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1.
Popul Health Metr ; 21(1): 10, 2023 07 28.
Article in English | MEDLINE | ID: mdl-37507749

ABSTRACT

INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.


Subject(s)
Infant Mortality , Perinatal Death , Infant , Infant, Newborn , Child , Humans , Female , Pregnancy , Latin America/epidemiology , Prospective Studies , Retrospective Studies , Africa South of the Sahara , Asia/epidemiology
2.
J Endocrinol Invest ; 46(11): 2299-2307, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37149543

ABSTRACT

PURPOSE: Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene cause familial isolated pituitary adenomas (FIPA). AIP mutations have also been found in patients with apparently sporadic pituitary adenomas, particularly in young patients with large adenomas. The aim of this study was to determine the frequency of AIP germline mutations in patients with young-onset sporadic pituitary macroadenomas. METHODS: The AIP gene was sequenced in 218 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years. RESULTS: Heterozygous rare sequence variants in AIP were identified in 18 (8.3%) patients. However, only four (1.8%) patients had pathogenic or likely pathogenic variants. These consisted of two already known mutations (p.Arg81* and p.Leu115Trpfs*41) and two novel mutations (p.Glu246*, p.Ser53Thrfs*36). All four patients had GH-secreting adenomas diagnosed between the ages of 14 and 25 years. The frequency of AIP pathogenic or likely pathogenic variants in patients under the age of 30 and 18 years was 3.4% and 5.0%, respectively. CONCLUSION: The frequency of AIP mutations in this cohort was lower than in other studies. Previous reports may have overestimated the contribution of AIP mutations due to the inclusion of genetic variants of uncertain significance. The identification of novel AIP mutations expands the known spectrum of genetic causes of pituitary adenomas and may help understand the role of AIP mutations in the molecular mechanisms underlying pituitary tumorigenesis.


Subject(s)
Adenoma , Growth Hormone-Secreting Pituitary Adenoma , Pituitary Neoplasms , Humans , Adolescent , Young Adult , Adult , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/genetics , Pituitary Neoplasms/diagnosis , Adenoma/metabolism , Growth Hormone-Secreting Pituitary Adenoma/genetics , Mutation , Germ-Line Mutation
3.
Cell Mol Neurobiol ; 42(3): 739-751, 2022 Apr.
Article in English | MEDLINE | ID: mdl-32918255

ABSTRACT

Intracerebral hemorrhage (ICH) is a severe stroke subtype caused by the rupture of blood vessels within the brain. Increased levels of S100B protein may contribute to neuroinflammation after ICH through activation of astrocytes and resident microglia, with the consequent production of proinflammatory cytokines and reactive oxygen species (ROS). Inhibition of astrocytic synthesis of S100B by arundic acid (AA) has shown beneficial effects in experimental central nervous system disorders. In present study, we administered AA in a collagenase-induced ICH rodent model in order to evaluate its effects on neurological deficits, S100B levels, astrocytic activation, inflammatory, and oxidative parameters. Rats underwent stereotactic surgery for injection of collagenase in the left striatum and AA (2 µg/µl; weight × 0.005) or vehicle in the left lateral ventricle. Neurological deficits were evaluated by the Ladder rung walking and Grip strength tests. Striatal S100B, astrogliosis, and microglial activation were assessed by immunofluorescence analysis. Striatal levels of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) were measured by ELISA, and the ROS production was analyzed by dichlorofluorescein (DCF) oxidation. AA treatment prevented motor dysfunction, reduced S100B levels, astrogliosis, and microglial activation in the damaged striatum, thus decreasing the release of proinflammatory cytokines IL-1ß and TNF-α, as well as ROS production. Taken together, present results suggest that AA could be a pharmacological tool to prevent the harmful effects of increased S100B, attenuating neuroinflammation and secondary brain damage after ICH.


