Leptin and leptin receptor expression in skeletal muscle and adipose tissue in response to in vivo porcine somatotropin treatment.
The present study was performed to examine the response of leptin and leptin receptor (Rb) genes to porcine somatotropin (pST) stimuli in finishing pigs. Twelve crossbred barrows (Yorkshire x Landrace) were used in this study. Animals were individually fed a basal diet containing 18% CP, 1.2% lysine, and 3.5 Mcal of DE/kg ad libitum (as-fed basis). At 90 kg, six pigs were treated with daily injections of recombinant pST (10 mg) in sterile bicarbonate buffer, whereas the other six pigs were injected with sterile bicarbonate buffer (controls). With initiation of pST treatment, the quantity of feed offered was 85% of calculated ad libitum intake based on BW and adjusted every 3 d. Diet restriction was designed to correct for the effects of the known inhibition in feed intake because of pST treatment in swine. Animals were maintained on treatment for 2 wk. A blood sample was obtained from each pig on d 14 of treatment, 6 h after pST injection. Tissue samples were collected on d 15, frozen in liquid N2, and stored at -80 degrees C before analysis for mRNA abundance. Total RNA was amplified by reverse transcription (RT) PCR with subsequent quantification of transcripts by capillary electrophoresis with laser-induced fluorescence detection. Samples included outer subcutaneous adipose tissue (OSQ), middle subcutaneous adipose tissue (MSQ), leaf fat (LF), liver, latissimus dorsi (LD), and biceps femoris (BF). Restricted feeding resulted in no change in BW of control pigs, whereas pST treatment increased BW by 6.9 +/- 0.5 kg (P < 0.001). Treatment with pST produced a 12-fold increase in serum ST concentration relative to control pigs (P < 0.002). Serum leptin concentration was increased by 17% in swine treated with pST relative to control pigs (P < 0.011). Leptin mRNA abundance was increased in liver by pST treatment (P < 0.05). Administration of pST decreased leptin Rb (Ob-Rb) mRNA abundance by 27% in liver (P < 0.044) and by 49.5% in OSQ (P < 0.025) relative to controls. The present data suggest that pST does not affect leptin expression independent of dietary intake because the restricted feeding regimen used in the present study precluded detection of major change in leptin gene expression. Changes in Ob-Rb mRNA abundance by pST treatment indicate that ST or the metabolic adaptations to ST have a role in regulating Ob-Rb expression.


In silico identification of potential therapeutic targets in the TGF-β signal transduction pathway.
The transforming growth factor-β (TGF-β) superfamily of cytokines controls fundamental cellular processes, such as proliferation, motility, differentiation, and apoptosis. This fundamental role is emphasized by the widespread presence of mutations of the core components of the TGF-β signal transduction pathway in a number of human diseases. Therefore, there is an increasing interest in the development of therapies to specifically target this pathway. Here we develop a computational approach to identify potential intervention points that are capable of restoring the normal signaling dynamics to the mutated system while maintaining the behavior of normal cells substantially unperturbed. We apply this approach explicitly to the TGF-β pathway to study the signaling dynamics of mutated and normal cells treated with inhibitory drugs and identify the processes in the pathway that are most susceptible to therapeutic intervention.


Potential-resolved electrochemiluminescence of ru(bpy)3(2+)/C2O4(2-) system on gold electrode.
The electrogenerated chemiluminescence of Ru(bpy)3(2+)/C2O4(2-) system on a pre-polarized Au electrode was studied using a potential-resolved electrochemiluminescence (PRECL) method. Two anodic ECL peaks were observed at 1.22 V (vs. SCE) (EP1), 1.41 V (vs. SCE) (EP2), respectively. The effects of the concentration of oxalate and Ru(bpy)3(2+), adsorbed sulphur, CO2, O2, pH of the solution and pretreatment of the Au electrode on the two PRECL peaks were examined. The surface state of the pre-oxidized gold electrode was also studied using the X-ray photoelectron spectroscopy (XPS) technique. Moreover, comparative studies on i-E and I-E curves were carried out and a possible mechanism involving both the catalytic and the direct electro-oxidation pathways was proposed for the ECL of Ru(bpy)3(2+)/C2O4(2-) system. EPI is attributed to the Ru(bpy)3(2/3+) reaction catalysed by C2O4(2-) to generate Ru(bpy)3(2+)*. EP2 is likely because C2O4(2-) was oxidized at the electrode to form CO2(-)*, followed by reaction with Ru(bpy)3(3+) to generate Ru(bpy)3(2+)*.


Early administration of intracoronary verapamil improves myocardial perfusion during percutaneous coronary interventions for acute myocardial infarction.
Intracoronary calcium-channel blockers administered in the event of no reflow during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) have been shown to improve myocardial perfusion. To evaluate the effects of the administration of intracoronary verapamil before the occurrence of no reflow during direct PCI. Single-center, nonrandomized, prospective study with a retrospective control group. From September 2001 to December 2003, 50 consecutive patients with AMI were prospectively enrolled for intracoronary verapamil treatment. Intracoronary verapamil was administered immediately prior to balloon inflation and at short intervals during the procedure thereafter. Retrospectively, 50 consecutive AMI patients who had undergone direct PCI and had not received intracoronary calcium-channel blockers were enrolled as control subjects. Patients with cardiogenic shock or platelet glycoprotein IIb/IIIa inhibitor were excluded. Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (CTFC), and TIMI myocardial perfusion grade (TMPG) were assessed prior to and following PCI by two independent cardiologists blinded to the procedures. The two groups had similar baseline and post-procedural angiographic characteristics, although the patients who been administered verapamil received more stent implantations than the control subjects (84% vs 60%, p = 0.008). Post-procedural TIMI flow < 3 (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.12 to 1.30; p = 0.18) and TMPG (OR, 1.24; 95% CI, 0.46 to 3.34; p = 0.68) were not associated with the implantation of the stents. There were no significant difference in post-PCI TIMI flow (p = 0.68) and CTFC (p = 0.36) between patients treated with verapamil and the control subjects. Post-PCI TMPG was significantly better in patients treated with intracoronary verapamil (p = 0.003). Forty-two percent of the patients treated with verapamil were found to have TMPG-3, while only 14% of the control subjects were found to have the same degree of TMPG (p = 0.004). Treatment with intracoronary verapamil (OR, 0.26; 95% CI, 0.12 to 0.58; p = 0.001) and pre-PCI TIMI flow (OR, 0.54; 95% CI, 0.35 to 0.84; p = 0.006) were found by multiple logistic regression to be independent predictors of TMPG. Early administration of intracoronary verapamil during direct PCI improves post-procedural myocardial perfusion, as evaluated by TMPG.


Preoperative blood pressure targets and effect on hemodynamics in pheochromocytoma and paraganglioma.
Patients with pheochromocytoma and paraganglioma (PPGL) are treated with α-adrenoceptor antagonists to improve peroperative hemodynamics. However, preoperative blood pressure targets differ between institutions. We retrospectively compared per- and postoperative hemodynamics in 30 patients with PPGL that were pretreated with phenoxybenzamine aiming at different blood pressure targets at two separate endocrine departments. All patients were subsequently undergoing laparoscopic surgery at Department of Urology, Herlev University hospital. Fourteen patients were treated targeting to symptomatic and significant orthostatic hypotension and 16 patients to a seated blood pressure below 130/80 mmHg. As a control group, we included 34 patients undergoing laparoscopic adrenalectomy for other reasons. The group titrated to orthostatic hypotension required a higher dose of phenoxybenzamine to achieve the blood pressure target. This group had less intraoperative systolic and diastolic blood pressure fluctuation (Mann-Whitney U test; P < 0.05) and less periods with heart rate above 100 b.p.m. (Mann-Whitney U test; P = 0.04) as compared to the group with a preoperative blood pressure target below 130/80 mmHg. Peroperative use of intravenous fluids were similar between the two groups, but postoperatively more intravenous fluids were administered in the group with a target of ortostatism. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. We conclude that phenoxybenzamine pretreatment targeting ortostatic hypotension may improve peroperative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.


Anti-invasion Effects of Cannabinoids Agonist and Antagonist on Human Breast Cancer Stem Cells.
Studies show that cancer cell invasion or metastasis is the primary cause of death in malignancies including breast cancer. The existence of cancer stem cells (CSCs) in breast cancer may account for tumor initiation, progression, and metastasis. Recent studies have reported different effects of cannabinoids on cancer cells via CB1 and CB2 cannabinoid receptors. In the present study, the effects of ACEA (a selective CB1 receptor agonist) and AM251 (a selective CB1 antagonist) on CSCs and their parental cells were investigated. Breast CSCs derived from MDA-MB-231 cell line were sorted and characterized with CD44+/CD24-/low/ESA+ phenotype. It was observed that ACEA decreased CD44+/CD24-/low/ESA+ cancer stem cell invasiveness. Conversely, AM251 increased the invasion by more than 20% (at the highest concentrations) in both MDA-MB-231 and CSCs. Our results did not show any correlation between reduced invasion and cytotoxic effects of the drug. Since one of the main cancer recurrence factors is anti-cancer drugs fail to inhibit CSC population, this observation would be useful for cancer treatment.


Enabling remote learning system for virtual personalized preferences during COVID-19 pandemic.
The education system worldwide has been affected by the Corona Virus Diseases 2019 (COVID-19) pandemic, resulting in the interruption of all educational institutions. Moreover, as a precautionary measure, the lockdown has been imposed that has severely affected the learning processes, especially assessment activities, including exams and viva. In such challenging situations, E-learning platforms could play a vital role in conducting seamless academic activities. In spite of all the advantages of remote learning systems, many hurdles and obstacles, like a selection of suitable learning resources/material encounter by individual users based on their interests or requirements. Especially those who are not well familiar with the internet technology in developing countries and are in need of a platform that could help them in resolving the issues related to the online virtual environment. Therefore, in this work, we have proposed a mechanism that intelligently and correctly predicts the appropriate preferences for the selection of resources relevant to a specific user by considering the capabilities of diverse perspectives users to provide quality online education and to make work from home policy more effective and progressive during the pandemic. The proposed system helps teachers in providing quality online education, familiarizing them with advanced technology in the online environment. It also semantically predicts the preferences for virtual assistance of those users who are in need of learning the new tools and technologies in short time as per their institutional requirements in order to meet the quality standards of online education. The experimental and statistical results have demonstrated that the proposed virtual personalized preferences system has improved overall academic activities as compared to the current method. The proposed system enhanced user's learning abilities and facilitated them in selecting short courses while using different online education tools adopted/suggested by the institutions to conduct online classes/seminars/webinars etc., as compared to the conventional classes/activities.


