Circatrigintan hormonal and skin surface temperature rhythms following hysterectomy.
Starting 2.5 weeks after removal of her uterus, but not of her ovaries, a 34-year-old, clinically healthy woman contributed a daily blood sample at 0900 and measured her skin surface temperature on her right breast above the nipple and just below the right breast daily for the ensuing 2 months. In aliquots of serum stored frozen, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined in the United States; these hormones and prolactin, estradiol (E2), progesterone, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), cortisol, triiodothyronine (T3), free thyroxine (T4), and free testosterone were determined in Italy. Hormonal data were analyzed by least-squares rhythmometry with and without the data obtained around the FSH-LH surge, to assess any circatrigintan variation. Technically, there is good agreement between the rhythm characteristics of the series of determinations made in Italy and the United States. A circatrigintan rhythm is thus quantified for LH, FSH, prolactin, E2, progesterone, and testosterone. Analyses of the differential skin surface temperature (DST) between the two sites were carried out to examine the usefulness of this variable as a marker rhythm for a noninvasive assessment of the time of ovulation. Features as prominent as the LH and FSH surge, which would render the noninvasive assessment of ovulation time more reliable, were not found in the DST of the subject under the conditions examined, even if a circatrigintan component is demonstrable for DST and some of the hormones examined after hysterectomy.


[Sebaceous gland carcinoma of the eyelids].
Sebaceous gland carcinoma is considered a relatively rare tumor and represents approximately 1 and 5% of all eyelid tumors. These tumors usually arise in the Meibomian glands of tarsus, in the Zeis glands, and the sebaceous glands of caruncle or eyebrow. In some instances it had multicentric origin, while in other cases the initial location was unable to be determined. It occurs more frequently in women than in men and presentation age varies from 50 to 90 years. Clinical diagnosis is difficult because is can be confused with chalazion, blepharoconjunctivitis, conjunctivitis, and basocellular carcinoma. Sebaceous gland carcinoma could go unnoticed; thus, it is necessary to carry out excision of conjunctiva as well as to inform the pathologist of the possibility of malignancy, because pagetoide spread can be easily incorrectly interpreted or not observed even by expert pathologists (up to 50%). Five-years mortality has been estimated at 30% due delayed diagnosis and treatment. The present work intends to describe incidence, and clinical and histopathologic presentation of sebaceous gland carcinoma during the last 40 years at the Dr. Luis Sanchez Bulnes Hospital, Association to Prevent Blindness in Mexico, as well as to review treatment modalities forecast for this entity.


How loud is the underwater noise from operating offshore wind turbines?
Offshore wind turbines are increasingly abundant sources of underwater low frequency noise. This increase raises concern for the cumulative contribution of wind farms to the underwater soundscape and possible impact on marine ecosystems. Here, available measurements of underwater noise from different wind turbines during operation are reviewed to show that source levels are at least 10-20 dB lower than ship noise in the same frequency range. The most important factor explaining the measured sound pressure levels from wind turbines is distance to the turbines with smaller effects of wind speed and turbine size. A simple multi-turbine model demonstrates that cumulative noise levels could be elevated up to a few kilometres from a wind farm under very low ambient noise conditions. In contrast, the noise is well below ambient levels unless it is very close to the individual turbines in locations with high ambient noise from shipping or high wind speeds. The rapid increase in the number and size of offshore wind farms means that the cumulative contribution from the many turbines may be considerable and should be included in assessments for maritime spatial planning purposes as well and environmental impact assessments of individual projects.


Echographic measurement of optic nerve thickness correlated with neuroretinal rim area and visual field defect in glaucoma.
To determine whether echographic measurements of the pial diameter of the optic nerve are significantly correlated with glaucomatous changes of the optic disk and retinal nerve fiber layer. In 31 patients with primary open-angle glaucoma and 16 normal control subjects, optic nerve thickness was determined by measuring the maximal pial diameter of the optic nerve using standardized A-scan echography. The optic disks were morphometrically examined using color stereo photographs, and the retinal nerve fiber layer was assessed using wide-angle red-free fundus photographs. Optic nerve thickness as measured echographically decreased significantly (P < .001) with decreasing neuroretinal rim area, diminishing visibility of the retinal nerve fiber layer, narrowing of the retinal arterioles, enlarging parapapillary atrophy, and increasing mean visual field defect. In an intraindividual bilateral comparison, side differences in the optic nerve thickness were significantly correlated with side differences in neuroretinal rim area (P < .0001), diameter of retinal arterioles (P = .003), and visual field defect (P < .0001). In the differentiation of normal and glaucomatous eyes, sensitivity and specificity were higher for echographic measurements of the optic nerve thickness than for parapapillary atrophy and diameter of retinal arterioles but worse than for determination of the neuroretinal rim area. Echographic measurements of optic nerve thickness are significantly correlated with glaucomatous changes of the optic disk and retinal nerve fiber layer. In patients with opaque media, echographic measurement of optic nerve thickness may be helpful in distinguishing among normal eyes, eyes with medium advanced glaucoma, and eyes with markedly progressed glaucoma.


Urinary nuclear matrix protein 22 for diagnosis of renal cell carcinoma.
To determine the incidence of positive urinary nuclear matrix protein 22 (NMP22) values, which are currently used to detect transitional cell carcinoma of the bladder, in renal cell carcinoma (RCC). Urinary NMP22 values were determined preoperatively in 41 patients in whom a solid renal mass had been detected using CT and who were scheduled for radical nephrectomy; 38 of these patients were diagnosed with RCC. Two patients had xanthogranulomatous pyelonephritis and one had metastasis of a small cell adenocarcinoma to the kidney; these patients were excluded from the study. A total of 30 patients with kidney stones and simple renal cysts were used as controls. The urinary NMP22 values of the RCC patients were significantly higher than those of the controls. Of the 38 patients with RCC, 23 (60.5%) had positive urinary NMP22 values > or =10 U/ml. There were four measurements above this cut-off level in the control group. Urinary NMP22 values increased with an increase in pathologic tumor stage, but the correlation was not statistically significant. There was no correlation between grade and urinary NMP22 or between tumor burden and urinary NMP22. The urinary NMP22 test may help to diagnose RCC and may also result in an increase in the incidental discovery of RCC. As elevated urinary NMP22 levels have also been found to occur in RCC, patients with suspected bladder cancer and positive urinary NMP22 levels should be more broadly evaluated. Specific NMP assays for renal tumor cells may increase the utility of the test for RCC.


Interhemispheric transmission of visuomotor information for motor implementation.
Using transcranial magnetic stimulation (TMS), we addressed the contribution of both hemispheres to the visuomotor control of each hand. The subjects had to press one of two buttons as quickly as possible after the go-signal. A precue preceding this conveyed full, partial or no advance information (hand and/or button), such that reaction time (RT) shortened with increasing amount of information. We gave TMS over each hemisphere at various time intervals (100-350 ms) after the go-signal and before the expected onset of response, and measured its effect on RT, movement time (MT) and error rate. At short intervals (100-200 ms), left hemisphere TMS delayed RT and prolonged MT of both hands, while right hemisphere TMS delayed RT only of the right hand, without affecting error rates. At long intervals (250-350 ms), TMS produced slightly more pronounced RT delays of the contralateral hand. RT was delayed more if the precues were less informative. The results suggest the importance of interhemispheric transmission of visuomotor information for motor implementation. The right hemisphere may play a role mainly in calculating target and effector information, determining RT, while the left hemisphere may play a role in elaborating the motor program and determining MT.


Efficacy of slow infusion of gadolinium contrast agent in three-dimensional MR coronary artery imaging.
The impact of the contrast infusion scheme on contrast-enhanced coronary artery imaging was investigated. The imaging technique was a retrospective respiratory-gated gradient-echo sequence. To improve the contrast between blood vessels and myocardium, an inversion pulse was applied to null the myocardial signal. Extravascular contrast agent was infused slowly during data acquisition. Two contrast infusion schemes were compared in animal and volunteer studies and with simulations. One scheme enhanced blood signals during acquisition of both peripheral and central k-space data, which resulted in a relatively flat low-pass k-space filter. The other scheme mainly enhanced blood signals during acquisition of central k-space data, which resulted in a sharp low-pass k-space filter. It is concluded that the former scheme improves the signal-to-noise ratio and edge definition of coronary arteries compared with the latter scheme. J. Magn. Reson. Imaging 1999;10:800-805.


X-ray microanalysis of the kidney.
The use of x-ray microanalysis for the localization of insoluble deposits in kidney tissue, the quantitation of micropuncture samples from tubular lumens, and the localization and quantitation of histochemical reaction products are becoming standard procedures in a variety of laboratories involved in renal research. The validity of these procedures has been established and exploitation of them should lead to new research insights. Even more exciting are the new analytical procedures for quantitative analysis of soluble substances in tissue sections. Shock frozen kidney can be analyzed in the frozen hydrated, frozen dried, or freeze substituted state. The promise of applying these technical achievements to renal research is a more precise understanding of the ion concentrations in lumens, intersititium, cells, and their organelles from various regions of the kidney in documented physiological and pathological states.


