[Intermittent fever: rare expression of an adenocarcinoma of the ampulla of Vater].
Prolonged intermittent fevers are frequently seen in internal medicine and they constitute a real diagnosis challenge. Infection, auto-immune disease and neoplasy are the most common causes. We report here a 48 year-old man with a prolonged intermittent fever. At first, all his assessments were negative and it's only secondary, as clinical and biological disturbances occur that the diagnosis of adenocarcinoma of the ampulla has been done. Neoplasms represent a rare cause of intermittent prolonged fever, but we must always keep them in mind. In this case, any specific symptom was initially present to end up quickly to the solution.


Uncovering and testing the fuzzy clusters based on lumped Markov chain in complex network.
Identifying clusters, namely groups of nodes with comparatively strong internal connectivity, is a fundamental task for deeply understanding the structure and function of a network. By means of a lumped Markov chain model of a random walker, we propose two novel ways of inferring the lumped markov transition matrix. Furthermore, some useful results are proposed based on the analysis of the properties of the lumped Markov process. To find the best partition of complex networks, a novel framework including two algorithms for network partition based on the optimal lumped Markovian dynamics is derived to solve this problem. The algorithms are constructed to minimize the objective function under this framework. It is demonstrated by the simulation experiments that our algorithms can efficiently determine the probabilities with which a node belongs to different clusters during the learning process and naturally supports the fuzzy partition. Moreover, they are successfully applied to real-world network, including the social interactions between members of a karate club.


Expression of immunoglobulin genes in transgenic mice and transfected cells.
Immunoglobulin (Ig) genes are expressed sequentially (first H-, then L-chain genes) during the development of B lymphocytes. These studies, performed with transgenic mice and transfected cells, were aimed at the regulation of turning on and off the rearrangement of Ig genes. The specific recombinase is active in pre-B cells, but not in plasma cells. Production of membrane mu, but not secreted mu or gamma-2b, turns off rearrangement of H genes. Feedback inhibition of kappa-gene rearrangement requires kappa and membrane mu. Kappa alone or in combination with secreted mu does not stop recombination. Mouse lambda genes were mapped by deletion analysis and pulsed-field gel electrophoresis. The gene order is V2-C2,4-V1-C3,C1. The distance between V2 and C2 is 74 kb, but that between V1 and C3, 1 is only 20 kb. V2 and C3, 1 are over 190 kb apart. Lambda genes appear to be rearranged in a subset of B cells that do not respond to feedback inhibition at the pre-B cell stage. Lambda and kappa genes are both rearranged and potentially functional in these cells. Kappa genes may then be deleted by recombination of a sequence (described by Selsing and Siminovitch et al.) downstream of C-kappa with sequences upstream of C-kappa. Presumably the recombinase is eventually inactivated in kappa-lambda cells by a mechanism that is different from H-kappa feedback.


In situ nick translation of human metaphase chromosomes with the restriction enzymes MspI and HpaII reveals an R-band pattern.
Several restriction enzymes (HindIII, HaeIII, MspI, HpaII, EcoRI, KpnI, and NotI) were evaluated for their ability to induce bands in human metaphase chromosomes during in situ nick translation. MspI and HpaII were able to induce a completely developed R-band pattern. Preferential cleavage of R-band chromatin is due to the presence of unmethylated CpG-residues present in CpG-rich islands, which are apparently unevenly distributed and mainly concentrated in R-bands.


Bond strength and monomer conversion of indirect composite resin restorations, Part 1: Light vs heat polymerization.
To assess the resin microtensile bond strength (MTBS) and the monomer conversion (MC) of indirect composite resin restorations made of three different materials. Two light-polymerized direct materials (Filtek Z100 and Premise) and one light- and heat-polymerized indirect material (Premise Indirect) were used. For MTBS testing, 42 cylindrical samples were fabricated (7 pairs per material). Surface conditioning included airborne-particle abrasion, cleaning, and application of a silane. Cylinders were bonded to each other using adhesive resin (Optibond FL). Specimens were stored in water for 24 h. Another 15 cylinders (5 per material) were fabricated for MC measurements (FT-IR) immediately and at 24 h. The MTBS data were submitted to one-way ANOVA and the MC to two-way ANOVA (material and storage time) (α=0.05), followed by post-hoc comparisons with the Tukey test. The MTBS to Z100 was 72.2 MPa, significantly higher than that to Premise (48.4 MPa) and Premise Indirect (52.7 MPa). The immediate MC was similar for all materials (range 51% to 56%) and significantly increased at 24 h (range 57% to 66%), except for Z100. Premise Indirect showed the highest MC (66% at 24 h). Z100 showed better "bondability" than Premise and Premise Indirect. Premise Indirect, with its heat initiator, did not present a higher MC.


Comparison of physicochemical properties of three nanostructure composite TiO2 films and their photocatalytic properties.
Three type of photocatalytic composite films, MPC500SGF-MC, ANPSGF-MC and P25SGF-MC, have been synthesized by a modified sol-gel method using different particle size of TiO2 nanopowder MPC500, ANP and P25, respectively. Methyl cellulose (MC) was added as a template to the sol for stress reduction which improved not only the amount of crystalline material immobilized on the support, but also the nanosize of the films calcined at 500 degrees C. The physicochemical properties, including surface morphology, crystallinity, crystal size and adhesion on glass substrate, of the three types of films were investigated by SEM, XRD and the scratch test. The photocatalytic activities of the films were compared using methyl orange (MO) as a model organic contaminant in water. The results on photocatalytic degradation of MO showed that the increase in photocatalytic activity for P25SGF-MC, compared with that of MPC500SGF-MC and ANPSGF-MC composite films. The optimum degradation conditions of MO solution are determined. This study proves that particle size of starting TiO2 material is important for the preparation of nanostructured TiO2 composite film with enhanced photocatalytic activity and excellent adhesion on the glass substrate.


Plasma prorenin and renin in childhood and adolescence.
We studied 108 subjects (age range, 4 to 76 years) to determine the effect of age on prorenin (inactive renin), active renin, and plasma renin activity in normal children, adolescents, and adults. Children and adolescents had lower prorenin concentrations and higher plasma renin activity and active renin concentrations than did adults. Prorenin concentrations were positively correlated with age over the range of 4 to 76 years, while plasma renin activity and active renin concentration were negatively correlated with age. Plasma prorenin and active renin concentrations from umbilical cord blood samples obtained from 11 newborns and arterial samples obtained from five infants were higher than those in samples obtained from children or adults.


[New physical methods in osteoarthritis treatment].
Osteoarthritis is a chronic disease in which the pathological processes start from the catabolism of cartilage extracellular matrix and next extend on the whole joint. Therefore, it is important to diagnose the disease and determining treatment, selecting individually for each patient. The main health problems presents by every patients is pain, which decreases the everyday functioning and quality of life. The paper presents the definition of the disease and new therapeutic methods which improve the quality of life, as well as reduce intensity of pain.


Effects of a continuous quality improvement program on helicopter liftoff times.
The continuous quality improvement (CQI) process addresses concerns from a systems approach, employing committees of employees rather than selected management personnel to identify and solve problems, improve patient care and efficiency, and enhance customer satisfaction. Little is known about the effects of the CQI process on an aeromedical program. To create a CQI program within an aeromedical program and to investigate its effect on helicopter liftoff times for scene responses. A CQI program was established at a busy aeromedical service that completed 897 missions in the previous year. A concern identified by the CQI committee was delays in helicopter liftoff time after receipt of mission requests for scene responses. Each component necessary for liftoff (dispatch, pilot weather check, and crew response) was identified, time limits were set for each, new procedures were developed, and all staff received training on the new procedures. Computer tracking of each of the identified component times allowed comparison of data pre and post procedure implementation of the CQI-developed procedures. After CQI changes in procedures were implemented, there were a total of 30 delays out of 323 calls (9% of liftoffs for on-scene flights). This represents a 6% reduction in total delays. The largest drop in component times was observed in crew response (2.6%). An unanticipated 10% drop in response times for interhospital liftoffs also occurred, presumably due to heightened awareness of the service to response times in general. These findings suggest that employing a program utilizing CQI concepts can shorten helicopter liftoff times and improve response times in aeromedical programs.


Impact of transport pathways on the time from symptom onset of ST-segment elevation myocardial infarction to door of coronary intervention facility.
Reducing total ischemic time is important in achieving better outcome in ST-segment elevation myocardial infarction (STEMI). Although the onset-to-door (OTD) time accounts for a large portion of the total ischemic time, factors affecting prolongation of the OTD time are not established. The purpose of this study was to determine the impact of transport pathways on OTD time in patients with STEMI. We retrospectively studied 416 STEMI patients who were divided into 4 groups according to their transport pathways; Group 1 (n = 41): self-transportation to percutaneous coronary intervention (PCI) facility; Group 2 (n = 215): emergency medical service (EMS) transportation to PCI facility; Group 3 (n = 103): self-transportation to non-PCI facility; and Group 4 (n = 57): EMS transportation to non-PCI facility. OTD time was compared among the 4 groups. Median OTD time for all groups combined was 113 (63-228.8)min [Group 1, 145 (70-256.5); Group 2, 71 (49-108); Group 3, 260 (142-433); and Group 4, 184 (130-256)min]. OTD time for EMS users (Groups 2 and 4) was 138 min shorter than non-EMS users (Groups 1 and 3). Inter-hospital transportation (Groups 3 and 4) prolonged OTD by a median of 132 min compared with direct transportation to PCI facility (Groups 1 and 2). Older age, history of myocardial infarction, prior PCI, shock at onset, high Killip classification, and high GRACE Risk Score were significantly more frequent in EMS users. Self-transportation without EMS and inter-hospital transportation were significant factors causing prolongation of the OTD time. Approximately 35% of STEMI patients did not use EMS and 21% of patients were transported to non-PCI facilities even though they called EMS. Awareness in the community as well as among medical professionals to reduce total ischemic time of STEMI is necessary; this involves educating the general public and EMS crews.


