Lipopolysaccharide and interleukin-1beta decrease sucrose intake but do not affect expression of place preference in rats.
Immune system activation has been shown to induce decreased interest in pleasurable stimuli. Studies of this phenomenon have assessed the effect of cytokines or lipopolysaccharide (LPS) on behavior maintained by primary reinforcers, stimuli, such as palatable solutions, that effectively reinforce behavior without prior training. The studies reported in this paper replicated findings of immune system activation decreasing intake of a palatable solution and assessed the effects of immune activation on behavior maintained by a conditioned reinforcer, a stimulus paired with a the palatable solution. Using a conditioned place preference procedure, the effects of LPS and interleukin-1beta (IL-1beta) on sucrose intake (primary reinforcer) and preference for a sucrose-paired environment (conditioned reinforcer) were tested. LPS and IL-1beta decreased sucrose intake but had no effect on the expression of a sucrose-induced place preference, indicating a differential effect of immune system activation on appetitive behaviors maintained by primary and conditioned reinforcers. Finally, it was shown that a sucrose-induced place preference is sensitive to the motivational state of the subjects at the time of testing; a sucrose-induced place preference was demonstrated if rats were tested when water deprived but not if tested after free access to water.


Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study.
Pirfenidone (PFD), an oral antifibrotic drug, has been authorized by the EMA and FDA for treatment of idiopathic pulmonary fibrosis. Few studies have addressed its use in advanced liver fibrosis (ALF). We evaluated a prolonged-release formulation (PR-PFD) plus standard of care on disease progression in ALF. 281 ALF patients from 12 centers receiving PR-PFD (600 mg bid) were screened; 122 completed 1 year of treatment. Additionally, 74 patients received only standard of care regimen. Average age was 64 ± 12 years, 58% female. 43.5% had fatty liver disease (NAFLD), 22.5% viral hepatitis C (VHC), 17% autoimmune hepatitis (AIH), and 17% alcoholic liver disease (ALD). Baseline fibrosis was F4 in 74% and F3 in 26%. Antifibrotic effects were assessed by transient elastography (Fibroscan®) and Fibro Test® (FT); Cytokines and PFD plasma levels were tracked and quality of life evaluated. We found a significant reduction in fibrosis in 35% of PR-PFD patients and only in 4.1% in non PR-PFD patients. Child-Pugh score improved in 29.7%. Biochemical values remained stable; 40.6% and 43.3% decreased ALT or AST, respectively. TGFβ1 (pg/mL) levels were lower in PFD-treated patients. PFD serum concentration (µg/mL) was higher (8.2 ± 1.7) in fibrosis regression profile (FRP) patients compared to fibrosis progression profile (FPP) patients (4.7 ± 0.3 µg/mL, p < 0.01). 12% reported transient burning or nausea and 7% photosensitivity. Quality of life (Euro-Qol scale) improved from 62 ± 5 to 84 ± 3 (p < 0.001) and from 32 ± 3 to 42 ± 2 (p < 0.008) (FACIT scale). PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. Clinical trial number: NCT04099407.


Two cases of tinea ciliaris with blepharitis due to Microsporum audouinii and Trichophyton verrucosum and review of the literature.
Dermatophytes are rarely taken into account among the causes of blepharitis. In our report, we describe a 69-year-old man and a 40-year-old woman with chronic blepharitis for 10 years and 4 years respectively, in whom we examined the scales and pulled eyelashes on direct microscopy and isolated Microsporum audouinii and Trichophyton verrrucosum in the culture. We emphasise that dermatophytes may play a role in the etiopathogenesis of chronic blepharitis. In chronic, treatment resistance blepharitis fungal infections may be considered as possible cause.


AI-based quantification of whole-body tumour burden on somatostatin receptor PET/CT.
Segmenting the whole-body somatostatin receptor-expressing tumour volume (SRETVwb) on positron emission tomography/computed tomography (PET/CT) images is highly time-consuming but has shown value as an independent prognostic factor for survival. An automatic method to measure SRETVwb could improve disease status assessment and provide a tool for prognostication. This study aimed to develop an artificial intelligence (AI)-based method to detect and quantify SRETVwb and total lesion somatostatin receptor expression (TLSREwb) from [68Ga]Ga-DOTA-TOC/TATE PET/CT images. A UNet3D convolutional neural network (CNN) was used to train an AI model with [68Ga]Ga-DOTA-TOC/TATE PET/CT images, where all tumours were manually segmented with a semi-automatic method. The training set consisted of 148 patients, of which 108 had PET-positive tumours. The test group consisted of 30 patients, of which 25 had PET-positive tumours. Two physicians segmented tumours in the test group for comparison with the AI model. There were good correlations between the segmented SRETVwb and TLSREwb by the AI model and the physicians, with Spearman rank correlation coefficients of r = 0.78 and r = 0.73, respectively, for SRETVwb and r = 0.83 and r = 0.81, respectively, for TLSREwb. The sensitivity on a lesion detection level was 80% and 79%, and the positive predictive value was 83% and 84% when comparing the AI model with the two physicians. It was possible to develop an AI model to segment SRETVwb and TLSREwb with high performance. A fully automated method makes quantification of tumour burden achievable and has the potential to be more widely used when assessing PET/CT images.


Ruptured mycotic aneurysm of the superior mesenteric artery secondary to bacterial endocarditis in a 6-year-old-girl.
By non-invasive examination we demonstrated a false mycotic aneurysm on a branch of the superior mesenteric artery (SMA). It suddenly ruptured but was managed successfully. The patient had mitral valve disease and probably bacterial endocarditis also.


Prenatal diagnosis and perinatal management of a fetal ovarian cyst.
A case of a prenatally diagnosed fetal ovarian cyst is presented. The pregnancy was complicated only by polyhydramnios, and some degree of fetal bowel obstruction could be recognized on sonogram. The newborn was delivered vaginally in the 39th week of pregnancy, and the cyst was removed by laparotomy on the day of the delivery. The etiology of this rare fetal condition is unknown.


Biofeedback vs. instructional control of skin temperature.
The purpose of this study was twofold: (1) to determine the effects of instructions vs. biofeedback on the development of skin temperature self-control and (2) to assess how well learned control over temperature can be retained over time. Sixty female subjects were assigned to one of six groups: (1) response-specific instructions plus feedback, (2) thermal suggestions plus feedback, (3) instructions to rest plus feedback, (4) response-specific instructions without feedback, (5) thermal suggestions without feedback, and (6) instructions to rest without feedback. All subjects participated in five training sessions on 5 consecutive days and two follow-up sessions spaced 1 week and 2 weeks after training. Subjects given either feedback and response-specific instructions, feedback and thermal suggestions, or no feedback and thermal suggestions were able to produce significant increases in digital skin temperature consistently after three training sessions. Subjects in these groups retained the ability to control skin temperature both 1 and 2 weeks after training. Subjects in the remaining conditions showed no evidence of learned control over skin temperature.


Application of Optical Coherence Tomography Angiography Macular Analysis for Systemic Hypertension. A Systematic Review and Meta-analysis.
Microvascular rarefaction due to hypertension has been linked to disease severity and end-organ complications. Optical coherence tomography angiography (OCTA) has been explored as a potential tool to evaluate the retinal microvascular network in hypertensive patients. PubMed, Scopus, Web of Science, and Cochrane were systematically searched to 10th of September of 2021, along with a manual search. Studies that used OCTA as a primary diagnostic method to evaluate the macular microvasculature of hypertensive patients were included. Meta-analysis was performed using a random-effects model. Primary outcomes were macular vessel density (VD) and foveal avascular zone (FAZ) at the superficial and deep capillary plexus. Of 947 screened articles, 9 were found eligible for qualitative and quantitative analysis. VD in hypertensive patients was reduced when compared with controls in the fovea (0.93, 95% confidence interval [CI] 0.87-0.99, P = 0.023) and the parafovea (0.95, 95% CI 0.93-0.97, P < 0.001) of the superficial capillary plexus. FAZ was larger in the deep plexus of hypertensive patients (1.10, 95% CI 1.03-1.18, P = 0.003). VD reduction was found in patients with worsening blood pressure control in 3 studies and prolonged disease in 2 studies. Microvascular rarefaction of the macula is found in hypertensive patients with a reduction of foveal and parafoveal VD and an increase of FAZ area. Disease duration and severity might be related to a microvascular rarefaction. OCTA could offer a novel tool for the assessment and follow-up of hypertensive patients.


Effect of captopril on renal vascular resistance, renin, prostaglandins and kinin in the isolated perfused kidney.
Vasodilatory and natriuretic effects of captopril were studied in the isolated hog kidney perfused with modified Krebs-Ringer solution. Renal arterial infusion of captopril caused increases in releases of renin, prostaglandins (PGE2, 6-keto-PGF1 alpha and PGF2 alpha) and kinin, and was accompanied by a decrease in the renal vascular resistance and an increase in urinary sodium excretion. Indomethacin administered with captopril diminished the saluretic effect of captopril and evoked an increase in kinin, but was associated with a marked decrease in prostaglandin and renin releases, while renal vascular resistance remained decreased. Indomethacin alone did not alter vascular resistance and kinin; however, renin and prostaglandin releases were decreased. Aprotinin administered with captopril showed a decrease in releases of prostaglandins, renin and kinin without any change in vascular resistance. These results suggest that increased release of kinin induced by captopril contributes to a reduction in renal vascular resistance. Increased prostaglandin release after captopril administration may be caused by an increase in kinin without direct involvement of captopril in prostaglandin synthesis. Renal prostaglandins may enhance sodium excretion and mediate renin secretion in captopril perfusion.


Clinical Features and Genetic Sequencing of Children with Fanconi-Bickel Syndrome.
The present paper reports 10 patients (9 families) with Fanconi-Bickel syndrome managed during 2010-2021. Patients presented with polyuria, polydipsia, hepatomegaly, rickets, and stunting at a median of 5 (3, 7.3) mo; one had transient neonatal diabetes. Glucosuria, generalized aminoaciduria, β2-microglobinuria, urinary phosphate wasting, and hypercalciuria were present in all patients; 3 patients had nephrocalcinosis. Other metabolic abnormalities included hypertriglyceridemia (n = 5/6), fasting hypoglycemia (n = 5/8), and postprandial hyperglycemia (n = 3/6). Genetic analysis showed 7 homozygous or compound heterozygous variants in SLC2A2. A pathogenic variant c.952G>A, common to 4 patients (3 families), might be a potential hotspot. At a median follow-up of 43 mo, 4 patients died at a median of 25 mo; short stature persisted in all except one patient who showed catch-up growth with uncooked corn-starch diet. The present findings suggest that the Fanconi-Bickel syndrome has a severe phenotype with an unsatisfactory outcome. A high index of suspicion for diagnosis and efforts for facilitation of dietary therapy are necessary.


