Prevalence and Characteristics of Hyperthyroidism Among Patients With Sarcoidosis in the United States.
We aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis. A national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis. Three percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P < .001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036). Hyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.


Biomarkers of outcome to weekly paclitaxel in epithelial ovarian cancer.
We sought to evaluate the role of intrinsic chromosomal aberrations in determining favorable outcome to weekly paclitaxel (WP) in patients with epithelial ovarian cancer (EOC). We evaluated the common genomic aberrations of two patients with EOC and exceptional WP response in the GENIUS study (NCT03740503). We then searched for potential markers of unusual outcomes to WP in a validation cohort. We performed shallow whole genome sequencing (sWGS) in the tumor tissue of women with EOC considered as short-responders (SR; progression with ≤3 cycles) and long-responders (LR; response at ≥8 cycles) to WP monotherapy. We identified two women with exceptional response to WP, lasting over four years, who shared chromosome 8 gain as a common genomic aberration. In order to validate our findings, we reviewed 188 patients with EOC treated with WP and selected 61 women (39 SR, 22 LR) with unusual responses. By sWGS, there was no differential alterations in the copy number changes in chromosome 8, or in genes related to angiogenesis, tubulin superfamily, cell-cycle, apoptosis and paclitaxel metabolism or transportation pathways. Amongst the LR group, we identified six exceptionally long responders (ExLR), with responses lasting over a year. In an exploratory analysis, there was increased amplification of angiogenesis (VEGFB, MMP9), tubulin superfamily (TSC2) and apoptosis related genes (BCL2L1, BAD) in ExLR compared to SR. We identified one patient with a complete response to WP for over 7 years. Molecular profiling identified unique amplifications in interleukin related genes (CXCR1, CXCR2, IL1A, IL1B), not detected in other patients. Intrinsic tumor pathways may impact outcome with weekly paclitaxel monotherapy and further investigations are required.


Secondary Neurulation Defects: Retained Medullary Cord.
Retained medullary cord (RMC) is a defect resulting from impaired secondary neurulation. Intraoperatively, RMC is recognizable as an elongated cord-like structure caudal to the conus, that contains histologically confirmed neuroglial components and a lumen with an ependymal lining. It characteristically does not possess neurological function. This chapter aims to summarize (1) the mechanisms that lead to the occurrence of RMC; (2) the various forms of RMC, such as cystic RMC and 'possible RMC', and (3) the treatment strategies, especially untethering through limited exposure.


Redox-active ligands as a challenge for electronic structure methods.
To improve the catalytic activity of 3d transition metal catalysts, redox-active ligands are a promising tool. These ligands influence the oxidation state of the metal center as well as the ground spin-state and make the experimental determination of both properties challenging. Therefore, first-principles calculations, in particular employing density functional theory with a proper choice of exchange-correlation (xc) functional, are crucial. Common xc functionals were tested on a simple class of metal complexes: homoleptic, octahedral tris(diimine) iron(II) complexes. The spin-state energy splittings for most of these complexes showed the expected linear dependence on the amount of exact exchange included in the xc functionals. Even though varying redox-activity affects the electronic structure of the complexes considerably, the sensitivity of the spin-state energetics to the exact exchange admixture is surprisingly small. For iron(II) complexes with highly redox-active ligands and for a broad range of ligands in the reduced tris(diimine) iron(I) complexes, self-consistent field convergence to local minima was observed, which differ from the global minimum in the redox state of the ligand. This may also result in convergence to a molecular structure that corresponds to an energetically higher-lying local minimum. One criterion to detect such behavior is a change in the sign of the slope for the dependence of the spin-state energy splittings on the amount of exact exchange. We discuss possible protocols for dealing with such artifacts in cases in which a large number of calculations makes checking by hand unfeasible.


Retrieval of Long-Term Implanted Leadless Pacemakers: A Single-Center Experience.
The authors report their single-center experience with the retrieval and replacement of long-term implanted leadless cardiac pacemakers (LPs) and the factors contributing to success. LPs are a clinically effective and safe alternative to standard transvenous pacemakers for single-chamber ventricular pacing. However, the feasibility of retrieving and replacing long-term implanted LPs is not well known. A total of 34 patients with implanted Nanostim LPs (mean implantation duration 1,570 ± 479 days) subsequently underwent retrieval. On the basis of fluoroscopic imaging, the cohort was divided into 2 groups: those with remarkable swinging movement (SM) of the LP docking button (n = 25) and those without SM (n = 9). The overall LP retrieval success rate was 85% (n = 29). New leadless devices were implanted in 27 patients immediately after LP retrieval. No procedure-related adverse events occurred. The rate of successful LP retrieval was significantly higher in the SM group (25 of 25 [100%]) than in the no-SM group (4 of 9 [44%]) (p < 0.001), and fluoroscopy time during the retrieval procedure was shorter in the SM group (12.7 ± 8.6 min) than in the no-SM group (45.6 ± 19 min) (p < 0.001). This study demonstrated the feasibility and safety of retrieval of long-term implanted LPs after a mean duration of 4 years. Retrieval was most successful in patients whose docking buttons exhibited significant SM.


Relationship between risk perception and occupational accidents: a study among foundry workers.
Risk perception is an effective factor in the determining of the incidence of unsafe behaviors and the occurrence of occupational accidents in the workplace. The purpose of this study is to determine the relationship between risk perception and occupational accidents among foundry workers in Tehran, Iran. In this cross-sectional study, all male workers in a foundry unit were initially selected (n = 245). After applying the study criteria and dismissing incomplete returned questionnaires, only 109 workers were included in the study. The General Health Questionnaire and the Flynn et al. Risk Perception Questionnaire were used to assess the mental health and risk perception of workers, respectively. Data regarding the occupational accidents of workers were also extracted from the accidents' records of the foundry. Workers with a record of occupational accidents during 2013-2016 were compared with workers without an occupational accident record. Findings showed that a one-unit increase in the risk perception score resulted into an increase of approximately 33% in the odds of the occurrence of occupational accidents, but this rate was not significant (p = 0.695). In addition, the study found no significant relation between the risk perception score and the frequency of occupational accidents (Spearman's r = 0.003, p = 0.977). There is no statistically significant relationship between risk perception and occupational accidents among foundry workers in Tehran, Iran.


Effects of bepridil, a new antianginal agent, on ambulatory electrocardiography in human volunteers.
We studied the effects of bepridil, a new antianginal agent, on the ambulatory electrocardiogram in seven human volunteers. The drug was administered in three sequential periods of 12 days separated by 24 days without treatment. Heart rate was not significantly altered at 200 mg/day, but fell from day 3 at 300 mg/day and from day 1 at 600 mg/day. Average fall in heart rate was approximately 8% at 300 mg/day and 11% at 600 mg/day (day 7). At 200 mg/day the peak plasma level was reached after 11 days of treatment (0.28 +/- 0.4 microgram/ml). At 300 mg/day, a plateau was reached on day 7 (0.44 +/- 0.04 micrograms/ml) and at 600 mg/day from day 8 (0.97 +/- 14 micrograms/ml). We found a highly significant relationship between blood concentration of bepridil and mean RR interval lengths over 24 h. The QTc interval was lengthened at all doses, but there was no significant correlation between plasma level and increase in QTc interval length.


B3 breast lesions determined by vacuum-assisted biopsy: how to reduce the frequency of benign excision biopsies.
The aim of this study was to identify parameters allowing differentiation among the diverse group of B3 lesion at stereotactic vacuum-assisted biopsy (VAB) to identify patients with a low risk of cancer and who can therefore be referred for follow-up rather than surgery and thus reduce the number of unnecessary surgical procedures. Among 608 VAB procedures performed for nonpalpable ultrasound (US)-occult mammographic abnormality, 102 cases of B3 were included in this study. Mammographic lesion type, lesion size, Breast Imaging Reporting and Data System (BIRADS) category, number of specimens per lesion and presence of atypia were retrospectively analysed. Results were compared with histological findings at surgery (53 cases) or mammographic findings during follow-up (49 cases). Statistical analysis was performed with univariate analysis (chi-square test), and statistical significance was set at p<0.05. The majority of cases were depicted as isolated microcalcifications (82.3%), were smaller than 10 mm (80.4%), had a low level of radiological suspicion (64.7%) and had 11 or more cores sampled (94.1%). Atypia at VAB was reported in 60 of 102 cases (58.8%). Carcinoma was found at excision in 5/60 (8%) B3 lesions with atypia and in no B3 lesions without atypia (p=0.146). Cancer at surgery was more frequent among cases of isolated microcalcifications (p=0.645), cases with high radiological suspicion (p=0.040) and those with a smaller number of cores sampled (borderline significant p=0.064). On the basis of our experience, the presence or absence of atypia in our series proved to be the reliable criterion to prompt or avoid surgery in cases with a VAB finding of B3 lesion. This criterion may therefore be adopted in practice to more accurately select patients for surgery.


Total Tau and Phosphorylated Tau Protein Serum Levels in Patients with Schizophrenia Compared with Controls.
Tau protein is located in the axons of neurons and in Alzheimer Disease, is abnormally phosphorylated and aggregates into paired helical filaments (neurofibrillary tangles) reflecting the degree of neurofibrillary pathology and neurodegeneration. Although tau and phosphorylated tau (p-Tau) pathology is a hallmark for dementia, few studies were performed in patients of schizophrenia. This preliminary serum study was designed to compare serum total tau and p-Tau levels of schizophrenia patients with healthy controls. The study was included 42 patients diagnosed with schizophrenia and 42 healthy control subjects. Sociodemographic form was applied to both groups and PANSS was applied to patient group. Serum total tau and p-Tau levels were measured by ELISA method. Total tau and p-Tau levels of patients were significantly lower than healthy controls. There was a positive correlation between amount of past electroconvulsive therapies and total tau level. However total tau and p-Tau levels were positively correlated. Our study results showed that serum total tau and p-Tau levels of patients with schizophrenia were significantly lower than healthy controls.


