[Reproduction and sexuality of parasitic copepods of fishes. I. The reproductive apparatus of Chondracanthus angustatus Heller, 1865: anatomy, histology, and spermiogenesis (author's transl)].
The pygmy males of Chondracanthus angustatus are fixed on the genital segment of the female on two anterior-ventral tubercules. The genital system is formed by two dorsal testes, two broad vas deferens and two seminal vesicles each one containing a spermatophore. Two types of cells can be seen in the interstitial tram: the sexual (normal and abortive) and the somatic ones. The plasmic and nuclear membranes joined together on one end of the spermatid; on the opposite pole, the mitochondria penetrate into the cytoplasmic expansions. The non-motile starfish spermatozoa present neither di-ferentiated acrosome nor centrioles. The male gametes are stocked in the spermatophore and enveloped by many kinds of secretions. Spermatozoa are discharged into the female integument folds and they reach the seminal receptacle with the help of the villosities movement; they stay there till fertilization occurs.


n-butylparaben exposure during perinatal period impairs fertility of the F1 generation female rats.
Parabens are a class of preservatives widely used in the majority of personal care products, cosmetics, medicines, and food products. However, current literature suggests its plausible role as an endocrine disruptor, hence the present study was undertaken to delineate the effects of n-butyl paraben on perinatally exposed F1 female rats. F0 dams were exposed subcutaneously to n-butylparaben from gestation day 6 (GD 6) to postnatal day (PND) 21 with doses of 10, 100, and 1000 mg/kg Bw/day in corn oil. The F1 female rats were monitored for pubertal development and sexual maturation through PND 30, 45, and 75; which were subsequently subjected to fertility assessment at PND 75. Perinatal exposure to n-butylparaben resulted in- This study documents impaired steroidogenesis and folliculogenesis might be the prime reason for the reduced fertility of F1 female rats. Hence, our study suggests that health monitors need to counsel potential females planning for pregnancy to avoid exposure to parabens.


A Morphomolecular Approach to Alveolar Capillary Dysplasia.
Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns. The current study analyzed the microvascular morphology and the underlying molecular background of ACD. One ACD group (n = 7), one pulmonary arterial hypertension group (n = 20), and one healthy con1trol group (n = 16) were generated. Samples of histologically confirmed ACD were examined by exome sequencing and array-based comparative genomic hybridization. Vascular morphology was analyzed using scanning electron microscopy of microvascular corrosion casts. Gene expression and biological pathways were analyzed using two panels on inflammation/kinase-specific genes and a comparison analysis tool. Compartment-specific protein expression was analyzed using immunostaining. In ACD, there was an altered capillary network, a high prevalence of intussusceptive angiogenesis, and increased activity of C-X-C motif chemokine receptor 4 (CXCR4), hypoxia-inducible factor 1α (HIF1A), and angiopoietin signaling pathways compared with pulmonary arterial hypertension/healthy controls. Histologically, there was a markedly increased prevalence of endothelial tyrosine kinase receptor (TEK/TIE2)+ macrophages in ACD, compared with the other groups, whereas the CXCR4 ligand CXCL12 and HIF1A showed high expression in all groups. ACD is characterized by dysfunctional capillaries and a high prevalence of intussusceptive angiogenesis. The results indicate that endothelial CXCR4, HIF1A, and angiopoietin signaling as well as TIE2+ macrophages are crucial for the induction of intussusceptive angiogenesis and vascular remodeling. Future studies should address the use of anti-angiogenic agents in ACD, where TIE2 appears as a promising target.


Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease.
The effectiveness of corticosteroids (GCs) varies greatly in interstitial lung diseases (ILDs). In this study, we aimed to compare the gene expression profiles of patients with cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF), and non-specific interstitial pneumonia (NSIP) and identify the molecules and pathways responsible for GCs sensitivity in ILDs. Three datasets (GSE21411, GSE47460, and GSE32537) were selected. Differentially expressed genes (DEGs) among COP, IPF, NSIP, and healthy control (CTRL) groups were identified. Functional enrichment analysis and protein-protein interaction network analysis were performed to examine the potential functions of DEGs. There were 128 DEGs when COP versus CTRL, 257 DEGs when IPF versus CTRL, 205 DEGs when NSIP versus CTRL, and 270 DEGs when COP versus IPF. The DEGs in different ILDs groups were mainly enriched in the inflammatory response. Further pathway analysis showed that "interleukin (IL)-17 signaling pathway" (hsa04657) and "tumor necrosis factor (TNF) signaling pathway" were associated with different types of ILDs. A total of 10 genes associated with inflammatory response were identified as hub genes and their expression levels in the IPF group were higher than those in the COP group. Finally, we identified two GCs' response-related differently expressed genes (FOSL1 and DDIT4). Our bioinformatics analysis demonstrated that the inflammatory response played a pathogenic role in the progression of ILDs. We also illustrated that the inflammatory reaction was more severe in the IPF group compared to the COP group and identified two GCs' response-related differently expressed genes (FOSL1 and DDIT4) in ILDs.


Complete Genome Sequence of PM105, a New Pseudomonas aeruginosa B3-Like Transposable Phage.
The complete genome of the Pseudomonas aeruginosa bacteriophage PM105 is 39,593 bp long. The phage belongs to the B3 family of transposable Mu-like phages, as confirmed by the presence of bacterial DNA joined to the phage genome ends. PM105, together with other B3-like phages, form a newly arising species.


The Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument.
Individuals with Parkinson's disease often experience periods of off time when their motor symptoms are poorly controlled, significantly impacting their lives. To identify the consequences of motor fluctuations on day-to-day activities and areas of unmet treatment priority among individuals with moderate to advanced Parkinson's disease, to assess whether existing patient-reported outcome instruments adequately capture these consequences and priorities, and based on these evaluations, to adapt an existing or develop a new instrument. The research was conducted in 2 stages: concept exploration and content confirmation. Concept exploration included direct input from individuals with Parkinson's disease representing the intended context of use via concept elicitation interviews. Content confirmation and item refinement was achieved through 5 rounds of cognitive debriefing. Final rounds of cognitive debriefing also included usability testing of the draft instrument for electronic data capture. Concept elicitation interviews were conducted among 29 individuals with Parkinson's disease (55% male; mean age 60.8 years). Concept saturation was achieved quickly with more than 90% of concepts identified by the end of the 16th interview. None of the existing outcome instruments were found to be fit for purpose in the intended context of use; therefore, a new instrument was developed. After 5 rounds, cognitive debriefing participants indicated clear and consistent interpretation of the items. Evidence from this study supports the content validity of the Parkinson's Disease Activities of Daily Living, Interference and Dependence Instrument as the basis of a clinical trial endpoint for capturing priority treatment benefit outcomes to individuals with moderate to advanced Parkinson's disease experiencing motor fluctuations.


Desmin myopathy with cardiomyopathy.
We report a case of abnormal desmin accumulation within the muscle of a 30-year-old female with a 2-year history of cardiomyopathy and axial muscle weakness. Serum creatine kinase was normal. A quadriceps muscle biopsy revealed pink hyaline inclusions, which stained for acid phosphatase and with PAS and were present in both fibre types. Electron microscopy showed these inclusions to consist of aggregates of irregularly arranged 6- to 15-nm-diameter filaments enmeshed within a central core of dense granulo-amorphous material. In other areas, the granulo-amorphous material lay as irregular patches within the sarcoplasm, mainly at the level of the "Z" band causing disruption of the sarcomere. Immunoelectron microscopy using colloidal gold showed that the dense amorphous material reacted strongly with desmin antisera and could, therefore, represent a defective or phosphorylated form of the protein.


Anticonvulsant drugs and malformations is there a drug specificity?
The distribution of anticonvulsant drug therapy was studied in 318 malformed infants with known histories of maternal epilepsy. Data on the infants was collected from six birth defect monitoring programs in Europe and South America. Use of specific types of anticonvulsants varies widely among reporting countries. Heterogeneity of drug-malformation distribution, was analyzed to determine whether use of specific drugs were linked to specific malformations. A significant association was seen between maternal use of valproic acid and spina bifida, and a weaker, non-significant one between carbamazepine and spina bifida. Facial clefts were associated with both diphenylhydantoin and phenobarbitone use and also with polytherapy. These differences indicate that the actual drug used is significant for the teratogenic process. The technique may be useful in analysis of other drug-related teratogenic questions.


Functionalization of a viscosity-sensitive fluorophore for probing of biological systems.
Functionalization of a viscosity-sensitive visible wavelength fluorophore 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP), with the intent to incorporate its favorable optical properties into a probe for structural and functional imaging by fluorescence microscopy, is described. Spiperone, a highly potent ligand for the dopamine D2 receptors, was conjugated via an ethylpiperazine moiety to the fluorophore giving fluorescent probes that can be excited in the UV and Vis range.


Our Better Angels and the Invention of Hope.
This 2020 Presidential Address was given at the American Pediatric Surgical Association 2021 Virtual Annual Meeting, May 20-22, 2021.


Optimized stereotactic volumetric modulated arc therapy as an alternative to brachytherapy for vaginal cuff boost. A dosimetric study.
We evaluate the role of stereotactic body radiotherapy using volumetric modulated arc therapy (VMAT) technique as an alternative to high-dose rate brachytherapy (HDR-BT) in the treatment of vaginal cuff in postoperative endometrial cancer. CT scans of 8 patients were used in this study. The clinical target volume (CTV) was defined as the 0.5 cm tissue around the applicator (then subtracting the applicator). Total dose was 30Gy delivered in 5 fractions. In HDR-BT, dose was prescribed at a distance of 0.5 cm from the surface applicator. For VMAT irradiation, a planning target volume (PTV) was obtained from CTV by an expansion of 3 mm. Two VMAT plans were generated using a full arc rotation. The first plan was optimized with an anatomy-based optimization module (PO-VMAT) using a 1mm multileaf collimator beam margin to enhance dose heterogeneity and dose fallout outside the target. The second plan was generated with a full-inverse planning module (FI-VMAT). Conformity (CI100, CI50, CI25), gradient (GI) indexes, and integral doses were calculated. To account for various dose heterogeneity distributions we calculated the equivalent uniform dose (EUD) using the Niemerko model. A Kruskal-Wallis analysis of variance followed by Dunn's-type multiple comparisons was performed. Dose distributions were more heterogeneous with HDR-BT: Dmean was 144.2% of prescription dose for CTV in HDR-BT and 118.5 and 108.6% for PTV in PO-VMAT and FI-VMAT, respectively. The mean values of EUD for CTV were 136.9%, 130.0 %, and 111.0% of prescription dose in HDR-BT, PO-VMAT, and FI-VMAT plans, respectively. GI indexes were 2.81, 3.41, and 4.14 for HDR-BT, PO-VMAT, and FI-VMAT, respectively. Near-maximal doses (D0.1cc) for rectum and bladder were significantly higher in HDR-BT plans compared to PO-VMAT and FI-VMAT plans (rectum: 131.2% vs112.8% vs 112.0%, respectively; bladder: 129.2% vs 108.7%, and 109.8%, respectively). PO-VMAT plans were able to mimic the HDR-BT dose distribution, showing a successful capability of highly conformal dose distribution, EUD values similar to HDR-BT, and steep dose-gradient outside PTV, then providing a reasonable alternative to brachytherapy.


