release syndrome, reactivation of tuberculosis, and immunosuppression. Further insights are needed regarding limitation of adverse effects, correct use in conjunction with existing drugs, and treatment of patients in whom resistance develops.


Architectural design of a self-sealing corneal tunnel, single-hinge incision.
This report describes a corneal tunnel incision that is self-sealing and does not leak when pressure is applied to the posterior lip of the wound. The success of the incision is in the construction of a single hinge. Results in patients who had the procedure are discussed.


Adverse effects of coumarin anticoagulants.
The biochemistry of vitamin K metabolism and the role of vitamin K-dependent gamma-carboxylation of the vitamin K-dependent coagulation factors are now well understood. Likewise, there is a clear understanding of the role of oral anticoagulants in the inhibition of these coagulation factors. However, the effect of oral anticoagulants on extrahepatic gamma-carboxylated proteins such as osteocalcin and matrix gamma-carboxyglutamate (Gla)-protein (MGP), and the effects of long term anticoagulants on bone mineral metabolism are just now being recognised. The relevance of these observations on mineral metabolism for elderly individuals, and in particular postmenopausal women who are on long term anticoagulants, is still unknown but worthy of continued close observation. The most significant hazard of oral anticoagulants is haemorrhage. Clinical trials continue to demonstrate that less intense (lower dosage) warfarin therapy can significantly decrease this risk of haemorrhage while at the same time providing equal efficacy when compared to more intense warfarin therapy. The more widespread use of the International Normalised Ratio (INR) for the control of anticoagulants will undoubtedly further decrease the risk of haemorrhage, but new innovations such as the use of ultra low-dose warfarin or newer techniques for the continued monitoring of oral anticoagulants are still required, particularly as the indications for oral anticoagulants continue to expand.


Accuracy of an autocalibrated pulse contour analysis in cardiac surgery patients: a bi-center clinical trial.
Less-invasive and easy to install monitoring systems for continuous estimation of cardiac index (CI) have gained increasing interest, especially in cardiac surgery patients who often exhibit abrupt haemodynamic changes. The aim of the present study was to compare the accuracy of CI by a new semi-invasive monitoring system with transpulmonary thermodilution before and after cardiopulmonary bypass (CPB). Sixty-five patients (41 Germany, 24 Spain) scheduled for elective coronary surgery were studied before and after CPB, respectively. Measurements included CI obtained by transpulmonary thermodilution (CITPTD) and autocalibrated semi-invasive pulse contour analysis (CIPFX). Percentage changes of CI were also calculated. There was only a poor correlation between CITPTD and CIPFX both before (r (2) = 0.34, p < 0.0001) and after (r (2) = 0.31, p < 0.0001) CPB, with a percentage error (PE) of 62 and 49 %, respectively. Four quadrant plots revealed a concordance rate over 90 % indicating an acceptable correlation of trends between CITPTD and CIPFX before (concordance: 93 %) and after (concordance: 94 %) CPB. In contrast, polar plot analysis showed poor trending before and an acceptable trending ability of changes in CI after CPB. Semi-invasive CI by autocalibrated pulse contour analysis showed a poor ability to estimate CI compared with transpulmonary thermodilution. Furthermore, the new semi-invasive device revealed an acceptable trending ability for haemodynamic changes only after CPB. ClinicalTrials.gov: NCT02312505 Date: 12.03.2012.


Starch multiscale structure and physicochemical property alterations in high-quality indica rice quality and cooked rice texture under different nitrogen panicle fertilizer applications.
The starch multiscale structure, physiochemical properties, grain quality and cooked rice texture of high-quality early and late indica were analyzed under nitrogen panicle fertilizer (low panicle fertilizer, LPF; middle panicle fertilizer, MPF; high panicle fertilizer, HPF) treatments and their internal relations were investigated. Compared to the MPF treatment, the starch granules in HPF and LPF had more surface-proteins and irregular voids for high-quality early and late indica rice cultivars, respectively. Nitrogen panicle fertilization application increased amylopectin medium and long chains as well as protein content, resulting in higher relative crystallinity and gelatinization temperatures. Moderate changes in starch multistructures and physicochemical properties such as branching degree, amylopectin medium chain, and pasting viscosities derived from MPF treatment significantly improved processing, appearance qualities and cooked rice texture. Additionally, the decrease in starch branching, gelatinization temperatures, and granule uniformity along with an increase in large granules, breakdown, and △Hgel under MPF treatment were the main reasons for improving rice textural properties.


Alcohol and inflammation and immune responses: summary of the 2005 Alcohol and Immunology Research Interest Group (AIRIG) meeting.
The 10th annual meeting of the Alcohol and Immunology Research Interest Group (AIRIG) was held at Loyola University Medical Center, Maywood, Illinois on November 18, 2005. The AIRIG meeting was held to exchange new findings and ideas regarding the profound suppressive effects of alcohol exposure on the immune system. The event consisted of five sessions, two of which featured plenary talks from invited speakers, two with oral presentations from selected abstracts, and a final poster session. Participants presented a range of novel information focused on ethanol-induced effects on innate and adaptive immunity after either acute or chronic exposure. In particular, participants offered insights into the negative effects of ethanol on the innate processes of adhesion, migration, inflammation, wound repair, and bone remodeling. Presentations also focused on the means by which ethanol disrupts activation of macrophages and dendritic cells (DC), especially stimulation mediated by Toll-like receptor ligands. Additional talks provided new data on the means by which ethanol suppresses adaptive immunity, with an emphasis on DC-mediated activation of T cells, effector T cell activity, and T cell-driven B cell responses.


