An immobilized hexokinase enzyme stirrer for a simple and economical assay of plasma glucose.
We have adapted the hexokinase glucose procedure to an immobilized enzyme stirrer for the determination of glucose concentrations in human blood plasma. The procedure is a fluorometric rate method measuring the formation of NADPH catalyzed by immobilized glucose-6-phosphate dehydrogenase and hexokinase held within a tiny stirrer. The enzyme stirrer is stable for at least two months and can be used over eight-hundred assays without any loss of activity.


Detection of Epstein-Barr virus and human T-cell lymphotropic virus type 1 in malignant nodal lymphoma, studied in Okinawa, a subtropical area in Japan.
Formalin-fixed paraffin-embedded lymph node samples were collected from 100 cases of malignant nodal lymphoma documented in Okinawa in the period from 1973 through 1998. According to the new World Health Organization classification, 12 cases were Hodgkin's lymphoma (HL). Eighty-eight cases of non-Hodgkin's lymphoma (NHL) included 54 cases of T-cell type and 34 cases of B-cell type. Using polymerase chain reaction (PCR), Epstein-Barr virus (EBV) was detected in 11 cases (91.7%) of HL and in 57 cases (64.8%) of NHL, and human T-cell lymphotropic virus type 1 (HTLV-1) was detected in 23 cases (26.1%) of NHL. Clonal integration of HTLV-1 was detected in 10 (43.5%) of 23 HTLV-1 PCR-positive cases by the inverse PCR technique. The EBV-infected cells were detected by EBER-1 in situ hybridization in 11 (91.7%) of 12 HL cases and in 64 (72.7%) of 88 NHL cases. Irrespective of phenotype and tissue type of the malignant lymphoma, the rate of EBV-positive infection in Okinawa was higher than that in any other districts reported in Japan. This characteristic high rate of EBV-positive infection in Okinawa can be ascribed to various factors, such as racial and geographical differences.


Conceptualising quality of life outcomes for women participating in testing for sexually transmitted infections: A systematic review and meta-synthesis of qualitative research.
Many public health interventions have aims which are broader than health alone; this means that there are difficulties in using outcome measures that capture health effects only, such as Quality Adjusted Life Years (QALYs). Sexually Transmitted Infections (STIs) are a major public health concern both in the UK and globally, with Chlamydia trachomatis being the most common bacterial STI worldwide. There is scope for the wider use of qualitative syntheses in health-related research; in this study we highlight their potential value in informing outcome identification, particularly for public health interventions where a broad range of outcomes may need to be considered. This article presents a systematic review and meta-ethnography of qualitative studies that investigated women's experiences of thinking about and participating in testing for chlamydia. The meta-ethnography highlights issues relating to beliefs about STIs and testing, assessing risk and interpreting symptoms, emotional responses to testing, coping with diagnosis, relationship with sex partners(s), informal support, and interaction with health care services. The study findings suggest that women can experience a range of impacts on their health and quality of life. It is important that this range of effects is taken into account within evaluations, to ensure that decision makers are fully informed about the outcomes associated with screening interventions, and ultimately, to make sure that appropriate interventions are available to support women in maintaining good sexual health.


Anti-inflammatory capacity of Apremilast in human chondrocytes is dependent on SOX-9.
Osteoarthritis (OA) impacts the quality of life in middle-aged and elderly people by inducing immobility. The severe inflammation in chondrocytes is reported to be related to the development and process of OA. The present study aims to investigate the protective effects of Apremilast on injured chondrocytes induced by interleukin-1α (IL-1α) and the underlying mechanism. 10 ng/mL IL-1α was used to induce the in vitro injured chondrocytes. QRT-PCR was used to evaluate the expression level of Sry-type high-mobility-group box 9 (SOX-9), collagen type II alpha-1 gene (COL2A1), Aggrecan (ACAN) and collagen type X alpha 1 chain (COL10A1). SiRNA technology was utilized to knock down the expression of SOX-9 in the chondrocytes. The expression of SOX-9 was determined by Western Blot assay and/or immunofluorescence assay. Western Blot was used to evaluate the expression level of phosphorylated cyclic AMP response element binding (CREB). SOX9, Col2a1 and Acan were significantly up-regulated and Col10a1 was significantly down-regulated in the chondrocytes by Apremilast in a dose-dependent manner. IL-1α induced the injured chondrocytes by decreasing the expression of SOX9, Col2a1, Acan and increasing the expression of Col10a1, which were greatly reversed by Apremilast. By silencing SOX-9, the effects of Apremilast on SOX9 and marker genes were abolished. Phosphorylated CREB was up-regulated by Apremilast in a time-dependent manner. The up-regulated SOX-9 by Apremilast was reversed by the protein kinase A (PKA)/CREB pathway inhibitor H89. Apremilast may protect chondrocytes from inflammation by up-regulating SOX9.


Natural-Killer-Cell-Inspired Nanorobots with Aggregation-Induced Emission Characteristics for Near-Infrared-II Fluorescence-Guided Glioma Theranostics.
Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. The "Terminator" in the science fiction film is a cybernetic organism with living tissue over a metal endoskeleton, which inspired us to develop natural-killer-cell-mimic nanorobots with aggregation-induced emission (AIE) characteristics (NK@AIEdots) by coating a natural kill cell membrane on an AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owing to the AIE and soft-matter characteristics of PBPTV, as-prepared NK@AIEdots maintained a superior NIR-II brightness (quantum yield ∼7.9% in water) and good biocompatibility. Besides, they can serve as a tight junction (TJ) modulator to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to form an intercellular "green channel" to help them to cross the blood-brain barrier (BBB) silently. Furthermore, they can initiatively accumulate in glioblastoma cells in the complex brain matrix for high-contrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these NK@AIEdots under the NIR light illumination. As far as we know, the quantum yield of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots showed great potential for BBB-crossing active delivery.


[Preliminary study on the feasibility of robot-assisted double mesh sacrocolpopexy in comparison to the laparoscopic approach].
The aim of our study was to demonstrate the feasibility of the laparoscopic robot-assisted anterior and posterior mesh sacrocolpopexy compared to the laparoscopic approach. Between November 2009 and August 2011, 36 women underwent sacrocolpopexy with anterior and posterior mesh, 16 by a robot-assisted approach and 20 by laparoscopy. The cases were systematically evaluated at 1 and 12 months postoperatively. All cases were contacted 6 months later to evaluate the functional results. Both groups were comparable in terms of age, ASA score, Body Mass Index, surgical history and grades of pelvic organ prolapse preoperatively. There was no difference in terms of hospital stay, per- and postoperative complications, especially concerning the rate of postoperative constipation. The mean operating time was significantly more important in the Robot group (P=0.001) with 318 min for the Robot group versus 260 min for the laparoscopic group. With a mean follow-up of 12 months, the anatomic result was satisfactory without recurrence in 97.2% of the cases. The urinary and sexual results, the restart of a sexual activity postoperatively, the surgical satisfaction and the return to daily activities were comparable between both groups. Robot-assisted laparoscopic sacrocolpopexy seems to be a reliable technique with morbidity, anatomic and functional outcomes comparable to that of laparoscopy.


[Functional activity of rat adenohypophysis cells in a primary monolayer culture and the effect of several regulators on it].
Some peculiarities of labeled growth hormone (GH) and prolactin (PL) secretion in the 5-day monolayer culture of the rat adenohypophysis was studied. The hormones from the culture medium were obtained by electrophoresis on polyacrylamide gel. Natrium-dibutyril of cyclic adenosine-3',5'-monophosphate and theophylline, stimulated the GH and PL secretion. Thyrotropin-releasing hormone (TRH) increased the incorporation of 14C-1-leucine into the cell protein, stimulated PL secretion, but did not act on the GH release. Somatostatin completely abolished the GH secretion mediated by theophyllin, but not that of PL. Some peculiarities in the formation of labeled GH and PL pool in the cells and secretion of these hormones into the culture medium are discussed.


Transcriptomic analysis of the orchestrated molecular mechanisms underlying fruiting body initiation in Chinese cordyceps.
Chinese cordyceps, the fruiting body of the Chinese caterpillar fungus (Ophiocordyceps sinensis, syn. Cordyceps sinensis), is among the most valuable traditional Chinese medicine fungi. Transcriptomic analysis of O. sinensis has revealed several aspects of its life cycle and ecological importance. However, the molecular mechanisms involved in fruiting body initiation remain unclear. The developmental transcriptomes were analyzed from three tissues at the fruiting body initiation stage, namely, the mycelium, sclerotium and primordium. Principal component analysis showed that in the three tissues, the gene expression patterns differed from each other. The functional analysis of differentially expressed genes showed that DNA synthesis and cell division were active in the primordium. In addition, the function of the mycelium was to absorb certain substances from the environment and the sclerotium was the metabolism center of O. sinensis. Genes participating in the mitogen-activated protein kinase (MAPK) signal pathway were involved in fruiting body initiation. Two environmental sensing genes, including a pheromone receptor gene (OSIN6252) and an amino acid sensing gene (OSIN6398), were highly expressed in the primordium, suggesting their important roles in initiation. These results provided insights into the orchestrated functions and gene profiles of different O. sinensis tissues at the key stage. These findings will aid in revealing the underlying mechanisms of fruiting body initiation, which will further benefit artificial cultivation.


Immunological detection of B-DNA to Z-DNA transition of polynucleotides by immobilization of the DNA conformation on a solid support.
We studied the B-DNA to Z-DNA transition of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) in the presence of NaCl using an enzyme immunoassay. The polynucleotides were coated on microtiter plates at varying concentrations of NaCl and treated with a monoclonal anti-Z-DNA antibody, Z22. The plates were subsequently treated with alkaline phosphatase conjugated polyvalent mouse immunoglobulins and the enzyme substrate, p-nitrophenyl phosphate. The color development due to the enzyme-substrate reaction was quantitated using a microplate autoreader. Our results show that the antibody does not recognize the polynucleotides in the B-DNA conformation and binds strongly to the Z-DNA conformation. A smooth transition curve is obtained at intermediate concentrations of the counterions. From the transition curves, we determined the concentration of the counterions at the midpoint of B-DNA to Z-DNA transition. The midpoint concentrations for poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) are 2.3 and 0.74 M NaCl, respectively. Using the immunological method, we also examined the B-DNA to Z-DNA transition of poly(dG-m5dC).poly(dG-m5dC) in the presence of naturally occurring polyamines. The midpoint concentrations of the polyamines are as follows: putrescine, 2.5 mM; spermidine, 34 microM; spermine, 1.8 microM. The midpoint values determined by the enzyme immunoassay are in good agreement with those determined by circular dichroism and ultraviolet absorption spectroscopic measurements. These results demonstrate that immobilization of a preexisting conformation or a mixture of conformations of DNA on a solid support followed by a titration of the DNA conformations using a monoclonal anti-DNA antibody is an excellent method to study the conformational dynamics of DNA.


