Enhancement of the antibiofilm activity of amphotericin B by polyamine biosynthesis inhibitors.
The aim of this study was to investigate the effect of polyamine biosynthesis inhibitors on the activity of amphotericin B (AmB) against Candida albicans biofilms and to clarify the underlying mechanisms. The antibiofilm activity of AmB was significantly enhanced when used in combination with the polyamine biosynthesis inhibitors 1,4-diamino-2-butanone (DAB) and α-difluoromethylornithine (DFMO). Further study showed that DAB and DFMO also enhanced the antibiofilm activity of several other antifungal agents. Moreover, the combination of AmB and polyamine biosynthesis inhibitors resulted in an increase in intracellular levels of reactive oxygen species. In addition, caspase activity and transcription of the caspase-encoding gene CaMCA1 were greatly increased upon combined treatment with polyamine biosynthesis inhibitors and AmB. Consistently, the biofilm formed by a Δcamca1 mutant exhibited greater viability and lower caspase activity than that of the wild-type strain upon combined treatment. These data provide useful information for the development of new strategies to enhance the antibiofilm activities of antifungal agents.


Endoscopic ultrasonography in the diagnosis of esophageal carcinoma.
In selection for esophageal cancer treatment, it is necessary to evaluate the tumor stage. We have used endoscopic ultrasonography (EUS) for diagnosis of the depth of cancer invasion and the presence of lymph node metastasis since 1983. The EUS image of the normal esophageal wall showed 5 layers. In all, 222 cases of esophageal cancer were examined with EUS, and a radical operation was performed on 139. In 78 of those cases, the scope was passed beyond the cancer site, and total observation was achieved (56%). The extent of cancer invasion was correctly determined in these 78 cases (84%). Thoracic lymph nodes that could be detected by EUS were located in the posterior mediastinum and measured more than 3 mm in diameter. Diagnostic criteria for lymph node metastasis were designated as follows: (1) spherical shape, (2) a distinct border, and (3) heterogenous echo spots within the nodes. The above criteria yielded a sensitivity of 87%, a specificity of 90%, and an overall accuracy of 89% according to the histological examination of the removed lymph nodes.


The induction of anti-erythrocyte antibodies in vivo by administration of lipopolysaccharide.
Experiments were designed to determine whether B-cell activation of control mouse strains with lipopolysaccharide (LPS) could induce the same anti-erythrocyte antibody responses observed to occur spontaneously in the NZB strain. When BALB/c and DBA/2 mice were injected intraperitoneally with 100 micrograms of LPS, antibodies to X, HB, and HOL antigens could be detected 2 weeks later at levels comparable to those found spontaneously in NZB mice. Injection of C3H/HeJ mice, nonresponders to LPS, resulted in no detectable anti-erythrocyte antibody responses. When NZB mice were treated with LPS in this way, serum levels of anti-RBC antibodies increased. A measure of the percentage hemolysis induced by sera from these animals in the presence of an exogenous complement source revealed a higher incidence and hemolytic titer in LPS-injected BALB/c and DBA/2 strains than in PBS-injected mice. In addition, injection of LPS induced the appearance of erythrocyte-bound IgM and IgG in BALB/c, DBA/2, and NZB mice. These data suggest that LPS-induced B-cell activation results in the appearance of anti-erythrocyte antibodies.


Chest radiography practice in critically ill patients: a postal survey in the Netherlands.
To ascertain current chest radiography practice in intensive care units (ICUs) in the Netherlands. Postal survey: a questionnaire was sent to all ICUs with > 5 beds suitable for mechanical ventilation; pediatric ICUs were excluded. When an ICU performed daily-routine chest radiographs in any group of patients it was considered to be a "daily-routine chest radiography" ICU. From the number of ICUs responding, 63% practice a daily-routine strategy, in which chest radiographs are obtained on a daily basis without any specific reason. A daily-routine chest radiography strategy is practiced less frequently in university-affiliated ICUs (50%) as compared to other ICUs (68%), as well as in larger ICUs (> 20 beds, 50%) as compared to smaller ICUs (< 20 beds, 65%) (P > 0.05). Remarkably, physicians that practice a daily-routine strategy consider daily-routine radiographs helpful in guiding daily practice in less than 30% of all performed radiographs. Chest radiographs are considered essential for verification of the position of invasive devices (81%) and for diagnosing pneumothorax, pneumonia or acute respiratory distress syndrome (82%, 74% and 69%, respectively). On demand chest radiographs are obtained after introduction of thoracic drains, central venous lines and endotracheal tubes in 98%, 84% and 75% of responding ICUs, respectively. Chest films are also obtained in case of ventilatory deterioration (49% of responding ICUs), and after cardiopulmonary resuscitation (59%), tracheotomy (58%) and mini-tracheotomy (23%). There is notable lack of consensus on chest radiography practice in the Netherlands. This survey suggests that a large number of intensivists may doubt the value of daily-routine chest radiography, but still practice a daily-routine strategy.


MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice.
Commensal bacterial sensing by Toll-like receptors is critical for maintaining intestinal homeostasis, but can lead to colitis in the absence of interleukin-10. Although Toll-like receptors are expressed in multiple cell types in the colon, the cell type(s) responsible for the development of colitis are currently unknown. Here we generated mice that are selectively deficient in MyD88 in various cellular compartments in an interleukin-10(-/-) setting. Although epithelial expression of MyD88 was dispensable, MyD88 expression in the mononuclear phagocyte compartment was required for colitis development. Specifically, phenotypically distinct populations of colonic mononuclear phagocytes expressed high levels of interleukin-1β, interleukin-23 and interleukin-6, and promoted T-helper 17 responses in the absence of interleukin-10. Thus, gut bacterial sensing through MyD88 in mononuclear phagocytes drives inflammatory bowel disease when unopposed by interleukin-10.


Prevalence of type 2 diabetes diagnoses in the perioperative and survivorship periods following surgical management of endometrial cancer: An opportunity for screening and intervention?
To determine the prevalence of Type 2 diabetes mellitus (T2DM) diagnoses during the peri-operative and survivorship periods in patients following surgical management of endometrial cancer (EC). An IRB-approved, retrospective single-institution cohort study was performed in patients who underwent surgical management of EC from 2014 to 2020. The perioperative period was defined as the 30 days before and after surgery. T2DM diagnoses occurring during survivorship were recorded. T2DM diagnoses were defined by a HgbA1c ≥6.5% or a random blood glucose ≥200 mg/dL. Sequelae of peri-operative T2DM and predictors of future T2DM were examined utilizing univariate analysis. Of 519 patients meeting inclusion criteria, 37 (7.1%) were diagnosed with T2DM in the perioperative period. Patients diagnosed with T2DM in the perioperative period had significantly higher BMI (p = 0.006) compared to no T2DM, but there were no significant differences in age (p = 0.20), ethnicity/race (p > 0.05) or ECOG score (p = 0.19). The rates of intraoperative complications between groups did not significantly differ, except for vascular complications (p = 0.005), and the incidence of any postoperative complication was higher in the perioperative T2DM group (p = 0.01). With a median follow-up of 29 months [range 11.6-49.0 months], an additional 18.3% (n = 88) of the cohort met diagnostic criteria for T2DM. BMI (p < 0.001), perioperative glucose (p < 0.001), and HgbA1c (p = 0.002) demonstrate risk for a T2DM diagnosis during survivorship. In this retrospective cohort of EC patients, 25.4% were diagnosed with T2DM, with the majority diagnosed in the survivorship period. Surgical management and subsequent surveillance of EC presents an opportunity to diagnose at-risk patients with T2DM.


[Study of the destruction of the sympathetic ganglia by the administration of guanethidine to newborn rats and mice].
Following the injection of guanethidine (25 mg/kg) to rats from the first day of life during 2 weeks, over 70% of sympathic neurons in the stellate ganglion die. If the injections are carried out during 4 weeks, over 99% of neurons die. The injection of guanethidine to mice during 5 weeks did not result in the destruction of nerve elements in the ganglion, as compared with the control.


Quality of life on home parenteral nutrition: a single centre study of 37 patients.
Quality of life was assessed in 37 patients receiving home parenteral nutrition (HPN) for intestinal failure. A questionnaire was developed specifically for this purpose and the results were compared with those obtained by subjective assessment using a simple linear scale. The majority of patients (n = 26, 70.3%) had a good objective quality of life and most (n = 16, 53.3%) of those eligible (n = 30, 81.1%) did not express an interest in intestinal transplantation. Despite the apparent good quality of life enjoyed by patients receiving HPN, there were numerous areas in which patients with intestinal failure felt that their quality of life left much to be desired: many patients reported significant psychological symptoms (n = 15, 40.5%) sexual (n = 10, 27.0%) and social dysfunction (n = 19, 51.3%) and most patients with intestinal failure were unable to return to work (n = 24, 88.9%). Detailed quality of life assessment reveals that there is much still to be done to ensure that provision of care for patients with intestinal failure involves not only prolongation of life but also an improvement in quality of life.


The safety-net story about macrocyclic lactone heartworm preventives: a review, an update, and recommendations.
A number of safe, effective, and convenient heartworm preventatives are currently available for virtually all canine and feline pets. Yet, a 2001 survey of over 18,000 veterinary clinics in the United States identified more than 240,000 dogs and 3000 cats infected with Dirofilaria immitis. This high level of owner compliance failure is alarming. Prolonged administration of some of the macrocyclic lactone (ML) preventatives kills young larvae, older larvae, "immatures," young adults, and/or old adults. Efficacy of 95% or more requires dosing for 9-30 months, with older worms being more difficult to kill. Of the various MLs, ivermectin (IVM) has the most potent safety-net and adulticidal activity, milbemycin oxime has the least, and selamectin and moxidectin injectable lie somewhere in between. The unique effects of IVM are related to the age of the heartworms at initiation of treatment. The earlier treatment is started, the more stunted and smaller the worms and the shorter their survival time. Conversely, the later treatment is started, the longer the worms live, and the more likely the dog will be antigen- and microfilariae-positive. Drug effects do not appear to be enhanced by increasing the dosage or administering at shorter intervals, and it appears that continuous monthly treatment is needed to produce the full effects of the drug. The American Heartworm Society (AHS) recognizes the safety-net (or reach-back effect) and adulticidal properties of some MLs, particularly IVM. The AHS 2003 (American Heartworm Society, 2004. 2003 Updated guidelines for the diagnosis, prevention, and management of heartworm (Dirofilaria immitis) infection in dogs. In: McCall, et al., (Eds.), Proceedings of the Symposium Session on Recent Advances in Heartworm Disease, The 19th International Conference of the World Association for the Advancement of Veterinary Parasitology, New Orleans, LA, 10-14 August, 2003. Vet. Parasitol. 125, 105-130) canine guidelines state that it is beneficial to administer prophylactic doses of IVM before treatment with melarsomine. Results of laboratory studies suggest that less active dogs are at low risk of severe thromboembolism and death. However, heartworm-positive working dogs might be more at risk. Worsened radiographic and echocardiographic images in a client-owned dog given IVM monthly for 2 years with greatly restricted exercise suggests that such treatment of dogs with clinical, radiographic, and/or echocardiographic evidence of heartworm disease as well as for asymptomatic working dogs is contraindicated. Furthermore, until further data are available, such treatment of even the less active asymptomatic dog should be administered only with much caution and with examination by a veterinarian at least once every 4-6 months. IVM clearly provides potent "safety-net" activity against older larvae, immatures, and young adults in cases of owner compliance failure, even when the owner and veterinarian are not aware that the animal is infected, and offers much promise as a unique "soft-kill" treatment for young, and possibly older adult heartworms, with reduced risks.