Subject(s)
Motor Disorders , Neuroinflammatory Diseases , Animals , Caprylates/pharmacology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/metabolism , Microglia/metabolism , Motor Disorders/complications , Rats
4.
Int J Behav Nutr Phys Act ; 19(1): 83, 2022 07 14.
Article in English | MEDLINE | ID: mdl-35836186

ABSTRACT

BACKGROUND: In the current Physical Activity Guidelines (PAG) for moderate- and vigorous-intensity physical activity (MVPA), abrupt transition from ≥ 60 min/day [youth PAG] to ≥ 150 min/week (≥ 22 min/day on average) [adult PAG] during emerging adulthood is poorly justified. The aim of this study was to examine body fat mass changes according to whether meeting the youth and adult PAGs in late adolescence (age 18 years) to early adulthood (age 22 years). METHODS: The study sample included 2,099 participants (1,113 females) from the 1993 Pelotas (Brazil) Study. At ages 18 and 22 years, MVPA was measured using wrist-worn accelerometry and fat mass was measured using dual-energy X-ray absorptiometry. MVPA at age 18 was categorized into two groups: 0-59 or ≥ 60 min/day (no [N] or yes [Y] for meeting the youth recommendation, respectively). MVPA at age 22 was categorized into three groups: 0-21, 22-59, or ≥ 60 min/day (N, Y22, or Y60 for not meeting the adult recommendation, meeting the adult recommendation, or meeting the youth recommendation, respectively). The combination of these groups created six MVPA groups (N&N, N&Y22, N&Y60, Y&N, Y&Y22, and Y&Y60). Sex-specific multivariable linear regression analyses were conducted to estimate change in fat mass index (FMI) from age 18 to 22 years in the six MVPA groups. RESULTS: Among males, compared to Y&Y60 (FMI increase = 1.2 kg/m2 [95% CI = 1.0, 1.4]), Y&Y22 and Y&N had larger FMI increases (1.9 [1.6, 2.1] and 1.9 [1.2, 2.5], respectively). Among females, Y&Y60 and Y&Y22 had an equal FMI increase (1.6 [1.4, 1.9] for both groups), while Y&N had a larger FMI increase (2.4 [1.8, 3.0]). CONCLUSIONS: These findings suggest that among those who were active in late adolescence, engaging in ≥ 22 min/day of MVPA in adulthood is associated with lower body fat gain for females, but not for males.


Subject(s)
Adiposity , Exercise , Adolescent , Adult , Body Mass Index , Cohort Studies , Female , Humans , Male , Obesity , Young Adult
5.
Microb Pathog ; 152: 104634, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33242643

ABSTRACT

Regenerative therapies such as dental pulpal revascularization appear as an option for traumatized immature permanent teeth. However, the triple antibiotic paste - TAP (metronidazole, minocycline, and ciprofloxacin), used for these therapies, can generate cytotoxicity and dentin discoloration. In contrast, host defense peptides (HDPs) are promising antimicrobial and immunomodulatory biomolecules for dentistry. This study aimed to evaluate in vitro the antimicrobial activity (against Staphylococcus aureus and Enterococcus faecalis) and the immunomodulatory potential (by the evaluation of IL-1α, IL-6, IL-12, IL-10, TNF-α and NO, in RAW 264.7 macrophages and IL-6, TGF-ß and NO, in L929 fibroblast) of synthetic peptides (DJK-6, IDR-1018, and IDR-1002), compared to TAP in an in vitro infection model containing heat-killed antigens from E. faecalis and S. aureus. Furthermore, the synergistic potential of ciprofloxacin and IDR-1002 was evaluated by checkerboard. Ciprofloxacin was the best antimicrobial of TAP, besides acting in synergism with IDR-1002. TAP was pro-inflammatory (p < 0.05), while the association of ciprofloxacin and IDR-1002 presented an anti-inflammatory profile mainly in the presence of both heat-killed antigens (p < 0.05). Based on these results, ciprofloxacin associated with IDR-1002 may demonstrate an efficient antimicrobial and immunomodulatory action in this in vitro model. Further in vivo studies may determine the real potential of this combination.


Subject(s)
Anti-Infective Agents , Ciprofloxacin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides , Ciprofloxacin/pharmacology , Dental Pulp , Minocycline , Staphylococcus aureus
6.
J Chem Phys ; 154(3): 034303, 2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33499610

ABSTRACT

A realistic double many-body expansion potential energy surface (PES) is developed for the 2A″ state of the carbon-nitrogen-oxygen (CNO) system based on MRCI-F12/cc-pVQZ-F12 ab initio energies. The new PES reproduces the fitted points with chemical accuracy (root mean square deviation up to 0.043 eV) and explicitly incorporates long range energy terms that can accurately describe the electrostatic and dispersion interactions. Thermal rate coefficients were computed for the C(3P) + NO(2Π) reaction for temperatures ranging from 15 K to 10 000 K, and the values are compared to previously reported results. The differences are rationalized, and the major importance of long range forces in predicting the rate coefficients for barrierless reactions is emphasized.

