Iron deficiency in healthy, term infants aged five months, in a pediatric outpatient clinic: a prospective study.

BACKGROUND: Iron deficiency (ID) is prevalent in Malaysian children. The incidence of ID in infants under 6 months of age is unknown. Our aim was to determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in healthy, term infants aged below 6 months in our hospital population. METHODS: A prospective longitudinal pilot study of mother-infant pairs was conducted on infants receiving routine immunizations in a mother and child clinic at a university hospital, in Kuala Lumpur, Malaysia. Mothers completed standardized questionnaires at 3- and 5-month postnatal visits. Maternal and infant full blood count, ferritin, and C-reactive protein (CRP) levels were measured at 3 months and for the infants repeated at 5 months. Infant anthropometric measurements were obtained at both visits. We conducted a univariate analysis to identify factors associated with ID and IDA. RESULTS: Altogether, 91 mother-infant pairs were enrolled, with 88 completing the study. No infant had ID or IDA at 3 months; the lowest ferritin level was 16.6 µg/L. At 5 months, 5.9% (5/85) of infants had ID, and 2.4% (2/85) had IDA. Median (interquartile range) infant ferritin levels significantly declined from 113.4 (65.0-183.6) µg/L at 3 months to 50.9 (29.2-70.4) µg/L at 5 months, p < 0.001. Exclusive breastfeeding until 3 or 5 months was significantly associated with ID at 5 months (p = 0.020, and p = 0.008, respectively) on univariate analysis. The drop in ferritin between 3-5 months was significantly associated with weight and length gains between 0-3 months (p = 0.018, p = 0.009, respectively). Altogether, 14.3% of infants exclusively breastfed until 5 months developed ID. At 5 months, 3.4% of infants were underweight, 1.1% stunted, and 10.2% wasted. CONCLUSIONS: In exclusively breastfed term infants, ID occurred by 5 months. Early introduction of iron-rich foods should be considered in exclusively breastfed babies. A high prevalence of wasting suggests a calorie deficit in this population and will lead to stunting if not addressed.

A Two-Phased Telehealth Model to Treat Post-Traumatic Stress Disorder in a Health Care Worker due to the COVID-19 Pandemic: A Case Report.

Background: We report a case describing the use of a two-step telehealth intervention to treat symptoms of post-traumatic stress disorder (PTSD) that developed in a frontline health care worker (HCW) during the COVID-19 pandemic. HCWs are at increased risk of adverse psychological outcomes, including PTSD, due to the nature of their work, which has been exacerbated by the global pandemic. Methods: This case represents the first successfully completed participant in a larger ongoing trial to address psychological distress, PTSD, and comorbidities in HCWs consequent to the COVID-19 pandemic. Following a two-step intervention of self-directed narrative writing delivered entirely online followed by prolonged exposure therapy using videoconferencing, the HCW displayed significant improvement in symptoms of PTSD, depression, anxiety, and substance use. Results: The treatment model described here offers preliminary support for a two-step remote delivery approach to meet the need for scalable self-directed distance technology-based mental health interventions for HCWs. This study is registered on clinicaltrials.gov (NCT04626050).

Racial/ethnic minority females smoke more cigarettes after social interaction with others who smoke.

The present study investigated the effects of social interaction with others who smoke on daily cigarette use among diverse females via ecological momentary assessment methods. Ninety-eight premenopausal females (29.6% White, 70.4% racial/ethnic minority) who smoke daily reported their social interactions and cigarette use over 35-days. Greater than usual levels of social interaction with others who smoke was associated with increased cigarette use that day among racial/ethnic minority females. Future smoking cessation interventions targeting racial/ethnic minority females should consider the impact of social environments on smoking behaviors, such as the frequency of peer interactions with others who smoke.

Culturally Responsive Cognitive Behavioral Therapy for Ethnically Diverse Populations.

