The effect of acute airway inflammation on bronchial reactivity in guinea pigs.
This study compared airways reactivity before and after an inflammatory response was induced in the airways by exposing them to cigarette smoke. Airways reactivity was measured to graded doses of histamine using a standard technique in 24 animals without drug pretreatment, in 17 pretreated with propranolol, in 17 pretreated with atropine, and in 18 pretreated with both atropine and propranolol. In each group, at least 5 animals not exposed to cigarette smoke served as controls, and the remaining animals were studied in groups of 4 or more at 30 min, 6, and 24 h after exposure to 100 puffs of whole cigarette smoke. The data show that airways reactivity was increased at 30 min but not at 6 and 24 h after exposure to cigarette smoke. Pretreatment with propranolol or the combination of propranolol and atropine prior to the histamine dose-response curve did not affect the increased response seen after cigarette smoke exposure, but pretreatment with atropine abolished it. Comparing this study with our previous histologic studies of the airways in similarly exposed animals, we conclude that the observed increase in airways reactivity occurs during the fluid exudative phase of the inflammatory response before the polymorphonuclear leukocytes migrate into the epithelium.


Reconstitution of galectin-3 alters glutathione content and potentiates TRAIL-induced cytotoxicity by dephosphorylation of Akt.
We investigated the role of galectin-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptotic death in human breast carcinoma BT549 cells. We observed that parental galectin-3 null BT549 cells (BT549(par)) as well as control vector transfected (BT549(neo)) cells were resistant to TRAIL, while galectin-3 cDNA-transfected BT549 cells (BT549(gal-3)) were sensitive to TRAIL. Data from flow cytometry and immunoblotting analyses reveal that reconstitution of galectin-3 promoted cell death and PARP cleavage as well as caspase (-8, -9, and -3) activation during TRAIL treatment. However, unlike TRAIL treatment, galectin-3 transfectants were resistant to UV-B-induced PARP cleavage. Data from cDNA array analysis show that galectin-3 did not significantly enhance or reduce any apoptosis-related gene expression. Moreover, although galectin-3 restored pre-mRNA splicing activity and resulted in elevation of FLIPs protein, experiments with FLIPs cDNA-transfected cells show that overexpression of FLIPs did not sensitize cells to TRAIL. Interestingly, BT549(gal-3) cells demonstrated a approximately 2-fold increase in total glutathione content as well as a approximately 5-fold increase in GSSG content in comparison to BT549(par) and BT549(neo) cells, suggesting that galectin-3 overexpression may alter intraceullular oxidation/reduction reactions affecting the metabolism of glutathione and other thiols. In addition, galectin-3 overexpression inactivated Akt by dephosphorylation. Finally, overexpression of constitutively activated Akt protected BT549(gal-3) cells from TRAIL-induced cytotoxicity. Taken together, our data suggest that galectin-3-enhanced TRAIL-induced cytotoxicity is mediated through dephosphorylation of Akt, possibly through a redox-dependent process.


Chromosome 2 hypersensitivity and clonal development in murine radiation acute myeloid leukaemia.
Acute myeloid leukaemias induced by ionizing radiation in mouse are characterized by chromosome (chr) 2 aberrations. While it is known that chr 2 aberrations form early and in abundance post-irradiation, unequivocal evidence for hypersensitivity of chr 2 in the first post-irradiation mitoses is lacking. Here it is established that chromosomal aberrations detected in bone marrow cells by chromosome painting are induced in all mice at an approximately 2-fold greater frequency in chr 2 by comparison with chrs 1 and 3 at 24 and 48 h following in vivo whole-body X-irradiation. Long-term follow up studies (to 15 months post-irradiation) indicated that chromosomal hypersensitivity is accounted for largely by the existence of hot-spots for aberration formation on sensitive chromosomes. Analysis of clonal developments suggested that chr 2 aberrant clones are selected for entry into the proliferating bone marrow cell compartment in preference to cells with other aberrations and that these clones in general have a higher proliferative potential. However, neither the induction of chr 2 aberrations nor the presence of a chr 2 aberrant clone specifically predict the development of AML in an individual irradiated mouse. Nonetheless these events or sub-groups of these events are necessary for AML development.


Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin. Pharmacologic inhibition or shRNA knockdown of ILK prevented periostin-induced Akt/mammalian target of rapamycin (mTOR) signaling and ADPKD cell proliferation in vitro Homozygous deletion of ILK in renal collecting ducts (CD) of Ilkfl/fl ;Pkhd1-Cre mice caused tubule dilations, apoptosis, fibrosis, and organ failure by 10 weeks of age. By contrast, Ilkfl/+ ;Pkhd1-Cre mice had normal renal morphology and function and survived >1 year. Reduced expression of ILK in Pkd1fl/fl ;Pkhd1-Cre mice, a rapidly progressive model of ADPKD, decreased renal Akt/mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis, and significantly improved renal function and animal survival. Additionally, CD-specific knockdown of ILK strikingly reduced renal cystic disease and fibrosis and extended the life of pcy/pcy mice, a slowly progressive PKD model. We conclude that ILK is critical for maintaining the CD epithelium and renal function and is a key intermediate for periostin activation of signaling pathways involved in cyst growth and fibrosis in PKD.


Follow up of patients after open heart surgery.
To determine the patient drop out to postoperative follow up for heart patients at the Kenyatta National Hospital. The study analysed the postoperative attendance of heart patients to the surgical outpatient clinic at the KNH. Data on clinic attendance was collected over a one-year period from patient files and from clinic attendance. A total of four hundred and seventy-five open heart operations have been performed at the Kenyatta National Hospital over the last twenty-five years. The patients' mean age is 18.0 years. Clinic follow up rate over this period is 85% at one-year, 62% at five-years, 32% at ten-years and 13% at fifteen-years. A number of patients who had since fallen out to clinic follow up were traced during the study period, when included into the analysis the revised figures are 85%, 70%, 40% and 24% respectively. The difference is statistically significant (p = 0.019). There was no significant statistical difference in the follow up between males and females (p = 0.278), however between patients operated for congenital heart diseases compared to valve patients, the difference was significant (p = 0.007), valve patients having a better follow up. The five-year follow up for isolated mitral, aortic and double valve replacements were 94%, 74% and 78% respectively. Despite deceptively good follow up figures, our figures are in fact poor when age is considered. Financial combined with logistical problems are the most likely causes of poor follow up.


Effects of chronic manganese exposure on attention and working memory in non-human primates.
Manganese (Mn) is essential for a variety of physiological processes, but at elevated levels, can be neurotoxic. While cognitive dysfunction has been recently appreciated to occur as a result of chronic Mn exposures, it is still unclear as to which cognitive domains are most susceptible to disruption by Mn exposure. We previously described early appearing Mn-induced changes in performance on a paired associate learning task in monkeys chronically exposed to Mn and suggested that performance of this task might be a sensitive tool for detecting cognitive dysfunction resulting from Mn exposure. As chronic Mn exposure has been suggested to be associated with attention, working memory and executive function deficits, the present study was conducted to assess the extent to which detrimental effects of chronic Mn exposure could be detected using tasks specifically designed to preferentially assess attention, working memory, and executive function. Six cynomolgus monkeys received Mn exposure over an approximate 12 month period and three served as control animals. All animals were trained to perform a self-ordered spatial search (SOSS) task and a five choice serial reaction time (5-CSRT) task. Deficits in performance of the SOSS task began to appear by the fourth month of Mn exposure but only became consistently significantly impaired beginning at the ninth month of Mn exposure. Performance on the 5-CSRT became significantly affected by the third month of Mn exposure. These data suggest that in addition to the paired associate learning task, cognitive processing speed (as measured by the 5-CSRT) may be a sensitive measure of Mn toxicity and that brain circuits involved in performance of the SOSS task may be somewhat less sensitive to disruption by chronic Mn exposure.


Introductions and early spread of SARS-CoV-2 in the New York City area.
New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.


The choice of conduits in coronary artery bypass surgery.
Choosing appropriate bypass conduits is important in the consideration of long-term outcomes after surgical revascularization. When deciding on a grafting strategy, attention should be given to technical, anatomic, and angiographic determinants of conduit properties, as well as the clinical characteristics of the patient. The aim of the study was to present a current review of available choices of conduits in coronary artery bypass surgery. To date, only 4 conduits have proven to be effective: the saphenous vein (SVG), the internal mammary arteries (IMAs), the radial artery (RA), and the right gastroepiploic artery (RGEA). The IMA has unique biological properties that confer protection to intimal growth and atherosclerotic plaque formation, making it the conduit of choice for coronary artery bypass grafting. SVG exhibits a lower patency rate than those of IMAs. The RGEA allows revascularization of the inferior wall but is less commonly used, given that it is more prone to spasms.