Neurometabolic and neurodegenerative diseases in children.
Neurometabolic and neurodegenerative diseases in children (NDDC) differ from those in adults in that most of the former are autosomal-recessively inherited - few have X-linked inheritance - while the latter are often sporadic or autosomal-dominantly inherited. NDDC may be catabolic and/or anabolic conditions, some of which combine maldevelopmental and degenerative features, for instance, peroxisomal biogenesis disorders or congenital disorders of glycosylation. NDDC are often multiorgan disorders, such as lysosomal, peroxisomal, and polyglucosan disorders. This multiorgan involvement may be marked by extracerebral formation of disease-specific neuropathologic findings, especially in lysosomal diseases allowing diagnostic biopsies in easily accessible tissues, e.g., blood lymphocytes, skin, skeletal muscle, and rectum to be investigated by electron microscopy. NDDC comprise nonvacuolar and vacuolar lysosomal, peroxisomal, polyglucosan, amino and organic acid, white-matter disorders, and congenital disorders of glycosylation.


HIV/AIDS among children in Ratodero, Pakistan amidst the COVID-19 pandemic: Challenges, efforts, and recommendations.
In Pakistan, HIV has increased at an alarming rate in recent decades, and the death toll has risen. It is a public health challenge amidst the COVID-19 pandemic that is not being given due importance. The present article looks at the challenges and efforts being made to deal with HIV among children in Ratodero, Pakistan, and addresses measures that can be taken to control the disease in the child population epidemiologically.


Measuring Suppressive Activity and Autophagy in Myeloid-Derived Suppressor Cells.
Myeloid-derived suppressor cells (MDSC) are potent suppressor cells that accumulate in tumor microenvironment and inhibit anti-tumor responses. Assessment of cell-autonomous MDSC responses allows the precise characterization of MDSCs in various disease settings and elucidates the underlying mechanisms of MDSC-mediated immune suppression. Here we describe a protocol for the isolation of tumor infiltrating or splenic MDSC, as well as their subpopulations, from melanoma-inoculated mice using Fluorescent Activated Cell Sorting (FACS). We further provide protocols for investigation of the autophagy pathway and ex vivo assessment of MDSC suppressive function using lymph node responder cells. These assays allow a comprehensive characterization of MDSC in murine experimental models.


Short-term effect of humid airflow on antimicrobial air filters using Sophora flavescens nanoparticles.
Bioaerosols have received social and scientific attention because they can be hazardous to human health. Recently, antimicrobial treatments using natural products have been used to improve indoor air quality (IAQ) since they are typically less toxic to humans compared to other antimicrobial substances such as silver, carbon nanotubes, and metal oxides. Few studies, however, have examined how environmental conditions such as the relative humidity (RH), surrounding temperature, and retention time of bacteria on filters affect the filtration and antimicrobial characteristics of a filter treated with such natural products. In this study, we investigated changes in the morphology of the natural nanoparticles, pressure drop, filtration efficiency, and the inactivation rate caused by the short-term effect of humid airflow on antimicrobial fiber filters. Nanoparticles of Sophora flavescens were deposited on the filter media surface using an aerosol process. We observed coalescence and morphological changes of the nanoparticles on fiber filters under humid conditions of an RH >50%. The level of coalescence in these nanoparticles increased with increasing RH. Filters exposed to an RH of 25% have a higher pressure drop than those exposed to an RH >50%. In an inactivation test against Staphylococcus epidermidis bacterial aerosol, the inactivation efficiency at an RH of 25% was higher than that at an RH of 57% or 82%. To effectively apply antimicrobial filters using natural products in the environment, one must characterize the filters under various environmental conditions. Thus, this study provides important information on the use of antimicrobial filters made of natural products.


Human acute microelectrode array recordings with broad cortical access, single-unit resolution, and parallel behavioral monitoring.
There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.


Severe ethanol stress inhibits yeast proteasome activity at moderate temperatures but not at low temperatures.
Since yeast research under laboratory conditions is usually conducted at 25-30°C (moderate temperature range), most of the findings on yeast physiology are based on analyses in this temperature range. Due to inefficiencies in cultivation and analysis, insufficient information is available on yeast physiology in the low-temperature range, although alcoholic beverage production is often conducted at relatively low temperatures (around 15°C). Recently, we reported that severe ethanol stress (10% v/v) inhibits proteasomal proteolysis in yeast cells under laboratory conditions at 28°C. In this study, proteasomal proteolysis at a low temperature (15°C) was evaluated using cycloheximide chase analysis of a short-lived protein (Gic2-3HA), an auxin-inducible degron system (Paf1-AID*-6FLAG), and Spe1-3HA, which is degraded ubiquitin-independently by the proteasome. At 15°C, proteasomal proteolysis was not inhibited under severe ethanol stress, and sufficient proteasomal activity was maintained. These results provide novel insights into the effects of low temperature and ethanol on yeast physiology.


Alcohol use and serious psychological distress among women of childbearing age.
The purpose of this study was to present nationally representative findings on the prevalence and co-occurrence of alcohol use and serious psychological distress among women aged 18-44 years, as well as their access to health care. A total of 24,900 women aged 18-44 years participated in the National Health Interview Survey (NHIS) during the years 2003-2005. Using data from the cross-sectional survey, we estimated the prevalence and co-occurrence of alcohol use and serious psychological distress among this population; this association was examined using logistic regression. Health care access among women who used alcohol and had serious psychological distress was characterized by co-occurring status. During the study period, the estimated annual prevalence was 4.1% for heavier alcohol use, 56.0% for non-heavier use, 39.8% for nonuse, and 3.6% for serious psychological distress among women aged 18-44 years. Women who experienced serious psychological distress were at an increased likelihood for alcohol use, particularly heavier use. Alcohol use and serious psychological distress co-occurred among an estimated 1.1 million women of childbearing age in the United States annually. Most women, regardless of their co-occurring status, reported being treated by clinicians in various health care settings during the previous 12 months. Alcohol use is common among women of childbearing age who experience serious psychological distress. The findings of this study provide support for enhancing efforts toward integrated assessment and intervention among women who have such co-occurring risk factors.


CDApps: integrated software for experimental planning and data processing at beamline B23, Diamond Light Source. Corrigendum.
In the paper by Hussain et al. [(2015), J. Synchrotron Rad. 22, 465-468], Daniel Myatt is missing from the list of authors. The complete list of authors should be Rohanah Hussain, Kristian Benning, Daniel Myatt, Tamas Javorfi, Edoardo Longo, Timothy R. Rudd, Bill Pulford and Giuliano Siligardi.


Cooperation between midwives and doulas in the context of perinatal care - a integrative review of qualitative and quantitative studies.
A doula is a person who provides support to women in the perinatal period without providing medical services. During childbirth, the doula becomes a member of the interdisciplinary team. This integrative review aims to analyse the nature of the cooperation between doulas and midwives, its efficiency and challenges and ways of strengthening this cooperation. A structured integrative review of empirical and theoretical studies written in English was conducted. The literature search included MEDLINE, Cochrane, Scopus, ProQuest, Science Direct, Web of Science, and Embase Health Source: Nursing/Academic Edition databases. The analysis included papers published in 1995-2020. Dedicated documents were searched for different combinations of terms and standard logical operators. A manual search of the studies was included for additional references. Twenty-three articles from 75 full-text records were analysed. Three main themes emerged. (1) doulas are needed to prop up the system (2) barriers in collaboration between midwives and doulas; and (3) how cooperation between midwives and doulas can be strengthened. None of the articles referred directly to the impact of collaboration between midwives and doulas on the quality of perinatal care. This is the first review to analyse the impact of collaboration between midwives and doulas on the quality of perinatal care. Ensuring adequate collaboration between doulas and midwives requires effort from both of these professional groups and the health care system. However, such collaboration is supportive for birthing women and the perinatal care system. Further research in terms of the impact of this collaboration on the quality of perinatal care is needed.


Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient.
Metformin has been shown to have various cardiovascular benefits beyond its antihyperglycemic effects, including a reduction in stroke, heart failure, myocardial infarction, cardiovascular death, and all-cause mortality. However, the roles of metformin in cardiac arrhythmias are still unclear. It has been shown that metformin was associated with decreased incidence of atrial fibrillation in diabetic patients with and without myocardial infarction. This could be due to the effects of metformin on preventing the structural and electrical remodeling of left atrium via attenuating intracellular reactive oxygen species, activating 5' adenosine monophosphate-activated protein kinase, improving calcium homeostasis, attenuating inflammation, increasing connexin-43 gap junction expression, and restoring small conductance calcium-activated potassium channels current. For ventricular arrhythmias, in vivo reports demonstrated that activation of 5' adenosine monophosphate-activated protein kinase and phosphorylated connexin-43 by metformin played a key role in ischemic ventricular arrhythmias reduction. However, metformin failed to show anti-ventricular arrhythmia benefits in clinical trials. In this review, in vitro and in vivo reports regarding the effects of metformin on both atrial arrhythmias and ventricular arrhythmias are comprehensively summarized and presented. Consistent and controversial findings from clinical trials are also summarized and discussed. Due to limited numbers of reports, further studies are needed to elucidate the mechanisms and effects of metformin on cardiac arrhythmias. Furthermore, randomized controlled trials are needed to clarify effects of metformin on cardiac arrhythmias in human.