Evaluation of the metal binding sites in a recombinant coagulation factor VIII identifies two sites with unique metal binding properties.
Coagulation factor VIII is a glycosylated, non-covalent heterodimer consisting of a heavy chain (A1-A2-B domains) and a light chain (A3-C1-C2 domains). The association of the chains, and the stability and function of the dimer depend on the presence of metal ions. We applied X-ray fluorescence, X-ray crystallographic structure determination with anomalous signals at different wavelengths, and colorimetric measurements to evaluate the metal binding sites in a recombinant factor VIII molecule, turoctocog alfa. We identified a metal binding site in domain A3 dominated by Cu(+) binding and a site in domain A1 dominated by Zn(2+) binding.


Cochlear implants and the deaf child: a nursing perspective.
Cochlear implants are no longer considered new or experimental technology and are available for children with profound sensorineural hearing loss. Pediatric cochlear implantation requires a multidisciplinary team approach with contributions from surgeons, audiologists, speech-language pathologists, psychologists, nurses, special educators, and parents. The decision to perform cochlear implantation in children must be seriously considered. Some in the deaf community voice strong objections to the procedure. Additionally, it requires an enormous commitment on the part of the family and the health care system in both personal and financial terms. The surgery has some risks, and the rehabilitation period is lengthy. Outcomes are variable, and many factors play a role in a child's successful use of implants. Nonetheless, gradual, steady improvement in speech perception, speech production, and language typically occurs. The approach of Children's Hospital in Boston to the assessment, the surgical procedure, and follow-up is detailed here.


Blastocystis hominis: an organism in search of a disease.
Blastocystis hominis is a protozoan organism frequently found in the human intestinal tract. Eleven consecutive patients with symptoms of enteritis and having B. hominis as the sole enteropathogen were studied in an attempt to define the association of blastocystosis with clinical disease. B. hominis could not be implicated as the etiologic agent of enteritis in any of these patients. All eleven had alternative (and usually noninfectious) explanations for their intestinal symptoms. There was no correlation between resolution of symptoms and either antiprotozoal therapy or disappearance of B. hominis from the stools. All prior reports associating B. hominis with human disease have been reviewed and provide no convincing proof of a causal relation. B. hominis is rarely, if ever, a human pathogen, and treatment directed at the eradication of B. hominis is not indicated.


Clients' knowledge, attitudes, and practices related to pet nutrition and exercise at a teaching hospital.
Nutrition and exercise are key components of an animal's overall health; however, these topics may not be discussed with clients during veterinary visits resulting in suboptimal practices. This study sought to i) estimate small animal clientele knowledge, attitudes, and practices on nutrition and exercise; and ii) evaluate client recall of (and interest in) veterinary recommendations related to nutrition and exercise. Clients visiting the Atlantic Veterinary College Small Animal Teaching Hospital over a 1-month period were invited to complete a 5-minute written questionnaire. Of the clients invited to participate, 71% (101/143) completed the questionnaire. An unexpectedly high proportion of clients reported feeding homemade (37%) and raw meat-based diets and products (30%). Most participants indicated an interest in veterinary directed discussions on nutrition (63%) and exercise (63%). Our study provides a benchmark for needed ongoing (and targeted) client education and has led to expansion of our hospital infection control policy.


BRAT1-related disease--identification of a patient without early lethality.
We present a patient with neonatal onset of hypertonia and seizures identified through whole exome sequencing to have compound heterozygous variants, c.294dupA (p.Leu99fs) and c.1925C>A (p.Ala642Glu), in the BRCA1-associated protein required for ATM activation-1 (BRAT1) gene. Variants in BRAT1 have been identified to cause lethal neonatal rigidity and multifocal seizure syndrome (OMIM# 614498), which consistently manifests a severe neurological phenotype that includes neonatal presentation of rigidity and hypertonia, microcephaly and arrested head growth, intractable seizures, absence of developmental progress, apneic episodes, and death usually by 6 months of age. Our patient initially had a similarly severe neurological picture but remains alive at 6 years of age, expanding the phenotype to include longer term survival and providing further insights into genotype-phenotype correlations and the natural history of this disease.


Seasonal variations of T-cell cytokine pattern in peripheral blood from atopic subjects.
Previous studies on the effect of seasonal exposure to the sensitizing antigen on T-cell cytokine pattern from atopic subjects evaluated T-cell cytokine production by titration in the serum or culture supernatants. The purpose of this study was to determine the seasonal variations of T-cell cytokine pattern from atopic subjects at the single-cell level. We examined the interleukin-4 (IL-4) and interferon-gamma expression in peripheral blood CD4 + and CD8 + T cells from 11 subjects with grass-pollen-sensitive allergy before and during the 1999 grass pollen season using a flow cytometric method of intracellular cytokine detection. Eight healthy volunteers served as the control group. Flow cytometric analysis of peripheral blood lymphocytes showed no seasonal variations of IL-4- and interferon-gamma-producing T cells in atopic subjects. However, there was a decreased percentage of IL-4-producing cells among peripheral blood CD4+ and CD8+ T cells from the atopic subjects both during and outside the pollen season in comparison to the controLs. We did not find seasonal variations of T-cell cytokine pattern in peripheral blood from atopic subjects. However, we observed a decreased percentage of IL-4-producing T cells in peripheral blood from these subjects in comparison to healthy controls. These data add to the view of a continuous migration of T helper 2 (TH2) cells from the blood to the tissues of primary allergen exposure.


Efficacy of XP-endo finisher files in the removal of calcium hydroxide paste from artificial standardized grooves in the apical third of oval root canals.
To compare the efficacy of the XP-endo finisher file (XP) (FKG Dentaire, La Chaux de Fonds, Switzerland) to that of passive ultrasonic irrigation (PUI) and conventional syringe and needle irrigation (SNI) in the removal of calcium hydroxide paste from an artificial standardized groove in the apical third of root canals. The root canals of 68 mandibular incisors with single oval canals were prepared using Mtwo instruments (VDW GmbH, Munich, Germany) up to size 40, .04 taper. Each tooth was split longitudinally, and in one half of the root, a standardized groove was prepared in the apical part of the specimen. The grooves were filled with Ca(OH)2 , and the root halves were reassembled. The roots were randomly divided into two control groups (n = 4) and three experimental groups (n = 20) according to the Ca(OH)2 methods used: XP, PUI and SNI. The amount of remaining medicament was evaluated under X25 magnification using a 4-grade scoring system. Kappa values were calculated for intra- and interobserver agreement evaluation. The differences in the Ca(OH)2 scores amongst the different groups were analysed using the Kruskal-Wallis test. None of the tested methods could completely clean the Ca(OH)2 from the artificial standardized groove in the apical third of the root canals. XP and PUI removed significantly more Ca(OH)2 than SNI (P < 0.001), with no significant differences between them (P = 0.238). XP and PUI were more effective in removing Ca(OH)2 from artificial standardized grooves in the apical third of root canals than SNI.


Supplementation with RRR- or all-rac-α-Tocopherol Differentially Affects the α-Tocopherol Stereoisomer Profile in the Milk and Plasma of Lactating Women.
Background: The naturally occurring α-tocopherol stereoisomer RRR-α-tocopherol is known to be more bioactive than synthetic α-tocopherol (all-rac-α-tocopherol). However, the influence of this difference on the α-tocopherol stereoisomer profile of human milk is not understood.Objective: We investigated whether supplemental RRR-α-tocopherol or all-rac-α-tocopherol differentially affected the distribution of α-tocopherol stereoisomers in milk and plasma from lactating women.Methods: Eighty-nine lactating women aged 19-40 y and with a body mass index (in kg/m2) ≤30 were randomly assigned at 4-6 wk postpartum to receive a daily supplement containing 45.5 mg all-rac-α-tocopherol acetate (ARAC), 22.8 mg all-rac-α-tocopherol acetate + 20.1 mg RRR-α-tocopherol (MIX), or 40.2 mg RRR-α-tocopherol (RRR). Milk and plasma were analyzed for α-tocopherol structural isomers and α-tocopherol stereoisomers at baseline and after 6 wk supplementation with the use of chiral HPLC.Results: There were no significant treatment group or time-dependent changes in milk or plasma α, γ, or δ-tocopherol. RRR-α-tocopherol was the most abundant stereoisomer in both milk and plasma in each group. Supplementation changed both milk and plasma percentage RRR-α-tocopherol (RRR > MIX > ARAC) (P < 0.05) and percentage non-RRR-α-tocopherol (ARAC > MIX > RRR) (P < 0.05). In the RRR group, percentage RRR-α-tocopherol increased in milk (mean ± SEM: 78% ± 2.3% compared with 82% ± 1.7%) (P < 0.05) and plasma (mean ± SEM: 77% ± 1.8% compared with 87% ± 1%) (P < 0.05). In contrast, the percentage RRR-α-tocopherol decreased in the MIX and ARAC groups (MIX, P < 0.05; ARAC, P < 0.0001), and percentage non-RRR-α-tocopherol stereoisomers increased (MIX, P < 0.05; ARAC, P < 0.0001) commensurate with an accumulation of 2S-α-tocopherol stereoisomers (P < 0.05) in both milk and plasma. Milk and plasma RRR-α-tocopherol was positively correlated at baseline (r = 0.67; P < 0.0001) and 6 wk (r = 0.80; P < 0.0001).Conclusion: The α-tocopherol supplementation strategy differentially affected the α-tocopherol milk and plasma stereoisomer profile in lactating women. RRR-α-tocopherol increased milk and plasma percentage RRR-α-tocopherol, whereas all-rac-α-tocopherol acetate reduced these percentages. Because RRR-α-tocopherol is the most bioactive stereoisomer, investigating the impact of supplement-driven changes in the milk α-tocopherol stereoisomer profile on the α-tocopherol status of breastfed infants is warranted.


