Clinical characteristics and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody-associated diseases in China.
Research on myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD) among Chinese children is relatively rare. Therefore, this study aimed to explore and analyze the clinical characteristics and prognoses of Chinese children with acquired demyelinating syndromes (ADSs) who tested positive or negative for MOG-Ab. The clinical data of children with MOGAD who were treated in the Department of Neurology at Shanghai Children's Hospital from January 2017 to October 2021 were retrospectively collected. Among 90 children with ADSs, 30 were MOG-Ab-positive, and 60 were MOG-Ab-negative. MOG-Ab-positive children experienced more prodromal infections than did MOG-Ab-negative children (P < 0.05). Acute disseminated encephalomyelitis was the most common ADSs in both groups. There were ten cases of a rebound increase in MOG-Ab titers. There were significant differences in the MOG titer-related prognosis and disease time course between the disease relapse group and the non-relapse group (P < 0.01). Among the MOG-Ab-positive patients, the most affected brain areas detected via magnetic resonance imaging (MRI) were the temporal lobe, cerebellar hemispheres, brainstem, and periventricular lesions. The most common shapes of the lesions were commas, triangles, or patches. The average improvement time based on brain MRI was much longer in MOG-Ab-positive than in MOG-Ab-negative children (P < 0.05). The initial treatment time correlated with the disease time course, and the prognosis may be affected by the disease time course and serum MOG-Ab titer (P < 0.05). The clinical characteristics and imaging features of ADSs differed between MOG-Ab-positive and MOG-Ab-negative children. In addition to existing treatment plans, additional diagnoses and treatment plans should be developed to reduce recurrence and improve the prognoses of children with MOGAD.


Lithium and rubidium: effects on the rhythmic swimming movement of jellyfish (Aurelia aurita).
The effects of adding LiCl, RbCl, KCl or NaCl to sea water at concentrations up to 30 mmoles/1 on the frequency of contraction of jellyfish (Aurelia aurita) suggest that studies on phylogenetically low animals with relatively simple nervous systems may be of use to determine mechanisms of action of lithium and rudidium on movements.


Papilledema and optic disc pit: The association of two pathologies in one patient.
Histologically, optic disc pit (ODP) is described as a small congenital defect in the cribriform plate where a herniation of the dysplastic retina extends to the subarachnoid space in the optic nerve, which is surrounded by a layer of collagen-rich tissue. Approximately 25-75% of cases are complicated by optic disc pit maculopathy (ODPM). The pathogenesis of maculopathies associated with ODP has not been fully elucidated. We present an unusual case of a patient with a history of papilledema secondary to a fronto-temporal meningioma. The patient underwent a successful surgical intervention with resolution of the papilledema 15 years before the detection of an ODP that was associated with retinal detachment in the macular region. Several studies have reported on the importance of intracranial pressure in the development of maculopathies associated with ODP. During the period of intracranial hypertension and papilledema in our patient, the hernia sac that was associated with ODP may have been small, which would have decreased the chances of developing a maculopathy that was associated with OPD.


Natural radioactivity levels and heavy metals in chemical and organic fertilizers used in Kingdom of Saudi Arabia.
The present work deals with identifying and determining the activity levels of natural occuring radionuclides, (226)Ra and (232)Th series, their decay products and (40)K, in chemical and organic fertilizers used in Kingdom of Saudi Arabia. A total of 30 samples: 20 phosphatic fertilizers (single super-phosphate SSP and triple super-phosphate,TSP) and 10 organic fertilizers (cow, sheep and chicken) collected from markets and farms. The gamma-ray spectrometer consists of NaI(Tl) detector and its electronic circuit was used for measuring γ-ray spectra. The ranges of radioactivity levels of (226)Ra, (232)Th and (40)K in chemical fertilizers are 51.5±5.2-106.3±7.5, 5.1±1.6-9.9±3.2. and 462.6±21-607.3±14Bqkg(-1), respectively. The activities of (226)Ra, (232)Th and (40)K in natural fertilizers (cow, sheep and chicken) are lower than the activities in chemical fertilizers. The obtained data are compared with available reported data from other countries in literature. The Ra(eq) in chemical fertilizer ranges from 100.37 to 161.43Bqkg(-1) and in organic fertilizer ranges from 34.07 to 102.19Bqkg(-1), which are lower than the limit of 370Bqkg(-1) adopted from NEA-OECD (1979). The average heavy metal (Pb, Cd, Ni, Co and Cr) contents of the fertilizers marketed in the Kingdom of Saudi Arabia are also determined and within the limits of those used worldwide.


Chemical Reporters for Exploring Microbiology and Microbiota Mechanisms.
The advances made in bioorthogonal chemistry and the development of chemical reporters have afforded new strategies to explore the targets and functions of specific metabolites in biology. These metabolite chemical reporters have been applied to diverse classes of bacteria including Gram-negative, Gram-positive, mycobacteria, and more complex microbiota communities. Herein we summarize the development and application of metabolite chemical reporters to study fundamental pathways in bacteria as well as microbiota mechanisms in health and disease.


Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro.
Changes within the immune system have been reported to contribute to the pathophysiology of bipolar disorder and epilepsy. Interestingly, overlapping results regarding the cytokine system have been found for both diseases, namely alterations of interleukins IL-1β, IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α). However, the effect of mood stabilizers and antiepileptic drugs (AEDs) on these cytokines has not been systematically evaluated, and their effect on IL-17 and IL-22, other immunologically important cytokines, has not been reported. Therefore, we systematically measured levels of IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in stimulated blood of 14 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was supplemented with the mood stabilizers or antiepileptic drugs primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), lithium, or no drug. IL-1β production was significantly decreased by PRM, CBZ, LEV, LTG, OXC, PB and lithium. IL-2 significantly decreased by PRM, CBZ, LEV, LTG, VPA, OXC, TPM and PB. IL-22 significantly increased by PRM, CBZ, LEV, OXC, TPM and lithium and decreased by VPA. TNF-α production significantly decreased under all applied drugs. The mechanism of action and side effects of mood stabilizers and AEDs may involve modulation of IL-1β, IL-2, IL-22 and TNF-α signaling pathways. IL-22 may be a research target for specific therapeutic effects of mood stabilizers and AEDs. These drugs might influence cytokine production by modulating ion channels and γ-aminobutyric acid (GABA) receptors of immune cells.


Treatment of autochthonous rat brain tumors with steroid plus heparin: a brief report.
Treatment of rats bearing intracranial gliomas induced by the avian sarcoma virus with heparin plus steroid has failed to effectively extend survival time.


Spontaneous remission of "methotrexate-associated lymphoproliferative disorders" after discontinuation of immunosuppressive treatment for autoimmune disease. Review of the literature.
There are a number of intriguing reports of lymphoproliferative disorders (LPDs) diagnosed during immunosuppressive treatment for underlying autoimmune disease, and spontaneously abated shortly after treatment discontinuation. Such LPDs, completely or partially regressing, occur in the clinical setting of "Methotrexate (MTX)-associated LPDs", recognized by the World Health Organization (WHO) among the "Immunodeficiency-associated LPDs". We identified 26 literature patients achieving spontaneous complete remission (CR) of their LPD, and eight others showing partial remission (PR). Most of them were affected by rheumatoid arthritis, received low-dose and long-term pulsed MTX alone or combined with other immunosuppressants, and developed a lymphoma. By reviewing the patients achieving CR, the following can be drawn: the absence of a unique type of LPD, the occurrence of an increased incidence of diffuse large B cell lymphoma as well as of frequent extranodal involvement, and EBV-infection. Further, CR mostly occurred within 4 weeks after discontinuation of immunosuppressant, and appeared to be persistent overtime. Conversely in the patients experiencing PR, the interval between discontinuation of immunosuppressive treatment and clinical response was mostly reported as longer than 4 weeks; moreover, in many cases the persistence of LPD or its progression induced to start cytotoxic therapy. Increased awareness is needed on the possible occurrence of LPD spontaneous remission following immunosuppressant discontinuation, after that it is therefore advisable to have a careful monitoring of the patient for some weeks, before starting cytotoxic therapy.


Nora's Story.
In this column, Nora Gibbons, 16 years old, describes the home births of four of her siblings. Nora's story captures the wonder and simplicity of home birth and demonstrates the impact the experience of being present at home birth can have on children. Nora's joy and confidence in birth because of her experiences will influence her own birth choices.


Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose.
Oral delivery of protein or polypeptide drugs remains a challenge due to gastric and enzymatic degradation as well as poor permeation across the intestinal epithelia. In this study, liposomes containing bile salts were developed as a new oral insulin delivery system. The primary goal was to investigate the effect of cholate type, particle size and dosage of the liposomes on the hypoglycemic activity and oral bioavailability. Liposomes containing sodium glycocholate (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a reversed-phase evaporation method. After oral administration, all liposomes elicited a certain degree of hypoglycemic effect in parallel with an increase in blood insulin level. The highest oral bioavailability of approximately 8.5% and 11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed slower and sustained action over a period of over 20 h with peak time around 8-12h. SGC-liposomes showed higher oral bioavailability than liposomes containing STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent with the highest at 150 nm or 400 nm and was proportionally correlated to the administered dose. The results supported the hypothesis of insulin absorption as intact liposomes.


Evaluation of CTA, time-resolved 4D CE-MRA and DSA in the follow-up of an intracranial aneurysm treated with a flow diverter stent: Experience from a single case.
Endovascular treatment of giant, fusiform and dissecting aneurysms with flow diverter stents is becoming more and more popular. However, very few studies on the follow-up have been published. We describe a patient with a dissecting aneurysm of the right vertebral artery treated with flow diverter stent placement. The patient was followed up with CT angiography (CTA), time-resolved contrast-enhanced MR angiography (CE-MRA) and digital subtraction angiography (DSA). CTA had false negative results in two instances, whereas time-resolved CE-MRA and DSA were the most accurate in depicting the residual flow in the aneurysmal sac. However, in the case of DSA the demonstration of residual flow proved quite difficult and required a very thorough examination with oblique projections. Our 2.5-year experience with this patient led us to believe that time-resolved CE-MRA is a valuable tool in the follow-up of flow diverter-treated stents.