Anti-HCV immunoglobulin M antibody in patients with hepatitis C.
Anti-hepatitis C virus (HCV) immunoglobulin M antibody titres were measured by an enzyme-linked immunosorbent assay method in 16 patients with non-A, non-B acute hepatitis (NANB AH), 13 with non-A, non-B fulminant hepatitis (NANB FH) and nine with type C chronic hepatitis. Anti-HCV IgM was positive in one of the 16 patients with NANB AH, six of the 13 with NANB FH, and five of the nine with type C chronic hepatitis. Anti-HCV IgG was positive in eight of the 16 patients with NANB AH and eight of the 13 with NANB FH. Either anti-HCV IgM or anti-HCV IgG were positive in 10 of the 13 patients with NANB FH. All of the five anti-HCV IgM positive patients with type C chronic hepatitis were undergoing an exacerbation of the diseases, while all of the anti-HCV IgM negative patients were in a remission stage which had lasted for more than 6 months. The findings of this study suggest that anti-HCV IgM is useful for the early diagnosis of type C FH and may be a useful marker of diseases activity in type C chronic hepatitis.


Serial passage of a street rabies virus in mouse neuroblastoma cells resulted in attenuation: potential role of the additional N-glycosylation of a viral glycoprotein in the reduced pathogenicity of street rabies virus.
Street rabies viruses are field isolates known to be highly neurotropic. However, the viral elements related to their pathogenicity have yet to be identified at the nucleotide or amino acid level. Here, through 30 passages in mouse neuroblastoma NA cells, we have established an attenuated variant of street rabies virus strain 1088, originating from a rabid woodchuck followed by 2 passages in the brains of suckling mice. The variant, 1088-N30, was well adapted to NA cells and highly attenuated in adult mice after intramuscular (i.m.) but not intracerebral (i.c.) inoculations. 1088-N30 had seven nucleotide substitutions, and the R196S mutation of the G protein led to an additional N-glycosylation. Street viruses usually possess one or two N-glycosylation sites on the G protein, 1088 has two, while an additional N-glycosylation site is observed in laboratory-adapted strains. We also established a cloned variant 1088-N4#14 by limiting dilution. Apart from the R196S mutation, 1088-N4#14 possessed only one amino acid substitution in the P protein, which is found in several field isolates. 1088-N4#14 also efficiently replicated in NA cells and was attenuated in adult mice after i.m. inoculations, although it was more pathogenic than 1088-N30. The spread of 1088-N30 in the brain was highly restricted after i.m. inoculations, although the pattern of 1088-N4#14's spread was intermediate between that of the parental 1088 and 1088-N30. Meanwhile, both variants strongly induced humoral immune responses in mice compared to 1088. Our results indicate that the additional N-glycosylation is likely related to the reduced pathogenicity. Taken together, we propose that the number of N-glycosylation sites in the G protein is one of the determinants of the pathogenicity of street rabies viruses.


Considerations of current methods for drug selection in treating malignant ventricular arrhythmias.
The current burgeoning interest in antiarrhythmic drugs derives in large measure from a growing concern with the enormous problem of sudden cardiac death. Until the latter half of the twentieth century, beyond a nodding acknowledgment of its massive prevalence, this syndrome received but scant attention from the medical profession. In the early 1960s a number of insights changed perceptions as well as practice. These related to 4 postulates: (1) sudden cardiac death, in the majority of victims, was due to ventricular tachyarrhythmias either initiated by or culminating rapidly in ventricular fibrillation; (2) the lethal arrhythmia was not the consequence of irreversible pathomorphologic impairment of the contractile apparatus, but rather the expression of an electrophysiologic derangement; (3) the triggering of ventricular fibrillation was the result of an electrical accident both reversible as well as preventable; (4) the potential victim was identifiable either by the presence of certain grades of ventricular ectopic activity or by exposure of repetitive ectopic activity or by exposure of repetitive ventricular arrhythmias by electrophysiologic techniques. The innovations that have led to these insights and their consequences have been numerous and continuous. Among these are direct current defibrillation, cardioversion, coronary care units, bystander-initiated cardiopulmonary resuscitation, ambulatory electrocardiographic monitoring and exercise stress testing for exposing ventricular arrhythmias, electrophysiologic provocative testing and mapping techniques, overdrive programmable pacemakers as well as implantable defibrillators and cardioverters, and surgical, electrical and laser techniques for ablating the nidus or interrupting the pathways of the arrhythmias.


An estrogenic effect of 5alpha-androstane-3beta, 17beta-diol on the behavioral response to stress and on CRH regulation.
The gender difference in behavioral and hormonal response to stress is well known, but the underlying mechanism remains elusive. Arginine-vasopressin (AVP) and corticotrophin-releasing hormone (CRH) are two major regulatory peptides in the brain involved in stress regulation. Their response to stress has been shown to be modulated by sex hormones. The androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3beta-diol), has been identified as an estrogenic hormone. It binds to estrogen receptors (ERs) and modulates estrogen response element mediated promoter activities via the ER pathway. The present study involved in vitro transfection assays to examine whether 3beta-diol can directly modulate CRH and AVP promoter activity. Our results demonstrate that in CHO-K1 cell lines, when ERs were over-expressed, 3beta-diol could significantly stimulate CRH and AVP promoter activity through an ER pathway. The effect of 3beta-diol on the behavioral, the CRH and the AVP response to stress in the rat was also investigated. We found that chronic, but not acute administration of 3beta-diol significantly decreased the immobile duration in the forced swim test. In rats exposed to the forced swim test, CRH mRNA expression in the hypothalamus was enhanced by chronic 3beta-diol administration, while the AVP mRNA expression was not affected. These results suggest that 3beta-diol may play an anti-depressive role in affective behavior and may have a direct effect on CRH expression.


[Mycoplasma infection: a disease of reproduction? Apropos of 271 cases].
We investigated by culture the presence of mycoplasmal infection in all reproductive abnormalities. 271 charts were studied, comprising problems of sterility with abnormal sperm, cystitis, urethritis, spontaneous abortions, fetal death in utero, premature deliveries and small for gestational age fetuses. Antimycoplasmal therapy lead to recovery in cases where this infection was the only cause, notably in sterility. Is Mycoplasma a risk factor or does it simply represent current infection?


Natural killer cell receptors: alterations and therapeutic targeting in malignancies.
Numerous newly identified activating and inhibitory NK cell receptors and their engagement by cognate ligands on target tumor cells regulate NK cell antitumor activity. Alterations in NK cell receptor expression and signaling underlie diminished cytotoxic NK cell function. Cytokines, IFN-α, IL-2, IL-12, IL-15 and IL-18, applied systemically and for ex vivo activation and expansion of NK cells have improved NK cell antitumor activity by increasing the expression of NK cell activating receptors and by inducing cytotoxic effector molecules. Moreover, it has been recognized that classical and novel pharmacological agents upregulate cognate ligands for activating receptors on tumor cells and provide better NK cell antitumor response. Some other immunotherapeutic approaches in cancer in the setting of donor-recipient KIR/HLA mismatch have evolved with the aim to potentiate NK cell activity in allogeneic hematopoietic stem cell transplantation that lead to beneficial graft vs. tumor effect. Therefore, better understanding of NK cell activating and inhibitory receptor biology is needed to assist in developing novel approaches to effectively manipulate NK cells and create effective NK cell-based immunotherapy for treatment of cancer patients.


Smoking has a dose-dependent effect on the incidence of preoperative opioid consumption in female geriatric patients with spine disease.
Tobacco use and narcotic medication have been associated with worse functional outcomes after surgery. Our goal was to investigate potential associations between smoking and preoperative opioid consumption in a geriatric population undergoing spine surgery, and their impact on postoperative outcomes. The records of 536 consecutive patients aged more than 65 years who underwent elective spinal surgery between November 2014 and August 2017 at a single institution were reviewed. Primary outcomes included rates of preoperative opioid consumption and postoperative hospital length of stay and complications. Males were more likely to be smokers than females (p < 0.001), whereas females were more likely to take opioid analgesics preoperatively (p = 0.022). Women with a history of smoking were more likely to have increased preoperative opioid consumption compared to those with no history of smoking (63.64% vs. 42.04%; p < 0.001). Such a relationship was not found in men. Subgroups analysis of female patients with a history of tobacco use comparing current and former smoker status showed that both groups exhibited increased preoperative opioid consumption compared to patients who never smoked (88.89% vs 42.04%; p < 0.001 for current users; 59.42% vs 42.04% for former users; p = 0.008). There was also a dose-depended relationship between smoking and increased preoperative opioid consumption. Geriatric female spine patients with a history of smoking have a higher incidence of preoperative opioid consumption. Opioid intake appears to increase with the number of pack-years, both in patients with a history of smoking and in those who currently smoke.


Positive and negative action-effects improve task-switching performance.
Anticipation of one's own actions' effects drives goal-directed behavior. In multitasking environments, the learning of stable action-effect associations seems particularly important, because establishing reliable response-effect associations for multiple competing tasks may help to differentiate between these tasks and thereby improve task-switching performance. Action-effects not only have cognitive, but also motivational aspects and often the consequences of our actions are hedonically marked. Thus, the anticipated hedonic quality of action-effects may also become part of the task representation, and positive and negative affect may distinctly modulate task-switching performance. We report a pre-registered experiment (N = 120) designed to examine how positive, negative, and neutral valence of action-effects impact performance in a cued task-switching paradigm. Pictures from the IAPS database were used to manipulate the action-effects' valence. Affective valence determined reaction times: participants who learned positive or negative action-effects responded faster than participants in the control condition. In particular, task-switch trials were faster in both conditions than in the control condition, while task-repetition trials were comparable across valence conditions. Our results further suggest that performance improvements in the positive and negative valence conditions occurred for different reasons. Negative action-effects expedited responses specifically for the task that produced the unpleasant outcome, while positive affect more generally promoted performance of both tasks. These findings point toward distinct roles of positive and negative valence of action-effects in regulating multitasking performance.


