Characterization of the differential interaction of the microheterogeneous forms of the gamma subunit of 7 S nerve growth factor with natural and synthetic ligands.
The effect of the structural heterogeneity of the gamma subunit of 7 S nerve growth factor (NGF) on its interaction with a variety of synthetic substrates and natural ligands was studied. The major gamma species, distinguished on the basis of charge under isoelectric focusing conditions, were examined for possible differences in affinity toward basic pancreatic trypsin inhibitor, beta NGF, and 7 S NGF and differences in activity toward three synthetic arginine substrates, N alpha-benzoyl-DL-arginine-p-nitroanilide, p-tosyl-L-arginine methyl ester, N alpha-benzoyl-L-arginine ethyl ester. The most proteolytically modified form of the gamma subunit, gamma 3, was found to have an affinity for the natural ligands that was consistently an order of magnitude greater than gamma 1, the least modified form, while gamma 2 was intermediate, tending toward gamma 1. These differences were found to hold true for the activities toward the synthetic substrates as determined by the kcat/Km ratios. The nature of the affinity and activity differences among the major gamma species is discussed in light of a model where the presence or absence of certain basic residues, which along with the presence or absence of specific peptide chain cleavages forming the basis of the gamma subunit structural heterogeneity influence the access of ligand to the active site.


Selection of Domestic Cell Lines for the Creation of Diagnostic and Preventive Preparations against Enterovirus 71.
We studied the sensitivity of domestic proprietary human and animal cell lines from the collection of M. P. Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products to infection with different enterovirus 71 strains. A cell system based on domestic proprietary permanent cell line 4647 was for the first time used for reproduction of four enterovirus 71 strains (BrCr, 42266, 42934, and 43374). It was shown that strain 4647 is the optimal cell substrate for enterovirus 71 reproduction. The titers of enterovirus 71 for all four strains considerably (by 2 lgTCID50/ml and more) increased during sequential passages in permanent cell line 4647. The prospects of using permanent cell line 4647 for creation of diagnostic and preventive preparations against 71 was demonstrated.


Jean-Alexandre Barré: Babinski's brilliant student.
Guillain-Barré Syndrome, (GBS), is a popular eponym that comes from a paper written in 1916 by Doctors. Guillain, Barré, and Strohl. Its spectrum has been enlarged considerably since the first description of it. Jean Alexandre Barré was a French neurologist, whose name is still widely associated with that of Georges Guillain, (1876-1961). He is also known for the leg manoeuvre. As Joseph Babinski's brilliant student, (1857-1932), we wanted to briefly retrace his biography in order to highlight some of the salient points within it and subjects that are topical for young neurologists today.


Effectiveness of biochar as an adsorbent for pesticides: Systematic review and meta-analysis.
The use of pesticides is intense in agriculture and has caused contamination in water, air and soil. This fact led to the need to study strategies that can minimize the effects that these pesticides have caused to the environment. In this context, biochar appears, as a type of material that has the ability to remove chemical substances, and because they can be activated with different chemical agents, they are extremely effective in the adsorption of toxic substances. Therefore, the aim of the study was to evaluate the use of biochar as a bioadsorbent for pesticides. This is a systematic review with meta-analysis and meta-regression, as the PRISMA protocol recommendations. Studies from the last 20 years were included, with at least the abstract available and considering preferentially experimental studies. Qualitative studies or studies with high risk of bias, other reviews and duplicates were excluded. The variables analyzed were the presence of factors that prove the effectiveness or not of pesticide adsorption. Studies with a superficial approach or those that do not show positivity or negativity in relation to the outcome were excluded. The search was conducted on the sources: Scopus, Web of Science electronic databases, PubMed (of the US National Library of Medicine, National Institutes of Health) and ScienceDirect (Elsevier). For better investigative determination, the data were searched separately. The descriptors used for the search were the following: Agrochemicals AND Activated Carbon AND Adsorption. Initially, 2431 references were found, from which 14 were selected to compose the meta-analysis review. With the joint analysis of the data, it was possible to verify using the random model (since the studies assess different contexts) that there is a proportion of effectiveness of the intervention of 81% (with a 95% confidence interval), ranging from 75 to 88%, which is represented by the meta-analysis diamond that is the final result of the statistical analysis. Biochar is effective in removing impurities, even including features such as low cost. There is a considerable lack of studies on the topic of pesticide adsorption with the use of biochar. The studies approach a very heterogeneous perspective on the subject, exposing different contexts.


A Systematic Review of Fish-Based Biomaterial on Wound Healing and Anti-Inflammatory Processes.
Objective: To conduct a systematic literature review to study the effects of fish-based biomaterials on wound healing in both in vivo and in vitro animal models. Approach: This review covers the study reported in different articles between 2016 and August 2022 concentrating mainly on the cytotoxicity evaluation of different fish-based biomaterials on inflammation, reepithelialization and wound healing. Significance: This review shows considerable amount of research work carried out with fish-based biomaterials and collagen for treating burn wounds. Surprisingly there are only a few commercial products developed so far in this particular regard for surgical purpose and therefore, there is a way out and need for developing medical support product from fish-based biomaterials to treat and cure wounds. Recent Advances: Three-dimensional skin bioprinting technique is a large-scale solution for severe burn wounds that requires collagen as a raw material for printing, wherein fish collagen can be used in place of bovine and porcine, as it is biocompatible, promotes cell proliferation, adhesion, and migration, and degrades enzymatically. In the recent times, there are a few fish-based surgical products that have been formulated by Kerecis in United States. Critical Issues: The different fish-based biomaterial products are all mere supplements taken in orally as food or supplements till date and there is no proper proven medications that has been formulated so far in the field of wound healing and inflammation based on fish biomaterials except the surgical products that can be finger counted. Future Directions: Fish-based biomaterials are known for the medicinal properties that are used throughout the world and further investigations should be carried out to understand the actual physiochemical properties of its derivatives for the discovery of novel products and drugs.


Cpd-1 null mice display a subtle neurological phenotype.
CPD1 (also known as ANP32-E) belongs to a family of evolutionarily conserved acidic proteins with leucine rich repeats implicated in a variety of cellular processes regulating gene expression, vesicular trafficking, intracellular signaling and apoptosis. Because of its spatiotemporal expression pattern, CPD1 has been proposed to play an important role in brain morphogenesis and synaptic development. We have generated CPD1 knock-out mice that we have subsequently characterized. These mice are viable and fertile. However, they display a subtle neurological clasping phenotype and mild motor deficits. CPD1 is not essential for normal development; however, it appears to play a role in the regulation of fine motor functions. The minimal phenotype suggests compensatory biological mechanisms.


Diverse synthesis of C2-linked functionalized molecules via molecular glue strategy with acetylene.
As the simplest alkyne and an abundant chemical feedstock, acetylene is an ideal two-carbon building block. However, in contrast to substituted alkynes, catalytic methods to incorporate acetylene into fine chemicals are quite limited. Herein, we developed a photoredox-catalyzed synthetic protocol for diverse C2-linked molecules via a molecular glue strategy using gaseous acetylene under mild conditions. Initiated by addition of an acyl radical to acetylene, two cascade transformations follow. One involves a double addition for the formation of 1,4-diketones and the other where the intermediate vinyl ketone is intercepted by a radical formed from a heterocycle. In addition to making two new C-C bonds, two C-H bonds are also created in two mechanistically distinct ways: one via a C-H abstraction and the other via protonation. This system offers a reliable and safe way to incorporate gaseous acetylene into fine chemicals and expands the utility of acetylene in organic synthesis.


The Effects of Patient Characteristics on the Management of Subclinical Hypothyroidism: A Survey of Faculty and Trainees.
There is no universal approach to the management of subclinical hypothyroidism (SCH). This study was designed to determine the impact of patient characteristics on management decisions in SCH amongst physician faculty members and trainees. An online survey was distributed to faculty members and medical trainees (ie, interns, residents, and fellows) at multiple academic medical centers. The survey included 9 clinical scenarios describing women with SCH with 5 management options sequenced from most "conservative" (no further treatment or monitoring) to most "aggressive" (treatment with levothyroxine). Of the 194 survey respondents, 95 (49.0%) were faculty members and 99 (51.0%) were trainees. Faculty members were more likely to report being "confident" or "very confident" in making the diagnosis of SCH compared to trainees (95.8% vs 46.5%, P < .001). Faculty members were also more likely to consider patient preference for treatment (60.0% vs 32.3%, P < .001). Among all respondents, the clinical factors that resulted in the highest predicted probability of treatment were hypothyroid symptoms (predicted probability [PP] 68.8%, 95% CI [65.7%-71.9%]), thyroid stimulating hormone >10 mIU/L in a 31-year-old (PP 63.9%, 95% CI [60.3%-67.3%]), and the desire for fertility (PP 52.2%, 95% CI [48.6%-56.0%]). In general, faculty members favored more aggressive treatment across all clinical scenarios. The presence of symptoms, thyroid stimulating hormone >10 mIU/L, and desire for fertility were most predictive of the decision to treat in SCH. In several clinical scenarios, both trainee and faculty decision-making demonstrated discordance with general SCH management principles.


N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines are opioid receptor pure antagonists.
N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a- octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines (4 and 5, respectively) were found to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (1 and 2, respectively) including N-substituent mediated potency and a lack of N-substituent mediated antagonism. These data suggest that compounds 4 and 5 and the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly.


