Neovascular glaucoma following stereotactic radiosurgery for an optic nerve glioma: a case report.
A 13-year-old girl with a right intraorbital optic nerve glioma (ONG) was referred to our glaucoma clinic because of uncontrolled intraocular pressure (IOP) in her right eye. The IOP reached as high as 80 mmHg. Several months earlier, she had undergone stereotactic image-guided robotic radiosurgery using the CyberKnife for her ONG; the mass had become smaller after treatment. Her visual acuity was no light perception. Slit lamp examination revealed rubeosis iridis, a swollen pale optic disc, and vitreous hemorrhage. After medical treatment, the IOP decreased to 34 mmHg, and no pain was reported. Although the mass effect of an ONG can cause neovascular glaucoma (NVG), this case shows that stereotactic radiosurgery may also cause NVG, even after reducing the mass of the tumor. Patients who undergo radiosurgery targeting the periocular area should be followed carefully for complications.


Organochlorine pesticide residues in Italian citrus essential oils, 1991-1996.
Organochlorine pesticide contamination in 148 lemon essential oils, 123 sweet orange oils, 121 mandarin oils, and 147 bergamot oils produced in Italy in the years 1991-1996 was studied by HRGC-ECD. Confirmation analyses were carried out by GC-MS. Tetradifon, dicofol and its decomposition product 4,4'-dichlorobenzophenone were found. Over the course of the study dicofol and tetradifon residues steadily decreased; the percentage of contaminated samples reflects this course and decreases considerably from 1991 to 1996.


Downregulation of N-cadherin expression inhibits invasiveness, arrests cell cycle and induces cell apoptosis in esophageal squamous cell carcinoma.
Some studies have demonstrated that N-cadherin is upregulated in more invasive cancer cell lines and tumors and plays a key role in intercellular adhesion. However, the understanding on the roles N-cadherin plays in esophageal squamous cell carcinoma (ESCC) is still poor. Our data showed that knock-down of N-cadherin in ESCC cell line (EC9706) could arrest cell cycle at G0/G1 phase, induce cell apoptosis, reduce the invasiveness in vitro, and inhibit the tumor formation in vivo. These results suggest that N-cadherin is an important factor in the progression and metastasis of ESCC and N-cadherin may serve as a potential molecular target for biotherapy of ESCC.


NEXMIF pathogenic variants in individuals of Korean, Vietnamese, and Mexican descent.
NEXMIF pathogenic variants have been known to produce a wide spectrum of X-linked intellectual disability (ID) in both males and females. Thus far, few individuals from diverse populations have been described with NEXMIF-related disorders. Herein, we report three individuals with NEXMIF pathogenic variants, the first two are the only males of Korean and Vietnamese descent described with this disorder to our knowledge. The last patient is a Hispanic female who harbors the same pathogenic variant as a previously described Caucasian individual, but with differing clinical presentation. These patients present with many classic symptoms of NEXMIF-related disorders including ID, epilepsy, developmental delay, and dysmorphic features. In addition, they have symptoms that have not been thoroughly described in the literature, including allergies with multiple anaphylactic events and hypothyroidism. This report is intended to raise awareness and educate about the clinical signs that may prompt testing for NEXMIF-related disorders.


Role of the primary care physician in problems of substance abuse.
Patients with substance abuse problems are common in general medical practice and include people of all ages and socioeconomic groups. Initial diagnosis and treatment of addiction problems are often done by the primary care practitioner before referral to a specialist. This article provides information to help in recognition of addiction, guidelines for treatment of intoxication and withdrawal of various drugs of abuse (such as opioids, sedative-hypnotics, stimulants, hallucinogens, and volatile inhalants), and techniques for brief intervention as well as long-term care of substance-abusing patients. The physician can be a powerful influence for getting the patient to accept treatment, especially when the physician is empathic without being judgmental. Addiction is a chronic disorder with remissions and relapses like any other chronic disease, so exacerbations should not be seen as failures but as time to intensify treatment. Patients with substance abuse problems can be frustrating to treat, but it can also be a rewarding experience when a physician helps a substance-abusing patient return to normal and productive functioning in society.


Temporal correlation of measurements of airway hyperresponsiveness in ovalbumin-sensitized mice.
Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histological data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin or vehicle (saline) and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or 22; we studied the same mice 24 h later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared with the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge (days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, in the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by three-dimensional microscopy. We conclude that, although ovalbumin treatment changed lung function in mice, correlation between noninvasive and invasive measures of peak airway hyperresponsiveness was inconsistent.


Developmental Programming: Does Prenatal Steroid Excess Disrupt the Ovarian VEGF System in Sheep?
Prenatal testosterone (T), but not dihydrotestosterone (DHT), excess disrupts ovarian cyclicity and increases follicular recruitment and persistence. We hypothesized that the disruption in the vascular endothelial growth factor (VEGF) system contributes to the enhancement of follicular recruitment and persistence in prenatal T-treated sheep. The impact of T/DHT treatments from Days 30 to 90 of gestation on VEGFA, VEGFB, and their receptor (VEGFR-1 [FLT1], VEGFR-2 [KDR], and VEGFR-3 [FLT4]) protein expression was examined by immunohistochemistry on Fetal Days 90 and 140, 22 wk, 10 mo (postpubertal), and 21 mo (adult) of age. Arterial morphometry was performed in Fetal Day 140 and postpubertal ovaries. VEGFA and VEGFB expression were found in granulosa cells at all stages of follicular development with increased expression in antral follicles. VEGFA was present in theca interna, while VEGFB was present in theca interna/externa and stromal cells. All three receptors were expressed in the granulosa, theca, and stromal cells during all stages of follicular development. VEGFR-3 increased with follicular differentiation with the highest level seen in the granulosa cells of antral follicles. None of the members of the VEGF family or their receptor expression were altered by age or prenatal T/DHT treatments. At Fetal Day 140, area, wall thickness, and wall area of arteries from the ovarian hilum were larger in prenatal T- and DHT-treated females, suggestive of early androgenic programming of arterial differentiation. This may facilitate increased delivery of endocrine factors and thus indirectly contribute to the development of the multifollicular phenotype.


Leucine: tRNA Ligase from Cultured Cells of Nicotiana tabacum var. Xanthi: Evidence for de Novo Synthesis and for Loss of Functional Enzyme Molecules.
Leucine:tRNA ligase was assayed in extracts from cultured tobacco (Nicotiana tabacum) XD cells by measuring the initial rate of aminoacylation of transfer RNA with l-[4,5-(3)H]leucine. Transfer RNA was purified from tobacco XD cells after the method of Vanderhoef et al. (Phytochemistry 9: 2291-2304). The buoyant density of leucine:tRNA ligase from cells grown for 100 generations in 2.5 mm [(15)N]nitrate and 30% deuterium oxide was 1.3397. After transfer of cells into light medium (2.5 mm [(14)N]nitrate and 100% H(2)O) the ligase activity increased and the buoyant density decreased with time to 1.3174 at 72 hours after transfer. It was concluded that leucine:tRNA ligase molecules were synthesized de novo from light amino acids during the period of activity increase. The width at half-peak height of the enzyme distribution profiles following isopycnic equilibrium centrifugation in caesium chloride remained constant at all times after transfer into light medium providing evidence for the loss of preexisting functional ligase molecules. It was concluded that during the period of activity increase the cellular level of enzyme activity was determined by a balance between de novo synthesis and the loss of functional enzyme molecules due to either inactivation or degradation.


Biochemical screening of type I collagen in osteogenesis imperfecta: detection of glycine substitutions in the amino end of the alpha chains requires supplementation by molecular analysis.
The biochemical test for osteogenesis imperfecta (OI) detects structural abnormalities in the helical region of type I collagen as delayed electrophoretic migration of alpha chains on SDS-urea-PAGE. Sensitivity of this test is based on overmodification of alpha chains in helices with a glycine substitution or other structural defect. The limits of detectability have not been reported. We compared the collagen electrophoretic migration of 30 probands (types III or IV OI) with known mutations in the amino half of the alpha1(I) and alpha2(I) chains. Differences in sensitivity were examined by 5% and 6% SDS-urea-PAGE, and with respect to alpha chain, location along the chain, and substituting amino acid. Sensitivity was enhanced on 5% gels, and by examination of intracellular and secreted collagen. In alpha1(I), substitutions in the first 100 residues were not detectable; 7% of cases in the current Mutation Consortium database are in this region. alpha1(I) substitutions between residues 100 and 230 were variably detectable, while those after residue 232 were all detected. In alpha2(I), variability of electrophoretic detection extended through residue 436. About a third of cases in the Consortium database are located in the combined variable detection region. Biochemical sensitivity did not correlate with substituting residue. Complete testing of probands with normal type I collagen biochemical results requires supplementation by molecular analysis of cDNA or gDNA in the amino third of alpha1(I) and amino half of alpha2(I). Mutation detection in OI is important for counselling, reproductive decisions, exclusion of child abuse, and genotype-phenotype correlations.


Self-assessment of pain and discomfort in patients with temporomandibular disorders: a comparison of five different scales with respect to their precision and sensitivity as well as their capacity to register memory of pain and discomfort.
Five different scales of self-assessment of pain were tested in patients with temporomandibular disorders. The precision and sensitivity and the capacity to register memory of pain and discomfort were compared for each of the five scales. The behaviour rating scale was found to be superior to the other four scales in respect of precision and sensitivity to pain and discomfort and when recording the memory of these two variables. This scale was also considered by the patients to be the most relevant and the simplest to understand. From these results, the behaviour rating scale can be recommended when measuring pain and discomfort in patients with temporomandibular disorders.