[Incidence and control of the American giant liver fluke, Fascioloides magna, in a population of wild ungulates in the Danubian wetlands east of Vienna].
Fascioloides magna,the giant liver fluke, is an introduced parasite imported to Europe with infected game which is endemic in the Austrian wetlands of the Danube from Vienna to the Slovakian border. Due to its pathogenicity (especially in roe deer) and its potential of transmission to domestic ruminants a project on the epidemiology and control of this parasite was carried out between 2000 and 2005. To assess distribution faecal droppings from red deer were collected in an area along the Danube and livers of red and roe deer shot or found dead were examined. Simultaneously, triclabendazole-medicated feed was offered repeatedly in several areas of known fluke presence from 2001. The average prevalence of infection as demonstrated by Fascioloides eggs in droppings (n = 145) was 6.3%, with > 50% in some areas. Infection rates decreased from 11.3% (01/2001) to 1.5% (04/2002) in the whole area. In Fischamend, a highly endemic area, prevalences in monthly samples (n = 25) decreased from 70% (01/2001) to less than 1% (01/2005). Similarly, the number of eggs per gram of faeces was significantly reduced. Of 457 red deer livers 15.8% were positive. In the Fischamend area, a reduction of positive livers was also found (2000:100%; 2005:13%), as well as a reduction of the numbers of flukes/liver. Control of F. magna in the Danubian wetlands by anthelmintic treatment proved to be successful although eradication was not achieved.


Distal Bypass Versus Infrageniculate Endovascular Intervention for Chronic Limb-Threatening Ischemia.
Chronic limb-threatening ischemia (CLTI) carries a high risk of amputation and warrants urgent intervention. CLTI involving the infrageniculate vessels, in particular, carries a considerably higher risk of major limb amputation. Open surgical bypass is the historical gold standard for the treatment of tibial arterial disease; however, endovascular therapy provides an attractive alternative in this high-risk patient population. In this article, we review the existing literature regarding distal bypass and infrageniculate endovascular intervention in patients with CLTI.


Synthesis of MoS2/graphene hybrid supported Au and Ag nanoparticles with multi-functional catalytic properties.
The detection and removal of nitroaromatic compounds is an important issue for environmental protection. In this study, a hybrid of molybdenum disulfide (MoS2) and graphene (GR) was first synthesized using a facile hydrothermal method. Au and Ag nanoparticles were then deposited onto the surface of the MoS2/GR hybrid with sodium citrate as the stabilizer and reductant. Compared to using pure MoS2 as the support, the obtained Au (Ag)-MoS2/GR composites showed improved activity for electrochemical detection and chemical reduction of 4-nitrophenol. The activity enhancement appears to be due to the addition of GR, which could improve the conductivity as well as provide more active sites. The successful synthesis of Au (Ag)-MoS2/GR composites could provide new multi-function catalysts for environmental protection.


When the Pandemic Will Be Over: Lots of Hope and Some Concerns.
The COVID-19 pandemic significantly threatened healthcare systems worldwide. The worst-hit population has been represented by older people with underlying chronic comorbidities, while children and adolescents developed mild or asymptomatic forms of the disease. However, certain medical conditions (i.e., obesity, respiratory, or neurological or immune disorders) may increase the risk for poor health outcomes even in young and middle-aged people. Beyond the direct negative effects of the infection, the pandemic posed several health challenges through an increase in psycho-social issues (i.e., anxiety, depression, fatigue, sleep alterations, loneliness, reduced assistance, and loss of income). Accordingly, the pandemic is negatively impacting the accumulation of the functional reserves of each individual, starting from early life. With the long-term effects of the pandemic to be seen in the coming years, clinicians must be prepared to manage such high clinical complexity of people they encounter, through the implementation of multidimensional and multidisciplinary interventions.


Studies on the beta-oxidation of valproic acid in rat liver mitochondrial preparations.
Incubation of valproic acid (VPA) with freshly isolated rat liver mitochondria led to the identification of the beta-keto acid, 3-oxo-VPA, together with three unsaturated metabolites, viz. delta 2(E)-VPA, delta 3-VPA, and delta 2(E),3'(E)-VPA. The corresponding beta-hydroxy acid, 3-hydroxy-VPA, was not detected as a metabolite of VPA in this in vitro system. Studies with subcellular fractions of rat liver and with inhibitors of fatty acid metabolism demonstrated that these metabolites are products of the beta-oxidation system in mitochondria, and are not formed to any significant extent by the related peroxisomal beta-oxidation complex. When incubations with mitochondria were carried out in a medium enriched in H218O, metabolites were labeled in a manner consistent with the involvement of coenzyme A thioester intermediates. Incubation of the authentic metabolites with mitochondrial preparations showed that delta 2(E)-VPA, delta 3-VPA, and delta 2(E),3'(E)-VPA are interconverted by isomerization and reduction processes, and that all three serve as precursors of 3-oxo-VPA. It is concluded that VPA is a substrate for beta-oxidation in liver mitochondria, and that competition by VPA for enzymes and/or cofactors of the fatty acid beta-oxidation complex may contribute to VPA-mediated inhibition of fatty acid metabolism and associated hepatic steatosis.


Comparison between capillary electrophoresis and liquid chromatography for the determination of diclofenac sodium in a pharmaceutical tablet.
Two novel analytical methodologies using capillary electrophoresis (CE) and liquid chromatography (LC) were developed and compared for the determination of diclofenac sodium in commercial and simulated tablet formulations. The CE analysis was performed in a bare fused-silica capillary with 75 microm id and total length of 50 cm (28 cm to the detector) with a buffer solution of 20 mM sodium tetraborate, pH 9.23. The applied voltage was 20 kV, and acetaminophen was used as the internal standard (IS). The LC analysis was performed with a LiChrospher 100 RP-18 (5 microm) column and a mobile phase of methanol-diluted glacial acetic acid (0.3 parts in 2500; 75 + 25) at a flow rate of 0.9 mL/min with propylparaben as the IS. In both analyses, detection was by ultraviolet absorption at 276 nm. Under optimized conditions, the CE migration times for the diclofenac sodium standard and acetaminophen (IS) were 2.07 and 1.59 min, respectively, and the LC retention times for the diclofenac sodium standard and propylparaben (IS) were 3.98 and 2.26 min, respectively. The resolution and efficiency for CE were 14.2 and 1.6 x 10(5) plates/m, respectively, and for LC, 5.0 and 8.6 x 10(3) plates/m, respectively. Calibration curves of peak area versus concentration gave correlation coefficients of 0.9992 for CE and 0.9994 for LC. The limits of detection and quantitation were 8.40 and 25.46 microg/mL, respectively, for CE and 4.60 and 13.93 microg/mL, respectively, for LC. Coefficients of variation were 1.68 and 0.37% for CE and LC, respectively. Average recoveries obtained with CE and LC were 103.12+/-0.90 and 99.59+/-0.21%, respectively. Although both methodologies were shown to be suitable for the determination of diclofenac sodium in tablets, performing in a similar manner with regard to several aspects (linearity, recovery, and specificity), CE provided faster analysis and better column efficiency, whereas LC provided superior repeatability and sensitivity.


Active Peripheral Osteoma in the Mandibular Notch: A Longitudinal Clinical Report.
Osteomas are benign osteogenic tumors composed of mature compact or cancellous bone and are characterized by slow, painless growth. A peripheral osteoma located in the mandibular notch is extremely rare. Here, we describe the case of a 38-year-old woman with an active peripheral osteoma in the mandibular notch for long-term follow up. Surgical resection of the lesion was performed, which resulted in the improvement of the mandibular function and temporomandibular dysfunction. This is the first report of resection surgery after confirming the activity of peripheral osteoma by bone scintigraphy. Creating a three-dimensional model of the mandible promises an accurate surgical plan.


Programmed cell death in developing grafts of fetal substantia nigra.
Intracerebral transplants of ventral mesencephalic (VM) tissue have been well characterized. VM grafts contain numerous tyrosine hydroxylase immunoreactive neurons which send axons into the host brain. Transplanted neurons in VM grafts develop normally in that they contain tyrosine hydroxylase and GAP43. An overlooked aspect of graft development is cell death. It has been suggested that cell death in VM grafts was mostly necrotic. However, recent work in this laboratory suggested that developing grafts contain numerous apoptotic cells. In the present paper morphological, histochemical, and molecular correlates of apoptosis were used to assay cell death during VM graft development. At early times (5-15 days) after grafting VM grafts contained numerous apoptotic cells. In older grafts (21 and 28 days) few apoptotic cells were observed. In situ end labeling of fragmented DNA with biotinylated dUTP showed that early grafts contained numerous positive cells. The expression of RP8, a molecular correlate of apoptotic cell death, occurred in early grafts, but was not detectable in older grafts. These results indicate that apoptosis is a normal part of VM graft development. As in naturally developing neural systems, cell death in grafts may function to eliminate cells that fail to connect to appropriate targets.


Ifosfamide-induced nephrogenic diabetes insipidus responsive to supraphysiologic doses of intravenous desmopressin.
Nephrogenic diabetes insipidus (DI) refers to the reduction in the ability of the kidney to concentrate urine, which can be caused by partial or complete resistance at the site of action of anti-diuretic hormone (ADH) in the collecting tubules. Ifosfamide-induced nephrogenic DI typically occurs concomitantly in patients who have other signs of tubular toxicity consistent with Fanconi syndrome including glucosuria, aminoaciduria, and hypophosphatemia. We present a case of a 36-year-old female with recurrent synovial cell sarcoma of the pleural membranes, treated with ifosfamide-based chemotherapy, who was admitted to the hospital for the management of polyuria, hypotension, as well as electrolyte derangements including hypokalemia, hypophosphatemia and non-anion gap metabolic acidosis, 1 week after receiving a cumulative ifosfamide dose of 7.5 g/m2. Nephrogenic DI was indicated by polyuria as well as a urine osmolality to plasma osmolality ratio of less than 1.5 following a trial of intravenous desmopressin, but the patient's acute kidney injury on presentation precluded the early employment of thiazides and non-steroidal anti-inflammatory drugs (NSAIDs). Instead, the patient's polyuria and urine osmolality improved only after the administration of repetitive supraphysiologic doses of intravenous desmopressin. Our case reiterates that patients with non-hereditary nephrogenic DI may have partial rather than complete resistance to ADH and highlights that desmopressin may be considered in patients with ifosfamide-induced nephrogenic DI to prevent severe volume depletion, especially in patients who have persistent symptomatic polyuria despite maintaining a careful fluid balance and pharmacological therapy with NSAIDs and diuretics, or if the patient's clinical condition precludes the use of these strategies.


Two Equals One: Two Human Actions During Social Interaction Are Grouped as One Unit in Working Memory.
Every day, people perceive other people performing interactive actions. Retaining these actions of human agents in working memory (WM) plays a pivotal role in a normal social life. However, whether the semantic knowledge embedded in the interactive actions has a pervasive impact on the storage of the actions in WM remains unknown. In the current study, we investigated two opposing hypotheses: (a) that WM stores the interactions individually (the individual-storage hypothesis) and (b) that WM stores the interactions as chunks (the chunk-storage hypothesis). We required participants to memorize a set of individual actions while ignoring the underlying social interactions. We found that although the social-interaction aspect was task irrelevant, the interactive actions were stored in WM as chunks that were not affected by memory load (Experiments 1 and 2); however, inverting the human actions vertically abolished this chunking effect (Experiment 3). These results suggest that WM automatically and efficiently used semantic knowledge about interactive actions to store them and support the chunk-storage hypothesis.


Structural basis for glycogen recognition by AMP-activated protein kinase.
AMP-activated protein kinase (AMPK) coordinates cellular metabolism in response to energy demand as well as to a variety of stimuli. The AMPK beta subunit acts as a scaffold for the alpha catalytic and gamma regulatory subunits and targets the AMPK heterotrimer to glycogen. We have determined the structure of the AMPK beta glycogen binding domain in complex with beta-cyclodextrin. The structure reveals a carbohydrate binding pocket that consolidates all known aspects of carbohydrate binding observed in starch binding domains into one site, with extensive contact between several residues and five glucose units. beta-cyclodextrin is held in a pincer-like grasp with two tryptophan residues cradling two beta-cyclodextrin glucose units and a leucine residue piercing the beta-cyclodextrin ring. Mutation of key beta-cyclodextrin binding residues either partially or completely prevents the glycogen binding domain from binding glycogen. Modeling suggests that this binding pocket enables AMPK to interact with glycogen anywhere across the carbohydrate's helical surface.


Time Geography, a Method in Psychiatric Nursing Care.
Patients' life history is of primary interest in psychiatric nursing care. Our aim was to illustrate how we used time geography as a method to identify individuals' patterns in relation to certain situations in place. We have used interviews and diaries to construct life charts by hand and with a computer software program. By using time geography, we provide a rich amount of information, which can generate a broader picture of a person's life, to identify stressful as well as social aspects of a person's life. Patients with mental ill health need and value the therapeutic relationship using time geography.


More bark than bite: Comparative studies are needed to determine the importance of canine zoonoses in Aboriginal communities. A critical review of published research.
The objective of this review was to identify and critique over forty years of peer-reviewed literature concerned with the transmission of canine zoonoses to Aboriginal people and determine the zoonotic organisms documented in dogs in Australian Aboriginal communities. A systematic literature search of public health, medical and veterinary databases identified 19 articles suitable for critical appraisal. Thirteen articles documented the occurrence of recognized zoonotic organisms in dogs in Aboriginal communities, including Toxocara canis, Dirofilaria immitis, Streptococcus dysgalactiae, Rickettsia felis, Sarcoptes scabiei and Giardia. Currently, there is definitive evidence indicating that dogs act as a reservoir for human scabies in Aboriginal communities. However, there is a need for large-scale, high-quality, comparative studies of dogs and humans from the same household to assess the occurrence and importance of transmission of S. scabiei and other diseases between dogs and humans. These studies should use current genetic and molecular techniques along with traditional techniques to identify and type organisms in order to better understand their epidemiology. This review has revealed that there is a lack of high-quality comparative studies to determine whether dogs are contributing to human disease by transmitting zoonoses. Our recommendations differ significantly from current public health policy and may have substantial implications for human and dog health.


Stochastic graph Voronoi tessellation reveals community structure.
Given a network, the statistical ensemble of its graph-Voronoi diagrams with randomly chosen cell centers exhibits properties convertible into information on the network's large scale structures. We define a node-pair level measure called Voronoi cohesion which describes the probability for sharing the same Voronoi cell, when randomly choosing g centers in the network. This measure provides information based on the global context (the network in its entirety), a type of information that is not carried by other similarity measures. We explore the mathematical background of this phenomenon and several of its potential applications. A special focus is laid on the possibilities and limitations pertaining to the exploitation of the phenomenon for community detection purposes.


Nivolumab Therapy for Synchronous ALK-Positive Lung Cancer and Gastric Cancer.
Nivolumab is an immune checkpoint inhibitor with demonstrated efficacy against several malignant tumors. Alterations in driver oncogenes such as EGFR and ALK are a poor prognostic factor in nivolumab therapy for non-small cell lung cancer (NSCLC), whereas a smoking history is a well-known, favorable prognostic factor. However, an efficacy of nivolumab therapy for multiple primary malignant tumors (MPMTs) has not been reported, and its efficacy for driver oncogene-positive NSCLC in smokers is unclear. Herein, we report the case of a patient with a history of heavy smoking who developed synchronous ALK-positive NSCLC and gastric cancer that responded to nivolumab therapy. A 76-year-old man who was a heavy smoker presented to our hospital with symptoms of hoarseness and dysphagia. He was ultimately diagnosed with ALK-positive advanced NSCLC. An ALK inhibitor (alectinib) was administered, and the lung cancer lesions showed improvement. The alectinib therapy was continued for 5 months. Thereafter, the lesions in the left lower lobe of the lung showed regrowth. During the same period, the patient experienced epigastric pain. Gastrointestinal endoscopy examination revealed gastric cancer. He was administered nivolumab to treat both the lung cancer and the gastric cancer. Two months later, both the lung lesions and the gastric lesions had diminished in size. Nivolumab therapy might be an effective therapy for synchronous MPMTs and NSCLC in heavy smokers, even if the lung cancer possesses driver oncogene mutations.


Response dynamics of bullfrog ON-OFF RGCs to different stimulus durations.
Stimulus duration is an important feature of visual stimulation. In the present study, response properties of bullfrog ON-OFF retinal ganglion cells (RGCs) in exposure to different visual stimulus durations were studied. By using a multi-electrode recording system, spike discharges from ON-OFF RGCs were simultaneously recorded, and the cells' ON and OFF responses were analyzed. It was found that the ON response characteristics, including response latency, spike count, as well as correlated activity and relative latency between pair-wise cells, were modulated by different light OFF intervals, while the OFF response characteristics were modulated by different light ON durations. Stimulus information carried by the ON and OFF responses was then analyzed, and it was found that information about different light ON durations was more carried by transient OFF response, whereas information about different light OFF intervals were more carried by transient ON response. Meanwhile, more than 80 % information about stimulus durations was carried by firing rate. These results suggest that ON-OFF RGCs are sensitive to different stimulus durations, and they can efficiently encode the information about visual stimulus duration by firing rate.


Confidentiality measures in mental health delivery settings: report of US health information managers.
Health and human service organizations are becoming increasingly liable for violations of patient privacy as a result of recent federal mandates at both state and federal levels of government. Under such conditions it would seem likely that managers would act to quickly implement such guidelines and mandates, especially in sensitive specialty areas such as mental health. This study sought to examine the degree and type of patient information confidentiality measures adopted in mental health delivery settings, through a national survey of accredited US health information managers. Results suggest that significant nonadoption of basic confidentiality measures continues to exist, despite federal mandates to the contrary. Further examined was the degree to which confidentiality management varies across adoption levels of computerized patient records. Significant variation was found in adoption of patient confidentiality measures between highly computerized and paper-based medical record functions. Similar levels of variation in adoption across practice settings was also discovered. Ramifications for national policy and patient information protection are discussed.


First report of Sclerotinia sclerotiorum causing stem canker on Cannabis sativa L. in Oregon.
In August of 2020, plants of Cannabis sativa L. grown in hoop houses at two farms located in Benton County, Oregon exhibited wilting and chlorosis, followed by shoot necrosis. Symptomatic plants had dry, tan-brown lesions or cankers, often accompanied by large, round to irregular or ribbon-shaped, black sclerotia and/or profuse white mycelial growth. Lesions or cankers were observed on the stems at both the plant crown (soil) level and higher in the canopy; flower infections were not observed. Sclerotia were removed from two infected plants and placed on potato dextrose agar (PDA) at room temperature. Fast-growing, pure white, largely appressed, sterile mycelium grew radially from plated sclerotia. Hyphal tips were transferred to obtain a pure culture. Additional sclerotia, solitary and aggregate, approximately 30 to more than 50 per plate, exhibiting identical features to those observed on plant tissue, formed in culture 6-7 days following transfer and ranged in size from 2 to 11 mm in length or width (n=50). Mycelia were aseptically harvested from cultures for DNA extraction (Quick-DNA Plant/Seed Miniprep Kit, Zymo Research). Primers ITS1-F (Gardes and Bruns 1993) and ITS4 (White et al. 1990) were used to amplify the internal transcribed spacer region (ITS) and primers G3PDHfor and G3PDHrev were used to amplify the glyceraldehyde 3-phosphate dehydrogenase (G3PDH) gene (Staats et al. 2005) from a single isolate, LAS01. The ITS region from LAS01 (MW079844) shared 100 to >99% homology to several Sclerotinia species isolates in GenBank. The LAS01 G3PDH gene (MW082601), shared >99% and 100% homology with S. sclerotiorum type specimens strains 484 (GenBank accession no. AJ705044) and 1980 (JQ036048), respectively, and only 97% and 96% sequence identity with S. minor (KF878364) and S. trifoliorum (KF878375), respectively. A phylogenetic tree (presented as an eXtra) identifies LAS01 as S. sclerotiorum. To confirm pathogenicity, isolate LAS01 was grown on PDA at room temperature. After 48 hours, 4mm plugs were cut from the colony and placed mycelium-side down onto the main stems of five healthy C. sativa plants that had been grown for approximately six weeks from rooted cuttings and secured using a minutien pin. Uncolonized PDA plugs placed on the stem of the same plants several leaf nodes away were used as controls. Plants were incubated at room temperature in a grow tent under 24-hour light and 70-95% humidity conditions. Elongate, tan-brown lesions were observed at the inoculation sites 4-5 days post inoculation; stems at mock inoculated sites remained green. After six days, tissue was excised from the margin of each lesion, surface sterilized with 1% NaOCl, rinsed in sterile water, and placed onto PDA. Resultant fungal growth was confirmed to be S. sclerotiorum based on morphology. Isolation attempts were also made from mock inoculations; no fungal growth was observed. Trials were repeated on two additional cultivars with similar results. This report is the first of S. sclerotiorum on C. sativa in Oregon; the only peer-reviewed reports that could be located for S. sclerotiorum on C. sativa in the United States were from host indices in Montana (Anon. 1960; Shaw 1973) and references cited by McPartland (1996). Sclerotinia sclerotiorum has been reported in Canada on hemp-type C. sativa (Bains et al. 2000). The economic impact of S. sclerotiorum on the emerging C. sativa industry in Oregon and the United States remains unclear.


The assessment of disability and handicap in musculoskeletal disease.
The method for assessment of disability and handicap is particularly important in chronic musculoskeletal diseases. Outcome measures should be valid and show a responsiveness to change such that longitudinal studies of the diseases and their interventions can be carried out effectively. Psychosocial aspects may significantly influence these diseases and the instruments themselves. Researchers need to take these issues into account.


[Spleen trauma during pregnancy (a case report)].
Splenic injury during pregnancy after blunt abdominal trauma is rare. The physiological and anatomical changes during pregnancy modify the clinical, biological and radiological signs. The authors report a case of a 30-year-old-woman in the 32nd week of pregnancy, with an isolate splenic injury after a motor vehicle accident. Splenectomy was realised 4 days after an initial decision of abstaining from surgery. In pregnancy, the frequency of recurrent bleeding, the possibility of concomitant uterine injuries and the risk of foetal loss should modify the surgeon's attitude to splenic rupture after abdominal blunt trauma.


Transfection of CXCR-4 using microbubble-mediated ultrasound irradiation and liposomes improves the migratory ability of bone marrow stromal cells.
Bone marrow stromal cells (BMSCs) have proven useful for the treatment of various human diseases and injuries. However, their reparative capacity is limited by their poor migration and homing ability, which are primarily dependent on the SDF-1/CXCR4 axis. Most subcultured BMSCs lack CXCR4 receptor expression on the cell surface and exhibit impaired migratory capacity. To increase responsiveness to SDF-1 and promote cell migration and survival of cultured BMSCs, we used a combination of ultrasound-targeted microbubble destruction (UTMD) and liposomes to increase CXCR4 expression in vitro. We isolated and cultured rat BMSCs to their third passage and transduced them with recombinant plasmid pDsRed-CXCR4 using microbubble-mediated ultrasound irradiation and liposomes. Compared to some viral vectors, the method we employed here resulted in significantly better transfection efficiency, CXCR4 expression, and technical reproducibility. The benefits of this approach are likely due to the combination of "sonoporation" caused by shockwaves and microjet flow resulting from UTMD-generated cavitation. Following transfection, we performed a transwell migration assay and found that the migration ability of CXCR4-modified BMSCs was 9-fold higher than controls. The methods we describe here provide an effective, safe, non-viral means to achieve high levels of CXCR4 expression. This is associated with enhanced migration of subcultured BMSCs and may be useful for clinical application as well.


Removal of an intraosseous hemangioma of the frontal bone through an anterior hairline incision: a case report.
An intraosseous hemangioma of the frontal bone is typically removed via a coronal incision. This procedure, while effective, can be lengthy and may result in complications such as a prominent scar and hair loss. An alternative approach involves a direct incision in the forehead, which leaves a less noticeable scar and allows a quicker recovery. However, in this specific case, the patient declined both coronal surgery and surgery through a direct forehead incision due to cosmetic concerns. Therefore, we proposed an anterior hairline incision. A 35-year-old woman presented with a firm, non-mobile, palpable mass on her right forehead. Preoperative non-contrast computed tomography revealed a heterogeneous osteolytic lesion. We performed an excisional biopsy through the anterior hairline. Postoperative non-contrast computed tomography was conducted 2 and 6 months after surgery. The wound was clean and free of complications, and there was no local recurrence. Partial resection can reduce scarring for patients who are concerned about cosmetic outcomes. However, the potential for recurrence remains a significant concern. We present this case of an anterior hairline incision for a hemangioma located in the forehead, evaluated using serial computed tomography for both preoperative and postoperative imaging.


How does HIV-related stigma correlate with HIV prevalence in African countries? Distinct perspectives from individuals living with and living without HIV.
Population-level research evaluating HIV-related stigma among countries with varied national HIV prevalence is scarce. To better understand HIV-related stigma and mitigate its potential negative effects, it is necessary to evaluate its relationship with HIV prevalence, as well as the mechanisms that influence it. This study aimed to analyze how HIV-related stigma correlates with subnational HIV prevalence in three African countries with varied HIV epidemics. This paper used data from the nationally representative Population-based HIV Impact Assessment (PHIA) surveys conducted from 2015-2017 in Malawi, Zambia, and Tanzania. Each country's sub-national geographic divisions were used to categorize them as low (0-5.4%), middle (5.5-11.2%), and high (11.3-17.1%) HIV prevalence regions in the main analysis. Questions from the survey stigma module were used to measure HIV-related stigma. Logistic regression and multilevel models were performed to assess the associations between the level of sub-national HIV prevalence and HIV-related stigma measures among persons living with, and without, HIV. The results show that the odds of people living without HIV expressing stigmatizing behavior towards PLWH was significantly lower in regions of middle (OR = 0.80, 90%CI = (0.68-0.96)) and high (OR = 0.65, 90%CI = (0.53-0.80)) HIV prevalence when compared to low prevalence regions. The odds of reporting discriminatory attitudes were also lower for those in middle (OR = 0.87, 90%CI = (0.78-0.98)) and high (OR = 0.64, 90%CI = (0.56-0.73)) HIV prevalence regions compared to others. Living in middle and high HIV prevalence regions was associated with lower odds of expressing prejudice toward PLWH (OR = 0.84, 90%CI = (0.71-0.99) and OR = 0.60, 90%CI = (0.45-0.80), respectively) among people living without HIV. Notably, PLWH living in high prevalence regions had higher odds of reporting internalized stigma (OR = 1.48, 90%CI = (1.02-2.14)) compared to those living in low prevalence regions. The results indicate that among people not living with HIV, subnational HIV prevalence was negatively associated with discriminatory attitudes and prejudice towards PLWH, but HIV prevalence was positively associated with self-reported internalized stigma among PLWH. These results provide insight on how resources could be invested to reduce HIV related stigma among both PLWH and those not living with HIV.


Macrolactins O-R, glycosylated 24-membered lactones from Bacillus sp. AH159-1.
In the course of screening for inhibitors of Staphylococcus aureus peptide deformylase, four new glycosylated macrolactin compounds, macrolactins O ( 1), P ( 2), Q ( 3), and R ( 4), along with the known macrolactins B ( 5) and C ( 6), have been isolated from the liquid cultures of Bacillus sp. AH159-1. The structures of compounds 1- 4 were assigned on the basis of MS and NMR data. They inhibited S. aureus peptide deformylase and also showed antibacterial activity against Escherichia coli and Staphylococcus aureus.


Ethical and legal aspects in medically assisted human reproduction in Romania.
Up to the present, there have not been any specific norms regarding medically assisted human reproduction in Romanian legislation. Due to this situation the general legislation regarding medical assistance (law no. 95/2006, regarding the Reform in Health Care System), the Penal and Civil law and the provisions of the Code of Deontology of the Romanian College of Physicians are applied to the field of medically assisted human reproduction. By analysing the ethical and legal conflicts regarding medically assisted human reproduction in Romania, some characteristics cannot be set apart because they derive from religious, cultural and socio-economic aspects. In this article the authors identify the development stages of medically assisted human reproduction in Romania, beginning from these characteristics and insisting upon the failure of the legal system in this specific field. The authors consider that the law regarding medically assisted human reproduction cannot be effective because it did not take into account the ethical and cultural aspects that might appear. Furthermore, in this framework of the legal process, no public debate involving the representatives of civil society was undertaken although the Council of Europe Oviedo Convention approved by our country according to law no. 17/2001 stipulated exactly this working method.


Washington State Retail Marijuana Legalization: Parent and Adolescent Preferences for Marijuana Messages in a Sample of Low-Income Families.
As legalization of nonmedical retail marijuana increases, states are implementing public health campaigns designed to prevent increases in youth marijuana use. This study investigated which types of marijuana-related messages were rated most highly by parents and their teens and whether these preferences differed by age and marijuana use. Nine marijuana-focused messages were developed as potential radio, newspaper, or television announcements. The messages fell into four categories: information about the law, general advice/conversation starters, consequences of marijuana use/positive alternatives, and information on potential harmful effects of teen marijuana use. The messages were presented through an online survey to 282 parent (84% female) and 283 teen (54% female) participants in an ongoing study in Washington State. Both parents and youth rated messages containing information about the law higher than other types of messages. Messages about potential harms of marijuana use were rated lower than other messages by both generations. Parents who had used marijuana within the past year (n = 80) rated consequence/positive alternative messages lower than parent nonusers (n = 199). Youth marijuana users (n = 77) and nonusers (n = 202) both rated messages containing information about the law higher than other types of messages. Youth users and nonusers were less likely than parents to believe messages on the harmful effects of marijuana. The high ratings for messages based on information about the marijuana law highlight the need for informational health campaigns to be established as a first step in the marijuana legalization process.


Pathogenic bacteria in milk--a review.
Pathogenic bacteria are transmissible to humans through milk and milk products. Recently, attention is focused on milk, cheese, and ice cream contaminated with pathogenic bacteria, viz., Listeria monocytogenes, Yersinia enterocolitica, Campylobacter jejuni, and enteropathogenic Escherichia coli. This review presents information on characteristics of these pathogens and illnesses caused by them.


The future of bioprosthetic valves. A pathologist's perspective.
The processes responsible for primary tissue failure of bioprostheses were illustrated. Calcification is the major cause of failure of porcine bioprosthetic valves, usually with superimposed tearing. Calcific deposits may be found grossly or microscopically in most bioprostheses removed from adult humans after four years. The predominate loci are the cuspal commissures and basal attachments, in the porcine spongiosa layer, in cells and in collagen. Pericardial valves also tear frequently, most often near the top of the stent post. The status of understanding of bioprosthetic valve calcification and studies of preventive therapies were summarized. Data concerning retardation of mineralization by use of diphosphonate in controlled-released drug delivering polymers and pretreatment with aluminum salts were presented.


