Miracle-dz/UniFAR-FTUs huggingface dataset:
A CaMKII/PDE4D negative feedback regulates cAMP signaling

Significance Cardiovascular disease is the leading cause of death worldwide. A better understanding of the pathophysiological mechanisms governing such disease states as heart failure is essential to the identification of novel therapeutic targets. We have discovered a regulatory loop that coordinates the function of proteins and secondary messengers involved in cardiac contractility and the development of heart failure. This regulatory loop may be a novel target for pharmacologic intervention to restore cardiac homeostasis. cAMP production and protein kinase A (PKA) are the most widely studied steps in β-adrenergic receptor (βAR) signaling in the heart; however, the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is also activated in response to βAR stimulation and is involved in the regulation of cardiac excitation-contraction coupling. Its activity and expression are increased during cardiac hypertrophy, in heart failure, and under conditions that promote arrhythmias both in animal models and in the human heart, underscoring the clinical relevance of CaMKII in cardiac pathophysiology. Both CaMKII and PKA phosphorylate a number of protein targets critical for Ca2+ handling and contraction with similar, but not always identical, functional consequences. How these two pathways communicate with each other remains incompletely understood, however. To maintain homeostasis, cyclic nucleotide levels are regulated by phosphodiesterases (PDEs), with PDE4s predominantly responsible for cAMP degradation in the rodent heart. Here we have reassessed the interaction between cAMP/PKA and Ca2+/CaMKII signaling. We demonstrate that CaMKII activity constrains basal and βAR-activated cAMP levels. Moreover, we show that these effects are mediated, at least in part, by CaMKII regulation of PDE4D. This regulation establishes a negative feedback loop necessary to maintain cAMP/CaMKII homeostasis, revealing a previously unidentified function for PDE4D as a critical integrator of cAMP/PKA and Ca2+/CaMKII signaling.
Parenting interventions and the prevention of unintentional injuries in childhood: systematic review and meta-analysis.

OBJECTIVES To evaluate the effectiveness of parenting interventions in preventing unintentional injury and increasing parental safety practices. DATA SOURCES A range of medical and social science electronic databases were searched. Abstracts from the first to seventh World conferences on injury prevention and control and the journal Injury Prevention were hand searched. REVIEW METHODS Randomized controlled trials (RCTs), non-randomized controlled trials (non-RCTs) and controlled before and after studies, providing parenting interventions to parents of children aged 0-18 years and reporting injuries, safety equipment or safety practices were included. Studies were selected, data extracted and quality appraised independently by two reviewers. Pooled relative risks were estimated using random effect models. RESULTS Fifteen studies (11 RCTs) were included, 11 of which were home visiting programmes and two of which were paediatric practice-based interventions. Thirteen studies recruited families at risk of adverse child health outcomes. Intervention arm families had a significantly lower risk of injury (RR 0.82, 95% CI 0.71-0.95), as measured by self-report of medically or non-medically attended injury. Several studies found fewer home hazards, a home environment more conducive to child safety, or a greater number of safety practices in intervention arm families. CONCLUSIONS Parenting interventions, most commonly provided within the home, using multi-faceted interventions appear to be effective in reducing unintentional child injury. Further research is required to explore the mechanisms by which parenting interventions reduce injury, the features of interventions that are necessary to reduce injury, and their generalizability to different population groups.
ESTUDO DAS ALTERAÇÕES MORFOLÓGICAS DO SISTEMA LOCOMOTOR: POSTURA CORPORAL X OBESIDADE

The locomotor system morphological changes related to obesity were studied in 19 subjects of both sexes. They were divided into 03 groups as follows: G1 = 03 (male individuals), G2 = 04 and G3 = 12 (female subjects). The data were collected by a computerized Postural Evaluation System (Micromed Biotechnology) from the Laboratory of the Electromyography and Postural Evaluation-FEF/UNICAMP. Results: a greater incidence of fallen shoulders was detected in the female group in comparison with the male one. Group 02 registered a significant elbow morphological change. Body fat concentration on the posterior gluteus region was greater to G1, whereas in G2 and G3 the greater concentration was observed in the lateral gluteus region. There was an incidence of postural deviations such as: cervical lordosis, kyphosis, hyperlordosis, increased sacrum convexity, pelvic inclination, excessive increase in abdomen region and reduction of the distance between the external auditory meatus and shoulders.
Anthropological and physicochemical investigation of the burnt remains of Tomb IX in the ‘Sa Figu’ hypogeal necropolis (Sassari, Italy) – Early Bronze Age

Excavations carried out in Tomb IX of the hypogeic necropolis of ‘Sa Figu’, near the village of Ittiri (Sassari, Italy), supplied burnt human bone remains and pottery unambiguously referred to the Early Bronze Age (characterised by the local culture of ‘Bonnannaro’). Besides the anthropological study, we have investigated and evaluated the possibility of a funerary cremation practice in Sardinian pre-history, a subject that has previously not been considered from a scientific point of view. Making use of a calibration procedure based on X-ray diffraction (XRD) line-broadening analysis, related to the microstructural properties, it was possible to estimate the combustion temperature to which the fragmented bones were subjected. It was found that the studied bones reached temperatures varying from 400°C up to a maximum of 850°C. This spread of values suggested inhomogeneous combustion of the bones, which seems compatible with funerary cremation practices. Copyright © 2007 John Wiley & Sons, Ltd.
Coagulation Abnormalities in Acute Pancreatitis

Acute pancreatitis (AP) is a potentially lethal disorder with no specific medical treatment. AP is characterized by a spectrum of symptoms, ranging from a local inflammatory process to the more severe form (acute necrotizing pancreatitis) which is associated with a systemic inflammatory response and a mortality rate of 27-45%. A number of risk factors have been identified for AP including alcohol abuse, gallstones, abdominal surgery/injury, cigarette smoking, cystic fibrosis, endoscopic retrograde cholangiopancreatography, hypercalcemia, hyperparathyroidism, hypertriglyceridemia, infection, pancreatic cancer, and injury to the abdomen (Pandol et al., 2007). Alcohol abuse and the development of gallstones account for the majority of AP cases. In AP, inappropriate intracellular activation of digestive enzymes within the pancreas (e.g. trypsin, chymotrypsin, elastase) is the main initiating event. The development of acute necrotizing pancreatitis is usually associated with pancreatic glandular necrosis. Acinar cell apoptosis, the release of cytokines, activation of coagulation, tissue ischemia, and tissue necrosis are key factors in the progression of the condition, as well as in the development of associated extrapancreatic complications (Steinberg & Tenner, 1994; McKay & Buter, 2003; Pandol et al., 2007).
An investigation on the effects of the Aloe Vera extract on the thickness of the retina in male diabetic rats

Summary Retina is a part of the central nervous system derived from the neuroectoderm and made up of 5 layers. In this study, the changes in the thickness of the retinal layers as a consequence of diabetes and effect of Aloe Vera gel extract in male rats were assessed. Thirty Sprague Dawley adult male rats (175 ± 25 g) in two age groups (4 and 8 weeks) were divided into 6 groups of 5 as control, diabetic and diabetic receiving 400 mg/kg Aloe Vera extract. Diabetes was induced by IP injection of 50 mg/kg of STZ (streptozotocin). The animals were weighed and their blood sugar was measured by glucometer before STZ administration and 24 h thereafter. Animals were anesthetized with sodium thiopental (40 mg/kg) via IP injection. After removal of eyes on both sides, retina was dissected out precisely and fixed in 4% glutaraldehyde, post fixed in osmium tetroxid 1%, dehydrated and then embedded in TAAB resin. Thin sections (1 µm) were stained with toluidine blue stain and viewed under light microscope. Ten slides were prepared from each animal. The results revealed reduction of the blood glucose levels and body weight in treated rats in comparison to diabetic groups. The thickness of neural retina and its layers were different as well. In the group treated with Aloe Vera the thickness of retina and its layers retained their normal histologic structures.
Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens

Significance The innate immune system provides a first line of defense against invading pathogens. The inflammasome is an innate immune complex that activates inflammatory caspases upon infection, causing cell death and IL-1 cytokine release, which initiate defense against gram-negative bacterial pathogens but also mediate septic shock. Many inflammasome studies have been performed using cells from mice, but mice and humans differ in their complement of inflammatory caspases. Instead of caspase-11, humans encode the putative orthologs caspase-4 and caspase-5. Here, we show that caspase-4 plays a conserved role in inflammasome activation in response to virulent gram-negative pathogens in primary human macrophages. Our findings provide important insight into how inflammasomes are regulated in human cells. Inflammasomes are critical for host defense against bacterial pathogens. In murine macrophages infected by gram-negative bacteria, the canonical inflammasome activates caspase-1 to mediate pyroptotic cell death and release of IL-1 family cytokines. Additionally, a noncanonical inflammasome controlled by caspase-11 induces cell death and IL-1 release. However, humans do not encode caspase-11. Instead, humans encode two putative orthologs: caspase-4 and caspase-5. Whether either ortholog functions similar to caspase-11 is poorly defined. Therefore, we sought to define the inflammatory caspases in primary human macrophages that regulate inflammasome responses to gram-negative bacteria. We find that human macrophages activate inflammasomes specifically in response to diverse gram-negative bacterial pathogens that introduce bacterial products into the host cytosol using specialized secretion systems. In primary human macrophages, IL-1β secretion requires the caspase-1 inflammasome, whereas IL-1α release and cell death are caspase-1–independent. Instead, caspase-4 mediates IL-1α release and cell death. Our findings implicate human caspase-4 as a critical regulator of noncanonical inflammasome activation that initiates defense against bacterial pathogens in primary human macrophages.
Airway covering during bed-sharing.

BACKGROUND Parent-infant bed-sharing is a common practice in Western post-industrial nations with up to 50% of infants sleeping with their parents at some point during early infancy. However, researchers have claimed that infants may be at risk of suffocation or sudden infant death syndrome related to airway covering or compression in the bed-sharing environment. To further understand the role of airway covering and compression in creating risks for bed-sharing infants, we report here on a sleep-lab trial of two infant sleep conditions. METHODS In a sleep-lab environment 20 infants aged 2-3 months old slept in their parents' bed, and in a cot by the bed, on adjacent nights. Infants' oxygen saturation and heart rate were monitored physiologically while infant and parental behaviours were recorded via ceiling-mounted infra-red cameras. Infants served as their own controls. Continuous 8-h recordings were obtained for covering of infant external airways, levels of infant oxygen saturation, infant heart rate, evidence of parental compression/overlying of infant, circumstances leading up to potential infant airway obstruction, and parental awareness of and responses to infant airway covering. RESULTS The majority of infants (14/20) spent some part of the bed night with their airways (both mouth and nose) covered, compared with 2/20 on the cot night; however, no consistent effect on either oxygen saturation levels or heart rate was revealed, even during prolonged bouts of airway covering. All cases of airway covering were initiated by parents; 70% were terminated by parents, the remainder by infants. Seven bouts of potential compression were observed with parental limbs resting across infant bodies for lengthy periods, however, in only two cases was the full weight of a parental limb resting on an infant, both events lasting less than 15 s, both being terminated by infant movement. CONCLUSION Although numerous authors have suggested that bed-sharing infants face risks because of airway covering by bed-clothes or parental bodies, the present trial does not lend support to this hypothesis.
Recognition and referral of girls with Attention Deficit Hyperactivity Disorder: case vignette study.

BACKGROUND Compared with boys, girls with Attention Deficit Hyperactivity Disorder (ADHD) are under-recognized. Parents commonly discuss concerns with teachers, who play an important role in the recognition and referral of children with ADHD. We investigated whether the predominating subtype of symptomatology influences teacher recognition of affected girls. METHODS A total of 212 teachers from 40 randomly selected primary schools in England participated in a postal questionnaire study. The questionnaire consisted of a case vignette (based on DSM-IV criteria) describing a girl with either combined or predominantly inattentive subtype ADHD. Each school received an equal number of each type of vignette for distribution. Further questions elicited teachers' conceptualization of the girl's difficulties and need for specialist referral, their views on treatment modalities and demographic data. RESULTS Most (98%) teachers recognized the presence of a problem but mainly conceptualized the girl's behaviour as reflecting attentional (89%) or emotional (62%) difficulties. Teachers were less likely to correctly identify a girl with inattentive than combined subtype ADHD (14% vs. 43%) or recommend clinical referral (50% vs. 59%) for her. Few (15%) teachers thought that medication might be helpful for a girl meeting diagnostic criteria for ADHD. CONCLUSIONS Teachers are able to recognize ADHD-related behaviours and impairments but conceptualize these as reflecting attentional or emotional difficulties rather than as relating to a disorder (ADHD). Teachers' conceptualization of ADHD and views about medication are important factors that could affect accurate recognition and referral. Improving teachers' knowledge about ADHD, especially the inattentive subtype, could assist in tackling gender-related barriers to care.
Infections of the central nervous system

Recent clinical studies and review articles concerning the epidemiology, clinical features, and antibiotic and adjunctive therapy of bacterial meningitis and brain abscess are presented. The type and frequency of complications that may occur during the course of bacterial meningitis are reported, and their intensive care management is discussed. The role of the polymerase chain reaction in viral diseases of the central nervous system is briefly presented, and further areas of research are mentioned.
Níveis tensionais de adultos indígenas Suruí, Rondônia, Brasil

Os povos indigenas no Brasil vivenciam acelerado processo de transicao nutricional e epidemiologica, verificando-se a emergencia de doencas e agravos nao transmissiveis, como hipertensao arterial (HA). Realizou-se, em 2005, um estudo transversal para descrever os niveis tensionais em adultos (> 20 anos) indigenas Surui, Rondonia, e investigar sua relacao com o estado nutricional e o nivel socioeconomico (SSE). Foram visitadas 9 aldeias e avaliados 251 individuos (87,4% dos elegiveis). As medias de pressao arterial sistolica (PAS) e pressao arterial diastolica (PAD) foram maiores no sexo masculino e superiores as verificadas em 1988, com incremento na media da PAS de 7,9 mmHg e de 1,4 mmHg, em mulheres e homens, respectivamente. A PAS correlacionou-se positivamente com a razao cintura quadril (RCQ) em ambos os sexos, e com a idade, no sexo feminino. A PAD apresentou correlacoes estatisticamente significativas com todas as variaveis antropometricas, exceto com estatura e area muscular do braco. A prevalencia de HA foi de 2,8% (M: 2,4%; F: 3,1%). Essa prevalencia foi maior nos individuos > 40 anos, com perimetro da cintura (PC) ou RCQ elevados, sobretudo no grupo feminino e tambem no grupo de mais baixo de SSE. A HA e um problema de saude emergente entre os Surui, devendo receber atencao do sistema de saude e dos pesquisadores.
Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: Role for omega-3 epoxides