Incremental prognostic value of stress echo positivity in the left anterior descending coronary artery territory.
Dipyridamole stress echo (DSE) positivity is usually titrated according to presence and severity of the induced wall motion abnormalities. The purpose of our study is to assess whether the location of DSE positivity might add to prognostic stratification. The study enrolled 112 patients with known or suspected coronary artery disease (CAD) and without a history of prior myocardial infarction. They were consecutively submitted to DSE (0.84 mg/Kg in 10 min followed by atropine administration, when needed) and coronary angiography (within a 15+/-7 day period). End points at follow-up were cardiac death and acute coronary syndromes. Twenty-seven patients had a negative, and 85 a positive DSE (47 in the LAD territory). Angiographically assessed CAD was present in 82 patients (LAD in 59). At a follow-up of 9+/-7 months, there were 28 events of cardiac deaths or acute coronary syndromes. Event-free survival was lower in patients with positive DSE (any location) compared to those with negative DSE (47% vs 89%, p=0.003). In the subset with positive DSE, event-free survival was lower in patients with wall motion abnormalities in the LAD territory compared to those with dysfunction in the left circumflex and right coronary artery territory (31% vs 72%, p=0.00012 ). At multivariate analysis, stress echo positivity in the LAD territory was independently associated with increased risk (HR: 9.51, CI: 1.61 to 56.11, p<0.013) and outperformed angiographically assessed LAD stenosis (HR: 0.36, CI: 0.06 to 2.24, p: NS). In CAD patients, wall motion abnormalities in the LAD territory during DSE identified a higher risk subgroup. Functional stress echo positivity on the LAD territory overcame the prognostic impact of an anatomic, angiographically assessed LAD disease.


Left ventricular wall stress and contractile function in transposition of the great arteries after the Rastelli operation.
Left ventricular wall stress and contractile function were determined by echocardiographic methods in 11 patients studied 0.7 to 13.8 years (mean +/- standard error of the mean = 5.6 +/- 1.2 years) after undergoing the Rastelli operation for transposition of the great arteries associated with ventricular septal defect and left ventricular outflow tract obstruction. Age at operation ranged from 4.6 to 11.3 years (mean +/- standard error of the mean = 7.4 +/- 0.7 years). Data were compared with data of 24 normal subjects of similar age and heart rate. Left ventricular end-diastolic dimension and end-diastolic volume were significantly higher than normal, averaging 134% +/- 8% of normal dimension (p less than 0.004) and 106 +/- 13 ml/m2 versus a normal volume of 60 +/- 3 ml/m2) (p less than 0.007). In addition left ventricular wall mass was 215 +/- 40 gm/m2 versus a normal value of 72 + 6 gm/m2 (p less than 0.004). Both meridional and circumferential end-systolic and peak systolic stress values were not significantly different between normal subjects and Rastelli patients. Estimates of ventricular pump function including shortening fraction, rate-corrected velocity of circumferential fiber shortening, and ejection fraction were all depressed when compared with normal values. Velocity of fiber shortening, evaluated as a function of end-systolic stress, demonstrated abnormal contractile function in eight of 11 (73%) patients. These data indicate that left ventricular function is usually abnormal and residual left ventricular dilation and wall hypertrophy remain despite successful use of the Rastelli operation for repair in patients with transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction.


Salivary gland manifestations of sinus histiocytosis with massive lymphadenopathy: fine-needle aspiration cytology findings. A case report.
Sinus histiocytosis with massive lymphadenopathy (SHML or Rosai-Dorfman disease) is a nonneoplastic, usually self-limiting disease. Alhough it affects all age groups, it is more commonly seen in young males in their first or second decades. The disease primarily manifests as painless lymphadenopathy of cervical region, but other nodal groups and extranodal sites may also be affected. Seldom SHML may involve the salivary glands. We present the cytologic features and differential diagnoses of one such case.A 45-yr-old woman presented with an enlarged submandibular gland on the left side with ipsilateral cervical lymphadenopathy that had been persisting for 1 mo. The gland and the two enlarged nodes measured 2.5 x 2.5 cm(2) each and were firm in consistency. Clinically, tumor of the salivary glands was suspected. Fine-needle aspiration (FNA) smears showed moderate cellularity, with large histiocytes dispersed in the background of intense lymphoplasmacytic infiltrate. These histiocytes showed lymphophagocytosis. Isolated stromal fragments consisting of fibrocytes were seen separate from salivary acinar clusters on repeat aspirations. The diagnosis of SHML involving left submandibular gland and ipsilateral lymph nodes was returned. When analyzed in the context of clinical findings (laboratory data), the cytologic features of SHML involving salivary gland could be differentiated from those of malignancies and other benign lesions, especially Kuttner's tumor of the submandibular gland, which mimics neoplasm clinically.


Amaurosis fugax: carotid endarterectomy without an angiogram.
The risks of carotid angiography--technical, allergic, cardiac, renal, or emotional--may be lessened or absented by the use of real-time B-mode ultrasound to evaluate carotid artery disease. A patient with amaurosis fugax, a positive fluorescein angiogram, ulceration on ultrasound, and an unremarkable computed tomography scan was operated on without angiography. The pathology was correct and the patient did well.


An overview on different aspects of hypodermosis: Current status and future prospects.
Livestock plays a vital role in economic development of a nation and is being used in agriculture for draft power, production of farmyard manure as well as milk and meat production. Bovine hypodermosis is the top culprit among all parasitic infections across the world. Hypodermosis is an endemic disease in the mountainous areas/plain areas and is regularly observed in the northern hemisphere of the globe affecting cattle, deer, yaks and buffaloes. There is a wide variation in geographical distribution of Hypoderma spp. during the years 1945-2015. The manuscript includes a geospatial study that tries to maps the global distribution of hypodermosis in different areas of the world in order to detect hotspots or endemic areas that may be a potential source for disease spread. This information's are very useful to predict the potential high risk areas that are prone to disease outbreak. The present review aims to evaluate the global distribution, molecular discrimination, diagnostics and vaccination of hypodermosis, focusing on its current status and future perspectives towards the management of the disease and its control strategies.


Slc4-like anion transporters of the larval mosquito alimentary canal.
Mosquito larvae exhibit luminal pH extremes along the axial length of their alimentary canal that range from very alkaline (pH>10) in the anterior midgut to slightly acid in the hindgut. The principal buffer in the system is thought to be bicarbonate and/or carbonate, because the lumen is known to contain high levels of bicarbonate/carbonate and is surrounded by various epithelial cell types which express a variety of carbonic anhydrases. However, the precise mechanisms responsible for the transport of bicarbonate/carbonate into and out of the lumen are unclear. In the present study, we test the hypothesis that SLC4-like anion transporters play a role in bicarbonate/carbonate accumulation in the larval mosquito alimentary canal. Molecular, physiological and immnuohistochemical characterizations of Slc4-like transporters in the gut of larval mosquitoes (Aedes aegypti and Anopheles gambiae) demonstrate the presence of both a Na(+)-independent chloride/bicarbonate anion exchanger (AE) as well as a Na(+)-dependent anion exchanger (NDAE). Notably, immunolocalization experiments in Malpighian tubules show that the two proteins can be located in the same tissue, but to different cell types. Immunolabeling experiments in the gastric caecae show that the two proteins can be found in the same cells, but on opposite sides (basal vs. apical). In summary, our results indicate that the alimentary canal of larval mosquitoes exhibits robust expression of two SLC4-like transporters in locations that are consistent with a role in the regulation of luminal pH. The precise physiological contributions of each transporter remain to be determined.


Stable longitudinal associations of family income with children's hippocampal volume and memory persist after controlling for polygenic scores of educational attainment.
Despite common notion that the correlation of socioeconomic status with child cognitive performance may be driven by both environmentally- and genetically-mediated transactional pathways, there is a lack of longitudinal and genetically informed research that examines these postulated associations. The present study addresses whether family income predicts associative memory growth and hippocampal development in middle childhood and tests whether these associations persist when controlling for DNA-based polygenic scores of educational attainment. Participants were 142 6-to-7-year-old children, of which 127 returned when they were 8-to-9 years old. Longitudinal analyses indicated that the association of family income with children's memory performance and hippocampal volume remained stable over this age range and did not predict change. On average, children from economically disadvantaged background showed lower memory performance and had a smaller hippocampal volume. There was no evidence to suggest that differences in memory performance were mediated by differences in hippocampal volume. Further exploratory results suggested that the relationship of income with hippocampal volume and memory in middle childhood is not primarily driven by genetic variance captured by polygenic scores of educational attainment, despite the fact that polygenic scores significantly predicted family income.


Staphylococcus aureus growth and survival during curding of Manchego type cheese produced with normal and subnormal starter activity.
Manchego type cheese was manufactured from milk from cows, goats and ewes artificially contaminated with 2 X 10(4) S. aureus cells ml. Lactic starter culture was added to the milk at the rate of 1.0 or 0.1% (v/v). the industrial process of Manchego type cheese manufacture was imitated. Cheeses were analyzed for both staphylococcal and non-staphylococcal total aerobic counts, as well as for the pH and enterotoxin production. Growth differences in staphylococcal counts in cheeses prepared with both starter concentrations were seen only after the brine treatment, the counts were 10 times greater with the 0.1% starter. Nevertheless, with the 1% starter culture the staphylococcal counts did not decrease from the moment of inoculation remaining high after brine treatment. For a similar inoculum, the strains used responded in a different manner, the highest values corresponding to strains FRI-100, S6 and FRI-472, and the lowest to FRI-137 and FRI-361. No differences in pH were seen between batches prepared with both starter concentrations.


[Kidney and smoking: literature review and focus].
Smoking remains a major public health problem. It is associated with a considerable number of deaths in the world's population. Smoking is just like high blood pressure, an independent predictor of progression to any primary renal disease and renal transplant patients. It seems that smoking cessation slows the progression of kidney disease in smokers. The literature data are sometimes contradictory about it because of some methodological weaknesses. However, experimental models highlight the harmful effects of tobacco by hemodynamic and non-hemodynamic factors. The conclusion is that a major effort should be further produced by the nephrology community to motivate our patients to stop smoking.


Primary self-expandable nitinol stent placement in focal lesions of infrarenal abdominal aorta: long term results.
To evaluate the technical and clinical success, safety and long term results of percutaneous transluminal angioplasty/self-expandable nitinol stent placement of infrarenal abdominal aorta focal lesions. Eighteen patients underwent PTA of focal atherosclerotic occlusive disease of distal abdominal aorta. Two symptomatic occlusions and 16 stenoses in 10 male and 8 female patients (mean age 68.2 years) were treated with primary self-expandable nitinol stent placement. Primary self-expandable nitinol stent placement was technically successful in all 18 procedures; clinical success was achieved in 100% of patients. No complications associated with the procedure occurred. During the 49.4 months of mean follow up (range 3-96, 4 months) all treated aortic segments remained patent. Endovascular treatment (primary self-expandable nitinol stent placement) of focal atherosclerotic lesions of distal abdominal aorta is a safe method with excellent primary technical and clinical success rates and favourable Long term results.


Of networks, large and small.
Computer networks are constantly and radically changing the way in which the medical professions thinks and works. This article briefly explores some of these innovations.


Hyperlipoproteinemia in spontaneously diabetic guinea pigs.
A colony of Hartley guinea pigs that exhibit hyperglycemia, glucosuria, and hypertriglyceridemia characteristic of human diabetes mellitus was developed. Initially, a group of guinea pigs that had normal serum glucose concentrations (less than or equal to 200 mg/dL of serum) at 3 to 4 weeks of age was obtained; however, in some of the animals progressively severe hyperglycemia (300 to 500 mg/dL of serum) and glucosuria (greater than 2 g of glucose/24 h) occurred as the animals matured. In addition, the animals exhibiting hyperglycemia and glucosuria had plasma insulin concentrations that were similar to those animals that were not hyperglycemic. The diabetic animals were found to be hypertriglyceridemic, with plasma triglyceride levels of 140 to 290 mg/dL at four months of age. Nondiabetic animals (plasma glucose concentration of less than or equal to 200 mg/dL and no glucosuria) had plasma triglyceride concentrations between 37 and 76 mg/dL. Lipoprotein analysis of plasma from nondiabetic and diabetic animals indicated that the diabetics had a fourfold increase in VLDL triglyceride and protein concentrations. The VLDL had an abnormal apolipoprotein composition and had reduced levels of apoprotein-E. The progeny from the mating of diabetic males and females also exhibited the diabetic trait, suggesting that the origin of the disease is genetic. This colony of guinea pigs is being further investigated as a suitable model for the study of the hyperlipoproteinemia of human noninsulin-dependent diabetes mellitus.


ChatGPT, Bard, and Large Language Models for Biomedical Research: Opportunities and Pitfalls.
Large Language Models (LLMs) such as ChatGPT and Bard have emerged as groundbreaking interactive chatbots, capturing significant attention and transforming the biomedical research landscape. These powerful tools offer immense potential for advancing scientific inquiry, but they also present challenges and pitfalls. Leveraging large language models, researchers can streamline literature reviews, summarize complex findings, and even generate novel hypotheses, enabling the exploration of uncharted scientific territories. However, the inherent risk of misinformation and misleading interpretations underscores the critical importance of rigorous validation and verification processes. This article provides a comprehensive overview of the current landscape and delves into the opportunities and pitfalls associated with employing LLMs in biomedical research. Furthermore, it sheds light on strategies to enhance the utility of LLMs in biomedical research, offering recommendations to ensure their responsible and effective implementation in this domain. The findings presented in this article contribute to the advancement of biomedical engineering by harnessing the potential of LLMs while addressing their limitations.


Synthesis and Dynamics of Ferrous Polychalcogenides [Fe(Ex)(CN)2(CO)2]2- (E = S, Se, or Te).
Elemental chalcogens react with [Fe(CN)2(CO)3]2- to give the following ferrous derivatives: [K(18-crown-6)]2[Fe(S5)(CN)2(CO)2], [K(18-crown-6)]2[Fe(S2)(CN)2(CO)2], [K(18-crown-6)]2[Fe(Se4)(CN)2(CO)2], [K(18-crown-6)]2[Fe(Te2)(CN)2(CO)2], and (NEt4)2[Fe(Te2)(CN)2(CO)2]. While these complex anions crystallized in a single stereochemistry (i.e., trans dicyanides or cis dicyanides), they isomerize in solution upon irradiation. The results are benchmarked by the corresponding studies on benzyl thiolate [K(18-crown-6)]2[Fe(SBn)2(CN)2(CO)2].


Comparison of a beta-lactamase induction test with a test that detects low-frequency resistance to cefotaxime.
A paper strip test that detects cefotaxime-resistant variants of gram-negative bacilli was described and compared with a beta-lactamase induction test. Both tests demonstrated a potential for resistance that is not indicated by standard agar dilution and agar diffusion tests.


The effect of massage therapy and/or exercise therapy on subacute or long-lasting neck pain--the Stockholm neck trial (STONE): study protocol for a randomized controlled trial.
Neck pain is a major health problem in populations worldwide and an economic burden in modern societies due to its high prevalence and costs in terms of health care expenditures and lost productivity. Massage and exercise therapy are widely used management options for neck pain. However, there is a lack of scientific evidence regarding their effectiveness for subacute and long-lasting neck pain. This study protocol describes a randomized controlled trial aiming to determine the effect of massage and/or exercise therapy on subacute and long-lasting neck pain over the course of 1 year. A randomized controlled trial in which at least 600 study participants with subacute or long-lasting nonspecific neck pain will be recruited and randomly allocated to one of four treatment arms: massage therapy (A), exercise therapy (B), exercise therapy plus massage therapy (C) and advice to stay active (D). The study has an E-health approach, and study participants are being recruited through advertising with a mix of traditional and online marketing channels. Web-based self-report questionnaires measure the main outcomes at 7, 12, 26 and 52 weeks after inclusion. The primary outcomes are a clinically important improvement in pain intensity and pain-related disability at follow-up, measured with a modified version of the Chronic Pain Questionnaire (CPQ). The secondary outcomes are global improvement, health-related quality of life (EQ-5D), sick leave, drug consumption and healthcare utilization. Adverse events are measured by questionnaires at return visits to the clinic, and automated text messages (SMSes) survey neck pain intensity and pain-related disability every week over one year. The results of this study will provide clinicians and stakeholders much needed knowledge to plan medical care for subacute and long-lasting neck pain disorders. Current Controlled Trials ISRCTN01453590. Date of registration: 3 July 2014.


Video-assisted neck surgery (VANS) using a gasless lifting procedure for thyroid and parathyroid diseases: "The VANS method from A to Z".
To describe and evaluate our video-assisted neck surgery (VANS) method for thyroid and parathyroid diseases. We describe in detail the VANS method for enucleation, lobectomy, total (nearly total) thyroidectomy, and lymph node dissection for malignancy and Graves' disease. In collaboration with the Japan Society of Endoscopic Surgery (JSES), we evaluated several aspects of this method. The JSES evaluated the method for working-space formation and surgical complications, whereas we examined the learning curve of the surgeons, and the cosmetic satisfaction of the patients and the degree of numbness and pain they experienced. We also asked patients who underwent conventional surgery whether they would have selected VANS had it been available. The working space for 81.5% of the procedures in Japan was created using the gasless lifting method. The learning curve, considering both blood loss and operating time, decreased after 30 cases. Both factors improved for tumors smaller than 5 cm in diameter. Over 60% of the patients who underwent conventional surgery stated that they would have selected VANS, had it been available. Postoperative pain was worse after conventional surgery than after VANS, but neck numbness after VANS was more frequent than expected. The VANS method is a feasible, safe, and cost-effective procedure with clear cosmetic advantages over conventional surgery.


Management of chronic airway obstruction: theophylline--is it still necessary?
Theophylline is a second-line drug for the symptomatic treatment of obstructive pulmonary diseases. It appears to be of particular value in the treatment of the more severe cases of airway obstruction. The likelihood of a therapeutic benefit and the safety of drug therapy can be increased markedly by an individually optimized theophylline therapy, that is, individual dosage and time of dosing, and monitoring the serum concentrations.


Tacaribe virus L gene encodes a protein of 2210 amino acid residues.
The nucleotide sequence of Tacaribe virus (TV) L gene was obtained from two sets of overlapping cDNA clones constructed by walking along the virus L RNA using two successive synthetic DNA primers. Analysis of the sequence indicated the existence of a unique long open reading frame in the viral complementary strand. The first in-phase AUG codon is in positions 31-33 from the 5' end of the viral complementary L RNA surrounded by a sequence favorable for initiation of protein synthesis. The open reading frame ends at positions 6661-6663. The predicted TV L protein is a 2210 amino acid long polypeptide with an estimated molecular weight of 251,942. Comparison of the amino acid sequence of TV L protein with peptide sequences predicted from L-derived cDNA clones of lymphocytic choriomeningitis virus shows an overall 42% of homology.


[Analysis of the bibliometrics score of surgical department from the academic hospitals of Paris: what is the rank of urology?].
Analyze the results of the bibliometric system and analysis of scientific publications (SIGAPS) in the Assistance publique-Hôpitaux de Paris (AP-HP) and compare the scientific production among the various surgical disciplines of the academic hospitals of Paris and define the place of urology. The publications from 115 surgical departments between 2006 and 2008 were included. Only surgical departments were considered in the current study. The following data were taken into account: the hospital department of origin, the number of articles published, the number of first place, last places, the number of full-time unit, the SIGAPS score. Statistical analysis focused on the quality and on the quantity of published articles per surgeons and per department. There were eight academic departments of urology identified within the AP-HP. The database contained information for 115 surgical departments. The mean number of articles published by department was 42.89±27.34 (13.2 to 110.75). The mean number of publications per full-time surgeon was 6.7±2.59 (3.77 to 12.84), or a mean of 2.25±0.86 released by full-time and by year. The median score SIGAPS of surgery was 304 with a wide interval (122 to 903.5). Urology was the specialty with the highest median score compared to other surgical specialties. The department, which published the most, was the center 1, in comparison with the center 6 which was publishing the most in A/B ranking journals. Urology was the absolute leader by far in terms of scientific publications in the AP-HP when compared to other surgical disciplines. The discipline is organized efficiently to juggle clinical work and research indicating a certain dynamism of the teams that invest there to fulfill the missions assigned to them in the University Hospital and the part of the autonomy of the universities.


Optimization of reversed-phase chromatography methods for peptide analytics.
The analytical description and quantification of peptide solutions is an essential part in the quality control of peptide production processes and in peptide mapping techniques. Traditionally, an important tool is analytical reversed phase liquid chromatography. In this work, we develop a model-based tool to find optimal analytical conditions in a clear, efficient and robust manner. The model, based on the Van't Hoff equation, the linear solvent strength correlation, and an analytical solution of the mass balance on a chromatographic column describing peptide retention in gradient conditions is used to optimize the analytical scale separation between components in a peptide mixture. The proposed tool is then applied in the design of analytical reversed phase liquid chromatography methods of five different peptide mixtures.


