Recurring pleural effusion secondary to walled-off pancreatic necrosis.
Recurring, exudative, lymphocytic-predominant pleural effusions have not been previously reported in association with walled-off pancreatic necrosis. We present a case of chronic pancreatitis complicated by a large pancreatic fluid collection and recurrent pleural effusion. Endoscopic drainage of the walled-off pancreatic necrosis was the definitive treatment for both fluid collections.


Orally active iron chelators in the treatment of iron overload.
Data from several trials have provided evidence for the efficacy of deferiprone in the treatment of iron overload in thalassemia major. Deferiprone has now been shown to induce sustained decreases in tissue iron to concentrations that are associated with survival free of the complications of iron overload in deferoxamine-treated patients. Despite this evidence of efficacy, the risk of agranulocytosis mandates a careful evaluation of the risk of this drug in patients willing and able to use deferoxamine. The incidence of agranulocytosis associated with deferiprone is under study in a prospective multicenter trial in Canada, Italy, and the United States, under corporate sponsorship by Apotex Research in Canada. The results of this study should determine the risk associated with the use of this agent and may provide the data required for a US Food and Drug Administration decision regarding licensing of this agent for the treatment of iron overload, a goal supported by investigators worldwide.


Differentiation of the health behavior patterns related to prostate cancer screening among African-American men in military settings.
The objectives of this study were to identify, describe, classify, and differentiate African-American men (AAM) in military settings according to the frequency with which they regularly, infrequently, or did not screen for prostate cancer using factors of the Health Belief Model. Participants in the study included 147 military health care beneficiaries who were AAM 40 years of age and older. Self-reporting questionnaires were used to collect data pertaining to the objectives. The results revealed that 85% of the men reported having screened for prostate cancer and more than 54% of them reported screening "annually." Discriminant analysis statistics revealed that age, education, and "perceived benefits" of the digital rectal examination and the prostate-specific antigen test best differentiated AAM who screened annually compared with nonscreeners. Educating AAM on the benefits and efficacy of the digital rectal examination and prostate-specific antigen tests may be helpful in increasing screening practices in this high-risk group.


A Mini Zinc-Finger Protein (MIF) from Gerbera hybrida Activates the GASA Protein Family Gene, GEG, to Inhibit Ray Petal Elongation.
Petal appearance is an important horticultural trail that is generally used to evaluate the ornamental value of plants. However, knowledge of the molecular regulation of petal growth is mostly derived from analyses of Arabidopsis thaliana, and relatively little is known about this process in ornamental plants. Previously, GEG (Gerbera hybrida homolog of the gibberellin [GA]-stimulated transcript 1 [GAST1] from tomato), a gene from the GA stimulated Arabidopsis (GASA) family, was reported to be an inhibitor of ray petal growth in the ornamental species, G. hybrida. To explore the molecular regulatory mechanism of GEG in petal growth inhibition, a mini zinc-finger protein (MIF) was identified using yeast one-hybrid (Y1H) screen. The direct binding of GhMIF to the GEG promoter was verified by using an electrophoretic mobility shift assay and a dual-luciferase assay. A yeast two-hybrid (Y2H) revealed that GhMIF acts as a transcriptional activator. Transient transformation assay indicated that GhMIF is involved in inhibiting ray petal elongation by activating the expression of GEG. Spatiotemporal expression analyses and hormone treatment assay showed that the expression of GhMIF and GEG is coordinated during petal development. Taken together, these results suggest that GhMIF acts as a direct transcriptional activator of GEG, a gene from the GASA protein family to regulate the petal elongation.


Comparison of transperitoneal versus retroperitoneal approach in laparoscopic radical nephrectomy for renal cell carcinoma: a single-center experience of 63 cases.
We report our experience with the retroperitoneal (RP) and transperitoneal (TP) approaches for laparoscopic nephrectomy for clinically localized renal cell carcinoma. Sixty-three patients with renal cell carcinoma were treated with laparoscopic nephrectomy, 34 by TP and 29 by RP approach between June 1999 and June 2003. Average age, ASA score, tumor stage and tumor size were similar in both groups. Early complications within 30 days and surgical time were retrospectively reviewed. Surgical time was with a mean of 183 and 190 minutes equal for the TP and RP approach. Intraoperative complications occurred in 4 patients and were vascular, requiring blood transfusion in 2 patients each per group. Postoperative complications were thromboembolism in 1 patient and subcutaneous seroma in 1 patient, both in the TP group. Although the sample size is small, it appears that the tumor control and surgical time in laparoscopic nephrectomy are not significantly influenced by the approach.


Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters.
Prenatal testing was offered in all pregnancies obtained after ICSI with ejaculated or non-ejaculated sperm as part of the evaluation of the safety of ICSI. Between 1990 and 2001, a chorionic villus sampling (CVS) or amniocentesis was offered for multiple or singleton pregnancies respectively during a genetic counselling session for all couples applying for ICSI. ICSI was carried out using ejaculated, epididymal or testicular sperm. In total, 1586 ICSI fetuses obtained after fresh embryo transfer were tested by CVS (n = 698) or by amniocentesis (n = 888). Abnormal fetal karyotypes were found in 47 samples [3.0%; 95% confidence interval (CI) 2.2-3.9%]; 25 anomalies (1.6%; 95% CI 1.0-2.3%) were de novo. These were 10 sex chromosomal anomalies and 15 autosomal anomalies [either numerical (n = 8) or structural (n = 7)], and 22 inherited abnormalities (1.4%; 95% CI 0.9-2.1%) (21 balanced, one unbalanced). In 17/22 inherited cases the chromosomal structural defect was inherited from the father. A significantly higher percentage of 2.1% de-novo prenatal chromosomal anomalies was observed for sperm concentrations of <20x10(6) sperm per ml, as compared with 0.24% if the sperm concentration was vertical line 20x10(6) sperm per ml (Fisher's exact test, P = 0.006). No statistical difference in frequency of chromosomal anomalies was observed for lower threshold values of sperm concentration (<1x10(6), <5x10(6), <10x10(6) and <15x10(6)). A statistical difference was observed for motility criteria, but not morphology. Three chromosomal anomalies were found prenatally after use of epididymal or testicular sperm in a total of 94 samples; two (of 83 tested) were from patients with obstructive and one (of nine tested) was from a patient with non-obstructive azoospermia. A significantly higher rate of de-novo chromosomal anomalies (1.6 versus 0.5% in amniocentesis for a mean maternal age of 33.5 years; P < 0.007) was observed in ICSI offspring, relating mainly to a higher number of sex chromosomal anomalies and partly to a higher number of autosomal structural anomalies. This finding was related to sperm concentration and motility. The significantly higher rate of observed inherited anomalies (1.4 versus 0.3-0.4% in prenatal tests in the general population; P < 0.001) was related to a higher rate of constitutional chromosomal anomalies, mainly in the fathers. The hypothesis of a higher risk of post-zygotic events as a consequence of the ICSI procedure leading to a higher proportion of chromosomal mosaicism was not confirmed in this study. Couples should be informed of the risks of an abnormal result related to sperm quality, and of the risk linked to a prenatal procedure as well as about the relatively benign character of some chromosomal anomalies such as de-novo structural anomalies or sex chromosomal anomalies in order to be able to make a choice for prenatal testing, or not.


Reflections on the Concomitants of the Restrictive Visitation Policy During the COVID-19 Pandemic: An Ubuntu Perspective.
Caregiving is a prominent concept in the Ubuntu philosophy, and caring and visitation of the sick is regarded as an example of Ubuntu. The restrictive visitation policy adopted in the hospitals during the coronavirus disease 2019 (COVID-19) pandemic affected the exhibition of this concept among patients, nurses, and families. The narrative inquiry was used to explore the reflections of the participants on the impact caused by the non-visitation policy experienced during the first and second waves of the COVID-19 pandemic in South Africa. The narrative inquiry approach allowed the participants to tell their story as it is unique to them. The study used purposive sampling technique to select five participants for the webinar. Three themes emerged from the narrated stories which are 1) moral anguish of the caregivers; 2) mental health instability, and 3) erosion of trust in health care practitioners (HCPs). The non-visitation hospital policy was intended to reduce the danger of spreading COVID-19 within and outside the hospital; however, the care provided was devoid of the values of Ubuntu such as mutual respect, relational, responsibility, reciprocity, and interconnectedness. In retrospect, a case-by-case application of the policy would reduce the non-desirable effect of the policy on the patients, nurses, and patients' family members.


Huge Langerhans cell histiocytosis granuloma of choroid plexus in a child with Hand-Schüller-Christian disease. Case report.
In the literature, only two previous cases of presumed Langerhans cell histiocytosis (LCH) granuloma involving choroid plexus have been reported in patients with Hand-Schüller-Christian (HSC) disease, but those cases were not verified by immunohistochemistry or electron microscopy. The authors report a case of LCH granuloma of the choroid plexuses of bilateral lateral ventricles and the fourth ventricle in a child affected by HSC disease. This disease was confirmed by the presence of Birbeck granules on electron microscopy and positive reactivity to S-100 protein. Clinical, radiographic, and histological features are discussed. This case illustrates that LCH granuloma should be considered in the differential diagnosis of intraventricular masses.


[Oral health promotion for children in boarding schools].
In Israel there are approximately 9,000 "sheltered" children who are lodged in several boarding schools. These children have been removed from their parents' guardianship, some with their parents permission and some by court order, usually due to neglect or abuse. This article describes these children and the efforts implemented regarding oral health: dental care insurance, a preventive program which has been conducted for approximately 10 years among 80 boarding schools and family care shelters, evaluation of these services and caries levels among the children. A sample of 123 children was examined in four Israeli boarding schools. The DMF(T) index was employed according to WHO guidelines, by one examiner, using a torch, plane dental mirror and probe when required. An average DMF(T) level of 4.62 was detected among 12 year olds. Among all the children from ages 1-18 years, only 30% were caries free. The rate of caries-free children decreased with age. Caries prevalence among this population was higher than levels reported in Israel and abroad. There is a clear need for oral health promotion among this community.


Note: Fabrication of tapered fibre tip using mechanical polishing method.
Tapered fibre tips fabricated using mechanical polishing method is studied. The fibre tips are formed by sequential polishing flat-ended single mode fibres with decreasing aluminium oxide polishing film grit size. Based on the proposed technique, tapered fibre tips with cone angle ranging from 30° to 130° are fabricated by controlling the polishing angle. Besides the variety of cone angle, considerable smoothness of the fibre tip surface may assist in good metal coating and hence a well-defined aperture can be obtained. In addition, this paper presents a two-step hybrid fabrication method combining the proposed polishing method with chemical etching method to increase the possible fibre tip cone angles achievable by chemical etching method.


Effects of general anesthesia on plasma colloid oncotic pressure in dogs.
To determine the magnitude of the change in colloid oncotic pressure (COP) associated with general anesthesia in dogs undergoing a variety of elective procedures. Cohort study. 50 client-owned dogs. For each dog, preanesthetic and postanesthetic PCV, plasma total solids (TS) concentration, and COP were determined. The procedures requiring anesthesia, volume of crystalloid fluids administered IV, duration of anesthesia, age, weight, and sex were recorded. Postanesthetic PCV (mean +/- SD, 41.8 +/- 5.4%), TS concentration (6.3 +/- 0.8 g/dL), and COP (19.4 +/- 3.6 mm Hg) were significantly decreased, compared with preanesthetic values (48.8 +/- 5.9%, 7.2 +/- 0.7 g/dL, and 24.4 +/- 4.2 mm Hg, respectively). None of the variables tested could be used to reliably predict changes in COP. Results suggested that COP in healthy dogs may decrease by 5 mm Hg on average after general anesthesia and that this decrease may not be reliably predicted by the volume of fluids administered IV during anesthesia or by the concurrent measured decrease in TS concentration.


The management of otolaryngological problems in the mucopolysaccharidoses: a retrospective review.
The mucopolysaccharidoses are rare, genetically transmitted metabolic disorders that affect children early in life. These potentially life-threatening diseases almost invariably involve the auditory apparatus and the upper respiratory tract. Thus, the otolaryngologist is frequently involved in the care of these patients. This paper presents a 10-year retrospective review of the management of these patients at the Hospital for Sick Children. Data concerning auditory and upper respiratory pathology are presented. Results indicate that persistent serous otitis, sensorineural hearing loss, and upper respiratory obstruction leading to sleep apnea, are frequent findings in these patients. Specific recommendations are made with regard to appropriate otolaryngologic intervention in children affected with these diseases.


In vivo stimulation of platelet production in a primate model using IL-1 and IL-3.
The in vivo administration of various cytokines for hematopoietic stimulation has led primarily to the enhancement of the myeloid response with an insignificant contribution toward stimulating any increase in platelet production. Current studies have suggested that interleukin 1 (IL-1) and interleukin 3 (IL-3) are two of several factors that have an effect on either megakaryocyte formation or platelet production. The objective of our research was to investigate how the in vivo administration of IL-1 or IL-3 or a combination could be used to regulate megakaryocytopoiesis and platelet production in nonhuman primates. A single dose of IL-1 was able to stimulate an increase in platelet production for 3 weeks. The response was shown to be biphasic, with increased platelet counts of 46% and 49% above baseline on days 8 and 17, respectively. In contrast, the administration of IL-3 for 6 days led to an increase of 29% above baseline on day 17. An interesting observation was that the increased platelet counts were accompanied by a transient increase in the peripheral blood of a highly proliferative megakaryocyte colony-forming cell (MK-CFC), which attained a maximum concentration on day 7. The administration of a sequential combination of IL-1, then IL-3, was further evaluated to elucidate a possible potentiation on platelet production. The result was a similar increase in platelets to that observed in IL-1-only-treated monkeys for the first 7 days. However, the most significant effect was observed on day 17, when the 85% increase in platelets was demonstrated to be additive of the single-agent effects on that day. A reversal in the order of cytokine administration did not affect platelet production in this manner. In IL-1, then IL-3-treated monkeys, the increased platelet counts were also accompanied by an increase in the concentration of the peripheral blood MK-CFC from days 7 through 14. These results demonstrate that a combination of factors may be required to enhance platelet production, stimulating not only the formation of megakaryocytes but also stimulating the production and release of platelets into the peripheral blood.


Sample Size Planning for Detecting Mediation Effects: A Power Analysis Procedure Considering Uncertainty in Effect Size Estimates.
When planning mediation studies, researchers are often interested in the sample size needed to achieve adequate power for testing mediation. Power depends on population effect sizes, which are unknown in practice. In conventional power analysis, effect size estimates, however, are often used as population values, which could result in underpowered studies. Uncertainty in effect size estimates has been considered in other sample size planning contexts (e.g., t-test, ANOVA), but has not been handled properly for planning mediation studies. In the current study, we proposed an easy-to-use sample size planning method for testing mediation with uncertainty in effect size estimates considered. We conducted simulation studies to demonstrate the impact of uncertainty in effect size estimates on power of testing mediation, and to provide sample size suggestions under different levels of uncertainty. Empirical examples were provided to illustrate the application of our method. R functions and a web application were developed to facilitate implementation.


Does integrated governance lead to integrated patient care? Findings from the innovation forum.
Good integration of services that aim to reduce avoidable acute hospital bed use by older people requires frontline staff to be aware of service options and access them in a timely manner. In three localities where closer inter-organisational integration was taking place, this research sought patients' perceptions of the care received across and within organisational boundaries. Between February and July 2008, qualitative methods were used to map the care journeys of 18 patients (six from each site). Patient interviews (46) covered care received before, at the time of and following a health crisis. Additional interviews (66) were undertaken with carers and frontline staff. Grounded theory-based approaches showed examples of well-integrated care against a background of underuse of services for preventing health crises and a reliance on 'traditional' referral patterns and services at the time of a health crisis. There was scope to raise both practitioner and patient awareness of alternative care options and to expand the availability and visibility of care 'closer to home' services such as rapid response teams. Concerns voiced by patients centred on the adequacy of arrangements for organising ongoing care, while family members reported being excluded from discussions about care arrangements and the roles they were expected to play. The coordination of care was also affected by communication difficulties between practitioners (particularly across organisational boundaries) and a lack of compatible technologies to facilitate information sharing. Finally, closer organisational integration seemed to have limited impact on care at the patient/practitioner interface. To improve care experienced by patients, organisational integration needs to be coupled with vertical integration within organisations to ensure that strategic goals influence the actions of frontline staff. As they experience the complete care journey, feedback from patients can play an important role in the service redesign agenda.


Detection of prognostic factors for oral allergy syndrome in patients with birch pollen hypersensitivity.
To determine why a significant proportion of birch pollen-sensitive patients do not have the oral allergy syndrome (OAS), possible predictive in vivo or in vitro tests for OAS were sought in a large retrospective and prospective follow-up study performed in 283 patients with clinical evidence of birch pollen hypersensitivity. OAS was associated with more severe respiratory symptoms and with higher birch-specific and total IgE levels; moreover, its onset was clearly related to duration of birch pollinosis. The prospective part of this study, performed in 63 patients without OAS, confirmed these findings and highlighted the very high negative predictive value of both skin prick tests with fresh foods and RAST with food allergens. This work suggests that about 15% of patients with birch pollen hypersensitivity are not prone to OAS and that their anti-birch IgE might be directed against determinants that do not crossreact with food allergens.


A longitudinal study of developmental and behavioral screening and referral in North Carolina's Assuring Better Child Health and Development participating practices.
Screening children for developmental and behavioral delays is an important part of primary care practice. Well-child visits provide an ideal opportunity to engage parents and to do periodic screening. Screening identifies children who may be at risk and need further evaluation. In North Carolina's Assuring Better Child Health and Development project best-practices process, screening was incorporated as a routine part of well-child visits regardless of payor. The schedule of screenings, using the Ages and Stages Questionnaire, was 6, 12, 18 or 24, 36, 48, and 60 months. From the practices' population, a cohort of 526 children, screened from the age of 6 months during August 2001 through November 2003, was retrospectively reviewed. The main objectives of this descriptive study were to determine the number of children who were screened and whether this rate improved with time, observe patterns and trajectories for children identified at risk in 1 or more of the 5 developmental domains, and examine referral rates and physician referral patterns.


[Effects of Mycobacterium tuberculosis on apoptosis of mouse dendritic cells and activation of caspase-3, caspase-8].
To investigate the effects of Mycobacterium tuberculosis on apoptosis of mouse dendritic cells (DC 2. 4) and the activation of caspase-3, caspase-8. Mycobacterium tuberculosis H37Rv strain was co-cultured with DC 2. 4 cells. The morphological changes of DC 2. 4 cells were observed with fluorescence microscope after DAPI staining and transmission electron microscope. The apoptosis of DC 2. 4 cells were examined by DNA agarose gel electrophoresis. The activities of caspase-3 and caspase-8 were detected by colorimetric assay. Bacterial invasion was observed while DC 2. 4 cells and H37Rv were co-cultured for 2 h; and the rates of invasion were (16.1 ± 4.3)%, (35.8 ± 5.1)%, (50.2 ± 5.7)%, (58.3 ± 6.2)% and(65.9 ± 6.9)% at 4, 6, 8,10, 12 h, respectively. The phenomenon of nuclear condensation and marginalization were shown by DAPI staining and transmission electron microscope in DC 2. 4 cells at 6 h of co-cultivation with H37Rv. The characteristic bands of apoptosis by DNA electrophoresis were detected. The activities of caspase-3 and caspase-8 were increased in a time-dependent manner. The rates of DC 2. 4 cell apoptosis were (6.4 ± 2.5)%, (11.8 ± 5.3)% and (31.1 ± 8.7)% at 6 h,12 h and 24 h after co-cultivation with H37Rv, respectively. The maximal activities of intracellular caspase-3 and caspase-8 at 10 h and 6 h were (2.01 ± 0.09) U/μg and (2.40 ± 0.07)U/μg, respectively, which was significantly different compared with the control groups(P<0.05). The activation of caspase-8 was earlier than that of caspase-3. Mycobacterium tuberculosis can induce the apoptosis of DC 2. 4 cells, which is associated with the activation of intracellular caspase-3 and caspase-8.