Cytokine mRNA profile of alveolar T lymphocytes and macrophages in patients with systemic sclerosis suggests a local Tr1 response.
The development of an autoimmune disease like systemic sclerosis (SSc) is suspected to be driven by an activated T lymphocyte subset, expressing a cytokine profile specific to the disease. To further characterize the type of immune reaction in SSc, we searched for a broad panel of cytokine messenger ribonucleic acids (mRNAs) in T lymphocytes and monocytes/macrophages from paired samples of bronchoalveolar lavage fluid and peripheral blood in 18 patients and 16 age- and sex-matched controls. RNA from CD3(+) T lymphocytes and CD14(+) monocytes/macrophages was examined by means of the reverse transcriptase polymerase chain reaction. SSc alveolar T lymphocytes expressed a cytokine profile suggestive of a mixed Th1/Th2 reaction, showing an increased frequency of mRNA for interleukin (IL)-10, IL-6 and interferon (IFN)γ, while IL-1β, IFNγ and tumour necrosis factor β were expressed in blood T lymphocytes in a higher percentage of patients with SSc than controls. SSc alveolar T cells expressed IL-10 mRNA more often than peripheral T cells, a phenomenon not found in controls and which may point at local IL-10 activation/response in SSc lung. Transforming growth factor β mRNA was present in all alveolar as well as peripheral blood T cell samples in patients and controls. The cytokine mRNA profile in SSc with interstitial lung disease (ILD) was similar to the profile found in SSc without ILD. Our findings point at a mixed Th1/Th2 reaction in SSc and may indicate regulatory T 1 cell activation/response in the lungs of patients with SSc.


Rapid evolution in plant chitinases: molecular targets of selection in plant-pathogen coevolution.
Many pathogen recognition genes, such as plant R-genes, undergo rapid adaptive evolution, providing evidence that these genes play a critical role in plant-pathogen coevolution. Surprisingly, whether rapid adaptive evolution also occurs in genes encoding other kinds of plant defense proteins is unknown. Unlike recognition proteins, plant chitinases attack pathogens directly, conferring disease resistance by degrading chitin, a component of fungal cell walls. Here, we show that nonsynonymous substitution rates in plant class I chitinase often exceed synonymous rates in the plant genus Arabis (Cruciferae) and in other dicots, indicating a succession of adaptively driven amino acid replacements. We identify individual residues that are likely subject to positive selection by using codon substitution models and determine the location of these residues on the three-dimensional structure of class I chitinase. In contrast to primate lysozymes and plant class III chitinases, structural and functional relatives of class I chitinase, the adaptive replacements of class I chitinase occur disproportionately in the active site cleft. This highly unusual pattern of replacements suggests that fungi directly defend against chitinolytic activity through enzymatic inhibition or other forms of chemical resistance and identifies target residues for manipulating chitinolytic activity. These data also provide empirical evidence that plant defense proteins not involved in pathogen recognition also evolve in a manner consistent with rapid coevolutionary interactions.


Memristors with Nociceptor Characteristics Using Threshold Switching of Pt/HfO2/TaOx/TaN Devices.
As artificial intelligence technology advances, it is necessary to imitate various biological functions to complete more complex tasks. Among them, studies have been reported on the nociceptor, a critical receptor of sensory neurons that can detect harmful stimuli. Although a complex CMOS circuit is required to electrically realize a nociceptor, a memristor with threshold switching characteristics can implement the nociceptor as a single device. Here, we suggest a memristor with a Pt/HfO2/TaOx/TaN bilayer structure. This device can mimic the characteristics of a nociceptor including the threshold, relaxation, allodynia, and hyperalgesia. Additionally, we contrast different electrical properties according to the thickness of the HfO2 layer. Moreover, Pt/HfO2/TaOx/TaN with a 3 nm thick HfO2 layer has a stable endurance of 1000 cycles and controllable threshold switching characteristics. Finally, this study emphasizes the importance of the material selection and fabrication method in the memristor by comparing Pt/HfO2/TaOx/TaN with Pt/TaOx/TaN, which has insufficient performance to be used as a nociceptor.


COVID-19 Critical Illness: A Data-Driven Review.
The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Noninvasive respiratory support modalities are being used with increasing frequency given their potential to reduce the need for intubation. Determining optimal patient selection for and timing of intubation remains a challenge. Management of mechanically ventilated patients with COVID-19 largely mirrors that of non-COVID-19 ARDS. Organ failure is common and portends a poor prognosis. Mortality rates have improved over the course of the pandemic, likely owing to increasing disease familiarity, data-driven pharmacologics, and improved adherence to evidence-based critical care.


The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the mu-opioid receptor.
Wild-type and mu-opioid receptor knockout (MORKO) mice were used to investigate the role of corticosterone (CORT) and the mu-opioid receptor (MOR) in chronic morphine-mediated immunosuppression. We found that although plasma CORT concentrations in CORT infusion (10 mg/kg/day) and morphine-pellet implantation (75 mg) mice were similar (400-450 ng/ml), chronic morphine treatment resulted in a significantly higher (two- to threefold) inhibition of thymic, splenic, and lymph node cellularity; inhibition of thymic-lymphocyte proliferation; inhibition of IL-2 synthesis; and activation of macrophage nitric oxide (NO) production when compared with CORT infusion. In addition, results show that the inhibition of IFN-gamma synthesis and splenic- and lymph node-lymphocyte proliferation and activation of macrophage TNF-alpha and IL-1beta synthesis occurred only with chronic morphine treatment but not with CORT infusion. These morphine effects were abolished in MORKO mice. The role of the sympathetic nervous system on morphine-mediated effects was investigated by using the ganglionic blocker chlorisondamine. Our results show that chlorisondamine was able to only partially reverse morphine's inhibitory effects. The results clearly show that morphine-induced immunosuppression is mediated by the MOR and that although some functions are amplified in the presence of CORT or sympathetic activation, the inhibition of IFN-gamma synthesis and activation of macrophage-cytokine synthesis is CORT-independent and only partially dependent on sympathetic activation.


Objects exhibit body model like shape distortions.
Accurate knowledge about size and shape of the body derived from somatosensation is important to locate one's own body in space. The internal representation of these body metrics (body model) has been assessed by contrasting the distortions of participants' body estimates across two types of tasks (localization task vs. template matching task). Here, we examined to which extent this contrast is linked to the human body. We compared participants' shape estimates of their own hand and non-corporeal objects (rake, post-it pad, CD-box) between a localization task and a template matching task. While most items were perceived accurately in the visual template matching task, they appeared to be distorted in the localization task. All items' distortions were characterized by larger length underestimation compared to width. This pattern of distortion was maintained across orientation for the rake item only, suggesting that the biases measured on the rake were bound to an item-centric reference frame. This was previously assumed to be the case only for the hand. Although similar results can be found between non-corporeal items and the hand, the hand appears significantly more distorted than other items in the localization task. Therefore, we conclude that the magnitude of the distortions measured in the localization task is specific to the hand. Our results are in line with the idea that the localization task for the hand measures contributions of both an implicit body model that is not utilized in landmark localization with objects and other factors that are common to objects and the hand.


Featured counter-trafficking program: Project intersect.
This invited article is one of several comprising part of a special issue of Child Abuse and Neglect focused on child trafficking and health. The purpose of each invited article is to describe a specific program serving trafficked children. Featuring these programs is intended to raise awareness of innovative counter-trafficking strategies emerging worldwide and facilitate collaboration on program development and outcomes research. This article describes Project Intersect, a program of mental health services and behavioral health professional training designed to address trauma-related psychological and behavioral problems experienced by adolescent survivors of commercial sexual exploitation and trafficking. The project is led by the Georgia Center for Child Advocacy in Atlanta, GA, USA. The primary goal of the program is to build a cadre of behavioral health specialists with skills to implement trauma-focused cognitive behavioral therapy to address the unique needs of trafficked/exploited youth. This involves intensive initial training, follow-up consultation, technical support, and program evaluation.


DMP1 C-terminal mutant mice recapture the human ARHR tooth phenotype.
DMP1 mutations in autosomal recessive hypophosphatemic rickets (ARHR) patients and mice lacking Dmp1 display an overlapping pathophysiology, such as hypophosphatemia. However, subtle differences exist between the mouse model and human ARHR patients. These differences could be due to a species specificity of human versus mouse, or it may be that the mutant DMP1 in humans maintains partial function of DMP1. In this study we report a deformed tooth phenotype in a human DMP1 deletion mutation case. Unexpectedly, the deletion of nucleotides 1484 to 1490 (c.1484_1490delCTATCAC, delMut, resulting in replacement of the last 18 residues with 33 random amino acids) showed a severe dentin and enamel defect similar to a dentinogenesis imperfecta (DI) III-like phenotype. To address the molecular mechanism behind this phenotype, we generated delMut transgenic mice with the endogenous Dmp1 gene removed. These mutant mice did not recapture the abnormal phenotype observed in the human patient but displayed a mild rachitic tooth phenotype in comparison with that in the Dmp1-null mice, suggesting that the DI III-like phenotype may be due to an as-yet-undetermined acquired gene modifier. The mechanism studies showed that the mutant fragment maintains partial function of DMP1 such as stimulating MAP kinase signaling in vitro. Last, the in vitro and in vivo data support a role of odontoblasts in the control of fibroblast growth factor 23 (FGF-23) regulation during early postnatal development, although this regulation on Pi homeostasis is likely limited.


Modulation of lateral geniculate nucleus cell responsiveness by visual activation of the corticogeniculate pathway.
A radial grating stimulus was used to assess the effect of stimulation of the region beyond the classical surround of monkey lateral geniculate nucleus (LGN) receptive fields. The effect was measured by the differences in the responsiveness of the LGN cell center to small flashing spots between two conditions: (1) grating stationary or (2) grating rotating. The grating was present only in regions beyond the classical center and surround. The rotating grating produced changes in the flash-evoked spike response but not in the spontaneous activity in about half of the X cells and all of the Y cells. The direction of the effect was independent of the sign of the receptive field center. In a control experiment, cryogenic blockade of striate cortex reversed the effect in all cells tested. The grating effect was still present for cells having fields in that part of visual space beyond the region represented by the cooled cortical area. The effect was not a result of activation of classical extra-receptive field influences, since cells showing the effect did not exhibit shift or periphery effects or outer disinhibitory surrounds. The effect was not seen in recordings from intrageniculate retinal axons. We conclude that the radial grating effects LGN cell responsivity by activation of the corticogeniculate pathway.