Different action of hormonal stimulation on the biosynthesis of three pancreatic enzymes.
The rates of biosynthesis of amylase, lipase and chymotrypsinogen were followed in rat pancreas in vivo after intravenous injection of the hormone cholecystokinin-pancreozymin (8 IDU/kg) associated with secretin (5 CU/kg). This pancreatic stimulation resulted in non-parallel variations of the rates of biosynthesis of the three studied enzymes, suggesting independent regulation of synthesis. The result of one stimulation was calculated in terms of quantities of enzymes synthesized by the pancreas in comparison to control. It was found that chymotrypsinogen, amylase and lipase productions were increased by 63, 26 and 10%, respectively, indicating that repeated cholecystokinin-pancreozymin plus secretin stimulations could induce "adaptation-like" modifications of the pancreatic enzyme content.


Exploring the Impact of Verbal Abuse on Recovery: A Mediation Study.
People with serious mental illnesses are exposed to high rates of verbal abuse. This study examines the impact of such experiences on loneliness and social support, which is hypothesized to ultimately diminish recovery. Fifty participants with serious mental illnesses reported on their experiences with verbal abuse, loneliness, social support, and recovery. Verbal abuse was found to be related to loneliness and social support, and both mediated the relationship between verbal abuse and recovery. Verbal abuse is an all too common experience of people with serious mental illnesses that ultimately affects their recovery. Specifically, exposure to verbal abuse may impact recovery by increasing sense of loneliness and perceived social support. The implications are that a heightened awareness of verbal abuse and its impact on recovery should draw attention to interventions that decrease exposure and increase self-advocacy to combat negative outcomes.


Metacognitive knowledge of attention in children with and without ADHD symptoms.
Children with ADHD (Attention Deficit Hyperactivity Disorder) experience difficulty in managing attention in school, but it is not sufficiently clear what their attentional beliefs are. Drawing is a means of expression that is habitually used to access knowledge or ideas of children regarding their classroom experience. The aim of this study is to verify whether children with ADHD use pictorial indicators analogous to children without ADHD (N-ADHD). 92 primary school students participated in this study, half of whom diagnosed with ADHD. Children were asked to produce two specific thematic drawings on attention vs. inattention; their pictorial representations were analyzed using the Children's Awareness of Attention through Drawing (CAAD). The analysis showed principally that children with ADHD have a metacognitive awareness of attention similar to N-ADHD except for a delay in acquisition of the correct posture, for less maturation in the management of school materials and greater expression of negative feelings over time. Children with ADHD are aware of what is required in the school context but they are not able to pursue it. Behavioral intervention and structured learning are two targets of intervention that can help children with ADHD to adapt and to stay at school.


New genes for focal epilepsies with speech and language disorders.
The last 2 years have seen exciting advances in the genetics of Landau-Kleffner syndrome and related disorders, encompassed within the epilepsy-aphasia spectrum (EAS). The striking finding of mutations in the N-methyl-D-aspartate (NMDA) receptor subunit gene GRIN2A as the first monogenic cause in up to 20% of patients with EAS suggests that excitatory glutamate receptors play a key role in these disorders. Patients with GRIN2A mutations have a recognizable speech and language phenotype that may assist with diagnosis. Other molecules involved in RNA binding and cell adhesion have been implicated in EAS; copy number variations are also found. The emerging picture highlights the overlap between the genetic determinants of EAS with speech and language disorders, intellectual disability, autism spectrum disorders and more complex developmental phenotypes.


Identification of an unexpected shunt pathway product provides new insights into tirandamycin biosynthesis.
Tirandamycin K (7), the first linear 7,13;9,13-diseco-tirandamycin derivative, was isolated from the tamI (encoding the TamI P450 monooxygenase) disruption mutant strain (ΔtamI) of marine Streptomyces sp. 307-9. Its chemical structure with relative and absolute configurations was elucidated by a combination of extensive spectroscopic analyses and biosynthetic inferences. Structural elucidation of this unusual compound provides new insights into tirandamycin biosynthesis. Moreover, examination of the biological activity of 7 confirms the essential function of the bicyclic ketal ring for antibiotic activities of tirandamycins.


Multistage carcinogenesis: implications for risk estimation.
In undertaking a quantitative estimation of carcinogenesis risk, it is essential to keep in mind that carcinogenesis is a multistage process, and that each stage can be affected by different classes of risk factors. Furthermore, different mechanisms are involved in the various stages of carcinogenesis. Thus, a dose-response analysis of one given factor cannot provide an accurate estimation of carcinogenic risk. Carcinogenic risk estimation is usually undertaken for a specific chemical or group of chemicals; however, the concept of multistage carcinogenesis is based on biological processes and not on the mechanisms of action of the agents involved. It is therefore important to consider three related, but different, factors involved in carcinogenesis: stage, agent, and activity of agent. This is especially important in developing a short-term test for stage-related risk factors, such as tumor-promoting agents. For this reason, carcinogens should not be classified according to only one chemical activity. This article briefly reviews the cellular and molecular mechanisms involved in multistage carcinogenesis, and discusses their implications for risk estimation. Special consideration is given to the effect of treatment frequency on the response of tumor-promoting agents, as seen in long-term tests in experimental animals. It is proposed that exposure frequency be taken into account together with exposure dose.


Adaptive Transfer Kernel Learning for Transfer Gaussian Process Regression.
Transfer regression is a practical and challenging problem with important applications in various domains, such as engineering design and localization. Capturing the relatedness of different domains is the key of adaptive knowledge transfer. In this paper, we investigate an effective way of explicitly modelling domain relatedness through transfer kernel, a transfer-specified kernel that considers domain information in the covariance calculation. Specifically, we first give the formal definition of transfer kernel, and introduce three basic general forms that well cover existing related works. To cope with the limitations of the basic forms in handling complex real-world data, we further propose two advanced forms. Corresponding instantiations of the two forms are developed, namely Trkαβ and Trkω based on multiple kernel learning and neural networks, respectively. For each instantiation, we present a condition with which the positive semi-definiteness is guaranteed and a semantic meaning is interpreted to the learned domain relatedness. Moreover, the condition can be easily used in the learning of TrGP αβ and TrGP ω that are the Gaussian process models with the transfer kernels Trkαβ and Trkω respectively. Extensive empirical studies show the effectiveness of TrGP αβ and TrGP ω on domain relatedness modelling and transfer adaptiveness.


Metallurgical manipulation of surface Volta potential in bimetals and cell response of human mesenchymal stem cells.
Bioelectricity plays an overriding role in directing cell migration, proliferation, differentiation etc. Tailoring the electro-extracellular environment through metallurgical manipulation could modulate the surrounding cell behaviors. In this study, different electric potential patterns, in terms of Volta potential distribution and gradient, were created on the metallic surface as an electric microenvironment, and their effects on adherent human mesenchymal stem cells were investigated. Periodically and randomly distributed Volta potential pattern, respectively, were generated on the surface through spark plasma sintering of two alternatively stacked dissimilar metals films and of a mixture of metallic powders. Actin cytoskeleton staining demonstrated that the Volta potential pattern strongly affected cell attachment and deformation. The cytoskeletons of cells were observed to elongate along the Volta potential gradient and across the border of adjacent regions with higher and lower potentials. Moreover, the steepest potential gradient resulting from the drastic compositional changes on the periodic borders gave rise to the strongest osteogenic tendency among all the samples. This study suggests that tailoring the Volta potential distribution and gradient of metallic biomaterials via metallurgical manipulation is a promising approach to activate surrounding cells, providing an extra degree of freedom for designing desirable bone-repairing metallic implants.


Potential toxicity of inorganic ions in particulate matter: Ion permeation in lung and disruption of cell metabolism.
Exposure to ambient particulate matter (PM) is associated with adverse health effects. Yet, due to the complexity of its chemical composition, the molecular effects of PM exposure and the mechanism of PM-mediated toxicity remain largely unknown. Here, we show that water-soluble inorganics such as nitrate and sulfate ions, rather than PM itself, rapidly penetrate the lung surfactant barrier to the alveolar region and perturb gene expression in the lungs. Through high-throughput sequencing of lung adenocarcinoma cells, we find that exposure to nitrate and sulfate ions activates the cholesterol biosynthetic metabolism and induces the expression of genes related to tumorigenesis. Transcriptome analysis of mouse lungs exposed to nitrate/sulfate aerosols reveals interferon gamma-associated immune response. Interestingly, we find that exposure to a nitrate/sulfate mixture leads to a unique gene expression pattern that is not observed when nitrate or sulfate is treated alone. Our work suggests that the water-soluble ions are a potential source of PM-mediated toxicity and provides a roadmap to unveil the molecular mechanism of health hazards from PM exposure.


Perceptual organization in moving patterns.
Is human motion perception based on a local piecemeal analysis of the image or do global effects play an important role? We used metastable apparent motion displays (Fig. 2) to try to answer this question. Two spots were flashed simultaneously on diagonally opposite corners of a square and then switched off and replaced by two spots appearing on the remaining corners. One could either see vertical or horizontal oscillation of the spots and the display was bistable just as a Necker cube is. We found that if several such bistable figures were randomly scattered on the screen (Fig. 3b), and presented simultaneously, then one always saw the same motion-axis in all of them, suggesting the presence of global field-like effects for resolving ambiguity in apparent motion. Surprisingly, the appearance of these displays could not be influenced by voluntary effort unless the speed of alternation was very slow. (Less than 3 frames per second.) It may be that if the events in the module that computes apparent motion are too rapid then it cannot be coupled with the "will" mechanism, which may have a long time constant.