Effects of torsion, detorsion and melatonin on testicular malondialdehyde level.
Unilateral testicular torsion is a cause of bilateral testicular damage, which has ischaemic and reperfusion components. The damage may involve lipid peroxidation leading to production of lipid peroxides in the testes, including malondialdehyde (MDA). To investigate the MDA variations in the ipsilateral and contralateral testes following ischaemia-reperfusion and the effect of melatonin. Mature adult male Sprague-Dawley rats were divided into 13 groups of 10 each. One control group underwent sham operation. Three groups were subjected to right sided testicular torsion by twisting the testes 720 degrees counterclockwise for one, three and five hours; three groups were subjected to de-torsion following torsion lasting one, three and five hours; three groups were treated with intra-peritoneal melatonin (1 mg/kg) before torsion lasting one, three and five hours, and three groups were treated with intra-peritoneal melatonin before de-torsion following torsion lasting one, three and five hours. At the end of the experiment all animals were sacrificed by decapitation and testes were collected for MDA level estimation. The MDA level was significantly higher in ipsilateral torted testis than the control testis in all groups (P < 0.05), with the levels increasing with the duration of torsion. Detorsion significantly increased the MDA level only if the initial torsion was for less than three hours. Melatonin did not significantly affect the MDA level in the ipsilateral testis if administered before torsion, but significantly reduced the level if administered before detorsion. Malondialdehyde levels are altered in the both testes following unilateral testicular torsion-detorsion injuries. The reperfusion component of the injury is significant and may be reduced by melatonin.


Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits.
A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response. In contrast, we report a potential underlying molecular program responsible for impairing neuronal crosstalk by scoring the transcriptomic and mutational profiles in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help predict the presence and subtype of metastasis.


Review of hemoglobin-induced myocardial lesions.
Over 100 preclinical studies in several small and large animal species were performed to evaluate the safety and efficacy of diaspirin cross-linked hemoglobin (DCLHb; Baxter Healthcare Corp.) as an oxygen therapeutic. During the preclinical evaluation of DCLHb, myocardial lesions were observed following the administration of DCLHb to certain species. These lesions were characterized as minimal to moderate, focal-to-multifocal myocardial degeneration and/or necrosis that were scored using a severity scale of minimal to marked in relative severity. The lesions were typically observed 24-48 h after single topload infusions of DCLHb into rhesus monkeys or pigs at doses as low as 200 or 700 mg/kg, respectively. Dogs, sheep, and rats did not develop these lesions after single-dose administrations of DCLHb. The left ventricular myocardium, typically near the base of or including the papillary muscles, was the most severely affected region, followed by the intraventricular septum and the right ventricle. The left and right atria were usually not affected. In a study in rhesus monkeys, morphometric analysis revealed that these lesions comprised less than 3% of the total myocardium. Although increases in serum enzyme activities (AST, CK, LDH) were observed after infusion of DCLHb, myocardial-related isoenzymes did not increase. ECG analysis and echocardiography were not altered by these lesions, and there was no observable adverse effect on myocardial function. Polymerization of DCLHb reduced, but did not eliminate, the incidence and severity of the lesions. However, infusion of hemoglobin solutions with reduced reaction rates with nitric oxide (NO) resulted in a significant decrease in lesion incidence and severity, while administration of L-NAME, an NO synthase inhibitor, resulted in the appearance of lesions that were indistinguishable from those induced by hemoglobin, suggesting that reduction in normal NO levels is an important mechanistic factor. Overall, the presence of myocardial lesions represents a histopathologic finding that must be considered during the preclinical testing and development of new HBOCs.


pH and Thermo Dual-Responsive Fluorescent Hydrogel Actuator.
As one of the most important smart materials, fluorescent hydrogel actuators can produce both color and shape changes under external stimuli. In the present work, an effective approach to develop a novel fluorescent hydrogel actuator with pH and thermo dual responsiveness is proposed. Through incorporating pH-responsive perylene tetracarboxylic acid (PTCA), which is a typical fluorescent moiety with aggregation-caused quenching (ACQ) effect, into an anisotropic poly(N-isopropylacrylamide)-polyacrylamide (PNIPAm-PAAm) structure, the obtained hydrogel exhibits stable thermoresponsive shape deformation and switchable fluorescence performance upon a pH trigger. Therefore, fluorescence-quenching-based and actuation-based information can be revealed when exposed to UV light and immersed into warm water, respectively. Moreover, the thermoresponsive actuating behavior can be applied to further hide the fluorescence-quenching-based images. The present work may provide new insights into the design and preparation of novel stimuli-responsive hydrogel actuators.


Canine dysautonomia in a litter of Havanese puppies.
Canine dysautonomia is a sporadic, generally fatal disease that rarely affects groups of related animals. Four 10-week-old Havanese puppies from a litter of 5 developed clinical signs of canine dysautonomia. The 4 affected dogs were exposed to an outdoor environment, whereas the fifth littermate was not exposed to the outdoors and remained clinically healthy. Clinical signs of dysautonomia developed 10-16 days after going outside the house. An unrelated dog also developed dysautonomia after exposure to 1 of the affected Havanese littermates. All 5 dogs had morphological changes consistent with dysautonomia (widespread neuronal degeneration in autonomic ganglia, select brainstem nuclei, and ventral horn motor neurons). Differential diagnoses were excluded through negative toxicological evaluation, fecal parasite screening, negative Canine distemper virus reverse transcription polymerase chain reaction, fluorescent antibody testing, attempted virus isolation, and electron microscopy. The 5 affected dogs were in the Kansas City, Missouri area, where there is a high incidence of dysautonomia.


The regulative capacity of prespore amoebae as demonstrated by fluorescence-activated cell sorting and green fluorescent protein.
The ability of prespore Dictyostelium discoideum amoebae to undergo redifferentiation so as to reestablish normal spore/stalk proportioning has been demonstrated in various ways over the years, beginning with the classic microdissection work of K. Raper. The discovery of anterior-like cells in the slug posterior, however, cast doubt on that ability, and more recent experiments using a cell-specific toxin suggested that prespore redifferentiation may not in fact occur. To reexamine this question, we performed fluorescence-activated cell sorting (FACS) upon amoebae expressing a mutated green fluorescent protein gene (S65T-GFP) under the control of a prespore-specific (PsA) promoter. FACS produced prespore cell populations with purities, measured by GFP expression, as high as 99. 5%. Sorted GFP(+) cells were developmentally competent and produced normally proportioned fruits, indistinguishable from those of "sham-sorted" (permissively gated, mixed GFP(+) and GFP(-)) amoebae. This result confirms the developmental totipotency of prespore amoebae.


Survival Analysis Using Albumin-Bilirubin (ALBI) Grade for Patients Treated with Drug-Eluting Embolic Transarterial Chemoembolization for Hepatocellular Carcinoma.
The albumin-bilirubin (ALBI) grade has been established as an improved predictor of survival in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization and yttrium-90 radioembolization. The purpose of the study was to investigate the utility of ALBI grade in prognosticating outcomes in patients with HCC treated with drug-eluting embolic (DEE) transarterial chemoembolization (TACE). A single-center retrospective review was performed to compare the efficacy of ALBI grade and Child-Pugh (CP) classification in predicting the survival of patients with HCC receiving DEE-TACE. A total of 303 patients with HCC were identified who had received DEE-TACE without concomitant locoregional therapy within 30 days. Survival analysis was performed using Kaplan-Meier methods and censored for curative therapy. Survival curves were stratified based on the ALBI grade, CP class, Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group performance status, and presence of ascites. The discriminatory ability of survival curves was calculated by C-Index. Kaplan-Meier survival curves stratified by the ALBI grade produced distinct, nonoverlapping curves (P < .001), showing greater discriminatory ability than the CP classification (C-index = 0.568 and 0.545, respectively). The substratification of the BCLC stage by the ALBI grade yielded greater discriminatory ability than the substratification by the CP classification (C-index = 0.573 and 0.565, respectively). For patients with BCLC stage B, the substratification by the ALBI grade yielded distinct curves, whereas the substratification by the CP classification did not (P = .011 and P = .379, respectively). ALBI grade showed improved discriminatory ability compared with CP classification in differentiating overall survival among patients with HCC receiving DEE-TACE. Furthermore, ALBI grade was effective in substratifying survival among patients categorized as CP class A and patients with BCLC stage B, whereas CP classification was not effective.


Charge-dependent insertion of beta-lactoglobulin into monoglyceride monolayers.
The interactions between beta-lactoglobulin and 1-monostearoyl-glycerol were studied in order to gain insight into protein-gel-phase monoglyceride interactions. Using a monomolecular layer at the air-water interface, we determined the insertion of beta-lactoglobulin into the monoglycerides under different conditions of protein and surface charge by varying the pH and/or incorporating charged amphiphiles into the monolayer, respectively, and using subphases with either a low or high ionic strength. The interactions were quantified by determining the binding of 14C-labeled beta-lactoglobulin to the monolayer. Our results show the importance of electrostatics for binding of beta-lactoglobulin to condensed monoglycerides. Moreover, electrostatic interactions were found to be important for specific insertion of beta-lactoglobulin into the monolayer. A negatively charged surface in particular allowed positively charged beta-lactoglobulin to insert in a surface charge density-dependent manner, even at surface pressures as high as 36 mN/m, whereas under other conditions, the limiting insertion pressure was 32 mN/m. The rheological properties of the monolayer were not affected by the interactions with beta-lactoglobulin.


An update on mosquito cell expressed dengue virus receptor proteins.
Dengue is the most important mosquito transmitted viral disease of humans worldwide. Despite intensive study over several decades, many of the fine details of the dengue virus (DENV) replication cycle remain unknown, although generally more is known about the phase of the replication cycle in mammalian cells as compared to the phase in mosquito cells. This results from a combination of less research emphasis on the mosquito stage, as well as fewer tools such as specific antibodies against mosquito proteins and insect informatics databases. The binding of a virus to a host cell is a first and critical stage in the infectious process and the mechanism and identity of cellular proteins involved in this process remains largely unknown. This short review aims to provide an update on our current understanding of the proteins expressed by mosquito cells that mediate DENV binding as a prerequisite to DENV entry and replication.


CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis.
Centrosomal protein 120 (CEP120) was originally identified as a daughter centriole-enriched protein that participates in centriole elongation. Recent studies showed that CEP120 gene mutations cause complex ciliopathy phenotypes in humans, including Joubert syndrome and Jeune asphyxiating thoracic dystrophy, suggesting that CEP120 plays an additional role in ciliogenesis. To investigate the potential roles of CEP120 in centriole elongation and cilia formation, we knocked out the CEP120 gene in p53-deficient RPE1 cells using the CRISPR/Cas9 editing system, and performed various analyses. We herein report that loss of CEP120 produces short centrioles with no apparent distal and subdistal appendages. CEP120 knockout was also associated with defective centriole elongation, impaired recruitment of C2CD3 and Talpid3 to the distal ends of centrioles, and consequent defects in centriole appendage assembly and cilia formation. Interestingly, wild-type CEP120 interacts with C2CD3 and Talpid3, whereas a disease-associated CEP120 mutant (I975S) has a low affinity for C2CD3 binding and perturbs cilia assembly. Together, our findings reveal a novel role of CEP120 in ciliogenesis by showing that it interacts with C2CD3 and Talpid3 to assemble centriole appendages and by illuminating the molecular mechanism through which the CEP120 (I975S) mutation causes complex ciliopathies.


Tissue expansion of the head and neck. Indications, technique, and complications.
Tissue expansion is indicated in the reconstruction of various defects of the head and neck in instances where there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It may also be indicated in instances where repair of a defect by an alternative method such as a local, regional, or distant flap will result in an unacceptable donor or recipient site deformity. Although tissue expansion is simplistic in concept, it does require judgment and indepth preoperative planning to ensure optimal results. The complication rate is high for tissue expansion in the head and neck, particularly in the cheek and neck area. Despite the frequency of complications, in the vast majority of cases the intended reconstruction is successful.


[Role of androgen in the elderly. Modulation of synaptic plasticity by brain-synthesized androgens].
Recently, brain synthesis of androgen and estrogen has been extensively investigated. Steroidogenic enzymes and receptors are expressed in glutamatergic neurons. The expression levels of mRNA or proteins for enzymes are as low as 1/200 - 1/1,000. However, hippocampal levels of androgen and estrogen are much higher than those of plasma. This is due to the fact that the volume of hippocampus is as small as 1/200 of the blood vessels. Androgen and estrogen can rapidly modulate synaptic plasticity of neural circuits. After andropause or menopause, the levels of androgen and estrogen in the hippocampus may significantly decrease, inducing dementia, Alzheimer's or depression. Hormone replacement therapy is valid for rescue of memory function, therefore synthesis and action of hippocampal androgen and estrogen is an important field for investigations.


A review of lung-to-blood absorption rates for radon progeny.
The International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) treats clearance of materials from the respiratory tract as a competitive process between absorption into blood and particle transport to the alimentary tract and lymphatics. The ICRP recommended default absorption rates for lead and polonium (Type M) in ICRP Publication 71 but stated that the values were not appropriate for short-lived radon progeny. This paper reviews and evaluates published data from volunteer and laboratory animal experiments to estimate the HRTM absorption parameter values for short-lived radon progeny. Animal studies showed that lead ions have two phases of absorption: ∼10 % absorbed with a half-time of ∼15 min, the rest with a half-time of ∼10 h. The studies also indicated that some of the lead ions were bound to respiratory tract components. Bound fractions, f(b), for lead were estimated from volunteer and animal studies and ranged from 0.2 to 0.8. Based on the evaluations of published data, the following HRTM absorption parameter values were derived for lead as a decay product of radon: f(r) = 0.1, s(r) = 100 d(-1), s(s) = 1.7 d(-1), f(b) = 0.5 and s(b) = 1.7 d(-1). Effective doses calculated assuming these absorption parameter values instead of a single absorption half-time of 10 h with no binding (as has generally been assumed) are only a few per cent higher. However, as there is some conflicting evidence on the absorption kinetics for radon progeny, dose calculations have been carried out for different sets of absorption parameter values derived from different studies. The results of these calculations are discussed.


The effect of fertility treatment on adverse perinatal outcomes in women aged at least 40 years.
To compare perinatal outcomes between spontaneous conception and assisted reproductive technologies (ART) among patients of advanced maternal age. The present retrospective study included data from singleton pregnancies of women aged at least 40 years who delivered between January 1, 1991, and December 31, 2013, at Soroka University Medical Center, Beer Sheva, Israel. Demographic, obstetric, and perinatal data were compared between pregnancies conceived with ART (in vitro fertilization [IVF] or ovulation induction) and those conceived spontaneously. Multiple regression models were used to define independent predictors of adverse outcomes. A total of 8244 singleton pregnancies were included; 229 (2.8%) following IVF, 86 (1.0%) following ovulation induction, and 7929 (96.2%) were spontaneous. Preterm delivery (P<0.001), fetal growth restriction (FGR) (P<0.001), and cesarean delivery (P<0.001) demonstrated linear associations with the conception mode; the highest rates for each were observed for IVF, with decreased rates for ovulation induction and spontaneous conception. The incidence of gestational diabetes and hypertensive disorders were highest among pregnancies following ART. No association was observed between conception mode and perinatal mortality. Multivariate logistic regression demonstrated that IVF was independently associated with increased odds of preterm delivery (P<0.001) and FGR (P=0.027) compared with spontaneous conception. Among patients of advanced maternal age, ART were independently associated with increased FGR and preterm delivery rates compared with spontaneous pregnancies; perinatal mortality was comparable.


Prosthetic rehabilitation of a maxillofacial defect in a chondrosarcoma patient.
Chondrosarcoma is a malignant tumor in which the tumor cells produce cartilage but not bone. The recommended management is wide local or radical excision, followed by surgical and prosthetic reconstruction. This article explains postsurgical prosthetic rehabilitation of a chondrosarcoma patient by means of intraoral acrylic, and extraoral silicone prosthesis for restoration of normal orofacial function and appearance.


Crystallographic analysis of active site contributions to regiospecificity in the diiron enzyme toluene 4-monooxygenase.
Crystal structures of toluene 4-monooxygenase hydroxylase in complex with reaction products and effector protein reveal active site interactions leading to regiospecificity. Complexes with phenolic products yield an asymmetric μ-phenoxo-bridged diiron center and a shift of diiron ligand E231 into a hydrogen bonding position with conserved T201. In contrast, complexes with inhibitors p-NH(2)-benzoate and p-Br-benzoate showed a μ-1,1 coordination of carboxylate oxygen between the iron atoms and only a partial shift in the position of E231. Among active site residues, F176 trapped the aromatic ring of products against a surface of the active site cavity formed by G103, E104 and A107, while F196 positioned the aromatic ring against this surface via a π-stacking interaction. The proximity of G103 and F176 to the para substituent of the substrate aromatic ring and the structure of G103L T4moHD suggest how changes in regiospecificity arise from mutations at G103. Although effector protein binding produced significant shifts in the positions of residues along the outer portion of the active site (T201, N202, and Q228) and in some iron ligands (E231 and E197), surprisingly minor shifts (<1 Å) were produced in F176, F196, and other interior residues of the active site. Likewise, products bound to the diiron center in either the presence or absence of effector protein did not significantly shift the position of the interior residues, suggesting that positioning of the cognate substrates will not be strongly influenced by effector protein binding. Thus, changes in product distributions in the absence of the effector protein are proposed to arise from differences in rates of chemical steps of the reaction relative to motion of substrates within the active site channel of the uncomplexed, less efficient enzyme, while structural changes in diiron ligand geometry associated with cycling between diferrous and diferric states are discussed for their potential contribution to product release.


Medicaid eligibility patterns for persons with AIDS in California and New York, 1982-1987.
An analysis of Medicaid eligibility patterns for persons with AIDS (PWAs) was conducted, based on the longitudinal Medicaid eligibility histories of 1,314 AIDS decedents in California and 6,273 AIDS decedents in New York between 1982 and 1987. The study analyzed what eligibility groups or categories and which financial standards PWAs were using to qualify for Medicaid. States have many options with regard to the categories of people they cover under Medicaid and where they set their financial thresholds. The study findings are useful in showing how these policy decisions affect PWAs. A major conclusion of the study is the importance of medically needy coverage for PWAs. Medically needy coverage, which is optional to states, opens up Medicaid to persons of any income level, assuming their medical expenses are high enough. The study also found that PWAs who qualify only through the medically needy provisions have much shorter enrollment and lower lifetime Medicaid expenditures than other PWAs on Medicaid. Presumably, most medically needy only enrollees have other sources of health care coverage in the early stages of the illness. Study data also suggested significant administrative obstacles for PWAs in dealing with the Medicaid eligibility process. Finally, an unexpected study result was that all states may not be aggressively utilizing federal Medicaid financing options for covering the medical assistance expenditures for a significant proportion of the low-income AIDS population.


Recombination between homoeologous chromosomes induced in durum wheat by the Aegilops speltoides Su1-Ph1 suppressor.
Su1-Ph1, which we previously introgressed into wheat from Aegilops speltoides, is a potent suppressor of Ph1 and a valuable tool for gene introgression in tetraploid wheat. We previously introgressed Su1-Ph1, a suppressor of the wheat Ph1 gene, from Aegilops speltoides into durum wheat cv Langdon (LDN). Here, we evaluated the utility of the introgressed suppressor for inducing introgression of alien germplasm into durum wheat. We built LDN plants heterozygous for Su1-Ph1 that simultaneously contained a single LDN chromosome 5B and a single Ae. searsii chromosome 5Sse, which targeted them for recombination. We genotyped 28 BC1F1 and 84 F2 progeny with the wheat 90-K Illumina single-nucleotide polymorphism assay and detected extensive recombination between the two chromosomes, which we confirmed by non-denaturing fluorescence in situ hybridization (ND-FISH). We constructed BC1F1 and F2 genetic maps that were 65.31 and 63.71 cM long, respectively. Recombination rates between the 5B and 5Sse chromosomes were double the expected rate computed from their meiotic pairing, which we attributed to selection against aneuploid gametes. Recombination rate between 5B and 5Sse was depressed compared to that between 5B chromosomes in the proximal region of the long arm. We integrated ND-FISH signals into the genetic map and constructed a physical map, which we used to map a 172,188,453-bp Ph1 region. Despite the location of the region in a low-recombination region of the 5B chromosome, we detected three crossovers in it. Our data show that Su1-Ph1 is a valuable tool for gene introgression and gene mapping based on recombination between homoeologous chromosomes in wheat.