Impact of SARS-CoV-2 Alpha and Gamma Variants among Symptomatic Pregnant Women: A Two-Center Retrospective Cohort Study between France and Brazil.
New variants of SARS-CoV-2 are a major source of concern, especially for pregnant women and in the perinatal context. The primary aim of this study was to compare the severity of COVID-19 infection in pregnant women depending on strain predominance between wild-type Alpha and Gamma variants. The secondary aim was to study the impact of these strains on obstetrical and neonatal outcomes. We conducted a two-center international retrospective cohort study, which included two type III maternity hospitals, one in France and one in Brazil, comparing the first period corresponding to the wild-type strain and the second period corresponding to the predominance of the Alpha variant in France and the Gamma variant in Brazil. We included 151 pregnant women with symptomatic SARS-CoV-2 infection confirmed by RT-PCR. The rate of severe-to-critical infection, according to the WHO definition, was seven-fold higher in patients infected during the "variant period" than in patients infected during the "wild-type period" (aOR = 7.07, 95CI [2.50−21.6], p < 0.001). There were no statistical differences concerning composite obstetrical and neonatal outcomes between the different periods. While analyzing each variant separately, it was found that, in France, the risk of developing a severe-to-critical infection was three times greater during the Alpha period than during the wild-type period (OR = 3.25, 95CI [0.70−15.6], p = 0.13) and, in Brazil, the risk was twelve times greater during the Gamma period than during the wild-type period (OR = 11.8, 95CI [2.46−72.3], p = 0.003). The Alpha and Gamma variants of SARS-CoV-2 seem to be more dangerous in the obstetrical context. With the rapid emergence of new variants, it is necessary to accelerate vaccination to protect women and newborn children.


Genetic variation in rotavirus serotype 4 subtypes.
Serotype 4 rotavirus strains have been classified into two antigenic "subtypes" by a solid phase immune electron microscopy technique in which cross-absorbed animal polyclonal immune sera are used as the source of antibodies. The sequences of the gene encoding the outer capsid glycoprotein VP7 from a single serotype 4 rotavirus field strain identified as subtype A ("ST3-like") and from three field strains identified as subtype B ("VA70-like") were determined. A comparison of the deduced amino acid sequences indicated that 15 amino acid residues were divergent between subtypes but were conserved within a subtype. Three of these 15 amino acid residues (at positions 96, 212, and 217) were located in regions of the VP7 that have been defined as serotype-specific antigenic sites. These data suggest that VP7 subtype differences may result from critical amino acid substitutions within an immunodominant serotype 4-specific antigenic site. Whether these differences are an important mechanism in the epidemiology of rotaviruses requires further investigation.


Preparation of the Mn/Co mixed oxide catalysts for low-temperature CO oxidation reaction.
The Mn/Co mixed powders with various Mn/Co molar ratios were prepared by the coprecipitation method and used in low-temperature CO oxidation. The physicochemical characteristics of these powders were characterized using the Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), temperature-programmed reduction (TPR), and scanning electron microscopy (SEM) analyses. The results demonstrated that the Mn/Co molar ratio significantly affected both the textural and catalytic properties and the sample with a Mn/Co = 1:1 possessed a BET area of 123.7 m2g-1 with a small mean pore size of 6.44 nm. The catalytic results revealed that the pure cobalt and manganese catalysts possessed the low catalytic activity and the pure Co catalyst is not active at temperatures lower than 140 °C. The highest catalytic activity was observed for the catalyst with a Mn/Co = 1. The obtained results showed that the incorporation of Pd into the Mn/Co catalyst significantly enhanced the catalytic activity for oxidation of carbon monoxide and the highest CO conversion was observed for the catalyst with 1 wt.% Pd and this catalyst exhibited a CO conversion of 100% at 80 °C.


Zinc oxide doped on reduced graphene oxide nanosheets activated by solar radiation for degradation of organic pollutants and bacterial inactivation.
Metal ion-based nanocomposite materials were recognized to exhibit a wide range of photocatalytic and biological applications. This study aims to synthesize zinc oxide doped reduced graphene oxide (ZnO/RGO) nanocomposite in sufficient quantities through the sol-gel method. The physical characters of the synthesized ZnO/RGO nanocomposite were determined by X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Scanning electron microscope (SEM), Energy-dispersive X-ray (EDS) and Transmission electron microscopy (TEM) techniques. The TEM image results revealed rod-like morphology of the ZnO/RGO nanocomposite. The X-ray photoelectron spectral data revealed the formation of ZnO nanostructures representing the banding energy gap value of 1044.6 and 1021.5 eV positions. Moreover, ZnO/RGO nanocomposites displayed excellent photocatalytic degradation with a degradation efficiency of 98.6%. This research not only demonstrates the photocatalytic efficiency of zinc oxide-doped RGO nanosheets but also illustrates the antibacterial efficacy against two different bacterial pathogens including Gram-positive E. coli and Gram-negative S. aureus. Furthermore, this research highlights an eco-friendly and inexpensive preparation of nanocomposite material for a wide range of environmental applications.


[Stimulation of hemopoiesis in irradiated mice using horse immunoglobulin G].
The injection of heterologous polyclonal immunoglobulin G promotes the recovery of CFUs pool and increases the amount of myelokaryocytes in irradiated mice, while in nonirradiated mice, it activates differentiation of bone marrow CFUs and enhances their migration.


A novel gut inflammatory rat model by laparotomic injection of peptidoglycan from Staphylococcus aureus.
Inflammatory bowel disease includes ulcerative colitis and Crohn's disease, and is globally increasing. An appropriate model system is required to dissect the disease pathogenesis and drugs screening for adequate treatment. In the present study, we established a novel model of gut inflammation by injecting peptidoglycan from Staphylococcus aureus using laparotomic procedure. For this, three different doses of peptidoglycan, i.e., 2.5, 5 and 10 mg/kg body weight were used. The treatment effect was evaluated by studying the macrophage phagocytic function, spleen lymphocytes' proliferation and qRT-PCR for the assessment of peritoneal cells' gene expression. In addition, histological analysis of gut sections, gastric acidity, immunoglobulins and cytokines were assessed. There was significant increase in phagocytic activity in 10 mg/kg body weight PGN group. A dose dependent increase in spleen lymphocytes' proliferation and a significant increase in total acid secretion in 5 and 10 mg/kg body weight PGN treated rats were observed. In addition, a significant increment in TLR-2 and CD-14 mRNA expression in peritoneal cells, TNF-α, IL-6 and IFN-γ level and maximum distortion of gut architecture was observed in 10 mg/kg body weight PGN group. Hence, peptidoglycan from S. aureus can be used for establishing the screening model to study the action and mechanism of anti-inflammatory food products and drugs.


Modulation by dietary fat and carbohydrate of IRS1 association with type 2 diabetes traits in two populations of different ancestries.
Insulin receptor substrate 1 (IRS1) is central to insulin signaling pathways. This study aimed to examine the association of IRS1 variants with insulin resistance (IR) and related phenotypes, as well as potential modification by diet. Two IRS1 variants (rs7578326 and rs2943641) identified by genome-wide association studies as related to type 2 diabetes were tested for their associations with IR and related traits and interaction with diet in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 820) and the Boston Puerto Rican Health Study (BPRHS) (n = 844). Meta-analysis indicated that rs7578326 G-allele carriers and rs2943641 T-allele carriers had a lower risk of IR, type 2 diabetes, and metabolic syndrome (MetS). Significant interactions on IR and MetS were found for these two variants and their haplotypes with diet. In GOLDN, rs7578326 G-allele carriers and rs2943641 T-allele carriers and their haplotype G-T carriers had a significantly lower risk of IR and MetS than noncarriers only when the dietary saturated fatty acid-to-carbohydrate ratio was low (≤ 0.24). In both GOLDN (P = 0.0008) and BPRHS (P = 0.011), rs7578326 G-allele carriers had a lower risk of MetS than noncarriers only when dietary monounsaturated fatty acids were lower than the median intake of each population. IRS1 variants are associated with IR and related traits and are modulated by diet in two populations of different ancestries. These findings suggest that IRS1 variants have important functions in various metabolic disorders and that dietary factors could modify these associations.


Actual and projected gaps in the provision of residential aged care in New South Wales, Australia.
Objective The need for residential care services will grow significantly over the coming years as the general population in Australia continues to age. The aim of this study was to assess the adequacy of residential care services across New South Wales (NSW), Australia, in relation to the current and predicted future aging population. Method This study was a secondary data analysis. Existing datasets were compiled for analysis by creation of a temporal geodatabase, with predicted population data from 2019 to 2029 linked to corresponding geographic zones. Results Demand for operational places was over capacity in 2019, at 101.5%. From 2019 to 2029, this will grow to 120.2% of 2019 capacity by 2024 and to 135.6% by 2029. An additional 25 800 operational places will be required by 2029 to meet targets. During the previous decade of 2008-18, operational places grew by only 11 502 places. Conclusions NSW was not providing an adequate level of residential aged care and, under current allocations, this problem will worsen substantially over time, with flow-on impacts for the health sector. With aged care reform a current federal government focus, the results of this study may guide decisions that better support the provision of residential aged care. What is known about this topic? The recently completed Australian Royal Commission into aged care noted widespread system failure and highlighted the gaps in medical services that older Australians were experiencing. What does this paper add? This paper reports that demand for residential aged care places in NSW was already over capacity in 2019 and that the availability of places varies considerably across the state. Further, an additional 25 800 operational places are required by 2029 to meet government targets. If the growth rate from the past decade is maintained, this will result in a shortfall of 14 298 aged care places in NSW alone. What are the implications? Without significant increases in the current rate of growth for aged care places, the mainstream medical and health sectors will face significant additional pressures arising from unmet need in both older patients and their informal carers.


3D-Printed Porous Tantalum Coated with Antitubercular Drugs Achieving Antibacterial Properties and Good Biocompatibility.
Treatment of bone and joint tuberculosis remains a challenge. The development of tissue-engineered drug-loaded biomaterials has increased the therapeutic options. However, for the treatment of osteoarticular tuberculosis with severe local infection risks and high weight-bearing requirements, it is still necessary to design materials consistent with bone biomechanics, cytocompatibility, and osteogenesis and to provide more effective antimicrobial functions. The antitubercular drugs isoniazid and rifampicin are loaded with gellan gum, and a 3D-printed porous tantalum surface is treated with polydopamine to increase adhesion. The osteogenic induction and differentiation are tested using alkaline phosphatase, alizarin red staining, sirius red staining, and polymerase chain reaction testing. Bone regeneration in vivo is measured by X-ray, micro-computerized tomography, hard tissue sections, and fluorescence staining. The drug is released slowly in vitro and in vivo, increasing the duration of antibacterial action. The composite bio-scaffolds inhibit Staphylococcus aureus growth, have good biocompatibility, and does not inhibit the induction of osteogenic differentiation of rat bone marrow mesenchymal stem cells. The composite bio-scaffold can simultaneously achieve localized long-term controlled drug release and bone regeneration and is a promising route for bone and joint tuberculosis treatment.


