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Background: Population-based linked datasets are vital to generate catchment area and population health research. The novel Cancer Information & Population Health Resource (CIPHR) links statewide cancer registry data, public and private insurance claims, and provider- and area-level data, representing more than 80% of North Carolina's large, diverse population of individuals diagnosed with cancer. This scoping review of articles that used CIPHR data characterizes the breadth of research generated and identifies further opportunities for population-based health research., Methods: Articles published January 2012 - August 2023 were categorized by cancer site and outcomes examined across the care continuum. Statistically significant associations between patient-, provider-, and system/policy-level factors and outcomes were summarized., Results: Among 51 articles, 42 reported results across 23 unique cancer sites and 13 aggregated across multiple sites. The most common outcomes examined were treatment initiation and/or adherence (n = 14), mortality/survival (n = 9), and health care resource utilization (n = 9). Few articles focused on cancer recurrence (n = 1) or distance to care (n = 1) as outcomes. Many articles discussed racial, ethnic, geographic, and socioeconomic inequities in care., Conclusions: These findings demonstrate the value of robust, longitudinal, linked, population-based databases to facilitate catchment area and population health research aimed at elucidating cancer risk factors, outcomes, care delivery trends, and inequities that warrant intervention and policy attention. Lessons learned from years of analytics using CIPHR highlight opportunities to explore less-frequently studied cancers and outcomes, motivate equity-focused interventions, and inform development of similar resources., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The American Indian (AI) population in North Carolina has limited access to the Indian Health Service. Consequently, cancer burden and disparities may differ from national estimates. We describe the AI cancer population and examine AI-White disparities in cancer incidence and mortality., Methods: We identified cancer cases diagnosed among adult AI and White populations between 2014 and 2018 from the North Carolina Central Cancer Registry. We estimated incidence and mortality rate ratios (IRR and MRR) by race. In addition, between the AI and White populations, we estimated the ratio of relative frequency differences [RRF, with 95% confidence limits (CL)] of clinical and sociodemographic characteristics. Finally, we evaluated the geographic distribution of incident diagnoses among AI populations., Results: Our analytic sample included 2,161 AI and 204,613 White individuals with cancer. Compared with the White population, the AI population was more likely to live in rural areas (48% vs. 25%; RRF, 1.89; 95% CL, 1.81-1.97) and to have Medicaid (18% vs. 7%; RRF, 2.49; 95% CL, 2.27-2.71). Among the AI population, the highest age-standardized incidence rates were female breast, followed by prostate and lung and bronchus. Liver cancer incidence was significantly higher among the AI population than White population (IRR, 1.27; 95% CL, 1.01-1.59). AI patients had higher mortality rates for prostate (MRR, 1.72; CL, 1.09-2.70), stomach (MRR, 1.82; 95% CL, 1.15-2.86), and liver (MRR, 1.70; 95% CL, 1.25-2.33) cancers compared with White patients., Conclusions: To reduce prostate, stomach, and liver cancer disparities among AI populations in North Carolina, multi-modal interventions targeting risk factors and increasing screening and treatment are needed., Impact: This study identifies cancer disparities that can inform targeted interventions to improve outcomes among AI populations in North Carolina., (©2024 American Association for Cancer Research.)

The development of anthropic activities during recent years has led to an increase in nutrient fluxes in the Río Grande de Comitán and Montebello Lakes National Park, Mexico. In turn, this has modified the dynamics of the biotic community, specifically favoring the presence of cyanobacteria tolerant to contamination. The continual and massive presence of Planktothrix species (spp.) in the system suggests a potential detrimental impact for economic issues and human health. In this study, we identify the morphological and molecular characteristics of Planktothrix populations from seven tropical (1,380-1,740 masl, 23.0-25.5°C) and calcareous lakes and two ponds from a water treatment plant. We also assess the ecological drivers that could be related to the presence of cyanotoxins in the system. The ecological preferences, morphology, 16S rRNA structure, and 16S-23S rRNA internal transcribed spacer found evidence for three species: P. agardhii distributed in neutral to slightly basic water (pH = 7.7-8.7), and P. spiroides and Planktothrix sp. in alkaline waters (pH = 9.1). The presence of the mcyE gene and its validation by liquid chromatography confirmed the presence of two microcystin variants (MC-RR and MC-LR) in at least three populations of P. agardhii . These microcystins put the health of the ecosystem and its inhabitants at risk, a condition that should be addressed and resolved with a water management and detoxification strategy in the basin., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2024 Javier Carmona Jiménez et al.)

