Impacts of Protecting Life in Global Health Assistance policy in Nepal: a qualitative study.
Despite the legalization of abortion in 2002 and the concerted efforts of the Ministry of Health and Population, abortion services remain inaccessible for many Nepali women. In 2017, the United States government enacted the Protecting Life in Global Health Assistance (PLGHA) policy, which prohibited international non-governmental organizations (INGOs) from receiving United States global health assistance from providing abortion services or referrals or engaging in advocacy on liberalizing abortion laws that may have had an impact on abortion services. Though this policy was revoked in January 2021, there is a need to assess its impacts in Nepal and mitigate its lingering effects, if any. We conducted in-depth interviews with 21 national-level stakeholders selected purposively on the basis of their experiences and expertise in sexual and reproductive health and rights (SRHR) in Nepal. Interviews were conducted two times: first between August and November 2020 when PLGHA was in place, and then between July and August 2021 after PLGHA was revoked. Interviews were digitally recorded, transcribed, translated and analysed thematically. Most participants reported that the implementation of PLGHA created gaps in SRHR services, affecting marginalized and underserved populations in Nepal. Participants reported that this policy has compromised the work of INGOs and civil society organizations (CSOs), posing additional risk to the sustainability of SRHR program achievements made so far. Beyond funding loss, participants also mentioned that PLGHA curtailed their freedom, with limited working areas and partnerships for CSOs leading to low or no utilization of services. Most participants welcomed the revocation of PLGHA and hoped it would have positive impacts on SRHR services by permanently repealing PLGHA. Most participants believed that the revocation of PLGHA opened opportunities for new funding and could re-establish partnerships and collaboration, though immediate results had not yet been seen. PLGHA had negative impacts on access to and quality of SRHR services. The Nepal government and other donor agencies need to bridge the funding gap created by the policy. The revocation of the policy has created the hope of bringing positive impacts in SRHR sector; however, the implementation of revocation at the ground level and impacts made on SRHR programs in Nepal remains to be explored.


[Ultrastructural changes in the microcirculatory bed of the lungs in endotoxin shock].
The electron microscopic study of the lungs during the initial and intermediate stages of endotoxin shock has revealed the manifestations of thrombo-hemorrhagic syndrome. Three days later interstitial fibrosis developed. Ultrastructural alterations of microcirculation become the basis for the formation of acute pulmonary failure.


Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome.
Erythroid dysplasia is the pathologic hallmark of myelodysplastic syndromes (MDS). To develop a quantitative flow-cytometry approach to its evaluation, we analyzed the expression of CD71, CD105, cytosolic H-ferritin (HF), cytosolic L-ferritin (LF) and mitochondrial ferritin (MtF) in erythroblasts from 104 MDS patients, 69 pathologic control patients and 19 healthy subjects. Six-parameter, 4-color flow cytometry was employed, and data were expressed as mean fluorescence intensity. Compared with pathologic and healthy controls, MDS patients had higher expression of HF (P < 0.001) and CD105 (P < 0.001), and lower expression of CD71 (P < 0.001). MtF was specifically detected in MDS with ringed sideroblasts, and there was a close relationship between its expression and Prussian blue staining (r = 0.89, P < 0.001). In vitro cultures of myelodysplastic hematopoietic progenitors showed that both HF and MtF were expressed at a very early stage of erythroid differentiation, and that MtF expression is specifically related to mitochondrial iron loading. A classification function based on expression levels of HF, CD71 and CD105 allowed us to correctly classify > 95% of MDS patients. This flow-cytometry approach provides an accurate quantitative evaluation of erythroid dysplasia and allows a reliable diagnosis of sideroblastic anemia, and may therefore be a useful tool in the work-up of patients with MDS.


Genomic organization of human 5 S rDNA and sequence of one tandem repeat.
An organization of human 5 S rDNA repeats is inferred from Southern analyses of restriction digests of genomic DNA fractionated by pulsed-field and conventional gel electrophoreses. A single unit of 2.2 kb is repeated approximately 90 times within a 200-kb fragment (defined by enzymes that do not cleave within individual units, i.e., EcoR1, BglII, HindIII, and PvuII); a comparable number of 5 S sequences are scattered elsewhere in the genome. A lambda clone containing six complete 5 S repeats was obtained from a human placental DNA library. One repeat contains 2231 bp and includes poly(dG-dT).(dC-dA), tracts of polypyrimidine, and an Alu sequence in the spacer region. Also, 5-S-hybridizing clones, containing DNA inserts with an average size of 250 kb, have been obtained as yeast artificial chromosomes. Thus far, four clones have been partially characterized and shown to be 5 S sequences from loci separate from the tandem repeat units.


Clinical and mycological spectra of Wangiella dermatitidis infections.
The article reviews 37 cases of phaeohyphomycosis from the world literature up to 1992 accepted as being caused by Wangiella dermatitidis. The various clinical aspects of these infections are characterized, and the nomenclatural implications in the history of this emerging pathogen are discussed.


Operational strategies enhancing sewage sludge minimization in a combined integrated fixed-film activated sludge - oxic settling anaerobic system.
A lab-scale integrated fixed-film activated sludge (IFAS) reactor was mplemented with the oxic-settling anaerobic (OSA) cycle for reducing sewage sludge production through the addition of an anoxic/anaerobic sludge holding tank (SHT) along the sludge recycle line. The IFAS-OSA system was operated under the different hydraulic retention time (HRT) in the SHT (HRTSHT) of 12 h and 6 h, at an oxidation-reduction potential (ORP) < -91 mV and solid retention time (SRT) between 39 and 126 d. Furthermore, the effect of temperature increase in the SHT (TSHT) from ambient (19.8-25.6 °C) to mesophilic (35 °C) conditions was investigated. The system performances were monitored in terms of sludge minimization and dewaterability efficiencies as well as carbon and nutrients reduction. The observed sludge yield (Yobs) for the IFAS system was 0.37(±0.06) mg VSS/mg COD. After OSA implementation Yobs decreased by 32% and 46-65% at HRTSHT of 12 h and 6 h, respectively, indicating that prolonged exposure to anoxic/anaerobic conditions was not beneficial for sludge reduction. The lowest Yobs of 0.09(±0.05) mg VSS/mg COD (76% lower than that in the IFAS system) was obtained at an HRTSHT of 6 h and when TSHT was set at 35 °C. OSA implementation did not affect COD and NH4+ oxidation of the IFAS system (90-96% and 99%, respectively) and improved total nitrogen (TN) reduction (31-53%) due to improved denitrification in the SHT. On the contrary, sludge dewaterability worsened following OSA implementation, which was linked to the increased levels of exopolymeric substances in the suspended biomass.


Age-related delay in recovery of beta-adrenergic sensitivity after abrupt propranolol withdrawal in rats.
We compared cardiovascular responses to various adrenergic agonists in conscious 3-month and 12-month old rats that had been treated with propranolol daily for 7 days, to determine whether changes in beta-adrenergic hypersensitivity induced by abrupt propranolol withdrawal would differ with age. Depressor and tachycardic responses elicited by beta-adrenergic stimulation with isoproterenol were still reduced during the first 3 days following propranolol withdrawal, but were restored to pretreatment levels, more slowly in 12-month than in 3-month-old rats. Opposite pressor and bradycardic responses to alpha-adrenergic stimulation with phenylephrine did not differ between age groups, either before or after propranolol withdrawal. By contrast, pressor and bradycardic responses produced by combined alpha- and beta-adrenergic stimulation with epinephrine after propranolol withdrawal, though unaltered in 3-month-old rats, were enhanced in 12-month-old rats. Hence after sudden propranolol withdrawal beta-adrenergic sensitivity in conscious rats was gradually restored, rather than being enhanced, but more slowly at 12 than at 3 months of age. These results suggest that following abrupt cessation of prolonged propranolol treatment, restoration of normal beta-adrenergic sensitivity becomes delayed in older rats.


Patients with back pain value the process, as well as outcomes, of care.
of May S (2001): An explorative, qualitative study into patients' satisfaction with physiotherapy.


Inhibition of EGFR Tyrosine Kinase by Erlotinib Prevents Sclerodermatous Graft-Versus-Host Disease in a Mouse Model.
Chronic graft-versus-host disease (GVHD) follows allogeneic hematopoietic stem cell transplantation. It results from alloreactive processes induced by minor histocompatibility antigen incompatibilities leading to the activation of CD4 T cells and the development of fibrosis and inflammation of the skin and visceral organs and autoimmunity that resemble systemic sclerosis. EGFR is a ubiquitous cell receptor deeply involved in cell proliferation, differentiation, and motility. EGFR has recently been implicated in autoimmune and fibrotic diseases. Therefore, we tested whether Erlotinib, an EGFR tyrosine kinase inhibitor, can prevent sclerodermatous GVHD (Scl-GVHD). Scl-GVHD was induced in BALB/c mice by B10.D2 bone marrow and spleen cell transplantation. Transplanted mice displayed severe clinical symptoms including alopecia, fibrosis of the skin and visceral organs, vasculitis, and diarrhea. The symptoms were reversed in mice treated with Erlotinib. These beneficial effects were mediated by the decreased production of activated/memory CD4(+) T cells and the reduction in T-cell infiltration of the skin and visceral organs along with a decrease in IFN-γ and IL-13 production and autoimmune B-cell activation. The improvement provided by Erlotinib in the mouse model of Scl-GVHD supplies a rationale for the evaluation of Erlotinib in the management of patients affected by chronic GVHD.


