Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte.
The frequency of normal murine B lymphocytes initiating growth in diluted suspension cultures in the presence of a B cell mitogen, such as lipopolysaccharide, can be increased approximately 10(4) fold by the addition of 2 X 10(6) normal thymus cells per ml. This increase in the frequency of growing cells by thymus cells can also be observed with X63-AG8 myeloma tumor cells secreting IgG1. Thus thymus cells may not contribute growth-stimulating factors, but may supply growth-supporting factors. Culture medium and plastic dishes can be conditioned by preincubation with thymus cells for a day after which the thymus cells may be omitted from further culture for maximal B cell growth. Irradiation of thymus cell abolishes their growth-enhancing properties. Thymus cells can be syngeneic and allogeneic with the growing B cells. The frequency of growing LPS-reactive, normal B cells in spleen of 6-8 week old C3H/Tif mice was determined by limiting dilution analysis to be one of three splenic B cells. With this limiting dilution analysis, it was also shown that the cloning efficiency of XB3-AG8 myeloma tumor cells in suspension culture in the presence of thymus cells is practically 100%. Analysis of the growth kinetics of single clones of LPS-reactive, normal B cells shown that these B cells divide every 18 hr. Within the first 126 hr of growth, every B cell in the clone divides, and every dividing B cell in this clone secretes sufficient immonoglobulin to form a hemolytic plaque. The conditions of in vitro suspension cultures of murine B lymphocytes are therefore perfect to the extent that every B cell capable of growth will grow as a single clone.


The road we must take: multidisciplinary team science.
Translational research is acknowledged to be complex and to require a diverse skill set. Many organizations, particularly academic institutions, have invested in educational programs, facilities, and enhanced resources to encourage translational research. Critically needed, however, is an emphasis on creating and sustaining multidisciplinary research teams. It is through the power of many and a diverse approach to our health care problems that we will realize lasting solutions.


Mechanistic connections between mitochondrial biology and regulated cell death.
The ancient, dynamic, and multifaceted functions of the mitochondrial network are essential for organismal homeostasis and contribute to numerous human diseases. As central hubs for metabolism, ion transport, and multiple macromolecular synthesis pathways, mitochondria establish and control extensive signaling networks to ensure cellular survival. In this review, we explore how these same mitochondrial functions also participate in the control of regulated cell death (RCD). We discuss the complementary essential mitochondrial functions as compartments that participate in the production and presentation of key molecules and platforms that actively enable, initiate, and execute RCD.


Analysis of tasks performed by certified ophthalmic medical personnel.
Proper delegation of routine tasks to trained personnel might increase cost efficiency by freeing the physician to concentrate on the medical and judgmental aspects of patient care. In ophthalmology, certified ophthalmic medical personnel (OMP) assist the physician by performing many tasks. The Joint Commission on Allied Health Personnel in Ophthalmology (JCAHPO) selected 77 specific tasks performed by OMP and conducted a task analysis survey to determine the importance of these tasks to ophthalmic practice. Individual and practice demographics were surveyed simultaneously to compare the effect of individual and practice differences on task importance. Certified OMP and their sponsoring ophthalmologists were surveyed independently. Each group was asked to rate the importance of the 77 selected tasks using a five-point scale of importance. Importance ratings from each survey group were used independently to generate a rank order listing of tasks. Only 3 of the 77 tasks differed significantly in importance between ophthalmologists and OMP. The same five tasks were rated as most important by both groups, whereas the second group of the five most important tasks varied only by +/-4. The similarity in task importance rankings indicates a common perception between ophthalmologists and OMP concerning the role played by OMP in ophthalmic eye care.


Recombinant antibodies derived from laser captured single plasma cells of multiple sclerosis brain identified phage peptides which may be used as tools for characterizing intrathecal IgG response.
Oligoclonal bands and increased IgG antibody levels can be detected in the cerebrospinal fluid in vast majority of patients with Multiple Sclerosis (MS). However, the antigenic specificity of oligoclonal IgG has yet to be determined. Using laser capture microdissection, we isolated single CD38+ plasma cells from lesion areas in two autopsy MS brains, and generated three recombinant antibodies (rAbs) from clonally expanded plasma cells. Panning phage-displayed random peptide libraries was carried out to determine peptide antigen specificities of these MS brain rAbs. We identified 25 high affinity phage peptides from which 5 peptides are unique. Database searches revealed that they shared sequence homologies with Epstein-Barr nuclear antigens 4 and 6, as well as with other viral proteins. Significantly, these peptides were recognized by intrathecal IgG and oligoclonal IgG bands in other MS patients. Our results demonstrate that functional recombinant antibodies can be generated from clonally expanded plasma cells in MS brain lesions by laser capture microdissection, and that these MS brain rAbs have the potential for determining the targets of intrathecal IgG and oligoclonal bands.


Surgery for recurrent goiter: complication rate and role of the thyroid-stimulating hormone-suppressive therapy after the first operation.
This report examines outcomes in our series of patients who underwent surgery for recurrent goiter to assess the efficacy of thyroid-stimulating hormone (TSH)-suppressive therapy after the first less than total thyroidectomy. A further outcome was to understand whether redo surgery was burdened with a higher rate of complications. We evaluated 214 patients undergoing a completion thyroidectomy for recurrent goiter who had received, as their first surgery, a bilateral subtotal thyroidectomy. After the first operation, 84 patients were given TSH-suppressive therapy with levothyroxine, 32 were treated with antithyroid drugs, and 92 did not receive any suppressive treatment but only a substitutive therapy. The 84 patients who received levothyroxine at a suppressive dosage (group A) were compared with 92 patients who did not receive levothyroxine or received it only at substitutive dosage (group B). We further compared the complication rate of a similar group of 175 patients who had undergone a primary thyroidectomy. The average age at intervention for relapse in group A patients was significantly lower than that of group B patients: 54.18 vs 60.8 years (p < 0.001). The average interval between the first intervention and the intervention for relapse was significantly shorter in group A than in group B: 24 vs 27 years (p = 0.03). After the operation, temporary hypoparathyroidism occurred in 37.7 % of patients and definitive hypoparathyroidism in 7.2 %. Our results clearly show that the interval between the two surgical interventions was significantly reduced in patients undergoing TSH-suppressive therapy with levothyroxine. The incidence of hypoparathyroidism dramatically increased.


A sensitive liquid chromatography-mass spectrometry method for simultaneous determination of three diterpenoid esters from Euphorbia lathyris L. in rat plasma.
A selective and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed for the simultaneous determination of Euphorbia factor L(1), Euphorbia factor L(2) and Euphorbia factor L(3) from Euphorbiae semen in rat plasma. Larotaxel was added to a 200 μL plasma sample as the internal standard (IS). The plasma sample was extracted by 2 mL ether and separated on an Elite C(18) column (150 mm × 4.6 mm, 5 μm) with the mobile phase of methanol-water performing gradient elution within 11.0 min. All the three analytes were detected in the selected ion monitoring (SIM) mode with positive electrospray ionization. The calibration curves were linear in the range of 2.0-200 ng/mL and the lower limits of quantification (LLOQ) were 2.0 ng/mL for all the three analytes. The intra-day and inter-day precisions were all within 8.6% and 14.6% for the three analytes, while the accuracy was less than 9.7% and 7.5%, respectively. The validated method was firstly and successfully applied to the pharmacokinetic study of Euphorbia factor L(1), Euphorbia factor L(2) and Euphorbia factor L(3) from Euphorbiae semen after oral administration in rat plasma.


Author Correction: A systematic literature review on the European, African and Amerindian genetic ancestry components on Brazilian health outcomes.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Aquaculture activities influencing the generation of geosmin and 2-methylisoborneol: a case study in the aquaculture regions of Hongze Lake, China.
Contamination by odor substances such as geosmin (GSM) and 2-methylisoborneol (2-MIB) was examined in the cultured water from aquaculture farming in the region of the Hongze Lake in 2022, and some factors influencing residual levels of them in the water were analyzed. Geographically, high concentrations of GSM were located mainly in the north and northeast culture areas of the lake, while those of 2-MIB were found in the northeast and southwest. Analysis of the water in the enclosure culture revealed significant differences in the concentrations of GSM and 2-MIB among the cultured species. The mean concentrations of GSM in culture water were ranked in the order: crab > the four major Chinese carps > silver and bighead carp, and silver and bighead carp > crab > the four major Chinese carps for 2-MIB. The concentration of GSM was significantly higher at 38.99 ± 18.93 ng/L in crab culture water compared to other fish culture water. Significant differences were observed in GSM concentrations between crab enclosure culture and pond culture, while 2-MIB levels were comparable. These findings suggest that cultural management practices significantly affect the generation of odor substances. The taste and odor (T&O) assessment revealed that the residual levels of GSM and 2-MIB in most samples were below the odor threshold concentrations (OTCs), although high levels of GSM and 2-MIB in all water bodies were at 30.9% and 27.5%, respectively. Compared with the corresponding data from other places and the regulation guidelines of Japan, USA, and China, the region in the Hongze Lake is generally classified as a slightly T&O area, capable of supporting the aquaculture production scale.