The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines.
We mixed various amounts of methotrexate with bone cement and measured the absorbance daily for 4 weeks. The cytotoxic effects on SaOS2 and MG63 osteosarcoma cells were examined by the MTT assay, and analysed according to the methotrexate concentration and the elapsed time. The amount of eluted methotrexate was greatest during the first day, and then decreased rapidly reaching a plateau in the third week. The number of viable tumour cells decreased significantly after 72 h, and they were hardly seen after 1 week.


[Nephrotoxicity of aminoglycosides].
The paper presents recent views on the aminoglycoside (AG) nephrotoxicity. The risk factors for nephrotoxicity in the patients treated with AG are discussed.


In Situ Radical Reaction-Modified Carbon Dot Nanocapsules with Macrophage Escape and Prolonged Imaging.
Carbon dots (CDs) have emerged as an extremely promising platform for biological imaging, owing to their optical properties and low toxicity. However, one of the major challenges in utilizing CDs for in vivo imaging is their high immunogenicity and rapid clearance, which limits their potential. Herein, a novel approach for mitigating these issues is presented through the development of carbon dot nanocapsules (nCDs). Specifically, CDs are encapsulated within a zwitterionic polymer shell composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) to create nCDs with a size of ≈40 nm. Notably, the nCDs exhibit excitation-dependent photoluminescence behavior in the range of 550-600 nm, with tunability based on the excitation wavelength. In confocal imaging, CDs display a strong fluorescence signal after 8 h of incubation with phagocytes, while nCDs show minimal signal, suggesting that nCDs may be capable of evading phagocyte uptake. Furthermore, imaging studies in zebrafish demonstrate that nCDs exhibit a retention time >10 times longer than that of CDs, with fluorescence intensity remaining at 81% after 10 h compared to only 8% for CDs. Taken together, the study presents a novel approach for enhancing the performance of CDs in in vivo imaging applications, offering significant potential for clinical translation.


Quality target negotiation in health care: evidence from the English NHS.
We examine how public sector third-party purchasers and hospitals negotiate quality targets when a fixed proportion of hospital revenue is required to be linked to quality. We develop a bargaining model linking the number of quality targets to purchaser and hospital characteristics. Using data extracted from 153 contracts for acute hospital services in England in 2010/2011, we find that the number of quality targets is associated with the purchaser's population health and its budget, the hospital type, whether the purchaser delegated negotiation to an agency, and the quality targets imposed by the supervising regional health authority.


Label-free, automated classification of microsatellite status in colorectal cancer by infrared imaging.
Challenging histopathological diagnostics in cancer include microsatellite instability-high (MSI-H) colorectal cancer (CRC), which occurs in 15% of early-stage CRC and is caused by a deficiency in the mismatch repair system. The diagnosis of MSI-H cannot be reliably achieved by visual inspection of a hematoxylin and eosin stained thin section alone, but additionally requires subsequent molecular analysis. Time- and sample-intensive immunohistochemistry with subsequent fragment length analysis is used. The aim of the presented feasibility study is to test the ability of quantum cascade laser (QCL)-based infrared (IR) imaging as an alternative diagnostic tool for MSI-H in CRC. We analyzed samples from 100 patients with sporadic CRC UICC stage II and III. Forty samples were used to develop the random forest classifier and 60 samples to verify the results on an independent blinded dataset. Specifically, 100% sensitivity and 93% specificity were achieved based on the independent 30 MSI-H- and 30 microsatellite stable (MSS)-patient validation cohort. This showed that QCL-based IR imaging is able to distinguish between MSI-H and MSS for sporadic CRC - a question that goes beyond morphological features - based on the use of spatially resolved infrared spectra used as biomolecular fingerprints.


The occurrence of atypical sexual experience among various female patient groups.
Clinical interviews with the use of a standard examination format were used to determine sexually atypical experiences in 373 women. The women were divided into three groups. Group 1: 167 women in fertile marriages, Group 2: 102 patients with sexual dysfunctions, Group 3: 104 patients of psychiatric outpatient clinics. Of these, 190 (50.9%) had encountered indecent exposure at least once; 76 women (20.4%) were the victims of attempted rape or rape; 60 women (16.1%) were sexually abused by an adult male prior to menarche; 36 women (9.6%) acknowledged homosexual contacts. Patients with a sexual dysfunction had been the object of sexual abuse in childhood significantly more often than women in the other groups.


Polychlorobiphenyl (PCB) congeners in striped bass (Morone saxatilis) from marine and estuarine waters of New York State determined by capillary gas chromatography.
Edible filets of striped-bass samples (60) from the Hudson River estuary, the Atlantic shore of Long Island, and Long Island Sound were analyzed by high-resolution glass-capillary gas chromatography for 74 polychlorobiphenyl (PCB) compounds. The fish, a non-random subset of a larger sample, contained the following concentrations of total PCB residue (mean +/- the standard error of the mean). The corresponding mean values for the entire survey (N = 717) are given in parentheses: eastern Long Island Sound 1.8 +/- 0.4 (1.91 +/- 0.1) mg/kg; western Long Island Sound, 1.9 +/- 0.2 (2.51 +/- 0.1) mg/kg; eastern Atlantic shore, 3.0 +/- 0.5 (2.45 +/- 0.2) mg/kg; western Atlantic shore, 7.5 +/- 1.9 (3.04 +/- 0.2) mg/kg; Hudson River, 15 +/- 3 (6.19 +/- 0.4) mg/kg. All the samples contained PCB residues derived from Aroclors 1242, 1016, 1254, and 1260 but none of the residue present came from Aroclor 1221 as evidenced by the complete absence of 4-chlorobiphenyl from the fish. Fish from the Hudson River and the majority from the Atlantic shore of Long Island contained 2,2'- and 2,6-dichlorobiphenyls indicating recent exposure to Hudson River PCBs. On this basis, there was evidence that a subpopulation of fish was not exposed to the Hudson River PCB source. The detailed PCB congener make-up of the typical residue found in these fish differs from that found in the majority of human food-stuff in that it contains a proportionately large amount of mono- through tetra-chlorinated PCB. The mean concentration of the more toxicologically suspect congeners which are not readily degraded by mammals and birds (those with two 4-substituents) comprise less than 1 ppm in Long Island Sound fish.


Is Wales ready for the reintroduction of eagles?
Georgina Mills discusses research on Wales' suitability as the home for golden and white-tailed eagles.


Glass wool filtration of bull cryopreserved semen: a rapid and effective method to obtain a high percentage of functional sperm.
Frozen-thawed bull sperm are widely used in assisted reproductive technologies, but cryopreservation negatively affects semen quality. Several sperm selection techniques have been developed to separate motile sperm from non-motile cells. The aim of the present study was to evaluate the effectiveness of the glass wool column filtration to select functional sperm from frozen-thawed bull semen samples. Frozen semen from six Holstein bulls was thawed and filtered through a glass wool column, followed by assessment of routine and functional sperm parameters. In a set of experiments, sperm aliquots were also processed by swim up to compare both selection methods. Samples recovered in the glass wool filtrate had high percentages of viable (94 ± 3%, mean ± SD), progressively motile (89 ± 4%), acrosome-intact (98 ± 1%), and non-capacitated (80 ± 10%) sperm; these values were higher (P < 0.05) than those obtained after performing the swim up procedure. Moreover, the glass wool filtration yielded 67 ± 19% motile cells, in comparison with 18 ± 8% obtained with swim up (P < 0.05), calculated as the concentration of progressively motile cells selected relative to their concentration in the sample before the selection procedure. Glass wool-filtered sperm were able to undergo capacitation-related events, based on the increase in the percentage of cells classified as capacitated by CTC staining (B-pattern) after incubation with heparin (50 ± 5%) in comparison with control conditions with no heparin (17 ± 4%) or heparin + glucose (16 ± 2%; P < 0.05). Moreover, they underwent acrosomal exocytosis in response to pharmacologic (calcium ionophore A23187 and lysophosphatidylcholine) and physiological (follicular fluid) stimuli, and they fertilized in vitro matured cumulus-oocyte complexes and denuded oocytes (two-cell embryos: 72 ± 4% and 52 ± 6%, respectively). We conclude that glass wool filtration is a low-cost, simple, and highly effective procedure to select functionally competent sperm for reproductive technologies in the bull, which may be useful for other domestic and farm animals, as well as for endangered species.


SEA you later alli-GATOR--a dynamic regulator of the TORC1 stress response pathway.
Cells constantly adapt to various environmental changes and stresses. The way in which nutrient and stress levels in a cell feed back to control metabolism and growth are, unsurprisingly, extremely complex, as responding with great sensitivity and speed to the 'feast or famine, slack or stress' status of its environment is a central goal for any organism. The highly conserved target of rapamycin complex 1 (TORC1) controls eukaryotic cell growth and response to a variety of signals, including nutrients, hormones and stresses, and plays the key role in the regulation of autophagy. A lot of attention has been paid recently to the factors in this pathway functioning upstream of TORC1. In this Commentary, we focus on a major, newly discovered upstream regulator of TORC1--the multiprotein SEA complex, also known as GATOR. We describe the structural and functional features of the yeast complex and its mammalian homolog, and their involvement in the regulation of the TORC1 pathway and TORC1-independent processes. We will also provide an overview of the consequences of GATOR deregulation in cancer and other diseases.


A cross-sectional survey on the psychological impact of the COVID-19 pandemic on inflammatory bowel disease patients in Saudi Arabia.
The coronavirus (COVID-19) pandemic has caused significant disruption to patients with chronic illnesses. We explored the emotional state, perception, and concerns of Saudi patients with inflammatory bowel disease (IBD) during the crisis. We conducted a cross-sectional survey from 30 March to 5 April, 2020 using a pre-designed questionnaire distributed through social media platforms to IBD patients. The five-part questionnaire included an assessment of psychological wellbeing using a previously validated Arabic version of the Hospital Anxiety and Depression Scale (HADS), which includes domains for anxiety (HADS-A) and depression (HADS-D). A logistic regression analysis was used to uncover possible associations between patient characteristics and anxiety and depression. The data from 1156 IBD patients were analyzed. Normal, borderline, and HADS-A scores consistent with a diagnosis of anxiety were reported by 423 (36.6%), 174 (15.1%), and 559 (48.4%) patients, respectively. However, 635 (69%) patients had normal scores and 273 (30.1%) had borderline HADS-D scores; no patients reported scores consistent with depression. Based on a multiple logistic regression analysis, patients educated till a high school diploma (OR = 2.57, 95% CI: 0.09-6.05, P = 0.03) and that had indeterminate colitis (OR = 2.23, 95% CI: 1.27-3.89, P = 0.005) were more likely to express anxiety. Many patients expressed symptoms of anxiety, although not depression. Female patients, patients educated till a high school diploma, and those with indeterminate colitis were more likely to have anxiety. IBD patients require greater attention during a pandemic to avoid adverse disease-related outcomes.


Perforalactones D and E, two new C-20 quassinoids with potential activity to induce lysosomal biogenesis from the twigs of Harrisonia perforata (Blanco) Merr.
Two new quassinoids (1 and 2) were isolated from the twigs of Harrisonia perforata (Blanco) Merr. Perforalactone E (2) possesses an uncommon hexacyclic 1α,12α:5α,13α-dicyclo-9βH-picrasane skeleton. Its structure was determined based on spectroscopic data and X-ray crystallography. Compounds 1 and 2 could significantly induce lysosomal biogenesis through transcriptional activation of lysosomal genes.


Emerging frontiers of pharmacy education in Saudi Arabia: The metamorphosis in the last fifty years.
The trends in the quality of biomedical education in pharmacy schools have witnessed significant changes in the 21st century. With the advent of continuous revision and standardization processes of medical curricula throughout the world, the focus has been on imparting quality education. This pedagogic paradigm has shifted to pharmacy schools. In Saudi Arabia, the concept of "medical and pharmacy education" is relatively new as mainstream pharmacy curriculum and universities were established only half a century ago. This period has seen major changes in the dimension of "pharmacy education" to keep pace with the education systems in the United States and Europe. As our knowledge and perceptions about pharmaceuticals change with time, this motivates educators to search for better teaching alternatives to the ever increasing number of enthusiastic and budding pharmacists. Recently, the academic system in Saudi Arabian Pharmacy has adopted a more clinically-oriented Pharm. D. curriculum. This paper deals with the major changes from the inception of a small pharmacy faculty in 1959, the College of Pharmacy at the King Saud University, Riyadh, to the model of progress and a prototype of pharmacy colleges in Saudi Arabia. The fifty year chronological array can be regarded as an epitome of progress in pharmacy education in Saudi Arabia from its traditional curriculum to the modern day Pharm. D. curriculum with a high population growth and expanding health care sector, the demand for qualified pharmacists is growing and is projected to grow considerably in the future. The number of pharmacy graduates is increasing each year by many folds and to meet the needs the system lays stress upon a constant revising and updating of the current curriculum from a global perspective.


Catecholaminergic alpha-receptors and shivering in the rat.
1. A rise or a fall in systemic blood pressure brought about by the I.V. infusion of peripherally acting drugs (adenosine, noradrenaline or methoxamine) inhibited shivering in the cold-exposed rat. 2. Since the injection of commonly used doses of noradrenaline (0.05-0.10 mumole) into a lateral cerebral ventricle of a rat was usually accompanied by a rise in blood pressure special precautious were required to determine whether noradrenaline had a specific central effect on shivering. 3. Small doses of noradrenaline (0.02-0.03 mumole) or clonidine (0.01 mumole) which had no effect on blood pressure when injected into a lateral cerebral ventricle still inhibited shivering in the cold-exposed rat and this effect was prevented by phentolamine. 4. It is concluded that noradrenaline can inhibit the cold sensor-shivering pathway in its central course by an action on alpha-receptors.


Pyridazine based inhibitors of p38 MAPK.
Trisubstituted pyridazines were synthesized and evaluated as in vitro inhibitors of p38MAPK. The most active isomers were those possessing an aryl group alpha and a heteroaryl group beta relative to the nitrogen atom in the 2-position of the central pyridazine. Additionally, substitution in the 6-position of the central pyridazine with a variety of dialkylamino substituents afforded a set of inhibitors having good (p38 IC50 1-20 nM) in vitro activity.


Quantification of mitochondrial DNA from peripheral tissues: Limitations in predicting the severity of neurometabolic disorders and proposal of a novel diagnostic test.
Neurometabolic disorders stem from errors in metabolic processes yielding a neurological phenotype. A subset of those disorders encompasses mitochondrial abnormalities partially due to mitochondrial DNA (mtDNA) depletion. mtDNA depletion can be attributed to inheritance, spontaneous mutations or acquired from drug-related toxicities. In the armamentarium of diagnostic procedures, mtDNA quantification is a standard for disease classification. However, alterations in mtDNA obtained from peripheral tissues such as skin fibroblasts and blood cells do not often reflect the severity of the affected organ, in this case, the brain. The purpose of this review is to highlight the pitfalls of quantitating mtDNA from peripheral -and not limited to-tissues for diagnosing patients suffering from a variety of mtDNA depletion syndromes exhibiting neurologic abnormalities. In lieu, a qualitative test of mitochondrial substrate-level phosphorylation -even from peripheral tissues-reflecting the ability of mitochondria to rely on glutaminolysis in the presence of respiratory chain defects is proposed as a novel diagnostic assessment of mitochondrial functionality.


Insight into the genomic diversity and relationship of Astragalus glycyphyllos symbionts by RAPD, ERIC-PCR, and AFLP fingerprinting.
We assessed the genomic diversity and genomic relationship of 28 Astragalus glycyphyllos symbionts by three methodologies based on PCR reaction, i.e., RAPD, ERIC-PCR, and AFLP. The AFLP method with one PstI restriction enzyme and selective PstI-GC primer pair had a comparable discriminatory power as ERIC-PCR one and these fingerprinting techniques distinguished among the studied 28 A. glycyphyllos symbionts 18 and 17 genomotypes, respectively. RAPD method was less discriminatory in the genomotyping of rhizobia analyzed and it efficiently resolved nine genomotypes. The cluster analysis of RAPD, ERIC-PCR, and AFLP profiles resulted in a generally similar grouping of the test strains on generated dendrograms supporting a great potential of these DNA fingerprinting techniques for study of genomic polymorphism and evolutionary relationship of A. glycyphyllos nodulators. The RAPD, ERIC-PCR, and AFLP pattern similarity coefficients between A. glycyphyllos symbionts studied was in the ranges 8-100, 18-100, and 23-100%, respectively.


Specificity of vascular endothelial growth factor treatment for radiation necrosis.
Recently, radiation induced necrosis in the brain has been treated using bevacizumab, an anti-VEGF antibody. We validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, we found that VEGF over-expression and RN developed simultaneously, which precludes preventative anti-VEGF treatment.


An alternative explanation for apparent satiating properties of peripherally administered bombesin and cholecystokinin in domestic fowls.
This paper describes a series of experiments with domestic fowls designed to investigate different effects of peripherally administered bombesin (BBS) and cholecystokinin octapeptide (CCK8), with a view to gaining a better understanding of their proposed roles as physiological satiety signals. Following intravenous injections of 1-10 micrograms/kg BBS or CCK8, short periods of complete inhibition of feeding coincided with periods of abnormal gizzard motility, and longer periods of reduced feeding were associated with periods of abnormal gastrointestinal (GI) motility. Increases in heart rate, measured in a separate experiment, coincided with the periods of altered GI and feeding activities. Effects of the peptides on GI motility and feeding were strongly related to dose with CCK8, but not with BBS, and effects of (2 micrograms/kg) BBS and CCK8 on feeding were additive. Evidence from conditioned avoidance tests suggested that consequences of (10 micrograms/kg) BBS and CCK8 injections may be mildly aversive, perhaps more so with BBS, and in another experiment inhibition of feeding by (8 micrograms/kg) BBS (but not CCK8) was almost abolished in birds tranquillised with a reserpine derivative drug. CCK8 was more potent than BBS at suppressing feeding only when relatively high doses (8 and 10 micrograms/kg) were injected. It is suggested that peripherally administered BBS and CCK8 may act on feeding in similar ways, with animals being distracted by possible abdominal discomfort associated with the abnormal GI responses. The results indicate that immediate discomfort may be more severe with BBS, but that discomfort associated with CCK8 may last longer. It is further suggested that satiating properties of the peptides are less apparent in situations where animals are less easily distracted by discomfort, when their arousal is reduced, when their perception of discomfort is reduced and when their motivation to feed is increased.


Circulating sTREM-1 as a predictive biomarker of pediatric multisystemic inflammatory syndrome (MIS-C).
The exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group); 54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64-317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-α concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions.


Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation.
Mortality or graft loss after renal transplantation might be influenced by hepatitis virus infection. Sera from time of transplantation of 927 renal transplant recipients were tested for hepatitis C (HCV) and hepatitis B virus (HBV) in order to investigate the impact of hepatitis virus infection on graft loss and mortality over an observation period of 20 yr. One hundred and twenty three of 927 patients were HCV positive, 30 patients HBV positive and seven patients HBV and HCV positive. The observation period was 9.2 +/- 4.4 yr. Mortality was significantly higher in patients with hepatitis B (p = 0.0005), as well as in patients with concomitant B and C hepatitis (p < 0.0001) and in those who acquired HCV infection after transplantation (n = 30, p = 0.0192) compared with non-infected patients. Patients with replicating HBV infection (HBeAg positive) had the worst prognosis (p < 0.0001). In the multivariate analysis the presence of HBeAg (p < 0.0001), patients' age (p < 0.0001) and HCV infection after transplantation (p = 0.0453) were predictors for death. Graft survival was significantly shorter in patients with concomitant hepatitis B and C (p = 0.0087) as well as in HBeAg positive patients (p = 0.002). HCV infection or HBs antigenemia did not have a significant impact on graft survival compared with non-infected patients. HCV infection after transplantation is associated with a high mortality whereas chronic HCV infection before trans plantation does not have a significant impact on mortality. Patients with replicating HBV infection or concomitant HBV and HCV infection have a high risk of graft loss and mortality.