Single-Nucleotide-Resolution Sequencing of N6-Methyldeoxyadenosine.
Use of methylation-specific antibodies with methylated-DNA-immunoprecipitation sequencing allows for the mapping of methylated DNA, such as N6-methyldeoxyadenosine (6mA). However, such mapping methods only detect methylated DNA at low resolution. Here, we describe 6mA Cross-linking Exonuclease sequencing (6mACE-seq), which utilizes 6mA-specific antibodies cross-linked to 6mA sites to protect 6mA-DNA fragments from subsequent exonuclease treatment. This allowed 6mACE-seq to map human-genome-wide 6mA at single-nucleotide resolution.


Microbial polyhydroxyalkanoates from extreme niches: Bioprospection status, opportunities and challenges.
Extreme niches are offered with unusual physiochemical conditions that impose stress to the life-forms including microbial communities. Microbes have evolved unique physiology and genetics to interact dynamically with extreme environments for their adaptation and survival. Amongst the several adaptive features of microbes in stressed conditions, polyhydroxyalkanoates synthesis is a crucial strategy of many bacteria and archaea to reserve carbon and energy inside the cell. Apart from the relevance of PHA to microbial world, these intracellular polyesters are seen as essential biological macromolecules for the bio-material industry owing to their plastic-like properties, biodegradable and eco-friendly nature. Recently, much attention has been attracted by the microbes of extreme habitats for a new source of industrially suited PHA producers and novel PHA with unique properties. Therefore, the current review is focused on the critical evaluation of microbes from extreme niches for PHA production and opportunities for the development of commercially feasible PHA bioprocess.


Molecular cloning and expression of a hexamerin cDNA from the honey bee, Apis mellifera.
A cDNA encoding a hexamerin subunit of the Africanized honey bee (Apis mellifera) was isolated and completely sequenced. In the deduced translation product we identified the N-terminal sequence typical of the honey bee HEX 70b hexamerin. The genomic sequence consists of seven exons flanked by GT/AT exon/intron splicing sites, which encode a 683 amino acid polypeptide with an estimated molecular mass of 79.5 kDa, and pI value of 6.72. Semi-quantitative RT-PCR revealed high levels of Hex 70b message in larval stages, followed by an abrupt decrease during prepupal-pupal transition. This coincides with decaying titers of juvenile hormone (JH) and ecdysteroids that is the signal for the metamorphic molt. To verify whether the high Hex 70b expression is dependent on high hormone levels, we treated 5th instar larvae with JH or 20-hydroxyecdysone (20E). In treated larvae, Hex 70b expression was maintained at high levels for a prolonged period of time than in the respective controls, thus indicating a positive hormone regulation at the transcriptional level. Experiments designed to verify the influence of the diet on Hex 70b expression showed similar transcript amounts in adult workers fed on a protein-enriched diet or fed exclusively on sugar. However, sugar-fed workers responded to the lack of dietary proteins by diminishing significantly the amount of HEX 70b subunits in hemolymph. Apparently, they use HEX 70b to compensate the lack of dietary proteins.


Media for 'total' Enterobacteriaceae, coliforms and Escherichia coli.
Selective and enrichment media for the isolation and enumeration of 'total' Enterobacteriaceae, coliforms, faecal coliforms and E. coli from foods are described. The effects of time and temperature of incubation are discussed. Reports of some comparative studies of these media and factors to be considered in the selection of media for this group of organisms are noted and the difficulties associated with the isolation and enumeration of pathogenic serotypes of E. coli considered.


Sun protection use and habits in the LGBTQI+ community in Lebanon: A cross sectional study.
Sun exposure is an extrinsic risk factor for skin aging, wrinkle formation, and the development of skin cancer, namely melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Sun protection measures have emerged as an important means of preventing these harmful effects. Studies have shown that sexual minority men have a greater prevalence of skin cancer than heterosexual men. There is limited research investigating the reasons behind this risk of skin cancer development. This is especially important because identifying preventable risk factors, like those pertaining to sun exposure behaviors, can be targeted in the fight against skin cancer and help establish screening tools and preventive interventions for the SGM community. This study focused on members of the SGM community and demonstrated their tendency not to use sun-protective measures, as well as their deficits in knowledge of skin cancer prevention. This study is a cross-sectional study that investigates sun protection practices and trends among adults in Lebanon's SGM community using a survey. It includes adults aged 18-80 that were recruited from the dermatology clinics at AUBMC as well as LGBTQ+ organizations Helm and SIDC. A total of 129 participants took part in the study and completed the survey. Reasons for tanning varied among our participants: tanning to get a color (13.1%), tanning to get vitamin D (4.6%), tanning socially (6.9%), and tanning for mood elevation (0.8%). No significant association was found between sexual orientation and SPF use (p = 0.167). No significant association was found between sexual orientation and tanning frequency during summer (p-value: 0.231). Similarly, no significant association was noted between sexual orientation and tanning bed use (0.951). No significant association was noted between the type of job and SPF use (p = 0.601). Despite no significance between SPF use and the highest educational degree attained (p = 0.070), the tendency to use SPF increased with higher levels of education. Moreover, awareness of sun-induced skin cancer did not significantly affect SPF use (p = 0.067). However, a significant association was found between the information source for skin cancer and SPF use (p < 0.001) where participants receiving information from dermatologists displayed notably higher SPF use (72.2%), compared to those obtaining information from media (18.2%) or family and friends (5.3%). Surveying the perception of the Lebanese SGM community towards sun damage and their adaptive practices to prevent it can help implement and gear a nation-wide campaign to spread proper awareness about this subject. Studying their behavioral tendencies for not using sunscreen can help overcome this contributing risk factor for skin cancers. Future investigations have yet to identify confounding variables contributing to higher levels of skin cancers in this population.


A stable room-temperature sodium-sulfur battery.
High-energy rechargeable batteries based on earth-abundant materials are important for mobile and stationary storage technologies. Rechargeable sodium-sulfur batteries able to operate stably at room temperature are among the most sought-after platforms because such cells take advantage of a two-electron-redox process to achieve high storage capacity from inexpensive electrode materials. Here we report a room-temperature sodium-sulfur battery that uses a microporous carbon-sulfur composite cathode, and a liquid carbonate electrolyte containing the ionic liquid 1-methyl-3-propylimidazolium-chlorate tethered to SiO2 nanoparticles. We show that these cells can cycle stably at a rate of 0.5 C (1 C=1675, mAh g(-1)) with 600 mAh g(-1) reversible capacity and nearly 100% Coulombic efficiency. By means of spectroscopic and electrochemical analysis, we find that the particles form a sodium-ion conductive film on the anode, which stabilizes deposition of sodium. We also find that sulfur remains interred in the carbon pores and undergo solid-state electrochemical reactions with sodium ions.


Evidence that atypical vasopressin V(2) receptor in inner medulla of kidney is V(1B) receptor.
Vasopressin V(2) receptors at high-density and V(1B) receptors are candidates for the V(2)-like receptor, which evokes an increase in [Ca(2+)](i) when stimulated by the vasopressin V(2) receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) in kidney inner medullary collecting duct. We compared the pharmacological characteristics of vasopressin V(2) and V(1B) receptors in Chinese hamster ovary (CHO) cells to those of vasopressin V(2)-like receptors in rat inner medullary collecting duct cells. The vasopressin V(1B) receptor-selective agonist [deamino-Cys(1), D-3-(Pyridyl)-Ala(2), Arg(8)]vasopressin (D3PVP) did not stimulate the [Ca(2+)](i) increase in high-density vasopressin V(2) receptor-expressing CHO cells, but did in inner medullary collecting duct cells. Moreover, the vasopressin V(1A)/V(2) receptor dual antagonist 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1] benzazepin-6-yl)carbonyl] 2-phenylbenzanilide (YM087), which has no effect on vasopressin V(1B) receptors, did not block the [Ca(2+)](i) increase in inner medullary collecting duct cells when stimulated by dDAVP and D3PVP. On reverse transcription-polymerase chain reaction (RT-PCR) analysis of kidney, vasopressin V(1B) receptor mRNA was detected only in the medulla. We propose that the true nature of the vasopressin V(2)-like receptor in the inner medullary collecting duct is the vasopressin V(1B) receptor, rather than the vasopressin V(2) receptor expressed at high-density.


Effects of intranasal oxytocin prior to encoding and retrieval on recognition memory.
The neuropeptide oxytocin (OXT) has been shown to modulate a variety of human social behaviors. However, little is known about its impact on emotional memory processing. Previous research demonstrated both memory-enhancing and memory-impairing oxytocinergic effects. We investigated the influence of a single (prior to encoding) and a repeated (prior to encoding and retrieval) intranasal administration of OXT on recognition memory for stimuli taken from the International Affective Picture System. In addition, we assessed the interaction of emotion regulation during encoding and OXT-induced memory effects. In a double-blind, placebo-controlled design, 80 healthy young males performed an emotion regulation task followed by a surprising recognition memory task after 60 min. Results show that repeated OXT administration significantly improved memory certainty for negative social stimuli. Regarding the influence of emotion regulation, the promnestic effect of OXT was more pronounced when participants had been instructed to increase their negative emotions during encoding. Our findings indicate that OXT facilitates the processing of negative social stimuli during memory encoding and retrieval, possibly by enhancing the perception of aversive aspects in social situations.