[Lipid composition of thrombocytes in diabetes mellitus depending on the degree of microangiopathy].
The paper is concerned with the results of a study of the content of platelet lipid fractions in 115 patients with type I and II diabetes mellitus with a different degree of vascular complications. The results showed that the development of vascular lesions caused the appearance of specific disorders of platelet lipid composition characteristic for type I and II diabetes mellitus. In type I disorders of neutral phospholipids and free fatty acids were noted whereas in type II the above changes were noted in parallel with changes in the levels of cholesterol and acid phospholipids. With an increase in vascular lesions in type II there was a significant increase in phospholipase A2 activity, in type I under the same conditions the activity of this enzyme was absent. These facts suggest correlation between the development of vascular complications of diabetes mellitus and disorders in platelet membrane lipid structure.


Analysis of factors affecting discharge with the personal consent of hospitalized patients: A cross-sectional study.
Discharge by personal satisfaction is a condition in which the patient leaves the hospital before completing the care period against medical advice. Thus, this study aims to identify and analyze the reasons for discharge with the personal satisfaction of hospitalized patients. The study was descriptive-analytical being performed in 2021. The study population was 2869 discharged inpatients with personal satisfaction. Sampling was done by random and census. The data were collected using a checklist and a researcher-made questionnaire whose validity and reliability were confirmed. The data were analyzed using SPSS24 by K-Score test for qualitative and variance for quantitative variables. The discharge rate by personal satisfaction was 7.01%, the average age was 42 years, and the average length of stay was 4 days. Further, 57.1% of patients were female, 63.7% were married, and 21% were babies. A total of 22.77% of the patients were discharged with the father's consent, of which 13.2% were re-admitted. The most common reasons for the discharge were feeling of recovery (47.2%), the hospital being educational (30%), and dissatisfaction with the services of doctors (51.6%). Discharge with personal satisfaction had a significant relationship with the length of hospitalization (p < 0.001) and type of hospital (p = 0.04). The feeling of recovery, the educational nature of the hospital, and dissatisfaction with the services of doctors were the most common reasons for discharge with personal satisfaction. Therefore, monitoring the provision of services, establishing proper patient-doctor communication, and increasing the awareness of patients and parents could reduce this type of discharge and its consequences.


Non-primate foamy viruses.
Foamy viruses (PFVs), also called spumaviruses, are complex retroviruses inducing a characteristic cytopathic effect in cell culture, leading rapidly to cell lysis. These viruses have been isolated mostly in non-human primates, but three non primate PFVs were characterized, namely the bovine foamy virus, the feline foamy virus and more recently the equine foamy virus. In their hosts, PFVs seem to be apathogenic, mirroring an efficient control of virus replication in vivo. Comparing the biology of the different virus isolates will certainly help to unravel the biology of these retroviruses.


Usefulness of cone-beam CT before and after percutaneous vertebroplasty.
The usefulness of cone-beam C-arm CT for percutaneous vertebroplasty has not been fully evaluated. The purpose of this study was to assess the feasibility of cone-beam CT for evaluation before and after vertebroplasty. This prospective study included 22 consecutive patients (15 women and seven men) with osteoporotic compression fractures (51 vertebrae). Cone-beam CT and 64-MDCT were performed before and after percutaneous vertebroplasty. Multiplanar reformations of the axial, sagittal, and coronal planes were obtained. We evaluated the presence of cortical defects, vacuum phenomena in adjacent disks, and cement leakage, and we calculated the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of cone-beam CT compared with MDCT. All 75 cortical defects in 51 vertebrae seen on MDCT were also observed on cone-beam CT (100% sensitivity and specificity). Vacuum phenomena were detected in 33 of 86 (38.4%) adjacent disk spaces on MDCT and in 29 on cone-beam CT (84.8% sensitivity, 98.1% specificity, and 93.0% accuracy). Cement leakage was noted at 17 disk spaces, 15 paravertebral soft tissues, and 12 veins on MDCT. All cement leakages were correctly identified on cone-beam CT. Cone-beam CT is able to correctly evaluate for vertebral fractures and vacuum phenomena in adjacent disks before vertebroplasty and for cement leakage after vertebroplasty.


Without Missing a Beat: Absence of Cilia Informs the Diagnosis of Histopathologically Challenging Spitzoid Melanocytic Neoplasms.
The diagnosis of Spitzoid melanocytic lesions remains a formidable challenge in dermatopathology. Numerous ancillary tests have evolved to improve accurate classification of histopathologically ambiguous lesions. A study by Lang et al. (2020b) demonstrates loss of primary cilia in Spitzoid melanoma compared with Spitz nevi and positions ciliation index as an informative ancillary test for Spitzoid lesions.