Nailfold capillaroscopy reveals early peripheral microcirculation abnormalities in children affected by heterozygous familial hypercholesterolemia.
nailfold capillaroscopy (NCF) is a non-invasive imaging technique to seek peripheral microcirculation abnormalities in children and adults. Familial hypercholesterolemia is a genetic disorder caused by mutations capable of increasing blood levels of low-density lipoproteins cholesterol (LDL-C), thus triggering early atherosclerosis. The study aims at evaluating peripheral microcirculation in children with heterozygous familial hypercholesterolemia (HeFH) by means of NFC in comparison with healthy peers and at searching for possible correlations between these abnormalities and patients' lipid panel. thirty-six HeFH patients were enrolled (13 males and 23 females. Mean age 8 ± 3 years; age range 3-13 years). They had increased levels of total cholesterol (237.9 ± 34.2 mg/dl) and LDL-C (154.2 ± 37.6 mg/dl). Both values were ≥95th gender and age specific centile. All the subjects in the study underwent NFC. In 69.4 % of HeFH children nailfold capillaries were tortuous (p < 0.00001 compared to healthy controls). In 41.6 % the number of capillaries was markedly reduced (<7 capillaries/mm). The mean number of capillaries was 8.4 ± 2.6/mm in HeFH and 12.2 ± 1.4/mm in healthy controls (p < 0.00001). In 100 % of the sample size capillary blood flow was slowed down (p < 0.00001). In 50 % of the sample size a blood "sludge" phenomenon was seen (p < 0.00001). No gender differences were detected. Sludge phenomenon was seen only in those with LDL-C over 99th centile (p < 0.00001). NCF allows the identification of an early peripheral microvascular dysfunction in HeFH children which is similar to that already seen in atherosclerotic disease. Prompt identification of these capillary abnormalities may be crucial in implementing early prevention measures.


Open versus closed oocyte vitrification system: a prospective randomized sibling-oocyte study.
Vitrification has been successfully applied in the cryopreservation of oocytes and embryos. It can be achieved either by direct (open system) or indirect (closed system) contact with liquid nitrogen. Unlike embryo vitrification, few reports have been published regarding oocyte vitrification in closed systems. In order to validate the effectiveness of a closed and aseptic vitrification approach for oocyte cryopreservation, a prospective, randomized study was performed. Sibling oocytes donated from the same donor were randomly and equally assigned into closed or open vitrification groups. A total of 75 vitrification-warming cycles were performed in each group. Apart from the survival rate (82.9% versus 91.0%, P<0.05), no statistically significant differences were observed in pregnancy (β-human chorionic gonadotrophin positive) (42.7% versus 33.3%), clinical pregnancy (36.0% versus 28.0%), implantation (13.8% versus 10.1%), ongoing pregnancy (33.3% versus 24.0%) and live birth (36.0% versus 24.0%) rates between the closed and open groups, and 27 and 18 healthy babies were born, respectively. This study shows that the replacement of the open vitrification system by a closed system has no impact on clinical pregnancy and implantation rates. Therefore, the closed vitrification system provides an aseptic alternative to the open method for oocyte vitrification.


Assessment of the importance of sorption for steroid estrogens removal during activated sludge treatment.
Distribution coefficients (K(d)) between water and activated sludge particles (f(oc)=27.7+/-0.1%) were measured for the steroid estrogens (SE), estrone (E1), 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) in batch experiments. Experimental concentration levels ranged from environmentally realistic low ng/l to the high microg/l. In this range K(d)s were independent of their water concentration. The experimentally obtained K(d)s (with 95% confidence intervals) were 402+/-126 l/kg, 476+/-192 l/kg and 584+/-136 l/kg for E1, E2 and EE2, respectively. K(d)s were used to estimate the fraction of the total SE concentration that is expected to be sorbed in the activated sludge treatment tanks of a typical STP assuming equilibrium conditions. Assuming a suspended solids concentration of 4 g/l dissolved solids (ds), it was estimated that 61+/-9%, 66+/-13% and 70+/-6% of the total concentration of E1, E2 and EE2, respectively, would be sorbed during activated sludge treatment. The fraction of the SEs that was expected to be sorbed to suspended sludge particles in the effluents from a typical Danish STP was estimated to be only 0.20+/-0.06%, 0.24+/-0.10% and 0.29+/-0.07% of the total concentration of E1, E2 and EE2, respectively, at a suspended solids concentration of 5 mg/lds. For a typical STP the removal of steroid estrogens with excess sludge was estimated to be only 1.5-1.8% of the total loading if equilibrium conditions exists. Sorption is therefore not important for the fate of SEs in STPs compared to biodegradation.


Role of Mg-ATP in norepinephrine biosynthesis in intact chromaffin granules.
Dopamine beta-monooxygenase converts dopamine to norepinephrine in intact chromaffin granules using intragranular ascorbic acid as a cosubstrate. Mg-ATP with external ascorbic acid is required for maximal norepinephrine biosynthesis. Mechanisms to explain these requirements were investigated specifically using intact granules. The effect of Mg-ATP was independent of membrane potential (delta psi) because norepinephrine biosynthesis was unchanged whether delta psi was positive or collapsed. Furthermore, the effect of Mg-ATP was independent of absolute intragranular and extragranular pH as well as the pH difference across the chromaffin granule membrane (delta pH). Nevertheless, norepinephrine biosynthesis was inhibited by N-ethylmaleimide, 4-chloro-7-nitrobenzofurazane, and N,N-dicyclohexylcarbodiimide, specific inhibitors of the secretory vesicle ATPase that may directly affect proton pumping. Biosynthesis occurred normally with other ATPase inhibitors that do not inhibit the ATPase in secretory vesicles. The data indicate that the effect of Mg-ATP with ascorbic acid is mediated by the granule membrane ATPase but independent of maintaining delta psi and delta pH. An explanation of these findings is that Mg-ATP, via the granule ATPase, may change the rate at which protons or dopamine are made available to dopamine beta-monooxygenase.


Government plans to reduce death by suicide in England.
Emeritus Professor Alan Glasper, from the University of Southampton, discusses a new cross-government initiative to reduce the incidence of suicide in the country.


Rapid identification of Lactobacillus acidophilus by restriction analysis of the 16S-23S rRNA intergenic spacer region and flanking 23S rRNA gene.
A rapid molecular approach was developed for the initial identification of Lactobacillus acidophilus strains which are difficult to identify using a single biochemical test. The 16S-23S rRNA intergenic spacer regions and flanking 23S rRNA genes of 19 strains of lactobacilli were amplified and the nucleotide sequences and restriction site polymorphisms were analyzed. AluI was the most useful of the restriction enzymes analyzed and produced reproducible digestion profiles in the L. helveticus, L. plantarum, and L. casei groups, as well as in L. acidophilus. This restriction fragment length polymorphism method may be useful for the identification of L. acidophilus strains in dairy products.


Translational Structural and Functional Signatures of Chronic Alcohol Effects in Mice.
Alcohol acts as an addictive substance that may lead to alcohol use disorder. In humans, magnetic resonance imaging showed diverse structural and functional brain alterations associated with this complex pathology. Single magnetic resonance imaging modalities are used mostly but are insufficient to portray and understand the broad neuroadaptations to alcohol. Here, we combined structural and functional magnetic resonance imaging and connectome mapping in mice to establish brain-wide fingerprints of alcohol effects with translatable potential. Mice underwent a chronic intermittent alcohol drinking protocol for 6 weeks before being imaged under medetomidine anesthesia. We performed open-ended multivariate analysis of structural data and functional connectivity mapping on the same subjects. Structural analysis showed alcohol effects for the prefrontal cortex/anterior insula, hippocampus, and somatosensory cortex. Integration with microglia histology revealed distinct alcohol signatures, suggestive of advanced (prefrontal cortex/anterior insula, somatosensory cortex) and early (hippocampus) inflammation. Functional analysis showed major alterations of insula, ventral tegmental area, and retrosplenial cortex connectivity, impacting communication patterns for salience (insula), reward (ventral tegmental area), and default mode (retrosplenial cortex) networks. The insula appeared as a most sensitive brain center across structural and functional analyses. This study demonstrates alcohol effects in mice, which possibly underlie lower top-down control and impaired hedonic balance documented at the behavioral level, and aligns with neuroimaging findings in humans despite the potential limitation induced by medetomidine sedation. This study paves the way to identify further biomarkers and to probe neurobiological mechanisms of alcohol effects using genetic and pharmacological manipulations in mouse models of alcohol drinking and dependence.


[Characteristics of azithromycin action on bacterial biofilms of pneumonia pathogens].
Azithromycin (Zitrolid) action on biofilms formed by gramnegative and grampositive microorganisms, isolated from patients with respiratory tract infections was investigated. The drug was effective at the stage of the biofilm formation and on exposition to the already formed biofilms.


Incidence and predictors of glaucoma following surgery for congenital cataract in the first year of life in Victoria, Australia.
To determine the incidence and predictors of glaucoma following surgery for congenital and infantile cataract in an Australian population. Retrospective cohort study. Infants (<12 months) having had lens extraction between January 1992 and May 2006, from two tertiary referral centres. Children with uveitis, anterior segment dysgenesis, aniridia, retinopathy of prematurity, and lens subluxation were excluded. Potential predictors of incident glaucoma were examined using Cox proportional hazards regression with adjustment for clustering between eyes. Incidence and predictors of secondary glaucoma. One hundred and forty-seven eyes of 101 patients (46 bilateral cataract; 55 unilateral cataract) were included, with median follow-up of 9.9 years (range 1.2-18.9 years). Cumulative incidence of glaucoma was 32.0% for eyes (n = 47) and 30.7% (n = 31) for subjects. Incidence was higher in children with bilateral cataract (38.9 vs. 17.1%, p = 0.004). There were 3.9 cases of glaucoma per 100 person years of follow-up, the incidence rate being highest for surgery performed in the first month of life. Children with glaucoma had longer median follow-up (11.8 vs. 9.3 years, p = 0.005). Risk of glaucoma decreased with increasing months of age at operation: hazard ratio 0.79, 95% confidence interval 0.69-0.91, p = 0.001. Median visual acuity was worse in children with unilateral cataract (p < 0.001). We identified an increased risk of glaucoma when cataract surgery was performed in younger infants, and in those with bilateral cataract. As glaucoma may develop over a decade following lens extraction, life-long surveillance is needed to prevent glaucoma-associated vision loss.


Oocyte donation and gamete intrafallopian transfer in premature ovarian failure.
Gamete intrafallopian transfer (GIFT) was performed in eight patients with premature ovarian failure (POF), using donated oocytes. The steroid replacement protocol consisted of the administration of increasing dosages of 17 beta-estradiol (E2) and progesterone (P). Hormonal replacement was maintained until day 100 of gestation. All patients underwent an evaluation cycle in which serum levels of E2 and P were monitored and an endometrial biopsy was performed on day 21 or 22. All cases of GIFT were performed between days 12 and 15. Six clinical pregnancies were achieved in eight cycles (75% success rate). Three patients delivered and three are in their second or third trimester. No ectopics or miscarriages occurred. These results offer a promising approach for the establishment of fertility in agonadal patients.