Cognitive behavioral therapy (CBT) is often referred to as the "gold standard" treatment for mental health problems, given the large body of evidence supporting its efficacy. However, there are persistent questions about the generalizability of CBTs to culturally diverse populations and whether culturally sensitive approaches are warranted. In this review, we synthesize the literature on CBT for ethnic minorities, with an emphasis on randomized trials that address cultural sensitivity within the context of CBT. In general, we find that CBT is effective for ethnic minorities with diverse mental health problems, although nonsignificant trends suggest that CBT effects may be somewhat weaker for ethnic minorities compared to Whites. We find mixed support for the cultural adaptation of CBTs, but evidence for cultural sensitivity training of CBT clinicians is lacking, given a dearth of relevant trials. Based on the limited evidence thus far, we summarize three broad models for addressing cultural issues when providing CBT to diverse populations.

The Immigrant Paradox in the Problem Behaviors of Youth in the United States: A Meta-analysis.

This meta-analysis synthesizes the empirical data on problem behaviors among foreign- (G1) and U.S-born (G2+) youth and explores the effects of immigrant status on youth internalizing and externalizing problems. A random effects meta-regression with robust variance estimates summarized effect sizes for internalizing and externalizing problems across 91 studies (N = 179,315, Mage  = 13.98). Results indicated that G1 youth reported significantly more internalizing problems (g = .06), and fewer externalizing problems than G2+ youth (g = -.06). Gender and sample type moderated the effects. The findings provide a first-step toward reconciling mixed support for the immigrant paradox by identifying for whom and under what conditions the immigrant experience serves as a risk or protective factor for youth.

Effects of COVID-19 related economic threat on political conservatism, xenophobia, and racial bias in the United States.

The uncertainty-threat model of conservatism posits that people turn to political conservatism to protect themselves from perceived threats; indeed, studies show increases in conservative ideology and outgroup bias following threat priming. The COVID-19 pandemic is an unprecedented threat that has had devastating effects on the health and economic lives of Americans. Concerns surrounding the threat of COVID-19 may have secondary effects on other aspects of American life, such as political and anti-Asian racial bias. The current studies explored the effects of COVID-19 related threats on expressed political conservatism, xenophobia, and racial bias under the uncertainty-threat model. Study 1 assessed the effects of priming health or economic risks of COVID-19 (vs. control), and found that economic threat led to increased xenophobia, but had no effects on overall conservatism. Study 2 then investigated whether the effects of COVID-related economic threat prime extended to racial bias, and explored moderators and mediators of effects. Results showed that the economic threat prime increased perceived group-status threat, and indirectly increased conservatism, xenophobia, and racial bias through the mechanism of perceived group-status threat. Effects were greatest for those impacted financially by the pandemic. In general, our studies provide support for the uncertainty-threat model with the novel threat of the COVID-19 pandemic. Implications for understanding potential shifts in conservatism and bias in response to future threats in the United States are discussed.

Dynamic insights into mitochondrial function: Monitoring viscosity and SO2 levels in living cells.

Mitochondria, central organelles pivotal for eukaryotic cell function, extend their influence beyond ATP production, encompassing roles in apoptosis, calcium signaling, and biosynthesis. Recent studies spotlight two emerging determinants of mitochondrial functionality: intramitochondrial viscosity and sulfur dioxide (SO2) levels. While optimal mitochondrial viscosity governs molecular diffusion and vital processes like oxidative phosphorylation, aberrations are linked with neurodegenerative conditions, diabetes, and cancer. Similarly, SO2, a gaseous signaling molecule, modulates energy pathways and oxidative stress responses; however, imbalances lead to cytotoxic sulfite and bisulfite accumulation, triggering disorders such as cancer and cardiovascular anomalies. Our research focused on development of a dual-channel fluorescent probe, applying electron-withdrawing acceptors within a coumarin dye matrix, facilitating monitoring of mitochondrial viscosity and SO2 in live cells. This probe distinguishes fluorescence peaks at 650 nm and 558 nm, allowing ratiometric quantification of SO2 without interference from other sulfur species. Moreover, it enables near-infrared viscosity determination, particularly within mitochondria. The investigation employed theoretical calculations utilizing Density Functional Theory (DFT) methods to ascertain molecular geometries and calculate rotational energies. Notably, the indolium segment of the probe exhibited the lowest rotational energy, quantified at 7.38 kcals/mol. The probe featured heightened mitochondrial viscosity dynamics when contained within HeLa cells subjected to agents like nystatin, monensin, and bacterial lipopolysaccharide (LPS). Overall, our innovative methodology elucidates intricate mitochondrial factors, presenting transformative insights into cellular energetics, redox homeostasis, and therapeutic avenues for mitochondrial-related disorders.

Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar.

How do neural circuits coordinate multiple behavioral responses to a single sensory cue? Here, we investigate how sweet taste drives appetitive behaviors in Drosophila, including feeding, locomotor suppression, spatial preference, and associative learning. We find that neural circuits mediating different innate responses to sugar are partially overlapping and diverge at the second and third layers. Connectomic analyses reveal distinct subcircuits that mediate different behaviors. Connectome-based simulations of neuronal activity predict that second-order sugar neurons act synergistically to promote downstream activity and that bitter input overrides the sugar circuit through multiple pathways acting at third- and fourth-order neurons. Consistent with the latter prediction, optogenetic experiments suggest that bitter input inhibits third- and fourth-order sugar neurons to override the sugar pathway, whereas hunger and diet act earlier in the circuit to modulate behavior. Together, these studies provide insight into how circuits are organized to drive diverse behavioral responses to a single stimulus.

Racial/ethnic differences in the acute effects of reduced nicotine content cigarettes among adolescents who smoke.

OBJECTIVE: Reducing the nicotine content in cigarettes decreases their addictiveness and abuse liability, including among adolescents. Whether these effects differ by race/ethnicity is unknown. This study is a secondary analysis of previously published data collected between 2014-2017. We examined racial/ethnic differences in the effects of smoking cigarettes with varying nicotine content levels on subjective effects and tobacco withdrawal among adolescents who smoke daily. METHODS: Across two counterbalanced sessions, 50 adolescents recruited from Rhode Island (ages 15-19; 30 % Underrepresented Minorities [URM], 20 % Asians and Pacific Islanders [API]; 50 % Non-Hispanic Whites) self-administered a very low nicotine content (VLNC; 0.4 mg nicotine/g of tobacco) or normal nicotine content control (NNC; 15.8 mg/g) research cigarette following overnight abstinence. Subjective effects were reported post-administration and tobacco withdrawal outcomes were calculated from pre- to post-administration scores. Multilevel linear models tested main and interactive effects between cigarette nicotine content and race/ethnicity on all study outcomes. RESULTS: Participants reported lower positive subjective effects and reductions in smoking urges after smoking a VLNC cigarette relative to smoking an NNC cigarette (ps < 0.01). A main effect of race/ethnicity emerged, such that API (vs. URM and White) adolescents reported lower positive subjective effects, greater craving reduction, and higher cigarette aversion after smoking, regardless of nicotine content (ps < 0.05). Significant interactions were found between race/ethnicity and nicotine content for cigarette aversion, such that API adolescents rated VLNC (vs. NNC) cigarettes as less aversive than White and URM adolescents did (p = 0.03). CONCLUSIONS: Findings provide evidence that VLNC cigarettes may reduce abuse liability and tobacco withdrawal symptoms for adolescents across racial/ethnic groups and particularly for API youth.

Empirically establishing drug exposure records directly from untargeted metabolomics data.

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N-acyl lipid changes in a cohort with human immunodeficiency virus. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.

High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV.

Increased baseline expression and lack of induction of interferon-stimulated genes (ISG) are strong negative predictors of therapeutic response to PegIFN/RBV in patients co-infected with HIV and hepatitis C virus (HCV). This study specifically addressed whether ISG-15 expression influences therapeutic responses in 20 HIV/HCV genotype-1 subjects undergoing HCV treatment. Non-responders had significantly higher baseline expression and selective induction of ISG-15 after IFN-α treatment relative to participants with sustained virological response. High baseline levels of ISG-15 were also associated with less induction of ISG with treatment. These results support a role for ISG-15 as a prognostic indicator and resistance factor to IFN-α.

Can a propensity score matching method be applied to assessing efficacy from single-arm proof-of-concept trials in oncology?