Interrelation of tissue temperature versus flow velocity in two different kinds of temperature controlled catheter radiofrequency energy applications.
The influence of blood flow cooling down the energy delivering electrode during temperature controlled radiofrequency energy application is an important factor for ablation success. In this experimental in-vitro study, using tempered saline as blood equivalent, we observed a highly significant increase in tissue temperature, lesion depth and required energy amount with increasing flow velocity. Second, we found significant deeper lesions with use of pulsed radiofrequency energy application compared to continuous application. We conclude that, even with lower electrode temperatures, success can be achieved dependent on the local blood flow velocity, and deeper lesions can be created with the use of pulsed radiofrequency energy application. Success in temperature-controlled radiofrequency (RF) catheter ablation of arrhythmogenic areas in human hearts depend largely (among others) on the size of the electrode, developed pressure of electrode against tissue, as well as on the localization of the thermistor sensor within the electrode. In addition, the blood flow velocity at various sites of ablation is an important factor for the calculation of heat transport from the electrode, which obviously has not been given much consideration of in the past. The aim of the present in-vitro study, therefore, was to evaluate this important factor's influence on the temperature developed at the electrode and within the myocardial tissue. All experiments were carried out in a bath containing NaCl solution at 37 degrees C. Four different flow velocities were applied (0, 110, 180, 320 ml/cm2 *min). During and after temperature-controlled unipolar radiofrequency energy delivery (60 degrees C, 40 sec) the electrode temperature, the tissue temperature 5 mm in depth, and the total energy delivered were measured, as well as the actual depth of the lesion. The amount of energy applied to the electrode was regulated by the thermosensor in the electrode to obtain a maximum temperature of 60 degrees C. Two different kinds of radiofrequency energy delivery have been used: (1) continuous radiofrequency energy delivery as usual regarding clinical use, (2) pulsed radiofrequency energy delivery with a duty cycle length of 10 ms and a pause of at least the same duration during two consecutive duty cycles. At pulsed radiofrequency energy application, the energy for each duty cycle was held constant during delivery. The amount of pulses delivered to the electrode was regulated by the electrode's thermosensor. With both modes of radiofrequency energy delivery a uniform observation could be made. The more the flow velocity applied accelerated, the more the tissue temperature rose (R = 0.85; p < 0.00000001), and the lesion depth increased in spite of electrode temperature being held constant. The amount of the total energy delivered rose in proportion to the cooling down of the electrode dependent on the flow velocity (R = 0.69, p < 0.0000004). Steady-state temperatures had not been accomplished after 40 sec time. When energy was delivered at the pulsed mode, intramyocardial temperatures proved higher compared to the continuous mode with significant differences (p < 0.05) at comparable flow velocities applied between 180 and 320 ml/cm2*min and at same electrode temperatures. This resulted in significantly (p < 0.05) larger lesion depths in pulsed radiofrequency energy delivery. We suppose that this significant difference can be explained by a higher amount of total energy delivered at comparable electrode temperature in the pulsed mode as compared to the continuous mode.


A load model based on antecedent dry periods for pollutants in stormwater.
A load model for stormwater constituents is proposed that describes mass retained on the drainage area after previous storms, as a function of a weighted sum of previous antecedent dry periods. It was used to compute the event load for 14 constituents--zinc, copper, cadmium, nickel, chromium, lead, mercury, silver, total suspended solids (TSS), E. coli, fecal coliform, total soluble phosphorus, total phosphorus, and 5-day biochemical oxygen demand. The results show acceptable fits for most constituents based on over 400 rain events (2000 to 2004) in Milwaukee, Wisconsin. Considering the retained pollutant mass after one previous storm rather than assuming the area to be clean after the previous storm gives more accurate results for all constituents, except TSS and silver. The model can be used for mixed land-use areas. The ratios of deposition fluxes of zinc and individual metals were determined at a major parking lot producing a profile characteristic of automobile emissions.


Early diagnosis of lung cancer using a SAFE-3000 autofluorescence bronchoscopy.
The aim of the study was to evaluate the double modality working of a new autofluorescence videobronchoscope SAFE-3000 for the detection and localization of precancerous and malignant lesions. From April to May 2009, 168 patients underwent SAFE-3000 bronchoscopy using 'Twin Mode' and 'Multiple Image Xposition (MIX)' technologies. The study considers only 97 patients with morphological alterations (visual score 2 or 3) of mucosa; four bronchial biopsies (two for every modality) have been performed on every patient. Histological diagnosis of the 388 biopsies revealed normal mucosa in 11 patients, four benign lesions, 27 precancerous lesions and 55 malignant lesions. The sensitivity of the 'Twin Mode' and 'MIX' techniques in the characterization of premalignant and malignant lesions was 96% vs. 100%. The specificity was 60% in both of these technologies. SAFE-3000 autofluorescence bronchoscopy allows an early diagnosis of preneoplastic or neoplastic lesions according to the careful analysis of the bronchial mucosa, due to the complementarity of two modalities 'Twin Mode' and 'MIX'. Based on the relationship between the bronchoscopic goal and the histological results the MIX method contributes more of the new endoscopic technique findings.


Crosslinking profiles of elastin from anatomically defined regions of the lung.
Elastin was isolated and purified by a procedure which sequentially removed lipids, collagen, structural glycoproteins and the microfibrillar proteins. Crosslinking profiles were obtained by column chromatography either after reduction with 3[H]NaBH4 or after reaction with 14[C]NaCN and NH3. Examination of the crosslinking profiles of the elastins from various tissue regions revealed differences in the type, distribution and quality of crosslinks.


ClpB and HtpG facilitate de novo protein folding in stressed Escherichia coli cells.
DnaK-DnaJ-GrpE and GroEL-GroES are the best-characterized molecular chaperone systems in the cytoplasm of Escherichia coli. A number of additional proteins, including ClpA, ClpB, HtpG and IbpA/B, act as molecular chaperones in vitro, but their function in cellular protein folding remains unclear. Here, we examine how these chaperones influence the folding of newly synthesized recombinant proteins under heat-shock conditions. We show that the absence of either CIpB or HtpG at 42 degrees C leads to increased aggregation of preS2-beta-galactosidase, a fusion protein whose folding depends on DnaK-DnaJ-GrpE, but not GroEL-GroES. However, only the deltaclpB mutation is deleterious to the folding of homodimeric Rubisco and cMBP, two proteins requiring the GroEL-GroES chaperonins to reach a proper conformation. Null mutations in clpA or the ibpAB operon do not affect the folding of these model substrates. Overexpression of ClpB, HtpG, IbpA/B or ClpA does not suppress inclusion body formation by the aggregation-prone protein preS2-S'-beta-galactosidase in wild-type cells or alleviate recombinant protein misfolding in dnaJ259, grpE280 or groES30 mutants. By contrast, higher levels of DnaK-DnaJ, but not GroEL-GroES, restore efficient folding in deltaclpB cells. These results indicate that ClpB, and to a lesser extent HtpG, participate in de novo protein folding in mildly stressed E. coli cells, presumably by expanding the ability of the DnaK-DnaJ-GrpE team to interact with newly synthesized polypeptides.


Stir bar sorptive extraction-liquid desorption applied to the analysis of hop-derived bitter acids in beer by micellar electrokinetic chromatography.
Stir bar sorptive extraction-liquid desorption (SBSE-LD) has been applied as an efficient sample preparation method for the analysis of beer bitter acids. Extracts free of almost all interfering compounds were obtained, allowing simultaneous analysis of iso-alpha-acids and reduced iso-alpha-acids. A robust micellar electrokinetic chromatography (MEKC) method was developed that enables fast separation of iso-alpha-acids and reduced iso-alpha-acids. Quantitative data are in good agreement with results obtained by high-performance liquid chromatography (HPLC) using direct beer injection.


Occurrence and translocation of ustiloxins in rice false smut-occurred paddy fields, Hubei, China.
Ustiloxin A (UA) and ustiloxin B (UB), two major mycotoxins produced by the pathogen of rice false smut (RFS) during rice cultivation, have attracted increasing attentions due to their potential health risks. However, limited data are available about their occurrence and fate in paddy fields and contamination profiles in rice. In this study, a field study was performed to investigate the occurrence and translocation of UA and UB in RFS-occurred paddies. For the first time to our knowledge, we reported a ubiquitous occurrence of the two ustiloxins in the paddy water (range: 0.01-3.46 μg/L for UA and <0.02-1.15 μg/L for UB) and brown rice (range: 0.09-154.08 μg/kg for UA and <0.09-23.57 μg/kg for UB). A significant positive correlation was observed between ustiloxin levels in paddy water and brown rice (rs = 0.48-0.79, p < 0.01). The occurrence of ustiloxin uptake in water-rice system was also evidenced by the rice exposure experiment, suggesting paddy water might be an important source for ustiloxin accumulation in rice. These results suggested that the contamination of ustiloxins in rice might occur widely, which was supported by the significantly high detection frequencies of UA (96.6%) and UB (62.4%) in polished rice (149 samples) from Hubei Province, China. The total concentrations of ustiloxins in the polished rice samples collected from Hubei Province ranged from <20.7 ng/kg (LOD) to 55.1 μg/kg (dry weight). Further studies are needed to evaluate the potential risks of ustiloxin exposure in the environment and humans.


Coordinating growth and maturation - insights from Drosophila.
Adult body size in higher animals is dependent on the amount of growth that occurs during the juvenile stage. The duration of juvenile development, therefore, must be flexible and responsive to environmental conditions. When immature animals experience environmental stresses such as malnutrition or disease, maturation can be delayed until conditions improve and normal growth can resume. In contrast, when animals are raised under ideal conditions that promote rapid growth, internal checkpoints ensure that maturation does not occur until juvenile development is complete. Although the mechanisms that regulate growth and gate the onset of maturation have been investigated for decades, the emerging links between childhood obesity, early onset puberty, and adult metabolic disease have placed a new emphasis on this field. Remarkably, genetic studies in the fruit fly Drosophila melanogaster have shown that the central regulatory pathways that control growth and the timing of sexual maturation are conserved through evolution, and suggest that this aspect of animal life history is regulated by a common genetic architecture. This review focuses on these conserved mechanisms and highlights recent studies that explore how Drosophila coordinates developmental growth with environmental conditions.


