Cesarean delivery surveillance system at a maternity hospital in Kabul, Afghanistan.
To use an active facility-based maternal and newborn surveillance system to describe cesarean delivery practices and outcomes in a resource-poor setting. Using data from operating room logbooks, 392 cesarean deliveries were evaluated between April 1 and June 30 2006 at a large public maternity hospital in Kabul, Afghanistan. The perinatal mortality rate was 89 per 1000 births: 57% antepartum and 37% intrapartum stillbirths. Fetuses with normal birth weight comprised 85% of intrapartum stillbirths. Obstructed labor, uterine rupture, and malpresentation accounted for more than 50% of perinatal deaths. The cesarean delivery rate was 10.2% and there were 2 maternal deaths. The high percentage of intrapartum stillbirths among normal birth weight fetuses suggests a need for improved labor monitoring and surgical obstetric practices. The use of a facility-based perinatal surveillance system is critical in guiding such quality assurance initiatives.


Large cell neuroendocrine carcinoma in the unusual location of the descending colon.
Neuroendocrine neoplasms are most often found in the small intestine, rectum, appendix, and stomach. The colon, excluding the appendix and the cecum, is a rare location for these neoplasms and often gives rise to highly proliferative, poorly differentiated tumors with aggressive features and dismal prognosis. A 32-year-old male presents with a large cell neuroendocrine carcinoma arising from an unusual location, the descending colon. The patient's clinical and imaging characteristics resembles those seen in the much more common neoplasm, colonic adenocarcinoma. Computed tomography and In-111 octreotide scan are limited in diagnosing large cell neuroendocrine carcinoma. Pathologic correlation of a surgical specimen is required to make the correct diagnosis.


Familial hemolytic-uremic syndrome in three generations.
The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are complex entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and variable impairment of renal function, occasionally complicated by neurological symptoms. In both syndromes, rare instances of familial forms have been reported. We present the case of a family in which signs and symptoms of HUS/TTP appeared in three generations. We also briefly review the literature on inherited forms of HUS/TTP and discuss the outcome of renal transplantation in adult patients with this syndrome.


Diagnosing major depression in cocaine abusers: the use of depression rating scales.
This study compared the sensitivity and specificity of three rating scales in detecting major depression in 149 hospitalized cocaine abusers. Patients were administered the Beck Depression Inventory (BDI), the Hamilton Rating Scale for Depression, and the Symptom Checklist-90 at admission and at 2 weeks and 4 weeks of hospitalization. The admission BDI score offered the best combination of sensitivity and specificity. However, the low specificity of all the scales and the low prevalence rate of major depression in this population made the positive predictive power of the instruments weak. The results support some limited use of the BDI as an initial screening instrument in cocaine abusers.


Effects of paced coital stimulation on termination of estrus and brain indoleamine levels in female rats.
Serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) levels were measured in brain regions of ovariectomized, steroid-primed rats at the end of behavioral estrus. At the onset of behavioral estrus three groups of rats received coital stimulation which included (1) mounts without penile intromission only, (2) temporally-controlled (paced) mounts with intromission, and (3) non-paced mounts with intromission. Within 12 hr after the initial treatment, sexual receptivity was significantly lower in females given paced intromissions than in the other two groups. Brain stem 5-HT and 5-HIAA concentrations were significantly higher in females which received intromissions, regardless of whether or not they were paced than in females given mounts only. Hypothalamic and cortical concentrations of 5-HT and 5-HIAA were equivalent in the two groups. These results suggest that the termination of behavioral estrus is not associated with increased metabolic activity in central serotonergic neurons.


Postharvest treatments with MnCl2 and ZnCl2 reduce enzymatic browning and enhance antioxidant accumulation in soya bean sprout.
Soya bean sprout is a nutrient-abundant vegetable. However, enzymatic browning of soya bean sprouts during storage remains a challenge. In this study, the effects of treatment with MnCl2 or ZnCl2 on the browning index, antioxidant nutrient accumulation, total antioxidant capacity and enzyme activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were investigated in soya bean sprouts after storage at 4 °C and 90% relative humidity for 0, 7, 14 and 21 days. The results showed that postharvest treatment with 1, 2 and 10 mM MnCl2 or ZnCl2 profoundly retarded enzymatic browning in soya bean sprouts to different extents. Compared with the control, the 10 mM MnCl2 and ZnCl2 treatments drastically enhanced ascorbic acid, total thiol and phenolic content, and enhanced FRAP (ferric-reducing ability of plasma) antioxidant capacity in stored soya bean sprouts. Moreover, the MnCl2 and ZnCl2 treatments enhanced SOD, CAT and PAL but decreased PPO and POD activities compared with the control. In addition, the Mn and Zn content in soya bean sprouts significantly increased, by approximately two- to threefold, compared with the control. This study provides a new method for improving the nutrient quality of soya bean sprouts based on postharvest Mn or Zn supplementation.


Household heads satisfaction and associated factors on community-based health insurance scheme in Gudeya Bila District, Oromia, Ethiopia.
Community-Based Health Insurance (CBHI) scheme refers to a non-profit type of health insurance for the informal sector. There is a paucity of information on this topic in Gudeya Bila, Ethiopia. This study aimed to assess the level of household (HH) satisfaction with the CBHI scheme and its associated factors. A community-based cross-sectional study design was employed from November 1-30, 2020, and a sample of 630 HHs who enrolled in the CBHI scheme were included. A multi-stage sampling and systematic random sampling were employed. Data was entered into Epidata version 3.1 and analyzed using SPSS for windows program version 25. A 95% CI was calculated and variables having p-value < 0.05 were considered statistically significant. Descriptive statistics, bivariate, and multivariable logistic regression analyses were performed. All HHs heads (630) with a response rate of 100% were involved in the study. The overall HH satisfaction on CBHI was 56.2%. Attending CBHI scheme-related meetings (AOR = 1.948, 95% CI = 1.16-3.27), healthcare provider respectfulness (AOR = 9.209, 95% CI = 2.73-31.06), able to get the ordered laboratory test service (AOR = 2.143, 95% CI = 1.127-4.072) and having paid extra money for drug supply at private health facilities (AOR = 0.492, 95% CI = 0.285-0.847) were independent predictors. HH satisfaction level on CBHI scheme was moderate. Attending CBHI scheme-related meetings, health-care provider respectfulness, being able to get the ordered laboratory test services and extra payments for drug supply were significant predictors of satisfaction with CBHI. Therefore, attention should be given to increasing the satisfaction of HHs with CBHI through improving the quality of health services.


NMR crystallography of monovalent cations in inorganic matrixes: Li(+) siting and the local structure of Li(+) sites in ferrierites.
(7)Li-(7)Li correlation MAS NMR spectroscopy, interpreted using periodic DFT including molecular dynamics conformational sampling of Li(+) sites, is employed to obtain the siting of Li(+) at exchangeable positions of ferrierites and the local structure of these Li(+) sites. The former is controlled by the Al siting in the zeolite framework.


Probabilistic scoring measures for profile-profile comparison yield more accurate short seed alignments.
The development of powerful automatic methods for the comparison of protein sequences has become increasingly important. Profile-to-profile comparisons allow for the use of broader information about protein families, resulting in more sensitive and accurate comparisons of distantly related sequences. A key part in the comparison of two profiles is the method for the calculation of scores for the position matches. A number of methods based on various theoretical considerations have been proposed. We implemented several previously reported scoring functions as well as our own functions, and compared them on the basis of their ability to produce accurate short ungapped alignments of a given length. Our results suggest that the family of the probabilistic methods (log-odds based methods and prof_sim) may be the more appropriate choice for the generation of initial 'seeds' as the first step to produce local profile-profile alignments. The most effective scoring systems were the closely related modifications of functions previously implemented in the COMPASS and Picasso methods.


Young's syndrome: an often unrecognized correctable cause of obstructive azoospermia.
Young's syndrome consists of azoospermia owing to bilateral epididymal obstruction in patients with chronic sinus and pulmonary infections. Azoospermia may be corrected by vasoepididymostomy in these patients but postoperative fertility rates are yet to be determined. Because the infertility of Young's syndrome potentially is remediable with vasoepididymostomy and because the syndrome is observed commonly by surgeons outside of this country, we report 2 cases to illustrate what may be a frequently unrecognized and potentially correctable cause of azoospermia.


Proliferative activity as revealed by Ki-67 in uterine adenocarcinoma of endometrioid type: comparison of tumours from patients with and without previous oestrogen therapy.
The Ki-67 antibody recognizes a nuclear antigen related to cell proliferation, which in some studies has been shown to reflect the aggressiveness of tumours. The percentage of Ki-67-positive cells was estimated by immunohistochemistry on frozen tissue sections from 73 adenocarcinomas of endometrioid type (EC) (40 tumours from patients who had never received postmenopausal oestrogen treatment and 33 tumours from patients with previous postmenopausal oestrogen treatment). The Ki-67 content was weakly but significantly (P < 0.05) correlated to nuclear grade, architectural grade, and crude mitotic count, but not to stage or progesterone receptors. Ki-67 expression in EC from patients with previous oestrogen therapy was much lower (median 10 per cent Ki-67) than that in EC from patients who had never received oestrogen treatment (median 24 per cent Ki-67), suggesting that a prognostic cut-off point may be different in tumours from the two groups of patients. The mitotic count discriminated the two groups of patients to a much smaller degree. It is also shown that a quick qualitative Ki-67 estimate can replace the time-consuming quantitative assessment.


Are loneliness and social isolation equal threats to health and well-being? An outcome-wide longitudinal approach.
The detrimental effects of loneliness and social isolation on health and well-being outcomes are well documented. In response, governments, corporations, and community-based organizations have begun leveraging tools to create interventions and policies aimed at reducing loneliness and social isolation at scale. However, these efforts are frequently hampered by a key knowledge gap: when attempting to improve specific health and well-being outcomes, decision-makers are often unsure whether to target loneliness, social isolation, or both. Filling this knowledge gap will inform the development and refinement of effective interventions. Using data from the Health and Retirement Study (13,752 participants (59% women and 41% men, mean [SD] age = 67 [10] years)), we examined how changes in loneliness and social isolation over a 4-year follow-up period (from t0:2008/2010 to t1:2012/2014) were associated with 32 indicators of physical-, behavioral-, and psychosocial-health outcomes 4-years later (t2:2016/2018). We used multiple logistic-, linear-, and generalized-linear regression models, and adjusted for sociodemographic, personality traits, pre-baseline levels of both exposures (loneliness and social isolation), and all outcomes (t0:2008/2010). We incorporated data from all participants into the overall estimate, regardless of whether their levels of loneliness and social isolation changed from the pre-baseline to baseline waves. After adjusting for a wide range of covariates, we observed that both loneliness and social isolation were associated with several physical health outcomes and health behaviors. However, social isolation was more predictive of mortality risk and loneliness was a stronger predictor of psychological outcomes. Loneliness and social isolation have independent effects on various health and well-being outcomes and thus constitute distinct targets for interventions aimed at improving population health and well-being.