As a result of the escalating number of new cancer treatments being developed and competition among pharmaceutical companies, decisions regarding how to proceed with phase III trials are frequently based on findings from either single-arm phase I expansion cohorts or phase II studies that compare the efficacy of the study drug to a standard-of-care benchmark derived from historical data. However, even when eligibility criteria are matched, differences in the distribution of baseline patient features may influence the outcome of single-arm trials in real-world scenarios. Therefore, novel methods are needed to enhance the accuracy of efficacy prediction from current cohorts relative to historical data. In this study, we demonstrated the feasibility of using the propensity score matching (PSM) method to improve decision making by matching relevant baseline features between current and historical cohorts. According to our findings, utilizing the PSM method may provide a less biased means of comparing outcomes between current and historical cohorts relative to a naïve approach, which relies solely on differences in average outcomes between the cohorts.

A Randomized Pilot Trial of Micronutrient Supplementation for Under-5 Children in an Urban Low-Cost Flat Community in Malaysia: A Framework for Community-Based Research Integration.

Early childhood nutritional deficiency has detrimental consequences on physical and cognitive development. We conducted a single-center, single-blind, two-arm pilot randomized no-treatment controlled trial (the Child of Urban Poverty Iron Project (CUPIP); NCT03819530) in a people's housing project locale in Selangor, Malaysia, between September 2019 and February 2020, to assess the trial's general feasibility and preliminary benefits of daily micronutrient supplementation for iron storage and anthropometric outcomes in under-5 children. Those with history of premature births, congenital abnormalities, or baseline hemoglobin <70 g/L were excluded. Participants received baseline deworming and were simply randomized in a 1:1 ratio to either micronutrient (4-month daily micronutrient packets) or control (no micronutrient supplementation) groups. Information on anthropometric, erythrocytic, and iron storage endpoints were collected. Overall, 45 (25 micronutrient and 20 controls) participants were enrolled and completed 4-month endpoint assessments. Micronutrient recipients demonstrated higher median mean corpuscular volume, serum ferritin level with no significant differences in all anthropometric endpoints. In conclusion, this pilot trial was implementable, demonstrating that micronutrient supplementation significantly improved hematological, but not anthropometric, endpoints, of under-5-year-old children living in an underprivileged environment. A definitive well-designed trial with larger sample sizes and greater attrition control should be contemplated in the future.

Synchronous Bilateral Primary Testicular Tumors With Discordant Histopathology.

Concomitant presentation of histologically distinct bilateral testicular tumors is exceedingly rare. Here we report the case of a 20-year-old male who presented with a left testicular mass. He was found to have bilateral testicular masses on ultrasound and underwent bilateral orchiectomy. Left testicular pathology revealed a mixed germ cell tumor consisting of teratoma, seminoma, and germ cell neoplasia in situ; right testicular pathology revealed two foci of pure seminomas. He is currently on active surveillance and remains in remission at 18-month follow-up. Our case demonstrates the rare occurrence of bilateral primary synchronous testicular tumors with different histopathology in each testis. Despite the rarity of this condition, its treatment is based on standard management of unilateral testicular carcinoma, with the added element of prioritization of one tumor over the other. It is important for clinicians to tailor management for bilateral testicular germ cell tumors according to the most aggressive component.

Assessing dehydration status in dengue patients using urine colourimetry and mobile phone technology.

BACKGROUND: Dengue is a systemic and dynamic disease with symptoms ranging from undifferentiated fever to dengue shock syndrome. Assessment of patients' severity of dehydration is integral to appropriate care and management. Urine colour has been shown to have a high correlation with overall assessment of hydration status. This study tests the feasibility of measuring dehydration severity in dengue fever patients by comparing urine colour captured by mobile phone cameras to established laboratory parameters. METHODOLOGY/PRINCIPAL FINDINGS: Photos of urine samples were taken in a customized photo booth, then processed using Adobe Photoshop to index urine colour into the red, green, and blue (RGB) colour space and assigned a unique RGB value. The RGB values were then correlated with patients' clinical and laboratory hydration indices using Pearson's correlation and multiple linear regression. There were strong correlations between urine osmolality and the RGB of urine colour, with r = -0.701 (red), r = -0.741 (green), and r = -0.761 (blue) (all p-value <0.05). There were strong correlations between urine specific gravity and the RGB of urine colour, with r = -0.759 (red), r = -0.785 (green), and r = -0.820 (blue) (all p-value <0.05). The blue component had the highest correlations with urine specific gravity and urine osmolality. There were moderate correlations between RGB components and serum urea, at r = -0.338 (red), -0.329 (green), -0.360 (blue). In terms of urine biochemical parameters linked to dehydration, multiple linear regression studies showed that the green colourimetry code was predictive of urine osmolality (ß coefficient -0.082, p-value <0.001) while the blue colourimetry code was predictive of urine specific gravity (ß coefficient -2,946.255, p-value 0.007). CONCLUSIONS/SIGNIFICANCE: Urine colourimetry using mobile phones was highly correlated with the hydration status of dengue patients, making it a potentially useful hydration status tool.

