Haemoglobin concentration and prognosis in new cases of heart failure.
Anaemia is common in severe chronic heart failure and is reported to be a predictor of death. We investigated 552 patients (median age 76 years, range 29-95; 54% men [n=296]), in whom the duration of heart failure was sufficiently short that it would be unlikely to affect haemoglobin concentrations. By contrast with studies in established chronic heart failure, haemoglobin was not independently associated with prognosis when age and serum creatinine concentration were included in the analysis. The adverse effects of anaemia on survival might be a consequence of chronic heart failure rather than a separate process causing disease progression.


[Liposuction].
Liposuction is a frequently applied technique in aesthetic plastic surgery, with which subcutaneous adipose tissue can be removed. In recent decades new techniques of liposuction were developed. This led to better results and fewer complications. Liposuction is indicated as symptomatic treatment of obesity and (or) lipomas. Liposuction is not without risks; patients have to be informed of practical consequences and possible complications of the technique.


Effects of lime and compost on earthworm (Eisenia fetida) reproduction in copper and arsenic contaminated soils from the Puchuncaví Valley, Chile.
The Puchuncaví Valley in central Chile has been exposed to atmospheric depositions from a copper smelter. Nowadays, soils in the surrounding area are acidic and contaminated with Cu and As. The objective of this study was to determine the effectiveness of lime and compost for in situ immobilization of trace elements in the soils of the Puchuncaví Valley by using earthworms as bioindicators of toxicity. The lime and compost treatments significantly increased soil pH and decreased the soluble and exchangeable Zn, exchangeable Cu, and free Cu(2+) activity. However, the compost treatment increased soluble Cu, and soluble and exchangeable As. Lime application had no effect on earthworm reproduction in comparison with the unamended control, whereas the application of compost increased cocoon and juvenile production. There was a spatial variability of soil properties within treatments in the field plots. This allowed the identification of which soil properties were actually having an impact on earthworm reproduction. For both cocoon and juvenile production, soil organic matter (SOM) was a positive factor, i.e., more SOM increased cocoon or juvenile production. The toxicity (negative) factor was total soil As. However, total Cu and total As were well correlated (R(2)=0.80, p<0.001), hence some of the trends could have been masked. In summary, compost treatment was effective in improving the quality of soils of Puchuncaví Valley, increasing earthworm reproduction. Future Chilean legislation on maximum permissible concentrations of trace elements in soils should consider SOM content due to its effect on trace element solubility and bioavailability.


Suture Tape Augmentation for Scapholunate Ligament Repair: A Biomechanical Study.
Scapholunate (SL) ligament tears in the acute setting can be treated by primary repair through various techniques. The purpose of this study was to compare repair of the SL ligament with suture anchors alone versus repair of the SL ligament augmented with suture tape. Twelve fresh-frozen cadavers (6 matched pairs) underwent a dorsal approach to the wrist and the SL ligament was sharply dissected off of its scaphoid attachment. Six cadavers underwent direct repair of the SL ligament using 2 suture anchors. The other 6 underwent repair of the SL ligament, which was then augmented with suture tape. All specimens then underwent load to failure testing using tensile distraction forces applied by a universal testing system. Maximum load to failure and mode of failure were recorded. Maximum load to failure (135 N; SD, 44.94 N) for specimens that were repaired and augmented with the internal brace was higher than that for specimens in the repair-only group (68 N; SD, 14.69 N). Biomechanical testing demonstrated a higher maximum load to failure in SL ligament repairs augmented with suture tape compared with a repair-only technique in this cadaveric model. Acute SL ligament injuries may benefit from suture tape augmentation by increasing the stability of the primary repair. This may prove to be beneficial in higher-demand patients.


[Influence of axial length in refractive outcome after cataract surgery].
To analyse the influence of axial length (AL) and age on refractive outcome after cataract surgery in terms of uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA) and subjective refraction. A retrospective review of 171 consecutive cases of uncomplicated cataract surgery was done. The refractive outcome was analysed (UCVA, BCVA and postoperative retraction) according AL before surgery (AL < 22 mm, between 22 and 25 mm and AL > 25 mm) and age (< 40, between 40-60 years and > 60 years). After surgery mean UCVA was 0.6 ± 0.33 Diopters (D) and mean BCVA was 0.93 ± 0.23 D. Mean refractive outcome was 0.89 ± 0.78 D. There were no significant differences in post-operative UCVA, BCVA and refraction between the three age groups. There were statistically significant differences (p = 0.004) in UCVA between the three AL groups. The group with AL between 22 and 25 mm had better UCVA. Mean refractive outcome was -0.95 ± 1.91 D in the group with AL < 22 mm, -0.36 ± 0.88 D in the group with AL between 22 and 25 mm and 0.23 ± 1.15 D in the group with AL > 25 mm. AL influences refractive outcome and UCVA after cataract surgery. Eyes with AL < 22 mm have a worse refractive outcome.


Severe Hypothermia Management in Mountain Rescue: A Survey Study.
Podsiadło, Paweł, Tomasz Darocha, Sylweriusz Kosiński, Kinga Sałapa, Mirosław Ziętkiewicz, Tomasz Sanak, Rachel Turner, and Hermann Brugger. Severe hypothermia management in mountain rescue: A survey study. High Alt Med Biol 18:411-416, 2017. Severe hypothermia is a rare but demanding medical emergency. Although mortality is high, if well managed, the neurological outcome of survivors can be excellent. The aim of the study was to assess whether mountain rescue teams (MRTs) are able to meet the guidelines in the management of severe hypothermia, regarding their equipment and procedures. Between August and December 2016, an online questionnaire, with 24 questions to be completed using Google Forms, was sent to 123 MRTs in 27 countries. Twenty-eight MRTs from 10 countries returned the completed questionnaire. Seventy-five percent of MRTs reportedly provide advanced life support (ALS) on-site and 89% are regularly trained in hypothermia management. Thirty-two percent of MRTs transport hypothermic patients in cardiac arrest to the nearest hospital instead of an Extracorporeal Life Support facility; 39% are equipped with mechanical chest compression devices; 36% measure core body temperature on-site and no MRT is equipped with a device to measure serum potassium concentration on-site in avalanche victims. Most MRTs are regularly trained in the treatment of severe hypothermia and provide ALS. The majority are not equipped to follow standard procedural guidelines for the treatment of severely hypothermic patients, especially with cardiac arrest. However, the low response rate-23% (28/123)-could have induced a bias.


Opening and closing kinematics of fresh and calcified aortic valve prostheses: an in vitro study.
In vitro testing of biologic valves has been performed using only fresh but treated valves suitable for patient implantation. The present study investigates changes in hemodynamic performance and leaflet kinematics in progressively calcified porcine and pericardial aortic valve prostheses. Edwards Perimount Magna (Edwards Lifesciences, Irvine, Calif) (n = 5) and Medtronic Mosaic Ultra (Medtronic Inc, Minneapolis, Minn) (n = 5) heart valves (23 mm) were investigated in an artificial circulation system (70 beats/min, cardiac output 5 L/min). Leaflet kinematics were visualized with a high-speed camera (3000 frames/sec). Valves were then exposed to a calcium-phosphate solution at a constant pulse rate of 300 beats/min for a total of 6 weeks. Repeated testing was performed after 1, 2, 3, 4, and 6 weeks of calcification. The calcification process might not be similar to in vivo performance. Initially, the Perimount Magna valves demonstrated lower pressure gradients compared with the Mosaic Ultra valves (9.7 +/- 0.36 mm Hg vs 14.0 +/- 1.16 mm Hg), but they showed higher closing volume and leakage flow. Total energy loss was equivalent after 1 week of calcification. Perimount Magna valves calcified significantly faster and more severely, leading to an increase in gradients and closure volume. Leaflet kinematics showed progressively longer opening and closing times for the pericardial valves (closing time Perimount Magna 135 +/- 11 msec vs Mosaic Ultra 85 +/- 9 msec after 6 weeks). On the basis of visual inspection, despite the new ThermaFix (Edwards Lifesciences) tissue treatment, the Perimount Magna pericardial valves calcified in vitro faster and more severely than did the Mosaic Ultra porcine valves, which demonstrated a more constant performance throughout the calcification process. Leaflet kinematics showed a progressive prolongation of opening and closing times for pericardial valves, leading to higher closing volume.


A prospective observational evaluation of treatment outcomes of patients with chronic obstructive pulmonary disease and peripheral blood eosinophilia.
This study aimed to compare two groups of patients with Chronic Obstructive Lung Disease (COPD) and blood eosinophil values of ≥300 cells/ µL. The patients were followed up for one year in two groups, one receiving inhaled corticosteroids (ICS) and the other not receiving ICS in terms of exacerbation rates, the incidence of pneumonia, mortality rates, FEV1, FVC and FEF25-75 changes, the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores. Stable patients, who presented to the University Medical Faculty Chest diseases outpatient clinic and diagnosed with COPD according to pulmonary function test results and GOLD stages 2-4 according to the 2017 GOLD criteria and with blood eosinophil counts of ≥ 300 cells/ µL were included in the study. 85 patients were included in the study, of which 76.5% (n= 65) were males. There were no significant differences between the 38 patients receiving ICS and the 47 patients not receiving ICS regarding baseline FEV1, FVC, FEF25- 75 absolute values and percentages, and FEV1, FVC values controlled at month six and month 12, and FEF25-75 absolute values and percentages at month six (p> 0.05). However, the difference between the baseline and month 12 absolute values and percentages of FEF25-75 was statistically significant, and the decrease from baseline was greater in the group receiving ICS (p< 0.05). The difference in CAT and mMRC scores were statistically significant at month six and month nine in favor of the group receiving ICS (p< 0.05). The median number of moderate and severe exacerbations were both one (min: 0, max:3) in the group receiving ICS (n= 38) and in the one not receiving ICS (n= 47). The difference of exacerbation rates in both groups were not statistically significant (p> 0.05). In this study, it was determined that exacerbation rates of eosinophilic COPD patients did not differ depending on the use of ICS in a one-year period. Nevertheless, the 12-month FEF25-75 values of patients not using ICS were lower to a lesser extent, while the CAT and mMRC scores improved in favor of ICS users at different months in the one-year follow-up.