Molecular and stable carbon isotopic characterization of PAH contaminants at McMurdo Station, Antarctica.
The molecular and stable carbon isotopic compositions of contaminant polycyclic aromatic hydrocarbons (PAHs) at McMurdo Station, Antarctica were analyzed in samples collected from land and sub-tidal area. PAHs in the study areas were characterized by high amounts of naphthalene and alkylated naphthalenes from petroleum products introduced by human activities in the area. Principal component analysis (PCA) of PAH composition data identified multiple sources of PAH contamination in the study area. Compositional assignments of origins were confirmed using compound specific stable carbon isotopic analysis.


Quantitative detection of α-Synuclein and Tau oligomers and other aggregates by digital single particle counting.
The pathological hallmark of neurodegenerative diseases is the formation of toxic oligomers by proteins such as alpha-synuclein (aSyn) or microtubule-associated protein tau (Tau). Consequently, such oligomers are promising biomarker candidates for diagnostics as well as drug development. However, measuring oligomers and other aggregates in human biofluids is still challenging as extreme sensitivity and specificity are required. We previously developed surface-based fluorescence intensity distribution analysis (sFIDA) featuring single-particle sensitivity and absolute specificity for aggregates. In this work, we measured aSyn and Tau aggregate concentrations of 237 cerebrospinal fluid (CSF) samples from five cohorts: Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and a neurologically-normal control group. aSyn aggregate concentration discriminates PD and DLB patients from normal controls (sensitivity 73%, specificity 65%, area under the receiver operating curve (AUC) 0.68). Tau aggregates were significantly elevated in PSP patients compared to all other groups (sensitivity 87%, specificity 70%, AUC 0.76). Further, we found a tight correlation between aSyn and Tau aggregate titers among all patient cohorts (Pearson coefficient of correlation r = 0.81). Our results demonstrate that aSyn and Tau aggregate concentrations measured by sFIDA differentiate neurodegenerative disease diagnostic groups. Moreover, sFIDA-based Tau aggregate measurements might be particularly useful in distinguishing PSP from other parkinsonisms. Finally, our findings suggest that sFIDA can improve pre-clinical and clinical studies by identifying those individuals that will most likely respond to compounds designed to eliminate specific oligomers or to prevent their formation.


Temporal strategy for discriminating noxious from non-noxious electrical stimuli by cortical and thalamic neural ensembles in rats.
Considerable evidence supports that pain is encoded in a large, widespread network that consists of the thalamus, cortex, as well as limbic system. However, the temporal properties of the neural matrix in pain processing were largely unknown. In the present study, we simultaneously recorded thalamic and cortical neuronal discharges elicited by brief noxious or innocuous electrical stimulus in awake rats. The discrimination performance of the neural ensembles in differentiating noxious from innocuous inputs was calculated using different window sizes at the millisecond and second level, respectively. The results demonstrated that coding information emerged in a quantum-like manner; the minimum spike-train length for discriminating noxious from innocuous inputs was 40 ms. The nociceptive coding activity was temporally dynamic, and could be preserved for a relatively long time (3-4 s) within the thalamocortical loops, independent of the initial brief stimuli. These results suggest that the nociceptive signals may be reverberatory within the thalamocortical loops, hence keeping the neurosignature for central pain representation.


IRX1 ameliorates sepsis-induced acute kidney injury in mice by promoting CXCL14.
Sepsis-induced acute kidney injury is a general critical complication having high relevance to kidney inflammation. In spite of advances in clinical and critical care, the specific and effective therapies for acute kidney injury are still insufficient. The present study aimed to investigate the protective effect of Iroquois homeobox genes (IRX) on sepsis-induced kidney dysfunction in mice. In order to gain insight into sepsis-related actions in acute kidney injury, the cecal puncture-induced kidney injury animal model was established. The hematoxylin and eosin staining was used to measure the pathology of kidney tissues. The kidney function-related biomarkers, including neutrophil gelatinase-associated lipocalin, creatinine, kidney injury molecule-1, blood urea nitrogen, and inflammatory cytokines, which included tumor necrosis factor α, interleukin 1β (IL-1β), IL-6, and monocyte chemotactic protein 1, were detected by automated biochemical analyzer or their corresponding test kits. The protein expression was measured using Western blot analysis, and the apoptotic rate of kidney tissue was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The present study revealed the protective ability of IRX1 in sepsis-induced acute kidney injury. This study also determined the potential mechanism of IRX1 on sepsis-induced inflammatory response and cell apoptosis. Finally, it highlighted that IRX1 exerted a protective influence on CLP-induced acute kidney injury by suppressing the activation of chemokine (C-X-C motif) ligand 14 (CXCL14). To conclude, the results suggest that overexpression of IRX1 could promote survival rate and suppress the CLP-induced apoptosis, inflammatory response, and kidney dysfunction through the activation of CXCL14. IRX1 and CXCL14 are essential to elucidate the mechanism of acute kidney injury. These findings may help to identify the promising targets for clinical sepsis therapy.


[Friend or Foe?--Psoriasin and Koebnerisin: multifunctional defence molecules in skin differentiation, tumorigenesis and inflammation].
Psoriasin (S100A7) and koebnerisin (S100A15) were first identified in inflamed psoriatic skin. They have lately evolved by gene duplications within the Epidermal Differentiation Complex (chromosome 1q21) and form a novel S100 subfamily in human. Despite highest homology (> 90 %), psoriasin and koebnerisin are distinct in tissue distribution, regulation, and function. They act differently as antimicrobial peptides (AMP) and synergize to promote inflammation and cell migration as endogenous danger signals ("alarmines") and chemoattractants. Their different properties are compelling reasons to discriminate psoriasin and koebnerisin in epithelial homeostasis, inflammation and epithelial carcinogenesis.


Evaluation of chloroform/methanol and dichloromethane/hexane extractable lipids as surrogate measures of sample partition capacity for organochlorines in fish tissues.
Organic contaminant concentration data are often lipid normalized to provide an indication of the chemical fugacity in the sample or to compare the relative equilibrium status of samples from the same environment. This study compared lipid normalized PCB and organochlorine concentration data for tissues of individual fish when lipids were measured using chloroform/methanol (CM) or dichloromethane/hexane (DH) extractions. The CM extraction produced higher lipid yields for dorsal muscle (8-fold difference) and carcass (1.7-fold difference) compared to DH extractions, while both methods yielded comparable lipid contents for liver and adipose tissue. Lipid normalized tissue/carcass PCB and organochlorine concentration ratios were variable across tissue types when lipid contents from the CM technique were used, whereas, tissue/carcass concentration ratios approached the expected value of unity for each tissue when DH-derived lipids were used. These data suggest that the tissue lipid content as derived using the DH extraction provided a better surrogate measure of sample partition capacity than tissue lipids determined using the CM technique.


Amniotic fluid acetylcholinesterase measurements: comparing immunochemical and polyacrylamide gel techniques.
In the present study, a recently reported immunochemical technique for measuring acetylcholinesterase (AChE) in amniotic fluid utilizing the 4F19 antibody was compared with the widely utilized polyacrylamide gel technique to determine whether the immunochemical assay provided an advantage in separating unaffected pregnancies from those associated with open spina bifida (OSB) and open ventral wall defects (OVWD). The study included (1) 73 amniotic fluid samples from unaffected pregnancies [alpha-fetoprotein (AFP) less than 2 MoM] with no visible gel AChE band, (2) nine bloodstained samples from unaffected pregnancies (AFP 2.2-4.0 MoM) with visible gel AChE bands, (3) 18 samples associated with OSB (AFP 2.2-7.0 MoM) with visible gel AChE bands, and (4) 20 samples associated with OVWD (AFP 3.2-53.5 MoM) with visible gel AChE bands. The immunochemical assay produced ranges of measurements in the four respective categories as follows: (1) 2-60 arbitrary units (AU): (2) 14-69 AU, (3) 61-593 AU, and (4) 22-476 AU. Eight of the nine unaffected pregnancies with visible gel AChE bands had immunochemical measurements below the highest measurement for the samples with no visible AChE band (60 AU), as did five out of 20 OVWD pregnancies. Two of the OSB cases had values of 61 and 62 AU. These data indicate that the 4F19 specific monoclonal antibody to AChE is capable of distinguishing unaffected from affected pregnancies with reasonable reliability but that more work needs to be done to establish the extent of overlap between the unaffected and affected populations.


Is diminished pubocervical fascia collagen content a risk factor for failure of surgical management of genuine stress urinary incontinence in women?
The assessment of relationship between pubocervical collagen content and clinical results of surgical treatment of genuine stress urinary incontinence (GSUI) in women. Twenty-four women treated for genuine stress urinary incontinence were included into the study. All women underwent the same surgical procedure. The samples of pubocervical fascia were taken at the time of surgery. The contents of acid soluble, pepsin soluble, insoluble fraction of collagen, total collagen and collagen crosslinks were measured. The study of pubocervical fascia collagen metabolism included also estimation of collagenase activity. At follow-up done 5 years following surgery, 20 patients reported symptoms of GSUI (study group). Four women were still without symptoms of urine leakage (control group). The biochemical parameters of pubocervical fascia did not show, statistically significant differences between compared groups. The pubocervical fascia collagen metabolism does not have impact on the results of anti-incontinence surgery.