Regulated suppression of NF-κB throughout pregnancy maintains a favourable cytokine environment necessary for pregnancy success.
Th1 immune responses are suppressed in pregnancy, but the temporal regulation and the mechanism(s) underlying this immune alteration are unknown. We assessed the expression of Th1 cytokines IFNγ, IL-2 and TNFα in response to stimulation in isolated T-cells from pregnant women throughout gestation. Using flow cytometry we demonstrated an early and sustained reduction in IFNγ and IL-2 production in CD3+ T-cells, but TNFα levels are not reduced until the third trimester. We assessed the expression of NF-κB and T-bet, transcription factors that play a central role in Th1 immune responses, throughout pregnancy. In isolated T-cells levels of available p65 were suppressed early in pregnancy, but T-bet expression was suppressed only in the third trimester. In contrast to p65, T-bet expression was transcriptionally regulated, with diminished T-bet mRNA in third-trimester samples. Re-expression of p65 in T-cells from third-trimester pregnant women resulted in an induction of T-bet expression in response to PMA stimulation and a concomitant increase in the production of IL-2 and IFNγ. The suppressive effect of pregnancy was ameliorated as early as 72h post-partum when p65 levels returned to normal as did the level of inducible IFNγ and IL-2. TNFα levels in post-partum women were significantly increased relative to non-pregnant controls. The pregnancy-specific suppression of p65 and subsequent loss of cytokine production suggest that this transcription factor acts specifically to regulate the cytokine environment that is required for pregnancy success.


Injection therapy for bleeding peptic ulcers.
In the treatment of bleeding peptic ulcers, the concept of dual therapy combining a second modality to epinephrine injection is theoretically appealing. The addition of a sclerosant has not been shown to be beneficial. Early evidence suggests that adding contact thermocoagulation of a thrombogenic agent improves patient outcome.


Clinical Presentation, Management, and Outcomes of Patients With Brain Abscess due to Nocardia Species.
Nocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess. Retrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020. Overall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica, followed by Nocardia wallacei and Nocardia cyriacigeorgica. Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection. Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control.


Engineering Philosophy: Theories of Technology, German Idealism, and Social Order in High-Industrial Germany.
During the so-called "Second Industrial Revolution," engineers were constituting themselves as a new social and professional group, and found themselves in often fierce competition with existing elites-the military, the nobility, and educated bourgeois mandarins-whose roots went back to medieval and early modern pre-industrial social orders. During that same time, engineers also discovered the discipline of philosophy: as a means to express their intellectual and social agendas, and to theorize technology and its relationship to art, history, culture, philosophy, and the state. This article analyzes engineers' own philosophical writings about technology as well as the institutions in which they composed them in 1910s and 1920s Germany. It emphasizes engineers' contributions to well-known discourses founded by canonical philosophers, the role of preindustrial economies and their imagination in such philosophies, and the role of both the history and the philosophy of technology in engineers' desire for upward social mobility.


Referral guidelines for suspected cancer of the head and neck.
To identify the impact of referral guidelines for head and neck cancer on the economics and effectiveness of the delivery of care. A retrospective review of the literature was performed to examine the current referral guidelines and referral models that have impacted the delivery of care. Advances in technology and changes in the diagnostic work up of head and neck cancer require that common symptoms and presentations of head and neck cancer are made available to primary care physicians to improve the expeditious referral of head and neck cancer patients. Physician awareness and symptom guidelines may prove effective in expediting the care of patients with head and neck cancer.


Role of Lipids in Phosphine Resistant Stored-Grain Insect Pests Tribolium castaneum and Rhyzopertha dominica.
Insects rely on lipids as an energy source to perform various activities, such as growth, flight, diapause, and metamorphosis. This study evaluated the role of lipids in phosphine resistance by stored-grain insects. Phosphine resistant and susceptible strains of the two main stored-grain insects, Tribolium castaneum and Rhyzopertha dominica, were analyzed using liquid chromatography-mass spectroscopy (LC-MS) to determine their lipid contents. Phosphine resistant strains of both species had a higher amount of lipids than susceptible stains. Significant variance ratios between the resistant and susceptible strains of T. castaneum were observed for glycerolipids (1.13- to 53.10-fold) and phospholipids (1.05- to 20.00-fold). Significant variance ratios between the resistant and susceptible strains of R. dominica for glycerolipids were 1.04- to 31.50-fold and for phospholipids were 1.04- to 10.10-fold. Glycerolipids are reservoirs to face the long-term energy shortage. Phospholipids act as a barrier to isolate the cells from the surrounding environment and allow each cell to perform its specific function. Thus, lipids offer a consistent energy source for the resistant insect to survive under the stress of phosphine fumigation and provide a suitable environment to protect the mitochondria from phosphine. Hence, it was proposed through this study that the lipid content of phosphine-resistant and phosphine-susceptible strains of T. castaneum and R. dominica could play an important role in the resistance of phosphine.


A tryptophan-rich peptide acts as a transcription activation domain.
Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures. We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide per se retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W5) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W7), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W7 mediates transcription activation through interacting with the general transcription factor, TFIIB. Since W7 shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.


Evaluation of sacral rhomboid dimensions to predict contracted pelvis: a pilot study of Indian primigravidae.
This prospective study aimed to evaluate dimensions of sacral rhomboid (quadrangular area at lower back) as predictors of Contracted pelvis (CP). In 300 uncomplicated primigravidae after 37 weeks gestation, transverse and vertical diagonal (TD and VD) of sacral rhomboid were recorded. Post- delivery, patients fell into two groups: Normal Deliveries (group 1) and CP (group 2, i.e., LSCS for contracted pelvis, instrumental delivery for Non Progress of Labor (NPOL) or birth mishaps). Analysis was done with SPSS version 10.5 and cross tabulation. Rhomboid dimensions were smaller in CP group (P value 0.003 and 0.012. On univariate analysis, 10th percentile cutoff of TD was the most significant risk factor with Odds ratio of 7.5 (95% CI 3.5-16.2). VD and height below 10th percentile had Odds ratio of 2.7 (95% CI 1.2-6.1) and 2.99 (95% CI 1.2-7.3), respectively. Both dimensions of sacral rhomboid below 10th percentile increased risk of CP by 13 times (OR 13, 95% CI 3.5-48.6) and detected 2 out of 3 at risk women. Smaller dimensions of sacral rhomboid are promising screening parameter for contracted pelvis which can be used in community to pick up high risk primigravidae.


Fracture of the femoral alignment stem of a hip resurfacing arthroplasty. A case report.
Metal-on-metal hip resurfacing arthroplasty has become increasingly popular for the treatment of osteoarthritis in a younger patient population. While the initial complication of femoral neck fracture is being addressed, we describe a fracture of the femoral alignment stem in a component two years from the primary procedure.


Analysis of the impact of controlled release formulations on oral drug absorption, gut wall metabolism and relative bioavailability of CYP3A substrates using a physiologically-based pharmacokinetic model.
Controlled release (CR) formulations are usually designed to achieve similar exposure (AUC) levels as the marketed immediate release (IR) formulation. However, the AUC is often lower following CR compared to IR formulations. There are a few exceptions when the CR formulations have shown higher AUC. This study investigated the impact of CR formulations on oral drug absorption and CYP3A4-mediated gut wall metabolism. A review of the current literature on relative bioavailability (Frel) between CR and IR formulations of CYP3A substrates was conducted. This was followed by a systematic analysis to assess the impact of the release characteristics and the drug-specific factors (including metabolism and permeability) on oral bioavailability employing a physiologically-based pharmacokinetic (PBPK) modelling and simulation approach. From the literature review, only three CYP3A4 substrates showed higher Frel when formulated as CR. Several scenarios were investigated using the PBPK approach; in most of them, the oral absorption of CR formulations was lower as compared to the IR formulations. However, for highly permeable compounds that were CYP3A4 substrates the reduction in absorption was compensated by an increase in the fraction that escapes from first pass metabolism in the gut wall (FG), where the magnitude was dependent on CYP3A4 affinity. The systematic simulations of various interplays between different parameters demonstrated that BCS class 1 highly-cleared CYP3A4 substrates can display up to 220% higher relative bioavailability when formulated as CR compared to IR, in agreement with the observed data collected from the literature. The results and methodology of this study can be employed during the formulation development process in order to optimize drug absorption, especially for CYP3A4 substrates.


Studies on the ultrastructure, histochemistry and cytochemistry of the uninfected digestive gland of Bithynia tentaculata (Mollusca: Gastropoda) and on the ultrastructure of this host organ in snails infected with larval digeneans.
The structure and function of the digestive gland of the gastropod mollusc, Bithynia tentaculata, was investigated using ultrastructural, histochemical, and cytochemical techniques. The digestive gland was shown to be composed of two main cell types, the "digestive" cells and "secretory" cells. The digestive cells appeared to be concerned with the absorption and digestion of nutrients, while secretory cells produced digestive enzymes and calcareous concretions. Undifferentiated cells were scattered between these two main cell types. The pathological effects of larval digeneans on the digestive gland were also investigated, at the ultrastructural level. In such infected snails the digestive gland appeared to be degenerating. The significance of this tissue destruction was briefly discussed.


Investigation of retardation effects on the titanium dioxide photodegradation system.
The photocatalytic bleaching of dyes using TiO2 has appeared promising in laboratory studies, but little attention has been focused on whether other species such as might be found in wastewater have a deleterious effect on the photobleaching. This study describes the effects that result from the presence of ionic species, organic solvents and humic substances on the photobleaching of several dyes. The manner in which the photobleaching was affected by the presence of adventitious materials was carefully examined with an eye toward elucidating the mechanistic origin of the loss of the photochemical efficiency in the reaction. The overall retardation effects can be attributed to the combination of light attenuation, inhibition and competition effects.