In addition to its essential role in the physiological control of longitudinal growth, growth-hormone (GH) is endowed with relevant metabolic functions, including anabolic actions in muscle, lipolysis in adipose-tissue and glycemic modulation. Adult obesity is known to negatively impact GH-axis, thereby promoting a vicious circle that may contribute to the exacerbation of the metabolic complications of overweight. Yet, to what extent early-overnutrition sensitizes the somatotropic-axis to the deleterious effects of obesity remains largely unexplored. Using a rat-model of sequential exposure to obesogenic insults, namely postnatal-overfeeding during lactation and high-fat diet (HFD) after weaning, we evaluated in both sexes the individual and combined impact of these nutritional challenges upon key elements of the somatotropic-axis. While feeding HFD per se had a modest impact on the adult GH-axis, early overnutrition had durable effects on key elements of the somatotropic-system, which were sexually different, with a significant inhibition of pituitary gene expression of GH-releasing hormone-receptor (GHRH-R) and somatostatin receptor-5 (SST5) in males, but an increase in pituitary GHRH-R, SST2, SST5, GH secretagogue-receptor (GHS-R) and ghrelin expression in females. Notably, early-overnutrition sensitized the GH-axis to the deleterious impact of HFD, with a significant suppression of pituitary GH expression in both sexes and lowering of circulating GH levels in females. Yet, despite their similar metabolic perturbations, males and females displayed rather distinct alterations of key somatotropic-regulators/ mediators. Our data document a synergistic effect of postnatal-overnutrition on the detrimental impact of HFD-induced obesity on key elements of the adult GH-axis, which is conducted via mechanisms that are sexually-divergent.

Chlamydia trachomatis is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM). Here, we report an LGV outbreak, mostly affecting human immunodeficiency virus-positive MSM engaging in high-risk sexual practices, caused by an L2b strain with a rather unique non-LGV ompA signature that precluded the laboratory notification of this outbreak as LGV. C. trachomatis whole-genome capture and sequencing directly from clinical samples was applied to deeply characterize the genomic backbone of this novel LGV outbreak-causing clone. It revealed a chimeric genome structure due to the genetic transfer of ompA and four neighbouring genes from a serovar D/Da strain, likely possessing the genomic backbone associated with the more prevalent urogenital genotypes (T1 clade), to an LGV (L2b) strain. The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (major outer membrane protein) (encoded by ompA ) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this novel C. trachomatis genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of variants with epidemic and pathogenic potential highlights the need for more focused surveillance strategies to capture C. trachomatis evolution in action.

Somatostatin (SST) and cortistatin (CORT) regulate numerous endocrine secretions and their absence [knockout (KO)-models] causes important endocrine-metabolic alterations, including pituitary dysregulations. We have demonstrated that the metabolic phenotype of single or combined SST/CORT KO-models is not drastically altered under normal conditions. However, the biological actions of SST/CORT are conditioned by the metabolic-status (e.g. obesity). Therefore, we used male/female SST- and CORT-KO mice fed low-fat (LF) or high-fat (HF) diet to explore the interplay between SST/CORT and obesity in the control of relevant pituitary-axes and whole-body metabolism. Our results showed that the SST/CORT role in the control of GH/prolactin secretions is maintained under LF- and HF-diet conditions as SST-KOs presented higher GH/prolactin-levels, while CORT-KOs displayed higher GH- and lower prolactin-levels than controls under both diets. Moreover, the impact of lack of SST/CORT on the metabolic-function was gender- and diet-dependent. Particularly, SST-KOs were more sensitive to HF-diet, exhibiting altered growth and body-composition (fat/lean percentage) and impaired glucose/insulin-metabolism, especially in males. Conversely, only males CORT-KO under LF-diet conditions exhibited significant alterations, displaying higher glucose-levels and insulin-resistance. Altogether, these data demonstrate a tight interplay between SST/CORT-axis and the metabolic status in the control of endocrine/metabolic functions and unveil a clear dissociation of SST/CORT roles.

Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

Background: Somatostatin (SST) and cortistatin (CORT), two structurally and functionally related peptides, share a family of widespread receptors (sst1-5) to exert apparently similar biological actions, including endocrine/metabolic regulation and suppression of tumor cell proliferation. However, despite their therapeutic potential, attempts to apply SST-analogs to treat breast cancer have yielded unsatisfactory results. Actually, the specific roles of SST and CORT in mammary gland tumorigenesis (MGT), particularly in relation to metabolic dysregulation (i.e. obesity), remain unknown., Methods: The role of endogenous SST and CORT in carcinogen-induced MGT was investigated under normal (lean) and obesity conditions. To that end, SST- and CORT-knockout (KO) mice and their respective littermate-controls, fed low-fat (LF) or high-fat (HF) diets, were treated with 7,12-dimethyl-benza-anthracene (DMBA) once a week (wk) for 3 wk, and MGT was monitored for 25 wk. Additionally, we examined the effect of SST or CORT removal in the development of the mammary gland., Results: Lack of SST did not alter DMBA-induced MGT incidence under lean conditions; conversely, lack of endogenous CORT severely aggravated DMBA-induced MGT in LF-fed mice. These differences were not attributable to altered mammary gland development. HF-diet modestly increased the sensitivity to DMBA-induced carcinogenesis in control mice, whereas, as observed in LF-fed CORT-KO, HF-fed CORT-KO mice exhibited aggravated tumor incidence, discarding a major influence of obesity on these CORT actions. In marked contrast, HF-fed SST-KO mice exhibited much higher tumor incidence than LF-fed SST-KO mice, which could be associated with higher mammary complexity., Conclusions: Endogenous SST and CORT distinctly impact on DMBA-induced MGT, in a manner that is strongly dependent on the metabolic/endocrine milieu (lean vs. obese status). Importantly, CORT, rather than SST, could represent a major inhibitor of MGT under normal/lean-conditions, whereas both neuropeptides would similarly influence MGT under obesity conditions. The mechanisms mediating these different effects likely involve mammary development and hormones, but the precise underlying factors are still to be fully elucidated. However, our findings comprise suggestive evidence that CORT-like molecules, rather than classic SST-analogs, may help to identify novel tools for the medical treatment of breast cancer.

Somatostatin (SST) and cortistatin (CORT) are two highly related neuropeptides involved in the regulation of various endocrine secretions. In particular, SST and CORT are two primary negative regulators of GH secretion. Consequently, single SST or CORT knockout mice exhibit elevated GH levels; however, this does not lead to increased IGF-1 levels or somatic growth. This apparent lack of correspondence has been suggested to result from compensatory mechanisms between both peptides. To test this hypothesis, in this study we explored, for the first time, the consequences of simultaneously deleting endogenous SST and CORT by generating a double SST/CORT knockout mouse model and exploring its endocrine and metabolic phenotype. Our results demonstrate that simultaneous deletion of SST and CORT induced a drastic elevation of endogenous GH levels, which, surprisingly, did not lead to changes in growth rate or IGF-1 levels, suggesting the existence of additional factors/systems that, in the absence of endogenous SST and CORT, could counteract GH actions. Notably, elevation in circulating GH levels were not accompanied by changes in pituitary GH expression or by alterations in the expression of its main regulators (GHRH and ghrelin) or their receptors (GHRH receptor, GHS receptor, or SST/CORT receptors) at the hypothalamic or pituitary level. However, although double-SST/CORT knockout male mice exhibited normal glucose and insulin levels, they had improved insulin sensitivity compared with the control mice. Therefore, these results suggest the existence of an intricate interplay among the known (SST/CORT), and likely unknown, inhibitory components of the GH/IGF-1 axis to regulate somatic growth and glucose/insulin homeostasis.