Botulinum toxin reduces anal spasm but has no effect on pain after haemorrhoidectomy.
Pain following haemorrhoidectomy is due to a combination of factors including spasm of the internal sphincter, an open wound and local infection. In this study, we investigated the effect of botulinum toxin on postoperative pain following Milligan-Morgan haemorrhoidectomy. A prospective randomized controlled trial was conducted in 32 patients undergoing haemorrhoidectomy. Routine postoperative care included metronidazole and bupivacaine. Patients were also given an inter-sphincteric injection of either placebo or botulinum toxin (150 units). Maximal resting pressure (MRP) and maximal squeeze pressure (MSP) were measured postoperatively. A linear analogue score was used to assess postoperative pain. The sample size calculation was calculated to show one standard deviation difference between groups. The primary endpoint was reduction in postoperative pain. The MRP was significantly lower in the botulinum toxin group (mean 50.5 mmHg; 95% CI 39.77-61.23) compared with the placebo group (mean 64.94 mmHg; 95% CI 55.65-74.22) (P = 0.04) at week 6. At week 12 there was no significant difference in MRP between the two groups. In contrast MSP was significantly lower in the botulinum toxin group at weeks 6 and 12 (mean 87.1 mmHg; 95% CI 66.9-107.1) compared with the placebo group (mean 185.8 mmHg; 95% CI 134.2-237.4) at week 12 (P = 0.0014). There was no significant effect on overall or maximal pain scores. Median time for return to normal activities was not significantly different between groups. Botulinum toxin reduces anal spasm but has no significant effect on postoperative pain.


Perspectives in agrobiotechnology.
This review surveys the most important and promising contributions of agricultural biotechnology to the development of sustainable, environment-friendly agriculture. It deals with the recent achievements of genetic technology for the development of new transgenic microbial, plant and animal products. It also deals with the newest developments and perspectives of microbial intervention in agricultural practices, such as biofertilizers, biocontrol agents, and various microbiological products used in modern agriculture. The review surveys the outlook for a waste-free, environment-friendly sustainable agricultural practice, including waste management, recycling and bioremediation technologies. The review lists the most important marketable agrobiotechnological products, and their present and projected sales volume.


Involvement of the epidermal growth factor receptor in Pb²+-induced activation of cPLA₂/COX-2 genes and PGE₂ production in vascular smooth muscle cells.
Lead (Pb²+) is one of the most common heavy metal pollutants, which can cause chronic cardiovascular diseases. To clarify the mechanism by which Pb²+ induces inflammatory reactions, we examined the expression of inflammatory genes including encoding cyclooxygenase-2 (COX-2), cytosolic phospholipase A₂ (cPLA₂), and their down stream product prostaglandin E₂ (PGE₂) in CRL1999 cells that is a vascular smooth muscle cell line from human aorta. The expression of COX-2/cPLA₂ genes and PGE₂ secretion was increased markedly after cells were exposed to 1 μM Pb²+. PD098059, a MEK inhibitor, suppressed Pb²+-mediated inflammatory reactions; this indicates the involvement of the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Furthermore, Pb²+-induced activation of the COX-2/cPLA₂ genes was inhibited by both epidermal growth factor receptor (EGFR) inhibitors (AG1478 and PD153035) and EGFR siRNA. Short-term stimulation with Pb²+ induced EGFR phosphorylation at the Tyr residue (position, 1173). Importantly, overexpression of EGFR resulted in a significant potentiation effect on Pb²+-induced gene expression. Taken together, our results indicate that 1 μM Pb²+ can induce PGE₂ secretion by upregulating the transcription of COX-2/cPLA₂ genes. EGFR is the key target in the plasma membrane responsible for transmitting Pb²+ signals in order to trigger downstream inflammatory cascades.


Haemophilus aphrophilus meningitis complicated by hydrocephalus in an immunocompetent adult.
A case of meningitis due to an unusual organism, Haemophilus aphrophilus in an adult is described. In spite of rapid clearance of the organism from the cerebrospinal fluid with intravenous cefotaxime, fever persisted over 8 days of therapy and infection was complicated by hydrocephalus. H. aphrophilus meningitis is uncommon and has not been previously reported in an adult male.


[Long-term evolution of vesicoureteral reflux in children].
Vesicoureteral reflux is very common in children, requiring a long follow-up period to reduce its progression toward chronic renal failure. This study aims to analyze the epidemiological diagnostic features, the management of vesicoureteral reflux and long term course of patients with this disease. We conducted a retrospective study of 42 patients with suspected vesicoureteral reflux hospitalized in the Department of Visceral Paediatric Surgery at the Hassan II University Hospital of Fez over a period of 6 years from January 2010 to December 2015. Mean age of patients at diagnosis was 3 years and 2 months. The boy is to girl sex ratio was 1.8. Vesicoureteral reflux was isolated in 81% of patients and secondary or associated in 19% of patients. The most common initial manifestation was urinary tract infection (90.4%). Renal function was impaired in 54.8% of children. The treatment was based on antibiotics against diagnosed UTI (90.4%), antibiotic prophylaxis in the case of recurrence and Cohen reimplantation (97.62%). Surgical indication readily concerned all patients with grades IV and V vesicoureteral reflux (73.9%) as well as patients with impaired kidneys and 26.1% of patients after medical treatment. Early and late postoperative course was in general satisfactory: disappearance of vesicoureteral reflux in 92.68% of cases. Upper urinary tract regressed except for 9.52% of patients; 95.23% of patients had complete recovery of renal function. There was a reduction in UTI recurrence (in 19.04% of cases after surgery). The majority of parents judged positively the clinical course of their children (54.76%) after surgery.


Changes in net charge of glucocorticoid receptors by activation, and evidence for a biphasic activation kinetics.
The kinetics of glucocorticoid receptor activation and the changes in molecular properties of the receptors by the activation were studied, employing aqueous two-phase partitioning of rat thymocyte, rat liver and mouse S49.1 lymphoma cell cytosol labelled with tritiated glucocorticoid. By a mathematical analysis of the time-course of the receptor partition coefficient during activation, we demonstrate that at least two different receptor conversions take place during this process. Partitionings at conditions excluding receptor aggregation allowed an evaluation of differences in net charge between activated and non-activated forms of native and chymotrypsin-treated receptors. The net charge of the chymotrypsinized receptor changes little by the activation, being between 0 and -10 at pH 8 both in the non-activated and the activated state. In contrast, the activation changes the net charge of the native receptor from around -50 to around -10.


Phase coherent electronics: a molecular switch based on quantum interference.
The phenomenon of quantum mechanical interference may be used to control the conductivity of ballistic molecular wires. Using a simple model we demonstrate plausible effects and discuss its potential uses for constructing coherence-based molecular electronics.


Burden of serious fungal diseases in Hungary.
Valid data on the prevalence of serious fungal diseases are difficult to derive as in most countries these conditions are not reportable infections. To assess the burden of these infections in Hungary prevalence estimates from international peer-reviewed papers and population statistics were utilised. In the intensive care unit (ICU) population at least 370 cases of serious yeast and 52 mould infections can be expected yearly. The total number of candidaemia cases may be as high as 1110 annually. In patients with acute leukaemia and recipients of haematopoietic stem cell and solid organ transplants the predicted incidence is more than 55 every year. Recurrent vulvovaginal candidiasis--though not a life-threatening condition--can adversely affect the quality of life of more than 177,000 Hungarian women. According to organisation for economic co-operation and development (OECD), 4.7% of total population older than 15 will suffer from chronic obstructive pulmonary disease (COPD) and 4.4% from asthma, adding another very broad risk group to the aforementioned categories susceptible for mycotic complications. Here more than 17,000 can have severe asthma with fungal sensitisation (SAFS) and more than 13,000 are at risk for developing allergic bronchopulmonary aspergillosis (ABPA). The incidence of dermatomycoses and other superficial fungal infections is even more difficult to assess but--according to international estimations--can affect around 14.3% of the total population. More than 1.6 million Hungarians may suffer from fungal diseases annually, with 33,000 cases being life threatening or very serious. This is an under-recognised problem of special importance for public health.


Brain metabolic differences between pure bulbar and pure spinal ALS: a 2-[18F]FDG-PET study.
MRI studies reported that ALS patients with bulbar and spinal onset showed focal cortical changes in corresponding regions of the motor homunculus. We evaluated the capability of brain 2-[18F]FDG-PET to disclose the metabolic features characterizing patients with pure bulbar or spinal motor impairment. We classified as pure bulbar (PB) patients with bulbar onset and a normal score in the spinal items of the ALSFRS-R, and as pure spinal (PS) patients with spinal onset and a normal score in the bulbar items at the time of PET. Forty healthy controls (HC) were enrolled. We compared PB and PS, and each patient group with HC. Metabolic clusters showing a statistically significant difference between PB and PS were tested to evaluate their accuracy in discriminating the two groups. We performed a leave-one-out cross-validation (LOOCV) over the entire dataset. Four classifiers were considered: support vector machines (SVM), K-nearest neighbours, linear classifier, and decision tree. Then, we used a separate test set, including 10% of patients, with the remaining 90% composing the training set. We included 63 PB, 271 PS, and 40 HC. PB showed a relative hypometabolism compared to PS in bilateral precentral gyrus in the regions of the motor cortex involved in the control of bulbar function. SVM showed the best performance, resulting in the lowest error rate in both LOOCV (4.19%) and test set (9.09 ± 2.02%). Our data support the concept of the focality of ALS onset and the use of 2-[18F]FDG-PET as a biomarker for precision medicine-oriented clinical trials.


Familial hypertrophic synovitis.
We describe here a 14-year old male patient with a life-long history of deformities of hands and feet, swelling of both knees and both wrists and limited motion of hips and elbows. His paternal aunt has similar findings. A two-month-old brother developed flexion deformities of the hands similar to those of the patients.