Spatial and temporal changes in tissue pH and ATP distribution in a new model of reversible focal forebrain ischemia in the rat.
The effects of reversible middle cerebral artery occlusion on regional pH and ATP distribution were studied in a new stroke model in rats by a planimetric method. Thirty minutes of ischemia was followed by 2, 4 and 24 hours of reperfusion. Ischemia resulted in acidosis and ATP depletion. In some areas tissue pH reached the threshold of the umbelliferone method (about pH 6.0). Areas with ATP depletion were significantly smaller than regions of pH alteration not only at the end of ischemia but during the first 4 hours of recirculation as well. By 4 hours of reperfusion large areas with altered pH were associated with ATP depletion in smaller regions, mostly in the hippocampus and the frontal cortex. The areas of ATP depletion were acidic initially, but by 4 hours alkaline pH could also be detected. Twenty four hours after ischemia alkaline areas (pH > 7.4) were found with ATP depletion, suggesting irreversible tissue damage, in cortical areas, in the hippocampus, and in the thalamus. By 24 hours of reperfusion there was no significant difference between the size of areas with altered pH and ATP depletion.


Yu's flap for lower lip and reverse Yu's flap for upper lip reconstruction: 20 years experience.
Reconstruction of defects of the lip caused by cancer with its requirements of a complicated anatomical structure, important physiological function, and acceptable cosmetic result, is a challenge for oral and maxillofacial and plastic surgeons. A method that combines rotation and advancement flaps was described by Yu in 1989 for the reconstruction of defects of the lower lip. In our department between January 1992 and December 2012, 8 patients had reverse Yu flaps for the reconstruction of upper lip defects and 56 patients had classic Yu flaps for lower lip defects. Patients with defects located laterally to the upper lips, ranging from ⅓ to ½, had unilateral reverse Yu flaps, and bilateral procedures were done for defects of less than ⅔ of the lips. However, if the defects were located in the centre of the upper lips, between ⅓ and ½, they were treated with bilateral reverse Yu flaps. Patients with defects between ⅓ and ⅔ of lower lips had unilateral Yu flaps, and if the defects were wider than ⅔ of the lower lips, the procedure was bilateral. No flap failed and desirable functional and aesthetic outcomes were recorded in all cases. Here we report our experience with the Yu flap for the benefit of other surgeons.


Association between maternal cervicovaginal swab positivity for Ureaplasma spp. or other microorganisms and neonatal respiratory outcome and mortality.
We investigated the association between maternal cervicovaginal cultures, its antibiotic treatment, and neonatal outcome. This retrospective cohort study enrolled 480 neonates born prior to 32 weeks' gestation. They were divided into groups according to maternal cervicovaginal culture results. Multivariate logistic regression analysis was used to predict neonatal outcome based on maternal culture results, adjusted for perinatal risk factors and neonatal morbidities. Maternal cervicovaginal Ureaplasma colonization was independently associated with bronchopulmonary dysplasia at 36 weeks (BPD) (OR 8.34; 95% CI 1.21-57.45). In neonates with and without maternal cervicovaginal Ureaplasma colonization BPD occurred in 12.3% and 3.8%, respectively. Maternal colonization with other microorganisms was associated with a higher neonatal mortality (p = 0.002), lower gestational age (p = 0.026), and birth weight (p = 0.036). This study underscores the role of the maternal cervicovaginal microbiome as a predictor of neonatal outcome. Cervicovaginal Ureaplasma colonization seems not to be an innocent bystander in the multifactorial etiology of BPD.


[The care of extremely preterm infants: A French view of the Swedish experience].
Extreme prematurity, defined as birth occurring before 27 weeks of gestation in Sweden, is managed according to the latest data of the most recent literature, with monitoring of the results through a continuous perinatal registry. National guidelines were issued in 2013. They highlight the importance of infant developmentally supportive and family-centered care focused on the child and the family, nutritional support, pain management, management of ductus arteriosus, and brain damage. However, there remain areas without national consensus including respiratory support management. The French vision of the Swedish approach highlights the proactive attitude of neonatologists, the coherent and narrow collaboration between neonatologists and obstetricians, and the active presence and involvement of parents in the care of their infants.


Growing applications and advancements in microarray technology and analysis tools.
In today's field of genomics, traditional gene-by-gene approach is not adequate to meet the demand of processing information generated from mapping the complex biology of the human genome. More global views of analyzing the magnitude of information are necessary, such as with microarrays. Microarray technology today is rapidly uncovering broad patterns of genetic activity and showing insight into gene functions, processes, and pathways. With the growing technology, imminent knowledge is being generated looking into transcriptional processes and biological mechanisms from many different organisms and phylogeny. Many tools are being developed to assist with the analysis of such high-throughput data, many applications are being utilized by this technology, and the field is growing and expanding rapidly to accommodate the expanding genomics era.


Investigation of Schizophrenia with Human Induced Pluripotent Stem Cells.
Schizophrenia is a chronic and severe neuropsychiatric condition manifested by cognitive, emotional, affective, perceptual, and behavioral abnormalities. Despite decades of research, the biological substrates driving the signs and symptoms of the disorder remain elusive, thus hampering progress in the development of treatments aimed at disease etiologies. The recent emergence of human induced pluripotent stem cell (hiPSC)-based models has provided the field with a highly innovative approach to generate, study, and manipulate living neural tissue derived from patients, making possible the exploration of fundamental roles of genes and early-life stressors in disease-relevant cell types. Here, we begin with a brief overview of the clinical, epidemiological, and genetic aspects of the condition, with a focus on schizophrenia as a neurodevelopmental disorder. We then highlight relevant technical advancements in hiPSC models and assess novel findings attained using hiPSC-based approaches and their implications for disease biology and treatment innovation. We close with a critical appraisal of the developments necessary for both further expanding knowledge of schizophrenia and the translation of new insights into therapeutic innovations.


Generation of a homozygous RANGRF knockout hiPSC line by CRISPR/Cas9 system.
The RAN Guanine Nucleotide Release Factor (RANGRF) gene encodes the protein MOG1, which binds to Nav1.5 and facilitates its transport to the cell membrane. Nav1.5 mutations have been linked to various cardiac arrhythmias and cardiomyopathy. To investigate the role of RANGRF in this process, we utilized the CRISPR/Cas9 gene editing system to generate a homozygous RANGRF knockout hiPSC line. The availability of the cell line will prove to be an invaluable asset in the study of disease mechanisms and the testing of gene therapies for cardiomyopathy.


Pre-emptive active drainage of reflux (PARD) in Ivor-Lewis oesophagectomy with negative pressure and simultaneous enteral nutrition using a double-lumen open-pore film drain (dOFD).
Postoperative reflux can compromise anastomotic healing after Ivor-Lewis oesophagectomy (ILE). We report on Pre-emptive Active Reflux Drainage (PARD) using a new double-lumen open-pore film drain (dOFD) with negative pressure to protect the anastomosis. To prepare a dOFD, the gastric channel of a triluminal tube (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over 25 cm. The ventilation channel is blocked. The filmcoated segment is placed in the stomach and the intestinal feeding tube in the duodenum. Negative pressure is applied with an electronic vacuum pump (- 125 mmHg, continuous suction) to the gastric channel. Depending on the findings in the endoscopic control, PARD will either be continued or terminated. PARD was used in 24 patients with ILE and started intraoperatively. Healing was observed in all the anastomoses. The median duration of PARD was 8 days (range 4-21). In 10 of 24 patients (40%) there were issues with anastomotic healing which we defined as "at-risk anastomosis". No additional endoscopic procedures or surgical revisions to the anastomoses were required. PARD with dOFD contributes to the protection of anastomosis after ILE. Negative pressure applied to the dOFD (a nasogastric tube) enables enteral nutrition to be delivered simultaneously with permanent evacuation and decompression.


Management of an infected pseudoaneurysm following an aortoventriculoplasty.
An 11-year-old child developed prosthetic valve endocarditis with associated infection of the prosthetic and pericardial patches 6 months following an aortoventriculoplasty. Angiography revealed an associated false aneurysm which communicated with both the ascending aorta and the right ventricular outflow tract. This report discusses the surgical management of this patient.


Ligand-regulated peptides: a general approach for modulating protein-peptide interactions with small molecules.
We engineered a novel ligand-regulated peptide (LiRP) system where the binding activity of intracellular peptides is controlled by a cell-permeable small molecule. In the absence of ligand, peptides expressed as fusions in an FKBP-peptide-FRB-GST LiRP scaffold protein are free to interact with target proteins. In the presence of the ligand rapamycin, or the nonimmunosuppressive rapamycin derivative AP23102, the scaffold protein undergoes a conformational change that prevents the interaction of the peptide with the target protein. The modular design of the scaffold enables the creation of LiRPs through rational design or selection from combinatorial peptide libraries. Using these methods, we identified LiRPs that interact with three independent targets: retinoblastoma protein, c-Src, and the AMP-activated protein kinase. The LiRP system should provide a general method to temporally and spatially regulate protein function in cells and organisms.


Maternal narcotic addiction: pregnancy outcome in patients managed by a specialized drug-dependency antenatal clinic.
A retrospective analysis has been made of the outcome of pregnancy in 174 women abusing narcotics, managed by a specialist team from a drug-dependency antenatal clinic. These women were cared for through 182 pregnancies of greater than 20 weeks' gestation, resulting in 183 live and 5 stillbirths. The majority of patients were enrolled in a methadone programme and stabilized on the drug before the third trimester. The group was characterized by a high prevalence of previous obstetric and medical problems. The most common antenatal complications were preterm labour (24%) and anaemia (12%). Preterm delivery and small-for-gestational-age each occurred in a quarter of pregnancies. The mean birth-weight for the group was 2,746 g +/- 721 g; mean +/- S.D. Eight perinatal deaths occurred (5 stillbirths, 3 neonatal deaths), giving a perinatal mortality rate of 43/1,000. The data on narcotic abusers have been compared with similar data obtained from randomly selected public antenatal clinic patients who delivered during the same period.