Locally produced growth hormone (GH) and IGF-I are key factors in the regulation of mammary gland (MG) development and may be important in breast cancer development/progression. Somatostatin (SST) and cortistatin (CORT) regulate GH/IGF-I axis at various levels, but their role in regulating GH/IGF-I in MGs remains unknown. Since obesity alters the expression of these systems in different tissues and is associated to MG (patho) physiology, we sought to investigate the role of SST/CORT in regulating GH/IGF-I system in the MGs of lean and obese mice. Therefore, we analyzed GH/IGF-I as well as SST/CORT and ghrelin systems expression in the mammary fat pads (MFPs) of SST- or CORT-knockout (KO) mice and their respective littermate-controls fed a low-fat (LF) or a high-fat (HF) diet for 16 wks. Our results demonstrate that the majority of the components of GH/IGF-I, SST/CORT and ghrelin systems are locally expressed in mouse MFP. Expression of elements of the GH/IGF-I axis was significantly increased in MFPs of HF-fed control mice while lack of endogenous SST partially suppressed, and lack of CORT completely blunted, the up-regulation observed in obese WT-controls. Since SST/CORT are known to exert an inhibitory role on the GH/IGFI axis, the increase in SST/CORT-receptor sst2 expression in MFPs of HF-fed CORT- and SST-KOs together with an elevation on circulating SST in CORT-KOs could explain the differences observed. These results offer new information on the factors (GH/IGF-I axis) involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology.

Lepeophtheirus simplex Ho, Gómez et Fajer-Avila, 2001 is a parasite of Sphoeroides annulatus (Jenyns), an economically important fish species, with potential for aquaculture, in northwestern Mexico. The goal of this study was to describe the developmental stages under experimental conditions and seasonal fecundity of this parasite on wild fish. There are two naupliar, one copepodid, two chalimus and two pre-adult stages preceding the adult of L. simplex. The results support previous findings, which point out that the life cycle of the caligid copepods includes only six post-naupliar stages. The generation time from egg extrusion to adult for L. simplex was approximately 10 days at 22 °C. The body length of the ovigerous females ranged between 2.2 and 4.1 mm, and its fecundity between 12 and 36 eggs per string. Fecundity was negatively correlated with the egg size and positively correlated with the egg string length. Our data did not reveal significant differences in fecundity among sampling months, but ovigerous females were significantly larger in March (when water temperature was 22 °C) than in June and July (when water temperature was 30 °C). To some extent, our fecundity results contrast with those found in species of sea lice from higher latitudes. Undoubtedly, biological information on different species of sea lice from different environmental conditions will enhance our understanding of their infection strategies and will be valuable, given the increasing interest in marine fish farming in Mexico.

l-arginine (l-Arg) rapidly stimulates GH and insulin release in vivo. It has been hypothesized that l-Arg stimulates GH release by lowering hypothalamic somatostatin (SST) tone. l-Arg may also act directly at the pituitary to stimulate GH release. Moreover, l-Arg has a direct stimulatory effect on β-cells, which is thought to be blunted by the release of SST from pancreatic δ-cells. To confirm the role of endogenous SST on l-Arg-induced GH and insulin release, wild-type (WT) and SST-knockout (SST-KO) mice were injected with l-Arg (ip; 0.8 g/kg), and pre-/post-injection GH, insulin, and glucose levels were measured. In WT mice, l-Arg evoked a 6-fold increase in circulating GH. However, there was only a modest increase in GH levels in WT pituitary cell cultures treated with l-Arg. In contrast, l-Arg failed to increase GH in SST-KO beyond their already elevated levels. These results further support the hypothesis that the primary mechanism by which l-Arg acutely increases GH in vivo is by lowering hypothalamic SST input to the pituitary and not via direct pituitary effects. Additionally, l-Arg induced a clear first-phase insulin secretion in WT mice, but not in SST-KO. However, SST-KO, but not WT mice, displayed a robust and sustained second-phase insulin release. These results further support a role for endogenous SST in regulating l-Arg-mediated insulin release.