Reconstruction of noise-driven nonlinear networks from node outputs by using high-order correlations.
Many practical systems can be described by dynamic networks, for which modern technique can measure their outputs, and accumulate extremely rich data. Nevertheless, the network structures producing these data are often deeply hidden in the data. The problem of inferring network structures by analyzing the available data, turns to be of great significance. On one hand, networks are often driven by various unknown facts, such as noises. On the other hand, network structures of practical systems are commonly nonlinear, and different nonlinearities can provide rich dynamic features and meaningful functions of realistic networks. Although many works have considered each fact in studying network reconstructions, much less papers have been found to systematically treat both difficulties together. Here we propose to use high-order correlation computations (HOCC) to treat nonlinear dynamics; use two-time correlations to decorrelate effects of network dynamics and noise driving; and use suitable basis and correlator vectors to unifiedly infer all dynamic nonlinearities, topological interaction links and noise statistical structures. All the above theoretical frameworks are constructed in a closed form and numerical simulations fully verify the validity of theoretical predictions.


A clinical study of post-cricoid carcinoma.
The local control rate following surgery was very high in patients with post-cricoid carcinoma; however, many of the patients undergoing surgery later developed distant metastasis. Therefore, establishment of chemotherapeutic regimens for preventing distant metastasis is desirable. To define the clinical course of the cancer, the problems that might be associated with its treatment, and the future course of treatment of this cancer at our hospital. This study included 21 patients with post-cricoid carcinoma who had undergone primary treatment at our hospital between 1989 and 2004. The present study was designed to retrospectively investigate the therapeutic outcome of post-cricoid carcinoma at our hospital. The 5-year cause-specific survival rate was 52%. All the patients who eventually died did so within 3 years of the treatment. Seven patients had distant metastases, representing a higher frequency as compared with that of patients with recurrence of the primary focus and cervical lymph node metastasis. All of these patients who had been treated by surgery died of the cancer.


Effects of marijuana use on prefrontal and parietal volumes and cognition in emerging adults.
Chronic marijuana (MJ) use among adolescents has been associated with structural and functional abnormalities, particularly in developing regions responsible for higher order cognition. This study investigated prefrontal (PFC) and parietal volumes and executive function in emerging adult MJ users and explored potential gender differences. Participants (ages 18-25) were 27 MJ users and 32 controls without neurologic or psychiatric disorders or heavy other drug use. A series of multiple regressions examined whether group status, past year MJ use, and their interactions with gender predicted ROI volumes. Post hoc analyses consisted of brain-behavior correlations between volumes and cognitive variables and Fisher's z tests to assess group differences. MJ users demonstrated significantly smaller medial orbitofrontal (mOFC; p = 0.004, FDR p = 0.024) and inferior parietal volumes (p = 0.04, FDR p = 0.12); follow-up regressions found that increased past year MJ use did not significantly dose-dependently predict smaller mOFC volume in a sub-sample of individuals with at least one past year MJ use. There were no significant gender interactions. There was a significant brain-behavior difference by group, such that smaller mOFC volumes were associated with poorer complex attention for MJ users (p < 0.05). Smaller mOFC volumes among MJ users suggest disruption of typical neurodevelopmental processes associated with regular MJ use for both genders. These results highlight the need for longitudinal, multi-modal imaging studies providing clearer information on timing of neurodevelopmental processes and neurocognitive impacts of youth MJ initiation.


Polyacrylate stabilized ZVI/Cu bimetallic nanoparticles for removal of hexavalent chromium from wastewater.
In this work, a magnetic core-shell composite zero-valent iron/copper-polyacrylate (ZVI/Cu-PAA) was synthesized by a simple liquid-phase reduction process and used for hexavalent chromium Cr(VI) removal from wastewater. The optimization experiments show that the optimal dosages of polyacrylate and Cu are 7.00 wt% and 8.25 wt%, respectively. The maximum adsorption capacity and removal rate of Cr(VI) by ZVI/Cu-PAA reached 106.12 mg g-1 and 99.05% at pH 5.5, respectively. Furthermore, the presence of coexisting ions such as Ca2+, Mg2+, Na+, and NO3- had no significant effect on its Cr(VI) removal performance. The excellent performance of ZVI/Cu-PAA is attributed to that the modification of polyacrylate can not only give more active sites but also inhibit agglomeration of nano-metallic particles, while Cu doping promotes the electron generation and transformation of Fe(III)/Fe(II) and Cu(II)/Cu(I) redox cycles. This makes ZVI/Cu-PAA has rich active sites and excellent stability, and has broad application prospects in the remediation of Cr (VI) polluted wastewater. The magnetic core-shell composite ZVI/Cu-PAA has excellent Cr (VI) removal performance because of its rich active sites and high electron transformation efficiency.


Implication of proteases in the respiration dependent inactivation of the lactose permease of E. coli.
The lactose permease of E. coli becomes irreversibly inactivated during lactose transport under conditions of high respiratory activity. This inactivation is characterized by a decrease in the steady state of lactose accumulation, a decrease in the influx rate of lactose, and a decrease in the transmembrane electrical potential. We report here that inhibitors of serine proteases (phenylmethylsulfonyl fluoride and N-alpha-P-tosyl-L-lysine chloromethyl ketone) prevent this inactivation, thus implicating proteases in this process.