Psychometric properties of the Spanish version of the Fear of COVID-19 scale in Paraguayan population.
The aim of this study is to test the psychometric properties of the Spanish validation of the Fear of COVID-19 Scale (FCV-19S) in a Paraguayan population. Participants were recruited through an Internet-based survey. All participants whose scores in the Hospital Anxiety and Depression Scale (HADS) and The Fear Questionnaire (FQ) were greater than zero were included. 1245 subjects responded voluntarily: 1077 subjects, scoring >0, were considered. To establish construct validity of the FCV-19S, an exploratory factor analysis was performed using the KMO test, which was adequate, and the Bartlett sphericity test, which was significant (p <.0001). The CFI, NFI, GFI, TLI and RMSEA indices were used to evaluate the model and showed good adjustment. Cronbach's α showed valid internal consistency (α = 0.86). This validation was supported by significant correlation (p <.001) with the HADS scale for anxiety and depression and with the FQ scale for specific phobia. The Spanish version of the FCV-19S is a 7-item scale with two dimensions, psychological symptoms and physiological symptoms, which demonstrated robust psychometric properties in a Paraguayan population.


Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex.
Clinical and preclinical evidence suggest a role of nicotinic acetylcholine receptors in major depression. In humans, both nicotine and the nonselective nicotinic acetylcholine receptor antagonist mecamylamine ameliorate depressive symptoms. Similarly, both drugs produce antidepressant-like effects in rodents. In rats, the most consistent finding is antidepressant-like effects of nicotine, but not mecamylamine. Conversely, in mice, several studies show antidepressant-like effects of mecamylamine, whereas nicotine has shown modest or no effects. These contradictory results might be because of genetic differences. Here, we compared the effects of nicotine and mecamylamine in females and males of NMRI, C57BL/6J and BALB/c mice using the mouse forced swim (mFST) and tail suspension tests (mTST). In the mFST, mecamylamine, but not nicotine, increased swim distance in NMRI mice. In contrast, nicotine, but not mecamylamine, increased swim distance in C57BL/6J mice. Both drugs increased swim distance in BALB/c mice. Effects in the mFST were independent of sex. In the mTST, mecamylamine decreased immobility in NMRI mice only, independent of sex. Nicotine was devoid of effects in the mTST, except in female C57BL/6J mice, where it increased immobility. We hypothesize that nicotine and mecamylamine produce antidepressant-like effects through partially different mechanisms.


Plasticity of neuropeptidergic neoplasm cells in the primary and metastatic Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous carcinoma with characteristics of neuroendocrine tumor. We performed immunohistochemical analysis to demonstrate the presence of various neuropeptides within cells of MCC resected from a 75-year old woman. The cells of primary tumor of cheek were compared with the cells of regional right submandibular metastatic tumor which was found eight months later. A double- staining IHC for the pan-neuronal marker, PGP 9.5, and selected neuropeptides in the tissue material obtained from both locations was performed. Single multipolar cells in the main mass of primary tumor stained positively for PGP 9.5 and such neuropeptides as GAL, VIP, PACAP, NPY and CGRP. Moreover, we demonstrated for the first time the presence of neuropeptides in metastatic MCC cells. In the metastatic tumor, cells showing the co-localization of PGP-9.5 and neuropeptides were more numerous, mostly of oval shape, and significantly smaller than in the primary tumor. Thus, the progression of MCC may be associated with the acquisition by its cells of new morphological and biological features.


Critical Preoperative Hemoglobin Value to Predict Anemia-Related Complications After Cardiac Surgery.
Preoperative anemia is frequent in patients undergoing cardiac surgery and is associated with increased postoperative complications. The purpose of this observational study was to estimate the critical preoperative hemoglobin threshold associated with the occurrence of complications after cardiac surgery. A retrospective observational cohort study. A tertiary-care medical center from January 2019 to April 2020. A total of 1,004 patients undergoing elective cardiac surgery were included. None (observational study). The primary study endpoint was to define the hemoglobin threshold that predicted the occurrence of postoperative major complications after elective cardiac surgery. Postoperative complications were a composite criterion, including transient ischemic attack or stroke, myocardial infarction, acute kidney injury, respiratory failure, mediastinitis, or mesenteric ischemia. A discrimination threshold was determined by using receiver operating characteristic curves. The discrimination threshold for hemoglobin concentration with the best sensitivity/specificity ratio for the occurrence of postoperative complications was 13 g/dL for male patients and 11.8 g/dL for female patients. The incidence of postoperative complications was 17.2% in the total population. Independent risks were preoperative hemoglobin concentration, red blood cell transfusion, European System for Cardiac Operative Risk Evaluation II, and the type of surgery. The critical preoperative hemoglobin thresholds associated with the occurrence of postoperative complications with the best sensitivity/specificity ratio were 13 g/dL for men and 11.8 g/dL for women, which were very similar to the World Health Organization criteria defining anemia.


Venlafaxine and asthma.
A 54-year-old man of Asian origin with major depression developed an asthma-like reaction during venlafaxine treatment. Two weeks after therapy was initiated, he experienced gradually worsening dry cough at night and periodically dyspnea during the daytime. After 5 weeks, clinical examination revealed marked signs of pulmonary obstruction and the forced expiratory volume (FEV1) was assessed to only 32% of the expected value. The venlafaxine medication was gradually decreased and eventually discontinued 9 weeks after its initiation, resulting in a successive improvement of the patient's respiratory complaints.


Severe cerebellar hemorrhage following transverse sinus stenting for idiopathic intracranial hypertension.
We report a severe adverse event occurring in the course of a cohort study (ISRCTN13784335) aimed at measuring the efficacy and safety of venous stenting in the treatment of patients with medically refractory idiopathic intracranial hypertension (IIH). The patient was a 41-year-old woman who was not overweight, who presented with severe headache, grade 1 bilateral papilledema and transient tinnitus, refractory to medical treatment. Right transverse sinus stenting was successfully performed. Following surgery, the patient's state of consciousness decreased acutely with rapid and progressive loss of brainstem reflex. CT scan revealed acute cerebellar and intraventricular hemorrhage with obstructive hydrocephalus. Angioscan revealed normal venous sinus patency and cerebral MRI showed acute mesencephalic ischemia. Mechanical impairment of cerebellar venous drainage by the stent or venous perforation with the large guidewire used in this technique are two logical ways to explain the cerebellar hemorrhage seen in our patient. The risk of such a complication could probably be reduced using alternative tools and technique. However, given the low level of evidence around the safety of transverse sinus stenting in IIH, its formal assessment in clinical trials is required.


Moisture-responsive graphene paper prepared by self-controlled photoreduction.
A facile and cost-effective preparation of moisture-responsive graphene bilayer paper by focused sunlight irradiation is reported. The smart graphene paper shows moisture-responsive properties due to selective adsorption of water molecules, leading to controllable actuation under humid conditions. In this way, graphene-based moisture-responsive actuators including a smart claw, an orientable transporter, and a crawler paper robot are successfully developed.


Using chimeric piggyBac transposase to achieve directed interplasmid transposition in silkworm Bombyx mori and fruit fly Drosophila cells.
The piggyBac transposon has been long used to integrate foreign DNA into insect genomes. However, undesirable transgene expression can result from random insertions into the genome. In this study, the efficiency of chimeric Gal4-piggyBac transposase in directing integration onto a DNA target plasmid was evaluated in cultured silkworm Bombyx mori Bm-12 and fruit fly Drosophila Schneider 2 (S2) cells. The Gal4-piggyBac transposase has a Gal4 DNA-binding domain (DBD), and the target plasmid has upstream activating sequences (UAS) to which the Gal4 DBD can bind with high affinity. The results indicate that, in the Bm-12 and S2 cells, transpositional activity of Gal4-piggyBac transposase was increased by 4.0 and 7.5 times, respectively, compared to controls, where Gal4-UAS interaction was absent. Moreover, the Gal4-piggyBac transposase had the ability of directing piggyBac element integration to certain sites of the target plasmid, although the target-directing specificity was not as high as expected. The chimeric piggyBac transposase has the potential for use in site-directed transgenesis and gene function research in B. mori.


Specific activation of the alpha 7 nicotinic acetylcholine receptor by a quaternary analog of cocaine.
Effects of cocaine and cocaine methiodide were evaluated on the homomeric alpha 7 neuronal nicotinic receptor (nAChR). Whereas cocaine itself is a general nAChR noncompetitive antagonist, we report here the characterization of cocaine methiodide, a novel selective agonist for the alpha 7 subtype of nAChR. Data from (125)I-alpha-bungarotoxin binding assays indicate that cocaine methiodide binds to alpha 7 nAChR with a K(i) value of approximately 200 nM while electrophysiology studies indicate that the addition of a methyl group at the amine moiety of cocaine changes the drug's activity profile from inhibitor to agonist. Cocaine methiodide activates alpha 7 nAChR with an EC(50) value of approximately 50 microM and shows comparable efficacy to ACh in oocyte experiments. While agonist effects are specific for the alpha 7 neuronal nAChR and are not observed with heteromeric neuronal or skeletal muscle nAChR, antagonist effects are present for heteromeric nAChR combinations. Studies of PC12 cells transiently transfected with human alpha 7 cDNA and expressing a variety of functional nicotinic receptor subtypes confirm the specificity of cocaine methiodide agonist effects. Our results indicate that a quaternary structural derivative of cocaine can be used as a specific agonist for the alpha 7 subtype of neuronal nicotinic receptor.