Molecular cloning and characterization of chicken prostaglandin E receptor subtypes 2 and 4 (EP2 and EP4).

Prostaglandin E(2) (PGE(2)) is an important chemical mediator responsible for regulation of many vital physiological processes. Four receptor subtypes have been identified to mediate its biological actions. Among these subtypes, prostaglandin E receptor subtypes 2 and 4 (EP(2) and EP(4)), both coupled to cAMP-protein kinase A (cAMP-PKA) signaling pathway, are proposed to play crucial roles under both physiological and pathological conditions. Though both receptors were extensively studied in mammals, little is known about their functionality and expression in non-mammalian species including chicken. In present study, the full-length cDNAs for chicken EP(2) and EP(4) receptors were first cloned from adult chicken ovary and testis, respectively. Chicken EP(2) is 356 amino acids in length and shows high amino acid identity to that of human (61%), mouse (63%), and rat (61%). On the other hand, the full-length cDNA of EP(4) gene encodes a precursor of 475 amino acids with a high degree of amino acid identity to that of mammals, including human (87%), mouse (86%), rat (84%), dog (85%), and cattle (83%), and a comparatively lower sequence identity to zebrafish (52%). RT-PCR assays revealed that EP(2) mRNA was expressed in all tissues examined including the oviduct, while EP(4) expression was detected only in a few tissues. Using the pGL3-CRE-luciferase reporter system, we also demonstrated that PGE(2) could induce luciferase activity in DF-1 cells expressing EP(2) and EP(4) in dose-dependent manners (EC(50): <1 nM), confirming that both receptors could be activated by PGE(2) and functionally coupled to the cAMP-PKA signaling pathway. Together, our study establishes a molecular basis to understand the physiological roles of PGE(2) in target tissues of chicken.

Case based simulation in MRI for suspected appendicitis in children.

PURPOSE: To establish the effect on diagnostic confidence of a simulation setting, in which radiologists re-interpret anonymized pediatric MRI cases. MATERIALS: In this IRB-approved study, participants completed surveys rating confidence before and after interpreting 10 MRI cases for suspected appendicitis in children. RESULTS: 18 radiologists (4 faculty, 5 fellows, and 9 residents) correctly identified an average of 7.44 cases (range 5-9). Self-described confidence regarding technique and interpretation increased from 2.0 (SD 0.77) and 2.33 (SD 0.69) to 2.83 (SD 0.71) and 2.94 (SD 0.73), respectively. CONCLUSION: Simulated interpretation of pediatric MRI in suspected appendicitis results in increased self-describe confidence without requiring additional capital/equipment expenses.

Identification of the endogenous ligands for chicken growth hormone-releasing hormone (GHRH) receptor: evidence for a separate gene encoding GHRH in submammalian vertebrates.