The Verbal Interaction Social Threat Task: A New Paradigm Investigating the Effects of Social Rejection in Men and Women.
In recent years, digital communication and social media have taken an indispensable role in human society. Social interactions are no longer bound to real-life encounters, but more often happen from behind a screen. Mimicking an online communication platform, we developed a new, fMRI compatible, social threat paradigm to investigate sex differences in reactions to social rejection. During the Verbal Interaction Social Threat Task (VISTTA), participants initiate 30 short conversations by selecting one of four predefined opening sentences. Two computerized interlocutors respond to the opening sentence mostly with negative comments and rejections toward the participant, which should induce social-evaluative threat. Physiological and subjective responses were measured, before, during, and after the VISTTA in 61 (29 male and 32 female) first year students who received either mostly negative (n = 31; threat group) or neutral comments (n = 30; control group). Two-level behavioral validation included social threat-induced mood changes in participants, and interlocutor evaluation. The latter consisted of multiple variables such as "willingness to cooperate" after every conversation, an overall fairness evaluation of interlocutors, and evaluations per reaction indicating how positive or negative it was received. We acquired additional physiological measures including cortisol assays via saliva samples, heart rate, and blood pressure. Confirming our hypotheses, peer rejection and exclusion during the VISTTA led to less willingness to cooperate and lower fairness evaluation of interlocutors. It also induced feelings of anger and surprise and lower happiness in the social-threat group. Women showed overall higher emotion ratings compared to men. Contrary to our a priori hypothesis, the VISTTA did not induce cortisol and heart rate increases. However, the stable cortisol response in women in the threat group does not follow the circadian decline and might reflect an endocrinological response. The decline in cortisol response in men in both the threat and control group could indicate faster habituation to the VISTTA. Taken together, these findings indicate effects of social-evaluative threat on a behavioral level, and more moderate effects on the emotional and physiological level. Sex differences in affective and cortisol responses may indicate that women are more susceptible for the social-evaluative threat than men. With a realistic implementation of verbal, interactive, and social components, the VISTTA is designed as an fMRI paradigm that can be applied to elucidate the neural representation of social-evaluative threat.


Intracellular glycation of nuclear DNA, mitochondrial DNA, and cytosolic proteins during senescence-like growth arrest.
To investigate the accumulation of intracellular advanced glycation end products (AGEs), a method was established for the simultaneous analysis of glycation products of cytosolic proteins, nuclear DNA, and mitochondrial DNA (mtDNA). Nuclear DNA, mtDNA, and cytosolic proteins were simultaneously isolated from one cell lysate by differential centrifugation and combined mechanical and chemical cell disruption methods. The major DNA-AGE N(2)-carboxyethyl-2'-deoxyguanosine (CEdG) was quantified in nuclear DNA and mtDNA by ELISA, whereas the protein-AGEs N(ɛ)-(carboxymethyl)lysine (CML) and N(ɛ)-(carboxyethyl)lysine (CEL) were determined by western blot. The method was used to analyze NIH3T3 fibroblasts. In untreated cells, CEdG levels of mtDNA (14.84 ± 3.07 pg CEdG/μg mtDNA) were significantly higher compared with nuclear DNA (4.40 ± 0.64 pg CEdG/μg DNA; p < 0.001). Then, fibroblasts were analyzed after 7 days of senescence-like growth arrest. In senescent fibroblasts, the CEdG content of nuclear DNA significantly increased by 25%. However, the CEdG level of mtDNA significantly decreased to 52%; in parallel, an increase in mitochondrial mass and mtDNA was observed. Senescence did not lead to general accumulation of protein-AGEs, but two protein bands at 32 and 34 kDa showed a significant increase in the CML/CEL modification rate (208%, p < 0.001; 196%, p = 0.0016) in senescent fibroblasts compared with control cells.


Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide-releasing diazeniumdiolate-based aspirin derivatives.
Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.


HLA-DPB1*0501-associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies.
In order to clarify the relationship between the clinical phenotype and the human leucocyte antigen (HLA) in multiple sclerosis in Asians, 93 Japanese patients with clinically definite multiple sclerosis underwent clinical MRI and HLA-DPB1 gene typing studies. According to a neurological examination, 29 patients were classified as opticospinal multiple sclerosis, 17 as spinal multiple sclerosis and 47 as Western type multiple sclerosis showing the involvement of multiple sites in the CNS including either the cerebrum, cerebellum or brainstem. The opticospinal multiple sclerosis showed a significantly higher age of onset, higher expanded disability status scale scores and higher CSF cell counts and protein content than the Western type multiple sclerosis. On brain and spinal cord MRI, the opticospinal multiple sclerosis showed a significantly lower number of brain lesions, but a higher frequency of gadolinium-enhancement of the optic nerve and a higher frequency of spinal cord atrophy than in Western type multiple sclerosis. The frequency of the HLA-DPB1*0501 allele was found to be significantly greater in opticospinal multiple sclerosis (93%) than in healthy controls (63%, corrected P value = 0.0091 and relative risk = 7.9), but not in Western type multiple sclerosis (66%) or spinal multiple sclerosis (82%). The marked differences in the clinical and MRI findings as well as in the immunogenetic backgrounds between the opticospinal multiple sclerosis and Western-type multiple sclerosis together suggest that HLA-DPB1*0501-associated opticospinal multiple sclerosis is a distinct subtype of multiple sclerosis.


Permanent hypertension after renal homotransplantation in man.
1. In forty-one patients who underwent renal homotransplantation the following measurements were made: (a) blood flow and its distribution in the transplanted kidney as measured by the 85-Kr washout method; (b) renin release in the renal vein of the transplant; (c) arteriovenous difference in plasma renin activity (PRA) of the recipient's remaining left kidney. 2. Eleven transplanted patients were normotensive. Renal haemodynamic data were comparable with those obtained in potential kidney donors. 3. Three hypertensive patients had chronic rejection. The mean renal blood flow and the percentage flow in the first component of the washout curve were reduced. Renin release from the transplant, however, was normal. 4. Ten hypertensive patients had transplant artery stenosis. In eight of them renin release from the grafts as well as peripheral PRA were within normal range. This result is similar to experimental data obtained in Goldblatt renovascular hypertension. The two patients with the tightest artery stenosis had an elevated renin release from the transplant. 5. Thirteen hypertensive patients had elevated arteriovenous difference in PRA of the recipient's own left kidney. Peripheral PRA was significantly higher than in normotensive patients. Left nephrectomy relieved hypertension in ten of them; three have not so far undergone nephrectomy. 6. In four other cases hypertension was also relieved by removal of the patient's own kidney; however, the arteriovenous difference in PRA of that kidney fell within normal range.


Coupling of glycosaminoglycans to agarose beads (sepharose 4B).
1. Heparin, heparan sulphate, chondroitin sulphate and dermatan sulphate were covalently attached to beads of agarose activated by cyanogen bromide. The bond is probably mediated by the amino group of a serine or peptide residue at the reducing end of the polysaccharide chain. 2. The uptake of glycosaminoglycan during the coupling procedure is about 0.9mg/ml of wet gel. However, direct analysis of washed and freeze-dried gels reveals that only about one-third of this amount is firmly attached to the gel. 3. The use of the gels for polysaccharidase analyses is exemplified by a hyaluronidase assay. Further applications, e.g. interaction studies and preparative purposes, are discussed.


Chemotactic peptide binding by intact neutrophils from human neonates.
Binding of the chemotactic peptide N-formyl-methionyl-L-leucyl-L-phenylalanine (FMLP) by neutrophils from neonates was measured to investigate whether an abnormality of this event that initiates chemotaxis could explain the decreased chemotaxis of neonatal neutrophils. No differences of FMLP binding by neonatal and control neutrophils were found at 4 and 22 degrees C when specific binding was assessed by analysis of binding isotherms and Scatchard plots. At 4 degrees C (n = 6) the average number of FMLP molecules bound per neutrophil was 13,854 (neonates) and 17,368 (controls); affinity expressed as Kd was 32 nM (neonates) and 34 nM (controls). At 22 degrees C (n = 5) the respective values were 22,587 FMLP molecules per neutrophil (neonates) and 21,082 (controls); Kd was 29 nM (neonates) and 23 nM (controls). Based on these data, we suggest that mechanisms responsible for decreased chemotaxis of neonatal neutrophils must involve events subsequent to initial FMLP-receptor interaction.


[The effect of tryptophan, 5-hydroxytryptophan, serotonin, histidine and histamine on the peroxidation of lipids in hepatic mitochondrial membranes].
The method of recording the superweak chemifluorescence was applied to the study of the effect of tryptophan, 5-oxytryptophan, sertonin, histidine and histamine on the peroxication of lipids in the membranes of mitochondria of rat liver in the presence of Fe++ ions inducing this process. 5-oxytryptophan and serotonin inhibited this process in a concentration of 10(-5)-10(-4) M (protein content -1.8 mg per 1 ml of mitochondrial suspension). On the basis of studying the kinetics of the initial portion of the ascending branch of the "slow flare up" constants of the antioxidatinve activity (constituting 2.2-10(3) and 9.8-10(3) M-1 for 5-oxytryptophan and serotonin, respectively) was calculated. The antioxidative action is associated with the presence of the phenol group in the molecule of the compound under study. It is supposed that the action of 5-oxytryptophan and serotonin on peroxidation of lipids in the membranes was of significance for the regulation of permeability of the biological membranes, along with their effect on the other membrane processes.


