Haemophilus ducreyi.
Haemophilus ducreyi is the etiologic agent of chancroid, an infection which is endemic in tropical and subtropical areas of the world and which is becoming more prevalent in Europe and North America. Recently, several strains have demonstrated resistance to several antimicrobials by plasmid acquisition and cell envelope alteration making control of the spread of this organism a challenge. Equally challenging is the growth of this organism in the clinical microbiology laboratory because of its in vitro fastidious nature. Currently, the therapy of choice for Haemophilus ducreyi infection is trimethoprim sulfamethoxazole or erythromycin. Plasmid enumeration and restriction endonuclease fingerprinting in addition to outer membrane protein profiles may provide a basis for subtyping which would be useful in epidemiologic studies.


Mixed depressive states: nosologic and therapeutic issues.
This paper focuses on the clinical importance of affective mixed states with special attention given to agitated depression, which has lost its status as a mixed state in the DSM and ICD systems. Following a historical review of the topic, the psychopathological elements are examined. Psychic and motor agitation are considered equally important for the definition of agitated depression and the concept of latent agitated depression is introduced for those major depressive episodes that become agitated following antidepressant treatment. The thesis is advanced that the erroneous nosologic position of agitated depression and its treatment as simple, unipolar depression is at least partly responsible for the problematic issues of the unfavourable treatment outcome and high suicide rates among depressive patients.


RAB25 coordinates filaggrin-containing keratohyalin granule maturation and affects atopic dermatitis severity.
Keratohyalin granules (KHGs) supply the critical epidermal protein constituents such as filaggrin for maintaining skin barrier function during epidermal differentiation; however, their regulating mechanism remains largely unelucidated. To investigate the role of Ras-related protein Rab-25 (RAB25) expression in skin disease, we utilized skin specimens of patients with moderate-to-severe atopic dermatitis (AD) and healthy controls. To investigate the susceptibility of Rab25 knockout mice to AD, we established an oxazolone-induced AD model. We investigated the role of RAB25 in KHG maturation and AD. RAB25-deficient mice showed a disrupted stratum corneum along with skin barrier dysfunction, decreased KHG production, and abnormal KHG processing. Consistently, in the human keratinocyte cell line HaCaT, RAB25 co-expressed with filaggrin-containing KHG and RAB25 silencing impaired KHG formation, which was attributable to abnormal actin dynamics. Most importantly, RAB25 expression was severely downregulated in the skin lesions of patients with AD, which was strongly correlated with disease severity scores. RAB25 coordinates KHG homeostasis by regulating actin dynamics and is critical for epidermal differentiation and the pathophysiology of AD.


Further studies on creatine kinase activity in human skeletal muscle.
Creatine kinase (CK) was measured in muscle samples from 9 female and 9 male adult subjects using comparatively two procedures. The improved method, using N-acetylcysteine as activator gives results about 1.5 times higher than that with reduced glutathione. The significant correlation existing between activities of CK and hexosephosphate isomerase was confirmed using the improved method. There also exists a correlation between CK and enolase activity. In this respect, there are no differences between muscle samples from male and female subjects.


Suspensions for intravenous (IV) injection: a review of development, preclinical and clinical aspects.
There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs. Besides enhanced dissolution rates, and thereby, improved bioavailability, nanoparticles can also provide targeting capabilities when injected intravenously. The latter property has led to increased research and development activities for intravenous suspensions. The first intravenously administered nanoparticulate product, Abraxane (a reformulation of paclitaxel), was approved by the FDA in 2006. Additional clinical trials have been conducted or are ongoing for multiple other indications such as oncology, infective diseases, and restenosis. This article reviews various challenges associated with developing intravenous nanosuspension dosage forms. In addition, various formulation considerations specific to intravenous nanosuspensions as well as reported findings from various clinical studies have been discussed.


The synergistic effect of waste cooking oil and endod (Phytolacca dodecandra) on the production of high-grade laundry soap.
A green viewpoint based on the production of soap using waste products such waste cooking oils (WCOs) and Endod (Phytolacca dodecandra) is presented. The process of saponification, which involves reacting triglycerides with fats and oils in an alkaline solution, produces soap. With the help of WCO and Endod as manufacturing inputs, this study intends to create high-quality, commercially viable eco-friendly soaps. The optimal blend of WCO and Endod with sodium hydroxide solution was used in the current investigation to create laundry soaps. Evaluations were done on the cleansing effects and physico-chemical makeup of prepared soap. As a reference control, the raw oil soaps made without and with frying were employed. The free caustic alkali content, chloride content, moisture content, ethanol-insoluble-matter, total fatty matter, pH, and foam height values of the prepared soap were found to be in the range of 0%, 0%, 16.56-22.52%, 0.1-3.05%, 63.41-75.46%, 9.22-9.82%, and 3.3-8.1 cm respectively. The results obtained by blending fried WCOs and Endod were comparable to the Physico-chemical properties of the Endod-free uncooked/fresh oil soap. The soap made by blending WCO and Endod has higher cleansing power and better lather formation than the prepared soap with WCO without Endod. Moreover, the observed data are comparable with similar data reported in other literature, recommended acceptable standards (EAS, CES), and from many countries including the British, Malaysia, and the Philippines. Cooking oils fried at different temperatures do not have much effect on the quality of soap making. This suggested that the blending of WCOs and Endod can be used as raw materials to prepare high-quality and economically feasible soaps by replacing imported oils and fats.


Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas.
The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model. The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma.


Role of cytochrome b5 in catalysis by cytochrome P450 2B4.
Cytochrome b5 has been shown to stimulate, inhibit or have no effect on catalysis by P450 cytochromes. Its action is known to depend on the isozyme of cytochrome P450, the substrate, and experimental conditions. Cytochrome P450 2B4 (CYP 2B4) has been used in our laboratory as a model isozyme to study the role of cytochrome b5 in cytochrome P450 catalysis using two substrates, methoxyflurane and benzphetamine. One substrate is the volatile anesthetic, methoxyflurane, whose metabolism is consistently markedly stimulated by cytochrome b5. The other is benzphetamine, whose metabolism is minimally modified by cytochrome b5. Determination of the stoichiometry of the metabolism of both substrates showed that the amount of product formed is the net result of the simultaneous stimulatory and inhibitory actions of cytochrome b5 on catalysis. Site-directed mutagenesis studies revealed that both cytochrome b5 and cytochrome P450 reductase interact with cytochrome P450 on its proximal surface on overlapping but non-identical binding sites. Comparison of the rate of reduction of oxyferrous CYP 2B4 and the rate of substrate oxidation by cyt b5 and reductase with stopped-flow spectrophotometric and rapid chemical quench experiments has demonstrated that although cytochrome b5 and reductase reduce oxyferrous CYP 2B4 at the same rate, substrate oxidation proceeds more slowly in the presence of the reductase.


[Conservative surgical treatment for diabetic foot ulcers under the metatarsal heads. A retrospective case-control study].
The plantar neuropathic ulcer is a classical and frequent complication of a pathology recognized as pandemic by the WHO: diabetes. Even if frequently encountered during medical practice, the neuropathic ulcer remains poorly understood in its pathophysiology. Its treatment is usually long and disappointing, resulting too often in an amputation. Paradoxically, medical literature is particularly scarce on the subject of surgical approaches to the plantar neuropathic ulcer. Beyond the cases of vascular lesions requiring above all a technique of revascularization, we have tested out an original approach enabling the surgical treatment of an overt neuropathic ulcer. Our purpose was to correct the architecture of the foot for a superior distribution of foot support points. We performed subtraction osteotomies ahead of the neuropathic ulcer in order to redress the deformed bone axis. Standing with full weight on the foot is prescribed from the following day of the intervention in almost all cases. We have evaluated the effectiveness of this innovative conservative surgical treatment on neuropathic ulcers of metatarsal heads by comparing it with the usual medical treatment. Two groups of patients have thus been analysed for this retrospective comparative study in order to determinate whether the use of this surgical technique benefits the patient. The studied criteria were healing time, recurrence rate, amputation rate and overall failure rate of the treatment, represented by the occurrence of the event "recurrence or amputation". All the differences found were in favour of the surgical technique with, in particular, significant differences in healing time, amputation rate and occurrence rate of the event "recurrence or amputation". The difference in recurrence rate was also clearly in favour of the surgery group, but it was not significant. The conservative surgical treatment by proximal osteotomy is therefore an innovative technique enabling a significant improvement in healing time and treatment after-effects of neuropathic ulcers in non-arteritis diabetic patients.


Natural history of acute kidney disease in patients with cirrhosis.
In 2012, the KDIGO group proposed new definitions for acute kidney injury (AKI), acute kidney disease (AKD) and chronic kidney disease (CKD). According to the definition adapted by the International Club of Ascites, AKI has been extensively investigated in patients with cirrhosis. On the contrary, there are currently no data on the epidemiology and clinical outcomes associated with AKD. The aim of the study was to assess the prevalence and the impact of AKD on the clinical course and survival of patients with cirrhosis. A total of 272 consecutive patients with cirrhosis attending our outpatient clinic were included in the study. Clinical and laboratory data were collected at inclusion. Patients were followed-up until death, liver transplant or the end of follow-up. During follow-up, 80 patients developed AKD (29.4%). Forty-two (52.5%) recovered from the first episode of AKD and 26 maintained a normal renal function up to the end of follow-up. Sixteen patients developed a second episode of AKD. Globally, 36 patients (45.0%) died with AKD. Finally, AKD progressed to CKD in 11 patients (13.8%). The 5-year survival rate was significantly lower in patients who developed AKD than in those who did not (34.8% vs. 88.8%, p <0.001). The 5-year rates of complications of cirrhosis and of hospitalizations were also higher in patients with AKD than in those without AKD. AKD is frequent in patients with cirrhosis. It can be reversible, but it may recur and progress to CKD. AKD has a very negative impact on morbidity and mortality in patients with cirrhosis. Renal impairment has a very negative impact on patients with cirrhosis. Renal impairment seems to be characterized by a very dynamic course, which is defined according to renal function and length of the impairment as acute kidney injury, acute kidney disease and chronic kidney disease. The role of acute kidney disease is currently unknown. Our study shows for the first time that acute kidney disease is frequent in patients with cirrhosis and has a very negative impact on survival.