[The microbiome and autoimmunity].
An abundant and diverse set of commensal microbial communities covers the body's surfaces, collectively so-called microbiome. It has a functional impact on various immune processes and modulates many health-related processes, including autoimmunity. An active site of microorganism-host interplay is the intestinal mucosa. Growing evidence has helped us to learn how a specific microbiota composition and its functionality determine the intestinal barrier function and, furthermore, modulate pro-inflammatory and anti-inflammatory immune mechanisms in remote organs. In addition, the microbial composition of the skin is important for the functionality of the skin barrier and autoimmune skin diseases. Here, we review the importance of the microbiome for the local and systemic immune system and how a disturbed microbiome-host interaction can affect the development and progression of autoimmune diseases. Understanding these associations will help to unravel new diagnostic and therapeutic approaches for those diseases.


An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models.
The aim of this study was to improve fluorescence laparoscopy of pancreatic cancer in an orthotopic mouse model with the use of a light-emitting diode (LED) light source and optimal fluorophore combinations. Human pancreatic cancer models were established with fluorescent FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, and BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks postimplantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail-vein injection of CEA antibodies conjugated with Alexa 488 or Alexa 555. Cancer lesions were detected and localized under each light mode. Intravital images were also obtained with the OV-100 Olympus and Maestro CRI Small Animal Imaging Systems, serving as a positive control. Tumors were collected for histologic analysis. Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor deposits in the peritoneal cavity. The simultaneous use of different fluorophores (Alexa 488 and Alexa 555), conjugated to antibodies, brightened the fluorescence signal, enhancing detection of submillimeter lesions without compromising background illumination. Adjustments to the LED light source permitted simultaneous detection of tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. Using an LED light source with adjustments to the red, blue, and green wavelengths, it is possible to simultaneously identify tumor metastases expressing fluorescent proteins of different wavelengths, which greatly enhanced the signal without compromising background illumination. Development of this fluorescence laparoscopy technology for clinical use can improve staging and resection of pancreatic cancer.


Regulation of T-cell death-associated gene 51 (TDAG51) expression in human T-cells.
T-cell death-associated gene 51 (TDAG51) has been described to regulate T-cell receptor/CD3-dependent induction of CD95/Fas and subsequent activation-induced cell death (AICD) in a murine T-cell hybridoma. Using well-defined pharmacological inhibitors, we investigated the regulation of TDAG51 expression in human T-cells and the correlation with cell death. TDAG51 was induced in resting T-cells, lymphoid cell lines and AICD-susceptible as well as AICD-resistant T-cell clones, and induction was inhibited by MAP-kinase inhibitors and PKC inhibitor Gö6983. No correlation between the effects of inhibitors on TDAG51 expression and cell death was observed. The constitutive TDAG51 expression in five pancreatic carcinoma cell lines was reduced by MAP-kinase inhibitors but not by Gö6983. Furthermore, the inducible overexpression of TDAG51 in TetOn Jurkat cells did not modulate cellular proliferation, phorbolester/ionomycin-induced growth arrest, or the expression of various cell surface molecules. Our results indicate that the expression of TDAG51 in human T-cells does not correlate with AICD.


Climate changes reproductive and children's health: a review of risks, exposures, and impacts.
Our climate has significantly changed, exceeding what the world has experienced over the last 650,000 years, and has been cited as the most significant health threat of the twenty-first century. Climate change is impacting health in unprecedented ways. While everyone is vulnerable to the health impacts associated with climate change, children are disproportionately affected because of their physical and cognitive immaturity. Climate change impacts that include rising temperatures, extreme weather, rising sea levels, and increasing carbon dioxide levels are associated with a wide range of health issues in children such as asthma, allergies, vector-borne diseases, malnutrition, low birth weight, and post-traumatic stress disorder. Pediatric health providers play a critical role in advancing the science and translating findings to improve public understanding about the link between climate changes and children's health, and establishing strategies to address these issues. This review will provide an overview of research exploring the impact of climate change on children's health impacts, as well as provide recommendations for pediatric research moving forward.


Production system influences color stability and lipid oxidation in gluteus medius muscle.
We aimed to evaluate the color and oxidative stability of beef gluteus medius (GM) from cattle raised in organic and non-organic production systems. The GM samples (n = 10) were obtained from organic (ORG; n = 5) or non-organic (NORG; n = 5) beef samples, sliced into 2.54-cm steaks, packaged in aerobic conditions, and stored for nine days at 4°C. ORG and NORG steaks were compared regarding myoglobin concentration, pH, instrumental color, delta E (ΔE), metmyoglobin reducing activity (MRA), and lipid oxidation on days 0, 5, and 9. Feeding system did not influence (p>0.05) the myoglobin concentration. ORG steaks exhibited greater (p<0.05) meat pH, yellowness, and MRA, whereas NORG steaks exhibited greater (p<0.05) redness, chroma, R630/580, delta E, and lipid oxidation. ORG and NORG steaks exhibited similar (p>0.05) lightness and hue angle. During storage, ORG and NORG exhibited an increase in muscle pH, hue angle, and lipid oxidation; and a decrease (p<0.05) in redness, yellowness, chroma, and color stability (R630/580). Both samples exhibited a stable (p>0.05) pattern for lightness and MRA. Therefore, the production system can affect beef color and lipid stability during storage.


Food of roach (Rutilus rutilus) and ide (Leusiscus idus): significance of diet shift for interspecific competition in omnivorous fishes.
Feeding relationships between roach and ide from two sites in a mesotrophic lake SE Norway are presented and discussed. When animal food supply was scarce, both fish species increased their consumption of macrophytes; roach sevenfold, and ide threefold. Along a typical littoral vegetation gradient, ide fed among helophytes, while roach fed in the zone outside. This different habitat selection was reflected in the most important plants consumed (ide: Equisetum fluviatile, roach: Characeae), and confirmed by gill net catches. During the vegetative season, roach avoided areas with dense vegetation. In shallow areas beyond the littoral, the most important food plant for both fish species was Potamogeton perfoliatus, which constituted 80% of the total food consumed (dry weight basis) in the roach and 35% in the ide. The diet shift to plants seemed to be strongly influenced by the supply of animal food and the intensity of intra-and interspecific competition.


Shifting gears: liver SR-BI drives reverse cholesterol transport in macrophages.
Cholesterol efflux from macrophages, the first step in reverse cholesterol transport (RCT), is assumed to play a critical role in the pathogenesis of atherosclerosis. However, in vivo proof supporting this hypothesis is lacking, due to difficulties in determining the activity of this first step in RCT. In this issue of the JCI, Zhang et al. apply their recently developed method for measuring RCT in vivo to estimate RCT in mouse models with varying levels of HDL turnover. A surprisingly efficient clearance of cholesterol to feces is observed in mice overexpressing hepatic scavenger receptor class B type I (SR-BI), whereas in SR-BI-knockout mice, cholesterol clearance is diminished. The study demonstrates that hepatic SR-BI is a positive regulator of macrophage RCT in vivo.


Enzyme-catalysed non-oxidative decarboxylation of aromatic acids: I. Purification and spectroscopic properties of 2,3 dihydroxybenzoic acid decarboxylase from Aspergillus niger.
In order to understand the molecular mechanism of non-oxidative decarboxylation of aromatic acids observed in microbial systems, 2,3 dihydroxybenzoic acid (DHBA) decarboxylase from Aspergillus niger was purified to homogeneity by affinity chromatography. The enzyme (Mr 120 kDa) had four identical subunits (28 kDa each) and was specific for DHBA. It had a pH optimum of 5.2 and Km was 0.34 mM. The decarboxylation did not require any cofactors, nor did the enzyme had any pyruvoyl group at the active site. The carboxyl group and hydroxyl group in the ortho-position were required for activity. The preliminary spectroscopic properties of the enzyme are also reported.


SHORT-ROOT 1 is critical to cell division and tracheary element development in rice roots.
The exocyst is a key factor in vesicle transport and is involved in cell secretion, cell growth, cell division and other cytological processes in eukaryotes. EXO70 is the key exocyst subunit. We obtained a gene, SHORT-ROOT 1 (SR1), through map-based cloning and genetic complementation. SR1 is a conserved protein with an EXO70 domain in plants. SR1 mutation affected the whole root-development process: producing shorter radicles, adventitious roots and lateral roots, and demonstrating abnormal xylem development, resulting in dwarfing and reduced water potential and moisture content. SR1 was largely expressed in the roots, but only in developing root meristems and tracheary elements. The shortness of the sr1 mutant roots was caused by the presence of fewer meristem cells. The in situ histone H4 expression patterns confirmed that cell proliferation during root development was impaired. Tracheary element dysplasia was caused by marked decreases in the inner diameters of and distances between the perforations of adjacent tracheary elements. The membrane transport of sr1 mutants was blocked, affecting cell division in the root apical region and the development of root tracheary elements. The study of SR1 will deepen our understanding of the function of EXO70 genes in Oryza sativa (rice) and guide future studies on the molecular mechanisms involved in plant root development.


Immunopathology of Hyperinflammation in COVID-19.
The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.


Long-term follow-up of tobacco cessation intervention in a dental setting: A randomized trial.
Tobacco dependence is widely prevalent and a harmful chronic disorder. Achieving long-term tobacco abstinence is an important public health goal. This study aims to assess the long-term effectiveness of moderate-intensity treatment for tobacco cessation in the dental clinic setting. Out of 1206 subjects registered to the Tobacco cessation clinic (TCC) during this time period, only 999 of them completed the 1-year follow-up period. The mean age was 45.9 ± 9 years. Six hundred and three (60.3%) of these subjects were male and 396 (39.6%) of them were females. Five hundred and fifty-eight (55.8%) used smoking tobacco and 441 (44.1%) used smokeless tobacco. Patients received tailored behavioral counseling, educational material, and pharmacotherapy consisting of nicotine replacement therapy (NRT) and\or NON-NRT. Patients were monitored by phone or clinic visits for 11 months. Outcomes assessed were complete abstinence, harm reduction (>50% reduction), no change and lost to follow-up. At the end of 12 months the tobacco quit rate was180 (18%), tobacco reduction >50% was 342 (34.2%), no change 415 (41.5%) and relapse 62 (6.2%). Our study has identified adequate quit-rates in a cohort of dental patients attending a hospital-based TCC.


The relative significance of human placental lactogen in the diagnosis of retarded fetal growth.
The purpose of this prospective study was to determine whether serial maternal venous hPL determinations could identify pregnancies resulting in growth-retarded infants from a selected population at presumed high risk for IUGR. Our results demonstrated that mean hPL levels in IUGR outcome pregnancies were significantly lower than normal after 33 weeks' gestation. Mean hPL was also lower in some pregnancies resulting in normal-weight neonates with abnormally low PI or short CHL, suggesting that these neonates, despite normal birth weight achievement, may represent previously unsuspected.