Use of solvent to regulate the degree of polymerisation in weakly associated supramolecular oligomers.
Using a tetrathiafulvalene functionalised calix[4]pyrrole (TTF-C[4]P; ) and alkyl diester-linked bis-dinitrophenols (), it was found that the solvent polarity and linker length have an effect on the molecular aggregation behaviour. 2D (1)H NOESY, DOSY NMR and UV-vis-NIR spectroscopic studies, as well as single crystal X-ray diffraction analyses support these conclusions.


The Role of Skull Modeling in EEG Source Imaging for Patients with Refractory Temporal Lobe Epilepsy.
We investigated the influence of different skull modeling approaches on EEG source imaging (ESI), using data of six patients with refractory temporal lobe epilepsy who later underwent successful epilepsy surgery. Four realistic head models with different skull compartments, based on finite difference methods, were constructed for each patient: (i) Three models had skulls with compact and spongy bone compartments as well as air-filled cavities, segmented from either computed tomography (CT), magnetic resonance imaging (MRI) or a CT-template and (ii) one model included a MRI-based skull with a single compact bone compartment. In all patients we performed ESI of single and averaged spikes marked in the clinical 27-channel EEG by the epileptologist. To analyze at which time point the dipole estimations were closer to the resected zone, ESI was performed at two time instants: the half-rising phase and peak of the spike. The estimated sources for each model were validated against the resected area, as indicated by the postoperative MRI. Our results showed that single spike analysis was highly influenced by the signal-to-noise ratio (SNR), yielding estimations with smaller distances to the resected volume at the peak of the spike. Although averaging reduced the SNR effects, it did not always result in dipole estimations lying closer to the resection. The proposed skull modeling approaches did not lead to significant differences in the localization of the irritative zone from clinical EEG data with low spatial sampling density. Furthermore, we showed that a simple skull model (MRI-based) resulted in similar accuracy in dipole estimation compared to more complex head models (based on CT- or CT-template). Therefore, all the considered head models can be used in the presurgical evaluation of patients with temporal lobe epilepsy to localize the irritative zone from low-density clinical EEG recordings.


Plantar approach for treatment of brachymetatarsia: A novel approach with an aesthetic consideration.
In the past, open osteotomy was always performed through a dorsal approach in the surgical treatment of brachymetatarsia, which created scar formation on the dorsal skin, subsequently resulting in dissatisfaction with cosmetic results. In this study, we provided a plantar approach to avoid forming scars on the dorsal side. A retrospective review was conducted in nine patients (13 feet) with brachymetatarsia treated with an open osteotomy and gradual bone lengthening through a plantar approach. Visual analogue scale (VAS) was used to evaluate the satisfaction of foot appearance, and we designed a questionnaire called appearance index (AI) to assess the influence of foot appearance on quality of life after surgery. The complications were also recorded during the follow-up. The patients were followed up for 34.8 ± 23.7 months. All cases were healed with a time of 64.4 ± 7.1 days and a healing index of 44.1 ± 7.8 d/cm. Satisfaction VAS for foot appearance improved from a preoperative score of 1.7 ± 1.3 points to a postoperative score of 9.3 ± 0.5 points. The AI improved from a preoperative score of 9.2 ± 0.8 points to a postoperative score of 0.6 ± 0.7 points. Complications were observed in three feet (23.1%), but none was related to the plantar approach. In conclusion, the plantar approach for metatarsal osteotomy and pins fixation was a safe and efficient technique with a satisfactory cosmetic result for the patients. No complications related to the novel approach, such as neurovascular injury, were reported.


[Intraocular high pressure in thyroid-associated orbitopathy: physiopathological mechanisms, diagnosis, and management. Three case reports].
To determine the mechanisms and treatment of ocular hypertension in patients with thyroid-associated orbitopathy and to differenciate it from glaucomatous damage. Three case reports. Retrospective review of clinical findings, course, and treatment of the three patients. Elevated intraocular pressure in thyroid-associated orbitopathy observed in the three cases may involve different physiopathological abnormalities such as disturbances of venous circulation, compression by infiltrative muscles, and long corticosteroid use. In the first two cases, defects demonstrated in the perimetry are in consistent with glaucomatous damage. In the third case, visual field abnormalities may be compatible with a glaucomatous disease, but all defects resolved after therapy. Treatement was of the greatest difficulty for the three cases, associating antiglaucomatous medication, steroids, orbital radiotherapy, orbital decompression and extraocular muscle surgery. Intraocular pressure was controlled in all cases. Elevated intraocular pressure in thyroid-associated orbitopathy is distinguished from glaucomatous disease by its physiopathological mechanisms, clinical course, visual field defects, and treatment. The management of this hypertension is closely related to the treatment of dysthyroid orbitopathy.