The microscopic double immunofluorescence technique, a method for quantitative differentiation between extra- and intracellularly located bacteria in isolated polymorphonuclear granulocytes.
A simple microscopic double immunofluorescence staining technique for the study of phagocytosis of living bacteria by human polymorphonuclear granulocytes (PMN) is presented. This technique enables the differentiation between cell-attached and ingested bacteria and allows the kinetics of phagocytosis to be monitored. The practicability and accuracy of this method is demonstrated by using two genetically defined Yersinia enterocolitica strains of different virulence, and isolated PMN resuspended in serum-free and serum-containing medium, respectively. The advantages of this method over other techniques are discussed.


Two antifungal active triterpenoid saponins from the seeds of Lathyrus plants.
Two novel triterpenoid glycosides have been isolated from butanolic seeds extract of two varieties of Lathyrus plants, i.e. Lathyrus ratan and Lathyrus aphaca. Their structures were elucidated as 3-O-[β-D-glucuronopyranosyl-(1 → 4)-α-L-arabinopyranosyl-(1 → 2)-α-L-arabinopyranosyl]-olean-11,13(18)-dien-28-oic acid (1) and 3-O-{β-D-xylopyranosyl-(1 → 2)-β-D-glcopyranosyl-(1 → 4)-[β-D-glucopyranosyl-(1 → 2)]-β-D-xylopyranosyl}-2,16α-dihydroxy-4-hydroxymethyl urs-12-en-28-oic acid (2) on the basis of spectral evidences, i.e. FTIR, (1)H-NMR, (13)C-NMR, ESI-MS and FAB-MS data. The isolated saponins were tested for their antifungal activity. Compound 1 showed maximum inhibition against Colletotrichum dematium (77.8%), whereas compound 2 showed maximum inhibition against Alternaria alternata (53.9%).


Multicenter Study on Observation of Acute-phase Responses After Infusion of Zoledronic Acid 5 mg in Chinese Women with Postmenopausal Osteoporosis.
It has been reported that acute-phase reactions (APR) after infusion of 5 mg zoledronic acid for the first time is common. This study surveyed the incidence and characteristics of APR in Chinese postmenopausal women receiving 5 mg zoledronic acid intravenously for osteoporosis and to evaluate the efficacy of non-steroidal anti-inflammatory drugs (NSAID) in preventing or alleviating APR following the first 5 mg zoledronic acid infusion. A total of 2601 patients with an average age of 68.14 ± 9.89 years and a mean body mass index of 22.90 ± 3.24 kg/m2 from 62 centers in China were treated with 5 mg zoledronic acid intravenously for the first time. The incidence of fever and pain were observed in these patients, and the time of fever or pain onset and duration, and the intensity of fever and grade of pain were also recorded. The dosage, duration, and efficacy of NSAID and safety outcomes were also documented. At the end of the study, 18 patients are eliminated due to incomplete records of temperature. The incidence of fever was 28.65% (740/2583) within 7 days following zoledronic acid infusion; 98.34% (727/740) occurred at 1.03 ± 0.66 days after infusion and lasted 1.72 ± 0.93 days. A total of 456 (17.53%) patients had newly onset pain (312 of 1187, 26.28%) or experienced pain aggravation (144 of 1414, 10.18%), which mostly occurred within 3 days after zoledronic acid infusion. A total of 1246 (47.6%) patients had received NSAID for a median time of 2.63 ± 2.45 days. Using NSAID for at least 2 days could decrease body temperature by 0.54 ± 0.86°C, increase the percentage of pain-free patients by 6.17%, and reduce the percentage of patients with moderate to severe pain by 8.7%. Compared with Western populations, Chinese patients had a higher rate of fever and pain after their first zoledronic acid infusion. These symptoms were often mild to moderate in intensity and transient in duration. NSAID could effectively reduce the incidence and severity of such APR.


Immunotoxicological investigation in rats dosed repeatedly with combinations of cypermethrin, As(III), and Hg(II).
The effects of the combined exposure of cypermethrin (CY), NaAsO2 (As), and HgCl2 (Hg) were investigated in male Wistar rats following 4 weeks of oral exposure. Standard toxicological (body weight gain, organ weights of brain, thymus, heart, lung, liver, kidneys, adrenals, testes, and popliteal lymph node), haematological (white blood cell, red blood cell, haematocrit, MCV-mean volume of red blood cells, and cell content of the femoral bone marrow), and immune function (IgM-PFC response, delayed type hypersensitivity (DTH) reaction) parameters were measured. The two doses selected for the combination were: a high (H) dose equal to lowest observed effect level determined in preliminary experiments (CY(H)=55.4 mg/kg, As(H)=13.3 mg/kg, Hg(H)=3.20 mg/kg), and a low (L) dose which was ineffective (non-observed effect level); CY(L)=11.1 mg/kg, As(L)=3.33 mg/kg, Hg(L)=0.40 mg/kg). CY(H) was combined with As(L) or Hg(L), and the H doses of the heavy metals were combined with CY(L). Beside vehicle control, the H dose components of the combinations were also used as internal controls. The main finding of this study was that certain combinations, when compared to H dose internal control, significantly altered the body weight gain (As(H)+CY(L)), the relative weight of adrenals and popliteal lymph node (CY(H)+As(L) and CY(H)+Hg(L)), the cell content of the femoral bone marrow (CY(H)+Hg(L)), and the time course of DTH reaction (CY(H)+As(L)). According to the present results, combined exposure with CY and the heavy metals investigated can modify the toxicity and/or the functional detection limit of the single substances.


Heterogeneous tumor vasculature in retinoblastoma: implications for vessel targeting therapy.
The aim of this study is to correlate tumor size of retinoblastoma tumor samples with blood vessel maturation to assess how these factors may affect vessel targeting therapy. Analysis was performed on retinoblastoma tumor specimens (n = 5) enucleated as primary treatment from May 2005 to February 2006. Tumor size was measured as the largest cross sectional area of the tumor, measured during pathologic assessment. Vessel density and heterogeneity was measured by immunohistochemical analysis. Total microvessel density was detected by staining endothelial cells using a lectin from Bandeira simplicifolia; novel vasculature was detected with the endothelial cell marker endoglin (CD105). Blood vessel basement membrane was detected with an antibody against type IV collagen. Vessel maturation was assessed by pericyte recruitment, detected with alpha smooth muscle actin (alpha-sma). A statistically significant correlation was detected between tumor burden and age at enucleation (P = 0.008). All retinoblastoma tumor samples harbored a high degree of blood vessel heterogeneity containing both immature neovessels as well as pericyte-committed mature vasculature. There was a statistically significant correlation between type IV collagen and age at enucleation (P = 0.045). This study provides a framework for a better understanding of tumor and vessel development in retinoblastoma. Results of this study provide insight into the relationship between age and tumor burden in these tumors. Knowledge of the degree of heterogeneity detected in these tumors will aid in the selection of novel blood vessel targeting strategies for children with this disease and other diseases with pathologic neovascularization.


Experiment and simulations on the energy reservoir effect in femtosecond light filaments.
We report the results of an experiment and numerical simulations that demonstrate the large spatial extent and the effect of the so-called energy reservoir during the filamentation of femtosecond laser pulses in air. By inserting pinholes of different sizes in the filament path we observe different stages of development ranging from the termination of the filament, through its partial survival, to undisturbed propagation. A background containing up to 50% of the pulse energy is found to be necessary to maintain the filament formation, including a first refocusing.


Behavior of cultured glandular cells obtained by flushing of the uterine cavity.
In 77 of 115 cultures from uterine/tubal flushes performed in women undergoing diagnostic laparoscopy for reasons of infertility, epithelioid colonies of "tadpole-like" cells appeared. In cultured jet washings from the uterine cavities in women with ligated tubes, the same tadpole-like cells are present. These cells are also observed in vitro in laparoscopic biopsy specimens of active endometriosis nodules. Judged by the presence of cytokeratin in these cells, demonstrated by polyvalent or monoclonal antikeratin antibodies (the latter as a marker for glandular epithelia), there can be no doubt about their origin from the lining and glandular epithelium of part of the genital tract. Peritoneal washings not preceded by uterine/tubal flushing never contained the tadpole-like cells in culture. True epithelial cells were observed in the peritoneal cavity after flushing, and the proliferative capacity of these cells in vitro during the preovulatory phase was proven.


Frontal cortex lesions eliminate the clock speed effect of dopaminergic drugs on interval timing.
Behavioral and pharmacological challenges using methamphetamine (MAP-0.5 and 1.0 mg/kg, i.p.), haloperidol (HAL-0.12 mg/kg, i.p.), and sulfated cholecystokinin octapeptide (CCK-0.05 and 0.1 mg/kg, i.p.) were used to evaluate the effects of excitotoxic lesions of cholinergic cell bodies in the medial septal area and the nucleus basalis magnocellularis, radiofrequency lesions of the fimbria-fornix, and aspiration lesions of the frontal cortex on interval timing in rats trained on a 40-s peak-interval procedure. Results demonstrated that lesions of the nucleus basalis magnocellularis and frontal cortex selectively reduced the modulatory control of clock speed which is likely mediated by dopamine D(2) receptors located on cortico-striatal neurons.


Laparoscopic adrenalectomy for a giant adrenal myelolipoma: A case report.
We describe a case of a patient who presented with a mildly symptomatic, giant myelolipoma which was excised by laparoscopic approach without complications. Adrenal myelolipoma (AML) is a rare tumour composed by fat and myeloid tissues. Usually it is asymptomatic, so the diagnosis is mostly incidental. It is generally located in the right adrenal gland, but it can also be found bilaterally. If its size exceeds 10 cm it is defined as a "giant myelolipoma"; in this case its treatment of choice would be adrenalectomy with an open surgical approach. Patient's signs and symptoms were mild pain in the right hypochondrium and a positive right Giordano's sign. The mass was detected by a contrast-enhanced CT scan. Once excised it measured 16 cm. Laparoscopic adrenalectomy for giant myelolipoma is a safe approach if performed by an expert surgeon, with low risk of bleeding and a better outcome for the patient.


Pelvic inflammatory disease attributable to the IUD: modeling risk in West Africa.
In Africa, use of the intrauterine device (IUD) is avoided because of perceived risk of pelvic inflammatory disease (PID) associated with sexually transmitted infections (STI). However, one recent model suggests that the risk of PID attributable to the IUD is very low, only 0.15% or less than 1 in 600. Using rates from a 2004 study of cervical STI prevalence in Benin, Burkina Faso, Ghana, Guinea, and Mali; we calculate PID risk attributable to the IUD in West Africa. Based on 4.4% combined prevalence of chlamydial and gonococcal infections, we estimate the risk is 0.075%, or less than 1 in 1,300. In West Africa, PID risk from IUDs is extremely low. This should be better communicated to family planning providers in the region who may under-provide the IUD based on erroneous perceptions of PID risk.


Recombinant human lactoferrin has preventive effects on lipopolysaccharide-induced preterm delivery and production of inflammatory cytokines in mice.
The following animal studies have been conducted to investigate whether recombinant human lactoferrin (rh-LF) has the same effect as bovine lactoferrin (b-LF) in the prevention of preterm delivery. Female C3H/HeNCrj mice were pair-mated with male Crj:B6D2F1 mice. On day 15 of gestation, as a model of preterm delivery, a 50 microg/kg intraperitoneal injection of lipopolysaccharide (LPS) was administered twice with a 3-h interval between injections (2:00 and 5:00 PM). One hour prior to each LPS injection (1:00 and 4:00 PM), an intraperitoneal injection of saline, b-LF, or rh-LF (1 mg/body) was administered. In non-LPS-treated controls, an intraperitoneal injection of saline was administered 4 times (1:00, 2:00, 4:00 and 5:00 PM). Body weights and delivery times were recorded. To compare plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) between experimental and other pregnant mice, prepared as above, were sacrificed 6 h after the second LPS injection, and then blood samples were obtained and analyzed. Preterm delivery occurred (16.2+/-0.4 days of gestation) in all LPS-treated mice that were not administered LF. LF significantly prolonged gestation of LPS-treated mice: b-LF+LPS, 17.8+/-0.3 days; rh-LF+LPS, 18.0+/-0.8 days (P<0.05). LF (1 mg/body) significantly suppressed plasma IL-6 in LPS-treated mice:b-LF+LPS, 1060+/-154; rh-LF+ LPSF, 244+/-59; LPS without LF, 1628+/-115 pg/mL (P<0.05). As well, LF (1 mg/body) significantly suppressed plasma TNF-alpha in LPS-treated mice: b-LF+LPS, 88+/-36; rh-LF+LPS, 37+/-30; LPS without LF, 114+/-49 pg/mL (P<0.05). Rh-LF may prolong gestation in LPS-induced preterm delivery in mice, by suppressing LPS-induced plasma IL-6 and TNF-alpha augmentation.


A case of 46,XY,t(1;13) (q24;q32) with mental retardation.
A 14-year-old mentally retarded boy with congenital malformations of unknown etiology was found to have a de novo apparently balanced reciprocal translocation between chromosomal arms 1q and 13q. There is only one other case where a similar translocation was observed but the breakpoints could be localized only by regions and the individual was not mentally retarded.


Clinical significance of serum transcobalamins in protein-energy malnutrition.
The serum concentrations of Unsaturated Vitamin B(12) binding (UBBC) capacity and the three individual transcobalamins were measured in 34 malnourished children aged 9 months-5 y. Levels of serum vitamin B12, aspartate aminotransferase, alanine aminotransferase, albumin and total proteins were also estimated. The serum UBBC, Transcobalamin I (TC I), Transcobalamin III (TC III), vitamin B12 and the enzyme activities were significantly higher in the kwashiorkor children when compared with both the marasmic and control children. There was also a marked reduction of serum Transcobalamin II (TC II), albumin and total proteins in the kwashiorkor children. In contrast with kwashiorkor, there was a slight increase of serum TC II in the marasmic children. Their serum UBBC, TC I, TC III and B12 were also raised but not as high as in kwashiorkor. These results are discussed in the light of the hepatic dysfunction in kwashiorkor affecting the production of TC II in the liver, while the elevated serum B12 in Protein-energy malnutrition (PEM) may be due to both hepatic damage and intensified release of TC I as a result of infection.


Effectiveness of airway clearance techniques in children hospitalized with acute bronchiolitis.
To evaluate the effectiveness of two airway clearance techniques (ACT's) in children <24 months hospitalized with mild to moderate bronchiolitis. One hundred and three children were randomly allocated to receive one 20-min session daily, either assisted autogenic drainage (AAD), intrapulmonary percussive ventilation (IPV), or bouncing (B) (control group), ninety-three finished the study. Mean time to recovery in days was our primary outcome measure. The impact of the treatment and the daily improvement was also assessed by a validated clinical and respiratory severity score (WANG score), heart rate (HR), and oxygen saturation (SaO2 ). Mean time to recovery was 4.5 ± 1.9 days for the control group, 3.6 ± 1.4 days, P < 0.05 for the AAD group and 3.5 ± 1.3 days, P = 0.03 for the IPV group. Wang scores improved significantly for both physiotherapy techniques compared to the control group. Both ACT's reduced significantly the length of hospital stay compared to no physiotherapy. Pediatr Pulmonol. 2017;52:225-231. © 2016 Wiley Periodicals, Inc.


The early ultrastructural alterations in the rabbit cerebral and cerebellar cortex after compression ischaemia.
The ultrastructural alterations in the rabbit cerebral and cerebellar cortex resulting from 30 minutes complete, permanent cerebral ischaemia were studied. The ischaemia was induced by raising the intracranial pressure (ICP) above the systolic arterial pressure (compression ischaemia). Immediately after releasing the ICP the brain was fixed by intravascular glutaraldehyde perfusion. Samples from the cerebral and cerebellar cortex were processed for electron microscopy. The ultrastructural changes were relatively minor; there was a generalised, slight intracellular oedema, most prominent in the subpial area; the nuclear chromatin was clumped, the endoplasmic reticulum and cisternae of the golgi apparatus became somewhat dilated, the inner matrix of the slightly swollen mitochondria showed increased electron lucency, and microtubules and ribosomes began to loose their compact structure. These changes, unaccompanied by any extensive volumetric change of any cellular compartment, agree well with the recently presented hypothesis of two different types of anoxic-ischaemic nerve cell injury. This cellular reaction to complete, permanent compression ischaemia represents the type of injury that is seen resulting from ischaemic insults during which no flow of fluid irrigates the ischaemically injured cells.


The cholesterol metabolite cholest-4-en-3-one and its 3-oxo derivatives suppress body weight gain, body fat accumulation and serum lipid concentration in mice.
Based on the findings that cholest-4-en-3-one, an intestinal metabolite of cholesterol, has an anti-obesity effect on animals, the structure-effect relationship of its 3-oxo derivatives and related compounds were investigated. Cholesten-3-ones, which possesses an enone structure with a carbonyl group at C3, markedly inhibit body weight gain and body fat accumulation, as well as the levels of serum triglyceride and cholesterol in animals without any clinical abnormalities.


Asymmetric hydroformylation.
Rhodium is currently the metal of choice to achieve high enantioselectivities in the hydroformylation of a relatively wide variety of alkene substrates. The elucidation of the different steps of the catalytic cycle and the characterization of the resting state, together with the discovery of several types of ligands that are able to provide high enantioselectivities, have made the rhodium-catalyzed hydroformylation a synthetically useful tool. For years, ligands containing phosphite moieties such as diphosphites and phosphine-phosphites were considered the most successful ligands to achieve high enantioselectivities for classical substrates such as styrene and vinyl acetate. In fact, the phosphite-phosphine BINAPHOS (43) and its derivatives are still today the most successful ligands in terms of selectivity and scope. For more substituted substrates, general trends can be extracted. However, recent studies showed that these general trends can be sometimes reversed by the use of the appropriate catalyst and choice of reaction conditions, clearly showing that these trends are only indicative and that there are still many challenges to be tackled in this area.


HIV-1 gp120 up-regulation of the mu opioid receptor in TPA-differentiated HL-60 cells.
Opioid abuse has been shown to exacerbate the immunosuppressive effects and pathogenesis of HIV infection. The mu opioid receptor (MOR) is present on immune cells, such as macrophages, and mediates the direct immunomodulatory effects of opioids. Through its surface glycoprotein, gp120, HIV-1 binds to surface receptors on target cells, including macrophages, to exert its pathological effects. Binding of gp120 to macrophages stimulates the cells to release various pro-inflammatory cytokines, including TNF-alpha, which has been shown to regulate transcription of the MOR gene. In this study, we examined the effects of HIV-1 gp120 on MOR expression in HL-60 human promyelocytic leukemia cells differentiated into macrophage-like cells by TPA. Using real time RT-PCR, we found that exposure to gp120 up-regulated MOR expression in TPA-differentiated HL-60 cells at the transcriptional level. The functionality of the gp120-induced MOR in these cells was confirmed based on morphine's inhibition of forskolin-induced intracellular cAMP, which was naloxone reversible. Exposure to gp120 also stimulated the release of TNF-alpha from TPA-differentiated HL-60 cells. Treatment with TNF-alpha neutralizing antibody, as well as blockage of TNF-alpha's actions by anti-TNF-alpha receptor type II (TNFR-II) antibody, inhibited gp120-induced up-regulation of MOR mRNA. Our data suggest that one of the mechanisms by which HIV-1 gp120 up-regulates the MOR in TPA-differentiated HL-60 cells is through autocrine/paracrine actions of TNF-alpha via the TNFR-II receptor.


Analysis of opioid peptides by on-line SPE-CE-ESI-MS.
In this study, SPE-CE-ESI-MS is explored for the preconcentration and separation of dilute solutions of six opioid peptides. First, a CE-ESI-MS methodology was developed and validated. LODs of around 1 microg/mL were obtained for all the studied peptides. For SPE-CE-ESI-MS experiments, a home-made SPE microcartridge containing a C18 sorbent was constructed near the inlet of the separation capillary. After optimizing the on-line preconcentration methodology, LODs between 10 and 0.1 ng/mL were achieved. Repeatability, reproducibility, durability of the microcartridges and linearity of the SPE-CE-ESI-MS methodology were also investigated and compared to the values obtained by CE-ESI-MS. Finally, human plasma samples fortified with opioid peptides were analyzed by SPE-CE-ESI-MS in order to show the potential of the methodology for the analysis of biological fluids.


A correlative study on the embryotrophic property of patient's serum and the outcome of in vitro fertilization of human oocytes.
The embryotrophic property of patient's serum previously used for in vitro fertilization (IVF) was studied by culturing postimplantation organogenesis-stage mouse embryos in a medium containing equal parts of Dulbecco's modified Eagle's medium and the patient's serum. Results of embryo culture experiments were generally found to correlate well with the outcome of IVF. Serum of patients whose oocytes were fertilized and developed to cleavage-stage embryos scored highest for embryotrophic parameters such as morphologic score and protein content of the mouse embryo. There was no significant difference in terms of serum embryotrophic activity between patients who became pregnant after embryo transfer and those who did not. When mouse embryos were cultured in serum from cycles with poor IVF results, i.e., oocytes failed to be fertilized or fertilized oocytes failed to cleave or cleave abnormally, significantly retarded embryonic growth and a higher incidence of malformed embryos were observed. However, in two cases where IVF failed as a result of poor semen quality, the patient's serum was found to be supportive of mouse embryonic development.