Ion-Assisted Resonant Injection and Charge Storage in Carbon-Based Molecular Junctions.
Resonant injection and resulting charge storage were examined in a large-area carbon/tetraphenylporphyrin(TPP)/LiF/carbon junction, where the LiF layer provides mobile ions in acetonitrile (ACN) vapor. Resonant electron transfer into TPP molecules occurs at <+1 V in the presence of mobile ions, enabled by ionic screening of the carbon electrode. Injection of holes, i.e. formation of the TPP radical cation, inside the junction was monitored by in situ photocurrent measurements. Following the injection, despite the lack of a redox counter-reaction or conventional electrolyte, persistent faradaic current peaks dominate the IV cycle of the junction (±2 V) in ACN vapor, enhancing the reversible charge storage by a factor of 78 compared to that in vacuum.


Development of a Novel Pyroptosis-Associated lncRNA Biomarker Signature in Lung Adenocarcinoma.
Pyroptosis is a novel type of cell death observed in various diseases. Our study aimed to investigate the relationship between pyroptosis-associated-long non-coding RNAs (lncRNAs), immune infiltration, and expression of immune checkpoints in the setting of lung adenocarcinoma and the prognostic value of pyroptosis-related lncRNAs. RNA-seq transcriptome data and clinical information from The Cancer Genome Atlas (TCGA) were downloaded, and consensus clustering analysis was used to separate the samples into two groups. Least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature. The association between pyroptosis-associated lncRNAs, immune infiltration, and expression of immune checkpoints were analysed. The cBioPortal tool was used to discover genomic alterations. Gene set enrichment analysis (GSEA) was utilized to investigate downstream pathways of the two clusters. Drug sensitivity was also examined. A total of 43 DEGs and 3643 differentially expressed lncRNAs were identified between 497 lung adenocarcinoma tissues and 54 normal samples. A signature consisting of 11 pyroptosis-related lncRNAs was established as prognostic for overall survival. Patients in the low-risk group have a significant overall survival advantage over those in the high-risk group in the training group. Immune checkpoints were expressed differently between the two risk groups. Risk scores were validated to develop an independent prognostic model based on multivariate Cox regression analysis. The area under time-dependent receiver operating characteristic curve (AUC of the ROC) at 1-, 3-, and 5-years measured0.778, 0.757, and 0.735, respectively. The high-risk group was more sensitive to chemotherapeutic drugs than the low-risk group. This study demonstrates the association between pyroptosis-associated lncRNAs and prognosis in lung adenocarcinoma and enables a robust predictive signature of 11 lncRNAs to inform overall survival.


Carbon dioxide and light curves and leaf gas exchange responses to shade levels in bell pepper (Capsicum annuum L.).
Vegetable crops grown under shade nets typically show increased yield and quality. However, little is known about the photosynthetic responses at various CO2 and light levels under nets. This study aimed to determine carbon dioxide (A/Cc) and light (A/I) curves and leaf gas exchange response of bell pepper plants grown under nets at various shade levels. Experiments were conducted in the spring-summer of 2016 and 2018 in Tifton, Georgia (GA), USA, with five shade treatments [0 % (open field), 30 %, 47 %, 63 %, and 80 %]. The A/Cc curves revealed that plants grown at 30 % shade and in the open field had similar carboxylation, electron transport, and triose phosphate utilization rates. The A/I curves showed that gross and net photosynthesis were highest at 30 % shade. The 30 % shade had similar stomatal conductance, intercellular CO2, electron transport rate, and water use efficiency compared to the open field. The A/Cc and A/I curves and the leaf gas exchange parameters explained the intrinsic causes for the higher net photosynthesis at 30 % shade than in open-field bell pepper. The information from A/Cc-curves, A/I-curves, and leaf gas exchange is applicable in modeling photosynthesis and predicting primary productivity for C3 plants in elevated-CO2 and altered-light environments.


Plumeria alba flower extract-mediated synthesis of recyclable chitosan-coated cadmium nanoparticles for pest control and dye degradation.
In the current scenario, many synthetic chemicals have used long-term to control pests and mosquitoes, leading to the resistance of strains and toxicity effect on human beings. To overcome the adverse problem in recent advances, the scientific community is looking into nanofabricated pesticides and mosquitoes. This study aims to synthesize the recyclable chitosan-coated cadmium nanoparticles (Ch-CdNps) using Plumeria alba flower extract, which was further applied for insecticidal and mosquitocidal activities. The synthesized Ch-CdNps were confirmed by UV spectroscopy and FTIR analysis. The XRD, TEM, and DLS results confirmed the crystallinity with a spherical shape at 80-100 nm. The insecticidal activity proves that Ch-CdNps inhibited Helicoverpa armigera and Spodoptera litura at 100 ppm. In mosquitocidal, LC50 values of larvicidal of 1st instar were 4.116, 4.33, and 4.564 µg/mL, and the remaining three stages of instars, pupicidal, adulticidal, longevity, fecundity, and ovicidal assays inhibit the Anopheles stephensi followed by Aedes aegypti and Culex quinquefasciatus. Further, the first-order kinetics of photocatalytic degradation of methylene blue and methyl orange was confirmed. Based on the obtained results, Ch-CdNps can inhibit the pest, mosquitoes, and photocatalytic degradation.


Characterization of the spontaneous diabetes obesity syndrome in mature male CBA/Ca mice.
A spontaneous maturity onset diabetes obesity syndrome occurs in a small proportion (10-20%) of male CBA/Ca mice. Inbreeding can increase the incidence to 80%. It occurs at 12-16 weeks of age, and is characterized by hyperphagia, obesity, hyperglycaemia, hypertriglyceridaemia, hyperinsulinaemia, and an impaired glucose tolerance. The mice are also resistant to exogenous insulin. Female mice remain normal except for a slight increase in serum insulin. The male obese diabetic mice have a normal life expectancy. It is proposed that CBA/Ca mice can provide examples of a useful model for investigating the aetiology of type 2 diabetes and obesity, and the effectiveness of antidiabetic and antiobesity drugs.


Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke.
Ischemic stroke is a medical emergency that primarily affects the elderly. A complex immune response in the post-stroke brain constitutes a key component of stroke pathophysiology. This study aimed to determine how stroke affects immune cell populations in the aged brain based on molecular profiles of individual cells. Single-cell RNA sequencing and a new transient ischemic stroke mouse model with late reperfusion were used. We generated, for the first time, a composite picture of immune cell populations in the stroke aged brain at single-cell resolution. We discovered at least 6 microglial subsets in the stroke aged brain, including a potentially stroke-specific subtype. Moreover, we identified major cell subpopulations formed by infiltrated myeloid cells after stroke, and revealed their unique molecular profiles. This study provided the first scRNA-seq data set for immune cells in the stroke aged brain, and offered novel insights into post-stroke immune cell heterogeneity.


[2,3]-sigmatropic rearrangements of allylic sulfur compounds.
Nine variations of [2,3]-sigmatropic rearrangements of allylic sulfur compounds are reviewedwith particular emphasis on newer developments and applications in target molecule oriented research.


"Reverse Bohlman" technique for the treatment of high grade spondylolisthesis in an adult population.
Surgical techniques for effective high-grade spondylolisthesis (HGS) remain controversial. This study aims to evaluate radiographic/clinical outcomes in HGS patients treated using modified "Reverse Bohlman" (RB) technique. Review of consecutive HGS patients undergoing RB at a single university-center from 2006 to 2013. Clinical, surgical, radiographic parameters collected. Six patients identified: five with L5-S1 HGS with L4-L5 instability and one had an L4-5 isthmic spondylolisthesis and grade 1 L5-S1 isthmic spondylolisthesis. Two interbody graft failures and one L5-S1 pseudoarthrosis. Postoperative improvement of anterolisthesis (62.3% vs. 49.6%, p = 0.003), slip angle (10 vs. 5°, p = 0.005), and lumbar lordosis (49 vs. 57.5°, p = 0.049). RB technique for HGS recommended when addressing adjacent level instability/slip.


Is There a Role for Comfort Care in Neonates With Severe Craniofacial Anomalies? Case Report and Review of Quality-of-Life Literature.
This article aims to determine how quality of life (QoL) is defined and assessed in cases of severe craniofacial anomalies, as well as the impact such considerations may have on the treatment of a neonate with these conditions with respect to palliative neonatal care. Our literature review found insufficient evidence to suggest that craniofacial anomalies result in consistently poor QoL. Based on these findings and in line with the current acceptable standards for the ethical care of neonates, with the exception of rare cases, resuscitative efforts should always be performed on patients with isolated craniofacial anomalies, as demonstrated in the management of this reported patient.


Fetal growth.
Fetal growth requires the correct balance of nutrients, oxygen, and growth factors operating under the direction of a genetic plan modified by maternal factors. The classic hormones of postnatal growth play differing roles with alternative controls compared to those after birth. The study of conditions of abnormal fetal growth illuminates the mechanism of normal fetal growth. It is now apparent that abnormal birth weight leads to long-term consequences.


EEG and evoked potentials in precocious puberty.
We recorded brain stem auditory evoked potentials, pattern reversal visual evoked potentials and electroencephalograms in 19 children, 2-8 years old. Sixteen had precocious puberty and three had precocious adrenarche. Two of the children with precocious puberty had hypothalamic hamartomas, one had an optic glioma, and one had a history of hydrocephalus. The EEG was abnormal in 7 patients: three had diffuse slowing, and four showed possible paroxysmal features. BAEPs and VEPs were normal in all patients. This study showed no abnormalities in two conduction pathways of the central nervous system and no evidence of a deleterious effect of hormonal aberrations in patients with precocious puberty. Abnormal EEG in these patients is more likely to reflect occult diencephalic disease than widespread neurophysiological dysfunction.