Comparison of the prognostic value of different skeletal muscle radiodensity parameters in endometrial cancer.
Recent data have shown that dividing skeletal muscle (SM) into sub-ranges of radiodensity can improve the prediction of short-term outcomes in the oncology setting. We aim to investigate whether the skeletal muscle mass, when divided into sub-ranges of low or high-radiodensity, improves the prediction of short-term survival in endometrial cancer (EC) patients when compared to average muscle attenuation and to the overall skeletal muscle radiodensity. EC patients who had computed tomography (CT) images available within 30 days before treatment were enrolled in this retrospective cohort (n = 232). CT images at the third lumbar vertebra (L3) were used to assess overall skeletal muscle index (SMI). Then we divided SMI into sub-ranges of radiation attenuation: low-radiodensity skeletal muscle index (LRSMI) and high-radiodensity skeletal muscle index (HRSMI). The average muscle radiation attenuation was also assessed. Low SMI was defined when SMI was <38.9 cm2/m2. One-year survival was evaluated by Kaplan-Meier method and Cox Regression. Sarcopenia was found in 25.8% of the patients. Roughly 80% of the patients in the highest quartile of LRSMI were obese. All the skeletal muscle parameters were significantly associated with shorter 1-year survival, LRSMI presented a trend for significance in the adjusted model. When the SM parameters were additionally adjusted for low SMI, only HRSMI and LRSMI remained in the model as early-mortality predictors. Classifying the skeletal muscle into sub-ranges of radiodensity have an additional value than using the average muscle attenuation of the overall skeletal muscle area and should be exploited in further studies.


Dorsal Dupuytren's disease causing a swan-neck deformity.
A previously undescribed lesion of Dupuytren's disease is presented. An oblique cord coursed parallel to the oblique retinacular ligament of Landsmeer, but inserted proximal to the proximal interphalangeal joint, tethering the central slip and radial lateral band across the intervening transverse retinacular ligament. Contraction of this cord caused a rigid swan-neck deformity. Excision of the cord resulted in complete resolution of the deformity and a full range of motion in the affected digit.


Benthic primary production during emersion: In situ measurements and potential primary production in the Seine Estuary (English Channel, France).
A two year survey of benthic primary production during periods of emersion was performed on two stations of an intertidal mudflat (a muddy-sand station and a muddy station) in the Seine Estuary (English Channel, France). The goals of this study were to investigate the seasonal variations of metabolism, to estimate daily potential primary production variation at the annual scale and to estimate the annual potential primary production of the mudflat. Primary production and respiration were estimated by in situ measurements of carbon dioxide fluxes. Chlorophyll a concentration exhibited a great variability on both locations. Gross community production ranged from ca. 0 to 77 mg C m(-2) h(-1) at the muddy-sand location and from ca. 0 to 122 mg C m(-2) h(-1) at the muddy location. Community respiration showed a seasonal trend following temperature variations (up to 28.51 mg C m(-2) h(-1) in the muddy-sand and up to 23.40 mg C m(-2) h(-1) in the mud). Daily potential primary production was calculated, according to seasonal variations of photosynthetic parameters calculated using three photosynthesis versus irradiance curves obtained for the muddy location. The annual gross community primary production was 135 g C m(-2) yr(-1), leading to a low autotrophic annual budget, considering an annual community respiration of 110 g C m(-2) yr(-1).


COVID_SCREENET: COVID-19 Screening in Chest Radiography Images Using Deep Transfer Stacking.
Infectious diseases are highly contagious due to rapid transmission and very challenging to diagnose in the early stage. Artificial Intelligence and Machine Learning now become a strategic weapon in assisting infectious disease prevention, rapid-response in diagnosis, surveillance, and management. In this paper, a bifold COVID_SCREENET architecture is introduced for providing COVID-19 screening solutions using Chest Radiography (CR) images. Transfer learning using nine pre-trained ImageNet models to extract the features of Normal, Pneumonia, and COVID-19 images is adapted in the first fold and classified using baseline Convolutional Neural Network (CNN). A Modified Stacked Ensemble Learning (MSEL) is proposed in the second fold by stacking the top five pre-trained models, and then the predictions resulted. Experimentation is carried out in two folds: In first fold, open-source samples are considered and in second fold 2216 real-time samples collected from Tamilnadu Government Hospitals, India, and the screening results for COVID data is 100% accurate in both the cases. The proposed approach is also validated and blind reviewed with the help of two radiologists at Thanjavur Medical College & Hospitals by collecting 2216 chest X-ray images between the month of April and May. Based on the reports, the measures are calculated for COVID_SCREENET and it showed 100% accuracy in performing multi-class classification.


Sliding-end-labelling. A method to avoid artifacts in nucleosome positioning.
A method, termed 'sliding-end-labelling', has been devised to avoid a frequent artifact in nucleosome positioning by indirect end labelling, namely the appearing of DNA fragments originated by two nuclease cuts, one of them lying within the region covered by the probe. The method is applied to the nucleosome positioning in the yeast SUC2 gene for invertase.


Association Between ART Adherence and Mental Health: Results from a National HIV Sero-Behavioural Survey in South Africa.
This paper assesses the levels of antiretroviral treatment (ART) adherence and mental health distress among study participants in a national behavioural HIV-sero prevalence study South Africa. The study was a cross-sectional population-based multi-stage stratified cluster random survey, (SABSSM V, 2017). Structured questionnaires were used to collect information on socio-demographics, HIV knowledge, perceptions, HIV testing and HIV treatment history. Study participants were tested for HIV infection, antiretroviral use, viral suppression, and ART drug resistance. A total of 2155 PLHIV aged 15 years or older who were on ART were included in the study. Incidence of either moderate or severe mental health distress was 19.7%. Self-reported ART adherence among study participants with no, mild, moderate, or severe mental distress was 82%, 83%, 86% and 78%, respectively. The adjusted odds ratio for ART non-adherence was 0.58 (95% CI 0.24; 1.40) for mild mental distress, 0.82 (95% CI 0.35; 1.91) for moderate mental distress and 2.19 (95% CI 1.14; 4.19) for severe mental distress groups compared to the no mental health distress group. The other factors that were associated with ART non-adherence in adjusted models included education level, alcohol use and province/region of residence. The study revealed that mental health remains a challenge to ART adherence in South Africa. To improve ART adherence, HIV continuum of care programs should include screening for mental health among people living with HIV.


Metabolic Syndrome, Cognitive Impairment and the Role of Diet: A Narrative Review.
This narrative review presents the association between metabolic syndrome (MetS), along with its components, and cognition-related disorders, as well as the potential reversal role of diet against cognitive impairment by modulating MetS. An electronic research in Medline (Pubmed) and Scopus was conducted. MetS and cognitive decline share common cardiometabolic pathways as MetS components can trigger cognitive impairment. On the other side, the risk factors for both MetS and cognitive impairment can be reduced by optimizing the nutritional intake. Clinical manifestations such as dyslipidemia, hypertension, diabetes and increased central body adiposity are nutrition-related risk factors present during the prodromal period before cognitive impairment. The Mediterranean dietary pattern stands among the most discussed predominantly plant-based diets in relation to cardiometabolic disorders that may prevent dementia, Alzheimer's disease and other cognition-related disorders. In addition, accumulating evidence suggests that the consumption of specific dietary food groups as a part of the overall diet can improve cognitive outcomes, maybe due to their involvement in cardiometabolic paths. Early MetS detection may be helpful to prevent or delay cognitive decline. Moreover, this review highlights the importance of healthy nutritional habits to reverse such conditions and the urgency of early lifestyle interventions.


Cleft palate patients--the social work approach.
From birth to maturity, the needs of cleft lip and cleft palate patients change. For such patients, fixed teams of specialists headed by a surgeon may not be the best answer. The authors outline theclinicl characteristics of both deformities and show how social workers are uniquely equipped to coordinate a changing constellation of helpers in an adaptable form of long-term treatment.


Separation and Size Determination of DNA over a 10-,200 kbp Range.
Some types of pulsed-field gel electrophoresis (PFGE), including CHEF (contour-clamped homogeneous electric field), give straight lanes and excellent separations of a wide range of DNA sizes on one gel (ref. 1 and Chapters 1 , 2 , 5 - 7 ). Here conditions are described for the separation of DNA in the l0-,200-kbp size range by CHEF. CHEF resolution in this range exceeds that of many commonly used size standards. Production and use of a size standard giving a 10-kbp ladder in the l0-,200-kbp range (2) is described and examples of separations are shown.


Prevalence of hookworm infection and its association with low haematocrit among resettlers in Gambela, Ethiopia.
A cross-sectional survey of hookworm infection and haematocrit (HCT) levels was conducted in 7 resettled villages and 3 indigenous villages on sample populations selected by two-stage random sampling. Of 614 resettled persons and 187 indigenous persons, 65.5% and 60.4% respectively were infected with hookworm. Mean haematocrits for 664 resettled and 222 indigenous persons were 33.1% and 35.2%, respectively. A significant association (odds ratio = 2.65) was found between low haematocrit level (below the median for the sample population) and hookworm infection in the resettled population. Suggestions are made on the need for further studies and intervention programmes.


Mechanical properties of anodized coatings over molten aluminum alloy.
A method to measure interfacial mechanical properties at high temperatures and in a controlled atmosphere has been developed to study anodized aluminum surface coatings at temperatures where the interior aluminum alloy is molten. This is the first time that the coating strength has been studied under these conditions. We have investigated the effects of ambient atmosphere, temperature, and surface finish on coating strength for samples of aluminum alloy 7075. Surprisingly, the effective Young's modulus or strength of the coating when tested in air was twice as high as when samples were tested in an inert nitrogen or argon atmosphere. Additionally, the effective Young's modulus of the anodized coating increased with temperature in an air atmosphere but was independent of temperature in an inert atmosphere. The effect of surface finish was also examined. Sandblasting the surface prior to anodization was found to increase the strength of the anodized coating with the greatest enhancement noted for a nitrogen atmosphere. Machining marks were not found to significantly affect the strength.