Abnormal P600 in heroin addicts with prolonged abstinence elicited during a working memory test.
The P600 component of event-related potentials, believed to be generated by anterior cingulate gyrus and basal ganglia, is considered as an index of aspects of second-pass parsing processes of information processing, having much in common with working memory (WM) systems. Moreover, dysfunction of these brain structures as well as WM deficits have been implicated in the pathophysiology of opioid addicts. The present study is focused on P600 elicited during a WM test in twenty heroin addicts with prolonged abstinence compared with an equal number of healthy controls. The results showed significantly prolonged latencies at right hemisphere, specifically at Fp2 abduction. Moreover, memory performance of patients did not differ from that of normal controls. These findings may indicate that abstinent heroin addicts manifest abnormal aspects of second-pass parsing processes as are reflected by the P600 latencies, elicited during a WM test. Additionally, the P600 might serve as a valuable investigative tool for a more comprehensive understanding of the neurobiological substrate of drug abuse.


Influence of the Dissolved Gas on the Interfacial Properties of Decane Surface Nanodroplets.
Surface nanodroplets have received extensive attention recently due to their potential in the fabrication of functional materials with nanostructures and chemical reactions at micro- and nanoscales. Although the effect of dissolved gas in water has been realized in some important processes such as spontaneous emulsification of oil droplets in water, its roles in the wetting behavior of surface nanodroplets at the hydrophobic interface have been largely neglected. Here, we focused on the influence of dissolved gas on the interfacial properties of surface nanodroplets and characterized their morphological evolution when exposed to different air-saturated water samples. Results indicated that the morphology of surface nanodroplets barely changed in air-oversaturated cold water. However, their contact angle first decreases gradually in deionized water, increases immediately after replacement with degassed water, and eventually decreases gradually with time. Furthermore, the surface tension of nanodroplets would change similarly after the injection of degassed water. We considered these changes to be caused by the removal or reduction of the enriched gas at the substrate interface, in which the surface hydrophobicity was changed. Our findings could shed some light on the wetting behavior of nanodroplets at the hydrophobic surface in different air-saturated water samples and inspire the microscale manipulation and reaction of surface nanodroplets.


Coping style, social support and psychological distress in the general Chinese population in the early stages of the COVID-19 epidemic.
The purpose of this study was to investigate the psychological status of the general population in mainland China during the outbreak of coronavirus disease 2019 (COVID-19), and to explore the factors influencing psychological distress, in order to provide the basis for further psychological intervention programs. We administered three questionnaires on-line to a convenience sample of the general population from different regions of mainland China from February 1 to February 4, 2020. We used the Mandarin versions of the six-item Kessler psychological distress scale (K6), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). We also collected demographic data and other information related to the COVID-19 outbreak. Multivariate binary logistic regression analysis was used to identify factors influencing psychological distress. Of 1607 respondents, 1588 returned valid questionnaires and were included in the analysis. Nearly one quarter (22.8%) had high levels of psychological distress (K6 score ≥ 13). Individuals with higher psychological distress were more likely to be unmarried, spend more than 6 h per day searching for information about COVID-19, more frequently adopt a passive coping style, and report less social support than those with lower psychological distress. The COVID-19 outbreak in China has a great impact on the mental health status of the general population. Active coping strategies and increased social support are significantly correlated with decreased psychological distress, and may serve as the basis for psychological interventions.


[Influence of hemodialysis on total and free malondialdehyde measured by a new HPLC method].
Accurate evaluation of oxidative stress is needed for patients on chronic hemodialysis (HD), as cardiovascular risk level seems related to it. Oxidative stress is often evaluated by measuring an end product of lipoperoxidation named malondialdehyde (MDA). However, the most common technique for measuring MDA, the Thio Barbituric Acid Reactive Substances method (TBARS), is known to be sensitive but poorly specific. We measured true total and free plasma MDA in fifty-four unselected patients on long-term HD, before and after HD sessions, by a new, highly specific HPLC method. Total and free MDA were higher before than after dialysis. Essentially, free MDA was decreased by HD but its fractional decrease was lower than that of urea or creatinine. This confirms that, in fact, free MDA is more or less bound to low molecular weight compounds and/or suggests that MDA may be produced mainly during HD sessions. We propose this new tool to further explore the relationship between oxidative stress, HD and true MDA.


Developmental toxicity study of piperonyl butoxide in CD rats.
Piperonyl butoxide was administered to pregnant rats by gavage at a level of 0 (control), 630, 1065, and 1800 mg/kg bw on days 11-12 of gestation. The animals were killed on day 20 of gestation. Average maternal body weight gain (gestational days 11-20) was significantly reduced in the 1065 and 1800 mg/kg bw groups. Total resorption rate was significantly increased in the 1800 mg/kg bw group and those effects were significantly dose-related. The average fetal body weight of each sex was significantly reduced in the 1065 and 1800 mg/kg bw groups. External limb deformity (oligodactyly, syndactyly, and polydactyly) was significantly increased in the 1065 and 1800 mg/kg bw groups in a dose-related manner. The dose levels of piperonyl butoxide in the present study produced limb deformities in rats.


Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice.
Alzheimer's disease (AD) is associated with accumulations of amyloid-beta (Abeta) peptides, oxidative damage, mitochondrial dysfunction, neurodegeneration, and dementia. The mitochondrial antioxidant manganese superoxide dismutase-2 (Sod2) might protect against these alterations. To test this hypothesis, we inactivated one Sod2 allele (Sod2(+/-)) in human amyloid precursor protein (hAPP) transgenic mice, reducing Sod2 activity to approximately 50% of that in Sod2 wild-type (Sod2(+/+)) mice. A reduction in Sod2 activity did not obviously impair mice without hAPP/Abeta expression. In hAPP mice, however, it accelerated the onset of behavioral alterations and of deficits in prepulse inhibition of acoustic startle, a measure of sensorimotor gating. In these mice, it also worsened hAPP/Abeta-dependent depletion of microtubule-associated protein 2, a marker of neuronal dendrites. Sod2 reduction decreased amyloid plaques in the brain parenchyma but promoted the development of cerebrovascular amyloidosis, gliosis, and plaque-independent neuritic dystrophy. Sod2 reduction also increased the DNA binding activity of the transcription factor nuclear factor kappaB. These results suggest that Sod2 protects the aging brain against hAPP/Abeta-induced impairments. Whereas reductions in Sod2 would be expected to trigger or exacerbate neuronal and vascular pathology in AD, increasing Sod2 activity might be of therapeutic benefit.


Polysiloxanes in Theranostics and Drug Delivery: A Review.
One of the historical problems of medicine is that often, diagnosis and therapy do not interface, at best. Moreover, especially in some areas, such as oncology, the stress for the organism during the two phases (diagnosis and therapy) can become excessive, and be fatal to the success of the treatment. The extraordinary progress of nanotechnology in the last 25 years has offered the opportunity to build a nanoplatform able to ferry drugs, and loads onto them both imaging and therapeutic functions, thus creating nanosystems capable of diagnosis, drug delivery, and monitoring of therapeutic response. The purpose of this unusual, and up to recent times, unimaginable, marriage between diagnosis and therapeutics is the reaching of protocols more specific to individuals. The dual use of particles/device lead to a personalized medicine. Due to their biocompatibility, versatility, physical and chemical resistance, and ability to be functionalized, silica nanoparticles and polysiloxanes are the heart and the shield of this nanoplatform, respectively. In this short review, I analyze the applications of these silicon-based materials in the field of controlled drug delivery.


Toxic Megacolon and Acute Ischemia of the Colon due to Sigmoid Stenosis Related to Diverticulitis.
We present a rare case of toxic megacolon accompanied by necrosis of the colon due to chronic dilation caused by stenosis of the sigmoid colon as a complication of diverticulitis. The patient presented at the emergency department with diffuse abdominal pain, fever (38.8°C) and tachycardia (120 beats/min). Physical examination revealed distension and tenderness on deep palpation on the left lower quadrant without peritoneal signs. Abdominal computed tomography showed located stenosis in the sigmoid colon and marked dilation of the descending (12 cm diameter) and transverse (7.5 cm diameter) colon. A few hours later, the patient developed severe septic shock with electrolyte abnormalities. He had a history of two prior admissions to our hospital due to crises of acute diverticulitis. Based on Jalan's criteria the diagnosis was compatible with toxic megacolon. The patient's condition deteriorated suddenly and an emergency colectomy was performed. The operative findings revealed a necrotic colon. Histology examination confirmed the diagnosis of ischemia of the colon. To our knowledge this is the first published report in the literature which refers to a rare complication of diverticulitis, namely chronic stenosis which complicated to colonic ischemia and toxic megacolon.


Evaluation of effect of acarbose consumption on weight losing in non-diabetic overweight or obese patients in Kerman.
High prevalence of obesity and the importance of this issue as a risk factor for chronic diseases such as severe cardiovascular diseases, diabetes, and cancer necessitate the need for treatment. The aim of this study was the evaluation of acarbose effect on the weight loss in non diabetic overweight or obese patients in Kerman. A double blind randomized controlled clinical trial was performed on 66 patients with the body mass index (BMI) between 25 and 35 kg/m(2). Patients were divided in treatment and control groups using the randomization. The treatment group took 100 mg acarbose 3 times a day for 20 weeks in combination with the low calorie diet and exercise. Control group was given placebo, low calorie diet, and exercise. BMI was measured after 20 weeks. The analyses were carried out using t-test and repeated measured ANOVA. Patients in acarbose and placebo group had a non significant difference in BMI at baseline. Reducing in weight was considered in every month in both groups, but this reduction was higher in the treatment group. At the 5(th) month, the difference of BMI in the treatment group was significantly lower than the placebo group (2.31 ± 0.6 vs. 0.76 ± 0.6 kg/m(2), P < 0.001). Acarbose, especially in combination with the low calorie diet and exercise, seems to lose weight effectively in obese and overweight patients in communities that have a high carbohydrate intake (like Persian diet).