Gut microbiota regulate migration of lymphocytes from gut to lung.
The community of microorganisms known as gut microbiota that lives in the intestine confers significant health benefits on its host, primarily in the form of immunological homeostasis regulation. Gut microbiota not only can shape immune responses in the gut but also in other organs. This review focus on the gut-lung axis. Aberrant gut microbiota development is associated with greater lung disease susceptibility and respiratory disease induced by a variety of pathogenic bacteria. They are known to cause changes in gut microbiota. Recent research has found that immune cells in the intestine migrate to distant lung to exert anti-infective effects. Moreover, evidence indicates that the gut microbiota and their metabolites influence intestinal immune cells. Therefore, we suspect that intestine-derived immune cells may play a significant role against pulmonary pathogenic infections by receiving instructions from gut microbiota.


Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence.
In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.


A PSD-95 peptidomimetic mitigates neurological deficits in a mouse model of Angelman syndrome.
Angelman Syndrome (AS) is a severe cognitive disorder caused by loss of neuronal expression of the E3 ubiquitin ligase UBE3A. In an AS mouse model, we previously reported a deficit in brain-derived neurotrophic factor (BDNF) signaling, and set out to develop a therapeutic that would restore normal signaling. We demonstrate that CN2097, a peptidomimetic compound that binds postsynaptic density protein-95 (PSD-95), a TrkB associated scaffolding protein, mitigates deficits in PLC-CaMKII and PI3K/mTOR pathways to restore synaptic plasticity and learning. Administration of CN2097 facilitated long-term potentiation (LTP) and corrected paired-pulse ratio. As the BDNF-mTORC1 pathway is critical for inhibition of autophagy, we investigated whether autophagy was disrupted in AS mice. We found aberrantly high autophagic activity attributable to a concomitant decrease in mTORC1 signaling, resulting in decreased levels of synaptic proteins, including Synapsin-1 and Shank3. CN2097 increased mTORC1 activity to normalize autophagy and restore hippocampal synaptic protein levels. Importantly, treatment mitigated cognitive and motor dysfunction. These findings support the use of neurotrophic therapeutics as a valuable approach for treating AS pathology.


Mycodegradation of diazinon pesticide utilizing fungal strains isolated from polluted soil.
The current study aimed to isolate biodegradable soil fungi capable of metabolizing diazinon. The collected soil samples were investigated for diazinon pollution to detect the pesticide level in the polluted soil samples. Food poisoning techniques were utilized to preliminary investigate the biodegradation efficiency of the isolated fungal strains to diazinon pesticide using solid and liquid medium and also to detect their tolerance to different concentrations. GC-MS analysis of control and treated flasks were achieved to determine the diazinon residues for confirmation of the biodegradation efficiency. The total diazinon residues in the collected soil samples was found to be 0.106 mg/kg. Out of thirteen fungal strains isolated form diazinon polluted soils, six strains were potentially active in diazinon biodegradation. Food poisoning technique showed that A. niger, B. antennata, F. graminearum, P. digitatum, R. stolonifer and T. viride strains recorded fungal growth diameters of 65.2 ± 0.18, 57.5 ± 0.41, 47.2 ± 0.36, 56.5 ± 0.27, 85.0 ± 0.01, 85.0 ± 0.06 mm respectively in the treated group which were non significantly different compared to that of control (P > 0.05), indicating the high efficiency of these strains in diazinon degradation compared to the other isolated strains. GC-MS analysis revealed that B. antennata was the most efficient strain in diazinon degradation recording 32.24 ± 0.15 ppm concentration after 10 days incubation. Linear regression analysis confirmed that B. antennata was the most effective biodegradable strain recording the highest diazinon dissipation (83.88%) with the lowest T1/2 value of 5.96 days while T. viride, A. niger, R. stolonifer and F. graminearum exhibited a high biodegradable activities reducing diazinon to 80.26%, 78.22%, 77.36% and 75.43% respectively after 10 days incubation. In conclusion, these tolerant fungi could be considered as promising, eco-friendly and biodegradable fungi for the efficient and potential removal of hazardous diazinon from polluted soil.


Extended sorption partitioning models for pesticide leaching risk assessments: Can we improve upon the koc concept?
Models used to assess leaching of pesticides to groundwater still rely on the sorption koc value, even though its limitations have been known for several decades, especially for soils of low organic carbon content (i.e. subsoils). This is mainly because the general applicability of any improved model approach that is also simple enough to use for regulatory purposes has not been demonstrated. The objective of this study was to test and compare alternative models of sorption that could be useful in pesticide risk assessment and management. To this end, a database containing the results of batch sorption experiments for pesticides was compiled from published studies in the literature, which placed at least as much emphasis on measurements in subsoil horizons as in topsoil. The database includes 785 data entries from 34 different published studies and for 21 different active substances. Overall, the apparent koc value, koc(app), roughly doubled as the soil organic carbon content decreased by a factor of ten. Nevertheless, in nearly half of the individual datasets, a constant koc value proved to be an adequate model. Further analysis showed that significant increases in koc(app) in subsoil were found primarily for the more weakly adsorbing compounds (koc values<ca. 100-200Lkg(-1)) and that sorption to clay in loamy and clayey-textured subsoil horizons was the main cause. Tests with the MACRO model demonstrated that sorption to clay minerals may significantly affect the outcome of regulatory exposure and risk assessments for leaching to groundwater. The koc concept currently used in leaching models should therefore be replaced by an alternative approach that gives a more realistic representation of pesticide sorption in subsoil. The two alternative models tested in this study appear to have widespread applicability and are also simple enough to parameterize for this purpose.


Heterotypic tumor spheroids: a platform for nanomedicine evaluation.
Nanomedicine has emerged as a promising therapeutic approach, but its translation to the clinic has been hindered by the lack of cellular models to anticipate how tumor cells will respond to therapy. Three-dimensional (3D) cell culture models are thought to more accurately recapitulate key features of primary tumors than two-dimensional (2D) cultures. Heterotypic 3D tumor spheroids, composed of multiple cell types, have become more popular than homotypic spheroids, which consist of a single cell type, as a superior model for mimicking in vivo tumor heterogeneity and physiology. The stromal interactions demonstrated in heterotypic 3D tumor spheroids can affect various aspects, including response to therapy, cancer progression, nanomedicine penetration, and drug resistance. Accordingly, to design more effective anticancer nanomedicinal therapeutics, not only tumor cells but also stromal cells (e.g., fibroblasts and immune cells) should be considered to create a more physiologically relevant in vivo microenvironment. This review aims to demonstrate current knowledge of heterotypic 3D tumor spheroids in cancer research, to illustrate current advances in utilizing these tumor models as a novel and versatile platform for in vitro evaluation of nanomedicine-based therapeutics in cancer research, and to discuss challenges, guidelines, and future directions in this field.


Crystal anisotropy explains structure-mechanics impact on tableting performance of flufenamic acid polymorphs.
Anisotropic features with other crystallographic properties like d-spacing, and attachment energy (Eatt) can predict material performance during the secondary pharmaceutical processing. A newly developed state-of-the-art compression cell lodged in a powder X-ray diffractometer was used to measure anisotropic Young's moduli (YM) of flufenamic acid (FFA) polymorphs in this study. Methodology is based on the generation of a single crystal deformation in this cell, which reflects as a change in the d-spacing in the PXRD pattern. Anisotropic YM was calculated from such information gathered along different FFA planes. Measured FFA crystallographic molecular features were concatenated to understand macroscopic compaction (Heckel and Shapirao's parameters) and tableting performance. Block shaped crystals of FFA form I, and III after initial characterization with SEM, DSC, PXRD, and FTIR were compressed normal to X, Y, and Z-planes, identified from calculated PXRD pattern using the reported single crystal structure. YM of X and Y planes of form I was significantly higher than corresponding planes of form III. Z plane of form III showed significantly higher YM than that for form I. Low YM of form III can be attributed to its large d-spacing regardless of their high Eatt than form I, as well as orientation of supramolecular acid dimer (OH⋯O) homosynthon chains in the FFA planes. FFA form I stiffness was further confirmed with lower densification and higher yield pressure of deformation than form III. Clearly, form III exhibited better compressibility, compactibility, and tableting performance than form I due to favorable molecular and macroscopic features. Thus, developed anisotropic measurement approach can be used to distinguish material performance in the early development stage of the pharmaceutical processes.


A small molecule inhibitor of alpha4 integrin-dependent cell migration.
A small molecule inhibitor of alpha4 integrin-dependent cell migration was identified through a cell-based screen of small molecule libraries. Biochemical and cellular experiments suggest that this molecule functions by interacting with gamma-parvin. This molecule should serve as a useful tool to study alpha4 integrin signaling and may lead to new therapeutics for the treatment of autoimmune diseases.


Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.
DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation.


Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity.
Efficient and sensitive LC-MS/MS methods have been developed for the rapid screening and determination of bioactive compounds in different fruit parts of four Myristica species, viz., Myristica beddomeii, Myristica fragrans, Myristica fatua and Myristica malabarica. Twenty-one compounds were identified and characterized on the basis of their accurate mass and MS/MS fragmentation pattern using HPLC-QTOF-MS/MS and NMR analysis. Quantitative determination of five major bioactive compounds was performed using multiple-reaction monitoring mode with continuous polarity switching by UHPLC-QqQLIT-MS/MS. Moreover, in vitro antiproliferative activity of these Myristica species was evaluated against five human cancer cell lines A549, DLD-1, DU145, FaDu and MCF-7 using SRB assay. Seventeen phytoconstituents were identified and reported for the first time from M. beddomeii and sixteen from M. fatua. Quantification result showed highest total content of five major bioactive compounds in mace of M. fragrans. Evaluation of in vitro antiproliferative activity revealed potent activity in all investigated species except M. fragrans.


Control of human coagulation by recombinant serine proteases. Blood clotting is activated by recombinant factor XII deleted of five regulatory domains.
The availability of engineered serine proteases allows one to study the activation, substrate specificity and regulation of human coagulation and fibrinolytic activities. Human coagulation factor XII is composed of the protease catalytic region at the C-terminus, a hinge proline-rich region and regulatory domains at the N-terminus. From cDNA clones coding for factor XII, two DNA molecules were constructed, one being full length and the other being deleted of exons coding for the regulatory domains. Engineered factor-XII cDNA species were inserted by a homologous recombination technique into vaccinia viruses, which were used to infect the human hepatoma cell line HepG2. Two recombinant proteins were prepared from the culture media and identified by their antigenic properties and electrophoretic mobilities. The recombinant protein of larger size was identified as the full-length factor XII of 80 kDa and its specific activities and activation patterns, determined both by the coagulation and the amidolytic assays, are very similar to these of native human factor XII. The recombinant protein of smaller size was identified as a 319-amino-acid-deleted factor-XII protein of 32 kDa, containing only the entire protease region and part of the proline-rich hinge. This protein was expected to be the 'minimal' portion of factor XII able to sustain protease but unable to recognize substrates and surfaces necessary to activate the contact phase of coagulation. However, this 'minimal' factor-XII protein displays a marked protease activity and, although lacking five regulatory domains of factor XII, is bound and activated by negative charges and promotes coagulation with high efficiency.


Prehospital Use of Ketamine in Mountain Rescue: A Survey of Emergency Physicians of a Single-Center Alpine Helicopter-Based Emergency Service.
Although ketamine use in emergency medicine is widespread, studies investigating prehospital use are scarce. Our goal was to assess the self-reported modalities of ketamine use, knowledge of contraindications, and occurrence of adverse events associated with its use by physicians through a prospective online survey. The survey was administered to physicians working for Air-Glaciers, a Swiss alpine helicopter-based emergency service, and was available between September 24 and November 23, 2018. We enrolled 39 participants (participation rate of 87%) in our study and collected data regarding their characteristics, methods of ketamine use, knowledge of contraindications, and encountered side effects linked to the administration of ketamine. We also included a clinical scenario to investigate an analgesic strategy. Ketamine was considered safe and judged irreplaceable by most physicians. The main reason for ketamine use was acute analgesia during painful procedures, such as manipulation of femur fractures. The doses of ketamine administered with or without fentanyl ranged from 0.2 to 0.7 mg·kg-1 intravenously. Most physicians reported using fentanyl and midazolam along with ketamine. The median dose of midazolam was 2 (interquartile range 1-2) mg for a 70-kg adult. Monitoring and oxygen administration were used infrequently. Hallucinations were the most common adverse events. Knowledge of ketamine contraindications was poor. Ketamine use was reported by mountain rescue physicians to be safe and useful for acute analgesia. Most physicians use fentanyl and midazolam along with ketamine. Adverse neuropsychiatric events were rare. Knowledge regarding contraindications to the administration of ketamine should be improved.


Further evidences of an emerging stingless bee-yeast symbiosis.
Symbiotic interactions between microorganisms and social insects have been described as crucial for the maintenance of these multitrophic systems, as observed for the stingless bee Scaptotrigona depilis and the yeast Zygosaccharomyces sp. SDBC30G1. The larvae of S. depilis ingest fungal filaments of Zygosaccharomyces sp. SDBC30G1 to obtain ergosterol, which is the precursor for the biosynthesis of ecdysteroids that modulate insect metamorphosis. In this work, we find a similar insect-microbe interaction in other species of stingless bees. We analyzed brood cell samples from 19 species of stingless bees collected in Brazil. The osmophilic yeast Zygosaccharomyces spp. was isolated from eight bee species, namely Scaptotrigona bipunctata, S. postica, S. tubiba, Tetragona clavipes, Melipona quadrifasciata, M. fasciculata, M. bicolor, and Partamona helleri. These yeasts form pseudohyphae and also accumulate ergosterol in lipid droplets, similar to the pattern observed for S. depilis. The phylogenetic analyses including various Zygosaccharomyces revealed that strains isolated from the brood cells formed a branch separated from the previously described Zygosaccharomyces species, suggesting that they are new species of this genus and reinforcing the symbiotic interaction with the host insects.


Finite-time stability for discrete-time system with time-varying delay and nonlinear perturbations.
In this paper, the problem of finite-time stability for discrete-time system with time-varying delay and nonlinear perturbations is investigated. By constructing a novel Lyapunov-Krasovskii functional and employing a new summation inequality named discrete Wirtinger-based inequality, reciprocally convex approach and zero equality, the improved finite-time stability criteria are derived to guarantee that the state of the system with time-varying delay does not exceed a given threshold when fixed time interval. Furthermore, the obtained conditions are formulated in forms of linear matrix inequalities which can be solved by using some standard numerical packages. Finally, three numerical examples are given to show the effectiveness and less conservatism of the proposed method.


The promise of prostaglandins: have they fulfilled their potential as therapeutic targets for the delay of preterm birth?
The elucidation some 30 years ago by Sir Mont Liggins that the activation of the hypothalamic-pituitary-adrenal-placental axis in fetal sheep led to elevated maternal prostaglandin (PG) concentrations and the initiation of labor provided hope that targeting PG synthesis or action would lead to effective tocolysis and lowering of the human preterm birth rate. This was the "promise of PGs." Although early trials showed that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit PG H synthase (PGHS), delayed preterm birth by 48 hours, other trials revealed an association between NSAIDs and adverse fetal effects, including oligohydramnios, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, and persistent pulmonary hypertension of the newborn (PPHN). Hope was revived when studies in the mid 1990s demonstrated that much of the PGs synthesized by intrauterine tissues at preterm labor were derived from the inducible isoenzyme PGHS-2. Unfortunately, administration of specific PGHS-2 inhibitors led to the same adverse fetal effects displayed by the mixed PGHS-1 and -2 NSAIDs, causing interest in the promise of PGs to wane. This led to the development of new strategies for specific PG inhibition or antagonism. One of these is the application of a specific PGF2alpha receptor blocker, Theratechnologies (THG)113.31. THG113.31 decreases the in vitro contractile activity of mouse, sheep, and human myometrium in response to exogenous PGF2alpha, delays lipopolysaccharide (LPS)-induced preterm birth in mice, and lowers uterine electromyographic activity and delays preterm birth in sheep administered RU486. There have been no observable maternal or fetal side effects with its use. By developing new strategies based on other therapeutic targets, the promise of PGs may once again offer hope for delaying preterm birth.


Patient-centredness in primary care walk-in clinics for refugees in Hamburg.
The huge increase of refugees to Germany caused a great challenge to the health system. We aimed to examine the level of patient-centredness in medical consultations with refugee patients, aided by video interpreters in primary care walk-in clinics (PCWC) in Hamburg. Videotaped consultations (N = 92) of 83 patients from 2017 to 2018 were analysed. Two raters used the Measure of Patient-Centered Communication (MPCC) and the International Classification of primary care (ICPC-2). MPCC scores with regard to patients' reason for seeking medical care and the procedures taken were explored using variance analyses adjusted for age, gender, and the duration of the consultation. The duration was further explored by Pearson correlations. Patient-centredness of all consultations on average was 64% (95% CI 60-67) according to MPCC, with health-related issues affecting the results. The highest level of patient-centredness was achieved in psychological health issues with 79% (65-94), the lowest in respiratory ones with 55% (49-61). Longer consultations resulted in higher MPCC scores. The level of patient-centredness varied in the addressed health issues as well as in the duration of the consultation. Despite the variation, video interpreting in consultations supports a solid patient-centredness. We recommend the use of remote video interpreting services for outpatient healthcare to support patient-centred communication and to fill the gap of underrepresentation of qualified interpreters on site, regarding a high diversity of spoken languages.


Renaissance of Topotactic Ion-Exchange for Functional Solids with Close Packed Structures.
Recently, many new, complex, functional oxides have been discovered with the surprising use of topotactic ion-exchange reactions on close-packed structures, such as found for wurtzite, rutile, perovskite, and other structure types. Despite a lack of apparent cation-diffusion pathways in these structure types, synthetic low-temperature transformations are possible with the interdiffusion and exchange of functional cations possessing ns2 stereoactive lone pairs (e. g., Sn(II)) or unpaired ndx electrons (e. g., Co(II)), targeting new and favorable modulations of their electronic, magnetic, or catalytic properties. This enables a synergistic blending of new functionality to an underlying three-dimensional connectivity, i. e., [-M-O-M-O-]n , that is maintained during the transformation. In many cases, this tactic represents the only known pathway to prepare thermodynamically unstable solids that otherwise would commonly decompose by phase segregation, such as that recently applied to the discovery of many new small bandgap semiconductors.