Presentation, Endoscopic Management, and Significance of Hemostatic Clip Migration into the Lower Urinary Tract Following Radical Prostatectomy.
Hemostatic clip migration into the lower urinary tract is a potential complication of radical prostatectomy that may cause symptoms, anxiety, and functional concern. Our objective was to evaluate initial presentation, endoscopic management, and outcomes of patients with hemostatic clip migration following radical prostatectomy. We retrospectively identified all patients with hemostatic clip migration at our institution from 1977 to 2012. Patient records were then reviewed to identify causative factors, presentation, and long-term functional outcomes. Seventeen patients were identified with clip migration following radical prostatectomy. Eight (47%) patients had undergone open retropubic radical prostatectomy, and 9 (53%) had received robot-assisted radical prostatectomy. Hemostatic clip migration was diagnosed at a median of 8 (range, 1-252) months after prostatectomy. The majority of patients (n = 16, 94%) were symptomatic upon the diagnosis of clip migration. Symptoms included irritative urinary symptoms (n = 14, 82%), perineal pain (n = 3, 18%), hematuria (n = 2, 12%), and infection (n = 2, 12%). Five (29%) had concomitant bladder neck contracture. Fifteen (88%) underwent successful endoscopic clip removal, whereas 2 (13%) patients required a repeat operation for recurrent clip erosion. With a median follow-up of 1.6 years, the majority (n = 13, 87%) had complete symptom resolution after clip removal, although 2 patients had recurrent bladder neck contracture. Hemostatic clip migration after prostatectomy is often symptomatic with irritative voiding complaints, perineal pain, hematuria, infection, or bladder neck contracture. Fortunately, clips can be removed endoscopically with expected symptom resolution in the vast majority of patients.


Penetration of various mononuclear ribonucleases into rat experimental granulation-tissue fibroblasts and their intracellular effects.
The penetration of five different mononuclear ribonucleases into the subcellular particles of rat experimental granulation-tissue fibroblasts was compared, along with the effects of the enzymes on the fibroblast RNA fractions. Ribonucleases from normal and silica-treated rat peritoneal macrophages have been shown before to regulate the nucleic acid and protein metabolism of rat experimental granulation-tissue fibroblasts. These biologically active enzymes were taken into the fibroblasts in a greater amount than the corresponding human monocyte enzymes and the biologically inactive rat macrophage ribonuclease. The biologically active macrophage enzymes were incorporated mainly into the nuclear fraction. The other three mononuclear ribonucleases were not found particularly in any subcellular compartment. Both biologically active macrophage enzymes degraded the nuclear RNA of fibroblasts and released it to the soluble fraction in contrast to the biologically inactive macrophage enzyme and ribonuclease from normal human monocytes. Instead the ribonuclease from normal human monocytes seemed to degrade RNA in the soluble fraction. There were no marked differences in the subcellular effects of ribonucleases from normal and silica-treated macrophages. However, the treatment of human monocytes with silica changed their ribonuclease so that it split the nuclear RNA of fibroblast and released it to the soluble fraction in the same way as the biologically active macrophage enzymes did.


The crystal structure of the extracellular 11-heme cytochrome UndA reveals a conserved 10-heme motif and defined binding site for soluble iron chelates.
Members of the genus Shewanella translocate deca- or undeca-heme cytochromes to the external cell surface thus enabling respiration using extracellular minerals and polynuclear Fe(III) chelates. The high resolution structure of the first undeca-heme outer membrane cytochrome, UndA, reveals a crossed heme chain with four potential electron ingress/egress sites arranged within four domains. Sequence and structural alignment of UndA and the deca-heme MtrF reveals the extra heme of UndA is inserted between MtrF hemes 6 and 7. The remaining UndA hemes can be superposed over the heme chain of the decaheme MtrF, suggesting that a ten heme core is conserved between outer membrane cytochromes. The UndA structure has also been crystallographically resolved in complex with substrates, an Fe(III)-nitrilotriacetate dimer or an Fe(III)-citrate trimer. The structural resolution of these UndA-Fe(III)-chelate complexes provides a rationale for previous kinetic measurements on UndA and other outer membrane cytochromes.


Sirt1 and HMGB1 Regulate the AGE-Induced Pro-Inflammatory Cytokines in Human Retinal Cells.
Advanced glycation end products (AGEs) accumulate in the retinal vascular cells, neurons, and glias of patients with diabetes mellitus and lead to the pathogenesis of diabetic retinopathy (DR). In the present study, to elucidate the orchestrated interactions of high mobility group box 1 (HMGB1) and silent mating type information regulation 2 homolog 1 (Sirt 1) in the AGE-induced pro-inflammatory toxicity in retinal epithelial cells, we investigated the role of HMGB1 and Sirt 1 in the AGE-induced pro-inflammatory cytokines and chemokines. It was demonstrated that the expression of TNF-α, IL-1β, IL-6, MCP-1, RANTES and IP-10 was promoted by the AGE-BSA treatment dose-dependently. The treatment with AGE-BSA also significantly promoted the HMGB1 at both mRNA and protein levels, dose-dependently. And in addition, we confirmed that HMGB1 mediated the AGE-induced pro-inflammatory cytokines and chemokines in the AGE-treated ARPE-19 cells. Moreover, we found that the Sirt 1 was downregulated by the AGE-BSA treatment at both mRNA and protein levels in the ARPE-19 cells, dose-dependently. Our further investigation recognized the regulatory role of Sirt 1 in the AGE-promoted pro-inflammatory cytokines and chemokines. The Sirt 1 inhibitor aggravated, whereas the Sirt 1 activator inhibited, the translocation of HMGB1 and the promotion of AGE-induced IL-1β and IL-6. Taken together, we confirmed that AGE-BSA promoted HMGB1 but down regulated Sirt 1 in human retinal cells. Sirt 1 was confirmed to regulate AGE-induced pro-inflammatory cytokines and chemokines via inhibiting the nuclear-to-cytoplasmic translocation and release of HMGB1 in retinal ARPE-19 cells.


Aluminum-catalyzed asymmetric alkylations of pyridyl-substituted alkynyl ketones with dialkylzinc reagents.
Alkylations of pyridyl-substituted ynones with Et2Zn and Me2Zn, promoted by amino acid-based chiral ligands in the presence of Al-based alkoxides, afford tertiary propargyl alcohols efficiently in 57% to >98% ee. Two easily accessible chiral ligands are identified as optimal for reactions of the two dialkylzinc reagents. Catalytic alkylations with Et2Zn require a chiral ligand carrying two amino acid moieties (valine and phenylalanine) along with a p-trifluoromethylphenylamide C-terminus. In contrast, reactions with Me2Zn are most effectively promoted in the presence of a chiral ligand containing a single amino acid (benzyl cysteine), capped by an n-butylamide. Enantiomerically enriched tertiary alcohols bearing a pyridyl and an alkyne substituent can be functionalized in a variety of manners to furnish a wide range of difficult-to-access acyclic and heterocyclic structures; two noteworthy examples are Cu-catalyzed protocols for conversion of tertiary propargyl alcohols to enantiomerically enriched tetrasubstituted allenes and bicyclic amides that bear an N-substituted quaternary carbon stereogenic center. Mechanistic models that account for the trends and enantioselectivity levels are provided.


Pacing techniques in assessing cardiac function in the horse.
The problem of transitory cardiac arrhythmias in equidae is discussed particularly with regard to the referral of suspect cases to specialist institutions for second opinion. Recently developed electro-stimulation techniques designed to uncover problem arrythmias, are briefly described and their potential in the analysis of cardiac electrical function under varying conditions is reviewed. The author cautions on the too rapid evaluation of the techniques for this purpose while remaining optimistic of the potential of electro-stimulation in the objective analysis of cardiac electric parameters.


[New correlation between absorption of calcium and activity of intestinal alkaline phosphatases].
From an homogeneous breeding one can occasionnally select a rat (rat +) showing an exceptionally high calcium absorption. For such a rat, high calcium absorption is accompained by a similar high alkaline phosphatase activity in the ileum. This fact was shown in six different assays. For rat +, this enzymatic excitation seems specific for intestinal phosphatase. Other characteristic enzymes of brush border such as maltase, invertase and leucylaminopeptidase do not vary much. Only slight modifications of phosphatase activity were observed in other organs or tissues: plasma, kidney, bone. The variations for liver are more important but unsignificant. The high calcium absorption is related to alkaline phosphatase. It is observed atdifferent steps of the preperation and can be increased by sorbitol, this last property being characteristic of the enzyme. The aptitude of a rat + for high calcium absorption is only momentany. When it goes back to usual calcium utilization, intestinal mucosa shows a normal phosphatasic activity.


Long Noncoding RNAs: An Overview.
Recently an explosion in the discovery of long noncoding RNAs (lncRNAs) was obtained by high-throughput sequencing. Genome-wide transcriptome analyses, in conjugation with research for epigenetic modifications of chromatins, identified a novel type of non-protein coding transcripts longer than 200 nucleotides named lncRNAs . They are gradually emerging as functional and critical participants in many physiological processes. Here we gave an overview of the characteristics, biological functions, and working mechanism for this new class of noncoding RNA molecules.