Interleukin-6 as a neurotrophic factor for promoting the survival of cultured catecholaminergic neurons in a chemically defined medium from fetal and postnatal rat midbrains.
Interleukin-6 (IL-6, human recombinant) promoted the survival of catecholaminergic neurons from fetal and postnatal rat midbrains as assessed by an immunohistochemical staining for tyrosine hydroxylase (TH) in culture using a chemically defined medium. The maximal dose of IL-6 for the cell survival of postnatal P15 rat mesencephalic TH-positive neurons in culture for 7 days was 50 ng/ml. The survival-promoting effects on P15 cultures were observed both in high- and low-density cultures. The survival effect of IL-6 on the cultured P15 TH-positive neurons was significant for only 4-15 days in vitro. However, the viable number of TH-positive neurons with IL-6 was less than that of the control at early points in the culture process (1-2 days in vitro). Continuous presentation of IL-6 was required for promoting survival. The optimal dose of IL-6 for the survival of fetal E16 midbrain TH-positive neurons was 5 ng/ml, and the survival promoting effect was less than that for the P15 cultures. The maximal dose of IL-6 for the survival of P2 TH-positive neurons was 5 ng/ml and that of P8 was 50 ng/ml, indicating that the response of rat mesencephalic TH-positive neurons to IL-6 changes during the first postnatal week.


BBox-Guided Segmentor: Leveraging expert knowledge for accurate stroke lesion segmentation using weakly supervised bounding box prior.
Stroke is one of the leading causes of death and disability in the world. Despite intensive research on automatic stroke lesion segmentation from non-invasive imaging modalities including diffusion-weighted imaging (DWI), challenges remain such as a lack of sufficient labeled data for training deep learning models and failure in detecting small lesions. In this paper, we propose BBox-Guided Segmentor, a method that significantly improves the accuracy of stroke lesion segmentation by leveraging expert knowledge. Specifically, our model uses a very coarse bounding box label provided by the expert and then performs accurate segmentation automatically. The small overhead of having the expert provide a rough bounding box leads to large performance improvement in segmentation, which is paramount to accurate stroke diagnosis. To train our model, we employ a weakly-supervised approach that uses a large number of weakly-labeled images with only bounding boxes and a small number of fully labeled images. The scarce fully labeled images are used to train a generator segmentation network, while adversarial training is used to leverage the large number of weakly-labeled images to provide additional learning signals. We evaluate our method extensively using a unique clinical dataset of 99 fully labeled cases (i.e., with full segmentation map labels) and 831 weakly labeled cases (i.e., with only bounding box labels), and the results demonstrate the superior performance of our approach over state-of-the-art stroke lesion segmentation models. We also achieve competitive performance as a SOTA fully supervised method using less than one-tenth of the complete labels. Our proposed approach has the potential to improve stroke diagnosis and treatment planning, which may lead to better patient outcomes.


Influenza pandemic preparedness and response: A review of legal frameworks in India.
the potential of pandemics to cause global destabilization calls for robust pandemic preparedness plans with supportive health legislation. Few international studies have investigated their national legal preparedness in case of a pandemic. This study reviews India's legal preparedness in the face of an epidemic. this study reviewed and analyzed seminal publications pertinent to pandemic preparedness and relevant legal frameworks in India. The analyses are presented in matrix formats and reviewed by national experts. current legal frameworks are largely 'policing' in nature. These provisions seem to be adequate to deal with small scale emergencies but do not appear to be sufficient for large scale health crises during pandemics. india needs a critical mass of public health legislations to make impact and not police acts to control epidemics. This study aims to assist policy makers to create comprehensive pandemic preparedness plans, translating preparedness 'on paper' to 'in practice'.


Advancing biological invasion hypothesis testing using functional diversity indices.
Pioneering investigations on the effects of introduced populations on community structure, ecosystem functioning and services have focused on the effects of invaders on taxonomic diversity. However, taxonomic-based diversity metrics overlook the heterogeneity of species roles within and among communities. As the homogenizing effects of biological invasions on community and ecosystem processes can be subtle, they may require the use of functional diversity indices to be properly evidenced. Starting from the listing of major functional diversity indices, alongside the presentation of their strengths and limitations, we focus on studies pertaining to the effects of invasive species on native communities and recipient ecosystems using functional diversity indices. By doing so, we reveal that functional diversity of the recipient community may strongly vary at the onset of the invasion process, while it stabilizes at intermediate and high levels of invasion. As functional changes occurring during the lag phase of an invasion have been poorly investigated, we show that it is still unknown whether there are consistent changes in functional diversity metrics that could indicate the end of the lag phase. Thus, we recommend providing information on the invasion stage under consideration when computing functional diversity metrics. For the existing literature, it is also surprising that very few studies explored the functional difference between organisms from the recipient communities and invaders of the same trophic levels, or assessed the effects of non-native organism establishment into a non-analogue versus an analogue community. By providing valuable tools for obtaining in-depth diagnostics of community structure and functioning, functional diversity indices can be applied for timely implementation of restoration plans and improved conservation strategies. To conclude, our work provides a first synthetic guide for their use in hypothesis testing in invasion biology.


Phase I and pharmacological trial of lapatinib in combination with gemcitabine in patients with advanced breast cancer.
Lapatinib has proven efficacy as monotherapy and in combination with capecitabine in patients with metastatic breast cancer (MBC) overexpressing HER2 and/or EGFR. Gemcitabine also has anti-tumor activity in MBC and a favourable toxicity profile. In this phase I study lapatinib and gemcitabine were combined. Female patients with advanced BC were given lapatinib once daily (QD) in 28-day cycles with gemcitabine administered on day 1, 8 and 15. Physical examinations, vital signs and blood sampling for hematology, clinical chemistry and pharmacokinetics (PK) and radiological assessments of disease were performed at regular intervals. In total, 33 patients were included. Six dose-limiting toxicities were observed, mostly grade 3 increases in liver function tests. Most common toxicities were fatigue (73%), nausea (70%), diarrhea (58%), increases in ALAT and ASAT (55 and 52%, respectively) and rash (46%). The maximum tolerated dose was lapatinib 1250 mg QD with gemcitabine 1000 mg/m(2). Lapatinib and gemcitabine PK did not appear to be influenced by each other. Anti-tumor activity was observed with one patient (4%) showing complete response and six (23%) partial response. Despite a slightly increased toxicity profile compared to their respective monotherapies, lapatinib and gemcitabine can be safely combined while showing signs of anti-tumor activity.


A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors.
Loss of heterozygosity for 10q23-26 is seen in over 80% of glioblastoma multiforme tumors. We have used a positional cloning strategy to isolate a novel gene, LGI1 (Leucine-rich gene-Glioma Inactivated), which is rearranged as a result of the t(10;19)(q24;q13) balanced translocation in the T98G glioblastoma cell line lacking any normal chromosome 10. Rearrangement of the LGI1 gene was also detected in the A172 glioblastoma cell line and several glioblastoma tumors. These rearrangements lead to a complete absence of LGI1 expression in glioblastoma cells. The LGI1 gene encodes a protein with a calculated molecular mass of 60 kD and contains 3.5 leucine-rich repeats (LRR) with conserved flanking sequences. In the LRR domain, LGI1 has the highest homology with a number of transmembrane and extracellular proteins which function as receptors and adhesion proteins. LGI1 is predominantly expressed in neural tissues, especially in brain; its expression is reduced in low grade brain tumors and it is significantly reduced or absent in malignant gliomas. Its localization to the 10q24 region, and rearrangements or inactivation in malignant brain tumors, suggest that LGI1 is a candidate tumor suppressor gene involved in progression of glial tumors.


Interaction between phosphorus removal and hybrid granular sludge formation under low hydraulic selection pressure at alternating anaerobic/aerobic conditions.
The hybrid granular sludge (HGS) formation and its performances on phosphorus removal were investigated in a sequencing batch airlift reactor. Under conditions of low superficial air velocity (SAV = 0.68 cm s(-1)) and relatively long settling time (15-30 min), aerobic granules appeared and coexisted with bio-flocs after 120 days operation. At the stable phase, 54% of total suspended solid (m/m) was granular sludge with the two typical sizes (D(mean) = 1.77 ± 0.33 and 0.89 ± 0.11 mm) in the reactor, where the settling velocity was 98.7 ± 12.4 and 37.8 ± 0.9 m h(-1) for the big and small granules. With progressive extension of anaerobic time from 15 to 60 min before aerobic condition per cycle during the whole experiment, the HGS system can be maintained at a high total phosphorus removal efficiency (ca. 99%) since Day-270. The phosphorus content (wt %) in biomass was respectively 9.54 ± 0.29, 7.60 ± 0.48 and 6.15 ± 0.59 for the big granules, small granules and flocs.


Immunogenicity and effectiveness of a bivalent influenza A/H1N2 vaccine strain against seasonal human influenza A viruses in mice.
Recent studies and reports have documented the ability of the co-circulating seasonal influenza A/H1N1 (ancestor: 2009 pandemic H1N1) and A/H3N2 to exchange their genetic segments, generating a novel H1N2 strain in different geographical localities around the world with an ability to infect human. This raises concerns and triggers alarms to develop a multivalent vaccine that can protect against the documented H1- and H3-type human influenza A viruses (IAVs). Here, we generated a PR8-based vaccine strain that carries the HA gene segment from the contemporary H1N1 virus while the NA gene segment was derived from a currently circulating influenza A/H3N2 strain. A recombinant PR8-based H1N2 vaccine strain (rgH1N2), engineered by reassortment between influenza A/H1N1 and A/H3N2 to mimic the documented human influenza A/H1N2, was used for immunization to provoke immunogenicity and cross-antigenicity against the H1- and H3-type human IAVs and was evaluated for its immunogenicity and effectiveness in mice. Following challenge infection of rgH1N2-vaccinated mice with contemporary influenza A/H1N1 and A/H3N2, results revealed that rgH1N2-vaccinated mice showed less viral shedding, more survival, and less body weight loss compared to control unvaccinated groups and vaccinated mice with rgH1N1 and rgH3N2. This study highlights the applicability of the PR8-based H1N2 vaccine strain to protect against seasonal IAVs and emphasizes the role of both surface proteins, HA and NA, to stimulate protective and neutralizing antibodies against circulating influenza A/H1N1 and A/H3N2 strains.