Selective recognition of D-tryptophan from d/l-tryptophan mixtures in the presence of Cu(II) by electropolymerized L-lysine film.
Selective recognition of D-tryptophan (D-Trp) in the presence of Cu(II) was investigated at poly-L-lysine (p-l-Lys) film using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). p-l-Lys film was immobilized on a glassy carbon electrode (GCE) by cyclic voltammetry between 0.0 and 1.9 V in 20 mM phosphate buffer solution (pH 8.6). After the p-l-Lys/GCE electrode was incubated with D-Trp solution containing Cu(II) ions, obvious enhancement of electron transfer resistance and decrease of voltammetric current could be observed. If D-Trp was replaced by L-tryptophan (l-Trp), there was no apparent resistance and current changes. Moreover, no resistance and current changes could be found in the absence of Cu(II). It may be due to the formation of Cu complex with L-lysine and D-tryptophan. Finally, this method was successfully applied to monitoring enantiomeric composition of the D-Trp and l-Trp mixtures.


Stretched intradural extramedullary tanycytic ependymoma of the thoracic spine.
Tanycytic ependymoma is a rare variant of ependymoma that commonly affects the cervical and thoracic spinal cord. It usually arises as intramedullary lesions and extramedullary cases are extremely rare. We present a 77-year-old woman with the complaints of a 2-year history of progressive paraparesis and sensory loss in her lower extremities. Magnetic resonance imaging revealed a stretched and fusiform intradural extramedullary lesion at T5-T10 level. Gross total removal of the tumor was achieved and a definitive diagnosis of tanycytic ependymoma was established. This case thus represents a rare case of thoracic intradural extramedullary tanycytic ependymoma and, to the best of our knowledge, it represents the longest intradural extramedullary tanycytic ependymoma in craniocaudal direction ever reported in the literature.


Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion.
In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy. HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0-2) and good (Higashida score, 3-4). A multiple logistic regression model was performed to detect independent markers of good collateral status. One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels (P=0.01), high MCP-1 levels (P<0.01), a low National Institute of Health Stroke Score (P=0.046), a high diastolic blood pressure (P=0.049), the absence of tandem occlusion (P=0.046), a high Alberta Stroke Program Early CT Score (P<0.01) and a low volume on the diffusion-weighted imaging (P<0.01) were associated with good collateral status. Following multivariate analysis, low MMP-9 levels (P=0.02) and high MCP-1 levels (P<0.01) remained associated with good collateral status. Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.


Seasonal and climatic factors have a significant influence on fertility associated sperm phenomic attributes in crossbred breeding bulls (Bos taurus × Bos indicus).
Although seasonal variations in semen quality and fertility have been studied to a considerable extent in breeding bulls, the effect of climatic variables on sperm functional competency has not been understood in detail. The present study analyzed sperm functional parameters in breeding bulls, over a period of 1 year, and assessed the effect of climatic variables on fertility associated sperm parameters. Seasons were categorized into summer, rainy, autumn, and winter based on the meteorological data. Semen was collected from crossbred bulls (n = 7) across the seasons and evaluated for functional membrane integrity, acrosome reaction status, protamine deficiency, capacitation, and lipid peroxidation status using specific fluorescent probes. The results of the present study revealed that bulls produced higher (p < 0.05) viable and acrosome intact spermatozoa during the autumn. The proportion of uncapacitated spermatozoa was also higher (p < 0.05) during autumn. Further, correlation of sperm functional attributes with environmental variables revealed that sperm viability was significantly (p < 0.05) and negatively correlated with daylength and temperature; acrosomal integrity was significantly (p < 0.05) and negatively correlated with day length; and protamine deficiency had significant (p < 0.05) positive correlation with day length and average temperature, and negative correlation with relative humidity. It was concluded that semen produced during autumn was superior to the semen produced during other seasons in terms of sperm functional competencies required for fertility.


SnSe2 quantum dot sensitized solar cells prepared employing molecular metal chalcogenide as precursors.
A kind of molecular metal chalcogenide, (N(2)H(4))(3)(N(2)H(5))(4)Sn(2)Se(6) complex, was synthesized in the hydrazine solution and employed as the precursors for SnSe(2) deposition on TiO(2) nanocrystalline porous films. A power conversion efficiency of 0.12% under AM 1.5, 1 sun was obtained for the SnSe(2) sensitized TiO(2) solar cells.


Pharmacokinetics and tissue distribution of a new heterocyclic N-phenylpiperazine derivative (LASSBio-581) in rats.
This work investigated the pharmacokinetics of a new N-phenylpiperazine derivative (LASSBio-581), active on dopaminergic system. LASSBio-581 plasma concentrations were determined in rats after bolus administration of 10mg/kg, i.v., 30 and 60 mg/kg, i.p. and p.o., by HPLC. Individual profiles were evaluated by non-compartmental and compartmental analysis using WinNonlin. Protein binding by ultrafiltration showed free fraction of 29+/-4%. The compound showed linear pharmacokinetics for the extravascular doses investigated. The oral bioavailability ( approximately 25%) was approximately half of the intra-peritoneal one ( approximately 47%). The 60 mg/kg oral dose showed an unusual profile with two peaks (1 and 6h). A two-compartment model better described all plasma profiles. The Vd (0.8+/-0.4l/kg) and the t(1/2) (1.2+/-0.4h) were smaller for i.v. than for the other routes. The CL(tot) was statistically similar for all three administration routes investigated (0.6+/-0.2l/(hkg)) (alpha=0.05). The compound distribution into different organs, evaluated in tissue homogenates after i.v. administration, showed a higher penetration in lungs (51.0%), followed by the brain (39.2%), where the half-life was three times bigger than in the other tissues (1.9h). The compound brain profile agreed with the central nervous system activity determined.


Molecular approach to the identification of fish in the South China Sea.
DNA barcoding is one means of establishing a rapid, accurate, and cost-effective system for the identification of species. It involves the use of short, standard gene targets to create sequence profiles of known species against sequences of unknowns that can be matched and subsequently identified. The Fish Barcode of Life (FISH-BOL) campaign has the primary goal of gathering DNA barcode records for all the world's fish species. As a contribution to FISH-BOL, we examined the degree to which DNA barcoding can discriminate marine fishes from the South China Sea. DNA barcodes of cytochrome oxidase subunit I (COI) were characterized using 1336 specimens that belong to 242 species fishes from the South China Sea. All specimen provenance data (including digital specimen images and geospatial coordinates of collection localities) and collateral sequence information were assembled using Barcode of Life Data System (BOLD; www.barcodinglife.org). Small intraspecific and large interspecific differences create distinct genetic boundaries among most species. In addition, the efficiency of two mitochondrial genes, 16S rRNA (16S) and cytochrome b (cytb), and one nuclear ribosomal gene, 18S rRNA (18S), was also evaluated for a few select groups of species. The present study provides evidence for the effectiveness of DNA barcoding as a tool for monitoring marine biodiversity. Open access data of fishes from the South China Sea can benefit relative applications in ecology and taxonomy.


Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.
Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.


Epidermoid carcinoma of the anal canal. A series of 276 cases.
During the past ten years, substantial progress has been made in the knowledge of the natural history of epidermoid carcinoma of the anal canal and of the response of the disease to radiotherapy alone or combined with chemotherapy. At the present time, the main problem in the management of this tumor concerns identification of the best modalities to achieve local control and preservation of anal function. From a series of 276 cases, followed for more than three years, the necessity for a careful pretreatment evaluation was stressed. This included a systematic search for pelvic metastatic lymph nodes by palpation and CT scan. All patients were treated initially by irradiation except those who underwent groin dissection for inguinal node metastasis or colostomy for complete anal obstruction. Three groups of patients have been identified: unresectable or disseminated tumors (33 cases), resectable tumors but not suitable for sphincter conservation (21 cases) treated by radiochemotherapy and delayed surgery, and resectable tumors suitable for sphincter conservation (222 cases) which were treated by a split-course regimen combining a short course of carefully planned external beam irradiation (19 days) followed by an iridium 192 implant after a two-month rest. In this group, which represents 80 percent of the whole series, 80 percent of patients have had their cancer controlled and 90 percent of controlled patients have retained normal anal function. The use of chemotherapy during the first days of irradiation is advisable in all cases to reinforce the efficacy of treatment and increase the chance of anal preservation. Results of the split-course regimen, combining external beam and interstitial irradiation, demonstrate a clear superiority over external beam irradiation alone, especially for large infiltrating tumors, which represent the majority of cases.


Purification and spectroscopic properties of 124-kDa oat phytochrome.
A simplified procedure for the isolation and purification of 124-kDa phytochrome from etiolated Avena seedlings has been developed using the method of ammonium sulfate back-extraction. After hydroxyapatite chromatography of seedling tissue extracts, the pooled phytochrome was subjected to ammonium sulfate back-extraction instead of the usual application to an Affi-Gel Blue column. The resulting phytochrome had specific absorbance ratios (SAR = A666/A280) ranging from 0.85 to 0.95. Subsequent Bio-Gel filtration chromatography yielded highly pure 124-kDa phytochrome with SAR values ranging from 0.99 to 1.13. The absorption maxima of 124-kDa phytochrome were at 280, 379, and 666 nm for the red absorbing form of phytochrome (Pr) and at 280, 400 and 730 nm for the far-red absorbing form (Pfr). The A730/A673 ratio in Pfr was found to be 1.5 to 1.6. The mole fraction of Pfr under red light photoequilibrium was 0.88. No dark reversion was detected within 5 h at 3 degrees C. A photoreversible far-uv-circular dichroism was observable with all phytochrome preparations examined. Fluorescence and phosphorescence lifetimes were measured to further characterize the differences between the phytochromes prepared under different conditions. The Trp fluorescence and phosphorescence lifetimes of Pr and Pfr with the chromophore "X", probably polyphenolic in nature, were significantly shorter than those of phytochrome without the contaminant X. The short lifetime of the fluorescence of the Pr chromophore is attributable to X in the former.