Dexmedetomidine attenuates cerebral ischemia-reperfusion injury in rats by inhibiting the JNK pathway.
Cerebral ischemic reperfusion injury (CI/RI) is a common cerebrovascular disease with high morbidity and disability that threatens human health. This study was conducted to explore the effects of dexmedetomidine (Dex) on the c-Jun N-terminal kinase (JNK) pathway in CI/RI, and to provide a theoretical basis for the recovery of brain function after cerebral ischemia. Sprague Dawley (SD) rats (n=24) were randomly divided into Sham, Sham + Dex, Sham + yohimbine (Yoh) + Dex, Sham + SP600125, ischemic reperfusion (I/R), I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups, and a focal cerebral ischemia reperfusion rat model was established by linear thrombus. The neurological deficit score and infarct volume were measured. Wet/dry weight ratios were used to measure brain water content, and cerebral infarct volume was determined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The cellular distribution of p-JNK and cleaved caspase-3 were examined using immunofluorescent staining (IF) and the total JNK and p-JNK were determined by Western blotting (WB). Compared with the Sham group, the rats in I/R, I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups developed hemiparesis of the left forelimb at different levels with a higher neurological deficit score, brain water content, infarct volume, and markedly upregulated expression of cleaved caspase-3, p-JNK (P<0.05). Compared with the I/R group, the neurological deficit score, brain water content, infarct volume, and expression of cleaved caspase-3, p-JNK were markedly decreased in I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups (P<0.05), and compared with the I/R + Dex group, the neurological deficit score, brain water content, infarct volume, and expression of cleaved caspase-3, p-JNK were markedly increased in the I/R + Yoh + Dex group (P<0.05). Double immunofluorescence staining showed there was a strong colocalization between p-JNK and the astroglial marker GFAP. The JNK signaling pathway is involved in CI/RI. Inhibition of the JNK pathway blocked caspase-3 activation which can decrease CI/RI. Dex can alleviate cerebral CI/RI in rats by increasing α2-adrenergic receptor and blocking JNK phosphorylation and activation of caspase-3.


Safely re-integrating silicone breast implants into the plastic surgery practice.
In the early 1990s, it was reported that silicone breast implants were possibly responsible for serious damage to women's health. In January 1992, the Food and Drug Administration issued a voluntary breast implant moratorium and, in April, issued a ban on the use of silicone gel-filled implants for cosmetic breast augmentation. Since that time, silicone gel-filled breast implants have been available to women only for select cases: women seeking breast reconstruction or revision of an existing breast implant, women who have had breast cancer surgery, a severe injury to the breast, a birth defect that affects the breast, or a medical condition causing a severe breast deformity. Since the ban on the use of silicone gel-filled breast implants for cosmetic breast augmentation, numerous scientific studies have been conducted. To ensure patient safety, the American Board of Plastic Surgery believes that these scientific studies and the Food and Drug Administration's scrutiny of silicone gel-filled breast implants have been appropriate and necessary.


PATTERNS OF PUFFING ACTIVITY AND CHROMOSOMAL POLYMORPHISM IN DROSOPHILA SUBOBSCURA. IV. EFFECT OF INVERSIONS ON GENE EXPRESSION.
We have observed that, contrary to a common assumption, the puffing patterns manifest in the salivary chromosomes of Drosophila subobscura are modified by chromosomal inversions as well as by genic content. An inversion effect is apparent in the E and A chromosomes of five strains coming from four different natural populations. An effect due to the geographical location of the populations is also detected in the J and O chromosomes. The chromosomal and geographic effects are distinguishable but not contradictory. Indeed, a statistical test using the DK2 coefficient of distance shows that, for a given chromosomal arrangement, strains of different geographic origin exhibit puffing patterns significantly different; these patterns are, however, more similar to each other than they are to those of strains carrying different chromosomal arrangements of the same chromosome.


Neurological Presentations of COVID-19: Characteristic Features in a Case Series of Hospitalized Patients from Abu Dhabi, UAE.
COVID-19 patients can present with neurological manifestations in the form of headache, dizziness, hyposmia, myalgia, peripheral neuropathy, acute cerebrovascular disease, and encephalopathy. Neurological involvement could be due to virus-induced brain hypoxia, brain infection, or immune reaction. We aim to describe the neurological presentation of COVID-19 patients and study their neuroimaging findings and disease outcome. The study is a single-centre, retrospective, observational study in Sheikh Shakhbout Medical City (SSMC), Abu Dhabi, UAE. Patients diagnosed with COVID-19 between March and May 2020 who presented with neuropathological features with or without respiratory manifestations of COVID-19 were enrolled. Electronic records were studied for age, sex, duration of hospitalization, detailed neurological presentation, history or documented concomitant fever and respiratory features of COVID-19, inflammatory markers, neuroimaging, progress, and disease outcome. Thirty-three patients of 10 nationalities presented with neurological manifestations. Mean (range) age was 51.4 (21-86) years. Twenty-four had comorbidities, and 18 had no prior or concomitant respiratory symptoms. Ten patients presented with encephalopathy and exhibited altered behavior/sensorium: 7 presented with myositis, 8 with stroke, and 4 with seizures, and 4 had peripheral and cranial nerve involvement. The mean (average) duration of hospital stay was 11.4 days (1-38) with the longest observed in stroke patients. Fifteen patients (45%) died and 3 (9%) had residual weakness. Serum ferritin, CRP, and procalcitonin were higher in the severe disease group and correlated with risk of death. Twelve of 22 brain images showed abnormalities including haemorrhage, infarcts, small vessel ischemia, and oedema. Risk of death was higher in older age but did not differ based on the underlying neuropathology. COVID-19 patients who present with neurological involvement have a higher risk of mortality which is aggravated by older age and higher inflammatory markers. The type of neurological pathology does not seem to influence the risk of mortality.


Complex surveillance of Streptococcus pyogenes. II. Resistance in human blood and bactericidal activity receptors of field and collection streptococci.
A comparative study of a series of 31 epidemic streptococci and 36 collection M protein producers showed no statistically significant difference in their resistance in human blood. Even highly resistant field strains did not produce M protein (as the main bactericidal activity receptor) under laboratory conditions, however, although under natural conditions they left an anti-M response in the exposed population. Streptococcal resistance is not generally associated with M protein, but is influenced by another factor.


Effects of age and weight on the metabolic activities of the cervical, thoracic and lumbar spines as measured by fluorine-18 fluorodeoxyglucose-positron emission tomography in healthy males.
This study aimed to explore the age and weight-related metabolic trends in the spines of healthy male subjects using fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging. Forty three healthy male subjects (age 23-75 years, weight 50-145kg) were selected from the CAMONA study. A global assessment methodology was applied to the subjects' 18F-FDG 180 minute scans, where each region of the spine (cervical, thoracic and lumbar) was individually encapsulated in a single region of interest, and standardized uptake value (SUVmean) was calculated per respective region. SUVmean increased significantly with weight in both the thoracic spine (Slope=0.0066, P=0.001) and lumbar spine (Slope=0.0087, P<0.0001), but not the cervical spine. There were no significant correlations between age and SUVmean in all three regions. The cervical spine (average SUVmean=1.84±0.31) illustrated elevated activity when compared to the thoracic (average SUVmean=1.46±0.27, P<0.0001) and lumbar (average SUVmean=1.41±0.28, P<0.0001) spines. This study illustrated the ability of 18F-FDG PET to assess metabolic processes in the spine. The data provided evidence of weight dependent metabolic activity, likely related to inflammation. This study offers a methodological precedent that can be applied to studies in populations with back pain.


Fourier-Legendre expansion of the one-electron density matrix of ground-state two-electron atoms.
The density matrix rho(r,r(')) of a spherically symmetric system can be expanded as a Fourier-Legendre series of Legendre polynomials P(l)(cos theta=rr(')rr(')). Application is here made to harmonically trapped electron pairs (i.e., Moshinsky's and Hooke's atoms), for which exact wavefunctions are known, and to the helium atom, using a near-exact wavefunction. In the present approach, generic closed form expressions are derived for the series coefficients of rho(r,r(')). The series expansions are shown to converge rapidly in each case, with respect to both the electron number and the kinetic energy. In practice, a two-term expansion accounts for most of the correlation effects, so that the correlated density matrices of the atoms at issue are essentially a linear functions of P(l)(cos theta)=cos theta. For example, in the case of Hooke's atom, a two-term expansion takes in 99.9% of the electrons and 99.6% of the kinetic energy. The correlated density matrices obtained are finally compared to their determinantal counterparts, using a simplified representation of the density matrix rho(r,r(')), suggested by the Legendre expansion. Interestingly, two-particle correlation is shown to impact the angular delocalization of each electron, in the one-particle space spanned by the r and r(') variables.


Interactions between adenosine, angiotensin II and nitric oxide on the afferent arteriole influence sensitivity of the tubuloglomerular feedback.
Adenosine, via activation of A1 receptors on the afferent arteriole (AA), mediates the tubuloglomerular feedback (TGF) mechanism. Angiotensin II and nitric oxide (NO) can modulate the sensitivity of the TGF mechanism. However, the interaction among these substances in regulating the TGF resetting phenomenon has been debated. Studies in isolated perfused AA have shown a biphasic response to accumulating doses of adenosine alone. In the nanomolar range adenosine has a weak contractile effect (7%), whereas vasodilatation is observed at high concentrations. However, a synergistic interaction between the contractile response by adenosine and that of angiotensin II has been demonstrated. Adenosine in low concentrations strongly enhances the response to angiotensin II. At the same time, angiotensin II in physiological concentrations increases significantly the contractile response to adenosine. Moreover, addition of a NO donor (spermine NONOate) to increase NO bioavailability abolished the contractile response from combined application of angiotensin II and adenosine. These mutual modulating effects of adenosine and angiotensin II, and the effect of NO on the response of AA can contribute to the resetting of the TGF sensitivity.


Cessation of oral anticoagulants in antiphospholipid syndrome.
Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.


The Emergency Radiology Dashboard: Facilitating Workflow With Realtime Data.
Emergency radiology imaging volume varies widely due to predictable (eg, day of the week) and unpredictable factors. This can lead to inefficient or insufficient staffing of radiologists, suboptimal workflow and poor trainee education. In collaboration with the radiology IT division we created and implemented a 2-tiered real-time dashboard to facilitate operational workflow. This allowed us to track overall emergency department patient census, ordered but not yet performed imaging studies, and performed but unread imaging studies. The capability of clicking to obtain information on specific studies was also incorporated. We describe our experience of how this information has improved our workflow, staffing, and trainee education.


Combinations of maternal-specific repressive epigenetic marks in the endosperm control seed dormancy.
Polycomb Repressive Complex 2 (PRC2)-mediated trimethylation of histone H3 on lysine 27 (H3K27me3) and methylation of histone 3 on lysine 9 (H3K9me) are two repressive epigenetic modifications that are typically localized in distinct regions of the genome. For reasons unknown, however, they co-occur in some organisms and special tissue types. In this study, we show that maternal alleles marked by H3K27me3 in the Arabidopsis endosperm were targeted by the H3K27me3 demethylase REF6 and became activated during germination. In contrast, maternal alleles marked by H3K27me3, H3K9me2, and CHG methylation (CHGm) are likely to be protected from REF6 targeting and remained silenced. Our study unveils that combinations of different repressive epigenetic modifications time a key adaptive trait by modulating access of REF6.


Oral thin films as a remedy for noncompliance in pediatric and geriatric patients.
Pediatric and geriatric patients experience swallowing difficulties for traditional oral dosage forms, such as tablets. Further, microbial contamination, chemical stability, unpleasant taste and swallowing large volumes of fluids have led to low therapeutic efficacy and patient noncompliance. The emergence of oral thin films has resulted in dramatic improvements in compliance and drug therapy outcomes in pediatric and geriatric patients. Oral thin films do not require water for administration, are readily hydrated upon contact with saliva, adhere to the mucosa and disintegrate ideally under 1 min. This article provides an overview of oral thin films, modern trends in their formulation and characterization, available commercial products, information to fill knowledge gaps and future potential and economic prospects of oral thin film technology, with emphasis on their use in the pediatric and geriatric patient groups.


The comparison of gasless and traditional robot-assisted transvaginal natural orifice transluminal endoscopic surgery in hysterectomy.
To describe the surgical technique and compare the operative outcomes of gasless and traditional robot-assisted transvaginal natural orifice transluminal endoscopic surgery (GR-vNOTES vs. TR-vNOTES) in hysterectomy. The patients undergoing hysterectomy via GR-vNOTES or TR-vNOTES between February 2020 and January 2022 in our hospital were included. Clinical data regarding patient demographics, operative time, blood loss, complications, and postoperative hospital stays were collected and analyzed. Five cases underwent hysterectomy via GR-vNOTES, and nine cases via TR-vNOTES. The baseline demographics and operative outcomes were not significantly different in GR-vNOTES and TR-vNOTES groups. There was no conversion to multiport robotic laparoscopy, conventional laparoscopy or laparotomy. No complications were seen in both groups, except two cases had fever postoperatively in the TR-vNOTES group. For those with early stage cervical/endometrial cancer, no recurrence or metastasis was observed in the follow-up of six months. Both GR-vNOTES and TR-vNOTES were feasible and safe for hysterectomy. GR-vNOTES was a promising alternative to TR-vNOTES in hysterectomy.


Responses of peripheral auditory neurons to two-tone stimuli during development: II. Factors related to neural responsiveness.
In an accompanying paper (Fitzakerley et al., 1994), it was demonstrated that there is a significant developmental correlation between the appearance of tuning and two-tone suppression. However, it was also found that some sharply tuned neurons meeting minimal adult standards did not exhibit suppression. Therefore, in order to investigate other factors that may be related to the demonstration of suppression in peripheral auditory neurons, the relationship of two-tone suppression with various parameters related to neural responsiveness was studied in perinatal kittens. A positive correlation was made between the observance of suppression and driven discharge rate, characteristic frequency (CF), and threshold, all properties which change significantly during the final stages of cochlear differentiation. In older animals, suppression was also observed in higher percentages of neurons having low spontaneous rates (< 1 spk/s). Suppression was evoked less often by test tones placed below CF than above CF in neurons recorded from younger animals, and was generally produced by a narrower range of test tone intensities than those recorded from adults. As a result, the conventional description of suppression as observed in peripheral auditory neurons in mature animals must be extended to include these factors when responses of immature neurons are considered.


Prevalence of bovine trypanosomosis and its vectors in two districts of East Wollega Zone, Ethiopia.
Trypanosomosis is a parasitic disease that causes serious economic losses in livestock, especially in sub-Saharan countries. This study was conducted from October 2010 to March 2011 in the Diga and Sasiga districts of the East Wollega zone in western Ethiopia to determine the prevalence of bovine trypanosomosis and its vectors. A total of 386 blood samples were collected from randomly selected animals. Packed cell volume (PCV) was determined and samples were examined for the presence of trypanosomes using the buffy coat technique. Out of 386 blood samples, 8.55% tested positive for trypanosomes. The majority of the infections were caused by Trypanosoma congolense (72.73%), followed by Trypanosoma vivax (27.27%). There were no statistically significant differences (p > 0.05) between districts, altitudes, sexes and ages, but the prevalence was significantly higher (p < 0.05) in cattle which were in poor body condition. The mean PCV value of infected animals (21.45 ± 3.62 s.d.) was significantly lower (p < 0.05) than that of non-infected animals (26.60 ± 4.60 s.d.). A total of 1151 flies were caught by deploying 21 monoconical shaped traps. Of these flies, 822 (71.42%) were Glossina, whilst the remaining flies were either Stomoxys (17.20%) or Tabanus (11.38%). The overall apparent densities of tsetse and biting flies were 1.45 and 0.58 flies per trap per day, respectively. In conclusion, this study confirmed that trypanosomes and their vectors are prevalent and still pose a threat to cattle production in the area. Therefore, proper strategies have to be designed and implemented to minimise their effect on livestock production.


[The value of dental imaging in the teaching and promotion of oral health].
In the context of the great diversity of oral microflora, including over 600 species, we highlight the educational value of electron micrographs and images of dental plaque cultures in dental models made with culture media, showing the bacterial colonies in the anatomic sites of the teeth that were most abundantly colonized. Such images allow for an easy understanding of the magnitude of the oral microbiome for students of biomedical careers--especially dentistry--and for the general public. As such, these images can be used in teaching programs and oral health campaigns.


Trade-offs in nutrient and sediment losses in tile drainage from no-till versus conventional conservation-till cropping systems.
Nutrient and soil loss from agricultural areas impairs surface water quality globally. In the Great Lakes region, increases in the frequency and magnitude of harmful and nuisance algal blooms in freshwater lakes have been linked to elevated phosphorus (P) losses from agricultural fields, some of which are transported via tile drainage. This study examined whether concentrations and loads of P fractions, total suspended sediments (TSS), nitrate (NO3 - ), and ammonium (NH4 + ) in tile drainage in a clay soil differed between a continuous no-till system combining cover crops and surface broadcast fertilizer (no-till cover crop [NTCC]), and a more conventional tillage system with shallow tillage, fertilizer incorporation and limited use of cover crops (conventional conservation-till, CT). Both sites had modest soil fertility levels. Year-round, high-frequency observations of tile drainage flow and chemistry are described over 4 full water years and related to management practices on the associated fields. There were similar water yields in tile drainage between the two systems; however, losses of TSS, particulate P (PP), and NO3 - were consistently greater from the CT site, which received larger quantities of fertilizer. In contrast, dissolved reactive P (DRP) losses were considerably greater from the NTCC site, offsetting the lower PP losses, such that there was little difference in TP losses between sites. Approximately 60% of the DRP losses from the NTCC site over the 4 years were associated with incidental losses following surface application of fertilizer in fall. This study provides insight into trade-offs in controlling losses of different nutrient fractions using different management systems.


Association between severe nausea and vomiting in pregnancy and lower rate of preterm births.
Nausea and vomiting in pregnancy has been associated with some reduction in miscarriage in other studies. However the relationship between nausea and vomiting during pregnancy and preterm birth/low birthweight in newborns is inconsistent; therefore the objective of the study was to clarify this possible association. The population-based large control (without any defects) data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities was evaluated. Of 38,151 controls, 3869 (10.1%) had medically recorded and treated nausea and vomiting during pregnancy. The proportion of mothers who later delivered girls was higher in this group. Mothers with nausea and vomiting in pregnancy had a somewhat (0.3 week) longer gestational age and a lower proportion of preterm births (6.4% vs. 9.5%). This finding may be connected with the favourable hormonal milieu (larger placenta, higher level of chorionic gonadotrophin and oestrogens) of pregnant women with nausea and vomiting.


Unsupervised reduction of random noise in complex data by a row-specific, sorted principal component-guided method.
Large biological data sets, such as expression profiles, benefit from reduction of random noise. Principal component (PC) analysis has been used for this purpose, but it tends to remove small features as well as random noise. We interpreted the PCs as a mere signal-rich coordinate system and sorted the squared PC-coordinates of each row in descending order. The sorted squared PC-coordinates were compared with the distribution of the ordered squared random noise, and PC-coordinates for insignificant contributions were treated as random noise and nullified. The processed data were transformed back to the initial coordinates as noise-reduced data. To increase the sensitivity of signal capture and reduce the effects of stochastic noise, this procedure was applied to multiple small subsets of rows randomly sampled from a large data set, and the results corresponding to each row of the data set from multiple subsets were averaged. We call this procedure Row-specific, Sorted PRincipal component-guided Noise Reduction (RSPR-NR). Robust performance of RSPR-NR, measured by noise reduction and retention of small features, was demonstrated using simulated data sets. Furthermore, when applied to an actual expression profile data set, RSPR-NR preferentially increased the correlations between genes that share the same Gene Ontology terms, strongly suggesting reduction of random noise in the data set. RSPR-NR is a robust random noise reduction method that retains small features well. It should be useful in improving the quality of large biological data sets.