Acute Interstitial Nephritis and Checkpoint Inhibitor Therapy: Single Center Experience of Management and Drug Rechallenge.
The objective of this case cohort study was to describe our experience in the care of patients with immune checkpoint inhibitor-related acute interstitial nephritis (ICI-AIN) including rechallenge. A descriptive case series of patients that received an ICI and had an AKI (defined as a ≥1.5-fold increase in serum creatinine) as an immune-related adverse event (irAE), with biopsy-proven or clinically suspected ICI-AIN from January 1, 2014 to December 1, 2018 at Mayo Clinic, Rochester. We studied details regarding diagnosis, clinical course, management, and outcomes of rechallenge of immunotherapy. Complete response (CR) was defined as return of kidney function back to baseline or <0.3 mg/dl above baseline creatinine; partial response (PR) was defined as creatinine >0.3 mg/dl from baseline, but less than twofold above the baseline by the end of steroid course. A total of 14 cases of biopsy-proven (35%) or clinically suspected (65%) ICI-AIN was identified. All patients had their ICI withheld and 12 patients received steroids. Steroid regimens were highly variable. The starting equivalent dose of prednisone was higher in those that had a CR versus a PR (median 0.77 mg/kg versus 0.66 mg/kg). Proton pump inhibitors (PPIs) were used in 11 patients and were stopped in eight (73%) patients at the time of the AKI event. A CR was seen in five (63%) of the eight patients who discontinued PPIs. Rechallenge was attempted in four of the 14 patients: three were successful with no recurrence of AKI, but one patient had recurrent AKI and fatal pneumonitis. Careful review, withholding ICI and concomitant known AIN-inducing medications, along with prompt initial steroid management were the key in complete renal kidney recovery. A kidney biopsy should be strongly considered. Rechallenge of immunotherapy after a kidney irAE, although challenging, is possible and would need careful evaluation on an individual basis. This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_01_30_KID0000152019.mp3.


MXene@Au based electrochemical biosensor with pretreatment by magnetic nanoparticles for determination of MRSA from clinical samples.
Pathogenic bacteria are associated with high morbidity rates and present significant diagnostic challenges in terms of rapid detection. This study introduces a magnetic separation-based electrochemical biosensor for the detection of Methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin (Van) was used to modify on the surface of polyethyleneimine (PEI) mediated MBs (MBs-PEI-Van) for separation and enrichment of MRSA. The MBs-PEI-Van shown a satisfactory stability and applicability with capture effective (CE) > 85% in both PBS and cerebrospinal fluid (CSF) samples. MXene@Au with controllable size of AuNPs was synthesized by a self-reduction method and employed to modify the glassy carbon electrode (GCE). Immunoglobulin G (IgG) was loaded onto the modified electrode to immobilize MRSA, and ferroceneboronic acid (Fc-BA) was used as a probe for quantitative determination. The differential pulse voltammetry (DPV) current was plotted against the concentration of MRSA from 3.8 × 101 to 3.8 × 107 CFU/mL with a limit of detection (LOD) of 3.8 × 101 CFU/mL. In addition, MRSA was successfully detected in spiked CSF samples with satisfactory recoveries (94.35-107.81 %) and validation results (RSD < 11 %). Overall, this study presents a promising method for the detection of MRSA, with the potential to be further developed into a universal pathogen detection method.


Palliative care delivery in residential aged care: bereaved family member experiences of the Supportive Hospice Aged Residential Exchange (SHARE) intervention.
The supportive hospice aged residential exchange (SHARE) is a new model of palliative care education that has been designed for residential aged care. The goal of SHARE is to help clinical staff improve palliative care within residential aged care facilities and to improve specialist palliative care nurses' knowledge and skill to care for frail older people. The experiences of 18 bereaved families concerning the palliative care journey (both at the start and finish of a one-year implementation of SHARE) were explored using semi-structured interviews. Three themes were important to bereaved families' experience: communication with staff, systems of care, and hospice involvement. Sub-themes indicating changes in these three components of care between the start and finish of SHARE was identified. A fourth theme highlighted challenges (relationship with GP, staff shortages, and turnover) that continued across SHARE. Findings indicated that SHARE benefited families (improved communication and support) through the end of life journey of their relatives, but challenges remained.


A microCT-based platform to quantify drug targeting.
Heterotopic ossification (HO) is a frequent and debilitating complication of traumatic musculoskeletal injuries and orthopedic procedures. Prophylactic dosing of botulinum toxin type A (BTxA) holds potential as a novel treatment option if accurately distributed throughout soft-tissue volumes where protection is clinically desired. We developed a high-resolution, microcomputed tomography (microCT)-based imaging strategy to assess drug distribution and validated this platform by quantifying distribution achieved via a prototype delivery system versus a single-bolus injection. We injected an iodine-containing contrast agent (iodixanol 320 mg I/mL) into dissected rabbit musculature followed by microCT imaging and analysis. To contrast the performance of distributed versus bolus injections, a three-dimensional (3D) 64-cm3-printed soft-tissue holder was developed. A centered 2-cm3 volume of interest (VOI) was targeted with a single-bolus injection or an equal volume distributed injection delivered via a 3D-printed prototype. VOI drug coverage was quantified as a percentage of the VOI volume that was < 1.0 mm from the injected fluid. The microCT-based approach enabled high-resolution quantification of injection distribution within soft tissue. The distributed dosing prototype provided significantly greater tissue coverage of the targeted VOI (72 ± 3%, mean ± standard deviation) when compared to an equal volume bolus dose (43 ± 5%, p = 0.031) while also enhancing the precision of injection targeting. A microCT-based imaging technique precisely quantifies drug distribution within a soft-tissue VOI, providing a path to overcome a barrier for clinical translation of prophylactic inhibition of HO by BTxA. This platform will facilitate rapid optimization of injection parameters for clinical devices used to effectively and safely inhibit the formation of heterotopic ossification. • MicroCT provides high-resolution quantification of soft-tissue drug distribution. • Distributed dosing is required to maximize soft-tissue drug coverage. • Imaging platform will enable rapid screening of 3D-printed drug distribution prototypes.


Nosocomial infection after septic shock among intensive care unit patients.
To measure the incidence of nosocomial infection (NI) among patients with septic shock according to the place of septic shock acquisition and to evaluate the increase in the risk of pulmonary infection associated with septic shock. Prospective cohort study. Two intensive care units (ICUs) of a French university hospital. The study included a total of 209 septic shock patients during the period December 1, 2001 through April 30, 2005. The place of septic shock acquisition for 108 patients was the community; for 87, the hospital; and for 14, the ICU. To evaluate the impact of septic shock on the development of pulmonary infection, a competitive and adjusted hazard ratio (aHR) model was applied to nontrauma ICU patients. Among the 209 study patients, 48 (23%) experienced 66 NIs after septic shock. There was no significant difference in the NI attack rates according to place of acquisition: for the community acquisition group, 24 cases per 100 patients (95% confidence interval [CI], 16-32); for the hospital acquisition group, 20 cases per 100 patients (95% CI, 11-28); and for the ICU acquisition group, 36 cases per 100 patients (95% CI, 11-61) (P = .3). For nontrauma ICU patients, the presence of community-acquired septic shock was found to be independently associated with a higher incidence of pulmonary infection, compared with the absence of septic shock (aHR, 2.12 [95% CI, 1.08-4.16]; P = .03). The risk of NI did not differ by the place of septic shock acquisition. The risk of pulmonary infection was higher for ICU patients with community-acquired septic shock who were admitted for underlying nontrauma disease. Studies are needed to investigate the pathogenic mechanisms that facilitate pulmonary infection in this population, taking into account exposure to invasive devices and immunosuppression after the initial phase of septic shock.


Assessment of nitrogen interaction with temperature on the growth and toxin production of mat-forming toxin-producing Anagnostidinema carotinosum.
Global warming and eutrophication contribute to the severity of cyanobacteria blooms. However, it is unclear how these factors influence the growth and toxin production of Anagnostidinema carotinosum. Based on morphological and molecular analysis, this is the first time A. carotinosum was identified in South Korea. The interactive effect of temperature (25, 30 or 34°C) and nitrogen (2.5, 3.5 or 4.5 mg NO3 -N l-1 ) on A. carotinosum growth and toxin production was studied. Increasing nitrogen limitation reflects reduced growth and chlorophyll-a content at all temperatures. However, the growth was effective under nitrogen limitation when temperatures exceeded 25°C. The maximum growth was found at 30°C, followed by 34°C under higher nitrate levels (3.5 and 4.5 mg l-1 ). In addition, the cell microcystin and anatoxin-a quota increased significantly at 25°C with increasing nitrate limitation, decreasing considerably at 30°C in the same nitrate gradient. These results suggested temperatures stimulate A. carotinosum growth at 30 and 34°C and cellular toxin quota at 25 and 34°C with increasing NO3 -N levels. These findings imply that limiting nitrogen input alone can effectively reduce biomass; however, controlling A. carotinosum and its toxins at higher temperatures under nitrate limitation is necessary for water quality.


Global value chains participation and carbon emissions embodied in exports of China: Perspective of firm heterogeneity.
This paper studies the impact of global value chains (GVCs) participation on carbon emissions embodied in exports (EEE) of China during 2005-2016, and analyses firm heterogeneity from the perspective of firm ownership and trade patterns; Then, industries are classified based on factor intensity and technology level, and the industrial heterogeneity of different firms is analyzed; Finally, through counterfactual analysis, this paper evaluates EEE under four anti-globalization scenarios. The empirical study shows that with the increase of GVCs position, EEE first increases and then decreases, showing an inverted U-shaped distribution. From the perspective of firm ownership, the relationship between GVCs position of domestic firms and EEE is inverted U-shaped distribution, while GVCs position of multinational enterprises (MNEs) is positively correlated with EEE. The relationship of capital-intensive and technology-intensive domestic firms, high-tech and medium-tech manufacturing domestic firms are also inverted U-shaped distribution. The positive correlation of MNEs is reflected in the low-tech manufacturing industries. From the perspective of trade patterns, with the increase of GVCs position, EEE of processing trade firms presents an inverted U-shaped distribution, while it is not significant for general trade firms. The inverted U-shaped relationship between GVCs position in capital-intensive industries and EEE are confirmed in all firms. Under anti-globalization scenarios of 50% backflow, EEE would increase. Under scenarios of 100% backflow, EEE would reduce. The results above provide useful references to achieve carbon emission reduction targets.