Regional differences in the lipolytic response of the subcutaneous fat depots to prolonged exercise and severe energy deficiency.
After five days of almost continuous strenuous combat exercise and energy deficiency, 12 well-trained young men had a mean body fat loss of 2.7 kg and the average fat cell size was reduced from 0.34 microgram to 0.24 microgram. No significant changes were found in the total number of fat cells. For the group as a whole, the decrease in fat cell size was most pronounced in the gluteal subcutaneous region, followed by the abdominal region. No significant decrease in fat cell size was encountered in tissue samples from the femoral site. Before the course, and on the last day, the subjects accomplished a short-term bicycle exercise at 50% of the individual's VO2. On day 5, positive correlations were found between the fat cell weights estimated in the gluteal tissue samples and the pre-exercise free fatty acid (FFA) levels (r = 0.87, p less than 0.01), and also with the plasma free glycerol obtained five minutes after the bicycle exercise (r = 0.93, p less than 0.001). These correlations were not apparent in the control experiment performed before the course. Further, no such relationship was found between the plasma metabolites and the fat cell size of the other body sites investigated. This finding may indicate that gluteal fat deposits are more important for energy provision than abdominal and, especially, femoral deposits.


Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation.
Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation.


MRI in intracranial tuberculosis: Have we seen it all?
Tuberculosis is emerging worldwide across diverse populations and geographies; unrestricted by the social divide and the geographical barriers in today's interconnected world. This rise in its prevalence can be linked to multiple factors including urbanisation, spurt in global travel, population explosion, migration and HIV infection. The varied and complex clinical presentation of intracranial tuberculosis tricks even the best of the clinicians. This along with the other facets associated with its management including drug resistance, paradoxical reaction, underlying HIV infection can make it particularly challenging. Imaging has a definitive role in the evaluation and follow-up of intracranial tuberculosis and MRI is the cornerstone in this regard. Typical features of intracranial tuberculosis are well-described. However, it is not infrequent to encounter atypical and bizarre presentations, both clinically and on imaging. A holistic clinical and imaging review of difficult cases, including newer MRI techniques, is necessary for the neuroradiologist, neurologist and the neurosurgeon to arrive at the right diagnosis in a timely fashion.


Replication properties and immunomodulatory effects of human cytomegalovirus infection impact the clinical presentation in congenital patients: A case series.
Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among newborns worldwide. Although both the host's and the virus' genetic backgrounds contribute to the outcome of infections, significant gaps remain in our understanding of the exact mechanisms that determine disease severity. In this study, we sought to identify a correlation between the virological features of different HCMV strains with the clinical and pathological features of congenitally infected newborns, therefore proposing new possible prognostic factors. This short communication presents five newborns with congenital cytomegalovirus infection, whose clinical phenotype during fetal, neonatal, and follow-up periods is correlated with in-vitro growth properties, immunomodulatory abilities and genome variability of HCMV strains isolated from organic samples (urine) of the patients. The five patients described in this short communication displayed a heterogeneous clinical phenotype and different virus replication properties, immunomodulatory abilities, and genetic polymorphisms. Interestingly, we observed that an attenuate viral replication in-vitro influences the immunomodulatory abilities of HCMV, leading to more severe congenital infections and long-term sequelae. Conversely, infection with viruses characterized by aggressive replicative behavior in-vitro resulted in asymptomatic patients' phenotypes. Overall, this case series suggests the hypothesis that genetic variability and differences in the replicative behavior of HCMV strains result in clinical phenotypes of different severity, most likely due to different immunomodulatory properties of the virus.


Widespread changes in the translation and adenylation of maternal messenger RNAs following fertilization of Spisula oocytes.
We have reported previously that sequence-specific adenylations and deadenylations accompany changes in the translation of maternal mRNA following fertilization of Spisula oocytes (E.T. Rosenthal, T.R. Tansey, and J.V. Ruderman, 1983, J. Mol. Biol. 166, 309-327). The data presented here confirm and extend those observations. We have identified four classes of maternal mRNA with respect to translation: Class 1-not translated in oocytes and translated at very high efficiency immediately after fertilization, Class 2-not translated in oocytes and partially utilized for translation following fertilization, Class 3-translated in oocytes and not translated in embryos, and Class 4-not translated either before or after fertilization. There is an excellent, although not perfect, correlation between the translation of an mRNA and its polyadenylation status. The poly(A) tails of all the mRNAs which are translated in oocytes and untranslated in embryos are shortened at fertilization, and the poly(A) tails of those mRNAs which are untranslated in oocytes and translated in embryos are lengthened at fertilization. These adenylations and deadenylations occur simultaneously during the first 20 min following fertilization.


Transcriptome analysis of the immunomodulatory effects of Salvia miltiorrhiza polysaccharide on hemocyte immune response in Procambarus clarkii.
Natural plant polysaccharide as immune modulator is considered an effective strategy for healthy aquaculture to reduce medicine treatment. Salvia miltiorrhiza polysaccharides (SMP) had applications to regulate immune activity and enhance antioxidant in vertebrates, but the potential function has been rarely reported in crustaceans. In this study, the immunological effects of SMP on hemocytes of Procambarus clarkii were analyzed. Results showed that total superoxide dismutase (T-SOD), phenoloxidase (PO) activity and respiratory burst were up-regulated after SMP treatment. After high-throughput sequencing, 2170 differentially expressed genes (DEGs) including 1294 up-regulated and 876 down-regulated genes were identified. KEGG function enrichment analysis indicated that DEGs are involved in crustaceans cellular immune-related signaling pathways, including lysosome, phagosome and endocytosis. Transcriptome mining and qRT-PCR showed that SMP up-regulated humoral immunity factors gene expression. Diets supplemented with 0.8% SMP significantly up-regulated the total number of hemocytes (THC), T-SOD and PO activity, improved the survival of crayfish after Citrobacter freundii infection. This study suggested that SMP could improve the cellular and humoral immunity of P. clarkii. Furthermore, this finding supplied a molecular foundation for further comprehending the immunopotentiator effects of plant polysaccharides in crustaceans.


Protective effect of P. fraternus against ethanol-induced mitochondrial dysfunction.
Chronic ethanol consumption (10 g per kg body weight) significantly decreased the rate of respiration, P/O ratio, and respiratory control ratio (RCR). The activities of NADH dehydrogenase and cytochrome oxidase were significantly decreased in submitochondrial particles by ethanol administration compared to control. No significant difference was observed in membrane potential of submitochondrial particles. Cytochrome b, c and aa3 content of mitochondria were significantly decreased by ethanol feeding. Ethanol-induced inhibition on rate of respiration, P/O ratio, and RCR was relieved to a great extent by the administration of the aqueous extract of Phyllanthus fraternus (100 mg dry powder of the plant per kg body weight) along with ethanol. The decrease in the content of cytochromes due to ethanol administration was revived partially by aqueous extract of P. fraternus.


[Construction of a lentiviral RNA interference system targeting heparanase based on miR30 and its silencing effect].
To construct a lentiviral RNA interference system targeting heparanase (HPSE) based on miR30 and to test its silencing effect. Three heparanase-shRNA structures were designed based miR30. The targeting fragments were obtained by PCR, then inserted into the vector LV PP-GFP to construct the recombinant lentiviral vector LV PP-GFP/miR-HPSE-shRNA, which was identified by PCR and sequencing. The 293T cells were co-transfect with LV PP-GFP/miR-HPSE-shRNA, pHelper 1.0 vector and pHelper 2.0 vector to produce lentiviruses, with which A375 cells were infected. Real-time fluorescence quantitative PCR and Western blot were performed to evaluate the expression of heparanase RNA and protein. The lentiviral miR30-based RNAi vector targeting heparanase was constructed and confirmed by PCR and sequencing. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression levels of both heparanase mRNA and protein in infected A375 cells were decreased significantly than those in control group. The lentiviral miR30-based RNAi vector targeting heparanase was been constructed successfully, which can be used for further study on RNAi-mediated oncolytic viruses.


[Short stature due to intrauterine growth retardation. Clinical and hormonal-metabolic features, possibilities of growth-stimulating therapy].
The article presents data about short stature due to intrauterine development delay. This type of short stature - separate nosology, unites children born small for gestation age. The majority of them in the first years of life have accelerated growth rates, allowing the child to normalize their weight-growth indicators and catch up in the development of peers. In the absence of an accelerated growth rates, children have a high risk of lagging behind in physical development throughout childhood, achieving low final growth and becoming short adults. In addition, the fact of birth with small body sizes is associated with a number of hormonal and metabolic features, a risk of metabolic syndrome in adult years.It is assumed that the absence of postnatal growth acceleration is due to various damages to the GH-IGF1 axis (partial GH deficiency, partial resistance to GH, partial resistance to IGF1). Growth hormone therapy, initiated early in life, is able to normalize growth rates in childhood and ultimately significantly improve or normalize the final growth of short stature children born small for gestational age.