Factors influencing early poult flip-overs in experimental populations of turkeys.
A large number of poults from a line (E) selected long-term for increased egg production were observed, in recent generations, to flip over during the week immediately after hatching. This condition, termed early poult flip-overs (EPF), is characterized by the poults falling on their back and being unable to right themselves without assistance. Poults that flip over more than once appear to lack neurological control, lying on their backs with their legs paddling. If handled, the affected poult moves its head laterally and after several seconds appears to go to sleep. When placed on litter, the poult has no sense of balance and falls to one side or the other and starts paddling its feet. Poults that flip over may also chirp loudly. Observations from previous years indicate that no bacterial infectious agent was associated with the EPF condition. Affected poults have increased mortality relative to normal poults that do not flip over. The objective of the present study was to evaluate the effects of inheritance, beak trimming, hatching time, genetic growth potential, and poult hydration on the incidence of EPF. The E line had a greater incidence of EPF than its randombred control line, indicating the possibility of a genetic basis for the condition. However, within the E line, the heritability, based on variation among full-sib families, of the occurrence of EPF (assuming that EPF is an all-or-none trait) was low, being 0.044 and 0.052 in 2 consecutive yr. The heritability of the number of days (out of five) a poult continued to flip over was somewhat higher [0.26+/-0.002 (SE)]. Genetic growth potential may influence incidence of EPF for, when the E line was crossed with a large-bodied experimental line selected for increased 16-wk BW, the frequency of EPF was reduced and BW at 13 d of age was increased in the cross relative to the pure E line even though poult weight was similar at hatching in the two genetic groups. In the E line, later hatching poults within a hatch had a greater incidence of EPF than those hatching earlier. Neither beak trimming with an electronic beak trimmer nor poult hydration influenced EPF.


Nervous wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth.
Regulation of synaptic morphology depends on endocytosis of activated growth signal receptors, but the mechanisms regulating this membrane-trafficking event are unclear. Actin polymerization mediated by Wiskott-Aldrich syndrome protein (WASp) and the actin-related protein 2/3 complex generates forces at multiple stages of endocytosis. FCH-BIN amphiphysin RVS (F-BAR)/SH3 domain proteins play key roles in this process by coordinating membrane deformation with WASp-dependent actin polymerization. However, it is not known how other WASp ligands, such as the small GTPase Cdc42, coordinate with F-BAR/SH3 proteins to regulate actin polymerization at membranes. Nervous Wreck (Nwk) is a conserved neuronal F-BAR/SH3 protein that localizes to periactive zones at the Drosophila larval neuromuscular junction (NMJ) and is required for regulation of synaptic growth via bone morphogenic protein signaling. Here, we show that Nwk interacts with the endocytic proteins dynamin and Dap160 and functions together with Cdc42 to promote WASp-mediated actin polymerization in vitro and to regulate synaptic growth in vivo. Cdc42 function is associated with Rab11-dependent recycling endosomes, and we show that Rab11 colocalizes with Nwk at the NMJ. Together, our results suggest that synaptic growth activated by growth factor signaling is controlled at an endosomal compartment via coordinated Nwk and Cdc42-dependent actin assembly.


New wave of research in the epilepsies.
The epilepsies affect at least 1 to 2 million people in the United States and 20 to 40 million people worldwide. Because the causes and basic mechanisms of the epilepsies have only started to unravel, there is still no cure for the disease. The purpose of this chapter is to present the new routes of navigation in epilepsy research, the salient theories on mechanisms of epilepsies, and their cogency to cause (generation of seizures) and effects (epileptic cell damage). In particular, it advances a comprehensible picture of the major cellular events involved in the generation, arrest, or spread of partial epileptic seizures; it also questions the major molecular events involved in the transmission and use of genetic information in the generalized epilepsies. In reviewing the many theories on mechanisms of epilepsies, this chapter establishes the connections between neurosciences, molecular genetics, and the epilepsies. The knowledge gained from such connections will certainly bear on the diagnosis of the subvarieties of epilepsies and is already promoting new methods of treatment of the disease. Indeed, it is this fusion between molecular genetics, neurosciences, and the clinical epilepsies that provides the excitement and new ferment in research of the epilepsies. This chapter also advances a conceptual blueprint for priority challenges in epilepsy research. It calls attention to the primary goal, namely, understanding the mechanisms of human epilepsies. In the most common of human epilepsies, namely, temporal lobe epilepsy, a priority challenge is to analyze paroxysmal depolarization shifts in hippocampal slices in vitro, slices excised from known sites of epileptogenicity. Parallel experiments exploring biochemical membrane abnormalities in neuronal and glial membranes isolated from the hippocampal seizure focus would be especially valuable. The role of kindling and the mirror focus in human temporal lobe epilepsy must be resolved. A second important goal is the search for polymorphisms of restriction endonuclease patterns in monogenic epilepsies in order to localize the abnormal gene to a specific chromosome. Because of the recent successful applications of positron emission tomography (PET), single-photon-emission computed tomography, and nuclear magnetic resonance computed tomography (NMR-CT), ion transport pathways, neurotransmitter systems, and metabolic processes may be constructed within the functioning brains of epileptic patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Splitting the leafmining shield-bearer moth genus Antispila Hübner (Lepidoptera, Heliozelidae): North American species with reduced venation placed in Aspilanta new genus, with a review of heliozelid morphology.
The new genus Aspilanta gen. n. is described to harbour Nearctic heliozelid moths with reduced venation, previously placed in Antispila Hübner, 1825, with type species Antispila oinophylla van Nieukerken & Wagner, 2012. The erection of this genus has become possible now that monophyly has been supported by a recent phylotranscriptomics analysis. Six species are combined in this genus: Aspilanta oinophylla (van Nieukerken & Wagner, 2012), comb. n., A. hydrangaeella (Chambers, 1874), comb. n., A. ampelopsifoliella (Chambers, 1874), comb. n., A. voraginella (Braun, 1927), comb. n., A. argentifera (Braun, 1927), comb. n., A. viticordifoliella (Clemens, 1860), comb. n. and two candidate species are recognised. DNA barcode COI sequences of Malaise trapped specimens suggest a rich fauna of Aspilanta in Central America. All are leafminers, with Vitaceae as main host family, and single species feeding respectively on Hydrangeaceae and Myricaceae. The species are briefly diagnosed, and data on biology, DNA barcodes and distribution are provided. To place the genus in context, a review of heliozelid morphology and phylogeny is presented and a key to Nearctic genera is given. The genus is confined to North and Central America, possibly also occurring in South America. Aspilanta oinophylla is also an invasive species on grapevine in Italy. The genus is sister to Coptodisca Walsingham, 1895. Another species is removed from Antispila: Heliozela eugeniella (Busck, 1900), comb. n., feeding on Eugenia (Myrtaceae), from Florida.


Using the new dietary reference intakes to assess diets: a map to the maze.
New Dietary Reference Intakes (DRIs) are being set by the Institute of Medicine, and represent a new way of defining nutrient intake recommendations. For the first time, the recommendations for the United States and Canada allow the calculation of the probability of adequacy for an individual, and the prevalence of inadequacy for a population. In addition, possible excessive consumption of many nutrients can be evaluated. The goal of this review is to provide a practical guide to the proper uses of the new DRIs when assessing intakes.


The finding of reduced estimated glomerular filtration rate is associated with increased mortality in a large UK population.
CKD as defined by KDIGO/KDOQI has been shown to affect ~ 8.5% of the UK population. The prevalence of CKD in the UK is similar to that in the USA, yet incident dialysis rates are dramatically different. This retrospective cohort study investigates the association between reduced kidney function and mortality in a large UK population. All serum creatinine results covering Northern Ireland's 1.7 million population were collected between 1 January 2001 and 31 December 2002. Estimated glomerular filtration rates (eGFR) were calculated for all serum creatinine measurements using four-variable MDRD equation (IDMS aligned). Patients were followed up for both all-cause and cardiovascular mortality data until the end of December 2006. Patients on renal replacement therapy were excluded. Subgroup analysis in the 75,345 subjects enrolled within a parallel primary care study permitted additional survival analysis with adjustment for traditional cardiovascular risk factors. A total of 1,967,827 serum creatinine results from 533,798 patients were collected. During the period of follow-up, 59,980 deaths occurred. In multivariate survival analysis, using eGFR as a time-varying covariate, a graded association between CKD (defined by eGFR) and all-cause mortality was identified. Compared with participants with an eGFR of > 60 mL/min/1.73 m(2), the adjusted hazard ratios (and 95% confidence intervals) for participants with an eGFR of 45-59 mL/min/1.73 m(2) was 1.02 (0.99-1.04), an eGFR of 30-44 mL/min/1.73 m(2) was 1.44 (1.40-1.47), an eGFR of 15-29 mL/min/1.73 m(2) was 2.12 (2.05-2.20) and an eGFR of < 15 mL/min/1.73 m(2) was 3.46 (3.24-3.70). Significantly, increased all-cause mortality was associated with an eGFR < 45 mL/min/1.73 m(2) following adjustment for age and gender. The association between cardiovascular mortality and reduced renal function continued to be significant for participants with an eGFR of 45-65 mL/min/1.73 m(2). Subgroup analysis in 75,345 individuals with more detailed clinical information available confirmed this association following adjustment for traditional cardiovascular risk factors in addition to age and gender. This study demonstrates a graded association between reduced renal function as represented by eGFR and mortality in a UK population. The all-cause and cardiovascular mortality risk increases sharply when estimated GFR falls < 45 mL/min/1.73 m(2). The association between an eGFR measured between 45 and 65 mL/min/1.73 m(2) and cardiovascular mortality persists in this cohort and highlights the ongoing uncertainty in accurately categorizing renal dysfunction.


A miniature Wright peak-flow meter.
A new miniature Wright peak-flow meter has been designed and produced. The meter is tubular with a spring-loaded piston and a longitudinal slot through which air escapes. Its dynamic characteristics have been carefully designed to make it respond only to peak flow and not to rate of rise. Performance tests on early instruments showed fairly close correlation with the Wright peak-flow meter but with a constant error of + 38 1/min. On later models the correlation was increased to 0.990 and the error reduced to + 3%. The mini-meter correlates as well with the standard instrument as two standard instruments correlate with each other and should prove useful clinically.


A vulnerability-based vehicle routing approach for solving capacitated arc routing problem in urban snow plowing operations.
Vehicle drivers usually perceive a higher risk when driving on snow covered roads. The city cleaning efficiency would directly influence the risk and mitigation of wintertime events, especially for snow covered roads. Under the risk-informed approach background, more attention is paid to the capacitated arc routing problem (CARP) of urban snow plowing operations. Current algorithms mainly relies on the topology of road network without considering snow covered pavement's negative effect on road capacity and traffic flow. This paper proposes a vulnerability-based parallel heuristic algorithms applied for the CARP by implementing risk-informed approach. First, a method is proposed to set service priorities based on the vulnerability evaluation by considering the added cost of travel demands. Second, a sub-process path-scanning approach is developed to avoid redundant path scans. Then verification and comparison between this newly proposed constructive heuristic and existing algorithms of whole-process path-scanning and sequential processing are conducted. Results show that the sub-process path-scanning approach obviously costs less service completion time than the existing algorithms for solving the CARP. However, this improved algorithm would also cause an increase of deadhead time upon dispatch. The balance between service completion time and deadhead time for more routing problems would be discussed in the near future.