High incidence of pericardial effusion in non-Hodgkin's lymphoma: usefulness of echocardiography.
In a consecutive group of patients with non-Hodgkin's lymphoma a prospective study was designed to detect pericardial and myocardial abnormalities at presentation for initial clinical staging. Thirty-two patients, ranging from 15 to 65 (mean, 46) years of age, were studied. Twenty-six (81%) were in Stages III and IV. Echocardiographic examination revealed that 17 patients (53%) had pericardial effusion (PE). Four subjects with lymphoblastic lymphoma and extensive mediastinal involvement had clinical and echographic signs of cardiac-tamponade. In 5 cases, pericardiocentesis was performed; abnormal lymphoblasts were demonstrated in 4. In one of these, the histological diagnosis of lymphoma was performed from analysis of the PE. The follow-up ranged from 3 to 32 (mean, 12.3) months. There was no difference in the survival rates whether or not PE was present: 70 and 68% respectively at 1 yr. No patient required intracavitary chemotherapy or surgery. We conclude that PE in advanced non-Hodgkin's lymphoma with large mediastinal masses is frequent. Once tamponade is treated, the presence of PE has no adverse effect on survival at 1 yr.


Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity.
K+ channels are known through electrophysiology and pharmacology to be an exceptionally diverse group of channels. Molecular studies of the Shaker (Sh) locus in Drosophila have provided the first glimpse of K+ channel structure. The sequences of several Sh cDNA clones have been reported; none are identical. We have isolated and examined 18 additional Sh cDNAs in an attempt to understand the origin, extent, and significance of the variability. The diversity is extensive: we have already identified cDNAs representing at least nine distinct types, and Sh could potentially encode 24 or more products. This diversity, however, fits a simple pattern in which variable 3' and 5' ends are spliced onto a central constant region to yield different cDNA types. These different Sh cDNAs encode proteins with distinct structural features.


Paraplegia due to non-osseous spinal tuberculosis: report of three cases and review of the literature.
In developing countries, a recognized etiology of paraplegia can be tuberculous radiculomyelitis or tuberculomas, especially in patients with evidence of either active or latent tuberculosis. These entities should also be considered in high-risk patients or in patients who have emigrated from regions with a high prevalence of tuberculosis (TB). Both arachnoiditis and intradural tuberculomas are uncommon forms of spinal TB. We report three cases of TB of the spinal cord in young males with paraplegia or paraparesis who were hospitalized over a one-year period. The clinical presentation and clinical course differed among the three patients: radiculomyelitis complicating tuberculous meningitis for the first patient and spinal tuberculomas in the other two. Neuroimaging with magnetic resonance imaging (MRI) was critical for diagnosis. The therapy for spinal TB should be conservative since the neurologic deficits are mainly secondary to the inflammatory process. Usually these lesions respond to medical therapy alone, and with early diagnosis one can avoid unnecessary surgical intervention. In our limited clinical experience, corticosteroids (IV, intrathecal, or both) appear to have a beneficial effect.


[Investigation of blood supply of bronchogenic carcinoma deriving from pulmonary artery].
Microfil perfusion technique was used to investigate the blood supply of bronchogenic carcinoma deriving from pulmonary artery on 20 fresh specimens of lung cancer, including 11 squamous carcinoma, 6 adenocarcinoma, 1 alveolar cell carcinoma and 2 undifferentiated carcinoma cases. The results showed that the appearance and quantity of pulmonary blood supply of bronchogenic carcinoma depended on and changed with the site, activity, growth mode as well as the local condition of tumor nodules; pulmonary artery supplied blood to the periphery of the tumor and its innermost part as well; vessels from pulmonary artery in tumor nodules were generally less in number than those in the surrouding normal lung tissues around. The results suggested that the tumor blood supply from pulmonary artery should be evaluated comprehensively and dynamically; during interventional chemotherapy via pulmonary artery, patients should be selected carefully and the catheter for infusion placed in suitable position so as to gain the best therapeutic effect.


Dataset on water quality monitoring from a wireless sensor network in a river in Kosovo.
This dataset was collected as part of the InWaterSense project with a wireless sensor network (WSN) installed in a site in river Sitnica in Kosovo, as a case study for monitoring remotely, continuously and in real-time the surface water quality in Kosovo and how it can be extended to all surface waters in the country for quality assurance. Values of four water quality parameters are provided in the dataset, i.e., temperature, electrical conductivity, pH, and dissolved oxygen measured by respective static sensors of WSN in the time frame between May 2015 to beginning of January 2016 and every 10 min, counting to slightly over 100k measurement records in total. The dataset is hosted at the Mendeley Data repository (Ahmedi and Ahmedi 2021), and is related to the research article entitled "InWaterSense: An Intelligent Wireless Sensor Network for Monitoring Surface Water Quality to a River in Kosovo" (Ahmedi et al., 2018). The reuse potential of the dataset to the scientific community is widespread, from environmental engineering to artificial intelligence to the health sector just to mention few. Moreover, practitioners might benefit from this dataset in driving forth the pollution prevention policies and techniques. Data were acquired measuring water quality using static sensors installed as part of a wireless sensor network in Sitnica river in the Plemetin village near Prishtina, then transmitted to the gateway device also in Plemetin via the ZigBee protocol, and finally transmitted remotely via GPRS to the server machine in the premises of the University of Prishtina. The data received from sensors are in real-time stored in the MS SQL server.


Synthesis and biological activity of some new 2-(aminoacyl- and dipeptidyl-)aminopyrazine derivatives.
Synthesis of some new 2-(N-tosyl- or N-phthalylaminoacyl or free aminoacyl or N-tosyldipeptidyl- or N-phthalyldipeptidyl)aminopyrazine derivatives (II-XXX) are described. All 2-(aminoacyl)aminopyrazines (XIV-XVIII) have been found to be biologically active against a number of microorganism.


[Association of lymphoma and granulomatosis: A case series].
The sarcoidosis-lymphoma syndrome is a recognised entity. However, the presence of granulomas in patients with a haematological disease should not lead too easily to a diagnosis of sarcoidosis. The presence of granulomatous lesions during the follow-up of these patients raises diagnostic and therapeutic issues. We included 25 patients followed by the department of haematology in a French hospital (Centre Léon-Bérard). These patients presented with granulomatous lesions. Patients with a history of sarcoidosis were excluded. We report the type of haematological disease, the time of onset of the granulomatous disease compared to that of lymphoma, associated symptoms, aetiology and outcome. Patients were divided into three groups according to the time of onset of the granulomatous lesions. Granulomatous lesions appeared before the haematological disease in 4 cases, was concomitant in 8 cases and appeared later in 13 remaining cases. The two main subtypes of lymphoma encountered were: diffuse large cell lymphoma (36%) and Hodgkin's lymphoma (28%). Granulomatous lesions were related to the progression of the hematological disease in 11 cases, to sarcoidosis in 4 cases, to infection in 3 cases, to drug allergy in one case, to inflammatory bowel disease in one case, to granuloma annulare in one case and was isolated in 4 cases (no identified etiology). In the group where granulomas appeared after the haematological disease, mean SUV was 11 for the haematological disease versus 6.4 for granulomas. Granulomatous diseases in lymphomas can be due to various aetiologies: infection, reaction to the haematological disease, or systemic sarcoidosis. It is an important challenge for clinicians, who can miss the diagnosis of lymphoma and or conclude to a treatment failure or a relapse. Computed tomography scan (CT-scan) or (18)F-deoxyglucose-positron emission tomography scan can help establish a diagnosis but do not replace biopsy.


Trust in scientific publishing.
Trust is an important phenomenon to reduce organizational complexity and uncertainty. In the literature many types of trust are distinguished. An important framework to understand the variety and development of trust in organisations is provided by Zucker. She distinguishes three types of trust: process-based trust, institutional-based trust, characteristic-based trust. In this article we will add a fourth type: values-based trust. Similarly, it is customary in scientific communication to distinguish four main communication functions: registration, archiving, certification, awareness. These types of trust and communication functions offer somewhat similar classification schemes. In this paper we will elaborate on these classification schemes with the aim to analyse possible similarities or even mapping. Such similarities will allow drawing conclusions on the development of trust in a (virtual) organisation in general and the process of scientific communication as a special kind of a (virtual) organisation in particular.


Crystal structures, spectroscopic properties of new cobalt(II), nickel(II), zinc(II) and palladium(II) complexes derived from 2-acetyl-5-chloro thiophene thiosemicarbazone: Anticancer evaluation.
The reactions of cobalt(II), nickel(II), zinc(II) chlorides and [Pd(DMSO)2Cl2] with 2-acetyl-5-chloro-thiophene thiosemicarbazone (HL) leads to the formation of a series of new complexes: [CoCl2(S-HL)2], 1; [Ni(N,S-L)2], 2 [ZnCl2(S-HL)2], 3 and [PdCl2(N,S-HL)], 4. All the complexes have been characterized by elemental analysis, IR, LC-MS. 1H and 13C NMR spectroscopy have been performed for Zn(II) and Pd(II) complexes. The crystal structures of the complexes 1-3 have been determined by single-crystal X-ray diffraction methods. The compounds, (1) and (3), crystallized in the monoclinic crystal system with C2/c space group. In both complexes, the metal centers are four-coordinated in a distorted tetrahedral configuration by two sulfur atoms from two thiosemicarbazone ligands and two Cl anions. The crystal structure of (2) consists of monomeric entities where the nickel(II) ion exhibit distorted square planar geometry. The coordination geometry around nickel ion is four-coordinate with four atoms of the two chelating thiosemicarbazone ligands which are in cis position. The τ4 value of 0.255 obtained from the τ4 analysis of complex (2) shows that the four-coordinate geometry around the central nickel ion is close to square planar. Complex (4) is mononuclear, the central ion is coordinated through the sulfur and the azomethine nitrogen atom of neutral ligand. The cytotoxic effects of all complexes were analyzed for three cancer cell lines, Caco-2, DLD-1, and SW620 compared to normal colon epithelial cell line, CCD18Co. Complex (4) is more active against DLD-1, SW620 and Caco-2 than CCD18Co. The efficiency of complex (4) is more effective in aggressive cancer cell lines. Therefore, it can be used as a new chemotherapeutic, especially in the treatment of resistant cancer types caused by long-term use of platinum-based drugs.