Ethanol does not alter the pharmacokinetic profile of the controlled-release formulation of carvedilol.
The concomitant ingestion of alcohol may alter the release of a drug from a modified-release dosage form, posing a potential risk to patients. In a randomized, open-label, 4-period cross-over study, the pharmacokinetic profiles of R(+) and S(-) carvedilol were compared after a single oral dose of carvedilol controlled-release formulation (administered following a standard meal) was given alone or concomitantly with ethanol. Thirty-nine healthy subjects participated in this study. Following coadministration of carvedilol controlled-release 40 mg with ethanol (approximately 38 g), ethanol ingestion 2 hours before or 2 hours after carvedilol controlled-release administration, area under the curve for the R(+) and S(-) carvedilol enantiomers was similar compared with carvedilol controlled-release given alone. Carvedilol exposure was not affected by the concomitant administration of ethanol and carvedilol controlled-release. Maximum plasma concentrations for the R(+) and S(-) carvedilol enantiomers were similar except when ethanol was ingested 2 hours after carvedilol controlled-release administration, where there was a modest decrease in maximum plasma concentration for R(+) and S(-) carvedilol (16% and 17%, respectively). Carvedilol controlled-release given alone or concomitantly with ethanol ingestion was generally well tolerated, and no serious or severe adverse events were reported. Ethanol did not alter the pharmacokinetic profile of carvedilol controlled-release.


A review of the diagnosis and treatment of Ochratoxin A inhalational exposure associated with human illness and kidney disease including focal segmental glomerulosclerosis.
Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. This paper reviews Ochratoxin A and its relationship to human health and kidney disease with a focus on a possible association with focal segmental glomerulosclerosis (FSGS) in humans. Prevention and treatment strategies for OTA-induced illness are also discussed, including cholestyramine, a bile-acid-binding resin used as a sequestrant to reduce the enterohepatic recirculation of OTA.


Diagnosis of ganglion in Guyon's canal by magnetic resonance imaging.
Compression of the ulnar nerve at the wrist can be caused by a multitude of intrinsic and extrinsic factors. The exact diagnosis and location of compression can frequently be difficult to determine. Magnetic resonance imaging can be a useful method in diagnosing the cause and location of ulnar nerve compression. A case is presented of ulnar nerve compression caused by a ganglion in Guyon's and diagnosed preoperatively by magnetic resonance imaging.


Shorter EGFR Dinucleotide Repeat Length Predicts Better Response of Patients with Advanced Non-small Cell Lung Cancer to EGFR Tyrosine Kinase Inhibitor.
The purpose of this study is to evaluate the association between intron 1 CA-repeat polymorphisms of the epidermal growth factor receptor gene (EGFR) and the clinical outcome of Chinese patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We genotyped the intron 1 CA-repeat genetic polymorphisms of EGFR in 84 Chinese patients with NSCLC. The relationship between the length of the CA repeats and EGFR mutations in exons 18-21 in the 84 patients was elucidated. We then analyzed the association between the length of the CA repeats and the clinical outcome of EGFR-TKI-treated patients with NSCLC. EGFR mutations in exon 19 were significantly associated with shorter CA repeats. Patients with shorter CA repeats had a significantly longer progression-free survival with EGFR-TKI treatment than those with longer CA repeats. Our results suggest that shorter CA repeats in intron 1 of EGFR are associated with EGFR mutations and the clinical outcomes of TKI-treated patients with NSCLC.


The morphological characteristics of paraspinal muscles in young patients with unilateral neurological symptoms of lumbar disc herniation.
The objective of this study was to explore the morphological characteristics of paraspinal muscles in young patients with unilateral neurological symptoms of lumbar disc herniation. This study retrospectively analyzed young patients aged 18-40 years who were hospitalized for lumbar disc herniation in our hospital from June 2017 to June 2020. Data on sex, age, body mass index (BMI), subcutaneous fat tissue thickness (SFTT) at the L1-L2 level, duration of symptoms, degree of lumbar disc herniation, visual analog scale (VAS) for the lower back, Mo-fi-disc score, relative cross-sectional area (RCAS) of the paravertebral muscles (psoas major [PM], multifidus [MF], and erector spinae [ES]), and degree of fat infiltration (DFF) of the paravertebral muscles were collected. The VAS was used to evaluate the intensity of low back pain. Patients with VAS-back >4 points were defined as the low back pain group, and patients with ≤4 points were defined as the control group. The demographic characteristics, as well as the bilateral and ipsilateral paravertebral muscles, of the two groups were compared and analyzed. A total of 129 patients were included in this study (52 patients in the LBP group and 77 patients in the control group). There were no significant differences in sex, BMI, or Pfirrmann grade of lumbar disc herniation between the two groups (P > 0.05). The age of the LBP group (33.58 ± 2.98 years) was greater than that of the control group (24.13 ± 2.15 years) (P = 0.002), and the SFTT at the L1-L2 level (13.5 ± 7.14 mm) was higher than that of the control group (7.75 ± 6.31 mm) (P < 0.05). Moreover, the duration of symptoms (9.15 ± 0.31 months) was longer than that of the control group (3.72 ± 0.48 months) (P < 0.05), and the Mo-fi-disc score (8.41 ± 3.16) was higher than that of the control group (5.53 ± 2.85) (P < 0.05). At L3/4 and L5/S1, there was no significant difference in the RCSA and DFF of the bilateral and ipsilateral paraspinal muscles between the LBP group and the control group. At L4/5, there was no significant difference in the RCSA and DFF of the paraspinal muscles on either side in the LBP group (P > 0.05). In the control group, the RCSA of the MF muscle on the diseased side was smaller than that on the normal side (P < 0.05), and the DFF of the MF muscle on the diseased side was larger than that on the normal side (P < 0.05). In addition, there was no significant difference in the ES and PM muscles on both sides (P > 0.05). At L4/5, the RCSA of the MF muscle on the normal side was significantly smaller in the LBP group than in the control group (P < 0.05), and the DFF of the MF muscle on the normal side was significantly larger in the LBP group than in the control group (P < 0.05). There was no significant difference in the ES and PM muscles on the same side between the two groups (P > 0.05). In young patients with unilateral neurological symptoms of lumbar disc herniation, symmetrical atrophy of the bilateral MF muscle is more prone to causing low back pain. Older age, higher SFTT at the L1-L2 levels, longer symptom duration, higher Mo-fi-di score, and greater muscle atrophy on the normal side of the MF increased the incidence of low back pain in young patients with unilateral lumbar disc herniation.


Efficacy and motor complications of original and generic levodopa in Parkinson's disease treatment.
In general, a generic drug is considered interchangeable with the original formulated drug. In Parkinson's disease (PD), generic drug use remains debated. This study was aimed to investigate whether the generic drug was as effective as the original in improving the symptoms of PD and the prevalence of motor complications. This study was a multicenter cohort study of patients with PD enrolled from three northeast hospitals in Thailand between February 2013 and February 2014. The patients were categorized into original and generic levodopa groups. The clinical characteristics, efficacy, and motor complications were compared between the groups. There were 400 eligible patients. Of these, 327 patients (81.75%) met the study criteria and were classified as the original levodopa group (200 patients, 61.16%) and the generic levodopa group (127 patients, 38.84%). The average age of all patients with PD was 65 years. The duration of PD and the modified Hoehn-Yahr stages were not different between the groups. The total doses of original and generic levodopa-equivalent doses were significantly different (199.97±127.08 versus 305.58±138.27 mg; P-value <0.001) and the actual doses were 198.10±117.92 versus 308.85±139.40 mg (P-value <0.001). Approximately 80% of patients with PD in both groups had good responses (P-value >0.999), but the development of motor complications was significantly greater in the original than in the generic group. Generic levodopa was effective in improving the symptoms of PD. The prevalence of motor complications in the original compound group, at a lower dose of levodopa equivalent, was higher than in the generic group.


Contributing factors to heterogeneity in the timing of the onset of major depressive episode: Results from a national study.
It remains unclear whether specific clinical factors contribute to heterogeneity in the timing of the onset of major depression. Using a nationally representative US adult sample, the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions, we compared the characteristics of 5 different groups of patients defined by their age at onset: (i) before 18 years, (ii) between 18 and 34 years, (iii) between 35 and 44 years, (iv) between 45 and 59 years, and (v) 60 years or older. Specifically, we examined parental history of psychiatric disorders, history of childhood maltreatment experiences, sociodemographic characteristics, lifetime psychiatric disorders, and psychiatric disorders that occurred before the first major depressive episode (MDE). Compared with first MDE occurring between 18 and 34 years, first MDE before 18 years was more strongly associated with childhood maltreatment and family history of psychiatric disorders, and less strongly linked to prior lifetime psychiatric disorders, whereas first MDE occurring at 60 years and older was more strongly associated with widowhood and a prior lifetime history of generalized anxiety disorder. Associations found cannot be interpzreted as causal relationships due to study design and the risk of recall bias. Our results suggest substantial age differences in risk factors for first MDE. Improving early detection and treatment of major depression and other psychiatric disorders, and preventing childhood maltreatment may have broad benefits to reduce the burden of MDE at all ages.