Early growth response genes regulate B cell development, proliferation, and immune response.
Egr-1 (early growth response gene-1) is an immediate early gene encoding a zinc finger motif-containing transcription factor. Upon cross-linking of BCR, mature B cells undergo proliferation with an increase in Egr-1 message. Immature B lymphoma cells that express Egr-1 message and protein constitutively are growth inhibited when Egr-1 is down-regulated by negative signals from BCR or by antisense oligonucleotides. To test the hypothesis that Egr-1 is important for B cell development, we examined B cells from primary and secondary lymphoid organs in Egr-1(-/-) mice. Marginal zone B cell development was arrested in these mice, whereas the B cells in all other compartments were increased. To test the hypothesis that Egr-1 function may be partially compensated by other Egr family members, we developed transgenic mice expressing a dominant negative form of Egr-1, which lacks the trans activation domain but retains the DNA-binding domain, in a B cell-specific manner. There was a decrease in B lymphopoiesis in the bone marrow accompanied by a reduction in splenic immature and mature B cells as well as marginal zone B cells in the transgenic mice. Moreover, transgenic mice respond poorly to BCR cross-linking in vitro and T-independent and T-dependent Ags in vivo.


A safe model for creating blunt and penetrating ballistic injury.
Minor modification of an existing readily available captive projectile weapon system has allowed development of a safe model for studying both penetrating ballistic and blunt tissue injury. A captive projectile weapon (defined as a firearm in which the projectile does not leave the weapon and in which the external wounding range is very limited) diminishes greatly the possibility of injury to personnel while it allows a high degree of reproducibility. The system has three parts: the pistol (wt 1.3 kg), a stainless steel stand, and a rack for holding the organ to be injured. It has been used 14 times in developing a canine model for the study of penetrating ballistic renal injury. When a 2 grain, .22 caliber charge is fired in the weapon, the .45 caliber captive projectile travels 7.5 cm and penetrates the kidney completely. The kinetic energy available for transfer from the projectile to the kidney and renal vessels totals 211 joules, which is comparable to the kinetic energy of projectiles for many law enforcement sidearms at 45.72 meters (50 yards) from the muzzle of the weapon. Comparison of the wounds showed complete reproducibility of injury (100%) over all 14 subjects [Entrance wound greater than or equal to .45 caliber (100%). Exit wound greater than or equal to .45 caliber (100%). Complete penetration (100%)]. This weapon system can be modified to duplicate the injury created by missiles from many small arms by modifying the captive projectile and/or the charge. Changing the leading surface of the captive projectile allows delivery of the energy over a broad surface such that blunt injuries can be simulated.


Determining the waist circumference cut off which best predicts the metabolic syndrome components in urban Africans: the SABPA study.
Various studies have shown that the relationship between waist circumference (WC) and abdominal obesity is age, gender as well as ethnicity-dependent. WC criteria for Sub Saharan Africans have not been defined by the International Diabetes Federation (IDF). The aim was to determine which WC cut off best predicted Metabolic Syndrome (MetS) in a group of urban African teachers (80 males and 93 females). We determined sphygmomanometer blood pressure, WC, glucose, high density lipoprotein cholesterol (HdL) and triglyceride (TRIG) values. The males' MetS profile was less favourable as their glucose, TRIG and blood pressure levels were higher than the proposed cut off for MetS. The females could be classified as obese, based on their mean BMI (32.78±6.36) and WC (93.48±15.68). Receiver operating characteristic (ROC) WC cut offs of 90, 91, 94 and 96 cm for the respective MetS components in males (blood pressure, HdL, glucose and TRIG) were suggested. In the females, cut offs of 92, 98, 94 and 94 cm for TRIG, blood pressure, HdL and glucose respectively, were put forward. Odds ratios revealed that increased blood pressure best predicted ROC WC in both males (OR 9.59; 95% CI 3.14-29.32) and females (OR 3.11; 95% CI 1.30-7.42) irrespective of age. We suggest that the optimal cut off point for the males be set at 90 cm, as opposed to the current 94 cm; whilst the female cut off be set at 98 cm as opposed to the existing cut off of 80 cm. Larger sample groups are recommended to justify our data.


Angucyclines: Biosynthesis, mode-of-action, new natural products, and synthesis.
Covering: 1997 to 2010. The angucycline group is the largest group of type II PKS-engineered natural products, rich in biological activities and chemical scaffolds. This stimulated synthetic creativity and biosynthetic inquisitiveness. The synthetic studies used five different strategies, involving Diels-Alder reactions, nucleophilic additions, electrophilic additions, transition-metal mediated cross-couplings and intramolecular cyclizations to generate the angucycline frames. Biosynthetic studies were particularly intriguing when unusual framework rearrangements by post-PKS tailoring oxidoreductases occurred, or when unusual glycosylation reactions were involved in decorating the benz[a]anthracene-derived cores. This review follows our previous reviews, which were published in 1992 and 1997, and covers new angucycline group antibiotics published between 1997 and 2010. However, in contrast to the previous reviews, the main focus of this article is on new synthetic approaches and biosynthetic investigations, most of which were published between 1997 and 2010, but go beyond, e.g. for some biosyntheses all the way back to the 1980s, to provide the necessary context of information.


Histopathological alterations in post-infectious irritable bowel syndrome in Bangladeshi population.
Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder encountered in general practice. Although enormous progress in the pathogenesis of IBS has been made, it is still poorly understood. A significant proportion of patients with IBS, report onset of symptoms following an episode of acute gastroenteritis. Aim of the study was to determine whether post infective irritable bowel syndrome (PI-IBS) has histological or clinical features that are distinct from those of IBS patients with no history of preceding infection. A total of 50 consecutive IBS out patients and 10 healthy control subjects completed a questionnaire detailing symptoms, mode of onset, and previous psychiatry history. All underwent a full diagnostic workup including colonic biopsy and histopathology. Patients were divided according to onset of symptoms into post infectious IBS (PI-IBS, N=18) and non-post infectious IBS (non-PI-IBS, N=32) patients. Diarrhea predominantly occurred more frequently in PI- IBS (70%) than in non-PI-IBS (40%) patients (p<0.05). Histopathological examination of the biopsy specimen from the sigmoid colon of the observed individuals showed a significant increase in the number of chronic inflammatory cells in both groups of IBS patients comparing to the control group (p<0.001). Lymphoid follicles were increased in both groups of IBS patients in comparison to control group (p<0.05). Mast cells were increased in IBS patients comparing to the control group (p<0.05) and it was significantly increased in the PI-IBS patients than the non-PI-IBS patients (p<0.001). Individuals with PI-IBS are clinically distinct subgroup characterized by predominant diarrheal symptoms and increased mast cells compared to those with non PI-IBS.


Autism in the criminal justice detention system: A review of the literature.
Little is known about the experience of people with autism in custody. A review of the literature that explored the relationship between autism and criminality and the criminal justice detention system was conducted. Literature suggests that people with autism are potentially overrepresented within the criminal justice system. There is little research that has examined the experiences of people with autism spectrum disorders in custody. There is very little to guide service design to develop autism support services for people in prison.


Effect of two new antisecretory drugs on fluid and electrolyte transport in a patient with secretory diarrhoea.
The effect of oral lidamidine hydrochloride and subcutaneous long acting somatostatin analogue, SMS 201-995, on stool output and salt and water transport in the small intestine was investigated in a patient with gross secretory diarrhoea caused by a vasoactive intestinal polypeptide (VIP) secreting tumour in the liver. Transport in the jejunum and ileum were assessed by steady state perfusion techniques. Under basal conditions, the patient was absorbing fluid and electrolytes from the jejunum and ileum, but at rates that were abnormally low. Lidamidine had no effect on either intestinal transport or stool frequency and output. SMS 201-995 increased intestinal absorption in the jejunum and ileum, reduced plasma VIP concentrations, daily stool frequency and weight, and enabled the patient to resume a normal diet without oral or intravenous fluid and electrolyte supplements. After two months of treatment, medical control was becoming increasingly difficult and stool output had risen again to 2 litres per day. Surgical resection, fortunately, was possible and led to resolution of symptoms and normal plasma VIP concentrations.


p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19.
Hepatoblastomas (HBs), representing malignant liver tumors of childhood, show frequent loss of heterozygosity (LOH) in the chromosomal region 11p15.5. This loss is of maternal origin suggesting the presence of a monoallelically expressed tumor suppressor gene in this region. p57(KIP2) (KIP2) located at 11p15.5 is predominantly expressed from the maternal allele and encodes a cyclin-dependent kinase inhibitor. We screened a series of 56 HB tumors and five HB cell lines for allelic loss (LOH) of the KIP2 locus by microsatellite analysis and KIP2 coding sequence mutations by single-strand conformation polymorphism analysis. Although LOH at the KIP2 locus occurred in 25% of the cases, no mutations were found. Analysis of KIP2 mRNA expression by competitive reverse transcriptase-polymerase chain reaction revealed up-regulation in nine of 12 HBs compared to matching liver samples. In contrast, mRNA levels of the putative suppressor gene H19 on 11p15.5 were decreased in 10 of 12 tumors, indicating that KIP2 and H19 are not co-regulated in HBs. IGF2 mRNA expression was increased in 11 of 12 HB samples. All HBs showed monoallelic KIP2 expression. However, the overexpression of KIP2 in HBs with maternal loss of 11p15.5 suggests a reactivation of the paternal allele in these cases. Overexpression of KIP2 in HBs argues against a role as a HB suppressor gene.


Instantaneous Spatial Light Interference Microscopy.
We present Instantaneous Spatial Light Interference Microscopy (iSLIM) as a new quantitative phase method that combines the benefits of white light illumination in Zernike's phase contrast microscopy and phase stability associated diffraction phase microscopy. iSLIM is implemented as an add-on module to a commercial phase contrast microscope, and enables new features to quantitative phase imaging: diminished speckle effects due to white light illumination, multimodal investigation potential due to overlaying with other modalities of the microscope (e.g. fluorescence, DIC, phase contrast), and spectroscopic potential due to the broad band light. We show proof of principle results by multicolor phase imaging of microsphere and red blood cells, and dynamic imaging of nanoscale cell membrane fluctuations.


Factors Required for Adhesion of Salmonella enterica Serovar Typhimurium to Lactuca sativa (Lettuce).
Salmonella enterica serovar Typhimurium is a major cause of foodborne gastroenteritis. Recent outbreaks of infections by S. enterica serovar Typhimurium are often associated with non-animal-related food, i.e., vegetables, fruits, herbs, sprouts, and nuts. One main problem related to the consumption of fresh produce is the minimal processing, especially for leafy green salads. In this study, we focused on butterhead lettuce (Lactuca sativa) to which S. enterica serovar Typhimurium adheres at higher rates compared to Valerianella locusta, resulting in prolonged persistence. Here, we systematically analyzed factors contributing to adhesion of S. enterica serovar Typhimurium to L. sativa leaves. Application of a reductionist, synthetic approach, including the controlled surface expression of specific adhesive structures of S. enterica serovar Typhimurium, one at a time, enabled the identification of relevant fimbrial and nonfimbrial adhesins, the O-antigen of lipopolysaccharide, the flagella, and chemotaxis being involved in binding to L. sativa leaves. The analyses revealed contributions of Lpf fimbriae, Sti fimbriae, autotransported adhesin MisL, T1SS-secreted BapA, intact lipopolysaccharide (LPS), and flagella-mediated motility to adhesion of S. enterica serovar Typhimurium to L. sativa leaves. In addition, we identified BapA as a potential adhesin involved in binding to V. locusta and L. sativa leaf surfaces. IMPORTANCE The number of produce-associated outbreaks by gastrointestinal pathogens is increasing and underlines the relevance to human health. The mechanisms involved in the colonization of, persistence on, and transmission by, fresh produce are poorly understood. Here, we investigated the contribution of adhesive factors of S. enterica serovar Typhimurium in the initial phase of plant colonization, i.e., the binding to the plant surface. We used the previously established reductionist, synthetic approach to identify factors that contribute to the surface binding of S. enterica serovar Typhimurium to leaves of L. sativa by expressing all known adhesive structures by remote control expression system.


Evaluation of the efficacy of blood glucose home monitoring devices.
An important component of diabetes care is self-monitoring blood glucose (BG). Up to now, no standard quality control procedure has verified the readings of various blood glucose meters in Iran. The purpose of this study was to compare the efficacy of three glucose meters and Betachek (a visual BG measurement test) with the measurement of a reference laboratory. The Betachek test strip and three other common glucometer devices in Iran (Glucotrend 2, GlucoMen, and GlucoCare) were used to determine BG levels in 110 patients suffering from diabetes. The results were then compared with a standard laboratory method. The mean measurement of blood glucose by GlucoCare showed the least deviation from the standard laboratory method (6.80% less than the standard method). Glucotrend 2 had the best correlation with the standard method. The mean deviations in BG level as read by GlucoMen, Glucotrend 2, and Betachek were 9.53%, 11.95%, and 10.26% higher than the standard method, respectively. Betachek showed the lowest correlation with the standard method. GlucoCare and Glucotrend 2 had the most advantageous results; however, no glucometer met the ADA criteria of reading within 5% of the laboratory reference results. Betachek had the least reliable readings.


[Treatment and prevention of monkeypox].
Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.


Application of deoxyribonucleic acid barcoding in Lauraceae plants.
This study aims to determine the candidate markers that can be used as DNA barcode in the Lauraceae family. Polymerase chain reaction amplification, sequencing efficiency, differential intra- and interspecific divergences, DNA barcoding gap, and identification efficiency were used to evaluate the four different DNA sequences of psbA-trnH, matK, rbcL, and ITS2. We tested the discrimination ability of psbA-trnH in 68 plant samples belonging to 42 species from 11 distinct genera and found that the rate of successful identification with the psbA-trnH was 82.4% at the species level. However, the correct identification of matK and rbcL were only 30.9% and 25.0%, respectively, using BLAST1. The PCR amplification efficiency of the ITS2 region was poor; thus, ITS2 was not included in subsequent experiments. To verify the capacity of the identification of psbA-trnH in more samples, 175 samples belonging to 117 species from the experimental data and from the GenBank database of the Lauraceae family were tested. Using the BLAST1 method, the identification efficiency were 84.0% and 92.3% at the species and genus level, respectively. Therefore, psbA-trnH is confirmed as a useful marker for differentiating closely related species within Lauraceae.


A compound chimeric antigen receptor strategy for targeting multiple myeloma.
Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.


Hands-Free System for Bronchoscopy Planning and Guidance.
Bronchoscopy is a commonly used minimally invasive procedure for lung-cancer staging. In standard practice, however, physicians differ greatly in their levels of performance. To address this concern, image-guided intervention (IGI) systems have been devised to improve procedure success. Current IGI bronchoscopy systems based on virtual bronchoscopic navigation (VBN), however, require involvement from the attending technician. This lessens physician control and hinders the overall acceptance of such systems. We propose a hands-free VBN system for planning and guiding bronchoscopy. The system introduces two major contributions. First, it incorporates a new procedure-planning method that automatically computes airway navigation plans conforming to the physician's bronchoscopy training and manual dexterity. Second, it incorporates a guidance strategy for bronchoscope navigation that enables user-friendly system control via a foot switch, coupled with a novel position-verification mechanism. Phantom studies verified that the system enables smooth operation under physician control, while also enabling faster navigation than an existing technician-assisted VBN system. In a clinical human study, we noted a 97% bronchoscopy navigation success rate, in line with existing VBN systems, and a mean guidance time per diagnostic site = 52 s. This represents a guidance time often nearly 3 min faster per diagnostic site than guidance times reported for other technician-assisted VBN systems. Finally, an ergonomic study further asserts the system's acceptability to the physician and long-term potential.


Development of the SPARK family member web pages to improve symptom management for pediatric patients receiving cancer treatments.
Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web-based application that facilitates symptom screening and access to supportive care clinical practice guidelines (CPGs) for children and adolescents receiving cancer treatments. Objective was to develop SPARK family member web pages for pediatric patient family members accessing: (1) proxy symptom screening and symptom reports, and (2) care recommendations for symptom management based on CPGs. SPARK family member web pages were developed and included access to symptom screening and care recommendations sections. Care recommendations for fatigue and mucositis were created. These were iteratively refined based upon cognitive interviews with English-speaking family members ≥16 years of age until less than two participants incorrectly understood sections as adjudicated by two independent raters. A total of 100 family members were enrolled who evaluated the SPARK family member web pages (n = 40), fatigue care recommendation (n = 30) and mucositis prevention care recommendation (n = 30). Among the last 10 participants, none said that the SPARK family member web pages were hard or very hard to use, one incorrectly understood one web page, none said either care recommendation was hard to understand and none were incorrect in their understanding of the care recommendations. We successfully developed SPARK web pages for use by family members of pediatric patients receiving cancer treatments. We also developed a process for translating CPG recommendations designed for healthcare professionals to lay language. The utility of SPARK family member web pages after clinical implementation could be a focus for future research.


Trends in the prevalence and treatment of hypertension in Halifax County from 1985 to 1995.
The objective of this study was to document changes in the prevalence and treatment of hypertension in Halifax County from 1985 to 1995 in an effort to observe, at the population level, the consequences of the availability of new antihypertensive medications. The study population comprised a random sample of Halifax County residents, aged 25-64 years, who responded to the 1985 and 1995 surveys of the Halifax County MONICA Project and residents who responded to the Nova Scotia Health Survey conducted in 1995. Data from the two 1995 surveys were pooled. Information on hypertension awareness and use of medication were obtained through questionnaires, and blood pressure was measured according to a standard protocol, using phase I and V of Korotkoff sounds as respective markers for systolic and diastolic pressures. Uncontrolled hypertension was defined as a systolic pressure of 140 mm Hg or greater and a diastolic pressure of 90 mm Hg or greater. Changes in the prevalence of hypertension, prescribing trends and medication costs were examined, and the association between the type of antihypertensive treatment and characteristics of the respondents with self-reported hypertension was investigated by multivariate logistic regression. Of the 917 people interviewed in 1985 and the 1338 in 1995, 274 (29.9%) and 356 (26.6%), respectively, reported a history of hypertension. When age was controlled for, the proportion of respondents reporting hypertension did not differ between survey years or between men and women. The proportion of treated respondents who had uncontrolled hypertension increased between 1985 and 1995, from 32.6% to 57.4% among men and from 38.0% to 42.6% among women. An increase was seen in the use of calcium-channel blockers (from 2.1% to 19.7%) and angiotensin-converting-enzyme inhibitors (from 5.2% to 25.4%); the proportion of patients receiving combination therapy or diuretics decreased (from 39.6% to 15.6% and from 31.3% to 17.2% respectively). These changes were associated with an increase in the average daily cost of medication from $0.48 to $0.85 per patient. The shift to new antihypertensive drugs was not associated with improved blood pressure control, but it was associated with an increase in average medication costs per patient. Uncontrolled hypertension remains a public health problem.


RegExpBlasting (REB), a Regular Expression Blasting algorithm based on multiply aligned sequences.
One of the most frequent uses of bioinformatics tools concerns functional characterization of a newly produced nucleotide sequence (a query sequence) by applying Blast or FASTA against a set of sequences (the subject sequences). However, in some specific contexts, it is useful to compare the query sequence against a cluster such as a MultiAlignment (MA). We present here the RegExpBlasting (REB) algorithm, which compares an unclassified sequence with a dataset of patterns defined by application of Regular Expression rules to a given-as-input MA datasets. The REB algorithm workflow consists in i. the definition of a dataset of multialignments ii. the association of each MA to a pattern, defined by application of regular expression rules; iii. automatic characterization of a submitted biosequence according to the function of the sequences described by the pattern best matching the query sequence. An application of this algorithm is used in the "characterize your sequence" tool available in the PPNEMA resource. PPNEMA is a resource of Ribosomal Cistron sequences from various species, grouped according to nematode genera. It allows the retrieval of plant nematode multialigned sequences or the classification of new nematode rDNA sequences by applying REB. The same algorithm also supports automatic updating of the PPNEMA database. The present paper gives examples of the use of REB within PPNEMA. The use of REB in PPNEMA updating, the PPNEMA "characterize your sequence" option clearly demonstrates the power of the method. Using REB can also rapidly solve any other bioinformatics problem, where the addition of a new sequence to a pre-existing cluster is required. The statistical tests carried out here show the powerful flexibility of the method.


Project Swaziland (Part 2): dental caries experience of 12 year old school children.
This investigation was conducted to determine the prevalence of dental caries and degree of dental fluorosis in 12-year-old Swazi school children. The prevalence of dental caries was low (33.7 per cent of children experienced caries and the mean DMFT was 0.92) and corresponded with that found in a neighbouring Swazi community (KaNgwane) but differed strikingly from the results of the baseline study by Klausen and Fanoe (1983). The need for curative dental care was mainly for one surface restorations. A need for selective school preventive programmes was identified.


'I do not share it with others. No, it's for me, it's my care': On sharing of patient accessible electronic health records.
This study explores patients' perspectives on sharing their personal health data, which is traditionally shared through discussions with peers and relatives. However, other possibilities for sharing have emerged through the introduction of online services such as Patient Accessible Electronic Health Records (PAEHR). In this article, we investigate strategies that patients adopt in sharing their PAEHR. Data were collected through a survey with 2587 patients and through 15 semi-structured interviews with cancer patients. Results show that surprisingly few patients share their information, and that older patients and patients with lower educational levels share more frequently. A large majority of patients trust the security of the system when sharing despite the high sensitivity of health information. Finally, we discuss the design implications addressing identified problems when sharing PAEHR, as well as security and privacy issues connected to sharing.


Maternal-fetal glucocorticoid milieu programs hypothalamic-pituitary-thyroid function of adult offspring.
To assess the role of maternal glucocorticoid milieu on the hypothalamic-pituitary-thyroid function of the offspring, we adrenalectomized (ADX) pregnant dams on gestation d 8 and implanted a placebo pellet or a continuous release 50- or 75-mg corticosterone (CORT) pellet. Maternal ADX led to realignment of the balance between maternal and fetal plasma CORT levels, resulting in an increase in CORT of fetal origin in the maternal compartment. Maternal ADX and low levels of CORT replacement had no discernable effect on maternal pituitary-thyroid measures. In contrast, the increase in fetal CORT, as a consequence of the absence of maternal glucocorticoids, decreased birth weight in neonates, decreased adult hypothalamic TRH mRNA levels, and increased plasma TSH levels in both male and female adult offspring, all of which were reversed by administration of basal levels of CORT to the pregnant ADX dam. Decreased plasma T3 concentrations in female offspring were reversed by administration of the higher levels of CORT to the ADX dams. Our data indicate that maternal glucocorticoids modulate the developing hypothalamic-pituitary-thyroid axis.


Human cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is dimeric in its disulfide-reduced state, with natively disordered N-terminal region.
CDK2AP1 (cyclin-dependent kinase 2-associated protein 1), corresponding to the gene doc-1 (deleted in oral cancer 1), is a tumor suppressor protein. The doc-1 gene is absent or down-regulated in hamster oral cancer cells and in many other cancer cell types. The ubiquitously expressed CDK2AP1 protein is the only known specific inhibitor of CDK2, making it an important component of cell cycle regulation during G(1)-to-S phase transition. Here, we report the solution structure of CDK2AP1 by combined methods of solution state NMR and amide hydrogen/deuterium exchange measurements with mass spectrometry. The homodimeric structure of CDK2AP1 includes an intrinsically disordered 60-residue N-terminal region and a four-helix bundle dimeric structure with reduced Cys-105 in the C-terminal region. The Cys-105 residues are, however, poised for disulfide bond formation. CDK2AP1 is phosphorylated at a conserved Ser-46 site in the N-terminal "intrinsically disordered" region by IκB kinase ε.


Applications of bismuth(III) compounds in organic synthesis.
This review article summarizes the applications of bismuth(III) compounds in organic synthesis since 2002. Although there are an increasing number of reports on applications of bismuth(III) salts in polymerization reactions, and their importance is acknowledged, they are not included in this review. This review is largely organized by the reaction type although some reactions can clearly be placed in multiple sections. While every effort has been made to include all relevant reports in this field, any omission is inadvertent and we apologize in advance for the same (358 references).


Food sources and intake of n-6 and n-3 fatty acids in low-income countries with emphasis on infants, young children (6-24 months), and pregnant and lactating women.
With increasing interest in the potential effects of n-6 and n-3 fatty acids in early life, there is a need for data on the dietary intake of polyunsaturated fatty acids (PUFA) in low-income countries. This review compiles information on the content in breast milk and in foods that are important in the diets of low-income countries from the few studies available. We also estimate the availability of fat and fatty acids in 13 low-income and middle-income countries based on national food balance sheets from the United Nations' Food and Agriculture Organization Statistical Database (FOASTAT). Breast milk docosahexaenoic acid content is very low in populations living mainly on a plant-based diet, but higher in fish-eating countries. Per capita supply of fat and n-3 fatty acids increases markedly with increasing gross domestic product (GDP). In most of the 13 countries, 70-80% of the supply of PUFA comes from cereals and vegetable oils, some of which have very low α-linolenic acid (ALA) content. The total n-3 fatty acid supply is below or close to the lower end of the recommended intake range [0.4%E (percentage of energy supply)] for infants and young children, and below the minimum recommended level (0.5%E) for pregnant and lactating women in the nine countries with the lowest GDP. Fish is important as a source of long-chain n-3 fatty acids, but intake is low in many countries. The supply of n-3 fatty acids can be increased by using vegetable oils with higher ALA content (e.g. soybean or rapeseed oil) and by increasing fish production (e.g. through fish farming).


Electroantennogram responses of the cabbage seed weevil,Ceutorhynchus assimilis, to oilseed rape,Brassica napus ssp.Oleifera, volatiles.
Electroantennograms (EAGs) were recorded from male and female cabbage seed weevils (Ceutorhynchus assimilis Payk.) in response to volatiles isolated and identified from the odor of oilseed rape (Brassica napus ssp.oleifera DC. cv. Ariana). Relatively large EAGs were obtained on stimulation with volatiles produced by the oilseed rape crop at the time when seed weevils were actively searching for host plants. Artificial rape odor without certain key volatile compounds was in most cases significantly less stimulatory than odor containing these volatiles. There were significant differences in the EAG response of the sexes ofC. assimilis to the green leaf volatiles of oilseed rape and several terpenes present in rape flower odor. The importance of the qualitative and quantitative composition of host-plant odor in host location byC. assimilis is discussed.


The collaborative role of molecular conformation and energetics in the binding of gas-phase non-covalent polymer/amine complexes.
A large series of similar non-covalent complexes were probed using ion mobility spectrometry, molecular mechanics/molecular dynamics (MM/MD), electrospray-tandem mass spectrometry (ESI-MS/MS) and RRKM theory in order to determine the effects of charge state and charge location upon the conformation, the 0 K activation energy (E(0)) and the entropy of activation (ΔS(‡)) of the dissociation of these complexes. The non-covalent complexes consisted of poly(methylmethacrylate) oligomers and singly and doubly charged diaminoalkanes of varying length. This allowed for control of the charge separation within the complexes, as well as the size of the complex. A destabilizing effect was observed in complexes containing protons in close proximity, and/or short oligomers. Interestingly, a multiple charge stabilizing effect was observed when charge sites were sufficiently separated and/or when the polymer moiety of the complex was large. ΔS(‡) values of doubly charged complexes showed a greater increase with increasing polymer size in comparison to singly charged complexes. This entropic observation is explained by structure, where IMS and MM/MD determined that the charge location was the determining factor of the overall conformation of these complexes and multiple charging resulted in more rigid arrangements. Dissociation of a tightly bound complex is more entropically favorable than a loosely bound complex. Also presented is a MM/MD refinement regime derived from IMS measurements.


Identification of two forms (31-33 and 48 kD) of the urinary soluble p55 tumor necrosis factor receptor that are differentially N- and O-glycosylated.
The structure and the activity of urinary soluble TNF receptor type 1 (sTNF-R1), isolated from the urine of normal individuals, has been characterized and compared with that of recombinant sTNF-R1 expressed in CHO cells and with that of a nonglycosylated form expressed in Escherichia coli. Urinary sTNF-R1 was resolved in a major band of 31-33 kD and in a 48 kD band (less than 5% of total) by reducing SDS-PAGE; CHO sTNF-R1 was resolved in two bands of 29 and 31 kD. All bands were recognized by various anti-sTNF-R1 antibodies as well as by TNF-alpha in western and ligand blotting assays. No cross-reaction was observed with anti-TNF-R2 antibodies. N- and O-glycosylation studies indicated that (1) the 29-31 kD recombinant form as well as the 31-33 kD urinary form are N-glycosylated; (2) the differences between the 29-31 and 31-33 kD recombinant and natural products are mainly related to differences in the N-linked sugar content; and (3) the 48 kD sTNF-R1 isolated from urine also contains O-linked sugars. The urinary sTNF-R1 antigen mixture was able to inhibit TNF-alpha cytotoxicity with a potency comparable to that of nonglycosylated E. coli sTNF-R1. At variance, urinary sTNF-R1 was able to inhibit TNF-beta sevenfold more efficiently than E. coli sTNF-R1. In conclusion, two subtypes of sTNF-R1 have been isolated from urine: a main N-glycosylated form of 31-33 kD and a N- and O-glycosylated form of 48 kD that appears to be a minor constituent of the urinary sTNF-R1 antigen.


Toward protein imprinting with polymer brushes.
The authors described an original approach for a surface protein imprinting employing grafting of polymer brushes. Protein molecules were first chemically bound to an ultrathin (1-3 nm) poly(glycidyl methacrylate) reactive polymer layer and later removed by protease treatment. Residual amino acids became grafted to the surface and to a certain extent imitated the surface chemical composition and shape of the template molecule on a nanolevel. The space surrounding the adsorbed biomolecules was modified with grafted poly(ethylene glycol) layer. This led to the formation of islands of spatial nanosized pockets complementary to the protein shape. The adsorbing protein recognized the surfaces imprinted and was anchored to the substrate.


Nickel-catalyzed amination of aryl chlorides with ammonia or ammonium salts.
The nickel-catalyzed amination of aryl chlorides to form primary arylamines occurs with ammonia or ammonium sulfate and a well-defined single-component nickel(0) precatalyst containing a Josiphos ligand and an η(2)-bound benzonitrile ligand. This system also catalyzes the coupling of aryl chlorides with gaseous amines in the form of their hydrochloride salts.


Salt Stress Signals on Demand: Cellular Events in the Right Context.
Plant stress is a real dilemma; it puzzles plant biologists and is a global problem that negatively affects people's daily lives. Of particular interest is salinity, because it represents one of the major water-related stress types. We aimed to determine the signals that guide the cellular-related events where various adaptation mechanisms cross-talk to cope with salinity-related water stress in plants. In an attempt to unravel these mechanisms and introduce cellular events in the right context, we expansively discussed how salt-related signals are sensed, with particular emphasis on aquaporins, nonselective cation channels (NSCCs), and glycosyl inositol phosphorylceramide (GIPC). We also elaborated on the critical role Ca2+, H+, and ROS in mediating signal transduction pathways associated with the response and tolerance to salt stress. In addition, the fragmentary results from the literature were compiled to develop a harmonized, informational, and contemplative model that is intended to improve our perception of these adaptative mechanisms and set a common platform for plant biologists to identify intriguing research questions in this area.


Designing, Conducting, and Reporting Survey Studies: A Primer for Researchers.
Survey studies have become instrumental in contributing to the evidence accumulation in rapidly developing medical disciplines such as medical education, public health, and nursing. The global medical community has seen an upsurge of surveys covering the experience and perceptions of health specialists, patients, and public representatives in the peri-pandemic coronavirus disease 2019 period. Currently, surveys can play a central role in increasing research activities in non-mainstream science countries where limited research funding and other barriers hinder science growth. Planning surveys starts with overviewing related reviews and other publications which may help to design questionnaires with comprehensive coverage of all related points. The validity and reliability of questionnaires rely on input from experts and potential responders who may suggest pertinent revisions to prepare forms with attractive designs, easily understandable questions, and correctly ordered points that appeal to target respondents. Currently available numerous online platforms such as Google Forms and Survey Monkey enable moderating online surveys and collecting responses from a large number of responders. Online surveys benefit from disseminating questionnaires via social media and other online platforms which facilitate the survey internationalization and participation of large groups of responders. Survey reporting can be arranged in line with related recommendations and reporting standards all of which have their strengths and limitations. The current article overviews available recommendations and presents pointers on designing, conducting, and reporting surveys.


Aftereffects of Self-Control on Positive Emotional Reactivity.
According to the process model of ego depletion, exercising self-control causes shifts in motivation and attention that may increase positive emotional reactivity. In an initial study and a preregistered replication, participants exercised self-control (or not) on a writing task before reporting their emotional responses to positive, negative, and neutral images. In Study 1 ( N = 256), we found that exercising (vs. not exercising) self-control increased positive emotional responses to positive images among more extroverted individuals. In Study 2 ( N = 301), we found that exercising self-control increased positive reactivity independent of extroversion. These findings support the process model of ego depletion and suggest that exercising self-control may influence responding that does not entail self-control (i.e., positive emotional reactivity)-an outcome that is not anticipated by the limited resource model of self-control.


Validity and acceptability of a high-fidelity physical simulation model for training of laparoscopic pyeloplasty.
The objective was to determine the acceptability and preliminary construct validity for a high-fidelity synthetic renal pelvis/ureter tissue analogue model for use as a simulation model for training of laparoscopic pyeloplasty. The pyeloplasty model was designed with incorporated assessment lines for use in post-task Black Light Assessment of Surgical Technique (BLAST)™. Practicing urologists participating in the 2011 and 2012 American Urological Association Mentored Renal Laparoscopy courses performed a simulated laparoscopic pyeloplasty procedure and completed a post-task evaluation of the model. Practicing urologists found the model acceptable and rated the model favorably in terms of content and face validity. Urologists who had performed a laparoscopic pyeloplasty procedure in the last 5 years outperformed those who had not by demonstrating increased patency (P<0.05), decreased twisting (P<0.05), and decreased leakage (P<0.10) at the anastomosis. The BLAST™ pyeloplasty model demonstrated evidence of acceptability and content, face, and construct validity for training practicing urologists to perform laparoscopic pyeloplasty.


Effect of age on response to rivastigmine or donepezil in patients with Alzheimer's disease.
Younger Alzheimer's disease (AD) patients appear to differ genetically and neuropathologically from older AD patients, and may experience a more aggressive disease course compared with older patients. A randomised trial investigated the efficacy and tolerability of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an AChE-selective inhibitor, in patients with AD over a 2-year period. This retrospective analysis investigated whether younger and older patients showed differential tolerability and efficacy responses to cholinesterase inhibitor treatment. For the current analysis, patients were divided according to age at baseline: those aged < 75 years and those aged >or= 75 years. Efficacy measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and the AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Changes in efficacy parameters and adverse event frequencies were calculated for rivastigmine and donepezil-treated patients in both age groups. Exploratory analyses were also conducted on SIB, ADCS-ADL and NPI in patients who consented to pharmacogenetic testing at baseline. Genotyping of the apolipoprotein E (APOE) epsilon4 allele and the BuChE K-variant was conducted using the TaqMan assay. Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT-LOCF) population. Of the 994 patients who received the study drug, 362 (36.4%) were younger than 75 years and 632 (63.6%) were aged 75 years or over. Rivastigmine provided significant benefits in younger patients compared with donepezil on the NPI-10, NPI-12, NPI-D, GDS and ADCS-ADL (all p < 0.05, ITT-LOCF). With the exception of the NPI-D in favour of donepezil (p < 0.05, ITT-LOCF), no significant treatment differences were observed in older patients. Younger patients with two wild-type BuChE alleles had a significantly greater response to rivastigmine than donepezil on the ADCS-ADL (p < 0.01, ITT-LOCF) and SIB (p < 0.05, ITT-LOCF). The most common adverse events were nausea and vomiting and these were more frequent in rivastigmine-treated patients. In this sub group analysis, patients younger than 75 years of age showed greater treatment responses to rivastigmine than donepezil. Analysis of response by BuChE genotype suggests that this differential effect may be due to the inhibition of BuChE, in addition to AChE, by rivastigmine.


Metal-Free SeBN Ternary-Doped Porous Carbon as Efficient Electrocatalysts for CO2 Reduction Reaction.
Cost-effective heteroatom-doped porous carbons are considered promising electrocatalysts for CO2 reduction reaction (CO2RR). Traditionally porous carbons with N doping or N/X codoping (X denotes the second type of heteroatom) have been widely studied, leaving ternary doping a much less studied yet exciting topic to be explored. Herein, a series of electrocatalysts based on metal-free Se, B, and N ternary-doped porous carbons (termed "SeBN-Cs") were synthesized and tested as metal-free electrocatalysts in CO2RR. Our study indicates that the major product of CO2RR on the SeBN-C electrocatalysts was CO with a small fraction (<5%) of H2 as the byproduct. The optimal electrocatalyst sample SeBN-C-1100 prepared at 1100 °C exhibits a high CO selectivity with a Faradaic efficiency of CO reaching 95.2%. After 10 h of continuous electrolysis operation, the Faradaic efficiency and the current density are maintained high at 97.6 and 84.7% of the initial values, respectively, indicative of a long-term operational stability. This study provides an excellent reference to deepen our understanding of the properties and functions of multi-heteroatom-doped porous carbon electrocatalysts in CO2RR.


A comparison of 15 year old children with excellent occlusion and with crowding of the teeth, Angle Class I malocclusion, in respect of face size and shape and tooth size.
The biological conflict that manifests itself in crowding of the teeth in man has fascinated orthodontists for generations. Correlations between tooth size and tooth arrangement can be shown, but such correlations tend to leave much unexplained in practical terms. The present report presents data from a preliminary examination of face size and shape and tooth size in boys and girls of 15-16 years, of which 47 had excellently arranged teeth and 91 showed crowding. Measurements were taken from lateral and posteroanterior cephalometric X-ray films and from dental casts. The statistical test used was the standard student t-test. Girls' faces were found to be on average significantly smaller than boys' whether the teeth were well arranged or were crowded. The comparisons of face size and shape of boys and girls with well arranged teeth with the faces of those with crowded teeth was less definite in its outcome. Girls' total tooth substance was on average significantly smaller than boys' whether the teeth were well arranged or crowded. Boys and girls with crowded teeth had a larger mean total tooth size than boys and girls with well arranged teeth.


The efficiency of endoclips in maintaining the gastrointestinal bleeding-related Dieulafoy's lesion.
Dieulafoy's lesion (DL) is a relatively uncommon medical condition characterized by a large tortuous arteriole in the submucosa of any part of gastrointestinal (GI) tract wall that bleeds via erosion likely caused in the submucosal surface by protrusion of the pulsatile arteriole. Compared with other endoscopic hemostatic techniques, clipping alone for DL is limited. The aim of the present case series study is to identify common clinical and endoscopic features, rates of occurrence, to review the outcome of endoscopic management of upper GI tract DL, and to illustrate the use and the efficiency of endoclips in maintaining the GI bleeding due to DL. This case series was conducted at Department of Gastroenterology, Dıskapı Yıldırım Beyazıt Educational and Research Hospital. The patients who were admitted to the emergency department of Dıskapı Yıldırım Beyazıt Educational and Research Hospital underwent gastrointestinal system (GIS) endoscopy between 2008 and 2013 and were assessed retrospectively. Five cases of GI bleeding related to DL were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. The median number of endoscopic hemoclips application in first endoscopy was 4 (2-9). Rebleeding developed in all patients who had hemoclips applied. Re-endoscopy was performed in three of these patients, which controlled the bleeding. Two patients were transferred to surgery. Combination of endoscopic injection and mechanical therapies seems a suitable method for maintaining upper GIS bleeding due to DL. Also, further studies are needed to better define the best endoscopic approach for the treatment of DL.


The efficacy of intratumoural 5-fluorouracil for the treatment of equine sarcoids.
To document the efficacy of intratumoural injections of 5-fluorouracil for the treatment of equine sarcoids. A prospective study that included 13 horses and one donkey. Sarcoids were confirmed by histological examination and treated with intratumoural 5-fluorouracil every 2 weeks. If the sarcoids did not resolve after seven treatments, treatment was considered a failure. All cases were re-examined 6 months after treatment commenced and owners were telephoned 3 years after commencement of treatment to report on tumour recurrence. Outcome comparisons were performed to determine the effect of previous treatment, tumour size and tumour location on sarcoid resolution. The efficacy of intratumoural 5-fluorouracil was compared with other previously documented treatments of equine sarcoids. Sarcoids smaller than 13.5 cm3 were significantly (P = 0.032) more likely to resolve with treatment than larger sarcoids. Sarcoids that were not responsive to previous therapies were significantly (P = 0.007) more likely to recur after 3 years than sarcoids that had not been treated prior to this study. In this study, there were similar rates of resolution in cases with mutiple tumours (66.6%) when compared to cases with single tumours (60%). The numbers in this study were too small to properly evaluate the effect of tumour location on the success of treatment. Intratumoural 5-fluorouracil appeared to have resolved sarcoids in 9 of 13 cases (61.5%) as determined by follow up conversation with the owners 3 years after the initial treatment. The use of intratumoural 5-fluorouracil compares favourably with other treatment modalities for sarcoids, with a long term successful resolution rate of 61.5%. Owners should be warned that resistant sarcoids and sarcoids larger than 13.5 cm3 have a poorer prognosis for resolution and more aggressive therapeutic options should be considered.


Stem cells as a good tool to investigate dysregulated biological systems in autism spectrum disorders.
Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n = 7) and control samples (n = 6). Nearly half of the 683 identified DEGs are expressed in the brain (P = 0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD.


Turning on Singlet Oxygen Generation by Outer-Sphere Microenvironment Modulation in Porphyrinic Covalent Organic Frameworks for Photocatalytic Oxidation.
Singlet oxygen (1 O2 ) is ubiquitously involved in various photocatalytic oxidation reactions; however, efficient and selective production of 1 O2 is still challenging. Herein, we reported the synthesis of nickel porphyrin-based covalent organic frameworks (COFs) incorporating functional groups with different electron-donating/-withdrawing features on their pore walls. These functional groups established a dedicated outer-sphere microenvironment surrounding the Ni catalytic center that tunes the activity of the COFs for 1 O2 -mediated thioether oxidation. With the increase of the electron-donating ability of functional groups, the modulated outer-sphere microenvironment turns on the catalytic activity from a yield of nearly zero by the cyano group functionalized COF to an excellent yield of 98 % by the methoxy group functionalized one. Electronic property investigation and density-functional theory (DFT) calculations suggested that the distinct excitonic behaviors attributed to the diverse band energy levels and orbital compositions are responsible for the different activities. This study represents the first regulation of generating reactive oxygen species (ROS) based on the strategy of outer-sphere microenvironment modulation in COFs.


Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group.
To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result. Prospective temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses. The rules comprised five ultrasonic features (including shape, size, solidity, and results of colour Doppler examination) to predict a malignant tumour (M features) and five to predict a benign tumour (B features). If one or more M features were present in the absence of a B feature, the mass was classified as malignant. If one or more B features were present in the absence of an M feature, it was classified as benign. If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive. 19 ultrasound centres in eight countries. 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a standardised research protocol. Reference standard Histological classification of the excised adnexal mass as benign or malignant. Diagnostic sensitivity and specificity. Of the 1938 patients with an adnexal mass, 1396 (72%) had benign tumours, 373 (19.2%) had primary invasive tumours, 111 (5.7%) had borderline malignant tumours, and 58 (3%) had metastatic tumours in the ovary. The simple rules yielded a conclusive result in 1501 (77%) masses, for which they resulted in a sensitivity of 92% (95% confidence interval 89% to 94%) and a specificity of 96% (94% to 97%). The corresponding sensitivity and specificity of subjective assessment were 91% (88% to 94%) and 96% (94% to 97%). In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements, the sensitivities were 89% (83% to 93%) for subjective assessment, 50% (42% to 58%) for the risk of malignancy index, 89% (83% to 93%) for logistic regression model 1, and 82% (75% to 87%) for logistic regression model 2; the corresponding specificities were 78% (72% to 83%), 84% (78% to 88%), 44% (38% to 51%), and 48% (42% to 55%). Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91% (88% to 93%) and a specificity of 93% (91% to 94%), compared with a sensitivity of 90% (88% to 93%) and a specificity of 93% (91% to 94%) when subjective assessment was used in all masses. The use of the simple rules has the potential to improve the management of women with adnexal masses. In adnexal masses for which the rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test; the risk of malignancy index and the two regression models were not useful.


Promoting safety--a component in health promotion in primary and secondary schools.
Accidents, especially accidents involving children or young people, are a key health problem that needs to find higher prominence in preventative measures. The school as the central socialisation institution plays a key role in the process of continual improvement. However, to date the prevailing approaches of technical accident prevention and behaviourled safety training have not led to sustained improvements in the safety of children and young people. This article presents the key elements and characteristics of a new approach that not only aims to make significant improvements in safety but is also aimed at schools having an improved perception of their key role--to instruct and educate. The authors assume that greater security can only be achieved in and through schools if safety promotion is at the same time school development. In this understanding, safety promotion focuses on the key players in the school and school life itself, and in particular endeavours to strengthen relationships and behaviour that promote safety and to minimise those that can have a negative effect. It emphasises practical changes to daily school life with regard to construction and fittings, education, training, organisation and politics, and involves the needs of everybody who lives and works at the school.


The cytoskeleton of the apical border of the lateral cells of freshwater mussel gill: structural integration of microtubule and actin filament-based organelles.
The coexistence of densely packed microtubule- and microfilament-based elements in the apex of ciliated epithelial cells, such as the lateral (L) cells of freshwater mussel gill, suggests that with this system it may be possible to define structural connections and interactions that permit integrated cytoskeletal responses to known physiological stimuli. In this study we examine the structure of the L cell apex in detail. The central elements of the elaborate cytoskeleton of the cortex are the basal bodies whose specialized accessory processes are points of integration and the focus of cortical microtubule and microfilament networks. Each basal body supports a cilium and interacts with adjacent basal bodies and with the cell periphery via a dual set of fibre-containing flat trabeculae, both of which are attached to a special organizing centre, the basal foot cap. The distal trabecula is composed of microtubules and the proximal of microfilaments. Connecting the trabeculae, at vertices in the filamentous grids, are core bundles of microfilaments from apical microvilli. In this way, a zig-zag pattern that characterizes microvillar organization at the cell surface is generated. At the cell periphery, the microfilaments from basal foot caps join a peripheral band of microfilaments that underlies the cell border and is associated with four special sites, one in each corner of the cell. Mussel gill epithelial cells contain a polypeptide that resembles actin in its mobility in sodium dodecyl sulphate/10% (w/v) polyacrylamide gels and its affinity for DNase I. Decoration with heavy meromyosin demonstrates that many microfilaments of the L cell apex contain actin, including the microvillar core and peripheral band microfilaments. Actin-associated proteins are also present in these epithelial cells. The actin filaments of the peripheral band are organized to support contraction of the cell border, which would also affect each element of the cortex. This structural complexity, combined with the limited number of modes of interaction between various elements, suggests that the L cell apical cytoskeleton endows the cell with significant positional and morphogenetic information that could be used to compute organellar and cytoskeletal lengths, spacing and changes upon stimulation.


