Leaf miner-induced changes in leaf transmittance cause variations in insect respiration rates.
Very little is known about alterations in microclimate when an herbivore feeds on host plant. Modifications of leaf transmittance properties induced by feeding activity of the leaf miner Phyllonorycter blancardella F. were measured using a spectrometer. Their effects on the herbivore's body temperature and respiration rate have been determined under controlled conditions and varying radiation level employing an infrared gas analyser. By feeding within leaf tissues, a miner induces the formation of feeding windows which transmit a large portion of incoming radiations within a mine. As a result, body temperature and respiration rate increase with radiation level when positioned below feeding windows. Therefore, the miner is not always protected from radiations despite living within plant tissues. The amount of CO(2) released by larvae below feeding windows at high radiation levels is about five-fold that recorded in the dark. By contrast, body temperature and respiration rate increase only slightly with radiation level when the insect is positioned below intact tissues through which radiation is only weakly transmitted. A mine offers its inhabitant a heterogeneous light environment that allows the insect larva to thermoregulate through behavioural modification. Our results highlight the importance of physical feedbacks induced by herbivory which alter significantly an insect's metabolism independently of its nutritional state.


Codon usage pattern in alpha 2(I) chain domain of chicken type I collagen and its implications for the secondary structure of the mRNA and the synthesis pauses of the collagen.
A stability map of local secondary structure of the mRNA of the triple-helical alpha 2(I) chain domain of chicken type I collagen was obtained by plotting the free energy of the optimal secondary structure of a local segment in mRNA against the segment position along a base sequence of the mRNA. It was found that the positions of the minima of free energy in the plot coincide with the positions where synthesis pauses of the alpha-chain polypeptides of the corresponding sizes translated from the mRNA have been reported to occur (1). The codon usage pattern of each of the three major amino acids of the alpha-chain domain of the collagen, Gly, Pro and Ala, fluctuates considerably along the base sequence segments of the mRNA and a deviation of the pattern from that of the average of the whole alpha 2(I) chain domain mRNA, particularly for Gly codons, leads to a loss of the stability of the local secondary structure of the mRNA. The results suggest that selection has operated on the codon usage to optimize the secondary structure characteristic of the mRNA of the chicken collagen alpha 2(I) chain domain which leads to a nonuniform polypeptide elongation pattern.


The role of apoptosis (programmed cell death) in haemopoiesis and the immune system.
Apoptosis, or programmed cell death, is a series of controlled sequential events resulting in the demise of cells without invoking an inflammatory response. It is a naturally occurring process which maintains a cellular balance during both animal development and in the mature adult. Although first described 20 years ago, there is now renewed interest in this phenomenon, particularly in the light of our greater understanding of cellular signalling pathways and their genetic control. This is especially pertinent to haemopoiesis and the overall maintenance of a functional immune system. This review broadly covers the biochemical events of apoptosis and the recognition of apoptotic cells by phagocytes. Reference is made to the selective development of T- and B-cells and to the control of inflammation. Molecular events in apoptosis are also discussed with special reference to aberrant bcl-2 gene expression in follicular B-cell lymphoma and the role of other death genes in the control of apoptosis.


Flotillin-1 in the substantia nigra of the Parkinson brain and a predominant localization in catecholaminergic nerves in the rat brain.
The substantia nigra cells of a normal and Parkinson's disease human brain were obtained by the micropunch procedure and total RNA was isolated. Differential display RT-PCR of the total RNA revealed differentially expressed cDNAs that were identified by sequencing. This resulted in the identification of a panel of known and unknown differentially expressed genes. Complex I (NADH ubiquinone oxidoreductase) and Complex IV (cytochrome oxidase) whose expressions are decreased in Parkinson's disease were reduced in the Parkinson brain. Of the various differentially expressed genes, flotillin-1, also known as reggie-2, was of great interest to us. It is a relatively new protein which is an integral membrane component of lipid rafts and has been implicated in signal transduction pathway events. In situ hybridization histochemical studies with human and rat brain sections revealed the presence of this mRNA in discrete neuronal (and possibly glial) cells of the substantia nigra, locus coeruleus, cortex, hippocampus, hypothalamus, thalamus, motor nuclei, nucleus basalis, raphe nucleus, and other brain regions. Immunohistochemical studies revealed that flotillin-1 is not present in all the regions where the message was found. In the rat brain, the most prominent observation was the revelation of all catecholamine cells (dopamine, norepinephrine, epinephrine) by the flotillin-1 antibody (1:100 dilution). At a more concentrated dilution (1:10) other neuronal cells (e.g., cortex, thalamus, hindbrain) were observed. At both dilutions dense dopaminergic fibers were observed in the rat caudate-putamen, nigrostriatal tract, and substantia nigra. It is significant that there is an increased gene expression of flotillin-1 in the Parkinson substantia nigra/ventral tegmental area. The role of flotillin in these cells is unclear although it is interesting that the reggie-2/flotillin-1 gene was upregulated during retinal axon regeneration in the goldfish visual pathway (Schulte et al., Development 124:577-87, 1997) which suggests that flotillin-1/reggie-2 might play a role in axonal growth from the remaining substantia nigra cells of the Parkinson brain.


Aetiologies of Hyperprolactinaemia: A retrospective analysis from a tertiary healthcare centre.
This study aimed to evaluate the aetiologies of hyperprolactinaemia in the United Arab Emirates (UAE). This retrospective study used laboratory databases to identify all patients who underwent evaluation for prolactin at Tawam Hospital, Al Ain, UAE, between 2009 and 2015. Of those 2,280 patients, all patients with low or normal prolactin (n = 1,315) were excluded. Subsequently, charts of the remaining patients (n = 965) with hyperprolactinaemia were reviewed and those with incomplete work-ups or insufficient documentation of the hyperprolactinaemia's aetiology were excluded (n = 458). A total of 507 patients were included in the study. The average age at prolactin evaluation was 36 ± 13.2 years and the majority (67.1%) of patients were female. The most common reasons for requesting prolactin were menstrual disorders (29.5%), infertility (18%), evaluation of sellar masses (14.3%), ruling out seizures (13.4 %) and monitoring while on psychiatric medications (8.7%). The most common causes of hyperprolactinaemia were prolactinoma (17%), transient hyperprolactinaemia (14.6%), drug-induced side effects (14.4%), polycystic ovarian syndrome (11.8%) and seizure disorder (7.7%). In females, common aetiologies were prolactinomas, transient and idiopathic hyperprolactinaemia, while sellar masses, seizures, chronic kidney disease and acute illnesses were common aetiologies of hyperprolactinaemia in males. The prolactin level varied between the different aetiologies and a level of >250 ng/mL was suggestive of macro-prolactinoma. A significant proportion of patients with hyperprolactinaemia have transient hyperprolactinaemia. Before further investigations are carried out, prolactin level assessment should be repeated, especially in patients with mild hyperprolactinaemia.


Angiotensin System Inhibitors May Improve Outcomes of Patients With Castration-Resistant Prostate Cancer During Abiraterone Acetate Treatment-A Cardio-Oncology Study.
Abiraterone acetate (ABI) therapy improves overall survival in metastatic prostate cancer (PC) patients; however, this effect may be diminished by concurrent comorbidities. We aimed to evaluate the influence of pre-existing chronic diseases and concomitant medications on the course of ABI treatment among post-chemotherapy patients with metastatic castration-resistant prostate cancer patients (mCRPC). From the Polish National Health Fund database, we identified 93 post-chemotherapy, mCRPC patients, who were qualified for ABI treatment in our oncology center between 2014 and 2018. Survival curves and Cox proportional hazard models (univariate and multivariate) were used to determine the predictors for longer time to treatment failure (TTF) of ABI therapy. Median TTF was 9,8 months (IQR: 0,6-56,5) Factors associated with longer TTF were: well controlled hypertension (HR, 0.59; 95% CI. 0.38-0.90; p = 0.02), stable coronary artery disease (HR, 0.56; 95% CI, 0.33-0.95; p=0.03), the use of angiotensin system inhibitor (ASi) (HR, 0.61; 95% CI 0.4-0.94; p = 0,02). Patients who were receiving ASi had median TTF of 12.2 months versus 5.8 months in men who did not receive ASi before ABI initiation. At the start of ABI therapy, the aforementioned groups did not differ in terms of well-known prognostic factors: Gleason score, PSA level, or the number of patients with visceral metastases. In a multivariate analysis, the use of ASi remained statistically significant, even after adjustment for well-known oncological factors (HR, 0.57; 95% CI, 0.34-0.98; p = 0.04). The use of ASi may enhance and prolong ABI therapy in post-docetaxel mCRPC patients and may potentially be considered a new, non-oncological, predictive factor for longer TTF. This association requires a prospective validation.


Sub-internal limiting membrane hemorrhage associated with Weil's disease.
Leptospirosis is a rare, typically tropical disease associated with water sources infected with rat urine. Symptoms can range from asymptomatic to a severe, deadly form known as Weil's disease, and ocular manifestations can arise. As global temperatures continue to rise, leptospirosis will become a larger problem worldwide. Here we describe the first case to our knowledge of foveal sub-internal limiting membrane (sub-ILM) hemorrhage due to Weil's disease. A 56-year-old female presented with floaters and decreased vision to 20/200 in the right eye after being hospitalized for Weil's disease. Funduscopic examination and optical coherence tomography (OCT) demonstrated a foveal sub-ILM hemorrhage in the right eye. The patient was treated with pars-plana vitrectomy with internal limiting membrane removal and blood aspiration, and her best corrected visual acuity improved to 20/60. Here we report the first case of sub-ILM hemorrhage following Weil's disease. Patients with leptospirosis and Weil's disease can develop retinal complications and therefore should be followed with fundoscopic eye examination after resolution of systemic symptoms. For those with retinal hemorrhages, OCT evaluation should be used to differentiate sub-hyaloid and sub-ILM hemorrhages.