Genomic organization of four novel nondisulfide-bridged peptides from scorpion Mesobuthus martensii Karsch: gaining insight into evolutionary mechanism.
At least 25 nondisulfide-bridged peptides (NDBPs) have been identified and characterized from scorpions. However, the genomic organization of the genes that encode these peptides have not been reported yet. BmKa1, BmKa2 and BmKb1 are three novel genes that code for NDBPs identified by our group from Mesobuthus martensii Karsch. Based on their cDNA sequences, the genomic DNA sequences encoding these peptides were obtained using the PCR method. Sequence analysis showed that three distinct genomic structural patterns are used to encode these three peptides. The BmKa1 gene is not interrupted by any introns. However, the BmKa2 gene is composed of two exons, interrupted by a 67 bp intron that is located in the DNA region encoding the mature peptide. Two genomic homologues of the BmKb1 cDNA sequence, named BmKb1' and BmKb2, respectively, were obtained. The BmKb1' gene contains one intron of 593 bp, inserted into the DNA region that encodes the signal peptide. Similarly, the BmKb2 gene also contains an intron that interrupts the exon that encodes the NDBP signal peptide. The amino acid sequences deduced for BmKb2 and BmKb1' differ only at one position. The data suggest that the genomic organizational pattern of NDBPs displays more divergence than that exhibited by the genes that encode disulfide-bridged peptides from scorpions.


Sperm immunity in infertile couples: antibody titers are higher against the husbands' sperm than to sperm from controls.
Titers of hemagglutination and cytotoxic antibodies to sperm were determined in the sera, seminal plasma, cervical mucus, and vaginal secretions from 69 infertile couples, using sperm from the husbands and from normal control subjects. Titers of hemagglutination and cytotoxic antibodies were significantly higher (p = 0.002 and p less than 0.001, respectively) against autologous sperm as contrasted with sperm from control subjects in sera from 55 autoimmune males. Hemagglutination and cytotoxic antibody titers were also significantly higher (p = 0.044 and p less than 0.001, respectively) against their husbands' sperm as contrasted with control sperm in sera from 46 females with isoimmunity to sperm. Ninety percent of males and females with sperm immunity were positive for histocompatibility antigens HLA-B7, HLA-B8, and/or HLA-BW35. In males, the presence of increased serum cytotoxic antibody titers against autologous versus control sperm was significantly associated with the presence of HLA-B7 allele (p = 0.0017) and with HLA-B7, HLA-B8, and/or HLA-BW35 in general (p less than 0.05). In the females, increased serum antibody titers to their own husbands' versus control sperm were not preferentially associated with HLA-B7, HLA-B8, or HLA-BW35 antigens.


Evolution of bamboo mosaic virus in a nonsystemic host results in mutations in the helicase-like domain that cause reduced RNA accumulation.
A mutant population of bamboo mosaic potexvirus (BaMV) was isolated after serial passage using Chenopodium quinoa plants. While the wild type inoculum induced indistinct chlorotic lesions, the mutant produced obvious lesions on C. quinoa although RNA accumulation of the mutant in Nicotiana benthamiana protoplasts was significantly reduced compared to wild type. Mutations were identified in the helicase-like domain. One RT-PCR-generated cDNA clone (designated pL1-33) representing the helicase-like region showed four nucleotide mutations encoding three amino acid changes that were shown to result in dramatically decreased viral accumulation. Independent analyses of the effects of these substitutions showed that nucleotide changes at position 1722 resulting in a leucine to proline switch and position 2129 resulting in a histidine to tyrosine switch had the greatest effect on viral accumulation. Combination of these two mutations resulted in a undetectable viral accumulation. We have identified that amino acids within the helicase domain but outside the universally conserved helicase-like motifs that play an important role in viral amplification.


Transfer Learning Approach to Vascular Permeability Changes in Brain Metastasis Post-Whole-Brain Radiotherapy.
The purpose of this study is to further validate the utility of our previously developed CNN in an alternative small animal model of BM through transfer learning. Unlike the glioma model, the BM mouse model develops multifocal intracranial metastases, including both contrast enhancing and non-enhancing lesions on DCE MRI, thus serving as an excellent brain tumor model to study tumor vascular permeability. Here, we conducted transfer learning by transferring the previously trained GBM CNN to DCE MRI datasets of BM mice. The CNN was re-trained to learn about the relationship between BM DCE images and target permeability maps extracted from the Extended Tofts Model (ETM). The transferred network was found to accurately predict BM permeability and presented with excellent spatial correlation with the target ETM PK maps. The CNN model was further tested in another cohort of BM mice treated with WBRT to assess vascular permeability changes induced via radiotherapy. The CNN detected significantly increased permeability parameter Ktrans in WBRT-treated tumors (p < 0.01), which was in good agreement with the target ETM PK maps. In conclusion, the proposed CNN can serve as an efficient and accurate tool for characterizing vascular permeability and treatment responses in small animal brain tumor models.


MusaNAC29-like transcription factor improves stress tolerance through modulation of phytohormone content and expression of stress responsive genes.
Understanding the molecular mechanisms governed by genes and cross-talks among stress signaling pathways is vital for generating a broad view on stress responses in plants. Here, we analysed the effects of MusaNAC29-like transcription factor of banana on stress responses and report the quantitative modulation of phytohormone and flavonoid content and analysed the growth parameters and yield trait in transgenic banana plants. Expression of MusaNAC29-like transcription factor was strongly altered in responses to stress conditions and application of signaling molecules. Under control conditions, PMusaNAC29-like-GUS is activated in cells bordering xylem vessel elements and is strongly triggered in other cells types after influence of salicylic acid and abscisic acid. Transgenic banana plants of cultivar Rasthali and Grand Naine overexpressing MusaNAC29-like transcription factor displayed superior tolerance towards drought and salinity stress. LC-MS analysis indicated elevated levels of jasmonic acid and salicylic acid while content of zeatin was significantly reduced in leaves of transgenic banana lines. Transgenic banana lines displayed increased levels of gallic acid, coumaric acid, naringenin, chlorogenic acid while levels of vanillic acid and piperine were significantly reduced. Expression of stress related genes coding for antioxidants, thiol peptidase proteins, cold-regulated proteins, late embryogenesis abundant proteins, ethylene-responsive transcription factors, bHLH proteins, jasmonate-zim-domain proteins and WRKY transcription factors were significantly induced in transgenic banana lines. Though MusaNAC29-like transcription factor improved stress tolerance, its overexpression resulted in retarded growth of transgenic lines resulting in reduced yield of banana fruits.


Sarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study.
To describe (1) the frequency and utility of clinically relevant spinal cord injury (SCI)-specific and general population thresholds for obesity and sarcopenic obesity; and (2) the fat and lean soft tissue distributions based on the neurologic level of injury and the American Spinal Injury Association Impairment Scale. Cross-sectional. Tertiary SCI rehabilitation hospital. Persons (N=136; men, n=100; women, n=36) with chronic (mean ± SD: 15.6±11.3y postinjury) tetraplegia (n=66) or paraplegia (n=70). Not applicable. Body composition was assessed with anthropometrics and whole-body dual-energy x-ray absorptiometry. Muscle atrophy was quantified using a sarcopenia threshold of appendicular lean mass index (ALMI) (men, ≤7.26kg/m2; women, ≤5.5kg/m2). Obesity was defined by percentage body fat (men, ≥25%; women, ≥35%), visceral adipose tissue (≥130cm2), and SCI-specific obesity thresholds (body mass index [BMI] ≥22kg/m2; waist circumference ≥94cm). Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Groups were compared based on impairment characteristics using an analysis of covariance. Sarcopenic obesity was prevalent in 41.9% of the sample. ALMI was lower among participants with motor-complete (6.2±1.3kg/m2) versus motor-incomplete (7.5±1.6kg/m2) injuries (P<.01). Whole-body fat was greater among participants with tetraplegia (28.8±11.2kg) versus paraplegia (24.1±8.7kg; P<.05). Compared with general population guidelines (20.6%), SCI-specific BMI thresholds identified all the participants with obesity (77.9%) based on percentage body fat (72.1%). The observed frequency of sarcopenic obesity in this sample of individuals with chronic SCI is very high, and identification of obesity is dissimilar when using SCI-specific versus general population criteria.


An Acoustic Password Enhances Auditory Learning in Juvenile Brood Parasitic Cowbirds.
How does a naive, young animal decide from which adults to learn behavior? Obligate brood parasitic birds, including brown-headed cowbirds (Molothrus ater), face a particular challenge in learning species-specific behaviors; they lay their eggs in the nest of another species, and juveniles are raised without exposure to adult conspecifics. Nevertheless, male cowbirds need to learn a conspecific song to attract appropriate mates, and female cowbirds need to learn to identify conspecific males for mating. Traditionally, it was thought that parasitic bird species rely purely on instinctual species recognition [1-4], but an alternative is that a species-specific trait serves as a "password" [5], a non-learned cue for naive animals that guides decisions regarding from whom to learn. Here, we tested the hypothesis that the adult "chatter call" enhances the learning of specific songs in juvenile cowbirds. We exposed acoustically naive juvenile male and female cowbirds to songs paired with chatter calls and found that the chatter call enhanced song production learning in males and induced a neurogenomic profile of song familiarity in females, even for heterospecific songs. Thus, a combination of experience-independent and -dependent mechanisms converges to explain how young cowbirds emerge from another species' nest yet learn behaviors from conspecifics. Identifying whether such password-based mechanisms relate to perceptual and behavioral learning in non-parasitic taxa will contribute to our general understanding of the development of social recognition systems.