Highly resilient and fatigue-resistant poly(4-methyl-ε-caprolactone) porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration.
Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min-1, the extremely low energy loss coefficient of <0.1, and the superior fatigue resistance, the PMCL20-DY porous scaffold was confirmed to harbor excellent elastic properties. In addition, the high resilience of the scaffold was confirmed to endow it with a minimally invasive application potential. In vitro testing revealed that the 3D porous scaffold was biocompatible with rat bone marrow stromal cells (BMSCs), inducing BMSCs to differentiate into chondrogenic cells. In addition, the elastic porous scaffold demonstrated good regenerative efficiency in a 12-week rabbit cartilage defect model. Thus, the novel polyester scaffold with adaptable mechanical properties may have extensive applications in soft tissue regeneration.


A new record of the rare Bigeye Sand Tiger shark Odontaspis noronhai Maul, 1955 (Lamniformes: Odontaspididae) from the northwestern Pacific, with notes on dentition.
In the Pacific Ocean, the rare Bigeye Sand Tiger shark Odontaspis noronhai has only been recorded twice, once from its central and once from its eastern part. Here we report the first record of this species from the northwestern Pacific. This specimen measuring 312 cm total length (TL) was captured off northeastern Taiwan (2525N, 12410E) from a depth of 100 m (in waters over 2100 m deep) in mid-December 2019, and was retrieved on 27 December 2019 when landed in port. Photo of the fresh specimen along with morphometric and meristic data and DNA information are provided herein. Dentition of the specimen is different from all other specimens by having two cusplets on at least one side of cusps on most of the teeth (vs. only one cusplet per side), and lower total tooth count (29/29 vs. 3438/3746). This record documents an extended distribution (about 7864 km westward from the central Pacific Ocean), and provides strong evidence for the wide distribution and mesopelagic characteristic of this poorly known species.


Extradiol cleavage of 3-substituted catechols by an intradiol dioxygenase, pyrocatechase, from a Pseudomonad.
Pyrocatechase (catechol 1,2-oxidoreductase (decyclizing), EC 126.96.36.199), a ferric ion-containing dioxygenase from Pseudomonas arvilla C-1, catalyzes the intradiol cleavage of catechol with insertion of 2 atoms of molecular oxygen to form cis,cis-muconic acid. The enzyme also catalyzed the oxidation of various catechol derivatives, including 4-methylcatechol, 4-chlorocatechol, 4-formylcatechol (protocatechualdehyde), 4,5-dichlorocatechol, 3,5-dichlorocatechol, 3-methylcatechol, 3-methoxycatechol, and 3-hydroxycatechol (pyrogallol). All of these substrates gave products having an absorption maximum at around 260 nm, which is characteristic of cis,cis-muconic acid derivatives. However, when 3-methylcatechol was used as substrate, the product formed showed two absorption maxima at 390 and 260 nm. These two absorption maxima were found to be attributable to two different products, 2-hydroxy-6-oxo-2,4-heptadienoic acid and 5-carboxy-2-methyl-2,4-pentadienoic acid (2-methylmuconic acid). The former was produced by the extradiol cleavage between the carbon atom carrying the hydroxyl group and the carbon atom carrying the hydroxyl group and the carbon atom carrying the methyl group; the latter by an intradiol cleavage between two hydroxyl groups. Since these products were unstable, they were converted to and identified as 6-methylpyridine-2-carboxylic acid and 2-methylmuconic acid dimethylester, respectively. Similarly, 3-methoxycatechol gave two products, namely, 2-hydroxy-5-methoxycarbonyl-2,4-pentadienoic acid and 5-carboxy-2-methoxy-2,4-pentadienoic acid (2-methoxymuconic acid). With 3-methylcatechol as substrate, the ratio of intradiol and extradiol cleavage activities of Pseudomonas pyrocatechase during purification was almost constant and was about 17. The final preparation of the enzyme was homogeneous when examined by disc gel electrophoresis and catalyzed both reactions simultaneously with the same ratio as during purification. All attempts to resolve the enzyme into two components with separate activities, including inactivation of the enzyme with urea or heat, treatment with sulfhydryl-blocking reagents or chelating agents, and inhibition of the enzyme with various inhibitors, proved unsuccessful. These results strongly suggest that Pseudomonas pyrocatechase is a single enzyme, which catalyzes simultaneously both intradiol and extradiol cleavages of some 3-substituted catechols.


Familial cold urticaria--a rare cause of lip swelling.
Cold urticaria is an unusual condition characterised by wealing of the skin or mucous membranes following exposure to cold. This report describes a presentation with recurrent lip swelling.


Toxicity antagonists in head and neck cancer.
Clinical trials of altered fractionation and concurrent chemoradiation regimens have better elucidated the limits of both acute and late normal tissue toxicities in the head and neck. Acute effects on mucosal epithelium represent the principal barrier to intensification of radiation or chemoradiation schedules. Late soft tissue injury and organ dysfunction limit efforts to escalate radiation total dose. New insights into the cellular and molecular mechanisms of injury repair allow new strategies in the management and prevention of treatment-related toxicity. Toxicity antagonists are agents that directly interfere with the mechanism of toxicity or modulate the normal tissue response to injury. This article reviews 10 agents under development. Not only could such interventions reduce treatment-related morbidity, but they may also allow treatment intensification in advanced disease.