Stable knockdown of CREB, HIF-1 and HIF-2 by replication-competent retroviruses abrogates the responses to hypoxia in hepatocellular carcinoma.
The fast proliferation of tumor cells develops faster than the vasculature, resulting, in most malignant tumors, in generation of hypoxic regions. Hypoxia renders solid tumors resistant to radiation and chemotherapeutics while providing opportunities for tumor-selective therapies targeting tumor hypoxia. Here we exploit two properties of tumors: propagation of tumor cells and ongoing generation of hypoxic regions to construct a system that preferentially leads to the death of tumor cells and thus hinders tumor growth. We constructed murine leukemia virus replication-competent (RCR) viruses that infect only propagating cells. These viruses express small hairpin RNAs (shRNAs) targeting cyclic AMP-response-element binding protein (CREB), hypoxia-inducible factors 1 (HIF)-1 or HIF-2 individually or all three together (X3). These viruses efficiently infected in vitro human hepatocellular carcinoma (HepG2 and FLC4) cells and established persistence of the virus and knocked down the expression of the regulators of the hypoxia-responding genes. Knockdown of either HIF-1 or CREB or both in hypoxia reduced the expression of hypoxia-response elements- and CRE-mediated gene expression, diminished cell proliferation and increased caspase-3 activity. We did not detect any significant effect of the efficiently knocked down HIF-2 on any of the functions tested in vitro. Moreover, severe combined immunodeficiency mice implanted subcutaneously with HepG2 stably infected with recombinant RCRs showed reduction of tumor growth and vascular endothelial growth factor expression, and no hypoxia-guided neovascularization. Combined treatment (RCRs+doxorubicin) improved efficacy in the context of in vitro hypoxia and in vivo (with either vACE-CREB or vACE-X3). This synergistic effect may lead to an improved efficacy and safety profile of the treatment that may result in fewer side effects.


The first finding of chromosome variations in wild-born western hoolock gibbons.
Hoolock gibbons (genus Hoolock) are a group of very endangered primate species that belong to the small ape family (family Hylobatidae). The entire population that is distributed in the northeast and southeast of Bangladesh is estimated to include only around 350 individuals. A conservation program is thus necessary as soon as possible. Genetic markers are significant tools for planning such programs. In this study, we examined chromosomal characteristics of two western hoolock gibbons that were captured in a Bangladesh forest. During chromosome analysis, we encountered two chromosome variations that were observed for the first time in the wild-born western hoolock gibbons (Hoolock hoolock). The first one was a nonhomologous centromere position in chromosome 8 that was observed in the two examined individuals. The alteration was identical in the two individuals, which were examined by G-band and DAPI-band analyses. Chromosome paint analyses revealed that the difference in the centromere position was due to a single small pericentric inversion. The second variation was a heterozygous elongation in chromosome 9. Analysis by sequential techniques of fluorescence in situ hybridization with 18S rDNA and silver nitrate staining revealed a single and an inverted tandem duplication, respectively, of the nucleolus organizer region in two individuals. These chromosome variations provide useful information for the next steps to consider the evolution and conservation of the hoolock gibbon.


Lipoic acid prevents Cr(6+) induced cell transformation and the associated genomic dysregulation.
Investigation of the transcription profile of cells transformed by Cr(6+) in vivo was undertaken. The objective was to elucidate genomic changes underlying the mechanism of action of the carcinogenic dose of Cr(6+)and their prevention using metabolic antioxidant lipoic acid (LA). Cr(6+) was administered intraperitoneally to LPS+TPA challenged Swiss albino mice in host mediated cell transformation assay using peritoneal macrophages in vivo. The cell transforming potential of Cr(6+) test doses was validated by gain of anchorage independent growth potential in soft agar and loss of Fc receptor on target cells. LA was administered in equimolar doses. Compared to non-transformed cells, the gene expression profile of transformed cells was found to be dysregulated substantially and in dose dependent manner. Genes showing down regulation were found to be involved in tumour suppression, apoptosis, DNA repair, and cell-cycle. A similar response was noted in the genes pertaining to immune system, morphogenesis, cell-communication, energy-metabolism, and biosynthesis. The co-administration of lipoic acid prevented the transcription dysregulation and cell transformation by Cr(6+) in vivo. The influenced pathways seem to be crucial for progression as well as mitigation of Cr toxicity; and their response to LA indicated their critical role in mechanism of anti-carcinogenic action of LA. Results are of importance to mitigate Cr(6+) induced occupational cancer hazard.


SPAK kinase is a substrate and target of PKCtheta in T-cell receptor-induced AP-1 activation pathway.
Protein kinase C-theta (PKCtheta) plays an important role in T-cell activation via stimulation of AP-1 and NF-kappaB. Here we report the isolation of SPAK, a Ste20-related upstream mitogen-activated protein kinase (MAPK), as a PKCtheta-interacting kinase. SPAK interacted with PKCtheta (but not with PKCalpha) via its 99 COOH-terminal residues. TCR/CD28 costimulation enhanced this association and stimulated the catalytic activity of SPAK. Recombinant SPAK was phosphorylated on Ser-311 in its kinase domain by PKCtheta, but not by PKCalpha. The magnitude and duration of TCR/CD28-induced endogenous SPAK activation were markedly impaired in PKCtheta-deficient T cells. Transfected SPAK synergized with constitutively active PKCtheta to activate AP-1, but not NF-kappaB. This synergistic activity, as well as the receptor-induced SPAK activation, required the PKCtheta-interacting region of SPAK, and Ser-311 mutation greatly reduced these activities of SPAK. Conversely, a SPAK-specific RNAi or a dominant-negative SPAK mutant inhibited PKCtheta- and TCR/CD28-induced AP-1, but not NF-kappaB, activation. These results define SPAK as a substrate and target of PKCtheta in a TCR/CD28-induced signaling pathway leading selectively to AP-1 (but not NF-kappaB) activation.


Immediate Lymphatic Reconstruction for Prevention of Secondary Lymphedema: A Meta-Analysis.
Secondary lymphedema remains one of the most notorious complications of axillary and pelvic lymph node surgery following mastectomy. There is a lack of high-level evidence found on the effectiveness of immediate lymphatic reconstruction (ILR) in preventing secondary lymphedema. This meta-analysis evaluates the outcomes of ILR for prevention of secondary lymphedema in patients undergoing different surgeries, and provides suggestions for lymphatic microsurgical preventive healing approach (LYMPHA). A review of PubMed, Embase, and Web of Science was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. All English-language studies published from January 1, 2009 to June 1, 2020 were included. We excluded non-ILR interventions, literature reviews/letters/commentaries, and nonhuman or cadaver studies. A total of 789 patients that were enrolled in 13 studies were included in our one-arm meta-analysis. A total of 13 studies (n=789) met inclusion criteria: upper extremity ILR (n=665) and lower extremity ILR (n=124). The overall incidence of lymphedema for upper extremity ILR was 2.7% (95%CI: 1.1%-4.4%) and lower extremity ILR was 3.6% (95%CI: 0.3%-10.1%). For upper extremity ILR, the average follow-up time was 11.6 ± 7.8 months and the LE incidence appeared to be the highest approximately 1 to 2 years postoperation. Lymphedema is a common complication in cancer treatment. ILR, especially LYMPHA, may be an effective technique to facilitate lymphatic drainage at the time of the index procedure but future studies will be required to show its short-term efficacy and long-term outcomes.


Lysine can replace arginine 67 in the mediation of covalent attachment of FAD to histidine 71 of 6-hydroxy-D-nicotine oxidase.
The requirements for FAD-attachment to His71 of 6-hydroxy-D-nicotine oxidase (6-HDNO) were investigated by site-directed mutagenesis. The following amino acid replacements were introduced into the sequence Arg67-Ser68-Gly69-Gly70-His71 of the 6-HDNO-polypeptide: 1) Arg67 was replaced with Ala (A1 mutant); 2) Ser68 was replaced with Ala (A2 mutant); and 3) Arg67 was replaced with Lys (K mutant). The substitution in mutant A2 had no effect on flavinylation, measured as [14C]FAD incorporation into apo-6-HDNO. Replacement of Arg67 with Ala prevented, but replacement with Lys permitted the flavinylation of His71. Mutant A1 showed no 6-HDNO activity, whereas the replacement of Ser with Ala in mutant A2 had only a slight effect on 6-HDNO activity. The substitution of Lys for Arg67, however, reduced the specific 6-HDNO activity in extracts of Escherichia coli cells expressing the mutant polypeptide from 50.3 to 17.5 milliunits/mg protein. It is concluded that a basic amino acid residue (Arg67 or Lys67) is required to mediate the attachment of FAD to His71, and while Lys can substitute for Arg67 in this function, it can only partially replace Arg67 in the enzyme reaction mechanism of 6-HDNO.


Protective role of simvastatin on isolated rabbit atrioventricular node during experimental atrial fibrillation model: role in rate control of ventricular beats.
The purpose of the present study was to determine (1) whether simvastatin (SV) modifies the rate-dependent conduction time and refractoriness of the atrioventricular (AV) node and (2) how it can change the protective mechanism of the AV node during atrial fibrillation (AF). Predefined stimulation protocols were applied to detect the electrophysiological parameters of the AV node, including atrial-His conduction time, effective refractory period (ERP), functional refractory period (FRP), concealed conduction, excitable index, and fatigue in two groups of isolated, perfused rabbit AV nodal preparations (N=16). The stimulation protocols (fatigue, recovery) were carried out during control and in the presence of SV (0.5, 0.8, 3, and 10 μM). Simulated AF was executed in a separate group (N=8), and specific indexes, including H-H mean, zone of concealment (ZOC), and concealed beats were recorded. SV, in a concentration-dependent manner, prolonged ERP, FRP, and Wenckebach cycle lengths. It (10 μM) significantly increased fatigue and the excitable index. In addition, SV elicited prolongation of ZOC and H-H mean at 3 and 10 μM. SV-evoked prolongation of nodal refractoriness and concealed conduction caused rate-dependent ventricular slowing effects during AF. The ability of simvastatin to decrease the excitable gap by its heterogeneous effects on nodal dual pathways proposes its protective role in AF.


Sequential and simultaneous "in series" hemodialysis and hemoperfusion in the management of theophylline intoxication.
Hemodialysis and hemoperfusion have been evaluated, and both are effective in removing theophylline. We report two consecutive cases of theophylline intoxication in which the sequential treatment of charcoal hemoperfusion and hemodialysis is contrasted to the simultaneous "in series" treatment of hemodialysis and charcoal hemoperfusion. Analysis of the two methodologies shows that the combined in series technique offers several advantages, including increased extraction efficiency, decreased time of hemoperfusion cartridge saturation, and rapid correction of electrolyte and acid-base abnormalities, and that it is well tolerated clinically. Simultaneous hemodialysis and charcoal hemoperfusion should be considered in cases of extreme theophylline intoxication.