Red eyes presenting with a fistulous lesion in the left lower extremity: a case report.
Very few cases of scar sarcoidosis affecting the eyes and bone together have been reported in the last few years. We report a case of a 49-year-old Spanish man with recurrent bilateral granulomatous uveitis and a fistulous nodular lesion in the left pre-tibial region (scar granuloma) on the site of an 8-year-old scar. He presented with bilateral hilar adenopathies and elevation of inflammatory markers and angiotensin-converting enzyme. A histologically confirmed sarcoid of the tibia with a radiologic appearance unusual for long tubular bone involvement was observed. He also had bilateral ophthalmologic involvement. Sarcoidosis is a disease of unknown cause histologically characterized by non-caseating granulomas that can involve any organ or tissue. Osseous sarcoidosis is a relatively rare presentation. However, on the basis of cases reported in the literature, sarcoid lesions on bones are generally asymptomatic. Biologic agents are considered an alternative therapy for sarcoidosis resistant to conventional treatment.


Expression of Rab27B-binding protein Slp1 in pancreatic acinar cells and its involvement in amylase secretion.
Slp1 is a putative Rab27 effector protein and implicated in intracellular membrane transport; however, the precise tissue distribution and function of Slp1 protein remain largely unknown. In this study we investigated the tissue distribution of Slp1 in mice and found that Slp1 is abundantly expressed in the pancreas, especially in the apical region of pancreatic acinar cells. Slp1 interacted with Rab27B in vivo and both proteins were co-localized on zymogen granules. Morphological analysis of fasted Slp1 knockout mice showed an increased number of zymogen granules in the pancreatic acinar cells, indicating that Slp1 is part of the machinery of amylase secretion by the exocrine pancreas.


Comparison of autologous conditioned plasma injection, extracorporeal shockwave therapy, and conventional treatment for plantar fasciitis: a randomized trial.
To evaluate the efficacy of autologous conditioned plasma (ACP) compared with extracorporeal shockwave (ESWT) and conventional treatments for plantar fasciitis. Randomized trial. Sports medicine center in a tertiary care hospital. Fifty-four subjects (age range, 29-71 years) with unilateral chronic plantar fasciitis with more than 4 months of symptoms. Subjects randomized to 3 groups: 19 to ACP and conventional treatment (ACP group), 19 to ESWT and conventional treatment (ESWT group), and 16 to conventional treatment alone. Conventional treatment included stretching exercises and orthotics if indicated. Outcomes were pain-Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and ultrasound plantar fascia thickness assessed at baseline before treatment and at 1 month, 3 months, and 6 months after treatment. VAS, AOFAS ankle-hindfoot scale, and plantar fascia thickness improved in all groups. Significant VAS pain score improvements in the ACP group compared with conventional treatment at month 1 (P = .037) and for the ESWT group compared with conventional treatment at months 1, 3, and 6 (P = .017, P = .022, and P = .042). The AOFAS ankle-hindfoot scale score improved in the ACP group at months 3 and 6 (P = .004 and P = .013) and, for the ESWT group, at months 1 and 3 (P = .011 and P = .003) compared with conventional treatment. Significant improvements in plantar fascia thickness were seen in the ACP group at months 1 and 3 compared with conventional treatments (P = .015 and P = .014) and at months 3 and 6 compared with the ESWT group (P = .019 and P = .027). No adverse events reported. Treatment of plantar fasciitis with ACP or ESWT plus conventional treatments resulted in improved pain and functional outcomes compared with conventional treatment alone. There was no significant difference between ACP and ESWT in terms of VAS and AOFAS ankle-hindfoot scale improvements, although the ACP group demonstrated greater reductions in plantar fascia thickness.


Localization of the human neonatal Fc receptor (FcRn) in human nasal epithelium.
The airway epithelium is a central player in the defense against pathogens including efficient mucociliary clearance and secretion of immunoglobulins, mainly polymeric IgA, but also IgG. Pulmonary administration of therapeutic antibodies on one hand, and intranasal immunization on the other, are powerful tools to treat airway infections. In either case, the airway epithelium is the primary site of antibody transfer. In various epithelia, bi-polar transcytosis of IgG and IgG immune complexes is mediated by the human neonatal Fc receptor, FcRn, but FcRn expression in the nasal epithelium had not been demonstrated, so far. We prepared affinity-purified antibodies against FcRn α-chain and confirmed their specificity by Western blotting and immunofluorescence microscopy. These antibodies were used to study the localization of FcRn α-chain in fixed nasal tissue. We here demonstrate for the first time that ciliated epithelial cells, basal cells, gland cells, and endothelial cells in the underlying connective tissue express the receptor. A predominant basolateral steady state distribution of the receptor was observed in ciliated epithelial as well as in gland cells. Co-localization of FcRn α-chain with IgG or with early sorting endosomes (EEA1-positive) but not with late endosomes/lysosomes (LAMP-2-positive) in ciliated cells was observed. This is indicative for the presence of the receptor in the recycling/transcytotic pathway but not in compartments involved in lysosomal degradation supporting the role of FcRn in IgG transcytosis in the nasal epithelium.


The Approach to Acute Lymphoblastic Leukemia in Older Patients: Conventional Treatments and Emerging Therapies.
Acute lymphoblastic leukemia (ALL) among older adult patients presents significant clinical challenges. As opposed to pediatric populations, in whom long-term outcomes are markedly superior, those for adults remain grim. Nevertheless, younger adults with ALL have experienced a steady improvement in long-term survival in the last few decades. This is significantly different for older ALL patients, for whom long-term outcomes remain poor. Conventional chemotherapies are associated with sub-optimal outcomes and increased toxicity in this population. However, several emerging therapies, including antibody-drug conjugates, bi-specific engagers, and chimeric antigen receptor (CAR) T cells, have demonstrated much promise and are either incorporated into the existing therapeutic paradigms or being actively investigated to improve outcomes.


Weight-loss diets modify glucose-dependent insulinotropic polypeptide receptor rs2287019 genotype effects on changes in body weight, fasting glucose, and insulin resistance: the Preventing Overweight Using Novel Dietary Strategies trial.
Glucose-dependent insulinotropic polypeptide [also known as gastric inhibitory polypeptide (GIP)] and its receptor (GIPR) may link overnutrition to obesity, insulin resistance, and type 2 diabetes. A GIPR variant rs2287019 was recently associated with obesity and glucose metabolism. We aimed to examine whether weight-loss diets that vary in fat content may modify the effect of this variant on changes in body weight, fasting glucose, and insulin resistance in the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. We genotyped the GIPR rs2287019 in 737 overweight adults who were randomly assigned to 1 of 4 weight-loss diets that varied in macronutrient contents for 2 y. We assessed the percentage changes in body weight, fasting glucose, and insulin resistance (HOMA-IR) across genotypes by the low-fat and high-fat diets. At 6 mo of diet intervention, the T allele of rs2287019 was associated with greater weight loss (β ± SE: -1.05 ± 0.56%; P = 0.06) and greater decreases in fasting glucose (β ± SE: -2.33 ± 0.86%; P = 0.006), fasting insulin (β ± SE: -8.76 ± 4.13%; P = 0.03), and HOMA-IR (β ± SE: -10.52 ± 4.39%; P = 0.01) in participants who were assigned to low-fat diets, whereas there was no significant genotype effect on changes in these traits in the group assigned to the high-fat diet (all P > 0.44; P-interaction = 0.08, 0.04, 0.10, and 0.07, respectively). After correction for multiple tests (significant P = 0.008), the genotype effect on changes in fasting glucose remained significant. Sensitivity analysis in white participants showed that the interactions were more evident on changes in insulin and HOMA-IR (P-interaction < 0.008). The T allele of GIPR rs2287019 is associated with greater improvement of glucose homeostasis in individuals who choose a low-fat, high-carbohydrate, and high-fiber diet. The POUNDS LOST trial was registered at clinicaltrials.gov as NCT00072995.


Modelling of forces in the human masticatory system with optimization of the angulations of the joint loads.
Numerical models of the human masticatory system were constructed using algorithms which minimized non-linear functions of the muscle forces or the joint loads. However, the predicted solutions for isometric biting were critically dependent upon the modelled angular freedom of the joint loads. The most complete mathematical minimization of any objective function occurs when the joint load angles are predicted. However, the predictions have to be sensible in relation to the actual morphology of the joints. Therefore, the models were tested in terms of the angles of joint load predicted for a dry skull, using muscle vectors reconstructed from the geometry of the skull. The minimizations of muscle force were intrinsically incapable of predicting the angles of joint load. Such models must rely on constrained angles and this produces a restricted minimization and also an indeterminacy. In contrast, the minimizations of joint load predicted angles of joint load which varied appropriately with condylar position. The condylar movement was achieved with a positioning model which adjusted the angulation of the muscle vectors as the jaw was positioned. This model also generated the optimal sagittal shape of the articular eminence. Muscle predictions from the various models were not examined in detail, but the general nature of the predicted muscle force patterns was shown to be reasonable in some of the models and unreasonable in others. The results supported the hypothesis that the temporomandibular joint develops functionally to allow an approximate minimization of the joint loads during isomeric biting. This does not necessarily imply that the neurophysiological control is actually based on a minimization of joint load.


Enhanced adaptive focusing through semi-transparent media.
Adaptive optics can focus light through opaque media by compensating the random phase delay acquired while crossing a scattering curtain. The technique is commonly exploited in many fields, including astrophysics, microscopy, biomedicine and biology. A turbid lens has the capability of producing foci with a resolution higher than conventional optics, however it has a fundamental limit: to obtain a sharp focus one has to introduce a strongly scattering medium in the optical path. Indeed a tight focusing needs strong scattering and, as a consequence, high resolution focusing is obtained only for weakly transmitting samples. Here we describe a novel method allowing to obtain highly concentrated optical spots even by introducing a minimum amount of scattering in the beam path with semi-transparent materials. By filtering the pseudo-ballistic components of the transmitted beam we are able to experimentally overcome the limits of the adaptive focus resolution, gathering light on a spot with a diameter which is one third of the original speckle correlation function.