Morehouse Community Physicians Network (CPN) hypertension registry: patterns of care and opportunities for targeted medical education.
Provider-focused strategies for improving outcomes in hypertension have produced mixed results. Studies suggest that the effectiveness of a chosen strategy increases when it is tailored to the specific situation. The hypertension registry includes data on African-American hypertensives who receive care in community-based primary care settings. We examined the registry to identify patterns of care and opportunities for provider-focused interventions to improve patient outcomes. The registry will include all records of hypertensive patients from 50 community-based primary care practices at full enrollment. Data from nine practices were manually abstracted into an electronic database and analyzed. Seven hundred and ten records were included in this report. Approximately 70% are female, average age 47 +/- 13 years, 5.3% are uninsured, and more than 60% have at least a high school education. Registry patients have multiple co-morbid conditions: 28% are diabetic, 8% have left ventricular hypertrophy, 5% have congestive heart failure, 6.5% have renal insufficiency, 5% have cerebrovascular disease, 3.5% have previous myocardial infarction and 2% have peripheral vascular disease. Among those with diabetes, mean glycosylated hemoglobin was 7.4 +/- 2. Pattern of antihypertensive use showed 43% on diuretics, 28% on calcium channel blockers, 24% on angiotensin converting enzyme inhibitors, 20% on beta blockers and 16% on angiotensin receptor blockers. Overall, 37% were at goal blood pressure and among those with diabetes, only 16% reached goal blood pressure. We conclude that the blood pressure control rates of African Americans in the registry trail those of the general population. This provides a unique opportunity to study the underlying factors and design tailored interventions to address this disparity in health outcome.


The association of very high hair manganese accumulation and high oxidative stress in Mongolian people.
Oxidative stress induces several diseases and early aging. Previously, we reported that Mongolians are exposed in high oxidative stress, which may cause their early aging. In this study, to know the reason of high oxidative stress, we measured hair metals. This investigation was performed in Murun city, in the northern area of this country, and 469 healthy subjects, ranging from 10 to 82 years of age, were randomly enrolled. Oxidative stress was evaluated by the levels of serum reactive oxygen metabolites (ROM), malondialdehyde-modified low-density lipoprotein (MDA-LDL) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Antioxidant capacity (AOC) was estimated by the levels of biological antioxidant potential (BAP) and superoxide dismutase (SOD) activity. Scalp hair metals were measured using an inductively coupled plasma mass spectrometry method. Murun subjects showed high ROM levels of 394+/-75 Carr U (n=342), compared with Japanese healthy subjects (n=356, 326+/-51 Carr U, p<0.001). MDA-LDL and 8-OHdG levels also showed high levels. While, BAP levels of Murun subjects were 2263+/-203 micromol/L (n=210), Japanese subjects (n=356, 2087+/-215 micromol/L, p<0.001). SOD activities were also high, suggesting that the high oxidative may accelerate the state of AOC. Murun subjects demonstrated high accumulation of several metals in the hairs. In particular, Mn accumulation exhibited from 2 fold to 40 fold increases of Japanese standard. These findings are indicative that the high Mn accumulation may contribute to the high oxidative stress. The mechanism of its high accumulation was not explained by food materials or drinking water. We should further investigate another influence such as sandy wind. In order to suppress the high oxidative stress, elimination of the high Mn accumulation should be urgently studied.


The physiology of scotopic vision, contrast vision, color vision, and circadian rhythmicity: can these parameters be influenced by blue-light-filter lenses?
Evaluation of the potential effects of blue-light-filter lenses on sensory and physiologic factors. Scientific knowledge on circadian rhythm and scotopic vision will be summarized and potential effects of blue-light-filtering lenses on these parameters will be assessed on a theoretical basis. Clinically relevant studies will also be discussed. As far as circadian rhythm is concerned, it should be noted that at 480 nm, i.e., at maximum visual excitation of the light intensity to be measured, blue-light-filtering lenses show roughly the same transmission characteristics as the human crystalline lens. Interference with the circadian rhythm due to blue-light-filtering lenses, therefore, is not to be expected. Regarding scotopic vision, no clinically significant impairment is to be expected from blue-light-filter lenses because maximum excitation in scotopic light reception occurs at 507 nm whereas the light transmission of blue-light-filter lenses is 85%--this is higher than that of a child's crystalline lens. Numerous clinical studies corroborate these findings and demonstrate that color vision and contrast vision are not compromised by blue-light-filter intraocular lenses. Based on current findings, we do not anticipate blue-light-filter lenses to have a clinically significant effect on physiologic parameters such as scotopic vision, color, and contrast vision or the circadian rhythm.


Sitosterolemia.
Sitosterolemia was first described 28 years ago in two sisters. They had tendonxanthomas, normal plasma cholesterol levels, and elevated plant sterol levels. The high plant sterol levels were shown to be due to the increased absorption and delayed removal of plant sterols from the body. The increased absorption of plant sterols does not affect cholesterol absorption in these patients. However, cholesterol biosynthesis pathway is downregulated and turnover rates are reduced. Bile acid binding resins and ileal bypass surgery are effective treatments for sitosterolemic patients, whereas statins are ineffective. Sitosterolemia is inherited as a recessive trait. Recent studies have shown that mutations in ABCG5 and ABCG8 genes contribute to sitosterolemia. Most likely, ABCG5 and ABCG8 proteins function as obligate heterodimers and play a role in the absorption of plant sterol or control their rate of absorption.


Application of Arrhenius kinetic theory to viral eclipse: selection of bacteriophage phi X174 mutants.
Analysis of the bacteriophage phi X174 eclipse period in terms of Arrhenius kinetic theory suggests the following hypothesis: mutants should exist with two concomitant physiological characteristics as their phenotype. These are an eclipse rate lower than that of the wild type at permissive temperatures for plaque formation and an eclipse rate too low at lower temperatures to permit plaque development. Thus, enrichment of a mutagenized virus population for mutants that fail to eclipse during a short period at permissive temperatures should yield eclipse mutants with the cold-sensitive (cs; nonpermissive temperature, 25 degrees C), and not the temperature-sensitive (ts; nonpermissive temperature, 42 degrees C), plaque phenotype. In several trials, the frequency of the cs phenotype in the population increased from less than 0.2% to between 2 and 4% after the enrichment step, whereas the frequency of the ts phenotype remained unchanged (less than 0.2%). Moreover, 80% of these cs mutants have eclipse rates that are 3- to 40-fold lower than that of the wild type at both 37 degrees C and 25 degrees C. The successful application of the Arrhenius theory to phi X eclipse may provide insights into the molecular mechanism whereby the phi X174 genome is delivered into the host cell. Since the eclipse kinetics of other nonenveloped viruses are similar to those of phi X174, kinetic theory may be broadly applicable in the selection and characterization of viral eclipse mutants.


On the speed of pop-out in feature search.
When something unique is present in a scene, this element may become immediately visible and one has the impression that it pops out from the scene. This phenomenon, known as pop-out in the visual search literature, is thought to produce the fastest search possible, and response times for the detection of the pop-out target do not vary as a function of the number of nontargets. In this study, we challenge this notion and show that the detection of a given visual feature is faster for multiple targets than for a single pop-out target. However, when the task requires a detailed target analysis, the pop-out condition can be faster than the multiple-target condition. Current models of visual search are discussed in light of the findings.


Calcium dependence of effects of endothelin on rat mesenteric microvessels.
We investigated the calcium dependence of the effects of endothelin (ET) on resistance vessels (less than 300 microns lumen diameter) from the mesenteric vascular bed of the rat, mounted on a wire myograph. ET-1 induced a potent sustained contraction with an ED50 of 12 nmol/L. The response to ET-3 and big ET at the maximum concentrations used (100 nmol/L) was less than 40% of that to ET-1, with an estimated ED50 of 45 nmol/L. Relaxation of the ET-1-induced contraction was slow, and resulted in a reduction of the maximum response to a second challenge with ET-1 to 60% of the initial contraction after 3 h. Long-lasting tachyphylaxis to arginine vasopressin (AVP) induced contraction also occurred. The response to 100 nmol/L ET-1 produced an active tension 88% greater than that induced by 124 mmol/L KCl, and similar to that produced by norepinephrine and AVP. The response to 100 nmol/L ET-1 in the absence of calcium + 1 mmol/L EGTA in the medium for 30 min resulted in a maximum contraction of 43% of the response in the presence of calcium, followed by a faster relaxation rate. The addition of calcium produced a further contraction, and stimulation with 100 nmol/L ET-1 at this point did not result in further response. The calcium channel blocker nitrendipine in concentrations of 1-10 mumol produced increasing reductions of the responses to 100 nmol/L ET-1 to 35% at the higher concentration. Nitrendipine (3 mumol/L) partially blocked the response to calcium after ET-1 was added in the absence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)


NR2F1 database: 112 variants and 84 patients support refining the clinical synopsis of Bosch-Boonstra-Schaaf optic atrophy syndrome.
Pathogenic variants of the nuclear receptor subfamily 2 group F member 1 gene (NR2F1) are responsible for Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), an autosomal dominant disorder characterized by optic atrophy associated with developmental delay and intellectual disability, but with a clinical presentation which appears to be multifaceted. We created the first public locus-specific database dedicated to NR2F1. All variants and clinical cases reported in the literature, as well as new unpublished cases, were integrated into the database using standard nomenclature to describe both molecular and phenotypic anomalies. We subsequently pursued a comprehensive approach based on computed representation and analysis suggesting a refinement of the BBSOAS clinical description with respect to neurological features and the inclusion of additional signs of hypotonia and feeding difficulties. This database is fully accessible for both clinician and molecular biologists and should prove useful in further refining the clinical synopsis of NR2F1 as new data is recorded.