The Arabidopsis SYN3 cohesin protein is important for early meiotic events.
α-Kleisins are core components of meiotic and mitotic cohesin complexes. Arabidopsis contains four genes that encode α-kleisin proteins: SYN1, SYN2, SYN3 and SYN4. SYN1, a REC8 ortholog, is essential for meiosis, while SYN2 and SYN4 appear to be SCC1 orthologs and function in mitosis. SYN3 is essential for megagametogenesis and is enriched in the nucleolus of meiotic and mitotic cells. In this study the role of SYN3 during meiosis was investigated by characterization of plants that express SYN3-RNAi constructs from either meiotic DMC1, native SYN3, or inducible PX7 promoters. Reduction of SYN3 caused defects in homologous chromosome synapsis and synaptonemal complex (SC) formation during male and female meiosis. Consistent with this observation, relatively little signal for the SC component ZYP1 was detected on the chromosomes of SYN3-RNAi plants. ZYP1 transcript levels were relatively normal, but several transcripts for genes that encode proteins involved in meiotic recombination were altered, which suggested that a reduction in SYN3 may inhibit meiotic progression by alteration of meiotic gene expression.


Influence of combinations of fenugreek, garlic, and black pepper powder on production traits of the broilers.
To study the effects of combinations of fenugreek (Trigonella foenum-graecum L.), garlic (Allium sativum), and black pepper (Piper nigrum) powder supplementation on production traits of broiler chickens. A total of 288 commercial broiler chicks were randomly assigned to 1-9 groups with 4 replicates each. An experiment was conducted in broilers with different feed formulations; control feed, with no added fenugreek, garlic, and black pepper powder; and 8 treatment groups receiving feed supplemented with different combinations of fenugreek, garlic, and black pepper powder. The individual broilers' body weight and feed consumption were recorded and calculate the body weight gain and feed conversion ratio (FCR). Broiler's weight gain and FCR were significantly higher in groups receiving feed supplemented with garlic and black pepper powder combinations (p<0.01). Cumulative feed consumption was significantly higher in groups receiving feed supplemented with garlic and black pepper powder combinations (p<0.01). The combination of garlic and black pepper powder supplemented broiler feed fed groups showed higher production performance. The 5 g/kg garlic powder+1 g/kg black pepper powder and 10 g/kg garlic powder+2 g/kg black pepper powder significantly improved the weight gain and FCR.


Contemporary approaches in medical management of patients with stable coronary artery disease.
CAD continues to be the principal cause of mortality in the United States, and the largest group of patients with CAD are those with stable angina. Among this group of patients, the most common manifestation of CAD is presence of transient episodes of myocardial ischemia. The presence of transient ischemia and not the severity of angina has been found to be associated with poor clinical outcome in patients with stable CAD. As part of a global treatment strategy for patients with stable CAD, changes in lifestyle and modification of coronary risk factors should be emphasized as an integral part of treatment. Conventional antianginal therapy is quite effective in controlling anginal attacks. Currently, several drugs and therapeutic strategies are available for the treatment of patients with angina (see Table 5). Nitrates are highly effective antianginal drugs with complex beneficial actions in patients with CAD, but their usefulness is limited by development of tolerance during long-term use. When clinically indicated, the use of nitrates should be supplemented with another longer-acting antianginal drug, such as a beta-blocker or a calcium channel blocker. Based on the available data, beta-blockers, when tolerated, seem to be the most effective antianginal drugs for most patients with stable CAD. Beta-blockers are also the most effective anti-ischemic drugs that reduce the magnitude of myocardial ischemia detected during routine daily activities. Calcium channel blockers are also effective vasodilators and good antianginal drugs. The clinician should become familiar with the different actions that this heterogeneous group of drugs has on the heart and vessels. This knowledge allows the clinician to choose the appropriate combination of different antianginal drugs for patients on an individualized basis. It is also critical to develop the treatment strategy by carefully taking into account other associated medical conditions that are frequently encountered in patients with CAD.


The size of the primary cilium and acetylated tubulin are modulated during adipocyte differentiation: Analysis of HDAC6 functions in these processes.
The primary cilium is an organelle present in most of the cells of the organism. Ciliopathies, such as the Bardet Biedl and the Alstrom syndromes are associated with obesity. We, and others, have shown that the primary cilium undergoes size modifications during adipocyte differentiation of human adipose stromal cells. We show here that the levels of acetylated α-tubulin, a constituent of the primary cilium, and the expression of HDAC6, the enzyme that deacetylates α-tubulin and is responsible for the loss of the cilium during mitosis, are modulated during adipogenesis. Moreover, during adipocyte differentiation cells that express higher level of HDAC6 are the first to lose their primary cilium. We have investigated the function of HDAC6 on adipocyte differentiation and on the primary cilium. We observe that inhibition of HDAC6 activity leads to a decrease in adipocyte differentiation. This is associated with an inhibition of the initial elongation of the cilium. Interestingly, overexpression of HDAC6 inhibits adipocyte differentiation and blunts the elongation of the primary cilium. In both situations, inhibition of adipocyte differentiation was not associated with an inhibition of the glucocorticoid receptor activity. This indicates that HDAC6 controls adipogenesis through the levels of acetylated α-tubulin. Moreover, we show that although HDAC6 expression increases during adipocyte differentiation it is not sufficient to provoke the loss of the cilium. This suggests the existence of a novel mechanism for the loss of the cilium. Together, these data indicate that HDAC6, and acetylated α-tubulin, are important regulator of adipocyte differentiation.