[Oxidation of erucic acid and erucyl-CoA by isolated rat heart mitochondria: comparison to oleic acid].
The oxidation of [14 14-C] or [1 14-C] erucic acid by isolated mitochondria from Rat heart has been studied and compared with that of [10 14-C] oleic acid in varying conditions of incubation. Erucic acid is converted to CO2 and acid-soluble compounds much more slowly than oleic acid. The acid-soluble compounds which have been identified are acylcarnitines, ketone bodies and intermediates from the Krebs cycle; they are found in similar proportions for both substrates. Moreover, the oxidation rate of erucyl-CoA is comparable, if not equal, to that of oleyl-CoA in the same conditions. These results are discussed here. They lead to the conclusion that erucic acid is oxidized by isolated Rat heart mitochondria through the beta oxidation pathway, and that its oxidation is limited owing to its slow activation rate.


Stimulation of prostaglandin output from rat stomach by hypertonic solutions.
A whole-cell preparation of rat stomach put out appreciable amounts of immunoassayable PGE. Buffers made hypertonic with either sodium chloride or mannitol effected several-fold increases in PGE output, while a comparable osmotic concentration of urea seemed to produce much less stimulation. Enhancement of PGE output by saline--hypertonic buffers was concentration-dependent. It is suggested that the osmolarity of the gastric contents may play a role in regulating gastric PG biosynthesis.


Removal of Fe(II) ions from aqueous solution by Calabrian pine bark wastes.
The ability of Calabrian pine bark wastes (Pinus brutia Ten) for the removal of Fe(II) ions from aqueous solution at different concentrations and temperatures at a fixed pH was investigated. While the amounts of Fe(II) ions adsorbed onto the bark increased with increasing concentration, it increased slightly with increasing the temperature. Kinetics studies showed that adsorption process followed the first-order kinetic model as well as intra-particle diffusion kinetics. Adsorption isotherm followed both Langmuir and Freundlich models. And it was determined that the adsorption was favorable from a dimensionless factor, R(L). Furthermore, the thermodynamic parameters demonstrated that the removal of Fe(II) by the bark was a physical process.


Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells.
Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells. The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation. Our findings therefore highlight the potential for combining human genome variation studies with genome editing approaches to improve cell and tissue production for regenerative medicine.


Molecular mechanisms for the regulation of penile smooth muscle contractility.
Relaxation of penile smooth muscle (arterial and trabecular) initiates and maintains penile erection. Relaxation of smooth muscle is viewed as a 'resetting' of contractile machinery by resumption of a precontractile state accomplished by lowering cytosolic Ca(+2) and/or by a decrease in sensitivity of the contractile machinery to Ca(+2). There are various mechanisms whereby cytosolic Ca(+2) can be reduced and relaxation achieved, but in general, all pathways depend on the accumulation of the nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) or activation of K channels with hyperpolarization. Another mechanism, activation of Na(+)/K(+) adenosine triphosphatase (ATPase) by nitric oxide, has been shown to be involved in relaxation of trabecular smooth muscle. Since Na(+)/K(+) ATPase is electrogenic, its stimulation would cause hyperpolarization. Hyperpolarization will prevent the opening of voltage-dependent calcium channels. Guanylate cyclase, which catalyzes the conversion of guanosine triphosphate to cGMP, is activated by nitric oxide. cGMP activates protein kinase G, which through multiple phosphorylations facilitates calcium sequestration and reduces the entry of calcium into the cell. Other muscle relaxants act by way of a cAMP-dependent mechanism such as prostaglandin E, vasoactive intestinal polypeptide, and catecholamines (via beta-receptors). These substances react with membrane receptors coupled to a GS-type protein that stimulates adenylate cyclase, which catalyzes the accumulation of cAMP. DOI: 10.1038/sj/ijir/3900790


Emerging roles for renal primary cilia in epithelial repair.
Primary cilia are microscopic sensory antennae that cells in many vertebrate tissues use to gather information about their environment. In the kidney, primary cilia sense urine flow and are essential for the maintenance of epithelial architecture. Defects of this organelle cause the cystic kidney disease characterized by epithelial abnormalities. These findings link primary cilia to the regulation of epithelial differentiation and proliferation, processes that must be precisely controlled during epithelial repair in the kidney. Here, we consider likely roles for primary cilium-based signaling during responses to renal injury and ensuing epithelial repair processes.


Bioelectromagnetic applications for multiple sclerosis.
There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.


Closing a Right Coronary Artery Fistula Draining Into the Coronary Sinus Using a Covered Stent in the Coronary Sinus.
This report describes the case of a symptomatic patient with a right coronary artery fistula draining into the coronary sinus who underwent transcatheter closure, which was deployed in the drainage site to seal off the exit of the fistula. (Level of Difficulty: Advanced.).


Hypericin-based fluorescence diagnosis of bladder carcinoma.
To determine the use of hypericin instillation for the fluorescent detection of papillary bladder cancer and carcinoma in situ. Eighty-seven patients with papillary bladder cancer and/or carcinoma in situ received instillations with 40 mL of an 8 micromol/L hypericin solution for at least 2 h. Fluorescent excitation with blue light was effective for up to 16 h, and biopsies were examined by fluorescence microscopy. There were no side-effects reported, no photobleaching and all papillary lesions fluoresced red. The sensitivity and specificity for detecting carcinoma in situ was 94% and 95%, respectively. An interval of 4 months is recommended after BCG instillations before using this test. Fluorescence microscopy showed that hypericin was selectively localized in the epithelium. Hypericin-induced fluorescence has a high sensitivity and specificity for detecting bladder cancer. After 4 months there are few false-positive results in patients treated with BCG.


The Improvement of Epothilone D Yield by the Disruption of epoK Gene in Sorangium cellulosum Using TALEN System.
Epothilones are a kind of 16-member macrolides with strong anticancer activity, which was produced by Sorangium cellulosum. Epothlione D shows better drug resistance and safety than taxol in clinical trials. However, the low yield of epothilone D in Sorangium cellulosum and thereof toxicity limited the application of epothilone D. In this study, the epoK gene in gene cluster for epothilone was firstly inactivated by the employment of TALEN gene knockout system. The qRT-PCR analysis and sequencing were performed to confirm the gene deletion of epoK, resulting in the epothilone D yield improvement by 34.9±1.6% and the decrease of epothilone B yield by 34.2±2.5%, which was demonstrated by LC-MS analysis. This study would lay a foundation for the yield improvement of epothilones D, B and thereof derivatives in S. cellulosum by genetic engineering, thus promoting the applications of epothilones in the field of anticancer.


Neutrophil-Related Gene Expression Signatures in Idiopathic Pulmonary Fibrosis: Implications for Disease Characteristic and Identification of Diagnostic Hub Genes.
Idiopathic pulmonary fibrosis (IPF) is a disease with unclear etiology and a poor prognosis. Although the involvement of neutrophils in IPF pathogenesis has been suggested, the exact nature of this relationship remains unclear. We analyzed data from the Gene Expression Omnibus (GEO) using immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and consensus cluster analysis. Neutrophil-related genes and hub genes related to neutrophils were identified and differentially expressed between IPF patients and healthy controls. We also validated the expression differences of hub genes in a bleomycin-induced mice model. Immune infiltration analysis revealed a significantly decreased percentage of neutrophils in the lung tissue of IPF patients compared with healthy controls (P<0.001) in both the train and validation sets. Neutrophil-related genes in IPF were identified by WGCNA, and functional enrichment analysis showed that these genes were mainly involved in the cytokine-cytokine receptor interaction pathway and correlated with lung disease, consistent with DEGs between IPF and healthy controls. Eight hub genes related to neutrophils were identified, including MMP16, ARG1, IL1R2, PROK2, MS4A2, PIR, and ZNF436. Consensus cluster analysis revealed a low neutrophil-infiltrating cluster that was correlated with IPF (P<0.001), and a principal component analysis-generated score could distinguish IPF patients from healthy controls, with an area under the curve of 0.930 in the train set and 0.768 in the validation set. We also constructed a diagnostic model using hub genes related to neutrophils, which showed a reliable diagnostic value with an area under the curve of 0.955 in the train set and 0.995 in the validation set. Our findings provide evidence of a low neutrophil-infiltrating characteristic in the IPF microenvironment and identify hub genes related to neutrophils that may serve as diagnostic biomarkers for the disease.


The effect of hepatic or renal impairment on the pharmacokinetics of edivoxetine, a selective norepinephrine transporter reuptake inhibitor.
To assess the impact of hepatic or renal impairment on the pharmacokinetics (PK) of edivoxetine. Two separate multi-center, open-label studies with males and females were conducted. Subjects were categorized according to their hepatic function, determined by the Child-Pugh classification, or renal function, determined by creatinine clearance using the Cockcroft-Gault equation. Subjects received a single dose of 18 mg in the hepatic impairment study or 6 mg in the renal impairment study. Noncompartmental PK parameters were computed from the edivoxetine plasma concentration-time data. In the hepatic study, the geometric least squares mean (GLSM) and 90 % confidence interval (CI) of the ratio [impaired : normal] of area under the concentration versus time curve from time zero to infinity (AUC0-∞; h × ng/mL) was 1.24 (0.93, 1.64) in the mild, 1.60 (1.21, 2.12) in the moderate, and 1.70 (1.28, 2.24) in the severe group. In the renal impairment study, the GLSM (90 % CI) of the ratio [impaired : normal] of AUC0-∞ was 1.13 (0.73, 1.73) in mild, 1.90 (1.28, 2.82) in moderate, 1.55 (0.94, 2.55) in severe, and 1.03 (0.66, 1.59) in ESRD groups. Overall, the GLSM of the ratio [impaired : normal] of Cmax was slightly less than or approximately 1 across the hepatic and renal impairment groups. Across both studies, there were no clinically significant changes in vital signs and laboratory values, the adverse events were mild in severity and mostly related to nervous system and gastrointestinal disorder-related events. PK changes in subjects with hepatic or renal impairment were of small magnitude and did not appear to impact overall subject tolerability. Daily dosing of edivoxetine in a larger population of impaired subjects, including those with dual impairment, would aid in establishing edivoxetine tolerability and PK in a clinical practice scenario.