Effect of superior trunk block on diaphragm function and respiratory parameters after shoulder surgery.
The interscalene brachial plexus block has been used effectively for intraoperative and postoperative analgesia in patients undergoing shoulder surgery, but it is associated with high rates of diaphragmatic dysfunction. Performing the block more distally, at the level of the superior trunk, may reduce the incidence of phrenic nerve palsy. We hypothesized that superior trunk block would result in diaphragmatic paralysis rate of less than 20%. 30 patients undergoing arthroscopic shoulder surgery received superior trunk block under ultrasound guidance. Measurements of diaphragm excursion were determined with ultrasound prior to the block, 15 min after the block, and postoperatively in phase II of postanesthesia care unit, in conjunction with clinical parameters of respiratory function. 10 patients (33.3%, 95% CI 17.3% to 52.8%) developed complete hemidiaphragmatic paralysis at the postoperative assessment. An additional eight patients (26.7%) developed paresis without paralysis. Of the 18 patients with diaphragm effects, seven (38.9%) reported dyspnea. 83.3% of patients with abnormal diaphragm motion (56.7% of the total sample) had audibly reduced breath sounds on auscultation. Oxygen saturation measurements did not correlate with diaphragm effect and were not significantly reduced by the postoperative assessment. Although injection of local anesthetic at the superior trunk level is associated with less diaphragmatic paralysis compared with traditional interscalene block, a significant portion of patients will continue to have ultrasonographic and clinical evidence of diaphragmatic weakness or paralysis.


Characterization of Salmonella enterica serotype newport isolated from humans and food animals.
Salmonella enterica serotype Newport isolates resistant to at least nine antimicrobials (including extended-spectrum cephalosporins), known as serotype Newport MDR-AmpC isolates, have been rapidly emerging as pathogens in both animals and humans throughout the United States. Resistance to extended-spectrum cephalosporins is associated with clinical failures, including death, in patients with systemic infections. In this study, 87 Salmonella serotype Newport strains were characterized by pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing and examined for the presence of class 1 integrons and bla(CMY) genes. Thirty-five PFGE patterns were observed with XbaI, and three of these patterns were indistinguishable among isolates from humans and animals. Fifty-three (60%) Salmonella serotype Newport isolates were identified as serotype Newport MDR-AmpC, including 16 (53%) of 30 human isolates, 27 (93%) of 29 cattle isolates, 7 (70%) of 10 swine isolates, and 3 (30%) of 10 chicken isolates. However, 28 (32%) Salmonella serotype Newport isolates were susceptible to all 16 antimicrobials tested. The bla(CMY) gene was present in all serotype Newport MDR-AmpC isolates. Furthermore, the plasmid-mediated bla(CMY) gene was transferable via conjugation to an Escherichia coli strain. The transconjugant showed the MDR-AmpC resistance profile. Thirty-five (40%) of the isolates possessed class 1 integrons. Sequence analyses of the integrons showed that they contained aadA, which confers resistance to streptomycin, or aadA and dhfr, which confer resistance to trimethoprim-sulfamethoxazole. One integron from a swine isolate contained the sat-1 gene, which encodes resistance to streptothricin, an antimicrobial agent that has never been approved for use in the United States. In conclusion, Salmonella serotype Newport MDR-AmpC was commonly identified among Salmonella serotype Newport isolates recovered from humans and food animals. These findings support the possibility of transmission of this organism to humans through the food chain.


Haloperidol and aripiprazole impact on the BDNF and glucocorticoid receptor levels in the rat hippocampus and prefrontal cortex: effect of the chronic mild stress.
Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.


Identification of the anabolic steroid 6β-chlorotestosterone in a dietary supplement.
Capsules that were labeled to be performance-enhancing dietary supplements obtained during an investigation were found to contain an unrecognized steroid-like substance. This compound was isolated by liquid chromatography (LC) fraction collection and characterized using several qualitative analytical techniques, including ultraviolet (UV) spectroscopy, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-high resolution accurate mass-mass spectrometry (LC-HRAM-MS), as well as 1 H, 13 C, and two-dimensional nuclear magnetic resonance (NMR) spectrometry. This multi-technique analytical approach was used to identify the designer steroid as 6β-chloro-4-androsten-17β-ol-3-one (6β-chlorotestosterone), an analog of testosterone about which little has been published.


Vitamin D in human reproduction: the more, the better? An evidence-based critical appraisal.
Vitamin D is a fat-soluble secosteroid hormone that regulates calcium, magnesium, and phosphate homeostasis and plays a pivotal role as antiproliferative and immunomodulatory mediator. Considering the different sources of synthesis and dietary intake as well as the pleiotropic actions in extremely diverse (micro)environments of the body, the supplementation of this Vitamin should be carefully evaluated taking into account the several pathways that it regulates. In the current brief review, we aimed to summarize the available evidence about the topic, in order to suggest the best evidence-based supplementation strategy for human reproduction, avoiding the unuseful (and sometimes hazardous) empiric supplementation. Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Accumulating evidence from in vitro fertilization (IVF) trials suggests that fertilization rate decreases significantly with increasing levels of 25OH-D in follicular fluid; in addition, Vitamin D levels in the follicular fluid are negatively correlated to the quality of embryos and the higher values of Vitamin D are associated with lower possibility to achieve pregnancy. Both low and high Vitamin D serum concentrations decrease not only spermatozoa count, but their progressive motility as well as increase morphological abnormalities. Finally, studies in animal models found that severe hypervitaminosis D can reduce the total skeletal calcium store in embryos and may compromise the postnatal survival. Based on the retrieved data, we solicit to be extremely selective in deciding for Vitamin D supplementation, since its excess may play a detrimental role in fertility.


Autoxidation of oxymyoglobin. An overall stoichiometry including subsequent side reactions.
Oxymyoglobin (MbO2) is oxidized easily to metmyoglobin (metMb) with generation of the superoxide anion, which can be converted by the spontaneous dismutation into H2O2, this being also a potent oxidant of MbO2. In the presence of sodium azide in stoichiometric amounts, however, the rate of autoxidation of MbO2 increased rapidly with increasing concentration of the anion, but soon reached a saturating level, the extent of which was about twice that of the normal autoxidation in buffer alone. Quantitative analysis has revealed that this enhancement is not due to the nucleophilic displacement of O2- from MbO2 by the anion (Satoh, Y., and Shikama, K. (1981) J. Biol. Chem. 256, 10272-10275), but is due to the additional oxidation of MbO2 by H2O2 freed from the metMb being occupied by the anion at the sixth coordination position. Based on these novel results and stoichiometric considerations, it is possible to propose a new view that H2O2 produced from O2- can be eliminated or decomposed mostly, if not completely, by the metMb resulting from the normal autoxidation reaction of MbO2, presumably via the formation of the ferryl species.


Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart.
The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy.


Risk Classifications Interfere with Preference-Sensitive Decision Support.
Many guidelines for prevention and treatment still locate persons in risk classes (e.g. low, moderate, high) on the basis of thresholds placed on a continuous metric for a single criterion (e.g. risk of developing x). These 'traffic light' signals can lead to inferior decisions through their mono-criterial focus and lack of preference-sensitivity to the multiple criteria relevant to the person. It is arguably unethical to communicate to someone that they are at low, moderate, or high risk of x solely on the basis of the unpublished and often unknown preferences of the group that has set the classification thresholds. Any prior classification and labelling will interfere with the individual's balanced processing of information on the performance of all treatment options on their multiple relevant criteria - including treatment side effects and burdens as well as main benefit - and jeopardise meeting the requirements for fully informed and preference-based consent to any subsequent action. Personalised decision support tools based on Multi-Criteria Decision Analysis can help fulfil these objectives, with apomediative (at home) e-decision support especially appealing because of its empowering and resource-saving potential. The individual's absolute risk score is required in these tools since any threshold-based risk classification will interfere with the coherence of the analysis across the multiple criteria.


Prostaglandins contribute to cardiovascular reflexes evoked by static muscular contraction.
The purpose of this study was to determine the contribution of prostaglandins to the reflex cardiovascular responses induced by static contraction of the hind limb in cats, i.e., the exercise reflex. To accomplish this, the cardiovascular responses to hind limb contraction induced by electrical stimulation of spinal cord ventral roots L6-7 and S1 were compared before and after inhibition of prostaglandin synthesis (indomethacin, 2-6 mg/kg i.v., n = 5, or sodium meclofenamate, 2-6 mg/kg i.v., n = 5) or after injection of prostaglandin E2 into the hind limb arterial blood supply. Treatment with indomethacin attenuated the contraction-induced increase in mean arterial pressure and left ventricular dP/dt by 76% and 86%, respectively. Heart rate and average developed triceps surae muscle tension were unchanged. After administering sodium meclofenamate, the reflex response was attenuated to a similar degree. In the indomethacin-treated animals, injection of exogenous prostaglandin E2 (PGE2) partially restored the pressor and myocardial contractile responses. In 6 animals, treatment with exogenous PGE2 without prior inhibition of prostaglandin synthesis did not significantly augment the contraction-induced cardiovascular response. Using the radioactive microsphere technique, we measured skeletal muscle blood flow during contraction before and after treatment with indomethacin (n = 6) to determine if an indomethacin-induced alteration in blood flow could account for the attenuated contraction-induced cardiovascular response. Blood flow during static muscle contraction was not significantly altered by indomethacin. We conclude that prostaglandins contribute to the exercise reflex through an action on afferent nerve endings rather than through a regional vascular effect.