The painful mouth.
The painful mouth presents a diagnostic challenge to the general practitioner. Despite curriculum revision of most medical courses, oro-pharyngeal diseases are still inadequately covered. This article aims to alert the GP to common causes of a painful mouth and provides a guide to diagnosis and management. Four case studies are presented to illustrate common problems presenting in general practice, and their optimal treatment.


CDR3 size spectratyping and sequencing of spectratype-derived TCR of spinal cord T cells in autoimmune encephalomyelitis.
To characterize the nature of autoimmune disease-inducing T cells in the target organ, oligoclonal expansion of spinal cord T cells of Lewis rats with experimental autoimmune encephalomyelitis (EAE) was examined by complementarity-determining region 3 (CDR3) size spectratyping. It is known that TCR of in vitro-established myelin basic protein-specific T cell clones and lines have a short CDR3 and that the amino acid sequence in this region is highly preserved. On the basis of these findings, we analyzed 22 spectratypes of the TCR beta-chain (Vbeta1-20). Among them, only Vbeta8.2 and Vbeta17 showed oligoclonal expansion of TCR with a short CDR3 at the early stage of EAE. More interestingly, the spectratype profile of Vbeta8.2 seen at the early stage was preserved throughout the course of EAE, whereas that of Vbeta17 became more diverse at the peak stage of the disease. Analysis of nucleotide and predicted amino acid sequences of Vbeta8.2 CDR3 derived from the spectratypes revealed that the clones with CASSDSSYEQYFGPG, which is one of the representative sequences of encephalitogenic T cell clones, constituted the predominant population not only at the early stage but also at the peak and recovery stages (71, 71, and 60%, respectively). These findings imply that although the phenotype of T cells in the target organ diversifies as the autoimmune disease progresses, disease-associated TCR spectratype(s) are preserved throughout the course of the disease. Thus, CDR3 size spectratyping is a powerful tool for the screening of disease-inducing T cells in an autoimmune disease of unknown pathomechanism.


Multiple roles for the receptor tyrosine kinase axl in tumor formation.
A focus of contemporary cancer therapeutic development is the targeting of both the transformed cell and the supporting cellular microenvironment. Cell migration is a fundamental cellular behavior required for the complex interplay between multiple cell types necessary for tumor development. We therefore developed a novel retroviral-based screening technology in primary human endothelial cells to discover genes that control cell migration. We identified the receptor tyrosine kinase Axl as a novel regulator of endothelial cell haptotactic migration towards the matrix factor vitronectin. Using small interfering RNA-mediated silencing and overexpression of wild-type or mutated receptor proteins, we show that Axl is a key regulator of multiple angiogenic behaviors including endothelial cell migration, proliferation, and tube formation in vitro. Moreover, using sustained, retrovirally delivered short hairpin RNA (shRNA) Axl knockdown, we show that Axl is necessary for in vivo angiogenesis in a mouse model. Furthermore, we show that Axl is also required for human breast carcinoma cells to form a tumor in vivo. These findings indicate that Axl regulates processes vital for both neovascularization and tumorigenesis. Disruption of Axl signaling using a small-molecule inhibitor will hence simultaneously affect both the tumor and stromal cell compartments and thus represents a unique approach for cancer therapeutic development.


[The influence of the addition of epinephrine and sodium bicarbonate on the hemodynamics after epidural anesthesia].
We examined the effects of epinephrine and sodium bicarbonate in the hemodynamics after epidural anesthesia. The solution was prepared by adding 2 ml of either 7% sodium bicarbonate or saline to 1% lidocaine 20 ml with or without epinephrine (1:200,000) and we gave 3 ml of each solution in the epidural space of dogs anesthetized with halothane. Epinephrine and sodium bicarbonate addition exerted no significant influence on the hemodynamics except tendency to continuous hypotension. Although sodium bicarbonate addition tended to decrease heart rate, the decrease was not significant and the duration of hypotension was short.


Organic Photoredox Catalysis.
In this review, we highlight the use of organic photoredox catalysts in a myriad of synthetic transformations with a range of applications. This overview is arranged by catalyst class where the photophysics and electrochemical characteristics of each is discussed to underscore the differences and advantages to each type of single electron redox agent. We highlight both net reductive and oxidative as well as redox neutral transformations that can be accomplished using purely organic photoredox-active catalysts. An overview of the basic photophysics and electron transfer theory is presented in order to provide a comprehensive guide for employing this class of catalysts in photoredox manifolds.


Toxoplasmosis in a bar-shouldered dove (Geopelia humeralis) from the Zoo of Clères, France.
Toxoplasmosis causes mortality in several avian species, especially passerine birds. Toxoplasmosis was diagnosed in a bar-shouldered dove (Geopelia humeralis) found dead at the zoo of Clères (France). The bird had necrotizing pneumonia and nephritis with intralesional tachyzoites of Toxoplasma gondii. The diagnosis was confirmed by immunostaining with polyclonal rabbit T. gondii antibodies and by transmission electron microscopy. To our knowledge, the bar-shouldered dove is a new host record for T. gondii.


Human sperm DNA damage has an effect on immunological interaction between spermatozoa and fallopian tube.
Toll-like receptors play a crucial role in the immunological interaction between the spermatozoa and fallopian tube and contribute to the ovulation, sperm capacitation, fertilization, and pregnancy. To investigate the expression of toll-like receptors and their adaptor molecules and cytokines under the effect of spermatozoa with high DNA fragmentation (high DF) in human fallopian tube cell line (OE-E6/E7) and compare to those in normal spermatozoa. Fresh semen samples were obtained from 10 unexplained infertile males with high DF (more than 20%) and from 10 healthy donors with a DF less than 3%. After sperm preparation, samples were co-cultured with OE-E6/E7. Toll-like receptors, myeloid differentiation factor 88 (MyD88), TIR domain-containing adapter protein (TIRAP), TIR domain-containing adapter-inducing IFN-b (TRIF), TRIF-related adapter molecule as well as IL-6, IL-8, IFN-β, and TNFα mRNA expression were evaluated by quantitative real-time PCR. Protein levels of these cytokines and chemokines were measured using ELISA method. TLR 1-6 mRNA expression in OE-E6/E7 was significantly higher under the effect of spermatozoa with high DF compared to the spermatozoa with low DF. Furthermore, significantly increased mRNA expression of MyD88, TIRAP, and TRIF was observed in the high DF group compared to the low DF group, except TRIF-related adapter molecule. Moreover, the expression of IL-6 and IL-8 in the high DF group was significantly higher than low DF group, although there was no significant difference in IFN-β and TNFα expression between the groups. Damage-associated molecular patterns from DNA damage activate TLR signaling pathway in human fallopian tubes and result in the upregulation of inflammatory cytokines and chemokines. This situation may provide pathologic environment for capacitation, fertilization, embryo development, and implantation in female reproductive tract and can be one of the mechanisms of infertility in men with high DF.


Lateral circumflex femoral artery false aneurysm as a complication of intertrochanteric hip fracture with displaced lesser trochanter.
We present a patient who suffered an unstable intertrochanteric hip fracture and underwent osteosynthesis with a trochanteric nail. During the postoperative period, he presented a pseudoaneurysm of the lateral circumflex branch of the deep femoral artery secondary to a displaced fracture of the lesser trochanter. With the suspected diagnosis due to indirect clinical and radiological signs and confirmation by Doppler ultrasound and computed tomography angiography, a transverse arterial embolization with resolution of the symptoms was carried out. The pseudoaneurysm of the deep femoral artery or its branches is a very rare complication after intertrochanteric hip fractures, which must be taken into account in the late appearance of edema and hematoma in the thigh and evidence of medial and superior displacement of the lesser trochanter. The diagnosis is confirmed by CT angiography and the treatment by percutaneous arterial embolization has good results without the need of excising the lesser trochanter.


HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.
Renal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.


Highly sensitive and specific LC-MS/MS method to determine endogenous leukotriene B4 levels in human plasma.
Aim: To develop a high sensitivity and specific analytical method to measure endogenous levels of leukotriene B4 (LTB4) in human plasma. Methodology: LC-MS/MS and ELISA. Results: An LC-MS/MS method was developed with a sensitivity of 1.0 pg/ml, and within and between batch precision of <16% and <13% RSD, respectively. Conclusion: We have developed a sensitive LC-MS/MS method that can detect endogenous LTB4 in human plasma. The LC-MS/MS method displayed correlation with a commercial LTB4 ELISA when analyzing in ex vivo ionophore-stimulated blood samples. For untreated plasma this correlation was lost. Endogenous LTB4 was shown to be unstable in plasma during storage at -20°C and subject to stereoisomer formation. Neither of the assays could quantify endogenous plasma LTB4 in samples stored for long term.


Multi‑strategy Equilibrium Optimizer: An improved meta-heuristic tested on numerical optimization and engineering problems.
The Equilibrium Optimizer (EO) is a recently proposed intelligent optimization algorithm based on mass balance equation. It has a novel principle to deal with global optimization. However, when solving complex numerical optimization problems and engineering problems, the algorithm will get stuck into local optima and degrade accuracy. To address the issue, an improved Equilibrium Optimizer (IEO) based on multi-strategy optimization is proposed. First, Tent mapping is used to generate the initial location of the particle population, which evenly distributes the particle population and lays the foundation for diversified global search process. Moreover, nonlinear time parameter is used to update the position equation, which dynamically balances the exploration and exploitation phases of improved algorithm. Finally, Lens Opposition‑based Learning (LOBL) is introduced, which avoids local optimization by improving the population diversity of the algorithm. Simulation experiments are carried out on 23 classical functions, IEEE CEC2017 problems and IEEE CEC2019 problems, and the stability of the algorithm is further analyzed by Friedman statistical test and box plots. Experimental results show that the algorithm has good solution accuracy and robustness. Additionally, six engineering design problems are solved, and the results show that improved algorithm has high optimization efficiency achieves cost minimization.