Mechanisms of defective erythropoiesis and anemia in pediatric acute lymphoblastic leukemia (ALL).
Anemia frequently accompanies the diagnosis of acute lymphoblastic leukemia (ALL) in children and is considered to be one of the most common clinical complications of the disease. In addition, a low hemoglobin (Hb) level is often responsible for fatigue and other associated symptoms that cause a decline in the quality of life of these children. Traditionally, a number of contributing factors such as overcrowding of the marrow, coexisting infections, and nutritional deficits have been used to explain this phenomenon. However, recent advances in in vivo modeling and real-time ultrastructural analytical techniques have enabled researchers to examine leukemic bone marrow (BM) microenvironment more closely and helped to build mechanistic models of this process. Importantly, data from these studies show that in the majority of cases, the required stem cell populations and the erythropoietic growth mechanisms remain intact in leukemia. In this report, we aim to review the current state of knowledge regarding the cellular and molecular mechanisms implicated in the altered erythropoiesis at the time of diagnosis of leukemia. We propose that further understanding of the mechanisms of anemia in leukemia may help to manage some of its clinical consequences more effectively as well as to yield key insight into the process of leukemogenesis itself.


Endoscopic versus microscopic transsphenoidal pituitary adenoma surgery: a meta-analysis.
Endoscopic transsphenoidal surgery has gradually come to be regarded as a preferred option in the treatment of pituitary adenomas because of its advantages of improved visualization and its minimal invasiveness. The aim of this study was to compare and evaluate the outcomes and complications of endoscopic and microscopic transsphenoidal surgery in the treatment of pituitary adenomas. We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library and the Web of Science between January 1992 and May 2013. Studies with consecutive patients that explicitly and fully compared endoscopic and microscopic approaches in the treatment of pituitary adenomas were included. A total of 15 studies (n = 1,014 patients) met the inclusion criteria among 487 studies that involved endoscopic surgery and 527 studies that dealt with microscopic surgery. The rate of gross tumor removal was higher in the endoscopic group than in the microscopic group. The post-operative rates of septal perforation were less frequent in patients who underwent endoscopic surgery. There was no significant difference between the two techniques in the incidence rates of meningitis, diabetes insipidus, cerebrospinal fluid leak, epistaxis or hypopituitarism. The post-operative hospital stay was significantly shorter for the endoscopic surgery group compared with the microscopic surgery group (P < 0.05). There was no significant difference in the length of the operation (P > 0.05). The present study indicates that the endoscopic transsphenoidal approach is safer and more effective than microscopic surgery in the treatment of pituitary adenomas.


Device for humidification and controlled oxygenation during spontaneous breathing.
A system for humidification with adjustable flows and oxygen concentrations for use in spontaneously breathing patients is described.


Nongenomic effects of aldosterone: cellular aspects and clinical implications.
Nongenomic action of aldosterone has been observed in many cell types which often are different from the classic target tissues for mineralocorticoid action, such as vascular cells. As judged from their time scale and insensitivity toward inhibitors of protein synthesis, effects are not mediated by the classic mineralocorticoid receptor pathway. Here we summarize studies on rapid in vitro aldosterone effects, e.g. ion fluxes, and second messengers involved therein. Furthermore, several clinical studies on in vivo aldosterone action have shown rapid effects on cardiovascular parameters, among them baroreflex and vascular resistance. Taken together with the beneficial effect of aldosterone antagonism in heart failure patients that was demonstrated in the Randomized Aldactone Evaluation Study (RALES), aldosterone may be an equally important factor of the renin-angiotensin-aldosterone system in cardiovascular pathogenesis.


ZONMAIZE: EU-SMT-Project for the production of Certified Reference Materials (CRM) for the determination of zearalenone in maize.
This paper decribes the course of the project "ZONMAIZE" which has been funded by the European Commission within the Standards, Measurement and Testing Programme (SM&T). The project deals with the preparation and certification of both a maize naturally contaminated with zearalenone (ZON) (c=40-120 μg/kg, ZON in maize) and a blank maize material (<5 μg/kg ZON in maize) to improve the quality and comparability, of ZON analysis. In addition, a certified ZON calibrant (in acetonitrile) has been produced and ampouled (cZON=10 μg/l). After pre-analyses, homogenisation, drying and packaging, homogeneity and short time stability tests, two preliminary intercomparison studies and one certification exercise were carried out by a consortium of 27 European laboratories from 11 different European countries.


Mapping the distribution of differentiation potential for intestine, muscle, and hypodermis during early development in Caenorhabditis elegans.
We have analyzed the differentiation potential of cells in early embryos of Caenorhabditis elegans by assessing the production of markers for intestinal, muscle, and hypodermal cell differentiation in cleavage-arrested blastomeres. Our results show that differentiation potential does not always segregate during cleavage in a linear fashion, i.e., a blastomere can express a differentiation potential that is absent in its parent blastomere and vice versa. Furthermore, the expression of a particular differentiation program by certain cleavage-arrested blastomeres is an exclusive event in that each cell will express only one program of differentiation, even though it may have the potential to express several.


DrGaP: a powerful tool for identifying driver genes and pathways in cancer sequencing studies.
Cancers are caused by the accumulation of genomic alterations. Driver mutations are required for the cancer phenotype, whereas passenger mutations are irrelevant to tumor development and accumulate through DNA replication. A major challenge facing the field of cancer genome sequencing is to identify cancer-associated genes with mutations that drive the cancer phenotype. Here, we describe a powerful and flexible statistical framework for identifying driver genes and driver signaling pathways in cancer genome-sequencing studies. Biological knowledge of the mutational process in tumors is fully integrated into our statistical models and includes such variables as the length of protein-coding regions, transcript isoforms, variation in mutation types, differences in background mutation rates, the redundancy of genetic code, and multiple mutations in one gene. This framework provides several significant features that are not addressed or naively obtained by previous methods. In particular, on the observation of low prevalence of somatic mutations in individual tumors, we propose a heuristic strategy to estimate the mixture proportion of chi-square distribution of likelihood ratio test (LRT) statistics. This provides significantly increased statistical power compared to regular LRT. Through a combination of simulation and analysis of TCGA cancer sequencing study data, we demonstrate high accuracy and sensitivity in our methods. Our statistical methods and several auxiliary bioinformatics tools have been incorporated into a computational tool, DrGaP. The newly developed tool is immediately applicable to cancer genome-sequencing studies and will lead to a more complete identification of altered driver genes and driver signaling pathways in cancer.


Parsimonious prediction of Wechsler Memory Scale, Fourth Edition scores: immediate and delayed memory indexes.
Research on previous versions of the Wechsler Memory Scale (WMS) found that index scores could be predicted using a parsimonious selection of subtests (e.g., Axelrod & Woodard, 2000). The release of the Fourth Edition (WMS-IV) requires a reassessment of these predictive formulas as well as the use of indices from the California Verbal Learning Test-II (CVLT-II). Complete WMS-IV and CVLT-II data were obtained from 295 individuals. Six regression models were fit using WMS-IV subtest scaled scores-Logical Memory (LM), Visual Reproduction (VR), and Verbal Paired Associates (VPA)-and CVLT-II substituted scores to predict Immediate Memory Index (IMI) and Delayed Memory Index (DMI) scores. All three predictions of IMI significantly correlated with the complete IMI (r = .92 to .97). Likewise, predicted DMI scores significantly correlated with complete DMI (r = .92 to .97). Statistical preference was indicated for the models using LM, VR, and VPA, in which 97% and 96% of the cases fell within two standard errors of measurement (SEMs) of full index scores, respectively. The present findings demonstrate that the IMI and DMI can be reliably estimated using two or three subtests from the WMS-IV, with preference for using three. In addition, evidence suggests little to no improvement in predictive accuracy with the inclusion of CVLT-II indices.


Outbreak of Pseudomonas aeruginosa infections caused by commercial piercing of upper ear cartilage.
Sporadic infections following ear piercing are well documented, but common-source outbreaks are rarely recognized. To investigate reports of auricular chondritis subsequent to commercial ear piercing. Outbreak investigation by Oregon public health agencies, including cohort study of persons pierced at a jewelry kiosk in August-September 2000, environmental sampling, and molecular subtyping of isolates. Confirmed cases had Pseudomonas aeruginosa cultured from ear wounds. Suspected cases had signs and symptoms of external ear infection, including drainage of pus or blood for at least 14 days. Risk factors for infection and comparison of bacterial isolates by molecular subtyping. From 186 piercings in 118 individuals, we identified 7 confirmed P aeruginosa infections and 18 suspected infections. Confirmed cases were 10 to 19 years old. Most were initially treated with antibiotics ineffective against Pseudomonas. Four were hospitalized, 4 underwent incision and drainage surgeries (1 as an outpatient), and several were cosmetically deformed. Upper ear cartilage piercing was more likely to result in either confirmed or suspected infection than was lobe piercing (confirmed: RR undefined, P<.001; suspected: RR, 3.6; 95% confidence interval, 1.5-8.5). All persons with confirmed infections had their ear cartilage pierced with an open, spring-loaded piercing gun. Patient isolates were indistinguishable by molecular subtyping, and matching isolates were recovered from a disinfectant bottle and nearby sink. At least 1 worker admitted sometimes spraying the disinfectant on the ear studs before piercing. Ear cartilage piercing is inherently more risky than lobe piercing. Clinicians should respond aggressively to potential auricular chondritis and consider Pseudomonas a possible cause pending culture results.


Inflammatory Markers in Suction Blister Fluid: A Comparative Study Between Interstitial Fluid and Plasma.
Biomarker analysis allows for the detection and prediction of disease as well as health monitoring. The use of interstitial fluid (ISF) as a matrix for biomarkers has recently gained interest. This study aimed to compare levels of inflammatory markers in ISF from suction blister fluid (SBF) and plasma. Plasma and SBF were collected from 18 healthy individuals. Samples were analyzed for 92 inflammation-related protein biomarkers by Proximity Extension Assay (PEA). Protein profiles in the two matrices were compared using traditional and multivariate statistics. Out of 92 targeted proteins, 70 were successfully quantified in both plasma and SBF. Overall, plasma and SBF displayed distinct protein profiles with up to 40-fold difference in abundance of specific proteins. The levels of 25 proteins were significantly correlated between plasma and SBF and several of these were recognized as potential markers to monitor health using ISF. Skin ISF and plasma have unique protein profiles but many inflammatory markers are proportionally related between the matrices at the individual level. ISF is a promising biofluid for the monitoring of biomarkers in clinical studies and routine analyses.