Combined intraoperative paracetamol and preoperative dexamethasone reduces postoperative sore throat: a prospective randomized study.
Postoperative sore throat (POST) after general anesthesia with endotracheal intubation is a common and undesirable complication. In this study, we evaluated the combined effects of paracetamol and dexamethasone on the prevention of POST in patients after general anesthesia. A total of 226 patients scheduled for urologic surgery under general anesthesia were randomly assigned to one of two groups. In the DexaPara group (n = 113), dexamethasone (10 mg) and paracetamol (1000 mg) was infused. In the Dexa group (n = 113), dexamethasone (10 mg) alone was given. POST, hoarseness, and dysphagia were monitored. The postoperative wound pain score and perioperative opioid requirements were compared. In addition, complications related to opioids were compared between the groups. The overall incidence of POST was lower in the DexaPara group than in the Dexa group [42 (37%) vs. 72 (64%), p < 0.001]. The incidence of POST while resting at postoperative 1 and 6 h was lower in the DexaPara group than in the Dexa group (p = 0.008 and p = 0.004, respectively). The incidence of postoperative nausea, vomiting, drowsiness, shivering, and headache was comparable between the groups. Paracetamol and dexamethasone infusion reduced the incidence of POST without serious complications in patients for urologic surgery under general anesthesia.


Deltamethrin and permethrin residue on long-lasting insecticidal nets after 18 months of use in a visceral leishmaniasis-endemic area in Nepal.
The insecticide residue on two types of long-lasting insecticidal nets (LLIN), Olyset Net and PermaNet 2.0, used in a visceral leishmaniasis-endemic village in eastern Nepal was quantified using HPLC. After two washes during 18 months of use the mean insecticide residues on PermaNet 2.0 and Olyset Net were 53.5 mg/m(2) (97.3% of the target dose) of deltamethrin and 911.8 mg/m(2) (91.2% of the target dose) of permethrin, respectively. These residues were close to the insecticide loads specified by the manufacturers of the two LLINs. The use of LLINs has been postulated as an alternative or complementary method to indoor residual spraying. Our results suggest that LLINs should be washed 4-5 times each year throughout their lifespan by specifically requesting villagers to wash nets on certain dates. The insecticide residue on the nets and their bioefficacy against sand fly vectors should be monitored after each wash, in various cultural settings, to assess their durability and long-term retention of the insectide.


A comparative study of endometrial acid phosphatase activity in the mid-luteal phase of the menstrual cycle and in the peri-implantation stage in the rhesus monkey (Macaca mulatta).
Acid phosphatase activity in both total and subcellular fractions of endometrium of rhesus monkey on day 5 of gestation was significantly (P less than 0.01) lower than levels found in tissues collected from normally menstruating monkeys on day 5 after ovulation. This endometrial response to preimplantation embryo may be related to the menstrual withdrawal in a fertile cycle.


The latent structure and predictors of non-medical prescription drug use and prescription drug use disorders: a national study.
Despite growing concerns about non-medical prescription drug use and prescription drug use disorders, whether vulnerability for these conditions is drug-specific or occurs through a shared liability and common risk factors is unknown. Exploratory and confirmatory factor analysis of Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions were used to examine the latent structure of non-medical prescription drug use and prescription drug use disorders. Multiple Indicators Multiple Causes (MIMIC) analysis was used to examine whether the effect of sociodemographic and psychiatric covariates occurred through the latent factor, directly on each drug class or both. A one-factor model described well the structure of both non-medical prescription drug use and prescription drug use disorders. Younger age, being White, having more intense pain or one of several psychiatric disorders increased the risk of non-medical prescription drug use through the latent factor. The same covariates, except for anxiety disorders also significantly increased the risk of prescription drug use disorders through the latent factor. Older age directly increased the risk of non-medical use of sedatives, and alcohol use disorders decreased the risk of non-medical tranquilizer use. No covariates had direct effects on the risk of any prescription drug use disorders beyond their effect through the latent factor. The risk for non-medical prescription drug use and prescription drug use disorders occurs through a shared liability. Treatment, prevention and policy approaches directed at these drugs as a group maybe more effective than those focused on individual classes of drugs.


Separation of rare cell subpopulations with the aid of biotin-labelled ligands.
A universal method for selection of surface marker-positive cells is described. The cells, admixed with an excess of surface marker-negative cells, are first labelled with a specific biotinylated ligand and then isolated with the aid of monoclonal, anti-biotin coated beads. The method enables selection and isolation of cells with a frequency as low as 10(-4). The ligand can be an antigen (for selection of infrequent antibody-producing cells), an antibody (for selection of surface antigen-positive cells) or other molecules (for selection of specific receptor-positive cells).


Glucose and glycogen levels in piglets that differ in birth weight and vitality.
In the pig, intrauterine crowding can greatly affect postnatal characteristics, among which birth weight and locomotion. In a previous study, we discovered that piglets with a low birth weight/low vitality (L piglets) have a reduced motor performance compared to piglets with a normal birth weight/normal vitality (N piglets). A possible explanation is that L piglets lack the energy to increase their motor performance to the level of that of N piglets. Blood glucose levels (GLU) and glycogen concentrations in skeletal muscle of the front (GLYFRONT) and hind leg (GLYHIND) and the liver (GLYLIVER) at birth and during the first 96 h postpartum were compared between L and N piglets. GLU at birth was the same for both groups. After birth, GLU immediately increased in N piglets, whereas it only increased after 8 h in L piglets. L piglets showed a lower GLYHIND at birth and did not use this glycogen during the first 8 h postpartum, while N piglets showed a gradual depletion. GLYLIVER at birth was 50% lower for L piglets and was unused during the studied period while N piglets consumed half of their GLYLIVER during the first 8 h. Based on these results, it is possible that lower glycogen concentrations at birth, the delayed increase in GLU and the lower use of glycogen during the first 8 h after birth negatively affect motor performance in L piglets. However, based on this study, it is unclear whether the low mobilization of glycogen by L piglets is a consequence, rather than a cause of their lower motor performance.


Electrospun highly porous poly(L-lactic acid)-dopamine-SiO2 fibrous membrane for bone regeneration.
Electrospinning has been widely used to fabricate polymer fibrous scaffolds for bone tissue engineering because of their highly porous structures. In order to improve the biocompatibility of polymer scaffolds, some nano particles have been introduced into electrospun fibres. For example, silica nanoparticles (SiNPs), with high surface area and good biocompatibility, have been used for bone tissue engineering for better bone cell attachment. In this work, porous poly(L-lactic acid) (PLLA) fibrous membrane with high surface area was fabricated by electrospinning and post-treatment process. The membrane can serve as substrates of SiNPs for bone tissue engineering. Dopamine (DOP) was applied to modify the surface of PLLA fibres, which improved the coating strength of SiNPs on PLLA fibres. SiNP coating significantly improved the mechanical properties and hydrophilicity of PLLA/DOP/SiNP composite membranes. As a result of SiNPs coating, PLLA/DOP/SiNP membrane exhibited better cellular biocompatibility, more cell attachment and proliferation. These results demonstrate that porous PLLA/DOP/SiNP composite membrane with high surface area has high potential for periosteum in the field of bone regeneration applications.


Purification of astrocyte subtype based on a double reporter mice approach for downstream transcription profiling.
Characterizing the molecular signature of a cell subtype leads to a better understanding of cell diversity, as this molecular data can identify new cellular markers and offer insights about cell function. Here, we describe an efficient protocol to separate a subtype of astrocytes, the Olig2-AS, from other glial cells by using a double reporter mouse approach and to determine the transcriptome profile of the Olig2-AS from the postnatal spinal cord using RNA-sequencing analysis. For complete details on the use and execution of this protocol, please refer to Ohayon et al. (2021).


Longitudinal assessment of clinical and inflammatory markers in patients with amyotrophic lateral sclerosis.
To evaluate potential associations between clinical features and inflammatory markers in patients with amyotrophic lateral sclerosis (ALS). A consecutive series of 68 patients (39 males and 29 females) with sporadic ALS were subjected to a comprehensive clinical assessment and blood draw. A subset of these patients underwent a new assessment within 6-12 months after the baseline visit. In addition, a group of 62 subjects composed by age and sex-matched healthy subjects (38 males and 24 females) was enrolled in this study. Peripheral blood was drawn and plasma levels of chemokines and cytokines were measured by cytometric bead array and enzyme-linked immunosorbent assay. Our sample was composed by patients with ALS with an average age of 58 (±12.3) years old and 3 (±2.7) years of disease length at the baseline visit. Patients with ALS presented increased plasma levels of interleukin (IL)-6 and IL-8 in comparison with controls. After multivariate analysis, higher levels of IL-6 and lower levels of IL-2 were significantly associated with increased likelihood of ALS diagnosis. When evaluating the subset of patients assessed longitudinally, we did not find any significant difference in the levels of inflammatory markers between the two time points. Older age at ALS onset was the only factor associated with a faster rate of disease progression. IL-6 levels could discriminate between ALS and controls and may be regarded as a potential biomarker of ALS diagnosis. An increase in IL-2 levels was associated with a protective effect on the odds of ALS diagnosis. Older age at ALS onset predicted a fast rate of disease progression.


Immunohistochemical localization of glucagon-like peptide 1. Use of poly- and monoclonal antibodies.
We report the use of poly- and monoclonal antibodies to study the immunohistochemical distribution of glucagon-like peptide-1 immunoreactivity (GLP-1-IR) in various tissues. The polyclonal antibodies against GLP-1 reacted with pancreatic A cells, enteroglucagon (L) cells in the gut, and some neurons in the central nervous system of all species tested. In pancreas and gut the monoclonal antibodies against GLP-1 exhibited a similar, but species specific distribution, relative to the polyclonal antibodies. The colocalization of GLP-1 and glucagon immunoreactivity in pancreatic, intestinal, and nervous tissues is in agreement with previously reported findings that both peptides are part of a single precursor molecule (preproglucagon).