[Benign lesions of the thyroid. Clinical methodology++ and therapeutic management in our personal experience].
Thyroid benign nodules are common (90-95%). A personal series of 544 cases forms the basis for a discussion of modern diagnostic techniques, their value and limitations. At the present time, subtotal or near total thyroidectomy is preferred, also in benign thyroid disease. The perfect anatomical knowledge of the neck is of paramount importance to minimize the risk of complications, such as a superior or inferior laryngeal nerve injury and hypoparathyroidism. Temporary suclinic, clinic, definitive hypoparathyroidism was never observed. Relapse was observed in 20 hypothyreosic patients with hormonal therapy.


The effects of axotomy on the development of the rat superior cervical ganglion.
The effects of division of the postganglionic axons of the adrenergic neurones in the superior cervical ganglion of the rat were examined with regard to the total ganglionic protein content and tyrosine hydroxylase and DOPA decarboxylase activities. Axotomy before the twelfth postnatal day results in a marked atrophy of the ganglion and a reduction in the total enzyme content of the ganglion. Axotomy after postnatal day 21 results in the normal adult ganglion response with a large increase in the total protein content of the ganglion and only minor changes in the total enzyme content of the ganglion. Axotomy between the postnatal days 12 and 21 results in an intermediate response. Thus it can be concluded there is a critical period during the development of the ganglion during which the adrenergic neurones undergo a maturation governed by their contact with the peripheral target cell via axons. These results suggest a trophic role of the end organ on the adrenergic neurone.


Purification and characterization of a glycosyltransferase complex from the culture broth of Streptococcus mutans FA1.
The extracellular glycosyltransferases from Streptococcus mutans FA1 were purified by using the following procedures: ammonium sulfate precipitation, poly-(acrylamide) gel filtration, DEAE-cellulose chromatography, and agarose-gel filtration. The dextransucrase and levansucrase activities were purified 350- and 500-fold, repsectively, and the ratio of the two activities remained almost constant throughout the purification. Both enzymes have a pH optimum of 6.0, a Km for sucrose of 55mM, and isoelectric points of 3.7 and 4.6. The enzymes are inactivated by repeated freezing and thawing, but retain partial activity even after heating at 100 degrees. The enzyme preparation contains a carbohydrate moiety which does not appear to be either bound levan or dextran.


[Pituitary adenomas with cells containing bêta MSH, alpha and bêta endorphins and without ACTH (author's transl)].
By using immunohistoenzymatic techniques, cells of 4 pituitary adenomas are revealed with beta MSH, alpha and beta endorphins antisera but do not react with 1--24 and 17--39 ACTH antisera. These data suggest that adenomatous cells are able to synthesize and LPH-like molecule without ACTH. The levels of plasmatic LPH and beta MSH, studied by RIA, stay normal. These results are discussed.


A crucible for murder: the social context of violent children and adolescents.
The author describes aspects of social context that are of importance in the genesis of murderous violence in children and adolescents. Case presentations illustrate the effects of family attachment pathology, differing outcomes in destructive children, and the copycat phenomenon. The author concludes by summarizing the continuum of responses of children and adolescents to various forms of threat: real attack, unconscious threat, kindled threat, suppressed threat, bully-victim-bystander sadomasochistic ritual attack, and peer-group-validated threat.


Poltransplant Recommendations on Organ Donation and Transplantation in the COVID-19 Era.
In this article, we present the standpoint and recommendations of Poltransplant on the use of organs, tissues, and cells other than hematopoietic cells for transplant in connection with SARS-CoV-2 infections (January 15, 2021).


Round worm infestation as a cause of small bowel anastomotic breakdown following urinary diversion for cervical cancer.
Vesicovaginal fistulae are well-recognized complications of radiotherapy for the treatment of cervical cancer. These patients often require some form of urinary diversion. Small bowel is often utilized for these purposes. A patient with stage IIB cervical cancer presented with a vesicovaginal fistula 6 years post-radiotherapy. An ileal conduit was performed. On day 9 post-surgery breakdown of the small bowel anastomosis was suspected. At laparotomy small bowel anastomotic breakdown was confirmed with round worms at the anastomotic site. Perforation of small bowel by round worm has been previously described in a patient with Meckel' s diverticulum. This report describes an unusual cause of small bowel anastomotic breakdown following urinary diversion.


Diagnostic imaging of pelvic and chest wall trauma.
Imaging of patients with pelvic trauma begins with a logical approach to plain radiographs. These films reveal the probable mechanism of injury and suggest a rationale for emergent reduction. Radiographs, along with the clinical impression, suggest the likelihood of associated soft tissue injury, possibly requiring further specific radiographic studies. Significant vascular injury most often accompanies disruption of the posterior pelvic ring. Bladder and urethral trauma may be suspected in any displaced type III pelvic fracture with suggestive clinical signs. Ideally, urethrography precedes bladder catheterization. Acetabular fractures must be recognized because of their implications for future hip joint function. CT is very helpful in definitive treatment planning of pelvic (especially acetabular) fractures but may be delayed until other life-threatening injuries have been addressed. Plain radiography is also well suited to evaluation of chest wall trauma. When multiple ribs are fractured in two places, the radiologist should suggest the possibility of flail chest. Sternal fractures and multiple rib fractures, including the first three ribs, may herald life-threatening vascular or cardiac damage. To summarize, the radiologist contributes most to the care of the trauma patient by recognizing roentgen patterns of injury, knowing which are commonly accompanied by damage to critical soft tissues, and performing the indicated radiographic studies efficiently.


Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
In patients with chronic congestive heart failure (CHF), aldosterone production may occur despite the administration of angiotensin-converting enzyme (ACE) inhibitors. This phenomenon has been termed aldosterone "escape"; its relation to the severity of the disease is unknown. We sought to assess whether aldosterone escape might be related to disease severity or functional impairment in patients with CHF. One hundred forty-one consecutive patients with CHF who received ACE inhibitors (> 6 months) underwent an evaluation of neurohormonal activation and body composition, an echo-Doppler examination, and a cardiopulmonary exercise test. Aldosterone escape was defined as plasma levels of aldosterone above the normal range in our laboratory (> 0.42 nmol/L). Fourteen patients (10%) had aldosterone escape. There were no differences between patients with and without aldosterone escape with regard to age, New York Heart Association class, neurohormonal activation, ACE inhibitor dose, hemodynamics, or skeletal muscle bulk. In contrast, mean peak oxygen consumption (14.2 +/- 3.5 vs 17.3 +/- 4.9 ml/min/kg, p < 0.05) and the slope of the relation between ventilation and carbon dioxide production (41 +/- 7 vs 36 +/- 6, p <0.05) were significantly worse in patients with aldosterone escape compared with those without it. Thus, aldosterone escape is associated with reduced exercise capacity in patients with CHF. This factor does not seem to be linked with hemodynamic mechanisms or with a reduced skeletal muscle bulk.


The use of morbidity questionnaires to identify communities with high prevalences of schistosome or geohelminth infections in Tanzania.
Parasitic infections were investigated in Morogoro Rural District, Tanzania, between October 1992 and June 1993. A total of 4589 schoolchildren (aged 7-17 years) from 30 primary schools was screened for infection with Ascaris lumbricoides, Trichuris trichiura, hookworms (3456 children only), Schistosoma mansoni and S. haematobium. The children were also asked about their recent experiences of the following: diarrhoea, abdominal pain, blood in stool, perception of suffering from schistosomiasis, and worm infection and examined for spleen and liver enlargement. Among schools, there were correlations between the prevalence of S. mansoni infection and bloody stools, spleen enlargement and liver enlargement, and between S. haematobium infection and the presence of blood in urine. To exclude ecological explanations for the correlations, logistic regression was used to estimate the adjusted odds ratio (OR) for each infection and each sign or symptom. No sign or symptom was significantly associated with any geohelminth infection. Reported blood in stool was significantly associated with S. mansoni infection (OR = 1.62, P = 0.045). Reported blood in urine was significantly associated with S. haematobium infection (OR = 7.71, P < 0.001), as was reported blood in stool (OR = 11.52, P < 0.001), indicating that presence of blood in either form of excreta was related to the local term for schistosomiasis. These results support the possibility of using reported blood in stool as a means of rapid assessment for identifying communities with a high prevalence of S. mansoni infection.


Caries outcomes after orthodontic treatment with fixed appliances: a longitudinal prospective study.
The aim of this study was to assess the relationship between orthodontic and the development of dental caries in the same patients who received single jaw orthodontic treatment. A consecutive sample consisted of 60 subjects who required single upper jaw orthodontic were recruited consecutively from the Department of Orthodontic at the Stomatology Hospital of Wenzhou Medical University. The dental examinations were routinely carried out by one dentists at the following stages: pre-treatment (T1); post-treatment (T2); more than 7 years after T1 (T3). The DMFS count which reflect the caries experience was recorded. There was no significant difference between the treated groups and untreated groups for the DMFS before received fixed orthodontic treatment. The same result was found after orthodontic treatment. However, the average number of DMFS in the treatment jaw after fixed orthodontic treatment was lower than in the without treatment jaw after long-term follow-up period. Fixed orthodontic appliances significant decrease the patients caries risk after orthodontic treatment.