Increased nuclear Olig1-expression in the pregenual anterior cingulate white matter of patients with major depression: a regenerative attempt to compensate oligodendrocyte loss?
Structural and functional oligodendrocyte deficits as well as impaired myelin integrity have been described in affective disorders and schizophrenia, and may disturb the connectivity between disease-relevant brain regions. Olig1, an oligodendroglial transcription factor, might be important in this context, but has not been systematically studied so far. Nissl- and Olig1-stained oligodendrocytes were quantified in the pregenual anterior cingulate (pACC)/dorsolateral prefrontal cortex (DLPFC), and adjacent white matter of patients with major depressive disorder (MDD, n = 9), bipolar disorder (BD, n = 8), schizophrenia (SZ, n = 13), and matched controls (n = 16). Potential downstream effects of increased Olig1-expression were analyzed. Antidepressant drug effects on Olig1-expression were further explored in OLN-93 oligodendrocyte cultures. Nissl-stainings of both white matter regions showed a 19-27% reduction of total oligodendrocyte densities in MDD and BD, but not in SZ. In contrast, nuclear Olig1-immunoreactivity was elevated in MDD in the pACC-adjacent white matter (left: p = 0.008; right: p = 0.018); this effect tended to increase with antidepressant dosage (r = 0.631, p = 0.069). This reactive increase of Olig1 was confirmed by partly dose-dependent effects of imipramine and amitriptyline in oligodendrocyte cultures. Correspondingly, MBP expression in the pACC-adjacent white matter tended to increase with antidepressant dosage (r = 0.637, p = 0.065). Other tested brain regions showed no diagnosis-dependent differences regarding Olig1-immunoreactivity. Since nuclear Olig1-expression marks oligodendrocyte precursor cells, its increased expression along with reduced total oligodendrocyte densities (Nissl-stained) in the pACC-adjacent white matter of MDD patients might indicate a (putatively medication-boosted) regenerative attempt to compensate oligodendrocyte loss.


Development of a sanitary risk index for Salmonella seroprevalence in Belgian pig farms.
The aim of this study was to develop a scientifically based Sanitary Risk Index (SRI), defined as an objective measure of the Salmonella seroprevalence in a pig herd based on the risk factors being present on the farm. Therefore, an observational epidemiological study was adopted to infer risk factors for the Salmonella seroprevalence of market pigs. A total of 204 Belgian farrow-to-finish pig herds were included in this cross-sectional study. The antibody titre to Salmonella in sera was analysed by means of an enzyme-linked immunosorbent assay (ELISA) for an average of 58 finisher pigs on each farm. A detailed questionnaire, covering an extensive range of potential risk factors was completed by each participating pig producer. Pearson correlation coefficients between the average sample to positive ratio (S/P)-value of a herd and the within-herd proportion of seropositive pigs were high. Significant risk factors associated with the average S/P-value of a herd were identified by a general linear mixed model. Feeding of meal, providing wet feed, having a hygienic-lock facility, using boot baths, applying the strict all in/all out procedure, programming the temperature in the zone of thermal neutrality and disinfecting between batches were all associated with lower average S/P-values. Sampling in summer, using a clean downtime, decreasing floor space per animal as well as increasing herd size were related with higher average S/P-values. The SRI consists of the above-specified risk factors together with their relative weight. Determining the Salmonella risk of a new herd by the SRI is primarily based on the quantification of the farm specific risk factors present and results in an average S/P-value of the herd. The model was validated using a set of conventional farms. In conclusion, the SRI is a useful preliminary screening tool which forms the basis for targeted sampling but cannot replace the serological herd classification with regard to Salmonella prevalence.


[Malignant melanoma].
There have been many prospective randomized clinical trials of IFNalpha as post-surgical adjuvant therapy for high-risk melanoma patients. High dose IFNalpha therapy(HDI) has been reported to be effective in disease-free survival (DFS). However, the usefulness of HDI therapy is still controversial due to its grave toxicity. Low dose IFNalpha therapy (LDI) has no consistent effects on DFS. Most trials showed little activity in patients with metastatic melanoma. In Japan, IFNbeta, in combination with chemotherapy, has been used as post-surgical adjuvant therapy, and has been considered to improve the prognosis of stage III melanoma patients. In addition, we have recently performed a phase I/IIa trial of IFNbeta gene therapy for advanced melanoma patients.


Ultrastructure and function of the labial nephridia and the rectum of Orchesella cincta (L.) (Collembola).
The collembolan Orchesella cincta possesses a well-developed coelomoduct kidney. The presence of podocytes in the wall of the sacculus and the fact that the epithelium of the nephridial tubule has the ultrastructural characteristics of resorbing cells, indicate that this is an "ultrafiltration-reabsorption" kidney. Apparently also the rectum is lined by a reabsorptive epithelium; the cells possess an extensive system of apical and basal infoldings. This view is sustained by the fact that the stereology of the apical channel system varies in animals kept under different moisture conditions. During the intermoult period, both organs are subject to strong morphological changes, which are obviously related to the feeding rhythm.


The differential effect of thyrotropin on the electrical responses of thyroid cells in monolayer cultures of varying duration.
The acute effects of thyrotropin on the membrane potential of thyroid cells maintained in the presence or absence of thyrotropin (0.2 U/ml) in the culture medium was determined. Monolayer cultures were prepared from porcine thyroid glands and cultured for 4--17 days after which the culture medium was exchanged for a buffered salt solution for intracellular measurements of the membrane potential. Cells were serially impaled with a microelectrode, first in the absence and then in the presence of 10 mU/ml thyrotropin. Cells cultured for 4--9 days depolarized from --29.6 +/- 1.7 (mean +/- S.E.) to --19.3 +/- 1.3 mV within 10 min after acute addition of 10 mU/ml thyrotropin. From 11 to 17 days of culture, basal membrane potentials were lower and, in most instances, cell hyperpolarization occurred within 30 min in response to thyrotropin. There was no difference in the electrical response of cells maintained in culture with or without thyrotropin. However, cells cultured with thyrotropin formed follicle-like structures in contrast to the monolayer formation of cells cultured without thyrotropin. The changes in the basal and stimulated electrical responses occur within a time frame similar to that reported for changes in the biosynthetic capacity of thyroid cells in culture. The data further emphasize the possible regulatory role of the cell membrane in stimulus-secretion coupling in the thyroid.


Relation of olfactory bulb and cortex. I. Spatial variation of bulbocortical interdependence.
Traces of extracellular electrical activity were simultaneously recorded from multiple electrode sites of the olfactory bulb and cortex of 10 alert, minimally restrained rabbits. Rhythmic bursts of 35-85 cps activity appeared concurrently in both structures on the inspiratory phase of a respiratory slow wave. Bulbocortical correlation was significantly higher during bursts than during interburst segments. Four conditions were expected to indicate interdependence of a bulbar and a cortical recording site: (1) a common bulbar and cortical burst frequency; (2) high bulbocortical burst correlation; (3) low bulbocortical burst phase dispersion; and (4) correlation between bulbar and cortical burst amplitudes. Pairs of sites were found which satisfied all 4 conditions. Mean bulbocortical correlation was inversely related to phase dispersion over all the site pairs examined. Significant variation in both correlation and phase dispersion was found with location of the recording sites in the bulb and in the cortex. Sites in the olfactory bulb thus differed significantly in their relation with cortical sites, and likewise, cortical sites differed significantly in their relation with bulbar sites. It is concluded that interdependence between the olfactory bulb and cortex can be detected in the relation of their field potentials and that the interdependence is spatially non-uniform.


Intraoperative near infrared fluorescence guided identification of the ureters using low dose methylene blue: a first in human experience.
Near infrared fluorescence imaging is a promising technique that offers real-time visual information during surgery. In this study we report the first clinical results to our knowledge of ureteral imaging using near infrared fluorescence after a simple peripheral infusion of methylene blue. Furthermore, we assessed the optimal timing and dose of methylene blue. A total of 12 patients who underwent lower abdominal surgery were included in this prospective feasibility study. Near infrared fluorescence imaging was performed using the Mini-FLARE™ imaging system. To determine optimal timing and dose, methylene blue was injected intravenously at doses of 0.25, 0.5 or 1 mg/kg after exposure of the ureters. Imaging was performed for up to 60 minutes after injection. In all patients both ureters could be clearly visualized within 10 minutes after infusion of methylene blue. The signal lasted at least up to 60 minutes after injection. The mean signal-to-background ratio of the ureter was 2.27 ± 1.22 (4), 2.61 ± 1.88 (4) and 3.58 ± 3.36 (4) for the 0.25, 0.5 and 1 mg/kg groups, respectively. A mixed model analysis was used to compare signal-to-background ratios among dose groups and times, and to assess the relationship between dose and time. A significant difference among time points (p <0.001) was found. However, no difference was observed among dose groups (p = 0.811). This study demonstrates the first successful use of near infrared fluorescence using low dose methylene blue for the identification of the ureters during lower abdominal surgery.


Effects of sequence and structure on the hypermutability of immunoglobulin genes.
Somatic hypermutation (SHM) is investigated in related immunoglobulin transgenes that differ in a short artificial sequence designed to vary the content of hotspot motifs and the potential to form RNA or DNA secondary structures. Mutability depends on hotspots, not secondary structure. Hotspot motifs predict about 50% of the mutations; the rest are in neutral and coldspots. Clusters of mutations and the sequential addition of mutations found in cell pedigrees suggest epigenetic attributes of SHM. Sometime in SHM, an essential factor seems to become limiting. Particular error-prone DNA polymerases appear to create mutations in hotspots on the top and bottom DNA strands throughout the target and the SHM process. One transgene is superhypermutable in all regions, suggesting the presence of a cis-element that enhances SHM.


Myxozoan infections of caecilians demonstrate broad host specificity and indicate a link with human activity.
Myxozoans are parasitic cnidarians that infect a wide variety of hosts. Vertebrates typically serve as intermediate hosts whereas definitive hosts are invertebrates, including annelids and bryozoans. Myxozoans are known to exploit species in two of the three extant amphibian orders (Anura: frogs and toads; Caudata: newts and salamanders). Here we use museum collections to determine, to our knowledge for the first time, whether myxozoans also exploit the third amphibian order (Gymnophiona: caecilians). Caecilians are a poorly known group of limbless amphibians, the ecologies of which range from aquatic to fully terrestrial. We examined 12 caecilian species in seven families (148 individuals total) characterised by a diversity of ecologies and life histories. Using morphological and molecular surveys, we discovered the presence of the myxozoan Cystodiscus axonis in two South American species (one of seven examined families) of aquatic caecilians - Typhlonectes natans and Typhlonectes compressicauda. All infected caecilians had been maintained in captivity in the United Kingdom prior to their preservation. Cystodiscus axonis is known from several Australian frog species and its presence in caecilians indicates a capacity for infecting highly divergent amphibian hosts. This first known report of myxozoan infections in caecilians provides evidence of a broad geographic and host range. However, the source of these infections remains unknown and could be related to exposure in South America, the U.K. or to conditions in captivity.