Laparoscopy in Turkish bariatric surgery: initial experience.
The recent application of the laparoscopic method combines minimal invasiveness with reversibility, adjustability and shorter hospital stay. The first laparoscopic bariatric operation in Turkey was performed by us in 1998. We report the results in 50 consecutive patients who underwent the laparoscopic application of SAGB between April 1998 and April 1999. The operation setting was the same as for the laparoscopic antireflux procedure. After a closed CO2 pneumoperitoneum (16-18 mmHg), in the first 20 cases five and in the remaining 30 cases four trocars were inserted. A 30 degrees laparoscope was placed on the line between the umbilicus and the xiphoid through a 10 mm trocar. We followed and respected the main steps of the operation as well. Pre and postoperative body weight (BW), body mass index (BMI) and percent excess weight (%EW) values were calculated and compared. Our early results were quite satisfactory and promising. After an average follow-up period of 1 year (range 6-18 months), the 50 patients of our laparoscopic series showed a BW of 74 kg (range 56-112), a BMI of 29 (range 21-40), and an EW of 62% (range 22-86). With its lower morbidity rate, shorter hospital stay and better cosmetic results, the laparoscopic approach may be considered the first choice in bariatric surgery.


Transforming growth factor-beta 1 (TGF-beta 1) and recombinant human tumor necrosis factor-alpha reciprocally regulate the generation of lymphokine-activated killer cell activity. Comparison between natural porcine platelet-derived TGF-beta 1 and TGF-beta 2, and recombinant human TGF-beta 1.
We have investigated the ability of porcine-platelet-derived transforming growth factor-beta 1 (TGF-beta 1) to inhibit the generation of lymphokine-activated killer (LAK) cells by human rIL-2. The results demonstrate that TGF-beta 1, in a dose-related manner, significantly inhibits rIL-2-induced LAK cell activity against Daudi and COLO target cells and, to a lesser degree, against K-562 cells. Maximal inhibition was obtained by the addition of TGF-beta 1 at the time of culture initiation and, to a lesser degree, on day 1. Only minimal inhibition was obtained when TGF-beta 1 addition was delayed until day 2 of culture or when added directly into the LAK cell assay. Additional studies demonstrated that porcine platelet-derived TGF-beta 2 and human rTGF-beta 1 inhibited LAK cell generation similar to that obtained with TGF-beta 1. The inhibition of LAK cell activity by TGF-beta 1 was reversed by the addition of human rTNF-alpha at the initiation of culture. In addition, rTNF-alpha synergized with suboptimal levels of rIL-2 in the generation of LAK activity. After stimulation with rIL-2, LAK cells produced significant levels of IFN-gamma, TNF-alpha, and TNF-beta. TGF-beta 1 inhibited the production of these cytokines in a dose-related manner. The results extend the previous known activities for human rTNF-alpha and TGF-beta 1 and further demonstrate the reciprocal relationship between these two molecules in the regulation of certain immune functions.


Attenuation of perceived motion smear during vergence and pursuit tracking.
When the eyes move, the images of stationary objects sweep across the retina. Despite this motion of the retinal image and the substantial integration of visual signals across time, physically stationary objects typically do not appear to be smeared during eye movements. Previous studies indicated that the extent of perceived motion smear is smaller when a stationary target is presented during pursuit or saccadic eye movements than when comparable motion of the retinal image occurs during steady fixation. In this study, we compared the extent of perceived motion smear for a stationary target during smooth pursuit and vergence eye movements with that for a physically moving target during fixation. For a target duration of 100 ms or longer, perceived motion smear is substantially less when the motion of the retinal image results from vergence or pursuit eye movements than when it results from the motion of a target during fixation. The reduced extent of perceived motion smear during eye movements compared to fixation cannot be accounted for by different spatio-temporal interactions between visual targets or by unequal attention to the moving test spot under these two types of conditions. We attribute the highly similar attenuation of perceived smear during vergence and pursuit to a comparable action of the extra-retinal signals for disjunctive and conjugate eye movements.


The Apaf-1-binding protein Aven is cleaved by Cathepsin D to unleash its anti-apoptotic potential.
The anti-apoptotic molecule Aven was originally identified in a yeast two-hybrid screen for Bcl-x(L)-interacting proteins and has also been found to bind Apaf-1, thereby interfering with Apaf-1 self-association during apoptosome assembly. Aven is expressed in a wide variety of adult tissues and cell lines, and there is increasing evidence that its overexpression correlates with tumorigenesis, particularly in acute leukemias. The mechanism by which the anti-apoptotic activity of Aven is regulated remains poorly understood. Here we shed light on this issue by demonstrating that proteolytic removal of an inhibitory N-terminal Aven domain is necessary to activate the anti-apoptotic potential of the molecule. Furthermore, we identify Cathepsin D (CathD) as the protease responsible for Aven cleavage. On the basis of our results, we propose a model of Aven activation by which its N-terminal inhibitory domain is removed by CathD-mediated proteolysis, thereby unleashing its cytoprotective function.


Modulation of CD1d-restricted NKT cell responses by CD4.
CD4+ and CD4- NKT cell populations have been shown to be functionally distinct, but the role of CD4 molecules in NKT cell activation is not clear. Here, we have used human CD1d-restricted NKT cell clones to investigate the contribution of CD4 to NKT cell functional responses. Coligation of CD4 with the TCR/CD3 complex resulted in enhanced cytokine secretion and increased calcium flux by CD4+ NKT cell clones, indicating that CD4 is functionally active in these cells. CD4 blockade specifically inhibited cytokine secretion and proliferation of CD4+ NKT cell clones in response to CD1d+ APCs but did not affect cytotoxicity, suggesting that CD4 preferentially modulates some NKT cell functional responses and not others. Anti-CD4 mAb treatment inhibited NKT cell responses to both MHC class II(+) and MHC class II(-) APCs, indicating that its effect was not due to blocking CD4 binding to MHC class II molecules on APCs. The inhibitory effect of the anti-CD4 mAb also did not require recognition of CD1d by the NKT cell, since calcium flux was reduced in response to anti-CD3 mAb stimulation. Western blot analysis revealed that anti-CD4 treatment resulted in increased phosphorylation of an inhibitory site of p56(lck) (tyrosine 505). Thus, CD4 blockade interferes with the course of CD3-mediated signaling events in NKT cells. These results indicate that CD4 can contribute to NKT cell activation independently of the presence of a CD4-ligand on APCs and suggest that it preferentially modulates cytokine and proliferative responses.


Intestinal-type gastric adenocarcinoma without Helicobacter pylori infection successfully treated with endoscopic submucosal dissection.
A 67-year-old woman was admitted to our hospital for further examination and for treatment of gastric neoplasia located on the posterior wall of the antrum of the stomach, as revealed by screening esophagogastroduodenoscopy. The patient had no history of Helicobacter pylori (H. pylori) eradication. Her serum H. pylori antibody and urea breath test results were negative, histopathological findings revealed no H. pylori bacteria, and endoscopic findings revealed no chronic gastritis. We performed endoscopic submucosal dissection (ESD). Histological examination of the resected tissues revealed the tumor to be composed of a well-differentiated tubular adenocarcinoma with a tubular-type adenoma confined to the mucosa. This adenocarcinoma exhibited immunohistochemical expression of CD10, MUC2, and Cdx2, but not MUC5AC or MUC6. This is an extremely rare case of H. pylori infection-negative, intestinal-type, differentiated gastric adenocarcinoma revealed by detailed immunohistochemical examination that was treated with ESD. The patient has had no recurrence of adenocarcinoma after ESD.


Positive fantasies or negative contrasts: the effect of media body ideals on restrained eaters' mood, weight satisfaction, and food intake.
Although viewing media body ideals promotes body dissatisfaction and problematic eating among women (e.g., extreme restraint/overeating), some argue that women only report such negative effects because they think that they are meant to (i.e., demand characteristics). Because restrained eaters are trying to lose weight, they might be vulnerable to such media exposure. However, because of demand characteristics, evidence is mixed. Therefore, we minimized demand characteristics and explored whether media body ideals would trigger restrained eaters to report negative (negative mood, weight dissatisfaction) or positive (positive mood, weight satisfaction) effects. We also hypothesized that this change (negative or positive) would encourage food intake. Restrained and unrestrained eaters (n=107) memorized media or control images. Restrained eaters exposed to media images reported decreased weight satisfaction and increased negative mood, but their food intake was not significantly affected. Perhaps paying advertent attention to the images caused goal-related negative affect, which triggered restraint.


Colonic mucosal changes in nude mice associated with orthotopic xenografts of human colon cancer cells.
We used the nude mouse tumour xenograft model to study the pathogenesis of mucosa alterations in the large bowel surrounding a carcinoma. In mouse colonic mucosa overlying HT-29 colonic carcinoma xenografts in the caecum, the crypts were elongated in comparison with those in distant mucosa and also frequently showed a shift towards sialomucin production. These features, which are comparable with socalled transitional mucosa (TM) in man, were absent in control animals inoculated with Indian Ink instead of HT-29 cells. Although the localization of the proliferative cell compartment in mouse colonic mucosa overlying HT-29 xenografts appeared to be confined to the lower half of the crypt as in normal mucosa, the relative length of the DNA synthesizing cell compartment along the crypts was slightly elongated. These data strongly suggest that TM should be regarded as a secondary phenomenon rather than a premalignant change in large intestinal epithelium and that higher proliferative activity of epithelial cells contributes little to the elongation of crypts in TM.


Determinants of blood pressure in 7th grade Jerusalem school children.
The determinants of blood pressure level were analyzed in a group of 1154 Jerusalem school children aged 12. After controlling for age, significant differences in blood pressure measurements were found between three groups: boys, pre-menarche girls and post-menarche girls. A comparison of the means of selected biological variables showed that girls who have reached menarche have levels of systolic blood pressure, weight, height and Quetelet's index higher than boys and pre-menarche girls. However, levels of triceps skinfold thickness and pulse rate were similar in the two groups of girls and higher than in boys. Using multiple regression analysis, we found that much of the variance (boys 29%, post-menarche girls 21% and pre-menarche girls 15%) of systolic blood pressure could be explained by a combination of biological variables (Quetelet, pulse rate, triceps skinfold thickness and height) while these variables explained a much smaller proportion (boys 12%, post-menarche girls 17% and pre-menarche 9%) of diastolic blood pressure variance. The predictive power of systolic blood pressure by the measured biological variables was higher in boys than in girls. However, diastolic blood pressure was better predicted by the biological variables in the group of girls with menarche than in other groups. Elevated blood pressure was observed in 3.2% of the examined children. High values for Quetelet's index were observed in 6.4%. The prevalence of elevated measurements of blood pressure and Quetelet's index were significantly higher in girls with menarche. Among children aged 12, the association between sociodemographic characteristics and blood pressure level was weak, as measured in multiple regression analysis.