P3 amplitude and time-on-task effects in distractible adolescents.
The aim of our study was to examine the role of brain activity related to stimulus evaluation processes in distractibility by analyzing the P3 event-related potential. We studied the P3 response to target stimuli at the beginning, in the middle, and at the end of a two-tone auditory oddball task in easily distractible (n = 16) and non-distractible (n = 16) adolescents. Easily distractible adolescents showed enhanced frontal and reduced parietal P3 amplitude across the blocks relative to non-distractible adolescents. Also, the usual decline in P3 amplitude at the end of the task was significantly larger in distractible than in non-distractible adolescents. These results suggests that the P3 effects are not limited to the neuropsychiatric disorders, and that increased distractibility may be characterized by reduced amount of resources allocated to the task with continued testing. The results of this study contribute to elucidation of the functional basis of distractibility.


Effects of exercise training at lactate threshold and detraining for 12 weeks on body composition, aerobic performance, and stress related variables in obese women.
The purpose of this study was to investigate the effect of diet plus exercise training and detraining for 12 weeks on body composition, aerobic performance, and stress-related variables in obese women. Twenty-five women in their 20s-40s with 30% body fat and body mass indices above 25 kg/m2 were divided into HRLT (heart rate at lactate threshold) and HRLT + 5% groups. Dietary intervention of 70% recommended dietary allowance (RDA) and exercise treatment composed of aerobic exercises on a bicycle (30 min) and treadmill (30 min) were then performed. These interventions were performed three times a week for 12 weeks. Dietary intake was significantly decreased, while daily activity significantly increased within the 12-week intervention period, and this effect was sustained after 12 weeks of detraining. Exercise training based on dietary intake and daily activity presented a significantly decreased weight and % body fat, improvement of aerobic performance, and a significant increase in heart rate variability (HRV) (e.g., average of all RR intervals and the square root mean squared differences of successive RR intervals) as stress-related variables. It was also confirmed that the improvement of body composition and stress-related variables were maintained even after detraining. Our results suggest that 70% RDA of dietary intervention and exercise training corresponding to HRLT and HRLT + 5% for 12 weeks were effective in improving body composition and aerobic performance, and relieving stress. In particular, enhanced HRV persisted for up to 12 weeks after the end of exercise training in obese women.


The importance of lutein-plant based nanoencapsulation studies - An effort to improve clinical studies on the stability and bioaccessibility of lutein for health vision.
Potential studies and evidence regarding nutrient nanoencapsulation combined with emulsion-based delivery systems are relatively limited. Therefore, for the importance issue of health vision, with this critical opinion to the editor is scientifically important to invite worldwide researchers to raise their concern for clinical research and the development of plant-based lutein nanoencapsulation in staple foods in alleviating nutritional problems for the eyes, which has not been reported before. This is in line with the WHO World Report which aimed to overcome the challenge regarding vision and galvanizing action, one of which is through innovation and research. With the hypothesis that, through this opinion will increase the awareness of scientists to improve clinical studies on the stability and bioaccessibility of lutein for health vision concern. As our hypothesis and objectives, we hope that this critical short opinion to the editor will assist efforts to reduce the burden of eye conditions and vision loss to achieve the Sustainable Development Goals (SDGs), particularly SDG 3.8 on universal health coverage through lutein-plant based nanoencapsulation clinical studies by worldwide researchers. Finally, it is very important and needed an effort to improve clinical studies focus on the stability and bioaccessibility of lutein for health vision via lutein-plant based nanoencapsulation approaches. Moreover, the benefit of lutein supplementation for the health vision might be limited by its bioaccessibility and bioavailability. Future studies and approaches should employ strategies that could overcome the foregoing limitations, of which is through nanoencapsulation approach. Something new has been synthesized in this work, "Because, every human eye, is the eye of the world".


Systematic identification of novel SLE related autoantibodies responsible for type I IFN production in human plasmacytoid dendritic cells.
Plasmacytoid dendritic cells [pDC], also known as type I interferon [IFN] producing cells, play a significant role in the pathogenesis of systemic lupus erythematosus [SLE]. The current study was undertaken to identify novel SLE autoantibody specificities associated with interferon-inducing activity in human pDCs. We found that immune complex mixtures from some Interferon signature negative [IFN-] and all interferon signature positive [IFN+] SLE patients could trigger type I IFN production by pDCs. IgGs from IFN- and IFN+ SLE patients were subsequently screened via a high throughput protein microarray to identify novel auto-antibody specifities that mediate type I IFN production by pDCs. This approach identified five novel autoantibodies that may contribute to type I IFN production by pDCs via a nucleic acid dependent mechanism. The newly identified autoantibody specificities function in a myriad of cell processess and, to date, have not been implicated in SLE pathogenesis.


[A sex chromosome mosaic in male pseudohermaphroditism in a horse].
In a 7 months old foal with a male pseudohermaphroditism the cytogenetic investigation revealed a XO/XYY-mosaic with a centric fusion of the Y-chromosomes.


Clinical effect of multimodal perioperative pain management protocol for minimally invasive colorectal cancer surgery: Propensity score matching study.
Reducing postoperative pain with less opioid is critical in postoperative care. Author developed our multimodal perioperative pain management protocol and it consists of preoperative medication, intraoperative ultrasound-guided laparoscopic transverse abdominis plane (LTAP) block and postoperative medication. This study aimed to evaluate the clinical effect of the multimodal perioperative pain management protocol for minimally invasive colorectal cancer surgery. Of 596 colorectal surgery cases for colorectal cancer, 133 patients managed with multimodal perioperative pain protocol (group 1) and 463 patients managed without multimodal perioperative pain protocol (group 2) were enrolled in this study. To adjust for baseline differences and selection bias, operative outcomes and complications were compared after propensity score matching (PSM). After 1:1 propensity score matching, well-matched 133 patients in each group were evaluated. The median VAS scores on post-operative day 1 (2.1 ± 1.1 vs. 3.9 ± 1.8, p < 0.001) and day 2 (2.0 ± 1.2 vs. 3.8 ± 1.7, p < 0.001) was significantly reduced in group 1. The length of postoperative hospital stays was also significantly shorter in Group 1 (4.4 ± 3.0 vs. 5.8 ± 5.6; p = 0.014). Implementing multimodal perioperative pain protocols reduced postoperative pain and hospital stay of minimally invasive colorectal surgery.


The ultrastructure of the Herring bodies in rats subjected to different experimental conditions.
A study of the morphology of Herring bodies of the posterior pituitary lobe of rats treated with colchicine and/or exposed to low temperatures has been performed. After treatment with colchicine (20 microgram in distilled water injected intracisternally) a predominance of Herring bodies with a large number of small "synaptic-like" vesicles surrounded by neurosecretory granules is found. Exposures to low temperature (4-6 degrees C) result in an increase in the neurosecretory material and the Herring bodies show many neurosecretory granules of different densities. After treatment with colchicine and subsequent exposure to low temperatures, the Herring bodies are characterized by having a great number of autophagic bodies which become more numerous as the length of the exposure is increased; later autophagic vacuoles and lamellar bodies become evident.


Delineation of altered brain proteins associated with furious rabies virus infection in dogs by quantitative proteomics.
Rabies is a fatal zoonotic disease caused by rabies virus (RABV). Despite the existence of control measures, dog-transmitted human rabies accounts for ˃95% reported cases due to unavailability of sensitive diagnostic methods, inadequate understanding of disease progression and absence of therapeutics. In addition, host factors and their role in RABV infection are poorly understood. In this study, we used 8-plex iTRAQ coupled with HRMS approach to identify differentially abundant proteins (DAPs) of dog brain associated with furious rabies virus infection. Total 40 DAPs including 26 down-regulated and 14 up-regulated proteins were statistically significant in infected samples. GO annotation and IPA showed that calcium signaling and calcium transport, efficient neuronal function, metabolic pathway associated proteins were mostly altered during this infection. Total 34 proteins including 10 down-regulated proteins pertaining to calcium signaling and calcium transport pathways were successfully verified by qRT-PCR and two proteins were verified by western blot, thereby suggesting these pathways may play an important role in this infection. This study provides the map of altered brain proteins and some insights into the molecular pathophysiology associated with furious rabies virus infection. However, further investigations are required to understand their role in disease mechanism. SIGNIFICANCE: Transmission of rabies by dogs poses the greatest hazard world-wide and the rare survival of post-symptomatic patients as well as severe neurological and immunological problems pose a question to understand the molecular mechanism involved in rabies pathogenesis. However, information regarding host factors and their function in RABV infection is still inadequate. Our study has used an advanced quantitative proteomics approach i.e. 8-plex iTRAQ coupled with HRMS and identified 40 DAPs in furious rabies infected dog brain tissues compared to the controls. Further analysis showed that calcium signaling and transport pathway, efficient neuronal functions and metabolic pathway associated brain proteins were most altered during furious rabies virus infection. This data provides a map of altered brain proteins which may have role in furious rabies virus infection. Hence, this will improve our understanding of the molecular pathogenesis of RABV infection.


Immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase II in the rat retina.
Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) consisting of alpha and beta isoforms is highly expressed in the central nervous system and is implicated in the regulation of various Ca(2+)-dependent physiological processes. We investigated the immunohistochemical distribution of the alpha and beta isoforms of this enzyme in the rat retina, using highly specific monoclonal antibodies which recognize each isoform. Immunoblotting revealed that not only the alpha but also the beta isoform of CaM kinase II were expressed in the retina. The immunohistochemical study showed that highly alpha-immunoreactive products were localized in amacrine cells in the inner nuclear layer and displaced amacrine cells and ganglion cells in the ganglion cell layer. In addition, two well-defined bands within the inner plexiform layer were densely stained with the anti-alpha antibody. By contrast, immunoreactivity against the anti-beta antibody was very weak in the same neuronal components of the retina. beta-Immunoreactive products were homogeneously distributed throughout the inner plexiform layer and no well-defined bands were detected in this layer. Glial cells such as Müller cells were immunoreactive neither to alpha nor beta antibody. A possible co-existence of choline acetyl transferase (ChAT) within CaM kinase II alpha-immunopositive neurons was examined by evaluating adjacent sections stained with anti-CaM kinase II alpha antibody and anti-ChAT antibody, respectively. The distribution of CaM kinase II alpha immunoreactivity in the rat retina was remarkably similar to that of ChAT immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)


Uveal melanoma, choroidal hemangioma, and simulating lesions. Role of MR imaging.
Malignant uveal melanomas are the most common primary intraocular malignant tumors in adults. Choroidal hemangiomas are congenital, benign, vascular lesions that may be confused with malignant uveal melanomas on clinical examination. The MR imaging characteristics of uveal melanomas and choroidal hemangiomas are different, making diagnostic differentiation possible with a high degree of accuracy. This article describes the MR imaging features of uveal melanoma, choroidal hemangioma, and other simulating lesions.