Age affects the latency of the erector spinae response to sudden loading.
Aging and a past history of low back pain are risk factors for a future low back pain. Recent findings have demonstrated an impaired feed-forward control of paraspinal muscles during upper limb loading in low back pain patients as well as decreased feed-forward mechanism in elderly. The aims of the current study were to assess the age-related changes in paraspinal reflex latencies, flexion movement as well as flexion moment of the lumbar spine during sudden upper limb loading and the expectation effects via feed-forward mechanism on these postural responses. The paraspinal reflex latencies for upper limb loading during unexpected and expected conditions were measured in erector spinae and multifidus muscles by surface electromyography from 23 young healthy subjects (aged 30 or younger) and 15 healthy elderly subjects (aged 60 or older). The kinematic and kinetic data were obtained simultaneously from a magnetic motion measurement system and a force plate, which were used to calculate flexion moments. The age was found to have a significant effect for delaying the paraspinal reflex latencies. Expectation shortened the reflex latencies, as well as decreasing the flexion movement and the flexion moment of the lumbar spine. The expectation effects on theses postural responses were reduced by subject's age. These findings suggest that aging process is associated with a decreased motor control of the spine, particularly via reduced feed-forward control of paraspinal muscles. These findings may contribute to decreased ability to stabilize the spine and development of low back injury in elderly.


Technoeconomic evaluation of urban plant factories: The case of basil (Ocimum basilicum).
Greece is currently in a turmoil, experiencing the effects of more than half a decade of economic crisis. Public health and welfare, jobs and wages, labor market concerning employment as long as employability of the work force, inequality, life satisfaction and housing, tourism and environment, economic and energy poverty are heavily impacted by Greece's disadvantageous economic situation. Real estate market could not have gotten away from the financial commotion, being currently in a halt after years of rapid decline. Fired from the present situation of Greece's real estate market, the present study is concerned with the investigation of alternative ways to support the local real estate market. With respect to sustainable development's ethics, the development, implementation, installation and operation of small, inexpensive plant factories within the urban environment is evaluated. Installations such are those, will encourage the penetration of a new market for the untapped buildings' resource, advancing new investing opportunities, promoting economic growth and productivity while creating a new labor market. The study will rely on the basic principles of Life Cycle Costing Assessment and develop a methodology upon which different scenarios will be evaluated against the "Do Nothing" scenario.


The delusion of inanimate doubles. Implications for understanding the Capgras phenomenon.
The Capgras delusion has long been held to be specific for close personal relationships. This paper presents evidence that this is not the case and the implications of this for accepting psychodynamic explanations of the phenomenon are discussed. Parallels are drawn with the condition prosopagnosia and a hypothesis presented that any specificity is apparent rather than real. It is proposed that both prosopagnosia and the Capgras symptom represent abnormalities of visual perception occurring at different stages of this neurophysiological process.


Effect and attributable burden of hot extremes on bacillary dysentery in 31 Chinese provincial capital cities.
High atmospheric temperature has been associated with the occurrence of bacillary dysentery (BD). Recent studies have suggested that hot extremes may influence health outcomes, however, none have examined the association between hot extremes and BD risk, especially at the national level. To assess the effect and attributable burden of hot extremes on BD cases and to identify populations at high risk of BD. Daily incident BD data of 31 provincial capital cities from 2010 to 2018 were collected from the Chinese Center for Disease Control and Prevention, weather data was obtained from the fifth generation of the European Re-Analysis Dataset. Three types of hot extremes, including hot day, hot night, and hot day and night, were defined according to single or sequential occurrence of daytime hot and nighttime hot within 24 h. A two-stage analytical strategy combined with distributed lag non-linear models (DLNM) was used to evaluate city-specific associations and national pooled estimates. Hot extremes were significantly associated with the risk of BD on lagged 1-6 days. The overall cumulative relative risk (RR) was 1.136 [95% confidence interval (CI): 1.022, 1.263] for hot day, 1.181 (95% CI: 1.019, 1.369) for hot night, and 1.154 (95% CI: 1.038, 1.283) for hot day and night. Northern residents, females, and children younger than or equal to 14 years old were vulnerable under hot night, southern residents were vulnerable under hot day, and males were vulnerable under hot day and night. 1.854% (95% CI: 1.294%, 2.205%) of BD cases can be attributable to hot extremes, among which, hot night accounted for a large proportion. Hot extremes may significantly increase the incidence risk and disease burden of BD. Type-specific protective measures should be taken to reduce the risk of BD, especially in those we found to be particularly vulnerable.


Diesel and kerosene degradation by Pseudomonas desmolyticum NCIM 2112 and Nocardia hydrocarbonoxydans NCIM 2386.
Pseudomonas desmolyticum NCIM 2112 (Pd 2112) and Nocardia hydrocarbonoxydans NCIM 2386 (Nh 2386) demonstrated an ability to degrade diesel and kerosene. Triton X-100 had enhanced the diesel degradation process by reducing the time required for the maximum utilization of total petroleum hydrocarbon. Fourier transform infrared spectroscopy spectrum of degraded diesel indicates the presence of aliphatic and aromatic aldehydes, C=C aromatic nuclei, and substituted benzenes. Surface tension reduction and stable emulsification was increased using consortium when compared to individual strains. Triton X-100 showed increase in microbial attachment to hydrocarbon among the various chemical surfactants tested. For generating a rapid assay to screen microorganisms capable of degrading kerosene, the acetaldehyde produced in the degradation process could be used as an indicator of degradation. These results indicate diesel and kerosene degradation ability of both of the strains.


Brunnian adenoma (inverted papilloma) of the urinary bladder: report of a case.
An additional case of a benign polypoid tumor of the urinary bladder is reported, the first one observed at autopsy and the first in which photographic documentation of the gross appearance is presented. The lesion was first described as an adenomatoid polyp in 1927. We consider the subsequent (1963) designation of inverted papilloma misleading. Because its histologic morphology bears a striking resemblance to Brunn's nests and because the term papilloma of the urinary bladder connotes potential malignant change, we propose the designation brunnian adenoma. All cases previously reported have been benign.


Variation in dissolution behavior among different nanoforms and its implication for grouping approaches in inhalation toxicity.
Different nanoforms (NF) of the same substance each need to be registered under REACH, but similarities in physiological interaction -among them biodissolution- can justify read-across within a group of NFs, thereby reducing the need to perform animal studies. Here we focused on the endpoint of inhalation toxicity and explored how differences in physical parameters of 17 NFs of silica, and organic and inorganic pigments impact dissolution rates, half-times, and transformation under both pH 7.4 lung lining conditions and pH 4.5 lysosomal conditions. We benchmarked our observations against well-known TiO2, BaSO4 and ZnO nanomaterials, representing very slow, partial and quick dissolution respectively. By automated image evaluation, structural transformations were observed for dissolution rates in the order of 0.1 to 10 ng/cm2/h, but did not provide additional decision criteria on the similarity of NFs. Dissolution half-times spanned nearly five orders of magnitude, mostly dictated by the substance and simulant fluid, but modulated up to ten-fold by the subtle differences between NFs. Physiological time scales and benchmark materials help to frame the biologically relevant range, proposed as 1 h to 1 y. NFs of ZnO, Ag, SiO2, BaSO4 were in this range. We proposed numerical rules of pairwise similarity within a group, of which the worst case NF would be further assessed by in vivo inhalation studies. These rules divided the colloidal silica NFs into two separate candidate groups, one with Al-doping, one without. Shape or silane surface treatment were less important. The dissolution halftimes of many organic and inorganic pigment NFs were longer than the biologically relevant range, such that dissolution behavior is not an obstacle for their groupings.


Excretion of F2-isoprostanes in bile: a novel index of hepatic lipid peroxidation.
Lipid peroxidation is believed to be an important mechanism of liver injury caused by some xenobiotics. However, it has been difficult to demonstrate and quantify this process in vivo. Moreover, little is known about the disposition of lipids oxidized in the liver. F2-isoprostanes are prostanoids produced by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid esterified to phospholipids. Hydrolysis of F2-isoprostanes from phospholipids by phospholipases yields free F2-isoprostanes. Excretion of F2-isoprostanes, both free and esterified to phospholipids, was measured in bile after administration of CCl4. The concentration of lipid-esterified F2-isoprostanes in bile exceeded that of free F2-isoprostanes. CCl4 caused a dose-dependent increase in biliary F2-isoprostane excretion that correlated better with the increase in liver F2-isoprostanes than it did with the increase in plasma F2-isoprostanes. Pretreatment with colchicine ameliorated CCl4-liver injury but did not affect baseline or CCl4-induced biliary F2-isoprostane excretion. Administration of diquat to selenium-deficient rats, which causes hepatic and renal necrosis, was associated with a 13-fold elevation of plasma F2-isoprostanes. However, both hepatic F2-isoprostane concentrations and biliary F2-isoprostane excretion were increased only threefold. These data suggest that quantification of F2-isoprostane excretion in bile may provide a sensitive and quantitative index of hepatic lipid peroxidation.