Alpha-tocopherol levels in brain are not altered in Parkinson's disease.
alpha-Tocopherol (vitamin E) levels in normal brain were lower in the cerebellum than in the cerebral cortex or basal ganglia. There was no difference in alpha-tocopherol levels in the cerebellum, basal ganglia, or cerebral cortex between control subjects and patients with Parkinson's disease.


Comparison between osteonecrosis of the humeral and femoral heads - epidemiological analysis of the surgical trend using the nationwide claims database of the republic of Korea.
The humeral head is the second most common site of osteonecrosis, after the femoral head. However, compared to osteonecrosis of the femoral head (ONFH), epidemiological information on osteonecrosis of the humeral head (ONHH) is scarce. We hypothesised that different biomechanical properties of the shoulder from the hip joint might present different epidemiological characteristics of ONHH from those of the ONFH. To evaluate epidemiological differences, we compared trends in the surgical treatment of ONHH and ONFH using the nationwide medical claims database of the Republic of Korea (ROK). We analysed epidemiological data from the Health Insurance Review and Assessment (HIRA) database of the ROK between 2008 and 2018. HIRA database contains almost all medical information in an anonymised form, including demographics, diagnoses, and types of surgical procedures, generated through healthcare practices in ROK. The annual incidence rates of ONHH and ONFH were calculated based on the total number of the general population. Demographics, annual incidence, and the proportion of post-traumatic osteonecrosis and surgical procedures were compared according to the anatomical site and the affected year. The total number of patients treated for ONHH and ONFH during the study period was 1,028 and 66,260, respectively. Although the incidence of ONHH increased, it is a relatively rare disease compared to ONFH. ONHH occurred more frequently in females, while ONFH occurred predominantly in male patients (p < 0.001). Surgical treatment for ONHH was most frequently performed in older patients (63.7%), whereas middle-aged patients had the largest proportion of ONFH (48.9%, p < 0.001). The proportion of post-traumatic osteonecrosis was significantly higher in the ONHH (5.1%) than in the ONFH (1.9%, p < 0.001). Arthroplasty was performed more frequently in the ONHH (96.0%) than in the ONFH (92.9%, p < 0.001). Despite the anatomical similarities between the hip and shoulder joints, the different biomechanical properties, such as weight-bearing functions, might cause epidemiological differences between ONHH and ONFH.


Halide permeation in wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels.
Permeation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl channels by halide ions was studied in stably transfected Chinese hamster ovary cells by using the patch clamp technique. In cell-attached patches with a high Cl pipette solution, the CFTR channel displayed outwardly rectifying currents and had a conductance near the membrane potential of 6.0 pS at 22 degrees C or 8.7 pS at 37 degrees C. The current-voltage relationship became linear when patches were excised into symmetrical, -tris(hydroxymethyl)methyl-2-aminomethane sulfonate (TES)-buffered solutions. Under these conditions, conductance increased from 7.0 pS at 22 degrees C to 10.9 pS at 37 degrees C. The conductance at 22 degrees C was approximately 1.0 pS higher when TES and HEPES were omitted from the solution, suggesting weak, voltage-independent block by pH buffers. The relationship between conductance and Cl activity was hyperbolic and well fitted by a Michaelis-Menten-type function having a of approximately 38 mM and maximum conductance of 10 pS at 22 degrees C. Dilution potentials measured with NaCl gradients indicated high anion selectivity (P/P = 0.003-0.028). Biionic reversal potentials measured immediately after exposure of the cytoplasmic side to various test anions indicated P(1.8) > P(1. 3) > P(1.0) > P(0.17), consistent with a "weak field strength" selectivity site. The same sequence was obtained for external halides, although inward F flow was not observed. Iodide currents were protocol dependent and became blocked after 1-2 min. This coincided with a large shift in the (extrapolated) reversal potential to values indicating a greatly reduced I/Cl permeability ratio (P/P< 0.4). The switch to low I permeability was enhanced at potentials that favored Cl entry into the pore and was not observed in the R347D mutant, which is thought to lack an anion binding site involved in multi-ion pore behavior. Interactions between Cl and I ions may influence I permeation and be responsible for the wide range of P/P ratios that have been reported for the CFTR channel. The low P/P ratio usually reported for CFTR only occurred after entry into an altered permeability state and thus may not be comparable with permeability ratios for other anions, which are obtained in the absence of iodide. We propose that CFTR displays a "weak field strength" anion selectivity sequence.


Electrical and magnetic anisotropies in van der Waals multiferroic CuCrP2S6.
Multiferroic materials have great potential in non-volatile devices for low-power and ultra-high density information storage, owing to their unique characteristic of coexisting ferroelectric and ferromagnetic orders. The effective manipulation of their intrinsic anisotropy makes it promising to control multiple degrees of the storage "medium". Here, we have discovered intriguing in-plane electrical and magnetic anisotropies in van der Waals (vdW) multiferroic CuCrP2S6. The uniaxial anisotropies of current rectifications, magnetic properties and magnon modes are demonstrated and manipulated by electric direction/polarity, temperature variation and magnetic field. More important, we have discovered the spin-flop transition corresponding to specific resonance modes, and determined the anisotropy parameters by consistent model fittings and theoretical calculations. Our work provides in-depth investigation and quantitative analysis of electrical and magnetic anisotropies with the same easy axis in vdW multiferroics, which will stimulate potential device applications of artificial bionic synapses, multi-terminal spintronic chips and magnetoelectric devices.


Age differences in the pulmonary and vascular pathophysiologic processes after long-term real-time exposure to particulate matter in rats.
Existing experimental data do not sufficiently explain which pathophysiologic processes are involved in different age of rats exposed to long-term particulate matter. This study explored the pulmonary and cardiovascular effects of long-term PM2.5 and PM10 exposure in juvenile, adult and senescent rats. Tail cuff plethysmography, whole-body plethysmographic system, myograph, enzyme-linked immunosorbent assay, and inductively coupled plasma-mass spectrometry were used to detect the blood pressure, lung function, endothelium-dependent relaxation, inflammatory cytokines and heavy metals, respectively. The exposure time was from November, 2017 to October, 2018, and the average concentrations of PM2.5 and PM10 were 78.7 and 128.2 μg/m3, respectively. Compared with the filtered air group, the body weight and survival rate in PM2.5 and PM10 exposure group were significantly decreased, and the survival rate of senescent exposed rats was only 30%. PM2.5 and PM10 exposure increased the blood pressure, elevated the levels of serum and bronchoalveolar lavage fluid inflammatory factors, and the senescent exposed rats showed an earlier rising trend in blood pressure and inflammatory factors than those of juvenile and adult exposed rats. Long-term PM2.5 and PM10 exposure could destroy intrapulmonary and small resistance arteries endothelial function, causing vasodilation disorders. PM2.5 and PM10 exposure caused particulate matter to accumulate in the lungs. Additionally, PM2.5 and PM10 exposure could also cause accumulation of cadmium (Cd) and lead in the liver, and chromium and Cd in the kidney. In conclusion, ambient PM2.5 and PM10 exposure induced particulate matter to accumulate in the body, caused severe pulmonary and vascular disorders, and demonstrated age-associated differences.


Molecular identification of the microbial diversity in two sequencing batch reactors with activated sludge.
The diversity of the microbial community was identified in two lab-scale, ideally mixed sequencing batch reactors which were run for 115 days. One of the reactors was intermittently aerated (2 h aerobically/2 h anaerobically) whereas the other was consistently aerated. The amount of biomass as dry matter, the degradation of organic carbon determined by chemical oxygen demand and nitrogen-degradation activity were followed over the operation of the two reactors and did not show significant differences between the two approaches at the end of the experiment. At this point, the composition of the microbial community was determined by a terminal restriction fragment length polymorphism approach using multiple restriction enzymes by which organisms were retrieved to the lowest taxonomic level. The microbial composition was then significantly different. The species richness was at least five-fold higher in the intermittently aerated reactor than in the permanently kept aerobic approach which is in line with the observation that ecosystem disturbances result in higher diversity.


Solvent modulation of the structural heterogeneity in FeIII myoglobin samples: a low temperature EPR investigation.
High spin FeIII myoglobin samples in solutions with different solvent composition have been investigated at low temperature by Electron Paramagnetic Resonance spectroscopy. The g = 6 line of the spectrum has been analyzed in terms of a distribution of the two crystal field parameters delta 1 and delta 2. By means of the Angular Overlap Method, it has been shown that these distributions entail, in turn, a distribution in the iron-heme displacement along the normal to the heme-plane. The spread in this iron-heme distance, which can be connected with the binding action of the proximal histidine, has been proposed as a quantitative measurement of the structural heterogeneity (conformational substate landscape) displayed by the protein molecules. The results point out, moreover, that the solvent composition can affect the structural heterogeneity of the protein system. In particular, addition of glycerol, ethylene glycol and sucrose yields a significant reduction in the spread of the iron-heme displacement, while the presence of ammonium sulfate induces a change in the average position of the iron in the heme-plane. The role played by the solvent in the structure and dynamics of the protein, in connection also with the conformational substate distribution, is discussed.


The Post-insertion Method for the Preparation of PEGylated Liposomes.
PEGylation is a crucial process for decorating the surface of liposomes with polyethylene glycol (PEG) for clinical use. This process endows the liposomes extended circulation time and improved stability in vivo. The post-insertion method is one of the well-established techniques for PEGylation. This method requires only one-step incubation to accomplish the transfer of PEGylated lipids from PEGylated lipid-based micelles into the membranes of preformed liposomes.