Effects of Composition Segregation in PMN-PT Crystals on Ultrasound Transducer Performance.
This study investigates the relationship between the composition segregation in lead magnesium niobate-lead titanate (PMN-PT; PMN-29%PT, PMN-29.5%PT, PMN-30%PT, PMN-30.5%PT, and PMN-31%PT) single crystals within morphotropic phase boundary (MPB) and the corresponding ultrasonic transducer performance through PiezoCAD modeling and real transducer testing. For five crystals with compositions distributed across the main body of a crystal ingot, the piezoelectric coefficient and free relative permittivity values were measured to vary by over 30%, whereas the transducer bandwidth and center frequency values were modeled to change by less than 10%. For the single-element ultrasonic transducers fabricated using those crystals without matching layers, the variations of -6-dB bandwidth, insertion loss, receiver-free field voltage response, and center frequency were measured to be 9.61%, -15.23%, 9.76%, and 1.41%, respectively, confirming the modeling results. Using the Mason and Krimholtz, Leedom, and Matthaei (KLM) models, it is found that the relatively stable transducer performance can be attributed to the relatively consistent electromechanical coupling coefficient, acoustic impedance, and clamped relative permittivity originated from the stable elastic compliance properties among the crystals of various compositions. It is expected that the relatively stable performance could be extended to multielement transducers with matching layers for the same contributing mechanisms. Our results suggest that it is possible to use crystal plates of different compositions within the MPB region, obtained from one and the same ingot, to fabricate a batch of ultrasonic transducers that will exhibit a similar performance, significantly reducing the cost of materials.


[Effect of anxiolytic drugs on the development and healing process of stress ulcer: application of endoscopic observation].
The present study was conducted to investigate the effect of anxiolytic drugs on the development and healing process of gastric mucosal lesions (GML). In order to produce the GML in mice and rats, we employed a communication box paradigm which can differentially induce a physical and psychological stress. The following drugs (2.5, 50.0, 7.5 mg/kg for mice and 5.0, 10.0 mg/kg for rats) were administered orally: diazepam, clotiazepam, ethyl loflazepate and vehicle (0.5% CMC solution). To define the drug effects on the healing process of GML in rats, we applied an endoscopic technique using the ultra-thin fiberscope. The endoscopic observation was performed under ether anesthesia at 1, 24, 36 and 60 hr after the termination of stress. Both diazepam and ethyl loflazepate significantly suppressed the development of GML in mice, while the preventive effect of clotiazepam was less potent than those of the other anxiolytics. In rats, only ethyl loflazepate showed a significant preventive effect. The curative effect of clotiazepam on the healing process of GML in rats was clearly demonstrated, whereas diazepam was ineffective on the healing process. Ethyl loflazepate also showed a tendency to facilitate the healing process of GML. The present study suggests that the application of the endoscopic technique to rats may provide a potential tool for evaluating the curative effect of drugs on the GML.


The parent between the child and the professional--some ethical implications.
In this paper ethical implications of parental participation in paediatric care are discussed. The paper is based on interviews with 20 parents, whose children were admitted and operated on at a paediatric surgery department in Sweden. In one part of the interview the parent was invited to speak about situations experienced as problematic during the hospitalization. Three different types of situations were described by the parents as especially problematic. In the first situation the parents' ability to influence their own situation was limited. Parents got upset when staff did not treat them as autonomous persons. In the second type of situation things 'had to be done' to the child, for example the surgery, the anaesthesia, removing an indwelling catheter and giving an enema. The parents understood and accepted this, but the child was sometimes unable to agree usually because of anxiety and fear. In the third type of situation parents felt that professionals did not take them or their child seriously. In order to avoid or alleviate such situations, the professionals ought to mediate a permissive attitude to the expressions of concern. Thus, when the parents worry, the professionals ought to listen more attentively and, whenever possible and adequate, respect their concerns.


A combination of quinidine/mexiletine reduces arrhythmia in dilated cardiomyopathy in two patients with R814W SCN5A mutation.
SCN5A gene mutations are described in 2% of patients with dilated cardiomyopathy (DCM) and different rhythm disturbances, including multifocal ectopic Purkinje-related premature contractions. Recent data indicate that sodium channel blockers are particularly effective monotherapy in carriers of the R222Q SCN5A variant. Our purpose is to describe the effectiveness of antiarrhythmic treatment in a family with genetically determined arrhythmogenic DCM associated with the R814W variant in the SCN5A gene. We examined a family with arrhythmogenic DCM (multifocal ectopic Purkinje-related premature contractions phenotype, atrial tachyarrhythmias, automatism, and conduction disorders) and described antiarrhythmic treatment efficacy in heart failure symptoms reduction and myocardial function improvement. We found a heterozygotic mutation R814W in SCN5A by whole exome sequencing in the proband and confirmed its presence in all affected subjects. There were two sudden cardiac deaths and one heart transplantation among first-degree relatives. The 58-year-old father and his 37-year-old daughter had full spectrum of symptoms associated with R814W SCN5A mutation. Both had implanted cardioverter defibrillator. In the father, adding mexiletine to quinidine therapy reduced ventricular arrhythmia (50-60% → 6-8% of whole rhythm) and reverted long-standing atrial fibrillation to sinus rhythm. In the daughter, mexiletine and overdrive pacing were effective in ventricular arrhythmia reduction (25% → 0.01%). Because of a growing number of atrial fibrillation recurrences, a reduced dose of quinidine (subsequently flecainide) was added, resulting in arrhythmia significant reduction. In both cases, antiarrhythmic effectiveness correlated with clinical improvement. In SCN5A R814W-associated DCM, a combination of Class I antiarrhythmics and overdrive pacing is an effective treatment of severe ventricular and atrial arrhythmias.


The prevelance of psichiatric symptoms in preschool children with adenotonsillar hypertrophy.
The aim of this study was to determine the prevalence of psychiatric disorders and symptoms in preschool-age children who are indicated for operation due to adenotonsillar hypertrophy. Forty-eight patients between the ages of three and five years with indication for adenotonsillectomy were included in the study, as well as 40 control patients. Cases underwent routine ear nose throat (ENT) examination, flexible nasopharyngoscopy and tympanometry. The Early Childhood Inventory-4 (ECI-4) parent form and Strengths and Difficulties Questionnaire (SDQ) parent form were completed by the parent caring for the child. The SPSS for Windows 16.0 program was used for statistical analysis. Groups were compared according to they received at least one psychiatric diagnosis measured by ECI-4, the group of adenotonsillar hypertrophy was diagnosed more than the control group. Attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and sleep disorders were detected at a higher rate in patients with adenotonsillar hypertrophy. It also was established that in the comparison of the severity of psychiatric symptoms determined by ECI-4, symptom severity of ADHD, ODD, anxiety disorders, and sleep disorders was higher in the adenotonsillar hypertrophy group than in the control group. In the evaluation of the SDQ parent form, it was determined that attention deficit, hyperactivity, behavioral, and peer relations problems occurred more frequently in the adenotonsillar hypertrophy group. In addition to oral respiration, snoring, and disordered breathing during sleep, adenotonsillar hypertrophy may also associated with psychiatric disorders and symptoms.


[Study on the damage of the tight junctions of nasal mucosal epithelial cells by artemisia annua pollen].
Objective: To investigate the damage and mechanism of artemisia annua pollen on tight junction of human nasal mucosa epithelial cells (HNEpC). Methods: HNEpC were cultured in vitro. Different concentrations of artemisia annua pollen (0, 20, 40, 80, 100, 160, 200 μg/ml) were used to intervene the cells for 24 h, and the cell proliferation activity was detected by the CCK-8 method. The expression and phosphorylation of p38MAPK signaling pathway were detected by Western Blot before and after the intervention of SB203580, a p38MAPK inhibitor in HNEpC. Immunofluorescence chemical staining, Western Blot and quantitative real-time PCR (qPCR) were used to observe the expression and distribution of tight junctions Occludin and Claudin-1. SPSS 21.1 software was used for statistical analysis. Results: CCK-8 results showed that, compared with the control group, the proliferation activity of HNEpC increased after 6 h intervention with different concentrations of artemisia annua pollen (all P<0.05). After 12 h of intervention, the proliferation activity of HNEpC in the 20, 40, 80, 100 and 160 μg/ml groups was not significantly changed (all P>0.05), while that in the 200 μg/ml group was decreased (P<0.05). After the intervention for 24 h, the proliferation activity of cells in the 20 and 40 μg/ml groups was not significantly changed (all P>0.05), while that in the 80, 100, 160 and 200 μg/ml groups was decreased (all P<0.05). Immunofluorescence staining showed that the Occludin and Claudin-1 proteins in the normal control group were localized on the cell membrane and expressed more and formed a ring structure around the cell membrane. However, under the intervention of high concentration artemisia annua pollen, its expression level decreased, appeared broken, fuzzy, and nonuniform distribution. Western Blot and qPCR results showed that after 24 h of intervention, the expression levels of HNEpC Claudin-1 protein and its mRNA in the pollen groups (40, 80, 100, 160, 200 μg/ml) of artemisia annua decreased compared with those of those of the control group (mRNA expression levels were 0.567±0.214, 0.443±0.109, 0.462±0.160, 0.497±0.134, 0.388±0.076 compared with 1.001±0.067, respectively, all P<0.05). However, the mRNA of Occludin protein and its mRNA only decreased in the 200 μg/ml treatment group (mRNA expression level was 0.631±0.109 compared with 1.016±0.026, P<0.05), while all the other treatment groups increased (mRNA expression levels were 1.258±0.134, 1.827±0.103, 2.429±0.077, 1.707±0.085, 1.477±0.066 compared with 1.016±0.026, respectively, all P<0.05). Western Blot showed that p-p38MAPK expression increased after intervention with 100, 160, 200 μg/ml artemisia annua pollen for 24 h. SB203580 could inhibit the decreasing expression of Occludin caused by artemisinin pollen (mRNA expression was 1.255±0.179 compared with 0.631±0.109, P<0.05), but had no effect on Claudin-1 protein expression. Conclusion: Pollen from artemisia annua may activate p38MAPK signaling pathway and destroy the close connection of HNEpC.


A new experimental evidence-weighted signaling pathway resource in FlyBase.
Research in model organisms is central to the characterization of signaling pathways in multicellular organisms. Here, we present the systematic curation of 17 Drosophila signaling pathways using the Gene Ontology framework to establish a comprehensive and dynamic resource that has been incorporated into FlyBase, providing visualization and data integration tools to aid research projects. By restricting to experimental evidence reported in the research literature and quantifying the amount of such evidence for each gene in a pathway, we captured the landscape of empirical knowledge of signaling pathways in Drosophila . Comprehensive curation of Drosophila signaling pathways and new visual displays of the pathways provides a new FlyBase resource for researchers, and new insights into signaling pathway architecture.


G-quadruplex recognition by bis-indole carboxamides.
Herein we report the de novo design and synthesis of a geometrically flexible bis-indole carboxamide and a constrained derivative, as a novel class of small molecule scaffold that exhibits high stabilization potential for DNA G-quadruplex sequences associated with the promoters of c-kit2 and c-myc.


Increased expression of heat shock protein, transferrin, and beta 2-microglobulin in astrocytes during scrapie.
Scrapie is a slow infection and neurodegenerative disease of animals characterized pathologically by formation of amyloid, astrocytosis, vacuolation and injury and death of neurons. Our previous studies of scrapie point to: (i) a critical role for the astrocyte in responding to, and perhaps inadvertently contributing to, the neuropathological manifestations of infection; and (ii), the hypothesis that the astrocyte executes a programed response to neurological injury analogous to the stress response. The expression of genes encoding transferrin and beta 2-microglobulin has been shown to increase during scrapie and we sought in the studies reported here to determine whether this modulated expression would map to astrocytes. We also looked for changes in a heat shock protein that is induced in the stress response. We show that transferrin, beta 2-microglobulin and heat shock 72 kD protein all increase in astrocytes in the course of infection. We speculate in the discussion on the possible functions of these and other proteins in neurodegenerative processes and why these functions so frequently reside in the astrocyte.


Problematic Dichotomization of Risk for Intensive Care Unit (ICU)-Acquired Invasive Candidiasis: Results Using a Risk-Predictive Model to Categorize 3 Levels of Risk From a Multicenter Prospective Cohort of Australian ICU Patients.
Delayed antifungal therapy for invasive candidiasis (IC) contributes to poor outcomes. Predictive risk models may allow targeted antifungal prophylaxis to those at greatest risk. A prospective cohort study of 6685 consecutive nonneutropenic patients admitted to 7 Australian intensive care units (ICUs) for ≥72 hours was performed. Clinical risk factors for IC occurring prior to and following ICU admission, colonization with Candida species on surveillance cultures from 3 sites assessed twice weekly, and the occurrence of IC ≥72 hours following ICU admission or ≤72 hours following ICU discharge were measured. From these parameters, a risk-predictive model for the development of ICU-acquired IC was then derived. Ninety-six patients (1.43%) developed ICU-acquired IC. A simple summation risk-predictive model using the 10 independently significant variables associated with IC demonstrated overall moderate accuracy (area under the receiver operating characteristic curve = 0.82). No single threshold score could categorize patients into clinically useful high- and low-risk groups. However, using 2 threshold scores, 3 patient cohorts could be identified: those at high risk (score ≥6, 4.8% of total cohort, positive predictive value [PPV] 11.7%), those at low risk (score ≤2, 43.1% of total cohort, PPV 0.24%), and those at intermediate risk (score 3-5, 52.1% of total cohort, PPV 1.46%). Dichotomization of ICU patients into high- and low-risk groups for IC risk is problematic. Categorizing patients into high-, intermediate-, and low-risk groups may more efficiently target early antifungal strategies and utilization of newer diagnostic tests.


Anti-inflammatory activity of glycolipids isolated from cyanobacterium Nodularia harveyana.
Activity-guided fractionations from the freshwater cyanobacterium Nodularia harveyana led to the isolation of two monogalactosyldiacylglycerols (MGDG), two digalactosyldiacylglycerols (DGDG), two monoglucosyldiacylglycerols (MGlcDG) and 1-(O-hexose)-3,25-hexacosanediol (HG). Structures were elucidated by a combination of 1D and 2D NMR analysis, HRMS and GC-MS. The potential for inhibition against TNF-α and NF-κB production of these seven compounds was tested in THP-1 cells. All compounds showed activity, but compound 7 showed higher inhibitory activity of TNF-α and NF-κB, with IC50 of 4.88 ± 0.13 and 3.64 ± 0.45 μM, respectively.


Functional study of the Caenorhabditis elegans secretory-excretory system using laser microsurgery.
Individual cells of the Caenorhabditis elegans secretory-excretory system were ablated by laser microbeam in various larval stages. Effects on growth, molting, osmoregulation, fertility, longevity, and dauer larva formation were tested. Single-cell ablations did not prevent subsequent molting, but ablation of the pore cell or the duct cell resulted in the absence of the normal cuticular lining of the excretory duct following a molt. When the pore cell, duct cell, or excretory cell was ablated, the animals filled with fluid within 12-24 hr and died within a few days, producing very few progeny. Ablation of the excretory gland cell, on the other hand, had no obvious developmental or behavioral effects. Excretory activity was monitored in dauer larvae by observing pulsation of the excretory duct in conditions of differing osmolarity. The rate of pulsation was quite variable over time in conditions of low osmotic strength, but average five- to six-fold higher than that observed in buffered saline. These observations, combined with the effects of laser ablation, lead to the conclusion that one function of the excretory system is osmoregulation.


Associable representations as field of influence for dynamic cognitive processes.
In earlier models, synaptic plasticity forms the basis for cellular signaling underlying learning and memory. However, synaptic computation of learning and memory in the brain remains controversial. In this paper, we discuss ways in which synaptic plasticity remodels subcellular networks by deflecting trajectories in neuronal state-space as regulating patterns for the synthesis of dynamic continuity that form cognitive networks of associable representations through endogenous dendritic coding to consolidate memory.


Distinguishing between bioactive and modeled compound conformations through mining of emerging chemical patterns.
To systematically compare bioactive and theoretically derived compound conformations, we have analyzed 18 different sets of active small molecules with experimentally determined binding conformations and modeled conformers using a pattern recognition approach. Compound class-specific descriptor value range patterns that accurately distinguish bioactive conformations from other low-energy conformers were identified for all 18 compound classes. Discriminatory patterns were often chemically intuitive and could be well rationalized on the basis of X-ray structures of the protein-ligand complexes. Target-specific descriptor patterns can be used as filters to screen conformational ensembles for bioactive conformations.


[Relationship between biliary excretion of conjugated sulfobromophthalein and glutathione disulfide in rats].
Relationship between biliary excretion of sulfobromophthalein conjugated with glutathione (BSP-GSH) and glutathione disulfide (GSSG) was investigated in Sprague-Dawley rats. BSP-GSH solution was infused intravenously at three different rates. After administration of a glutathione-oxidizing agent, diamide, biliary excretion of GSSG increased temporarily and that of BSP-GSH decreased during the same period. A linear correlation was found between the increments in biliary excretion of GSSG and the decrements in that of BSP-GSH only when BSP-GSH was infused at a rate near its biliary transport maximum. The results may indicate competition in vivo between GSSG and BSP-GSH for a common transporter on canalicular membrane.


Comparison of 23S polymerase chain reaction-restriction fragment length polymorphism and amplified fragment length polymorphism techniques as typing systems for thermophilic campylobacters.
In this study, we evaluated the combination of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplified fragment length polymorphism (AFLP) molecular typing techniques for the analysis of thermophilic campylobacter species isolated from clinical and poultry samples. 23S PCR-RFLP analysis performed to fingerprint 69 strains exhibited an excellent level of typability. Eleven different types were defined at 100% linkage level following numerical analysis of band patterns. Differentiation of Campylobacter jejuni and Campylobacter coli at species level was achieved although no significant relationship could be observed between the profiles and the origin of the strains. Simplified AFLP analysis of the isolates disclosed the presence of 66 different banding patterns. The resulting dendrogram showed a high diversity among the strains studied. All the isolates were grouped within eight main types with a 69% homology degree among them. Differentiation at subspecies level was possible but no significant relationship could be observed between the AFLP profiles and the origin of the strains. When used in combination, 23S PCR-RFLP and single-enzyme AFLP methods can be applied to determine taxonomic and epidemiological relationships among thermophilic campylobacters.


Acoustic rhinometry in children: some practical aspects and influence of age and body surface area on results.
Since acoustic rhinometry was described there has been a lack of normal values for minimal cross-sectional area (MCA), especially for children. There has also been debate about factors influencing normal values. The purpose of this study was to find the normal values for children in a Finnish population and whether there is any correlation between age or body surface area (BSA) and MCA. We measured 74 children (age, 1-12 years) with an acoustic rhinometer. The values of MCA were compared with age and BSA determined from height and weight. The mean of unilateral MCA was 0.225 cm2 (SD, 0.041). We found positive correlation between unilateral volume on the left side and age and between MCA from the right side and age or BSA as a constant predictor. As much as 28.4% of the measurements had to be rejected because of acoustic leakage between nostril and nosepiece. Only 6.8% had to be rejected because of a lack of cooperation. It is possible to find normal values for children. Acoustic rhinometry is well tolerated among children. The method is rapid, reliable and noninvasive, and minimal cooperation is required. The measurements must be performed in a standard way, and some important causes of errors must be kept in mind.