Simultaneous optical and infrared thermal imaging of isotachophoresis.
Joule heating in isotachophoresis (ITP) can limit minimum assay times and efforts to scale up processed sample volumes. Despite its significance, the dynamics of Joule heating on spatiotemporal temperature fields in ITP systems have not been investigated. We here present novel measurements of spatiotemporal temperature and electromigration fields in ITP. To achieve this, we obtain simultaneous and registered optical and infrared thermal images of the ITP process. We conduct a series of experiments at constant current operation and vary the leading electrolyte concentration to study and highlight the importance of buffer-dependent ionic conductivity on the resulted temperature rise. The measurements demonstrate a substantial increase of temperature in the adjusted trailing electrolyte region, and the propagation of a thermal wave in the ITP channel with a velocity equal to that of the electromigration front. We present scaling of the experimental data that indicates the dependence of front velocity and temperature rise on current density and ionic conductivity. The current study has direct application to the design and optimization of scaled-up ITP systems and the validation of numerical models of Joule heating.


Ethanol-induced increased endogenous homocysteine levels and decreased ratios of SAM/SAH are only partially attenuated by exogenous glycine in developing chick brains.
The effects of exogenous ethanol (EtOH) and/or glycine on chick (Gallus gallus) embryo viability, brain apoptosis (caspase-3 activities), and the endogenous levels of brain homocysteine (HoCys), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and SAM/SAH were studied. Embryonic EtOH exposure caused decreased embryo viability as measured by EtOH-induced reductions in % living embryos at theoretical stage 37, EtOH-induced reductions in embryo masses, and EtOH-induced reductions in brain caspase-3 (Casp-3) activities. Exogenous glycine failed to attenuate EtOH-induced decreased embryo viability and EtOH-induced increased brain Casp-3 activities. Embryonic EtOH exposure caused elevated levels of endogenous HoCys, decreased levels of SAM, increased levels of SAH, and decreased SAM/SAH ratios in embryonic chick brains. While exogenous glycine failed to attenuate EtOH-induced increased HoCys levels, exogenous glycine attenuated EtOH-induced decreased levels of SAM, increased levels of SAH, and decreased SAM/SAH levels in embryonic chick brains.


Microplate ELISA for detection of antibodies to DNA in patients with systemic lupus erythematosus: specificity and correlation with Farr radioimmunoassay.
A 96-well microplate ELISA for the detection of antibodies to DNA is described. A number of buffers and precoating treatments were used to evaluate the optimal method for coating the plate with DNA. These included pretreatment of the plates with poly-L-lysine or protamine sulfate, and posttreatment with glutaraldehyde, none of which improved the performance of the assay. Whereas bicarbonate and borate coating buffers gave equivalent and satisfactory results, TRIS buffer resulted in very high binding of immunoglobulin to wells not coated with antigen. Sera from groups of patients with autoimmune disease as well as normal sera were tested against plates optimally coated with native E. coli DNA, calf thymus DNA, and heat-denatured DNA. Using native E. coli DNA, virtually none of 35 normal sera had any detectable antibody. With this antigen, as well as with native calf thymus DNA, significant levels of DNA antibody were found only in SLE patients. Most patients with SLE or drug-induced lupus, as well as some patients with rheumatoid arthritis and normal individuals had antibodies that bound to heat-denatured (single-stranded) DNA. Using either native E. coli or calf thymus DNA, a good correlation was found between the amount of DNA antibody detected by ELISA and the Farr-type radioimmunoassay.


The role of mu-opioid receptor signaling in the dorsolateral periaqueductal gray on conditional and unconditional responding to threatening and aversive stimuli.
Here we examined how mu-opioid receptor signaling in the periaqueductal gray (PAG) mediates conditional and unconditional responses to aversive stimuli. The mu-opioid agonist morphine (MOR) and/or the partially mu-selective antagonist naltrexone (NAL) were infused into dorsolateral PAG (dlPAG) during a fear conditioning task, in which rats were trained to fear an auditory conditional stimulus (CS) by pairing it with a unilateral eyelid shock unconditional stimulus (US). During drug-free test sessions, the CS elicited movement suppression responses (indicative of freezing) from trained rats that had not recently encountered the US. In trained rats that had recently encountered the US, the CS elicited flight behavior characterized by turning in the direction away from the eyelid where US delivery was anticipated. Infusions of MOR (30 nmol/side) into dlPAG prior to the test session did not impair CS-evoked movement suppression, but did impair CS-evoked turning behaviors. MOR infusions also reduced baseline motor movement, but US-evoked reflex movements remained largely intact. NAL was infused at two dosages, denoted 1x (26 nmol/side) and 10x (260 nmol/side). Infusions of NAL into dlPAG did not affect CS- or US-evoked behavioral responses at the 1x dosage, but impaired CS-evoked movement suppression at the 10x dosage, both in the presence and absence of MOR. When rats were co-infused with MOR and NAL, MOR-induced effects were not reversed by either dosage of NAL, and some measures of MOR-induced movement suppression were enhanced by NAL at the 1x dosage. Based on these findings, we conclude that mu-opioid receptors in dlPAG may selectively regulate descending supraspinal motor pathways that drive active movement behaviors, and that interactions between MOR and NAL in dlPAG may be more complex than simple competition for binding at the mu receptor.


Beliefs and counseling practices among dermatologists regarding sexual and other adverse effects of finasteride.
Finasteride may cause low libido and erectile dysfunction and the product label of finasteride also includes post-marketing reactions of sexual dysfunction that continued after discontinuation of treatment, as well as male infertility and depression. The aim of this study was to evaluate the beliefs and counseling practices among dermatologists regarding adverse effects of finasteride. Anonymous paper surveys were personally distributed to 122 attendees at two annual major dermatology meetings. The participation rate was 82% with 47% women and 77% residents of the United States. 51% of respondents believed that finasteride could cause sexual side effects and 18% believed that it could cause persistent sexual side effects. Fewer than a quarter believed that finasteride could cause depression or lower sperm counts. When initiating finasteride, 69% of respondents counseled at least half of their patients about potential sexual side effects with 52% for persistent sexual side effects and 30% for depression. This study identifies the need for greater awareness of the potential adverse effects of finasteride and identifies opportunities for improvement in counseling practices that reflect finasteride's product labeling.


Percutaneous balloon dilatation of stenotic truncal valve in a newborn.
We describe the use of percutaneous balloon angioplasty of a stenotic truncal valve in a newborn with a common arterial trunk. A 12 mm balloon catheter was chosen, this representing 80% of the diameter of the ventriculo-truncal junction. The peak systolic gradient dropped from 45 to 15 mm Hg. The procedure can avoid, or certainly delay, surgical treatment of the stenotic truncal valve.


CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.
The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.


Natural history of COVID-19: back to basics.
We retrospectively reconstituted the history of evolution and onset of the main symptoms of COVID-19 in 70 patients ([29 males, 41%] with a mean age of 56.7 ± 19.3 [19-96] years). Firstly, pain syndrome defined by headache and/or myalgia and/or arthralgia (87%, n = 61) appeared as the first manifestation 1.6 day after the onset of the illness. Secondly, fever (76%, n = 53), followed by cough (80%, n = 56) and diarrhea (40%, n = 28). Thirty three patients (47.1%) were hospitalized on day 7 (±3) with a mean duration of hospitalization of 6.9 (±5.8 [1-21]) days. Twenty-three patients (32.9%) required oxygen therapy 6.7 (±4.1 [1-13]) days from illness onset. Fifteen patients had a respiratory rate ≥22/min on day 9 (±0.8) and only 8 patients (15%) were admitted or transferred in an ICU on day 10 (±2.7) with a mean duration of hospitalization in ICU of 7.9 (±6.6 [2-21]) days.


Study of possible teratogenic effects of the fungicide maneb on chick embryos.
The teratogenicity of the fungicide maneb (80% active ingredient and 20% inert ingredients) in chick embryos was evaluated. Eggs, before incubation, were dipped in 0.2% or 1.2% aqueous dispersions of maneb for 30 seconds. An untreated group, a water group and a formulation ingredient group, at the concentration present in the 1.2% maneb group, ensured control in the study. Eggs were incubated for 18 days then transferred to hatching racks and allowed to hatch normally. Viable chicks and chicks "dead in shell" were assessed for external deformities. There was no evidence that maneb or its formulation ingredients were teratogenic or embryotoxic to developing chick embryos.


Plant-Derived Exosomal Nanoparticles Inhibit Pathogenicity of Porphyromonas gingivalis.
Plant exosomes protect plants against infection; however, whether edible plant exosomes can protect mammalian hosts against infection is not known. In this study, we show that ginger exosome-like nanoparticles (GELNs) are selectively taken up by the periodontal pathogen Porphyromonas gingivalis in a GELN phosphatidic acid (PA) dependent manner via interactions with hemin-binding protein 35 (HBP35) on the surface of P. gingivalis. Compared with PA (34:2), PA (34:1) did not interact with HBP35, indicating that the degree of unsaturation of PA plays a critical role in GELN-mediated interaction with HBP35. On binding to HBP35, pathogenic mechanisms of P. gingivalis were significantly reduced following interaction with GELN cargo molecules, including PA and miRs. These cargo molecules interacted with multiple pathogenic factors in the recipient bacteria simultaneously. Using edible plant exosome-like nanoparticles as a potential therapeutic agent to prevent/treat chronic periodontitis was further demonstrated in a mouse model.


Excess HLA antigens after transfusion of sickle cell patient with AIDS.
A woman with sickle cell-hemoglobin C disease developed the acquired immunodeficiency syndrome (AIDS), possibly as the result of blood transfusions administered 4 years earlier. Three months after subsequent transfusions, she had excess HLA-A and DR antigens (triplets) on her circulating lymphocytes. Three of her first-degree relatives were HLA-typed, and none had excess antigens. Family studies also indicated that the patient had at least one HLA-A antigen that was probably not inherited. These findings suggest the possibility that transient hemopoietic engraftment can occur in transfused sickle cell patients with AIDS.