Structure and NLO properties of halogen (F, Cl) substituted formic acid dimers.
In this work, using ab initio and density functional theory (DFT) methods halogen substituted formic acid (FA) dimer is studied. The dimer stability is due to the hydrogen bonds, either conventional (OH⋯O, OH⋯F, OH⋯Cl) or non-conventional (CH⋯O, CH⋯F, CH⋯Cl). Among all the dimers, trans-trans form is more stable than the trans-cis, and cis-cis form. Basis set extrapolated counterpoise corrected interaction energy results for the FA dimer are in excellent agreement with BSSE corrected MP2 interaction energy. Symmetry Adopted Perturbation Theory (SAPT) analysis reveals that the electrostatic effect plays a dominant role in stabilization among the dimers with maximum interaction energy. Chlorine substituted FA dimer has high hyperpolarizability, which makes them excellent candidate for nonlinear optical materials (NLO). The halogen substituted formic acid dimers have higher stability and polarizability value than the unsubstituted formic acid dimer. The hyperpolarizability values depend on the geometrical structures of halogenated formic acid dimers than the type of hydrogen bonds. The small excitation energy and HOMO-LUMO gap in the halogenated formic acid dimer has led to the strong nonlinear optical response. The depolarization ratio and Rayleigh scattering increases in formic acid dimer after the halogen atom substitution.


Reduced hypothalamic thermosensitivity following intraventricular injection of pyrogen in conscious rabbits.
Hypothalamic temperature thresholds for vasodilatory and respiratory reactions were determined before and after i.c.v. injection of pyrogen in rabbits. During the rising phase of fever the increases in the hypothalamic thresholds for vasodilatory and respiratory reactions differed from those found in the pre-pyrogen preoptic anterior hypothalamic area (POAH) heating by 2.1 +/- 0.2 degrees C and 1.89 +/- 0.31 degrees C, respectively. During the plateau phase of fever the threshold for vasodilatory reaction was further increased (by 0.7 +/- 0.23 degrees C), whereas that for panting remained at the same level. It is concluded that pyrogen exerts a depressive action on POAH thermosensitivity.


Is Human Papillomavirus and Helicobacter pylori Related in Gastric Lesions?
Human papillomavirus (HPV), the causative agent of cervical cancer, is also suggested as a risk factor for gastric adenocarcinoma. Many infectious agents besides Helicobacter pylori have been associated with gastritis. The aim of this study was to investigate HPV DNA and genotyping HPV type 16 DNA in gastric adenocarcinoma and Helicobacter pylori gastritis cases. A hundred and six gastric adenocarcinoma and Helicobacter pylori gastritis samples and 26 controls were included. After deparaffinization by xylene, DNA extraction was performed by the phenol-chloroform-isoamyl alcohol method and 106 samples were studied with a G6PDH control kit (Eurogentec, Seraing, Belgium). Fifty-three adenocarcinoma and 43 Helicobacter pylori samples were thought to have enough tissue and were studied for HPV DNA. HPV types other than 16 and HPV type 16 DNA were detected by Real Time PCR using the L1 region. Amplifications of MY09/11 products were done by GP5+/GP6+ primers and Cyanine-5 labeled HPV DNA and HPV 16 DNA specific probe in Light Cycler 2.0 (Roche Diagnostics, Germany) device. Among gastric adenocarcinoma and Helicobacter pylori gastritis samples, 20/53 (38%) and 18/43 (41.8%) were HPV DNA positive, respectively. Five (19.2%) of 26 controls were HPV DNA positive. Our 38% positive result in the gastric carcinoma group is in concordance with previous reports. This is the first study revealing the HPV-H. pylori relationship in gastritis cases and we concluded that with regard to the nearly three-fold higher HPV DNA (41.8%) in gastritis cases compared to controls, Helicobacter pylori positive cases should also be evaluated in favor of HPV in the gastritis group.


Biomechanical design framework for prosthetic feet: Experimentally validated non-linear finite element procedure.
Performance evaluation of prosthetic feet during their design is typically performed experimentally, which may be time and cost intensive. This work presents a first-of-its-kind application of a numerical procedure for the a priori determination of various stance phase biomechanical parameters of a prosthetic foot, such as its roll-over characteristics, centre of pressure trajectory, ankle flexion moment arm and ankle range of motion, to aid in its design. The numerical procedure is based on finite element analysis, which includes geometric, material and contact non-linearity. Boundary conditions emulating the rocker-based inverted pendulum model were employed to evaluate the biomechanical parameters. The finite element model was validated by employing an inverted pendulum-based apparatus using the structurally complex Ottobock Solid Ankle Cushioned Heel (SACH) prosthetic foot as the test device. A comparison of the numerical and experimental results showed low magnitude of errors. For example, the percentage error of the radius of curvature of the roll-over shape was ~0.1%. The differences found appear to be clinically insignificant, which substantiates the reliability of the model. The proposed numerical model can be employed to obtain detailed a priori insights into the biomechanical parameters influencing a prosthetic foot's characteristics during gait, which can better inform the design, analysis and prescription of prosthetic feet.


The potential of ex vivo lung perfusion on improving organ quality and ameliorating ischemia reperfusion injury.
Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status. In this work, we review potential mechanisms of EVLP that may attenuate IRI and improve organ quality. Moreover, we dissect experimental treatment approaches during EVLP that may further attenuate inflammatory events deriving from tissue ischemia, shear forces or allograft rejection associated with LuTx.


Treatment of refractory localized pulmonary nocardiosis caused by Nocardia mexicana with a combination of medication and surgery.
Pulmonary nocardiosis is a rare disease that is often difficult to cure because of its tendency to recur. Here, we report a case of refractory localized pulmonary nocardiosis caused by Nocardia mexicana. A 60-year-old Japanese woman had recurring pulmonary nocardiosis four times previously and each time she was treated with antibiotics for a sufficient duration; nevertheless, the disease continued to recur, probably because of resistance to antibiotics. As a fifth treatment, we performed middle lobe resection and pre- and post-operative antimicrobial therapy for 6 months. The combination of medication and surgery was useful for treating refractory localized pulmonary nocardiosis.


Ureteral diverticulum.
Twelve patients with ureteral diverticula encountered in a 25-year period are presented. Although the potential for the development of such lesions may arise from congenital maldevelopments, we believe that in the natural history much depends on the abnormal hydrodynamic states that may be acquired in childhood or adult life. Ureteral diverticula are frequently asymptomatic, requiring no treatment.


Two-year results of renal transplantation in kidney recipients from > or = 65-year-old deceased donors: a French region experience.
The use of elderly deceased donors requires refining criteria for both the donor and the recipient. This report attempted to identify parameters susceptible to further improvement. This retrospective multicenter study analyzed the outcomes of kidney recipients from 15 consecutive elderly deceased donors in the south French region (IR9). Donors were 65 to 74 years old. Mean creatinine clearance was 80 mL/min/1.73 m(2). The donor risk factors for allograft dysfunction were stroke, hypertension, cardiovascular disease, cardiac death, smoking, arrhythmia, and diabetes. The recipients were 35 to 70 years old. The median cold ischemia time was 24 hours. Four patients (16%) suffered delayed graft function (DGF). Three recipients (12%) died within the first 2 months after transplantation. The postoperative complications (29%) were 2 renal artery thromboses, 4 renal artery stenoses, and 1 toe ischemia. Two years after transplantation, their mean serum creatinine was 157 micromol/L. The patient and graft survivals were 88% and 70%, respectively. These results seemed worse than those reported in the literature, but it was a small cohort and a new experience. DGF is probably linked to improvable management to reduce cold ischemia time. The elevated rate of surgical complications might be related to a lack of experience in donor and recipient evaluations. Kidney transplantation from elderly donors requires an efficient organization and an accurate evaluation of both donor renal function and recipient cardiovascular state.


A naturally occurring mutation in ATP synthase subunit c is associated with increased damage following hypoxia/reoxygenation in STEMI patients.
Preclinical models of ischemia/reperfusion injury (RI) demonstrate the deleterious effects of permeability transition pore complex (PTPC) opening in the first minutes upon revascularization of the occluded vessel. The ATP synthase c subunit (Csub) influences PTPC activity in cells, thus impacting tissue injury. A conserved glycine-rich domain in Csub is classified as critical because, when mutated, it modifies ATP synthase properties, protein interaction with the mitochondrial calcium (Ca2+) uniporter complex, and the conductance of the PTPC. Here, we document the role of a naturally occurring mutation in the Csub-encoding ATP5G1 gene at the G87 position found in two ST-segment elevation myocardial infarction (STEMI) patients and how PTPC opening is related to RI in patients affected by the same disease. We report a link between the expression of ATP5G1G87E and the response to hypoxia/reoxygenation of human cardiomyocytes, which worsen when compared to those expressing the wild-type protein, and a positive correlation between PTPC and RI.