Countermarketing About Fruit Drinks, Alone or With Water Promotion: A 2019 Randomized Controlled Trial in Latinx Parents.
Objectives. To test whether fruit drink countermarketing messages alone or combined with water promotion messages reduce Latinx parents' purchases of fruit drinks for children aged 0 to 5 years. Methods. We performed a 3-arm randomized controlled online trial enrolling 1628 Latinx parents in the United States during October and November 2019. We assessed the effect of culturally tailored fruit drink countermarketing messages (fruit drink‒only group), countermarketing and water promotion messages combined (combination group), or car-seat safety messages (control) delivered via Facebook groups for 6 weeks on parental beverage choices from a simulated online store. Results. The proportion of parents choosing fruit drinks decreased by 13.7 percentage points in the fruit drink‒only group (95% confidence interval [CI] = -20.0, -7.4; P < .001) and by 19.2 percentage points in the combination group (95% CI = -25.0, -13.4; P < .001) relative to control. Water selection increased in both groups. Conclusions. Fruit drink countermarketing messages, alone or combined with water promotion messages, significantly decreased parental selection of fruit drinks and increased water selection for their children. Public Health Implications. Countermarketing social media messages may be an effective and low-cost intervention for reducing parents' fruit drink purchases for their children. (Am J Public Health. 2021;111(11):1997-2007. https://doi.org/10.2105/AJPH.2021.306488).


A method for characterizing the complete settling process of activated sludge.
Based on batch settling tests, a model describing the compression settling process of activated sludge was developed and validated by experiments. Furthermore, a theoretical equation for determining the critical point when the compression settling stage commences, and a new velocity function for the compression settling were deduced from the model. By combining the new model and the conservation of mass, it was proved that the Vesilind function was also capable of describing the compression settling velocity on condition that the appropriate parameters were estimated. Dividing the complete settling process of activated sludge into the zone settling and compression settling stages, and describing them by the Vesilind function with different parameter sets was more reasonable for characterizing the complete settling process of activated sludge. The method was applied to predict the sludge blanket height during batch settling tests, and the results showed that the settling processes could be simulated well.


Long-term care insurance and public policy: an analysis of obstacles to utilization.
This article investigates the phenomenon of long-term care insurance and the policy environment in which it has evolved. Further discussion focuses on the obstacles that may exist to wide acceptance of long-term care insurance by those who derive the most benefit from the protection it could provide. The authors review the role of employers and the advantages of long-term care insurance as an employee benefit as compared to individual policies.


Risperidone reduction of amphetamine-induced self-injurious behavior in mice.
The behavioral and neurochemical effects of high doses of amphetamine administered to BALB/c mice were examined in the presence and absence of co-administered haloperidol (a D2 antagonist), SCH 23390 (a D1 antagonist) and risperidone (a mixed 5-HT2/D2 antagonist). It was observed that mice displayed a dose-dependent increase in stereotypic behavior, oral dyskinesia, and self-injurious behavior (SIB) in response to amphetamine treatment. Furthermore, agents that blocked the SIB reversed the amphetamine-induced release of serotonin. This effect was unrelated to hyperthermia or non-specific sedation (as assessed by measurement of motor activity). These data are interpreted in the context of the underlying basis of murine SIB involving both dopaminergic and serotonergic activation and demonstrate the efficacy of risperidone in treating these behaviors.


The prion protein selectively binds to and modulates the content of purinergic receptor P2X4R.
The GPI-anchored prion protein (PrP(C)) is involved in neurodegeneration, either through misfolding in the Transmissible Spongiform Encephalopathies (TSE), or as a mediator of the neurotoxicity of peptide oligomers in Alzheimer's Disease. PrP(C) has been attributed pleiotropic functions, and appears to scaffold a variety of cell surface signaling modules, for example through its binding to several neurotransmitter receptors. Here we used transfected HEK293 cells to test for an interaction of PrP(C) with purinergic receptor P2X4R. The prion protein bound P2X4R in both overlay and co-immunoprecipitation assays, and co-localized mostly intracellularly, but occasionaly at the cell surface in confocal micrographs. Functional PrP(C):P2X4R interaction was tested by the uptake of a P2X4R-permeant compound, and by modulation of intracellular calcium. Unexpectedly, however, this interaction was traced to a selective effect of PrP(C) upon the content of co-transfected P2X4R. The results suggest a role of PrP(C) in proteostasis, dysfunctions of which may be involved in the pathogenesis of neurodegenerative diseases such as TSE and Alzheimer's Disease.


The effect of a neurotoxin (benzalkonium chloride) on the lower esophagus.
Achalasia of the esophagus may be associated with abnormalities of the myenteric plexus (hypo- and anganglionosis). This report evaluates this relationship by studying the effect of benzalkonium chloride (BK, a topical neurotoxin) on the lower esophagus. Following midline laparotomy, topical BK (0.5%) was applied to the muscularis of the lower 1.0 cm of the esophagus for 30 min in 38 Sprague-Dawley rats (200 g). Thirty-eight additional rats acted as controls (unoperated, n = 19; sham laparotomy, n = 19). At 1 and 3 months animals were evaluated for weight gain, daily food intake (g/100 gm body wt), lower esophageal sphincter (LES) manometry, and contrast esophagram. At 3 months, the esophagus was evaluated for histologic study and acetylcholinesterase staining. Esophagram showed distal narrowing with proximal dilatation in BK rats (inner diameter 4.71 +/- 0.61 vs 6.17 +/- 0.58 in controls, P less than 0.001). Daily food intake was significantly less in BK rats (5.57 +/- 0.41 g vs controls 7.69 +/- 0.33 g P less than 0.001). Daily weight gain was also less in BK rats (1.13 +/- 0.34 vs controls 1.83 +/- 0.25, P less than 0.001). An increased LES pressure was noted in BK rats (5.45 +/- 0.89 mmHg vs controls 4.04 +/- 1.04 mmHg; P less than 0.1). A histologic study showed aganglionosis in BK rats with positive cholinesterase staining fibers compared to controls. Topical BK results in distal esophageal aganglionosis characterized by distal narrowing, proximal dilatation, decreased food intake, and limited weight gain when compared to controls. These findings are similar to those observed in achalasia and support a primary neurogenic cause for its etiology.


French trends in carpal tunnel surgery: An online survey of members of the French Society for Surgery of the Hand.
Several surgical and anesthesia techniques are used in carpal tunnel surgery. The practices of members of the American Society for Surgery of the Hand and the Canadian Society of Plastic Surgery were recently published and compared. Because of the great difference in these practices, we investigated the practices of the members of the French Society for Surgery of the Hand and how they would change. An online survey including 14 systematic and 12 conditional questions was sent by email to all 685 surgeons who were members of the French Society for Surgery of the Hand in July 2019. Data were analyzed using descriptive statistics. The survey was completed by 129 members (19%). The open approach was used by 56% of the surgeons (8% by traditional open technique, 48% by minimally invasive open technique), endoscopic techniques by 40% and ultrasound-guided techniques by 4%. Most surgeons used regional anesthesia (69%) or local anesthesia (25%). Half of the surgeons (50%) would consider changing their surgical technique. Sixty-one percent were interested in ultrasound-guided techniques and 34% in endoscopic techniques. Almost half the surgeons (48%) would consider changing their anesthesia technique and 97% were interested in local anesthesia. Our study showed that the open approach and regional anesthesia were the most frequently used techniques but that an increase in endoscopic and ultrasound-guided techniques as well as local anesthesia techniques was likely. LEVEL OF EVIDENCE: Economic and decision analysis V.


Third contribution on Rovno amber silken fungus beetles: a new Eocene species of Cryptophagus (Coleoptera, Clavicornia, Cryptophagidae).
Cryptophagus alexagrestis Lyubarsky & Perkovsky, sp. n. is described based on a fossil inclusion in Late Eocene Rovno amber (Ukraine). The new species is similar to the extant Cryptophagus skalitzkyi Reitter and Cryptophagus dilutus Reitter, differing from the latter by having a very transverse, short and dilated 10th antennal segment, and from the former by the very elongate segments of the flagellum.


Optimizing Sleep in the Military: Challenges and Opportunities.
Historically, scientific knowledge gaps-including a lack of information regarding the minimum amount of sleep needed to sustain nominally adequate, militarily relevant performance, and nescience of the potential impact of chronic sleep restriction on health and psychological well-being-have hindered decision-making vis-à-vis sleep/alertness management in operational environments. However, against a backdrop of increasing awareness of the importance of sleep for sustaining both performance and health, military researchers are currently doing the following: (1) developing a comprehensive, individualized sleep/alertness management system to optimize the general effectiveness of military personnel (ie, without regard to the potential relationship between sleep and specific aspects of military performance, thus sidestepping what has historically been an impediment to development of such a system); and (2) investigating the prevalence, potentially unique etiology (eg, resulting from the interaction of long-term exposure to combat-related stressors and sleep restriction), and treatment of sleep disorders and comorbidities in the military population.


Factors affecting early and long-term outcomes after completion pneumonectomy.
To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n=19; local recurrence, n=17; or metastasis, n=11). There were 50 males and 19 females with a mean age of 60 years (range, 29-80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p=0.005), coronary artery disease (p=0.03), removal of the right lung (p=0.02), advanced age (p=0.02), and renal failure (p<0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p=0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p=0.04) and mechanical stump closure (p=0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.