Establishing New Norms for Developmental Milestones.
Pediatric surveillance of young children depends on providers' assessment of developmental milestones, yet normative data are sparse. Our objectives were to develop new norms for common milestones to aid in clinical interpretation of milestone attainment. We analyzed responses to the developmental screening form of the Survey of Well-being of Young Children from 41 465 screens across 3 states. Associations between developmental status and a range of child characteristics were analyzed, and norms for individual questions were compared to guidelines regarding attainment of critical milestones from the Centers for Disease Control and Prevention (CDC). A contemporary resource of normative data for developmental milestone attainment was established. Lower developmental status was associated with child age in the presence of positive behavioral screening scores (P < .01), social determinants of health (P < .01), Medicaid (P < .01), male sex (P < .01), and child race (P < .01). Comparisons between Survey of Well-being of Young Children developmental questions and CDC guidelines reveal that a high percentage of children are reported to pass milestones by the age at which the CDC states that "most children pass" and that an even higher percentage of children are reported to pass milestones by the age at which the CDC states that parents should "act early." An interactive data visualization tool that can assist clinicians in real-time developmental screening and surveillance interpretation is also provided. Detailed normative data on individual developmental milestones can help clinicians guide caregivers' expectations for milestone attainment, thereby offering greater specificity to CDC guidelines.


Effect of topographical features on hydrologically connected riparian landscapes across different land-use patterns in colossal dams and reservoirs.
Topographic features impact the riparian landscape, which shapes reservoir ecosystems. We know little about ecological network parameter (ENP) responses to topographical features (riparian width, stream-channel width, slope, and elevation) from three land-use areas (rural, urban, and rural-urban transitional) in larger dams and reservoirs globally. This study used a field-based approach with 305 transects on an inundated area of 58,000 km2 inside the Three Gorges Dam Reservoir (TGDR) in China. We discovered that topographical features influenced ENPs differently, involving parameters of plant cover, regeneration, exotics, erosion, habitat, and stressors. As per the Pearson correlation (p < 0.05), riparian width had the most significant effect on transitional ENPs and the least impact on urban ENPs. Riparian width showed the most important influence on the parameters of exotics (with r ≤ -0.44) and erosion (r ≤ 0.56). In contrast, stream-channel widths had the greatest effect on rural ENPs and the least on urban and transitional ENPs. The erosion parameters were the most affected (r ≤ -0.26) by stream width. The slope showed relationships with the fewest ENPs in all three areas and influenced the stress (with a range of -0.51 <r < 0.85) and erosion (r ≤ -0.39) parameters. The impact of elevation was higher in urban areas and was positively correlated with the parameters of plant cover (r ≤ 0.70), erosion (r ≤ 0.58), and habitat (r ≤ 0.69). These results justify the policy emphasis on riparian areas that are managed using the same techniques, which generally ignores their topographical features.


The Relationship Between Spiritual Health and Quality of Life of Heart Transplant Candidates.
The heart transplantation is a stressful event, and its waiting time is often associated with worsening of clinical conditions and deterioration of the patient's quality of life. Spirituality plays an important role in mental health, so the present study was conducted to investigate the relationship between spiritual health and quality of life of patients undergoing cardiac transplantation. The present descriptive study was performed on 48 patients undergoing cardiac transplantation at the Shahid Rajaee Cardiovascular Center in Tehran during the first half of 2016. The data were collected by Ellisan-Palutzian Spiritual Well-Being Scale, Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Iranian Heart Failure Quality of Life Questionnaire (IHF-QOL). We used the SPSS v.20 software to analyze the data via descriptive statistics, parametric and non-parametric correlation and regression tests. The majority of patients (60.4%) had high spiritual health with a median score of 105, and its religious dimension was reported better (P < 0.001 and r = 0.591). With a mean of 63.23 ± 23.25, the quality of life of the majority of patients (75%) was at a poor level based on the Minnesota questionnaire. According to the IHF-QOL, the median total score was 39.50. There was a significant relationship between spiritual health score and quality of life in both questionnaires (MLHFQ: P = 0.006 and r = - 394; IHF-QOL: P = 0.022 and r = 0.329). Considering the positive relationship between spiritual health and quality of life of patients in this study, it is recommended to implement spiritual care and provide fulfillment for various needs of patients along with other medical care services.


Uptake and toxicity of spiked nickel to earthworm Eisenia fetida in a range of Chinese soils.
Bioavailability and toxicity of metals to soil organisms varies among different soils, and knowledge of this variance is useful for the development of soil environmental quality guidelines. In the present study, laboratory experiments were performed to investigate the effects of variations in nickel (Ni) uptake and toxicity on growth, cocoon output, and juvenile production in the earthworm Eisenia fetida in 13 Chinese soils spiked with nickel chloride. Body weight development of E. fetida was rather insensitive to Ni, and significant inhibition of growth was observed only at high Ni concentrations, such as 560 and 1000 mg/kg. The 50% inhibition effect concentrations (EC50s) for cocoon and juvenile production, based on measured Ni concentrations in soils, varied from 169 to 684 mg/kg and from 159 to 350 mg/kg, respectively. The EC50s represented approximately fourfold variation for cocoon output and twofold variation for juvenile production among 13 Chinese soils. Juvenile production, compared to cocoon output, was a more sensitive endpoint parameter to Ni. Nickel uptake in E. fetida increased as simple linear functions of increasing soil Ni concentrations. Tissue Ni-based EC50s (based on Ni concentrations in earthworm tissues) for cocoon production varied from 37 to 121 mg/kg (threefold variation) in 12 of 13 soils, suggesting a similar variation to that of soil Ni-based EC50s. Relationship analysis between soil properties and Ni toxicity showed that neither the EC50s for cocoon output nor those for juvenile production presented significant correlation with soil properties (pH, organic matter content, cation exchange capacity, clay content, Ca²⁺ and Mg²⁺). This may be ascribed to the narrow range of properties of selected soils. The soil factors that determined Ni toxicity to earthworm reproduction remain undetermined in the present study, and these data should be used cautiously when developing toxicity prediction models because of the narrow selection of soil properties.


Online Health Information Seeking Among Patients With Chronic Conditions: Integrating the Health Belief Model and Social Support Theory.
Chronic diseases are the leading causes of death and disability. With the growing patient population and climbing health care expenditures, researchers and policy makers are seeking new approaches to improve the accessibility of health information on chronic diseases while lowering costs. Online health information sources can play a substantial role in effective patient education and health communication. However, some contradictory evidence suggests that patients with chronic conditions may not necessarily seek online health information. This study aims to integrate 2 theories (ie, the health belief model and social support theory) and a critical health literacy perspective to understand online health information seeking (OHIS) among patients with chronic conditions. We used the survey method to collect data from online chronic disease communities and groups on social media platforms. Eligible participants were consumers with at least 1 chronic condition and those who have experience with OHIS. A total of 390 valid questionnaires were collected. The partial least squares approach to structural equation modeling was employed to analyze the data. The results suggested that perceived risk (t=3.989, P<.001) and perceived benefits (t=3.632, P<.001) significantly affected patients' OHIS. Perceived susceptibility (t=7.743, P<.001) and perceived severity (t=8.852, P<.001) were found to influence the perceived risk of chronic diseases significantly. Informational support (t=5.761, P<.001) and emotional support (t=5.748, P<.001) also impacted the perceived benefits of online sources for patients. In addition, moderation analysis showed that critical health literacy significantly moderated the link between perceived risk and OHIS (t=3.097, P=.002) but not the relationship between perceived benefits and OHIS (t=0.288, P=.774). This study shows that the health belief model, when combined with social support theory, can predict patients' OHIS. The perceived susceptibility and severity can effectively explain perceived risk, further predicting patients' OHIS. Informational support and emotional support can contribute to perceived benefits, thereby positively affecting patients' OHIS. This study also demonstrated the important negative moderating effects of critical health literacy on the association between perceived risk and OHIS.


A faster PISTOL for 1 H MR-based quantitative tissue oximetry.
Quantitative mapping of oxygen tension (pO2 ), noninvasively, could potentially be beneficial in cancer and stroke therapy for monitoring therapy and predicting response to certain therapies. Intracellular pO2 measurements may also prove useful in tracking the health of labeled cells and understanding the dynamics of cell therapy in vivo. Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) is a relatively new oximetry technique that measures the T1 of administered siloxanes such as hexamethyldisiloxane (HMDSO), to map the tissue pO2 at various locations with a temporal resolution of 3.5 minutes. We have now developed a siloxane-selective Look-Locker imaging sequence equipped with an echo planar imaging (EPI) readout to accelerate PISTOL acquisitions. The new tissue oximetry sequence, referred to as PISTOL-LL, enables the mapping of HMDSO T1 , and hence tissue pO2 in under one minute. PISTOL-LL was tested and compared with PISTOL in vitro and in vivo. Both sequences were used to record dynamic changes in pO2 of the rat thigh muscle (healthy Fischer rats, n = 6), and showed similar results (P > 0.05) as the other, with each sequence reporting a significant increase in pO2 (P < 0.05) under hyperoxia compared with steady state normoxia. This study demonstrates the ability of the new sequence in rapidly and accurately mapping the pO2 changes and accelerating quantitative 1 H MR tissue oximetry by approximately 4-fold. The faster PISTOL-LL technique could enable dynamic 1 H oximetry with higher temporal resolution for assesing tissue oxygentation and tracking the health of transplanted cells labeled with siloxane-based probes. With minor modifications, this sequence can be useful for 19 F applications as well.


Macrophage PPAR gamma Co-activator-1 alpha participates in repressing foam cell formation and atherosclerosis in response to conjugated linoleic acid.
Conjugated linoleic acid (CLA) has the unique property of inducing regression of pre-established murine atherosclerosis. Understanding the mechanism(s) involved may help identify endogenous pathways that reverse human atherosclerosis. Here, we provide evidence that CLA inhibits foam cell formation via regulation of the nuclear receptor coactivator, peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, and that macrophage PGC-1α plays a role in atheroprotection in vivo. PGC-1α was identified as a hub gene within a cluster in the aorta of the apoE(-/-) mouse in the CLA-induced regression model. PGC-1α was localized to macrophage/foam cells in the murine aorta where its expression was increased during CLA-induced regression. PGC-1α expression was also detected in macrophages in human atherosclerosis and was inversely linked to disease progression in patients with the disease. Deletion of PGC-1α in bone marrow derived macrophages promoted, whilst over expression of the gene inhibited foam cell formation. Importantly, macrophage specific deletion of PGC-1α accelerated atherosclerosis in the LDLR(-/-) mouse in vivo. These novel data support a functional role for PGC-1α in atheroprotection.