Virtual unrolling and deciphering of Herculaneum papyri by X-ray phase-contrast tomography.
A collection of more than 1800 carbonized papyri, discovered in the Roman 'Villa dei Papiri' at Herculaneum is the unique classical library survived from antiquity. These papyri were charred during 79 A.D. Vesuvius eruption, a circumstance which providentially preserved them until now. This magnificent collection contains an impressive amount of treatises by Greek philosophers and, especially, Philodemus of Gadara, an Epicurean thinker of 1st century BC. We read many portions of text hidden inside carbonized Herculaneum papyri using enhanced X-ray phase-contrast tomography non-destructive technique and a new set of numerical algorithms for 'virtual-unrolling'. Our success lies in revealing the largest portion of Greek text ever detected so far inside unopened scrolls, with unprecedented spatial resolution and contrast, all without damaging these precious historical manuscripts. Parts of text have been decoded and the 'voice' of the Epicurean philosopher Philodemus is brought back again after 2000 years from Herculaneum papyri.


Comment on Rogers et al. The Combined Effects of Cannabis, Methamphetamine, and HIV on Neurocognition. Viruses 2023, 15, 674.
We read with great interest the article by Rogers et al. (2023), The Combined Effects of Cannabis, Methamphetamine, and HIV on Neurocognition, published in Viruses [...].


The role of acculturative stress and body dissatisfaction in predicting bulimic symptomatology across ethnic groups.
This study examines the interactive effects of acculturative stress and body dissatisfaction in prediction of bulimic symptoms, particularly in non-White females. We administered questionnaires to White, Black, and Hispanic females on acculturative stress, body dissatisfaction, and bulimic symptoms. Our results show that among minority women who report low levels of acculturative stress, body dissatisfaction and bulimia were not correlated. However, among minority women who reported high levels of acculturative stress, body dissatisfaction and bulimia were highly and significantly correlated. The combination of acculturative stress and body dissatisfaction may render minority women more vulnerable to bulimic symptoms; the absence of acculturative stress among minority women may buffer them against bulimic symptoms, even in the presence of body dissatisfaction.


Impact of iliac crest bone graft harvesting on fusion rates and postoperative pain during instrumented posterolateral lumbar fusion.
This study aims to evaluate the influence of bone harvesting on postoperative pain and fusion rates. Group 1 patients received iliac crest bone graft (ICBG) either alone or augmented with local bone. Group 2 received only local bone. No statistical significance was found in radiological union or in the Oswestry Disability Index scores. Visual Analogue Scale scores showed less pain in group 2. Logistic regression showed no correlation between residual pain and occurrence of fusion. Harvesting ICBG did not appear to increase fusion rates and no relation was found between radiological non-union and pain.


Postocclusive reactive hyperaemia of cutaneous blood flow in premature newborn infants.
Reactive hyperaemia, which occurs after a period of arterial occlusion is the result of an autoregulatory mechanism, involving local factors and autonomic nerve system control. To determine this autoregulatory mechanism in cutaneous blood flow in premature newborns measured the cutaneous reactive hyperaemia response after a 1 min occlusion, using a diode laser Doppler flowmeter applied to the skin. Twenty-four infants with a gestational age ranging from 25 to 37 weeks and a postnatal age of 0.3 to 72 days were studied. The reactive hyperaemia response is described by the parameters maximal cutaneous blood flow (Vmax), the time to reach maximal flow (tmax), the time taken for blood flow to return to baseline following Vmax (t(end)) and the % increase in cutaneous blood flow above preocclusional level (overshoot). A cutaneous reactive hyperaemia response could be elicited in all infants. Following occlusion the Vmax was 2,640 +/- 1,050 mV (mean +/- SD), the tmax was 7.6 +/- 3.9 sec (mean +/- SD), the t(end) was 35.6 +/- 14.6 sec (mean +/- SD) and the overshoot was 74.6 +/- 34% (mean +/- SD). A negative correlation was found between hematocrit and tmax (r = -0.62, p less than 0.01). No influence of postconceptional age, postnatal age, skin and rectal temperature, incubator temperature, weight, and transcutaneous oxygen tension on the reactive hyperaemia parameters could be found. We conclude that reactive hyperaemia of cutaneous blood flow can be elicited in premature newborn infants irrespective of postconceptional age, and that the hematocrit is inversely related to the time to reach maximal flow after occlusion.


NMR assignments of the N-terminal domain of Staphylococcus aureus hibernation promoting factor (SaHPF).
Staphylococcus aureus: hibernation-promoting factor (SaHPF) is a 22.2 kDa stationary-phase protein that binds to the ribosome and turns it to the inactive form favoring survival under stress. Sequence analysis has shown that this protein is combination of two homolog proteins obtained in Escherichia coli-ribosome hibernation promoting factor (HPF) (11,000 Da) and ribosome modulation factor RMF (6500 Da). Binding site of E. coli HPF on the ribosome have been shown by X-ray study of Thermus thermophilus ribosome complex. Hence, recent studies reported that the interface is markedly different between 100S from S. aureus and E. coli. Cryo-electron microscopy structure of 100S S. aureus ribosomes reveal that the SaHPF-NTD binds to the 30S subunit as observed for shorter variants of HPF in other species and the C-terminal domain (CTD) protrudes out of each ribosome in order to mediate dimerization. SaHPF-NTD binds to the small subunit similarly to its homologs EcHPF, EcYfiA, and a plastid-specific YfiA. Furthermore, upon binding to the small subunit, the SaHPF-NTD occludes several antibiotic binding sites at the A site (hygromycin B, tetracycline), P site (edeine) and E site (pactamycin, kasugamycin). In order to elucidate the structure, dynamics and function of SaHPF-NTD from S. aureus, here we report the backbone and side chain resonance assignments for SaHPF-NTD. Analysis of the backbone chemical shifts by TALOS+ suggests that SaHPF-NTD contains two α-helices and four β-strands (β1-α1-β2-β3-β4-α2 topology). Investigating the long-term survival of S. aureus and other bacteria under antibiotic pressure could lead to advances in antibiotherapy.


Schistosomal myelopathy: urologic manifestations and urodynamic findings.
To describe the clinical and urodynamic features of patients with voiding dysfunction secondary to schistosomal myelopathy. Schistosomiasis mansoni is an endemic fluke infection in South America, the Caribbean, and Africa. In the United States and Europe, people may be infected mainly through travel to endemic areas and immigration of infected individuals. Clinical involvement of the spinal cord is a well-recognized complication of the disease. The typical manifestations are those of an acute transverse myelitis, with sudden onset of lower extremity neuropathy associated with bladder and bowel dysfunction. We reviewed the records and urodynamic studies of 14 consecutive patients (10 men and 4 women, age range 23 to 49 years) with schistosomal myelopathy confirmed by cerebrospinal fluid serology for S. mansoni, who were referred for evaluation of voiding dysfunction during a 2-year period. At the time of the urologic evaluation, 9 patients had chronic neurologic and urinary symptoms and 5 had recent onset of acute symptoms. The voiding function history, urologic complications, and outcomes after therapy for schistosomiasis were reviewed. Of the patients with acute disease (5 patients), the urologic symptoms included urinary retention (3 patients) and incontinence (2 patients). Three of them had concurrent lower back pain and lower limb neurologic deficits. Urodynamic studies were performed in 3 patients and revealed bladder areflexia in 2 patients and detrusor hyperreflexia with external sphincter dyssynergia in 1 patient. The patients were started on clean intermittent catheterization and received praziquantel and corticosteroids. Three patients had complete resolution of their symptoms, one recovered normal voiding function but the neurologic deficits persisted, and one had no clinical improvement. All patients with chronic schistosomal myelopathy presented with lower limb neurologic deficits of varying degrees and urinary symptoms, including difficulty emptying the bladder (7 patients), urinary incontinence (6 patients), and urgency and frequency (2 patients). Laboratory and radiographic evaluation of patients with chronic disease revealed urinary tract infection in 5 patients, hydronephrosis in 2 patients, and bladder calculi in 2 patients. Urologic management consisted of antibiotics, clean intermittent catheterization, anticholinergic medication, and stone removal, as appropriate. In 1 patient, conservative treatment failed and that patient required ileocystoplasty. Schistosomal myelopathy is a potential cause of severe voiding dysfunction secondary to spinal cord disease. A high index of suspicion is paramount because early medical intervention can abort the progression of neurologic deterioration.


Purification, characterization of GH11 endo-β-1,4-xylanase from thermotolerant Streptomyces sp. SWU10 and overexpression in Pichia pastoris KM71H.
We have previously described two forms of an endo-β-1,4-xylanase (XynSW2A and XynSW2B) synthesized by thermotolerant Streptomyces sp. SWU10. Here, we describe another xylanolytic enzyme, designated XynSW1. The enzyme was purified to homogeneity from 2 L of culture filtrate. Its apparent molecular mass was 24 kDa. The optimal pH and temperature were pH 5.0 and 40 °C, respectively. The enzyme was stable in a wide pH ranges (pH 1-11), more than 80 % of initial activity remained at pH 2-11 after 16 h of incubation at 4 °C and stable up to 50 °C for 1 h. Xylobiose and xylotriose were the major xylooligosaccharides released from oat spelt xylan by the action of XynSW1, indicating of endo-type xylanase. The complete xynSW1 gene contains 1,011 bp in length and encode a polypeptide of 336 with 41 amino acids of signal peptide. The amino acid sequence analysis revealed that it belongs to glycoside hydrolase family 11 (GH11). The mature xynSW1 gene without signal peptide sequence was overexpressed in Pichia pastoris KM71H. The recombinant XynSW1 protein showed higher molecular mass due to the differences in glycosylation levels at the six N-glycosylation sites in the amino acid sequence and exhibited better physicochemical properties than those of the native enzyme including higher optimal temperature (60 °C), and specific activity, but lower optimal pH (4.0). Because of their stability in a wide pH ranges, both of native and recombinant enzymes of XynSW1, may have potential application in several industries including food, textile, biofuel, and also waste treatment.