Ephrin-Eph signaling usage by a variety of viruses.
Ephrin-Eph signaling is a receptor tyrosine kinase signaling pathway involved in a variety of cellular mechanisms, of which many are related to the adhesion or migration of cells. Both the Eph receptor and ephrin ligand are abundantly present on a wide variety of cell types, and strongly evolutionary conserved. This review provides an overview of how 18 genetically diverse viruses utilize the Eph receptor (Eph), ephrin ligand (ephrin) or ephrin-Eph signaling to their advantage in their viral life cycle. Both Ephs and ephrins have been shown to serve as entry receptors for a variety of viruses, via both membrane fusion and endocytosis. Ephs and ephrins are also involved in viral transmission by vectors, associated with viral replication or persistence and lastly to neurological damage caused by viral infection. Although therapeutic opportunities targeting Ephs or ephrins do not seem feasible yet, the current research does propose two models for the viral usage of ephrin-Eph signaling. Firstly, the viral entry model, in which membrane molecules are used for viral entry, leading to cells being used for replication or as a transporter. Secondly, the advantageous expression ephrin-Eph signaling model, where viruses adapt the expression of Ephs or ephrins to change cell-cell interaction to their advantage. These models can guide future research questions on the usage of Ephs or ephrins by viruses and therapeutic opportunities.


The pattern of diseases of the skin in the Nigerian guinea savanna.
Eight thousand and thirteen patients were seen in dermatological clinics at Kaduna and Zaria in the Northern guinea savanna of Nigeria. Fungal infections were found in 1,224 cases and scabies in 923 cases, of which 765 patients had secondary infections. Similar results were found in other surveys from Sub-Saharan Africa.


Future Directions in the Treatment of Thyroid and Parathyroid Disease.
The surgical management of thyroid and parathyroid disease has evolved considerably since the era of Theodor Kocher. We review the current trends in thyroid and parathyroid surgery concerning robotic surgery for remote access, the use of parathyroid autofluorescence detection technology to aid in the prevention of hypocalcemia as well as the use of thermal ablation to target thyroid nodules in a minimally invasive way. We also discuss how artificial intelligence is being used to improve the workflow and diagnostics preoperatively as well as for intraoperative decision-making. We also discuss potential areas where future research may enhance outcomes.


Permeability of the blood-brain barrier to mannitol in the rat following 2450 MHz microwave irradiation.
The radiotracer method of Oldendorf was used to determine if 2450 MHz continuous wave (CW) microwave energy increases blood-brain barrier permeability to [14C]mannitol, which is normally excluded from entering the brain. Anesthetized, adult rats were irradiated singly for 30 min in the quiet zone of an anechoic chamber, at average power densities from 0.1 to 30 mW/sq.cm. Afterwards each rat received an intracarotid bolus injection of [14C]mannitol/[3H]water mixture and was decapitated 15 sec later. Uptake of [14C]mannitol relative to the highly permeable reference substance, [3H]water, was calculated as the brain uptake index (BUI) for 4 brain regions. Mean BUI values for tissues from the microwave-irradiated rats did not differ significantly from sham-irradiated animals, and a microwave influence on barrier permeability was not evident. Irrespective of treatment, BUI values for cerebellum and medulla were much higher and more variable than values for cortex or diencephalon, and were associated with reduced absorbance or retention of [3H]water. Because of a compromising influence of the vertebral arterial supply on the distribution of intracarotid-injected radiotracers, BUI measurements in caudal brain regions are probably unreliable unless accompanied by data on regional radioisotope concentrations. The absence of such data in an earlier BUI study, suggests that increases in BUI for cerebellum and medulla attributed to microwaves were possibly misinterpreted as differences in barrier permeability to [14C]saccharides, when in fact changes in blood flow and [3H]water influx or egress were responsible.


Highly efficient iridium-catalyzed oxidation of organosilanes to silanols.
Hydrolytic oxidation of organosilanes to the corresponding silanols can be performed highly efficiently with a catalyst system of [IrCl(C(8)H(12))](2) under essentially neutral and mild conditions, and various types of silanols are produced in good to excellent yields.