Stiffness control in dual color tomographic volumetric 3D printing.
Tomographic volumetric printing (TVP) physically reverses tomography to offer fast and auxiliary-free 3D printing. Here we show that wavelength-sensitive photoresins can be cured using visible ([Formula: see text] nm) and UV ([Formula: see text] nm) sources simultaneously in a TVP setup to generate internal mechanical property gradients with high precision. We develop solutions of mixed acrylate and epoxy monomers and utilize the orthogonal chemistry between free radical and cationic polymerization to realize fully 3D stiffness control. The radial resolution of stiffness control is 300 µm or better and an average modulus gradient of 5 MPa/µm is achieved. We further show that the reactive transport of radical inhibitors defines a workpiece's shape and limits the achievable stiffness contrast to a range from 127 MPa to 201 MPa according to standard tensile tests after post-processing. Our result presents a strategy for controlling the stiffness of material spatially in light-based volumetric additive manufacturing.


Prospective trial of combined hyperfractionated radiotherapy and bronchial arterial infusion of chemotherapy for locally advanced nonsmall cell lung cancer.
This article is a prospective trial of hyperfractional radiotherapy with bronchial arterial infusion of anticancer drugs to treat locally advanced bronchogenic cancer. The treatment results, the complications of bronchial arterial infusion, the failure patterns, the relationship of technical aspects of delivery of radiotherapy, and the protocol of anticancer drugs are presented. One hundred and twenty-six patients with locally advanced bronchogenic cancer, treated from January 1988 to January 1990, were divided randomly into four groups in our hospital. Group 1: combination of hyperfractional radiotherapy with bronchial arterial infusion of anticancer drugs (30 cases); Group 2: combination of conventional radiotherapy with bronchial arterial infusion of anticancer (33 cases); Group 3: combination of systemic chemotherapy and split-course radiotherapy (33 cases); Group 4: conventional radiotherapy only (30 cases). All the patients were followed for 3 years. The 1-year survival rates for Groups 1, 2, 3, and 4 are 80, 63.6, 48.5, and 30%, respectively. The 2-year survival rates for Groups 1, 2, 3, and 4 are 23.3, 15.15, 9.1, and 6.6%, respectively. The 3-year survival rates for Groups 1, 2, 3, and 4 are 10, 3.3, 0, and 0%, respectively. This study demonstrated that the combination of hyperfractional radiotherapy with bronchial arterial infusion anticancer drugs can be performed safely and effectively for locally advanced bronchogenic carcinoma.


View-invariance learning in object recognition by pigeons depends on error-driven associative learning processes.
A model hypothesizing that basic mechanisms of associative learning and generalization underlie object categorization in vertebrates can account for a large body of animal and human data. Here, we report two experiments which implicate error-driven associative learning in pigeons' recognition of objects across changes in viewpoint. Experiment 1 found that object recognition across changes in viewpoint depends on how well each view predicts reward. Analyses of generalization performance, spatial position of pecks to images, and learning curves all showed behavioral patterns analogous to those found in prior studies of relative validity in associative learning. In Experiment 2, pigeons were trained to recognize objects from multiple viewpoints, which usually promotes robust performance at novel views of the trained objects. However, when the objects possessed a salient, informative metric property for solving the task, the pigeons did not show view-invariant recognition of the training objects, a result analogous to the overshadowing effect in associative learning.


Role of talocalcaneal osteotomy in clubfoot surgery: results in 31 surgically treated feet.
The most important deformities in clubfeet can be demonstrated by simultaneous arthrography of the talonavicular and talocrural joints. In patients with a severe talar deformity, wedge osteotomy through the talar neck and calcaneus has been performed as a prerequisite for correction. Our series consisted of 20 patients with 31 idiopathic clubfeet with pronounced talar deformity. The mean observation time after osteotomy was 11 years 3 months. The principles and aims are described, as are the indications for talocalcaneal osteotomy. Results were good in 19 feet (60%), fair in six (20%), and poor in six (20%).


Erythema nodosum in children: a cohort study from a tertiary pediatric hospital in Italy.
Erythema nodosum (EN), although relatively uncommon in the pediatric population, is the most frequent type of panniculitis in children. The present study aimed to report all the cases of children admitted to our tertiary pediatric hospital with the diagnosis of EN to evaluate the epidemiology, clinical manifestations, etiology, treatment, and the course of this disease in the pediatric age. This observational study retrospectively considered all children evaluated to the emergency room (ER) of Meyer Children's University Hospital, Florence, Italy, discharged with a diagnosis of EN over a 12-year period (from January 2009 to December 2021). Clinical and laboratory data were recorded using a standardized report form. Sixty-eight patients with EN were included. The etiologic diagnosis of EN was made in 38 children (55.9%): 29 (42.6%) had infection-related EN (in particular EBV and β-hemolytic streptococcus), 6 (8.8%) had Crohn's disease, 1 celiac disease, 1 Sjogren syndrome, and 1 Hodgkin lymphoma. In 30 patients (45%), no definitive diagnosis was reached, and they were defined as having idiopathic EN. Most of the laboratory tests were nonspecific. No statistical differences were found in the demographic and clinical data, and the main diagnostic laboratory parameters between patients with idiopathic EN versus those with secondary EN. Conclusion: Since EN can be isolated or the first manifestation of heterogeneous underlying pathologies, some of which can be severe and life-threatening, it is important to recognize it and carry out all the necessary etiological diagnostic investigations to understand its etiology and start the specific treatment. What is Known: • Erythema nodosum (EN) is the most frequent type of panniculitis in children. • It has been associated with a wide spectrum of disorders, such as different types of infection, malignancies, chronic inflammations, and drugs. What is New: • No statistical differences can be found in clinical features as well as laboratory data, between patients with idiopathic EN versus those with secondary EN. • A broad spectrum of investigations and a proper follow-up should be taken into account in order to prevent a delayed or missed secondary EN diagnosis.


Pathogenicity of porcine deltacoronavirus (PDCoV) strain NH and immunization of pregnant sows with an inactivated PDCoV vaccine protects 5-day-old neonatal piglets from virulent challenge.
In this study, the pathogenicity of porcine deltacoronavirus (PDCoV) strain NH (passage 10, P10) was evaluated. We found that PDCoV strain NH is enteropathogenic in 5-day-old pigs. Pathogenicity experiments provided a challenge model for studying the protection efficiency of passive immunity. In order to investigate the protective efficacy of passive immunity in newborn piglets, pregnant sows were vaccinated with either a PDCoV-inactivated vaccine at the Houhai acupoint (n = 5) or DMEM as a negative control (n = 2) using a prime/boost strategy 20 and 40 days before delivery. PDCoV spike (S)-specific IgG and neutralizing antibody (NA) responses were detected in immunized sows and piglets born to immunized sows. PDCoV spike (S)-specific sIgA was also detected in the colostrum and milk of immunized sows. Five days post-farrowing, piglets were orally challenged with PDCoV strain NH (105 TCID50 /piglet). Severe diarrhoea, high levels of viral RNA copies and substantial intestinal villus atrophy were detected in piglets born to unimmunized sows. Only 4 of 31 piglets (12.9%) born to immunized sows in the challenge group displayed mild to moderate diarrhoea, lower viral RNA copies and minor intestinal villi damage compared to piglets born to unimmunized sows post-challenge. Mock piglets exhibited no typical clinical symptoms. The challenge experiment results indicated that the inactivated PDCoV vaccine exhibited 87.1% protective efficacy in the piglets. These findings suggest that the inactivated PDCoV vaccine has the potential to be an effective vaccine, providing protection against virulent PDCoV.


Use of finite-memory Wiener filters in scintigram processing.
Scintigraphic images are subject to two forms of imperfection: blurring due to the components of the detector (collimator, photomultiplier, analog processing devices) and noise resulting from radioactive disintegration. We use Wiener filters operating within a limited area of the spatial domain in processing these images. After defining statistical models of ideal image and degrading processes, we study the effects of parameters on filter features. Finally, we present examples demonstrating filter performance.


Risk factors for laboratory-confirmed household transmission of pandemic H1N1 2009 infection.
Household transmission of the pandemic H1N1 2009 virus infection (pH1N1) frequently occurred in children and adolescents within several days after development of index cases. However, antiviral therapy for index cases did not seem to prevent household transmission of pH1N1.


A scoring system to predict outcome following neonatal seizures.
Ninety-six newborn infants with seizures were scored during the initial hospitalization on abnormality of EEG, neurologic examination, etiology of seizures, length of seizure, type of seizure, and birth weight under or over 1,500 gm. At 3 months, corrected for gestational age, the 80 surviving infants were scored on abnormality of current EEG, neurologic examination, etiology of seizure, presence or absence of seizure since hospital discharge, and birth weight under or over 1,500 gm. At age 10 months, 76 of 77 surviving infants were evaluated with the Gesell Developmental Inventory, physical examination, and neurologic examination. Chi square analysis documented that the scoring system was an accurate predictor of those infants with seizure disorders, mental retardation, and motor dysfunction. The score may assist the clinician in making decisions in regard to anticonvulsant therapy during initial hospitalization or at age 3 months.