Evaluation of thermally-modified calcium-rich attapulgite as a low-cost substrate for rapid phosphorus removal in constructed wetlands.
The cost-effective and geographically available substrates are vital for the design of constructed wetlands (CWs), especially the saturated subsurface flow CWs, which are deemed as an efficient way to remove the inlet-lake phosphorus concentrations. In this study, phosphorus removal of thermally-treated calcium-rich attapulgite (TCAP) with varied particle sizes (0.2-0.5 mm, 0.5-1 mm and 1-2 mm) was assessed using batch and long-term column experiments to evaluate its feasibility as a CWs substrate. The phosphorus-bound mechanism in TCAP was identified in various initial phosphorus concentrations. Batch studies indicated that more than 95% of P can be rapidly (<1 h) removed by TCAP from solution with a concentration of 20 mg P/L, and P sorption can be well fitted by a pseudo-second-order equation. The maximum P sorption capacity of TCAP was in the range of 4.46-5.99 mg P/g, and the availability of Ca2+ concentration might limit the P removal capacity of TCAP at high phosphorus concentrations. Both the P removal rate and capacities decreased with the increase of TCAP particle sizes. Column P removal experiments indicated that hydraulic retention time (HRT) exerts great influence on P removal performance and longer HRTs favor the dissolution of CaO in TCAP, consequently increasing the P removal rate. In a 150-day P removal experiment, TCAP removed an average of 93.1%-95.4% of the influent P with a HRT of eight hours. Both the batch and chemical extraction of the P fraction of TCAP showed that the P removed by TCAP was mainly through formation of Ca phosphate precipitation. However, the species of Ca-P precipitation formed might be varied in different phosphorus concentrations. All results indicated that TCAP can be a suitable substrate when used in CWs, and field experiments should be carried out to test its real P removal performance in the future.


K-Cl cotransport function and its potential contribution to cardiovascular disease.
K-Cl cotransport is the coupled electroneutral movement of K and Cl ions carried out by at least four protein isoforms, KCC1-4. These transporters belong to the SLC12A family of coupled cotransporters and, due to their multiple functions, play an important role in the maintenance of cellular homeostasis. Significant information exists on the overall function of these transporters, but less is known about the role of the specific isoforms. Most functional studies were done on K-Cl cotransport fluxes without knowing the molecular details, and only recently attention has been paid to the isoforms and their individual contribution to the fluxes. This review summarizes briefly and updates the information on the overall functions of this transporter, and offers some ideas on its potential contribution to the pathophysiological basis of cardiovascular disease. By virtue of its properties and the cellular ionic distribution, K-Cl cotransport participates in volume regulation of the nucleated and some enucleated cells studied thus far. One of the hallmarks in cardiovascular disease is the inability of the organism to maintain water and electrolyte balance in effectors and/or target tissues. Oxidative stress is another compounding factor in cardiovascular disease and of great significance in our modern life styles. Several functions of the transporter are modulated by oxidative stress, which in turn may cause the transporter to operate in either "overdrive" with the purpose to counteract homeostatic changes, or not to respond at all, again setting the stage for pathological changes leading to cardiovascular disease. Intracellular Mg, a second messenger, acts as an inhibitor of K-Cl cotransport and plays a crucial role in regulating the activity of protein kinases and phosphatases, which, in turn, regulate a myriad of cellular functions. Although the role of Mg in cardiovascular disease has been dealt with for several decades, this chapter is evolving nowadays at a faster pace and the relationships between Mg, K-Cl cotransport, and cardiovascular disease is an area that awaits further experimentation. We envision that further studies on the role of K-Cl cotransport, and ideally on its specific isoforms, in mammalian cells will add missing links and help to understand the cellular mechanisms involved in the pathophysiology of cardiovascular disease.


ORACLE reveals a bright future to fight bacteria.
A new way to alter the genome of bacteriophages helps produce large libraries of variants, allowing these bacteria-killing viruses to be designed to target species harmful to human health.


Smart 3D-FISH: automation of distance analysis in nuclei of interphase cells by image processing.
Detection of fluorescent probes by fluorescence in situ hybridization in cells with preserved three-dimensional nuclear structures (3D-FISH) is useful for studying the organization of chromatin and localization of genes in interphase nuclei. Fast and reliable measurements of the relative positioning of fluorescent spots specific to subchromosomal regions and genes would improve understanding of cell structure and function. 3D-FISH protocol, confocal microscopy, and digital image analysis were used. New software (Smart 3D-FISH) has been developed to automate the process of spot segmentation and distance measurements in images from 3D-FISH experiments. It can handle any number of fluorescent spots and incorporate images of 4',6-diamino-2-phenylindole counterstained nuclei to measure the relative positioning of spot loci in the nucleus and inter-spot distance. Results from a pilot experiment using Smart 3D-FISH on ENL, MLL, and AF4 genes in two lymphoblastic cell lines were satisfactory and consistent with data published in the literature. Smart 3D-FISH should greatly facilitate image processing and analysis of 3D-FISH images by providing a useful tool to overcome the laborious task of image segmentation based on user-defined parameters and decrease subjectivity in data analysis. It is available as a set of plugins for ImageJ software.


Peptide chain elongation rate and ribosomal activity in Saccharomyces cerevisiae as a function of the growth rate.
The peptide-chain elongation rate of Saccharomyces cerevisiae at two different growth rates was estimated by the kinetics of radioactive labelling of nascent and finished polypeptides as described by Gausing, 1972, and Young and Bremer, 1976. The elongation rates of a diploid strain cultured in yeast nitrogen base supplemented with glucose or acetate were 9.3 amino acids/s and 5.5 amino acids/s at 30 degrees C, respectively. These data together with published values on the "ribosomal efficency" as a function of growth rate (Waldron and Lacroute, (1975) enable us to estimate the rate of synthesis of ribosomal proteins as a function of the rate of total protein synthesis, alpha r, and the fraction of ribosomes that one active in protein synthesis. We conclude that in S. cerevisiae alpha r is largely independent of the growth rate while the fraction of active ribosomes decreases with decreasing growth rate.


The association between risky decision making and cocaine conditioned place preference is moderated by sex.
Excessive risk taking is a characteristic trait of several psychiatric conditions, including substance use disorders. High risk-taking (HiR) rats self-administer more cocaine compared to low risk-taking (LoR) rats. However, research has not determined if risk taking is associated with enhanced cocaine conditioned place preference (CPP). Male and female Sprague Dawley rats (n = 48 each sex) were first tested in the risky decision task (RDT), in which a response on one lever resulted in safe delivery of one food pellet, and a response on a different lever resulted in delivery of two pellets and probabilistic delivery of foot shock. Following RDT training, rats were tested for cocaine CPP. The first session was a pretest that measured rats' preference for three compartments that provided different visual and tactile cues. Rats then learned to associate one compartment with cocaine (either 10.0 mg/kg or 20.0 mg/kg; i.p.) and one compartment with saline (1.0 ml/kg; i.p.) across eight conditioning sessions. Finally, rats explored all three compartments in a drug-free state. Sex significantly moderated the association between risky decision making and cocaine CPP. While increased risk aversion was somewhat positively associated with cocaine CPP in males, increased risk taking was positively correlated with cocaine CPP in females. These results highlight the moderating role of sex on the relationship between risky decision making and cocaine reward.


Association of body dysmorphic disorder with anxiety, depression, and stress among university students.
This study aims to estimate the prevalence of body dysmorphic disorder (BDD) and identify its association with depression, anxiety, and stress. We conducted a cross-sectional study in Jeddah, KSA. In 2019, a validated questionnaire with items on sociodemographic characteristics and body dysmorphic disorder, as well as the Depression, Anxiety, and Stress Scale - 21 items (DASS 21) was distributed to 1,112 students of King Abdulaziz University. SPSS version 23 was used for data analysis, which included descriptive statistics, chi-square tests, and binary logistic regression models. The association was presented as an odds ratio (OR) along with its 95% confidence Interval (CI). The overall prevalence of BDD was 13.9% (95% CI of 11.8-16.2.) with the highest reported sites being the skin (81.6%) and waist (68.8%). BDD was found to be a significant predictor of depression with an OR of 4.2 (95% CI 2.9-6.1), anxiety OR of 2.2 (95%1.6-3.2), and stress OR of 3.2 (2.2-4.7). Females were significantly associated with anxiety, OR of 1.4 (95% CI 1.1-1.9) and stress, OR of 1.5 (1.1-2). Affiliation to the administration, arts, humanities, and social colleges was also a significant predictor of anxiety as reflected by an OR of 1.4 (95% CI 1.1-1.8). Our study shows that BDD is relatively common among university students in Jeddah and associated with depression, anxiety, and stress.


Dimorpholinoacetylene and Its Use for the Synthesis of Tetraaminocyclobutadiene Species.
The new diaminoacetylene (DAA) dimorpholinoacetylene (3) was prepared from 1,1-dimorpholinoethene (1) by bromination to form the dibromoketene aminal 2, which upon lithiation afforded 3 through a Fritsch-Buttenberg-Wiechell rearrangement. Heating 3 at elevated temperatures resulted in a complete conversion into the dimer 1,1,2,4-tetramorpholino-1-buten-3-yne (4), which was used for the synthesis of four-membered cyclic bent allene (CBA) transition-metal complexes of the type [(CBA)MLn ] (5-7; MLn =AuCl, RhCl(COD), RhCl(CO)2 ; CBA=1,3,4,4-tetramorpholino-1,2-cyclobutadiene; COD=1,5-cyclooctadiene). The reaction of 3 with tetraethylammonium bromide gave 1,2,3,4-tetramorpholinocyclobutenylium bromide (8), which reacted with bromine to form 1,2,3,4-tetra(morpholino)cyclobutenediylium bis(tribromide) (9). Compound 9 represents the first fully characterized compound containing a tetraaminocyclobutadiene dication and displays a nearly planar C4 N4 core as shown by X-ray diffraction analysis. Detailed quantum chemical calculations were performed to assess the aromaticity of tetraaminocyclubutadiene dications by employing the Nucleus Independent Chemical Shift (NICS) method and current density analysis.