Characterization of post-COVID syndromes by symptom cluster and time period up to 12 months post-infection: A systematic review and meta-analysis.
The objective of this study was to characterize post-COVID condition symptoms and symptom clusters, their duration, and prevalence. We conducted a systematic review and random-effects meta-analysis of studies reporting post-COVID-19 symptoms and clusters, respectively. We searched MEDLINE (via PubMed), Scopus, Web of Science, Science Direct, Google Scholar, EBSCOhost, EMBASE, PsycINFO, Cochrane Library, and Mednar for literature reporting on the post-COVID condition up to August 2022. In the 76 included studies, we found that although most symptoms were reported less frequently 7-12 months after infection compared to earlier, over 20% of patients reported at least one post-COVID condition-compatible symptom. In the seven studies reporting post-COVID symptom clusters, neurological clustering was consistently identified, followed by cardiorespiratory and systemic/inflammatory. Post-COVID symptom clustering provides direction for research into the etiology, diagnosis, and management of post-COVID conditions. Studies reporting post-COVID symptom clusters remain rare due to the focus on individual symptom reporting. Studies on post-COVID symptom clusters should replace individual symptom reporting to accelerate our understanding of this emerging public health issue.


LYL1 degradation by the proteasome is directed by a N-terminal PEST rich site in a phosphorylation-independent manner.
The Lymphoblastic leukemia 1 (LYL1) gene is a proto-oncogenic transcription factor found upregulated in patients with T-cell acute lymphoblastic leukemia (T-cell ALL). Initially, the upregulation was described to be as a result of a translocation. However, further studies revealed that transcriptional upregulation of LYL1could also occur without translocations. In addition, post-translational mechanisms, such as protein degradation could influence LYL1 expression as well. In this study, we considered possible post-translational regulation of Lyl1, and investigated fundamental mechanisms governing LYL1 degradation in cell-based culture assays. We identify a PEST sequence motif located in the N-terminus of LYL1, which determines the efficiency of LYL1 degradation by the proteasome. The absence of the PEST degradation site leads to accumulation or upregulation of LYL1. We also show that LYL1 is phosphorylated by MAPK at S36, and determined that proteasomal degradation of LYL1 occurs in a phosphorylation-independent manner. Understanding LYL1 degradation is a step forward not only towards deciphering the normal function and regulation of LYL1, but could suggest post-translational mechanisms for upregulation of LYL1 that may contribute to its oncogenic role.


Partial denervation of the locus coeruleus projections by treatment with the selective neurotoxin DSP-4 potentiates the long-term effect of parachloroamphetamine on 5-hydroxytryptamine metabolism in the rat.
Pretreatment with N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4), a neurotoxin highly selective for the locus coeruleus (LC) projections, has recently been found to increase the vulnerability of dopaminergic nerve terminals to their selective neurotoxins. In the present study, combined treatment with a selective serotonergic (5-HT-ergic) neurotoxin parachloroamphetamine (PCA) at low doses (1 or 2 mg/kg) and a low dose of DSP-4 (10 mg/kg) led to larger decreases in 5-hydroxyindoleacetic acid (5-HIAA) levels in several brain regions than with either toxin alone. A reduction in 5-hydroxytryptamine (5-HT) turnover was observed only after the combined treatment with low doses of DSP-4 and PCA. When DSP-4 (10 mg/kg) was administered 2 months before PCA (2 mg/kg), the effect of PCA on cortical 5-HT levels was augmented, as was the effect on cortical and hypothalamic 5-HIAA levels. Conclusively, after limited alterations in the LC projections, there is an enhanced sensitivity of 5-HT-ergic nerve terminals to PCA.


miR-1975 serves as an indicator of clinical severity upon influenza infection.
Emerging evidence highlights the role of non-coding small RNAs in host-influenza interaction. We have identified a Y RNA-derived small RNA, miR-1975, which is upregulated upon influenza A virus infection in A549 cells. The aim of this study is to investigate whether miR-1975 serves as an indicator of clinical severity upon influenza infection. We investigate the abundance of miR-1975 in sera from clinical patients and its correlation with hypoxemia status. We quantified its amounts in sera from influenza virus-infected patients and healthy volunteers by means of stem-loop RT-PCR. Median values of miR-1975 were significantly higher in influenza virus-infected patients, especially in hypoxemic patients. miR-1975 levels at the acute stage of the disease were highly correlated with the fraction of inspired oxygen used by the patients and total ventilator days. Receiver operator characteristic curve analysis revealed that miR-1975 levels in combination with days of fever before presenting to hospital had significant predictive value for hypoxemia and respiratory failure for patients infected with influenza virus. Our results reveal that circulating miR-1975 has great potential to serve as a biomarker for predicting prognosis in patients infected with influenza virus.


The prevalence of hypoxemia detected by pulse oximetry during recovery from anesthesia.
Pulse oximetry was used to assess the prevalence of hypoxemia (arterial oxygen saturation of 90% or less) at various times in the immediate postoperative period: five minutes after arrival, 30 minutes later, and just before discharge. Among 149 inpatients studied, one or more hypoxemic measurements were made in 21 (14%) during their postoperative course. Of 92 outpatients, 1 (1%) was found to be hypoxemic. For inpatients, the prevalence of hypoxemia preoperatively, 5 minutes after arrival in recovery, 30 minutes later, and at discharge was 2%, 4%, 6%, and 9%, respectively. Patient factors associated with a significantly higher prevalence of hypoxemia were obesity (22%), body cavity surgical procedures (24%), age over 40 years (18%), American Society of Anesthesiologists physical status (I, 7%; II, 17%; III, 18%; IV, 100%), duration of anesthesia longer than 90 minutes (18%), and intraoperative administration of greater than 1,500 ml of fluid (20%). Unrecognized hypoxemia in postsurgical inpatients with or without these risk factors is common. Therefore routine monitoring of these patients with a pulse oximeter is suggested.


Cytology of cystic nephroma: a case report.
Cystic nephroma is a rare benign multiloculated cystic renal neoplasm that is often confused with multicystic renal cell carcinoma radiographically and cytologically. A 58-year-old woman was incidentally found to have a multiloculated cystic right renal lesion. Cytologic examination of the fluid aspirated from the lesion was reported as highly suspicious for renal cell carcinoma, but a right nephrectomy revealed a cystic nephroma. Cystic nephroma fluid is characterized by the presence of sparse epithelial cells with moderate nuclear atypia. Conversely, the fluid of multicystic renal cell carcinoma is moderately cellular with no or mild nuclear atypia.


Substantial Intestinal Microbiota Differences Between Patients With Ulcerative Colitis From Ghana and Denmark.
Ulcerative colitis (UC) is a relapsing nontransmural inflammatory disease that is restricted to the colon and is characterized by flare-ups of bloody diarrhea. In this study, we aimed to investigate intestinal bacterial diversity in healthy controls and patients with UC with and without active disease, from Ghana and Denmark. The study included 18 UC patients (9 with active and 9 with inactive disease) and 18 healthy controls from Ghana. In addition 16 UC patients from Denmark (8 UC with active and 8 UC with inactive disease) and 19 healthy controls from Denmark. Microbiota diversity analysis relied on sequencing of ribosomal small subunit genes. Purified genomic DNA was submitted to PCR using a primer set targeting prokaryotes and eukaryotes. The purified DNA was sequenced on the Illumina MiSeq system in a 2 × 250 bp set up (Illumina, San Diego, CA, USA). Blinded analysis of the taxonomy table was performed using BioNumerics-7.5 (Applied Maths NV, Sint-Martens-Latem, Belgium). When analyzing the taxonomy data for prokaryotes, cluster and principal component analysis shows Danish healthy controls clustered together, but separate from healthy controls from Ghana, which also clustered together. The Shannon diversity index (SDI) for prokaryotes shows significant differences between Danish healthy controls and patients in comparison with the corresponding groups from Ghana (p = 0.0056). Significant increased abundance of Escherichia coli was detected in healthy controls from Ghana in comparison with healthy controls from Denmark. The SDI of the prokaryotes ranges between 0 and 3.1 in the Ghana study groups, while in the Danish study groups it ranges between 1.4 and 3.2, the difference is however not significant (p = 0.138). Our data show a significant increased abundance of eukaryotes species in the healthy control group from Ghana and Denmark in comparison with patient groups from Ghana and Denmark. Overall, healthy controls and patients with UC from Denmark have increased diversity of prokaryotes. Healthy controls from Denmark and Ghana have increased abundance of eukaryotes in comparison with UC patient groups from Denmark and Ghana.


Fine-scale genetic diversity among Burkholderia pseudomallei soil isolates in northeast Thailand.
Burkholderia pseudomallei soil isolates from northeast Thailand were genotyped using multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) and multilocus sequence typing (MLST). MLVA identified 19 genotypes within three clades, while MLST revealed two genotypes. These close genetic relationships imply a recent colonization followed by localized expansion, similar to what occurs in an outbreak situation.


Resynchronizing Right and Left Ventricles With Right Bundle Branch Block in the Congenital Heart Disease Population.
This study describes a single center experience with the use of cardiac resynchronization therapy (CRT) in a difficult patient population, including single systemic right ventricles (RVs), subpulmonary RVs, and left ventricles (LVs) with right bundle branch block (RBBB). CRT remains challenging in the congenital heart disease population. Consecutive patients undergoing resynchronization of single RVs, subpulmonary RVs, or LVs in the setting of RBBB were identified between 2016 and 2019. Patients who had CRT performed for complete heart block or had <3 months of follow-up were excluded. Patients underwent pre-procedural advanced imaging by echocardiogram, computed tomography, or cardiac magnetic resonance to assess ventricular function and synchrony; intraoperative mapping was performed to identify optimal lead placement. All patients undergoing resynchronization presented with at least moderate systolic ventricular dysfunction in the setting of intrinsic atrioventricular nodal conduction and RBBB. Seven patients were identified. Two patients underwent CRT of a single RV, 3 with subpulmonary RVs and 2 with systemic LVs. The median age at CRT was 5 years (range 0.6 to 48 years). The median follow-up was 9 months (range 3 to 18 months). The median baseline QRS duration was 180 ms (range 115 to 260ms). Post-CRT, the QRS duration decreased by a median of 34% (range 19% to 38%). All patients had improvement in their systolic ventricular function. Targeted resynchronization in systemic and subpulmonary RVs can be used to improve ventricular function and heart failure in the congenital heart disease population. Similar techniques can be applied to successfully treat patients with LV dysfunction and RBBB and improve their long-term outcomes.