Significance Our study demonstrates that stabilization of cytochrome P-450 epoxides derived from omega-3 polyunsaturated fatty acids through inhibition of the inactivating enzyme soluble epoxide hydrolase (sEH) exerts beneficial actions in counteracting metabolic disorders associated with obesity. In addition, our study sheds more light on the role of sEH in cellular homeostasis by providing evidence that omega-3 epoxides and sEH inhibition regulate autophagy and endoplasmic reticulum stress in insulin-sensitive tissues, especially the liver. Therefore, administration of a sEH inhibitor is a promising strategy to prevent obesity-related comorbidities. Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in a number of diseases that have inflammation as a common underlying cause. sEH limits tissue levels of cytochrome P450 (CYP) epoxides derived from omega-6 and omega-3 polyunsaturated fatty acids (PUFA) by converting these antiinflammatory mediators into their less active diols. Here, we explored the metabolic effects of a sEH inhibitor (t-TUCB) in fat-1 mice with transgenic expression of an omega-3 desaturase capable of enriching tissues with endogenous omega-3 PUFA. These mice exhibited increased CYP1A1, CYP2E1, and CYP2U1 expression and abundant levels of the omega-3–derived epoxides 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic (19,20-EDP) in insulin-sensitive tissues, especially liver, as determined by LC-ESI-MS/MS. In obese fat-1 mice, t-TUCB raised hepatic 17,18-EEQ and 19,20-EDP levels and reinforced the omega-3–dependent reduction observed in tissue inflammation and lipid peroxidation. t-TUCB also produced a more intense antisteatotic action in obese fat-1 mice, as revealed by magnetic resonance spectroscopy. Notably, t-TUCB skewed macrophage polarization toward an antiinflammatory M2 phenotype and expanded the interscapular brown adipose tissue volume. Moreover, t-TUCB restored hepatic levels of Atg12-Atg5 and LC3-II conjugates and reduced p62 expression, indicating up-regulation of hepatic autophagy. t-TUCB consistently reduced endoplasmic reticulum stress demonstrated by the attenuation of IRE-1α and eIF2α phosphorylation. These actions were recapitulated in vitro in palmitate-primed hepatocytes and adipocytes incubated with 19,20-EDP or 17,18-EEQ. Relatively similar but less pronounced actions were observed with the omega-6 epoxide, 14,15-EET, and nonoxidized DHA. Together, these findings identify omega-3 epoxides as important regulators of inflammation and autophagy in insulin-sensitive tissues and postulate sEH as a druggable target in metabolic diseases.
The relationship between Developmental Co-ordination Disorders, child's perceived self-efficacy and preference to participate in daily activities.

BACKGROUND Developmental Co-ordination Disorder (DCD) may negatively impact children's self-efficacy and limit their performance and participation in school as well as in leisure activities performed after school hours. However, a lack of information exists regarding the relationships between DCD, child's self-efficacy and participation. Moreover, the literature about the way children with DCD experience these limitations and report about them is scarce. This study aimed to compare the perceived self-efficacy and the preference to participate in leisure activities of children with DCD and typical peers and to illuminate the relationship between self-efficacy, activity preference and DCD severity. METHODS Participants were 37 children with DCD and 37 typical peers, aged 5.08-9.83 years. All children performed the Movement Assessment Battery for Children, the Perceived Efficacy and Goal Setting System and the Preference for Activities of Children. RESULTS The scores of the Movement Assessment Battery for Children confirmed the motor gaps between the two groups. Children with DCD scored significantly lower in self-efficacy on all the Perceived Efficacy and Goal Setting System subscales and demonstrated a lower preference to participate in leisure activities according to all scales of the Preference for Activities of Children. The lower their self-efficacy, the lower their motor performance and their preference to participate in activities. CONCLUSIONS Children's preference to participate in activities may be limited by motor difficulties, but further hindered by low self-efficacy. Early identification of DCD and associated negative outcomes, also based on child's self-reports, should receive special attention in intervention programmes in order to enhance children's self-confidence, feelings of belonging, optimal development and participation in daily activities.
Use of the Griffiths Mental Development Scales in an agro-industrial province in the Philippines.

BACKGROUND There is a need to assess neurobehavioral performance of children in developing countries using standardized developmental tools. METHODS The Griffiths Mental Development Scales was evaluated in the Philippines by comparing the performance of 742 Filipino children longitudinally at 6, 12 and 24 months old to those of their British counterparts. RESULTS The mean general and subquotient scores of Filipino children were all within average for age. Comparison with British children showed that except for performance subscales, Filipino children had significantly higher developmental subquotients at 6 months old. As the Filipino infants grew older, their developmental subquotients in all subscales were significantly lower, except for personal and social skills at 24 months old. The genetic predisposition as evidenced by modest maternal scores on the Wechsler Intelligence Scales and lack of familiarity with test materials are factors that may influence the developmental patterns of Filipino children. CONCLUSION Although the performance of the Filipino children in the Griffiths test were within average with age, their performance on developmental subquotients at later ages of 12 and 24 months were significantly lower than British children and may have been influenced by differences in ethnicity, cultural traditions and limited environmental resources.