Ghrelin-system components [native ghrelin, In1-ghrelin, Ghrelin-O-acyltransferase enzyme (GOAT) and receptors (GHS-Rs)] are expressed in a wide variety of tissues, including the pancreas, where they exert different biological actions including regulation of neuroendocrine secretions, food intake and pancreatic function. The expression of ghrelin system is regulated by metabolic conditions (fasting/obesity) and is associated with the progression of obesity and insulin resistance. Cortistatin (CORT), a neuropeptide able to activate GHS-R, has emerged as an additional link in gut-brain interplay. Indeed, we recently reported that male CORT deficient mice (cort-/-) are insulin-resistant and present a clear dysregulation in the stomach ghrelin-system. The present work was focused at analyzing the expression pattern of ghrelin-system components at pancreas level in cort-/- mice and their control littermates (cort +/+) under low- or high-fat diet. Our data reveal that all the ghrelin-system components are expressed at the mouse pancreatic level, where, interestingly, In1-ghrelin was expressed at higher levels than native-ghrelin. Thus, GOAT mRNA levels were significantly lower in cort-/- mice compared with controls while native ghrelin, In1-ghrelin and GHS-R transcript levels remained unaltered under normal metabolic conditions. Moreover, under obese condition, a significant increase in pancreatic expression of native-ghrelin, In1-ghrelin and GHS-R was observed in obese cort+/+ but not in cort-/- mice. Interestingly, insulin expression and release was elevated in obese cort+/+, while these changes were not observed in obese cort-/- mice. Altogether, our results indicate that the ghrelin-system expression is clearly regulated in the pancreas of cort+/+ and cort -/- under normal and/or obesity conditions suggesting that this system may play relevant roles in the endocrine pancreas. Most importantly, our data demonstrate, for the first time, that endogenous CORT is essential for the obesity-induced changes in insulin expression/secretion observed in mice, suggesting that CORT is a key regulatory component of the pancreatic function.

It has been suggested that adult metabolic dysfunction may be more severe in individuals who become obese as children compared with those who become obese later in life. To determine whether adult metabolic function differs if diet-induced weight gain occurs during the peripubertal age vs. if excess weight gain occurs after puberty, male C57Bl/6J mice were fed a low-fat (LF; 10% kcal from fat) or high-fat (HF; 60% kcal from fat) diet starting during the peripubertal period (pHF; 4 wk of age) or as adults (aHF; 12 wk of age). Both pHF and aHF mice were hyperinsulinemic and hyperglycemic, and both showed impaired glucose tolerance and insulin resistance compared with their LF-fed controls. However, despite a longer time on diet, pHF mice were relatively more insulin sensitive than aHF mice, which was associated with higher lean mass and circulating IGF-I levels. In addition, HF feeding had an overall stimulatory effect on circulating corticosterone levels; however, this rise was associated only with elevated plasma ACTH in the aHF mice. Despite the belief that adult metabolic dysfunction may be more severe in individuals who become obese as children, data generated using a diet-induced obese mouse model suggest that adult metabolic dysfunction associated with peripubertal onset of obesity is not worse than that associated with adult-onset obesity.

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1-5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort-/-) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort-/- mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort-/- in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort-/- mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort-/- mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.

Somatostatin and cortistatin exert multiple biological actions through five receptors (sst1-5); however, not all their effects can be explained by activation of sst1-5. Indeed, we recently identified novel truncated but functional human sst5-variants, present in normal and tumoral tissues. In this study, we identified and characterized three novel truncated sst5 variants in mice and one in rats displaying different numbers of transmembrane-domains [TMD; sst5TMD4, sst5TMD2, sst5TMD1 (mouse-variants) and sst5TMD1 (rat-variant)]. These sst5 variants: (1) are functional to mediate ligand-selective-induced variations in [Ca(2+)]i and cAMP despite being truncated; (2) display preferential intracellular distribution; (3) mostly share full-length sst5 tissue distribution, but exhibit unique differences; (4) are differentially regulated by changes in hormonal/metabolic environment in a tissue- (e.g., central vs. systemic) and ligand-dependent manner. Altogether, our results demonstrate the existence of new truncated sst5-variants with unique ligand-selective signaling properties, which could contribute to further understanding the complex, distinct pathophysiological roles of somatostatin and cortistatin.