It is generally believed that hypothalamic GHRH activates GHRH receptor (GHRHR) to stimulate GH synthesis and release in the pituitary of mammals. However, the identity of the endogenous ligand of GHRHR is still unresolved in submammalian vertebrates including birds. In this study, we have successfully identified the chicken GHRH (cGHRH) gene, which consists of seven exons including two exons (exons 4 and 5) coding for the predicted mature GHRH peptide of 47 amino acids. Interestingly, the differential usage of splice donor sites at exon 6 results in the generation of two prepro-GHRHs (172 and 188 amino acids in length) with different C-terminal tails. Similar to mammals, cGHRH was detected to be predominantly expressed in the hypothalamus by RT-PCR assay. Using the pGL3-CRE-luciferase reporter system, we further demonstrated that both the synthetic cGHRH peptides (cGHRH(1-47) and cGHRH(1-31)) and conditioned medium from CHO cells expressing cGHRH could strongly induce luciferase activity via activation of cGHRHR, indicating that cGHRH could bind cGHRHR and activate downstream cAMP-protein kinase A signaling pathway. Using the same system, cGHRH-like peptide was also shown to be capable of activating cGHRHR in vitro. As in chicken, a conserved GHRH gene was identified in the genomes of lower vertebrate species including zebrafish, fugu, tetraodon, and Xenopus by synteny analysis. Collectively, our data suggest that GHRH, perhaps together with GHRH-like peptide (chicken/carp-like), may function as the authentic endogenous ligands of GHRHR in chicken as well as in other lower vertebrate species.

Epidermal growth factor (EGF) receptor ligands in the chicken ovary: I. Evidence for heparin-binding EGF-like growth factor (HB-EGF) as a potential oocyte-derived signal to control granulosa cell proliferation and HB-EGF and kit ligand expression.

There is increasing evidence that epidermal growth factor (EGF) receptor (EGFR) ligand and Kit ligand (KL) play critical roles in controlling follicular development in mammals. Because little is known about their expressions in the ovary of nonmammalian vertebrate, our study aimed to examine the expression, hormonal regulation, and interaction of HB-EGF and KL in the chicken ovary. Using semiquantitative RT-PCR, we demonstrated that ovarian HB-EGF expression increased dramatically with the posthatching ovarian growth. In line with this finding, HB-EGF was shown to be produced primarily by the growing oocytes and capable of stimulating the proliferation of granulosa cells in prehierarchal (3 mm) and preovulatory follicles (F5 and F1). Although HB-EGF expression is mainly restricted to the oocytes, its expression in cultured granulosa cells could be transiently yet strongly induced by HB-EGF and other EGFR ligands including EGF and TGF-alpha. And the inducing effect of HB-EGF was completely abolished by AG1478 (10 microM) or PD98059 (100 microM), indicating that the action of HB-EGF is mediated by EGFR and intracellular MAPK/ERK signaling pathway. Unlike mammals, only KL-1, not the other three isoforms identified (KL-2, -3, and -4), was detected to be predominantly expressed in the chicken ovary. Interestingly, KL expression in undifferentiated and differentiated granulosa cells could be transiently down-regulated by HB-EGF, implying an intrafollicular communication between growing oocyte and surrounding granulosa cells through the interplay of EGFR ligand and KL. Collectively, our data suggest that HB-EGF is likely a paracrine signal from the oocyte to regulate granulosa cell proliferation and HB-EGF and KL expression during ovarian follicular development.

Microfluidics Cell Loading-Dock System: Ordered Cellular Array for Dynamic Lymphocyte-Communication Study.

It remains a great challenge to establish a high-throughput platform that can explore the interactions among multiple lymphocytes (>2 cells) and retrieve the interested cells for downstream analysis. This study demonstrates a microfluidics cell loading-dock system (Cell-Dock) to enclose multiple cells in 1D, 2D, and 3D chambers with high throughput and efficiency and single-cell accuracy. The loading efficiencies of 95%, 85%, and 74% for one-, three-, and five-cell systems are achieved, respectively. The Cell-Dock system provides precise and dynamic cell packing models to facilitate lymphocyte-interaction studies. The results demonstrate that individual natural killer (NK) cells may function independently rather than cooperate to lyse target cells in the defined microenvironment. Furthermore, the strong/weak NK cells are retrieved based on their on-chip cytotoxicity and mRNA sequencing is conducted to find the possible mechanisms for "serial killing," an important but unsolved issue. This study finds that the stronger NK cells overexpress multiple genes involved in cytotoxicity and adhesion molecules (including the well-known ICAM1 and seldom reported B4GALT1) might play important roles in the regulation of NK cytolysis.