Postembryonic brain development in the monarch butterfly,Danaus plexippus plexippus L. : II. The optic lobes.
1. Temporal and spatial aspects of postembryonic optic lobe development in a Lepidopteran,Danaus plexippus plexippus L., were analyzed using serial section reconstructions and H3-thymidine radioautography to display loci of cell production and progressive movements of populations of cells. 2. Optic lobe development begins early in larval life and is continuous without perceptible fluctuations corresponding to molting. The production of new cells begins during the first larval stages and is completed within a few days after pupation. 3. Development of adult optic centers appears to be independent of the larval optic center and also of adult eye development which does not get underway until pupation. At pupation the larval stemmata migrate toward the brain along the stemmatal nerve which persists and later serves as the framework by which ommatidial neurones reach the brain. 4. Ganglion cells of the adult optic lobe are produced by two coiled rod-like aggregates of neuroblasts, the inner and outer optic lobe anlagen, which lie lateral to the protocerebrum and are already present in the brain of the newly hatched larva. Neuroblasts of the anlagen divide both symetrically to produce more neuroblasts and asymmetrically to yield one neuroblast and one smaller cell, the ganglion-mother cell. Subsequent ganglion-mother cell divisions produce the new ganglion cells which are continuously displaced from the anlage by additional cells. Following pupation mitotic activity in the anlagen diminishes and neuroblasts degenerate. By the fourth day after pupation the anlagen have disappeared. 5. Fiber differentiation begins within a few days of cell formation. Fibers travel in bundles usually toward the center of the coiled anlagen where they form the neuropile masses. With contributions from a growing population of ganglion cells, fibermasses grow rapidly in size and complexity. 6. The geometric arrangement of anlagen, cortices, and neuropile is dynamic and interdependent. Progressive changes in anlagen configuration result from the combined effects of an increasing neuroblast population, growing optic cortices, and expanding fibermasses between the arms of the anlagen. In turn, the cortices and fibermasses which follow anlagen contours also change form. The complex of these parts, initially small and coiled, gradually enlarges and uncoils until at the time of anlagen degeneration the three optic fibermasses and their cortices are in approximately their final arrangement. 7. The outer anlage forms cells of the lamina cortex at its lateral rim and cells of the medulla at its medial rim. Cells of the lobula cortex are produced by strands of inner anlage neuroblasts extending laterally between the arms of the coiled outer anlage. 8. Cells of the medulla cortex are first seen during the second larval instar and several days later the medulla fibermass is discernible. Cortex and fibermass lie medial to the outer anlage which is moved progressively more laterally as more cells are produced. Cells labelled with H3-Td R at the beginning of the third instar become the tangential cells of the adult optic lobe. Those labelled at the fourth and fith stages occupy positions near the tangential cells, and those labelled at pupation ultimately lie at the lateral edge of the cortex. 9. Production of the lamina cortex begins later and procedes more slowly. Cells here are first apparent during the fourth instar and form a cellular cap covering the lateral part of the optic lobe. Labelling studies show that the earliest formed cells finally occupy the most posterior region of the lamina cortex. The lamina fibermass is first seen in the mid-fifth instar brain. 10. For most of larval life the lobula cortex forms a plug of cells just inside the lamina. While the anlage remains coiled, the first-formed cells are at the center of the plug, but ultimately they lie at the most medial part of the cortex. Production of lobula cells begins during the third instar and by the mid-fourth instar the lobula neuropile can be seen medial to them. 11. As a result of these studies with H3-Td R injection and fixation after varying intervals it has been possible to estimate the age of cells at a particular developmental stage. Because this material offers an organized arrangement of cells of a wide range of identifiable ages and levels of maturation within a single individual, it provides an excellent model for the study of progressive neurone differentiation.


Degenerative cervical myelopathy caused by posttraumatic severe atlantoaxial dislocation over 10 years in patients with right vertebral artery hypoplasia: A case report of successful management.
Degenerative cervical myelopathy caused by long-standing neglected AAD is rare, especially in severe cases. Combined with the exceptional right vertebral artery hypoplasia condition, treatment must be integrated into multitherapy to avoid fatal complications. A 55-year-old man presented with degenerative cervical myelopathy caused by posttraumatic severe atlantoaxial dislocation for more than 10 years in patients with right vertebral artery hypoplasia. After treatment with halo traction and C1 lateral mass, as well as C2 pedicle screw fixation combined with bone autoplasty, the condition was resolved. This is an extremely rare and severe condition (anatomical damage, long-term sequelae, degree of paralysis on admission, and complete hypoplasia of the right vertebral artery). The treatment strategy is consistent with early favorable outcomes.


Fetal urinary tract dilation: What to tell the parents.
Urinary tract dilation (UTD), which refers to the abnormal dilation of the urinary collection system, is the most common finding on prenatal ultrasound and presents with varying severity, presentation, etiology, and prognosis. Prenatal classification and risk stratification aim to prevent postnatal complications, such as urinary tract infections and further kidney dysfunction. Parents expecting a child with UTD should be counseled by a multidisciplinary team consisting of maternal-fetal medicine specialists, and pediatric urology and nephrology providers. This review summarizes the key points in the diagnostic evaluation and management during the prenatal and initial postnatal period, focusing on the information that should be provided to future parents. We address frequently asked parental questions and concerns that our multidisciplinary clinical practice faces.


The Antitumor Efficacy of CpG Oligonucleotides is Improved by Encapsulation in Plant Virus-Like Particles.
Oligodeoxynucleotides (ODNs) with CpG motifs have potent immunostimulatory effects on many subsets of immune cells. For example, Class B CpG-ODNs, such as ODN1826 induce the phagocytic activity of macrophages by activating the Toll-like receptor 9 signaling pathway. Systemic ODN delivery results in unfavorable pharmacokinetic profiles and can trigger adverse effects. To address this issue, plant virus-like particles (VLPs) are developed for the targeted delivery of ODN1826 to tumor-associated macrophages (TAMs). ODN1826 is encapsulated by the in vitro disassembly and reassembly of Cowpea chlorotic mottle virus (CCMV), producing VLPs that are structurally analogous to the native virus. The encapsulation of ODN1826 in CCMV-derived VLPs promotes ODN uptake by TAMs ex vivo and significantly enhance their phagocytic activity. The antitumor activity of the VLPs in vivo is also evaluated, revealing that the direct injection of ODN1826 VLPs into established tumors induces a robust antitumor response by increasing the phagocytic activity of TAMs in the tumor microenvironment. CCMV encapsulation significantly enhances the efficacy of ODN1826 compared to the free drug, slowing tumor growth and prolonging survival in mouse models of colon cancer and melanoma.


Photorefractive keratectomy followed by cross-linking versus cross-linking alone for management of progressive keratoconus: two-year follow-up.
To compare visual, refractive, topographic, and corneal higher-order aberration outcome at the 2-year follow-up after customized photorefractive keratectomy (PRK) followed by cross-linking (CXL) as a single procedure versus CXL alone in eyes with progressive keratoconus. Prospective, interventional, nonrandomized clinical trial. Seventeen patients (34 eyes) with progressive keratoconus were assigned to 2 groups: the worse eye (17 eyes) was assigned to the PRK plus CXL group and the better eye (17 fellow eyes) was assigned to the CXL group. In the PRK plus CXL group, uncorrected distance acuity improved significantly, from a mean ± standard deviation of 0.63 ± 0.36 logarithm of the minimal angle of resolution (logMAR) units to 0.19 ± 0.17 logMAR units (P < .05) and best distance acuity from 0.06 ± 0.08 logMAR to 0.03 ± 0.06 logMAR (P < .05). Manifest refraction spherical equivalent and spherical and cylindrical power improved significantly (P < .05). Simulated keratometry, flattest, steepest, average, cylindrical, apex keratometry, and inferior-superior value decreased significantly (P < .05). Total and coma-like aberrations significantly decreased for all pupil diameters (P < .05). In the CXL group, uncorrected distance acuity improved, but not significantly, from 0.59 ± 0.29 logMAR units to 0.52 ± 0.29 logMAR units, and best distance acuity improved from 0.06 ± 0.11 logMAR units to 0.04 ± 0.07 logMAR units (P > .05). Manifest refraction spherical equivalent and cylindrical power improvement was not significant (P > .05), unlike spherical power (P < .05). Steepest simulated keratometry, average simulated keratometry, and inferior-superior value significantly decreased (P < .05), unlike flattest simulated keratometry, cylindrical simulated keratometry, and apex keratometry (P > .05). Total and coma-like aberrations were not decreased significantly for all pupil diameters (P > .05). No significant endothelial changes were observed in either group. The PRK plus CXL procedure may be a good option to reduce corneal aberrations and stabilize corneas with progressive keratoconus.


Influence of past reproductive performance on risk of spontaneous abortion.
To investigate the incidence of spontaneous abortion in a population of women in order to establish their risk of spontaneous abortion and the obstetric factors predisposing to it. Prospective study of women recruited by radio and poster appeal and from hospital outpatient clinics. English provincial community. 630 Women from the general population intending to become pregnant. The viability of the pregnancy was assessed by abdominal ultrasonography before completion of the eighth week, and the assessment was repeated if vaginal bleeding occurred. Spontaneous abortion or live births in women with or without a previous history of spontaneous abortion. The overall incidence of clinically recognisable spontaneous abortion before 20 weeks of gestation was 12% (50/407 pregnancies). The risk of spontaneous abortion in each category of patient was classified with respect to the patient's past reproductive performance and found to be influenced greatly by her previous obstetric history. In primigravidas and women with a history of consistently successful pregnancies the incidences of abortion were low (5% (4/87) and 4% (3/73) respectively), whereas women with only unsuccessful histories had a much greater risk of aborting the study pregnancy (24% (24/98)), even when their sole pregnancy had ended in abortion (20% (12/59)). The outcome of the last pregnancy also influenced the outcome of the study pregnancy; only 5% of women (5/95) whose previous pregnancy had been successful aborted, whereas the incidence of loss of pregnancy among women whose last pregnancy had aborted was 19% (40/214). A knowledge of the patient's reproductive history is essential for the clinical assessment of her risk of spontaneous abortion. As the most important predictive factor for spontaneous abortion is a previous abortion, the outcome of a woman's first pregnancy has profound consequences for all subsequent pregnancies.


The development of the O2-sensing system in an amphibious fish: consequences of variation in environmental O2 levels.
Proper development of the O2-sensing system is essential for survival. Here, we characterized the development of the O2-sensing system in the mangrove rivulus (Kryptolebias marmoratus), an amphibious fish that transitions between hypoxic aquatic environments and O2-rich terrestrial environments. We found that NECs formed in the gills and skin of K. marmoratus during embryonic development and that both NEC populations are retained from the embryonic stage to adulthood. We also found that the hyperventilatory response to acute hypoxia was present in embryonic K. marmoratus, indicating that functional O2-sensing pathways are formed during embryonic development. We then exposed embryos to aquatic normoxia, aquatic hyperoxia, aquatic hypoxia, or terrestrial conditions for the first 30 days of embryonic development and tested the hypothesis that environmental O2 availability during embryonic development modulates the development of the O2-sensing system in amphibious fishes. Surprisingly, we found that O2 availability during embryonic development had little impact on the density and morphology of NECs in the gills and skin of K. marmoratus. Collectively, our results demonstrate that, unlike the only other species of fish in which NEC development has been studied to date (i.e., zebrafish), NEC development in K. marmoratus is largely unaffected by environmental O2 levels during the embryonic stage, indicating that there is interspecies variation in O2-induced plasticity in the O2-sensing system of fishes.