Enhancing the effectiveness of contact tracing interviews: A randomized controlled experiment of an enhanced cognitive interview protocol.
To compare the efficacy of a psychologically-based contact tracing interview protocol to a control protocol that emulated current practices under both interviewer-led and self-led modalities. This randomized controlled experiment utilized a 2 × 2 factorial design (Enhanced Cognitive protocol vs Control protocol; Interviewer-led call vs Self-led online survey). Data were collected online (n = 200; Mage = 44; 56.5% female; 79.5% White) during the COVID-19 pandemic (July 2, 2020 - September 15, 2020). The Enhanced Cognitive protocol increased reported close contacts by 51% compared with the Control protocol (d = 0.44 [0.15, 0.71]). This effect was present for both interview modalities and for both identifiable and non-identifiable contacts. The Enhanced Cognitive protocol also increased both the quantity of person descriptors (d = 1.36 [0.87, 1.85]) and the utility of descriptions (r = 0.35 [0.13, 0.53]). The application of cognitive principles in contact tracing interviews can significantly enhance the quantity and quality of information provided by respondents. Epidemiologists and public health investigators could benefit from utilizing cognitive principles and self-led modalities in contact tracing interviews.


Somatic cell nuclear transfer: infinite reproduction of a unique diploid genome.
In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the "Hayflick limit". However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to "passage" a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the "passage" of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels.


5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice.
The 5'AMP-activated protein kinase is an important mediator of muscle contraction-induced glucose transport and a target for pharmacological treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP-activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide ribonucleoside treatment could restore glucose homeostasis in ob/ob mice. Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7 days. Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment normalised glucose concentrations in ob/ob mice within 1 h, with effects persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4-carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal muscle, but had deleterious effects on plasma non-esterified fatty acids and triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside treatment. While ex vivo insulin-stimulated glucose transport was reduced in isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide ribonucleoside stimulated response was normal. The 5-aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose homeostasis in ob/ob mice can be explained by effects in skeletal muscle and liver. Due to the apparently deleterious effects of 5-aminoimidazole-4-carboxamide ribonucleoside on the blood lipid profile, strategies to develop tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase should be considered in order to improve glucose homeostasis.


Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production.
Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative disease which is triggered by infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV contains an open reading frame, K14, that has significant homology with cellular OX2, designated viral OX2 (vOX2). In this report, we demonstrate that vOX2 encodes a glycosylated cell surface protein with an apparent molecular mass of 55 kDa. Purified glycosylated vOX2 protein dramatically stimulated primary monocytes, macrophages, and dendritic cells to produce the inflammatory cytokines interleukin 1beta (IL-1beta), IL-6, monocyte chemoattractant protein 1, and TNF-alpha. Furthermore, expression of vOX2 on B lymphocytes stimulated monocytes to produce inflammatory cytokines in mixed culture. These results demonstrate that like its cellular counterpart, vOX2 targets myeloid-lineage cells, but unlike cellular OX2, which delivers a restrictive signal, KSHV vOX2 provides an activating signal, resulting in the production of inflammatory cytokines. Thus, this is a novel viral strategy where KSHV has acquired the cellular OX2 gene to induce inflammatory cytokine production, which potentially promotes the cytokine-mediated angiogenic proliferation of KSHV-infected cells.


Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia.
Acute myeloid leukemia (AML) patients with CEBPA double mutation (CEBPAdm ) were associated with distinct immunophenotypes and prognosis. Recently, both International Consensus Classification (ICC) and World Health Organization (WHO) classifications incorporated BZIP single mutations (CEBPAsmBZIP ) into the favorable risk group. However, the immunophenotypes of CEBPAsmBZIP mutations have not been characterized, especially when compared with the immunophenotypes of CEBPAdm . Retrospectively, we investigated and compared the immunophenotypes of AML with CEBPA mutations. Randomforest model and XGBoost algorithm were used to set up a scoring system based on the immunophenotypes of those patients. In a total of 967 AML patients: 218 were CEBPAdm (198 consisted of mutations in the BZIP region [CEBPAdmBZIP ], 20 were double mutations outside BZIP region [CEBPAdm-woBZIP ]), 117 were CEBPAsm (54 CEBPAsmBZIP and 63 were single mutations outside BZIP region [CEBPAsm-woBZIP ]) and the others were wildtype CEBPA (CEBPAwt ). Patients with CEBPAdmBZIP , CEBPAdm-woBZIP and CEBPAsmBZIP shared the distinct immunophenotype of CD7+ CD34+ MPO+ HLA-DR+ CD19- , in contrast to patients with CEBPAsm-woBZIP and CEBPAwt who showed reduced expression of CD7, HLA-DR, MPO, CD34 and a higher expression of CD19. Based on these immunophenotypes, we developed a scoring system to preemptively identify AML with CEBPAsmBZIP and CEBPAdm and validated it internally and externally. AML with CEBPAdmBZIP , CEBPAdm-woBZIP , and CEBPAsmBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPAsm-woBZIP and CEBPAwt AML.


Does a tetracycline resistance determinant of class N exist?
pMV120 was reported to carry the tetracycline resistance (Tcr) determinant of class N. We obtained tetracycline-susceptible transconjugants harboring plasmids with restriction enzyme profiles indistinguishable from those of pMV120 isolated from tetracycline-resistant clones. We conclude that pMV120 is a cryptic plasmid and that class N of Tcr determinants does not exist.


Hypoechoic thyroid nodules on ultrasound 4 years after prenatal exposure to radioiodine: resolution with thyroxine therapy.
We describe an infant inadvertently exposed to radioiodine at 17 weeks gestation. His mother had received 400 MBq of (131)I for hyperthyroidism (total T4 178 nmol/L, thyroid stimulating hormone (TSH) <0.1 mU/L, 4-h (131)I uptake 16%). Following cordocentesis at 27 weeks (free T4 12.7 pmol/L, TSH 35.4 mU/L) intra-amniotic thyroxine was withheld and a male infant was born at 39 weeks gestation, birthweight 3520 g. Cord TSH was low (0.1 mU/L), total T4 151 nmol/L on day 4, the mother having received no medication during pregnancy. Postnatal follow-up showed mild TSH elevation (11.0-19.4 mU/L) but normal free T4 (9-12.7 pmol/L) during the first 2 years of life following which the child was discharged still untreated. On recall at 4.3 years, TSH elevation persisted (15.4 mU/L) and ultrasound showed several hypoechoic thyroid nodules within the left lobe that disappeared after thyroxine treatment. In the event of inadvertent exposure to radioiodine in utero, the infant should receive thyroxine therapy from birth in order to protect the thyroid gland from TSH over-stimulation, however mild.


Coordination, redox properties and SOD activity of Cu(II) complexes of multihistidine peptides.
The results of electrochemical and SOD activity measurements of such copper(II) complexes of terminally protected multihistidine peptides that may mimic the active site of CuZnSOD enzyme are submitted and completed with solution equilibrium studies of some copper(II)-ligand systems. The equilibrium data confirm that the thermodynamic stabilities increase with the increasing number of histidyl residues in the amino acid sequence, the stability order, however, can be finely tuned by the number and quality of amino acids between histidine residues. Based on the cyclic voltammetric studies we concluded that the formal reduction potential values of imidazole nitrogen coordinated complexes decrease with the increasing number of imidazole donor atoms in the coordination sphere. However, the redox parameters of [CuH-1L]+ and [CuH-2L] complexes containing amide nitrogen coordination can be determined as well. All formal potential values of [CuL]2+, [CuH-1L]+ and [CuH-2L] complexes fall in the middle potential range of SOD activity. Finally, after the detailed analysis of species distribution curves based upon the equilibrium data SOD activity of copper(II) containing systems at two pH (pH=6.8 and 7.4) were determined. The imidazole coordinated [CuL]2+ complexes of the multihistidine peptide containing the HXH sequence exhibit the most significant activity, but the presence of amide nitrogen coordinated species with slightly distorted geometry could considerably contribute to the SOD activity.


Addressing Challenges of Patients With Chronic Pulmonary Disease Using Makerspace Environments.
Patients with chronic progressive pulmonary disease suffer from physiological and psychological consequences. These patients experience functional disability, depression and anxiety, and decreased quality of life. Their ability to perform activities of daily living can be severely impaired. Direct patient care nurses are well suited to assist these patients and their caregivers, identifying challenges through interactions and active listening and assisting in the identification of solutions. Even simple solutions to everyday issues can reduce the disease burden for this population. This article describes how direct patient care nurses can address the challenges of these patients through an innovative environment known as a makerspace.


Studies of the accuracy of measurements of serum high density lipoprotein cholesterol levels.
Titration of serum lipoproteins with three different precipitants--heparin-MnCl2 92 mmol.L-1, dextran sulfate-MgSO4, and phosphotungstate-MgCl2--revealed gross errors in the high density lipoprotein cholesterol (HDL-C) levels measured in some hyperlipidemic sera. Dilution studies of eight normal sera with the phosphotungstate method revealed that the most reliable estimate of the HDL-C level was the level measured in the least diluted aliquot that yielded a good precipitate. With a heparin-MnCl2 kit, serial dilution of a lipemic serum demonstrated a requirement for a blank correction. Establishing an accurate estimate of the HDL-C level sometimes requires knowledge of the titration curve of the lipoprotein precipitant being used, a blank correction, and data obtained from dilution studies (or studies with increased precipitant levels) on the serum in question.


A simple model for phase locking of biological oscillators.
A mathematical model is presented for phase locking of a biological oscillator to a sinusoidal stimulus. Analytical, numerical and topological considerations are used to discuss the patterns of phase locking as a function of amplitude of the sinusoidal stimulus and the relative frequencies of the osillator and the sinusoidal stimulus. The sorts of experimental data which are needed to make comparisons between theory and experiment are discussed.