Imperfect DNA mirror repeats in the gag gene of HIV-1 (HXB2) identify key functional domains and coincide with protein structural elements in each of the mature proteins.
A DNA mirror repeat is a sequence segment delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5'-GCATGGTACG-3'. It is most frequently described in association with a functionally significant site in a genomic sequence, and its occurrence is regarded as noteworthy, if not unusual. However, imperfect mirror repeats (IMRs) having > or = 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements - helices, beta sheets and turns. In this study, the distribution of IMRs is evaluated in a polyprotein - to determine whether IMRs may be related to the position or order of protein cleavage or other hierarchal aspects of protein function. The gag gene of HIV-1 [GenBank:K03455] was selected for the study because its protein motifs and structural components are well documented. There is a highly specific relationship between IMRs and structural and functional aspects of the Gag polyprotein. The five longest IMRs in the polyprotein translate a key functional segment in each of the five cleavage products. Throughout the protein, IMRs coincide with functionally significant segments of the protein. A detailed annotation of the protein, which combines structural, functional and IMR data illustrates these associations. There is a significant statistical correlation between the ends of IMRs and the ends of PSEs in each of the mature proteins. Weakly symmetric IMRs (> or 33%) are related to cleavage positions and processes. The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein. The interaction between IMRs and protein structure and function is precise and interwoven over the entire length of the polyprotein. The distribution of IMRs and their relationship to structural and functional motifs in the protein that they translate, suggest that DNA-driven processes, including the selection of mirror repeats, may be a constraining factor in molecular evolution.


The role of preoperative intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation for bladder cancer.
Twenty patients with bladder cancer (T1, 3 patients; T2, 6 patients; T3, 8 patients; T4a, 3 patients) were preoperatively treated with intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation. The originally scheduled operations were as follows: total cystectomy in 16 patients (T1 + cis, 1 patients; T2, 5 patients; T3, 7 patients; T4a, 3 patients), segmental cystectomy in 2 patients, and transurethral resection in 2 patients. The total dose of doxorubicin ranged from 120 to 540 mg (251.5 +/- 100.2 mg), and that of irradiation was from 4 to 36 Gy (24.4 +/- 7.3 Gy). Clinical and pathological effects were evaluated in all of the cases. Clinically, complete remission (CR) was observed in 14 cases (70.0%), partial remission (PR) was seen in 3 cases, a minor response (MR) occurred in 2 cases, and no response (NR) was seen in 1 patient; non patient showed progressive disease (PD). The pathological effects (according to the criteria of Shimosato et al.) were as follows: grade IV was seen in 10 cases, grade III in 3 cases, and less than grade II in 7 cases; however, viable tumor cell were not seen in 13 (65.0%) of the 20 cases. The bladder was preserved in 13 (81.3%) of the 16 cases for which total cystectomy had been recommended. All of the patients were followed up for periods ranging from 3 to 54 months (26.3 +/- 16.5 months), during which time 6 patients (30.0%) died (3 with cancer, 1 without cancer, and 2 unknown causes). The actual survival rate according to the stage of disease was 100.0% at 50 months in T1-T2 and 40.9% at 54 months in T3-T4a. In T3-T4a, the actual survival rate in pathologically complete responders was 60% (relative rate 68.8%) at 54 months, and the actual survival rate in incomplete responders was 25.0% (relative rate 27.1%) at 36 months. The results of our study are encouraging, especially in T1-T2 and T3-T4a cases, who showed a complete response. It is concluded that doxorubicin intra-arterial chemotherapy combined with low-dose irradiation could be the first treatment of choice for locally invasive bladder cancer.


Effects of wastewater effluent-borne nutrients on phytoplankton off the coast of Jeju Island.
The spatiotemporal distributions of nutrients in coastal waters surrounding eight wastewater treatment plants (WWTPs) in four seasons were investigated to determine the effects of WWTP effluents on seawater off Jeju Island, Korea. The highest concentrations of nutrients were observed in the outlets of WWTPs with relatively high ammonium concentrations among dissolved inorganic nitrogen (DIN). The reduced DIN (NO2- and NH4+)/total DIN ratios are used as a potential short-term index for marine environmental conditions. In seawater surrounding the WWTPs, relatively low nutrient concentrations were observed in spring and fall, due to enhanced biological production, which is closely linked to decreased N/P ratios. Because the highest WWTP effluent fluxes of ammonium in this study were similar to the fluxes of nutrients from submarine groundwater discharge, diffusion from bottom sediments, and discharge from land-based fish farm wastewater, WWTP effluent-derived nutrients are potentially important in oligotrophic environments and can be readily utilized by phytoplankton.


Visceral adipose tissue and risk of COVID-19 susceptibility, hospitalization, and severity: A Mendelian randomization study.
Coronavirus Disease 2019 (COVID-19) has rapidly evolved as a global pandemic. Observational studies found that visceral adipose tissue (VAT) increased the likelihood of worse clinical outcomes in COVID-19 patients. Whereas, whether VAT is causally associated with the susceptibility, hospitalization, or severity of COVID-19 remains unconfirmed. We aimed to investigate the causal associations between VAT and susceptibility, hospitalization, and severity of COVID-19. We applied a two-sample Mendelian randomization (MR) study to infer causal associations between VAT and COVID-19 outcomes. Single-nucleotide polymorphisms significantly associated with VAT were derived from a large-scale genome-wide association study. The random-effects inverse-variance weighted method was used as the main MR approach, complemented by three other MR methods. Additional sensitivity analyses were also performed. Genetically predicted higher VAT mass was causally associated with higher risks of COVID-19 susceptibility [odds ratios (ORs) = 1.13; 95% confidence interval (CI), 1.09-1.17; P = 4.37 × 10-12], hospitalization (OR = 1.51; 95% CI = 1.38-1.65; P = 4.14 × 10-20), and severity (OR = 1.58; 95% CI = 1.38-1.82; P = 7.34 × 10-11). This study provided genetic evidence that higher VAT mass was causally associated with higher risks of susceptibility, hospitalization, and severity of COVID-19. VAT can be a useful tool for risk assessment in the general population and COVID-19 patients, as well as an important prevention target.


Intracellular free calcium level and its response to cAMP stimulation in developing Dictyostelium cells transformed with jellyfish apoaequorin cDNA.
A new method is described for measuring intracellular free calcium concentrations, [(Ca2+)i], in the cells of Dictyostelium discoideum transformed with apoaequorin cDNA of the jellyfish, Aequorea victoria. Aequorin, a calcium-specific indicator, was regenerated in vivo from apoaequorin produced in the cells by incubation with coelenterazine. The results showed that [(Ca2+)i] in developing cells markedly increases at the aggregation stage and again at the culmination stage after a temporary drop at the migration stage. Except for the vegetative stage, the cells at all stages of development exhibit a sharp transient increase in [(Ca2+)i] upon stimulation with a cAMP (50 nM) pulse, high responses being observed at the migration and culmination stages. Separated prestalk cells of migrating slugs contain more than twice as much [(Ca2+)i] and show three times as large a response to cAMP stimulation as prespore cells.


The impact of yoga on components of energy balance in adults with overweight or obesity: A systematic review.
Yoga may reduce body weight in individuals with overweight or obesity, but whether this occurs through decreased energy intake (EI) or increased energy expenditure (EE)/physical activity (PA) is unclear. A systematic search of PubMed, Web of Science, Embase, and PsychINFO was conducted from inception until April 26, 2021. Eligible studies included randomized controlled trials or single-arm pre-post studies with any type and duration of yoga intervention in adults with overweight or obesity. Studies with measures related to EI , EE, or PA were eligible. The review initially identified 1,373 articles. Of the 10 included studies, one used indirect calorimeter measures of resting EE, while nine used self-reported measures of EI and PA. Of the seven studies measuring parameters related to EI, only one found greater decreases in EI relative to the control group, although three other investigations reported trends toward improved dietary intake. Of the eight studies measuring PA, two reported greater increases in resting EE or PA in the yoga group relative to the control group. Two reported significant within-group increases in PA from pre-post intervention, and four studies reported a trend for increased PA with no p-values reported. Limited evidence suggests yoga may reduce EI and increase PA in adults with overweight or obesity. Additional studies that investigate the effects of yoga interventions on energy balance parameters using objective techniques are warranted.


Effects of self-affirmation on university students' processing of health risk messages related to sedentary behavior.
Examine effects of self-affirmation on university students' processing of health risk messages related to sedentary behavior. Eighty-eight students from a Canadian university (females = 53; males = 35; Mage = 21.74, SD = 5.36) participated during the 2018-2019 academic year. Participants were randomized to a self-affirmation (n = 43) or control group (n = 45), watched a video conveying sedentary behavior risk messages, and completed measures of acceptance, derogation, risk perceptions, negative affect, and intentions. A one-way between-groups multivariate analysis of variance (MANOVA) examined effects of condition on the combined set of outcome variables. Self-affirmation had no observable effect on any outcome variables. Self-affirmation did not appear to impact students' reactions to sedentary behavior risk messages. Given the lack of a manipulation check, however, this finding must be interpreted with caution. The Trigger and Channel framework offers a useful account of factors that influence self-affirmation effects. Implications and future research directions are discussed.


Intraventricular Bronchogenic Cyst: A Rare Congenital Anomaly.
Intracardiac bronchogenic cyst is a rare congenital anomaly. This tumor is usually found in the mediastinum (12% to 18% of all primary mediastinal masses) or in the lung parenchyma (15% to 30% of them). Although rare, it should be included in the differential diagnosis of intracardiac tumors. Complete resection is recommended for diagnosis and for therapeutic reasons. We present here a rare case of an intracardiac left ventricular bronchogenic cyst in an asymptomatic 41-year-old woman.


Intracranial arterial aneurysms in early childhood.
Cerebral saccular aneurysms are rare in early childhood. Seventy-one cases in children under 5 years of age found in the literature, plus one case of our own, are analyzed. In early childhood these aneurysms seem to have features that distinguish them from the same variety in adults. In children a congenital pathogenesis appears more convincing because of the higher frequency in the first 2 years of life, the often peripheral site (41.6%), the high frequency of large (50%) or giant (26.8%) aneurysms, and the association with other cerebral and vascular congenital abnormalities. Onset was nonhemorrhagic in 18.1% of cases compared with 2.5% in adults. The surgical outcome seems better in children than in adult patients in terms of both morbidity and mortality.


Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction.
Recognition of autoimmunity as a cause of encephalopathy has increased. Recent studies have validated the use of Antibody-Prevalence-in-Epilepsy (APE) and Responsive-to-immunotherapy-in-Epilepsy (RITE) scores in the evaluation and management of autoimmune-epilepsy. We aim to assess the utility of these models for patients with cognitive dysfunction. Among the evaluated patients, 17% had antibodies universally associated with autoimmune-encephalopathy. NMDA-R-IgG and LGI1-IgG were the most common antibody specificities. Antibody-Prevalence-in-Epilepsy-and-Encephalopathy (APE2) score ≥ 4 was 99% sensitive and 93% specific for neural-specific-antibodies. Responsive-to-immunotherapy-in-Epilepsy-and-Encephalopathy (RITE2) score ≥ 7 had 96% sensitivity and 86% specificity for favorable initial immunotherapy response. Application of these models may optimize autoantibody evaluations and immunotherapeutic trials.


Safety and effectiveness of stent implantation without predilation for small coronary arteries.
The purpose of this study was to examine the safety and effectiveness of stenting without predilation (direct stenting) in small (< 2.5 mm) coronary arteries. Clinical and angiographic data from the multicenter randomized PREDICT trial was examined. Direct stenting was performed on 42 small and 158 large vessels. Predilation was performed prior to stenting for 37 small vessels. In the small-vessel group, mean reference vessel diameter was 2.24 +/- 0.19 mm for direct stenting vs. 2.24 +/- 0.22 mm for predilation (P = NS). Mean reference vessel diameter was 3.17 +/- 0.48 mm in the large-vessel group. Device success for direct stenting was similar for small vs. large vessels (90.5% vs. 92.4%; P = NS). At 180 days, a trend toward increased MACE between small vs. large vessels in the direct-stenting group was observed (26.8% vs.16.7%; P = NS), and significantly higher target lesion revascularizations (TLRs) in the small-vessel group (19.5% vs.7.7%; P = 0.03) were observed. In small vessels, differences in device success rate (90.5% vs. 100 %; P = NS) and lesion success rate (100% vs. 100%; P = NS) for direct stenting vs. predilation were not significant. At 180 days, no differences between direct stenting and predilation for MACE (26.8% vs. 29.7%; P = NS) or TLR (22.0% vs. 21.6%; P = NS) were seen in small vessels, although binary angiographic restenosis rate tended to be higher in direct-stenting group (38.2% vs. 18.5%; P = NS). Direct stenting of small vessels can be performed safely and successfully in selected cases. Restenosis rates may be higher for small vessel treated by direct stenting compared to predilation.


Characterisation of stem and proliferating cells on the retina and lens of loach Misgurnus anguillicaudatus.
The eye of the fish has a lifelong persistent neurogenesis unlike eye of mammals, so it's highly interesting to study retinal neurogenesis and its genetic control to give complete knowledge about the cause of this property in fish in comparison to mammals. We performed fluorescent in situ hybridisation for loach Misgurnus anguillicaudatus bmi1, msi1 and sox2 genes, which are used as an indicator of the sites of multipotent stem cells. Proliferating cell nuclear antigen (PCNA), bromodeoxyuridine (BRDU) and KI67 markers were used as indicators of proliferating cells and glial fibrillary acidic protein (GFAP) immunofluorescence was used for detection of the glial property of cells, as well as, immunohistochemistry detected the role of peroxisome proliferator-activated receptor (PPAR)α and γ in retinal neurogenesis. Our results determined that the lens and the retina of loach M. anguillicaudatus contain proliferative and pluripotent stem cells that have both glial and neuroepithelial properties, which add new cells continuously throughout life even without injury-induced proliferation. The PPARα has an essential function in providing energy supply for retinal neurogenesis more than PPARγ.


Both sedentary time and physical activity are associated with cardiometabolic health in overweight adults in a 1 month accelerometer measurement.
The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m2. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA1c, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.Trial Registration: ClinicalTrials.gov NCT03101228, registered 05/04/2017, https://clinicaltrials.gov/show/NCT03101228 .


Oligonucleotide aptamers: A next-generation technology for the capture and detection of circulating tumor cells.
A critical challenge for treating cancer is the early identification of those patients who are at greatest risk of developing metastatic disease. The number of circulating tumor cells (CTCs) in cancer patients has recently been shown to be a valuable (and non-invasively accessible) diagnostic indicator of the state of metastatic disease. CTCs are rare cancer cells found in the blood circulation of cancer patients believed to provide a means of diagnosing the likelihood for metastatic spread and assessing response to therapy in advanced, as well as early stage disease settings. Numerous technical efforts have been made to reliably detect and quantify CTCs, but the development of a universal assay has proven quite difficult. Notable challenges for developing a broadly useful CTC-based diagnostic assay are the development of easy-to-operate methods that (1) are sufficiently sensitive to reliably detect the small number of CTCs that are present in the circulation and (2) can capture the molecular heterogeneity of tumor cells. In this review, we describe recent progress towards the application of synthetic oligonucleotide aptamers as promising, novel, robust tools for the isolation and detection of CTCs. Advantages and challenges of the aptamer approach are also discussed.


A method for the detection and differentiation of cellulase components in polyacrylamide gels.
Endoglucanase and exoglucanase components of cellulase can be detected and differentiated after polyacrylamide gel electrophoresis by performing activity stains. Endoglucanase activity was visualized in carboxymethyl cellulose agar replicas of gels by staining with Congo red. General beta-1,4-glucanase activity was located by soaking the gel in a solution of NaBH4-reduced cellulooligosaccharides, and detecting the formation of reducing sugars by reaction with triphenyl tetrazolium chloride. Endoglucanases are active in both assays, while exoglucanases can be distinguished by their activity in the cellulo-oligosaccharide assay only. This methodology has facilitated the purification and characterization of cellulase components from Trichoderma reesei and Microbispora bispora.


Prevalence, determinants, and outcomes of unintended pregnancy in Sohag district, Egypt.
Unintended pregnancies may be mistimed or unwanted. It represents 40% of all pregnancies, and it had multiple risky health outcomes. It is essential to understand the factors affecting unintended pregnancies and their consequences to develop strategies that help prevent them. The present study is conducted to identify the prevalence, determinants, and outcomes of unintended pregnancies in Sohag district, Egypt. A cross-sectional study was conducted in Sohag district, 2016. Five hundred fifty-four ever married women aged 18-49 years whose last pregnancy was in the 3 years preceding the data collection date were randomly selected from rural and urban localities. Data were collected through home visits using a validated questionnaire. In this study, Sohag city represents the urban place, while Tunis and El-Sheikh Makram villages represent the rural places. Nearly one third (30.7%) of the study sample had an unintended pregnancy within the last 3 years from the time of interview. Regression analysis showed that young women < 30 (OR = 2.24, 95% CI 1.12-4.48, p = 0.02), young husbands ≤ 30 (OR = 5.44, 95% CI 1.14-26.11, p = 0.03), women working for cash (OR = 6.16, 95% CI 3.15-13.92, p < 0.0001), monthly income ≤ 1200 LE (OR = 34, 95% CI 6.41-187.52, p < 0.0001), and spacing < 24 months (OR = 8.79, 95% CI 4.33-17.80, p < 0.0001) were risk factors for mistimed pregnancy. On the other hand, women working for cash (OR = 11.43, 95% CI 3.22-40.62, p < 0.0001), living children ≥ 5 (OR = 11.45, 95% CI 2.84-46.07, p = 0.001), and the woman's perception of her family size as higher than the ideal (OR = 394.8, 95% CI 97.36-1601.17, p < 0.0001) were risk factors for unwanted pregnancy. Mistimed and unwanted pregnancies were significantly associated with late start of antenatal care (ANC), low birth weight (LBW), and no breastfeeding. In addition, unwanted pregnancies were associated with more pregnancy complications. Unintended pregnancy represents a public health problem in Sohag. Therefore, improving services in rural areas and improving the economic level and effective use of family planning methods could reduce the risks associated with the unintended pregnancy.


[Medical aspects of the medical treatment in dystonia].
Dystonias encompass a wide range of movement disorders characterized mainly by abnormal postures or movements. Because of this semiological and etiological heterogeneity, robust clinical trials are rare. Specific etiological treatments are available for only a few forms (e.g. Wilson's disease and dopa-responsive dystonia), which places the emphasis on symptomatic treatment. This is based on the combinations of three complementary approaches: drug therapy (anticholinergics, tetrabenazine and benzodiazepines are first-line drugs, but many others have been tested in small clinical trials), botulinium toxin injections in case of focal dystonia or focal targets in patients with more widespread dystonia, and physiotherapy. This review provides a short overview of available treatments and proposes a basic therapeutic strategy for dystonic patients.


On rat poison and human medicines: personalizing warfarin therapy.
Teaching old dogs new tricks is difficult, but lessons learned from such efforts can be invaluable. Warfarin is an old drug, difficult to administer and a leading cause of drug-related mortality and hospitalizations. New genetic tests for optimizing warfarin therapy have not been adopted. The debate over precise clinical utility and cost-effectiveness of these tests misses more important points of building a better, cheaper, and more efficient infrastructure to measure the true real-world impact of personalized medicine. However, this same debate about how, when, and where such testing is appropriate has been invaluable to the field of personalized medicine: progress beyond science, in policy, regulations, and logistics can be highlighted along the path to safer and more efficacious warfarin therapy.