Ricin-resistant Madin-Darby canine kidney cells missort a major endogenous apical sialoglycoprotein.
gp114 is a major sialoglycoprotein expressed on the apical membrane of Madin-Darby canine kidney (MDCK) II cells. We investigated its distribution in two lectin-resistant mutant cell lines derived from MDCKII cells, MDCKII-RCAr and MDCKII-ConAr cells. gp114 was present on the apical membrane of MDCKII-ConAr cells but was predominantly basolateral in MDCKII-RCAr cells. No change of polarity was observed for several apical and basolateral markers in this cell line. Reversal of polarity of gp114 mainly resulted from a modification of its intracellular sorting. gp114 showed altered endocytosis in MDCKII-RCAr cells. In MDCKII cells gp114 was slowly endocytosed, whereas in MDCKII-RCAr cells endocytosis of gp114 was highly increased. Using mannosidase I and II inhibitors we found that N-glycosylation only slightly affects gp114 sorting and endocytosis. Our results suggest that gp114 or an associated component in MDCK-RCAr fails to express apical information or that a mutation creates a basolateral sorting signal which could be related to endocytic signals.


Is the Berg Balance Scale an internally valid and reliable measure of balance across different etiologies in neurorehabilitation? A revisited Rasch analysis study.
To assess, within the context of Rasch analysis, (1) the internal validity and reliability of the Berg Balance Scale (BBS) in a sample of rehabilitation patients with varied balance abilities; and (2) the comparability of the BBS measures across different neurologic diseases. Observational prospective study. Rehabilitation ward of an Italian district hospital. Consecutively admitted inpatients and outpatients (N=217); for 85 participants, data were collected both on admission and discharge, giving a total sample of 302 observations. Not applicable. BBS. Most of the BBS items had to be rescored, and 2 items (static sitting and standing balance) had to be deleted, to attain adequate internal construct validity (χ(2)(24)=35.68; P=.059). The reliability of the Rasch-modified BBS (BBS-12) (total score, 0-35) was high (.957), indicating precision of measurement at the individual level. The analysis of differential item functioning (DIF) showed invariance of the item calibrations across patients' sex, age, and etiology. After adjusting for the possible effect of repeated measurements on person estimates, the analysis of DIF by timing of assessment confirmed the stability of the item hierarchy across time. A practical ruler was provided to convert item raw scores into Rasch estimates of balance ability. This study supports the internal validity and reliability of the BBS-12 as a measurement tool independent of the etiology of the neurologic disease causing the balance impairment. In view of some sample-related issues and that not all possible etiologies encountered in the neurorehabilitation settings were tested, a larger multicenter study is warranted to confirm these findings.


Complete genome sequences of Streptomyces griseus phages Spelly and Phredrick.
We present the complete genome sequences of two viruses with siphovirus morphology, isolated from soils collected in Southwestern Indiana using the host Streptomyces griseus. Spelly is a BE2 cluster phage with a 131,347-bp genome. Phredrick is a BK1 cluster phage with a 128,873-bp genome.


Ocular changes in the mucopolysaccharidoses after bone marrow transplantation. A preliminary report.
Metabolic correction and physiologic response were evaluated after bone marrow transplantation in mucopolysaccharidosis. Eleven patients were prospectively evaluated to determine the effect of bone marrow transplantation on the progressive ocular manifestations of these disorders. Follow-up of 0.6 to 2.8 years after successful donor stem cell engraftment showed that some patients had slow clearing of the corneal clouding, reduction of intracytoplasmic inclusions in the conjunctiva, resolution of optic nerve edema, and stabilized or improved retinal function as determined by electroretinography. These preliminary results suggest that early bone marrow transplantation may alter some of the progressive ophthalmic characteristics of the mucopolysaccharidoses. Long-term follow-up is necessary to determine if these early alterations in the ocular features are predictive of a prolonged functional improvement in the visual status.


Glucocorticoid receptor signaling and prostate cancer.
Glucocorticoids (GCs) are provided to hormone-refractory prostate cancer (HRPC) patients partly due to the inhibitory effects on adrenal androgen production acting as a pituitary suppressant. Nowadays, the combination of chemotherapy and dexamethasone is a standard treatment for HRPC patients while increasing evidence suggests that a lot of local tissue factors like growth factors, angiogenic/lymphogenic factors, apoptosis-related factors, cytokines related to the transition of prostate cancer from androgen dependence to hormone-refractory status, are among the targets of GR signaling. However, although glucocorticoids have been recognized to be one of a limited number of treatment options for HRPC, the molecular basis of GC-induced effects in prostate cancer remains poorly defined. In this review, we focus on how GCs induce effects via the GR-mediated transcriptional regulation of specific genes known to play key roles in cellular/tissue functions, including growth, apoptosis, inflammation, metastasis, differentiation, cell survival and angiogenesis. In our effort to unravel the molecular interplay of GR signaling with other signaling cascades prevalent in prostate cancer, we also include a detailed description of GR gene and protein structure/function and provide the knowledge gained recently into the mechanism(s) of the cross talk between GR and other signaling cascades via which GCs exert their multiple effects.


Analysing the possibility of utilizing CBCT radiomics as an independent modality: a phantom study.
To verify if computed tomography (CT) radiomics were reproducible by cone beam CT (CBCT) radiomics by using Catphan® 504. Catphan® 504 was imaged using the default IGRT OBI CBCT imaging protocols and CT scanner. Seven known density image regions of the phantom were segmented and image feature was extracted by Imaging Biomarker Explorer (IBEX) software. The 49 selected features from four feature categories were analyzed by considering each region of interest (ROI) segment as individual image set. Correlation was studies using interclass correlation coefficient (ICC) and Pearson's correlation coefficient. The ICC of the three feature categories, namely intensity, GLCM, and GLRLM was significant (p-value<0.05) in comparison with CT, while the ICC of the fourth feature category, NID, was no significant. The average absolute Pearson's correlation coefficient from the features of the images was as follows: CT: r=0.679±0.257, CBCThead: r=0.707±0.231, CBCTthorax: r=0.643±0.260, and CBCTpelvis: r=0.594±0.276. It seems that the various densities of Catphan® 504 ROI image segments of the CT radiomics are reproducible with CBCT radiomics and CBCT radiomics can be used as an independent modality.


Anaphylaxis to SARS-CoV-2 Vaccines in the Setting of a Nationwide Passive Epidemiological Surveillance Program.
Information on anaphylaxis among recipients of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains scarce. To identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. A nationwide observational study among recipients of 61,414,803 doses of seven different anti-SARS-CoV-2 vaccines, describing the incidence and characteristics of adult patients (age ≥ 18 years) who developed anaphylaxis as an adverse event following immunization (AEFI) against SARS-CoV-2 vaccines between December 24, 2020, and October 15, 2021, in Mexico. Sixty-six patients developed anaphylaxis as an AEFI, for an overall observed incidence of 1.07 cases per 1,000,000 (95% CI 0.84-1.37) administered doses. Eighty-six percent of the patients were female, consistent with previous reports of AEFI to COVID-19 vaccines. mRNA-based vaccine recipients had the highest frequency of anaphylaxis, followed by adenovirus-vectored vaccines and inactivated virus recipients, with an observed incidence of 2.5, 0.7, and 0.2 cases per 1,000,000 doses administered, respectively. Only 46% of the patients received correct treatment with epinephrine as the first-line treatment through the appropriate route and dose. We detected one case of anaphylactic reaction-related death occurring 5 min following immunization with ChAdOx1 nCov-19 for a mortality rate of 1.5% among those who developed this AEFI. In our population, anaphylactic reactions were infrequent. Our study provides further evidence supporting the security of these newly developed vaccines.


OVOL1 Regulates Psoriasis-Like Skin Inflammation and Epidermal Hyperplasia.
Psoriasis is a common inflammatory skin disease characterized by aberrant inflammation and epidermal hyperplasia. Molecular mechanisms that regulate psoriasis-like skin inflammation remain to be fully understood. Here, we show that the expression of Ovol1 (encoding ovo-like 1 transcription factor) is upregulated in psoriatic skin, and its deletion results in aggravated psoriasis-like skin symptoms following stimulation with imiquimod. Using bulk and single-cell RNA sequencing, we identify molecular changes in the epidermal, fibroblast, and immune cells of Ovol1-deficient skin that reflect an altered course of epidermal differentiation and enhanced inflammatory responses. Furthermore, we provide evidence for excessive full-length IL-1α signaling in the microenvironment of imiquimod-treated Ovol1-deficient skin that functionally contributes to immune cell infiltration and epidermal hyperplasia. Collectively, our study uncovers a protective role for OVOL1 in curtailing psoriasis-like inflammation and the associated skin pathology.


Tropomyosin Receptor Kinase Inhibitors for the Treatment of TRK Fusion Cancer.
Chromosomal rearrangements of NTRK1-3 resulting in gene fusions (NTRK gene fusions) have been clinically validated as oncogenic drivers in a wide range of human cancers. Typically, NTRK gene fusions involve both inter- and intrachromosomal fusions of the 5' regions of a variety of genes with the 3' regions of NTRK genes leading to TRK fusion proteins with constitutive, ligand-independent activation of the intrinsic tyrosine kinase. The incidence of NTRK gene fusions can range from the majority of cases in certain rare cancers to lower rates in a wide range of more common cancers. Two small-molecule TRK inhibitors have recently received regulatory approval for the treatment of patients with solid tumors harboring NTRK gene fusions, including the selective TRK inhibitor larotrectinib and the TRK/ROS1/ALK multikinase inhibitor entrectinib. In this review, we consider the practicalities of detecting tumors harboring NTRK gene fusions, the pharmacologic properties of TRK inhibitors currently in clinical development, the clinical evidence for larotrectinib and entrectinib efficacy, and possible resistance mechanisms.


Evaluation of water matrix effects, experimental parameters, and the degradation pathway during the TiO2 photocatalytical treatment of the antibiotic dicloxacillin.
The photocalytic degradation of dicloxacillin (DXC) using TiO2 was studied in synthetic and natural waters. The degradation route and the effect of different experimental variables such as pH, applied power, and the initial concentrations of DXC and the catalyst were investigated. The best performances were achieved at a natural pH 5.8 and using 2.0 g L(-1) of TiO2 with 150 W of applied power. The photodegradation process followed Langmuir-Hinshelwood kinetics. The water matrix effect was evaluated in terms of degradation efficiency in the presence of organic compounds (oxalic acid, glucose), Fe(2+) ion and natural water. An increase in degradation was observed when ferrous ion was part of the solution, but the process was inhibited with all evaluated organic compounds. Similarly, inhibition was observed when natural water was used instead of distilled water. The extent of degradation of the process was evaluated following the evolution of chemical oxygen demand (COD), antimicrobial activity (AA), total organic carbon (TOC) and biochemical oxygen demand (BOD5). Total removal of DXC was achieved after 120 min of treatment and 95% mineralization was observed after 480 min of treatment. Additionally, the total removal of antimicrobial activity and a high level of biodegradability were observed after the photocalytical system had been operating for 240 min.