Boosting peroxymonosulfate activation by iron-based dual active site for efficient sulfamethoxazole degradation: synergism of Fe and N-doped carbon.
Persulfate activation is emerged as an alternative applied in environment remediation, but it is still a great challenge to develop highly active catalysts for efficient degradation of organic pollutants. Herein, a heterogeneous iron-based catalyst with dual-active sites was synthesized by embedding Fe nanoparticles (FeNPs) onto the nitrogen-doped carbon, which was used to activate peroxymonosulfate (PMS) for antibiotics decomposition. The systematic investigation indicated the optimal catalyst exhibited a significant and stable degradation efficiency of sulfamethoxazole (SMX), in which the SMX can be completely removed in 30 min even after 5 cycle tests. Such satisfactory performance was mainly attributed to the successful construction of electron-deficient C centers and electron-rich Fe centers via the short C-Fe bonds. These short C-Fe bonds accelerated electrons to shuttle from SMX molecules to electron-rich Fe centers with a low transmission resistance and short transmission distance, enabling Fe (III) to receive electrons to promote the regeneration of Fe (II) for durable and efficient PMS activation during SMX degradation. Meanwhile, the N-doped defects in the carbon also provided reactive bridges that accelerated the electron transfer between FeNPs and PMS, ensuring the synergistic effects toward Fe (II)/Fe (III) cycle to some extent. The quenching tests and electron paramagnetic resonance (EPR) indicated O2·- and 1O2 were the dominant active species during the SMX decomposition. As a result, this work provides an innovative method to construct a high-performance catalyst to active sulfate for organic contaminant degradation.


The nitrone spin trap PBN alters the cellular response to H(2)O(2): activation of the EGF receptor/ERK pathway.
The nitrone spin trap PBN has been shown to protect neuronal cells from reactive oxygen species both in culture and in vivo. As an approach to understanding the molecular mechanisms by which PBN may function to protect cells, we examined whether PBN alters the cellular response to reactive oxygen species. H(2)O(2) stimulation of PC-12 cells results in weak activation of both the ERK and JNK signal transduction pathways. PBN pretreatment of PC-12 cells, followed by H(2)O(2) stimulation, results in strong and selective activation of the pro-survival ERK pathway. H(2)O(2) induction of ERK activity in PBN-pretreated cells was shown to be dependent on extracellular Ca(+2) influx. Further analysis of the ERK pathway showed that in PBN-pretreated cells, EGF receptor and the adapter protein SHC were phosphorylated in a Ca(+2)-dependent, ligand-independent manner following H(2)O(2) stimulation. Interestingly, H(2)O(2) stimulation of PBN-pretreated cells results in only 30% of the increase in intracellular Ca(+2) as compared to untreated cells following H(2)O(2) stimulation. These data suggest a model in which PBN attenuates H(2)O(2)-induced Ca(+2) entry, yet magnifies or alters Ca(+2) action, resulting in the activation of the EGF receptor/ERK pathway.


[Transthyretin cardiac amyloidosis].
Transthyretin (TTR) cardiac amyloidosis results from the dissociation of the tetrameric, liver-synthetized transport protein, either because of a mutation (hereditary CA), or spontaneously due to ageing (wild type CA). Monomers self-associate into amyloid fibrils within the myocardium, causing heart failure, arrhythmias and conduction defects. This overlooked disease must be recognized in case of unexplained increased thickness of the myocardium, particularly in subjects of African descent, in patients with heart failure and preserved ejection fraction, and in those with aortic stenosis. Some extra-cardiac symptoms must also be considered as red flags: carpal tunnel syndrome, lumbar canal stenosis, recent deafness, peripheral neuropathy, or dysautonomia. Medical assessment includes an electrocardiogram, biological assessment including troponin, natriuretic peptide and monoclonal protein assay, echocardiography with 2-D strain study, MRI and bone scintigraphy. Once the diagnosis established, cardiologic management must avoid beta-blockers and other rate-slowing drugs, which are deleterious in restrictive cardiomyopathy, and restrain the use of renin-angiotensin system inhibitors, of little use and often poorly tolerated. Congestion must be treated with diuretics. Anticoagulants are often necessary due to the risk of arrhythmias and stroke. Pacemaker or defibrillator implantation should be determined in patients with high risk of sudden death. Until now, etiologic treatments were liver and/or heart transplantation in some rare cases. Tafamidis, a TTR stabilizer has recently been approved, and new therapeutic approaches targeting TTR at the transcriptional level are under investigation.


Are routine preoperative cardiac catheterization and angiography necessary before repair of ostium primum atrial septal defect?
Two-dimensional and Doppler echocardiography were compared with cardiac catheterization and angiography in the preoperative evaluation of ostium primum atrial septal defect. Preoperative echocardiographic examinations as well as operative reports of all patients (33 patients aged 2 months to 23 years at surgery) with ostium primum atrial septal defect or transitional atrioventricular (AV) canal defect having had echocardiography and surgical repair at The Children's Hospital, Boston from July 1983 to January 1986 were retrospectively reviewed. Original cardiac catheterization and angiographic reports also were reviewed. Preoperative echocardiography resulted in no false positive or false negative primary diagnoses when compared with the diagnoses obtained at preoperative angiography or surgery. Doppler assessment of mitral regurgitation correlated well with angiographic (93% agreement) and intraoperative (85% agreement) assessments of mitral regurgitation to within two diagnostic categories on the six level scoring system used. There was reasonably good agreement between the two-dimensional echocardiographic estimate of right ventricular systolic pressure and that measured at catheterization when expressed as percent of the simultaneous left ventricular pressure. Seven of nine ventricular septal defects observed intraoperatively were noted on preoperative echocardiography; five of these defects were detected on preoperative angiography. A variety of other surgically confirmed associated cardiovascular defects were observed by both preoperative techniques. However, echocardiography appeared to be superior to angiography for evaluation of AV valve morphology and papillary muscle architecture. This study implies that in children with typical clinical and two-dimensional echocardiographic and Doppler findings for ostium primum atrial septal defect or transitional AV canal defect, routine preoperative cardiac catheterization and angiography are unnecessary.


The influence of diet and environment.
I have reviewed a small fraction of the vast literature on the influence of diet, food antigens, and environment on the immune response and would like to emphasize three points. Excess dietary lipid is thought to have a crucial role in inducing obesity and many age-related diseases including cardiovascular disease, malignancy and autoimmune diseases. Micronutrients are involved in protecting the functional integrity of the immune system, particularly to overcome the anti-oxidant deficiency present in refined diet components. Finally, environmental influences such as UV radiation or air pollutants may have an adverse effect in the modification of immune functions when combined with dietary and nutritional factors. It appears that future studies should be directed to understanding the overall interactions of diet and environmental factors, including those of food and viral antigens, and the impact that these have on the maintenance and gene expression of an active and vigorous immune system in healthy and diseased states.


A comparison study of brachial blood pressure recorded with Spacelabs 90217A and Mobil-O-Graph NG devices under static and ambulatory conditions.
Ambulatory blood pressure monitoring is an important tool in hypertension diagnosis and management. Although several ambulatory devices exist, comparative studies are scarce. This study aimed to compare for the first time brachial blood pressure levels of Spacelabs 90217A and Mobil-O-Graph NG, under static and ambulatory conditions. We examined 40 healthy individuals under static (study A) and ambulatory (study B) conditions. In study A, participants were randomized into two groups that included blood pressure measurements with mercury sphygmomanometer, Spacelabs and Mobil-O-Graph devices with reverse order of recordings. In study B, simultaneous 6-h recordings with both devices were performed with participants randomized in two sequences of device positioning with arm reversal at 3 h. Finally, all the participants filled in a questionnaire rating their overall preference for a device. In study A, brachial systolic blood pressure (117.2±10.3 vs 117.1±9.8 mm Hg, P=0.943) and diastolic blood pressure (73.3±9.4 mm Hg vs 74.1±9.4 mm Hg, P=0.611) did not differ between Spacelabs and Mobil-O-Graph or vs sphygmomanometer (117.8±11.1 mm Hg, P=0.791 vs Spacelabs, P=0.753 vs Mobil-O-Graph). Similarly, no differences were found in ambulatory systolic blood pressure (117.9±11.4 vs 118.3±11.0 mm Hg, P=0.864), diastolic blood pressure (73.7±7.4 vs 74.7±8.0 mm Hg, P=0.571), mean blood pressure and heart rate between Spacelabs and Mobil-O-Graph. Correlation analyses and Bland-Altman plots showed agreement between the monitors. Overall, the participants showed a preference for the Mobil-O-Graph. Spacelabs 90217A and Mobil-O-Graph NG provide practically identical measurements during the static and ambulatory conditions in healthy individuals and can be rather used interchangeably in clinical practice.


Estimation of linear and cyclic electron flows in photosynthesis based on 13C-metabolic flux analysis.
Photosynthetic organisms produce ATP and NADPH using light as an energy source and further utilize these cofactors during metabolism. Photosynthesis involves linear and cyclic electron flows; as the cyclic electron flow produces ATP more effectively than the linear electron flow without NADPH, the cell efficiently adjusts ATP and NADPH production using the two different pathways. Nevertheless, direct measurement of ATP and NADPH production during photosynthesis has been difficult. In the present study, the photosynthetic ATP and NADPH production rates of Synechocystis sp. PCC 6803 under three different single peak wavelength lights (blue: 470 nm, R630: 630 nm, and R680: 680 nm) were evaluated based on 13C-metabolic flux analysis (13C-MFA) by considering the mass balance of ATP and NADPH between photosynthesis and metabolism. The ratios of ATP/NADPH production via photosynthesis were estimated as 3.13, 1.70, and 2.10 under blue, R630, and R680 light conditions, respectively. Moreover, the linear and cyclic electron flow ratios were estimated to be 1.1-2.2, 0.2-0.5, and 0.5-1.0 under blue, R630, and R680 light conditions, respectively. The predicted linear and cyclic electron flow ratios were consistent with the excitation ratio between photosystems I and II, as observed in the steady-state fluorescence spectra.


Comparison of different fixation methods following sagittal split ramus osteotomies using three-dimensional finite elements analysis. Part 1: advancement surgery-posterior loading.
The purpose of this study was to evaluate the mechanical behavior of different fixation methods used in bilateral sagittal split ramus osteotomy (BSSRO). Part 1 comprises of the results of the analysis for mandibular advancement, four different fixation configurations of six hole fragmentation mini plates with monocortical screws and lag screws and posterior loading conditions in the molar and premolar region. The finite element analysis method (FEA) appears suitable for simulating complex mechanical stress situations in the maxillofacial region. The mechanical behavior of selected lag screws with linear or triangular configuration and double parallel or single oblique six hole mini plates with monocortical screws were compared by FEA after 5 mm BSSRO advancement procedure. Four separate three-dimensional finite element models of the mandible were created to simulate the BSSRO and corresponding fixation methods. These models consisted of 122,717 elements and 25,048 nodes. The mechanical parameters of the materials studied were adopted from the literature or were based on manufacturer's information. 500 N posterior occlusal loads were simulated on the distal segments. The commercial finite element solver MSC Marc software was utilized to calculate the stress fields on both the segments and fixative appliances. It was concluded that the use of 2.0mm lag screws placed in a triangular configuration following the BSSRO advancement surgery provides sufficient stability with any rotational movement and less stress fields at the osteotomy site, when compared with the other rigid fixation methods used in the current study.