Noise level and surgeon stress during thyroidectomy in an endocrine surgery operating room.
Noise in the operating room is an ongoing problem that impacts the outcome of any surgery. Noise as a stressor can produce a startling reaction and activate the fight or flight response of the autonomic and endocrine systems. The psychobiology of stress as assessed by salivary cortisol level is a sensitive measure of allostatic load. This study aims to correlate, both subjectively and objectively, the salivary cortisol levels of the surgeon with noise level measurement in an endocrine surgery operating room (OR). A prospective observational study was conducted in the Endocrine surgery OR of a tertiary care center. We recorded the noise from the shifting in of patients in the OR to shifting out using a digital sound level meter. The operating surgeon (S) provided two salivary cortisol samples (normal salivary cortisol <5 nmol/L), one baseline and another after the procedure. The questionnaire for the assessment of distraction during thyroidectomy was filled in by the S at the end of the procedure. Salivary cortisol levels were analyzed using SLV-4635 (formerly SLV-2930) DRG Instruments GmbH German using the ELISA technique. Statistical analysis was performed using SPSS 22.0. A total of 37 procedures with 74 salivary cortisol samples and 259 questionnaire responses from S were analyzed. All patients with only benign FNAC were operated upon (64.9% colloid). Mean TSH levels were 3.5 ± 6.7 mIU/L. The majority had a solitary thyroid nodule (STN) (25/37, 67.6%). Nineteen patients (51.3%) underwent open hemithyroidectomy, 10 patients total thyroidectomy, and eight patients endoscopic hemithyroidectomy. The mean noise level in the OR was 70 db. The maximum and minimum noise level in the OR was 90.06 and 51.81 dB, respectively. A total of 74 salivary cortisol samples from the S were collected (baseline and post-noise exposure) and mean cortisol levels were recorded. The surgeon was more significantly affected by surrounding noise, especially during critical phases 3 of surgery, mainly, RLN dissection and parathyroid dissection as recorded by their responses in the questionnaire (p = 0.003). The maximum value of post-operative salivary cortisol of surgeon was recorded as 23. 48 ng/mL and the minimum value recorded was 0.49 ng/mL. The difference in baseline cortisol and post-noise exposure cortisol levels of surgeon was found to be significant (p < 0.001). Maximum and mean noise levels were significantly associated with post-noise exposure salivary cortisol elevation in the surgeon (p = 0.032 and 0.014, respectively). The noise levels during RLN dissection were borderline significant with the post-noise exposure salivary cortisol of the surgeon (p = 0.055). Our research is the first such study which has been done to assess noise levels and their effect on thyroidectomy using objective salivary cortisol measurement. It challenges the misconstrued notion that visceral surgeries requiring lesser instruments are not associated with noise-related stress. Noise is a major distraction and the effect of long-term effect on the entire surgical team needs to be studied.


Inhibition by corticosterone of calcium inflow and insulin release in rat pancreatic islets.
Corticosterone (0.6 mumol/l) inhibited both 45Ca outflow and insulin release evoked by glucose, the combination of leucine and glutamine, 2-ketoisocaproate, gliclazide or the association of gliclazide and a tumour-promoting phorbol ester in rat pancreatic islets perifused at normal extracellular Ca2+ concentration (1.0 mmol/l). In all cases, the inhibitory action of corticosterone reached statistical significance within 10-22 min of exposure to this steroid and failed to be rapidly reversible. Corticosterone failed to affect basal 45Ca outflow and insulin release. The steroid also failed to affect the inhibitory action of glucose upon 45Ca outflow, as judged from either the glucose-induced early fall in effluent radioactivity from islets maintained at normal extracellular Ca2+ concentration or the steady-state values for 45Ca outflow from glucose-stimulated but Ca2+-deprived islets. Corticosterone caused a modest increase in 86Rb outflow from islets perifused in the presence of glucose (16.7 mmol/l). It is concluded that corticosterone impairs Ca2+ inflow into the islet cells and, by doing so, causes a progressive inhibition of insulin release. The pancreatic B cell might thus serve as a further model for the study of the rapid biological response to steroids, as presumably mediated by alteration in the biophysical properties of the plasma membrane.


The Bumps and BaBies Longitudinal Study (BaBBLeS): a multi-site cohort study of first-time mothers to evaluate the effectiveness of the Baby Buddy app.
Health mobile applications (apps) have become very popular, including apps specifically designed to support women during the ante- and post-natal periods. However, there is currently limited evidence for the effectiveness of such apps at improving pregnancy and parenting outcomes. This study aims to assess the effectiveness of a pregnancy and parenting app, Baby Buddy, in improving maternal self-efficacy at 3 months post-birth. Participants were 16 years old or over, first-time mothers, 12-16 weeks gestation, recruited by midwives from five English study sites. The Tool to Measure Parenting Self-Efficacy (TOPSE) (primary outcome) was used to compare mothers at 3 months post-birth who had downloaded the Baby Buddy app with those who had not downloaded the app, controlling for confounding factors. Four hundred and eighty-eight participants provided valid data at baseline (12-16 weeks gestation), 296 participants provided valid data at 3 months post-birth, 114 (38.5%) of whom reported that they had used the Baby Buddy app. Baby Buddy app users were more likely to use pregnancy or parenting apps (80.7% vs. 69.6%, P=0.035), more likely to have been introduced to the app by a healthcare professional (P=0.005) and have a lower median score for perceived social support (81 vs. 83, P=0.034) than non-app users. The Baby Buddy app did not elicit a statistically significant change in TOPSE scores from baseline to 3 months post-birth [adjusted odds ratio (OR) 1.12, 95% confidence interval (CI): 0.59 to 2.13, P=0.730]. Finding out about the Baby Buddy app from a healthcare professional appeared to grant no additional benefit to app users compared to all other participants in terms of self-efficacy at 3 months post-birth (adjusted OR 1.16, 95% CI: 0.60 to 2.23, P=0.666). There were no statistically significant differences in the TOPSE scores for the in-app data, in terms of passive use of the app between high and low app users (adjusted OR 0.82, 95% CI: 0.21 to 3.12, P=0.766), nor in terms of active use (adjusted OR 0.47, 95% CI: 0.12 to 1.86, P=0.283). This study is one of few, to date, that has investigated the effectiveness of a pregnancy and early parenthood app. No evidence for the effectiveness of the Baby Buddy app was found. New technologies can enhance traditional healthcare services and empower users to take more control over their healthcare but app effectiveness needs to be assessed. Further work is needed to consider: (I) how we can best use this new technology to deliver better health outcomes for health service users and, (II) methodological issues of evaluating digital health interventions.


Influence of exercise on excitation-contraction coupling in rat myocardium.
The present studies were conducted to investigate further the mechanisms by which the myocardium adapts to exercise training. Sixty female rats were randomly divided into sedentary control (group C) and trained (group T) groups. Group T was progressively trained for 12 wk. After the rats were killed, left ventricular papillary muscles were mounted in a tissue bath for mechanical studies. Muscles from group T generated greater peak isometric twitch tension per unit cross-sectional area than muscles from group C with [Ca2+]o ranging from 0.25 to 3.5 mM. Analyses of these data indicated that the Km for Ca2+ was not different but that the predicted number of sarcolemmal Ca2+ binding sites was 63% higher in group T. The ATPase activity of the purified cardiac myofibrils was not different between the two groups in the pCa range of 8.53-4.42. Action potentials were recorded with microelectrodes impaled into left ventricular muscle fibers of the subendocardium. Although there was no difference in the resting membrane potential, overshoot, or 90% duration, there was a significant prolongation of the action potential at 0 mV (20.2 +/- 1.0 vs 30.0 +/- 1.3 ms) in group T. These data further support the hypothesis that treadmill exercise enhances cardiac performance by increasing Ca2+ availability to the contractile element. This adaptation is mediated, at least in part, by a sarcolemmal adaptation induced by the exercise paradigm.


Direct stimulation of bone mass by increased GH signalling in the osteoblasts of Socs2-/- mice.
The suppressor of cytokine signalling (Socs2(-/-))-knockout mouse is characterised by an overgrowth phenotype due to enhanced GH signalling. The objective of this study was to define the Socs2(-/-) bone phenotype and determine whether GH promotes bone mass via IGF1-dependent mechanisms. Despite no elevation in systemic IGF1 levels, increased body weight in 4-week-old Socs2(-/-) mice following GH treatment was associated with increased cortical bone area (Ct.Ar) (P<0.01). Furthermore, detailed bone analysis of male and female juvenile and adult Socs2(-/-) mice revealed an altered cortical and trabecular phenotype consistent with the known anabolic effects of GH. Indeed, male Socs2(-/-) mice had increased Ct.Ar (P<0.05) and thickness associated with increased strength. Despite this, there was no elevation in hepatic Igf1 expression, suggesting that the anabolic bone phenotype was the result of increased local GH action. Mechanistic studies showed that in osteoblasts and bone of Socs2(-/-) mice, STAT5 phosphorylation was significantly increased in response to GH. Conversely, overexpression of SOCS2 decreased GH-induced STAT5 signalling. Although an increase in Igf1 expression was observed in Socs2(-/-) osteoblasts following GH, it was not evident in vivo. Igf1 expression levels were not elevated in response to GH in 4-week-old mice and no alterations in expression was observed in bone samples of 6-week-old Socs2(-/-) mice. These studies emphasise the critical role of SOCS2 in controlling the local GH anabolic bone effects. We provide compelling evidence implicating SOCS2 in the regulation of GH osteoblast signalling and ultimately bone accrual, which maybe via mechanisms that are independent of IGF1 production in vivo.