Batch anaerobic co-digestion of Kimchi factory waste silage and swine manure under mesophilic conditions.
The objective of this study was to investigate the feasibility of anaerobic co-digestion of Kimchi factory waste silage (KFWS) with swine manure (SM). Chinese cabbage (CC) is the major waste generated by a Kimchi factory and KFWS was prepared by mixing CC and rice bran (RB) (70:30 on a dry matter basis). In Experiment I, the biogas potential of CC and RB were measured and, in Experiment II, the test was conducted with different ratios of KFWS and SM (KFWS: SM=0:100; 33:67; 67:33; 100:0 by% volatile solids (VS) basis). KFWS produced a 27% higher biogas yield and a 59% higher methane yield compared to CC. The specific biogas yields increased by 19, 40 and 57% with KFWS-33%, KFWS-67% and KFWS-100%, respectively compared to SM-100% (394 mL/g VS). Similarly, VS removal increased by 37, 51 and 74% with KFWS-33%, KFWS-67% and KFWS-100%, respectively compared to SM-100%. These results suggested that Kimchi factory waste could be effectively treated by making silage, and the silage could be used as a potential co-substrate to enhance biogas production from SM digesters.


Classification of Building Damage Using a Novel Convolutional Neural Network Based on Post-Disaster Aerial Images.
The accurate and timely identification of the degree of building damage is critical for disaster emergency response and loss assessment. Although many methods have been proposed, most of them divide damaged buildings into two categories-intact and damaged-which is insufficient to meet practical needs. To address this issue, we present a novel convolutional neural network-namely, the earthquake building damage classification net (EBDC-Net)-for assessment of building damage based on post-disaster aerial images. The proposed network comprises two components: a feature extraction encoder module, and a damage classification module. The feature extraction encoder module is employed to extract semantic information on building damage and enhance the ability to distinguish between different damage levels, while the classification module improves accuracy by combining global and contextual features. The performance of EBDC-Net was evaluated using a public dataset, and a large-scale damage assessment was performed using a dataset of post-earthquake unmanned aerial vehicle (UAV) images. The results of the experiments indicate that this approach can accurately classify buildings with different damage levels. The overall classification accuracy was 94.44%, 85.53%, and 77.49% when the damage to the buildings was divided into two, three, and four categories, respectively.


Pediatric Resident Training in the Community Hospital Setting: A Survey of Program Directors.
The role of a hospitalist differs in a community hospital (CH) compared to a university/children's hospital. Residents are required to practice in a variety of relevant clinical settings, but little is known about current trends regarding pediatric resident training in different hospital settings. This study explores CH rotations including their value for resident training, characteristics, benefits, and drawbacks. This study also seeks to define "community hospital." Authors conducted an online cross-sectional survey of pediatric residency program directors distributed by the Association of Pediatric Program Directors. The survey was developed and revised based on review of the literature and iterative input from experts in pediatric resident training and CH medicine. It assessed residency program demographics, availability of CH rotations, value of CH rotations, and their characteristics including benefits and drawbacks. Response rate was 56%. CH rotations were required at 24% of residency programs, available as an elective at 46% of programs, and unavailable at 48% of programs. Residency program directors viewed these rotations as valuable for resident training. CH rotations were found to have multiple benefits and drawbacks. Definitions of "community hospital" varied and can be categorized according to positive or negative characteristics. Resident rotations at a CH provide valuable learning opportunities with multiple potential benefits that should be weighed against drawbacks in the context of a residency program's curriculum. There are many characteristics that potentially distinguish CH from university/children's hospitals.


The use of anakinra in juvenile arthritis.
Interleukin-1 (IL-1), one of the major pro-inflammatory cytokines, plays an important role in the pathophysiology and progression of adult and pediatric arthritis. Inhibiting IL-1 activity by using a recombinant human IL-1 receptor antagonist (anakinra) given alone or in combination with methotrexate, moderately reduced the signs and symptoms of active arthritis in adults and slowed the rate of radiographic destruction. Preliminary results from an open label portion of a trial in children with polyarticular arthritis show similar outcomes with 58% of children exhibiting clinical improvements based on the Juvenile Arthritis 30% Core Set Criteria. The drug has an overall favorable safety profile and injection-site reactions are the most commonly reported adverse event in both groups. However despite its rather disappointing effect in polyarticular arthritis, anakinra is being discovered as an effective treatment of systemic arthritis and children with mutations in the NALP3/CIAS1/PYPAF1 genes leading to autoimmune inflammatory disorders such as neonatal- onset multisystem inflammatory disease.


The growth factor independence-1 transcription factor: new functions and new insights.
The growth factor independence-1 (Gfi1) transcription factor is required for proper development of neuroendocrine cells, sensory neurons, and blood. Patients with mutations in Gfi1 exhibit severe congenital neutropenia (SCN) or non-immune chronic idiopathic neutropenia of adults. Gfi1 was initially described as an oncoprotein that mediates tumor progression in a mouse model of leukemia; however, recent data suggest that Gfi1 may act as either an oncogene or an anti-proliferative tumor suppressor gene depending on the cell type. Here we review the latest literature on Gfi1, and emphasize its role in the hematopoietic, sensory and neuroendocrine systems.


Phthalide derivative CD21 attenuates tissue plasminogen activator-induced hemorrhagic transformation in ischemic stroke by enhancing macrophage scavenger receptor 1-mediated DAMP (peroxiredoxin 1) clearance.
Hemorrhagic transformation (HT) is a critical issue in thrombolytic therapy in acute ischemic stroke. Damage-associated molecular pattern (DAMP)-stimulated sterile neuroinflammation plays a crucial role in the development of thrombolysis-associated HT. Our previous study showed that the phthalide derivative CD21 attenuated neuroinflammation and brain injury in rodent models of ischemic stroke. The present study explored the effects and underlying mechanism of action of CD21 on tissue plasminogen activator (tPA)-induced HT in a mouse model of transient middle cerebral artery occlusion (tMCAO) and cultured primary microglial cells. The tMCAO model was induced by 2 h occlusion of the left middle cerebral artery with polylysine-coated sutures in wildtype (WT) mice and macrophage scavenger receptor 1 knockout (MSR1-/-) mice. At the onset of reperfusion, tPA (10 mg/kg) was intravenously administered within 30 min, followed by an intravenous injection of CD21 (13.79 mg/kg/day). Neuropathological changes were detected in mice 3 days after surgery. The effect of CD21 on phagocytosis of the DAMP peroxiredoxin 1 (Prx1) in lysosomes was observed in cultured primary microglial cells from brain tissues of WT and MSR1-/- mice. Seventy-two hours after brain ischemia, CD21 significantly attenuated neurobehavioral dysfunction and infarct volume. The tPA-infused group exhibited more severe brain dysfunction and hemorrhage. Compared with tPA alone, combined treatment with tPA and CD21 significantly attenuated ischemic brain injury and hemorrhage. Combined treatment significantly decreased Evans blue extravasation, matrix metalloproteinase 9 expression and activity, extracellular Prx1 content, proinflammatory cytokine mRNA levels, glial cells, and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway activation and increased the expression of tight junction proteins (zonula occludens-1 and claudin-5), V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, and MSR1. MSR1 knockout significantly abolished the protective effect of CD21 against tPA-induced HT in tMCAO mice. Moreover, the CD21-induced phagocytosis of Prx1 was MSR1-dependent in cultured primary microglial cells from WT and MSR1-/- mice, respectively. The phthalide derivative CD21 attenuated tPA-induced HT in acute ischemic stroke by promoting MSR1-induced DAMP (Prx1) clearance and inhibition of the TLR4/NF-κB pathway and neuroinflammation.


Evidence-based interventions for children and adolescents with fetal alcohol spectrum disorders - A systematic review.
Brain function deficits cause strong negative impacts for the everyday lives of children and adolescents with fetal alcohol spectrum disorders (FASD). Therefore, evidence-based intervention programs that are specifically designed for patients with FASD are needed but still scarce. The aim of the presented article is a systematic literature review of evidence-based intervention strategies for children and adolescents with FASD. A comprehensive systematic literature search was conducted in several relevant databases to identify randomized-controlled intervention studies for children and adolescents with FASD. We identified 25 randomized-controlled studies regarding interventions in FASD. Overall, evidence indicating that some therapeutic interventions are effective in children and adolescents with FASD was found. Even though evidence-based interventions rarely lead to improvements of performance into a "normal range", those measures can alleviate negative consequences of prenatal alcohol exposure and relieve daily burdens. There are only a few randomized-controlled trials regarding therapy research for children and adolescents with FASD. Their results indicate that especially the combination of parent and child sessions present a promising approach for the treatment of FASD. Positive treatment effects of interventions seem to be domain specific, except for interventions regarding self-regulation or social interaction.


Long-term simulation of lead concentrations in agricultural soils in relation to human adverse health effects.
Lead (Pb) exposure of consumers and the environment has been reduced over the past decades. Despite all measures taken, immission of Pb onto agricultural soils still occurs, with fertilizer application, lead shot from hunting activities, and Pb from air deposition representing major sources. Little is known about the intermediate and long-term consequences of these emissions. To gain more insight, we established a mathematical model that considers input from fertilizer, ammunition, deposition from air, uptake of Pb by crops, and wash-out to simulate the resulting Pb concentrations in soil over extended periods. In a further step, human oral exposure by crop-based food was simulated and blood concentrations were derived to estimate the margin of exposure to Pb-induced toxic effects. Simulating current farming scenarios, a new equilibrium concentration of Pb in soil would be established after several centuries. Developmental neurotoxicity represents the most critical toxicological effect of Pb for humans. According to our model, a Pb concentration of ~ 5 mg/kg in agricultural soil leads to an intake of approximately 10 µg Pb per person per day by the consumption of agricultural products, the dose corresponding to the tolerable daily intake (TDI). Therefore, 5 mg Pb/kg represents a critical concentration in soil that should not be exceeded. Starting with a soil concentration of 0.1 mg/kg, the current control level for crop fields, our simulation predicts periods of ~ 50 and ~ 175 years for two Pb immission scenarios for mass of Pb per area and year [scenario 1: ~ 400 g Pb/(ha × a); scenario 2: ~ 175 g Pb/(ha × a)], until the critical concentration of ~ 5 mg/kg Pb in soil would be reached. The two scenarios, which differ in their Pb input via fertilizer, represent relatively high but not unrealistic Pb immissions. From these scenarios, we calculated that the annual deposition of Pb onto soil should remain below ~ 100 g/(ha × a) in order not to exceed the critical soil level of 5 mg/kg. We propose as efficient measures to reduce Pb input into agricultural soil to lower the Pb content of compost and to use alternatives to Pb ammunition for hunting.


Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.
Cancer, a major public health problem, is one of the world's top leading causes of death. Common treatments for cancer include cytotoxic chemotherapy, surgery, targeted drugs, endocrine therapy, and immunotherapy. However, despite the outstanding achievements in cancer therapies during the last years, resistance to conventional chemotherapeutic agents and new targeted drugs is still the major challenge. In the present review, we explain the different mechanisms involved in cancer therapy and the detailed outlines of cancer drug resistance regarding multidrug resistance-associated proteins (MRPs) and their role in treatment failures by common chemotherapeutic agents. Further, different modulators of MRPs are presented. Finally, we outlined the models used to analyze MRP transporters and proposed a future impact that may set up a base or pave the way for many researchers to investigate the cancer MRP further.


β-cyclodextrin-functionalized magnetic graphene oxide for the efficient enrichment of bisphenols in milk and milk packaging.
In this work, β-cyclodextrin-functionalized magnetic graphene oxide (NiFe2O4@GO@β-CD) was synthesized and employed as magnetic solid-phase extraction adsorbent for the extraction of bisphenols before high performance liquid chromatography analysis. The modification of β-cyclodextrin could enhance the adsorption performance of NiFe2O4@GO@β-CD towards bisphenols through the host-guest interaction and hydrogen-bond interaction. Under the optimal conditions, good linearities between peak area and concentration of bisphenols (1 - 300 μg L-1, r ≥ 0.9989) were obtained with the limits of detection (S/N = 3) in the range of 0.050 - 0.10 μg L-1. The recoveries of bisphenols in milk and milk packaging ranged from 78.0% to 101.6%. Moreover, NiFe2O4@GO@β-CD showed stable chemical properties and good reusability with the recoveries of bisphenols remained above 80.0% after 12 MSPE cycles. The adsorption characteristics of NiFe2O4@GO@β-CD towards bisphenols fitted well with the pseudo-second-order kinetic model and Langmuir model. The hydrogen-bond interaction, π-π interaction, host-guest interaction and electrostatic interaction between sorbent and bisphenols played important role during the adsorption process. The developed method showed potential applications for the analysis of trace bisphenols in milk and milk packaging.


Fat from contused adipose tissue may cause yellow discoloration of clothes in blunt trauma victims.
In some fatalities from intense blunt trauma, the victims' clothes show strikingly yellow discoloration being in topographic correspondence with lacerated skin and crush damage to the underlying fatty tissue. This phenomenon is especially pronounced in light-colored textiles such as underwear made of cotton and in the absence of concomitant blood-staining. The constellation of findings seems to indicate that the fabric has been soaked with liquid body fat deriving from the contused adipose tissue. To check this hypothesis, textiles suspected to be contaminated with fat were investigated in 6 relevant cases. GC-MS-analysis proved the presence of 11 fatty acids. The fatty acid composition was similar to that of human adipose tissue with a high proportion of oleic acid (18:1). In total, the morphological and chemical findings demonstrated that the yellow discoloration of the victims' clothes was caused by fat from traumatized adipose tissue.


Gold nanoparticles-embedded ceria with enhanced antioxidant activities for treating inflammatory bowel disease.
The excessive reactive oxygen species (ROS) is a hallmark associated with the initiation and progression of inflammatory bowel disease (IBD), which execrably form a vicious cycle of ROS and inflammation to continually promote disease progression. Here, the gold nanoparticles-embedded ceria nanoparticles (Au/CeO2) with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced ROS. The Au/CeO2 with core-shell and porous structure exhibits significantly higher enzymatic catalytic activities compared with commercial ceria nanoparticles, likely due to the effective exposure of catalytic sites, higher content of Ce (III) and oxygen vacancy, and accelerated reduction from Ce (IV) to Ce (III). Being coated with negatively-charged hyaluronic acid, the Au/CeO2@HA facilitates accumulation in inflamed colon tissues via oral administration, reduces pro-inflammatory cytokines, and effectively alleviates colon injury in colitis mice. Overall, the Au/CeO2@HA with good biocompatibility is a promising nano-therapeutic for treating IBD.


Vocal Fry Patterns While Reading.
The use of vocal fry is common in running speech and has potential psychosocial and vocal health consequences. Determining the different patterns of vocal fry is relevant to differentiating phonatory function, understanding cultural and linguistic use of vocal fry, and clinical diagnostics and intervention. The purpose of this project was to study and categorize patterns of vocal fry in running speech. Analyses were performed on recordings of the Rainbow Passage read out loud by five healthy females 18-21 years old. Praat was used to create audio files with text grids. The audio recordings were examined visually (the audio signal and its spectrogram) and perceptually in order to determine different patterns of vocal fry seen in the audio signal. Criteria for detecting vocal fry were (1) the presence of an acoustic transient (a relatively large and fast dip in acoustic pressure, presumably near glottal closure) with a relatively long cycle period compared to normal phonation periods, or (2) a frequency at or lower than approximately an octave below the nearby normal speaking fundamental frequency. There were 174 total vocal fry samples obtained from the recordings. Six vocal fry patterns were observed. The patterns were: single pulse fry (FRY1), double pulse fry (FRY2), multiple pulse fry (FRY3), period doubling fry (FRY4), inaudible fry (FRY5), and indeterminate vocal fry (FRY6). Single pulse fry was divided into a single (one) pulse fry cycle (FRY1a), a series of even single pulse fry cycles (FRY1b), and a series of uneven single pulse fry cycles (FRY1c). Double pulse fry was divided into a primary then another primary pulse fry cycle (FRY2a), a secondary then a primary pulse fry cycle (FRY2b), and a primary then a secondary pulse fry cycle (FRY2c). Multiple pulse fry, where a higher frequency was modulated by a lower frequency, was divided into the higher frequency being near the speaking fundamental frequency (FRY3a) and the higher frequency being inconsistent or well below the expected speaking fundamental frequency (FRY3b). The category single pulse fry had the most samples, with 76% of the total occurrences, followed by period doubling 13%, and the rest 11%. Relative to where the fry patterns occurred within syllables, 36% occurred at the onset of the syllable, 26% early in the syllable, 25% later in the syllable, and 13% at the end of the syllable. These tallies did not include the sixth category, indeterminate vocal fry (FRY6), which was not included in the study proper but recognized as indicating complicated patterns that did not fall within the first five categories. Vocal fry is a complex, multifaceted phenomenon. The results of this study suggest that there are identifiable patterns of vocal fry. These patterns need to be differentiated especially regarding the glottal adductory nature and phonatory function of each pattern, glottal closure appearing to be the primary physiological causative factor of the salient negative pressure dips (the adduction behavior will be reported in a study in progress). Further research is necessary to determine other potential categories of vocal fry, determine if there are individual idiosyncratic patterns of vocal fry, determine possible differences in vocal fry produced by individuals of different ages and gender expression and other factors, and research the physiologic, acoustic, aerodynamic, and perceptual reality of each pattern.


Antibody responses to tetanus and diphtheria vaccine in chronic and recurrent rhinosinusitis.
Chronic rhinosinusitis may be accompanied by impaired immunity despite normal levels of serum immunoglobulins. Immune responses in sinusitis patients have previously been evaluated using polysaccharide vaccines. Our AIM was to assess the immune status by evaluating responses to diphtheria and tetanus vaccine. Specific antibodies were measured before and 2 weeks after vaccination in 25 patients with chronic or recurrent sinusitis and in 30 healthy individuals. The mean age of the patients was 46 years and that of healthy controls 43 years. After vaccination the patients had on average 4.08-fold lower responses to diphtheria toxoid and 2.20-fold lower responses to tetanus than the controls. Fourteen out of 25 patients had antibody levels that did not reach the 95% normal distribution range of healthy controls after either diphtheria or tetanus vaccination. All the patients had normal levels of serum immunoglobulins. A significant proportion of patients with persisting symptoms of rhinosinisitis may have impaired responses to protein vaccines. Responses to protein vaccines may be used to evaluate immune function of sinusitis patients.


[The legal concept of personhood in Colombia: are there biological reasons to change it?].
Nowadays, as a consequence of scientific advances in embryology, genetics and assisted reproduction techniques, the scientific community ask for new laws to establish new parameters to use with these recent discoveries. Discoveries that have changed the legal concept of "person". In many countries this concept is absolutely useless when facing new techniques such as cloning, stem cell research and embryo storage. That is why it is necessary to change its definition to guarantee the right to life and give a better protection to human embryos.


Factors Associated With Cannabis Use During the Reproductive Cycle: A Retrospective Cross-Sectional Study of Women in States With Recreational and Medical Cannabis Legalization.
Passage of cannabis laws may impact cannabis use and the use of other substances. The suggested association is of particular concern in pregnant women where exposure to substances can cause harm to both the pregnant woman and fetus. The present study contributes to the minimal literature on factors associated with cannabis use during the preconception, prenatal, and postpartum periods including state legalization status, concurrent use of tobacco and e-cigarettes and adequacy of prenatal care. We conducted a cross-sectional analysis using combined survey data from the 2016-2018 Pregnancy Risk Assessment Monitoring System (PRAMS) collected from 36,391 women. Logistic regression was used to estimate the impact of state-legalization, adequacy of prenatal care, and other substance use on cannabis use during the preconception, prenatal, and post-partum periods. In the preconception model, residence in a recreationally legal state (OR: 2.37; 95% CI, 2.04-2.75) or medically legal state (OR:3.32; 95% CI, 2.90-3.80) compared to a non-legal state was associated with higher odds of cannabis use. In the prenatal model, residence in a recreationally legal state was associated with higher odds of cannabis use (OR: 1.51; 95% CI, 1.29-1.79) whereas there was no association with residence in a medically legal state. Tobacco use including e-cigarettes and moderate prenatal alcohol use were also significantly associated with cannabis use. Recreational cannabis legalization is associated with the use of cannabis prior to, during, and after pregnancy. Renewed clinical and policy efforts may be warranted to update prenatal substance use prevention programs, educational campaigns, and provider education as cannabis legalization evolves.