Cardiac surgery and operative mortality in 1992 and 2002: the St Antonius experience.
Comparing the changes in open-heart surgical procedures and hospital mortality in 1992 with 2002. Retrospective investigation at St Antonius Hospital in Nieuwegein. A comparison of the open-heart surgical procedures, hospital mortality and age distribution of the operated patients was made, using the database of the Department of Cardiothoracic Surgery. The total number of open-heart surgical procedures increased. There were more combined procedures, aortic valve replacements and reconstructions of the thoracic aorta. The total number of reoperations decreased. In 2002 the use of an arterial conduit for coronary bypass procedures reached 94%, and the radial artery was used for the first time. The mean patient age and the hospital mortality were higher in 2002. Comparing cardiovascular surgery in 1992 to 2002 showed an increase in complicated procedures and older age groups of patients. This may be the reason for higher overall mortality. The mean patient age increased considerably from 1992 to 2002, together with the number of combined procedures and aortic valve replacements with biological valve prostheses. These trends give cardiovascular surgery a challenging future, to treat the patient adequately and keeping the mortality and complication rates low.


Fibrin glue for closure of conjunctival incision in strabismus surgery: a report by the american academy of ophthalmology.
To evaluate the severity of postoperative inflammation, degree of patient discomfort, adequacy of wound closure, and length of operating time when using fibrin glue compared with sutures to close limbal conjunctival incisions after strabismus surgery. Literature searches of the PubMed and Cochrane Library databases were last conducted on January 24, 2013, and resulted in 24 citations, including 2 not in the English language. All citations were reviewed in full text. Five studies compared fibrin glue (68 eyes) with sutures (74 eyes) for closure of limbal conjunctival incisions in patients undergoing strabismus surgery and were included in this assessment; no studies were found that evaluated fornix incisions. A quality rating was assigned to each study using criteria specifically developed for this assessment. No level I studies were found, and 5 level II studies were identified. There was significantly less postoperative inflammation and patient discomfort for 1 to 3 weeks after strabismus surgery for eyes treated with fibrin glue compared with sutures. In 3 studies that evaluated wound apposition, 2 of 50 eyes (4%) with conjunctival incisions that were initially closed using fibrin glue subsequently developed a wound gap that required suture repair. In the 2 studies that compared surgical time, fibrin glue required 1 to 5 minutes less time than suturing in 1 study and 55% less time (3.8 vs. 8.4 minutes) in a second study. These 5 studies did not evaluate the cost-effectiveness or risk of viral transmission from fibrin glue. Studies in the literature suggest that the off-label use of fibrin glue to close limbal conjunctival incisions in strabismus surgery resulted in less postoperative inflammation and required shorter operating time compared with sutures, but it increased the percentage of wounds requiring subsequent repair with sutures. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


How children's anxiety symptoms impact the functioning of the hypothalamus-pituitary-adrenal axis over time: A cross-lagged panel approach using hierarchical linear modeling.
Anxiety symptoms in childhood and adolescence can have a long-term negative impact on mental and physical health. Although studies have shown dysregulation of the hypothalamus-pituitary-adrenal axis is associated with anxiety disorders, it is unclear how and in what direction children's experiences of anxiety symptoms, which include physiological and cognitive-emotional dimensions, impact the functioning of the hypothalamus-pituitary-adrenal axis over time. We hypothesized that higher physiological symptoms would be contemporaneously associated with hypercortisolism, whereas cognitive-emotional symptoms would be more chronic, reflecting traitlike stability, and would predict hypocortisolism over time. One hundred twenty children from the Concordia Longitudinal Risk Research Project were followed in successive data collection waves approximately 3 years apart from childhood through midadolescence. Between ages 10-12 and 13-15, children completed self-report questionnaires of anxiety symptoms and provided salivary cortisol samples at 2-hr intervals over 2 consecutive days. The results from hierarchical linear modeling showed that higher physiological symptoms were concurrently associated with hypercortisolism, involving cortisol levels that remained elevated over the day. In contrast, longitudinal results over the 3 years between data collection waves showed that chronic worry and social concerns predicted hypocortisolism, showing a low and blunted diurnal cortisol profile. These results have implications for broadening our understanding of the links between anxiety, the stress response system, and health across the course of development.


Immunomodulatory dendritic cells inhibit Th1 responses and arthritis via different mechanisms.
Dendritic cells (DCs) are professional APCs which have the unique ability to present both foreign and self-Ags to T cells and steer the outcome of immune responses. Because of these characteristics, DCs are attractive vehicles for the delivery of therapeutic vaccines. Fully matured DCs are relatively well-defined and even used in clinical trials in cancer. DCs also have the potential to influence the outcome of autoimmunity by modulating the underlying autoimmune response. To gain a better appreciation of the abilities and mechanisms by which immunomodulatory DCs influence the outcome of T cell responses, we studied several immunomodulatory DCs (TNF-, IL-10-, or dexamethasone-stimulated bone marrow-derived DCs) side by side for their ability to modulate T cell responses and autoimmune diseases. Our data show that these differentially modulated DCs display a different composition of molecules involved in T cell activation. Although, all DC subsets analyzed were able to inhibit the induction of collagen-induced arthritis, the modulation of the underlying immune response was different. Vaccination with TNF- or IL-10-modulated DCs altered the Th1/Th2 balance as evidenced by the induction of IL-5- and IL-10-secreting T cells and the concomitant reduction of the IgG2a-IgG1 ratio against the immunizing Ag. In contrast, DCs modulated with dexamethasone did not affect the ratio of IL-5-producing vs IFN-gamma-producing T cells and tended to affect the Ab response in a nonspecific manner. These data indicate that distinct mechanisms can be used by distinct DC subsets to change the outcome of autoimmunity.


A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation.
The AMP-activated protein kinase (AMPK) is a highly conserved trimeric protein complex that is responsible for energy homeostasis in eukaryotic cells. Here, a 1.9 A resolution crystal structure of the isolated kinase domain from the alpha2 subunit of human AMPK, the first from a multicellular organism, is presented. This human form adopts a catalytically inactive state with distorted ATP-binding and substrate-binding sites. The ATP site is affected by changes in the base of the activation loop, which has moved into an inhibited DFG-out conformation. The substrate-binding site is disturbed by changes within the AMPKalpha2 catalytic loop that further distort the enzyme from a catalytically active form. Similar structural rearrangements have been observed in a yeast AMPK homologue in response to the binding of its auto-inhibitory domain; restructuring of the kinase catalytic loop is therefore a conserved feature of the AMPK protein family and is likely to represent an inhibitory mechanism that is utilized during function.


Protein quality and calcium availability from extruded and autoclaved turkey hatchery residue.
The protein quality of an extruded mixture of hatchery by-product meal and soybean meal (EHSM) and the calcium availability of autoclaved hatchery by-product meal (AHBM) were determined. In Experiments 1 and 2, EHSM or soybean meal (SBM) were the only protein sources in diets formulated to contain 16, 20, or 24% CP. In both experiments, there were five or six replicate pens randomly allotted to each level of dietary protein and each pen contained five poults. In Experiment 1, there was a significant increase in the Protein Efficiency Ratio (PER; P < or = 0.005) in poults from a fast-growing line compared with poults from a slow-growing line selected for egg production but no significant differences between EHSM and SBM. In Experiment 2, PER was increased in poults fed EHSM (P < or = 0.002). In both studies, there was a large decline in PER in those poults fed the 16% SBM diet, and this resulted in a significant source by level interaction. There were no significant source or level of protein effects on the Net Protein Ratio (NPR) or Net Protein Utilization (NPU) in Experiment 2. In Experiment 3, AHBM, steamed bone meal and limestone were the primary sources of calcium in diets containing 0.6, 0.8, 1.0, and 1.2% calcium. There were four replicate pens per level and source of calcium. The length and width of the femur and tibia were measured along with fat-extracted bone weight and ash. Poults fed diets containing AHBM and limestone had improved feed efficiency (P < or = 0.008) compared with those fed bone meal. There were no significant diet effects on any bone measurements.


SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence.
Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.