Pulmonary hypertension associated with sickle cell disease: pathophysiology and rationale for treatment.
Approximately one third of patients with sickle cell disease (SCD) have pulmonary hypertension (PH), which increases their risk of death. Endothelin (ET)-1 is elevated in SCD and appears to play a key role in many of the pathologic processes in this disease, including PH, suggesting that endothelin receptor antagonists such as bosentan may be effective in treating patients with SCD, particularly those with PH. Other possible treatments include sildenafil, epoprostenol, and oral arginine. Data from controlled clinical trials are needed to establish the most effective treatment of patients with PH associated with SCD.


Shock wave treatment improves nerve regeneration in the rat.
The aims of the experiments were to: (1) determine whether low-energy shock wave treatment accelerates the recovery of muscle sensitivity and functionality after a nerve lesion; and (2) assess the effect of shock waves on the regeneration of injured nerve fibers. After compression of a muscle nerve in rats the effects of shock wave treatment on the sequelae of the lesion were tested. In non-anesthetized animals, pressure pain thresholds and exploratory activity were determined. The influence of the treatment on the distance of nerve regeneration was studied in immunohistochemical experiments. Both behavioral and immunohistochemical data show that shock wave treatment accelerates the recovery of muscle sensitivity and functionality and promotes regeneration of injured nerve fibers. Treatment with focused shock waves induces an improvement of nerve regeneration in a rodent model of nerve compression.


Metabolic effects of GH antagonism in patients with acromegaly.
Pegvisomant is a growth hormone (GH) receptor antagonist that represents a major advance in the treatment of acromegaly. Initial results with pegvisomant indicate this novel form of therapy to be the most effective treatment available for achieving biochemical disease control as ascertained by circulating IGF-I.


Observing functional actions affects semantic processing of tools: evidence of a motor-to-semantic priming.
Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools' function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool-recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact.


Measuring the cost of reproduction : III. The correlation structure of the early life history of Daphnia pulex.
The timing of the first two broods and the number and size of offspring in each was measured in a series of three experiments for monoclonal cultures of the cladoceran Daphnia pulex reared under standard conditions of ration, temperature and photoperiod. The pattern of total correlations between pairs of life-history variables did not in general support predictions made by hypotheses of reproductive cost. A partial correlation analysis, involving initial size and subsequent growth as well as the life history variables themselves, was performed in an attempt to avoid potential fallacies introduced by the use of total correlations. The only consistent effect found was a positive relationship between the age at reproductive maturity and the mean size of offspring in the first brood. The structure of this segment of the life history is strongly influenced by interactions between size and reproduction, to an extent that precludes the use of simple optimality models.


Comparative effects of zopiclone, triazolam and placebo on memory and psychomotor performance in healthy volunteers.
This study evaluated the effects of acute doses of zopiclone (7.5 mg), triazolam (0.25 mg) and placebo on memory and psychomotor performance of 12 normal volunteers. The subjects received both drugs in a repeated measure, double-blind Latin square design. The tests (CFF, CRT, DSST, memory assessments) were performed before and 2 and 6 hr after treatment. Zopiclone and triazolam induced an anterograde amnesia affecting short-term and long-term memory which lasted less than 6 hr. No retrograde amnesia was observed. Two hr after drug intake of both hypnotics psychomotor performances were significantly altered compared with placebo. The subjects also felt more drowsy, dizzy, clumsy and tired, and less alert and energetic 2 hr after zopiclone and triazolam compared to placebo. There was no difference between the effects of the two hypnotics at the doses studied.


Effect of radial artery or saphenous vein conduit for the second graft on 6-year clinical outcome after coronary artery bypass grafting. Results of a randomised trial.
In order to determine the best conduit for coronary targets other than the left anterior descending (LAD) artery, long-term clinical outcomes following revascularisation with a radial artery or saphenous vein graft were evaluated as part of the radial artery patency and clinical outcomes (RAPCO) study. As part of the RAPCO protocol for this prospective, randomised, single-centre trial, patients aged over 70 years undergoing primary CABG were randomly assigned to use of a radial artery (n=113) or saphenous vein (n=112) to revascularise the best non-LAD coronary vessel. Follow-up was annual. Primary clinical end-points were death, myocardial infarction or need for revascularisation. Data were analysed by intention to treat. The preoperative demographics (age, gender, presence of hypertension or diabetes mellitus) and urgency of surgery did not differ significantly between the two groups. The allocated arterial or venous conduit was utilised as intended in 104/113 and 110/112 patients, respectively. Mean number of grafts was 3.2+/-0.9 and 3.3+/-0.7 in the two groups. During follow-up of mean duration 6.2 years (maximum 10.8 years) there were 16 deaths in each group and 9 vs 13 other events in the radial artery and saphenous vein groups, respectively. These clinical outcomes did not differ significantly (log rank p=0.98 for survival and p=0.52 for event-free survival). Use of a radial artery or saphenous vein for the second graft during primary CABG does not significantly influence clinical outcome at 6 years. Mean 5-year angiographic patency data are awaited, but from the patient's perspective the likelihood of a satisfactory long-term result is equivalent, whichever conduit is used.


Analysis of thymidylate synthase gene amplification and of mRNA levels in the cell cycle.
We report that the gene for thymidylate synthase (TS) is amplified in the mouse cell line L1210:C15 that was selectively grown in increasing concentrations of the competitive inhibitor of thymidylate synthase, CB3717. The gene is amplified 50-fold compared to the parental cell line. Amplification has not been accompanied by any major rearrangements, and the increase in gene copy number is reflected in elevation of thymidylate synthase mRNA levels. The amplification is relatively stable as there was only a 2- to 3-fold decrease in the number of amplified TS genes when cells were grown in the absence of selection for 375 generations. We also observe a 30- to 40-fold increase in number of copies of the dihydrofolate reductase gene with 7-fold elevation of the RNA product, and we suggest that this may be due to cross-inhibition of dihydrofolate reductase by CB3717. Thymidylate synthase mRNA levels in L1210 and L1210:C15 show no variation within the different phases of the cell cycle but are significantly reduced during quiescence.


A Cross-Cultural Examination of the Role of Youth Emotion Regulation in Mentoring Relationships.
Youth mentoring programs have grown in popularity, both within the United States (U.S.) and abroad, as an intervention to support youth with common behavioral and emotional difficulties. However, it is unclear whether certain dimensions of youth risk may diminish the positive impact of formalized mentoring relationships. The current study therefore examined whether youth emotion regulation, a transdiagnostic risk factor for both externalizing and internalizing behavioral difficulties, predicted mentoring relationship quality and the likelihood of early match closure. Participants included 1,298 randomized mentor-youth dyads from two nationwide mentoring programs, one with chapters across the U.S. (youth: 56% female; 37% White), and another with chapters across Mexico (youth: 49% female; 100% non-Indigenous). At baseline, youth completed the Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA). At program completion, youth and mentors completed measures of mentoring relationship quality. Multigroup structural equation models of youth outcomes revealed that greater youth use of cognitive reappraisal predicted better mentoring relationship quality in both countries when co-varying for sex, and that this relationship was stronger for mentor-youth pairs in the U.S. compared to those in Mexico. These findings have important implications for understanding the ways in which youth characteristics might shape the quality and impact of mentoring relationships across different cultural settings.


Duodenal transection and vertebral injury occurring in combination in a patient wearing a seat belt.
A case is described of complete transection of the first part of the duodenum combined with a vertebral injury in a patient wearing a lap-diagonal seat belt when involved in a head-on collision. A review of the literature is presented, the mechanism of injury discussed and attention drawn to the delay in diagnosis.


COVID-19 Vaccination and Intent Among Healthcare Personnel, U.S.
Healthcare personnel are at increased risk for COVID-19 from workplace exposure. National estimates on COVID-19 vaccination coverage among healthcare personnel are limited. Data from an opt-in Internet panel survey of 2,434 healthcare personnel, conducted on March 30, 2021-April 15, 2021, were analyzed to assess the receipt of ≥1 dose of a COVID-19 vaccine and vaccination intent. Multivariable logistic regression was used to assess the factors associated with COVID-19 vaccination and intent for vaccination. Overall, 68.2% of healthcare personnel reported a receipt of ≥1 dose of a COVID-19 vaccine, 9.8% would probably/definitely get vaccinated, 7.1% were unsure, and 14.9% would probably/definitely not get vaccinated. COVID-19 vaccination coverage was highest among physicians (89.0%), healthcare personnel working in hospitals (75.0%), and healthcare personnel of non-Hispanic White or other race (75.7%-77.4%). Healthcare personnel who received influenza vaccine in 2020-2021 (adjusted prevalence ratio=1.92) and those aged ≥60 years (adjusted prevalence ratio=1.37) were more likely to report a receipt of ≥1 dose of a COVID-19 vaccine. Non-Hispanic Black healthcare personnel (adjusted prevalence ratio=0.74), nurse practitioners/physician assistants (adjusted prevalence ratio=0.55), assistants/aides (adjusted prevalence ratio=0.73), and nonclinical healthcare personnel (adjusted prevalence ratio=0.79) were less likely to have received a COVID-19 vaccine. The common reasons for vaccination included protecting self (88.1%), family and friends (86.3%), and patients (69.2%) from COVID-19. The most common reason for nonvaccination was concern about side effects and safety of COVID-19 vaccine (59.7%). Understanding vaccination status and intent among healthcare personnel is important for addressing barriers to vaccination. Addressing concerns on side effects, safety, and effectiveness of COVID-19 vaccines as well as their fast development and approval may help improve vaccination coverage among healthcare personnel.


Exploring prostate cancer in the post-genomic era.
In the Special Issue on Prostate Cancer, we have invited 25 researchers or clinicians from prostate cancer community to review the cutting-edge topics in this field. In particular, the mini-reviews have covered various basic science and clinical aspects in prostate cancer, including prostate epithelial stem cells or progenitors, androgen and androgen receptor pathways, tumor modeling, genomics, different cell-autonomous and non-cell-autonomous mechanisms as well as various clinical issues encompassing diagnosis, risk stratification and treatments.


Improvement of diagnostic performance of hyperacute ischemic stroke in head CT using an image-based noise reduction technique with non-black-boxed process.
This study aims to investigate whether an image-based noise reduction (INR) technique with a conventional rule-based algorithm involving no black-boxed processes can outperform an existing hybrid-type iterative reconstruction (HIR) technique, when applied to brain CT images for diagnosis of early CT signs, which generally exhibit low-contrast lesions that are difficult to detect. The subjects comprised 27 patients having infarctions within 4.5 h of onset and 27 patients with no change in brain parenchyma. Images with thicknesses of 5 mm and 0.625 mm were reconstructed by HIR. Images with a thickness of 0.625 mm reconstructed by filter back projection (FBP) were processed by INR. The contrast-to-noise ratios (CNRs) were calculated between gray and white matters; lentiform nucleus and internal capsule; infarcted and non-infarcted areas. Two radiologists subjectively evaluated the presence of hyperdense artery signs (HASs) and infarctions and visually scored three properties regarding image quality (0.625-mm HIR images were excluded because of their notably worse noise appearances). The CNRs of INR were significantly better than those of HIR with P < 0.001 for all the indicators. INR yielded significantly higher areas under the curve for both infarction and HAS detections than HIR (P < 0.001). Also, INR significantly improved the visual scores of all the three indicators. The INR incorporating a simple and reproducible algorithm was more effective than HIR in detecting early CT signs and can be potentially applied to CT images from a large variety of CT systems.


Mirex residues in nontarget organisms after application of 10-5 bait for fire ant control, northeast Florida--1972-74.
The 10-5 bait formulation of mirex insecticide was applied to a 20,000-acre area of northeast Florida. For 24 months after application, samples of a wide variety of fauna were collected and analyzed for mirex content. Insects accumulated mirex to the greatest extent in the first 6 months after application; most residues had decreased greatly by 12 months. Other invertebrates showed low mirex levels during the first 9 months after application and none after 12 months. Fish possessed low levels of insecticides for 9 months; amphibians showed mirex residues for 12 months after application. In general, reptiles had low levels throughout the 24-month period and mammals had higher levels, particularly in fat tissues. Birds consistently had low to moderate mirex levels. After a single application of 10-5 mirex bait, only relatively low levels of insecticide were detected in exposed fauna. After 24-months, mirex was found infrequently and at low levels.


A randomized, placebo-controlled trial using a novel PAP delivery platform to treat patients with OSA and comorbid PTSD.
Positive airway pressure (PAP) adherence is poor in comorbid OSA/PTSD. SensAwake™ (SA) is a wake-sensing PAP algorithm that lowers pressure when wake is detected. We compared auto-PAP (aPAP) with and without SA for comorbid OSA/PTSD. Prospective, randomized crossover study comparing aPAP to aPAP + SA. We enrolled patients with OSA/PTSD who were PAP naïve. Four weeks after randomization, the patients were crossed over to the alternate treatment group, with final follow-up at eight weeks. Sleep questionnaires (ESS, ISI, FSS, and FOSQ-10) were assessed at baseline and follow-up. We enrolled 85 patients with OSA/PTSD. aPAP reduced AHI to < 5/h in both groups. Our primary endpoint, average hours of aPAP adherence (total) after 4 weeks, was significantly increased in the SA group in our intention-to-treat (ITT) analysis (ß = 1.13 (95% CI 0.16-2.1); p = 0.02), after adjustment for ESS differences at baseline. After adjustment for ESS, SA (ITT analysis) also showed significant improvement in percentage of nights used for ≥ 4 h (ß = 14.9 (95% CI 1.02-28.9); p = 0.04). There were trends toward an increase in percentage nights used total (ß = 17.4 (95% CI - 0.1 to 34.9); p = 0.05), average hours of aPAP adherence (nights used) (ß = 1.04 (95% CI - 0.07 to 2.1); p = 0.07), and regular use (OR = 7.5 (95% CI 0.9-64.7); p = 0.07) after adjustment for ESS at baseline. After adjustment for ESS and days to cross over, SA by actual assignment did not show any effect on adherence variables. The ESS, ISI, FSS, and FOSQ-10 all showed significant improvements with PAP, but there were no differences in the magnitude of improvement in any score between groups. Adherence to aPAP may be improved with the addition of SA and deserves further study. SA is as effective as standard aPAP for normalizing the AHI and improving sleep-related symptoms. ClinicalTrials.gov NCT02549508 https://clinicaltrials.gov/ct2/show/NCT02549508?term=NCT02549508&rank=1 "Comparison Study Using APAP With and Without SensAwake in Patients With OSA and PTSD".


Effect of human immunodeficiency virus on the brain: A review.
Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV-associated neurocognitive disorder (HAND) is one of the most common comorbidities of HIV. However, the effect of HIV on the brain has not been fully investigated. This article aimed to review the changes to the brain due to HIV in terms of atrophy, diffusion changes, and hyperintensities. Studies have observed significant atrophy in subcortical gray matter, as well as in cortical white and gray matter. Moreover, the ventricles enlarge, and the sulci widen. Although HIV causes changes to the white and gray matter of the brain, few diffusion tensor imaging studies have investigated the changes to gray matter integrity. White and gray matter hyperintensities have frequently been observed in HIV-positive individuals, with the subcortical gray matter (caudate nucleus and putamen) and periventricular white matter frequently affected. In conclusion, subcortical gray matter is the first brain region to be affected and is affected most severely. Additionally, this review highlights the gaps in the literature, since the effect of HIV on the brain is not fully known. Future studies should continue to investigate the effect of HIV on the brain in different stages of the disease, and alternate therapies should be developed since highly active antiretroviral therapy is currently ineffective at treating HAND.


Electrochemical disinfection of irrigation water with a graphite electrode flow cell.
In this work, we report experimental studies on the disinfection of irrigation water using a flow cell assembled with low-cost graphite plates as both anode and cathode. Natural irrigation waters collected from two irrigation locations (Reservoir 225 and Bott Well Pond) in Hawaii were used, and synthetic irrigation waters were prepared based on the chemical analysis of natural irrigation waters. The concentration of chloride was 10.2 mg/L in the synthetic Reservoir 225 water and 6.9 mg/L in the synthetic Bott Well pond water. Escherichia coli K12 ER2738 was selected as a model bacterium to evaluate the disinfection capability of the flow cell. Experiments performed in the synthetic irrigation waters showed that E. coli was inactivated by free chlorine species electro-generated from oxidation of chloride ions at the graphite anode. Complete removal of E. coli was achieved within 10 min in the synthetic irrigation waters. The disinfection of the natural irrigation waters took about four times longer than the disinfection of the synthetic irrigation waters. This result is most likely due to the presence of organic matter (and possibly other oxidizable species) in the natural irrigation waters. PRACTITIONER POINTS: Electrochemical flow cell disinfects to 99.9% with commercial graphite electrodes. E. coli is removed in 10 min from synthetic irrigation water by a flow cell. E. coli removal takes 4× longer in natural irrigation water. A minimum current density of ≥1 mA/cm2 is required for disinfection. The primary disinfection mechanism is through chlorine generated from chloride ions.


The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI.
While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population.


Confined compression experiments on bovine nucleus pulposus and annulus fibrosus: sensitivity of the experiment in the determination of compressive modulus and hydraulic permeability.
The biphasic material properties for nucleus pulposus tissue in confined compression have not been reported previously, and are required for a better understanding of intervertebral disc function and to provide material properties for use in finite-element models. The aims of this study were to determine linear and non-linear material properties for nucleus pulposus and annulus fibrosus tissues in confined compression, to define the influence of swelling conditions on these properties, and to determine the changes in the compressive modulus and hydraulic permeability induced by the repetition of the stress-relaxation experiment after a return to swelling pressure equilibrium. Specimens from caudal bovine nucleus and annulus were tested in confined compression stress-relaxation experiments and analyzed to quantify the compressive modulus and hydraulic permeability using linear and non-linear biphasic models. Our results suggested the use of confined swelling pre-test condition and non-linear biphasic model, which provided the material parameters with lowest relative variance and water content most representative of physiological conditions. Smaller compressive modulus and higher hydraulic permeability were obtained for the nucleus (H(A0)=0.31+/-0.04 MPa, k(0)=0.67+/-0.09 x 10(-15)m(4)/Ns) than for the annulus (H(A0)=0.74+/-0.13 MPa, k(0)=0.23+/-0.19 x 10(-15)m(4)/Ns), with relatively weak non-linearities. Strains up to 20% resulted in material properties that were significantly altered upon retesting. These altered material properties are an effort to quantify non-recoverable damage that occurs in disc tissue and suggest that in vivo exposure of disc tissues to low strain-rate and high-deformation loading conditions which outpace biological repair may result in altered mechanical behaviors.