Increased stool sampling during a waterborne outbreak of cryptosporidiosis does not increase the detection of other faecal pathogens.
To ascertain the effect of enhanced surveillance following an outbreak of waterborne cryptosporidiosis on the number of faecal specimens submitted to the local microbiology laboratory and the number positive for common enteric pathogens. The outbreak provided an opportunity to estimate the extent of routine under ascertainment of common enteric pathogens. Retrospective search of the computerised microbiology system database for details of faecal examination requests for the period 26 April to 6 June in 1998 and 1999 (period of outbreak). Specimens were received from 378 community patients during the six week period 26 April to 6 June 1999. This was double that for the same period in 1998 (a non-outbreak year). Oocysts of Cryptosporidium parvum were detected in 59 patients, an eightfold increase compared with the same period in 1998. Despite the greater number of patients tested, the detection of other pathogens in patients with gastroenteritis was not altered when compared with the same period in the previous year. This study found no evidence of under ascertainment of gastrointestinal infection (common bacterial pathogens and rotavirus) by local general practitioners.


[Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase].
Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. The aim of this study was to evaluate the clinical usefulness of screening of genetic thrombophilic mutations and uterine artery Doppler flow velocimetry at 24 weeks of gestation in the prediction of pre-eclampsia in low risk pregnant women. We performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 24 weeks at our Department. The frequency of heterozygous carriers of the Leiden FV was 17.4% in women with pre-eclampsia and abnormal artery Doppler flow velocimetry compared with 3.12% in patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of PT gene was 1.5% vs 4.3% between women with normal pregnancies and with pre-eclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among patients with pre-eclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic genes variants were found in women with pre-eclampsia and normal uterine artery Doppler flow velocimetry. We demonstrated the important association between FV Leiden mutation, abnormal uterine artery Doppler flow velocimetry at 24 weeks and pre-eclampsia in our low-risk population.


Self-reported participation in cervical cancer screening among Polish women in 2004-2019.
We aimed to assess self-reported participation in cervical cancer screening among Polish women between 2004 and 2019 and to identify the groups with the lowest participation rate. Data on declared participation in cervical cancer screening were obtained from the European Health Interview Survey from 2004 to 2019. In 2019, 86.7% of Polish women aged ≥ 15 years declared that they had ever undergone a Pap test. Compared to 2004, the coverage of ever-screened women improved by 16.6 percentage points. The proxy population coverage was 72.9%. The highest proportion of women who underwent a Pap smear in the last three years was observed among those aged 35-44 years and 25-34 years (84.0% and 83.2%, respectively), and the lowest among women aged ≥ 75 years (20.5%). The proportion screened within the last three years also varied by education (up to lower secondary education 26.4%, up to post-secondary non-tertiary education 62.8%, and the highest level of education 83.7%), urbanization (large cities 66.7%, suburbs, and smaller cities 62.8%, and rural areas 59.0%), income (poorest households 42.5%, wealthiest households 70.6%), and declared health status (best 68.9%, worst 41.4%). The lowest participation in screening was observed in the southeastern regions and the highest in the northwestern regions of Poland. In Poland, in 2019, the approximate coverage of cervical cancer screening was high compared to other European countries and has improved over the last 15 years. A complete screening registry is required to confirm questionnaire-based self-reported data. Targeted interventions should be implemented to address low participation in the identified regions and socioeconomic groups.


Uncovering the molecular basis of positive affect using rough-and-tumble play in rats: a role for insulin-like growth factor I.
Positive emotional states have been shown to confer resilience to depression and anxiety in humans, but the molecular mechanisms underlying these effects have not yet been elucidated. In laboratory rats, positive emotional states can be measured by 50-kHz ultrasonic vocalizations (hedonic USVs), which are maximally elicited by juvenile rough-and-tumble play behavior. Using a focused microarray platform, insulin-like growth factor I (IGFI) extracellular signaling genes were found to be upregulated by hedonic rough-and-tumble play but not depressogenic social defeat. Administration of IGFI into the lateral ventricle increased rates of hedonic USVs in an IGFI receptor (IGFIR)-dependent manner. Lateral ventricle infusions of an siRNA specific to the IGFIR decreased rates of hedonic 50-kHz USVs. These results show that IGFI plays a functional role in the generation of positive affective states and that IGFI-dependent signaling is a potential therapeutic target for the treatment of depression and anxiety.


Farnesoid X receptor immunolocalization in reproductive tissues of adult female rabbits.
Farnesoid X receptor (FXR) has been involved in lipid metabolism, cell proliferation, apoptosis, and aromatase expression, as well as in the steroid synthesis and signaling. Considering that these events occur in reproductive tissues in females, the aim of the present study was to determine the immunolocalization of FXR in the ovary, oviduct, uterus, and vagina of rabbits. Rabbits were sacrificed and their reproductive tissues were excised and histologically processed. Immunohistochemistry for FXR was done and reproductive tissues were photographed. FXR immunoreactivity was found in all types of ovarian follicles, ovarian stroma, and corpus luteum of virgin and pregnant rabbits. Also, oviductal and vaginal epithelium of virgins, as well as the oviductal smooth muscle, showed anti-FXR immunoreactivity. The uterine epithelium and musculature of virgins had scarce anti-FXR immunoreactivity. Although the role of FXR in female reproductive tissues is still not known, it is possible to consider various functions related to the reproductive tissue.


Tissue eosinophil levels as a marker of disease severity in bullous pemphigoid.
Eosinophils play an important role in bullous pemphigoid (BP) pathogenesis. Although tissue infiltration with eosinophils has been known for a long time, there is a lack of knowledge about the relationship between tissue eosinophil levels and disease severity and clinical characteristics of the patients. Fifty-nine patients diagnosed with BP between January 2008 and December 2018 were reviewed. Haematoxylin-Eosin (H&E)-stained preparations were re-evaluated in terms of tissue eosinophil levels. For disease severity, Bullous Pemphigoid Disease Area Index (BPDAI) was used. The relationship between tissue eosinophil levels and disease severity and clinical features were evaluated. Erosion/blister and urticaria/erythema BPDAI scores were higher in the group with high tissue eosinophil level than the group with low tissue eosinophil level. Tissue and peripheral blood eosinophil count were correlated with total urticaria/erythema BPDAI scores. There was no correlation between blood and tissue eosinophil count. The mortality rate was 64.7% vs 44.0% in the high vs low tissue eosinophil groups. Tissue eosinophil levels were high in patients with BP accompanying neurological disease. Tissue eosinophil count and peripheral blood eosinophil count were correlated with disease severity in BP. Tissue eosinophil levels were also high in patients with BP accompanying neurological disease.


Treatment of rats with an anti-(+)-methamphetamine monoclonal antibody shortens the duration of action of repeated (+)-methamphetamine challenges over a one month period.
This study assessed clinical scenarios of continuing monoclonal antibody (mAb) treatment for (+)-methamphetamine (METH) addiction, and the implications of missing or discontinuing this therapy. We hypothesized that chronic anti-METH mAb7F9 (METH KD=9 nM) treatment of rats could significantly decrease METH-induced behaviors; even with repeated METH challenges, use of METH doses in excess of mAb binding sites, and after discontinuing mAb treatment which results in a 10-fold reduction in mAb7F9 serum concentrations. Male Sprague Dawley rats (n=6/group) were treated with i.v. saline or a loading dose of mAb7F9 to achieve instant steady-state conditions followed by two weekly (141 mg/kg) doses ending on day 14. METH (0.56 mg/kg) was administered 4h and three days after each saline or mAb7F9 treatment, and on day 21. This produced locomotion and rearing behavior that lasted about 120 min in control rats. In mAb7F9 treated rats, METH-induced distance traveled was significantly reduced from 60 to 120 min (P<0.05) on days 0-21 and rearing was significantly reduced from 60 to 120 min on days 0-17. METH serum concentrations determined 5h after METH dosing was significantly increased in mAb7F9-treated rats after all METH challenges. On days 24 and 28 (the final day), the rats were administered a 3-fold higher METH dose (1.68 mg/kg). MAb7F9 treated rats showed a substantially earlier termination of the METH-induced locomotion on both days, even though the METH dose exceeded mAb7F9s binding capacity. METH brain concentrations determined 5h after METH on day 28 were also significantly decreased in mAb7F9-treated rats. In conclusion, over one month, mAb7F9 significantly and continuously bound METH and reduced METH-induced locomotor effects even after discontinuation of mAb treatment and challenge with higher METH doses.


A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese.
Adrenomedullin, a vasodilatory peptide, facilitates the differentiation of pre-adipocytes, and affects lipolysis and glucose uptake. We investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding adrenomedullin (ADM) with dysglycemia in the Hong Kong Chinese population. Four SNPs were genotyped in 1391 subjects without dysglycemia at baseline from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, which had a median follow-up time of 6.4 years. Dysglycemia included impaired fasting glucose, impaired glucose tolerance, and diabetes according to the WHO 1998 criteria. At follow-up, 382 subjects had developed dysglycemia. In stepwise logistic regression, the SNP rs11042725 was a significant independent predictor of the development of dysglycemia (OR=1.31, P=0.012), together with baseline age (P<0.001), plasma triglycerides (P<0.001), body mass index (P=0.004), 2-h glucose after oral glucose tolerance test (P<0.001), homeostasis model assessment of insulin resistance index (P=0.045), and follow-up duration (P=0.009). The association was more significant in women (P=0.002) and in subjects without regular exercise (P=0.001). Our study suggests a potential role of genetic variants in the ADM gene in the development of dysglycemia in our local Chinese population.