[The biomechanics of screws, cerclage wire and cerclage cable].
In contrast to fracture fixation, when performing an osteotomy the surgeon is able to plan preoperatively. The resulting fixation and compression of the bone fragments are the most important points. A stable osteosynthesis should prevent dislocation of bone fragments and improve bone healing. Beside plates, cerclages can be used for tension band or diaphysis bone fixation. Moreover, cortical or cancellous screws can be used for osteotomy fixation. This work describes biomechanical principles for fixation after an osteotomy with cerclages and cortical or cancellous screws. It also summarizes the materials and geometries used, as well as their influence on the stability of the osteosynthesis.


A qualitative assessment of factors influencing implementation and sustainability of evidence-based tobacco use treatment in Vietnam health centers.
Effective strategies are needed to increase implementation and sustainability of evidence-based tobacco dependence treatment (TDT) in public health systems in low- and middle-income countries (LMICs). Our two-arm cluster randomized controlled trial (VQuit) found that a multicomponent implementation strategy was effective in increasing provider adherence to TDT guidelines in commune health center (CHCs) in Vietnam. In this paper, we present findings from a post-implementation qualitative assessment of factors influencing effective implementation and program sustainability. We conducted semi-structured qualitative interviews (n = 52) with 13 CHC medical directors (i.e., physicians), 25 CHC health care providers (e.g., nurses), and 14 village health workers (VHWs) in 13 study sites. Interviews were transcribed and translated into English. Two qualitative researchers used both deductive (guided by the Consolidated Framework for Implementation Research) and inductive approaches to analysis. Facilitators of effective implementing of TDT included training and point-of-service tools (e.g., desktop chart with prompts for offering brief counseling) that increased knowledge and self-efficacy, patient demand for TDT, and a referral system, available in arm 2, which reduced the provider burden by shifting more intensive cessation counseling to a trained VHW. The primary challenges to sustainability were competing priorities that are driven by the Ministry of Health and may result in fewer resources for TDT compared with other health programs. However, providers and VHWs suggested several options for adapting the intervention and implementation strategies to address challenges and increasing engagement of local government committees and other sectors to sustain gains. Our findings offer insights into how a multicomponent implementation strategy influenced changes in the delivery of evidence-based TDT. In addition, the results illustrate the dynamic interplay between barriers and facilitators for sustaining TDT at the policy and community/practice level, particularly in the context of centralized public health systems like Vietnam's. Sustaining gains in practice improvement and clinical outcomes will require strategies that include ongoing engagement with policymakers and other stakeholders at the national and local level, and planning for adaptations and subsequent resource allocations in order to meet the World Health Organization's goals promoting access to effective treatment for all tobacco users. NCT02564653 , registered September 2015.


Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue.
We previously showed that Cidea(-/-) mice are resistant to diet-induced obesity through the upregulation of energy expenditure. The AMP-activated protein kinase (AMPK), consisting of catalytic alpha subunit and regulatory subunits beta and gamma, has a pivotal function in energy homoeostasis. We show here that AMPK protein levels and enzymatic activity were significantly increased in the brown adipose tissue of Cidea(-/-) mice. We also found that Cidea is colocalized with AMPK in the endoplasmic reticulum and forms a complex with AMPK in vivo through specific interaction with the beta subunit of AMPK, but not with the alpha or gamma subunit. When co-expressed with Cidea, the stability of AMPK-beta subunit was dramatically reduced due to increased ubiquitination-mediated degradation, which depends on a physical interaction between Cidea and AMPK. Furthermore, AMPK stability and enzymatic activity were increased in Cidea(-/-) adipocytes differentiated from mouse embryonic fibroblasts or preadipocytes. Our data strongly suggest that AMPK can be regulated by Cidea-mediated ubiquitin-dependent proteosome degradation, and provide a molecular explanation for the increased energy expenditure and lean phenotype in Cidea-null mice.


Inhibition of corneal inflammation following keratoplasty by birch leaf extract.
The objective of this study was to determine the effect of birch leaf (Betula pendula) extract (BPE) on corneal inflammation following keratoplasty in the rat model. T cells were stimulated in vitro in the presence of BPE. Proliferation, activation phenotype and the number of apoptotic/necrotic cells in cell culture were analyzed by flow cytometry. Corneal transplantation was performed between Fisher and Lewis rats. Recipient rats were either treated with cyclosporine A at a low dosage (Low-dose CsA=LDCsA) or received LDCsA in combination with BPE (2×1ml/day). Clinical signs for corneal inflammation and rejection time points were determined. Infiltrating leukocytes were analyzed histologically. BPE specifically inhibited T cell proliferation in vitro by inducing apoptosis. The phenotype was not affected. In vivo, BPE significantly delayed the onset of corneal opacification (p<0.05). The amount of infiltrating CD45(+) leukocytes and CD4(+) T cells (p<0.001) was significantly reduced by BPE, whereas infiltration of CD163(+) macrophages was not significantly different between the two groups. BPE selectively induces apoptosis of activated T cells. Accordingly, BPE treatment significantly reduces infiltrating T cells and subsequent corneal opacification following keratoplasty. Our findings suggest BPE as a promising anti-inflammatory drug to treat corneal inflammation.


Sustained CD8+ T-cell immune response to a novel immunodominant HLA-B*0702-associated epitope derived from an Epstein-Barr virus helicase-primase-associated protein.
Generation of a peptide-based vaccine against persistent viral infections, such as Epstein-Barr virus (EBV), requires identification of immunodominant epitopes recognized by anti-viral cytotoxic T-cells. Using available computer algorithms, we have screened the entire translated EBV genome for potential HLA-B7-binding peptides. The binding to HLA-B7 of 18 selected peptides was assessed by competitive binding assays and was found to correlate with the computer-assigned scores, confirming the predictive value of these algorithms in selection of HLA-B7-associated peptides. Screening of the immune responses to these peptides by ELISpot assays identified a novel immunodominant epitope, termed LPRA, derived from an EBV helicase-primase-associated protein encoded by BBLF2/3. Peptide-specific cells constituted up to 0.8% LPRA-specific CD8+ T-cells in the matured anti-viral response. Cytotoxic and proliferative cytotoxic T lymphocytes (CTL) responses to the LPRA peptide were readily demonstrated ex vivo. In addition, mutational studies of this epitope demonstrated a highly specific recognition by LPRA-specific CD8+ T-cells. Taken together, our data suggest that the novel lytic-phase HLA-B7-associated epitope contains essential features required of a component in an EBV peptide-based vaccine.


Ho and Ti Co-Substitution Tailored Structural Phase Transition and Enhanced Magnetic Properties of BiFeO3 Thin Films.
The polycrystalline thin films of BiFeO3 (BFO) and Bi0.90Ho0.10Fe1-xTixO (x = 0, 0.025, 0.05, 0.10, 0.15, and 0.20) were successfully synthesized by the simple sol-gel method. X-ray diffraction and Raman spectra revealed the substitution of Bi and Fe by Ho and Ti, respectively, and correspondingly a structural phase transition from the rhombohedral phase to orthorhombic phase. The field-emission scanning electron microscopy and transmission electron microscopy images indicated that the average size of the particles was decreased and the surface homogeneous agglomeration was enhanced with the increased concentration of Ti to x = 0.05. The X-ray photoelectron spectroscopy measurements illustrated that Fe3+ and O2- ions tended to increase with the Ti concentration increase, which accounted for the enhanced super-exchange interaction between Fe3+ and O2-. Because of the reduced concentration of oxygen vacancies, Ho and Ti ions with a smaller ionic radius and denser surface structure, the Ho and Ti co-substituted films with an appropriate concentration of Ti (x = 0.05) showed an optimal saturation magnetization (M s) of 44.23 emu/cm3 and remanent magnetization (M r) of 4.62 emu/cm3, which were approximately 1.8 times and 1.9 times than that of the pure BFO, respectively. This work opened up an effective way to modulate the structure and properties of BFO-based materials.


Determination using liquid-chromatography-electrospray tandem mass spectroscopy of ethinylestradiol serum pharmacokinetics in adult Sprague-Dawley rats.
The pharmacokinetics of ethinylestradiol (EE2), a potent synthetic estrogen, was investigated in male and female Sprague-Dawley rats as part of a series of endocrine-active compounds, including genistein and nonylphenol. A method based on solid-phase extraction and LC with negative ion electrospray tandem mass spectrometric detection was developed and validated. The limit of detection in untreated rat serum was below 0.01 ng/ml (0.03 nM), the limit of quantification was 0.03 ng/ml (0.10 nM), the intra- and inter-day precision was 2-9%, and the intra- and inter-day accuracy was 89-94%. This method was used to determine the serum pharmacokinetics of EE2 in rats following oral gavage administration of 1 mg/kg body weight. EE2 was present in serum primarily in the unconjugated form at concentrations below 0.5 ng/ml. The maximal serum concentration was proportional to dose over the range of 0.04-0.5 mg/kg body weight and pharmacokinetic parameters were determined using model-independent analysis. Significant sex differences were observed for elimination half-times and volumes of distribution, but not for total serum clearance or maximal concentrations. The pharmacokinetic analysis of EE2 will be useful for comparing the toxicological effects of EE2 to those of other environmental estrogens in related rodent endocrine disruptor studies.


[Ganglioside lactones in human stomach and breast tumors].
Ganglioside lactones absent in homologous normal tissues have been found in minute amounts in human gastric and mammary tumours. In mammary gland tumours only the ganglioside GM3 lactone has been identified. Gastric tumours also contain the GM3 lactone; in one case a ganglioside GD3 lactone was identified.