A rare case of pyosalpinx in adolescent girl with Hirschsprung's disease who underwent transvaginal ultrasound-guided drainage.
Hydrosalpinx and pyosalpinx are rare gynecologic problems during adolescence, especially in girls without a history of sexual activity. They are even rarer in women with Hirschsprung's disease (HD). We herein report a case of pyosalpinx in an adolescent girl with HD treated by transvaginal ultrasound-guided drainage. The present patient was a 12-year-old girl (weight 83 kg; height 159 cm; body mass index 32.8 kg/m2). She had undergone five laparotomies for long-segment HD by 2 years. Her menarche had occurred at 10 years. She was admitted with lower abdominal and anal pain. Computed tomography (CT), magnetic resonance imaging (MRI), and transvaginal ultrasound showed left pyosalpinx and abdominal abscess. Surgical drainage was necessary; however, she had a history of polysurgery and was severely obese, so laparotomy was considered to carry a high risk. Transvaginal ultrasound was deemed more likely to reach the abscess safely. Therefore, she was treated with transvaginal ultrasound-guided drainage by a gynecologist skilled in the procedure. She was discharged home after 52 days. One year and nine months after discharge, there was no reformation of either the abscess or pyosalpinx. Adolescent girls with HD are at risk of developing hydrosalpinx. Depending on the defecation status, pyosalpinx may also develop. As a less-invasive surgical treatment, transvaginal ultrasound-guided drainage can avoid laparotomy. Collaboration with a gynecologist is essential for the diagnosis and treatment of this clinical condition. Pediatric surgeons should communicate with gynecologists for such cases beginning around puberty for continuous follow-up.


What are killer cells and what do they do?
Cytotoxic effector function of the immune system is mediated predominantly by killer cells and with the exception of complement-mediated lysis all forms of immune-directed cell death are attributable to these cells. The heterogeneous collection of cells with cytotoxic properties ranges from the phylogenetically primitive granulocyte and natural killer (NK) cell lineages to the more complex and versatile macrophage and antigen-specific cytotoxic T lymphocyte. Most killer cells are capable of the dual functions of cytotoxicity and immunoregulation. Granulocytes, macrophages and NK cells constitute an effective 'first line' cellular defence against invasive microbial pathogens and emerging malignancies. Through direct cytotoxicity or by the secretion of cytokines, NK cells also prevent overproliferation of precursor cell populations, thereby exerting a more discriminating control over antigen-specific T and B cell responses. The ultimate refinement of the killer cell is the cytotoxic T cell which is directed by an antigen receptor comparable in specificity and diversity to the immunoglobulin molecule. The mechanisms underlying the initial interaction between killer cell and target and the subsequent lytic event are imperfectly understood. Although many cytokines with lytic properties have been identified and in some cases cloned, their relative importance and intricate interactions with other components of the immune system are still largely unknown. In addition to the prevention of infection and malignancy, killer cells of all lineages are important in the pathogenesis of human disease. Of particular interest is the role of macrophages, NK cells and cytotoxic T cells in autoimmunity.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of alpha adrenergic blockade on thermoregulation in adrenal demedullated burned rats.
This study in burned rats studied at two ambient temperatures (22 degrees and 28 degrees C) and housed at 28 degrees C was designed to investigate the role of catecholamines in the maintenance of thermal homeostasis following burn injury. Two weeks prior to burn or sham burn, animals underwent adrenal medullectomy or sham adrenal medullectomy. Between postburn days 9 and 13, simultaneous direct and indirect calorimetry was performed following administration of 2mg/kg of phentolamine (alpha adrenergic blocking agent) via a carotid arterial line. Following administration of phentolamine, heat production and body temperature decreased and heat loss increased immediately. The cooling slopes for the burn groups were significantly steeper than for the control groups, within ambient temperatures. Within ambient temperatures, the presence or absence of the adrenal medulla had no discernible effect on the cooling slope of the burns or the controls. The burned animals cooled 1.9-3.5 times faster at 22 degrees than at 28 degrees C, and controls cooled 2.0-3.9 times faster at 22 degrees than at 28 degrees C. Phentolamine produced a several-fold increase in serum concentrations of both norephinephrine (NE) and epinephrine (E), indicating a gross overlap in alpha and beta adrenergic receptor utilization for E and NE. The progressive cooling of the adrenal demedullated burn group at 22 degrees C following phentolamine administration seems to indicate that norepinephrine is calorigenic for rats under these experimental circumstances. These experimental results indicate a relatively non-essential role for catecholamines in the maintenance of thermal homeostasis within the thermal neutral zone in the rat.


Biological matrix composites from cultured plant cells.
We present an approach to fabricate biological matrix composites made entirely from cultured plant cells. We utilize the cell's innate ability to synthesize nanofibrillar cell walls, which serve as the composite's fundamental building blocks. Following a controlled compression/dehydration process, the cells arrange into lamellar structures with hierarchical features. We demonstrate that the native cell wall nanofibrils tether adjacent cells together through fibrillar interlocking and intermolecular hydrogen bonding. These interactions facilitate intercellular adhesion and eliminate the need for other binders. Our fabrication process utilizes the entire plant cell, grown in an in vitro culture; requires no harsh chemical treatments or waste-generating extraction or selection processes; and leads to bulk biocomposites that can be produced in situ and biodegrade in soil. The final mechanical properties are comparable to commodity plastics and can be further modulated by introducing filler particles.


Effects of tobacco smoking on plasma selenium, zinc, copper and iron concentrations and related antioxidative enzyme activities.
The aim of the study was to investigate whether alterations in antioxidative enzyme activities are dependent on their cofactor concentrations in tobacco smokers. Plasma selenium, copper, zinc and iron concentrations, and the activities of related erythrocyte antioxidative enzymes copper-zinc superoxide dismutase (Cu-Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tobacco smokers and compared with those of nonsmokers. Plasma thiocyanate levels were measured as an index of smoking status. While plasma copper concentration and erythrocyte Cu-Zn SOD activity were significantly higher, plasma selenium concentration and erythrocyte GSH-Px activities were significantly lower in tobacco smokers than in nonsmokers. There was no significant difference in plasma iron and zinc concentrations or erythrocyte CAT activity between the two groups. There were significant positive correlations between erythrocyte GSH-Px and plasma selenium levels, between Cu-Zn SOD and copper levels, and between CAT and iron levels, and a negative correlation between plasma thiocyanate and selenium content in tobacco smokers. These findings suggest that antioxidative enzyme activities change depending on their cofactor concentrations in tobacco smokers.


Wilms tumour: diagnosis and treatment.
Wilms tumour is the most common intra-abdominal solid tumour of childhood. Treatment includes surgical resection and chemotherapy for virtually all affected children and additional radiotherapy for those with advanced disease or adverse prognostic features. This approach leads to cure rates exceeding 80%. During the last decade there have been a number of advances which have increased our understanding of the biology of Wilms tumour. The development of Wilms tumour, for example, involves several genes, including WT1, the Wilms tumour suppressor gene at 11p13, and WT2, the putative Wilms tumour suppressor gene at 11p15. In addition, certain chromosomal regions, most notably 16q and 1p, might predict outcome and hence serve as a prognostic factor, useful for determining the intensity of therapy. This novel information is now being incorporated into current therapeutic protocols. We reviewed the medical literature and present a summary of the advances made, outlining the current treatment of Wilms tumour. Future protocols will continue incorporating biological markers. The goal is to identify patients at low risk for relapse, which will allow a reduction in treatment intensity and subsequent toxicity. Children at an increased risk for relapse can be selected for more intensive treatment.


The Role of Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions.
The use of Bruton's tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKis are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib was the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies have evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in early-phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, and drug-drug interactions associated with the treatment of CLL with BTK inhibitors and examines their further implications.


Concanavalin-A binding sites, pemphigus antigens, and beta 2 microglobulin in epidermal hyperproliferation, premalignant and malignant lesions.
Three cell surface parameters of epidermal cells have been studied by immunofluorescence, pemphigus antigens, concanavalin-A binding sugars, and beta 2 microglobulin. Biopsy specimens were taken from a total of 59 patients with psoriasis, seborrheic and solar keratosis, squamous cell carcinoma, and basal cell epithelioma. We found a loss of demonstrability of all parameters in dedifferentiated tumors or tumor areas in squamous cell carcinoma, premonitory changes in solar keratosis, and no changes in seborrheic keratosis. In the psoriatic epidermis a granular redistribution of the cell surface parameters was occasionally observed in circumscribed areas of the epidermis. A selective loss of the demonstrability of beta 2 microglobulin was the prominent feature in basal cell epithelioma. Our findings demonstrate that the alterations of the cell surface differ in malignant and premalignant skin tumors, in basal cell epithelioma, and in benign psoriatic hyperplasia.


Increasing anaphylaxis hospitalizations in the first 2 decades of life: New York State, 1990 -2006.
Although an increase in the occurrence of anaphylaxis has been reported in several parts of the world, this phenomenon has not been described in the United States. To characterize anaphylaxis hospitalizations in New York State in patients younger than 20 years. Using a statewide administrative database, hospital admissions of patients with an allergic disease (anaphylaxis, angioedema, urticaria, and allergy unspecified) as the primary diagnosis were analyzed from 1990 through 2006 in New York State. Admission rates were calculated for the allergic disease groups, as were hospitalization characteristics. Statistical modeling and group comparisons were performed with the use of negative binomial distribution analysis. For patients younger than 20 years, the anaphylaxis hospitalization rate increased by more than 4-fold during the study period and by 2002 exceeded the combined hospitalization rates for urticaria, angioedema, and unspecified allergy. After the widespread adoption of food anaphylaxis codes in 1994, food anaphylaxis predominated hospitalizations for anaphylaxis. Peanut was the most common food allergen in food anaphylaxis admissions. The anaphylaxis hospitalization rate for males was significantly greater than that of females (risk ratio, 1.45; 95% confidence interval, 1.26-1.66). Blacks were not disproportionately hospitalized for anaphylaxis. An overall bimodal age distribution showed peaks in the very young and in teens. These data demonstrate that in a populous Northeastern state in the United States, anaphylaxis requiring hospitalization is increasing in the age group younger than 20 years.