A case report of two instances of colorectal hepatoid adenocarcinoma, accompanied by a comprehensive literature review.
The study aimed to explore the clinical and pathological characteristics, survival outcomes, and prognostic factors of colorectal hepatoid adenocarcinoma. We performed two cases of colorectal hepatoid adenocarcinoma treated at the Oncology Department of the First Affiliated Hospital of Nanchang University. We also reviewed literature up to the present and performed a retrospective study of colorectal hepatoid adenocarcinoma. Among the 39 patients included in this study, 28 had primary tumors in the colon, 9 in the rectum, and 2 in the rectosigmoid junction. The median age was 52 years (range 31-75 years); 28 patients (71.8%) were male. Out of the 32 patients for whom survival data were available, 24 patients succumbed to disease-related causes. The median overall survival of 32 patients was 8 months, with 1-year and 2-year overall survival rates of 31.0% and 16.0%, respectively. Univariate analysis revealed that depth of infiltration, presence of liver metastases, TNM stage, and the completeness of surgical resection were significantly associated with the overall survival period of colorectal hepatoid adenocarcinoma. Colorectal hepatoid adenocarcinoma exhibits a high degree of aggressiveness and poor prognosis. The major strategy for early-stage HAC was radical surgery and chemoradiotherapy demonstrates limited efficacy for extending survival.


[Cardiac involvement in Lyme disease].
Cardiac manifestations of Lyme Borreliosis are relatively infrequent, occurring within weeks after the infectious tick bite (median of 21 days), and resulting at this stage from a direct borrelial infection of the myocardium, as indicated by reports of spirochete isolation from pericardium and myocardium. They may persist or appear in the late, tertiary phase of the illness, being then more likely due to infection-triggered autoimmunity. Lyme carditis typically presents with a fluctuating degree of atrioventricular block that spontaneously resolves in several days. Rarely, myocarditis may occur with or without pericardial involvement, in patients presenting with chest pain, ST depression or T wave inversion, mimicking an acute myocardial infarction, and various arrhythmias are reported, as well as pericardial effusion or heart failure. A complete recovery is usually observed, spontaneous or after antibiotherapy. Severe myocarditis or Pericarditis leading to death is exceptional. The diagnosis of Lyme carditis is based on the same association of clinical and laboratory features as in Lyme disease without cardiac involvement. But the occurrence of conduction disturbances in healthy young people suggests screening for other criteria of Lyme disease. The management of Lyme carditis does not differ from the treatment of Lyme disease without carditis and is mainly based upon the use of doxycycline or ceftriaxone.


Micropapillary or solid component predicts worse prognosis in pathological IA stage lung adenocarcinoma: A meta-analysis.
Micropapillary and solid patterns indicate worse survival in lung adenocarcinoma patients, even in pathological stage IB patients. However, whether the presence of micropapillary or solid components is related to worse prognosis in pathological IA stage lung adenocarcinoma remains unclear. Several databases were searched up to December 31, 2022 for relevant studies investigating the association between micropapillary and solid components and the survival of IA stage lung adenocarcinoma patients. Primary and secondary outcomes are disease-free survival (DFS) and overall survival (OS), respectively. Hazard ratios (HRs) and 95% confident intervals (CIs) were combined, and subgroup analysis stratified by the pathological subtype and proportion of components was further performed. A total of 19 studies with 12,562 cases were included. Pooled results indicated that micropapillary or solid components obviously predicted worse DFS (HR = 2.40, 95% CI: 1.96-2.94, P < .001) and OS (HR = 2.30, 95% CI: 1.68-3.15, P < .001). Subgroup analysis based on pathological subtype showed that both micropapillary and solid components were significantly associated with worse DFS (micropapillary: HR = 2.70, 95% CI: 1.70-4.28, P < .001; solid: HR = 3.98, 95% CI: 2.10-7.54, P < .001) and OS (micropapillary: HR = 2.29, 95% CI: 1.17-4.48, P = .015; solid: HR = 4.18, 95% CI: 1.72-10.17, P = .002). In addition, further subgroup analysis stratified by the proportion of micropapillary and solid components (>5%/1% or predominant) showed similar results. Micropapillary and solid patterns predicted a significantly worse prognosis in pathological IA stage lung adenocarcinoma patients.


European illegal puppy trade and organised crime.
Organised crime groups' involvement in illicit markets is a common focus of law enforcement and governments. Drug, weapon, human and wildlife trafficking (and others) are all illegal activities with link to organised crime. This paper explores the overlooked illicit market of puppies. We detail the state of knowledge about the organisation of the UK puppy trade, which includes irresponsible and illegal breeding of puppies throughout Europe and their often-illegal movement into the UK. In 2017, we conducted an analysis of hundreds of online advertisements in Scotland, 12 expert interviews, a stakeholder survey of 53 participants, and 40 focus groups across Great Britain. Our data suggest an organised illicit market running in parallel to the legal trade. We speculate as to whether at some point along the supply chain organised crime groups are responsible for the suffering and death of the puppies and the economic and emotional damage to 'consumers'. Online monitoring and physical scrutiny at the ports must be improved to reduce non-human animal abuse. People buying puppies must also be made aware that their purchase could be profiting organised crime.


T-cell/periodic acid-Schiff stain: a useful tool in the evaluation of tubulointerstitial infiltrates as a component of renal allograft rejection.
Distinguishing between tubulitis and tubulointerstitial mononuclear cell infiltrates and determining the severity of tubulitis are critical components of diagnosing and grading renal allograft rejection using the 1993 Banff schema, the revised 1997 Banff schema, or the Cooperative Clinical Trials in Transplantation grading system. We describe a novel staining method, the T-PAS stain (CD3 and periodic acid-Schiff), which removes some of the subjectivity in the evaluation of tubulointerstitial infiltrates in renal allograft biopsies. The method simply combines two routine stains, immunoperoxidase staining for T cells (CD3) and periodic acid-Schiff (PAS) staining for tubular basement membrane, on the same section.


Thermal plasticity in the invasive south American tomato pinworm Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae).
South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is a devastating invasive global insect pest of tomato, Solanum lycopersicum (Solanaceae). In nature, pests face multiple overlapping environmental stressors, which may significantly influence survival. To cope with rapidly changing environments, insects often employ a suite of mechanisms at both acute and chronic time-scales, thereby improving fitness at sub-optimal thermal environments. For T. absoluta, physiological responses to transient thermal variability remain under explored. Moreso, environmental effects and physiological responses may differ across insect life stages and this can have implications for population dynamics. Against this background, we investigated short and long term plastic responses to temperature of T. absoluta larvae (4th instar) and adults (24-48 h old) from field populations. We measured traits of temperature tolerance vis critical thermal limits [critical thermal minima (CTmin) and maxima (CTmax)], heat knockdown time (HKDT), chill coma recovery time (CCRT) and supercooling points (SCP). Our results showed that at the larval stage, Rapid Cold Hardening (RCH) significantly improved CTmin and HKDT but impaired SCP and CCRT. Heat hardening in larvae impaired CTmin, CCRT, SCP, CTmax but not HKDT. In adults, both heat and cold hardening generally impaired CTmin and CTmax, but had no effects on HKDT, SCP and CCRT. Low temperature acclimation significantly improved CTmin and HKDT while marginally compromising CCRT and CTmax, whereas high temperature acclimation had no significant effects on any traits except for HKDT in larvae. Similarly, low and high temperature acclimation had no effects on CTmin, SCPs and CTmax, while high temperature acclimation significantly compromised adult CCRT. Our results show that larvae are more thermally plastic than adults and can shift their thermal tolerance in short and long timescales. The larval plasticity reported here could be advantageous in new envirnments, suggesting an asymmetrical ecological role of larva relative to adults in facilitating T. absoluta invasion.


[Respiratory complications in 44 patients with acquired immunodeficiency syndrome].
Observation was carried out of 44 patients affected with pulmonary pathology during the course of AIDS, each of whom presented a severe respiratory insufficiency, admitted to the Clinic of Infectious Diseases between May 1987 and March 1989. In the patients suffering from their first respiratory infection, a lower mortality rate was observed (11/28, 39.2%) compared with the patients suffering from a second or successive infection (10/16, 62.5%). In sixteen cases, the etiological agent was Pneumocystis carinii while in 14 subjects it was impossible to perform bronchoscopy due to particular conditions of the respiratory apparatus and diagnosis was made according to CDC clinical criteria. Several parameters were furthermore evaluated (age, duration of the symptoms prior to admittance, LDH, PaO2, WBC) as potential prognostic indices; at the conclusion of the study, no statistically significant differences were found, however, between the group of survivors and the deceased. For the specific anti PCP therapy, a great variety of drugs were administered; among them, first choice was given to cotrimoxazole. In particularly critical patients, methylprednisolone was added. In 21 patients, a mechanical respiratory aid (C-PAP) was applied with favourable results in 16 of them.


A new species of Inosperma, and first record of I. afromelliolens (Inocybaceae, Fungi) from West Africa.
Here, we present the newly identified Inosperma macrocarpa and the first record of I. afromelliolens from West Africa. Inosperma macrocarpa is nested in an Old World Tropical clade, based on a molecular phylogeny inferred from the sequences of ITS, LSU, RPB2, and TEF1. Complete descriptions and illustrations, including photographs and line drawings, of the new species are presented. Morphological and molecular analyses based on collections from Benin confirmed the presence of I. afromelliolens in West Africa. Toxicity analysis showed that neither species contained muscarine, which further supports the hypothesis that the ability to produce muscarine is a derived trait of Inosperma.


Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging.
Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating antineoplastic therapies. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tumor growth and response to therapy have been assessed in intraperitoneal, and subcutaneous, and intravascular cancer models. However, use of this approach for evaluating orthotopic tumor models has not been demonstrated. In this report, the ability of BLI to noninvasively quantitate the growth and therapeutic-induced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luciferase (9LLuc) was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryogenically cooled CCD camera and magnetic resonance imaging (MRI), respectively. There was excellent correlation (r=0.91) between detected photons and tumor volume. A quantitative comparison of tumor cell kill determined from serial MRI volume measurements and BLI photon counts following 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment revealed that both imaging modalities yielded statistically similar cell kill values (P=.951). These results provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.


Diverse metabolites from corn silk with anti-Aβ1-42 aggregation activity.
Five pairs of enantiomeric compounds (1a/1b-5a/5b) including seven undescribed compounds (1a/1b-3a/3b, 4b) along with two known ones (. and .) have been isolated from corn silk (Stigma maydis). Racemic mixtures of these enantiomers were separated by HPLC with different types of chiral columns. Their structures were elucidated based on comprehensive spectroscopic analyses together with quantum chemical calculations of 13C NMR data and electronic circular dichroism (ECD) curves. All the isolates were evaluated for their inhibition ability of self-induced Aβ1-42 aggregation. Among them, compounds 4a (88.36%), 4b (74.66%) and . (85.65%) showed stronger inhibitory activity than the positive control curcumin (61.90%). The different inhibition profiles of enantiomers 4a and 4b were explained by docking simulation studies.


Patient opinion of the doctor-patient relationship in a public hospital in Qatar.
To analyze the factors associated with the level of satisfaction of outpatients in their relationship with their doctor at the largest public hospital in Qatar. This study was a cross-sectional survey of attitudes. Researchers surveyed 626 outpatients at Hamad General Hospital in Doha, Qatar from September 2009 to January 2010 using a novel questionnaire assessing satisfaction with patients' interaction(s) with their doctor (spent time with patient, took case seriously, maintained confidentiality, and the overall quality of visit). Mean responses on 4 Likert scale items (one to 5) were as follows: "spent enough time with patient" = 4.39; "doctor took case seriously" = 4.57; "satisfaction with doctor-patient confidentiality" = 4.71; "overall quality of visit" = 4.46. Age, gender, citizenship, level of education, and number of visits did not significantly impact the level of satisfaction. For 73.1% of patients, the physician's qualification was the most important factor in choosing a doctor. Of those surveyed, 40.7% of men and 28.1% of women preferred to see a doctor of their own gender. A positive correlation between perceived communication and satisfaction with the doctor-patient encounter was established. This study found that patients in the Out-Patient Department at Hamad Hospital were highly satisfied with their relationships with their doctors, and physician qualification was the most significant factor in choosing a doctor. A significant number of males and females preferred a physician of their own gender. Communication difficulty correlated with lower satisfaction.


Lyso-phosphatidylethanolamine triggers immunity against necrotrophs by promoting JA-signaling and ROS-homeostasis.
Modulation of the plant defense response by bioactive molecules is of increasing interest. However, despite plant cell lipids being one of the major cellular components, their role in plant immunity remains elusive. We found that the exogenous application of the cell-membrane localized phospholipid lyso-phosphatidylethanolamine (LPE) reprograms the plant transcript profile in favor of defense-associated genes thereby priming the plant immune system. Exogenous LPE application to different Arabidopsis accessions increases resistance against the necrotrophic pathogens, Botrytis cinerea and Cochliobolus heterostrophus. We found that the immunity-promoting effect of LPE is repealed in the jasmonic acid (JA) receptor mutant coi1, but multiplied in the JA-hypersensitive mutant feronia (fer-4). The JA-signaling repressor JAZ1 is degraded following LPE administration, suggesting that JA-signaling is promoted by LPE. Following LPE-treatment, reactive oxygen species (ROS) accumulation is affected in coi1 and fer-4. Moreover, FER signaling inhibitors of the RALF family are strongly expressed after LPE application, and RALF23 is internalized in stress granules, suggesting the LPE-mediated repression of FER-signaling by promoting RALF function. The in-situ increase of LPE-abundance in the LPE-catabolic mutants lpeat1 and lpeat2 elevates plant resistance to B. cinerea, in contrast to the endogenous LPE-deficient mutant pla2-alpha. We show that LPE increases plant resistance against necrotrophs by promoting JA-signaling and ROS-homeostasis, thereby paving the way for the LPE-targeted genomic engineering of crops to raise their ability to resist biotic threats.


[Occupational allergic "march". Rapid evolution of contact dermatitis to ammonium persulfate into airborne contact dermatitis with rhinitis and asthma in a hairdresser].
Hairdressers are exposed to irritants and allergenic compounds that may cause contact dermatitis, rhinitis and asthma. In this paper we describe the case of a female, age 33 years, who developed contact dermatitis after 10 years of exposure to ammonium persulfate. After 7 months of progressively extensive and persistent skin lesions, respiratory symptoms appeared that were related to the occupational exposure (on-off test). SIDAPA and specific occupational patch test for hairdressers and occupational challenge with ammonium persulfate were performed. Clinical parameters of inflammation, ECP (eosinophil cationic protein) and exhaled nitric oxide (FeNO) were detected before and after the specific bronchial challenge. The patch test was positive to ammonium persulfate (++), and bronchial challenge for ammonium persulfate showed a significant late response (FEV1 decrease--33%). Both FeNO and ECP showed a significant increase after 24 hours. Dermatitis, urticaria and angioedema occurred on the uncovered skin due to airborne contact. Topic steroids and anti-histaminic drugs resolved the clinical symptoms. Bronchial challenge is, in fact, considered to be the gold standard for the diagnosis of occupational asthma, although new inflammatory parameters can contribute to the diagnosis and can be useful for monitoring after a specific inhalation test with occupational agents. The described case summarizes the evolution from contact dermatitis to inhalation allergy, suggesting the occurrence of an allergic "march" for occupational allergy.


Acute effect of dietary stanyl ester dose on post-absorptive alpha-tocopherol, beta-carotene, retinol and retinyl palmitate concentrations.
Stanyl esters dissolved in margarine inhibit cholesterol absorption, lower sterol absorption in general, and lower serum total cholesterol, LDL-cholesterol and plant sterol levels. To find out whether stanyl esters inhibit absorption of fat-soluble vitamins and beta-carotene in acute experiments, we performed two fat-tolerance tests fortified with vitamins (retinol 0.9-3.7 mg, alpha-tocopherol 70-581 mg), beta-carotene (25-150 mg) and squalene (0.5 g) with and without 1 g of stanyl ester added to the test meal in ten healthy men. The concentrations or areas under the curves (AUC) of cholesterol, triacylglycerols, squalene and alpha-tocopherol, beta-carotene and retinyl palmitate showed typical postprandial changes in serum, chylomicrons, VLDL and VLDL infranatant (intermediate-density lipoproteins, LDL and HDL) over 24 h after the test meal without stanyl esters, and they were not affected by the addition of stanyl esters. The post-absorptive serum campesterol concentration and campesterol : cholesterol were significantly lowered at 6-9 h by stanyl ester supplementation, reflecting reduced sterol absorption efficiency. Changes in vitamin and beta-carotene AUC did not correlate with the given doses. In conclusion, the present study shows that stanyl esters dissolved in margarine do not detectably interfere in a short-term study with the absorption of alpha-tocopherol, beta-carotene or retinol measured by a 24 h oral fat-load test.


Carbon dioxide in the ocean surface: the homogeneous buffer factor.
The amount of carbon dioxide that can be dissolved in surface seawater depends at least partially on the homogeneous buffer factor, which is a mathematical function of the chemical equilibrium conditions among the various dissolved inorganic species. Because these equilibria are well known, the homogeneous buffer factor is well known. Natural spatial variations depend very systematically on sea surface temperatures, and do not contribute significantly to uncertainties in the present or future carbon dioxide budget.