A call for diversity, equity, and inclusion: Highlights from the Consortium of Universities for Global Health 2021 conference.
Beryne Odeny reports from the CUGH 2021 virtual conference.


UV/ozone irradiation manipulates immune response for antibacterial activity and bone regeneration on titanium.
The immunomodulatory antibacterial activity and osteoimmunomodulatory properties of implantable biomaterials significantly influence bone regeneration. Various types of ultraviolet (UV) instrument are currently in use to greatly enhance the antibacterial activity and osteoconductive capability of titanium, it remains unclear how UV treatment modulates immune response. Compared to traditional UV treatment, the combination of low-dose ozone with UV irradiation is considered a new option to give benefits to surface modification and reduce the drawbacks of UV and ozone individually. Herein, the aim of this study was to elucidate the immune-modulatory properties of macrophages on UV/ozone-irradiated titanium that serve as defense against S. aureus and the crosstalk between immune cells and osteoblasts. Three different cell and bacteria co-culture systems were developed in order to investigate the race between host cells and bacteria to occupy the surface. In vitro immunological experiments indicated that UV/ozone irradiation significantly enhanced the phagocytic and bactericidal activity of macrophages against S. aureus. Further, in vitro and in vivo studies evidenced the favorable osteoimmune environment for osteogenic differentiation and bone formation. This research suggests vital therapeutic potential of UV/ozone irradiation for preventing the biomaterial-associated infections and achieving favorable bone formation simultaneously.


Cause of and factors associated with stillbirth: a systematic review of classification systems.
An estimated 2.6 million stillbirths occur worldwide each year. A standardized classification system setting out possible cause of death and contributing factors is useful to help obtain comparative data across different settings. We undertook a systematic review of stillbirth classification systems to highlight their strengths and weaknesses for practitioners and policymakers. We conducted a systematic search and review of the literature to identify the classification systems used to aggregate information for stillbirth and perinatal deaths. Narrative synthesis was used to compare the range and depth of information required to apply the systems, and the different categories provided for cause of and factors contributing to stillbirth. A total of 118 documents were screened; 31 classification systems were included, of which six were designed specifically for stillbirth, 14 for perinatal death, three systems included neonatal deaths and two included infant deaths. Most (27/31) were developed in and first tested using data obtained from high-income settings. All systems required information from clinical records. One-third of the classification systems (11/31) included information obtained from histology or autopsy. The percentage where cause of death remained unknown ranged from 0.39% using the Nordic-Baltic classification to 46.4% using the Keeling system. Over time, classification systems have become more complex. The success of application is dependent on the availability of detailed clinical information and laboratory investigations. Systems that adopt a layered approach allow for classification of cause of death to a broad as well as to a more detailed level.


Severe hypotension during junctional rhythm in a patient with multiple cerebral infarcts.
An 82-year-old woman with parkinsonism and Lewy body dementia was re-admitted to our hospital due to convulsions and the recurrence of cerebral infarction. Parasternal transthoracic echocardiography showed normal left ventricular wall thickness and wall motion. To treat marked bradycardia and hypotension, she underwent temporary pacing. However, she lost her consciousness, when her blood pressure could not be measured. Simultaneous electrocardiogram and blood pressure monitoring showed that systolic blood pressure decreased by almost 30 mmHg from sinus rhythm to junctional rhythm. In the present case of acute cerebral infarction, severe hypotension occurred during junctional rhythm possibly contributed by parkinsonism and Lewy body dementia. As patients with junctional rhythm usually have no or mild symptoms, there are no specific guidelines for its evaluation and treatment. However, severe symptoms such as hypotension, cerebral infarction, loss of consciousness, or breathlessness may occur in some cases. Holter electrocardiogram with 24-hour noninvasive blood pressure monitoring may be helpful in such severe cases.


The acclimation potential of Acacia longifolia to water stress: implications for invasiveness.
The ability of an invasive species to establish and spread to new areas may depend on its ability to tolerate a broad range of environmental conditions. Due to climate change, increasing occurrences of extreme events such as droughts are expected in the Mediterranean region and invasive species may expand if they cope with water stress. Limited information is available on the responses of Acacia longifolia, one of the most aggressive plant species in Portuguese coastal sand dune ecosystems, to prolonged water stress. In this study, we exposed A. longifolia plants from two distinct populations, one from the wet (northern) and another from the dry (southern) climate regions of Portugal, to drought conditions, and monitored morphological, physiological and biochemical responses. One-month-old seedlings were submitted to three different water treatments which involved watering twice a week, every 7 days and every 10 days, respectively, for three months, under controlled conditions. Overall, the progressive drought stress significantly affected most of the growth parameters considered, except the root:shoot ratio. Water stress also increased the uptake of ions (Ca²⁺, Mg²⁺, K⁺ and Na⁺) and N concentration. On the contrary, the C/N ratio decreased under water stress conditions. Isotopic analysis did not reveal significant differences in δ¹³C with water treatments but the same pattern was not observed in δ¹⁵N values. Compared with the wet climate population, the dry climate population showed somewhat differing responses to water stress, indicating a genetic difference between populations. These results provide insights into limitations and opportunities for establishment of A. longifolia in a drought-prone scenario.


Trajectories in HbA1c and other risk factors among adults with type 1 diabetes by age at onset.
In type 1 diabetes, potential loss of life-years is greatest in those who are youngest at the time of onset. Using data from a nationwide cohort of patients with type 1 diabetes, we aimed to study risk factor trajectories by age at diagnosis. We stratified 30 005 patients with type 1 diabetes aged 18-75 years into categories based on age at onset: 0-10, 11-15, 16-20, 21-25, and 26-30 years. HbA1c, albuminuria, estimated glomerular filtration rate (eGFR), body mass index (BMI), low-denisty lipoprotein (LDL)-cholesterol, systolic blood pressure (SBP), and diastolic blood pressure trends were analyzed using mixed models. Variable importance for baseline HbA1c was analyzed using conditional random forest and gradient boosting machine approaches. Individuals aged ≥16 years at onset displayed a relatively low mean HbA1c level (~55-57 mmol/mol) that gradually increased. In contrast, individuals diagnosed at ≤15 years old entered adulthood with a mean HbA1c of approximately 70 mmol/mol. For all groups, HbA1c levels stabilized at a mean of approximately 65 mmol/mol by about 40 years old. In patients who were young at the time of onset, albuminuria appeared at an earlier age, suggesting a more rapid decrease in eGFR, while there were no distinct differences in BMI, SBP, and LDL-cholesterol trajectories between groups. Low education, higher age, and poor risk factor control were associated with higher HbA1c levels. Young age at the diabetes onset plays a substantial role in subsequent glycemic control and the presence of albuminuria, where patients with early onset may accrue a substantial glycemic load during this period.


Significance of spinal cord perfusion pressure following spinal cord injury: A systematic scoping review.
This scoping review systematically reviewed relevant research to summarize the literature addressing the significance of monitoring spinal cord perfusion pressure (SCPP) in acute traumatic spinal cord injury (SCI). The objectives of the review were to (1) examine the nature of research in the field of SCPP monitoring in SCI, (2) summarize the key research findings in the field, and (3) identify research gaps in the existing literature and future research priorities. Primary literature searches were conducted using databases (Medline and Embase) and expanded searches were conducted by reviewing the references of eligible articles and searches of Scopus, Web of Science core collection, Google Scholar, and conference abstracts. Relevant data were extracted from the studies and synthesis of findings was guided by the identification of patterns across studies to identify key themes and research gaps within the literature. Following primary and expanded searches, a total of 883 articles were screened. Seventy-three articles met the review inclusion criteria, including 34 original research articles. Other articles were categorized as conference abstracts, literature reviews, systematic reviews, letters to the editor, perspective articles, and editorials. Key themes relevant to the research question that emerged from the review included the relationship between SCPP and neurological recovery, the safety of monitoring pressures within the intrathecal space, and methods of intervention to enhance SCPP in the setting of acute traumatic SCI. Original research that aims to enhance SCPP by targeting increases in mean arterial pressure or reducing pressure in the intrathecal space is reviewed. Further discussion regarding where pressure within the intrathecal space should be measured is provided. Finally, we highlight research gaps in the literature such as determining the feasibility of invasive monitoring at smaller centers, the need for a better understanding of cerebrospinal fluid physiology following SCI, and novel pharmacological interventions to enhance SCPP in the setting of acute traumatic SCI. Ultimately, despite a growing body of literature on the significance of SCPP monitoring following SCI, there are still a number of important knowledge gaps that will require further investigation.


Understanding children's healthiness and hedonic perception of school meals via structured sorting.
Trends in the prevalence of childhood overweight and obesity in Europe and especially in Spain have continuously increased in the last three decades. The aim of this work was to study the healthiness understanding (healthy and unhealthy food) in children with different ages and to evaluate liking towards a set of school meals: first courses, second courses and fruit/dessert. Two hundred and seventy-seven children between the ages of six and twelve from three primary schools in northern Spain, Bizkaia, took part in this study. All the groups showed a good knowledge of the healthiness of the dishes offered in the school canteen. However, some dishes were difficult to assess for the 6-7- and 8-9-year old groups. Pasta and croquettes with chips were the most preferred dishes. Vegetables and fish dishes were the least preferred. Results suggest that children become increasingly aware of their preferences and critical in their choices with growing age. It was found in this study that there was a strongly inverse relationship between children's perceptions of the healthiness of foods and their preferences for them. The structured sorting task was a good tool for children to classify various dishes (complex food) considering healthiness and hedonic perception at the same time. In conclusion, these results contribute to a better understanding of children's nutritional perception (healthy/unhealthy food) and its relation to preferences of school meals, which is important for quality improvement and nutritional planning in school food services.