ALP-assisted chemical redox cycling signal amplification for ultrasensitive fluorescence detection of DNA methylation.
Affinity assays allow direct detection of DNA methylation events without requiring a special sequence. However, the signal amplification of these methods heavily depends on nanocatalysts and bioenzymes, making them suffer from low sensitivity. In this work, alkaline phosphatase (ALP)-assisted chemical redox cycling was employed to amplify the sensitivity of fluorescence affinity assays for DNA methylation detection using Ru@SiO2@MnO2 nanocomposites as fluorescent probes. In the ALP-assisted chemical redox cycling reaction system, ALP hydrolyzed 2-phosphate-L-ascorbic acid trisodium salt (AAP) to produce AA, which could reduce MnO2 nanosheets to form Mn2+, making the fluorescence recovery of Ru@SiO2 nanoparticles possible. Meanwhile, AA was oxidized to dehydroascorbic acid (DHA), which was re-reduced by tris(2-carboxyethyl) phosphine (TCEP) to trigger a redox cycling reaction. The constantly generated AA could etch large amounts of MnO2 nanosheets and greatly recover Ru@SiO2 fluorescence, amplifying the signal of the fluorescence assay. Employing the proposed ALP-assisted chemical redox cycling signal amplification strategy, a sensitive affinity assay for DNA methylation detection was achieved using ALP encapsulated liposomes that were linked with the 5mC antibody (Ab) to bind with methylated sites. A detection limit down to 2.9 fM was obtained for DNA methylation detection and a DNA methylation level as low as 0.1% could be distinguished, which was superior to conventional affinity assays. Moreover, the affinity assays could detect DNA methylation more specifically and directly, implying their great potential for the analysis of tumor-specific genes in liquid biopsy.


Adsorption of endotoxin by beta2-microglobulin adsorbent column (Lixelle): the new approach for endotoxinemia.
We previously reported that Lixelle, which was used for beta2-microglobulin (BMG) adsorption columns, could adsorb not only BMG but also inflammatory cytokines. We became interested in the application of Lixelle for patients with endotoxinemia and researched its ability to adsorb microorganism components in vitro using lipopolysaccharide (LPS) (Escherichia coli B8), endotoxin (ET) contaminated water. The initial concentrations of each water solution were LPS (ET 29,135 EU/L) and contaminated water (ET 3,523 EU/L) whole blood solution was LPS (ET 1,197.6 EU/L). Each 2.5 ml of the stock solution and adjusted diluted solutions contained 0.5 ml of Lixelle beads. After shaking at 37 degrees C for 2 h, ET in the solutions was determined using the endotoxin specific-limulus amebocyte lysate method. The results revealed that even though ET concentrations in LPS and contaminated water incubated in water solution and in whole blood were high, the samples containing Lixelle beads showed significant decreases. Thus, Lixelle beads can adsorb not only BMG but also microorganism components such as LPS and ET. These findings together with the ability of Lixelle to adsorb ET show the possibility of the application for treatment of endotoxinemia.


Effect of alkali lignins with different molecular weights from alkali pretreated rice straw hydrolyzate on enzymatic hydrolysis.
This study investigated the effect of alkali lignins with different molecular weights on enzymatic hydrolysis of lignocellulose. Different alkali lignins fractions, which were obtained from cascade ultrafiltration, were added into the dilute acid pretreated (DAP) and alkali pretreated (AP) rice straws respectively during enzymatic hydrolysis. The results showed that the addition of alkali lignins enhanced the hydrolysis and the enhancement for hydrolysis increased with increasing molecular weights of alkali lignins, with maximum enhancement being 28.69% for DAP and 20.05% for AP, respectively. The enhancement was partly attributed to the improved cellulase activity, and filter paper activity increased by 18.03% when adding lignin with highest molecular weight. It was found that the enhancement of enzymatic hydrolysis was correlated with the adsorption affinity of cellulase on alkali lignins, and the difference in surface charge and hydrophobicity of alkali lignins were responsible for the difference in affinity between cellulase and lignins.


A New Adjuvant MTOM Mediates Mycobacterium tuberculosis Subunit Vaccine to Enhance Th1-Type T Cell Immune Responses and IL-2+ T Cells.
The only licensed vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cannot prevent the prevalence of tuberculosis (TB), which remains a major public health problem worldwide. A more effective TB vaccine than BCG is urgently needed. Subunit vaccine is a promising strategy, and suitable adjuvants will benefit the development of effective TB subunit vaccines. MTO, consisting of monophosphoryl lipid A (MPLA), trehalose-6,6'-dibehenate (TDB), and MF59, was developed as an adjuvant of TB vaccine because of its ability to evoke the Th1-type T cell responses, while it is insufficient to induce single and multifunctional IL-2+ T cells and has a limited ability to confer protection against Mycobacterium tuberculosis infection. Heat-killed Mycobacterium vaccae (Mv), which can evoke cytotoxic CD8+ and CD4+ T cell responses and has adjuvanticity, was, in this study, combined with MTO to produce a new adjuvant, called MTOM. The TB fusion protein Rv3407-PhoY2-Ag85A-Rv2626c-RpfB (WH121) was mixed with MTO, Mv, and MTOM to produce three subunit vaccines, and the protective efficacy and immune responses were compared in C57BL/6 mice. WH121/MTOM provided better protection against TB than the other two vaccines, matching the performance of BCG vaccine. MTOM showed stronger ability to increase single and multifunctional IL-2+ T cells and induce Th1-type responses than MTO or Mv. Therefore, MTOM might be a promising adjuvant that could contribute to the development of TB subunit vaccines.


Accuracy of body mass index categories based on self-reported height and weight among women in the United States.
The purpose of this study was to assess the accuracy of BMI categories based on self-reported height and weight in adult women. BMI categories from self-reported responses were compared to categories measured during physical examination from women, age 18 or older, who participated in the National Health and Examination Survey, 1999-2004. We first examined strength of agreement using Cohen's kappa, which, unlike sensitivity and specificity, allows for the comparison of polychotomous measures beyond chance agreement. Kappa regression identifies potential threats to accuracy. Likelihood of bias, as measured by under-reporting, was examined using logistic regression. Cohen's kappa estimates were 0.443 for pregnant women (N = 724) and 0.705 for non-pregnant women (N = 5,910). Kappa varied by age and race, but was largely unrelated to socioeconomic status, health and health behaviors. Women who visited a physician in the last year or been diagnosed with osteoporosis were more accurate, while women most likely to under-report were older, white, non-Hispanic, and college-educated. Our results suggest substantial agreement between self-reported and measured categories, except for women who are pregnant, above the age of 75 or without physician visits. Under-reporting may be more prevalent in well-educated, white populations than minority populations.


Corticosteroids in the management of lymphocytic hypophysitis: Case series.
The diagnosis of lymphocytic hypophysitis (LYH) is a clinical challenge. Medical management with steroids may result in complete resolution of the symptoms and radiological features. We report our approach to the diagnosis and treatment of LYH. Retrospective analysis of data of nine consecutive patients of LYH from August 2013 to August 2015 was done. The average age of the study population was 38.4 ± 19.8 years, with five (55.5%) women. Presumptive diagnosis of LYH was made in six patients who were treated with steroids. Among the medical intervention group, one patient developed progressive ocular symptoms involving the third cranial nerve, which required surgical intervention. Out of the five remaining patients under medical treatment, four patients showed improvement in clinical symptoms and resolution of radiological features and one patient showed recurrence of the lesion. In the surgical group, the diagnosis was made after the histopathological confirmation. In the surgical group, the diagnosis was made after the histopathological confirmation in all patients except one. All the patients in this group presented with optic nerve compression requiring surgical decompression. All the patients in this group showed symptomatic improvement postoperatively. Symptoms for deficiency of hormones required supplementation dose of steroids. Steroids should be considered as the first line of management in LYH. Surgical resection should be considered in the presence of optic nerve and/or chiasmal compression and for lesions nonresponsive to medical management.


A Novel Hybrid Model for Drawing Trace Reconstruction from Multichannel Surface Electromyographic Activity.
Recently, several researchers have considered the problem of reconstruction of handwriting and other meaningful arm and hand movements from surface electromyography (sEMG). Although much progress has been made, several practical limitations may still affect the clinical applicability of sEMG-based techniques. In this paper, a novel three-step hybrid model of coordinate state transition, sEMG feature extraction and gene expression programming (GEP) prediction is proposed for reconstructing drawing traces of 12 basic one-stroke shapes from multichannel surface electromyography. Using a specially designed coordinate data acquisition system, we recorded the coordinate data of drawing traces collected in accordance with the time series while 7-channel EMG signals were recorded. As a widely-used time domain feature, Root Mean Square (RMS) was extracted with the analysis window. The preliminary reconstruction models can be established by GEP. Then, the original drawing traces can be approximated by a constructed prediction model. Applying the three-step hybrid model, we were able to convert seven channels of EMG activity recorded from the arm muscles into smooth reconstructions of drawing traces. The hybrid model can yield a mean accuracy of 74% in within-group design (one set of prediction models for all shapes) and 86% in between-group design (one separate set of prediction models for each shape), averaged for the reconstructed x and y coordinates. It can be concluded that it is feasible for the proposed three-step hybrid model to improve the reconstruction ability of drawing traces from sEMG.


[Results of treatment of Itsenko-Cushing disease using proton irradiation of the hypophysis].
The application of protons (heavy charged particles) for irradiation of the pituitary body has some essential advantages over other types of teletherapy: insignificant destruction of surrounding tissues, a possibility of a single therapeutic session as well as the absence of post-radiation effects. Proton beam therapy was given to 98 patients with Icenko-Cushing disease aged 15 to 40. Mild cases were treated by proton beam irradiation only while severe cases were managed using proton beam therapy combined with unilateral adrenalectomy or oral administration of ortho-para-DDD. Catamnesis duration varied from 3 to 5 years. In most cases the exposure dose was 80-90 Gy (50-110 Gy). The procedure was well tolerated by all the patients. A dynamic multipolar converting method with 15-20 entrance poles in the left temporal area was employed (with the beam energy of 200 MeV). Stabilization of the course of disease and some clinical improvement were observed in most of the patients 3-4 months after proton beam therapy. In 6-36 months after irradiation 90% of the patients showed normal biochemical indices and the absence of any clinical signs of the disease. Three-five years after treatment, 94% of the patients were in steady remission. A 24-hour ACTH and cortisol normalization pattern was observed in all the patients in parallel with an increase in GH and gonadotropin secretion and a decrease in the prolactin level. Sex function renewal appeared to be the first clinical sign of remission. Young patients aged 15 to 20 with a short duration of disease reached remission faster than patients of the other age groups. Thus the results of proton beam therapy of 98 patients with Icenko-Cushing disease after a follow-up of 3-5 years showed a high efficacy of this type of treatment. The method can be used alone or in combination with unilateral adrenalectomy as well as with oral administration of ortho-para-DDD.


Translational research in diagnosis and management of soft tissue tumours.
Finding a soft tissue mass in the superficial regions is a common event in daily clinical practice. Correct management of the diagnostic process is crucial to avoid blunders. Diagnosis is posed by pathology, although both imaging and a better understanding of the cellular and molecular mechanisms play an important a role in the characterization, staging and follow-up of soft tissue masses. Cellular and molecular mechanisms can explain either the development of chemo-resistance and the underlying pre- and post-surgery metastasis formation. These are mandatory to improve prognosis and unveil novel parameters predicting therapeutic response. Imaging mainly involves ultrasound and MR and is fundamental not only in diagnosis but also in the first step of therapy: the biopsy. Novel imaging techniques like Ultrasound Elastosonography, Dynamic Contrast-Enhanced MR imaging (DCE), Diffusion Weighted MR imaging (DWI) and MR Spectroscopy (MRS) are discussed. This paper aims at reviewing and discussing pathological methods and imaging in the diagnosis of soft tissue masses underscoring that the most appropriate treatment depends on advanced molecular and radiological studies.


The quality of psychotropic drug prescribing in patients in psychiatric units for the elderly.
The quality of written prescriptions has not been examined in a psychiatric setting. The aim of this study was to examine the quality of drug prescribing by medical staff for elderly patients hospitalized with dementia in comparison with the quality of prescribing for elderly patients hospitalized for functional psychiatric illness (depression, anxiety and psychosis). We studied a cohort of 112 elderly psychiatric inpatients in two hospitals over a seven-year period. A standardized assessment sheet was used to assess 320 prescriptions of psychotropic drugs, using medical notes and drug charts. Patients with dementia and functional illness were defined by ICD-9 or ICD-10 criteria. Severity of illness was measured by the presence or absence of symptoms in six discrete symptom clusters. Two raters examined prescription quality. Twenty percent of prescriptions for patients with dementia were illegible, significantly higher than in functional illness. In both groups, among prescriptions of regular medication, one third contained missing information on either, dose, intended frequency, or, indications for use. Among prescriptions for as-required medication, two-thirds of prescriptions contained this missing information. Prescriptions were legible and free of all errors in only 20 of 112 cases (18%). Quality of as-required medication prescribing was inferior to the prescription of regular medication, particularly for dementia patients. In addition, prescribing for patients with dementia carried significantly more errors in notation of dose than prescribing for patients with functional illness. We conclude that errors are common in prescribing for elderly psychiatric patients, particularly for as-required medication and for patients with dementia.


[A crazy patient or an additional weird experience vestibular in origin ?]
We present a patient suffering from persistence of images after cessation of the visual stimulus, a phenomenon called palinopsia. As none of classical causes existed in this patient, we hypothethized that the phenomenon is related to the particular dysfunction of his right inner ear associating a canalar deficit with a preserved otolithic function. In such a situation, the vestibular inputs are slower than normal. Therefore, palinopsia could result from an abnormal temporal integration of visual and vestibular informations.


Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors.
Cooperativity and antagonism between transcription factors (TFs) can drastically modify their binding to regulatory DNA elements. While mapping these relationships between TFs is important for understanding their context-specific functions, existing approaches either rely on DNA binding motif predictions, interrogate one TF at a time, or study individual TFs in parallel. Here, we introduce paired yeast one-hybrid (pY1H) assays to detect cooperativity and antagonism across hundreds of TF-pairs at DNA regions of interest. We provide evidence that a wide variety of TFs are subject to modulation by other TFs in a DNA region-specific manner. We also demonstrate that TF-TF relationships are often affected by alternative isoform usage and identify cooperativity and antagonism between human TFs and viral proteins from human papillomaviruses, Epstein-Barr virus, and other viruses. Altogether, pY1H assays provide a broadly applicable framework to study how different functional relationships affect protein occupancy at regulatory DNA regions.


Urea creams in the treatment of dry skin and hand dermatitis.
Two randomized, double-blind comparison studies were conducted to evaluate the efforts of 2 emollient dry skin creams containing urea in the management of dry skin in atopic patients. Cream with 10% urea was shown to be effective in the management of dry skin and hand dermatitis. The cream with a pH of 6 caused less burning.


The Home Situations Questionnaire-PDD version: factor structure and psychometric properties.
The Home Situations Questionnaire (HSQ) is a caregiver-rated scale designed to assess behavioural non-compliance in everyday settings that has been used in several studies in typically developing children. Currently there is no accepted measure of behavioural non-compliance in children with pervasive developmental disorders (PDDs). Investigators of the Research Units on Pediatric Psychopharmacology Autism Network modified the HSQ for children with PDDs by adding five items (making 25 total items), and used it as the primary outcome measure in a clinical trial. In the current investigation, we examined the factor structure and psychometric properties of the modified scale, the HSQ-PDD. An exploratory factor analysis with oblique rotations yielded two factors: 'Socially Inflexible' (14 items) and 'Demand-Specific' (six items). Item content of both factors appeared to fit well with the rubric of PDDs. Internal consistency, using Cronbach's alpha statistic, was 0.90 for 'Socially Inflexible', and 0.80 for 'Demand-Specific.' The obtained sub-scales and HSQ-PDD Total score showed moderate correlations with selected sub-scales of the Aberrant Behavior Checklist, Child and Adolescent Symptom Inventory, and Children's Yale-Brown Obsessive Compulsive Scale, and low correlations with the Vineland Adaptive Behavior sub-scales. The HSQ-PDD appears to be well suited for children with PDDs, although the Demand-Specific sub-scale may benefit from addition of more items. We provided sub-scale means and standard deviations for this relatively severe group of children with PDDs, and discussed the factor structure with respect to previous research.


Potent carcinogenicity of uncovered halogen lamps in hairless mice.
Uncovered halogen quartz lamps, which are potently genotoxic both in prokaryotic and human cells due to the emission of far-UV radiation (UVB and UVC), were assayed for carcinogenicity in three strains of hairless mice (SKH-1, MF-1, and C3H) of both sexes. As assessed in 5 independent experiments, no spontaneous skin tumor was observed, even after more than 2 years, in 49 animals used as unexposed controls or in 29 animals exposed to halogen lamps equipped with a common glass cover. In contrast, almost all of the 185 mice exposed to the light emitted by low-voltage (12 V) and low-power (50 W) tungsten bulbs, equipped with dichroic diffusers, contracted multiple skin tumors of various histological type, both benign and malignant. Tumors were induced over a range of illuminance levels (1,000, 3,333, 5,000, and 10,000 lux) and daily exposure times (1.5, 3, 6, and 12 h). The tumor latency times were quite short and significantly correlated with the daily exposure times, as well as with the square of the distance (46-194 cm) from the illumination source. A carcinogenic effect was even observed when exposure was discontinued well before the appearance of skin lesions. Both in vitro genotoxicity data and animal carcinogenicity data support the view that the light emitted by uncovered halogen lamps, to which an enormous number of individuals are exposed, may pose carcinogenic risks to humans. Without renouncing the benefits of this modern illumination system, UV-blocking devices should be compulsory.


Helicobacter pylori infection altered gastric microbiota in patients with chronic gastritis.
The present study aims to investigate the effect of Helicobacter pylori (Hp) infection on gastric mucosal microbiota in patients with chronic gastritis. Here recruited a population of 193 patients with both chronic gastritis and positive rapid urease, including 124 patients with chronic atrophic gastritis (CAG) and 69 patients with chronic non-atrophic gastritis (nCAG). Immunoblotting was used to detect four serum Hp antibodies (UreA, UreB, VacA and CagA) to determine the types of virulent Hp-I and avirulent Hp-II infections. Gastric microbiota was profiled by 16S rRNA gene V3-V4 region, and R software was used to present the relationship between the microbial characteristics and the type of Hp infection. In the stomach of patients with Hp-positive gastritis, the dominant gastric bacterial genera included Ralstonia (23.94%), Helicobacter (20.28%), Pseudonocardia (9.99%), Mesorhizobium (9.21%), Bradyrhizobium (5.05%), and Labrys (4.75%). The proportion of Hp-I infection was significantly higher in CAG patients (91.1%) than in nCAG patients (71.0%) (P < 0.001). The gastric microbiota richness index (observed OTUs, Chao) was significantly lower in CAG patients than in nCAG patients (P <0.05). Compared with avirulent Hp-II infection, virulent Hp-I infection significantly decreased the Shannon index in CAG patients (P <0.05). In nCAG patients, Hp-I infected patients had lower abundances of several dominant gastric bacteria (Aliidiomarina, Reyranella, Halomonas, Pseudomonas, Acidovorax) than Hp-II infected patients. Meanwhile, in CAG patients, Hp-I infected patients occupied lower abundances of several dominant oral bacteria (Neisseria, Staphylococcus and Haemophilus) than Hp-II infected patients. In addition, bile reflux significantly promoted the colonization of dominant oral microbiota (Veillonella, Prevotella 7 and Rothia) in the stomach of CAG patients. There was no significant symbiotic relationship between Helicobacter bacteria and non-Helicobacter bacteria in the stomach of nCAG patients, while Helicobacter bacteria distinctly linked with the non-Helicobacter bacteria (Pseudolabrys, Ralstonia, Bradyrhizobium, Mesorhizobium and Variovorax) in CAG patients. Virulent Hp infection alters the gastric microbiota, reduces microbial diversity, and enhances the symbiotic relationship between the Helicobacter bacteria and non-Helicobacter bacteria in patients with chronic gastritis. The data provides new evidence for treating Hp infection by improving the gastric microbiota.