Radiation safety standards and their application: international policies and current issues.
This paper briefly describes the current policies of the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection and how these policies are converted into international radiation safety standards by the International Atomic Energy Agency, which is the only global organization-within the United Nations family of international agencies-with a statutory mandate not only to establish such standards but also to provide for their application. It also summarizes the current status of the established corpus of such international standards, and of it foreseeable evolution, as well as of legally binding undertakings by countries around the world that are linked to these standards. Moreover, this paper also reviews some major current global issues related to the application of international standards, including the following: strengthening of national infrastructures for radiation safety, including technical cooperation programs for assisting developing countries; occupational radiation safety challenges, including the protection of pregnant workers and their unborn children, dealing with working environments with high natural radiation levels, and occupational attributability of health effects (probability of occupational causation); restricting discharges of radioactive substances into the environment: reviewing current international policies vis-a-vis the growing concern on the radiation protection of the "environment;" radiological protection of patients undergoing radiodiagnostic and radiotherapeutic procedures: the current International Action Plan; safety and security of radiation sources: post-11 September developments; preparedness and response to radiation emergencies: enhancing the international network; safe transport of radioactive materials: new apprehensions; safety of radioactive waste management: concerns and connections with radiation protection; and radioactive residues remaining after the termination of activities: radiation protection response to the forthcoming wave of decommissioning of installations with radioactive materials. The ultimate aim of this paper is to encourage information exchange, cooperation, and collaboration within the radiation protection professional community. In particular, the paper tries to facilitate consolidation of the growing international regime on radiation safety, including the expansion of legally binding undertakings by countries, the strengthening of the current corpus of international radiation safety standards, and the development of international provisions for ensuring the proper worldwide application of these standards, such as a system of international appraisals by peer review.


Complementary protein and peptide OFFGEL fractionation for high-throughput proteomic analysis.
OFFGEL fractionation of mouse kidney protein lysate and its tryptic peptide digest has been examined in this study for better understanding the differences between protein and peptide fractionation methods and attaining maximum recruitment of this modern methodology for in-depth proteomic analysis. With the same initial protein/peptide load for both fractionation methods, protein OFFGEL fractionation showed a preponderance in terms of protein identification, fractionation efficiency, and focusing resolution, while peptide OFFGEL was better in recovery, number of peptide matches, and protein coverage. This result suggests that the protein fractionation method is more suitable for shotgun analysis while peptide fractionation suits well quantitative peptide analysis [isobaric tags for relative and absolute quantitation (iTRAQ) or tandem mass tags (TMT)]. Taken together, utilization of the advantages of both fractionation approaches could be attained by coupling both methods to be applied on complex biological tissue. A typical result is shown in this article by identification of 8262 confident proteins of whole mouse kidney under stringent condition. We therefore consider OFFGEL fractionation as an effective and efficient addition to both label-free and quantitative label proteomics workflow.


Attachment reorganization following divorce: normative processes and individual differences.
This paper uses attachment theory as a lens for reviewing contemporary research on how adults cope with marital separation and loss. The first section of the paper discusses the process of normative attachment reorganization, or the psychology of adaptive grief responses following relationship transitions. We argue that changes two processes, in particular, can be uses to track changes in this normative reorganization process: narrative coherence and self-concept clarity. The second section of the paper suggest that individual differences in attachment anxiety and avoidance shape the variability in this normative reorganization process, largely as a result of the characteristic ways in which these styles organize emotion-regulatory tendencies. The paper closes with a series of integrative questions for future research, including a call for new studies aimed at understanding under what contexts anxiety and avoidance may be adaptive in promoting emotion recovery to separation and divorce experiences.


First-time parents' prenatal to postpartum changes in health, and the relation of postpartum health to work and partner characteristics.
The purpose of this study was to evaluate prenatal to postnatal changes in first-time parents' physical and mental health, and to describe social and health predictors of parents' postpartum health. This prospective study surveyed 261 expectant fathers and mothers during pregnancy and again at 6 months' postpartum regarding their health, partner, and work characteristics. Postpartum changes in health were evaluated by paired t tests, and predictors of postpartum health were determined using multiple regression analyses. Both fathers and mothers experienced significant postpartum declines in perceived quality of life. In addition, fathers reported an increase in the number of days ill and a decrease in general health and vitality after childbirth. Mothers perceived an increase in vitality despite their diminishing sleep. Parents' postpartum health was associated with mothers' partner satisfaction, fewer illness days, and certain work characteristics, such as total work time and the balance of work between mothers and fathers. Both mothers and fathers experienced declines in health that persisted at least 6 months after the birth of their first child. Notably, postpartum health was associated with partner satisfaction and work characteristics. This information might be used to develop interventions for improving parents' health during this vulnerable time.


Working for a dustbath: are hens increasing pleasure rather than reducing suffering?
Dustbathing is one of the major behavioural systems of domestic fowl that is constrained by commercial caging systems. Although research conducted over the last 20 years has revealed a great deal about causation of dustbathing, attempts at measuring the importance to hens of having access to dustbathing substrate have proven difficult. Various economic techniques, operant conditioning and learning trials have been used to determine whether hens have a 'need' for dustbathing substrate or 'think' about dustbathing in the absence of substrate. In this study, we measured hens' willingness to work to obtain substrate for dustbathing using a vertically swinging door to which weights could be added. Hens were trained to push through the door to enter a goal box containing peat moss. The hens were subjected to two series of trials to compare the maximum weight that they would push to open the door when living in a cage and deprived of dustbathing substrate, with the maximum weight that they would push when living in a pen furnished with litter and a dustbath (non-deprived). Of the 10 hens that opened the door for access to peat moss, six hens pushed more weight when deprived, three hens pushed more weight when non-deprived and one hen pushed an equal amount of weight. Overall, the hens tended to push more weight (860+/-95.6 vs. 682.5+/-83.3 g; P<0.10, one-tailed paired t-test) and tended to make more attempts to open the door (P<0.10) when they were deprived than when they were non-deprived. Significantly more trials resulted in dustbathing when hens were deprived (P<0.01) suggesting that following deprivation, the hens were, in fact, more motivated to dustbathe. The results of these trials indicate that although deprived hens may be more motivated to dustbathe, and that most hens may be willing to work to obtain a dusty substrate when they can see it, they are not necessarily willing to work harder when they are in a state of deprivation than when they have recently dustbathed. These results are very difficult to explain using a 'needs' model of motivation in which deprivation leads to a state of suffering. They are much more consistent with an 'opportunity' model of motivation in which performance of the behaviour, when the opportunity presents itself, leads to a state of pleasure.


[Effect of acetylcholine on cyclic guanosine monophosphate levels in the hearts of rats of different ages].
The effect of various doses of acetylcholine on the content of myocardial cGMP was studied in rats of different age. The degree of changes was shown to depend on acetylcholine dosage and animals' age. Low doses produced more potent effect in adult rats. It is suggested that these features of alteration of cGMP content may be a reason for increased myocardial sensitivity to acetylcholine in old age.


Estimates of Social Contact in a Middle School Based on Self-Report and Wireless Sensor Data.
Estimates of contact among children, used for infectious disease transmission models and understanding social patterns, historically rely on self-report logs. Recently, wireless sensor technology has enabled objective measurement of proximal contact and comparison of data from the two methods. These are mostly small-scale studies, and knowledge gaps remain in understanding contact and mixing patterns and also in the advantages and disadvantages of data collection methods. We collected contact data from a middle school, with 7th and 8th grades, for one day using self-report contact logs and wireless sensors. The data were linked for students with unique initials, gender, and grade within the school. This paper presents the results of a comparison of two approaches to characterize school contact networks, wireless proximity sensors and self-report logs. Accounting for incomplete capture and lack of participation, we estimate that "sensor-detectable", proximal contacts longer than 20 seconds during lunch and class-time occurred at 2 fold higher frequency than "self-reportable" talk/touch contacts. Overall, 55% of estimated talk-touch contacts were also sensor-detectable whereas only 15% of estimated sensor-detectable contacts were also talk-touch. Contacts detected by sensors and also in self-report logs had longer mean duration than contacts detected only by sensors (6.3 vs 2.4 minutes). During both lunch and class-time, sensor-detectable contacts demonstrated substantially less gender and grade assortativity than talk-touch contacts. Hallway contacts, which were ascertainable only by proximity sensors, were characterized by extremely high degree and short duration. We conclude that the use of wireless sensors and self-report logs provide complementary insight on in-school mixing patterns and contact frequency.


Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study.
Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset. Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls. Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively. We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.


Physician Burnout in Pediatric Gastroenterology.
Physicians are prone to burnout which can negatively affect the quality of patient care and lead to medical errors. Burnout can also affect physicians by impacting their personal relationships, their sense of career fulfillment, and job satisfaction. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a taskforce to investigate burnout among pediatric gastroenterologists. A 35-item electronic survey was developed to collect demographic and practice information and characterize the well-being of pediatric gastroenterologists. Burnout was assessed employing 2 single-item measures adapted from the Maslach Burnout Inventory. The survey was distributed to NASPGHAN members 3 times from February 2020 to March 2020. Descriptive statistics, Chi-square, and Fisher exact tests were used. One thousand seven hundred ninety-one e-mails were successfully sent and 408 participants (22.7%) returned surveys. A total of 28.8% reported high risk for emotional exhaustion, 17.5% reported high risk for depersonalization, and 33% reported overall burnout. Participants 44 years of age or younger reported significantly more burnout than those 45 years and older ( P = 0.018). Contributors to high burnout identified included increased patient load/demands, insufficient nursing support, electronic health record (EHR) use, insufficient administrative staff, excessive on-call coverage, and more complex patients. Forty-four percent reported not having enough time for their personal life including family. A total of 16.2% of participants reported that they would not choose to be a pediatric gastroenterologist again. Pediatric gastroenterologists are at risk for emotional exhaustion, depersonalization, and overall burnout. Strategies to prevent physician burnout should be implemented as soon as feasibly possible to improve individual mental health and patient care.