Encoded dendrimers with defined chiral composition via'click' reaction of enantiopure building blocks.
Dendrimers with end-groups of defined chiral composition have been prepared from alkyne functional enantio-pure building blocks obtained by selective enzymatic (ADH) ketone reductions using click chemistry. Optical rotation and enantioselective enzymatic modification is in agreement with the chiral composition of the dendrimers and permits unique molecular-level encoding of stereoisomeric dendritic libraries.


[The effects of the pandemic on students in a psychodynamic setting].
The health crisis brought on by the Covid-19 pandemic has resulted in a particularly severe impact on the mental health of students. This period of their lives, between adolescence and adulthood, is fraught with decisive issues: changes in familial relationships, self-reliance, involvement in romantic and erotic relationships, essential choices: profession, partner. For some students, we could add to the list mobility or exile when studies require it, as well as economic concerns. It is therefore a pivotal period, which for the most part is productive, but also one of great psychological vulnerability. This vulnerability was heightened by the isolation and disruption of their education. These were the most striking effects of the health crisis on students. BAPU FSEF Paris V's mission is to provide students with access to psychodynamic psychotherapy. The team had to adapt its protocols to the qualitative and quantitative changes in demand during the health crisis. We discuss these changes by illustrating them with a clinical example. The long-term effects of the crisis are also discussed.


Genetic background influences muscular dystrophy.
Mutations in the genes encoding dystrophin and its associated proteins, the sarcoglycans, lead to muscular dystrophy in humans and in mouse models. In the presence of identical gene mutations, the muscular dystrophy phenotype can be highly variable. Using a mouse model of limb girdle muscular dystrophy engineered with a null allele of gamma-sarcoglycan, we bred the identical gamma-sarcoglycan mutation into four different genetic backgrounds. We found that the gamma-sarcoglycan mutation is least severe in the129SV/J (129) strain and most severe on the DBA 2J JAX (DBA) strain using quantitative measures of Evan's blue dye uptake, as a marker of membrane permeability defects, and hydroxyproline content, as a marker of fibrosis. In addition we show that the DBA mice are most severely affected regardless of gender and age. The enhanced phenotype observed in the DBA strain was not caused by exercise as the DBA mice scored the lowest in a voluntary activity test. The milder phenotype seen in the 129SV/J and C57B6/J strains suggests that these backgrounds contain modifier loci that partially suppress the muscular dystrophy phenotype. Identification of these modifier genes and the associated pathways may lead to novel therapeutic strategies.


Unveiling hidden toxin diversity: Discovery of novel venom components through manual curation of highly expressed sequences annotated as "no hits" in Phoneutria nigriventer spider venom gland transcriptome.
Spider venoms have evolved over thousands of years, optimizing feeding and defense mechanisms. Venom components show pharmacological and biotechnological potential, rising interest in their study. However, the isolation of spider toxins for experimental evaluation poses significant challenges. To address this, transcriptomic analysis combined with computational tools has emerged as an appealing approach to characterizing spider venoms. However, many sequences remain unidentified after automatic annotation. In this study, we manually curated a subset of previously unannotated sequences from the Phoneutria nigriventer transcriptome and identified new putative venom components. Our manual analysis revealed 29 % of the analyzed sequences were potential venom components, 29 % hypothetical/uncharacterized proteins, and 17 % cellular function proteins. Only 25 % of the originally unannotated dataset remained without any identification. Most reclassified components were cysteine-rich peptides, including 23 novel putative toxins. We also found glycine-rich peptides (GRP), corroborating the previous description of GRPs in Phoneutria pertyi venom glands. Furthermore, to emphasize the recurrence of the lack of annotation in spider venom glands transcripts, we provide a survey of the percentage of unidentified sequences in several published spider venom transcriptomics studies. In conclusion, our study highlights the importance of manual curation in uncovering novel venom components and underscores the need for improved annotation strategies to fully exploit the medical and biotechnological potential of spider venoms.


The Representation of Women and Ethnic Minorities among Integrated Plastic Surgery Trainees: A Persistent Need for Diversification.
Diversity in the workplace is crucial. As the United States population continues to diversify, the composition of graduate medical trainees (GMTs) among various medical specialties is not diversifying at nearly the same rate. This study aims to identify gender and ethnic minority disparities present in medicine, specifically among GMTs in the field of plastic surgery. The field of plastic surgery is vast, with the patient population ranging from newborns to elders of all different races, religions, and ethnicities. However, the representation of women and minorities among the current plastic surgery trainees is not equivalent to the population they serve. Data from the Graduate Medical Education (GME) census published in the Journal of the American Medical Association (JAMA) was analyzed to compare trends of female and underrepresented ethnic minorities over the academic period from 2015 through 2019. Data regarding all GMTs and specifically those in the integrated plastic surgery (IPS) program was collected. Over the five-year study period, females were consistently underrepresented in plastic surgery when compared to the total number of female medical trainees. Currently, females represent 42.7% of GMTs in IPS, a small increase from 40.9% in 2015. Furthermore, Whites and Asians encompassed 87.7% (65.6% and 22.1%, respectively) of plastic surgery GMTs in 2019-2020. In the same academic year, Blacks and Hispanics together made up only 9.1% (2.5% and 6.6%, respectively) of GMTs in plastic surgery. This study portrays the importance of highlighting gender and ethnic minority disparities in the field of plastic surgery, thereby promoting initiatives for change in the coming future.


Stress generation in social anxiety and depression: A two-study community assessment.
Stress generation theory suggests that people engage in certain behaviors that causally generate "dependent" stressful life events. Stress generation has primarily been studied in the context of depression with limited consideration of anxiety. People with social anxiety exhibit maladaptive social and regulatory behaviors that may uniquely generate stress. Across two studies, we examined if people with elevated social anxiety experienced more dependent stressful life events than those lower in social anxiety. On an exploratory basis, we examined differences in perceived intensity, chronicity, and self-blame of stressful life events. As a conservative test, we examined whether observed relationships held after covarying depression symptoms. Community adults (Ns = 303; 87) completed semi-structured interviews about recent stressful life events. Participants with higher social anxiety symptoms (Study 1) and social anxiety disorder (SAD; Study 2) reported more dependent stressful life events than those with lower social anxiety. In Study 2, healthy controls rated dependent events as less impactful than independent events; those with SAD rated dependent and independent events as equally impactful. Regardless of social anxiety symptoms, participants placed greater blame on themselves for the occurrence of dependent than independent events. Life events interviews are retrospective and preclude conclusions about short-term changes. Mechanisms of stress generation were not assessed. Results provide initial evidence for the role of stress generation in social anxiety that may be distinct from depression. Implications for assessing and treating unique and shared features of affective disorders are discussed.


Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin.
Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity.


Serological Evaluation of Gastric Cancer Risk Based on Pepsinogen and Helicobacter pylori Antibody: Relationship to Endoscopic Findings.
The serological risk-prediction system combined the pepsinogen (PG) test, and anti-Helicobacter pylori antibody is available for evaluation of gastric cancer risk. In this system, chronic atrophic gastritis (CAG) or H. pylori infection is diagnosed. Subjects with H. pylori negative and PG test negative (group A) are supposed to be those who have never been infected with H. pylori and are at extremely low risk for gastric cancer. However, a certain proportion of patients with CAG has been identified as the extremely low-risk group (group A). Here we examined endoscopic atrophy and investigated its relationship with the ABC classification system. We examined 540 patients. All patients underwent an endoscopic examination for evaluating corpus atrophy. Fasting sera were collected and serum PGs and anti-H. pylori antibody (Hp-Ab) titer (E-plate Eiken) were evaluated. Of the 540 patients, 306 were classified into group A. However, 136 of them showed signs of endoscopic atrophy (group A with CAG). Group A with CAG frequently comprised the elderly. A new titer cut-off (<3 U/mL) of the Hp-Ab improved the discrimination of group A with CAG by 8%. The prevalence of group A with CAG patients is a critical problem, especially in elderly subjects.


Global and regional burden of aortic dissection and aneurysms: mortality trends in 21 world regions, 1990 to 2010.
A comprehensive and systematic assessment of the global burden of aortic aneurysms (AA) has been lacking. Therefore, we estimated AA regional deaths and years of life lost (YLL) in 21 regions worldwide for 1990 and 2010. We used the GBD (Global Burden of Disease) 2010 study causes of death database and the cause of death ensemble modeling approach to assess levels and trends of AA deaths by age, sex, and GBD region. The global AA death rate per 100,000 population was 2.49 (95% CI: 1.78 to 3.27) in 1990 and 2.78 (95% CI: 2.04 to 3.62) in 2010. In 1990 and 2010, the highest mean death rates were in Australasia and Western Europe: 8.82 (95% CI: 6.96 to 10.79) and 7.69 (95% CI: 6.11 to 9.57) in 1990 and 8.38 (95% CI: 6.48 to 10.86) and 7.68 (95% CI: 6.13 to 9.54) in 2010. YLL rates by GBD region mirrored the mortality rate pattern. Overall, men had higher AA death rates than women: 2.86 (95% CI: 1.90 to 4.22) versus 2.12 (95% CI: 1.33 to 3.00) in 1990 and 3.40 (95% CI: 2.26 to 5.01) versus 2.15 (95% CI: 1.44 to 2.89) in 2010. The relative change in median death rate was +0.22 (95% CI: 0.10 to 0.33) in developed nations versus +0.71 (95% CI: 0.28 to 1.40) in developing nations. The smallest relative changes in median death rate were noted in North America high income, Central Europe, Western Europe, and Australasia, with estimates of +0.07 (95% CI: -0.26 to 0.37), +0.08 (95% CI: -0.02 to 0.23), +0.09 (95% CI: -0.02 to 0.21), and +0.22 (95% CI: -0.08 to 0.46), respectively. The largest increases were in Asia Pacific high income, Southeast Asia, Latin America tropical, Oceania, South Asia, and Central Sub-Saharan Africa. Women rather than men drove the increase in the Asia Pacific high-income region: the relative change in median rates was +2.92 (95% CI: 0.6 to 4.35) versus +1.05 (95% CI: 0.61 to 2.42). In contrast to high-income regions, the observed pattern in developing regions suggests increasing AA burden, which portends future health system challenges in these regions.