Understanding auditory verbal hallucinations in healthy individuals and individuals with psychiatric disorders.
Auditory verbal hallucinations(AVHs) are psychiatric manifestations that are common in patients with psychiatric disorders and can occur in healthy individuals. This review summarizes the existing literature on the phenomenological features of auditory verbal hallucinations, imaging findings, and interventions, focusing on patients with schizophrenia who experience auditory verbal hallucinations, in addition to patients with borderline personality disorder, bipolar disorder, major depressive disorder, and posttraumatic stress disorder, as well as healthy individuals. The phenomenological features of AVHs vary in different psychiatric disorders, and the symptoms are associated with changes in specific brain structures and disturbances in brain function, blood flow, and metabolism. Interventions for auditory verbal hallucinations include antipsychotic drugs, neurostimulation, and cognitive behavioral therapy.


MicroRNA target prediction using thermodynamic and sequence curves.
MicroRNAs (miRNAs) are small regulatory RNA that mediate RNA interference by binding to various mRNA target regions. There have been several computational methods for the identification of target mRNAs for miRNAs. However, these have considered all contributory features as scalar representations, primarily, as thermodynamic or sequence-based features. Further, a majority of these methods solely target canonical sites, which are sites with "seed" complementarity. Here, we present a machine-learning classification scheme, titled Avishkar, which captures the spatial profile of miRNA-mRNA interactions via smooth B-spline curves, separately for various input features, such as thermodynamic and sequence features. Further, we use a principled approach to uniformly model canonical and non-canonical seed matches, using a novel seed enrichment metric. We demonstrate that large number of seed-match patterns have high enrichment values, conserved across species, and that majority of miRNA binding sites involve non-canonical matches, corroborating recent findings. Using spatial curves and popular categorical features, such as target site length and location, we train a linear SVM model, utilizing experimental CLIP-seq data. Our model significantly outperforms all established methods, for both canonical and non-canonical sites. We achieve this while using a much larger candidate miRNA-mRNA interaction set than prior work. We have developed an efficient SVM-based model for miRNA target prediction using recent CLIP-seq data, demonstrating superior performance, evaluated using ROC curves, specifically about 20% better than the state-of-the-art, for different species (human or mouse), or different target types (canonical or non-canonical). To the best of our knowledge we provide the first distributed framework for microRNA target prediction based on Apache Hadoop and Spark. All source code and data is publicly available at https://bitbucket.org/cellsandmachines/avishkar.


Endothelial cell dysfunction in response to intracellular overexpression of amyloid precursor protein.
Previous reports have shown that exposure of vascular endothelial and smooth muscle cells to exogenous amyloid beta (Abeta) peptide results in cell damage and toxicity via oxidative injury. In this study we demonstrate that overexpression of the amyloid precursor protein (APP) is toxic to bovine aortic endothelial cells but not to bovine aortic smooth muscle cells. Intracellular coexpression of the free radical scavenger proteins metallothionein or MnSOD abolished the toxic effect of APP overexpression in endothelial cells. Our results demonstrate that endothelial cells are specifically susceptible to intracellular overexpression of APP and free radical generation is the likely mechanism of cell damage due to APP overexpression.


Movement initiation and preparation in subjects with schizophrenia - The amplitude of the readiness potential as a biological marker for negative symptom severity.
Despite extensive research, the etiology of negative symptoms is not well understood. Preliminary findings are linking motor disturbances to negative symptom severity. We aimed to further the understanding to what extent motor movement preparation influences negative symptom severity. In a cohort of 31 subjects with schizophrenia and 20 control subjects we recorded the readiness potential amplitude over Cz during spontaneous movements of the right and left thumb. We further assessed negative and positive symptom severity (scale for the assessment of negative and positive symptoms) as well as neurological soft signs (NSS). In subjects with schizophrenia the severity of negative symptoms was best predicted by the readiness potential amplitude and the NSS subdomain motor coordination. The correlation between deficits in motor coordination and negative symptom severity was partially mediated by the readiness potential amplitude in subjects with schizophrenia. Deficits in motor processing are linked to negative symptom severity in schizophrenia. The readiness potential may represent a biological marker of these basal deficits. In combination with the assessment of NSS, the readiness potential may be a marker of the course of negative symptom severity and help clarifying interdependencies between (pre)frontal networks for action initiation and coordination, as well as negative symptoms.


A key serine for the GTPase-activating protein function of regulator of G protein signaling proteins is not a general target for 14-3-3 interactions.
Mammalian regulator of G protein signaling (RGS) proteins are highly conserved within the RGS domain. Of amino acids that are universal, a serine residue at the C terminus of this domain has been described as the binding site in RGS7 for 14-3-3 proteins. However, studies with the related RGS3 indicate that the site of interaction is not within the RGS domain. We confirm that the interaction of RGS3 with 14-3-3tau and 14-3-3zeta requires Ser264 and not the RGS domain and show both that mutation of the conserved RGS domain serine, Ser496 in RGS3, to either alanine or aspartate does not prevent binding of 14-3-3 proteins and that 14-3-3 proteins do not inhibit GTPase-activating protein (GAP) activity against receptor-activated Galpha(o1). However, mutation of Ser496 does directly impair the action of RGS3 as a GAP against receptor-activated Galpha(o1). We mutated the equivalent serine residue in the family B/R4 RGS proteins RGS1 and RGS16. Using two distinct assay formats, conversion to aspartate virtually abolished GAP activity, whereas conversion to alanine decreased potency 20-fold. Neither alteration modulated interactions with 14-3-3tau or 14-3-3zeta, but the 14-3-3 proteins did not modulate the GAP activity of the wild-type or mutant RGS proteins. Although interactions between 14-3-3 proteins and many RGS proteins can be observed, this does not involve this conserved serine and does not inherently modify GAP function.


[Body dysmorphic disorder and psychosis. Case reports and discussion].
The diagnosis of patients who have a preoccupation about physical ugliness is not easy. Many diagnoses can be made. Body dysmorphic disorder (BDD) is defined as a preoccupation with an imaginary defect in physical appearance. What seems difficult in this diagnosis is to make the difference between the psychotic and the non-psychotic form of the disorder. If the patient becomes delusional, we have to make the diagnosis of delusional disorder, somatic subtype. Sometimes it is not easy to make the difference between the delusional and non-delusional form of the illness. A good example is the so-called "olfactory reference syndrome" (ORS), which involves the persistent preoccupation with one's body odour. To make it more difficult, the preoccupation with one's appearance can be seen in many other disorders, such as schizophrenia, or major depressive disorders. We present three cases of dysmorphophobic patients, to discuss their diagnosis and show how we have to be careful about this delusional versus non-delusional difference. The first case is a young man, aged 20 year, who exhibits the typical picture of an ORS. He has probable olfactory hallucinations. He had good response to a treatment combining escitalopram 15mg and risperidone 1mg. The second case had a first appearance of BDD, but he had auditive hallucinations and the evolution showed a pattern more typical of schizophrenia, paranoid subtype. He responded initially to citalopram 20mg and ripseridone 2mg. Sleepy with risperidone, it was shifted to amisulpiride 200mg. After five years, it was possible to stop the amisulpiride, but we had to maintain it to avoid a relapse. The third case is typical of schizophrenia, with a pseudo neurotic aspect, and its course was terrible, with poor response to all neuroleptic therapy, including clozapine. These three cases are typical of a feature rarely reported in the literature: the delusional aspect of a dysmorphophobic concern. The literature mainly focuses on the more anxious pattern, and so emphasises the treatment with serotoninergic antidepressants. Our cases demonstrate a gradation in the delusional and psychotic aspect. The first case is dubitatively psychotic, the second is an "ambulatory" schizophrenia with a good response to treatment, the third a very destructive disease. In our cases, some features showed in the typical BDD are also present. We question the obsessive compulsive aspect of the disorder, which was present in our three cases. This supports the fact that the dysmorphophobic feature could be considered more like a symptom than a disorder itself. It reminds us to be always looking for the delusional features of a disorder so as to give the appropriate treatment.


Clinical utility of magnetic resonance imaging and ultrasonography for diagnosis of polycystic ovary syndrome in adolescent girls.
To evaluate ovarian morphology using three-dimensional magnetic resonance imaging (MRI) in adolescent girls with and without polycystic ovary syndrome (PCOS). Also compare the utility of MRI versus ultrasonography (US) for diagnosis of PCOS. Cross-sectional study. Urban academic tertiary-care children's hospital. Thirty-nine adolescent girls with untreated PCOS and 22 age/body mass index (BMI)-matched controls. Magnetic resonance imaging and/or transvaginal/transabdominal US. Ovarian volume (OV); follicle number per section (FNPS); correlation between OV on MRI and US; proportion of subjects with features of polycystic ovaries (PCOs) on MRI and US. Magnetic resonance imaging demonstrated larger OV and higher FNPS in subjects with PCOS compared with controls. Within the PCOS group, median OV was 11.9 (7.7) cm(3) by MRI compared with 8.8 (7.8) cm(3) by US. Correlation coefficient between OV by MRI and US was 0.701. Due to poor resolution, FNPS could not be determined by US or compared with MRI. The receiver operating characteristic curve analysis for MRI demonstrated that increasing volume cutoffs for PCOs from 10-14 cm(3) increased specificity from 77%-95%. For FNPS on MRI, specificity increased from 82%-98% by increasing cutoffs from ≥ 12 to ≥ 17. Using Rotterdam cutoffs, 91% of subjects with PCOS met PCO criteria on MRI, whereas only 52% met criteria by US. Ultrasonography measures smaller OV than MRI, cannot accurately detect follicle number, and is a poor imaging modality for characterizing PCOs in adolescents with suspected PCOS. For adolescents in whom diagnosis of PCOS remains uncertain after clinical and laboratory evaluation, MRI should be considered as a diagnostic imaging modality.