Atrial fibrillation in heart failure: The sword of Damocles revisited.
Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and affects patients with both reduced as well as preserved LV systolic function. There has been a general move in clinical practice from a rhythm control to a rate control strategy in HF patients with AF, although recent data suggests that rhythm control strategies may provide better outcomes in selected subgroups of HF patients. Furthermore, various therapeutic modalities including pace and ablate strategies with cardiac resynchronisation or radiofrequency ablation have become increasingly adopted, although their role in the management of AF in patients with HF remains uncertain. This article presents an overview of the multidimensional impact of AF in patients with HF. Relevant literature is highlighted and the effect of various therapeutic modalities on prognosis is discussed. Finally, while novel anticoagulants usher in a new era in thromboprophylaxis, research continues in a variety of new pathways including selective atrial anti-arrhythmic agents and genomic polymorphisms in AF with HF.


Effect of protein kinase and phosphatase inhibitors on expression of hypoxia-inducible factor 1.
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric bHLH-PAS protein essential for erythropoietin gene transcription in hypoxic cells. Here we show that both 2-aminopurine and sodium fluoride, inhibitors of serine/threonine kinases and phosphatases, respectively, interfered with the hypoxic induction of HIF-1 DNA-binding activity and expression of HIF-1 alpha and HIF-1 beta(ARNT) subunits. Genistein, an inhibitor of tyrosine kinases, completely blocked the synthesis of both HIF-1 subunits as well as HIF-1 DNA-binding activity. Sodium orthovanadate, an inhibitor of tyrosine phosphatases increased the basal level of HIF-1 proteins and HIF-1 activity. These data suggest that protein phosphorylation events play an important role in the hypoxia signal-transduction pathway that leads to synthesis of HIF-1 alpha and HIF-1 beta proteins and the induction of HIF-1 DNA-binding activity.


Applications of transcranial magnetic stimulation (TMS) in child and adolescent psychiatry.
Transcranial magnetic stimulation (TMS) is emerging as a new treatment and neurophysiological research tool for psychiatric disorders. Recent publications suggest that this modality will also serve as a treatment and research tool in child and adolescent psychiatry. Current reports on therapeutic trials of repetitive transcranial magnetic stimulation (rTMS) in adolescents have primarily focused on depression. However, other pilot work involves the treatment of attention-deficit/hyperactivity disorder (ADHD), autism and schizophrenia. Neurophysiological studies typically utilize single and paired-pulse TMS paradigms which index cortical excitability and inhibition. Initial studies have focused on ADHD, autism, and depression. General knowledge regarding TMS among child and adolescent psychiatrists is lacking. The aim of this review is to provide an overview of TMS in the context of child and adolescent psychiatry, discuss recent therapeutic and neurophysiological studies, and examine relevant ethical considerations.


Autophagy-regulating microRNAs: two-sided coin in the therapies of breast cancer.
Despite recent advances in the treatment of breast cancer (BC), it still remains as a prevalent and deadly cancer in the world. Given that BC is a heterogeneous disease, it is necessary to clarify molecular mechanisms in tumor cells to improve various therapy outcomes and overcome therapy resistance. Autophagy represents one of the most important intracellular degradation pathways involved in diverse biological processes and plays an important bi-directional role in tumor formation and progression. Among the several mechanisms that affect autophagy, microRNAs (miRNAs) play a crucial role as gene regulators. Several in vivo and in vitro studies have reported multiple miRNAs regulating autophagy in BC that affect tumor initiation, progression, and response to various therapies. In the present review, we highlighted the mechanisms through which miRNAs regulate autophagy in BC and their potential use as therapeutic targets.


Recurrent acute pancreatitis: an additional manifestation of the "wandering spleen" syndrome".
A case of "wandering spleen" associated with recurrent pancreatitis and diagnosed with computed tomography (CT), is reported. The entity was also associated with a rotated, distended stomach, gastric outlet obstruction secondary to extrinsic compression of the duodenum, and partial small bowel obstruction secondary to extrinsic compression of a mobile, distended cecum that lay under the right diaphragm.


Mineral loss and color change of enamel after bleaching and staining solutions combination.
Pigments of food and beverages could affect dental bleaching efficacy. The aim of this investigation was to evaluate color change and mineral loss of tooth enamel as well as the influence of staining solutions normally used by adolescent patients undergoing home bleaching. Initial hardness and baseline color were measured on enamel blocks. Specimens were divided into five groups (n=5): G1 (control) specimens were kept in artificial saliva throughout the experiment (3 weeks); G2 enamel was exposed to 10% carbamide peroxide for 6 h daily, and after this period, the teeth were cleaned and stored in artificial saliva until the next bleaching session; and G3, G4, and G5 received the same treatments as G2, but after bleaching, they were stored for 1 h in cola soft drink, melted chocolate, or red wine, respectively. Mineral loss was obtained by the percentage of hardness reduction, and color change was determined by the difference between the data obtained before and after treatments. Data were subjected to analysis of variance and Fisher's test (α=0.05). G3 and G5 showed higher mineral loss (92.96 ± 5.50 and 94.46 ± 1.00, respectively) compared to the other groups (p ≤ 0.05). G5 showed high-color change (9.34 ± 2.90), whereas G1 presented lower color change (2.22 ± 0.44) (p ≤ 0.05). Acidic drinks cause mineral loss of the enamel, which could modify the surface and reduce staining resistance after bleaching.


Subclinical hypothyroidism is associated with early insulin resistance in Kuwaiti women.
Subclinical hypothyroidism (SH), defined as an asymptomatic state characterized by normal serum concentrations of free thyroxine and elevated serum concentrations of TSH. The aim of this study is to investigate the complex interplay between insulin resistance and low grade chronic inflammation in Kuwaiti women with subclinical hypothyroidism. Thirty four women with subclinical hypothyroidism (SH) and 20 healthy women as controls matched to the patient group for sex, age and body mass index (BMI), were enrolled in this prospective study. TSH, FT4, C reactive protein, glucose, insulin, Homeostasis Model assessment (HOMA), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were estimated. Total cholesterol and LDL-C were significantly higher in patients with SCH as compared with control subjects, however triglyceride and HDL-C were not statistically different. CRP was not statistically different between the SCH patients and control group (3.64 +/- 0.94 Vs 3.18 +/- 0.71 P>0.05). Insulin levels were significantly higher in the SCH group comparable to the control (12.5 +/- 2.67 Vs 10.80 +/- 2.01 p<0.05), however HOMA-IR was not statistically different (2.85 +/- 0.64 Vs 2.54 +/- 0.64 P>0.05). Patients with subclinical hypothyroidism exhibited elevated atherogenic parameters (hyperinsulinemia, total cholesterol, LDL-C). Therefore screening and treatment for subclinical hypothyroidism may be warranted due to its adverse effects on lipid metabolism.


Effect of a single 30-minute treatment of high voltage pulsed current on edema formation in frog hind limbs.
The purpose of this study was to investigate the effect of a single treatment of high voltage pulsed current (HVPC) on edema formation. Twenty-four frogs were anesthetized, and both hind limbs of each frog were traumatized by impact. Limb volumes were measured by water displacement immediately before and after trauma and at predetermined intervals for 24.0 hours posttrauma. One limb of each frog was randomly selected to receive 30 minutes of continuous, 120-pulse per second, cathodal HVPC at voltages 10% less than motor threshold levels. Data were analyzed by an analysis of variance for repeated measures. Sources of significant differences were determined by paired t tests (probability values determined by Bonferroni adjustment). A single 30-minute application of HVPC significantly curbed edema formation for between 4.0 and 7.5 hours following treatment (ie, volumes of treated limbs were significantly less than those of untreated limbs). These results suggest that regimens currently applied to humans (ie, one treatment per day or three times per week) may be insufficiently aggressive to provide sustained treatment effects.


Parafoveal X-masks interfere with foveal word recognition: evidence from fixation-related brain potentials.
The boundary paradigm, in combination with parafoveal masks, is the main technique for studying parafoveal preprocessing during reading. The rationale is that the masks (e.g., strings of X's) prevent parafoveal preprocessing, but do not interfere with foveal processing. A recent study, however, raised doubts about the neutrality of parafoveal masks. In the present study, we explored this issue by means of fixation-related brain potentials (FRPs). Two FRP conditions presented rows of five words. The task of the participant was to judge whether the final word of a list was a "new" word, or whether it was a repeated (i.e., "old") word. The critical manipulation was that the final word was X-masked during parafoveal preview in one condition, whereas another condition presented a valid preview of the word. In two additional event-related brain potential (ERP) conditions, the words were presented serially with no parafoveal preview available; in one of the conditions with a fixed timing, in the other word presentation was self-paced by the participants. Expectedly, the valid-preview FRP condition elicited the shortest processing times. Processing times did not differ between the two ERP conditions indicating that "cognitive readiness" during self-paced processing can be ruled out as an alternative explanation for differences in processing times between the ERP and the FRP conditions. The longest processing times were found in the X-mask FRP condition indicating that parafoveal X-masks interfere with foveal word recognition.