Validation of Wearable Digital Devices for Heart Rate Measurement During Exercise Test in Patients With Coronary Artery Disease.
To assess the accuracy of recently commercialized wearable devices in heart rate (HR) measurement during cardiopulmonary exercise test (CPX) under gradual increase in exercise intensity, while wearable devices with HR monitors are reported to be less accurate in different exercise intensities. CPX was performed for patients with coronary artery disease (CAD). Twelve lead electrocardiograph (ECG) was the gold standard and Apple watch 7 (AW7), Galaxy watch 4 (GW4) and Bio Patch Mobicare 200 (MC200) were applied for comparison. Paired absolute difference (PAD), mean absolute percentage error (MAPE) and intraclass correlation coefficient (ICC) were evaluated for each device. Forty-four participants with CAD were included. All the devices showed MAPE under 2% and ICC above 0.9 in rest, exercise and recovery phases (MC200=0.999, GW4=0.997, AW7=0.998). When comparing exercise and recovery phase, PAD of MC200 and AW7 in recovery phase were significantly bigger than PAD of exercise phase (p<0.05). Although not significant, PAD of GW4 tended to be bigger in recovery phase, too. Also, when stratified by HR 20, ICC of all the devices were highest under HR of 100, and ICC decreased as HR increased. However, except for ICC of GW4 at HR above 160 (=0.867), all ICCs exceeded 0.9 indicating excellent accuracy. The HR measurement of the devices validated in this study shows a high concordance with the ECG device, so CAD patients may benefit from the devices during high-intensity exercise under conditions where HR is measured reliably.


DPPIV/CD26: a tumor suppressor or a marker of malignancy?
Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional protein with intrinsic peptidase activity that inactivates or degrades some bioactive peptides. It is the main cellular binding protein for ecto-adenosine deaminase and interacts with extracellular matrix proteins, besides participating in different signaling pathways. Due to these multiple functions, DPPIV/CD26 has been shown to be closely related to the tumor process. It has been reported that the progression of certain types of cancer is accompanied by a decrease in DPPIV/CD26 expression, and studies have shown that the malignant phenotype can be reverted when DPPIV/CD26 expression is induced in these cancer cells, characterizing this protein as a tumor suppressor. On the other hand, DPPIV/CD26 was described as a protein associated with invasion and metastatic spread, characterizing it as a marker of malignancy. Thus, this review explores the roles of DPPIV/CD26 expression in tumor progression in different types of cancer and demonstrates the importance of this protein as a promising therapeutic target and tumor biomarker.


Maternal mortality in a maternity hospital in Turkey.
To determine the leading causes of maternal mortality in a large maternity hospital and to define priorities regarding this subject throughout Turkey. Retrospective, institutional study among 100,531 live births between 1983 and 1992. Seventeen maternal deaths took place in this institution. Thus, the overall maternal mortality ratio was 16.9 per 100,000. The leading causes of maternal mortality were hemorrhage in seven (41.2%) and pulmonary embolism in six (35.3%) patients. The majority of deaths were observed in the 25-29 and 30-34 age groups and in patients with parity more than two. The relatively low figure of 16.9/100,000 for maternal mortality may be seen as a promising health index. However, obstetric hemorrhage is still the leading cause of this series. Pregnant women less than 20 years old and greater than 35 years old, and grand multiparous women as well as women with hypertension and heart disease are at high mortality risk. The observation of such cases demands further efforts for improved obstetric care in the hospital and throughout Turkey.


Recent ultrasound advancements for the manipulation of nanobiomaterials and nanoformulations for drug delivery.
Recent advances in ultrasound (US) have shown its great potential in biomedical applications as diagnostic and therapeutic tools. The coupling of US-assisted drug delivery systems with nanobiomaterials possessing tailor-made functions has been shown to remove the limitations of conventional drug delivery systems. The low-frequency US has significantly enhanced the targeted drug delivery effect and efficacy, reducing limitations posed by conventional treatments such as a limited therapeutic window. The acoustic cavitation effect induced by the US-mediated microbubbles (MBs) has been reported to replace drugs in certain acute diseases such as ischemic stroke. This review briefly discusses the US principles, with particular attention to the recent advancements in drug delivery applications. Furthermore, US-assisted drug delivery coupled with nanobiomaterials to treat different diseases (cancer, neurodegenerative disease, diabetes, thrombosis, and COVID-19) are discussed in detail. Finally, this review covers the future perspectives and challenges on the applications of US-mediated nanobiomaterials.


Decrease in salivary cortisol levels after glucocorticoid dose reduction in patients with adrenal insufficiency: A prospective proof-of-concept study.
Patients with adrenal insufficiency (AI) require lifelong glucocorticoid (GC) replacement therapy. Cortisol measurement in saliva is increasingly being used: we assessed salivary cortisol rhythm in outpatients with AI, to provide new insights regarding the management of GC treatment. Nineteen AI outpatients collected six saliva samples from awakening (Fa , before taking the morning GC therapy), during the day (F1.5 h , F6 h before the afternoon GC dose, F8.5 h , F12 h ) until bedtime (Fb ). We measured daily cortisol exposure by calculating the area under the curve (AUCFa→Fb ). Saliva samples were collected at baseline and one year after GG dose reduction (by at least 5 mg of hydrocortisone). Hydrocortisone equivalents decreased from median 25 mg/d (baseline, interquartile range IQR 20-27.5) to 15 mg/d (IQR 15-20, P < .01). As expected, we observed a reduction in both daily cortisol exposure (AUCFa→Fb 23 982 nmol·h/L, IQR 12 635-45 369, to 14 689 nmol·h/L, IQR 7168-25 378, P < .001) and salivary cortisol levels at F6 h (24.8 nmol/L, IQR 20.1-35.7, to 21 nmol/L, IQR 8.7-29.2, P < .05) and Fb (8.7 nmol/L, IQR 3.4-20.2, to 3.7 nmol/L, IQR 3.0-5.8, P < .05). None of the patients developed signs or symptoms consistent with AI after GC reduction. Median diastolic blood pressure (DPB) values fell from baseline to the end of follow-up (87.5 mm Hg, IQR 80-90, to 80 mm Hg, IQR 80-85, P < .05). The AUCFa→Fb of patients at baseline was above the reference value (90th percentile of controls) in 12 patients (60%); after the dosage reduction, 30% of patients normalized their daily cortisol exposure (AUCFa→Fb ). The reduction in GC treatment in patients with AI resulted in better control of daily cortisol rhythm, measured with salivary cortisol, and in an improvement of DPB. Further studies are needed to ascertain if salivary cortisol could be used as a biomarker to manage GC replacement therapy.


Intraventricular Hematoma Removal with Combined Drainage Techniques in Patients with High-Grade Subarachnoid Hemorrhage: A Surgical Technique.
To describe a surgical technique for removal of hematomas in the third ventricle in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH) and report our intraoperative observations and surgical and clinical outcomes. Ninety-four patients with high-grade aneurysmal subarachnoid hemorrhagic were included in the study. Prior to Sylvian dissection, a ventricular catheter was inserted as soon as possible. After surgical corridor opening and aneurysm clipping, the lamina terminalis (LT) was fenestrated. The free flow of isotonic solution from the back-side open syringe to the distal end of the catheter inside the third ventricle was allowed under gravitational force. The blood clot trapped in the third ventricle was removed through the aperture of the LT by propulsion of blood through the anterior movement of the solution. The procedure was continued until the clearance of solution was observed. The study population consisted of two groups, the combined surgical technique group and the control group, which included patients who underwent operation before the planned study, with 47 patients in each group. The Glasgow Coma, Hunt and Hess, and Fisher scales were used to determine the clinical and radiological severities of the cases. The Modified Rankin Scale was used to evaluate the surgical outcomes at presentation and the 6 < sup > th < /sup > and 12 < sup > th < /sup > postoperative months. Our reported surgical technique, which combines ventricular drainage and opening of the LT, will be useful for removing blood clots and blood breakdown products, and recirculating cerebrospinal fluid as much and as soon as possible in high-grade SAH patients with ventricular hemorrhage. Although combining these two well-known procedures as a novel technique does not have any reducing effect on mortality, it may have a significant reducing effect on hydrocephalus and shunt dependency.


Arrival to and location of Bufo woodhousei in the breeding pond: effect on the operational sex ratio.
Individual male and female Bufo woodhousei spent only two or three nights of the several week breeding season in the pond. In spite of the continual arriving and leaving of individuals the operational sex ratio (the number of females available to mate/number of males attempting to mate) varied little, either temporally across the breeding season or spatially between male groups in the pond. Male body size distributions also varied little between nights and between male groups.


Analyzing and Discussing Human Factors Affecting Surgical Patient Safety Using Innovative Technology: Creating a Safer Operating Culture.
Surgical errors often occur because of human factor-related issues. A medical data recorder (MDR) may be used to analyze human factors in the operating room. The aims of this study were to assess intraoperative safety threats and resilience support events by using an MDR and to identify frequently discussed safety and quality improvement issues during structured postoperative multidisciplinary debriefings using the MDR outcome report. In a cross-sectional study, 35 standard laparoscopic procedures were performed and recorded using the MDR. Outcome data were analyzed using the automated Systems Engineering Initiative for Patient Safety model. The video-assisted MDR outcome report reflects on safety threat and resilience support events (categories: person, tasks, tools and technology, psychical and external environment, and organization). Surgeries were debriefed by the entire team using this report. Qualitative data analysis was used to evaluate the debriefings. A mean (SD) of 52.5 (15.0) relevant events were identified per surgery. Both resilience support and safety threat events were most often related to the interaction between persons (272 of 360 versus 279 of 400). During the debriefings, communication failures (also category person) were the main topic of discussion. Patient safety threats identified by the MDR and discussed by the operating room team were most frequently related to communication, teamwork, and situational awareness. To create an even safer operating culture, educational and quality improvement initiatives should aim at training the entire operating team, as it contributes to a shared mental model of relevant safety issues.