A Fe3N/carbon composite electrocatalyst for effective polysulfides regulation in room-temperature Na-S batteries.
The practical application of room-temperature Na-S batteries is hindered by the low sulfur utilization, inadequate rate capability and poor cycling performance. To circumvent these issues, here, we propose an electrocatalyst composite material comprising of N-doped nanocarbon and Fe3N. The multilayered porous network of the carbon accommodates large amounts of sulfur, decreases the detrimental effect of volume expansion, and stabilizes the electrodes structure during cycling. Experimental and theoretical results testify the Fe3N affinity to sodium polysulfides via Na-N and Fe-S bonds, leading to strong adsorption and fast dissociation of sodium polysulfides. With a sulfur content of 85 wt.%, the positive electrode tested at room-temperature in non-aqueous Na metal coin cell configuration delivers a reversible capacity of about 1165 mA h g-1 at 167.5 mA g-1, satisfactory rate capability and stable capacity of about 696 mA h g-1 for 2800 cycles at 8375 mA g-1.


Safety and feasibility of dobutamine stress echocardiography in patients with implantable cardioverter defibrillators.
Coronary artery disease is the underlying etiology of left ventricular dysfunction and arrhythmias in most patients who receive implantable cardioverter defibrillators (ICDs). The aim of this study was to assess the safety and feasibility of dobutamine stress echocardiography (DSE) in patients with an ICD. DSE (dobutamine up to 50 microg/kg/min, atropine up to 2 mg) was performed in 87 patients with an ICD and known or suspected coronary artery disease. The ICD was inactivated before the stress test and reactivated after the study; no serious complications occurred. DSE is a safe and feasible method for evaluating myocardial ischemia in patients with an ICD.


Long-term loss of paired pulse inhibition in the kainic acid-lesioned hippocampus of the rat.
A paired pulse stimulation protocol was employed to examine the loss of inhibition in the hippocampus of the kainic acid-treated rat in vivo. Extracellular recordings were obtained from the CA1 pyramidal cell layer 1, 4, 8 and 16 weeks after a unilateral intracerebroventricular injection of kainic acid. Recordings were made both ipsilateral and contralateral to the site of kainic acid injection. The results demonstrated a loss of paired pulse inhibition in hippocampal CA1 area ipsilateral to the site of kainic acid injection which did not alter over 16 weeks. While the contralateral hippocampus showed no change 1 week after kainic acid injection, a reduction of paired pulse inhibition was seen after 4, 8 and 16 weeks. It is therefore apparent that the effects of kainic acid on the state of inhibition of the hippocampus are long-lasting and, furthermore, that the response to an injection of kainic acid is widespread, affecting the inhibitory control of the contralateral hippocampus.


Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARS-CoV-2 viral proteins in metabolic dysregulation in COVID-19 patients.
Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.


Factors affecting oral and dental services` utilization among Elderly: a scoping review.
Regular use of oral and dental services by the elderly is one of the important factors in reducing oral and dental diseases. This study aimed to identify the factors affecting oral and dental services` utilization among elderly. The published articles on the factors affecting oral and dental services` utilization among elderly were found through a scoping search and using related keywords in PubMed, Scopus, Embase, and Web of Science databases within January 2000 - December 2022 according to the PRISMA guidelines. The data were analyzed using the thematic analysis method. Among the 2381 articles retrieved from the databases, forty-two were extracted. The factors affecting oral and dental services` utilization among elderly were classified into five main components as follows: access, demographic factors, social factors, health level, and mental factors. The results showed that income, education level, living area, number of teeth, and importance of care were the most frequent in the main components of access, demographic factors, social factors, health level, and mental factors, respectively. Equitable utilization of oral and dental services is the right of all members of the society, especially the elderly. Therefore, it is necessary to provide the elderly with suitable conditions to utilize such services, which are mostly luxury items. Furthermore, increasing the elderly's awareness and encouraging them to use oral and dental services regularly can help reduce the burden of oral and dental diseases.


A new method giving a two criteria diagnosis of venous occlusion using isotope imaging of 99mTc-labelled fibrinogen.
A new method for the diagnosis of venous occlusion involves three stages: first, injection of 99mTc-labelled fibrinogen into a distal vein in the suspected limb with a dynamic gamma scan of venous flow; second, a static pool scan of both limbs to show the anatomy of the veins seen in the dynamic scan and third, a later static scan showing 99mTc-fibrinogen associated with thrombus. In occlusion, absence of flow in the dynamic scan corresponds to the presence of isotope in thrombus in the second static scan. The test uses a low-volume, low-radioactivity injection and may be repeated many times.


Phototherapeutic keratectomy with amniotic membrane for severe subepithelial fibrosis following excimer laser refractive surgery.
We report 2 patients who developed subepithelial opacities and myopic regression after photorefractive keratectomy (PRK) and laser-assisted subepithelial keratectomy. Both cases were treated successfully with manual debridement of the epithelium, phototherapeutic keratectomy, and PRK with amniotic membrane application.


Muscle MRI findings in patients with an apparently exclusive cardiac phenotype due to a novel LMNA gene mutation.
The case of a family in which several members displayed conduction defects inherited as a dominant trait is reported. The proband was a young woman with a 1st degree atrio-ventricular block and high serum creatine kinase. Several members of the family featured cardiologic symptoms. All adult family members were clinically evaluated and blood tests including serum creatine-kinase levels, standard and Holter ECG, echocardiogram and muscle MRI were performed. LMNA gene analysis was carried out and a novel missense mutation consisting in substitution of exon 4 c.799 T/C, p.Tyr267His was revealed. The mutation was present in seven family members, five of whom displayed cardiac defects alone with no involvement of the skeletal muscle. In all mutated individuals muscle MRI featured a pattern of skeletal muscle involvement similar to that observed in autosomal dominant Emery Dreifuss muscular dystrophy, suggesting that even patients bearing a LMNA gene mutation associated to an apparently selective cardiac phenotype may present subclinical skeletal muscle involvement.


Focused electric field across the voltage sensor of potassium channels.
Voltage-gated ion channels respond to changes in membrane potential by movement of their voltage sensors across the electric field between cytoplasmic and extracellular solutions. The principal voltage sensors in these proteins are positively charged S4 segments. The absolute magnitude of S4 movement discriminates two competing classes of gating models. In one class, the movement is <10 Angstrom due to the fact that the electric field is focused by aqueous crevices in the channel protein. In an alternative model, based in part on the crystal structure of a potassium channel, the side chains of S4 arginines move their charges across the bilayer's electric field, a distance of >25 Angstrom. Here, using tethered charges attached to an S4 segment, we provide evidence that the electric field falls across a distance of <4 Angstrom, supporting a model in which the relative movement between S4 and the electric field is very small.


Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson's disease is related to disability of the patients.
We investigated neuronal number and size in the pars compacta of the pedunculopontine nucleus (PPN) in Parkinson's disease (PD). In PD, the number of Luxol fast blue (LFB) neurons was reduced by 27% from the mean control value (p=0.04) and the cholinergic (choline acetyltransferase, ChAT-positive) neuron number was reduced by 36% (p=0.03). In addition to neuronal loss, the remaining neurons in the PPN in PD were smaller than in controls. The profile area of LFB neurons was reduced by 14% (p=0.009) and that of ChAT-positive neurons by 26% (p=0.001). There was more severe loss of ChAT-positive neurons with a more severe stage of the disease, evaluated by the modified Hoehn and Yahr scale (r=-0.66, p=0.03). The neuron number decreased much more than could be expected on the basis of decrease in cell size alone.


Results of current endovascular treatments for visceral artery aneurysms.
This single-center retrospective cohort study aimed to analyze the early and long-term results of endovascular treatment for true visceral artery aneurysms (VAAs). Moreover, a comparison with the results of our previously published historical series of open surgical procedures was performed. From January 2008 to December 2021, 78 consecutive patients were treated at our institution for true VAAs. All demographic data, procedural details, perioperative outcomes, and follow-up data were collected prospectively from a dedicated database. A retrospective analysis identified 72 patients who underwent endovascular surgery. Early results were analyzed in terms of technical success, conversion to open surgery, mortality, and local and systemic morbidities. Follow-up results were analyzed in terms of survival, need for open or endovascular reintervention, and freedom from complications at the level of the treated visceral artery. These results were then compared with those of our historical open surgical group (1982-2007), which included 54 interventions. In four cases, the planned endovascular procedure could not be completed, and the overall technical success rate was 94.5%. No deaths occurred during the hospital stay or within 30 days after surgery. Overall, the 30-day perioperative complication rate was 5.8%, with an early reintervention rate of 2.9%. The median follow-up time was 29 months (range, 1-132 months). The estimated 7-year survival rate was 88% (standard error [SE]. 0.05). The estimated 7-year aneurysm-related complication-free rate was 85.5% (SE, 0.06), with reintervention-free and aneurysm-related complication-free survival rates of 93.3% (SE, 0.04) and 75.6% (SE, 0.07), respectively. At the 7-year follow-up, the survival rate was similar between the endovascular and open groups. There was a trend toward a higher aneurysm-related complication rate in the endovascular group than in the open group (14.5% vs 6.4%; P = .07). However, no significant differences in reintervention-free and overall estimated aneurysm-related complication-free survival rates were found between the two groups. Endovascular repair is safe and effective in patients with VAAs, with low perioperative complication rates. The long-term outcomes were satisfactory and comparable with those of the historical series of open surgical repairs. Even if there is a trend toward a higher risk of late aneurysm-related complications among endovascular patients, it does not imply an increased need for late reinterventions.