Changes in hypothalamic mu-opioid receptor expression following acute olanzapine treatment in female rats: Implications for feeding behavior.
Advances have been made in recent years in using opioid receptor antagonists as an adjunct therapy to psychotropic medication to reduce debilitating weight gain and metabolic adverse effects associated with in particular second generation antipsychotics. However, it is unknown whether second generation antipsychotics produce a change in opioid receptor expression in the brain. The present study investigated early changes in opioid receptor expression in the female rat hypothalamus, a master controller of hunger and metabolic regulation, after acute treatment with olanzapine, a commonly used second generation antipsychotic. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the three opioid receptors; kappa, mu and delta, were determined at mRNA and protein level, respectively, in the five hypothalamic areas: paraventricular nucleus, arcuate nucleus, ventromedial nucleus, dorsomedial nucleus and lateral hypothalamus. After 48 h of olanzapine treatment at clinically relevant plasma concentration weight gain and food intake changes, and increased plasma glucose were observed in female rats. Olanzapine treatment also led to a significant increase in mu opioid receptor availability in the arcuate nucleus, which contains both satiety and hunger controlling neurons. No other areas showed any opioid receptor expressional changes with olanzapine treatment on neither at mRNA nor protein level. Technical difficulties made it impossible to analyze mRNA levels in the lateral hypothalamus and overall binding of delta opioid receptors. Thus, the present study provided insights in to how olanzapine at clinically relevant plasma levels already at an early stage modulated the opioid system in the hypothalamus.


Effect of basic fibroblast growth factor (FGF2) on cumulus cell expansion, in vitro embryo production and gene expression in buffalo (Bubalus bubalis).
The present study was undertaken to evaluate the effect of different concentration of FGF2 viz. 5 ng (T1), 10 ng (T2), and 20 ng/mL (T3) on cumulus cell expansion, oocyte maturation, in vitro embryo production, total cell number (TCN) of the blastocyst, and expression of the FGF2 and FGFR2 transcripts in buffalo oocytes and the embryos. Results showed that the effect of FGF2 on the diameter of buffalo COC was significantly higher (P < 0.05) in the T1 group than the other groups at 24h of maturation. The maturation and cleavage rate of oocytes was significantly higher (P < 0.05) in the T3 group than the control, however, the values did not different (P> 0.05) from other groups. The effect of FGF2 on morula and blastocyst yield did not different (P > 0.05) between treatment groups. However, the TCN of the blastocyst was slightly higher (P > 0.05) in the T3 group than the control and other groups. In subsequent trials, the expression of the FGF2 transcript was higher (P < 0.05) in A-grade of oocytes than the C- and D-grade of oocytes, but the expression was not different (P> 0.05) from the B-grade of oocytes. While the FGFR2 expression was higher (P < 0.05) in cumulus cells than any grades of oocytes. The relative abundance of FGF2 and FGFR2 transcripts was significantly higher (P < 0.05) in the 2-cell stage of the embryo than the other stages of embryos. This study was further extended to characterize the FGF2 ligand-binding site in the D3 domain of the buffalo FGF2 receptor. Bioinformatics analysis showed that the bovine FGF2 ligand-binding site in the D3 domain of buffalo was different from the D3 domain of the cattle.


Facing the future for grassland restoration - What about the farmers?
In line with the 2010 Aichi Convention for Biological Diversity, the European Union has a goal to restore 15% of degraded ecosystems and their services by the year 2020 (target 2, Europe 2020). This includes restoration of semi-natural grasslands (SNGs). Management of both intact and restored SNGs is dependent on people's willingness to manage them. Due to low profitability, management abandonment still occurs all over Europe, which highlights the need to raise farmers' and landowners' perspectives. In this study, we combined survey data and in-depth interviews with farmers/landowners managing previously restored SNGs, to understand how they perceive the restoration process, the outcome and future management. Survey and interview data were analysed in relation to biodiversity and Agri-environmental payments data from the restored sites. Almost all respondents considered the restoration successful and the re-inventoried restored SNGs also showed an increase in plant diversity. Nevertheless, 10% of the restored SNGs were abandoned again post-restoration and 40% of the respondents were unsure if they would continue the management in the future. Abandoned management may cause a negative trend in terms of decreased biological, cultural and aesthetic values, in the local community, as well as for the society in general. Most respondents explained a strong dependency on Agri-environmental payments, both as a restoration incentive and for post-restoration management. Also non-financial support from authorities in form of feedback and advice was requested, as well as support from the local community and society as a whole. Future management in a longer time perspective was strongly coupled to the farm economy, i.e. received Agri-environmental payments at farm-level and profit from selling agricultural products, and whether the farmers had successors. We conclude that both social and ecological factors, here farm economy, authority support and proper management, must be in place for long-term success of grassland restoration.


Analysis of Heart Transplant Survival According to Difference in Age Between Donor and Recipient.
The age of heart transplant (HTx) donors and recipients is progressively increasing. The combination of donor-recipient ages has been shown to have prognostic implications. The objective of this study is to analyze survival in the first year and in the long-term based on the difference in age between donor and recipient of HTx. We performed a retrospective analysis of all consecutive HTxs performed in 1 center from 1987 to December 2021. Patients younger than 16 years, retransplants, and combined transplants were excluded. Three groups were considered according to the age of the donor and recipient: group 1: recipient and donor of the same age ± 10 years; group 2: donor >10 years older than recipient; and group 3: donor >10 years younger than recipient. A total of 841 HTxs were included (81% men, 31% urgent HTxs, donor mean (standard deviation) age 38.5 [12.3] years and recipient age 51.2 [12]). The most frequent group was group 3 with 476 patients (56%) followed by group 1 with 305 patients (36%). Figure 1 shows that long-term survival is similar in groups 1 and 2, being worse in group 3, P = .026. Mortality at the end of follow-up is 38.7% in group 1, 34.9% in group 2, and 71.9% in group 3 (P < .0001). These differences occurred in the long-term without finding significant differences the first year after HTx. No differences were found in early graft failure between the 3 groups. Using donors of a different age from the recipient does not seem to have an impact on long-term survival, except when donors are used who are more than 10 years younger than the recipient, where survival is lower. This consolidates the concept that the use of elderly donors does not affect survival, allowing the pool of donors to be expanded.


Reaction of bobwhites, coturnix quail, guinea fowl, and mallards to avirulent and virulent Pasteurella multocida.
The CU strain of Pasteurella multocida was moderately virulent for coturnix quail by the oral route and highly virulent for bobwhites by stick-wing. The strain was avirulent for guinea fowl and provided protective immunity by oral or stick-wing routes. Mallards did not react to virulent P. multocida.


Interpretation of HLA single antigen bead assays.
The introduction of single antigen bead (SAB) assays for detection and quantitation of HLA antibodies has improved our ability to identify and manage allosensitized transplant candidates and recipients and to improve organ allocation, and was critical to the creation of national paired kidney exchanges. The principal limitations of the technology have been detailed in the literature and include artifacts resulting in non-specific background, variability, lack of standardization, and interpretive challenges. Accurate interpretation of SAB assays requires consideration of a number of factors, including identification of epitope reactivity patterns, mean fluorescence intensity (MFI) values, patient history, and appreciation of individual bead and assay nuances. The MFI value provides an estimate of relative HLA antibody levels although limited by saturation and epitope distribution effects. A better understanding of SAB assays and MFI values will be necessary to ensure appropriate application of these assays clinically and a higher quality of antibody data used in support of published clinical studies.


Photophysics of DNA staining dye Propidium Iodide encapsulated in bio-mimetic micelle and genomic fish sperm DNA.
Photophysical processes in Propidium Iodide (PI), the well known DNA staining dye, have been exploited in homogeneous as well as heterogeneous medium by steady state and time resolved spectroscopy. The DNA staining dye PI exhibits intermolecular proton transfer reaction in aqueous and hydrogen-bonding acceptor solvents due to the formation of quinonoid structure which is acidic in nature. Time resolved emission spectroscopy also predicts the hydrogen bond donor ability of PI. The target dye interacts only with anionic surfactant sodium dodecylsulphate but not with cationic surfactant cetyltrimethylammonium bromide and neutral surfactant Triton X-100 and this interaction is found to be electrostatic in nature. We have further scrutinized the mode of binding of PI with fish sperm DNA. The effect of addition of urea, fluorescence quenching phenomenon, CD measurements reveal that the probe binds to DNA through intercalative style.


Coexistence of acute takotsubo syndrome and acute coronary syndrome.
Takotsubo syndrome (TS) is an acute cardiac condition with presentation indistinguishable from acute coronary syndrome (ACS), and mechanism independent of epicardial coronary obstruction. Acute coronary artery plaque rupture/occlusion is not expected in TS. Nonetheless, the physiologic stress of ACS might itself trigger TS, leading to coexistence of both conditions, and diagnostic uncertainty. From 2011 to 2014, we encountered 137 consecutive patients with typical TS (without acute coronary plaque rupture/occlusion). During this time, among a population of 3,506 consecutive ACS patients, nine (0.3%) presented with features of both ACS and TS, that is, acute onset, troponin elevation, acute plaque rupture/occlusion, and reversible LV ballooning not corresponding to culprit coronary distribution. The nine patients (seven female) with TS-ACS coexistence, average age 70 ± 13 years, presented with chest pain (n = 6), nausea/vomiting (n = 2), or cardiac arrest (n = 1), ST-elevation (n = 5), all with troponin elevation (peak 1.3 ± 1.2 ng/ml). Each had single vessel coronary disease; right coronary (n = 3), circumflex (n = 3), mid-LAD (n = 2), ramus intermedius (n = 1), with percutaneous coronary intervention in seven patients (78%). Initial ejection fraction was 26 ± 7%, with apical ballooning in eight patients and mid-LV ballooning in one patient. Each patient had LV ballooning resolution and ejection fraction normalization to 57 ± 3%, hospital survival was 89%. Among patients with ACS, a subset have evidence of coexisting TS, findings which further expand the clinical profile of both conditions, raising the possibility that ACS itself may trigger TS.


Synthesis, biological evaluation, and metabolic stability of chlorogenic acid derivatives possessing thiazole as potent inhibitors of α-MSH-stimulated melanogenesis.
A series of catechol and dioxolane analogs containing thiazole CGA derivatives have been synthesized and evaluated for their inhibitory activity against α-MSH. The inhibitory activity was improved by replacing an α,β-unsaturated carbonyl of previously reported caffeamides with thiazole motif. Surprisingly, compound 7d, one of the derivatives of dioxolane analogs, displayed the most potent inhibitory activity with an IC50 of 0.90μM. Further studies on metabolic stability and bioactivation potential were also accomplished.