Fermentation in 24-well plates is an efficient screening platform for filamentous fungi.
Fermentation by filamentous fungi in Erlenmeyer flasks is a favoured method for comparing different fermentation conditions. However, significant inter-flask variation often occurs when using Erlenmeyer flasks, which makes the comparison of fermentation product levels less reliable. We have investigated the use of a 24-well plate method for citric acid, ethanol and glycerol batch fermentation using the filamentous fungi Aspergillus carbonarius and compared the relative standard deviation (RSD) from sextuplicates obtained using Erlenmeyer flasks and 24-well plates. The production levels using the Erlenmeyer flasks showed a combined average RSD of 29%, which is two and a half-fold higher than what was measured using the 24-well plates showing an average RSD of 12%. We conclude that fermentation in 24-well plates is a more reliable screening method for metabolite production by filamentous fungi and possibly for screening metabolites in general. Fermentation studies with filamentous fungi and especially screening experiments often struggle with high inter-vessel variations in metabolite production. This study compares two different types of frequently used screening methods namely batch fermentation in Erlenmeyer flasks with batch fermentation in 24-well plates. The results demonstrate that the variance potentially can be reduced two and a half-fold using 24-well plates leading to improved resolution when testing the impact of varying fermentation parameters on product formation.


Standardizing Endoscopy Training: A Workshop for Endoscopy Educators.
Endoscopy education in the US traditionally follows the apprenticeship model, in which educators often have little formal training in education, and the acquisition of procedural skills by trainees relies heavily on procedure volume and learning by doing. A growing appreciation of the need to formally educate endoscopy trainers has led to the development of mandatory training curricula in other countries, but the implementation of such courses in the US has been limited. This 1-hour workshop aimed to provide educators the rationale and skills to offer a more standardized approach to procedural training. We implemented a 1-hour interactive workshop designed for both gastroenterology faculty and trainees. The four sections of the workshop focused on: (1) rationale for standardized approach, (2) verbal and physical preparation for training, (3) training using standardized language and avoidance of cognitive overload, and (4) providing feedback. Four interactive video cases followed by large-group discussion were included. A total of 13 gastroenterology faculty and trainees attended the workshop. Eight additional members of the gastroenterology faculty watched an online video of the workshop. Survey data revealed that the workshop was effective in helping faculty set goals with trainees (Mpre = 2.4, Mpost = 3.6), identify standardized language to use during endoscopy (Mpre = 3.1, Mpost = 3.8), and give feedback after sessions (Mpre = 3.4, Mpost = 4.1). A 1-hour lecture-based interactive workshop with video cases was an engaging and effective introduction to formal endoscopy education techniques. The format was easy to incorporate into faculty conferences and can help bridge the current gap in formal endoscopy faculty training.


[Surgical treatment of calcifying insertional Achilles tendinopathy via a lateral approach].
Reduction of pain and swelling over the Achilles tendon insertion while maintaining function. Strong, intolerable pain over the Achilles tendon insertion with chronic, calcifying insertional tendinopathy that does not respond to non-operative treatment over a minimum of 6 months. Chronic wounds or severe circulatory deficits at the foot or ankle, irradiating or projected pain, complex regional pain syndrome (CRPS). The intratendinous heel spur is resected via a lateral approach. The superior surface of the calcaneal tuberosity is trimmed by resection of the dorsal heel spur with the oscillating saw. A second osteotomy at the medial edge of the tuberosity extends to the insertion of the plantaris tendon. With the third osteotomy, the Haglund deformity is resected. At the resulting area with cancellous bone, the Achilles tendon is reinserted with a suture anchor. A ventral plastic splint in 20° plantar flexion is worn for a week. Full weight-bearing is allowed in a walking boot with 4 cm heel lift for 6 weeks. The heel lift is then gradually reduced for another 2 weeks. After 8 weeks only an elastic wedge of 1 cm is worn. Physical therapy (isometric exercises) starts in the boot and is intensified after removal of the boot. Seven of 12 patients treated with that technique for calcifying insertional Achilles tendinopathy (58%) stated being pain free according to the Likert scale, while the remaining 5 patients (42%) reported a "substantial improvement". The VISA‑A score averaged 84 of 100 points. Postoperative complications have not been observed.


Systematic review and meta-analysis of the incidence of incisional hernia at the site of stoma closure.
The incidence of incisional hernias at the site of stoma closure is surprisingly unclear. A review of the current literature was undertaken to determine how commonly this complication may occur and to assess the quality of evidence available. A systematic review was performed to identify studies reporting the incidence of incisional hernia after closure of an ileostomy or colostomy. Studies including children (<16 years old) and studies in which >10% of the total number were trauma patients were excluded. Thirty-four studies provided outcomes for 2,729 closed stomas. Median follow-up time was 36 months but was only described in seven studies. Closure of loop ileostomies was the most commonly performed procedure (48%). The overall reported hernia rate was 7%, but with a wide range among studies (0-48%). Most studies based their hernia rates on retrospective clinical findings only. A separate analysis of three studies that were specifically designed to assess for stoma site hernias found the clinical hernia rate to be 30% (28/93) and the combined clinical/radiological hernia rate to be 35% (33/93). From 11 studies reporting reoperation rates, 51% of patients who developed a hernia required a surgical repair (34/66). There was a lower risk of hernia following reversal of ileostomy versus colostomy (odds ratio 0.28, 95% confidence interval 0.12-0.65). One in three patients may develop a hernia after stoma closure, and around half of hernias that are detected require repair. Risk of hernia is greater after colostomy closure than after ileostomy closure. Clinical measures to reduce the development of these hernias warrant consideration.


Isolation of genes encoding photoreceptor-specific proteins by immunoscreening with antibodies directed against purified blowfly rhabdoms.
The proteins which perform and regulate key steps in phototransduction are assumed to be localized in the rhabdomeric membrane of invertebrate photoreceptor cells. We have employed antibodies raised against rhabdoms purified from blowfly eyes in order to isolate copy deoxyribonucleic acid (cDNA) clones encoding proteins that are required in the phototransduction machinery. By immunoscreening a Calliphora retinal cDNA library, we obtained clones of genes coding for five different proteins. As revealed by partial cDNA sequence analysis, three of these genes represent the Calliphora homologs of Drosophila trp, inaC and InaD, while the other two displayed no homology to known genes. Northern blot analysis confirmed that trp, inaC and InaD transcripts were present in RNA isolated from the retina, but not in RNA isolated from brain or thorax. Specific antibodies directed against trp, inaC and InaD protein were raised using recombinantly expressed proteins or synthetic peptides. Western blot analyses revealed that trp, inaC and InaD protein are specifically associated with the rhabdomeral photoreceptor membrane. Extraction of membranes with buffers of different ionic strengths suggested that the trp gene product is an integral membrane protein, whilst the inaC and InaD gene products are peripherally bound membrane proteins. This demonstrates that the immunoscreening approach used here can be successfully applied to isolate genes that code for either integral or peripheral photoreceptor membrane proteins.


Detection of tumours with nuclear magnetic resonance spectroscopy of plasma.
A systematic investigation of cancer detection by water-suppressed nuclear magnetic resonance (NMR) of plasma is reported. With additional suppression of lactate, a statistically significant difference between the linewidths of the methylene group signal of patients with untreated cancer (average linewidth 26.9 +/- 3.9 Hz) and normal controls (average linewidth 31.1 +/- 4.9 Hz) has been found. However, overlap was found between these two groups. It is shown that recognition of malignancy could be improved by consideration of the different relations of the linewidths on the content of serum triglycerides and the observation of a shoulder at the high field side of the methylene signal. Preliminary investigations on lipid fractions separated by ultracentrifugation (UC) indicate a connection of the appearance of the high field shoulder and the HDL lipoprotein.


Semiquantifying regional cerebral blood flow by 123I-amphetamine (IMP) SPECT in cerebrovascular disorders: correlations with CBF indices by 133Xe inhalation method.
To examine the capacity of detecting regional cerebral blood flow (rCBF) disturbances in stroke, measurements with 133Xe inhalation and 123I-amphetamine (IMP) SPECT were performed within 1-2 days in 19 patients. IMP SPECT images in transverse sections consisting of outer and inner areas were correlated with 32 regions of 133Xe rCBF. 133Xe rCBF was assessed by ISI, CBF15, and F1. Inter hemispheric ratio correlation showed outer IMP uptake correlated better with 133Xe CBF indices than the inner one. With higher ratios of 133Xe rCBF. IMP uptake ratios were variable, suggesting less usefulness of this parameter in evaluation of mild ischemia. Values of IMP in outer regional hypo and hyperemic areas correlated better with those of 133Xe rCBF than the inner ones. In regional ratios of hypo and hyperemic areas from hemispheric mean, outer IMP uptake correlated with 133Xe CBF indices, reflecting regional disturbances of fast clearing tissue perfusion. Regression lines between ratios in 133Xe CBF and IMP uptake were located below one to one correlation, and dissociated more for hyperemic regions. IMP SPECT correlated better with 133Xe rCBF for tissues with reduced perfusion but underestimated hyperemic regions as measured with the 133Xe method. The data suggest outer cerebral IMP uptake evaluated by SPECT could reflect flow disturbances in the brain cortex.


Verbal abuse during pregnancy increases frequency of newborn hearing screening referral: The Japan Environment and Children's Study.
Verbal abuse during pregnancy has a greater impact than physical and sexual violence on the incidence of postnatal depression and maternal abuse behavior towards their children. In addition, exposure of children (aged 12 months to adolescence) to verbal abuse from their parents exerts an adverse impact to the children's auditory function. However, the effect of verbal abuse during pregnancy on fetal auditory function has not yet been thoroughly investigated. The objective of the study was to examine the relationship between intimate partner verbal abuse during pregnancy and newborn hearing screening (NHS) referral, which indicates immature or impaired auditory function. The Japan Environment and Children's Study is an ongoing nationwide population-based birth-cohort study designed to determine environmental factors during and after pregnancy that affect the development, health, or wellbeing of children. Pregnant women living in 15 areas of Japan were recruited between January 2011 and March 2014. Multiple imputation for missing data was performed, followed by multiple logistic regression using 16 confounding variables. Of 104,102 records in the dataset, 79,985 mother-infant pairs submitted complete data for questions related to verbal and physical abuse and the results of NHS. Of 79,985 pregnant women, 10,786 (13.5%) experienced verbal abuse and 978 (1.2%) experienced physical abuse. Of 79,985 newborns, 787 (0.98%) received a NHS referral. Verbal abuse was significantly associated with NHS referral (adjusted odds ratio: 1.44; 95% confidence interval: 1.05-1.98). Verbal abuse should be avoided during pregnancy to preserve the newborn's auditory function.