Translational repression by bacteriophage MS2 coat protein expressed from a plasmid. A system for genetic analysis of a protein-RNA interaction.
The coat protein of bacteriophage MS2 is a translational repressor. It inhibits the synthesis of the viral replicase by binding a specific RNA structure that contains the replicase translation initiation region. In order to begin a genetic dissection of the repressor activity of coat protein, a two-plasmid system has been constructed that expresses coat protein and a replicase-beta-galactosidase fusion protein from different, compatible plasmids containing different antibiotic-resistant determinants. The coat protein expressed from the first plasmid (pCT1) represses synthesis of a replicase-beta-galactosidase fusion protein encoded on the other plasmid (pRZ5). Mutations in the translational operator or in coat protein result in constitutive synthesis of the enzyme. This permits the straightforward isolation of mutations in the coat sequence that affect repressor function. Because of the potential importance of cysteine residues for RNA binding, mutations were constructed that substitute serines for the cysteine residues normally present at positions 46 and 101. Both of these mutations result in translational repressor defects. Chromatographic and electron microscopic analyses indicate that the plasmid-encoded wild-type coat protein forms capsids in vivo. The ability of the mutants to adopt and/or maintain the appropriate conformation was assayed by comparing them to the wild-type protein for their ability to form capsids. Both mutants exhibited evidence of improper folding and/or instability as indicated by their aberrant elution behavior on a column of Sepharose CL-4B. Methods were developed for the rapid purification of plasmid-encoded coat protein, facilitating future biochemical analyses of mutant coat proteins.


The use of amniotic membrane in acute massive full-thickness loss of the abdominal wall from clostridial myonecrosis.
A patient who developed clostridial infection of the abdominal wall following laparotomy for small bowel perforation is described. Immediate debridement resulted in the loss of the entire abdominal wall. Dressing of the exposed viscera during the period of stabilization and prior to reconstruction was achieved using amniotic membranes.


Characterizations of an Emerging Disease: Apple Blotch Caused by Diplocarpon coronariae (syn. Marssonina coronaria) in the Mid-Atlantic United States.
Apple orchards with minimal or reduced fungicide inputs in the Mid-Atlantic region of the United States have experienced outbreaks of severe premature defoliation with symptoms that matched those of apple blotch disease (ABD) caused by Diplocarpon coronariae. Fungal isolates obtained from symptomatic apple leaves and fruit produced uniform slow-growing, dark-gray colonies on peptone potato dextrose agar and had conidia. Internal transcribed spacer DNA sequences matched with D. coronariae and Koch's postulates were fulfilled when typical ABD symptoms occurred when reinoculated onto apple leaves and fruit. Spore dispersal in nonfungicide-treated orchards detected with quantitative PCR was low in early spring and dropped to undetectable levels in late May and early June before rising exponentially to highs in July and August, which coincided with symptom development. Only low spore numbers were detected in fungicide-treated orchards and nearby forests. In preliminary fungicide tests, fluxapyroxad, thiophanate methyl, and difenoconazole effectively inhibited mycelial growth of isolates in vitro. When apple cultivars Fuji and Honeycrisp were inoculated with D. coronariae, Honeycrisp showed delayed onset of symptoms and lower disease severity, and the transcription profile of seven host defense-related genes showed that PR-2, PR-8, LYK4, and CERK1 were highly induced in Honeycrisp at 2 and 5 days postinoculation. This is the first report of ABD in the Mid-Atlantic United States, which includes studies of seasonal D. coronariae spore dispersal patterns, preliminary fungicide efficacy, and host defense-related gene expression to assist development of best ABD management practices.


Maximum growth rate, size and commonness in a community of bactivorous ciliates.
Adaptions which confer competitive ability or resistance to predation are thought to be evolved with a resultant loss in intrinsic rate of increase (r m). Therefore species which are opportunistic should retain high values of r m, whereas competitively superior species which employ a strategy of persistance will have low values of r m. Whether a ciliate species is slow or fast-growing can be judged by comparison with the empirically derived equation relating growth rate and size given by Fenchel (1968).This hypothesis was tested on a group of eleven species of bactivorous ciliates inhabiting a small pond. Species' measured and predicted r m'S [Formula: see text] were compared with their commonness in the field. The prediction that species with high values of [Formula: see text] would be less common, as measured by the number of samples in which they are found, was satisfied by the data. The implications of the data for the ciliate community studied and the potential of [Formula: see text] as a predictor of ecological characteristics of species are discussed.


Stroke in patients treated with thrombolytic therapy for acute myocardial infarction. The thrombosis in myocardial infarction clinical trial and a review of placebo-controlled trials.
The frequency of stroke among patients in six recent placebo-controlled trials of thrombolytic therapy for acute myocardial infarction is reviewed. Three trials used streptokinase and three used tissue plasminogen activator as the thrombolytic agent. While thrombolytic therapy greatly reduces the morbidity and mortality of acute myocardial infarction, it increases the rate of intracerebral hemorrhage.


Mapping the energy landscape of repeat proteins using NMR-detected hydrogen exchange.
Repeat proteins contain tandem arrays of a simple structural motif. In contrast to globular proteins, repeat proteins are stabilized only by interactions between residues that are relatively close together in the sequence, with no "long-range" interactions. Our work focuses on the tetratricopeptide repeat (TPR), a 34 amino acid helix-turn-helix motif found in tandem arrays in many natural proteins. Earlier, we reported the design and characterization of a series of consensus TPR (CTPR) proteins, which are built as arrays of multiple tandem copies of a 34 amino acid consensus sequence. Here, we present the results of extensive hydrogen exchange (HX) studies of the folding-unfolding behavior of two CTPR proteins (CTPR2 and CTPR3). We used HX to detect and characterize partially folded species that are populated at low frequency in the nominally folded state. We show that for both proteins the equilibrium folding-unfolding transition is non-two-state, but sequential, with the outermost helices showing a significantly higher probability than inner helices of being unfolded. We show that the experimentally observed unfolding behavior is consistent with the predictions of a simple Ising model, in which individual helices are treated as "spin-equivalents". The results that we present have general implications for our understanding of the thermodynamic properties of repeat proteins.


Pharmacokinetic differences between pantoprazole enantiomers in rats.
The purpose of this study was to quantitatively clarify the contribution of the absorption, protein binding, and metabolism of cytochrome P450 enzymes to the enantioselective pharmacokinetics of pantoprazole enantiomers in rats. The enantioselective pharmacokinetics of pantoprazole enantiomers was estimated by an oral administration of racemic pantoprazole to rats. The pharmacokinetic differences between pantoprazole enantiomers were evaluated by the experiments of the in situ perfusion into rat small intestine, the protein binding, and the in vitro metabolism in rat liver microsomes of pantoprazole enantiomers. The mean area under the curve value of S-pantoprazole was 1.5 times greater than that of R-pantoprazole after administration of racemic pantoprazole to rats (20 mg/kg, p.o.). There were significant differences in k(e) (p < 0.05), t1/2 (p < 0.01), and mean residence time (p < 0.01) values between the two enantiomers. In the in situ absorption study, the absorption rate constants were of no significant differences between the two enantiomers. The mean unbound fraction of R-pantoprazole was slightly greater than that of S-pantoprazole. The intrinsic clearance (CLint) of the formation of the 5'-O-demethyl metabolite from S-pantoprazole was 4-fold lower than that from R-pantoprazole. However, the CLint value for the sulfone and 6-hydroxy metabolites from S-pantoprazole was higher than that from R-pantoprazole. The sum of the CLint of the formation of all three metabolites was 3.06 and 4.82 mL/min/mg protein for S- and R-pantoprazole, respectively. This study suggests that the enantioselective pharmacokinetics of pantoprazole enantiomers in rats is probably ascribable to their enantioselective metabolism, which is contributed by all the three metabolic pathways, including sulfoxide oxidation, 4'-O-demethylation, and 6-hydroxylation.


Can plasma exchange therapy induce regulatory T lymphocytes in multiple sclerosis patients?
Plasma exchange is used increasingly as an individual therapeutic decision for treating of severe, steroid-resistant relapses of multiple sclerosis (MS). However, given that its mechanism of action in this CD4(+) T cell-mediated autoimmune disease remains unknown, it is not yet considered as a routine therapy for this prevalent neuroimmune disorder. In this regard, we hypothesized that plasma exchange, by depleting the body of inflammatory mediators that acts as providers of co-stimulatory signals for the adaptive immune system, provides the immune system with an exceptional break for de-novo recognition of autoantigens in a tolerogenic manner. This may lead to an increase in the frequency and function of myelin-specific regulatory T cells. For evaluating this we suggest some in vitro and in vivo studies to analyse the effects of varied dilutions of normal and MS plasmas on the induction of regulatory T cells or on the function of isolated and purified regulatory T cells. Clarifying the effects of therapeutic plasma exchange on regulatory T cells as the major controllers of autoimmune responses may provide us with strong evidence to use this procedure as a disease-modifying treatment in remission phase for reducing the rate and severity of future attacks, in addition to more trustworthy therapy in severe relapses of MS.


Structure and function of the spleen.
The spleen combines the innate and adaptive immune system in a uniquely organized way. The structure of the spleen enables it to remove older erythrocytes from the circulation and leads to the efficient removal of blood-borne microorganisms and cellular debris. This function, in combination with a highly organized lymphoid compartment, makes the spleen the most important organ for antibacterial and antifungal immune reactivity. A better understanding of the function of this complex organ has been gained from recent studies, as outlined in this Review article.


Postembedding immunocytochemical GABA labeling in rat neocortex cultures: applicability in quantitative studies.
The value of gamma-aminobutyric acid (GABA) immunogold labeling in the quantification of nerve endings was studied in dissociated rat neocortex cultures. Adjacent sections were processed in 3 series according to the same staining protocol. Of all nerve ending profiles examined, 20% appeared to be GABA-positive, while 7% could not be classified. In cultures pretreated with gabaculine, GABA-positive endings were labeled more heavily. Cell bodies could always be discriminated as GABA-positive or GABA-negative. Of all neuronal cell profiles, 14% appeared to be GABA-positive. These neurons could also be identified by light microscopy using the peroxidase-anti-peroxidase method.