Acoustic and ultrasonographic characterization of polychloroprene, beeswax, and carbomer-gel to mimic soft-tissue for diagnostic ultrasound.
Materials with acoustic properties similar to soft-tissue are essential as tissue-mimicking materials (TMMs) for diagnostic ultrasound (US). The velocity (cus), acoustic impedance (AI) and attenuation coefficient of US (µ) in a material collectively define its acoustic property. In this work, the acoustic properties of polychloroprene rubber, beeswax, and Carbomer-gel are determined. The pulse-echo technique is used to estimate cus and µ. The product of a sample density (ρ) and cus gives its AI. Using a reference based on the International Commission on Radiation Units and Measurements Report-61, Tissue Substitutes, Phantoms and Computational Modelling in Medical Ultrasound, the results are evaluated. The acceptance criteria are 1.043 ± 0.021 g/cm3 (ρ), 1561 ± 31.22 m/s (cus), 1.63 ± 0.065 MRayls (AI) and µ within 0.5-0.7 dB/cm/MHz. Sample computerized tomography (CT) and US scanning are performed to evaluate their similarities (contrast and speckle pattern) with respective images of the human liver (a clinical soft-tissue). The average errors in measuring cus and µ were 0.14% and 1.2% respectively. From the present findings, acoustic properties of polychloroprene and beeswax are unacceptable. However, the results of Carbomer-gel ρ = 1.03 g/cm3, cus = 1567 m/s, AI = 1.61 MRayls are satisfactory and µ = 0.73 dB/cm/MHz, is higher than the reference (4.3%). Carbomer-gel could produce CT and US images, efficiently mimicking the respective liver images. Carbomer-gel containing 95% water is a low-cost material with a simple formulation. Present results suggest, Carbomer- gel mimics soft-tissue and can be used as a TMM for diagnostic US.


Paligenosis: Cellular Remodeling During Tissue Repair.
Complex multicellular organisms have evolved specific mechanisms to replenish cells in homeostasis and during repair. Here, we discuss how emerging technologies (e.g., single-cell RNA sequencing) challenge the concept that tissue renewal is fueled by unidirectional differentiation from a resident stem cell. We now understand that cell plasticity, i.e., cells adaptively changing differentiation state or identity, is a central tissue renewal mechanism. For example, mature cells can access an evolutionarily conserved program (paligenosis) to reenter the cell cycle and regenerate damaged tissue. Most tissues lack dedicated stem cells and rely on plasticity to regenerate lost cells. Plasticity benefits multicellular organisms, yet it also carries risks. For one, when long-lived cells undergo paligenotic, cyclical proliferation and redif-ferentiation, they can accumulate and propagate acquired mutations that activate oncogenes and increase the potential for developing cancer. Lastly, we propose a new framework for classifying patterns of cell proliferation in homeostasis and regeneration, with stem cells representing just one of the diverse methods that adult tissues employ.


Protocol for ex vivo competition and sequencing of mycobacterium isolated from infected guinea pigs.
We describe steps for gDNA isolation from mycobacterium strains isolated from guinea pig lungs. We detail steps for infection of guinea pigs with Mycobacterium tuberculosis, followed by in vitro growth, gDNA isolation, and whole genome sequencing. We also describe an ex vivo competition experiment to determine the selective advantage of one strain over another. We include details for WGS and mutation spectrum analysis. The protocol can be used to identify mutations that arise in other pathogenic bacteria. For complete details on the use and execution of this protocol, please refer to Naz et al. (2021).


Expression of oncofoetal pancreatic antigens in hamster adult pancreas during experimental carcinogenesis.
Foetal acinar components associated with the development of the hamster pancreas have been previously defined with the aid of an antifoetal pancreas serum. In immunohistology this antiserum also stained malignant ductal cells in N-nitrobis (2-oxopropyl) amine (BOP)-induced pancreatic adenocarcinoma. It did not stain adult pancreas structures including acini, ducts and islets of Langerhans. In this study, re-expression of foetal acinar antigens was disclosed before formation of tumours. Adenocarcinomas were not detected by conventional histology before the 24th week following initiation of the chemical treatment. However, staining with the antiserum was observed from the 7th week appearing in the apex of some acini cells having an almost normal histological appearance. Later, foetal acinar expression was frequently associated with evident morphological alterations in acini like dyskaryosis, enlarged cytoplasm or lumina. Staining of ducts with marked atypical epithelium and (as already reported) of neoplastic ducts was also observed. It was not detected in other pancreatic lesions viz. cystadenomas, mucoid glands and regular hyperplastic ducts. Acinar dedifferentiation as assessed by expression of foetal components preceded formation of tumours in all instances.


Digital geographies of the bug: A case study of China's contact tracing systems in the COVID-19.
The COVID-19 pandemic has radically expanded the role of algorithmic governance in everyday mobility. In China, urban and provincial governments have introduced health codes app as a national contract tracing and quarantine enforcement method to restrict the movements of "risky" individuals through malls, subways, railways, as well as between regions. Yet the health codes have been implemented with uneven efficacy and unexpected consequences. Drawing on glitch politics, we read these unintended consequences as "bugs" emerging from the introduction of platform-based management into everyday life. These bugs mediated individuals' lived experiences of the digital app and the hybrid space constituted by population governance, individual digital navigation, and technology. Drawing on a database of posts scraped from Zhihu, a popular Chinese question-and-answer site, we examine three dimensions of the bug: the algorithmic bug, the territorial bug, and the corporeal bug. This paper sheds light on the significance of end-user experiences in digital infrastructure and contributes to our understanding of the digital geographies of bugs in algorithmic governance and platform urbanism.