Old males reduce melanin-pigmented traits and increase reproductive outcome under worse environmental conditions in common kestrels.
Secondary sexual traits displayed by males and females may have evolved as a signal of individual quality. However, both individual quality and investment on producing or maintaining enhanced sexual traits change as individuals age. At the same time, the costs associated to produce sexual traits might be attenuated or increased if environmental conditions are benign or worse respectively. Accordingly, environmental conditions are expected to shape the association between the expression of sexual traits and their reproductive outcome as individuals age. Nonetheless, little is known about the environmental influence on the co-variation between sexual traits and reproductive outcome throughout the life of individuals. We studied the age-dependency of the number and size of back spots, a melanin-based and sexual trait in adults of common kestrels (Falco tinnunculus). We analysed the age-dependence of reproductive traits and the environmental influence, defined as vole abundance, using a 10-year individual-based dataset. We broke down age-related changes of reproductive traits into within- and between-individual variation to assess their contribution to population-level patterns. Our results showed a within-individual decrease in the number, but not the size, of back spots in males. The size of back spots was positively correlated with food availability in males. Reproductive performance of males increased as they aged, in agreement with the life-history theory but depending of vole abundance. Remarkably, we found that having fewer back spots was positively associated with clutch size only for old individuals under low-food conditions. We suggest that environmental variation may shape the association between the expression of a sexual signal and reproductive outcome. We speculate that the reliability of sexual traits is higher when environmental conditions are poor only for old individuals. Within an evolutionary context, we suggest that the expression of sexual traits might be constrained by environmental conditions at later stages of life.


Acute lymphoblastic leukemia incidence during socioeconomic transition: selective increase in children from 1 to 4 years.
Pre-school acute lymphoblastic leukemia (ALL) peak is consistent in developed but not in developing countries and its magnitude apparently correlates with the socioeconomic status. A population-based study describing ALL incidence during socioeconomic transition has been lacking. Central European post-communist countries (with very low foreign migration and centralized statistics) offer reliable data for the period before and during major socioeconomic changes. Population-based data on Czech ALL patients younger than 18 years were taken from two independent Czech national registries partially overlapping in time (1980-1998, n = 1236 and 1991-1999, n = 570). During the 1980s and 1990s, ALL incidence among children 1-4 years increased 1.5 times (P = 0.01). This increase was more prominent in females than in males (slopes 0.13 and 0.09, P values 0.03 and >0.05, respectively). No significant change was observed in other age groups (0, 5-9, 10-14, 15-17 years or all others combined). We discuss possible underlying socioeconomic factors including infant care and breast-feeding, hygiene, birth order, industry and pollution. Moreover, we try to pinpoint the immunophenotypic/molecular-genetic subsets of ALL that might be socioeconomically affected. Selective increase of ALL in children 1-4 years old provides epidemiological evidence that etiology and/or trigger mechanisms are different for a considerable proportion of these children and that these mechanisms are exogenous.


Automated approach for quality assessment of RDF resources.
The Semantic Web community provides a common Resource Description Framework (RDF) that allows representation of resources such that they can be linked. To maximize the potential of linked data - machine-actionable interlinked resources on the Web - a certain level of quality of RDF resources should be established, particularly in the biomedical domain in which concepts are complex and high-quality biomedical ontologies are in high demand. However, it is unclear which quality metrics for RDF resources exist that can be automated, which is required given the multitude of RDF resources. Therefore, we aim to determine these metrics and demonstrate an automated approach to assess such metrics of RDF resources. An initial set of metrics are identified through literature, standards, and existing tooling. Of these, metrics are selected that fulfil these criteria: (1) objective; (2) automatable; and (3) foundational. Selected metrics are represented in RDF and semantically aligned to existing standards. These metrics are then implemented in an open-source tool. To demonstrate the tool, eight commonly used RDF resources were assessed, including data models in the healthcare domain (HL7 RIM, HL7 FHIR, CDISC CDASH), ontologies (DCT, SIO, FOAF, ORDO), and a metadata profile (GRDDL). Six objective metrics are identified in 3 categories: Resolvability (1), Parsability (1), and Consistency (4), and represented in RDF. The tool demonstrates that these metrics can be automated, and application in the healthcare domain shows non-resolvable URIs (ranging from 0.3% to 97%) among all eight resources and undefined URIs in HL7 RIM, and FHIR. In the tested resources no errors were found for parsability and the other three consistency metrics for correct usage of classes and properties. We extracted six objective and automatable metrics from literature, as the foundational quality requirements of RDF resources to maximize the potential of linked data. Automated tooling to assess resources has shown to be effective to identify quality issues that must be avoided. This approach can be expanded to incorporate more automatable metrics so as to reflect additional quality dimensions with the assessment tool implementing more metrics.


Germline sex determination regulates sex-specific signaling between germline stem cells and their niche.
Establishing germ cell sexual identity is critical for development of male and female germline stem cells (GSCs) and production of sperm or eggs. Germ cells depend on signals from the somatic gonad to determine sex, but in organisms such as flies, mice, and humans, the sex chromosome genotype of the germ cells is also important for germline sexual development. How somatic signals and germ-cell-intrinsic cues combine to regulate germline sex determination is thus a key question. We find that JAK/STAT signaling in the GSC niche promotes male identity in germ cells, in part by activating the chromatin reader Phf7. Further, we find that JAK/STAT signaling is blocked in XX (female) germ cells through the action of the sex determination gene Sex lethal to preserve female identity. Thus, an important function of germline sexual identity is to control how GSCs respond to signals in their niche environment.


Mechanism of TLR-4/NF-κB pathway in myocardial ischemia reperfusion injury of mouse.
To detect the expression of Toll-like receptor 4 (TLR-4) and NF-κB and to discuss the mechanism of TLR-4/NF-κB pathway in the myocardial ischemia reperfusion injury of mouse. TLR-4 mutant mice and wild homozygous mice were divided into the model group and sham group. Mice in the model group were given the ligation of left anterior descending coronary artery for the modeling, while mice in the sham group were not given the ligation after threading. The cardiac muscle tissues were collected for the morphological observation. The immunohistochemistry was employed to detect the expression of NF-κB, Western blot was used to detect the expression of TLR-4 and ELISA to detect the expression of serum inflammatory factors. The expression of NF-κB in TLR-4 null mice after the myocardial ischemia reperfusion was significantly lower than that in wild homozygous mice. For the model group and sham group, the expression of TLR-4 in wild homozygous mice was all significantly higher than that in TLR-4 null mice, while the expression of TLR-4 in TLR-4 null mice in the model group was significantly higher than that in sham group, with the statistical difference (P < 0.05). The expression of inflammatory factors in TLR-4 null mice and wild homozygous mice in the model group was significantly higher than that in sham group. The expression of all factors in group A with TLR-4 null was significantly lower than that in group B with wild homozygous type, with the statistical difference (P < 0.05). TLR-4/NF-κB pathway is closely related to the myocardial ischemia reperfusion injury, which plays its role through the release of inflammatory cytokines.


Childhood Sexual Abuse: Identification, Screening, and Treatment Recommendations in Primary Care Settings.
It is estimated that 8% to 12% of American youths have experienced at least one sexual assault in their lifetime, making childhood sexual abuse (CSA) an important public health problem that is likely to be encountered by primary care providers. Use of screening tools and understanding the principles behind targeted clinical evaluation can aid in identification of CSA victims despite highly variable presentation. The primary care provider must be aware of potential signs and symptoms as well as differential diagnoses in order to identify children who may benefit from further mental health evaluation and intervention.


Peptide Mimetics of Apolipoproteins Improve HDL Function.
Over the past decade evidence has accumulated that suggests that the anti-inflammatory properties of HDL may be at least as important as the levels of HDL-cholesterol. The recent failure of the torcetrapib clinical trails has highlighted the potential differences between HDL-cholesterol levels and HDL function. Agents to improve HDL function including HDL anti-inflammatory properties provide a new therapeutic strategy for ameliorating atherosclerosis and other chronic inflammatory conditions related to dyslipidemia. Seeking guidance from the structure of the apolipoproteins of the plasma lipoproteins has allowed the creation of a series of polypeptides that have interesting functionality with therapeutic implications. In animal models of atherosclerosis, peptide mimetics of apolipoproteins have been shown to improve the anti-inflammatory properties of HDL, significantly reduce lesions and improve vascular inflammation and function without necessarily altering HDL-cholesterol levels. Some of these are now entering the clinical arena as interventions in pharmacologic and pharmacodynamic studies.


Cardiovascular recovery after workload in German shift workers in the hotel and catering industry: results of 24-hour-ambulatory monitoring of heart rate and blood pressure.
Shift work is associated with an impairment of sleep-wake cycles that can affect cardiovascular recovery (CR) negatively. The aim of this study was to examine CR of shift and day workers in the hotel and catering industry (HCI) and identify predictors of CR. The sample consisted of 64 alternating and 96 day workers in the HCI. Monitoring of blood pressure (BP) and heart rate (HR) was conducted for 24 hours per working day during work, leisure and sleep. The CR process was examined for differences between work and leisure, work and sleep regarding a reduction in BP and HR. Lifestyle (physical activity, smoking, drinking) was assessed through questionnaires, BP over a four-day, self-assessment period (38% hypertensives). Participants taking BP medication (n = 12) were excluded from analyses. Shift workers had significantly higher BP (Ø 146/87 vs. Ø 140/84 mmHg; p = 0.034-0.044) and HR (Ø 86 vs. 82 bpm; p = 0.032) during their work phase verses day workers. There were no differences found for the CR between work and leisure nor work and sleep. As predictors of the CR, classic cardiovascular indicators (blood pressure status, smoking, age, physical activity, sex) were found which explains between 14% (HR) and 30% (BP) of the variance. Shift work was not a predictor for CR. Employees in the HCI show that their CR is mainly determined by the known cardiovascular indicators and less by shift work. This effect needs to be discussed in relation to the job requirements and the cardiovascular health of the employees.


State pre-emption, local control, and alcohol retail outlet density regulation.
The substantial health and economic costs of excessive alcohol consumption make its reduction a major public health and economic concern. The Community Preventive Services Task Force, based on a systematic review of the research literature, concluded that restricting alcohol retail outlet density through local land use and zoning regulations is an effective strategy for reducing these costs. Yet the implementation of the Task Force's recommendation is limited by state pre-emption, which determines the extent to which states allow local government to adopt policies and enact legislation. This article summarizes the state pre-emption doctrine, its status in the 50 states pertaining to alcohol retail outlet density regulation, and findings from state legal analyses conducted in six states. Data reflect state laws in effect as of January 1, 2012. Analyses were conducted during the 2012 calendar year. An examination of relevant state laws found five distinct pre-emption categories: exclusive state licensing, exclusive state licensing and concurrent local zoning, joint licensing, exclusive local licensing, and a mixed system. The analysis demonstrated wide variability across the states, ranging from exclusive state pre-emption to broad state delegation of authority to local governments. Pre-emption is applied differentially in many states based on retail outlet characteristics. In many cases, state pre-emption laws are ambiguous in terms of their application, leading to inconsistent and confusing court interpretations. Reforms targeting the adverse impact of state pre-emption on alcohol retail outlet density have the potential for reducing the harm associated with excessive alcohol consumption. State and local public health departments can support such reforms by implementing educational, analytic, monitoring, and technical assistance activities.


Reference values of serum transferrin receptor (sTfR) and sTfR/log ferritin index in healthy children.
ABSTARCT The aims of this study were to determine appropriate reference ranges for serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) in healthy children and their relationship with iron parameters, erythropoiesis, and other conditions presented by the subject. A total of 902 children with normal iron status, aged 1-11 years, were included in a cross-sectional study. A physical examination was conducted and z-score of body mass index (zBMI) obtained. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, sTfR, and sTfR/log ferritin were determined. Linear multiple regression was applied to identify the factors that determined sTfR and sTfR-F index variability. Mean values for sTfR and sTfR-F index were 1.22 ± 0.28 mg/L (95% confidence interval [CI]: 1.2-1.23) and 0.87 ± 0.25 (95% CI: 0.85-0.88). The reference intervals (2.5th to 97.5th percentiles [P2.5-P97.5]) were 0.78-1.9 mg/L and 0.49-1.46, respectively. sTfR and sTfR-F values decreased with age (P <.03 and P <.0001, respectively). No changes were observed with sex. Changes in sTfR and sTfR-F index were consistent with ferritin and erythropoietin variations. Iron biomarkers, erythropoietin, and zBMI predicted 19% and 18.1% of the sTfR and sTfR-F index variability. The results provide reference ranges for sTfR and sTfR-F index in healthy children for clinical use in the assessment of body iron status. Both biomarkers are predicted by iron parameters, erythropoietin, and zBMI.


Pre-Existing Cardiovascular Conditions as Clinical Predictors of Myocarditis Reporting with Immune Checkpoint Inhibitors: A VigiBase Study.
Although rare, immune checkpoint inhibitor (ICI)-related myocarditis can be life-threatening, even fatal. In view of increased ICI prescription, identification of clinical risk factors for ICI-related myocarditis is of primary importance. This study aimed to assess whether pre-existing cardiovascular (CV) patient conditions are associated with the reporting of ICI-related myocarditis in VigiBase, the WHO global database of suspected adverse drug reactions (ADRs). In a (retrospective) matched case-control study, 108 cases of ICI-related myocarditis and 108 controls of ICI-related ADRs other than myocarditis were selected from VigiBase. Drugs labeled as treatment for CV conditions (used as a proxy for concomitant CV risk factors and/or CV diseases) were found to be associated more strongly with the reporting of ICI-related myocarditis than with other ICI-related ADRs (McNemar's chi-square test of marginal homogeneity: p = 0.026, Cramer's coefficient of effect size: Φ = 0.214). No significant association was found between pre-existing diabetes and ICI-related myocarditis reporting (McNemar's test of marginal homogeneity: p = 0.752). These findings offer an invitation for future prospective pharmacoepidemiological studies to assess the causal relationship between pre-existing CV conditions and myocarditis onset in a cohort of cancer patients followed during ICI treatment.


Silencing of purinergic receptor P2Y2 inhibited enteric neural crest cell proliferation, invasion and migration via suppressing ERK signaling pathway in Hirschsprung disease.
The current study aimed to explore the effect and underlying mechanism of the purinergic receptor P2Y2 in regulating the loss of intestinal neurons and the intestinal neural crest in Hirschsprung's disease (HSCR). Western blotting was used to assess the expression levels of P2Y2 in colon tissues. An in vivo HSCR mouse model was established following treatment with benzalkonium chloride (BAC). We overexpressed or silenced P2Y2 in SH-SY5Y cells, and cell proliferation, migration, and invasion were subsequently investigated by CCK-8, wound healing, and transwell assays, respectively. Additionally, we implemented a xenograft model to assess the impact of P2Y2 on tumor growth as well as the expression of extracellular signal-regulated kinase (ERK). The results showed that the expression of P2Y2 protein in the colon tissues of patients with HSCR was lower than that in the normal colon tissues. P2Y2 expression is downregulated in the colon tissues of mice with HSCR. Additionally, P2Y2 silencing inhibited SH-SY5Y cell proliferation, invasion, and migration. Furthermore, adenosine 5'-triphosphate (ATP, a strong agonist of P2Y2)-induced P2Y2 overexpression enhanced the proliferation, invasion, and migration of SH-SY5Y cells. Immunofluorescence staining and western blot analysis revealed that P2Y2 silencing downregulated phosphorylated (p)-ERK in SH-SY5Y cells. In addition, treatment with PD98059, a p-ERK inhibitor, reversed the effects of ATP on SH-SY5Y cell proliferation, invasion, and migration. Finally, we demonstrated that P2Y2 silencing suppressed tumor growth and decreased p-ERK expression. Overall, the results of the present study suggest that P2Y2 plays an important role in HSCR pathogenesis. P2Y2 silencing inhibited the proliferation, invasion, and migration of nerve cells by suppressing the ERK signaling pathway. P2Y2 silencing could be considered an innovative and possible target for treating HSCR.


The Dorsolateral Prefrontal Cortex Presents Structural Variations Associated with Empathy and Emotion Regulation in Psychotherapists.
Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic abilities, as shown in psychometric differences in cognitive empathy and emotional regulation, we aimed to identify cortical thickness (CT) differences between a group of professional psychotherapists and a control group. In line with the recently emphasized urge to employ more than a single workflow in cortical analyses, we utilized two cortical surface extraction and thickness estimation pipelines-CIVET and FreeSurfer. Eighteen psychotherapists and eighteen controls underwent MRI scanning and completed empathy-related psychometric assessments. We evaluated how CT measures differed between groups and if there was an association with individual empathy-related scores in a series of regions of interest (ROIs). Our analysis with CIVET shows that psychotherapists display a significantly greater CT at a ROI in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). With FreeSurfer, a whole-brain vertex-wise analysis identified a statistically significant cluster in the left PFC that partially overlaps with the previous ROI. These results were reinforced by a structural covariance analysis revealing that, in psychotherapists, the left dlPFC ROI seemed to vary independently from the rest of the cortex. These findings are relevant because the dlPFC region importantly participates in the cognitive components of the empathic response, such as emotion regulation and perspective taking. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.


Growth behavior of fibroblasts on microgrooved polystyrene.
We investigated the contact guidance phenomenon of rat dermal fibroblasts (RDF) on microgrooved polystyrene substrates. Grooves were 1 microm deep, and between 1 and 10 microm wide. Light microscopy and digital image analysis (DIA) showed that RDF were oriented on all microgrooved substrates. Scanning electron microscopy showed that RDF cultured on 1 or 2 microm wide grooves were positioned on top of the ridges. On the wider 5 and 10 microm grooves, the cells were able to descend into the grooves. In confocal laser scanning microscopy, focal adhesions were lying in the same direction as the actin filament where they attached to. DIA confirmed an orientational behavior of focal adhesions and actin filaments on microgrooves. There were no differences in the measured orientation between the different grooves. Besides, no obvious preference was found for focal adhesions to lie along edges of the surface ridges. Transmission electron microscopy showed that focal adhesions were able to bend along the edges of ridges. On the basis of our observations, we suggest that the breakdown and formation of fibrous cellular components, especially in the filopodium, is influenced by the microgrooves. The microgrooves create a pattern of mechanical stress, which influences cell spreading and cause the cell to be aligned with surface microgrooves.


Consecutive One-Pot versus Domino Multicomponent Approaches to 3-(Diarylmethylene)oxindoles.
Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important factors to achieve high yields and stereoselectivity.


Polyclonal antibody-forming cell activation and immunomodulation of the in vitro immune response induced by streptococcal extracellular products.
The capacity of three different extracellular streptococcal products to induce polyclonal activation of precursors of plaque-forming cells (PFC) was investigated. The gamma fraction (pI = 4.2), previously shown to be only weakly mitogenic, was the most potent activator of rabbit and mouse immunoglobulin-secreting cells. The polyclonal stimulation induced by the two other fractions (kappa: pI = 4.8 and epsilon: pI = 10.3), shown to be mitogenic in both systems, was only observed in the rabbit system. Using these fractions, the in vitro immunomodulation of the anti-sheep red blood cell immune response was also investigated. Both gamma and epsilon fractions were shown to possess adjuvant properties, whereas the kappa fraction was a suppressor of the specific immune response. It appears, therefore, that the diversified immunological activities observed with extracellular streptococcal products can be dissociated and belong to different entities.