Successful use of human semen cryobanking for in vitro fertilization.
Frozen-thawed donor semen was compared with freshly ejaculated donor semen for in vitro fertilization of human oocytes in patients with infertile husbands. There was no significant difference in the fertilization rates between frozen-thawed (85%) and fresh spermatozoa (78%). Fertilization occurred with semen stored for as long as 27 months and with numbers of spermatozoa as low as 20,000/ml culture medium for insemination of oocytes. Pregnancy rates of embryos, fertilized with frozen-thawed and freshly ejaculated spermatozoa, were similar following embryo transfer.


Stereochemistry of the transmetalation of Grignard reagents to copper (I) and manganese (II).
Transmetalation of a chiral secondary Grignard reagent to Cu(I) or Mn(II) occurs with partial racemization in a manner that suggests the sequence of two transmetalation cycles, one with racemization (caused by ET ?) and the other one with (predominant) retention of configuration.


Induction of interleukin 1 secretion by murine macrophages and human monocytes after stimulation by RU 41740, a bacterial immunomodulator.
RU 41740, a glycoprotein extract from K. pneumoniae K2O1 strain, is an immunomodulating compound which has been shown to reduce infectious episodes in patients prone to recurrent infections. Data from preliminary experiments suggest that RU 41740 may affect several target cells, including T cells, B cells or macrophages. In the present report we show that RU 41740 can trigger mouse macrophages and human adherent mononuclear cells to produce interleukin 1 activity. Indeed, supernatants from mouse peritoneal adherent cells and human monocytes incubated in presence of RU 41740, can stimulate blastogenesis in thymocytes from C3H/HeJ mice. The data suggest that the immunomodulating effect of RU 41740 could be related to its ability to induce interleukin 1 production.


Lecithin:retinol acyltransferase in retinal pigment epithelial microsomes.
Microsomal preparations from retinal pigment epithelium carry out phosphatidylcholine synthesis upon incubation with 1-palmitoyllysophosphatidylcholine and fatty acyl-CoA. Phosphatidylcholine synthesized in situ in this manner is an acyl donor for retinyl ester synthesis, demonstrating the existence of lecithin:retinol acyltransferase. Although acyl transfer to retinol is from the 1-position of phosphatidylcholine, the fatty acid in the 2-position is important in substrate recognition. The finding of this novel enzyme activity in retinal pigment epithelial microsomes suggests that phosphatidylcholine is the endogenous acyl donor in CoA-independent retinol esterification observed in these preparations.


Six minute walk test in Italian children with cystic fibrosis aged 6 and 11.
Six minute walk test (6MWT) is a field exercise test widely used in clinical practice, both in adults and in pediatric patients. The primary aim of the study is to evaluate the physical performance of the subjects and compare them with the predicted Italian values. The secondary aim is to verify the possible relationship between the 6MWT distance (6MWD) and the clinical variables of the sample. Italian children between 6-11 years affected by CF were recruited from 9 regional centers for CF. Short questionnaire assessments about their health state and physical activity routine was administered. Anthropometric characteristics were measured before the test and, peripheral oxygen saturation (SpO2), heart and respiratory rate were measured before and after a 6-minute walk test. The tests were performed according to the American Thoracic Society (ATS) guidelines. 6MWD was compared with the predicted distance calculated by the reference equation for healthy subjects of the same age. A total of 132 children were recruited (70 male) and completed the assessment. The mean (±SD) for 6MWD was 557.4 (±69.9), male = 551.4 (±80.0), female = 560.4 (±63.3), however the predicted distance mean was 605 m. A total of 101(76.5%) subjects practice regular physical activity. A total of 31 (23%) had a FEV1 lower than their lower limits of normal (LLN). Functional performance on the 6MWT was poorer among the CF patients than among the predicted distance estimated with Italian values. The correlation with the amount of physical activity and 6MWD has been verified.


Evaluation of biliary disease by scintigraphy.
The value of biliary scintigraphy was studied in 180 patients with suspected biliary tract disease. Scintigraphy was performed after intravenous injection of technetium-99m labelled (1) N-substituted iminodiacetic acid derivative (HIDA) in 91 patients, and (2) butyl derivative of iminodiacetic acid (BIDA) in 89 patients. Most of the patients were investigated additionally by conventional techniques such as cholecystography, cholangiography and ultrasonography. It is concluded that biliary scintigraphy is a simple and safe technique for visualization of the biliary tract. It is particularly useful in the evaluation of acute cholecystitis, in patients with iodine sensitivity requiring imaging of biliary tract, and in the differentiation of obstructive from nonobstructive jaundice. Its value in kinetic disturbances of the gallbladder and in quantitative evaluation of hepatobiliary function needs further study.


Combining microchip and cell technology for creation of novel biodevices.
Microchip technology has matured over the years into an important field in which novel technologies are being constantly invented, and down-sizing and incorporation of already existing methodologies into the microscale is increasing assay performance and bearing the promise of future total integration for simple, widespread use. One rapidly growing sub-discipline of the microchip research field is focused around the integration of microchip technology and cell biology. In this review, we recapitulate progress here at the Kitamori laboratory in direct relation to cell and microchip technologies, and show some examples of successful integration of the two, going from controlled patterning of cells, on-chip cell culture stimulation, and cardiovascular systems on a chip, to bio-microdevices integrating cardiovascular cells and microtechnology to create novel biodevices such as biocompatible, miniature pumps.


Impact of a critical pathway on acute myocardial infarction quality indicators.
To determine the impact of a critical pathway on acute myocardial infarction (AMI) quality indicators. Retrospective chart review. Large university hospital. One hundred seventy-five patients who underwent primary percutaneous transluminal angioplasty for AMI (control group 89 patients, intervention group 86 patients). The medical records of the control group (1998-1999) were reviewed for door-to-balloon (DtB) time (the time between the patient's arrival at the emergency department and the first balloon inflation during a percutaneous transluminal coronary angioplasty procedure). Drug therapy prescribed at hospital discharge (aspirin, beta-blocker, angiotensin-converting enzyme [ACE] inhibitor, and lipid-lowering therapy) was also reviewed. The data collected for the control group were compared with the intervention group data (2000-2001). The impact of the pathway was evaluated using the Wilcoxon rank sum test, odds ratios (ORs), and chi2 tests. The DtB time was significantly lower in the intervention group versus the control group (91.5 vs 108 min, p < 0.01), and fewer intervention patients exceeded the guidelines with a DtB time longer than 120 minutes (OR 0.38, p < 0.01). In addition, the intervention group was more likely than the control group to be prescribed an ACE inhibitor (OR 3.7, p < 0.01) or lipid-lowering therapy (OR 3.7, p = 0.02) at discharge. Aspirin and beta-blockers were not prescribed differently in the intervention versus control groups (aspirin 95.2% vs 96.2%, beta-blockers 93.5% vs 92.6%). These data suggest that in the current era of published treatment guidelines, implementation of a critical pathway can further improve AMI quality indicators and clinical care.


Clinical responsibility and client autonomy: dilemmas in mental health work at the margins.
Mental health outreach to homeless persons requires practice standards for cases in which clinical assessment and client autonomy conflict. After reviewing the principles of mental health outreach and presenting case examples, conditions and boundaries within which outreach workers negotiate the clinical responsibility/client autonomy dilemma are discussed. Guidelines to support sound clinical practice while respecting client autonomy are also discussed.


Vesico-uterine Fistula Following C-section - A Case Report and Literature Review.
Vesico-uterine fistulas represent a rare type of genito-urinary fistulas; however, due to the increasing incidence of Caesarean section (C-section) in the last decade, this abnormal communication between the urinary and genital tracts has been reported more often after such surgical procedures. The aim of the current article was to report the case of a 28-year-old patient who was submitted to surgery for a vesico-uterine fistula seven years after a C-section. The 28-year-old patient with a previous history of four vaginal deliveries and one C-section was self-presented to the Gynecology Department for cyclic hematuria and diagnosed with a vesico-uterine fistula after injecting methylene blue in the uterine cavity during hysteroscopy. The patient was further submitted to surgery, and a parcelar myometrectomy en bloc with parcelar cystectomy, cystography, and prophylactic salpingectomy was performed. The postoperative outcome was uneventful. Although vesico-uterine fistulas represent rare events, they should be considered, especially in young patients with a previous history of C-section.


Splenic irradiation prior to allogeneic transplant conditioning in myelofibrosis: A pilot experience.
In the era of JAK inhibitors, allogeneic stem cell transplantation (HSCT) remains the only curative treatment for patients with Myelofibrosis (MF). Splenic irradiation (SI) may be used to reduce spleen size and related symptoms. We conducted a retrospective analysis on 14 patients with MF who underwent HSCT with SI from any donor source at our center between June 2016 and March 2021. All patients received a conditioning backbone based on treosulfan and fludarabine, with post-transplant cyclophosphamide (PTCy) and sirolimus as graft-versus-host disease (GvHD) prophylaxis. Patients received SI with 10 Gy involved-field radiotherapy in five 2-Gy fractions over the course of a week prior to the beginning of conditioning. At transplant all patients were transfusion-dependent and had splenomegaly (median bipolar diameter by ultrasound: 20.75 cm). Overall, 12 patients had received ruxolitinib prior to transplant. Re-evaluation of spleen dimensions was available for 13 patients: median splenic bipolar diameter after at least 3 months from transplant decreased by a median of 25%. With a median post-transplant follow-up of 25 months, 6 patients remain in CR with full-donor chimerism, 3 patients died due to NRM. Overall, 4 patients relapsed. At last follow-up, nine patients are currently alive and achieved transfusion-independence. In a small cohort of mostly ruxolitinib pre-treated patients, SI and treosulfan-based conditioning appeared a safe and effective tool to reduce spleen dimensions and ameliorate symptoms. Future prospective studies with adequate sample size are warranted to further investigate the usefulness and safety of this approach in MF.