Temperature dependence of calcium-induced fusion of sonicated phosphatidylserine vesicles.
We have measured the temperature dependence calcium-induced fusion of sonicated phosphatidylserine vesicles. The vesicles were incubated in the presence of calcium at a specified temperature until the resulting aggregation or fusion process had gone to completion. EDTA was then added and the resulting final size of the vesicle population was measured by using dynamic light scattering. This final size was plotted against incubation temperature to show the temperature dependence of calcium-induced fusion. This curve has a peak near 11 degrees C which may be associated with the phase transition of the sonicated phosphatidylserine vesicles in the presence of calcium prior to the aggregation or fusion process.


A novel p.E311K mutation of thyroid receptor beta gene in resistance to thyroid hormone syndrome, inherited in autosomal recessive trait.
Resistance to thyroid hormone (RTH) syndrome is caused by mutations in THRB gene and is inherited mainly as an autosomal dominant trait with dominant negative effect. Most of up-to-now described RTH cases were heterozygous. We studied a 19-year-old woman presenting severe mental impairment, hyperkinetic behavior, learning disability, hearing loss, tachycardia, goiter, strabismus, nystagmus, and normal stature. The laboratory findings revealed elevated TSH, T3, and T4 serum levels. Her parents were healthy with normal serum level of TSH, fT3, and fT4. Sequence based prediction of a substitution was analyzed by SDM, PolPhen, and SNAP software whereas structural visualizations were performed in UCSF Chimera. We found a novel mutation in THRB gene in position 1216 (G to A transition, codon 311) resulting in novel Glu-311-Lys (p.E311K) substitution, homozygous in proband presenting with severe symptoms of RTH and heterozygous in both of her healthy parents, thus suggesting autosomal recessive mode of inheritance. p.E311K substitution was not found in 50 healthy, unrelated individuals. p.E311K was shown to be deleterious by SDM, PolPhen, and SNAP software. Structural visualizations of mutated protein performed by UCSF Chimera software disclosed a loss of hydrogen bonds between E311, R383, and R429 along with abnormal residue-residue contact between K311 and L377. This is a very rare case of a homozygous mutation in a patient with severe symptoms of RTH and lack of symptoms in both heterozygous parents. Although, computational analyses have provided the evidence that p.E311K substitution may affect THRB function, lack of dominant negative effect typical for THRB mutations could not be explained by structure-based modeling. Further in vitro analysis is required to assess the functional consequences of this substitution.


Pattern of Anti-hypertensives Usage in Hypertension with or without Comorbidities in a Tertiary Care Hospital.
Hypertension is a chronic illness associated with high morbidity & mortality. A large number of antihypertensive drugs alone or in various combinations are available and physicians need to choose the most appropriate drug for a particular patient. The standard treatment guidelines and drug utilization studies at regular intervals help physicians to prescribe drugs rationally. The present study was conducted to evaluate the use of antihypertensive in hypertension with or without ischemic heart disease and diabetes mellitus at Department of Cardiology in Mymensingh Medical College Hospital, Mymensingh from July 2015 to October 2015. It was an observational type of descriptive cross sectional study. The study was performed among 400 hypertensive patients in Cardiology department in MMCH who received antihypertensive drug. Out of 400 hypertensive patients 67% were male and 33% were female. Maximum patients (54%) found in 40 - <60 years age group and ≤60 years age group (37.5%). Mean age of the patients was 55.02±12.47 years. Mean systolic BP was 146.74±28.28 and diastolic BP was 90.60±14.27mmHg. In overall prescription combination therapy (63.25%) was prescribed more frequently than mono-therapy (36.75%). In monotherapy ramipril was the most commonly prescribed (27.89%) antihypertensive drug and ARB was the most commonly prescribed group (37.41%). In our study 5 groups of antihypertensive were found (ARB, ACEI, BB, Diuretics, and CCB). In combination therapy 2-drugs combination were found most frequently (37.50%) and ACEI + Diuretics (23.72%) was the most common combination followed by ARB + Diuretics (12.25%), ACEI + BB (11.86%). Average number of antihypertensive drug per prescription was 1.9.


The baubellum is more developmentally and evolutionarily labile than the baculum.
Understanding the evolutionary forces that influence sexual dimorphism is a fundamental goal in biology. Here, we focus on one particularly extreme example of sexual dimorphism. Many mammal species possess a bone in their penis called a baculum. The female equivalent of this bone is called the baubellum and occurs in the clitoris, which is developmentally homologous to the male penis. To understand the potential linkage between these two structures, we scored baculum/baubellum presence/absence across 163 species and analyzed their distribution in a phylogenetic framework. The majority of species (N = 134) shared the same state in males and females (both baculum and baubellum present or absent). However, the baubellum has experienced significantly more transitions, and more recent transitions, so that the remaining 29 species have a baculum but not a well-developed baubellum. Even in species where both bones are present, the baubellum shows more ontogenetic variability and harbors more morphological variation than the baculum. Our study demonstrates that the baculum and baubellum are generally correlated across mammals, but that the baubellum is more evolutionarily and developmentally labile than the baculum. The accumulation of more evolutionary transitions, especially losses in the baubellum, as well as noisier developmental patterns, suggests that the baubellum may be nonfunctional, and lost over time.


Population-level relationships between alcohol consumption measures and Ischemic Heart Disease mortality in U.S. time-series.
Individual-level studies indicate the possibility of both protective and harmful effects of alcohol consumption on Ischemic Heart Disease (IHD) mortality depending on the pattern of consumption. Population-level relationships could be in either direction and previous studies have found mixed results. Population-level relationships between IHD mortality rates and per capita consumption of alcoholic beverages, cirrhosis mortality rates, cigarettes, and sugar sweetened soda for the period from 1950 to 2002 are modeled using autoregressive integrated moving average (ARIMA) and vector error correction methods. In multivariate ARIMA models controlling for accumulated heavy drinking as represented by cirrhosis mortality, a protective effect of 4%/l was found for total alcohol consumption while cirrhosis mortality rates had significant positive effects on IHD rates. Beverage-specific models found no effect for wine, positive risks for spirits, and significant protective effects for beer. The protective effects for both total alcohol and beer were also found in vector error correction models. Significant positive effects of cigarette sales on IHD rates were also found in both types of models. The complexity of alcohol's relationship with IHD is highlighted. Aspects of pattern represented by beverage-specific consumption and cirrhosis mortality indicate potential protective effects from moderate drinking and harmful effects from heavy drinking in accord with individual-level findings.


The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.
Mycobacterium tuberculosis, responsible for Tuberculosis (TB), remains the leading cause of mortality among infectious diseases worldwide from a single infectious agent, with an estimated 1.7 million deaths in 2016. Biotin is an essential cofactor in M. tuberculosis that is required for lipid biosynthesis and gluconeogenesis. M. tuberculosis relies on de novo biotin biosynthesis to obtain this vital cofactor since it cannot scavenge sufficient biotin from a mammalian host. The biotin biosynthetic pathway in M. tuberculosis has been well studied and rigorously genetically validated providing a solid foundation for medicinal chemistry efforts. This review examines the mechanism and structure of the enzymes involved in biotin biosynthesis and ligation, summarizes the reported genetic validation studies of the pathway, and then analyzes the most promising inhibitors and natural products obtained from structure-based drug design and phenotypic screening.


Comparative analysis of KNOX genes and their expression patterns under various treatments in Dendrobium huoshanense.
KNOX plays a pivotal role in governing plant growth, development, and responses to diverse abiotic and biotic stresses. However, information on the relationship between the KNOX gene family and expression levels under different treatments in Dendrobium is still limited. To address this problem, we first used bioinformatics methods and revealed the presence of 19 KNOX genes distributed among 13 chromosomes in the Dendrobium huoshanense genome. Through an analysis of phylogenetic relationships, these genes were classified into three distinct clades: class I, class II, and class M. Our investigation included promoter analysis, revealing various cis-acting elements associated with hormones, growth and development, and abiotic stress responses. Additionally, qRT-PCR experiments were conducted to assess the expression patterns of DhKNOX genes under different treatments, including ABA, MeJA, SA, and drought. The results demonstrated differential expression of DhKNOX genes in response to these treatments, thereby highlighting their potential roles in stress adaptation. Overall, our results contribute important insights for further investigations into the functional characterization of the Dendrobium KNOX gene family, shedding light on their roles in plant development and stress responses.


Unusual High-Temperature Reversible Phase-Transition Behavior, Structures, and Dielectric-Ferroelectric Properties of Two New Crown Ether Clathrates.
Molecular ferroelectrics with high-temperature reversible phase-transition behaviors are very rare and have currently become one of the hotspots in the field of ferroelectric materials. Herein we display two new crown ether clathrates possessing unusual high-temperature ferroelectric phase-transition behaviors, cyclohexyl ammonium 18-crown-6 tetrafluoroborate (or perchlorate), [Hcha-(18-crown-6)](+) [BF4](-) (1) and [Hcha-(18-crown-6)](+)[ClO4](-) (2) (Hcha = protonated cyclohexyl ammonium). We have proven their reversible structural phase transitions by variable-temperature PXRD measurements and temperature evolutions of Raman bands. Both clathrates exhibit clear ferroelectric phase transitions at about 397 and 390 K, respectively, revealed by the thermal anomalies of differential scanning calorimetry (DSC) measurements, together with abrupt dielectric anomalies in the heating and cooling processes. The measurements on ferroelectric properties using the single crystals showed optimized spontaneous polarization (Ps) of ca. 3.27 μC cm(-2) for 1 and 3.78 μC cm(-2) for 2.


Fibular allograft after anterior cervical corpectomy: long term follow-up.
The purpose of this study was to provide clinical and radiographic evaluation after a minimum of two years in patients who had an anterior cervical corpectomy and a fibular allograft strut. Nineteen patients returned for a follow-up visit which included independent radiographic evaluation as well as completing a Visual Analogue Scale and Oswestry and Short-Form 36 questionnaires. The categories of fusion were as follows: 1) definitely fused (84%) 2) questionably fused (11%) 3) definitely not fused (5%). The average VAS was 29 mm (range 0-85). The Oswestry Back Scores showed relatively low levels of significant pain with an average score of 29 (range 0-73). Anterior cervical corpectomy followed by an allograft fibular strut provides for relatively high rates of arthrodesis without severe loss of height or sagittal alignment at long term radiographic follow-up.