Neutrophil gelatinase-associated lipocalin is a marker for dysregulated keratinocyte differentiation in human skin.
Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein initially isolated from the specific granules of human neutrophils. It is a member of the highly heterogeneous lipocalin protein family, which shares a common tertiary structure. Its synthesis is induced in gastrointestinal epithelium in association with inflammation and malignancy. To gain insight into its potential role in other epithelia we have investigated the expression of NGAL in human skin embryonic development, in normal adult skin, and in skin associated with inflammation and neoplastic transformation. In the present study we report that the embryonic expression of NGAL appears to be regulated in a spatio-temporal pattern. It was induced in the interfollicular epidermis at 20-24 weeks of gestational age but thereafter progressively receded towards the hair follicles. In normal adult skin, NGAL was detected solely in association with hair follicles. However, strong induction of NGAL in the epidermis was seen in a variety of skin disorders characterized by dysregulated epithelial differentiation such as psoriasis, pityriasis rubra and squamous cell carcinoma. In these tissues production of NGAL was confined to spatially distinct subpopulations of keratinocytes underlying areas of parakeratosis, whereas skin samples lacking parakeratotic epithelium such as lichen ruber planus, acute contact eczema and basal cell carcinoma were negative for NGAL. Consistent with being a marker for disturbed terminal differentiation, NGAL immunoreactivity showed an inverse pattern when compared with that of the differentiation marker filaggrin. The biologic functions of NGAL in epithelia are not fully known, although an immunomodulatory role in host defense has been proposed. In addition, the transient interfollicular NGAL expression during skin embryogenesis along with the induction of NGAL in adult parakeratotic epidermis suggests it play a role in epithelial differentiation pathways.


The long noncoding RNA Malat1: Its physiological and pathophysiological functions.
Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest of the transcripts result in RNA transcripts without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members in the lncRNA family, the metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 is one of the first identified lncRNAs associated with human disease, and cumulative studies have indicated that Malat1 plays critical roles in the development and progression of various cancers. Malat1 is also actively involved in various physiologic processes, including alternative splicing, epigenetic modification of gene expression, synapse formation, and myogenesis. Furthermore, extensive evidences show that Malat1 plays pivotal roles in multiple pathological conditions as well. In this review, we will summarize latest findings related to the physiologic and pathophysiological processes of Malat1 and discuss its therapeutic potentials.


Comparison of the Ivermectin and Lopinavir/Ritonavir Treatment Outcomes among COVID-19 Mild to Moderate Cases in Kaduna State.
Ivermectin has been a popular anti-parasitic drug since the late 1970s. The promising result of in-vitro studies on the antiviral activity of the drug has led clinicians in many countries to use this drug to treat COVID-19 patients. This study determined and compared the mean number of days at clinical recovery for mild to moderate cases of COVID -19 treated with Lopinavir/Ritonavir (Alluvia) and Ivermectin at the Kaduna State Infectious Disease Control Centres. This was a comparative cross-sectional study conducted among 300 mild to moderate COVID- 19 cases enrolled for the study. The outcome variables were the time required for the resolution of symptoms from the onset and at commencement of the treatment regimens. Data were collected from patient folders using a questionnaire. Data were analysed with the IBM SPSS Version 25.0 and STATA/SE 13. Statistical significance was set at p<0.05. The mean recovery time (MRT) from symptom onset was significantly lower for Covid-19 patients treated with ivermectin (7.15±4.18 days) compared to lopinavir/ritonavir (9.7±5.3 days), 95%CI=7.37-9.62. Multivariate logistic regression showed that there was no significant relationship between the patients age (AOR=0.36, 95%CI=0.09-1.49), sex (AOR=0.34,95%CI=0.54-5.93), educational status (AOR=1.04, 95%CI=0.3-3.57), marital status (AOR=0.55,95%CI=0.14-2.11) place of treatment (AOR=1.66, 95%CI=0.54-5.11) and MRT. There was also no significant relationship between patients' comorbid chronic illness (AOR=0.83, 95%CI=0.27-2.61) and MRT. The mean recovery time for COVID-19 patients managed with ivermectin was slightly lower than for the lopinavir/ ritonavir regimen. Clinical trials to further prove the efficacy of Ivermectin as a supportive therapy in clinical management of mild to moderate cases of COVID-19 in this setting should be carried out.


"It Hurts a Latina When They Tell Us Anything About Our Children": Implications of Mexican-Origin Mothers' Maternal Identities, Aspirations, and Attitudes About Cultural Transmission for Childhood Obesity Prevention.
This qualitative study explored values, attitudes, and beliefs held by Mexican-origin mothers of preschool-aged children to enhance understanding of cultural influences on behaviors associated with childhood obesity risk. During face-to-face interviews, 39 Mexican-origin mothers of preschool-aged children discussed their hopes for their children, their image of the perfect mother, Mexican and American foods, why they taught their children about these foods, and their opinions about television (TV) viewing language. Participants wanted their children to become successful, "good" people, which necessitated doing well in school. Mothers also wanted their children to know them, which required understanding the mothers' Mexican backgrounds. Mothers wanted their children to maintain Mexican values and identities. Some mothers viewed American culture as harmful. Many participants prepared their child for going to Mexico by exposing them to Mexican culture and foods. Some mothers fed their children American foods to prepare them for school. Perceptions of American foods generally reflected stereotypical unhealthy foods. TV helped teach children Spanish and English. Being a good mother was core to participants' identities; thus, hearing about child overweight made some mothers feel like failures. Health promotion programs may be more salient to mothers if they: underscore how a healthy weight can help children in school; teach mothers to prepare healthy American foods that their children will encounter in kindergarten; assist mothers in teaching their children about Mexico; and present information about childhood obesity in ways that reinforce what mothers are doing well, enhance mothers' self-efficacy, and allay feelings of failure.


Effects of 1 to 3 years' treatment with alendronate on mechanical properties of the femoral shaft in a canine model: implications for subtrochanteric femoral fracture risk.
Bisphosphonate (BP) treatment used to prevent bone loss in postmenopausal osteoporosis has recently been implicated in an apparent increase in subtrochanteric femoral fractures. Previous work showed that BPs can reduce the energy to fracture of cancellous bone, but limited data exist on material-level mechanical properties of compact bone from the long bones. This study examined intrinsic mechanical properties of the femoral diaphysis of a canine model treated for 1 or 3 years with alendronate at two different doses. Seventy-two dogs were treated orally with 0.2 mg/kg/day alendronate or 1.0 mg/kg/day alendronate; a control group was administered saline. Prismatic beam specimens were tested in four-point bending under displacement control, and the intrinsic mechanical properties were calculated. No significant differences were found among groups in any mechanical property at either 1 or 3 years of treatment. We conclude that the material properties of the femoral diaphysis are not degraded following 1 to 3 years treatment with alendronate, even at high doses. Longer periods of treatment have not been studied using clinical doses of alendronate, but such studies need to be carried out to confirm a lack of effect of alendronate on mechanical properties of cortical bone in the subtrochanteric region of the femur.


N-Vinylcarbazole as Versatile Photoinaddimer of Photopolymerization under Household UV LED Bulb (392 nm).
N-vinylcarbazole (NVK) can act simultaneously as a photoinitiator, an additive, and a mono-mer (photoinaddimer) of photopolymerization upon exposure to the household ultraviolet (UV) light-emitting diode (LED) bulb (emission wavelength centered at 392 nm). Even though the light absorption spectrum of NVK exhibits weak overlapping with the emission spectrum of the UV LED, the active species (i.e., radicals and cations) can be generated from the interaction between NVK and diphenyliodonium hexafluorophosphate (Iod) under irradiation of this LED device, which is investigated by steady state photolysis and electron spin resonance spin-trapping methods. Interestingly, the generated radicals and cations from the NVK/Iod system demonstrate high efficiency to initiate the free radical photopolymerization of (meth)acrylates and the cationic photopolymerization of epoxide and divinyl ether under the UV LED irradiation, and the one-step simultaneous catonic/radical photopolymerization of expoxide/acrylate blend can lead to the formation of tack free polyacrylate/polyether-based interpenetrated polymer network film within 10 min even when the polymerization process is exposed to the atmosphere highlighting the high efficiency of the system to reduce the oxygen inhibition effect. More interestingly, NVK/Iod system can also initiate the photopolymerization of NVK under the UV LED irradiation to produce polyvinylcarbazole, and NVK acts as both a photoinitiator and a monomer in the system.


Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study.
Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN) is usually considered a non-inflammatory disease. We examined a marker of inflammation, C-reactive protein (CRP), in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models. Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only), serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function. Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.


Understanding Factors to COVID-19 Vaccine Adoption in Gujarat, India.
The COVID-19 pandemic has posed threats to human life across the globe, including India. Vaccinating is an effective means of addressing the pandemic threat. The government of India has implemented a massive vaccination drive to save its citizens from the deadly virus. However, the effort has faced multiple challenges, including vaccine hesitancy. This research understands respondents' perspectives on factors contributing to the lower vaccination uptake in Gujarat, India. Forty-four semi-structured interviews were conducted through convenience sampling representing different demographic backgrounds. Factors influencing vaccine adoption included religious leadership, political leadership and the government, and fear of side effects, especially among children and those with co-morbidities, resulting primarily from fake news and misinformation circulated through social media. Compared with nine countries from across the world, the study found similarities to vaccine hesitancy from misinformation and the fear of side effects among children. In contrast, the role of government and the influence of religious and political leaders was considered positive. The study recommends strategies to overcome people's apprehensions about the adoption of vaccination. These include offering incentives, providing positive peer-to-peer communication, recruiting influencers such as religious and community leaders and early adopters such as the elderly population to endorse vaccination, targeting youth through social media, and reaching rural sections by involving NGOs and social service groups.


Drug injection in jugular veins: a new risk factor for vascular diseases in HIV-infected patients? A case report.
The authors describe a rare case of diffused thrombosis of the superficial veins in the whole body and periphlebitis with perivascular abscesses in an human immunodeficiency virus (HIV)-infected drug abuser who was using neck veins to inject cocaine and heroin. In addition the patient presented oral candidiasis, hepatitis C virus infection, bronchopneumonitis, and endocarditis of the tricuspid valve with valvular failure. The conditions of the patient needed repeated vascular catheterizations for therapy administration. Similar pathologies, in HIV-infected patients, highly increase the risk of opportunistic infections, especially in the encephalic territory; in addition the need for vascular catheterizations represents a further risk factor for bacterial infections.