Public health impact of a novel smoking cessation outreach program in Ontario, Canada.
Provision of evidence-based smoking cessation treatment may contribute to health disparities if barriers to treatment are greater for more disadvantaged groups. We describe and evaluate the public health impact of a novel outreach program to improve access to smoking cessation treatment in Ontario, Canada. We partnered with Public Health Units (PHUs) located across the province to deliver single-session workshops providing standardized evidence-based content and 10 weeks (2007-2008) or 5 weeks (2008-2016) of nicotine replacement therapy (NRT). Participants completed a baseline assessment and were followed up by phone or e-mail at 6 months. We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework to evaluate the public health impact of the program from 2007 to 2016. Given the iterative design and changes in implementation over time, data is presented annually or bi-annually. There were 26,122 enrollments from 2007 to 2016. Between 31 and 442 workshops were held annually. The annual reach was estimated to be 0.1-0.3% of eligible smokers in Ontario. Participants were older, smoked more heavily, had a lower household income, were more likely to be female and be diagnosed with a mood or anxiety disorder, and less likely to have a postsecondary degree compared to average Ontario smokers eligible for participation. The intervention was effective; at 6-month follow-up 22-33% of respondents reported abstinence from smoking. Adoption by PHUs was 81% by the second year of operation and remained high (72-97%) thereafter, with the exception of 2009-2010 (33-56%) when the program was temporarily unavailable to PHUs due to lack of funding. Implementation at the organizational level was not tracked; however, at the individual level, approximately half of participants used most or all of the NRT received. On average, maintenance of the program was high, with PHUs conducting workshops for 7 of the 10 years (2007-2016) and 4 of the 5 most recent years (2012-2016). The smoking cessation program had a high rate of adoption and maintenance, reached smokers over a large geographic area, including individuals more likely to experience disparities, and helped them make successful quit attempts. This novel model can be adopted in other jurisdictions with limited resources.


[Radiology in ear, nose and throat medicine--the clinical picture of ear diseases and demands on the radiologist].
Due to the hidden location of the ear, deep inside the head, the otologist often requires the collaboration of the radiologist for the diagnosis of ear diseases. Arranged in an anatomical classification (outer, middle and inner ear), such problems are discussed with regard to their clinical appearance.


Therapy of Crohn's disease in childhood.
Crohn's disease in childhood is a chronic relapsing condition with a high morbidity. Growth failure is common. The aim of therapy is to induce and then maintain disease remission and thereby promote well-being and normal growth and development. Enteral nutrition (either polymeric or elemental) is effective and used as initial therapy. This is employed as sole therapy over a 6- to 8-week period followed by a period of controlled food reintroduction. The relapse rate is high and further courses of enteral nutrition or alternative therapies are frequently required. Corticosteroids are also effective as initial therapy and are required in difficult cases but there are problems with their long term use, particularly their adverse effects on growth. Many patients develop either corticosteroid-dependent or corticosteroid-resistant disease. In this instance, additional immunosuppression, such as azathioprine, can be used. Surgery is required for those patients with disease resistant to medical therapy and this will result in remission; however, the relapse rate with surgery is high. There are many areas for future research. Very little is known about why enteral nutrition works, how long it should be given or its role as maintenance therapy. Newer immunosuppressive strategies based on cytokine modulation may be helpful in children once more experience is gained from their use in adults.


Radionuclide evaluation of right ventricular wall motion after surgery in tetralogy of Fallot.
Regional wall motion patterns in tetralogy of Fallot and its postoperative modifications by electrical and hemodynamic factors were assessed by Fourier analysis of gated radionuclide angiograms in 24 studies performed in children after surgical correction of tetralogy of Fallot. The range of right ventricular (RV) phase angles (standard deviation of the peak [SDP] of RV) as well as the difference between RV and LV (delta MPh) were used as indices of the synchronicity of wall motion and were correlated with RV apical electrical activation time determined by endocardial electrical mapping. Postoperative studies were divided into two groups according to apical activation: (a) those involving right bundle branch block (RBBB) (nine patients), and (b) those involving distal RBBB (15 patients). delta MPh was longer in proximal than in distal RBBB. Best discrimination between the two groups was obtained with SDP of RV (proximal = 24 degrees +/- 3 degrees, and distal = 17 degrees +/- 2 degrees; p less than 0.0001). These results showed that the range of ventricular phases measured by the SD of the phase distribution of the right ventricle is a good index for distinguishing between proximal and distal RBBB after cardiac surgery.


Waste mitigation and resource recovery from food industry wastewater employing microalgae-bacterial consortium.
Wastewater generated by the food industry is rich in nitrogen and phosphorus with possible presence of heavy metals. Physical and chemical methods of treatment, although effective, are expensive and may cause secondary environmental pollution damaging aquatic and human life. Traditional biological methods are eco-friendly and cost-effective but involve standalone microorganisms that pose risk of contamination and are not as effective. This review discusses the application of novel microalgal-bacterial consortium as a solution for the resource recovery and treatment of dairy, starch and aquaculture wastewater. Use of biofilm reactors containing anaerobic and aerobic sludge has shown 80-90% and > 90% COD and nutrient removal efficiency in treatment of dairy and starch processing wastewater, respectively. The treatment of aquaculture processing wastewater can be challenging due to high sality and requires salt-tolerant bacteria-microalgae consortium. In this regard, the identification of dominant microalgae and bacteria using 16S rRNA and 18S rRNA genes is recommended.


The intraocular foreign body. Principles and problems in the management of complicated cases by pars plana vitrectomy.
In a retrospective study, the results of pars plana vitrectomy in treatment of injuries with intraocular foreign bodies were described. The patient material was subdivided into five different groups. In 41.6% of the cases, practical blinding could not be prevented. A visual acuity of 0.2 and better was present in 26.6% of the cases. The preoperative (45%) and postoperative (30%) traumatic retinal detachment have an extremely unfavorable prognosis with a reattachment rate of 40 or 21% respectively. The results in the treatment of injuries with magnetic splitters and their sequelae are very much better than those with nonmagnetic foreign bodies. The gunshot and air rifle pellet injuries were the most unfavorable group.


Rationale and Design of a Randomized, Double-Blind Trial Evaluating the Efficacy of Tranexamic Acid on Hematoma Expansion and Peri-hematomal Edema in Patients with Spontaneous Intracerebral Hemorrhage within 4.5 h after Symptom Onset: The THE-ICH Trial Protocol.
Hematoma expansion (HE) and peri-hematomal edema (PHE) are associated with adverse outcomes of patients with acute spontaneous intracerebral hemorrhage (sICH). Due to a lack of proven treatments, it is critical to explore novel treatments for HE and PHE to improve functional recovery after sICH. This is a prospective, multicenter, placebo-controlled, double-blind, and randomized clinical study of approximately 2400 patients with sICH. Patients within 4.5 h of sICH onset that fulfilling the clinical criteria for diagnosis (e.g. age more than 18 years old, the Glasgow Coma Scal>7, and no planned surgery) will randomly receive either intravenous tranexamic acid (TXA) 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo (sodium chloride 0.9%). Clinical data including the ICH score and the Glasgow Coma Scale score will be collected on admission. After assessment of HE and PHE expansion, follow-up will be conducted with enrolled patients for 90 days. Primary outcome metrics are HE (defined as either >33% or >6 ml increase from baseline) and PHE expansion rate at 24 ± 3 h and 72 ± 3 h post-sICH. Secondary outcome metrics include mortality and the modified Rankin Scale on day 90 after sICH. Appropriate statistic methods will be used to evaluate the efficacy of TXA on patients with sICH within 4.5 h of symptom onset. HE usually occurs within the first few hours after onset of symptoms. It is essential to evaluate the efficacy of TXA on HE within a narrow window of time. This will be the first trial to evaluate the efficacy of TXA on HE and PHE expansion in sICH patients within 4.5 h after symptom onset. This trial is registered as ChiCTR1900027065 at http://www.chictr.org.cn.


The role of protein kinase C in arachidonic acid release and prostaglandin E production from CHO cells transfected with EGF receptors.
Arachidonic acid release and prostaglandin production are stimulated by both phorbol esters and growth factors in various cell types. Whereas phorbol esters activate and transmit a signal via protein kinase C, this pathway is not necessarily involved in growth factor signal transduction. We investigated the involvement of protein kinase C in the pathway of arachidonic acid metabolism by CHO cells transfected with full-length EGF receptor (CHOwt). Two isoforms of protein kinase C were identified in CHOwt cells, alpha and zeta. On downregulation, the parallel loss of phorbol ester-stimulated arachidonic acid release and the alpha-isoform suggests a possible involvement of this isoform in phospholipase A2 activation in these cells. In addition, we propose that the zeta-isoform may be separately involved in prostaglandin production as residual phorbol ester-stimulation of PGE production occurs in downregulated cells where PKC zeta is the sole remaining isoform. EGF stimulation of arachidonic acid release, as a measure of phospholipase A2 activation, and subsequent prostaglandin production are unaffected by inhibition of protein kinase C in CHOwt cells. Indeed one such inhibitor, staurosporine, augmented the EGF effect. These results suggest that PKC is not required for EGF activation of phospholipase A2 in these cells.


Scanning electron-microscopic study of sperm retention and migration in the vagino-cervical region of the rabbit.
The pattern of sperm retention and migration in the vagino-cervical region of rabbit was studied by means of scanning electron microscopy. The following phenomena were observed: 1) Spermatozoa located in the vagina and at the orifice of the ectocervix are usually distributed diffusely. They appear to be resting on the epithelial surface; many are structurally abnormal or decapitated. 2) The great majority of spermatozoa, however, seems to be anchored or retained in narrow epithelial channels with their heads in close file formations. This phenomenon was observed particularly in the fornix vaginae as late as 24 h post coitum. 3) A great number of spermatozoa invading the cervix evidently migrates in groups along the mucosal surface. Their heads are oriented toward the uterus and contact the epithelial cells. Spermatozoa that migrate beyond the cervico-uterine junction are distributed in the same manner. 4) Spermatozoa colonizing the cervical crypts appear to be attached via the anterior margins of their heads to the epithelial cells or to the tips of kinocilia. Their tails project into the crypt lumen. It is suggested that mainly three factors may be responsible for these phenomena: (i) the fact that only motile spermatozoa overcome the vagino-cervical barrier; (ii) the tendency of spermatozoa to move along the mucosa in close vicinity to the epithelial cells; and (iii) the inability to recognize mechanical barriers on the migration route (e.g., cervical crypts) and to overcome them quickly. This may be one of many possible causes leading to sperm retention in the vagino-cervical region.