Associations of systemic oxygen consumption with age and body temperature under general anesthesia: retrospective cohort study.
Body temperature (BT) is thought to have associations with oxygen consumption (VO2). However, there have been few studies in which the association between systemic VO2 and BT in humans was investigated in a wide range of BTs. The aims of this study were 1) to determine the association between VO2 and age and 2) to determine the association between VO2 and BT. This study was a retrospective study of patients who underwent surgery under general anesthesia at a tertiary teaching hospital. VO2 was measured by the Dräger Perseus A500 anesthesia workstation (Dräger Medical, Lubeck, Germany). The associations of VO2 with age and BT were examined using spline regression and multivariable regression analysis with a random effect. A total of 7,567 cases were included in this study. A linear spline with one knot shows that VO2 was reduced by 2.1 ml/kg/min with one year of age (p < 0.001) among patients less than 18 years of age and that there was no significant change in VO2 among patients 18 years of age or older (estimate: 0.014 ml/kg/min, p = 0.08). VO2 in all bands of BT < 36.0 °C was not significantly different from VO2 in BT > = 36 °C and < 36.5 °C. Multivariable linear regression analysis showed that compared with VO2 in BT > = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher by 0.57 ml/kg/min in BT > = 36.5 °C and < 37 °C (p < 0.001), by 1.8 ml/kg/min in BT > = 37 °C and < 37.5 °C (p < 0.001), by 3.6 ml/kg/min in BT > = 37.5 °C and < 38 °C (p < 0.001), by 4.9 ml/kg/min in BT > = 38 °C and < 38.5 °C (p < 0.001), and by 5.7 ml/kg/min in BT > = 38.5 °C (p < 0.001). The associations between VO2 and BT were significantly different among categorized age groups (p = 0.03). VO2 increases in parallel with increase in body temperature in a hyperthermic state but remains constant in a hypothermic state. Neonates and infants, who have high VO2, may have a large systemic organ response in VO2 to change in BT.


Platelet-fibrin interaction in the suspension and under flow conditions.
Interactions between platelets and fibrin are important in hemostasis but often confused with platelet-fibrinogen interactions. A stirred mixture of solubilized fibrin and washed platelets at neutral pH range showed drastic reduction in turbidity and concomitant platelet adhesion onto newly formed fibrin strands. This platelet-fibrin interaction did not require platelet activation nor did it cause platelet aggregation. A device consisting of a parallel-plate flow chamber mounted on a fluorescence microscope has been constructed to allow direct visualization and recording of platelet-fibrin interaction under flow conditions. Platelets in whole blood adhered to the fibrin-coated portion but not to the uncoated portion of the flow chamber. Slow motion playback of video tapes indicated that the adhesion phenomenon was a dynamic process that involved attaching, detaching, relocation and transient contact. The fibrin coating influenced platelet adhesion both by increasing the number of cells making short-term attachments to the surface and by increasing the duration of cells attached to the surface. These observations provided basic characteristics of platelet-fibrin interaction.


Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC).
To compare the efficacy and safety of CAPIRI+bevacizumab (Bev) in comparison with FOLFIRI+Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC). Patients were randomised to receive either FOLFIRI plus Bev 5 mg kg(-1) every 2 weeks (Arm-A) or CAPIRI plus Bev 7.5 mg kg(-1) every 3 weeks (Arm-B). Three hundred thirty-three patients (Arm-A=167; Arm-B=166) were enrolled into the study. No difference was observed in median progression-free survival (PFS) (10.0 and 8.9 months; P=0.64), overall survival (25.7 and 27.5 months; P=0.55) or response rates (45.5 and 39.8.7%; P=0.32) for FOLFIRI-Bev and CAPIRI-Bev, respectively. Patients treated with CAPIRI-Bev presented significantly higher incidence of diarrhoea (P=0.005), febrile neutropenia (P=0.003) and hand-foot skin reactions (P=0.02) compared with patients treated with FOLFIRI-Bev. Treatment delays (P=0.05), dose reduction (P<0.001) and treatment discontinuation owing to toxicity (P=0.01) occurred more frequently in the CAPIRI-Bev arm. The PFS of FOLFIRI-BEV is not superior to that observed with the CAPIRI-Bev regimen. CAPIRI-Bev has a less favourable toxicity profile, requiring dose reductions, in order to be considered as an option in first-line treatment of patients with mCRC.


Oxidative stress, growth inhibition, and DNA damage in earthworms induced by the combined pollution of typical neonicotinoid insecticides and heavy metals.
Heavy metals pollution of soil and widespread application of neonicotinoid insecticides have caused environmental problems worldwide. To evaluate ecological toxicity resulting from the combined pollution of neonicotinoids and heavy metals, typical representatives of neonicotinoid insecticides (imidacloprid, thiamethoxam, dinotefuran) and heavy metals (cadmium, copper, zinc) were selected as soil pollutants; earthworms were used as test organisms. Analysis of the main and interaction effects of a combined pollution process were performed using a uniform design method. Results showed that the reactive oxygen species (ROS) content of earthworms in most treatment groups was higher during exposure than that of the control group. The malondialdehyde (MDA) and ROS content of earthworms demonstrated relatively low values on the 21st day and increased by the 28th day. The interaction between dinotefuran and Cd had significant antagonistic effects on ROS and MDA. The combined pollution adversely affected both the growth and genes of earthworms and also caused damage to the epidermis, midgut, and DNA. The interaction between imidacloprid and Cd was synergistic to ROS, weight inhibition rate, and Olive tail moment (OTM), but was antagonistic to MDA. Of all the single and combined exposures, Zn as a single chemical affected ROS and DNA damage the most, and MDA was significantly enhanced by imidacloprid. Composite pollutants may create different primary effects and interactions causing potential harm to soil organisms.


CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia/lymphoma.
Cell adhesion molecule 1 (CADM1), initially identified as a tumor suppressor gene, has recently been reported to be ectopically expressed in primary adult T-cell leukemia-lymphoma (ATL) cells. We incorporated CADM1 into flow-cytometric analysis to reveal oncogenic mechanisms in human T-cell lymphotrophic virus type I (HTLV-I) infection by purifying cells from the intermediate stages of ATL development. We isolated CADM1- and CD7-expressing peripheral blood mononuclear cells of asymptomatic carriers and ATLs using multicolor flow cytometry. Fluorescence-activated cell sorted (FACS) subpopulations were subjected to clonal expansion and gene expression analysis. HTLV-I-infected cells were efficiently enriched in CADM1(+) subpopulations (D, CADM1(pos)CD7(dim) and N, CADM1(pos)CD7(neg)). Clonally expanding cells were detected exclusively in these subpopulations in asymptomatic carriers with high proviral load, suggesting that the appearance of D and N could be a surrogate marker of progression from asymptomatic carrier to early ATL. Further disease progression was accompanied by an increase in N with a reciprocal decrease in D, indicating clonal evolution from D to N. The gene expression profiles of D and N in asymptomatic carriers showed similarities to those of indolent ATLs, suggesting that these subpopulations represent premalignant cells. This is further supported by the molecular hallmarks of ATL, that is, drastic downregulation of miR-31 and upregulation of abnormal Helios transcripts. The CADM1 versus CD7 plot accurately reflects disease progression in HTLV-I infection, and CADM1(+) cells with downregulated CD7 in asymptomatic carriers have common properties with those in indolent ATLs.


Antigenic differences between clinical and environmental isolates of Burkholderia pseudomallei.
Burkholderia pseudomallei is a free-living organism that causes the potentially lethal tropical infection melioidosis. The disease is endemic in many parts of eastern Asia and northern Australia. The presence of two distinct biotypes in soil can be reliably distinguished by their ability to assimilate L-arabinose. Whereas some soil isolates could utilize this substrate (Ara+), the remaining soil isolates and all clinical isolates tested so far could not (Ara-). Only the Ara- isolates were virulent in animal models. We have raised a murine monoclonal antibody (MAb) that can readily distinguish Ara- from Ara+ biotypes. The MAb reacted with a high molecular weight component present only on the Ara- biotype. With this MAb, clinical and soil Ara- isolates gave identical positive reactions in agglutination, immunofluorescence, ELISA and immunoblot assays. Using these same assay systems, the soil Ara+ biotype did not react with the MAb. Similar but distinct immunoblot patterns were also noted when these two Ara biotypes were probed with sera from patients with melioidosis or with polyclonal immune rabbit sera. These data showed that the Ara- biotype from both clinical and environmental isolates is antigenically different from its Ara+ environmental counterpart. The SDS-PAGE protein and lectin-binding profiles of both groups of Ara- isolates were also found to be different from those of the Ara+ biotype.


Reducing the risk of iodine-based and MRI contrast media administration: recommendation for a questionnaire at the time of booking.
This paper presents a practical questionnaire to be used when a contrast medium examination is requested. The questionnaire is based on the guidelines from the European Society of Urogenital Radiology. Its aim is to identify patients at increased risk of clinically relevant renal and non-renal adverse reactions to iodine-based and MRI contrast agents. The questionnaire should be completed by the referring physician when the examination is requested.


Characterization of late gene expression factor LEF-10 from Bombyx mori nucleopolyhedrovirus.
The LEF-10 expression factor from the Bombyx mori nuclear polyhedrosis virus (BmNPV) does not have significant homology with other late expression factors and is thought to be a transcriptional cofactor. To investigate the function of LEF-10, a Red recombination system was used to knock out the lef-10 gene from the BmNPV genome and a lef-10 gene knockout virus (ko-Bacmid) was constructed. The lef-10 gene was repaired back to the viral genome using a Bac-to-Bac system to create the repaired virus (re-Bacmid). When ko-Bacmid was transfected into BmN cells, the detected titer of progeny virus in the medium was zero, whereas the titer of the progeny re-Bacmid remained at a level similar to that of the wild type virus (wt-Bacmid). The viral DNA replication, transcription and expression of viral early, late and very late genes after ko-Bacmid transfection into BmN cells were evaluated. The quantitative polymerase chain reaction showed that the ko-Bacmid viral genome replication level remained low and that the ko-Bacmid viral gene transcription level was significantly lower than those of wt-Bacmid and re-Bacmid. No expression of the early gene lef-3 was detected. These results suggest that the lef-10 gene has significant effects on DNA replication of the viral genome and BmNPV gene transcription at each phase and deletion of the lef-10 gene affects the level of expression of the viral early gene directly.