7.
Qual Life Res ; 29(10): 2641-2650, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32356277

ABSTRACT

PURPOSE: The diagnosis of multiple myeloma (MM) has a significant impact on patients. This study analyzed the mediating role of patients' unmet needs in the relationship between psychological morbidity/social support and quality of life (QoL). METHODS: This study included 213 patients with MM recruited from the outpatient medical oncology and clinical hematology services from five hospitals. Patients who meet the study criteria were referred by physicians and invited to participate in the study by the researcher. All participants answered the following questionnaires: Hospital Anxiety and Depression Scale, Satisfaction with Social Support Scale, Short-Form Survivor Unmet Needs Survey, and The European Organization for Research and Treatment of Cancer's Multiple Myeloma Module. Descriptive statistics, bivariate correlations, and structural equation modeling were performed to analyze the data. RESULTS: The indirect effect of psychological morbidity on patients' future perspectives (MYFP) was partially mediated by information unmet needs (INF), while the indirect effect of psychological morbidity on treatment side effects (MYSE) was partially mediated by relationship and emotional unmet needs (REH). In turn, the indirect effect of psychological morbidity on disease symptoms (MYDS) was fully mediated by REH. Social support had an indirect effect on MYDS and MYSE fully mediated by REH. CONCLUSION: Intervention programs tailored to promote MM patients' QoL should specifically address information and emotional needs, raising awareness and training health professionals, caregivers, and family members to attend  MM patients' unmet needs.


Subject(s)
Multiple Myeloma/psychology , Needs Assessment/standards , Quality of Life/psychology , Adult , Aged , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
8.
Molecules ; 25(22)2020 Nov 18.
Article in English | MEDLINE | ID: mdl-33218181

ABSTRACT

The genus Cedrela P. Browne, which belongs to the Meliaceae family, has eighteen species. Trees of this genus are of economic interest due to wood quality, as well as being the focus of studies because of relevant biologic activities as in other Meliaceae species. These activities are mainly related to limonoids, a characteristic class of compounds in this family. Therefore, the aim of this review is to perform a survey of the citations in the literature on the Cedrela genus species. Articles were found on quantitative and qualitative phytochemical studies of the Cedrela species, revealing the chemical compounds identified, such as aliphatics acid and alcohol, flavonoids, tocopherol, monoterpenes, sesquiterpenes, triterpenes, cycloartanes, steroids, and limonoids. Although some activities were tested, the majority of studies focused on the insecticidal, antifeedant, or insect growth inhibitor activities of this genus. Nonetheless, the most promising activities were related to their antimalarial and antitripanocidal effects, although further investigations are still needed.


Subject(s)
Cedrela/chemistry , Phytochemicals/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Cedrela/growth & development , Inhibitory Concentration 50 , Phytochemicals/chemistry , Plant Development/drug effects
9.
J Phys Chem A ; 123(33): 7195-7200, 2019 Aug 22.
Article in English | MEDLINE | ID: mdl-31356075

ABSTRACT

The predicted rate constants for C + NO and O + CN collisions in three potential energy surfaces (PESs) for the 2A' state of the CNO molecule are compared using quasiclassical trajectories. Different temperature dependencies are obtained for the C + NO reaction, which are explained in terms of the long-range properties of the PESs. Recommended values and mechanistic details are also reported. For O + CN collisions, a better agreement between the theoretical results is found, except for temperatures below 100 K.

10.
BMC Pediatr ; 19(1): 165, 2019 05 24.
Article in English | MEDLINE | ID: mdl-31126263

ABSTRACT

BACKGROUND: Non-supine infant sleep position is an important modifiable risk factor for sudden unexpected death in infancy. The aim of this study was to assess the prevalence of supine sleep position and associated factors among 3-month-old infants from a birth cohort in the city of Pelotas, southern Brazil. METHODS: The present study evaluated longitudinal data from the 2015 Pelotas Birth Cohort. Study outcome was supine infant sleep position, defined as the appropriate position, among 3-month-old children. Demographic, socioeconomic, behavioral, and health characteristics collected at birth and at the 3-month follow-up were investigated as possible associated factors. The prevalence of each associated factor was investigated, and crude and hierarchical adjusted analyses were performed using Poisson regression. RESULTS: Among the 4108 infants assessed in this study, 2274 (55.4%) slept in supine position at 3 months and only 66 (1.6%) in prone position. Maternal white skin color, higher family income and maternal schooling, advanced maternal age, maternal cohabiting with a partner, receiving counseling from health care professionals and non-bed-sharing were associated with higher prevalence of infants sleeping in supine position at 3 months. All these variables remained associated in our hierarchical adjusted analyses except maternal cohabitation with a partner. Participants with white mothers were more likely to sleep in supine position (PR: 1.23; 95%CI: 0.75-0.89) compared to participants with black mothers. Those belonging to the richest quintile were more likely to sleep in supine position (PR: 1.49; 95%CI: 1.35-1.65) compared to those who belong to the poorest. Mothers aged 31-36 years were more likely to choose supine sleep position (PR: 1.65; 95%CI: 1.42-1.92) compared to mothers younger than 19 years. CONCLUSIONS: The findings of the present study showed the influence of maternal age, socioeconomic status, and counseling on infant sleep habits as predictors of choice of infant sleep position in a Brazilian population. It is recommended to implement informative campaigns and public policies to at-risk population and to improve recommendations from health care professionals.


Subject(s)
Infant Care/statistics & numerical data , Sleep , Supine Position , Adolescent , Adult , Brazil , Counseling , Female , Health Education , Humans , Infant , Longitudinal Studies , Male , Prevalence , Racial Groups , Socioeconomic Factors , Sudden Infant Death/prevention & control
11.
Lupus ; 27(13): 2041-2049, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30376438

ABSTRACT

BACKGROUND: The aim of this study was to investigate serum S100B and brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE) patients, with and without neuropsychiatric (NP) manifestation activity. METHODS: We assessed 47 SLE patients and 20 selected healthy individuals. Disease activity was assessed according to the SLE disease activity index (SLEDAI). Serum BDNF and S100B were measured by enzyme-linked immunosorbent assay. RESULTS: Serum S100B protein was significantly higher in SLE patients. BDNF levels were significantly decreased in active SLE, when compared with inactive SLE, but not when compared with controls. S100B was clearly higher in the NPSLE group, when compared with the non-NPSLE or control groups. Receiver operating characteristic analysis of S100B revealed an area under the curve of 0.706 that discriminated NPSLE patients with peripheral polyneuropathy. CONCLUSIONS: Our findings reinforce the use of serum S100B as a biomarker in SLE, particularly for NPSLE. Moreover, we found a strong association between serum S100B and peripheral neuropathy, indicating a specific utility for this biomarker in SLE that warrants clinical investigation.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Lupus Vasculitis, Central Nervous System/blood , S100 Calcium Binding Protein beta Subunit/blood , Adult , Biomarkers/blood , Case-Control Studies , Cuba , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lupus Vasculitis, Central Nervous System/immunology , Male , Middle Aged , ROC Curve , Severity of Illness Index
12.
J Phys Chem A ; 122(16): 4198-4207, 2018 Apr 26.
Article in English | MEDLINE | ID: mdl-29620887

ABSTRACT

We report a new global double many-body expansion potential energy surface for the ground state of the CNO(2A') manifold, calculated by the explicit correlation multireference configuration interaction method. The functional form was accurately fitted to 3701 ab initio points with a root mean squared deviation of 0.99 kcal mol-1. All stationary points reported in previous forms are systematically described and improved, in addition to three new ones and a characterization of an isomerization transition state between the CNO and NCO minima. The novel proposed form gives a realistic description of both short-range and long-range interactions and hence is commended for dynamics studies.

13.
Soc Psychiatry Psychiatr Epidemiol ; 53(7): 717-726, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29721592

ABSTRACT

PURPOSE: To investigate the association between mental disorders and substance misuse at 30 years of age with gender, socioeconomic position at birth, and family income trajectories. METHODS: The 1982 Pelotas Birth Cohort was used; all 5914 children born alive at hospital were originally enrolled (99.2% of all city births). In 2012, 3701 subjects were located and interviewed (68% retention rate). Mental disorders and substance misuse were assessed, and their prevalence analysed according to gender, socioeconomic status at birth, and four different income trajectories: always poor, never poor, poor at birth/non-poor at age 30, and non-poor at birth/poor at age 30. RESULTS: While women presented higher prevalence of mental disorders, substance misuse was much more frequent among men. Individuals in the lowest income quintile at birth presented 2-5 times more mental disorders and substance misuse than those in the highest quintile. Young adults who were always poor or were not poor at birth but were poor at 30 years of age had a higher prevalence of mental disorders than the other groups. CONCLUSIONS: The high rates of mental disorders and lifetime suicide attempts in young adults, especially those who were always poor or became poor after childhood, suggest that recent socioeconomic-related stressful situations may have a higher impact on the current mental health than events earlier in life. However, we could not identify at what specific ages socioeconomic changes were more important.


Subject(s)
Health Status Disparities , Mental Disorders/epidemiology , Socioeconomic Factors , Substance-Related Disorders/epidemiology , Adult , Brazil/epidemiology , Cohort Studies , Female , Humans , Income/statistics & numerical data , Male , Mental Disorders/etiology , Poverty/psychology , Social Class , Substance-Related Disorders/etiology , Suicide, Attempted/psychology , Suicide, Attempted/statistics & numerical data
14.
J R Army Med Corps ; 164(6): 419-422, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30076199

ABSTRACT

INTRODUCTION: Gastrointestinal infections are among the most common foodborne and waterborne diseases in military populations, with direct implications in operational efficiency and force readiness. Through the surveillance system of reportable acute gastrointestinal illness in the Portuguese Army, four norovirus outbreaks were identified between October 2015 and October 2017 in mainland Portugal and the Azores archipelago. The present study documents the epidemiological, clinical and laboratory investigations of these norovirus outbreaks. METHODS: Cases were investigated and epidemiological questionnaires were distributed to all soldiers in each military setting where the outbreaks occurred. Stool samples from soldiers with acute gastroenteritis illness were collected and screened for common enteropathogenic agents. Food and water samples served on the settings were also collected for microbiological investigation. Norovirus-positive samples were further characterised by sequence analysis using a public automated genotyping tool. RESULTS: The four outbreaks affected a total of 99 soldiers among the 618 stationed on base units and in a military exercise. A total of 27 soldiers provided a stool sample, of which 20 were positive for norovirus by real-time PCR. Phylogenetic analysis showed that the noroviruses involved were all genogroup II, namely GII.17, GII.Pe-GII.4 Sydney 2012, GII.P2-GII.2 and GII.P16-GII.2. Of note, 30 soldiers had to receive treatment at the military hospital due to severity of symptoms. CONCLUSION: In this short, two-year surveillance period, a total of four norovirus gastroenteritis outbreaks were detected in the Portuguese Army which caused a considerable morbidity, showing once again the impact of norovirus on Army effectiveness and force readiness.


Subject(s)
Caliciviridae Infections/epidemiology , Gastroenteritis/virology , Military Personnel/statistics & numerical data , Norovirus , Disease Outbreaks , Feces/virology , Gastroenteritis/epidemiology , Genotype , Humans , Norovirus/genetics , Population Surveillance , Portugal/epidemiology
15.
Gene Ther ; 24(7): 416-424, 2017 07.
Article in English | MEDLINE | ID: mdl-28504656

ABSTRACT

When administrated in the blood circulation, plasmid DNA (pDNA) complexed with synthetic vectors must pass through a vascular endothelium to transfect underlying tissues. Under inflammatory condition, cytokines can modify the endothelium integrity. Here, the trans-endothelial passage (TEP) of DNA complexes including polyplexes, lipoplexes and lipopolyplexes was investigated in the presence of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) or insulin-like growth factor-1 (IGF-1). The experiments were performed by using an in vitro model comprising a monolayer of mouse cardiac endothelial cells (MCEC) seeded on a trans-well insert and the transfection of C2C12 myoblasts cultured on the lower chamber as read out of TEP. We report that polyplexes made with a histidinylated derivative of lPEI (His-lPEI) exhibit the highest capacity (10.5 µg cm-2 h versus 0.324 µg cm-2 h) to cross TNF-α-induced inflamed endothelium model, but this positive effect is counterbalanced by the presence of IL-1ß. His-lPEI polyplex TEP is also increased in the presence of IGF-1 (2.58 µg cm-2 h). TEP of lipid-based DNA complexes including lipoplexes and lipopolyplexes was lowest compared with polymer-based DNA complexes. Overall, the results indicate that under inflammation, His-lPEI polyplexes have a good profile to cross a vascular endothelium of striated muscle with low cytotoxicity and high transfection efficiency of C2C12 myoblasts. These data provide insights concerning the endothelial passage of vectors in inflammatory conditions and can serve as a basis towards in vivo studies.


Subject(s)
Endothelial Cells/metabolism , Gene Transfer Techniques , Insulin-Like Growth Factor I/pharmacology , Interleukin-1beta/pharmacology , Myoblasts/metabolism , Transendothelial and Transepithelial Migration/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Animals , Cell Line , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Mice , Muscle, Striated/cytology , Muscle, Striated/metabolism , Plasmids/genetics
16.
Hum Reprod ; 32(3): 704-711, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28122887

ABSTRACT

STUDY QUESTION: What is the prevalence and functional consequence of ANOS1 (KAL1) mutations in a group of men with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Three of forty-two (7.1%) patients presented ANOS1 mutations, including a novel splice site mutation leading to exon skipping and a novel contiguous gene deletion associated with ichthyosis. WHAT IS KNOWN ALREADY: CHH is characterized by lack of pubertal development and infertility, due to deficient production, secretion or action of GnRH, and can be associated with anosmia/hyposmia (Kallmann syndrome, KS) or with a normal sense of smell (normosmic CHH). Mutations in the anosmin-1 (ANOS1) gene are responsible for the X-linked recessive form of KS. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 42 unrelated men with CHH (20 with KS and 22 with normosmic CHH). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were screened for mutations in the ANOS1 gene by DNA sequencing. Identified mutations were further investigated by RT-PCR analysis and multiplex ligation-dependent probe amplification (MLPA) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Hemizygous mutations were identified in three (7.1%) KS cases: a novel splice acceptor site mutation (c.542-1G>C), leading to skipping of exon 5 in the ANOS1 transcript in a patient with self-reported normosmia (but hyposmic upon testing); a recurrent nonsense mutation (c.571C>T, p.Arg191*); and a novel 4.8 Mb deletion involving ANOS1 and eight other genes (VCX3B, VCX2, PNPLA4, VCX, STS, HDHD1, VCX3A and NLGN4X) in KS associated with ichthyosis. LIMITATIONS, REASONS FOR CAUTION: Objective olfactory testing was not performed in all cases of self-reported normosmia and this may have underestimated the olfactory deficits. WIDER IMPLICATIONS OF THE FINDINGS: This study further expands the spectrum of known genetic defects associated with CHH and suggests that patients with self-reported normal olfactory function should not be excluded from ANOS1 genetic testing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Portuguese Foundation for Science and Technology. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Extracellular Matrix Proteins/genetics , Hypogonadism/genetics , Kallmann Syndrome/genetics , Mutation , Nerve Tissue Proteins/genetics , Alleles , Cross-Sectional Studies , DNA Mutational Analysis , Exons , Female , Gene Frequency , Humans , Hypogonadism/congenital , Male , Pedigree
17.
Mol Psychiatry ; 21(4): 554-64, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26169974

ABSTRACT

The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.


Subject(s)
Antipsychotic Agents/therapeutic use , C-Reactive Protein/metabolism , Schizophrenia/blood , Schizophrenia/drug therapy , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Humans , Longitudinal Studies
18.
Int J Behav Nutr Phys Act ; 14(1): 82, 2017 06 23.
Article in English | MEDLINE | ID: mdl-28645330

ABSTRACT

BACKGROUND: Adolescents spend many hours in sitting activities as television viewing, video game playing and computer use. The relationship between sedentary behavior and respiratory health remains poorly elucidated. To date there have been no studies evaluating the relationship between sedentary behavior and pulmonary function in young populations. The purpose of this study is to examine the association between the trajectory of screen-based sedentary behavior from 11 to 18 years and pulmonary function at 18 years in a Brazilian birth cohort. METHODS: Data from a longitudinal prospective study conducted among the participants of the 1993 Pelotas (Brazil) Birth Cohort. Time spent on television, video games, and computers during a weekday was self-reported at ages 11, 15 and 18 years. For each age, sedentary behavior was defined as the sum of time spent on these screen-based activities. To evaluate the sedentary behavior trajectory during adolescence group-based trajectory modeling was used. Outcome variables were three pulmonary function parameters: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), evaluated by spirometry, at 18 years expressed as z-scores. Crude and adjusted linear regressions, stratified by sex, were performed. RESULTS: The three-group trajectory of sedentary behavior was the best fitting model. The trajectory groups were: always high (representing 38.8% of the individuals), always moderate (54.1%), and always low (7.1%). In the adjusted analyses, boys in the always-low group for sedentary behavior had higher FVC at 18 years (ß = 0.177; 95% CI:0.027;0.327; p = 0.021) than boys in the always-high group. There were no differences for other pulmonary function parameters in boys. No significant association was found for girls. CONCLUSION: The trajectory of screen-based sedentary behavior throughout adolescence was not consistent associated with pulmonary function at 18 years.


Subject(s)
Computers , Lung/physiology , Sedentary Behavior , Television , Video Games , Adolescent , Brazil , Child , Exercise , Female , Forced Expiratory Volume , Humans , Linear Models , Male , Peak Expiratory Flow Rate , Prospective Studies , Self Report , Sex Factors , Spirometry , Vital Capacity
19.
J Dairy Sci ; 100(5): 3513-3525, 2017 May.
Article in English | MEDLINE | ID: mdl-28259413

ABSTRACT

This study aimed to evaluate the rheological behavior and thermal conductivity of dairy products, composed of the same chemical components but with different formulations, as a function of temperature. Subsequently, thermal conductivity was related to the apparent viscosity of yogurt, fermented dairy beverage, and fermented milk. Thermal conductivity measures and rheological tests were performed at 5, 10, 15, 20, and 25°C using linear probe heating and an oscillatory rheometer with concentric cylinder geometry, respectively. The results were compared with those calculated using the parallel, series, and Maxwell-Eucken models as a function of temperature, and the discrepancies in the results are discussed. Linear equations were fitted to evaluate the influence of temperature on the thermal conductivity of the dairy products. The rheological behavior, specifically apparent viscosity versus shear rate, was influenced by temperature. Herschel-Bulkley, power law, and Newton's law models were used to fit the experimental data. The Herschel-Bulkley model best described the adjustments for yogurt, the power law model did so for fermented dairy beverages, and Newton's law model did so for fermented milk and was then used to determine the rheological parameters. Fermented milk showed a Newtonian trend, whereas yogurt and fermented dairy beverage were shear thinning. Apparent viscosity was correlated with temperature by the Arrhenius equation. The formulation influenced the effective thermal conductivity. The relationship between the 2 properties was established by fixing the temperature and expressing conductivity as a function of apparent viscosity. Thermal conductivity increased with viscosity and decreased with increasing temperature.


Subject(s)
Dairy Products , Temperature , Thermal Conductivity , Animals , Models, Theoretical , Rheology , Viscosity
20.
J Anim Physiol Anim Nutr (Berl) ; 101(6): 1194-1204, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27862400

ABSTRACT

An ideal amino acid ratio (IAAR) for breeder hens is needed for maximum nitrogen retention (NR) taking into account nitrogen deposition in body (NDB ), feathers (NDF ) and egg mass (NEM) to improve dietary protein efficiency. Thus, the aim of this study was to apply the deletion method to derive the IAAR for broiler breeder hens. The nitrogen balance trials were performed from 31 to 35 weeks and from 46 to 50 weeks. Twelve treatments with eight replicates and one hen per cage were used. A balanced diet (BD) was formulated to meet the requirement of all nutrients. The other diets were formulated diluting 55% of BD with corn starch and refilled with amino acids (AAs) and other ingredients, except the AA tested. Each trial lasted 25 days. Feather losses, egg production and egg weight were recorded daily, and the samples were stored to further determine NEM and nitrogen in feather losses (NDFL ). At the start and the end of each period, a group of birds were slaughtered to further determine NDB and NDF . The NR was calculated as the sum of NDB , NDF , NDFL , NEM and the nitrogen maintenance requirement (NMR). The deletion of valine greatly depressed the NR in peak production (31 to 35 weeks) while the deletion of the isoleucine greatly depressed the NR of the hens from 46 to 50 weeks of age. The percentual reduction in NR and the per cent of the AA to delete from the BD were used to calculate the AA requirement. The average IAAR was Lys 100, Met+Cys 86, Trp 23, Thr 80, Arg 113, Val 90, Ile 91, Leu 133, Phe+Tyr 108, Gly+Ser 94 and His 35. The IAAR was in line with the recommendation from the literature, validating deletion method with the advantages from a rapid and low-cost procedure.


Subject(s)
Amino Acids/administration & dosage , Animal Feed/analysis , Chickens/physiology , Diet/veterinary , Dietary Proteins/administration & dosage , Animal Nutritional Physiological Phenomena , Animals , Dose-Response Relationship, Drug , Feathers , Female , Nitrogen , Nutritional Requirements , Oviposition
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