A strategy for thoracoscopic resection of small pulmonary nodules.
Preoperative procedures are often necessary to localize pulmonary nodules during thoracoscopic resection in order to reduce the necessity of resorting to thoracotomy. The aim of this report is to describe the strategy we developed to limit preoperative techniques without reducing the thoracoscopic success rate of localization. Between January 2000 and December 2003, 183 patients underwent video thoracoscopic resection of small pulmonary nodules. The patients were divided into two groups on the basis of the radiological features of the nodule. The subjects in group 1 were operated on directly, and endothoracic ultrasonography was performed when necessary. The subjects in group 2 underwent preoperative radionuclide labeling of the nodule. In group 1, 112 out of 119 nodules (94%) were localized. Twenty-five out of 32 lesions, neither visible nor palpable, were found by endothoracic ultrasonography. In group 2, we localized 62 out of 64 nodules (97%). Currently, we cannot completely avoid preoperative labeling techniques for thoracoscopic resection of small pulmonary nodules. However, correct patient selection may limit this necessity, without an increased conversion rate to thoracotomy, if endothoracic ultrasonography is available.


Development of a hookworm egg hatching assay to determine the ovicidal effects of anthelminthics.
Few anthelminthics are currently available, manifesting the urgent need for new treatment options. In vitro profiling of current anthelminthics against larval and adult stage helminths displayed varying effects on closely related worm species and between life stages of the same species. Conversely, limited research has been performed on the egg stage of human hookworms, and the effects of investigational compounds on the egg stage are not routinely assessed. We profiled the development and hatching of Heligmosomoides polygyrus, Ancylostoma duodenale and Necator americanus eggs isolated from rodent faeces in liquid media with various nutrient levels, osmolar concentrations, and acidities in dependence on incubation temperature and light exposure. Incubation conditions were optimised to allow the study of drug effect on immature and embryonated eggs. We analysed concentration-effect relationships of commercially available anthelminthics over 72 h. Rapid embryonation and hatching were observed at room temperature with and without light exposure without nutrient supplementation in a wide range of acidities. Hookworms hatched optimally at room temperature in PBS achieving > 75% hatching over 34 h. Developmental delays were seen when eggs were stored at 4 °C with no effect on viability. Similar delays were also seen with increased osmolar concentrations resulting in decreased viability. Benzimidazole anthelminthics effectively reduced the viability and prevented hatching of hookworm eggs, with albendazole and thiabendazole eliciting particularly potent effects at EC50 values below 1 µM. Macrolide anthelminthics as well as emodepside, oxantel pamoate, and pyrantel pamoate were inactive while monepantel, levamisole, and tribendimidine displayed varied potencies among the hookworm species. The presented egg-hatching assay will complement ongoing anthelminthic drug discovery and allow a full characterisation of drug activity against all life stages. In the development and application of the egg-hatching assay, good accordance was observed between the three hookworm species evaluated. Marketed anthelminthics show differences of drug action compared to larval and adult stages highlighting the importance of profiling drug activity against all life stages.


Characteristics of the electromyogram recorded from the mesometrium of the pregnant ewe from 106 days' gestation to delivery: similarities with and differences from the electromyogram obtained from the myometrium.
Electromyographic recordings from 12 pregnant sheep were analyzed in four gestational age groups (106 to 115, 116 to 125, 126 to 135, and 136 to 145 days) and by the day of delivery. Mesometrial electromyographic activity was present in all animals studied. Contracture activity was synchronous in both mesometrium and myometrium. The frequency distribution of electromyographic events of different duration in the mesometrium was qualitatively identical to that recorded from the myometrium. The frequency of events less than 180 seconds was greater in the myometrium, while no difference was observed in contracture frequency. Mean contracture duration in myometrium and mesometrium shortened as gestation progressed (p less than 0.01), and was of significantly shorter duration on the day of delivery when compared with all gestational age intervals (p less than 0.05). Except at 135 to 145 days' gestation and at the day of delivery, myometrial contractures were of significantly longer duration than mesometrial contractures. The presence of the endometrium and fetal membranes in the pregnant ewe may stimulate the myometrium, and account for the difference observed. In vivo recording of mesometrial electromyographic activity may provide an opportunity to study the paracrine regulation of myometrial activity.


Ciliary body melanoma treated with helium particle irradiation.
Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.


Effect of citric acid and vermi-wash on growth and metal accumulation of Sorghum bicolor cultivated in lead and nickel contaminated soil.
The aim of the present study is to assess the influence of vermi-wash (VW) and citric acid (CA) on Sorghum bicolor growth and phytoaccumulation of lead (Pb) and nickel (Ni) contaminated soil. The biomass of the S. bicolor has been enhanced by the addition of VW (24 and 26%) and CA (11 and 9%) in Pb and Ni contaminated soil, respectively. The VW treatment showed enhanced shoot and root lengths and chlorophyll concentrations compared to CA. The shoot anatomic structure showed an accumulation of Pb and Ni were positively impacted by the amendment of VW and CA. In addition, VW treatment showed enhanced antioxidant enzymes activity (140, 125 and 152 U/mg of CAT, SOD and POD). Further, the plants grown in Pb contaminated soil treated with VW showed enhanced Rubisco activity of 1.49 U/ml, whereas, CA treatment showed 1.23 U/ml of Rubisco. It has been observed that the VW showed as a potential chelator as well as plant beneficial formulation for the enhanced phyto-remediation of Pb and Ni.


[Intravascular sclerosing bronchioloalveolar tumor].
A case of ISBAT in a 42 year old woman was described. Tumour consisted of two foci in the right lung found incidentally during x-ray examination. Discussion introduced modern views on its denotation and pathogenesis resulting from the latest electron microscopical and immunological studies.


Identification and stabilization of a highly selective gastrin-releasing peptide receptor agonist.
The gastrin-releasing peptide receptor (GRPR) is part of the bombesin receptor family and a well-known target in cancer diagnosis and therapy. In the last decade, promising results have been achieved by using peptide-drug conjugates, which allow selective targeting of GRPR expressing tumor cells. Most ligands, however, have been antagonists even though agonists can lead to higher tumor uptake owing to their internalization. So far, only a few studies focused on the identification of small GRPR-selective agonists that are metabolically stable. Here, we developed novel bombesin analogs with high selectivity for the GRPR and improved blood plasma stability. The most promising analog [d-Phe6 , β-Ala11 , NMe-Ala13 , Nle14 ]Bn(6-14) displays an activity of 0.3nM at the GRPR, a more than 4000-fold selectivity over the other two bombesin receptors and more than 75% stability in human blood plasma after 24 hours. This analog is proposed as a promising drug shuttle for the intracellular delivery of different payloads in targeted tumor therapy approaches.


Walled-off pancreatic necrosis: wishing our pancreatitis nomenclature was correct.
The ultimate reason why pancreatologists have strived to establish definitions for inflammatory pathologies of the pancreas is to improve patient care. Although the Atlanta Classification has been used for around for 17 years, considerable misunderstanding of the key elements of the nomenclature still persists. While a recent article by Stamatakos et al aimed to deal with an entity not clearly defined in the 1993 document, it is replete with factual and conceptual errors as well as contradictory statements.


Health-related quality of life in children and youth with acquired brain injury: Two years after injury.
To determine health-related quality of life (HRQoL) in children and youth with acquired brain injury (ABI) two years post-injury and explore associated factors. Cross-sectional. Children and youth (n = 72; aged 6-22 years) with mild to severe ABI (87% mild). The primary outcome measures self-reported and parent-reported HRQoL were assessed with the Paediatric Quality of Life Inventory (PedsQL) and compared with age-appropriate reference values of the Dutch population. Spearman correlation coefficients (Rs) were used to explore relationships between HRQoL and sociodemographic and ABI characteristics, severity of impairments and presence of post-injury problems. Children and youth with ABI and the reference population had similar self-reported HRQoL. However, as reported by parents, children with ABI aged 6-7 years and youth aged 13-18 years had poorer HRQoL regarding psychosocial health. Children's post-injury cognitive, behavioural and social problems were moderately associated with poorer HRQoL, especially psychosocial health (Rs ≥ 0.40). Severity nor type of injury were associated with children's HRQoL. Two years post-injury, in children and youth with mild to severe ABI, reported HRQoL is similar to that in the general population, whereas parents reported less favourable outcomes. Post-injury cognitive, behavioural and social problems require ongoing attention during long-term follow-up.


Focal hyperemia in Wernicke's encephalopathy: a preliminary arterial spin labeling MRI study.
Although a perturbed cerebral blood flow (CBF) has been reported in patients with Wernicke's encephalopathy (WE), its clinical meaning is still elusive. A retrospective analysis of 10 patients (male, 6; mean age, 57.7 years) with WE between October 2012 and May 2018 was performed. Brain imaging was performed using fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), arterial spin labeling (ASL) perfusion-weighted imaging (PWI), and contrasted enhanced T1-weighted imaging. All patients had symmetric high signal intensity lesions in the vulnerable areas on FLAIR or DWI with focal hyperintensity on ASL-PWI (100% sensitivity). CBFlesion was variable (from 70 mL/100 g/min to 190.0 mL/100 g/min). CBFlesion/CBFwhite matter was elevated, ranging from 2.5 to 5.5. Focal hyperintensity on ASL in the vulnerable areas can be a diagnostic clue for WE.


Correlation of alpha- and beta-rotameric forms of 2-substituted octahydrobenzo[f]quinoline dopamine congeners with high and low affinity states of the anterior pituitary dopamine receptor and prolactin inhibition.
The flexible dopamine (DA) molecule exists in one or the other of its two conformational extremes (alpha- or beta-rotamer) and its receptor in the anterior pituitary gland exists in a high and a low affinity state. A series of novel, rigid DA congeners (2-substituted octahydrobenzo[f]quinolines) was synthesized and used to investigate the conformation of DA preferred by its anterior pituitary receptor and the significance of recognition of the two affinity states to the inhibition of prolactin (PRL) secretion. Analysis of competition curves of congeners for [3H]spiperone binding to bovine anterior pituitary membranes was used to calculate affinity constants. Congeners in the beta-rotamer conformation showed a biphasic competition curve as observed for DA. The curves were resolved into high (nM) and low (microM) affinity binding sites. This biphasic binding could be converted to monophasic low affinity binding in the presence of a nonhydrolyzable GTP analog. The congeners in the alpha-rotameric conformation showed monophasic low affinity binding. The potency of congeners to suppress PRL release was evaluated in cell cultures of dispersed bovine anterior pituitary. Congeners recognizing the high affinity binding site were 100-fold more potent in suppressing PRL release than those recognizing only low affinity binding sites. Dihydroxy congeners versus monohydroxy congeners and cyanomethyl group substituted versus methylthiomethyl substituted congeners occupied greater proportions of high affinity binding sites. Increasing proportions of high affinity sites occupied increased the potency of the congener to suppress PRL release. These results suggest that the beta-rotameric conformational extreme of DA is preferred by its receptor in the anterior pituitary gland and that the high affinity state of this receptor is functionally important in mediating the inhibition of PRL secretion.