Demographics, clinical characteristics, and prognostic factors of amyotrophic lateral sclerosis in Midwest.
The Midwest has the highest regional prevalence of self-reported amyotrophic lateral sclerosis (ALS) in the United States, but with limited epidemiological studies. We aimed to explore the characteristics of patients with ALS in the Midwest. This was a retrospective cohort study of participants with ALS deceased between January, 2010, and September, 2020, registered with the ALS Association Mid-America Chapter. Demographics and clinical variables included gender, race/ethnicity, military status, site of onset, interventions (gastrostomy, non-invasive ventilation, tracheostomy), and visits to ALS Association-registered clinics. Disease characteristics were compared to the National ALS Registry, and survival analysis was performed followed by sample augmentation with historical data to estimate survival with hypothetical censoring. The database included 1447 participants with a mean age at diagnosis of 65.7 ± 11.9 y (>60 y at diagnosis: 72%). The median survival from symptom onset was 28.0 mo (95% confidence limit: 26.3, 29.7); sample augmentation increased this to 41.0 mo (38.5, 43.5). Bulbar onset disease and older age at diagnosis were associated with shorter survival. Participants not followed in ALS-Association registered clinics were more frequently male, had familial onset and tracheostomy. Veterans (N = 298) were older at diagnosis but had similar survival after adjustment for age. Our cohort had an older age at onset and more frequent bulbar onset than the National ALS Registry, perhaps reflecting ascertainment biases in each registry. Prospective cohort studies with more clinical and functional data are needed to better characterize ALS in Midwest, veterans, and non-clinic populations, and to optimize care.


Live cell imaging of DNA and RNA with fluorescent signal amplification and background reduction techniques.
Illuminating DNA and RNA dynamics in live cell can elucidate their life cycle and related biochemical activities. Various protocols have been developed for labeling the regions of interest in DNA and RNA molecules with different types of fluorescent probes. For example, CRISPR-based techniques have been extensively used for imaging genomic loci. However, some DNA and RNA molecules can still be difficult to tag and observe dynamically, such as genomic loci in non-repetitive regions. In this review, we will discuss the toolbox of techniques and methodologies that have been developed for imaging DNA and RNA. We will also introduce optimized systems that provide enhanced signal intensity or low background fluorescence for those difficult-to-tag molecules. These strategies can provide new insights for researchers when designing and using techniques to visualize DNA or RNA molecules.


Noninvasive measurement of stiffness and density of bone for its diagnosis using ultrasound.
Because the acoustic and elastic properties of bone evaluated using ultrasound-based methods have proved so useful in the direct evaluation of bone characteristics, many workers have developed methods and systems based on thein vivo measurement of velocity, attenuation, or both, of ultrasound in bone. These include the acoustic emission (AE), apparent velocity of ultrasound (AVU), and speed of sound-broadband ultrasound attenuation (SOS-BUA) methods. Bone stiffness is accepted as an effective index in the diagnosis of such bone diseases as osteoporosis. The literature contains reports of the estimation of bone stiffness from velocity (speed of sound [SOS]) and attenuation (broadband ultrasound attenuation [BUA]). The physical explanation of the methods of evaluating stiffness from the obtained values of BUA and SOS is still not clear, however. Here we propose a new diagnostic method and system based on ultrasound measurement of the stiffness of bone. The proposed method determines stiffness from the velocity of the leaky surface skimming compressional waves (LSSCWs) obtained with the microdefocusing method and the acoustic impedance obtained with the reflectance method. Thus this method can evaluate stiffness without exposing the patient to X-rays; moreover, the physical basis of the calculation of stiffness from velocity and impedance is well understood. We applied this system to the human tibiain vivo: stiffness and density in a young volunteer were successfully evaluated at 24.9 GPa and 2.01×10(3) kg/m(3), respectively.


Maintenance of adult cardiac function requires the chromatin factor Asxl2.
During development and differentiation, cell type-specific chromatin configurations are set up to facilitate cell type-specific gene expression. Defects in the establishment or the maintenance of the correct chromatin configuration have been associated with diseases ranging from leukemia to muscular dystrophy. The heart expresses many chromatin factors, and we are only beginning to understand their roles in heart development and function. We have previously shown that the chromatin regulator Asxl2 is highly expressed in the murine heart both during development and adulthood. In the absence of Asxl2, there is a significant reduction in trimethylation of histone H3 lysine 27 (H3K27), a histone mark associated with lineage-specific silencing of developmental genes. Here we present evidence that Asxl2 is required for the long-term maintenance of ventricular function and for the maintenance of normal cardiac gene expression. Asxl2(-/-) hearts displayed progressive deterioration of ventricular function. By 10 months of age, there was ~37% reduction in fractional shortening in Asxl2(-/-) hearts compared to wild-type. Analysis of the expression of myofibril proteins suggests that Asxl2 is required for the repression of β-MHC. Asxl2(-/-) hearts did not exhibit hypertrophy, suggesting that the de-repression of β-MHC was not the result of hypertrophic response. Instead, Asxl2 and the histone methyltansferase Ezh2 co-localize to β-MHC promoter, suggesting that Asxl2 directly represses β-MHC. Interrogation of the CardioGenomics database revealed that ASXL2 is down-regulated in the hearts of patients with ischemic or idiopathic dilated cardiomyopathy. We propose that chromatin factors like Asxl2 function in the adult heart to regulate cell type- and stage-specific patterns of gene expression, and the disruption of such regulation may be involved in the etiology and/or development of certain forms of human heart disease.


Surgery for Type III-IV hiatal hernia: anatomical recurrence and global results after elective treatment of short oesophagus with open and minimally invasive surgery.
Type III-IV hiatal hernia (HH) is associated with a true short oesophagus in more than 50% of cases; dedicated treatment of this condition might be appropriate to reduce the recurrence rate after surgery. A case series of patients receiving surgery for Type III-IV hernia was examined for short oesophagus, and the results were analysed. From 1980 to 1994, 60 patients underwent an open surgical approach, and the position of the oesophago-gastric junction was visually localized; from 1995 to 2013, 48 patients underwent a minimally invasive approach, and the oesophago-gastric junction was objectively localized using a laparoscopic-endoscopic method. The patients underwent a timed clinical-instrumental follow-up that included symptoms assessment, barium swallow and endoscopy. The results were considered to be excellent in the absence of symptoms and oesophagitis; good, if symptoms occurred two to four times a month in the absence of oesophagitis; fair, if symptoms occurred two to four times a week in the presence of hyperaemia, oedema and/or microscopic oesophagitis; and poor, if symptoms occurred on a daily basis in the presence of any grade of endoscopic oesophagitis, HH of any size or type, or the need for antireflux medical therapy. The follow-up time was calculated from the time of surgery to the last complete follow-up. Among the open surgery patients, 78% underwent abdominal fundoplication, 10% the Belsey Mark IV procedure, 8% laparotomic Collis-Nissen fundoplication and 3% the Pearson operation. Among the minimally invasive surgery patients, 44% underwent a laparoscopic floppy Nissen procedure and 56% a left thoracoscopic Collis-laparoscopic Nissen procedure. The postoperative mortality and complication rates were 1.6% (1/60) and 15% for open surgery and 4.1% (2/48) and 12.5% for minimally invasive surgery. A total of 105 patients were followed up for a median period of 96 months. Five relapses occurred after open surgery (5/59, 8%) and two after minimally invasive surgery (2/46, 4%). Among the 105 patients, excellent, good, fair and poor outcomes were observed in 38%, 44%, 9% and 9%, respectively. These data suggested that the selective treatment of short oesophagus in association with a Type III-IV hernia reduced the anatomical recurrence rate and achieved satisfactory outcomes. NCT01606449.


High dietary cholesterol and ovariectomy in rats repress gene expression of key markers of VLDL and bile acid metabolism in liver.
The purpose of the study was to evaluate the effects of high dietary cholesterol in ovariectomized (Ovx) rats on several key markers of hepatic cholesterol and bile acid metabolism. Ovx and sham operated (Sham) rats were given either a standard diet (SD), a SD diet supplemented with 0.25% cholesterol (SD + Chol), or a high fat diet supplemented with 0.25% cholesterol (HF + Chol) for 5 weeks. Ovx was associated with higher (P < 0.05) liver total cholesterol (TC) under the SD and the SD + Chol diet, while liver triglyceride (TG) content was higher in Ovx than in Sham rats in all 3 diet conditions. Surprisingly, the SD + Chol diet was associated with lower (P < 0.001) plasma TC and TG levels in Ovx than in Sham rats, suggesting a decrease in VLDL secretion. Accordingly, several transcripts of key markers of VLDL synthesis including microsomal TG transfer protein (Mttp) and Apob-100 were decreased (P < 0.05) in Ovx compared to Sham rats under the three dietary conditions and even more so for Mttp and Apob-100 when rats were fed the SD + Chol diet. Transcripts of bile acid transporters including bile salt export pump (Bsep) and Na + -taurocholate cotransporting polypeptide (Ntcp) were decreased by the addition of cholesterol to the SD diet in both Ovx and Sham rats. These results indicate that a high cholesterol feeding and ovariectomy combine to reduce the gene expression of key markers of VLDL synthesis suggesting a reduction in excretion of cholesterol from the liver.


Dopamine (D1) receptor activation and nitrinergic agents influence somatostatin levels in rat retina.
Somatostatin (SRIF) influences the release of two important neuromodulators of retinal circuitry, dopamine (DA) and nitric oxide (NO). The aim of the present study was to examine whether DA and NO modulate SRIF release in rat retina, and the mechanisms involved in their actions. Retinas of adult female Sprague--Dawley rats (250--300 g) were mechanically detached from the eyecup and ex vivo experiments were performed. Retinal explants were incubated in the presence of dopaminergic [DA (10 microM, 100 microM and 200 microM), apomorphine (nonselective D1/D2 agonist, 0.50 mM, 1.0 microM and 10 microM), A68930 (D1 selective agonist, 0.50 microM, 1.0 microM and 10 microM), quinpirole (D2 selective agonist, 0.50 microM, 1.0 microM and 10 microM), SCH 23390 (D1 selective antagonist, 250 nM and 500 nM) and sulpiride (D2 selective antagonist, 100 microM and 200 microM)], and nitrinergic agents [arginine (62.5 microM--5mM), SIN-1 (50 microM, 100 microM and 500 microM) and 8-Br-cGMP (50 microM, 250 microM and 500 microM)]. SRIF levels were quantified using radioimmunoassay (RIA). Dopamine had no effect on SRIF levels. Apomorphine produced a concentration dependent decrease and increase in SRIF levels, suggestive of pre- and postsynaptic effects. A68930 (10 microM) and SCH 23390 (250 nM and 500 nM) mimicked and reversed apomorphine's postsynaptic actions, respectively. Quinpirole had no effect, but blockade of D2 autoreceptors by sulpiride (200 microM) afforded an increase in SRIF levels. Arginine and SIN-1 increased, and 8-Br-cGMP attenuated SRIF levels. These results show that dopamine D1 receptors, and NO/peroxynitrite agents modulate SRIF release in the retina suggesting that the triad SRIF--DA--NO have reciprocal interactions via which they regulate retinal circuitry and vision transduction.