Trends and Seasonality of Emergency Department Visits and Hospitalizations for Suicidality Among Children and Adolescents in the US from 2016 to 2021.
The detection of seasonal patterns in suicidality should be of interest to clinicians and US public health officials, as intervention efforts can benefit by targeting periods of heightened risk. To examine recent trends in suicidality rates, quantify the seasonality in suicidality, and demonstrate the disrupted seasonality patterns during the spring 2020 COVID-19-related school closures among US children and adolescents. This population-based, descriptive cross-sectional study used administrative claims data from Optum's deidentifed Clinformatics Data Mart Database. Participants included children aged 10 to 12 years and adolescents aged 13 to 18 years who were commercially insured from January 1, 2016, to December 31, 2021. Statistical analysis was conducted between April and November 2022. Month of the year and COVID-19 pandemic. Rates and seasonal patterns of emergency department (ED) visits and hospitalizations for suicidality. The analysis included 73 123 ED visits and hospitalizations for suicidality reported between 2016 and 2021. Among these events, 66.1% were reported for females, and the mean (SD) age at the time of the event was 15.4 (2.0) years. The mean annual incidence of ED visits and hospitalizations for suicidality was 964 per 100 000 children and adolescents (95% CI, 956-972 per 100 000), which increased from 760 per 100 000 (95% CI, 745-775 per 100 000) in 2016 to 1006 per 100 000 (95% CI, 988-10 024 per 100 000) in 2019, with a temporary decrease to 942 per 100 000 (95% CI, 924-960 per 100 000) in 2020 and a subsequent increase to 1160 per 100 000 (95% CI, 1140-1181 per 100 000) in 2021. Compared with January, seasonal patterns showed peaks in April (incidence rate ratio [IRR], 1.15 [95% CI, 1.11-1.19]) and October (IRR, 1.24 [95% CI, 1.19-1.29]) and a nadir in July (IRR, 0.63 [95% CI, 0.61-0.66]) during pre-COVID-19 years and 2021. However, during the spring of 2020, which coincided with school closures, seasonal patterns were disrupted and April and May exhibited the lowest rates. The findings of this study indicated the presence of seasonal patterns and an observed unexpected decrease in suicidality among children and adolescents after COVID-19-related school closures in March 2020, which suggest a potential association between suicidality and the school calendar.


A case of Lemierre's syndrome in association with liver abscess without any other metastatic lesions.
Lemierre's syndrome (LS) is characterized by pharyngitis followed by septicemia, internal jugular vein thrombophlebitis, and metastatic embolization in general. LS is commonly caused by Fusobacterium necrophorum. Herein, we present a case of LS with liver abscesses that presented as a sole metastatic lesion. We were not able to diagnose LS until Fusobacterium necrophorum was isolated due to the lack of the common involvement. Doripenem was effective against the pathologic features including the liver abscesses. LS should be taken into consideration when clinicians find liver abscesses following pharyngitis even when the common complications of LS are not detected.


Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology.
Widespread use of DNA restriction fragment length polymorphism (RFLP) to differentiate strains of Mycobacterium tuberculosis to monitor the transmission of tuberculosis has been hampered by the need to culture this slow-growing organism and by the level of technical sophistication needed for RFLP typing. We have developed a simple method which allows simultaneous detection and typing of M. tuberculosis in clinical specimens and reduces the time between suspicion of the disease and typing from 1 or several months to 1 or 3 days. The method is based on polymorphism of the chromosomal DR locus, which contains a variable number of short direct repeats interspersed with nonrepetitive spacers. The method is referred to as spacer oligotyping or "spoligotyping" because it is based on strain-dependent hybridization patterns of in vitro-amplified DNA with multiple spacer oligonucleotides. Most of the clinical isolates tested showed unique hybridization patterns, whereas outbreak strains shared the same spoligotype. The types obtained from direct examination of clinical samples were identical to those obtained by using DNA from cultured M. tuberculosis. This novel preliminary study shows that the novel method may be a useful tool for rapid disclosure of linked outbreak cases in a community, in hospitals, or in other institutions and for monitoring of transmission of multidrug-resistant M. tuberculosis. Unexpectedly, spoligotyping was found to differentiate M. bovis from M. tuberculosis, a distinction which is often difficult to make by traditional methods.


Spontaneous apoptosis in a rat hepatoma cell line and its inhibition by dexamethasone.
Cultures of dedifferentiated rat hepatoma Rab1-5-1 cells exhibit spontaneously a high level of mortality during the exponential growth phase. We demonstrate that these cells die by apoptosis, showing chromatin condensation and internucleosomal DNA fragmentation. Cells of the original H4II cell line and of its differentiated and dedifferentiated derivatives also die by apoptosis, but only in heavily confluent cultures. We evaluated mortality with time in Rab1-5-1 cultures by establishing growth curves, including quantification of floating cells, and conclude that up to half of the cells in a culture are lost to apoptosis. The production of apoptotic cells is abolished by the presence of 10(-6) M dexamethasone and this inhibition is reversible in 48 hours. Rab1-5-1 cells that spontaneously die by apoptosis with high frequency represent a novel model to investigate factors that regulate the spontaneous frequency of death, and to study the nature and the kinetics of commitment to the apoptotic pathway.


Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway.
Spinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, and it causes severe motor and sensory deficits. Due to the complicated pathological process of SCI, there is currently still a lack of effective treatment for SCI. Microglia, a type of immune cell residing in the central nervous system (CNS), need to respond to various stimuli to protect neuronal cells from death. It was also reported that microRNAs (miRNAs) had been identified in microglia-derived exosomes that can be taken up by neurons. However, the kinds of miRNAs in exosome cargo derived from microglia and the underlying mechanisms by which they contribute to neuroprotection after SCI remain unknown. In the present study, a contusive SCI mouse model and in vitro experiments were applied to explore the therapeutic effects of microglia-derived exosomes on neuronal apoptosis, axonal regrowth, and functional recovery after SCI. Then, miRNA analysis, rescue experiments, and luciferase activity assays for target genes were performed to confirm the role and underlying mechanism of microglia-derived exosomal miRNAs in SCI. We revealed that microglia-derived exosomes could promote neurological functional recovery by suppressing neuronal apoptosis and promoting axonal regrowth both in vivo and in vitro. MicroRNA-151-3p is abundant in microglia-derived exosomes and is necessary for mediating the neuroprotective effect of microglia-derived exosomes for SCI repair. Luciferase activity assays reported that P53 was the target gene for miR-151-3p and that p53/p21/CDK1 signaling cascades may be involved in the modulation of neuronal apoptosis and axonal regrowth by microglia-derived exosomal microRNA-151-3p. In conclusion, our data demonstrated that microglia-derived exosomes (microglia-Exos) might be a promising, cell-free approach for the treatment of SCI. MicroRNA-151-3p is the key molecule in microglia-derived exosomes that mediates the neuroprotective effects of SCI treatments.


[Clinical effects of a clonidine-chlorthalidone combination in the treatment of arterial hypertension].
Clonidine (0.075-0.225 mg/day) and chlorthalidone (0.15-0.45 mg/day) were associated in the management of 23 cases of arterial hypertension of varying nature and gravity. A significant and satisfactory decrease in pressure was accompanied by reduced cardiac frequency. Diuresis, body weight and the main biohumoral indices were not significantly affected. The mechanism of action of the two drugs is explained and the reason why success was obtained with their combination in less-than-normal doses is discussed.


The dosimetry of bone incorporating alpha-emitting radionuclides.
The previous work on the dosimetry of alpha-emitting radionuclides incorporated in bone is briefly reviewed. The application of cavity ionisation theory to problems of bone dosimetry is propounded and recent developments of the cavity theory for alpha particle fields are applied to bone dosimetry problems. The mean marrow dose over a large range of bone cavity size calculated by a simple theory using a mean chord length to characterise a cavity is compared with results of a more elaborate theory employing the chord length distribution for a sphere. The difference is not great. The influence of the shape of the cavity is explored by considering cylindrical cavities of different elongation. Data are presented for both volume-seeking and surface-seeking radioactive nuclides. The endosteal dose to a 10 mu layer is calculated as a function of cavity size for both volume-seeking and surface-seeking radioactive nuclides. The endosteal dose is also calculated for a surface seeker as a function of endosteal layer thickness. Finally, the results of these calculations are shown to be generally in good agreement with those of the calculations of earlier workers. It is concluded that a simple and reliable method of calculating the mean marrow dose and endosteal dose for both volume- and surface-seeking alpha emitters has been established.


Unmet Clinical Needs in Women with Aesthetic Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Study.
Background: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. There is an accurate, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE). However, it remains unclear to which extent, if at all, the guideline is followed by health care providers. The aim was to explore the subjectively perceived quality of gynecological medical care in women with PCOS suffering from aesthetic complaints. Materials and Methods: A nonvalidated questionnaire was constructed in a standardized manner covering the domains: aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic noncommunicable diseases. Results: A total of 1960 participants with aesthetic complaints, such as acne (66.2%), alopecia (43.9%), hirsutism (77.9%), or overweight/obesity (72.3%) were included. The percentage of women being counseled was low (acne 20.3%, alopecia 12.9%, hirsutism 17.5%, overweight/obesity 36.2%). Satisfaction with counseling was moderate (40.4-44.1 points). Many women tried at least one therapeutic method (75.9%), whereas only a few were counseled for therapy (acne 27.0%, alopecia 24.6%, hirsutism 24.0%, overweight/obesity 18.8%) with moderate satisfaction for hyperandrogenism (mean 55.1-59.5 points) and good satisfaction for overweight/obesity (mean 60.8 points). Overall satisfaction was rated with a mean of 30.5 points (standard deviation 27.1) on a scale from 0 to 100 and thus considered "not satisfied." Fewer complaints were significantly correlated with higher satisfaction. Most women wished for more counseling (80.8%), as well as more diagnostic (63.2%) and therapeutic options (70.2%). Conclusions: Women affected by PCOS are not properly managed according to the ESHRE guideline. Indeed, this guideline recommends comprehensive history and physical examination for clinical hyperandrogenism as well as holistic approaches in therapy, including education and counseling of patients. Still, overall consultation rates and satisfaction were poor.


Novel stachyflin derivatives from Stachybotrys sp. RF-7260. Fermentation, isolation, structure elucidation and biological activities.
Stachybotrys sp. RF-7260 was found to produce stachyflins, novel anti-influenza virus agents, under solid-state fermentation conditions. Feeding DL-lysine to a culture of Stachybotrys sp. RF-7260 induced the formation of the novel compounds, SQ-02-S-L2 and -L1, and feeding DL-valine the formation of SQ-02-S-VI and -V2. The structures of these metabolites were determined by detailed 2D NMR analyses in comparison with acetylstachyflin. SQ-02-S-L2 and -L1 have the lysine moiety and SQ-02-S-V1 has the valine moiety. SQ-02-S-V2 has an amidine moiety instead of the lactam moiety in acetylstachyflin. SQ-02-S-L2, -L1 and -V1, substituted on the lactam amide hydrogen, displayed only a low level of the antiviral activity. However, deacetyl SQ-02-S-V2 showed potent antiviral activity similar to stachyflin.