The influence of artificial saliva on the cleaning force of interdental rubber picks: an in-vitro comparison.
The familiar aids for interdental cleaning such as dental floss or interdental brushes (IDB) are often associated with difficult handling or an increased potential for trauma. Interdental picks (IRP), which have no metal core and silicone flaps instead of nylon brushes, offer the alternative. However, in-vitro studies found a lower cleaning effectiveness combined with higher forces for cleaning compared with conventional IDBs. The aim of this in-vitro study was to measure the experimental cleaning forces (ECF) using IRP with versus without an artificial saliva (AS; GUM Hydral, Sunstar Suisse SA, Etoy, Switzerland). The test set-up was developed to investigate the cleaning of 3D-printed interdental area (IDR) mimicking human teeth (Form 2, Formlabs Sommerville, MA, USA) under standardized conditions. Three different morphologies (isosceles triangle, convex, concave) and three different sizes (1.0 mm,1.1 mm,1.3 mm) were used. Two different IRPs (GUM Soft-picks Advanced: SPA versus GUM Soft-picks Advanced Plus: SPA+, Sunstar Suisse SA, Etoy, Switzerland) in three sizes (small, regular, large), were used with versus without AS. ECF during ten cleaning cycles were recorded by a load cell [N]. Using AS leaded to significant lower values for ECF than without (1.04 ± 0.66 N versus 1.97 ± 1.01 N, p < 0.001). In general, a lower ECF was recorded for convex IDR compared to isosceles triangle and concave morphologies (p < 0.001) as well as for gap sizes of 1.3 mm compared to the smaller sizes (p < 0.001). For SPA+ we found significantly higher force values than for SPA (1.67 ± 0.93 N versus 1.31 ± 0.97 N, p < 0.001) independent of the use of AS. Within the study´s in-vitro limitations, we found AS reduced ECF of IRPs by half and allowed using larger diameters interdentally, which could be associated with (1) a higher cleaning effectiveness and (2) a higher acceptance e.g. of patients with dry mouth. This has to be confirmed by further clinical investigations.


Spondyloepiphyseal dysplasia tarda: four cases from two families.
Spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) is an autosomal recessively inherited skeletal dysplasia. We present four patients (three patients-a brother and a sister and their third cousin-in a family and one patient in another family) with SEDT-PA. All patients had short stature and stubby hands and feet. Their radiographs revealed typical changes for SEDT-PA including platyspondyly, severe osteopenia and dysplastic bone changes. Physical therapy and exercises were performed to all patients in order to decrease in pain and increase or at least maintain joint motion and mobility. Symptomatic relief was achieved in all patients for about a couple of months. The major clinical importance of this rather rare disorder is its similarity to juvenile idiopathic arthritis which has rather different treatment protocol.


Bisoprolol reversed small conductance calcium-activated potassium channel (SK) remodeling in a volume-overload rat model.
A recent study indicated that apamin-sensitive current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) density significantly increased in heart failure and led to recurrent spontaneous ventricular fibrillation. While the underlying molecular correlation with SK channels is still undetermined, we hypothesized that they are remodeled in HF and that bisoprolol could reverse the remodeling. Volume-overload models were created on male Sprague-Dawley rats by producing an abdominal arteriovenous fistula. Confocal microscopy, quantitative real-time PCR, and western blot were performed to investigate the expression of SK channels and observe the influence of β-blocker bisoprolol on the expression of SK channels I KAS, and the effect of bisoprolol on I KAS and the sensitivity of I KAS to [Ca(2+)]i at single isolated cells were also explored using whole-cell patch clamp techniques. SK channels were remodeled in HF rats, displaying the significant increase of SK1 and SK3 channel expression. After the treatment of HF rats with bisoprolol, the expression of SK1 and SK3 channels was significantly downregulated, and bisoprolol effectively downregulated I KAS density as well as the sensitivity of I KAS to [Ca(2+)]i. Our data indicated that the expression of SK1 and SK3 increased in HF. Bisoprolol effectively attenuated the change and downregulated I KAS density as well as the sensitivity of I KAS to [Ca(2+)]i.


Concise Asymmetric Construction of C2 -symmetric 1,9-Diarylnonanoids Using a Hypervalent Silicon Complex: Total Synthesis of (-)-Ericanone.
By using a phosphine oxide-catalyzed enantioselective double aldol reaction, we achieved the concise construction of C2 -symmetric 1,9-diarylnonanoids, enabling the synthesis of (-)-ericanone from p-hydroxybenzaldehyde in 6 steps with 65 % overall yield. The enantioselective double aldol reaction is useful for establishing C2 -symmetric 1,9-diaryl-3,7-dihydroxy-5-nonanones with a single operation. Furthermore, the use of o-nosyl-protected p-hydroxybenzaldehyde and a 4,4'-disubstituted BINAP dioxide catalyst dramatically improved the reactivity and selectivity in the double aldol reaction, enabling the total synthesis of (-)-ericanone with high yield and with excellent enantiopurity.


Transforming Direct Care Jobs, Reimagining Long-Term Services and Supports.
The diverse array of individuals who receive long-term services and supports share one common experience, which is the need for assistance with personal care and/or other daily activities. The direct care workers (including nursing assistants, home health aides, and personal care aides) who provide this assistance play a critical role in keeping individuals safe, supporting their health and well-being, and helping prevent adverse outcomes. Yet despite decades of research, advocacy, and incremental policy and practice reform, direct care workers remain inadequately compensated, supported, and respected. Long-standing direct care job quality concerns are linked to high turnover and job vacancy rates in this workforce, which in turn compromise the availability and quality of essential care for older adults and people with disabilities-which has never been more evident than during the COVID-19 pandemic. This special article makes the case for transforming direct care jobs and stabilizing this workforce as a centerpiece of efforts to reimagine long-term services and supports system in the United States, as a public health priority, and as a social justice imperative. Drawing on research evidence and examples from the field, the article demonstrates that a strong, stable direct care workforce requires: a competitive wage and adequate employment benefits for direct care workers; updated training standards and delivery systems that prepare these workers to meet increasingly complex care needs across settings, while also enhancing career mobility and workforce flexibility; investment in well-trained frontline supervisors and peer mentors to help direct care workers navigate their challenging roles; and an elevated position for direct care workers in relation to the interdisciplinary care team. The article concludes by highlighting federal and state policy opportunities to achieve direct care job transformation, as well as discussing research and practice implications.


The incidence and features of Delphian lymph node involvement in patients with papillary thyroid carcinoma.
In papillary thyroid cancer patients, the extent of dissection is still a matter of debate. Evaluating Delphian lymph nodes (DLNs) during the surgery has been speculated as a valuable tool to determine the extent of dissection. Herein, we aimed to evaluate the incidence and features of DLNs involvement in patients with papillary thyroid carcinoma. We conducted this cross-sectional study among surgical cases of papillary thyroid cancer. Patients were divided based on their DLNs involvement status. Their age, gender, location of the mass, lymphatic involvement, tumor size, tumor characteristics, pathology report, and operation note features were compared between the two groups. Definitive pathology slides of the patients were evaluated regarding DLN features. Of the 61 patients (mean age: 38.2 ± 12.0), 45 (73.8%) were females. In 13 (21.3%) patients, DLNs involvement was reported. A statistically significant relationship was noted between DLNs involvement and other lymph nodes' involvement on the same side of the mass (P < 0.001), the opposite side (P = 0.041), and also central lymph nodes (P < 0.001). Vascular invasion was also significantly higher among patients with DLNs involvement (P = 0.012). Since DLNs involvement is significantly associated with extensive nodal involvement, intraoperative evaluation of DLNs is recommended to establish the extent to which dissection should be performed.


Challenges and opportunities for the future of recreational boat scrapping: The Spanish case.
Recreational boating is a leisure and sports activity that has aroused growing interest among users, tourists, and the general public. However, in the last decade, a problem has arisen concerning the abandonment of recreational boats. It is a problem that has become even more acute in times of economic recession. It is, therefore, necessary to find an urgent solution in order to reduce potential environmental risks. This work aims to analyze the state of the question through bibliometrics to know which topics are trending and contrast these findings with a Delphi analysis. The main results focus on the need for greater agility in the court adjudication process and the need for a specific legal framework for the scrapping of recreational craft. In conclusion, it is vital to integrate the circular economy into shipbuilding and scrapping processes to ensure the sustainability of the sector and the environment.


PRMT4 promotes ferroptosis to aggravate doxorubicin-induced cardiomyopathy via inhibition of the Nrf2/GPX4 pathway.
Doxorubicin (DOX), a commonly used antitumor agent, is often accompanied by its dosage-dependent cardiotoxicity, which incorporates ferroptosis in its pathogenesis. Protein arginine methyltransferase 4 (PRMT4) is a transcription regulator involved in the modulation of oxidative stress and autophagy, but its role in DOX-induced cardiomyopathy (DIC) and ferroptosis remains elusive. Herein, we aimed to investigate the involvement and the underlying mechanisms of PRMT4 in the pathogenesis of DIC. Our present study revealed that the expression level of PRMT4 was markedly decreased in DOX-treated cardiomyocytes. Interestingly, it is noted that PRMT4 overexpression accelerated ferroptosis to aggravate DIC, while its gene disruption or pharmaceutical inhibition exhibited the opposite effect. Mechanistically, our observation demonstrated that PRMT4 interacted with the nuclear factor erythroid 2-related factor 2 (Nrf2) to promote its enzymatic methylation, which restricted the nuclear translocation of Nrf2 and subsequently suppressed the transcription of glutathione peroxidase 4 (GPX4). Importantly, the detrimental role of PRMT4 in DOX-induced cardiomyocyte ferroptosis was abolished by Nrf2 activation or Fer-1 administration. Collectively, our data reveal that PRMT4 inhibits Nrf2/GPX4 signaling to accelerate ferroptosis in DIC, suggesting that targeting PRMT4 may present as a potential preventive strategy against the development of DIC.