Association between depression, patient scar assessment and burn-specific health in hospitalized burn patients.
Depression is one of the most common psychological problems arising after a burn, but its relationship with patient scar assessment and burn-specific health are poorly understood. The aim of this study was to identify the incidence of in-hospital symptoms of depression, compare level of patient scar assessment, and burn-specific health by depression cutoff point, and identify the relationship between depression and these variables. In a cross-sectional descriptive study, 113 burn patients from two inpatient burn centers were divided into two groups based on the cutoff point of the Korean Center for Epidemiologic Studies Depression Scale (Korean CES-D): ≥25 or <25. Patient Scar Assessment Scale and Korean Burn-Specific Health Scale-Brief (BSHS-B-K) were used to identify associations with depression. Incidence of severe, definite depression as assessed by a score of 25 or above on the Korean CES-D was approximately 50% on an average at 60.9 days after injury. Burn patients with the Korean CES-D≥25 had significantly higher total mean patient scar assessment scores (43.34±11.49 vs. 36.84±9.56, t=3.265, p=.001), and lower burn-specific health subscale scores compared to patients with Korean CES-D<25. Depression was positively correlated with all subscales of the Patient Scar Assessment, ranging from r=.196 to .335 except scar color. Depression was significantly correlated with all subscales of the BSHS-B-K, range from r=-.320 to -.725. Results indicate that incidence of symptoms of depression is relatively high, and depressed burn patients report worse burn scar or sensation and lower levels of burn-specific health. Early, timely recognition and management of depression in these patients are warranted.


Role of Electronystagmography in Diagnosis of Secondary BPPV in Elderly Patients with Vertigo: A Retrospective Study.
Elderly population is frequently affected by vertigo which affects their mobility and makes them vulnerable to fall and other morbidities. Often these patient visit neurologist and are often subjected to CT scan, MRI brain etc. to rule out a central cause of vertigo; whereas majority of these patients suffer from vestibular cause of vertigo. A schematic approach by detailed history, simple tests for vestibular functions like Dix Hallpike, supine roll and head impulse test give important clue to diagnosis. Often the diagnosis is benign paroxysmal positional vertigo (BPPV) which is treated by repositioning maneuver. There are often other vestibular causes which may be diagnosed by Electronystagmography (ENG), electrocochleography and other tests. This study was undertaken to study occurrence of secondary BPPV utilizing various parameters of ENG. The study group comprised of 131 patients from the neuro-otology proforma data base at ENT centre and vertigo clinic from January 2015 to December 2017. Inclusion criterion was male and female aged 51 years and above presenting with dizziness, imbalance, rotational vertigo, unsteadiness as the chief complaint. Exclusion criterion was BPPV relieved after Epley's maneuver, Otitis externa, acute Otitis media, Suppurative Otitis media, pre existing neurological condition and history of ear surgery. Neuro-otology Data obtained and the ENG findings were tabulated in the master chart and the observations interpreted and transferred to Claussen's butterfly chart. The study group comprised of 58 male (44.27%) and 73 female (55.73%) with a male female ratio of 1:1.25. ENG exhibited 36 patients (27.49) to have recurrent BPPV, 53 (40.45%) were found to have unilateral/bilateral canal paresis. Meniere's disease was diagnosed in 39 (29.77%) patients and brain stem pathology identified in 3 (2.29%) cases.


Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization.
This study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization. The physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown. Global and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization. Severely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone. CFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.


Auxiliary diagnosis of lymph node metastasis in early gastric cancer using quantitative evaluation of sentinel node radioactivity.
Sentinel node (SN) mapping using dye and radioisotope (RI) tracer has been reported to be feasible in cases of early gastric cancer. Because accurate diagnosis of micrometastasis is sometimes difficult in the limited time available during surgery, a faster and simpler method of improving the intraoperative diagnostic precision of lymph node metastasis is needed. The amount of tracer deposited in an SN can be determined from its radioactivity; however, the significance of the RI count has not been fully discussed. We investigated the clinical impact of the RI count when used as an adjunct to conventional lymph node dissection when diagnosing lymphatic metastasis in cases of early gastric cancer. From 2008 to 2009, patients with clinically diagnosed T1N0M0 gastric cancers who underwent gastrectomy and SN mapping were enrolled. SNs were examined by intraoperative and postoperative pathology. The RI count was measured for each SN with a handheld gamma probe; the correlation between nodal metastasis and the RI count was assessed. A total of 308 SNs were harvested from 72 patients. Patients with SN metastasis had significantly higher total RI counts than those without SN metastasis (p = 0.007). Among cases with SN metastasis, RI counts were also significantly elevated in metastasis-positive nodes, stations, and basins. In these cases, the most of SNs having the highest RI count in each case had metastasis including isolated tumor cells. In early gastric cancer patients, a high RI count from an SN was correlated with lymph node metastasis. Therefore, RI counting may aid efficient pathological diagnosis and focused lymph node dissection.


Oestrogen treatment of constitutionally tall girls with 0.1 mg/day ethinyl oestradiol.
For the treatment of tall stature in girls, oestrogens are usually given in high doses. In this study, growth data of 35 constitutionally tall girls treated with only 0.1 mg/day ethinyl oestradiol (EE) are reported (Group 1). The data were compared with those of 23 untreated girls with comparable bone ages and growth potential (Group 2), and with those of 5 girls treated with 0.3 mg/day EE (Group 3). All groups were followed until cessation of growth. In group 1, the median bone age at the onset of treatment was 12.50 years (Greulich-Pyle, range 10.50-13.75), and the median height prediction was calculated to be 184.4 cm (Bayley-Pinneau, range 179.5-191.5). Following oestrogen treatment of 21 months duration (range 10-37) the median adult height was reduced by 4.3 cm (range 0.0-9.0), or 3.9 cm if corrected for the error of prediction in the control group. The effect was greater in those girls with bone ages below 12.5 years at the onset of treatment (6.7 cm/corrected value 7.4 cm) than in the older girls (4.2 cm/3.6 cm). In Group 2 (controls) the median final adult height was over-estimated by 0.4 cm (range-4.9 to 4.9), but was under-estimated by 0.7 cm in those girls with bone ages below 12.5 years. In girls of comparable bone age similar reductions were obtained whether 0.3 mg/day EE (Group 3) or 0.1 mg/day was given (4.4 vs. 4.2 cm). A comparison of these results with published data indicates that higher EE doses (0.3-0.5 mg/day) have only little, if any, greater effect on the growth of girls than the dosage of 0.1 mg/day EE used in this study.


What evidence is available on end-of-life (EOL) care and Latino elders? A literature review.
Low-income and minority persons, such as Latinos, encounter substantial barriers in accessing effective end-of-life (EOL) care. This study intends to review current evidence on how to deliver EOL care to Latino elders. Literature search in PubMed and Ovid Web sites of articles indexed in Medline (1948-2011), Cochrane (2005-2011), Embase, and PsychInfo (1967-2011) databases. Articles were included if they contained (1) study participants' race/ethnicity, (2) adults or population older than 60 years, and (3) information related to EOL care. A total of 64 abstracts were reviewed, and 38 articles met the inclusion criteria. After reviewing the quality of evidence, 4 themes were identified and summarized: EOL preferences, hospice, Latino culture, and caregiving. Latino elders have traditional acculturation practices, face EOL decisions with family support, and, if educated, are receptive toward hospice and caregiver support.


Chemometric approach to evaluate the parameters affecting electrospray: application of a statistical design of experiments for the study of arginine ionization.
The effects of different experimental parameters on arginine electrospray ionization have been investigated with response surface modelling design. This chemometric technique allows a study of the effects of selected experimental variables and their interactions on the response of an experiment by performing a limited number of analyses. Six variables were studied: methanol content in the liquid phase, formic acid concentration, electrospray voltage, orifice voltage, mobile phase flow rate, and sheath gas flow rate. Signal abundance and signal-to-noise ratio of the protonated molecule and the protonated dimer were measured from the electrospray mass spectra and these four responses were tested by the design. The factor that exhibits the greatest influence on MH+ abundance is shown to be the liquid flow rate whereas the formation of protonated dimer is mainly controlled by the percentage of methanol in the mobile phase. A strong synergic effect of methanol content and formic acid concentration in the liquid has also been demonstrated in the study of noise level. Moreover, the capabilities of the multicriteria optimization method have been demonstrated through a successful prediction of a set of optimal experimental conditions.


Identification of proteins specifically interacting with YB-1 mRNA 3' UTR and the effect of hnRNP Q on YB-1 mRNA translation.
In this study, proteins specifically interacting with the 3' untranslated region (UTR) of mRNA of the multifunctional Y-box-binding protein 1 (YB-1) were identified. One of these, hnRNP Q, was shown to specifically interact with the regulatory element (RE) in YB-1 mRNA 3' UTR and to inhibit translation of this mRNA. Its binding to the RE was accompanied by displacement from this element of the poly(A)-binding protein (PABP), a positive regulator of YB-1 mRNA translation, and by enhanced binding of the negative YB-1 mRNA translation regulator - YB-1 itself.