Mesencephalic hemorrhage--a report of 3 cases.
We studied three patients with spontaneous mesencephalic hemorrhages. All presented with some degree of impaired consciousness and abnormal ocular movements. One patient had a convergence-retraction nystagmus with a unilateral hemorrhage confined to the dorsal midbrain. Another patient showed left third nerve palsy due to a unilateral hemorrhage that involved ventral midbrain. The third patient revealed left internuclear ophthalmoplegia with ataxia due to a pinpoint hemorrhage in the tegmentum of the left midbrain. The patients survived and major neurologic deficits recovered, but abnormal ocular movements persisted.


Designing a low-cost pollution prevention plan to pay off at the University of Houston.
The University of Houston is located just south of downtown Houston, TX. Many different chemical substances are used in scientific research and teaching activities throughout the campus. These activities generate a significant amount of waste materials that must be discarded as regulated hazardous waste per U.S. Environmental Protection Agency (EPA) rules. The Texas Commission on Environmental Quality (TCEQ) is the state regulatory agency that has enforcement authority for EPA hazardous waste rules in Texas. Currently, the University is classified as a large quantity generator and generates >1000 kg per month of hazardous waste. In addition, the University has experienced a major surge in research activities during the past several years, and overall the quantity of the hazardous waste generated has increased. The TCEQ requires large quantity generators to prepare a 5-yr Pollution Prevention (P2) Plan, which describes efforts to eliminate or minimize the amount of hazardous waste generated. This paper addresses the design and development of a low-cost P2 plan with minimal implementation obstacles and strong payoff potentials for the University. The projects identified can be implemented with existing University staff resources. This benefits the University by enhancing its environmental compliance efforts, and the disposal cost savings can be used for other purposes. Other educational institutions may benefit by undertaking a similar process.


Chemical Constituents of the Vietnamese Marine Sponge Gelliodes sp. and Their Cytotoxic Activities.
A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D- and 2D-NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF-7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC50 values ranging from 23.6 to 75.5 μM against the three cell lines, and that 1H-indole-3-carboxylic acid showed cytotoxicity with an IC50 value of 89.2 μM against A549 cancer cell lines.


Localization and quantification of platelet-rich thrombi in large blood vessels with near-infrared fluorescence imaging.
Imaging of thrombus formation in vivo has been limited by the inability to directly visualize and measure thrombi in large blood vessels in real time. Near-infrared light, with its superior tissue penetration and reduced scatter, could potentially solve this problem. Platelets were labeled with the near-infrared fluorophore IR-786. Optimal total fluorescence yield occurred at 6 attomoles of IR-786 per platelet. IR-786-labeled platelets were tested for their ability to detect thrombus formation in large animal model systems relevant to common human vascular procedures. Invisible near-infrared light did not distort the surgical field in any way, and even after optimization of per-platelet fluorescent yield, platelets remained fully functional. Intravenous infusion of just 3.6x10(10) labeled platelets into a 35-kg Yorkshire pig permitted thrombus visualization, with a signal-to-background ratio > or = 2, for at least 2 hours in coronary, carotid, and femoral vessels. Platelet-rich, actively growing clots were monitored in real time and quantified with respect to size and kinetics after injury to vessels, cutaneous incisions, intravascular stent insertion, or introduction of embolic coils. Similarly, formed clots were monitored in real time during thrombolysis with streptokinase and heparin. Vessel patency was assessed independently with a second near-infrared fluorescent blood pool agent. IR-786-labeled platelets provide sensitive, specific, and real-time visualization of thrombi in thick-walled blood vessels. In addition to immediate application in cardiac, transplant, and vascular surgery, the mechanisms that underlie thrombus formation in large blood vessels can now be investigated.


An Overview of Missed Nursing Care and Its Predictors in Saudi Arabia: A Cross-Sectional Study.
Nursing care is holistic, and missing any aspect of care can be critical to patients' health. However, due to the complex and intense nature of the nursing practice, nurses have to unintentionally prioritize some activities, forcing them to omit some aspects of nursing care. To explore the dimensions of missed nursing care and its predictors within the Saudi Arabian healthcare system. Quantitative, cross-sectional study used the MISSCARE survey by utilizing nonprobability convenience sampling to collect the data of 604 staff nurses working in inpatient wards in Jazan, Saudi Arabia. The overall mean of missed nursing care is (m = 1.37, SD = 0.45). Missed nursing care activities were mostly failure to attend interdisciplinary care conferences (m = 1.66, SD = 0.96) and patient ambulation thrice a day (m = 1.63, SD = 0.97). Missed nursing care was mainly caused by human resource shortage (m = 3.53, SD = 0.88). Missed nursing care is predicted by the turnover intention (B = 2.380, t = 3.829, p < 001) and job satisfaction (B = -0.864, t = -4.788, p < 001). Although missed nursing care is evident in Saudi Arabia, it is significantly lower than the international rates, and it is mainly caused by labor resource shortage which directly influences nurses' job satisfaction and intention to leave. Optimizing the recruitment process, resource allocation and effective nurses' retention programs are proposed solutions that may be beneficial to mitigate missed nursing care.


Evidence for the involvement of the 16kD gene promoter in initiation of chromosomal replication of Escherichia coli strains carrying a B/r-derived replication origin.
Initiation of chromosomal DNA replication of several Escherichia coli dnaA (Ts) strains is diminished in cell harbouring pBR322 hybrid plasmids carrying both oriC and the adjacent 16kD gene promoter of E. coli K12. This perturbance, resulting in very slow growth, is caused both by the dnaA allele and the E. coli B/r-derived region of the replication origin of these strains. Cloning and DNA sequence analysis of the E. coli B/r replication origin revealed several base differences as compared to the E. coli K12 sequence. The replication origin of temperature sensitive fast growing mutants, originating from a homologous exchange between chromosomal and plasmid DNA sequences were also cloned. Sequence data showed that a single base change within the promoter of the 16kD gene of these dnaA (Ts) strains is able to suppress the inhibition of chromosomal DNA replication by the mentioned pBR322 hybrid plasmids. Our results strongly indicate a role of the 16kD gene promoter in control of initiation of chromosomal DNA replication.


Vital Signs: Deficiencies in Environmental Control Identified in Outbreaks of Legionnaires' Disease - North America, 2000-2014.
The number of reported cases of Legionnaires' disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000-2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100,000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires' disease to identify gaps in building water system maintenance and guide prevention efforts. Information from summaries of CDC Legionnaires' disease outbreak investigations during 2000-2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes. During 2000-2014, CDC participated in 38 field investigations of Legionnaires' disease. Among 27 land-based outbreaks, the median number of cases was 10 (range = 3-82) and median outbreak case fatality rate was 7% (range = 0%-80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in ≥2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes. Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires' disease outbreaks and reducing disease.


Effects of Protein-Induced Local Bending and Sequence Dependence on the Configurations of Supercoiled DNA Minicircles.
The statistical mechanics of a short circularized DNA molecule, a DNA minicircle, with a prescribed linking number depends heavily on the mechanical and geometrical properties of the DNA, which are known to be functions of the sequence. A description of a general numerical scheme used for the performed advanced simulation is presented with examples that reveal the effects of sequence dependence and local deformations, caused by protein binding, on the configurations in a canonical ensemble of a supercoiled minicircle. Using a realistic course grain model in which the sequence-dependent elasticity, the intramolecular electrostatic interactions, and the impenetrability of the DNA molecule are taken into account, the bifurcation of equilibria of supercoiled minicircle DNA with the induced bending as a parameter is shown. The unique Monte Carlo scheme for constrained DNA molecules was utilized in order to calculate site-to-site distance probabilities for each pair of sites in the molecule. The simulated examples show not only that the sequence alone can play a significant role in bringing two remote sites to a contact but also the possible existence of several competing regions of contact. The results suggest that the local deformation caused by protein binding can yield a global configurational change, dominated by slithering motion, which brings two (originally) remote sites to close proximity, and that the nature of such effect is related to the sequence architecture.


Bioinformatics and functional magnetic resonance imaging in clinical populations: practical aspects of data collection, analysis, interpretation, and management.
In this paper the authors review the issues associated with bioinformatics and functional magnetic resonance (fMR) imaging in the context of neurosurgery. They discuss the practical aspects of data collection, analysis, interpretation, and the management of large data sets, and they consider the challenges involved in the adoption of fMR imaging into clinical neurosurgical practice. Their goal is to provide neurosurgeons and other clinicians with a better understanding of some of the current issues associated with bioinformatics or neuroinformatics and fMR imaging. Thousands to tens of thousands of images are typically acquired during an fMR imaging session. It is essential to follow an activation task paradigm exactly to obtain an accurate representation of cortical activation. These images are then interactively postprocessed offline to produce an activation map, or in some cases a series of maps. The maps may then be viewed and interpreted in consultation with a neurosurgeon and/or other clinicians. After this consultation, long-term archiving of the processed fMR activation maps along with the standard structural MR images is a complex but necessary final step in this process. The fMR modality represents a valuable tool in the neurosurgical planning process that is still in the developmental stages for routine clinical use, but holds exceptional promise for patient care.


Localized and stationary light wave modes in dispersive media.
In recent experiments, localized and stationary optical wave packets have been generated in second-order nonlinear processes with femtosecond pulses, whose asymptotic features relate to those of nondiffracting and nondispersing polychromatic Bessel beams in linear dispersive media. We investigate the nature of these linear waves and show that they can be identified with the X-shaped (O-shaped) modes of the hyperbolic (elliptic) wave equation in media with normal (anomalous) dispersion. Depending on the relative strengths of mode phase mismatch, group velocity mismatch with respect to a plane pulse, and the defeated group velocity dispersion, these modes can adopt the form of pulsed Bessel beams, focus wave modes, and X waves (O waves), respectively.