Electrophysiology of phagocytic membranes: intracellular K+ activity and K+ equilibrium potential in macrophage polykaryons.
The role of K+ as current carrier during the slow membrane hyperpolarizations (SH) elicited by iontophoretic Ca2+ injections into macrophage polykaryons is studied. The intracellular K+ activity (ak) and the K+ equilibrium potential (Ek) are measured using ion-sensitive microelectrodes. The mean value of ak is 84 +/- 5 mM in a culture medium containing 5.3 mM K+, but increases to 100 +/- 8 mM when the extracellular K+ concentration is raised to 30.3 mM. Under the same conditions the values of Ek obtained from the Nernst equation are -81 +/- 2 mV and -40 +/- 2 mV, respectively. The reversal potentials (ER) of the SH are calculated from changes observed in transmembrane potential and input resistance, according to an equivalent model based only on passive ionic fluxes. The mean ER values obtained are -74 +/- 8 mV in the presence of low K+ concentration and -37 +/- 3 mV for the high K+ medium. These values are significantly smaller than the estimated Ek for the corresponding situations. Evidence for the existence of an electrogenic (Na+ + K+)-ATPase activity is also presented. The evidence indicates that an increase in the membrane potassium permeability can account for about 90% of the total permeability change occurring during the SH.


Electron microscopic characterization of gels formed by blood cells of leukemia patients at hypertonicity.
At hypertonicity some blood cells of patients suffering chronic leukemia can form gel like layers around themselves. These gels, which are sensitive to hyaluronidase, but not to trypsin are investigated by electron microscopy. The study revealed that the gels comprise a network of nanoparticles, which have diameters between 50 and 150 nm, are regularly ordered and linked to each other.


Protective effects of the sickle cell gene against malaria morbidity and mortality.
The high frequency of the sickle-cell haemoglobin (HbS) gene in malaria endemic regions is believed to be due to a heterozygote (HbAS) advantage against fatal malaria. Data to prospectively confirm the protection associated with HbAS against mortality are lacking. We show that HbAS provides significant protection against all-cause mortality, severe malarial anaemia, and high-density parasitaemia. This significant reduction in mortality was detected between the ages of 2 and 16 months, the highest risk period for severe malarial anaemia in this area. These data are important in understanding the role of malaria in the selection and maintenance of the sickle cell gene.


The role of prophylactic antibiotics in elective hand surgery.
The current literature has poorly defined the role of antibiotic agents in elective hand surgery. The reason for this may be due to a small number of well-designed studies specifically addressing the efficacy of antibiotics in hand surgery. Our purpose is to critically review the current literature in an attempt to more precisely define the role of prophylactic antibiotics in elective hand surgery.


Titre and affinity of propylthiouracil-induced anti-myeloperoxidase antibodies are closely associated with the development of clinical vasculitis.
Substantial evidences suggested that propylthiouracil (PTU) could induced anti-myeloperoxidase (MPO) antibodies in sera from patients with hyperthyroidism, however, only a subgroup of the PTU-induced anti-MPO antibody positive patients developed clinical evident vasculitis. The aim of this study is to compare the titres and affinities of PTU induced anti-MPO antibodies in sera from patients with hyperthyroidism with and without clinical vasculitis. Anti-MPO antibody positive sera from patients diagnosed hyperthyroidism with (n = 13) and without (n = 14) clinical evident vasculitis were collected. The titre was determined by MPO-ELISA and expressed as logarithm value (lgT). The affinity constant (aK) of anti-MPO IgG was measured by antigen inhibition assay. The titre and aK values were compared between patients with and without vasculitis. In patients with vasculitis, the mean lgT of anti-MPO antibodies was 3.62 +/- 0.66; the median aK was 4.47 x 10(7)M(-1). In patients without vasculitis, the mean lgT was 2.54 +/- 0.29; the median aK was 0.14 x 10(7)M(-1), and both were significant lower than those in patients with vasculitis (t = 5.464; P = 0.000 & z = -4.373; P = 0.000, respectively). We concluded that the titre and affinity of anti-MPO antibodies might be associated with the development of clinical vasculitis in patients with PTU-induced ANCA.


Studies of interactions between fibronectin and a specific antibody against fibronectin using SPRi and QCM.
Surface Plasmon Resonance Imaging (SPRi) and the Quartz Crystal Microbalance (QCM) technique were used to characterize the interactions between fibronectin and a specific monoclonal antibody against fibronectin. These techniques were used to investigate the formation of successive layers of the biosensor and how they affect the biosensor's response. The analytical response of both detectors to fibronectin concentration is linear in the range 5-100 ng/mL. The changes in mass on the surface of a quartz crystal covered with a layer of gold during biosensor formation were investigated with a QCM. The equilibrium constant was determined to be KC = 1.22∙108 dm3/mol and the dissociation constant to be KD= 8.20 ∙ 10-9 mol/dm3.


[Is spectrophotometric analysis of the amniotic fluid a simple method for the determination of fetal pulmonary maturity? (author's transl)].
The samples of amniotic fluid from 55 transabdominal amniocenteses were examined with a simple spectrophotometric test for the predictive value on the risk of respiratory distress syndrome. There was a highly significant correlation between the lecithin content and the optical density of the amniotic fluid at 650 nm (r = 0.065 at p <0.001). No infant with an extinction threshold value of less than 0.15 had neonatal respiratory distress syndrome.


Implications of immune cells in oncolytic herpes simplex virotherapy for glioma.
Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune checkpoint inhibitors (ICIs) for GBM have shown anti-tumor efficacy in clinical trials. GBM has a characteristic immunosuppressive tumor microenvironment (TME) that results in the failure of ICIs. Oncolytic herpes simplex virotherapy (oHSV) is the most advanced United States Food and Drug Administration-approved virotherapy for advanced metastatic melanoma patients. Recently, another oHSV, Delytact®, was granted conditional approval in Japan against GBM, highlighting it as a promising treatment. Since oncolytic virotherapy can recruit abundant immune cells and modify the immune TME, oncolytic virotherapy for immunologically cold GBM will be an attractive therapeutic option for GBM. However, as these immune cells have roles in both anti-tumor and anti-viral immunity, fine-tuning of the TME using oncolytic virotherapy will be important to maximize the therapeutic efficacy. In this review, we discuss the current knowledge of oHSV, with a focus on the role of immune cells as friend or foe in oncolytic virotherapy.


Partial purification and characterization of pentalenene synthase.
Pentalenene synthase, an enzyme which catalyzes the cyclization of farnesyl pyrophosphate to the sesquiterpene hydrocarbon pentalenene, has been partially purified from the supernatant fraction of Streptomyces UC5319 by a combination of anion-exchange, hydroxylapatite, and gel-filtration chromatography. The molecular weight of the partially purified synthase was estimated by gel filtration chromatography to be 57,000 and the cyclase activity was shown to be associated with a major protein band among eight visible by nondenaturing polyacrylamide disc gel electrophoresis. The Km for farnesyl pyrophosphate was 0.77 +/- 0.21 microM and the Vmax for the partially purified synthase was 287 +/- 21 nmol of pentalenene/mg protein per hour. Cyclase activity required the presence of a divalent metal cation. Although either Mg2+ or Mn2+ could be used, Mn2+ was inhibitory at concentrations above 2.5 mM. No other cofactors were required. Whereas neither product, pentalenene nor inorganic pyrophosphate, showed significant inhibition of cyclase activity at concentrations of ca 10 microM, the combination of the two resulted in an approximate sevenfold increase in the apparent Km for farnesyl pyrophosphate, suggesting that both products can bind cooperatively at the active site to inhibit pentalenene synthase competitively.


Estimated burden of blood lead levels 5 microg/dl in 1999-2002 and declines from 1988 to 1994.
In light of recent data suggesting adverse health effects at blood lead levels (PbB) <10 microg/dl, lowering the current definition of elevated blood lead (>or=10 microg/dl) has been recommended. To ascertain the population level impact of such a change, we calculated the prevalence of PbB >or=5 microg/dl in 1-21-year-old population in the United States. Furthermore, we characterized changes in PbB between 1988-1994 and 1999-2002. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) III (n=10,755) and NHANES 1999-2002 (n=8013). In 1999-2002, about 91.7% of study children had detectable levels of lead in the blood. Among them, 7.3%, 2.8%, and 1.0% children and adolescents aged 1-5, 6-11, and 12-21 years, respectively, had PbB between 5 and 9.9 microg/dl. This number translates to approximately 2.4 million individuals. Between 1988-1994 and 1999-2002, the geometric mean PbB declined from 2.88 to 1.94 microg/dl in children 1-5 years, 1.80 to 1.36 microg/dl in children 6-11 years, and 1.24-1.02 microg/dl in children and adolescents 12-21 years of age. Also, the prevalence of PbB >or=5 microg/dl declined from 25.7% to 8.8%, 12.8% to 3.0%, and 7.5% to 1.2% in these age groups, respectively.A substantial proportion of children may be at risk for adverse health effects from lead exposure below 10 microg/dl and a large number of children will be classified as having elevated PbB if 5 microg/dl is considered the threshold. Significant public health resources will have to be mobilized for intervention, screening, and case management of these children.


Effects of anticonvulsant drugs on the cerebral enzymes metabolizing GABA.
The effect of anticonvulsant drugs on the activity of enzymes responsible for the further metabolism of GABA has been studied in mouse brain homogenates. Slight inhibition (5 to 20%) of GABA-T activity was seen with chlordiazepoxide (0.1 mM), ethosuximide (0.1 mM) and di-n-propylacetate (0.1 mM). No anticonvulsant drug (even at a concentration of 10 mM) produced inhibition comparable to that seen with amino-oxyacetic acid (65% at 0.01 mM). Succinic semialdehyde dehydrogenase activity was inhibited by 10 to 20% at low concentrations (0.01 to 0.1 mM) of diazepam, carbamazepine, beclamide, acetazolamide, and di-n-propylacetate, and by 40% or more at high concentrations (2.5 to 10.0 mM) of diazepam, phenobarbital, carbamazepine, beclamide, and di-n-propylacetate. Interference with the further metabolism of GABA may contribute to the antiepileptic action of drugs or to the acute neurological toxicity of anticonvulsant agents.


Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial.
We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.


Application of sol-gel based octyl-functionalized mesoporous materials coated fiber for solid-phase microextraction.
Octyl-functionalizd mesoporous SBA-15 was first used as precursor and selective stationary phase to prepare solid-phase microextraction (SPME) fiber by using the sol-gel technique. The new SPME coating possessed honeycomb-like porous structure and rough surface and showed excellent chemical stability and longer life span (over 200 cycles of usage). The performance of the octyl-SBA-15-coated fiber was tested through extraction of eight polycyclic aromatic hydrocarbons (PAHs). The results showed that the home-made SPME fiber exhibited higher extraction efficiency compared with the commercial SPME (30 μm and 100 μm PDMS) fibers. For PAHs analysis, the new fiber showed good precision (<4.8%), low detection limits (0.024-0.050 μg/L), and wide linearity (0.1-200 μg/L) under the optimized conditions. The repeatability of fiber-to-fiber and batch-to-batch was 3.2-8.4% and 4.4-9.5%, respectively. The method was applied to simultaneous analysis of eight PAHs with satisfactory recoveries in different spiking levels, which were 85.7-103.4% (10 μg/L) and 87.0-107.2% (50 μg/L) for water samples and 76.2-89.0% (10 μg/g) and 75.6%-91.2% (50 μg/g) for soil samples, respectively.


The Fabrication and Function of Strontium-modified Hierarchical Micro/Nano Titanium Implant.
Relying on surface topography alone to enhance the osteointegration of implants is still inadequate. An effective way to combine long-term ion release and surface topography to enhance osteogenic property is urgently needed. The objective of this study is to fabricate a long-term strontium ion release implant system and confirm the biological function in vitro and in vivo. The biomimic surface was fabricated through alkali-heat treatment and magnetron sputtering. The in vitro biological function assays were determined by MTT, fluorescence staining, alkaline phosphatase activity, extracellular mineralization, and quantitative real-time polymerase chain reaction assays. The in vivo experiments were detected by micro-CT, HE staining and Masson staining. The biomimic surface structure has been successfully fabricated. The in vitro cell assays determined that AH-Ti/Sr90 possessed the best biological function. The in vivo experiments demonstrated that AH-Ti/Sr90 could promote osteointegration significantly under both in normal and osteoporotic conditions. We determined that AH-Ti/Sr90 possesses the best osteogenic property, long-term ion release capacity and osteointegration promotion ability. It has potential clinic application prospects.


[A clinico-thermographic assessment of the efficacy of naphthalan therapy in patients with diabetic microangiopathies of the lower extremities].
Naphthalan was applied in 58 patients with diabetic microangiopathy of the lower limbs. Clinical and infra-red imaging proved high effectiveness of the treatment as naphthalan relieved symptoms of diabetic microangiopathy by means of correction of microcirculation and peripheral blood flow. Infra-red imaging showed that exercise and single procedure tests are able to give prognosis of the treatment effect. The success of naphthalan therapy is very important as microangiopathy of the lower limbs underlies serious complications in diabetics.


Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control.
Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n = 5) and (2) elite controllers (ECs; n = 6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes. Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were < 1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (< 1%); all VCs showed a high number of mutations, with significant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure. The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants.


No association of CTLA4 gene with celiac disease in the Basque population.
Celiac disease (CD) is an autoimmune disorder caused by intolerance to ingested gluten that develops in genetically susceptible individuals. The contribution of human leukocyte antigen (HLA) genes to the genetic risk to CD has been known for a long time; however, non-HLA genetic factors are likely to be required for the development of the disease. Several studies have associated the CD28/CTLA4 region on chromosome 2q33 with the disease in different populations. The CTLA4 gene encodes a receptor involved in the control of T-cell proliferation and mediates T-cell apoptosis. AIM To determine the contribution of two polymorphisms of the CTLA4 to the disease: the A/G dimorphism at position +49 in exon 1 and the (AT)(n) microsatellite in the 3' untranslated region. Forty-one celiac families of Basque origin (43 patients with CD and 80 first-degree relatives). Restriction enzyme digestion of polymerase chain reaction amplified genomic DNA for the A/G dimorphism and polymerase chain reaction followed by high-resolution electrophoresis for the (AT)(n) microsatellite. For disease association studies, the Affected Family Based Controls approach was used. The frequency of the A allele of 49 A/G polymorphism was 67.47% in the celiac allele group compared with 70.13% in the Affected Family Based Controls group. These differences were not significant. Analysis of the (AT)(n) polymorphism identified 17 different alleles, ranging from 262 to 312 bp in length, but no allele was significantly associated with the disease. Our results did not show any evidence of association of any of the CTLA4 gene polymorphisms with the disease. This may result from population-specific differences in genetics and environmental susceptibility to CD.


Adherence to the central line bundle in intensive care: An integrative review.
Central line-associated bloodstream infections (CLABSI) occurring in intensive care units are associated with increased morbidity and mortality, increased length of hospitalization, and cost of care associated with treating CLABSIs. The Centers for Disease Control and Prevention guidelines and checklist bundle are intended to provide evidence-based recommendations for the prevention of CLABSIs. Despite the promotion of central line bundle policies, wide variability exists in compliance and infection rates in intensive care units. To evaluate and synthesize the existing literature on adherence to the central line bundle recommendations for the prevention of CLABSI. Integrative literature review. CINHAL, PubMed, and SCOPUS databases were searched. Whittmore and Knafl's integrative review method. A total of 608 articles were identified, 407 articles were screened for topic of interest and adherence to the inclusion criteria, and 19 articles were included in this review. None of the 19 studies addressed adherence to all 14 recommendations of the central line bundle checklist. This integrative review identified gaps in adherence to the central line bundle. Research is needed to determine the actual adherence to each item in the bundle, and to investigate factors that contribute to nonadherence. To achieve complete compliance with all the bundle items creative and innovative technology is needed.


[The ambivalent role of spirituality in explaining conspiracy belief and protest intentions in the context of the COVID-19 pandemic].
In the course of the COVID-19-pandemic, groups that present themselves as anchors in problem solving and provide supposed solutions for dealing with insecurities are becoming increasingly visible. There seems to be a tendency for conspiracy belief and esoteric attitudes, which are increasingly being expressed in the protests against measures to contain the pandemic. This raises the question of the role of religious affiliations and spiritual worldviews within such groups. In the present study, spirituality is differentiated and measured independently of religion in order to shed light on these questions. The results show two forms of spirituality that differ in the dimensions of worldviews and ethics, values and meaning of life. Both forms can be found in religious as well as non-religious groups. Analyses show different effects of these forms of spirituality on the openness towards alternative and esoteric explanations of the world as well as a skepticism towards science. Additionally, all spiritual elements also contribute to clarifying the belief in conspiracy stories, the support of COVID-related demonstrations and the willingness to participate in these demonstrations. Active spirituality acts as a protective factor and passive spirituality as a reinforcing (risk) factor for these phenomena. Overall, this multi-dimensional measurement of spiritual worldviews can explain attitudes relevant to conspiracy belief and protests, and in this way can break down the previous ambivalent effects of spirituality as a resilience vs. risk factor for such attitudes.


Surgical treatment of intraventricular meningiomas in childhood.
In the last ten years (1973-1983) we operated and followed up 6 patients with intraventricular meningiomas, of these 4 were children and 2 adults. In 3 of the children the meningiomas occupied the lateral ventricles and were attached to the choroid plexus and the medial brain structures. The fourth childhood tumor was localized in the posterior third of the third ventricle. The first three children were operated by the established procedure for ventricular tumors, while the fourth was subjected to the procedure of Cl. Lapras (Lyon, France) for meningiomas and other tumors in the posterior part of the third ventricle. All four children survived the procedure. In the follow-up period they showed normal mental and physical development.


Contraction of the stapedius and tensor tympani muscles explored by tympanometry and pressure measurement in the external auditory canal.
It has been suggested that tensor tympani muscle (TTM) contraction may be involved in the development of ear-related pathologies such as tinnitus, hyperacusis and otalgia, called the tonic tensor tympani syndrome (TTTS). However, as there is no precise measure of TTM function under normal and pathological states, its involvement remains speculative. When the TTM or the stapedius muscle (SM) contracts, they both generate an increase of middle ear stiffness that can be measured through middle ear admittance. However, this technique cannot differentiate the contraction between the two muscles. On the other hand, the air pressure measured in a sealed external auditory canal can provide a measure of the eardrum displacement that may be able to differentiate SM from TTM contraction. TTM is attached to the malleus, and its contraction causes a retraction of the eardrum inside the middle ear cavity, while SM can have a small but reversed effect on TTM displacement. To investigate this issue, we compared the middle ear admittance and air pressure in a sealed external ear canal upon auditory stimulation (sMEMC) and voluntary middle ear muscle contraction (vMEMC). In addition, we assessed the perceptual effect of vMEMC, including pitch and loudness matching of the fluttering noise produced by vMEMC and the threshold shifts, were measured. Out of the 14 ears tested, sMEMC was associated with a decrease of admittance in 93% (mean peak average: -0.06 ml, SD:0.04) and an increase of air pressure in 29% of ears (mean peak average: 8.1 Pa, SD:5.1). No decrease in air pressure was found upon sMEMC. For vMEMC (n = 8 ears), decreases were found for both admittance and air pressure in 100% and 88%, with a mean peak average of -0.38 ml, SD: 0.54 and -149 Pa, SD:156, for admittance and pressure respectively. These results suggest that SM and TTM are involved in sMEMC and vMEMC, respectively. In addition, vMEMC was associated with perceptual effects including a low-frequency sound, pitch-matched at ∼30 Hz (>15 dB SL), and a low-frequency hearing loss of at least 10 dB between 20 and 200 Hz. In conclusion, admittance and air pressure recordings provide useful and complementary information on middle ear muscle contraction and can be used to explore the middle ear function.