Robotic-assisted percutaneous pelvis fixation: A case report.
It may be possible to extend the use of the robotic arm to pelvic and acetabular surgery leading to safe, repeatable screw placement, and less radiation exposure for patients, surgeons and OR staff. In this case, a novel, robotic-assisted technique was used to place a sacroiliac screw in a patient with unstable injuries of the pelvic ring. Intraoperative and postoperative fluoroscopic, radiographic, and CT imaging demonstrated a safely positioned 6.5 mm cannulated screw without unplanned cortical violation or impingement on neurovascular structures. To our knowledge, this is the first such reported case using a robot widely available in the Americas or Europe.


Relationships among perceived quality of healthcare services, satisfaction and behavioural intentions of international students in Kuala Lumpur, Malaysia: a cross-sectional study.
The current study aimed to investigate the relationships among the perceived quality of healthcare services, satisfaction and behavioural intentions among international students in Kuala Lumpur, Malaysia. A cross-sectional study on public universities in Kuala Lumpur, Malaysia. All participants in this study were international students joining public universities in Kuala Lumpur, Malaysia. Perceived quality of healthcare services measured on a SERVQUAL scale. Participants' satisfaction of healthcare services assessed using five items. Behavioural intentions measured on six items. Of the 556 international students, 500 (90%) completed the survey. The study used structural equation modelling (SEM) through the AMOS (Analysis of Moment Structures) software to analyse the data. SEM analyses showed that the perceived quality of healthcare services significantly and directly affected satisfaction, with a value of 89% and an effect size of 0.78. It also had a significant indirect impact on the behavioural intentions (0.78) of international students. The results indicated that participants' satisfaction had a statistically significant impact on their behavioural intentions (0.77). Perceived quality of care is an important driver of international students' satisfaction and their behavioural intention with healthcare services. Such relations of effects among the three investigated factors were also positive and significant.


Generic physiologically based kinetic modelling for farm animals: Part I. Data collection of physiological parameters in swine, cattle and sheep.
Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and application of these models requires data for physiological, anatomical and chemical specific parameters. Here, we present the results of a structured data collection of anatomical and physiological parameters in three key farm animal species (swine, cattle and sheep). We performed an extensive literature search and meta-analyses to quantify intra-species variability and associated uncertainty of the parameters. Parameters were collected for organ weights and blood flows in all available breeds from 110 scientific publications, of which 29, 48 and 33 for cattle, sheep, and swine, respectively. Organ weights were available in literature for all three species. Blood flow parameter values were available for all organs in sheep but were scarcer in swine and cattle. Furthermore, the parameter values showed a large intra-species variation. Overall, the parameter values and associated variability provide reference values which can be used as input for generic PBK models in these species.


Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy.
A genetic association study was conducted to assess whether genetically determined alterations of the nitric oxide system are associated with clinical markers of pre-eclampsia. A large number of Caucasian women were consecutively included after delivery and genotyped for the endothelial nitric oxide synthase gene (NOS3) polymorphisms G894T, T789C (n=1502) and intron 4a/b (n=2186). There are no significant differences in mean blood pressure (BP), protein excretion or new-onset peripheral oedema between any of the genotypes over the course of pregnancy. Neither particular haplotypes nor the combined presence of any two alleles is associated with those markers of pre-eclampsia. The maternal polymorphisms do not seem to influence fetal growth, birth weight or the incidence of congenital malformations. We demonstrate in a large Caucasian population that maternal polymorphisms of the NOS3 gene are not related to clinical markers of pre-eclampsia. The functional relevance of the NOS3 variants alone does not seem to be strong enough to affect BP regulation during pregnancy.


Dystonia in a patient with deletion of 18p.
18p- syndrome from chromosomal deletion of the short arm of chromosome 18 shows a wide range of clinical manifestations. Mental retardation is the most frequent neurological complication; other neurological deficits are more rarely reported. Only one 18p- patient with focal dystonia at the lower limbs has been reported, while there have been no reported cases of generalized dystonia. We report a 27-year-old male with 18p- de novo complete deletion (karyotype 46,XY,18p-) who was affected by severe generalized dystonia, hypokinesia, mental retardation and dysmorphic features. The 18p- syndrome should be added to the list of genetic causes of secondary dystonia. A karyotype analysis should be considered in secondary dystonias, particularly when there are associated dysmorphic features and mental retardation.


COVID-19: mortality rates of patients on hemodialysis and peritoneal dialysis.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection might have a higher mortality rate in patients with end-stage renal disease due to immunosuppression. This study investigates the mortality rates of SARS-CoV-2 infection and the factors affecting mortality among patients who were on maintenance hemodialysis and continuous ambulatory peritoneal dialysis. A total of 200 patients, including 157 maintenance hemodialysis and 43 continuous ambulatory peritoneal dialysis patients followed in our hospital, were included in the study. The patients' sociodemographic characteristics, comorbidities, history of SARS-CoV-2 infection in the previous year, death event, source of death (SARS-CoV-2 or not), presence of hospitalization due to SARS-CoV-2 infection, need for intensive care unit, need for ventilatory support in intensive care unit were obtained from the clinical file records. 85 of the 200 patients had a history of SARS-Cov-2 infection during the last 12 months. Forty-two (49.5%) patients with SARS-CoV-2 infection were hospitalized. Patients with SARS-CoV-2 had longer dialysis time, increased mortality, and significantly higher comorbidities such as coronary artery disease, congestive heart failure. Besides, heart failure and hypertension were the determining factors in the risk factor analysis for SARS-CoV-2 infection. In dialysis patients, the mortality rate in the last year, due to all causes, including SARS-CoV-2 infection, was 23% while the mortality rate due to "SARS-CoV-2 infection only" was 13%) (p > 0.05). Our findings are important in guiding clinical decision-making and informing the public and health authorities about the risk of death associated with COVID-19 in this patient group.


Machine learning to predict in-hospital cardiac arrest from patients presenting to the emergency department.
In-hospital cardiac arrest (IHCA) in the emergency department (ED) is not uncommon but often fatal. Using the machine learning (ML) approach, we sought to predict ED-based IHCA (EDCA) in patients presenting to the ED based on triage data. We retrieved 733,398 ED records from a tertiary teaching hospital over a 7 year period (Jan. 1, 2009-Dec. 31, 2015). We included only adult patients (≥ 18 y) and excluded cases presenting as out-of-hospital cardiac arrest. Primary outcome (EDCA) was identified via a resuscitation code. Patient demographics, triage data, and structured chief complaints (CCs), were extracted. Stratified split was used to divide the dataset into the training and testing cohort at a 3-to-1 ratio. Three supervised ML models were trained and performances were evaluated and compared to the National Early Warning Score 2 (NEWS2) and logistic regression (LR) model by the area under the receiver operating characteristic curve (AUC). We included 316,465 adult ED records for analysis. Of them, 636 (0.2%) developed EDCA. Of the constructed ML models, Random Forest outperformed the others with the best AUC result (0.931, 95% CI 0.911-0.949), followed by Gradient Boosting (0.930, 95% CI 0.909-0.948) and Extra Trees classifier (0.915, 95% CI 0.892-0.936). Although the differences between each of ML models and LR (AUC: 0.905, 95% CI 0.882-0.926) were not significant, all constructed ML models performed significantly better than using the NEWS2 scoring system (AUC 0.678, 95% CI 0.635-0.722). Our ML models showed excellent discriminatory performance to identify EDCA based only on the triage information. This ML approach has the potential to reduce unexpected resuscitation events if successfully implemented in the ED information system.


Naïve human pluripotent stem cells respond to Wnt, Nodal and LIF signalling to produce expandable naïve extra-embryonic endoderm.
Embryonic stem cells (ESCs) exist in at least two states that transcriptionally resemble different stages of embryonic development. Naïve ESCs resemble peri-implantation stages and primed ESCs the pre-gastrulation epiblast. In mouse, primed ESCs give rise to definitive endoderm in response to the pathways downstream of Nodal and Wnt signalling. However, when these pathways are activated in naïve ESCs, they differentiate to a cell type resembling early primitive endoderm (PrE), the blastocyst-stage progenitor of the extra-embryonic endoderm. Here, we apply this context dependency to human ESCs, showing that activation of Nodal and Wnt signalling drives the differentiation of naïve pluripotent cells toward extra-embryonic PrE, or hypoblast, and these can be expanded as an in vitro model for naïve extra-embryonic endoderm (nEnd). Consistent with observations made in mouse, human PrE differentiation is dependent on FGF signalling in vitro, and we show that, by inhibiting FGF receptor signalling, we can simplify naïve pluripotent culture conditions, such that the inhibitor requirements closer resemble those used in mouse. The expandable nEnd cultures reported here represent stable extra-embryonic endoderm, or human hypoblast, cell lines.This article has an associated 'The people behind the papers' interview.


Characterization of a panel of somatic cell hybrids for subregional mapping along 11p and within band 11p13. Subdivision of the WAGR complex region.
The short arm of chromosome 11 carries genes involved in malformation syndromes, including the aniridia/genitourinary abnormalities/mental retardation (WAGR) syndrome and the Beckwith-Wiedemann syndrome, both of which are associated with an increased risk of childhood malignancy. Evidence comes from constitutional chromosomal aberrations and from losses of heterozygosity, limited to tumor cells, involving regions 11p13 and 11p15. In order to map the genes involved more precisely, we have fused a mouse cell line with cell lines from patients with constitutional deletions or translocations. Characterization of somatic cell hybrids with 11p-specific DNA markers has allowed us to subdivide the short arm into 11 subregions, 7 of which belong to band 11p13. We have thus defined the smallest region of overlap for the Wilms' tumor locus bracketed by the closest proximal and distal breakpoints in two of these hybrids. The region associated with the Beckwith-Wiedemann syndrome spans the region flanked by two 11p15.5 markers, HRAS1 and HBB. These hybrids also represent useful tools for mapping new markers to this region of the human genome.


Development of sediment load estimation models by using artificial neural networking techniques.
This study aims at the development of an artificial neural network-based model for the estimation of weekly sediment load at a catchment located in northern part of Pakistan. The adopted methodology has been based upon antecedent sediment conditions, discharge, and temperature information. Model input and data length selection was carried out using a novel mathematical tool, Gamma test. Model training was carried out by using three popular algorithms namely Broyden-Fletcher-Goldfarb-Shanno (BFGS), back propagation (BP), and local linear regression (LLR) using forward selection of input variables. Evaluation of the best model was carried out on the basis of basic statistical parameters namely R-square, root mean squared error (RMSE), and mean biased error (MBE). Results indicated that BFGS-based ANN model outperformed all other models with significantly low values of RMSE and MBE. A strong correlation was also found between the observed and estimated sediment load values for the same model as the value of Nash-Sutcliffe model efficiency coefficient (R-square) was found to be quite high as well.


Age at menopause and menopause-related symptoms in human immunodeficiency virus-infected Thai women.
There are limited data for age at menopause (AM) and menopause-related symptoms in human immunodeficiency virus (HIV)-infected Asian women. We investigated AM and menopause-related symptoms in HIV-infected Thai women. HIV-infected Thai women 40 years or older who did not receive any hormone therapy in the 8-week period preceding the study were enrolled. Participants completed the Menopause-Specific Quality of Life survey for their symptoms in the past 30 days. Menopause was defined as having the last menstrual period more than 1 year ago. Multivariate Cox proportional hazard regression analysis was used to identify factors associated with menopause. Two hundred sixty-eight HIV-infected women were enrolled; their median age was 44.6 (41.8-48.7) years, and the ratio of their Centers for Disease Control and Prevention clinical classifications (A:B:C) was 53%:34%:13%; 95% were using highly active antiretroviral therapy. The median (interquartile range [IQR]) CD4 count was 575 (437-758) cells/μL, and 93% had HIV-RNA of less than 1.7log10 copies/mL. Among the 55 women who had reached menopause, the mean (SD) AM was 47.3 (5.1) years. The mean (SD) AM in our study was earlier than the previous report of 49.5 (3.6) years in non-HIV-infected Thai women (difference, -2.2 y; 95% CI, -3.2 to -1.2, P < 0.01). Postmenopausal women had more symptoms, including night sweats (P = 0.03), change in sexual desire (P = 0.01), and avoiding intimacy (P = 0.01), compared with nonpostmenopausal women. No differences in psychosocial or physical domains between groups were found. Factors associated with menopause were Centers for Disease Control and Prevention clinical classification B or C (hazard ratio, 1.7; 95% CI, 1.0-3.03, P = 0.04), and no sexual act in the past month (hazard ratio, 4.9; 95% CI, 1.5-16.0, P = 0.01). No associations of later age of menarche, parity, marital status, educational level, income, body mass index, CD4 count, and HIV-RNA with menopause were found. AM in HIV-infected Thai women was 47.3 years, which is significantly earlier than the findings of a previous AM report on non-HIV-infected women. Postmenopausal HIV-infected women had more vasomotor and sexual symptoms. More studies are needed to investigate the cause and appropriate interventions for accelerated menopause in HIV-infected women.


Cyanide, carboxyhemoglobin and blood acid-base state in animals exposed to combustion products of various combinations of acrylic fiber and gauze.
In order to examine the usefulness of blood cyanide concentrations as an indicator of whether or not a victim was alive at the start of a fire, blood cyanide concentrations were measured in the bodies that we autopsied in our institute between January 1986 and March, 1987. In the present study, bodies with advanced decomposition were excluded. Thirty-six bodies were included: cyanide as well as carboxyhemoglobin (COHb) were detected in four charred bodies found at the scene of a fire. On the other hand, cyanide was not detected in any of the remaining 30 bodies except in two cases suspected of having ingested a cyanide compound. Rats and rabbits were made to inhale the combustion products of various combinations of acrylic fiber (hydrogen cyanide generating material when heated) and gauze (carbon monoxide generating material when heated). The exposure to the combustion products was continued until death in the rat and until apnea in the rabbit. The concentration of hydrogen cyanide in the exposure chamber and that of blood cyanide, at the time the animal died, correlated with the amount of acrylic fiber heated. In addition to differences in blood COHb and cyanide concentrations, there were also differences in blood gas concentrations between the acrylic fiber and the gauze groups. When the rabbits were switched to room air after the occurrence of apnea, the blood gas value began to normalize.


The extracellular matrix regulates MaeuCath1a gene expression.
We have previously shown that the gene for MaeuCath1, a cathelicidin secreted in wallaby milk is alternately spliced into two variants, MaeuCath1a and MaeuCath1b which are temporally regulated in order to provide antimicrobial protection to the newborn and stimulate mammary growth, respectively. The current study investigated the extracellular matrix (ECM) for its regulatory role in MaeuCath1 gene expression. Reverse transcription qPCR using RNA isolated from mammary epithelial cells (WallMEC) cultured on ECM showed that ECM regulates MaeuCath1a gene expression in a lactation phase-dependent manner. Luciferase reporter-based assays and in silico analysis of deletion fragments of the 2245bp sequence upstream of the translation start site identified ECM-dependent positive regulatory activity in the -709 to -15 region and repressor activity in the -919 to -710 region. Electrophoretic Gel Mobility Shift Assays (EMSA) using nuclear extract from ECM-treated WallMEC showed differential band shift in the -839 to -710 region.


Acid sensing ion channel (ASIC) inhibitors exhibit anxiolytic-like activity in preclinical pharmacological models.
Acid sensing ion channels (ASICs) are proton-gated ion channels located in the central and peripheral nervous systems. Of particular interest is ASIC1a, which is located in areas associated with fear and anxiety behaviors. Recent reports suggest a role for ASIC1a in preclinical models of fear conditioning and anxiety. The present experiments evaluated various ASIC inhibitors in preclinical models of autonomic and behavioral parameters of anxiety. In addition, neurochemical studies evaluated the effects of an ASIC inhibitor (A-317567) on neurotransmitter levels in the amygdala. In electrophysiological studies using hippocampal primary neuronal cultures, three ASIC inhibitors (PcTX-1, A-317567, and amiloride) produced concentration-dependent inhibition of acid-evoked currents. In the stress-induced hyperthermia model, acute administration of psalmotoxin 1 (PcTX-1; 10-56 ng, i.c.v.), A-317567 (0.1-1.0 mg/kg, i.p.), and amiloride (10-100 mg/kg, i.p.) prevented stress-induced elevations in core body temperature. In the four-plate test, acute treatment with PcTX-1 (10-56 ng, i.c.v.) and A-317567 (0.01-0.1 mg/kg, i.p.), but not amiloride (3-100 mg/kg, i.p.), produced dose-dependent and significant increases in the number of punished crossings relative to vehicle-treated animals. Additionally, PcTX-1 (56-178 ng, i.c.v.), A-317567 (0.1-10 mg/kg, i.p.), and amiloride (10-100 mg/kg, i.p.) lacked significant anxiolytic-like activity in the elevated zero maze. In neurochemical studies, an infusion of A-317567 (100 microM) into the amygdala significantly elevated the extracellular levels of GABA, but not glutamate, in this brain region. These findings demonstrate that ASIC inhibition produces anxiolytic-like effects in some behavioral models and indicate a potential role for GABAergic mechanisms to underlie these anxiolytic-like effects.


Should sex differences be considered when applying mathematical indices and formulas for discriminating β- thalassemia minor from iron deficiency?
β-thalassemia minor (BTM) and iron deficiency (ID) are common disorders characterized by microcytosis and/or hypochromasia, leading to a challenge in their discrimination during mass-screening programs especially in developing countries where resources are limited. It has been shown with varying reliability that quick exclusion of either disorder could be achieved mathematically using RBC-based indices and formulas. However, none of these proposed indices and formulas considered the sex-based hematological differences. This comparative retrospective study examined the efficacy of using sex-based RBC indices in the mathematical discrimination BTM and ID in adult males and females. The CBC of randomly selected eight hundred adults diagnosed with BTM or ID (200M & 200F BTM, and 200M & 200F ID) were used in the comparisons. The discrimination power, in terms of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Youden index were calculated for all subjects and separately for males and females for 20 mathematical indices and formulas. Data revealed significant differences in the RBC-based indices between males and females for both BTM and ID groups. Significant variation in reliability indicators for the different indices and formulas were discovered between males and females samples. Sex-based indices and formulas are necessary to improve the reliability in mathematically discriminating between BTM and ID in mass screening programs. We also advocate for a large-scale multicenter study to establish the parameters of such indices and formulas with sex and age.


Antibodies against monocytes and endothelial cells in the sera of patients with atherosclerotic peripheral arterial disease.
We looked for antibodies against endothelial cells, monocytes, fibroblasts, lymphocytes and Epstein-Barr virus transformed lymphocytes in the sera of 28 elderly and 18 middle-aged patients with atherosclerotic peripheral arterial disease and 13 controls. Inclusion criteria were symptomatic peripheral arterial disease with intermittent claudication and ankle/radial Doppler pressure ratio less than 0.7 in the patient group and greater than 1 in the controls. The sera were tested using a standard cytotoxic technique against a cell panel of monocytes, T and B lymphocytes from 5 donors, and against endothelial cells, fibroblasts and Epstein-Barr virus transformed lymphocytes from one umbilical cord vein and blood. The sera of 30 of 46 (65.2%) patients showed toxicity against monocytes from at least one member of the cell panel and 12 of 19 sera tested (63%) reacted with endothelial cells. Only one of the control sera was positive against monocytes and none reacted with endothelial cells. None of the sera of either patients or controls contained cytotoxic antibodies against T and B lymphocytes, Epstein-Barr virus transformed lymphocytes or fibroblasts. The selective cytotoxicity suggests that the antibodies detected are not against HLA-antigens (which are expressed by normal lymphocytes and Epstein-Barr virus lymphocytes). Our results suggest that immune phenomena occur in atherosclerosis.