Selective androgen insensitivity of hepatic drug-metabolizing enzymes in senescent mice.
The normal sexual dimorphism in murine hepatic hexobarbital metabolism (i.e. females greater than males) was found to be absent in senescent animals. Hexobarbital metabolism, expressed as microsomal activity of hexobarbital hydroxylase and hexobarbital-induced sleep time, in senescent male mice was similar to that in females, but significantly greater than that found in young adult males. No age-related changes in hexobarbital metabolism were observed in intact females. In addition, experiments involving gonadectomies and testosterone administration indicated that both male and female senescent mice were insensitive to the normally repressive effects of androgens on hexobarbital hydroxylase. In contrast, the sexual dimorphism in the activity of p-nitrophenol UDP-glucuronosyltransferase was maintained in the senescent mice as well as the usual responsiveness to testosterone regulation. Furthermore, the growth-promoting effects of androgen on the kidneys and seminal vesicles were similarly expressed in young and old mice. Thus, our results suggest the development of an age-dependent and selective insensitivity of hexobarbital hydroxylase to androgenic regulation in the aging mouse.


A debriefing tool to acquire non-technical skills in trauma courses.
The study reports the use of a nominal group technique (NGT) to evaluate the PEARLS Healthcare debriefing tool as a tool to foster non-technical skills in trauma simulation courses. Additionally, it introduces a debriefing card to be used in trauma courses. A nominal group technique was used to evaluate the main strategies for PEARLS. The experts had the opportunity to share their opinions in an online survey and online meeting. Seven participants participated in the nominal group. Based on the online survey results, the self-assessment debriefing strategy (from PEARLS) was rated 4.83/5 in relevance, the focused facilitation 5/5, and the provision of information 4.5/5. Participants felt that PEARLS was appropriate and useful for fostering non-technical skills: all the debriefing strategies contained in PEARLS were felt to be valid and worth using; and cue cards for the instructors were suggested to assist them in conducting structured formal debriefings. A specific debriefing tool for trauma scenarios was designed based on these suggestions, which is presented in this article. A nominal group of experts in education, simulation, and trauma support PEARLS strategies for non-technical skills training in trauma courses.


Cost Effectiveness of Pembrolizumab for Advanced Melanoma Treatment in Portugal.
The aim of this study was to assess the cost-effectiveness of pembrolizumab in treating patients with ipilimumab-naïve advanced melanoma in Portugal. A cost-effectiveness model was developed to analyze the costs and consequences of treatment with pembrolizumab compared to treatment with ipilimumab in patients with advanced melanoma not previously treated with ipilimumab. The model was parameterized by using data from a head-to-head phase III randomized clinical trial, KEYNOTE-006. Extrapolation of long-term outcomes was based on approaches previously applied, combining ipilimumab data and melanoma patients' registry data. The analysis was conducted from the perspective of the Portuguese National Health Service, and a lifetime horizon (40 years) was used. Portugal-specific disease management costs were estimated by convening a panel of six clinical experts to derive health state resource use and multiplying the results by national unit costs. To test for the robustness of the conclusions, we conducted deterministic and probabilistic sensitivity analyses. Pembrolizumab increases life expectancy in 1.57 undiscounted life-years (LYs) and is associated with an increase in costs versus that of ipilimumab. The estimated incremental cost-effectiveness ratio is €47,221 per quality-adjusted life-year (QALY) and €42,956 per LY. Deterministic sensitivity analysis showed that the results were robust to the change of most input values or assumptions and were sensitive to time on treatment scenarios. According to the probabilistic sensitivity analysis performed, pembrolizumab is associated with a cost per QALY gained inferior to €50,000 in 75% of the cases. Considering the usually accepted thresholds in oncology, pembrolizumab is a cost-effective alternative for treating patients with advanced melanoma in Portugal.


A possible evaporation site in the guard cell wall and the influence of leaf structure on the humidity response by stomata of woody plants.
Gas exchange measurements made with single leaves from Wych elm (Ulmus glabra Huds.), Lombardy poplar (Populus nigra 'Italica' L.) and common oak (Quercus robur L.) seedlings grown at high irradiance showed significant interspecific differences in the stomatal response to variation in atmospheric humidity. Elm and poplar seedlings showed low conductances at high vapour pressure differences (VPD), while the stomatal conductance of oak was little influenced by an increase in VPD between the leaf and the surrounding air. Mild water stress (leaf water potentials of approximately 0.4 MPa) reduced the sensitivity of stomata of elm to humidity and caused almost complete stomatal closure in poplar. Oak seedlings grown at low irradiance showed enhanced stomatal sensitivity to changes in VPD and comparatively high water use efficiencies.Significant reductions in stomatal conductance and transpiration of elm leaves at high VPD suggest that some water loss must occur directly from the external surfaces of the guard cell complex. At high VPD, this loss may maintain the guard cells in a flaccid condition and therefore the stomatal pore will remain closed, even though the plant may be relatively turgid. Differential staining of guard cell walls in light microscope sections of elm and oak leaves suggested an area of the wall that may be permeable to water and transmission electron micrographs revealed a corresponding cuticle-free area on the inner wall of the guard cells of elm leaves. S.E.M. and T.E.M. pictures and light micrographs form the basis of a hypothesis to explain the modifying influence of mild water stress and leaf structure on the response of elm and oak stomata to humidity.


Foliage acceptability to browsing ruminants in relation to seasonal changes in the leaf chemistry of woody plants in a South African savanna.
We investigated seasonal changes in food selection by hand-reared kudus and impalas in savanna vegetation in northern Transvaal, South Africa. The acceptability of the leaves of woody plants to these animals was compared with leaf concentrations of nutrients, fibre components and old leaf phenophases. No consistently significant correlation was found between acceptability and any single chemical factor. Based on an a priori palatability classification, discriminant function analysis separated relatively palatable species from unpalatable species in terms of a linear combination of protein and condensed tannin concentrations. The high acceptability of certain otherwise unpalatable species during the new leaf phenophase was related to elevation of protein levels relative to condensed tannin contents. Species were added to the diet during the dry season approximately in the order of their relative protein-condensed tannin difference.


Transcriptional targeting in ovarian cancer cells using the human epididymis protein 4 promoter.
Limitations of current ovarian cancer gene therapies include lack of specificity and transduction of normal tissues. One strategy toward overcoming these limitations is to direct gene therapy specifically to ovarian cancer cells by using tissue- and tumor-specific promoters. The whey-acidic protein human epididymis protein 4 (HE4) is frequently overexpressed in ovarian cancer, suggesting that the HE4 promoter is highly transcriptionally active in the disease. The objective of this study was to isolate the HE4 promoter and examine its ability to selectively activate reporter gene expression in an ovarian cancer-specific manner. To investigate transcriptional targeting in ovarian cancer gene therapy, we isolated a region of the HE4 promoter from -530 to +122 (pHE4-652; relative to the ATG start site of HE4) and placed it upstream of a luciferase reporter gene plasmid to generate pHE4-652-luc. The activity of the pHE4-652-luc reporter construct was characterized in transient transfection assays in a panel of epithelial ovarian cancer cell lines (SKOV-3, SKOV-3x, CP70, HeyC2, A2780, A2780CP, OVCAR-3), non-ovarian tumor cell lines, and primary cultures of normal cells. The activity of two other candidate gene therapy promoters, human telomerase reverse transcriptase (hTERT) and OSP1, was also characterized in these cell lines. The HE4 promoter was active in 5/7 ovarian cancer cell lines with the range of activity spanning 0.06- to 3-fold that observed for a positive control, cotransfected reporter construct (SV-40-luc). Minimal pHE4-652 promoter activity, defined as < or =5% of the activity detected with the SV-40-luc construct, was observed in the non-ovarian tumor cell lines and normal cells. The hTERT and the OSP1 promoters were active in the ovarian cancer lines. hTERT activity was highest in the CP70 cell line, and OSP1 activity was highest in the SKOV-3x cell line. Modest OSP1 and hTERT promoter activity was observed in normal cell lines and in selected non-ovarian cancer cell lines. This is the first report using the pHE4-652 promoter to drive specific reporter gene expression in epithelial ovarian cancer cell lines, and we are continuing to develop this promoter for use in transcriptional targeting in ovarian cancer gene therapy.


Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value.
Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. In naïve rats, we assessed (1) the ability of the cocaine (0.250-0.125 mg/kg/infusion) and caffeine (0.125-0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. Cocaine combined with caffeine and cocaine alone was self-administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self-administration behavior in naïve rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs.


Callithrix penicillata as a nonhuman primate model for strongyloidiasis.
In order to better understand experimental strongyloidiasis in small New World primates, and to evaluate aspects of reinfection and immunosuppression induced by glucocorticoids, nine specimens of Callithrix penicillata (Primates: Cebidae) were administered (by subcutaneous injection, sc) 3000 infective larvae of a strain of Strongyloides venezuelensis (Rhabditida: Strongyloididae) that had been maintained in successive passages through AKR/J mice since 1987. The mean prepatent period was 5.6 ± 0.7 days post-infection (DPI). The mean patent period of infection among the untreated animals (marmosets 1-7) was 123.4 ± 61.4 DPI. Two animals (marmosets 8 and 9) received dexamethasone (2.5 mg/kg, sc) for five consecutive days starting on the 20th day after infection, but this treatment did not alter the course of the infection, and the patent period for these animals was 100.5 ± 58.7 DPI (59 and 142, respectively). Stool examination showed that the highest quantities of parasite eggs were expelled between the 8th and 19th days after inoculation of the larvae. Thereafter, there was a gradual reduction in the number of parasite eggs in feces of all marmosets. During the chronic phase of the infection, before completely negative parasitological findings were obtained, the parasitological examinations were intermittently positive. Reinfection of three of these animals did not result in new positive examinations. However, given the receptiveness of these animals to initial infection with S. venezuelensis and their similarities to human beings, it is proposed that C. penicillata could be used as a nonhuman primate model for experimental strongyloidiasis.