New media for the semiselective isolation and enumeration of Xanthomonas campestris pv. mangiferaeindicae, the causal agent of mango bacterial black spot.
Mango bacterial black spot, caused by Xanthomonas campestris pv. mangiferaeindicae, is a potentially severe disease in several tropical and subtropical areas. Data describing the life cycle of the pathogen are needed for improving integrated pest management strategies. Because of the important bacterial microflora associated with mango leaves, isolation of the pathogen is often difficult using nonselective agar media. A previously developed medium, BVGA, failed to inhibit several Gram-negative saprophytic bacteria, especially those belonging to Enterobacteriaceae. Two new semiselective media were developed. The selectivity of KC and NCTM3 media was achieved using cephalexin 40 mg l(-1), kasugamycin 20 mg l(-1) and neomycin 1 mg l(-1), cephalexin 100 mg l(-1), trimethoprime 5 mg l(-1), pivmecillinam 100 mg l(-1) respectively. Plating efficiencies ranged from 76 to 104% and from 78 to 132% for KC and NCTM3 respectively. The new media allowed the growth of X. campestris pv. mangiferaeindicae whatever its country of isolation. The pathogen was repeatedly isolated with these media from asymptomatic leaves sampled in growth chamber experiments. This work provides a description of new semiselective media, which should be valuable tools to study the ecology and epidemiology of X. campestris pv. mangiferaeindicae.


Ultrastructural changes in acinar cells of hamster pancreas in chemically induced carcinogenesis.
Ultrastructural changes arising in the pancreas of the Syrian golden hamster after treatment with N-nitrosobis (2-oxopropyl) amine (BOP) were studied at short intervals. Alterations were found in acinar cells i.e. loss of zymogen granules, dilatation of granular endoplasmic reticulum, depolarization, irregular nucleus and separation of lateral surfaces (intermembranary spaces). As a result, the compact morphology of normal acini switched towards a new structure resembling a pseudo-ductule. Such alterations occurred from the 3rd month and preceded tumor formation. It is noteworthy that ducts and islets of Langerhans appeared unaltered in all instances. These results are consistent with the hypothesis that BOP induced pancreatic adenocarcinoma in hamsters originates in the acinar cell.


No lens changes caused by simvastatin results from a prospective drug safety study.
45 patients suffering from a primary hypercholesterolemia were treated with Simvastatin. Additionally to internal visits regular ophthalmologic examinations were performed. The main interest concerning the ophthalmologic examination was directed toward the documentation and measurement of lens opacities by means of Scheimpflug photography. Moreover, every 6 months a complete regular ophthalmologic examination was carried out. We present the results after a time period of 2 years. Relevant changes in clinical findings could not be found. In some patients the Scheimpflug measurement revealed an increase in light scattering. These findings, however, were within the limit of normal age related changes.


Control of bacterial contamination of washbasin taps and output water using Ecasol: a one-year study.
Contaminated washbasin taps and output water are an important source of bacteria that may cause nosocomial infection. A five-week pretreatment study of hot and cold water from 15 washbasin taps at Dublin Dental Hospital showed consistently heavy contamination by aerobic heterotrophic bacteria: mean bacterial counts of 482.5 [standard deviation (SD) 293] colony-forming units (cfu)/mL and 5022 (SD 4322) cfu/mL, respectively. To minimize microbial contamination of washbasin taps and output water in the long term using the electrochemically generated, pH-neutral disinfectant, Ecasol. Initially, the 15,000-L water tank providing cold and hot water to washbasins, calorifiers and the distribution network were drained and sediment was removed. The system was shock-dosed with Ecasol 100 ppm to eradicate gross contamination and biofilms. Thereafter, tank water was automatically maintained at Ecasol 2.5 ppm prior to distribution. The microbiological quality of water from five sentinel washbasin taps was monitored weekly for 54 weeks using R2A agar. The mean counts for hot, cold, mains and tank water during the 54-week study period were 1 (SD 4) cfu/mL, 2 (SD 4) cfu/mL, 205 (SD 160) cfu/mL and 0 cfu/mL, respectively. Swab samples of 33/40 taps, each tested on three separate occasions, yielded no growth on R2A agar, while five samples yielded <20 cfu/swab and two samples yielded >200 cfu/swab. No detrimental effects due to Ecasol were observed in the water network. Ecasol consistently minimized bacterial contamination of washbasin taps and output water in a dental hospital setting.


Spirituality of health workers: a descriptive study.
The World Health Organisation defines health as "a state of complete physical, mental and social well-being, not merely the absence of disease or infermity". In May 1984 the spiritual dimension became part of WHO Member States' strategies for health. The WHO defines quality of life as "individuals' perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns." To test health workers' quality of life (QOL) with regard to their spirituality. The WHOQOL SRPB-domain 6 was used. It denotes an individual's perception of quality of life, as far as spirituality is concerned. The sample was formed by 116 health workers from three wards of three Rehabilitation Hospitals owned by the Brothers of Saint John of God, in Northern Italy. The sample shows means above the mid-point in all facets denoting reasonably good quality of life in the domain of spirituality. The most significative variables are: health conditions (p = .001*), religiousness (p < or = .0005**), personal creed (p < or = .0005**). The sample's quality of life in the domain of spirituality is reasonably good. Our findings suggest that spirituality is associated with the subjective perception of people's health status.


No "back to normal" after COVID-19 for our failed drug policies.
Before COVID-19 pandemic, advocates had long urged drug policy reforms based on health, security, civil rights, racial justice, fiscal stewardship, and other considerations. In the United States, such calls went largely unanswered. In response to COVID-19, public health and occupational safety concerns have rapidly transformed some drug policies, along with their enforcement. Almost contemporaneously, nationwide protests against violence and racism by militarized police have highlighted the enduring legacy of the Drug War in fueling carceral systems. Disruption from these historical events provides a once-in-a-century opportunity to reconsider the legal architecture of drug policy and policing-both in the U.S. and elsewhere. Rather than returning to a fundamentally broken and inequitable status quo, we urge envisioning a new drug policy in service to life, liberty, and the pursuit of happiness.


A clinical follow up of unemployed. I: Lifestyle, diagnoses, treatment and re-employment.
To describe morbidity, lifestyle and re-employment in a representative sample of unemployed people. A two-year follow up of a routine health examination consisting of a structured interview, a clinical examination and the doctor's conclusions and advice. Four municipalities in Greenland, southern Norway. A representative sample aged 16 to 63 who had been registered with the labour market authorities for more than 12 weeks. Self-reported diseases were more common in the study group than were found in employed people, especially musculoskeletal and mental disorders. The prevalence of medical diagnoses was high. Smoking was reported by nearly twice as many unemployed as the reference population. Heavy alcohol consumption was more prevalent in the unemployed men. Blood pressure was lower than in the reference population. Cholesterol was higher in the unemployed women. Many needed counselling or referrals. Having a medical diagnosis reduced the chances of re-employment two years later. Thus, health-related selection for re-employment seems to explain some of the excess morbidity among unemployed people. The long-term unemployed is a group with high morbidity and unhealthy lifestyle. General practitioners should be aware of this pattern in clinical and preventive work.


Interspecies differences in plasma protein binding of MS-275, a novel histone deacetylase inhibitor.
MS-275 (MS-27-275; 3-pyridylmethyl-N-[4-[(2-aminophenyl)-carbamoyl]-benzyl-carbamate) is a histone deacetylase inhibitor under clinical development as an anticancer agent. Here, we examined the role of protein binding as a possible determinant of the pharmacokinetic behavior of MS-275. The distribution of MS-275 in plasma was studied in vitro using equilibrium dialysis and ex vivo in five cancer patients receiving the drug orally at a dose of 10 mg/m(2). The dialysis method uses a tracer amount of [G-(3)H]MS-275 on a 96-well microdialysis plate with a 5-kDa cut-off membrane, and requires 250 microl sample. The time to equilibrium was established to be within 5 h, and the mean unbound fraction of MS-275 (f (u)) over a presumed therapeutic concentration range in healthy volunteer human plasma was 0.188 +/- 0.0075 as compared to 0.168 +/- 0.0144 in cancer patients. The binding was concentration-independent, indicating a low affinity, possibly non-specific and non-saturable process. MS-275 was found to bind in decreasing order to plasma > alpha(1)-acid glycoprotein > albumin. Among 19 tested drugs, a slightly increased f (u) was observed in the presence of only ibuprofen (f (u), 0.236 +/- 0.001) and metoclopramide (f (u), 0.270 +/- 0.042), suggesting weakly competitive displacement from protein-binding sites (P < 0.01). Compared to humans, f (u) was significantly higher in plasma from mouse (0.376), rat (0.393), rabbit (0.355), dog (0.436), and pig (0.439) (P < 0.01), which may explain, in part, the species-dependent pharmacokinetic profile of MS-275 observed previously.


Liver transplantation and hepatitis C.
Hepatitis C virus (HCV)-related end-stage cirrhosis with/without hepatocellular carcinoma is the primary indication for liver transplantation in many countries. Unfortunately, HCV is not eliminated by transplantation and graft re-infection is the rule, resulting in HCV-related graft disease. The natural history of recurrent hepatitis is variable; overall, progression to cirrhosis occurs in 20-30% and allograft failure in 10% after 5-10 years from transplantation. The use of poor quality organs, particularly from old donors, has a significant negative impact on disease severity and transplant outcome. In contrast, antiviral therapy, particularly if it results in permanent eradication of the virus, is associated with improved histology, reduced rate of graft decompensation and enhanced outcome. Disease monitoring, through protocol liver biopsies and new non-invasive tools, is essential to select patients at need of antiviral therapy. Peginterferon with ribavirin, used similarly to what is done in the non-transplant setting, is currently the treatment of choice; sustained viral response is achieved in about 35% of cases. Side effects, particularly anemia, are extremely frequent and sometimes severe (rejection, de novo autoimmune hepatitis). Retransplantation (RT) is the last option for the small subset of patients with allograft failure due to HCV recurrence who fulfil minimum criteria based on RT survival models.