Exploring the XIST axis as oxidative stress-related signatures in systemic lupus erythematosus.
In the pathogenesis of systemic lupus erythematosus (SLE), oxidative stress (OS) plays an complex role; nevertheless, few investigations have indicated a ceRNA-based mechanism involved. The aim of this study was to explore the ceRNA regulation mechanism of oxidative stress in SLE and provide new therapeutic targets for SLE. Three datasets from the Gene Expression Omnibus (GEO) database were used to obtain differentially expressed lncRNAs, miRNAs, and mRNAs (DElncRNAs, DEmiRNAs, and DEmRNAs). Functional analysis was explored and a triple ceRNA network was built. Least absolute shrinkage and selection operator regression was used to find optimal signatures. The sensitivity and specificity of the signatures were examined and validated using receiver operating characteristic (ROC) analysis. The CIBERSORT algorithm was used to investigate immune infiltration features. Moreover, the hub mRNAs were validated by quantitative real-time PCR. 42 DEmRNAs were identified. Enrichment analysis showed that the DEmRNAs were primarily concentrated in neutrophil-associated biological processes. The ROC curve found FOS and MME provided potential biomarkers for identifying SLE patients. And the XIST/FOS and XIST/MME axes were identified the possible OS-related regulatory pathway in SLE. Immune infiltration showed that resting memory CD4 T cells presented a lower level. This study constructed the ceRNA-based XIST/FOS and XIST/MME axes as prospective OS-related signatures for SLE. Our findings provide new insights into the pathogenesis of SLE and shed a novel light on therapeutic strategies.


A new subspecies of Peucedanum officinale L. subsp. album (Apiaceae) from the eastern part of the Iberian Peninsula.
We describe Peucedanum officinale L. subsp. album Martínez-Fort & Donat-Torres subsp. nov., in which we grouped the thermomediterranean populations scattered along the eastern part of the Iberian Peninsula. The characters that differentiate this new subspecies from other infraspecific taxa in Peucedanum officinale are its canaliculated leaflet, the inflorescences much branched and lack of dominant terminal umbels, the umbels are few rayed, sometimes sessile and lateral, the petals are white and the fruit pedicels short, the same or shorter in length than the fruit. We provide here a full description of the new subspecies based on herbarium specimens and field measurements, as well as providing dichotomous keys to the subspecies within P. officinale. In addition, we provide a comparison of the ITS sequences of nrDNA with the most closely related taxons.


[Functional interrelations between the thermo-topographic indicators in healthy persons with hemodynamic status of the body].
++Thermo-topography was studied by decimeter radiothermometry on a DPT-30 apparatus which determined the integral ++sub-superficial temperature of a tissue layer at a depth of 3-5 cm. Thermal probing was performed at point 41 onto the dorsal and ventral surfaces of the human body. Hemodynamics was explored by tetrapolar thoracic rheography. A total of 83 young healthy males were studied. Associated changes in temperatures and hemodynamic parameters were established. The radioluminance thermal profile of patients with tachycardia was significantly altered as compared to those with bradycardia. The ++sub-superficial temperatures in the proximal regions of the body rose by 0.3-0.7 degree C. The feet in subjects with rapid pulse were colder, which led to significantly higher values of distal and proximal lower extremity, temperature gradients. In persons with hyperkinetic circulation, the temperatures in the ++cranio-corporeal regions were significantly greater by 0.2-0.6 degree C than those in subjects with eu- and hypokinetic circulations.


Diagnostic cross-linking of paired cysteine pairs demonstrates homologous structures for two chemoreceptor domains with low sequence identity.
Hundreds of bacterial chemoreceptors from many species have periplasmic, ligand-recognition domains of approximately the same size, but little or no sequence identity. The only structure determined is for the periplasmic domain of chemoreceptor Tar from Salmonella and Escherichia coli. Do sequence-divergent but similarly sized chemoreceptor periplasmic domains have related structures? We addressed this issue for the periplasmic domain of chemoreceptor Trg(E) from E. coli, which has a low level of sequence similarity to Tar, by combining homology modeling and diagnostic cross-linking between pairs of introduced cysteines. A homology model of the Trg(E) domain was created using the homodimeric, four-helix bundle structure of the Tar(S) domain from Salmonella. In this model, we chose four pairs of positions at which introduced cysteines would be sufficiently close to form disulfides across each of four different helical interfaces. For each pair we chose a second pair, in which one cysteine of the original pair was shifted by one position around the helix and thus would be less favorably placed for disulfide formation. We created genes coding for proteins containing four such pairs of cysteine pairs and investigated disulfide formation in vivo as well as functional consequences of the substitutions and disulfides between neighboring helices. Results of the experimental tests provided strong support for the accuracy of the model, indicating that the Trg(E) periplasmic domain is very similar to the Tar(S) domain. Diagnostic cross-linking of paired pairs of introduced cysteines could be applied generally as a stringent test of homology models.


The role of complementary and alternative medicine in diabetes.
Complementary and alternative medicine (CAM) describes a diverse group of medical and health care systems, practices, and products not currently considered to be part of conventional medicine. Inadequacies in current treatments for diabetes have led 2 to 3.6 million Americans to use CAM for diabetes treatment, despite limited studies of safety and efficacy of CAM methods. CAM is used mostly by West Indians, Africans, Indians, Latin Americans, or Asians. Prayer, acupuncture, massage, hot tub therapy, biofeedback, and yoga have been used as well as various plant remedies for treating diabetes. Several CAM practices and herbal remedies are promising for diabetes treatment, but further rigorous study is needed in order to establish safety, efficacy, and mechanism of action. In the meantime, it is important to be aware that many patients with diabetes may be using CAM and to consider potential interactions with conventional medicines being used.


Giant solitary fibrous tumour of pleura -an uncommon intrathoracic entity- a case report and review of the literature.
A 43-year-old woman presented to us with progressive breathlessness, dry cough and weight loss. A chest radiograph showed homogeneous opacification of the entire left hemithorax. A contrast enhanced computed tomography (CECT) scan of the thorax showed a large intrathoracic mass occupying almost the entire left hemithorax and appeared grossly inoperable. A transcutaneous CT guided tru-cut biopsy revealed a solitary fibrous tumour. We reviewed the CT scans based on the biopsy report, and, in retrospect, the mediastinal vessels seemed more stretched and pushed by the tumor rather than directly infiltrated by it. We performed an exploratory thoracotomy and to our surprise, were able to dissect the mass quite easily off the mediastinum. She had an uneventful postoperative recovery, and the final histopathology confirmed a solitary fibrous tumor. We report this case to emphasize that a cursory clinico-radiological interpretation can dissuade surgical intervention in these patients.


Abrupt Change in Electrophysiological Properties Begins From Postnatal Day 7 Before Hearing Onset in the Developing Mice Auditory Cortical Layer II/III Neurons.
In the developing auditory cortex, maturation of electrophysiological properties and cell types before and after hearing onset has been reported previously. However, the exact timing of firing pattern change has not been reported. In this study, firing pattern change was investigated from postnatal day 3 (P3) to P12 in auditory cortical layer II/III neurons to investigate whether firing pattern changes dramatically after a specific point during development. ICR mice pups aged from P3 to P12 were sacrificed to obtain 300-mm-thick brain slices containing the primary auditory cortex. From cortical layer II/III neurons, the patterns of action potential firing generated by current injection were examined using whole cell current clamp technique and the characteristics of Na+ currents involved in action potential firing were investigated using whole cell voltage clamp technique. From P3 to P6, most cells did not show action potential firing (29 of 46 cells), and some cells responding to current injection showed a single action potential at the initial depolarizing current step (17 of 46 cells). This firing pattern changes from P7. From P7 to P9, cells begin to show regular spiking to current injection. The spiking frequency increased after P10. In studying Na+ current with whole cell voltage clamp, Na+ current densities increased gradually (32.0±2.0 pA/pF [P3-P6, n=7], 51.2±2.0 pA/pF [P7-P9, n=13], and 69.5±3.7 pA/pF [P10-P12, n=13]) in low external [Na+] condition. Na+ current recovery was accelerated and inactivation curves shifted to hyperpolarization with age. As regular spiking cells were observed from P7 but never from P3 to P6, P7 might be regarded as an important milestone in the development of auditory cortical layer II/III neurons. This change might mainly result from the increase in Na+ current density.


Endothelin B receptor-mediated regulation of ATP-driven drug secretion in renal proximal tubule.
In the kidney, endothelins (ETs) are important regulators of blood flow, glomerular hemodynamics, and sodium and water homeostasis. They have been implicated in the pathophysiology of acute ischemic renal failure, nephrotoxicity by cyclosporine, cisplatin and radiocontrast agents, and vascular rejection of kidney transplants. Here, we used intact killifish renal proximal tubules, fluorescent substrates for Mrp2 (fluorescein-methotrexate, FL-MTX) and P-glycoprotein (a fluorescent CSA derivative, NBD-CSA), and confocal microscopy to reveal a new role for renal ET: regulation of ATP-driven drug transport in proximal tubule. Subnanomolar to nanomolar concentrations of ET-1 rapidly reduced the cell-to-tubular lumen transport of both fluorescent compounds. These effects were prevented by an ET(B) receptor antagonist but not by an ET(A) receptor antagonist. Immunostaining with an antibody to mammalian ET(B) receptors showed specific localization to the basolateral membrane of the fish tubular epithelial cells. ET-1 effects on transport were blocked by protein kinase C-selective inhibitors, implicating protein kinase C in ET-1 signaling. Finally, the nephrotoxic radiocontrast agent iohexol reduced cell-to-lumen FL-MTX and NBD-CSA transport, and these effects were abolished by an ET(B) receptor antagonist. These are the first results linking ET to the control of xenobiotic transport and the first demonstrating control of renal multidrug resistance-associated protein 2 and P-glycoprotein by a hormone.


Lateral reorganization of plasma membrane is involved in the yeast resistance to severe dehydration.
In this study, we investigated the kinetic and the magnitude of dehydrations on yeast plasma membrane (PM) modifications because this parameter is crucial to cell survival. Functional (permeability) and structural (morphology, ultrastructure, and distribution of the protein Sur7-GFP contained in sterol-rich membrane microdomains) PM modifications were investigated by confocal and electron microscopy after progressive (non-lethal) and rapid (lethal) hyperosmotic perturbations. Rapid cell dehydration induced the formation of many PM invaginations followed by membrane internalization of low sterol content PM regions with time. Permeabilization of the plasma membrane occurred during the rehydration stage because of inadequacies in the membrane surface and led to cell death. Progressive dehydration conducted to the formation of some big PM pleats without membrane internalization. It also led to the modification of the distribution of the Sur7-GFP microdomains, suggesting that a lateral rearrangement of membrane components occurred. This event is a function of time and is involved in the particular deformations of the PM during a progressive perturbation. The maintenance of the repartition of the microdomains during rapid perturbations consolidates this assumption. These findings highlight that the perturbation kinetic influences the evolution of the PM organization and indicate the crucial role of PM lateral reorganization in cell survival to hydric perturbations.


Role of ET(A) receptors in experimental ANG II-induced hypertension in rats.
The objectives were to determine if ANG II-induced hypertension is maintained by activation of endothelin type A (ET(A)) receptors by endogenous ET-1 and if this effect is influenced by salt intake. Male rats were maintained on high sodium intake (HS; 6 meq/day) or on normal sodium intake (NS; 2 meq/day). Hypertension was produced by intravenous infusion of ANG II (5 ng/min) for 15 days. Five-day oral dosing with the selective ET(A)-receptor antagonist ABT-627 (~2 mg. kg(-1). day(-1)) reduced mean arterial pressure (MAP) to baseline levels in rats on HS receiving ANG II infusion, but it did not affect MAP in normotensive HS controls. In rats on NS, ABT-627 only transiently decreased MAP in rats receiving ANG II and slightly reduced MAP in normotensive controls. ABT-627 produced mild retention of sodium and water in NS rats receiving ANG II, but not in any other group. These results indicate that ET-1 plays a role in ANG II-induced hypertension via activation of ET(A) receptors and that this role is more prominent in rats on HS.


Simultaneous patch testing with fragrance markers in the baseline series and the ingredients of fragrance mixes: An update from southern Sweden.
Regularly updating the prevalence of fragrance contact allergy (CA) is important. Patch testing with fragrance markers in the baseline series and the ingredients of fragrance mixes (FMs) is still debated. To update the prevalence and clinical characteristics of patients with fragrance CA. To establish the results of patch testing with individual allergens of FMs. A retrospective analysis of 3539 patients with dermatitis who were patch tested with the baseline series and FMs ingredients during 2016 to 2020 was performed. The prevalence of fragrance CA was 13%. About 10% of these patients with fragrance CA would be missed if the individual ingredients were not tested. Unlike hydroxyisohexyl 3-cyclohexene carboxaldehyde, there was no decreasing trend of CA to Evernia prunastri (oakmoss) extract after the EU regulation came into force. Patients with CA from only one ingredient of the mixes or having a weak positive reaction to the ingredients were significantly missed when tested with only the fragrance markers in the baseline series. Patch testing with individual fragrance allergens is crucial for experts to expand knowledge in the fragrance CA field. The concentrations of the allergens in FMs may need to be adjusted to detect patients with fragrance CA, since some were significantly overlooked.


State-Dependent and Bandwidth-Specific Effects of Ketamine and Propofol on Electroencephalographic Complexity in Rats.
There is an ongoing debate as to whether ketamine anesthesia suppresses neurophysiologic complexity at doses sufficient for surgical anesthesia, with previous human studies reporting surrogates of both suppressed and preserved levels of cortical complexity. However, these studies have not assessed cortical dynamics in higher gamma frequencies, which have previously been demonstrated to correlate with the level of consciousness during anesthesia. In this study, we used Lempel-Ziv complexity (LZc) to characterize frontal and parietal electroencephalographic complexity (0.5-175 Hz, 0.5-55 Hz, 65-175 Hz) before, during, and after ketamine or propofol anesthesia in the rat. To control for the potential influence of spectral changes in complexity estimation, LZc was normalized with phase-shuffled surrogate data. We demonstrate that ketamine and propofol anesthesia were characterized by a significant reduction in broadband (0.5-175 Hz) LZc. Further analysis showed that while the reduction of LZc during ketamine anesthesia was significant in 65-175 Hz range, during propofol anesthesia, a significant decrease was observed in 0.5-55 Hz bandwidth. LZc in broadband and 0.5-55 Hz range showed a significant increase during emergence from ketamine anesthesia. Phase-shuffled normalized LZc revealed that (1) decrease in complexity during ketamine and propofol anesthesia-not increase in complexity during emergence-were dissociable from the influence of spectral changes, and (2) reduced LZc during ketamine anesthesia was present across all three bandwidths. Ketamine anesthesia was characterized by reduced complexity in high gamma bandwidth, as reflected in both raw and phase-shuffled normalized LZc, which suggests that reduced high gamma complexity is a neurophysiological feature of ketamine anesthesia.


Elevation of serum 3,5,3'-triiodothyronine and thyroxine levels in rats fed Remington diets; opposing effects of nutritional deficiency and iodine deficiency.
In the course of experiments on iodine deficiency induced by Remington diets in rats, we observed that the Remington diet supplied by ICN Nutritional Laboratories, though very deficient in iodine (less than 20 micrograms I/kg), did not lead to the rapid loss of thyroid iodine and the rapid decrease in serum T4 expected on the basis of previous studies with a similarly iodine-deficient Remington diet from another source. In searching for an explanation for this observation, we noted that the ICN Remington diet was nutritionally much more deficient than Remington diets from other suppliers. We also noted that when rats were placed on the iodide-supplemented ICN Remington diet there was a marked increase in serum T3 and T4. In one experiment, rats receiving the ICN Remington diet plus KI in the drinking water for 16 days showed a serum T3 level of 109 +/- 16 ng/dl and a serum T4 level of 6.6 micrograms/dl compared to 52 +/- 7.8 and 4.4 +/- 0.8, respectively, in control rats on a stock diet. These elevations were not simply the result of increased binding to serum proteins. Serum protein-binding studies by the method of equilibrium dialysis showed a very slight decrease in the percent dialyzable fraction for T3 and T4. However, calculated free T3 levels were significantly elevated (P less than 0.001), and increases in free T4, though less striking, were also significant. These elevations were not accompanied by evidence of hyperthyroidism, as judged by measurements of O2 consumption or serum TSH. Although the specific nutritional factors and mechanisms have not yet been defined, our studies demonstrate that nutritional deficiencies in a Remington diet may act to oppose the effects of the iodine deficiency itself. Our observation that the iodide-supplemented ICN Remington diet has a marked serum T3- and T4-elevating effect offers a possible explanation for the blunted thyroidal responses of rats to the same diet lacking added iodide. Our studies also suggest that alteration of peripheral T4 and T3 conversion may not be the only mechanism by which nutritional factors affect serum T3 and T4 levels.


[Repeated intraperitoneal injection of low-dose CDDP for gastric cancer with ascites owing to peritonitis carcinomatosa].
We attempted treating 5 patients with ascites from peritonitis carcinomatosa of gastric carcinoma using TS-1 as systemic chemotherapy, and repeated intraperitoneal injection of low-dose CDDP for the carcinomatous ascites. TS-1 was administered in the usual manner and repeated intraperitoneal injection of CDDP (10 mg/body) dissolved in physiological saline 20-500 ml was given with an implantable reservoir. In 3 patients, the carcinomatous ascites disappeared, and in 2 other patients they decreased remarkably. As a result, the QOL and PS of all patients were improved. Serum concentration of CDDP suggested that weekly repeated intraperitoneally injected CDDP not only has an effect on peritonitis carcinomatosa, but also functions as a modulator for 5-FU.


Cholesterol and fats in Brazilian foods: implications for prevention of atherosclerosis.
In order to perform food surveys and prescribe diets, food composition tables have to be consulted. However, these tables are limited to the description of fatty acids and cholesterol contents and do not provide information on the different preparation methods. Based on data derived from an extensive analysis of the chemical composition of Brazilian foods, we assessed the impact of certain types of foods on diets recommended for the prevention of coronary disease. The fatty acid and cholesterol composition of some types of foods and different preparation methods were analyzed. These results were used according to the recommendations of the American Heart Association for an 1,800 calorie diet. Cholesterol found in 100g of eggs (400mg) or fried beef liver (453mg) exceeds the amount recommended for secondary prevention, and there is no difference in cholesterol content between factory-farmed eggs and free-range eggs. The eggs had an average of 400mg of cholesterol per 100g, thus exceeding the recommended amount of up to 300mg. Each egg has 50g on average; one egg can be consumed provided that not more than 100mg of cholesterol are consumed per day. As regards saturated fat, butter (55.2g), margarine (19.4g), tilsit cheese (20.4g), Brazilian Dutch Edam cheese (19.9g), yellow (16.8g) and fresh white cheese (15.5g) exceed the 14g recommended if 100g or more are consumed. The same is true for soy oil (17.5g) and corn oil (16.1g). Better knowledge on fat and cholesterol contents in foods allows the prescription of amounts not exceeding the recommended values for prevention, and this may result in better compliance to diets.


Effects of robotic rehabilitation on walking and balance in pediatric patients with hemiparetic cerebral palsy.
The most prominent characteristics of hemiparetic cerebral palsy (hCP) children are structural and functional asymmetries. These children have low walking speeds, endurance and poor balance. The robotic walking devices repeat and experience symmetrical stepping at the corresponding speed and angles of the lower extremities. RESEARCH QUESTION 1: Are robotic walking devices effective in the development of walking in hCP children who can walk? RESEARCH QUESTION 2: How does the aerobic exercise experience with assisted and symmetrical movement affect the walking and local muscle, peripheral oxygenation of children with hCP? This prospective, controlled study included 24 children with hCP. All children attended to a standard physiotherapy rehabilitation (PTR) program (three days a week for 12 weeks); those in the study group (n=12) also attended to an Robotic Gait Training (RGT) program three times a week. Evaluations performed before treatment, after treatment, and at the 3rd month after treatment included assessment of balance, functionality walking and measurements for oxygenation of vastus lateralis muscle and peripheral oxygenation. The evaluations were similar for both groups before treatment. After treatment, walking speed, endurance and peripheral O2 saturation were increased and balance abilities and functional performances improved in the RGT group as compared with the pre-treatment evaluations; these improvements in balance and functional performance were generally preserved after 3 months of treatment. An increase in 6-min walking distance and a partial increase in gross motor functions and functional muscle strength were observed in the control group; however, these abilities were not preserved after the treatment. RGT can provide a faster and higher effect on the development of functional muscle strength, balance, walking speed and endurance than the standard PTR program. It improves functional walking performance. RGT can be used for aerobic exercise training in children with walking hCP.