Fundus Autofluorescence Changes After Ranibizumab Treatment for Subfoveal Choroidal Neovascularization Secondary to Pathologic Myopia.
To describe fundus autofluorescence (FAF) patterns of myopic choroidal neovascularization (CNV) treated with intravitreal ranibizumab and their correlation with visual acuity. Prospective interventional case series. Twenty-seven eyes (27 patients) affected by myopic CNV were enrolled from January 2011 to January 2013. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) determination and fundus autofluorescence (FAF). The patients underwent ranibizumab injections following a pro re nata treatment regimen. The main outcome measure was the identification of the FAF patterns of myopic CNV over a 12-month follow-up. The secondary outcome was the correlation of the FAF patterns with the BCVA. At baseline 17 eyes (63%) showed a hyperautofluorescent pattern and 10 eyes (37%) a patchy pattern. BCVA changed from 0.48 ± 0.23 (logMAR) to 0.30 ± 0.32 at the 12-month examination (P = .027) in the hyper-FAF subgroup. In the subgroup showing the patchy pattern, the BCVA declined slightly from 0.51 ± 0.27 to 0.56 ± 0.37 (P = .53). The 14 eyes preserving the hyper-FAF pattern during the follow-up had a final BCVA of 0.20 ± 0.17, whereas the 9 eyes maintaining the patchy pattern showed a final BCVA of 0.60 ± 0.37 (P = .002). The atrophic area of the retinal pigment epithelium assessed on the basis of FAF increased from 1.27 ± 2.80 mm(2) to 1.83 ± 3.74 mm(2) at the 12-month examination (P = .016). The mean atrophic area increased by 0.37 mm(2) in the hyper-FAF subgroup and by 0.90 mm(2) in the patchy FAF subgroup. Two main patterns were identified on FAF in myopic CNV and were related to the prognostic evolution, the hyperautofluorescent CNV being associated with a greater visual gain and fewer atrophic changes over a 12-month follow-up.


Women's experiences of doing long-term pelvic floor muscle exercises for the treatment of pelvic organ prolapse symptoms.
This study investigated women's experiences of doing prescribed pelvic floor muscle exercise (PFME) after participation in the Pelvic Organ Prolapse Physiotherapy (POPPY) trial. The aim was to understand post-supervised treatment adherence to PFME and to inform future advice for women being treated for pelvic organ prolapse (POP). Five women were purposively selected from the New Zealand branch of the multi-centre, multi-national POPPY trial and took part in a semi-structured interviews about their experiences of PFME. The interviews were subjected to an interpretative phenomenological analysis (IPA). Three core themes were identified in the analysis. The first theme, "Patterns of PFME behaviour", described exercise characteristics and behaviours. The second theme, "Influences on PFME maintenance cycles", captured the participants' responses to and evaluations of their exercise practice and related PFME self-efficacy. The "cycle" referred to the changing influences on exercise behaviour. The third theme, "Family as priority", was expressed in terms of either putting family first or successfully combining the priorities of family and self. This study revealed the importance of family in influencing PFME patterns and behaviours in the treatment of POP. It is possible that identifying strategies to help women reach their PFME goals within the context of their families will promote more successful PFME adherence. The importance of family when prescribing exercise for women with other chronic health conditions is also worth exploring.


The morphology of the central nervous system of the barnacle, Semibalanus cariosus (Pallas).
The central nervous system of the sessile barnacle, Semibalanus cariosus (Pallas), has been studied with the particular aim of determining the locations of neuron somata in relation to peripheral nerves. This was accomplished by tracing peripheral nerves using dissection and methylene blue staining techniques, histological methods, and by permitting cobaltous chloride to diffuse via axons into ganglia ("backfilling"). The neuron maps resulting from the study reveal some well-defined sub-systems, a considerable degree of functional clumping of neuron somata, and some unexpected projections of neurons in the CNS. Neurophysiological studies based on these findings are in progress.


One Stop: Examining the Reasons Patients Use the Emergency Department for Nonurgent Care and the Barriers They Face.
Despite the plethora of research on the use of emergency department services for nonurgent primary health care, the vast majority of this research is quantitative in nature. To date, there is little research that reports on the problem from the patients' perspective and/or lived experience, which compromises health care providers' understanding of the essence of the problem as described by the patients. Thus, this study will provide a qualitative description of nonurgent ED visits from the patients' perspective. Specifically, this study answers the following research questions: 1) What are the reasons for patients and/or caregivers visiting the emergency department for nonurgent health conditions? and 2) What are the barriers experienced by patients and/or caregivers when seeking access to health care? A qualitative descriptive design with face-to-face interviews of 33 consenting participants was conducted at 4 emergency departments. All interviewed participants were triaged as nonurgent patients by the ED personnel. Three themes surfaced from the data regarding reasons for using the emergency department: 1) Practitioner referral; 2) Efficacy of care; and 3) Time saver. When describing barriers that participants experienced when seeking care outside of the emergency department for their nonurgent conditions, 3 themes that emerged are lack of primary care provider, financial difficulties, and lack of comprehensive care outside the emergency department. The results of the study can help inform patient-centered care and future policy initiatives that will address the practices and barriers contributing to nonurgent ED visits.


Rotundum psoas hitch: a new method for colpohysteropexy in girls with bladder exstrophy.
Female patients with bladder exstrophy frequently suffer from uterine prolapse, which is due to a defective pelvic floor anatomy. Different techniques for the correction of procidentia in this patient population have been described; however, since the numbers of patients are very small and no series with long-term follow-up exists, it is unclear which technique yields superior results. We describe here a new technique for uteropexy in girls and women with bladder exstrophy. In the rotundum psoas hitch procedure (RPH), the round ligaments are detached from the inner inguinal ring and fixed to the psoas muscle on both sides, thereby fixing the uterus in a more cranial and dorsal position. This procedure has been applied successfully in nine patients with a mean follow-up of 23.8 months. In six cases RPH was done prophylactically and in three cases therapeutically to correct an existing uterine prolapse. The mean age at operation was 9.6 years. In all but one case, RPH was combined with continent urinary reconstruction. No postoperative morbidity due to this technique has been described. RPH is an effective means of preventing or correcting procidentia in patients with bladder exstrophy; we emphasize that it should be combined with other abdominal operations, such as continent reconstruction, in girls or women with this condition.


Usefulness of 3-D reconstructed images of the human cerebral cortex for localization of subdural electrodes in epilepsy surgery.
Three-dimensional (3-D) images of 14 patients, in whom subdural electrodes were implanted for epilepsy surgery evaluation, were produced by fusing computerized tomography (CT) scans and magnetic resonance images (MRI) to determine the exact location of the electrodes. In 25% (198 of 806) of the subdural electrodes an exact location for resection strategy was not evident from the X-rays. The location of these electrodes ('doubtful location', DL) was compared to the 3-D images. Intraoperative inspection served as the gold standard. Concordance score was defined as good for 75-100% concordance, moderate for 50-75%, and poor for less than 50% concordance of the DL electrodes to the intraoperatively determined location. A comparative analysis of the 3-D images and X-ray films showed a highly significant difference (P < 0.0002) in favor of 3-D images. The concordance score for the DL electrodes in the 3-D images was good in 93% of the patients and moderate in 7%. In contrast, the concordance score was good in only 7% of the patients for the two-dimensional (2-D) skull films, moderate in 57%, and poor in 36%. Interobserver reliability was better for 3-D images (93%) than for the 2-D X-rays (43%). These findings suggest that 3-D images aid preoperative planning for resective epilepsy surgery.


Temporal effects of gamma interferon deficiency on the course of Friend retrovirus infection in mice.
The current studies demonstrate complex and seemingly contradictory effects by gamma interferon (IFN-gamma) on Friend virus (FV) infection. Both temporal and tissue-specific effects were observed. During the first week of infection, IFN-gamma-deficiency caused increased levels of FV infection in multiple tissues. Surprisingly, however, by 2 weeks postinfection, IFN-gamma-deficient mice had significantly lower levels of infection in both the spleen and bone marrow compared to wild-type mice. The rapid reduction of virus in the IFN-gamma-deficient mice correlated with a more rapid virus-neutralizing antibody response than was observed in the wild-type mice. Furthermore, the virus-neutralizing antibody response in wild-type mice could be accelerated by ablation of their IFN-gamma response. Although the IFN-gamma-deficient mice developed an accelerated virus-neutralizing antibody response, they did not class-switch to immunoglobulin G class immunoglobulins nor could they maintain long-term virus-neutralizing antibody titers. Eventually, all of the IFN-gamma-deficient mice failed to keep persistent virus in check and developed fatal FV-induced erythroleukemia.


Opioid-reduced anesthesia based on esketamine in gynecological day surgery: a randomized double-blind controlled study.
Opioid-reduced anesthesia may accelerate postoperative rehabilitation by reducing opioid-related side effects. The objective was to investigate the feasibility of opioid-reduced general anesthesia based on esketamine and to observe postoperative nausea and vomiting (PONV), postoperative pain, hemodynamics and other adverse reactions in gynecological day surgery compared with the traditional opioid-based anesthesia program. This study was conducted as a prospective parallel-group randomized controlled trial. A total of 141 adult women undergoing gynecological day surgery were included. Patients were randomly assigned to receive traditional opioid-based anesthesia (Group C) with alfentanil, or opioid-reduced anesthesia (a moderate-opioid group (Group MO) and low-opioid group (Group LO) with esketamine and alfentanil). For anesthesia induction, the three groups received 20, 20, 10 μg/kg alfentanil respectively and Group LO received an additional 0.2 mg/kg esketamine. For maintenance of anesthesia, the patients in Group C received 40 μg/kg/h alfentanil, and those in Group MO and Group LO received 0.5 mg/kg/h esketamine. Patients in the three groups had comparable clinical and surgical data. A total of 33.3% of patients in Group C, 18.4% of patients in Group MO and 43.2% of patients in Group LO met the primary endpoint (p = 0.033), and the incidence of nausea within 24 hours after surgery in Group MO was lower than in Group LO (p < 0.05). The extubation time, median length of stay in the hospital after surgery and visual analog scale (VAS) of postoperative pain were equivalent in the three groups. The frequencies of adverse hemodynamic events in the MO 1(0, 2) and LO 0(0, 1) groups were significantly decreased (p < 0.05). Compared with Group C, the median length of stay in the postanesthesia care unit (PACU) in Group LO was increased, 60.0 (36.25, 88.75) vs. 42.5 (25, 73.75) minutes (p < 0.05). Opioid-reduced anesthesia based on esketamine is feasible and provides effective analgesia for patients. Esketamine provided a positive analgesic effect and the opioid-reduced groups showed more stable hemodynamics. However, less or no use of opioids did not result in a more comfortable prognosis. This study was registered at Chictr.org.cn (NO. ChiCTR2100053153 ); November 13, 2021.