Treatment regimens in patients over 64 years with acute myeloid leukaemia: a retrospective single-institution, multi-site analysis.
The aim of this study is to investigate the effect of treatment choice on survival, transfusion needs and hospitalizations in patients > 64 years old with newly diagnosed acute myeloid leukaemia (AML). This study retrospectively analysed patients over 64 years with AML diagnosed at a regional healthcare network in Switzerland between 2017 and 2020. Patients underwent four therapy groups: intensive chemotherapy (IC), hypomethylating agent in combination with the BCL2-Inhibitor venetoclax (HMA + VEN), hypomethylating agents alone (HMA) or best supportive care (BSC). Of 54 patients 12 (22%) were selected for IC, 13 (24%) for HMA + VEN, 17 (32%) for HMA and 12 (22%) for BSC. The median overall survival of the patients was 76 days, with a significant difference in the four therapy groups (IC 119 days, HMA + VEN 732 days, HMA monotherapy 73 days and BSC 12 days Log-Rank Test Chi2(2): p < 0.001). Patients with HMA + VEN spent significantly less time in the hospital 6.8 days/month compared to IC (19.5 days/month), HMA (20.5 days/month) and BSC (10.5 days/month) (p = 0.005). Transfusion needs were the highest in IC (7.0 RBC/month, 8.0 PC/month) (p = 0.023), whereas there was no difference between HMA + VEN (2.5 RBC/month, 3.2 PC/month), HMA monotherapy (5.3 RBC/month, 6.2 PC/month) and BSC (3.0 RBC/month, 1.4 PC/month). Our real-world data demonstrate superior OS rates of HMA + VEN when compared to IC, HMC or BSC, with a favourable side effect profile with regard to transfusion needs or hospitalization days. Abbreviations: AML, acute myeloid leukaemia; BCL2, B-cell leukaemia/lymphoma-2; BSC, best supportive care; CR, complete response; Cri, complete response with incomplete haematologic regeneration; FLT3, Fms Related Receptor Tyrosine Kinase 3; EKOS, Ethikkomission Ostschweiz; ELN, European Leukaemia Net; HMA, hypomethylating agent; IC, intensive chemotherapy; IDH, Isocitratdehydrogenase; LDAC, low-dose Cytarabine; NCCN, National Comprehensive Cancer Network; OS, overall survival; PC, platelet concentrate; RBC, red blood cell; RCT, randomized controlled trials; t-AML, therapy relative acute myeloid leukaemia'; VEN, venetoclax.


Methods for sampling of airborne viruses.
To better understand the underlying mechanisms of aerovirology, accurate sampling of airborne viruses is fundamental. The sampling instruments commonly used in aerobiology have also been used to recover viruses suspended in the air. We reviewed over 100 papers to evaluate the methods currently used for viral aerosol sampling. Differentiating infections caused by direct contact from those caused by airborne dissemination can be a very demanding task given the wide variety of sources of viral aerosols. While epidemiological data can help to determine the source of the contamination, direct data obtained from air samples can provide very useful information for risk assessment purposes. Many types of samplers have been used over the years, including liquid impingers, solid impactors, filters, electrostatic precipitators, and many others. The efficiencies of these samplers depend on a variety of environmental and methodological factors that can affect the integrity of the virus structure. The aerodynamic size distribution of the aerosol also has a direct effect on sampler efficiency. Viral aerosols can be studied under controlled laboratory conditions, using biological or nonbiological tracers and surrogate viruses, which are also discussed in this review. Lastly, general recommendations are made regarding future studies on the sampling of airborne viruses.


Invited review: Remediation strategies for mycotoxin control in feed.
Mycotoxins are secondary metabolites of different species of fungi. Aflatoxin B1 (AFB1), deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) are the main mycotoxins contaminating animal feedstuffs. These mycotoxins can primarily induce hepatotoxicity, immunotoxicity, neurotoxicity and nephrotoxicity, consequently cause adverse effects on the health and performance of animals. Therefore, physical, chemical, biological and nutritional regulation approaches have been developed as primary strategies for the decontamination and detoxification of these mycotoxins in the feed industry. Meanwhile, each of these techniques has its drawbacks, including inefficient, costly, or impractically applied on large scale. This review summarized the advantages and disadvantages of the different remediation strategies, as well as updates of the research progress of these strategies for AFB1, DON, ZEN and FB1 control in the feed industry.


Hydrogen gas therapy induced shrinkage of metastatic gallbladder cancer: A case report.
We present the case of a 72-year-old female patient with gallbladder cancer (GBC) who developed in situ recurrence and liver metastases 9 mo after irreversible electroporation ablation and oral tegafur (a fluoropyrimidine derivative) chemotherapy, which failed to control the progression of the disease. The patient further developed metastases in the lymph nodes around the head of the pancreas. The patient had severe anemia, requiring weekly blood transfusions. The gallbladder tumor invaded the descending part of the duodenum, causing intestinal leakage and hepatic colonic adhesion. The patient refused other treatments and began daily hydrogen inhalation therapy. After 1 mo of treatment, the gallbladder and liver tumors continued to progress, and intestinal obstruction occurred. After continuous hydrogen therapy and symptomatic treatments including gastrointestinal decompression and intravenous nutrition support, the intestinal obstruction was gradually relieved. Three months after hydrogen therapy, the metastases in the abdominal cavity gradually reduced in size, her anemia and hypoalbuminemia were corrected, lymphocyte and tumor marker levels returned to normal, and the patient was able to resume normal life. This is the first report of an efficacy and safety study about hydrogen therapy in patient with metastatic GBC and a critical general condition, who has remained stable for more than 4 months.


Tissue engineering of urinary organs.
Tissue engineering can serve as an alternative treatment for a malfunctioning or lost organ. Isolated and expanded cells adhere to a temporary scaffold, proliferate, and secrete their own extracellular matrices (ECM) replacing the biodegrading scaffold. The genitourinary system, composed of the kidney, ureter, bladder, urethra, and genital organs, is exposed to a variety of possible injury sites from the time of fetal development. All the urinary organs are mainly composed of smooth muscle and uroepithelial cells and which may be approached by tissue engineering techniques. A large number of materials, including naturally-derived and synthetic polymers have been utilized to fabricate prostheses for the genitourinary system. Usually, whenever there is a lack of native urologic tissue, reconstruction is considered with native non-urologic tissue, such as, gastrointestinal segments, or skin or mucosa from multiple body sites. Engineering tissues using selective cell transplantation may provide a means to create functional new genitourinary tissues. This review concerns urinary tissues reconstructed with bladder uroepithelial cells and smooth muscle cells (SMCs) implanted on biodegradable polymer matrices.


Vascular Stiffness in Children With Chronic Kidney Disease.
Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m2 Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.


The lived experiences of single Taiwanese mothers being resilient after divorce.
The lived experiences of being resilient as described by 13 single Taiwanese mothers after divorce was the focus of this study. A descriptive phenomenological approach to inquiry was the theoretical framework underpinning the study. Information was gathered through two in-depth face-to-face digitally recorded interviews with each participant. Each of the participants had suffered from depression. For the analysis of the participants' transcripts of interview the authors used Colaizzi's method. Four themes emerged from the analysis process: having faith in God, bending with the ebb and flow of daily life, finding strength in the support and friendship of others, and new found freedom and hope for the future. Findings of this study have the potential to enhance understanding of the mental health needs of single mothers and their children in the provision of holistic health care delivery.


[Histochemical study of zinc].
A comparative pattern of zinc distribution in cells of verious organs is given, investigated under various experimental conditions, changing the functional state of cells. Topochemical interrelations of zinc, and the main histochemical components (nucleic acids, protein, enzymes etc.) are studied.


[Metabolic syndrome: more questions than answers].
Metabolic syndrome has a close association with "diseases of civilization" and widespread in economically developed countries. By the end of XX century, unification in clusters of cardiovascular diseases risk factors showed, that simultaneous presence of obesity, type 2 diabetes mellitus, arterial hypertension, insulin resistance, hyperinsulinemia and hyperlipidemia contributed to significant increase in mortality.


Role of Special Olympics for mothers of adult athletes with intellectual disability.
The role of Special Olympics in the lives of mothers of adult athletes was examined. Forty-six mothers participated in a longitudinal study, completing a parenting stress questionnaire, a measure of their child's maladaptive behavior, and a survey of athlete involvement in Special Olympics at two time periods, 42 months apart. Results confirm that involvement in Special Olympics is negatively correlated with mothers' role restriction, isolation, depression, and problems with competence and attachment. Involvement in Special Olympics fully mediated the effect of child social maladjustment on maternal role restriction and depression and partially mediated its effect on maternal problems with competence. Taken together, these findings suggest that Special Olympics can function as a formal support for mothers.