Retrospective single center cohort study: effect of intensive home hemodialysis on right ventricular systolic pressure and clinical outcomes.
Increased right ventricular systolic pressure (RVSP), a surrogate marker for pulmonary hypertension, is common in patients with end-stage kidney disease. Limited data suggest improvement of RVSP with intensive dialysis, but it is unknown whether these improvements translate to better clinical outcomes. We conducted a retrospective single center cohort study at the Toronto General Hospital. All patients who performed intensive home hemodialysis (IHHD) for at least a year between 1999 and 2017, and who had a baseline as well as a follow-up echocardiogram more than a year after IHHD, were included. Patients were categorized into two groups based on the RVSP at follow-up: elevated (≥ 35 mmHg) and normal RVSP. Multivariate and cox regression analyses were done to identify risk factors for elevated RVSP at follow-up and reaching the composite endpoint (death, cardiovascular hospitalization, treatment failure), respectively. One hundred eight patients were included in the study. At baseline, 63% (68/108) of patients had normal RVSP and 37% (40/108) having elevated RVSP. After a follow-up of 4 years, 70% (76/108) patient had normal RVSP while 30% (32/108) had elevated RVSP. 8 (10%) out of the 76 patients with normal RVSP and 15 (47%) out of the 32 patients with elevated RVSP reached the composite endpoint of death, cardiovascular hospitalization or technique failure. In a multivariate analysis, age, diabetes and smoking were not associated with elevated RVSP at follow-up. Elevated RVSP at baseline was not associated with a higher likelihood in reaching the composite endpoint or mortality. Mean RVSP did not increase in patients on IHHD over time, and maintenance of normal RVSP was associated with better clinical outcomes.


Hyperosmolar coma as etiological factor in the CNS radiation syndrome of rats.
Supralethal dose of whole-body or trunk but not head-irradiation in rats induced hyperosmolar coma accompanied by hypernatremia and hyperkalemia. This clinical entity has presented the symptoms of the CNS radiation syndrome with a characteristic short survival time.


Palliative care and end-of-life issues.
As stated, the goal of palliative care is the achievement of the best quality of life for patients and their families. It incorporates many aspects of care: providing physical comfort, psychosocial and spiritual support, and providing various services in order to achieve this goal. The skills described should be a priority in the practice of all types of medicine because the goal of palliative care is among the central tenets of the medical profession.


Ingestion of microplastic by ontogenetic phases of Stellifer brasiliensis (Perciformes, Sciaenidae) from the surf zone of tropical beaches.
Microplastics (<5 mm) are present in marine ecosystems worldwide where they can be ingested by a wide range of organisms from different trophic levels. In this study we analyzed the gastrointestinal tract of 443 specimens of Stellifer brasiliensis (124 juveniles, 254 subadults, and 65 adults) sampled in tropical beaches adjacent to the Paraíba River estuary. We found 1-3 microplastics in 42 fishes (9.48%), averaging 1.31 ± 0.52 microplastics per fish. The number of ingested microplastics by the different ontogenetic stages was statistically similar, but the adults had a higher ingestion frequency (13.8%). Among subadults, the condition factor of fishes that ingested microplastics was significantly smaller (p < 0.05) than those that had not ingested them. The ingestion of microplastics by the different ontogenetic stages of S. brasiliensis reflects the availability of this pollutant in the studied environment and highlights the vulnerability of fishes and other organisms through food webs.


Critical incidents connected to nurses' leadership in Intensive Care Units.
The goal of this study is to analyze nurses' leadership in intensive care units at hospitals in the state of São Paulo, Brazil, in the face of positive and negative critical incidents. Exploratory, descriptive study, conducted with 24 nurses by using the Critical Incident Technique as a methodological benchmark. Results were grouped into 61 critical incidents distributed into categories. Researchers came to the conclusion that leadership-related situations interfere with IC nurses' behaviors. Among these situations they found: difficulty in the communication process; conflicts in the daily exercise of nurses' activities; people management; and the setting of high quality care targets. Researchers identified a mixed leadership model, leading them to the conclusion that nurses' knowledge and practice of contemporary leadership theories/styles are crucial because they facilitate the communication process, focusing on behavioral aspects and beliefs, in addition to valuing flexibility. This positively impacts the organization's results. Analisar a liderança do enfermeiro em Centros de Terapia Intensiva de hospitais localizados no interior do estado de São Paulo, diante de incidentes críticos positivos e negativos. Estudo exploratório, descritivo, realizado com 24 enfermeiros, que utilizou a Técnica do Incidente Crítico como referencial metodológico. Os resultados foram agrupados em 61 incidentes críticos distribuídos em categorias. Identificou-se que situações relacionadas à liderança interferem no comportamento do enfermeiro de Terapia Intensiva, dentre elas: dificuldade no processo de comunicação, conflitos existentes no dia a dia do exercício profissional, gerenciamento de pessoas e estabelecimento de metas para o alcance da assistência qualificada. Encontrou-se um modelo misto de liderança, o que permite concluir que o conhecimento e a prática dos enfermeiros acerca de teorias/estilos contemporâneos de liderança tornam-se fundamentais, pois facilitam o processo de comunicação, focando nos aspectos comportamentais e crenças, e valorizam a flexibilidade, impactando positivamente os resultados da organização.


Lupus anti-coagulant hypoprothrombinemia syndrome across different ages: a case report and review of the literature.
Lupus anti-coagulant hypoprothrombinemia syndrome (LAHPS) is a rare condition that can be difficult to treat. It increases the risk of thrombosis and bleeding due to the presence of lupus anti-coagulant and factor II deficiency, respectively. There are a limited number of cases described in the literature. Herein we describe a case of LAHPS with bleeding symptoms as a first clinical manifestation of systemic lupus erythematosus (SLE) in an 8-year-old female. She has had multiple recurrences of her bleeding symptoms, requiring treatment with steroids, cyclophosphamide, mycophenolate mofetil, and rituximab. Her course was later complicated by development of arthritis and lupus nephritis. Her complicated course provides a new perspective on the clinical course and treatment of LAHPS. We also present a comprehensive literature review which demonstrates the difficulty in treating patients with LAHPS with underlying SLE and the variability of the clinical course and management of LAHPS depending on the age at presentation.


Diverse Genome Topologies Characterize Dosage Compensation across Species.
Dosage compensation is the process by which transcript levels of the X chromosome are equalized with those of autosomes. Although diverse mechanisms of dosage compensation have evolved across species, these mechanisms all involve distinguishing the X chromosome from autosomes. Because one chromosome is singled out from other chromosomes for precise regulation, dosage compensation serves as an important model for understanding how specific cis-elements are identified within the highly compacted 3D genome to co-regulate thousands of genes. Recently, multiple genomic approaches have provided key insights into the mechanisms of dosage compensation, extending what we have learned from classical genetic studies. In the future, newer genomic approaches that require little starting material show great promise to provide an understanding of the heterogeneity of dosage compensation between cells and how it functions in nonmodel organisms.


A comprehensive review on soft rot disease management in ginger (Zingiber officinale) for enhancing its pharmaceutical and industrial values.
Zingiber officinale L. Roscoe is a significant herb that possesses many medicinal and ethnomedicinal properties. Due to the presence of various bioactive compounds, it has immense healing capacity. However, ginger as a crop is susceptible to several fungal pathogens. Among all the fungal pathogens, Pythium and Fusarium spp. are of most concern, causing soft rot (rhizome rot) disease, majorly responsible for the downfall in its production by 50-90%. Pesticides and fungicides spray is generally recommended for the control of soft rot. Ample use of chemicals not only affects the quality of the crop but also disturbs ecological integrity. Therefore, biological methods of disease management involving suitable microbial agents such as Trichoderma harzianum, Pseudomonas spp., Bacillus subtilis, Streptomyces spp. and plant extracts are attracting and gaining importance as a part of integrated approaches (IPM) to manage the soft rot and sustainably enhance the production and improve the medicinal and pharmaceutical values of ginger. The present review is aimed to discuss various means of controlling soft rot disease by physical, chemical, biological, and nanotechnology-based methods. Moreover, various bioactive constituents of ginger and their pharmaceutical importance have been also discussed.


Microglia mediated neuroinflammation in autism spectrum disorder.
Although the precise pathophysiologies underlying autism spectrum disorder (ASD) has not yet been fully clarified, growing evidence supports the involvement of neuroinflammation in the pathogenesis of this disorder, with microglia being particular relevance in the pathophysiologic processes. The present review aimed to systematically characterize existing literature regarding the role of microglia mediated neuroinflammation in the etiology of ASD. A systematic search was conducted for records indexed within Pubmed, EMBASE, or Web of Science to identify potentially eligible publications. Study selection and data extraction were performed by two authors, and the discrepancies in each step were settled through discussions. A total of 14 studies comprising 1007 subjects met the eligibility criteria for this review, including 8 immunohistochemistry (IHC) studies, 5 genetic analysis studies, and 1 positron emission tomography (PET) studies. Although small in quantity, the included studies collectively pointed to a role of microglia mediated neuroinflammation in the pathogenesis of ASD. Findings generated from this review consistently supported the involvement of neuroinflammation in the development of ASD, confirmed by the activation of microglia in different brain regions, involving increased cell number or cell density, morphological alterations, and phenotypic shifts.


Effect of inoculum on the anaerobic digestion of food waste accounting for the concentration of trace elements.
The production of renewable energy in the form of methane from the anaerobic digestion (AD) of food waste (FW) varies depending on factors such as the quantity and quality of the inoculum. This research evaluated the influence of trace elements (Ca, K, Fe, Zn, Al, Mg, Co, Ni, and Mo) present in inoculum from different sources (wastewater treatment plants (WWTPs): 2 agro-industrial WWTPs and 1 municipal WWTP) on the AD of FW. This study found that the source of the inoculum determines the content of macronutrients and trace elements, which can alter the requirements of the AD process and therefore affect methane production. The inoculum obtained from municipal WWTPs contain potentially inhibitory concentrations of Zn and Al that negatively affect methane production (<70 mL CH4·gVS-1), the hydrolysis constant (<0.19 d-1), and the lag-phase (>7 days). It was also found that high concentrations of trace elements such as Ni (35.2 mg kg-1) and Mo (15.4 mg kg-1) in the inoculum increase methane production (140.7 mL CH4·gVS-1) and hydrolysis constant (>0.18d-1) in addition to presenting short lag-phase (<1 day) in the AD of food waste.