Vinculin presents unfavorable prediction in ovarian cancer and prevents proliferation and migration of ovarian cancer cells.
The influences of Vinculin on many cancers were blurry, including ovarian cancer. Thus, we concentrated on the efficient role of Vinculin in ovarian cancer and explored the potential mechanism(s). Expression of Vinculin in ovarian cancer tissues and cell lines was investigated by real-time polymerase chain reaction, immunohistochemistry, and Western blot. The Kaplan-Meier manner with the logrank was performed to assess overall survival. We further evaluated the relations between Vinculin expression and clinicopathological features of ovarian cancer. Moreover, Vinculin was overexpressed or silenced by respectively transfection with pcDNA-Vinculin or small interfering (si-Vinculin) into human ovarian cancer cell line Caov3 or human ovarian epithelial cell line (HOEpiC). Thereafter, cell viability, cell apoptosis, and migration were checked by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometer, and scratch assay, respectively. Likewise, the apoptosis- and migration-related proteins were distinguished by Western blot. Compared to the nontumor tissues or HOEpiC cells, Vinculin was significantly lower expressed in the ovarian cancer tissues and cells. Furthermore, we found out that Vinculin was primarily distributed at the cell membrane and cytoplasm. Moreover, Vinculin was negatively associated with International Federation of Gynecology and Obstetrics stage, grade, and distant metastasis. Overexpression of Vinculin dramatically weakened cell viability and migration and stimulated apoptosis. Conversely, suppression of Vinculin showed opposite results. Vinculin presents unfavorable prediction in ovarian cancer and inhibits ovarian cancer proliferation and migration.


Skin diseases following a Christmas tree pattern.
Pattern analysis of skin lesions is an art and a key competence of every dermatologist. Three major line patterns cover the human body-the dermatomes or Head zones, the nevoid lines of Blaschko, and the relaxed skin tension lines, or Langer lines. Head zones represent skin areas innervated from the same sensory neuronal segment or spinal nerve zone. Blaschko lines are borderlines of epidermal aberration caused by genetic mosaicism occurring in the early stages of embryogenesis. Langer lines show the direction of the lowest naturally occurring skin tension, and its thoracodorsal manifestation is the Christmas tree pattern. Here we review clinical aspects of pityriasis rosea, mycosis fungoides, stage 2 syphilis, exanthematic Kaposi sarcoma, exanthematic psoriasis, Leser-Trelat syndrome, and other primary skin diseases with a Christmas tree pattern. Secondary skin diseases, such as herpes zoster or indeterminate cell histiocytosis, may follow this pattern if they are linked to a primary skin disease by the Wolf isotopic response.


The effect of acute haemorrhage and of delayed blood replacement on wound healing: an experimental study.
Haemorrhage whether untreated or with volume replacement delayed for 1 h has been shown by other workers to result in weaker scars 7-10 days after wounding. Studies have been carried out 6 weeks and 3 months after median laparotomy in three groups of Wistar rat: control, bled 10 ml/kg without replacement and bled 10 ml/kg with replacement of heparinized shed blood after 1 h. At 6 weeks the burst pressure of the laparotomy scar was significantly less (Mann-Witney U) in both the haemorrhage group (n = 6; 181.7 +/- 30.5 mmHg s.e.m.; P = 0.026) and the replacement group (n = 6; 207.8 +/- 27.4 mmHg s.e.m.; P = 0.037) than in the control animals (n = 7; 301.9 +/- 42.0 mmHg s.e.m.) At 3 months there were no significant differences between the groups. On histology there was no difference in cellularity between the groups, but in both the haemorrhage and replacement animals collagen was less abundant and less well organized. These differences also had disappeared by 3 months. Neigher collagen nor the fibroblast ultrastructure showed significant differences between groups, all animals showing patchy vacuolation of endoplasmic reticulum of fibroblasts at 6 weeks. It is concluded that oligaemia slows wound healing but does not affect the ultimate strength of the scar.


Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis.
Deferiprone is an iron chelator that has recently been used to treat patients with infratentorial superficial siderosis (iSS). It is considered to have a generally favourable safety profile but concerns have been raised due to the risk of agranulocytosis. We aimed to evaluate the safety and tolerability of oral deferiprone as a treatment for patients with iSS. We present a case series of 10 consecutive patients presenting with classical iSS treated with deferiprone. Ten patients were followed up for a mean period of 2.3 years (range 0.5-5.5 years). Four patients (40%) were withdrawn from treatment because of treatment-related side effects. The reasons for treatment discontinuation were neutropenic sepsis (n = 3) and fatigue (n = 1). In 2 out of the 3 cases of neutropenic sepsis, patients initially developed neutropenia without sepsis. The mean time to neutropenic sepsis following deferiprone was 1.2 years (range 0.3-2.5) with mean neutrophil count of 0.4 (range 0.3-0.5). Six patients (60%) reported no change in neurological function while on treatment, and four patients (40%) reported that their condition deteriorated. Deferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis, after an average of 2 years on treatment. This study increases the number of reported cases of agranulocytosis in patients with iSS treated with deferiprone. Clinicians treating iSS patients with deferiprone should be aware that this drug has a potentially life-threatening side effect of neutropenic sepsis, and should ensure that appropriate haematological monitoring is in place.


Mechanisms of length-dependent recognition of viral double-stranded RNA by RIG-I.
Retinoic acid-inducible gene I (RIG-I) is the most front-line cytoplasmic viral RNA sensor and induces antiviral immune responses. RIG-I recognizes short double-stranded (dsRNA) (< 500 bp), but not long dsRNA (> 500 bp) to trigger antiviral signaling. Since RIG-I is capable of binding with dsRNA irrespective of size, length-dependent RIG-I signaling remains elusive. Here, we demonstrated that RIG-I bound to long dsRNA with slow kinetics. Remarkably, RIG-I/short dsRNA complex efficiently dissociated in an ATP hydrolysis-dependent manner, whereas RIG-I/long dsRNA was stable and did not dissociate. Our study suggests that the dissociation of RIG-I from RIG-I/dsRNA complex could be a step for efficient antiviral signaling. Dissociated RIG-I exhibited homo-oligomerization, acquiring ability to physically associate with MAVS, and biological activity upon introduction into living cells. We herein discuss common and unique mechanisms of viral dsRNA recognition by RIG-I and MDA5.


A case of early gastric cancer in which the degree of histological atypia was correctly predicted by magnifying endoscopy combined with narrow band imaging.
We herein report a case of early gastric cancer with mixed components having different grades of atypia, which was correctly predicted by magnifying endoscopy combined with narrow band imaging. A 67-year-old man had a flat elevated lesion (0-IIa) in the anterior wall of the gastric antrum. With narrow band imaging, a flat lateral extension (0-IIb), not recognized with white light imaging was seen in the anal side of the main tumor. Magnifying endoscopy combined with narrow band imaging saw a relatively regular fine network pattern of micro-vessels in the surface of the 0-IIa area. However, in the surface of the 0-IIb area, a villous structure with villi of various size and heterogeneity, micro-vessels showing tortuousity were observed. We judged the grade of atypia to be higher in the 0-IIb area than in the 0-IIa area. Histological examination of the resected specimen verified the 0-IIa area and 0-IIb area as adenoma and adenocarcinoma, respectively.


Terpinolene as an enhancer for ultrasonic disinfection of multi-drug-resistant bacteria in hospital wastewater.
The present study reports for the first time, a novel disinfection method that combines ultrasonication with a natural biocide terpinolene to inhibit tough and opportunistic antimicrobial-resistant (AMR) microorganisms isolated from hospital wastewater treatment plant (HWWTP). The enhancement of the disinfection process was evaluated for the effect of ultrasonication power, operating temperature, and inoculum size. A hybrid methodology combining terpinolene with traditional physico-chemical method of acoustic cavitation delivered efficient disinfection of the secondary effluent of field scale HWWTP, amended with a higher inoculum size of multi-drug-resistant coliform bacteria Enterobactor sp., Citrobacter freundii, and Klebsiella pneumonia. A bacterial load of 6.4 log CFU/mL was completely eliminated in 25 min. The present study also reports that due to the hybrid process, a very small concentration of 0.312 mM (0.25 × Minimum Inhibitory Concentration or MBC) of terpinolene was enough to completely disinfect the multi-drug-resistant coliforms. The leakage of intracellular nucleic acids during the disinfection process suggested disruption of cell membrane as the primary mechanism of disinfection followed by disruption of cellular metabolic function measured by respiratory chain dehydrogenase activity. Moreover, this study is the first to prove that terpinolene remained stable even after the cavitation process, thus revealing possibilities of recycling of the natural compound for wastewater disinfection. The results of the present research suggest that using terpinolene as a bio-additive can efficiently eliminate hazardous multi-drug-resistant bacteria and drastically reduce operational time and cost thus rendering it suitable to replace conventional wastewater disinfection.


Improved procedure for the purification of an iodinated protein: beta nerve growth factor.
An improved procedure for the isolation of iodinated beta Nerve Growth Factor (125I-beta NGF) has been devised. Use of Centricon microconcentrators (Amicon) has allowed the facile and efficient recovery of ultrapure 125I-beta NGF in high yields. Centricon microconcentrators are supplied with two molecular weight cutoffs of 10 K and 30 K daltons. beta NGF is a basic protein with a molecular weight of 26 K daltons. It is therefore possible to filter the 125I-beta NGF through the 30 K filter (30 K Filtrate) leaving behind any aggregates or reactants greater than 30 K while the 125I-beta NGF can be retained and concentrated on the 10 K filter (10 K Retentate). Any free 125I is easily removed, passing through the 10 K filter and then being discarded. In this way 125I-beta NGF can be easily purified.


Self-esteem modulates medial prefrontal cortical responses to evaluative social feedback.
Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing.


Chemotherapy vs. Immunotherapy in combating nCOVID19: An update.
The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis.