Association between caffeine use disorder and socio-demographic characteristics (sex, employment and smoking status) of Quezon City residents: An analytical cross-sectional study / The Health Sciences Journal

Introduction@#Caffeine use disorder (CUD), a problematic caffeine use pattern, is yet to be recognized under DSM-5 and is under consideration for further research. This study aimed to determine if the sex, employment status, and smoking status of Quezon City residents aged 18 years old and above are associated with CUD, and to determine the mean daily caffeine consumption (MDCC) of caffeinated products and the proportion of individuals meeting the CUD criteria.@*Methods@#A total of 334 respondents accomplished the online survey that collected socio-demographic information and evaluated CUD using an 8-point Caffeine Consumption Questionnaire (CCQ). @*Results@#The study population was mostly composed of females, unemployed, and non-smokers. Results showed that 17% of respondents have CUD, that brewed coffee was most consumed daily, the MDCC of the study population was 158.31 mg; and females were at an increased risk for CUD, while nonsmokers and unemployed individuals were at reduced risk. @*Conclusion@#The proportion of Quezon city residents that have CUD is at 17%, consuming an average of 158.31 mg of coffee daily, with brewed coffee being consumed most. Female residents are at an increased risk of having CUD, while nonsmokers and unemployed individuals are at a decreased risk.

A likely cranial osteodystrophy (Paget's disease of bone) in a Precolumbian, Mesoamerican stone sculpture.

This short note illustrates facial and head features found in a stone sculpture of the ancient, Precolumbian period in a temple of the Mayan city of Copan (Honduras). The authors believe that this observation may support paleoanthropological evidence of Paget's disease of bone, an osteodystrophy described in the Mesoamerican Indian populations before the first millennium A.D.

Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring.

Prolonged ovarian hormone deprivation alters the effects of 17ß-estradiol on microRNA expression in the aged female rat hypothalamus.

Administration of 17ß-estradiol (E2) has beneficial effects on cognitive function in peri- but not post-menopausal women, yet the molecular mechanisms underlying age-related changes in E2 action remain unclear. We propose that there is a biological switch in E2 action that occurs coincident with age and length of time after ovarian hormone depletion, and we hypothesized that age-dependent regulation of microRNAs (miRNAs) could be the molecular basis for that switch. Previously we showed that miRNAs are regulated by E2 in young compared to aged female rats. Here we tested whether increasing lengths of ovarian hormone deprivation in aged females altered E2 regulation of these mature miRNAs. In addition, we determined where along the miRNA biogenesis pathway E2 exerted its effects. Our results showed that age and increased lengths of ovarian hormone deprivation abolished the ability of E2 to regulate mature miRNA expression in the brain. Further, we show that E2 acted at specific points along the miRNA biogenesis pathway.

Parental binge alcohol abuse alters F1 generation hypothalamic gene expression in the absence of direct fetal alcohol exposure.

Adolescent binge alcohol exposure has long-lasting effects on the expression of hypothalamic genes that regulate the stress response, even in the absence of subsequent adult alcohol exposure. This suggests that alcohol can induce permanent gene expression changes, potentially through epigenetic modifications to specific genes. Epigenetic modifications can be transmitted to future generations therefore, and in these studies we investigated the effects of adolescent binge alcohol exposure on hypothalamic gene expression patterns in the F1 generation offspring. It has been well documented that maternal alcohol exposure during fetal development can have devastating neurological consequences. However, less is known about the consequences of maternal and/or paternal alcohol exposure outside of the gestational time frame. Here, we exposed adolescent male and female rats to a repeated binge EtOH exposure paradigm and then mated them in adulthood. Hypothalamic samples were taken from the offspring of these animals at postnatal day (PND) 7 and subjected to a genome-wide microarray analysis followed by qRT-PCR for selected genes. Importantly, the parents were not intoxicated at the time of mating and were not exposed to EtOH at any time during gestation therefore the offspring were never directly exposed to EtOH. Our results showed that the offspring of alcohol-exposed parents had significant differences compared to offspring from alcohol-naïve parents. Specifically, major differences were observed in the expression of genes that mediate neurogenesis and synaptic plasticity during neurodevelopment, genes important for directing chromatin remodeling, posttranslational modifications or transcription regulation, as well as genes involved in regulation of obesity and reproductive function. These data demonstrate that repeated binge alcohol exposure during pubertal development can potentially have detrimental effects on future offspring even in the absence of direct fetal alcohol exposure.

Differential fibroblast growth factor 8 (FGF8)-mediated autoregulation of its cognate receptors, Fgfr1 and Fgfr3, in neuronal cell lines.

Fibroblast growth factors (FGFs) mediate a vast range of CNS developmental processes including neural induction, proliferation, migration, and cell survival. Despite the critical role of FGF signaling for normal CNS development, few reports describe the mechanisms that regulate FGF receptor gene expression in the brain. We tested whether FGF8 could autoregulate two of its cognate receptors, Fgfr1 and Fgfr3, in three murine cell lines with different lineages: fibroblast-derived cells (3T3 cells), neuronal cells derived from hippocampus (HT-22 cells), and neuroendocrine cells derived from hypothalamic gonadotropin-releasing hormone (GnRH) neurons (GT1-7 cells). GnRH is produced by neurons in the hypothalamus and is absolutely required for reproductive competence in vertebrate animals. Several lines of evidence strongly suggest that Fgf8 is critical for normal development of the GnRH system, therefore, the GT1-7 cells provided us with an additional endpoint, Gnrh gene expression and promoter activity, to assess potential downstream consequences of FGF8-induced modulation of FGF receptor levels. Results from this study suggest that the autoregulation of its cognate receptor represents a common downstream effect of FGF8. Further, we show that Fgfr1 and Fgfr3 are differentially regulated within the same cell type, implicating these two receptors in different biological roles. Moreover, Fgfr1 and Fgfr3 are differentially regulated among different cell types, suggesting such autoregulation occurs in a cell type-specific fashion. Lastly, we demonstrate that FGF8b decreases Gnrh promoter activity and gene expression, possibly reflecting a downstream consequence of altered FGF receptor populations. Together, our data bring forth the possibility that, in addition to the FGF synexpression group, autoregulation of FGFR expression by FGF8 represents a mechanism by which FGF8 could fine-tune its regulatory actions.

The neuroendocrine system: organization and homeostatic role.

The neuroendocrine system (NES) of Vertebrates can be defined as a set of cells organized in single organs and diffuse elements, sharing co-production of amine hormone/transmitters, peptide hormone/transmitters and specific markers of neural determination. In this perspective, the hypothalamic-pituitary-target organ axis (H-P axis), the autonomic nervous system (ANS) and the diffuse neuroendocrine or APUD system contribute to the NES. However, in Mammals and man virtually any compartment of the body harbors elements, often with different embryologic origin, having at least some of the NES features. Thus, all anatomical structures may be part of a wide functional circuitry, based on "internal secretions", that supersedes the current view of the NES. Historically, metaphysical antecedents of this concept can be found in the biomedical tradition dealing with the idea of the so called "vital energy". Currently, the "internal secretions" circuitry can be envisaged as an informational supersystem encompassing the H-P axis, ANS, APUD, immune and any other body system performing autocrine, paracrine and/or endocrine regulations, that superintends the homeostatic balance. Evolutionary evidence shows that diffuse autocrine/paracrine/endocrine, peptidergic secretions would be the oldest and hierachically simplest signals, with respect to the later and hierarchically more complex ANS and H-P axis outputs, to regulate body homeostasis. Therefore, the new acronym "Triune Information Network" (TIN) is proposed for the informational supersystem of internal secretions acting in Mammals and man via progressively higher levels of control (diffuse autocrine/paracrine/endocrine secretions, ANS and H-P axis) on a common energetic substrate: the internal body milieu.

The human hypothalamus: a morpho-functional perspective.