Mid-infrared spectrometry of milk for dairy metabolomics: a comparison of two sampling techniques and effect of homogenization.
Milk production is a dominant factor in the metabolism of dairy cows involving a very intensive interaction with the blood circulation. As a result, the extracted milk contains valuable information on the metabolic status of the cow. On-line measurement of milk components during milking two or more times a day would promote early detection of systemic and local alterations, thus providing a great input for strategic and management decisions. The objective of this study was to investigate the potential of mid-infrared (mid-IR) spectroscopy to measure the milk composition using two different measurement modes: micro attenuated total reflection (μATR) and high throughput transmission (HTT). Partial least squares (PLS) regression was used for prediction of fat, crude protein, lactose and urea after preprocessing IR data and selecting the most informative wavenumber variables. The prediction accuracies were determined separately for raw and homogenized copies of a wide range of milk samples in order to estimate the possibility for on-line analysis of the milk. In case of fat content both measurement modes resulted in an excellent prediction for homogenized samples (R(2)>0.92) but in poor results for raw samples (R(2)<0.70). Homogenization was however not mandatory to achieve good predictions for crude protein and lactose with both μATR and HTT, and urea with μATR spectroscopy. Excellent results were obtained for prediction of crude protein, lactose and urea content (R(2)>0.99, 0.98 and 0.86 respectively) in raw and homogenized milk using μATR IR spectroscopy. These results were significantly better than those obtained by HTT IR spectroscopy. However, the prediction performance of HTT was still good for crude protein and lactose content (R(2)>0.86 and 0.78 respectively) in raw and homogenized samples. However, the detection of urea in milk with HTT spectroscopy was significantly better (R(2)=0.69 versus 0.16) after homogenization of the milk samples. Based on these observations it can be concluded that μATR approach is most suitable for rapid at line or even on-line milk composition measurement, although homogenization is crucial to achieve good prediction of the fat content.


(E)-1-{4-[Bis(4-bromo-phen-yl)meth-yl]piperazin-1-yl}-3-(4-eth-oxy-3-meth-oxy-phen-yl)prop-2-en-1-one.
In the title mol-ecule, C(29)H(30)Br(2)N(2)O(3), the piperazine ring has a chair conformation and the C=C double bond has an E conformation. The dihedral angle between the bromo-benzene rings is 79.1 (3)°. In the crystal, mol-ecules are linked through C-H⋯O and C-H⋯Br hydrogen bonds.


Molecular spectroscopic and molecular simulation studies on the interaction of oral contraceptive drug Ormeloxifene with CT-DNA.
The interaction between oral contraceptive drug Ormeloxifene (ORM) and calf thymus DNA (CT-DNA) was studied using UV-Vis, fluorescence, circular dichroism (CD) and 1H NMR spectral techniques under physiological buffer (pH 7.4). Competitive binding assays with ethidium bromide (EB) and Hoechst 33258, viscosity measurements, KI quenching studies, molecular docking and metadynamics simulation studies were also substantiated the spectroscopic results. ORM is found to binds in the minor groove of CT-DNA as evidenced by: (1) non-displacement of EB from EB/CT-DNA complex; (2) appreciable displacement of Hoechst 33258 from its CT-DNA complex; (3) slight alteration in the CD signal; (4) small shifts (Δδ < 0.033 ppm) without broadening in 1H NMR signals and (5) the nearly equal extent of quenching of fluorescence of ORM by KI in the absence and presence of CT-DNA. Negative values of both enthalpy and entropy changes pointed out that the interaction between ORM and CT-DNA is governed mainly by H-bonding and van der Waals forces. Negative free energy change suggested a spontaneous interaction between ORM and CT-DNA. The free energy landscape of the binding process was computed using metadynamics simulation. The simulation study results disclosed that ORM binds to the minor groove of DNA through H-bonding and π-π stacking interactions. The results of molecular docking and simulation studies corroborate the available experimental data.


Epidemiology of suicide and suicide attempts in Belgium: results from the sentinel network of general practitioners.
To estimate the evolution of incidence of (attempted) suicide between 1993 and 2001 in Belgium and to examine trends in methods, first caretaker and aspects of seasonality. In 1993-1995 and 2000-2001, the national sentinel network of general practitioners registered, for each case of (attempted) suicide, age, sex, date, place of the event, first caretaker, method, and survival. Between 1993-1995 and 2000-2001, the incidence of suicide increased among men from 29/ 100,000 to 35/ 100,000, and decreased among women from 14/ 100,000 to 11/ 100,000. The incidence of attempted suicide increased among men (from 67/ 100,000 to 71/ 100,000) and women (from 131/ 100,000 to 141/ 100,000). None of the above mentioned changes were statistically significant however. The use of violent methods as opposed to non-violent methods remained unchanged in women (OR: 0.95 [0.63-1.41]). No statistically significant trends were observed in the incidence of suicide, the fraction of cases with fatal outcome and the use of violent methods.


Platelet kinetics in Crohn's disease.
The pathogenesis of thrombocytosis in Crohn's disease was analized in ten non-treated patients using the 51Cr labelling method. The data obtained were compared to those taken from a control group. Besides platelet survival time, platelet turnover, surface radioactivity, platelet adhesiveness and morphological aspects of bone marrow were investigated. Platelet survival time in patients with Crohn's disease proved to be significantly shortened (p less than 0.001), whereas platelet turnover appeared augmented. No additional radioactivity is encountered from the organs scanned. The relative platelet adhesiveness is diminished while thrombocytopoesis in bone marrow is augmented.


Evaluation of physiologic and abnormal glucose uptake in palatine tonsils: differential diagnostics with sequential dual-time-point 2-deoxy-2-[18F]FDG PET/CT.
The aim of this article was to evaluate the usefulness of sequential dual-time-point 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (DTP [18F]FDG PET/CT) in distinguishing physiologic, inflammatory and malignant palatine tonsils as difficult to differentiate in the oncological practice. A total of 90 patients before the treatment underwent sequential DTP [18F]FDG PET/CT examinations. We analyzed 104 structures in 90 patients: 31 physiologic tonsils, 28 histopathologically confirmed inflammatory tonsils of non-specified origin, 31 histopathologically confirmed palatine tonsils cancer and 14 non-malignant contralateral tonsils in patients with histopathologically confirmed unilateral palatine tonsil malignancy. Patients underwent sequential [18F]FDG PET/CT examinations at 60 and 90 minutes post-injection of the [18F]FDG. We analyzed the SUVmax and SUVmean values at 60 and 90 minutes post-injection changes over time and the Retention Index (RI-SUVmax). To find the predictive SUV value and the RI cut-off between physiology, inflammatory and malignancy, we used the ROC analysis. The average SUVmax values at 60 and 90minutes post-injection within physiologic palatine tonsils were 1.36±0.26 and 1.31±0.26, respectively, P>0.05. The average SUVmax values at 60 and 90 minutes post-injection within inflammatory and malignant tonsils were 3.74±1.45, 3.80±1.47 (P>0.05) and 5.19±2.19, 5.81±2.50 (P<0.05), respectively. The RI-SUVmax fluctuation over time were 5±28% within physiologic, -4±11% within contralateral non-malignant tonsils in patients with one tonsil involved, 2±11% within inflammatory and 13±13% within malignant tonsils. The sequential dual-time-point [18F]FDG PET/CT examinations may increase the sensitivity and the specificity of the PET/CT method in differential palatine tonsils diagnosis.


Evaluation of radiological risks due to natural radioactivity around Lynas Advanced Material Plant environment, Kuantan, Pahang, Malaysia.
Understanding the public awareness concerning the Lynas Advanced Material Plant (LAMP), an Australian rare earths processing plant located in Malaysia, a radiological study in soil and water samples collected at random surrounding the LAMP environment was undertaken using HPGe gamma-ray spectrometry. The mean soil activities for (226)Ra, (232)Th, and (40)K were found to be 6.56 ± 0.20, 10.62 ± 0.42, and 41.02 ± 0.67 Bq/kg, respectively, while for water samples were 0.33 ± 0.05, 0.18 ± 0.04, and 4.72 ± 0.29 Bq/l, respectively. The studied areas show typical local level of radioactivity from natural background radiation. The mean gamma absorbed dose rate in soils at 1 m above the ground was found to be 11.16 nGy/h. Assuming a 20 % outdoor occupancy factor, the corresponding annual effective dose showed a mean value of 0.014 mSv year(-1), significantly lower than the worldwide average value of 0.07 mSv year(-1) for the annual outdoor effective dose as reported by UNSCEAR (2000). Some other representative radiation indices such as activity utilization index (AUI), H ex, H in, excess lifetime cancer risk (ELCR), and annual gonadal dose equivalent (AGDE) were derived and also compared with the world average values. Statistical analysis performed on the obtained data showed a strong positive correlation between the radiological variables and (226)Ra and (232)Th.


Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study.
Clinical data demonstrating efficacy for nutraceutical compounds marketed for the symptom relief of osteoarthritis (OA) have been largely contentious. Furthermore, no association has been linked between clinical trial inconsistencies and gastrointestinal (GI) dysfunction. The aim of this study was to primarily investigate the efficacy of a high-dose New Zealand green-lipped mussel (GLM) extract in patients diagnosed with OA of the knee and concurrently assess GLM impact on GI function. An open label, single group allocation study was conducted, that administered 3,000 mg/day of GLM extract over 8 weeks to 21 subjects diagnosed with knee OA. Outcome measures were scored using the WOMAC, the Lequesne algofunctional index, and the Gastrointestinal Symptom Rating Scale (GSRS) tools. An intention-to-treat analysis was employed and subject data collected at T₀, T₄ and T₈ weeks. Paired t tests showed significant improvement for the Lequesne, WOMAC (p < 0.001) and GSRS (p = 0.005) scores. A repeated measures ANOVA analysis showed significant improvement in scores for the Lequesne (F = 20.317, p < 0.001), WOMAC (F = 28.383, p < 0.001) and the GSRS (F = 9.221, p = 0.002). Green-lipped mussel significantly improved knee joint pain, stiffness and mobility. We report for the first time that the administration of GLM extract also significantly improved GI symptoms by 49% in OA patients. Given that GI dysfunction is linked to analgesic medication use, we further conclude that the therapeutic efficacy of the GLM extract used was possibly correlated to its effects on GI function by improving GSRS scores from baseline. Results from this trial highlight the requisite for further clinical investigations of gastrointestinal tract function in OA patients.


Larvicidal and repellent activity of medicinal plant extracts from Eastern Ghats of South India against malaria and filariasis vectors.
To evaluate the larvicidal and repellent activities of ethyl acetate and methanol extracts of Acacia concinna (A. concinna), Cassia siamea (C. siamea), Coriandrum sativum (C. sativum),Cuminum cyminum (C. cyminum), Lantana camara (L. camara), Nelumbo nucifera (N. nucifera) Phyllanthus amarus (P. amarus), Piper nigrum (P. nigrum) and Trachyspermum ammi (T. ammi) against Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus). The larvicidal activity of medicinal plant extracts were tested against early fourth-instar larvae of malaria and filariasis vectors. The mortality was observed 24 h and 48 h after treatment, data were subjected to probit analysis to determine the lethal concentrations (LC(50) and LC(90)) to kill 50 and 90 per cent of the treated larvae of the tested species. The repellent efficacy was determined against two mosquito species at five concentrations (31.25, 62.50, 125.00, 250.00, and 500.00 ppm) under the laboratory conditions. All plant extracts showed moderate effects after 24 h and 48 h of exposure; however, the highest activity was observed after 24 h in the leaf methanol extract of N. nucifera, seed ethyl acetate and methanol extract of P. nigrum against the larvae of An. stephensi (LC(50) = 34.76, 24.54 and 30.20 ppm) and against Cx. quinquefasciatus (LC(50) = 37.49, 43.94 and 57.39 ppm), respectively. The toxic effect of leaf methanol extract of C. siamea, seed methanol extract of C. cyminum, leaf ethyl acetate extract of N. nucifera, leaf ethyl acetate and methanol extract of P. amarus and seed methanol extract of T. ammi were showed 100% mortality against An. stephensi and Cx. quinquefasciatus after 48 h exposer. The maximum repellent activity was observed at 500 ppm in methanol extracts of N. nucifera, ethyl acetate and methanol extract of P. nigrum and methanol extract of T. ammi and the mean complete protection time ranged from 30 to 150 min with the different extracts tested. These results suggest that the leaf and seed extracts of C. siamea, N. nucifera, P. amarus, P. nigrum and T. ammi have the potential to be used as an ideal ecofriendly approach for the control of the An. stephensi and Cx. quinquefasciatus.


Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study.
To evaluate the efficacy of canakinumab, a high-affinity human monoclonal anti-interleukin-1β antibody, in inducing complete or almost complete responses in patients with active tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Twenty patients (aged 7-78 years) with active recurrent or chronic TRAPS were treated with canakinumab 150 mg every 4 weeks for 4 months (2 mg/kg for those ≤40 kg) in this open-label, proof-of-concept, phase II study. Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months. The primary efficacy variable was the proportion of patients achieving complete or almost complete response at day 15, defined as clinical remission (Physician's Global Assessment score ≤1) and full or partial serological remission. Nineteen patients (19/20, 95%; 95% CI 75.1% to 99.9%) achieved the primary efficacy variable. Responses to canakinumab occurred rapidly; median time to clinical remission 4 days (95% CI 3 to 8 days). All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days). On reintroduction of canakinumab, clinical and serological responses were similar to those seen during the first phase, and were sustained throughout treatment. Canakinumab was well tolerated and clinical responses were accompanied by rapid and sustained improvement in health-related quality of life. Weight normalised pharmacokinetics of canakinumab, although limited, appeared to be consistent with historical canakinumab data. Canakinumab induces rapid disease control in patients with active TRAPS, and clinical benefits are sustained during long-term treatment. NCT01242813; Results.


Epididymal sperm reserve in Buffalo-bulls (Bubalus bubalis).
Epididymal sperm reserve was determined in 6 sexually mature fertile buffalo-bulls having normal process of spermatogenesis. The relative distribution of spermatozoa in the caput, corpus and cauda epididymidis averaged 5.42, 0.75 and 11.45 billion respectively. Total epididymal sperm reserve per bull averaged 36.2 billion. In terms of percentage the caput, corpus and cauda epididymidis contained 30.76, 4.25 and 64.99 per cent sperm respectively.


Antimicrobial effects of mesenchymal stem cells primed by modified LPS on bacterial clearance in sepsis.
Mesenchymal stem cells (MSCs)-based regenerative therapy is now considered as an alternative approach to revive infectious diseases, including sepsis. Nevertheless, the efficiency of MSC application is limited by the poor survival rate of engrafted MSCs. Hence, preconditioning was established as a strategy to increase the cells' efficiency. MSCs were preconditioned with 1 μg/ml of three different lipopolysaccharides (LPSs) of Pseudomonas (Pse-LPS), Acinetobacter (Ac-LPS), and Acinetobacter inactivated lipid A by PagL (Ac-LPS-PagL). Then, preconditioned MSCs were exposed to oxidative stress and serum deprivation followed by evaluation of the antibacterial activity, survival, and apoptosis of MSCs. Then, the murine sepsis model treated with 100 μl phosphate-buffered saline (control group, sepsis group), 100 μl of 1 × 10 6 wild MSCs (MSC group), and three remained groups received 100 μl of 1 × 10 6 LPS-preconditioned MSCs (Pse-LPS-MSCs group: LPS purified from Pseudomonas, or Ac-LPS-MSCs group: LPS purified from Acinetobacter, and Ac-PagL-LPS-MSCs group: detoxified LPS Pagl). After 4 days, LPS-preconditioned MSC transplantation modulated the immune response and reduced inflammation in septic mice. Apoptosis of Pse-LPS/Ac-LPS-preconditioned-MSCs was obviously reduced in vitro, and the survival rate of engrafted mice was evidently elevated in Pse-LPS-MSCs and Ac-LPS-MSCs groups compared with other three groups. LPS preconditioning provides an innovative strategy for evolving functional and biological properties of MSCs and ameliorates the survival rate of the mouse model of sepsis after MSC transplantation, protects cells from apoptosis and organ damages, and evaluates therapeutic properties, including immunemodulatory.


Alterations of purine and pyrimidine nucleotide contents in rat corticoencephalic cell cultures following metabolic damage and treatment with openers and blockers of ATP-sensitive potassium channels.
Rat corticoencephalic cell cultures were investigated by high performance liquid chromatography for changes in the levels of adenosine 5'-triphosphate (ATP), guanosine 5'-triphosphate (GTP), uridine 5'-triphosphate (UTP), cytidine 5'-triphosphate (CTP), and the respective nucleoside diphosphates. Hypoxia was induced by gassing the incubation medium for 30 min with 100% argon. Removal of glucose was caused by washing the cultures in glucose-free medium at the beginning of the 30 min incubation period. Whereas hypoxia or glucose-deficiency alone failed to alter the nucleotide levels, the combination of these two manipulations was clearly inhibitory. Diazoxide (300 microM) an opener of ATP-dependent potassium channels (K(ATP)) did not alter the nucleotide contents either in a normoxic and glucose-containing medium, or a hypoxic and glucose-free medium. By contrast, the K(ATP) channel antagonist tolbutamide (300 microM) aggravated the hypoxic decrease of nucleotide levels in a glucose-free medium, although it was ineffective in a normoxic and glucose-containing medium. Hypoxia and glucose-deficiency decreased the ATP/ADP and UTP/UDP ratios, but failed to change the GTP/GDP ratio. Diazoxide and tolbutamide (300 microM each) had no effect on the nucleoside triphosphate/diphosphate ratios either during normoxic or during hypoxic conditions. In conclusion, corticoencephalic cultures are rather resistant to in vitro ischemia. Although they clearly respond to the blockade of plasmalemmal K(ATP) channels (plasmaK(ATP)) by tolbutamide, these channels appear to be maximally open as a consequence of the fall in intracellular nucleotides and, therefore, diazoxide has no further effect.


A single training center's experience with 200 consecutive cases of diverticulitis: can all patients be approached laparoscopically?
This study aimed to evaluate the outcomes for consecutive patients with diverticular disease who underwent elective laparoscopic sigmoid colectomy. Data for this patient population were collected by chart review and analyzed retrospectively. Between December 2001 and March 2007, 200 consecutive patients (93 men and 107 women) with an average age of 55 years were identified. All cases were managed by one of two colorectal surgeons. Of the 200 patients, 158 had recurrent diverticulitis, 20 had fistulas, 12 had abscesses, 8 had strictures, 1 had a mass, and 1 had a bleed. The mean operative time was 159 min, and the conversion rate was 8%. A total of 30 early postoperative complications occurred for 26 patients including wound infection (n = 9), ileus (n = 8), Clostridium difficile colitis (n = 3), urinary retention (n = 3), pelvic abscess (n = 2), deep vein thrombosis and pulmonary embolism (n = 1), pneumonia (n = 1) urinary tract infection (n = 1), anastomotic leak (n = 1), and small bowel obstruction (n = 1). Late complications experienced by 11 patients included Clostridium difficile colitis (n = 3), incisional hernia (n = 3), wound infection (n = 3), wound hematoma (n = 1), and intraabdominal hemorrhage (n = 1). The authors believe it is feasible to offer elective laparoscopic sigmoid colectomy to all patients with symptomatic diverticular disease despite preoperative risk factors.