Comparison and risk factors analysis of multiple breast cancer screening methods in the evaluation of breast non-mass-like lesions.
To compare multiple breast cancer screening methods for evaluating breast non-mass-like lesions (NMLs), and investigate new best screening method for breast non-mass-like lesions and the value of the lexicon of ACR BI-RADS in NML evaluation. This retrospective study examined 253 patients aged 24-68 years who were diagnosed with breast NMLs and described the lexicon of ACR BI-RADS from April 2017 to December 2019. All lesions were evaluated by HHUS, MG, and ABUS to determine BI-RADS category, and underwent pathological examination within six months or at least 2 years of follow-up. The sensitivity, specificity, accuracy, positive predictive values (PPV), and negative predictive values (NPV) of MG, HHUS and ABUS in the prediction of malignancy were compared. Independent risk factors for malignancy were assessed using non-conditional logistic regression. HHUS, MG and ABUS findings significantly differed between benign and malignant breast NML, including internal echo, hyperechoic spot, peripheral blood flow, internal blood flow, catheter change, peripheral change, coronal features of ABUS, and structural distortion, asymmetry, and calcification in MG. ABUS is superior to MG and HHUS in sensitivity, specificity, PPV, NPV, as well as in evaluating the necessity of biopsy and accuracy in identifying malignancy. MG was superior to HHUS in specificity, PPV, and accuracy in evaluating the need for biopsy. ABUS was superior to HHUS and MG in evaluating the need for biopsy in breast NMLs. Compared to each other, HHUS and MG had their own relative advantages. Internal blood flow, calcification, and coronal plane feature was independent risk factors in NMLs Management, and different screening methods had their own advantages in NML management. The lexicon of ACR BI-RADS could be used not only in the evaluation of mass lesions, but also in the evaluation of NML.


Detection of Cryptosporidium parvum in horses: thresholds of acid-fast stain, immunofluorescence assay, and flow cytometry.
Feces collected from three asymptomatic horses and seeded with Cryptosporidium parvum oocysts (10(1) to 10(6)/g of feces) were evaluated by acid-fast staining (AF), an immunofluorescent antibody (IFA) technique, and flow cytometry. The thresholds of detection were 5 x 10(5) oocysts/g of feces for the IFA and AF techniques and 5 x 10(4) oocysts/g for flow cytometry.


Dwindling of cardio damaging effect of isoproterenol by Punica granatum L. peel extract involve activation of nitric oxide-mediated Nrf2/ARE signaling pathway and apoptosis inhibition.
Punica granatum L. (Punicaceae) peel is often considered as a food waste in-spite of its high bioactive metabolite composition. Primarily it is rich in therapeutically active phenolics that act on multiple cellular sites, through diverse mechanisms. Hence, the present study was envisaged to investigate the effect of standardised peel extract of P. granatum against isoproterenol (ISO)-induced myocardial infarction (MI). ISO administration at a dose of 150 mg/kg; s.c., twice at 24 h interval resulted in electrocardiographic abnormalities with increased heart weight and myocardial tissue damage signifying MI. Pretreatment with the extract at 50, 100 and 200 mg/kg; p.o., for 21 days prior to ISO intoxication (30 min prior to intoxication on day 22 and 23) attenuated the observed changes, along with increased myocardial tissue superoxide dismutase activity, reduced glutathione and nitrite levels, and decreased lipid peroxidation. The extract treated groups also showed reduced serum marker enzymes of MI, showing maximum effect at highest tested dose. Immunohistochemical studies revealed increased myocardial expression of nuclear factor erythroid 2-related factor 2 (Nrf2), endothelial nitric oxide synthase (eNOS) and Bcl-2 proteins in the extract treated groups with decreased Bax expression. From the results it can be concluded that the extract pretreatment prevents ISO-induced MI through increased myocardial expression of eNOS, leading to nitric oxide-mediated Nrf2 activation, thus upregulating antioxidant mechanisms, along with inhibition of apoptosis.


Status of Vitamin B12, Zinc, Copper, Selenium, Manganese, Molybdenum and Cobalt in Severe Acute Malnutrition.
To define the vitamin B12 levels and other micronutrients status in severe acute malnutrition (SAM) children. This was a prospective hospital based cross-sectional study. Children with severe acute malnutrition as per WHO criteria. (i) Pernicious anemia (ii) Autoimmune gastritis (iii) SAM children on exclusive vitamin B12 supplementation. All enrolled children underwent a detailed clinical history, general physical examination with more emphasis on clinical features of vitamin B12 and other micronutrients deficiencies. Three ml of venous blood was collected to estimate vitamin B12 and other micronutrients. Primary outcome was percentage of deficiency of serum vitamin B12, zinc, copper, selenium, manganese, molybdenum and cobalt in SAM children. Fifty children were included in the study. The mean age of children was 15.60±12.90 mo with male to female ratio 0.85:1. The common clinical presentation in order of frequency were upper respiratory infection (URI) symptoms 35 (70%), hepatomegaly 24 (48%), Hyperpigmentation 17 (34%), angular cheilitis 14 (28%), tremors 11 (22%), edema 07 (14%), and hypotonia 05 (10%). Anemia was found in 44 (88%) children. Prevalence of vitamin B12 deficiency was 34%. Other micronutrient deficiencies observed were cobalt 24 (100%), copper 05 (12%), zinc 04 (9.5%), and molybdenum 03 (12.5%). No statistical significance was found between clinical symptoms and levels of vitamin B12 with different age and sex. Prevalence of low vitamin B12 and cobalt were more common than other micronutrients.


Evidence that stimulation of megakaryocytopoiesis by low dose vincristine results from an effect on platelets.
Appropriate low dosages of vincristine stimulate megakaryocytopoiesis and produce thrombocytosis. In this study of the thrombocytotic action of vincristine, administration of a single dose of 0.1 mg/kg to rats produced an increase in megakaryocyte concentration, diameter and 24 h [3H]thymidine labelling index. Transfusion of one body equivalent of platelets from normal donors prevented stimulation of megakaryocytopoiesis by vincristine whereas platelets from vincristine-treated donors did not. These results suggest that vincristine stimulates megakaryocytopoiesis by altering the functional role of circulating platelets in the regulation of thrombopoiesis.


Nitrogen-rich carbon composite fabricated from waste shrimp shells for highly efficient oxo-vanadate adsorption-coupled reduction.
Protein, calcium carbonate, and chitin are abundant in shrimp shells. In this study, chemical treatment followed by hydrothermal carbonization was used to synthesize the nitrogen-rich hydrochar (HSHC) from shrimp shells. The untreated hydrochar exhibited a higher amount of calcium (25.37%) and less amount of nitrogen (2.68%) with alkaline pH (9.1). Interestingly chemical pre-treatment on shrimp shells boosted the nitrogen content to 6.81% and eliminated the calcium while controlling the pH to 6.4, which was beneficial for oxo-vanadate removal. The HSHC achieved vanadium(V) adsorption capacity of 21.20 mg/g at an optimal solution pH of 3.0, whereas the pristine hydrochar performed poorly (0.66 mg/g). The abundance of oxygen and nitrogen-based functional groups that developed through the chemical treatment resulted in improved adsorption coupled reduction performance of HSHC. This study proposed an inexpensive and environmentally friendly method for converting waste shrimp shells into value-added adsorbent.


People are curious about immoral and morally ambiguous others.
Looking to the popularity of superheroes, true crime stories, and anti-heroic characters like Tony Soprano, we investigated whether moral extremity, especially moral badness, piques curiosity. Across five experiments (N = 2429), we examine moral curiosity, testing under what conditions the moral minds of others spark explanation-seeking behavior. In Experiment 1, we find that among the most widely watched Netflix shows in the US over a five-month period, the more immoral the protagonist, the more hours people spent watching. In Experiments 2a and 2b, we find that when given a choice to learn more about morally good, bad, ambiguous, or average others, people preferred to learn more about morally extreme people, both good and bad. Experiment 3 reveals that people are more curious for explanations about (vs. descriptions of) morally bad and ambiguous people compared to morally good ones. Finally, Experiment 4 tests the uniqueness of curiosity for moral ambiguity. We find that people are more drawn to moral rather than aesthetic ambiguity, suggesting that ambiguity, which is cognitively taxing and sometimes avoided, preferentially engenders information seeking in the moral domain. These findings suggest deviations from moral normativity, especially badness, spur curiosity. People are curious about immorality and agents who differ from the norm.


Effects of subcutaneously implanted sustained-release cyclophosphamide capsules on Walker 256 solid rat tumor.
Complete regression of Walker 256 solid rat tumor was brought about by the subcutaneous implantation of a single sustained-release cyclophosphamide capsule adjacent to the tumor mass. Untreated control animals died within 3 weeks after receiving the tumor with large necrotic masses. Rats with sustained-release capsules experienced complete tumor regression within 28 days. Upon examination, the tissues around the previous tumor mass has regenerated, and no viable tumor cells could be found in the area where the previous tumor mass was. Around the implanted sustained-release cyclophosphamide capsule a fibrous sheath has developed over the 3 weeks it was in situ. This study suggests an alternate means of cytoxic drug administration in the treatment of solid tumors in experimental animals.


A risk factor for relapse in Hodgkin's disease: female gender?
A retrospective study of 163 patients with Hodgkin's disease treated between 1969 and 1987 was performed to identify adverse prognostic factors. One hundred and thirty-five patients (83 per cent) attained a complete remission and 42 (31 per cent) of these have relapsed (median follow-up--43 months). Using multivariate analysis, no independent factors predicted for the event of relapse. However, analysis of disease-free survival revealed that females fared significantly worse than males (p less than 0.05) and this was independent of other prognostic variables. Female sex has not been recognized as an independent prognostic factor predictive of inferior survival and inferior disease-free survival.


Lassa antiviral LHF-535 protects guinea pigs from lethal challenge.
LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, a zoonotic disease endemic in West Africa that generates significant morbidity and mortality. Current treatment options are inadequate, and there are no approved therapeutics or vaccines for Lassa fever. LHF-535 was evaluated in a lethal guinea pig model of Lassa pathogenesis, using once-daily administration of a fixed dose (50 mg/kg/day) initiating either 1 or 3 days after inoculation with a lethal dose of Lassa virus. LHF-535 reduced viremia and clinical signs and protected all animals from lethality. A subset of surviving animals was rechallenged four months later with a second lethal challenge of Lassa virus and were found to be protected from disease. LHF-535 pharmacokinetics at the protective dose in guinea pigs showed plasma concentrations well within the range observed in clinical trials in healthy volunteers, supporting the continued development of LHF-535 as a Lassa therapeutic.


Neuromuscular junction blocking agents: an initial screening bioassay.
A simple, rapid and sensitive in vivo bioassay for the initial screening of neuromuscular junction (NMJ) blocking agents has been accomplished. The i.v. retro-orbital plexus (IVROP) mode of injection was utilized, for the first time, in conjunction with the mouse inclined screen bioassay.