Cerebral emboli during cardiopulmonary bypass: effect of perfusionist interventions and aortic cannulas.
Neuropsychological impairment is a very common complication of cardiopulmonary bypass (CPB). The principal cause of postoperative cognitive impairment is thought to be cerebral microemboli during CPB. We recently investigated the effects of perfusionist interventions and aortic cannulation techniques on cerebral emboli production during coronary bypass (CABG) surgery. Patients undergoing isolated CABG were monitored with continuous transcranial Doppler ultrasonography of the middle cerebral artery. Perfusionist interventions were defined as injections of drugs into the CPB circuit or acquisition of blood samples from the CPB circuit. Patients were randomized to receive either standard cannulation of the ascending aorta or cannulation of the distal aortic arch. Cerebral emboli were detected in all patients. The number of emboli per minute was markedly higher during perfusionist interventions than during other time periods. Patients with increased perfusionist interventions had worse neuropsychological outcomes. Cannulation of the distal aortic arch, with placement of the cannula tip beyond the cerebral vessels, resulted in significantly less cerebral emboli than cannulation of the ascending aorta. Perfusionist interventions are a common source of cerebral microemboli during CPB, and may contribute to postoperative neuropsychological impairment. Care should be taken to minimize the introduction of air into the bypass circuit during CPB. Provided it is performed safely, distal aortic arch cannulation is a useful technique for reducing cerebral emboli during cardiac surgery.


MOB-1 and TNF-alpha interact to induce microvascular lung injury.
We have recently identified the alpha-chemokine mob-1 as a highly inducible gene in several rat models of microvascular lung injury, whose expression was suppressed by inhibition of tumor necrosis TNF-alpha (TNF-alpha). This work provides further insight into the relationship between mob-1 and TNF-alpha in the development of lung injury assessed by pulmonary edema and leukosequestration. First, pulmonary mob-1 and TNF-alpha were upregulated in animals subjected to lung injury produced by the intratracheal administration of recombinant TNF-alpha and recombinant mob-1, respectively. Second, mob-1 inhibition by intratracheal anti-mob-1 antibody attenuated lung injury induced by recombinant TNF-alpha. Third, pretreatment with anti-TNF-alpha monoclonal antibody administered intratracheally abrogated recombinant mob-1-induced microvascular lung injury. In vitro, mob-1 and TNF-alpha increased each other's production in RAW 264.7 cells and mob-1 or TNF-alpha inhibition prevented endotoxin-induced upregulation of TNF-alpha or mob-1, respectively, from these cells. Together, these data suggest that mob-1 and TNF-alpha interact to promote lung inflammation.


It's the Culture!-How systemic and societal constructs impact well-being.
Pediatric anesthesiologists practice within a culture, a system, and a society. In this article, we provide an overview of the influence these have on the well-being or the unwellness of pediatric anesthesiologists. The scope of these issues is broad and far-reaching; thus, our goal has been to highlight those areas which would be likely to have the largest impact on well-being if addressed fully by society, institutions, and leaders in our field. We discuss the burnout-promoting aspects of medical education and training. We survey occupational factors, such as the high-stake pediatric anesthesia environment, occupational health hazards, time pressure, and the reduction in physician autonomy. We then describe societal barriers, such as the marginalization of certain populations, the US system of malpractice litigation, the stigma surrounding psychiatric care, and some of the issues related to physician reimbursement in the United States. We conclude that in order to move forward, improving physician wellness must be a focus of society, of the medical system as a whole, and of individual departments and leaders in pediatric anesthesia.


Plasma transferrin receptor helps to predict iron deficiency in the anemia of chronic disease.
A recent study by Ahluwalia and colleagues used a discriminant statistical analysis approach to determine that a combination of serum ferritin, plasma transferrin receptor concentration, and erythrocyte sedimentation rate was the optimal set of variables for differentiating iron deficiency and the anemia associated with chronic disease in a group of elderly women. Iron deficiency was defined as a significant response in hemoglobin concentration after iron supplementation. The findings of this study suggest that iron deficiency can be relatively common among elderly anemic women with rheumatoid arthritis. Use of these three biochemical measures should be clinically useful to differentiate iron deficiency in the anemia of chronic disease.


Poisoning due to yam flour consumption in five families in Ilorin, Central Nigeria.
Food poisoning is known to occur sporadically from time to time due to poor hygienic preparation. Its occurrence rarely assumes epidemic proportion. To report the ccurrence of food poisoning due to yam flour consumption among five families and to create public awareness about the condition. Food poisoning due to yam flour consumption which occurred almost in quick succession between February and July 2005 among five family clusters in Ilorin is reported. They presented variedly with diarrhoea, vomiting, abdominal pain, convulsion and loss of consciousness. They all recovered within 48 hours of admission. Even though we could not carry out toxicological tests, yam flour consumption was highly implicated as the cause. Investigations indicated that the use of certain lethal preservatives for the processing of the yam flour might be responsible. Poisoning from consumption of yam flour should be a differential diagnosis of acute seizure disorder or the occurrence of vomiting, diarrhoea and abdominal pain in the tropics. We recommend education on proper processing of all food products in view of the public health implication of doing otherwise.


Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium.
Influenza virus neuraminidase (NA) plays an essential role in release and spread of progeny virions, following the intracellular viral replication cycle. To test whether NA could also facilitate virus entry into cell, we infected cultures of human airway epithelium with human and avian influenza viruses in the presence of the NA inhibitor oseltamivir carboxylate. Twenty- to 500-fold less cells became infected in drug-treated versus nontreated cultures (P < 0.0001) 7 h after virus application, indicating that the drug suppressed the initiation of infection. These data demonstrate that viral NA plays a role early in infection, and they provide further rationale for the prophylactic use of NA inhibitors.


A psychosocial follow-up study of deaf preschool children using cochlear implants.
The aim of the study was to explore patterns of communication between 22 children with cochlear implants (CI) and their parents, teachers and peers in natural interactions over a 2-year period. The children, between 2 and 5 years old when implanted, had used the implant between 1 and 3.5 years at the end of the study. Analyses of videorecorded interactions showed that meaningful oral communication was more easily obtained in the home setting than in the preschool setting. Patterns of communication between parent-child, content and complexity of dialogues, quality of peer interactions, communicative styles of adults, and the use of sign language in communication turned out to be important factors when explaining the result of the CI on the individual child's development. The children with the best oral skills were also good signers.


Reexamining empathy in autism: Empathic disequilibrium as a novel predictor of autism diagnosis and autistic traits.
A large body of research showed that autistic people have intact emotional (affective) empathy alongside reduced cognitive empathy. However, there are mixed findings and these call for a more subtle understanding of empathy in autism. Empathic disequilibrium refers to the imbalance between emotional and cognitive empathy and is associated with a higher number of autistic traits in the typical population. Here we examined whether empathic disequilibrium predicts both the number of autistic traits and autism diagnosis. In a large sample of autistic (N = 1905) and typical individuals (N = 3009), we examined empathic disequilibrium and empathy as predictors of autistic traits and autism diagnosis, using a polynomial regression with response surface analysis. Empathy and autistic traits were measured using validated self-report questionnaires. Both empathic disequilibrium and empathy predicted linearly and non-linearly autism diagnosis and autistic traits. Specifically, a tendency towards higher emotional than cognitive empathy (empathic disequilibrium towards emotional empathy) predicted both autism diagnosis and the social domain of autistic traits, while higher cognitive than emotional empathy was associated with the non-social domain of autism. Empathic disequilibrium was also more prominent in autistic females. This study provides evidence that beyond empathy as was measured thus far, empathic disequilibrium offers a novel analytical approach for examining the role of empathy. Empathic disequilibrium allows for a more nuanced understanding of the links between empathy and autism. LAY SUMMARY: Many autistic individuals report feelings of excessive empathy, yet their experience is not reflected by most of the current literature, typically suggesting that autism is characterized by intact emotional and reduced cognitive empathy. To fill this gap, we looked at both ends of the imbalance between these components, termed empathic disequilibrium. We show that, like empathy, empathic disequilibrium is related to autism diagnosis and traits, and thus may provide a more nuanced understanding of empathy and its link with autism.


The Danish Nonmelanoma Skin Cancer Dermatology Database.
The Danish Nonmelanoma Skin Cancer Dermatology Database was established in 2008. The aim of this database was to collect data on nonmelanoma skin cancer (NMSC) treatment and improve its treatment in Denmark. NMSC is the most common malignancy in the western countries and represents a significant challenge in terms of public health management and health care costs. However, high-quality epidemiological and treatment data on NMSC are sparse. The NMSC database includes patients with the following skin tumors: basal cell carcinoma (BCC), squamous cell carcinoma, Bowen's disease, and keratoacanthoma diagnosed by the participating office-based dermatologists in Denmark. Clinical and histological diagnoses, BCC subtype, localization, size, skin cancer history, skin phototype, and evidence of metastases and treatment modality are the main variables in the NMSC database. Information on recurrence, cosmetic results, and complications are registered at two follow-up visits at 3 months (between 0 and 6 months) and 12 months (between 6 and 15 months) after treatment. In 2014, 11,522 patients with 17,575 tumors were registered in the database. Of tumors with a histological diagnosis, 13,571 were BCCs, 840 squamous cell carcinomas, 504 Bowen's disease, and 173 keratoakanthomas. The NMSC database encompasses detailed information on the type of tumor, a variety of prognostic factors, treatment modalities, and outcomes after treatment. The database has revealed that overall, the quality of care of NMSC in Danish dermatological clinics is high, and the database provides the necessary data for continuous quality assurance.


[Pathomorphosis of contemporary forms of occupational diseases].
Studies on pathogenetic mechanisms of development, formation and course of occupational diseases revealed pathomorphosis of major specification forms (diseases of bronchopulmonary system, skin, nervous system, locomotory apparatus). Developing pathomorphosis of occupational and occupationally mediated diseases is caused by changed work conditions, lower acting concentrations and levels of occupational factors, influence of harmful ecologic factors, metabolic features, immune state, individual sensitivity to occupational and environmental factors.


Finerenone Added to Treatment Guidelines for Type 2 Diabetes and Chronic Kidney Disease.
The use of finerenone is now included in the 2022 revision to standard treatment guidelines for patients with type 2 diabetes and chronic kidney disease.Finerenone is a costly addition to standard treatment. Patients may need to receive prescription preauthorization from their insurer.