Crystal structure and cap binding analysis of the methyltransferase of langat virus.
Tick-borne encephalitis virus (TBEV) is a major dangerous human pathogen, as TBEV infection can cause serious illness that can lead to irreversible neurological sequelae and even death. Langat virus (LGTV), a member of the tick-borne encephalitis virus (TBEV) serogroup, belongs to the family Flaviviridae, genus Flavivirus. Its nonstructural protein 5 (NS5) protein contains a methyltransferase (MTase) domain that can methylate RNA cap structures, which is critical for viral replication. We determined the structure of LGTV NS5 methyltransferase bound to S-adenosyl-L-homocysteine (SAH) at a 1.70 Å resolution. Sequence analysis and structural comparison of homologous MTases suggests that folds and structures are closely conserved throughout Flavivirus species and play important roles. This study provides the key structural information on LGTV MTase and the foundation for research on antiviral drugs targeting LGTV MTase.


Impact of Ionic Strength of Carrier Liquid on Recovery in Flow Field-Flow Fractionation.
Asymmetrical flow field-flow fractionation (AF4) and hollow-fiber flow field-flow fractionation (HF5) are techniques widely used in analytical, industrial and biological analyses. The main problem in all AF4 and HF5 analyses is sample loss due to analyte-membrane interactions. In this work the impact of liquid carrier composition on latex nanoparticles (NPs) separation in water and two different concentrations of NH4NO3 was studied. In AF4, a constant trend of decreasing the size of 60 and 121.9 nm particles induced by the ionic strength of the carrier liquid has been observed. In contrast, an agglomeration effect of the biggest 356 nm particles was observed when increasing ionic strength, which induced a significant drop of recovery to 35%. H5F provides better resolution and intensified peaks of NPs, but careful optimisation of system parameters is mandatory to obtain good separation.


Metabolic inhibition and electrical properties of type-1-like cortical astrocytes.
Type-1-like cortical mouse astrocytes were studied in homogeneous cultures. Membrane input resistance and membrane potential were measured during drug-induced inhibition of glycolysis (sodium fluoride), mitochondrial respiration (antimycin-a) and Na+/K+ pump activity (ouabain). It was found that the electrical properties of the astrocytes recovered after a 60 min period with inhibited glycolysis or mitochondrial respiration, exhibiting only small reversible depolarizations. A 60 min period of high K(+)-induced depolarization, of cell swelling or of Na+/K+ pump inhibition does not lead to irreversible changes. Total block of energy metabolism, however, causes (1) a large depolarization, which is mainly mediated by external calcium, and (2) a 10-fold increase in input resistance, suggestive of an uncoupling of gap junctions. After an exposure period ranging between 45 and 60 min these conditions lead to irreversible damage. This damage appears to be independent of extracellular calcium and the degree of depolarization and to be specifically mediated by events occurring after the 60-min period of inhibited cell metabolism, that is during the recovery period.


Stigma and discrimination against people living with HIV by health care providers in Egypt.
HIV/AIDS has been recently increasingly observed in developing countries including Egypt. This study aimed to explore stigma and discrimination attitudes of health care providers (HCPs) in Egypt, as elimination of stigma in healthcare settings is a priority to improve case detection and management. A Google form questionnaire using the validated Arabic version of Health Care Provider HIV/AIDS Stigma Scale (HPASS) was sent to physicians and nurses of Ministry of health (MOH) hospitals and University hospitals in 10 randomly selected Governorates in Egypt. Data was collected from July to August, 2022 from 1577 physicians and 787 nurses. Bivariate and multivariable linear regression analyses were used to identify the predictors of the stigmatizing attitude of HCPs towards People living with HIV (PLHIV). The majority of HCPs had worries about contracting HIV infection from their patients (75.8% of physicians and 77% of nurses). They believed that protective measures are not good enough to protect them from getting infected (73.9% of physicians and 74.7% of nurses). About half of the participants had worries about the safety of performing blood investigations to PLHIV (54% of physicians and 59.9% of nurses). Less than half of HCPs believed they have the right to refuse providing care to patients to protect themselves (44.6% of physicians and 50.1% of nurses). Only 10.5% of physicians and 11.9% of nurses have previously refused to provide health care to PLHIV. There was a significantly higher mean score of prejudice and stereotype among nurses compared to physicians (prejudice; 27.34 ± 7.88 vs 26.17 ± 7.5, stereotype; 18.54 ± 4.61 vs 16.43 ± 5.21, for nurses and physicians, respectively). Less years of physicians' experience (B = -0.10, p < 0.01) and rural residence (B = 1.48, p < 0.05) were significantly associated with higher prejudice score while having lower qualification (B = -1.47, p < 0.001) was significantly associated with higher stereotype score. Standards of practice should be developed to adjust the services and prepare HCPs to provide medical care free from stigma and discrimination against PLHIV. Improving knowledge of HCPs regarding the methods of transmission of HIV, the use of infection control measures and the emotional factors shaping lives of PLHIV should be targeted through updated training programs. More concern should be directed to young providers in the training programs.


Vertebroplasty increases compression of adjacent IVDs and vertebrae in osteoporotic spines.
Approximately 25% of vertebroplasty patients experience subsequent fractures within 1 year of treatment, and vertebrae adjacent to the cemented level are up to three times more likely to fracture than those further away. The increased risk of adjacent fractures postaugmentation raises concerns that treatment of osteoporotic compression fractures with vertebroplasty may negatively impact spine biomechanics. To quantify the biomechanical effects of vertebroplasty on adjacent intervertebral discs (IVDs) and vertebral bodies (VBs). A biomechanics study was conducted using cadaveric thoracolumbar spinal columns from elderly women (age range, 51-98 years). Five level motion segments (T11-L3) were assigned to a vertebroplasty treated or untreated control group (n=10/group) such that bone mineral density (BMD), trabecular architecture, and age were similar between groups. Compression fractures were created in the L1 vertebra of all specimens, and polymethylmethacrylate bone cement was injected into the fractured vertebra of vertebroplasty specimens. All spine segments underwent cyclic axial compression for 115,000 cycles. Microcomputed tomography imaging was performed before and after cyclic loading to quantify compression in adjacent VBs and IVDs. Cyclic loading increased strains 3% on average in the vertebroplasty group when compared with controls after 115,000 cycles. This global strain manifested locally as approximately fourfold more compression in the superior VB (T12) and two- to fourfold higher axial and circumferential deformations in the superior IVD (T12-L1) of vertebroplasty-treated specimens when compared with untreated controls. Low BMD and high cement fill were significant factors that explained the increased strain in the vertebroplasty-treated group. These data indicate that vertebroplasty alters spine biomechanics resulting in increased compression of adjacent VB and IVD in severely osteoporotic women and may be the basis for clinical reports of adjacent fractures after vertebroplasty.


LncRNA PWRN2 promotes polycystic ovary syndrome progression via epigenetically reducing ATRX by recruiting LSD1.
Long non-coding RNA has been shown to mediate the progression of polycystic ovary syndrome (PCOS). However, the role and mechanism of Prader-Willi region nonprotein coding RNA 2 (PWRN2) in PCOS progression remain unclear. In our study, Sprague-Dawley rat was injected with dehydroepiandrosterone to mimic PCOS rat models. HE staining was used to assess the number of benign granular cells, and serum insulin and hormone levels were detected by ELISA kit. The expression of PWRN2 was examined by qRT-PCR. Ovarian granulosa cells (GCs) proliferation and apoptosis were examined by CCK-8 assay and flow cytometry. The protein levels of apoptosis markers and Alpha thalassemia retardation syndrome X-linked (ATRX) were determined by western blot. The interaction between lysine-specific demethylase 1 (LSD1) and PWRN2 or ATRX was confirmed by RIP and ChIP assay. Our data showed that PWRN2 was upregulated and ATRX was downregulated in the ovarium tissues and serum of PCOS rat. PWRN2 knockdown promoted GCs proliferation and inhibited apoptosis. In the mechanism, PWRN2 inhibited ATRX transcription by binding with LSD1. In addition, downregulation of ATRX also eliminated the effect of sh-PWRN2 on GCs growth. In conclusion, our data suggested that PWRN2 might restrain GCs growth to promote PCOS progression, which was achieved by binding with LSD1 to inhibit ATRX transcription.


Identification of transferrin receptors in reticulocytes.
Experiments were performed to obtain definitive evidence for the presence of membrane receptors for transferrin on reticulocytes. Rabbit reticulocytes were incubated with 125I-labelled rabbit transferrin. The transferrin taken up by the cells was solubilized using the non-ionic detergent, Teric 12A9 (polyoxyethylene (n=9) dodecyl alcohol). The soluble extracts of the cells were examined by gel filtration and a transferrin-binding moiety of approximate molecular weight 275 000 was identified. This binding moiety was found only in reticulocytes, not in mature erythrocytes. The membrane component could bind only transferrin and not the other plasma proteins studied. Only transferrin could displace bound transferrin from the complex. Rabbit transferrin was bound more strongly than human transferrin. The binding of transferrin to the component was shown to be reversible and saturable. It is concluded from these studies that the transferrin binding component identified in the reticulocyte stroma is a true physiological receptor for transferrin.


Homeopathically prepared gibberellic acid and barley seed germination.
The potentisation process by which homeopathic preparations are produced raises the concern that these medicines have placebo effects only, since they theoretically no longer contain active molecules of the diluted substance. Plant models offer a method of examining the efficacy of homeopathically prepared solutions. This study examined the effects of homeopathically prepared gibberellic acid (HGA3) on the germination performance of barley (Hordeum vulgare L.) seeds. The effect of HGA3 (4-200 cH) on seed germination rate and seedling development was compared to that of the most commonly used form of gibberellic acid (GA3), 0.5 g l(-1), and control (distilled water). The extent and type of response was dependent on the vigour level of the seedlot. Treating seeds from three vigour groups in HGA3 consistently resulted in larger seedlings. High-vigour seeds treated with HGA3 4, 30 and 200 cH germinated faster, and roots of medium-vigour seedlots treated in HGA3 15 cH were longer. Biphasic effects of HGA3 were also demonstrated. As a plant model, germinating barley seeds successfully demonstrated the ability of HGA3 to produce a biological response.


Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism.
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.