How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation.
Sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease of the liver, is one of the most relevant complications of endothelial origin that appears early after haematopoietic cell transplantation (HCT). Despite its relatively low incidence and the fact that most cases of SOS resolve spontaneously, the cases that evolve to multi-organ failure (MOF; severe SOS) have a mortality rate higher than 80% and represent one of the major clinical problems after HCT. For this reason, transplantation teams must have a pre-established policy regarding preventive measures in high-risk patients, strict daily control of weight and fluid balance during HCT, homogeneous diagnostic criteria, appropriate complementary studies for a correct differential diagnosis and measures to prevent and manage hepatorenal syndrome; in addition they must also be ready to start early treatment with defibrotide in patients with a possible severe SOS. Due to the lack of definitive evidence to enable the establishment of general recommendations in the management of SOS, this review analyses all of these aspects based on the author's personal experience.


Surface and intra-pulpal temperature variation during tooth whitening photoactivated with LED/laser.
This study evaluated the variation of surface and intra-pulpal temperature, during bleaching protocol, using LED/laser. The 35% (HP35), 15% (HP15) and 6% (HP6) gels were used associated with LED/laser applied every 1 min for 30 min in a human canine. The evaluation of surface temperature variation (∆Ts) was performed using a pHmeter and the intra-pulpal temperature variation (∆Ti) was performed using a digital thermometer, at times of 1-, 5-, 10- 15- and 30-min. Statistical analysis was performed using the two-way repeated measures ANOVA test and Bonferroni post-hoc test was used at a significance level of 5%. HP35 and HP15 showed greater temperature variation than HP6 up to 10 min of surface evaluation, showing no differences between them. In the intra-pulpal evaluation, no group showed differences throughout the procedure.


COVID-19: the implications and consequences of prolonged lockdown and COVID-19 vaccine cost in a low-middle income country.
Lockdowns and just recently, the COVID-19 vaccines, are amongst the disease containment measures instituted globally to check the spread of COVID-19. Prolonged lockdowns are however, not sustainable in low resource economies like Nigeria, where up to 70% of her population live on less than a dollar a day, with the majority, either unemployed, or working in the private/informal sector and depending on daily earnings for survival. If the lockdown remains sustained, it would not be long before the largely poor citizens starve to death. Also, spending over US $3.9 billion on COVID-19 vaccines for more than 200 million Nigerians, as intended by the Nigerian government, is not plausible, given that neglected tropical diseases (NTDs) like Lassa fever, and other more common causes of morbidity and mortality, continue to kill more Nigerians than COVID-19. Public enlightenment of the populace on the need to strictly adhere to non-pharmacologic preventive measures, including social distancing, use of face masks, good personal hygiene, covering of the mouth and nose when coughing and sneezing, frequent hand washing and sanitizing with alcohol-based hand-sanitizers and disinfection of surfaces, is what is sustainable, feasible and compatible with the economic reality in our setting. As Sir Robert Hutchison, the highly revered doyen of medicine, wrote in his petition over 85 years ago, "And from making the cure of the disease more grievous than the endurance of the same, Good Lord, deliver us", we must be careful not to make the cure of COVID-19 worse than COVID-19 itself.


Resistance determinants and clonal diversity in group A streptococci collected during a period of increasing macrolide resistance.
Susceptibility to macrolides and lincosamides was investigated with 299 consecutive nonduplicate Streptococcus pyogenes clinical isolates collected over a 6-year period (1992 to 1997) from an area of central Italy. During this period, macrolide resistance rates steadily increased (from 9% in 1992 to 53% in 1997; P < 0.001). The increase was caused by isolates with a macrolide-lincosamide-streptogramin B resistance phenotype, carrying mostly erm(B) but also erm(TR) genes, that were not detected in the first 2 years and were detected with increasing prevalence (8, 5, 26, and 37%, respectively) during the following 4 years. During the same period, the prevalence of isolates with a macrolide resistance phenotype, carrying mef(A) determinants, did not vary significantly; on average it was 13%, with modest rate fluctuations in different years and no definite trend. Molecular typing revealed a remarkable clonal diversity among susceptible and resistant isolates and a notable heterogeneity of the genetic environment of the resistance genes. The analysis of clonal diversity in relation with resistance phenotypes and genotypes revealed that increased macrolide resistance rates were due to a complex interplay of different mechanisms, with a relevant contribution played by an "epidemic" spread of genetic elements carrying the erm(B) gene among the circulating streptococcal population.


Deal or no deal? The prevalence and nutritional quality of price promotions among U.S. food and beverage purchases.
This study examines trends in the prevalence of price promotions among packaged food and beverage purchases, differences in prevalence by household race/ethnicity or income, and the association between price promotions and the nutritional profile of purchases. This cross-sectional study utilizes a dataset of 90 million purchases from 38,744 (2008) to 45,042 (2012) US households in 2008-2012. Chi-square tests were used to examine whether the proportion of purchases with price promotions changed over time or differed by household race/ethnicity or income. T-tests were used to compare purchased products' nutritional profiles. Prevalence of price promotions among packaged food and beverage purchases increased by 8% and 6%, respectively, from 2008 to 2012, with both reaching 34% by 2012. Higher-income households had greater proportions of purchases with price promotions than lower-income households. Asian households had the highest proportion of purchases with any price promotion, followed by non-Hispanic whites. While total price-promoted packaged food purchases had higher mean energy, total sugar, and saturated fat densities than purchases with no price promotions, absolute differences were small. Prevalence of price promotions among US household purchases increased from 2008 to 2012 and was greater for higher-income households. No clear associations emerged between presence of price promotions and nutritional quality of purchases.


Humans with obesity have disordered brain responses to food images during physiological hyperglycemia.
Blood glucose levels influence brain regulation of food intake. This study assessed the effect of mild physiological hyperglycemia on brain response to food cues in individuals with obesity (OB) versus normal weight individuals (NW). Brain responses in 10 OB and 10 NW nondiabetic healthy adults [body mass index: 34 (3) vs. 23 (2) kg/m2, means (SD), P < 0.0001] were measured with functional MRI (blood oxygen level-dependent contrast) in combination with a two-step normoglycemic-hyperglycemic clamp. Participants were shown food and nonfood images during normoglycemia (~95 mg/dl) and hyperglycemia (~130 mg/dl). Plasma glucose levels were comparable in both groups during the two-step clamp ( P = not significant). Insulin and leptin levels were higher in the OB group compared with NW, whereas ghrelin levels were lower (all P < 0.05). During hyperglycemia, insula activity showed a group-by-glucose level effect. When compared with normoglycemia, hyperglycemia resulted in decreased activity in the hypothalamus and putamen in response to food images ( P < 0.001) in the NW group, whereas the OB group exhibited increased activity in insula, putamen, and anterior and dorsolateral prefrontal cortex (aPFC/dlPFC; P < 0.001). These data suggest that OB, compared with NW, appears to have disruption of brain responses to food cues during hyperglycemia, with reduced insula response in NW but increased insula response in OB, an area involved in food perception and interoception. In a post hoc analysis, brain activity in obesity appears to be associated with dysregulated motivation (striatum) and inappropriate self-control (aPFC/dlPFC) to food cues during hyperglycemia. Hyperstimulation for food and insensitivity to internal homeostatic signals may favor food consumption to possibly play a role in the pathogenesis of obesity.


Regional and age variations in growing tendon.
Gastrocnemius tendons of 10 White Leghorn chickens at 6, 8, and 12 weeks of age were divided into proximal, middle, and distal portions to assess regional variability in composition and growth. Body weight increases approximately 150% during the period examined, whereas the lateral gastrocnemius muscle and tendon increase approximately 193% and 227%, respectively. No significant changes in cellularity (DNA concentration) or hydroxypyridinium (OHP) crosslinks occur with increasing age. Hydroxyproline (HYP) concentration increases by 12 weeks of age, as hexuronate, glucosamine, and galactosamine decrease. Composition shows some regional variation: the distal region of the tendon has a lower HYP concentration and increased GAGs and OHP crosslinks compared to either the proximal or middle regions, which do not differ from each other. The mean collagen fibril diameter increases with age, but the oldest tendons also contain more small diameter fibrils (< 40 nm). There is a unimodal fibril distribution at all three ages, although this has broadened by 12 weeks. The data from this study suggest that rapid tendon growth occurs throughout the time period examined and that changes characteristic of mature tendon, such as increased OHP crosslink concentration, have not yet developed in hatchlings because of the large amount of new tissue being produced. Whereas all three regions of the tendon are similar in size, composition of the distal region differs from that of the proximal and middle regions, suggesting that this portion of the tendon should be avoided when sampling a tendon.


[ST52 treatment of cancer of the prostate during the hormonal resistance phase].
Stilboestrol phosphate (ST 52) was evaluated on pain, general status, life expectancy and PSA, in a retrospective study of patients with prostatic carcinoma and relapse to hormonal treatment. 32 patients were treated by infusion of Stilboestrol phosphate at a daily escalating dose from 1.2 to 3 g over a period of 10 days, then subsequently oral administration. Minor complications, especially nausea were observed in 12 cases but no major complication or interruption of treatment. Improvement for pain alone or with general status was obtained in 50% (16 cases) at 3 months, but at one year only 10% were still improved. Median survival was 8 months, with 19.4 months for responders at the end of infusions and 4.2 months for non-responders-respectively. Stilboestrol phosphate can obtain a clinical response with low morbidity when relapse to hormonal treatment occurs. Infusion responders have a better life expectancy.


Synthesis and anticonvulsant activity of some new 3-(p-sulfamoylphenyl)-4(3H)-quinazolinones.
In view of their expected anticonvulsant property, a series of 3-(p-sulfamoylphenyl)-4(3H)-quinazolinone derivatives (V) were synthesized by condensation of sulfanilamide with various 4H-3,1-benzoxazin-4-ones (III). Some 2-amido-N-(p-sulfamoylphenyl)benzamides (IV) were isolated as reaction intermediates. The structures of V were confirmed by IR, 1H-NMR, MS and elemental analyses. Some of the compounds V showed significant anticonvulsant effects against pentetrazol-induced convulsions.