Historical investigation suggests that the role of the hypothalamus as a site of integration for endocrine with autonomic and behavioral responses in man rises from ideas and observations first appearing between the 14th and 18th centuries. Research on human, post-mortem brains and by in vivo magnetic resonance techniques reveal that the functional morphology of the hypothalamus in man is very similar to that in Rodents and Primates. As such, the adult human hypothalamus can be subdivided in three longitudinal zones, representing the source and target of neural informations traveling back and forth the brain stem, thalamus, limbic system, basal ganglia and neocortex. In addition, the human hypothalamus can be further partitioned in three anterior-posterior regions, of which the rostral one exerts a prominent regulation in predictive homeostasis, as opposed to the two caudal ones, primarily involved in reactive homeostasis. Finally, nuclear distribution in the human hypothalamus largely coincides with that in higher Mammals. Nevertheless, it is still unclear how the hypothalamus may give rise to specific homeostatic behaviors like hunger, thirst, reproductive and parental attitude, thermoregulation, aggressive-defensive performance, affective-motivational tone, circadian rhythmicity, sleep-wake cycle and immune regulation. The recent advent of new theories for nervous communication, like volume transmission and neural Darwinism, is progressively enlightening our understanding of the role played by the hypothalamic architecture in homeostatic responses, both in Mammals and man.

Acromegaly and intestinal neoplasms.

Acromegalic subjects show increased frequency of neoplastic lesions in the colon and rectum with respect to the general population. Recent prospective studies using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and up to 4 time increased presence of colorectal cancer in acromegaly, independently of sex, age, duration of disease and clinical status of the patients. The polyps are distributed throughout the extension of the large bowel and are often multiple, showing at least two different histologic types: hyperplastic and adenomatous. Sometimes they are associated with intestinal carcinomas. Pancolonoscopy is the procedure of choice for the diagnosis of large bowel neoplasms, even though it may be difficult to complete in these subjects because of the frequent presence of an enlarged and elongated colon. It shows a higher sensitivity and specificity compared to other tests such as the barium enema, fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore, it is recommended to follow up acromegalic patients using pancolonoscopy to obtain early detection of neoplastic lesions in the large bowel.

Acromegaly and intestinal neoplasms.

Acromegalic subjects show increased frequency of neoplastic lesions in the colon and rectum with respect to the general population. Recent prospective studies using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and up to 4 time increased presence of colorectal cancer in acromegaly, independently of sex, age, duration of disease and clinical status of the patients. The polyps are distributed throughout the extension of the large bowel and are often multiple, showing at least two different histologic types: hyperplastic and adenomatous. Sometimes they are associated with intestinal carcinomas. Pancolonoscopy is the procedure of choice for the diagnosis of large bowel neoplasms, even though it may be difficult to complete in these subjects because of the frequent presence of an enlarged and elongated colon. It shows a higher sensitivity and specificity compared to other tests such as the barium enema, fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore, it is recommended to follow up acromegalic patients using pancolonoscopy to obtain early detection of neoplastic lesions in the large bowel.

Neuroendocrine regulation of thyrotropin-releasing hormone (TRH) in the tuberoinfundibular system.

[...] It is now required to list each part needed for mucous excretion. They are two ducts in the brain substance, then a thin portion of membrane shaped as the infundibulum, then the gland that receives the tip of this infundibulum and the ducts that drive the mucus (pituita) from this gland to the palate and nares. [...] and I said that one (duct) [...] from the middle of the common cavity (third ventricle) descends [...] into the brain substance, and the end of this duct is [...] the sinus of the gland where the brain mucus is collected [...].

Cholecystokinin neuron systems and their interactions with the presynaptic features of the dopamine neuron systems. A morphometric and neurochemical analysis involving studies on the action of cholecystokinin-8 and cholecystokinin-58.

A unique role for CCK-58 compared to that for CCK-8 has been demonstrated in the modulation of central catecholaminergic mechanisms and neuroendocrine functions. It is of paramount importance to localize CCK-58 immunoreactivity within the brain in order to establish if separate CCK-58- and CCK-8-immunoreactive neuron systems exist. The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium.